FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Reid, GSD Shan, XC Coughlin, CM Lassoued, W Pawel, BR Wexler, LH Thiele, CJ Tsokos, M Pinkus, JL Pinkus, GS Grupp, SA Vonderheide, RH AF Reid, Gregor S. D. Shan, Xiaochuan Coughlin, Christina M. Lassoued, Wiem Pawel, Bruce R. Wexler, Leonard H. Thiele, Carol J. Tsokos, Maria Pinkus, Jack L. Pinkus, Geraldine S. Grupp, Stephan A. Vonderheide, Robert H. TI Interferon-gamma-Dependent Infiltration of Human T Cells into Neuroblastoma Tumors In vivo SO CLINICAL CANCER RESEARCH LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; ANTIGEN-PROCESSING MACHINERY; MHC CLASS-I; MALIGNANT-MELANOMA; DOWN-REGULATION; ANTITUMOR IMMUNITY; HLA; ASSOCIATION; EXPRESSION; IMMUNOTHERAPY AB Purpose: To investigate the impact of interferon-gamma-mediated upregulation of major histocompatibility complex class I expression on tumor-specific T-cell cytotoxicity and T-cell trafficking into neuroblastoma tumors in vivo. Experimental Design: Restoration of major histocompatibility complex class I expression by interferon-gamma treatment enhances killing of neuroblastoma cells. To understand the potential of this approach in vivo, we developed a novel model of neuroblastoma in which NOD/scid/IL2R gamma(null) immunodeficient mice are engrafted with both human T cells and tumor cells. Results: Here, we show enhanced killing of neuroblastoma cells by patient-derived, tumor-specific T cells in vitro. In addition, interferon-gamma treatment in vivo induces efficient upregulation of major histocompatibility complex class I expression on neuroblastoma tumor cells, and this is accompanied by significantly enhanced infiltration of T cells into the tumor. In a pilot clinical trial in patients with high-risk neuroblastoma, we similarly observed augmented T-cell trafficking into neuroblastoma nests in tumor biopsy specimens obtained from patients after 5 days of systemic interferon-gamma therapy. Conclusions: Interferon-gamma overcomes critical obstacles to the killing of human neuroblastoma cells by specific T cells. Together, these findings provide a rationale for the further testing of interferon-gamma as an approach for improving the efficacy of T cell-based therapies for neuroblastoma and other major histocompatibility complex class I-deficient malignancies. In addition, we describe a model that may expedite the preclinical screening of approaches aimed at augmenting T-cell trafficking into human tumors. (Clin Cancer Res 2009;15(21):6602-8) C1 [Grupp, Stephan A.; Vonderheide, Robert H.] Univ Penn, Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Reid, Gregor S. D.; Coughlin, Christina M.; Grupp, Stephan A.] Univ Penn, Sch Med, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. [Pawel, Bruce R.; Grupp, Stephan A.] Univ Penn, Sch Med, Dept Pathol, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Shan, Xiaochuan; Lassoued, Wiem; Vonderheide, Robert H.] Univ Penn, Sch Med, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. [Thiele, Carol J.; Tsokos, Maria] NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Pinkus, Jack L.; Pinkus, Geraldine S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Wexler, Leonard H.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Vonderheide, RH (reprint author), Univ Penn, Sch Med, Abramson Canc Ctr, 551 Basic Res Bldg 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM grupp@email.chop.edu; rhv@exchange.upenn.edu RI Reid, Gregor/F-6260-2011 OI Reid, Gregor/0000-0002-7567-3424 FU Alliance for Cancer Gene Therapy; WW Smith Charitable Trust [R21 CA1 10516]; Sanford Funds of the Children's Hospital of Philadelphia FX Alliance for Cancer Gene Therapy (R.H. Vonderheide); and R21 CA1 10516, The WW Smith Charitable Trust, and the Foerderer-Murray, Weinberg and Sanford Funds of the Children's Hospital of Philadelphia (S.A. Grupp). NR 28 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2009 VL 15 IS 21 BP 6602 EP 6608 DI 10.1158/1078-0432.CCR-09-0829 PG 7 WC Oncology SC Oncology GA 513CP UT WOS:000271300200017 PM 19825945 ER PT J AU Herbertson, RA Tebbutt, NC Lee, FT MacFarlane, DJ Chappell, B Micallef, N Lee, ST Saunder, T Hopkins, W Smyth, FE Wyld, DK Bellen, J Sonnichsen, DS Brechbiel, MW Murone, C Scott, AM AF Herbertson, Rebecca A. Tebbutt, Niall C. Lee, Fook-Thean MacFarlane, David J. Chappell, Bridget Micallef, Noel Lee, Sze-Ting Saunder, Timothy Hopkins, Wendie Smyth, Fiona E. Wyld, David K. Bellen, John Sonnichsen, Daryl S. Brechbiel, Martin W. Murone, Carmel Scott, Andrew M. TI Phase I Biodistribution and Pharmacokinetic Study of Lewis Y-Targeting Immunoconjugate CMD-193 in Patients with Advanced Epithelial Cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; BLOOD-GROUP ANTIGENS; GEMTUZUMAB OZOGAMICIN; OVARIAN-CANCER; SOLID TUMORS; LUNG-CANCER; ANTIBODY; EXPRESSION; CARCINOMA; CELLS AB Purpose: This phase I study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 [a humanized anti-Lewis Y (Le(y)) antibody conjugated with calicheamicin in patients with advanced cancers expressing the Ley antigen. Experimental Design: The primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. Secondary objectives included response rates and change in tumor metabolism. Patients with progressive, measurable, and Ley positive malignancies were eligible for enrollment in one of two dose cohorts, 1.0 and 2.6 mg/m(2). The first cycle was trace labeled with (111)In for biodistribution assessment using y camera imaging. Subsequent cycles were administered every 3 weeks up to a maximum of six cycles, depending on toxicity and response. Pharmacokinetic analysis was based on radioassay and ELISA. Results: Nine patients were enrolled in the study. Biodistribution images showed initial blood pool activity, followed by markedly increased hepatic uptake by day 2, and fast blood clearance in all patients. There was low uptake in tumor in all patients. The overall T1/2 beta of (111)In-CMD-193 was 102.88 +/- 35.67 hours, with no statistically significant difference between the two dose levels. One patient had a partial metabolic response on (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) after four cycles, but no radiological responses were observed. Myelosuppression and effects on liver function were the most significant adverse effects. Conclusions: CMD-193 shows rapid blood clearance and increased hepatic uptake compared with prior studies of the parental antibody hu3S193. These results highlight the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics to assist in clinical development. (Clin Cancer Res 2009;15(21):6709-15) C1 [Herbertson, Rebecca A.; Lee, Fook-Thean; Lee, Sze-Ting; Hopkins, Wendie; Smyth, Fiona E.; Murone, Carmel; Scott, Andrew M.] Austin Hosp, Ludwig Inst Canc Res, Melbourne, Vic 3084, Australia. [Tebbutt, Niall C.; Micallef, Noel] Austin Hosp, Ludwig Inst, Oncol Unit, Melbourne, Vic 3084, Australia. [Chappell, Bridget; Lee, Sze-Ting; Saunder, Timothy; Scott, Andrew M.] Austin Hosp, Dept Nucl Med, Melbourne, Vic 3084, Australia. [Chappell, Bridget; Lee, Sze-Ting; Saunder, Timothy; Scott, Andrew M.] Austin Hosp, Ctr PET, Melbourne, Vic 3084, Australia. [Murone, Carmel] Austin Hosp, Dept Anat Pathol, Melbourne, Vic 3084, Australia. [MacFarlane, David J.; Bellen, John] Royal Brisbane & Womens Hosp, Dept Nucl Med, Brisbane, Qld, Australia. [MacFarlane, David J.; Bellen, John] Royal Brisbane & Womens Hosp, Queensland PET Serv, Brisbane, Qld, Australia. [Wyld, David K.] Royal Brisbane & Womens Hosp, Canc Care Serv, Brisbane, Qld, Australia. [Sonnichsen, Daryl S.] Wyeth Res, Collegeville, PA USA. [Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Scott, AM (reprint author), Austin Hosp, Ludwig Inst Canc Res, Level 6,Harold Stokes Bldg,Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au RI Wyld, David/B-8893-2015 OI Wyld, David/0000-0001-9523-4333 FU Wyeth Pharmaceuticals, Inc FX Wyeth Pharmaceuticals, Inc. provided financial support and pharmaceutical investigation compound CMD-193 for the study. The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research supports Martin W. Brechbiel. NR 30 TC 29 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2009 VL 15 IS 21 BP 6709 EP 6715 DI 10.1158/1078-0432.CCR-09-0536 PG 7 WC Oncology SC Oncology GA 513CP UT WOS:000271300200029 PM 19825951 ER PT J AU Bosker, WM Huestis, MA AF Bosker, Wendy M. Huestis, Marilyn A. TI Oral Fluid Testing for Drugs of Abuse SO CLINICAL CHEMISTRY LA English DT Review ID CHROMATOGRAPHY-MASS SPECTROMETRY; SOLID-PHASE EXTRACTION; LC-MS-MS; PERFORMANCE LIQUID-CHROMATOGRAPHY; METABOLITE 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; COZART(R) MICROPLATE EIA; CANNABIS SMOKE EXPOSURE; MULTIPLE ILLICIT DRUGS; GAS-CHROMATOGRAPHY; GC-MS AB BACKGROUND: Oral fluid (OF) is an exciting alternative matrix for monitoring drugs of abuse in workplace, clinical toxicology, criminal justice, and driving under the influence of drugs (DUID) programs. During the last 5 years, scientific and technological advances in OF collection, point-of-collection testing devices, and screening and confirmation methods were achieved. Guidelines were proposed for workplace OF testing by the Substance Abuse and Mental Health Services Administration, DUID testing by the European Union's Driving under the Influence of Drugs, Alcohol and Medicines (DRUID) program, and standardization of DUID research. Although OF testing is now commonplace in many monitoring programs, the greatest current limitation is the scarcity of controlled drug administration studies available to guide interpretation. CONTENT: This review outlines OF testing advantages and limitations, and the progress in OF that has occurred during the last 5 years in collection, screening, confirmation, and interpretation of cannabinoids, opioids, amphetamines, cocaine, and benzodiazepines. We examine controlled drug administration studies, immunoassay and chromatographic methods, collection devices, point-of-collection testing device performance, and recent applications of OF testing. SUMMARY: Substance Abuse and Mental Health Services Administration approval of OF testing was delayed because questions about drug OF disposition were not yet resolved, and collection device performance and testing assays required improvement. Here, we document the many advances achieved in the use Of OF. Additional research is needed to identify new biomarkers, determine drug detection windows, characterize OF adulteration techniques, and evaluate analyte stability. Nevertheless, there is no doubt that OF offers multiple advantages as an alternative matrix for drug monitoring and has an important role in DUID, treatment, workplace, and criminal justice programs. (C) 2009 American Association for Clinical Chemistry C1 [Bosker, Wendy M.] Maastricht Univ, Fac Psychol & Neurosci Neuropsychol Psychopharmac, Expt Psychopharmacol Unit, Maastricht, Netherlands. [Bosker, Wendy M.; Huestis, Marilyn A.] Natl Inst Drug Abuse, NIH, Baltimore, MD USA. RP Huestis, MA (reprint author), 251 Bayview Blvd, Baltimore, MD 21224 USA. FU Intramural NIH HHS [ZIA DA000412-13] NR 130 TC 157 Z9 158 U1 3 U2 51 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2009 VL 55 IS 11 BP 1910 EP 1931 DI 10.1373/clinchem.2008.108670 PG 22 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 512SC UT WOS:000271269700006 PM 19745062 ER PT J AU Seegmiller, JC Sviridov, D Larson, TS Borland, TM Hortin, GL Lieske, JC AF Seegmiller, Jesse C. Sviridov, Denis Larson, Timothy S. Borland, Timothy M. Hortin, Glen L. Lieske, John C. TI Comparison of Urinary Albumin Quantification by Immunoturbidimetry, Competitive Immunoassay, and Protein-Cleavage Liquid Chromatography-Tandem Mass Spectrometry SO CLINICAL CHEMISTRY LA English DT Article AB BACKGROUND: Increased urinary albumin excretion is a well-documented diagnostic and prognostic biomarker for renal disease. Urinary albumin is typically measured in clinical settings by immunoassay methods. However, neither a reference method nor a urine albumin calibration reference material is currently available. METHODS: We quantified Urinary albumin in patient samples by using 3 commercially available reagent systems: DiaSorin SPQ (TM) and Beckman Coulter LX (R) 20 (immunoturbidimetric), and Siemens Immulite (R) (competitive immunoassay). Results were compared to values obtained by protein-cleavage liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In general, results from the 3 immunoassays agreed with results from LC-MS/MS. However, the SPQ results showed a negative bias across all ranges of albuminuria [(0-200 mg/L, y = 0.91x - 3.74 (CI 0.86-0.96); > 200 mg/L, y = 0.88x- 40.30 (CI 0.76-1 00)], whereas the I,X 20 showed minimal bias in the 0-200 mg/L range [y = 0.97x - 88 (CI 0.92-1.02)] and the Immulite assay showed positive bias in the 0-200 mg/L range [y = 1.15x - 4.38 (CI 1.09-1.20)]. CONCLUSIONS: These results showed a reasonable quantification of urinary albumin by representative polyclonal and monoclonal immunoassays compared to an LC-MS/MS assay. In addition, the results do not suggest the presence of nonimmunoreactive albumin in urine. However, differences in analytic performance between assays support the need for a reference calibration material and reference method to standardize clinical laboratory measurements of urinary albumin. (C) 2009 American Association for Clinical Chemistry C1 [Lieske, John C.] Mayo Clin, Renal Funct Lab, Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Larson, Timothy S.; Lieske, John C.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN 55905 USA. [Sviridov, Denis; Hortin, Glen L.] NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Lieske, JC (reprint author), Mayo Clin, Renal Funct Lab, Dept Lab Med & Pathol, 200 1st St SW, Rochester, MN 55905 USA. FU NIH Clinical Center, Department of Health and Human Services FX Work at the NIH was supported by the intramural research program of the NIH Clinical Center, Department of Health and Human Services NR 9 TC 21 Z9 23 U1 1 U2 14 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2009 VL 55 IS 11 BP 1991 EP 1994 DI 10.1373/clinchem.2009.129833 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 512SC UT WOS:000271269700014 PM 19745060 ER PT J AU Kopp, JB AF Kopp, Jeffrey B. TI Dystroglycan in the Molecular Diagnosis of the Podocytopathies SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID GLYCOPROTEIN COMPLEX; ALPHA-DYSTROGLYCAN; BASEMENT-MEMBRANE; SIALIC-ACID; DYSTROPHIN; UTROPHIN; PODOCYTE; EXPRESSION; TISSUE C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10 Ctr Dr,Room 3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2009 VL 4 IS 11 BP 1696 EP 1698 DI 10.2215/CJN.06910909 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 517PN UT WOS:000271628400002 PM 19850772 ER PT J AU Battapady, H Lin, P Holroyd, T Hallett, M Chen, XD Fei, DY Bai, O AF Battapady, Harsha Lin, Peter Holroyd, Tom Hallett, Mark Chen, Xuedong Fei, Ding-Yu Bai, Ou TI Spatial detection of multiple movement intentions from SAM-filtered single-trial MEG signals SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE Magnetoencephalography (MEG); Synthetic aperture magnetometry (SAM); Virtual channels; Event-related desynchronization/synchronization (ERD/ERS); Brain-computer interface (BCI); Movement intention; Motor control ID EVENT-RELATED DESYNCHRONIZATION; COMPUTER INTERFACE TECHNOLOGY; HIGH-RESOLUTION EEG; FINGER MOVEMENTS; VOLUNTARY MOVEMENT; BRAIN; CORTEX; CLASSIFICATION; MAGNETOENCEPHALOGRAPHY; HANDEDNESS AB Objective: To test whether human intentions to sustain or cease movements in right and left hands can be decoded reliably from spatially filtered single-trial magnetoencephalographic (MEG) signals for motor execution and motor imagery. Methods: Seven healthy volunteers, naive to BCI technology, participated in this study. Signals were recorded from 275-channel MEG, and synthetic aperture magnetometry (SAM) was employed as the spatial filter. The four-class classification was performed offline. Genetic algorithm based Mahalanobis linear distance (GA-MLD) and direct-decision tree classifier (DTC) techniques were adopted for the classification through 10-fold cross-validation. Results: Through SAM imaging, strong and distinct event-related desynchronization (ERD) associated with sustaining, and event-related synchronization (ERS) patterns associated with ceasing of right and left hand movements were observed in the beta band (15-30 Hz) on the contralateral hemispheres for motor execution and motor imagery sessions. Virtual channels were selected from these areas of high activity for the corresponding events as per the paradigm of the study. Through a statistical comparison between SAM-filtered virtual channels from single-trial MEG signals and basic MEG sensors, it was found that SAM-filtered virtual channels significantly increased the classification accuracy for motor execution (GA-MLD: 96.51 +/- 2.43%) as well as motor imagery sessions (GA-MLD: 89.69 +/- 3.34%). Conclusion: Multiple movement intentions can be reliably detected from SAM-based spatially filtered single-trial MEG signals. Significance: MEG signals associated with natural motor behavior may be utilized for a reliable high-performance brain-computer interface (BCI) and may reduce long-term training compared with conventional BCI methods using rhythm control. (C) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Battapady, Harsha; Fei, Ding-Yu; Bai, Ou] Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, Richmond, VA 23284 USA. [Lin, Peter; Hallett, Mark; Bai, Ou] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. [Holroyd, Tom] NIMH, MEG Core Facil, Bethesda, MD 20892 USA. [Chen, Xuedong] Huazhong Univ Sci & Technol, State Key Lab Digital Mfg Equipment & Technol, Wuhan 430074, Hubei, Peoples R China. RP Bai, O (reprint author), Virginia Commonwealth Univ, Dept Biomed Engn, EEG & BCI Lab, 401 W Grace St,Room 2405,POB 843067, Richmond, VA 23284 USA. EM obai@vcu.edu FU NIH, National Institute of Neurological Disorders and Stroke FX This research was partly supported by the Intramural Research Program of the NIH, National Institute of Neurological Disorders and Stroke. NR 42 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2009 VL 120 IS 11 BP 1978 EP 1987 DI 10.1016/j.clinph.2009.08.017 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 529UT UT WOS:000272545000013 PM 19781986 ER PT J AU Nager, CW Brubaker, L Daneshgari, F Litman, HJ Dandreo, KJ Sirls, L Lemack, GE Richter, HE Leng, W Norton, P Kraus, SR Chai, TC Chang, D Amundsen, CL Stoddard, AM Tennstedt, SL AF Nager, Charles W. Brubaker, Linda Daneshgari, Firouz Litman, Heather J. Dandreo, Kimberly J. Sirls, Larry Lemack, Gary E. Richter, Holly E. Leng, Wendy Norton, Peggy Kraus, Stephen R. Chai, Toby C. Chang, Debuene Amundsen, Cindy L. Stoddard, Anne M. Tennstedt, Sharon L. CA Urinary Incontinence Treatment Net TI Design of the Value of Urodynamic Evaluation (ValUE) trial: A non-inferiority randomized trial of preoperative urodynamic investigations SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Randomized trial; Stress urinary incontinence; Urodynamic studies; Non-inferiority trial ID QUALITY-OF-LIFE; STRESS URINARY-INCONTINENCE; CLINICAL-TRIALS; WOMEN; PREVALENCE; INSTRUMENT; SURGERY; COSTS AB Background and purpose: Urodynamic studies (UDS) are routinely obtained prior to surgery for stress urinary incontinence (SUI) despite a lack of evidence that UDS information has an actual impact on outcome. The primary aim of this non-inferiority randomized clinical trial is to determine whether women with symptomatic. uncomplicated SUI who undergo only a basic office evaluation (BOE) prior to SUI surgery (No UDS arm) have non-inferior treatment outcomes compared to women who have BOE and UDS (UDS arm). Secondary aims are: 1) to determine how often physicians use preoperative UDS results to alter clinical and surgical decision-making, 2)to compare the amount of improvement in incontinence outcomes, and 3) to determine the incremental cost and utility of performing UDS compared with not performing UDS. Methods: After an initial basic office evaluation, women planning surgery for uncomplicated SUI who consent to study participation will be randomized to receive preoperative UDS or No UDS. Treatment will be planned and performed by the surgeon utilizing all the data available to them. We will compare results from the basic office evaluation (No UDS) with results from the basic office evaluation and preoperative UDS. Results: The primary outcome will be measured at 12 months using responses to the Urogenital Distress Inventory and the Patient Global Index-improvement. C1 [Nager, Charles W.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA. [Brubaker, Linda] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA. [Daneshgari, Firouz] Upstate Med Univ, Dept Urol, Syracuse, NY USA. [Litman, Heather J.; Dandreo, Kimberly J.; Stoddard, Anne M.; Tennstedt, Sharon L.] New England Res Inst, Watertown, MA 02172 USA. [Sirls, Larry] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48072 USA. [Lemack, Gary E.] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX USA. [Richter, Holly E.] Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [Leng, Wendy] Univ Pittsburgh, Dept Urol, Pittsburgh, PA USA. [Norton, Peggy] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. [Kraus, Stephen R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA. [Chai, Toby C.] Univ Maryland, Dept Urol, College Pk, MD 20742 USA. [Chang, Debuene] NIDDK, NIH, Bethesda, MD USA. [Amundsen, Cindy L.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. RP Nager, CW (reprint author), Univ Calif San Diego, San Diego Med Ctr, Mail Code 0974,9350 Campus Point Dr,Ste 2A, La Jolla, CA 92037 USA. EM cnager@ucsd.edu OI Wadie, Bassem/0000-0002-6977-6849; Rasooly, Rebekah/0000-0002-6357-5528 FU NIDDK NIH HHS [U01 DK060395, U01 DK058229, U01 DK60397, U01 DK58229, U01 DK60395, U01 DK60380, U01 DK060401, U01 DK060401-07, U01 DK060397, U01 DK58234, U01 DK060393, U01 DK58225, U01 DK060401-06, U01 DK58231, U01 DK60393, U01 DK060380, U01 DK058231, U01 DK060379, U01 DK058234, U01 DK60379, U01 DK60401, U01 DK060401-08, U01 DK060401-08S1, U01 DK058225, U01 DK060401-05] NR 32 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2009 VL 30 IS 6 BP 531 EP 539 DI 10.1016/j.cct.2009.07.001 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 523YM UT WOS:000272111000005 PM 19635587 ER PT J AU Galban, S Gorospe, M AF Galban, Stefanie Gorospe, Myriam TI Factors Interacting with HIF-1 alpha mRNA: Novel Therapeutic Targets SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE Post-transcriptional gene regulation; RNA-binding proteins; microRNA; antisense RNA; IRES ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; BINDING PROTEIN HUR; ENDOTHELIAL GROWTH-FACTOR; RIBOSOME ENTRY SITE; IRES-MEDIATED TRANSLATION; MARINE NATURAL-PRODUCT; SMOOTH-MUSCLE-CELLS; FACTOR-KAPPA-B; PATEAMINE-A; POSTTRANSCRIPTIONAL EVENTS AB The heterodimeric transcription factor HIF-1 (hypoxia-inducible factor-1) induces angiogenesis, a process that is aberrantly elevated in cancer. The HIF-1 beta subunit is constitutively expressed, but the levels of the HIF-1 alpha subunit are robustly regulated, increasing under hypoxic conditions and decreasing in normoxia. These changes result from rapid alterations in the rates of HIF-1 alpha production and degradation. While the regulation of HIF-1 alpha degradation is understood in significant detail, much less is known about the regulation of HIF-1 alpha biosynthesis. Here, we review recent evidence that HIF-1 alpha production is effectively controlled by post-transcriptional mechanisms. We focus on the RNA-binding proteins (RBPs) and the non-coding RNAs that interact with the HIF-1 alpha mRNA and influence its half-life and translation rate. HIF-1 alpha mRNA-binding factors are emerging as promising pharmacological targets to control HIF-1 alpha production selectively and efficiently. C1 [Gorospe, Myriam] NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. [Galban, Stefanie] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU National Institute on Aging; National Institutes of Health; [NIH T32 HL07517] FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. S. G. is supported by a post-doctoral award (Lung Immunopathology Training Grant, NIH T32 HL07517). NR 77 TC 33 Z9 35 U1 1 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD NOV PY 2009 VL 15 IS 33 BP 3853 EP 3860 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 514HP UT WOS:000271385300004 PM 19671045 ER PT J AU Kim, YS Alarcon, SV Lee, S Lee, MJ Giaccone, G Neckers, L Trepel, JB AF Kim, Y. S. Alarcon, S. V. Lee, S. Lee, M. -J. Giaccone, G. Neckers, L. Trepel, J. B. TI Update on Hsp90 Inhibitors in Clinical Trial SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Hsp90 inhibitors; targeted therapy; clinical trial ID PHASE-I TRIAL; PACLITAXEL-MEDIATED CYTOTOXICITY; REFRACTORY ADVANCED CANCERS; GROWTH-FACTOR RECEPTOR; SHOCK-PROTEIN 90; SOLID TUMORS; ADULT PATIENTS; BREAST-CANCER; 17-ALLYLAMINO GELDANAMYCIN; PEDIATRIC-PATIENTS AB Twenty-five years ago the first small molecule inhibitors of Hsp90 were identified. In the intervening years there has been dramatic progress in basic scientific understanding of the Hsp90 chaperone machinery and in the role of Hsp90 in malignancy. The first-in-class Hsp90 inhibitor 17-AAG entered into Phase I clinical trials in 1999. There are now 13 Hsp90 inhibitors in clinical trial, representing multiple drug classes, and hundreds of patients have been treated in adult oncology and pediatric oncology trials. This review will provide an overview of the clinical trial results thus far. In addition, pivotal issues in further development of Hsp90 inhibitors as anticancer drugs will be discussed. C1 [Kim, Y. S.; Alarcon, S. V.; Lee, S.; Lee, M. -J.; Giaccone, G.; Trepel, J. B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Neckers, L.] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10,Rm 12N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 86 TC 169 Z9 171 U1 4 U2 23 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PD NOV PY 2009 VL 9 IS 15 BP 1479 EP 1492 PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 532WZ UT WOS:000272782400010 PM 19860730 ER PT J AU Gronborg, M Kreitman, RJ Stetler-Stevenson, M Yuan, C AF Groenborg, Marlene Kreitman, Robert J. Stetler-Stevenson, Maryalice Yuan, Constance TI FLOW CYTOMETRY PROLIFERATION RATE STUDIES IN HAIRY CELL LEUKEMIA AND HAIRY CELL LEUKEMIA VARIANT USING THE DNA STAIN DRAQ5 SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 24th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2009 CL Jacksonville, FL SP Clin Cytometry Soc C1 [Groenborg, Marlene; Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Pathol Lab, Dept Flow Cytometry, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Clin Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2009 VL 76B IS 6 BP 400 EP 400 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 508UK UT WOS:000270962200022 ER PT J AU Liu, QY Stetler-Stevenson, M Yuan, C AF Liu, Qingyan Stetler-Stevenson, Maryalice Yuan, Constance TI IMMUNOPHENOTYPIC FEATURES OF FOLLICULAR LYMPHOMA: 45 CASES WITH HISTOPATHOLOGIC CORRELATION SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 24th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2009 CL Jacksonville, FL SP Clin Cytometry Soc C1 [Liu, Qingyan; Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Pathol Lab, Flow Cytometry Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2009 VL 76B IS 6 BP 402 EP 402 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 508UK UT WOS:000270962200027 ER PT J AU Stetler-Stevenson, M Wilson, W AF Stetler-Stevenson, Maryalice Wilson, Wyndham TI LEPTOMENINGEAL LOCALIZATION OF HEMATOLOGICAL MALIGNANCIES: DIAGNOSIS, MONITORING SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 24th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2009 CL Jacksonville, FL SP Clin Cytometry Soc C1 [Stetler-Stevenson, Maryalice; Wilson, Wyndham] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2009 VL 76B IS 6 BP 419 EP 419 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 508UK UT WOS:000270962200071 ER PT J AU Mellman, TA Alim, T Brown, DD Gorodetsky, E Buzas, B Lawson, WB Goldman, D Charney, DS AF Mellman, Thomas A. Alim, Tanya Brown, Denver D. Gorodetsky, Elena Buzas, Beata Lawson, William B. Goldman, David Charney, Dennis S. TI SEROTONIN POLYMORPHISMS AND POSTTRAUMATIC STRESS DISORDER IN A TRAUMA EXPOSED AFRICAN AMERICAN POPULATION SO DEPRESSION AND ANXIETY LA English DT Article DE Trauma; 5HT2A; 5HTTLPR; genetic variation; African American ID NATIONAL COMORBIDITY SURVEY; TRANSPORTER GENOTYPE; GENE POLYMORPHISM; RISK; ASSOCIATION; METAANALYSIS; DEPRESSION; RECEPTOR; ADULTS; PTSD AB Background: Genetic polymorphisms that influence serotonin (5-hydroxytryptamine, 5HT) neurotransmission are candidates for contributing to susceptibility to posttraumatic stress disorder (PTSD). The objective of our study was to determine if a variable length polymorphism for the promoter regions of the 5HT transporter (5HTTLPR), and/or a substitution polymorphism. in the promoter region for the 5HT2A receptor, would be associated with PTSD in a trauma exposed population of adult African-Americans. Methods: Using a case control design, 118 participants recruited from the primary care clinics and the campus of a historically black university who met inclusion criteria including trauma exposure provided blood samples for genomic DNA. PTSD criteria were determined by the Clinician Assessment of PTSD Scale (CAPS) and criteria for other psychiatric disorders by the Structured Clinical Interview for DSM-IV (SCID). 5HTTLPR and 5HT2A-1438A/G were genotyped using established methods. Associations of genotypes with lifetime PTSD, and models testing associations of allele "dose", were analyzed. Results: Fifty-five (47%) participants met lifetime criteria for PTSD and 26 (22%) met criteria for (mostly comorbid) major depression. The 5HT2A (lower expressing) G allele was significantly associated with PTSD. We did not find significant associations with 5HTTLPR. Conclusions: Our findings suggest a relationship between genetic variation in the 5HT2A promoter region and PTSD. Depression and Anxiety 26:993-997, 2009. Published 2009 Wiley-Liss, Inc C1 [Mellman, Thomas A.; Alim, Tanya; Brown, Denver D.; Lawson, William B.] Howard Univ, Coll Med, Dept Psychiat, Washington, DC USA. [Gorodetsky, Elena; Buzas, Beata; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. [Charney, Dennis S.] Mt Sinai Sch Med, New York, NY USA. RP Mellman, TA (reprint author), Howard Univ Hosp, Dept Psychiat, 2041 Georgia Ave, Washington, DC 20060 USA. EM TMellman@Howard.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lawson, William/0000-0002-9324-7090 FU NIMH [NIMH-01-DI-0017, K24 MH001917-07, M01 RR010284] FX The authors acknowledge the assistance of Colin Hodgkinson, Pei-Hong Shen, Elaine R. Graves, Donna Barnes, Benjamin Mellman, and John Kwaygan. Supported by Collaborative Contract NIMH-01-DI-0017 (P.I. WB. Lawson), NIMH Grant K24 MH001917-07 to Dr. Mellman, and M01 RR010284 (Howard University GCRC). NR 38 TC 34 Z9 36 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2009 VL 26 IS 11 BP 993 EP 997 DI 10.1002/da.20627 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 515DV UT WOS:000271447900005 PM 19842167 ER PT J AU Tanegashima, K Zhao, H Rebbert, ML Dawid, IB AF Tanegashima, Kosuke Zhao, Hui Rebbert, Martha L. Dawid, Igor B. TI Coordinated activation of the secretory pathway during notochord formation in the Xenopus embryo SO DEVELOPMENT LA English DT Article DE Notochord; Protein trafficking; Protein secretion; Unfolded protein response; DNA microarray; Xenopus ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; TRANSCRIPTION FACTOR; MESSENGER-RNA; ZEBRAFISH; TRANSPORT; MEMBRANE; IDENTIFY; LAEVIS; ATF6 AB We compared the transcriptome in the developing notochord of Xenopus laevis embryos with that of other embryonic regions. A coordinated and intense activation of a large set of secretory pathway genes was observed in the notochord, but not in notochord precursors in the axial mesoderm at early gastrula stage. The genes encoding Xbp1 and Creb3l2 were also activated in the notochord. These two transcription factors are implicated in the activation of secretory pathway genes during the unfolded protein response, where cells react to the stress of a build-up of unfolded proteins in their endoplasmic reticulum. Xbp1 and Creb3l2 are differentially expressed but not differentially activated in the notochord. Reduction of expression of Xbp1 or Creb3l2 by injection of antisense morpholinos led to strong deficits in notochord but not somitic muscle development. In addition, the expression of some, but not all, genes encoding secretory proteins was inhibited by injection of xbp1 morpholinos. Furthermore, expression of activated forms of Xbp1 or Creb3l2 in animal explants could activate a similar subset of secretory pathway genes. We conclude that coordinated activation of a battery of secretory pathway genes mediated by Xbp1 and Creb/ATF factors is a characteristic and necessary feature of notochord formation. C1 [Tanegashima, Kosuke; Zhao, Hui; Rebbert, Martha L.; Dawid, Igor B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Dawid, IB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. EM idawid@nih.gov RI Zhao, Hui/B-8429-2016 FU NICHD, NIH FX We thank Lina Gugliotti for help with quantitative PCR. This work has been supported by the intramural research program of the NICHD, NIH. Deposited in PMC for release after 12 months. NR 34 TC 6 Z9 7 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 1 PY 2009 VL 136 IS 21 BP 3543 EP 3548 DI 10.1242/dev.036715 PG 6 WC Developmental Biology SC Developmental Biology GA 505AI UT WOS:000270659400003 PM 19793890 ER PT J AU Morikawa, Y Zehir, A Maska, E Deng, CX Schneider, MD Mishina, Y Cserjesi, P AF Morikawa, Yuka Zehir, Ahmet Maska, Emily Deng, Chuxia Schneider, Michael D. Mishina, Yuji Cserjesi, Peter TI BMP signaling regulates sympathetic nervous system development through Smad4-dependent and -independent pathways SO DEVELOPMENT LA English DT Article DE BMP; Neural crest; Smad4 independent; Mouse ID NEURAL CREST CELLS; CONDITIONAL KNOCKOUT MICE; CARDIAC OUTFLOW TRACT; NORADRENERGIC DIFFERENTIATION; NEURONAL DIFFERENTIATION; TRANSCRIPTION FACTORS; ADRENERGIC CELLS; ENTERIC NEURONS; MOUSE EMBRYOS; TGF-BETA/BMP AB Induction of the sympathetic nervous system (SNS) from its neural crest (NC) precursors is dependent on BMP signaling from the dorsal aorta. To determine the roles of BMP signaling and the pathways involved in SNS development, we conditionally knocked out components of the BMP pathways. To determine if BMP signaling is a cell-autonomous requirement of SNS development, the Alk3 (BMP receptor IA) was deleted in the NC lineage. The loss of Alk3 does not prevent NC cell migration, but the cells die immediately after reaching the dorsal aorta. The paired homeodomain factor Phox2b, known to be essential for survival of SNS precursors, is downregulated, suggesting that Phox2b is a target of BMP signaling. To determine if Alk3 signals through the canonical BMP pathway, Smad4 was deleted in the NC lineage. Loss of Smad4 does not affect neurogenesis and ganglia formation; however, proliferation and noradrenergic differentiation are reduced. Analysis of transcription factors regulating SNS development shows that the basic helix-loop-helix factor Ascl1 is downregulated by loss of Smad4 and that Ascl1 regulates SNS proliferation but not noradrenergic differentiation. To determine if the BMP-activated Tak1 (Map3k7) pathway plays a role in SNS development, Tak1 was deleted in the NC lineage. We show that Tak1 is not involved in SNS development. Taken together, our results suggest multiple roles for BMP signaling during SNS development. The Smad4-independent pathway acts through the activation of Phox2b to regulate survival of SNS precursors, whereas the Smad4-dependent pathway controls noradrenergic differentiation and regulates proliferation by maintaining Ascl1 expression. C1 [Morikawa, Yuka; Zehir, Ahmet; Maska, Emily; Cserjesi, Peter] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. [Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Schneider, Michael D.] Univ London Imperial Coll Sci Technol & Med, Fac Med, London SW7 2AZ, England. [Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. [Cserjesi, Peter] Columbia Univ, Dept Pathol, New York, NY 10032 USA. [Cserjesi, Peter] Columbia Univ, Dept Cell Biol, New York, NY 10032 USA. RP Cserjesi, P (reprint author), Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA. EM pcserj@tulane.edu RI Morikawa, Yuka/E-3092-2010; OI Morikawa, Yuka/0000-0002-4571-8409; Schneider, Michael/0000-0001-9645-1938 FU NSF [0609086]; NIH [RO1-NS015547] FX We wish to thank Jane Johnson, David Anderson and Jean-Francois Brunet for providing the Ascl1, Sox10 and Phox2b antibodies and Heather Brody, Lisa Hua and Meghan Garstka for technical assistance. This work was supported by an AHA Postdoctoral Fellowship and Scientist Development Grant to Y.M. and an AHA Grant in Aid, NSF grant 0609086 to P. C., and by NIH grant RO1-NS015547. Deposited in PMC for release after 12 months. NR 55 TC 51 Z9 51 U1 1 U2 3 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 1 PY 2009 VL 136 IS 21 BP 3575 EP 3584 DI 10.1242/dev.038133 PG 10 WC Developmental Biology SC Developmental Biology GA 505AI UT WOS:000270659400007 PM 19793887 ER PT J AU Nie, SY Kee, Y Bronner-Fraser, M AF Nie, Shuyi Kee, Yun Bronner-Fraser, Marianne TI Myosin-X is critical for migratory ability of Xenopus cranial neural crest cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Myosin-X; Cranial neural crest; Migration; Adhesion ID FILOPODIA FORMATION; IN-VIVO; MOLECULAR MOTOR; EXPRESSION; EPHRIN; ACTIN; RECEPTORS; INDUCTION; ADHESION; GUIDANCE AB The neural crest is a highly migratory cell population, unique to vertebrates, that forms much of the craniofacial skeleton and peripheral nervous system. In exploring the cell biological basis underlying this behavior, we have identified an unconventional myosin, myosin-X (Myo10) that is required for neural crest migration. Myo10 is highly expressed in both premigratory and migrating cranial neural crest (CNC) cells in Xenopus embryos. Disrupting Myo10 expression using antisense morpholino oligonucleotides leads to impaired neural crest migration and subsequent cartilage formation, but only a slight delay in induction. In vivo grafting experiments reveal that Myo-10-depleted CNC cells migrate a shorter distance and fail to segregate into distinct migratory streams. Finally, in vitro cultures and cell dissociation-reaggregation assays suggest that Myo10 may be critical for cell protrusion and cell-cell adhesion. These results demonstrate an essential role for Myo10 in normal cranial neural crest migration and suggest a link to cell-cell interactions and formation of processes. (C) 2009 Published by Elsevier Inc C1 [Nie, Shuyi; Bronner-Fraser, Marianne] CALTECH, Div Biol 139 74, Pasadena, CA 91125 USA. [Kee, Yun] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bronner-Fraser, M (reprint author), CALTECH, Div Biol 139 74, Pasadena, CA 91125 USA. EM mbronner@caltech.edu FU [NS36585]; [HD037105] FX We thank Dr. Williarn M. Bement for providing us full-length Xenopus Myo10 constructs, Dr. Dominique Alfandari for providing protocols for grafting experiment, Dr. Chenbei Chang for providing Wnt3a and Noggin constructs, and Dr. Ken Cho for providing microarray analysis tool. This work was supported by NS36585 and HD037105 to MBF. NR 45 TC 19 Z9 20 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 1 PY 2009 VL 335 IS 1 BP 132 EP 142 DI 10.1016/j.ydbio.2009.08.018 PG 11 WC Developmental Biology SC Developmental Biology GA 510IA UT WOS:000271080300011 PM 19712673 ER PT J AU Hwang, CH Simeone, A Lai, E Wu, DK AF Hwang, Chan Ho Simeone, Antonio Lai, Eseng Wu, Doris K. TI Foxg1 is Required for Proper Separation and Formation of Sensory Cristae During Inner Ear Development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Foxg1; ear; crista; semicircular; septum cruciatum; mouse; Otx1; YFP; cre ID MICE LACKING; HOMEOBOX GENE; MOUSE EMBRYO; MORPHOGENESIS; TELENCEPHALON; EXPRESSION; DEFECTS; GROWTH; BF-1; DLX5 AB The vestibular portion of the inner ear, the three semicircular canals and their sensory cristae, is responsible for detecting angular head movements. It was proposed that sensory cristae induce formation of their non-sensory components, the semicircular canals. Here, we analyzed the inner ears of Foxg1(-/-) mouse mutants, which display vestibular defects that are in conflict with the above model. In Foxg1(-/-) ears, the lateral canal is present without the lateral ampulla, which houses the lateral crista. Our gene expression analyses indicate that at the time when canal specification is thought to occur, the prospective lateral crista is present, which could have induced lateral canal formation prior to its demise. Our genetic fate-mapping analyses indicate an improper separation between anterior and lateral cristae in Foxg1(-/-) mutants. Our data further suggest that a function of Foxg1 in the inner ear is to restrict sensory fate. Developmental Dynamics 238:2725-2734, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Hwang, Chan Ho; Wu, Doris K.] Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Rockville, MD USA. [Simeone, Antonio] SEMM European Sch Mol Med, CEINGE Biotecnol Avanzate, Naples, Italy. [Simeone, Antonio] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy. [Lai, Eseng] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. RP Wu, DK (reprint author), NIDCD, Mol Biol Lab, NIH, 5 Res Court,Rm 2B34, Rockville, MD 20850 USA. EM wud@nidcd.nih.gov FU NIDCD; Italian Association for Cancer Research (AIRC); Fondazione Roma; NIH [HD29584] FX Grant sponsors: Intramural Research Program of the NIDCD; Italian Association for Cancer Research (AIRC) and the "Stem Cell Project" of Fondazione Roma; NIH; Grant number: HD29584. NR 38 TC 18 Z9 21 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2009 VL 238 IS 11 BP 2725 EP 2734 DI 10.1002/dvdy.22111 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 516NI UT WOS:000271548800002 PM 19842177 ER PT J AU Herold, KC Brooks-Worrell, B Palmer, J Dosch, HM Peakman, M Gottlieb, P Reijonen, H Arif, S Spain, LM Thompson, C Lachin, JM AF Herold, Kevan C. Brooks-Worrell, Barbara Palmer, Jerry Dosch, H. Michael Peakman, Mark Gottlieb, Peter Reijonen, Helena Arif, Sefina Spain, Lisa M. Thompson, Clinton Lachin, John M. CA Type 1 Diabet TrialNet Res Grp TI Validity and Reproducibility of Measurement of Islet Autoreactivity by T-Cell Assays in Subjects With Early Type 1 Diabetes SO DIABETES LA English DT Article ID CLASS-II TETRAMERS; TRANSLATIONAL MINIREVIEW SERIES; ANTIGEN; AUTOANTIBODIES; RESPONSES; INSULIN; DISEASE; RISK; INDIVIDUALS; PERFORMANCE AB OBJECTIVE-Type 1 diabetes results from an immune-mediated destruction of P-cells, likely to be mediated by T lymphocytes, but the sensitivity, specificity, and other measures of validity of existing assays for islet autoreactive T-cells are not well established. Such assays are vital for monitoring responses to interventions that may modulate disease progression. RESEARCH DESIGN AND METHODS-We studied the ability of cellular assays to discriminate responses in patients with type 1 diabetes and normal control subjects in a randomized blinded study in the U.S. and U.K. We evaluated the reproducibility of these measurements overall and to individual analytes from repeat collections. RESULTS-Responses in the cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays could differentiate patients from control subjects with odds ratios of 21.7, 3.44, and 3.36, respectively, with sensitivity and specificity as high as 74 and 88%. The class II tetramer and U.S. ELISPOT assays performed less well. Despite the significant association of the responses with type I diabetes, the reproducibility of the measured responses, both overall and individual analytes, was relatively low. Positive samples from normal control subjects (i.e., false positives) were generally isolated to single assays. CONCLUSIONS-The cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays can distinguish responses from patients with type 1 diabetes and healthy control subjects. The limited reproducibility of the measurements overall and of responses to individual analytes may reflect the difficulty in detection of low frequency of antigen-specific T-cells or variability in their appearance in peripheral blood. Diabetes 58:2588-2595, 2009 C1 [Herold, Kevan C.; Thompson, Clinton; Lachin, John M.] Yale Univ, New Haven, CT 06520 USA. [Brooks-Worrell, Barbara] Univ Washington, Seattle, WA 98195 USA. [Palmer, Jerry] Univ Toronto, Toronto, ON, Canada. [Dosch, H. Michael] Guys & St Thomas Natl Hlth Serv Fdn Trust, Dept Immunobiol, London, England. [Dosch, H. Michael] Guys & St Thomas Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr, London, England. [Dosch, H. Michael] Kings Coll London, London WC2R 2LS, England. [Peakman, Mark; Arif, Sefina] Univ Colorado, Boulder, CO 80309 USA. [Gottlieb, Peter] Benaroya Res Inst, Seattle, WA USA. [Reijonen, Helena] NIDDKD, Bethesda, MD 20892 USA. [Spain, Lisa M.] George Washington Univ, Ctr Biostat, Rockville, MD USA. RP Herold, KC (reprint author), Yale Univ, New Haven, CT 06520 USA. EM kevan.herold@yale.edu OI Lachin, John/0000-0001-9838-2841 FU TolerRx; GlaxoSmithKline; Bayhill Therapeutics; Andromeda Biotech FX J.M.L. has consulted with the following companies: TolerRx, GlaxoSmithKline, Bayhill Therapeutics, and Andromeda Biotech. No other potential conflicts of interest relevant to this article were reported. NR 29 TC 50 Z9 51 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD NOV PY 2009 VL 58 IS 11 BP 2588 EP 2595 DI 10.2337/db09-0249 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515RQ UT WOS:000271490900020 PM 19675135 ER PT J AU Park, SW Goodpaster, BH Lee, JS Kuller, LH Boudreau, R de Rekeneire, N Harris, TB Kritchevsky, S Tylavsky, FA Nevitt, M Cho, YW Newman, AB AF Park, Seok Won Goodpaster, Bret H. Lee, Jung Sun Kuller, Lewis H. Boudreau, Robert de Rekeneire, Nathalie Harris, Tamara B. Kritchevsky, Stephen Tylavsky, Frances A. Nevitt, Michael Cho, Yong-wook Newman, Anne B. CA Hlth Aging Body Composition Study TI Excessive Loss of Skeletal Muscle Mass in Older Adults With Type 2 Diabetes SO DIABETES CARE LA English DT Article ID BODY-COMPOSITION; PROTEIN-METABOLISM; WEIGHT CHANGE; STRENGTH; INSULIN; HEALTH; MELLITUS; WOMEN; MEN; COHORT AB OBJECTIVE - A loss of skeletal muscle mass is frequently observed in older adults. The aim of the study was to investigate the impact of type 2 diabetes on the changes in body composition, with particular interest in the skeletal muscle mass. RESEARCH DESIGN AND METHODS - We examined total body composition with dual-energy X-ray absorptiometry annually for 6 years in 2,675 older adults. We also measured mid-thigh muscle cross-sectional area (CSA) with computed tomography in year 1 and year 6. At baseline, 75-g oral glucose challenge tests were performed. Diagnosed diabetes (n = 402, 15.0%) was identified by self-report or use of hypoglycemic agents. Undiagnosed diabetes (n = 226, 8.4%) was defined by fasting plasma glucose (>= 7 mmol/l) or 2-h postchallenge plasma glucose (>= 11.1 mmol/l). Longitudinal regression models were fit to examine the effect of diabetes on the changes in body composition variables. RESULTS - Older adults with either diagnosed or undiagnosed type 2 diabetes showed excessive loss of appendicular lean mass and trunk fat mass compared with nondiabetic subjects. Thigh muscle CSA declined two times faster in older women with diabetes than their nondiabetic counterparts. These findings remained significant after adjusting for age, sex, race, clinic site, baseline BMI, weight change intention, and actual weight changes over time. CONCLUSIONS - Type 2 diabetes is associated with excessive loss of skeletal muscle and trunk fat mass in community-dwelling older adults. Older women with type 2 diabetes are at especially high risk for loss of skeletal muscle mass. C1 [Park, Seok Won; Cho, Yong-wook] CHA Univ, Dept Internal Med, Songnam, South Korea. [Goodpaster, Bret H.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Lee, Jung Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Kuller, Lewis H.; Boudreau, Robert; Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [de Rekeneire, Nathalie] Yale Univ, Sch Med, Ctr Disabil & Disabling Disorders, New Haven, CT USA. [Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kritchevsky, Stephen] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sticht Ctr Aging, Winston Salem, NC 27103 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Internal Med, Memphis, TN USA. [Nevitt, Michael] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Park, SW (reprint author), CHA Univ, Dept Internal Med, Songnam, South Korea. EM spark@cha.ac.kr RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institutes of Health National Institute on Aging; [N01-AG-6-2101]; [N01-AG-6-2103]; [N01-AG-6-2106] FX This study was supported by contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 and in part by the Intramural Research Program of the National Institutes of Health National Institute on Aging. NR 22 TC 173 Z9 175 U1 5 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2009 VL 32 IS 11 BP 1993 EP 1997 DI 10.2337/dc09-0264 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 518HW UT WOS:000271682800009 PM 19549734 ER PT J AU Cheng, YJ Gregg, EW Geiss, LS Imperatore, G Williams, DE Zhang, XZ Albright, AL Cowie, CC Klein, R Saaddine, JB AF Cheng, Yiling J. Gregg, Edward W. Geiss, Linda S. Imperatore, Giuseppina Williams, Desmond E. Zhang, Xinzhi Albright, Ann L. Cowie, Catherine C. Klein, Ronald Saaddine, Jinan B. TI Association of A1C and Fasting Plasma Glucose Levels With Diabetic Retinopathy Prevalence in the US Population Implications for diabetes diagnostic thresholds SO DIABETES CARE LA English DT Article ID PREVENTION PROGRAM; HEMOGLOBIN A(1C); BLOOD-GLUCOSE; MELLITUS; CRITERIA; TOLERANCE; HBA(1C); TESTS AB OBJECTIVE - To examine the association of A1C levels and fasting plasma glucose (FPG) with diabetic retinopathy in the U.S. population and to compare the ability of the two glycemic measures to discriminate between people with and without retinopathy. RESEARCH DESIGN AND METHODS - This study included 1,066 individuals aged >= 40 years from the 2005-2006 National Health and Nutrition Examination Survey. A1C, FPG, and 45 color digital retinal images were assessed. Retinopathy was defined as a level >= 1.4 on the Early Treatment Diabetic Retinopathy Study severity scale. We used joinpoint regression to identify linear inflections of prevalence of retinopathy in the association between A1C and FPG. RESULTS - The overall prevalence of retinopathy was 11%, which is appreciably lower than the prevalence in people with diagnosed diabetes (36%). There was a sharp increase in retinopathy prevalence in those with A1C >= 5.5% or FPG >= 5.8 mmol/l. After excluding 144 people using hypoglycemic medication, the change points for the greatest increase in retinopathy prevalence were A1C 5.5% and FPG 7.0 mmol/l. The coefficients of variation were 15.6 for A1C and 28.8 for FPG. Based on the areas under the receiver operating characteristic curves, A1C was a stronger discriminator of retinopathy (0.71 [95% CI 0.66-0.76]) than FPG (0.65 [0.60 - 0.701, P for difference = 0.009). CONCLUSIONS - The steepest increase in retinopathy prevalence occurs among individuals with A1C >= 5.5% and FPG >= 5.8 mmol/l. A1C discriminates prevalence of retinopathy better than FPG. C1 [Cheng, Yiling J.; Gregg, Edward W.; Geiss, Linda S.; Imperatore, Giuseppina; Williams, Desmond E.; Zhang, Xinzhi; Albright, Ann L.; Saaddine, Jinan B.] Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Cowie, Catherine C.] NIDDKD, Bethesda, MD 20892 USA. [Klein, Ronald] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Cheng, YJ (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. EM ycheng@cdc.gov OI Klein, Ronald/0000-0002-4428-6237 NR 25 TC 63 Z9 66 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2009 VL 32 IS 11 BP 2027 EP 2032 DI 10.2337/dc09-0440 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 518HW UT WOS:000271682800015 PM 19875604 ER PT J AU Ferrucci, L Studenski, S AF Ferrucci, Luigi Studenski, Stephanie TI Diabetes, Muscles, and the Myth of Ulysses' Bow SO DIABETES CARE LA English DT Editorial Material ID UBIQUITIN-PROTEASOME PATHWAY; BODY-COMPOSITION; SKELETAL-MUSCLE; OLDER-ADULTS; SARCOPENIA; DISEASE; MORTALITY; STRENGTH; PROTEIN; HEALTH C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Studenski, Stephanie] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. EM ferruccilu@grc.nia.nih.gov FU Intramural NIH HHS; NIA NIH HHS [K07 AG023641, AG023641, P30 AG024827, AG024827] NR 21 TC 6 Z9 6 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2009 VL 32 IS 11 BP 2136 EP 2137 DI 10.2337/dc09-1592 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 518HW UT WOS:000271682800037 PM 19875609 ER PT J AU Li, RL O'Sullivan, MJ Robinson, J Safford, MM Curb, D Johnson, KC AF Li, Rongling O'Sullivan, Mary J. Robinson, Jennifer Safford, Monika M. Curb, David Johnson, Karen C. TI Family history of myocardial infarction predicts incident coronary heart disease in postmenopausal women with diabetes: the Women's Health Initiative Observational Study SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE family history; CHD; diabetes; women's health ID CARDIOVASCULAR RISK-FACTORS; ATHEROSCLEROSIS RISK; PARENTAL HISTORY; ARTERY DISEASE; MENOPAUSE; AGE; EPIDEMIOLOGY; FRAMINGHAM; COHORT AB Background Diabetes is a risk factor for coronary heart disease (CHD) but CHD does not occur in all diabetic individuals. The goal of this study was to assess the relationship between family history of myocardial infarction (MI) and incident CHD in diabetic postmenopausal women. Methods We conducted a prospective cohort study among 2642 diabetic postmenopausal women without CHD at baseline in the Women's Health Initiative Observational Study. Family history was defined as a proband report of MI in first-degree relatives. Incident CHD was defined as non-fatal MI, coronary revascularization, or CHD death. Results During 7.3 (+/- 1.8) years of follow-up, 14.3% of the participants had incident CHD. The risk of incident CHD was 50% higher (HR = 1.50, 95% Cl: 1.20-1.87, p = 0.0003) in those with a family history of an MI in at least one first-degree relative, and 79% higher (HR = 1.79, 95% Cl: 1.36-2.35, P < 0.0001) if two or more first-degree relatives had an MI, compared to participants without a family history, after adjustment for covariates. The CHD risk increased with elevated systolic blood pressure (SBP) (HR = 1.01, 95% Cl: 1.003-1.02, p = 0.001) but decreased with elevated diastolic BP (HR = 0.98, 95% Cl: 0.97-0-999, p = 0.005) and with two or more episodes per week of physical activity (HR = 0.70, 95% Cl: 0.52-0.93, p = 0.02). Conclusions The results suggest that a family history of MI predicts CHD in diabetic postmenopausal women. Close attention should be paid to BP control and physical activity in these women. Copyright (C) 2009 John Wiley & Sons Ltd,. C1 [Li, Rongling; Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [O'Sullivan, Mary J.] Univ Miami, Miller Sch Med, Dept Obstet & Gynecol, Miami, FL 33136 USA. [Robinson, Jennifer] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA USA. [Safford, Monika M.] Univ Alabama, Birmingham, AL USA. [Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. [Curb, David] Pacific Hlth Res Inst, Honolulu, HI USA. RP Li, RL (reprint author), NHGRI, OPG, NIH, 5635 Fishers Lane,Suite 4076,MSC 9305, Bethesda, MD 20892 USA. EM lir2@mail.nih.gov FU National Heart, Lung, and Blood Institute, NIH [NO1-WH-3-2100, NO1-WH-3-2101, NO1-WH-3-2102, NO1-WH-3-2105, NO1-WH-3-2106, NO1-WH-3-2108, NO1-WH-3-2109, NO1-WH-3-2110, NO1-WH-3-2111, NO1-WH-3-2112, NO1-WH-3-2113, NO1-WH-3-2115, NO1-WH-3-2118, NO1-WH-3-2119, NO1-WH-3-2120, NO1-WH-3-2122, NO1-WH-4-2107, NO1-WH-4-2108] FX We acknowledge all WHI-OS participants and NIH for making the funds available for the study. The WHI program is funded by NIH Contracts: NO1-WH-3-2100, NO1-WH-3-2101, NO1-WH-3-2102, NO1-WH-3-2105, NO1-WH-3-2106, NO1-WH-3-2108, NO1-WH-3-2109, NO1-WH-3-2110, NO1-WH-3-2111, NO1-WH-3-2112, NO1-WH-3-2113, NO1-WH-3-2115, NO1-WH-3-2118, NO1-WH-3-2119, NO1-WH-3-2120, NO1-WH-3-2122, NO1-WH-4-2107, NO1-WH-4-2108, NO1-WH-4-2109, NO1-WH-4-2110, NO1-WH-4-2111, NO1-WH-4-2112, NO1-WH-4-2113, NO1-WH-4-2114, NO1-WH-4-2115, NO1-WH-4-2116, NO1-WH-4-2117, NO1-WH-4-2118, NO1-WH-4-2119, NO1-WH-4-2120, NO1-WH-4-2121, NO1-WH-4-2122, NO1-WH-4-2123, NO1-WH-4-2124, NO1-WH-4-2125, NO1-WH-4-2126, NO1-WH-4-2129, NO1-WH-4-2130, NO1-WH-4-2131, and NO1-WH-4-2132 from the National Heart, Lung, and Blood Institute, NIH. NR 26 TC 1 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2009 VL 25 IS 8 BP 725 EP 732 DI 10.1002/dmrr.1010 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 522RP UT WOS:000272016300005 PM 19780066 ER PT J AU Njajou, OT Kanaya, AM Holvoet, P Connelly, S Strotmeyer, ES Harris, TB Cummings, SR Hsueh, WC AF Njajou, Omer T. Kanaya, Alka M. Holvoet, Paul Connelly, Stephanie Strotmeyer, Elsa S. Harris, Tamara B. Cummings, Steve R. Hsueh, Wen-Chi CA Hlth ABC Study TI Association between oxidized LDL, obesity and type 2 diabetes in a population-based cohort, the Health, Aging and Body Composition Study SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE oxLDL; diabetes; oxidation; obesity ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS; INSULIN-RESISTANCE; METABOLIC SYNDROME; ABDOMINAL OBESITY; VISCERAL OBESITY; OXIDANT STRESS; PLASMA; RISK; GLUCOSE AB Background Accumulating evidence suggests a cross-sectional association between oxidative stress and type 2 diabetes (T2D). Systemic oxidative stress, as measured by oxidized LDL (oxLDL), has been correlated with visceral fat. We examined the relationship between oxLDL, and T2D- and obesity-related traits in a bi-racial sample of 2985 subjects at baseline and after 7 years of follow-up. Methods We examined six T2D-related traits (T2D status, HbA(1c), fasting glucose, insulin, adiponectin and HOMA-IR) as well as six obesity-related traits (obesity status, BMI, leptin, % body fat, visceral and subcutaneous fat mass) using logistic and linear regression models. Results In all subjects at baseline, oxLDL was positively associated with T2D (OR = 1.3, 95% CI:1.1-1.5), fasting glucose (beta = 0.03 +/- 0.006), HbA(1c) (beta = 0.02 +/- 0.004), fasting insulin (beta = 0.12 +/- 0.02), HOMA-IR (beta = 0.13 +/- 0.02) and negatively with adiponectin (beta = -0.16 +/- 0.03), (all p < 0.001). The strength and magnitude of these associations did not differ much between blacks and whites. in both blacks and whites, oxLDL was also associated with obesity (OR = 1.3, 95% CI:1.1-1.4) and three of its related traits (beta = 0.60 +/- 0.14 for BMI, beta = 0.74 +/- 0.17 for % body fat, beta = 0.29 +/- 0.06 for visceral fat; all p < 0.001). Furthermore, of four traits measured after 7 years of follow-up (fasting glucose, HbA1c, BMI and % fat), their relationship with oxLDL was similar to baseline observations. No significant association was found between oxLDL and incident T2D. interestingly oxLDL was significantly associated with % change in T2D- and, obesity-related traits in whites but not in blacks. Conclusion/Interpretation Our data suggest that systemic oxidative stress may be a novel risk factor for T2D and obesity. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Hsueh, Wen-Chi] Univ Calif San Francisco, Sch Med, Dept Med, Inst Human Genet, San Francisco, CA 94143 USA. [Holvoet, Paul] Katholieke Univ Leuven, Louvain, Belgium. [Connelly, Stephanie] Univ Tennessee, Memphis, TN USA. [Strotmeyer, Elsa S.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Hsueh, WC (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Inst Human Genet, 513 Parnassus Ave,HSE 672C, San Francisco, CA 94143 USA. EM wen-chi.hsueh@ucsf.edu RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural Research Program of the National Institute on Aging; NIH [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; Interuniversity Attraction Poles Program [P6/30]; [K01 AG022782] FX This study was supported in part by the Intramural Research Program of the National Institute on Aging, NIH contracts (N01-AG-6-2101, N01-AG-6-2103 and N01-AG-6-2106) and grant K01 AG022782. This work was also supported by the Interuniversity Attraction Poles Program P6/30 (Belgian Science Policy). NR 39 TC 50 Z9 51 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2009 VL 25 IS 8 BP 733 EP 739 DI 10.1002/dmrr.1011 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 522RP UT WOS:000272016300006 PM 19780064 ER PT J AU Malhotra, A Igo, RP Thameem, F Kao, WHL Abboud, HE Adler, SG Arar, NH Bowden, DW Duggirala, R Freedman, BI Goddard, KAB Ipp, E Iyengar, SK Kimmel, PL Knowler, WC Kohn, O Leehey, D Meoni, LA Nelson, RG Nicholas, SB Parekh, RS Rich, SS Chen, YDI Saad, MF Scavini, M Schelling, JR Sedor, JR Shah, VO Taylor, KD Thornley-Brown, D Zager, PG Horvath, A Hanson, RL AF Malhotra, Alka Igo, Robert P., Jr. Thameem, Farook Kao, W. H. Linda Abboud, Hanna E. Adler, Sharon G. Arar, Nedal H. Bowden, Donald W. Duggirala, Ravindranath Freedman, Barry I. Goddard, Katrina A. B. Ipp, Eli Iyengar, Sudha K. Kimmel, Paul L. Knowler, William C. Kohn, Orly Leehey, David Meoni, Lucy A. Nelson, Robert G. Nicholas, Susanne B. Parekh, Rulan S. Rich, Stephen S. Chen, Yii-Der I. Saad, Mohammed F. Scavini, Marina Schelling, Jeffrey R. Sedor, John R. Shah, Vallabh O. Taylor, Kent D. Thornley-Brown, Denyse Zager, Philip G. Horvath, Amanda Hanson, Robert L. CA Family Invest Nephropathy & Diabet TI Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations - significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article DE FIND; type 2 diabetes; linkage analysis; ethnicity ID OLD ORDER AMISH; SUSCEPTIBILITY GENES; INSULIN-SECRETION; PIMA-INDIANS; INDEPENDENT REPLICATION; MEXICAN-AMERICANS; BETACELLULIN GENE; FINNISH FAMILIES; ASSOCIATION; LOCI AB Background Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Methods Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Results Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD >1.71 have been identified in previously published studies. Conclusions The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Iyengar, Sudha K.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Malhotra, Alka; Knowler, William C.; Nelson, Robert G.; Hanson, Robert L.] NIDDK, Phoenix, AZ USA. [Thameem, Farook; Abboud, Hanna E.; Arar, Nedal H.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kao, W. H. Linda; Meoni, Lucy A.; Parekh, Rulan S.] Johns Hopkins Univ, Baltimore, MD USA. [Adler, Sharon G.; Ipp, Eli] Harbor Univ Calif Los Angeles, Med Ctr, Torrance, CA USA. [Bowden, Donald W.; Freedman, Barry I.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Duggirala, Ravindranath] SW Fdn Biomed Res, San Antonio, TX 78284 USA. [Kimmel, Paul L.] NIDDKD, Program Off, Bethesda, MD 20892 USA. [Kohn, Orly] Univ Chicago, Chicago, IL 60637 USA. [Leehey, David] Loyola Univ, Chicago, IL 60611 USA. [Nicholas, Susanne B.; Chen, Yii-Der I.; Taylor, Kent D.] Univ Calif Los Angeles, Los Angeles, CA USA. [Rich, Stephen S.] Univ Virginia, Charlottesville, VA USA. [Saad, Mohammed F.] Caritas Carney Hosp, Dorchester, MA USA. [Scavini, Marina; Shah, Vallabh O.; Zager, Philip G.] Univ New Mexico, Albuquerque, NM 87131 USA. [Scavini, Marina] Ist Sci San Raffaele, I-20132 Milan, Italy. [Thornley-Brown, Denyse] Univ Alabama, Birmingham, AL USA. RP Iyengar, SK (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM ski@case.edu RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Jun, Gyungah/0000-0002-3230-8697 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000080, M01 RR000425, M01 RR000827, M01 RR000997, M01 RR001346, M01 RR007122, M01-RR-000080, M01-RR-00425, M01-RR-00827-29, M01-RR-00997, M01-RR-01346, M01-RR-07122, P41 RR003655, RR03655]; NHGRI NIH HHS [N01HG65403]; NIDDK NIH HHS [R01 DK059997, R01 DK059997-04, R01 DK067528, R01 DK067528-05, R01 DK072348, R01 DK072348-04, U01 DK057292, U01 DK057292-06, U01DK57292-05] NR 50 TC 2 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV PY 2009 VL 25 IS 8 BP 740 EP 747 DI 10.1002/dmrr.1031 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 522RP UT WOS:000272016300007 PM 19795399 ER PT J AU Yang, H Wei, Y Gao, X Xu, X Fan, L He, J Hu, Y Liu, X Chen, X Yang, Z Zhang, C AF Yang, H. Wei, Y. Gao, X. Xu, X. Fan, L. He, J. Hu, Y. Liu, X. Chen, X. Yang, Z. Zhang, C. CA China Natl GDM Survey Working Grp TI Risk factors for gestational diabetes mellitus in Chinese women-a prospective study of 16 286 pregnant women in China SO DIABETIC MEDICINE LA English DT Article DE China; gestational diabetes; pregnancy; risk factor ID MATERNAL HYPERGLYCEMIA; INCREASING PREVALENCE; SPONTANEOUS-ABORTION; ETHNICITY; CITY AB Aims To determine the incidence of gestational diabetes mellitus (GDM) in China and to further identify population specific risk factors for GDM. Methods Following a universal GDM screening recommendation, 16 286 pregnant women who underwent a 50-g glucose challenge test from 18 cities in China were followed up through pregnancy. GDM was confirmed by oral glucose tolerance test according to American Diabetes Association criteria. Results The incidence of GDM was 4.3%. Previously reported risk factors for GDM, including advanced maternal age, pre-pregnancy obesity and family history of diabetes, were strongly associated with an elevated GDM risk. Moreover, after the adjustment for the above-mentioned risk factors, a history of recurrent vulvovaginal candidiasis, residency in south China and a history of spontaneous abortion were significantly associated with an increased GDM risk; adjusted odds ratio (OR) [95% confidence interval (95% CI)] were 1.97 (1.39, 2.80), 1.84 (1.59-2.13), and 1.46 (1.12, 1.91), respectively. Conclusions In this large study of GDM in Chinese women, advanced maternal age, pre-pregnancy overweight or obesity and family history of diabetes were confirmed to be risk factors. In addition, a history of recurrent vulvovaginal candidiasis or spontaneous abortion and residency in south China appeared to be novel risk factors in this population. C1 [Zhang, C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. [Xu, X.] Shanghai First Peoples Hosp, Shanghai, Peoples R China. [Yang, H.; Wei, Y.; Gao, X.] Peking Univ, Hosp 1, Dept Obstet & Gynecol, Beijing 100871, Peoples R China. [Fan, L.] Beijing Obstet & Gynecol Hosp, Beijing, Peoples R China. [He, J.] Zhejiang Univ, Sch Med, Womens Hosp, Hangzhou 310003, Zhejiang, Peoples R China. [Hu, Y.] Nanjing Drum Tower Hosp, Nanjing, Peoples R China. [Liu, X.] W China Second Univ Hosp, Chengdu, Peoples R China. [Chen, X.] Tianjin Cent Hosp Obstet & Gynecol, Tianjin, Peoples R China. [Yang, Z.] Peking Univ, Hosp 3, Beijing 100871, Peoples R China. RP Zhang, C (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, 6100 Executive Blvd,Rm 7B03,MSC 7510, Rockville, MD 20852 USA. EM yanghuixia@bjmu.edu.cn; zhangcu@mail.nih.gov FU national '211' Project Peking University Evidence-Based Medicine Group [91000-242156028]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This research was supported by a grant from the national '211' Project Peking University Evidence-Based Medicine Group (No. 91000-242156028). CZ was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 34 TC 36 Z9 53 U1 0 U2 12 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD NOV PY 2009 VL 26 IS 11 BP 1099 EP 1104 DI 10.1111/j.1464-5491.2009.02845.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515ST UT WOS:000271493900004 PM 19929987 ER PT J AU Lowe, RH Abraham, TT Darwin, WD Herning, R Cadet, JL Huestis, MA AF Lowe, Ross H. Abraham, Tsadik T. Darwin, William D. Herning, Ronald Cadet, Jean Lud Huestis, Marilyn A. TI Extended urinary Delta 9-tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Tetrahydrocannabinol; Urine; Cannabinoids; Cannabis; THC; Chronic cannabis use ID HEAVY MARIJUANA USERS; HALF-LIFE; GC-MS; MONITORED ABSTINENCE; CREATININE RATIO; METABOLITES; PLASMA; 11-NOR-9-CARBOXY-DELTA(9)-TETRAHYDROCANNABINOL; HUMANS; TETRAHYDROCANNABINOL AB Background: Generally, urinary 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THCCOOH) after alkaline hydrolysis is monitored to detect cannabis exposure, although last use may have been weeks prior in chronic cannabis users. Delta 9-Tetrahydrocannabinol (THC) and 11-hydroxy-THC (11-OH-THC) concentrations in urine following Escherichia coli (beta-glucuronidase hydrolysis were proposed as biomarkers of recent (within 8 h) cannabis use. Objective: To test the validity of THC and 11-OH-THC in urine as indicators of recent cannabis use. Methods: Monitor urinary cannabinoid excretion in 33 chronic cannabis smokers who resided on a secure research unit under 24 h continuous medical surveillance. All urine specimens were collected individually ad libidum for up to 30 days, were hydrolyzed with a tandem E. coli beta-glucuronidase/base procedure, and analyzed for THC, 11-OH-THC and THCCOOH by one-and two-dimensional-cryotrap gas chromatography mass spectrometry (2D-GCMS) with limits of quantification of 2.5 ng/mL. Results: Extended excretion of THC and 11-OH-THC in chronic cannabis users' urine was observed during monitored abstinence; 14 of 33 participants had measurable THC in specimens collected at least 24 h after abstinence initiation. Seven subjects had measurable THC in urine for 3, 3, 4, 7, 7, 12, and 24 days after cannabis cessation. 11-OH-THC and THCCOOH were detectable in urine specimens from one heavy, chronic cannabis user for at least 24 days. Conclusion: For the first time, extended urinary excretion of THC and 11-OH-THC is documented for at least 24 days, negating their effectiveness as biomarkers of recent cannabis exposure, and substantiating long terminal elimination times for urinary cannabinoids following chronic cannabis smoking. Published by Elsevier Ireland Ltd. C1 [Lowe, Ross H.; Abraham, Tsadik T.; Darwin, William D.; Herning, Ronald; Cadet, Jean Lud; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institutes of Health Intramural Research Program of the National institute on Drug Abuse FX This research was supported by the National Institutes of Health Intramural Research Program of the National institute on Drug Abuse. This clinical study was approved by the Institutional Review Board (IRB) of the Intramural Research Program of the National Institute on Drug Abuse. NR 30 TC 33 Z9 34 U1 1 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2009 VL 105 IS 1-2 BP 24 EP 32 DI 10.1016/j.drugalcdep.2009.05.027 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 502RK UT WOS:000270477500004 PM 19631478 ER PT J AU Baumann, MH Zolkowska, D Kim, I Scheidweiler, KB Rothman, RB Huestis, MA AF Baumann, Michael H. Zolkowska, Dorota Kim, Insook Scheidweiler, Karl B. Rothman, Richard B. Huestis, Marilyn A. TI Effects of Dose and Route of Administration on Pharmacokinetics of (+/-)-3,4-Methylenedioxymethamphetamine in the Rat SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; NONLINEAR PHARMACOKINETICS; SQUIRREL-MONKEYS; ECSTASY; HUMANS; METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; DISPOSITION; METABOLITES; SEROTONIN AB Based on animal data, there is speculation that (+/-)-3,4-methylenedioxymethamphetamine (MDMA) is neurotoxic to humans. Extrapolation of MDMA findings from animals to humans requires assessment of pharmacokinetics in various species, and low-dose administration data from rats are lacking. In this study, we examine MDMA pharmacokinetics in rats given low (2 mg/kg) and high (10 mg/kg) doses of racemic MDMA via intraperitoneal, subcutaneous, and oral routes. Repeated blood specimens were collected from venous catheters, and plasma was assayed for MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA), by gas chromatography-mass spectrometry. After 2 mg/kg, maximum MDMA concentrations (C(max)) were similar to 200 ng/ml for intraperitoneal and subcutaneous routes, but less for the oral route. MDMA plasma half-lives were < 1 h for low-dose groups, whereas HMMA and MDA half-lives were > 2 h. After 10 mg/kg, MDMA areas under the curve (AUCs) were 21-fold (intraperitoneal), 10-fold (subcutaneous), and 36-fold (oral) greater than those at 2 mg/kg. In contrast, HMMA AUC values in high-dose groups were < 3-fold above those at 2 mg/kg. Several new findings emerge from this report of low-dose MDMA pharmacokinetics in rats. First, 2 mg/kg MDMA in rats can produce MDMA Cmax values similar to those in humans, perhaps explaining why both species discriminate 1.5 mg/kg MDMA in laboratory paradigms. Second, our data provide additional support for nonlinear kinetics of MDMA in rats, and, analogous to humans, this phenomenon appears to involve impaired drug metabolism. Finally, given key similarities between MDMA pharmacokinetics in rats and humans, data from rats may be clinically relevant when appropriate dosing conditions are used. C1 [Baumann, Michael H.; Zolkowska, Dorota; Rothman, Richard B.] NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Kim, Insook; Scheidweiler, Karl B.; Huestis, Marilyn A.] NIDA, Chem & Drug Metab Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Zolkowska, Dorota] Med Univ Lublin, Dept Hyg, Lublin, Poland. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, 333 Cassell Dr,Suite 4500, Baltimore, MD 21224 USA. EM mbaumann@mail.nih.gov FU National Institutes of Health National Institute of Drug Abuse FX This work was supported by the Intramural Research Program of the National Institutes of Health National Institute of Drug Abuse. NR 41 TC 37 Z9 37 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2009 VL 37 IS 11 BP 2163 EP 2170 DI 10.1124/dmd.109.028506 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507TA UT WOS:000270876600007 PM 19679675 ER PT J AU Knudsen, GA Cheng, Y Kuester, RK Hooth, MJ Sipes, IG AF Knudsen, G. A. Cheng, Y. Kuester, R. K. Hooth, M. J. Sipes, I. G. TI Effects of Dose and Route on the Disposition and Kinetics of 1-Butyl-1-methylpyrrolidinium Chloride in Male F-344 Rats SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ORGANIC CATION TRANSPORTERS; TEMPERATURE IONIC LIQUIDS; MALE FISCHER-344 RATS; FEMALE B6C3F1 MICE; TETRABROMOBISPHENOL; TOXICOKINETICS; METABOLISM; ABSORPTION; EXCRETION; OCT2 AB Studies were conducted to characterize the effects of dose and route of administration on the disposition of 1-butyl-1-methylpyrrolidinium (BmPy-Cl) in male Fischer-344 rats. After a single oral administration of [(14)C]BmPy-Cl (50 mg/kg), BmPy-Cl in the blood decreased rapidly after C(max) of 89.1 min with a distribution half-life (t(1/2 alpha)) of 21 min, an elimination half-life (t(1/2 beta)) of 5.6 h, and a total body clearance of 7.6 ml/min. After oral administration (50, 5, and 0.5 mg/kg), 50 to 70% of the administered radioactivity was recovered in the feces, with the remainder recovered in the urine. Serial daily oral administrations of [(14)C]BmPy-Cl (50 mg/kg/day for 5 days) did not result in a notable alteration in disposition or elimination. After each administration, 88 to 94% of the dose was eliminated in a 24-h period, with 63 to 76% of dose recovered in the feces. Intravenous administration of [(14)C]BmPy-Cl (5 mg/kg) resulted in biphasic elimination. Oral systemic bioavailability was 43.4%, approximately equal to the dose recovered in urine after oral administration (29-38%). Total dermal absorption of [(14)C]BmPy-Cl (5 mg/kg) was moderate when it was applied in dimethylformamide-water (34 +/- 13%), variable in water (22 +/- 8%), or minimal in ethanol-water (13 +/- 1%) vehicles. Urine was the predominant route of elimination regardless of vehicle. Only parent [(14)C]BmPy-Cl was detected in the urine after all doses and routes of administration. BmPy-Cl was found to be a substrate for (K(t) = 37 mu M) and inhibitor of (IC(50/tetraethylammonium) = 0.5 mu M) human organic cation transporter 2. In summary, BmPy-Cl is moderately absorbed, extracted by the kidney, and eliminated in the urine as parent compound, independent of dose, number, or route of administration. C1 [Knudsen, G. A.; Cheng, Y.; Kuester, R. K.; Sipes, I. G.] Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. [Hooth, M. J.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. RP Sipes, IG (reprint author), Univ Arizona, Coll Med, Dept Pharmacol, POB 245050, Tucson, AZ 85724 USA. EM sipes@email.arizona.edu RI Knudsen, Gabriel/G-3706-2013 OI Knudsen, Gabriel/0000-0002-7208-6451 FU National Institutes of Health National Institute of Environmental Health Sciences [N01-ES45529, N01-ES06694]; National Institutes of Health National Institute of Environmental Health Sciences, Intramural Research Program, Research Project Number 1 [Z01ES045004-11 BB]; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK58251] FX This work was supported in part by the National Institutes of Health National Institute of Environmental Health Sciences [Grants N01-ES45529, ES06694]; the National Institutes of Health National Institute of Environmental Health Sciences, Intramural Research Program, Research Project Number 1 [Grant Z01ES045004-11 BB]; and the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK58251]. NR 25 TC 6 Z9 6 U1 1 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 2009 VL 37 IS 11 BP 2171 EP 2177 DI 10.1124/dmd.109.029082 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507TA UT WOS:000270876600008 PM 19704025 ER PT J AU O'Shea, TM Allred, EN Dammann, O Hirtz, D Kuban, KCK Paneth, N Leviton, A AF O'Shea, T. M. Allred, E. N. Dammann, O. Hirtz, D. Kuban, K. C. K. Paneth, N. Leviton, A. CA ELGAN Study Investigators TI The ELGAN study of the brain and related disorders in extremely low gestational age newborns SO EARLY HUMAN DEVELOPMENT LA English DT Article DE Prematurity; Developmental disability; Autism spectrum disorder; Autism; Cerebral palsy; Chorioamnionitis; Pregnancy; Preeclampsia ID WHITE-MATTER DAMAGE; LOW-BIRTH-WEIGHT; FETAL INFLAMMATORY RESPONSE; CEREBRAL-PALSY; BRONCHOPULMONARY DYSPLASIA; PRETERM NEWBORNS; 28TH WEEK; PERINATAL INFECTION; MATERNAL INFECTION; PREMATURE-INFANTS AB Background: Extremely low gestational age newborns (ELGANs) are at increased risk for structural and functional brain abnormalities. Aim: To identify factors that contribute to brain damage in ELGANs. Study design: Multi-center cohort study. Subjects: We enrolled 1506 ELGANs born before 28 weeks gestation at 14 sites; 1201 (80%) survived to 2 years corrected age. Information about exposures and characteristics was collected by maternal interview, from chart review, microbiologic and histological examination of placentas, and measurement of proteins in umbilical cord and early postnatal blood spots, Outcome measures: Indicators of white matter damage, i.e. ventriculomegaly and echolucent lesions, on protocol cranial ultrasound scans; head circumference and developmental outcomes at 24 months adjusted age. i.e., cerebral palsy, mental and motor scales of the Bayley Scales of Infant Development, and a screen for autism spectrum disorders. Results: ELGAN Study publications thus far provide evidence that the following are associated with ultrasongraphically detected white matter damage, cerebral palsy, or both: preterm delivery attributed to preterm labor, prelabor premature rupture of membranes, or cervical insufficiency; recovery of microorganisms in the placenta parenchyma, including species categorized as human skin microflora; histological evidence of placental inflammation; lower gestational age at delivery: greater neonatal illness severity: severe chronic lung disease; neonatal bacteremia; and necrotizing enterocolitis. Conclusions: In addition to supporting a potential role for many previously identified antecedents of brain damage in ELGANs, our study is the first to provide strong evidence that brain damage in extremely preterm infants is associated with microorganisms in placenta parenchyma. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [O'Shea, T. M.] Wake Forest Univ Hlth Sci, Dept Pediat Neonatol, Winston Salem, NC 27157 USA. [Allred, E. N.; Dammann, O.; Leviton, A.] Childrens Hosp, Neuroepidemiol Unit, Boston, MA 02115 USA. [Dammann, O.] Floating Hosp Children, Tufts Med Ctr, Dept Pediat Newborn Med, Boston, MA USA. [Dammann, O.] Hannover Med Sch, Perinatal Neuroepidemiol Unit, Dept Gynecol, Hannover, Germany. [Dammann, O.] Hannover Med Sch, Perinatal Neuroepidemiol Unit, Dept Pediat, Hannover, Germany. [Hirtz, D.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Kuban, K. C. K.] Boston Med Ctr, Dept Pediat Pediat Neurol, Boston, MA USA. [Paneth, N.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. RP O'Shea, TM (reprint author), Wake Forest Univ Hlth Sci, Dept Pediat Neonatol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM moshea@wfubmc.edu OI Kuban, Karl/0000-0001-5299-3567 FU National Institute of Neurological Disorders and Stroke (NINDS) [5U01NS040069-05] FX This study was supported by a cooperative agreement with The National Institute of Neurological Disorders and Stroke (NINDS) (5U01NS040069-05). The authors gratefully acknowledge the contributions of our subjects and their families, as well as those of our colleagues. NR 78 TC 108 Z9 109 U1 0 U2 18 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD NOV PY 2009 VL 85 IS 11 BP 719 EP 725 DI 10.1016/j.earlhumdev.2009.08.060 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 522IL UT WOS:000271991000009 PM 19765918 ER PT J AU Shizukuda, Y Bolan, CD Tripodi, DJ Sachdev, V Nguyen, TT Botello, G Yau, YY Sidenko, S Inez, E Ali, MI Waclawiw, MA Leitman, SF Rosing, DR AF Shizukuda, Yukitaka Bolan, Charles D. Tripodi, Dorothy J. Sachdev, Vandana Nguyen, Tammy T. Botello, Gilberto Yau, Yu-Ying Sidenko, Stanislav Inez, Ernst Ali, Mir I. Waclawiw, Myron A. Leitman, Susan F. Rosing, Douglas R. TI Does Oxidative Stress Modulate Left Ventricular Diastolic Function in Asymptomatic Subjects with Hereditary Hemochromatosis ? SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE hereditary hemochromatosis; left ventricular diastolic function; oxidative stress; strain rate; iron overload; cohort study ID IDIOPATHIC HEMOCHROMATOSIS; IRON OVERLOAD; MALONDIALDEHYDE; CARDIOMYOPATHY; GLUTATHIONE; DYSFUNCTION; RADICALS; FAILURE; DISEASE AB Background: Little is known about the early mechanisms mediating left ventricular (LV) diastolic dysfunction in patients with hereditary hemochromatosis (HH). However, the increased oxidative stress related to iron overload may be involved in this process, and strain rate (SR), a sensitive echocardiography-derived measure of diastolic function, may detect such changes. Aim: we evaluated the relationship between left ventricular diastolic function measured with tissue Doppler SR and oxidative stress in asymptomatic HH subjects and control normal subjects. Materials and Methods: Ninety-four consecutive visits of 43 HH subjects, age 30-74 (50 +/- 10, mean +/- SD), and 37 consecutive visits of 21 normal volunteers, age 30-63 (48 +/- 8), were evaluated over a 3-year period. SR was obtained from the basal septum in apical four-chamber views. All patients had confirmed C282Y homozygosity, a documented history of iron overload, and were New York Heart Association functional class I. Normal volunteers lacked HFE gene mutations causing HH. Results: In the HH subjects, the SR demonstrated moderate but significant correlations with biomarkers of oxidative stress; however, no correlations were noted in normal subjects. The biomarkers of iron overload per se did not show significant correlations with the SR. Conclusion: Although our study was limited by the relatively small subject number, these results suggest that a possible role of oxidative stress to affect LV diastolic function in asymptomatic HH subjects and SR imaging may be a sensitive measure to detect that effect. (ECHOCARDIOGRAPHY, Volume 26, November 2009) C1 [Shizukuda, Yukitaka] Univ Cincinnati, Dept Internal Med, Div Cardiovasc Dis, Med Ctr, Cincinnati, OH 45219 USA. [Shizukuda, Yukitaka; Tripodi, Dorothy J.; Sachdev, Vandana; Nguyen, Tammy T.; Botello, Gilberto; Sidenko, Stanislav; Inez, Ernst; Ali, Mir I.; Rosing, Douglas R.] NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. [Waclawiw, Myron A.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [Bolan, Charles D.; Yau, Yu-Ying; Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shizukuda, Y (reprint author), Univ Cincinnati, Dept Internal Med, Div Cardiovasc Dis, Med Ctr, 234 Goodman Ave,Rm 2205,ML 0802, Cincinnati, OH 45219 USA. EM shizukya@uc.edu FU National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD FX This study was supported by funds from the intramural research program of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD. NR 23 TC 13 Z9 13 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD NOV PY 2009 VL 26 IS 10 BP 1153 EP 1158 DI 10.1111/j.1540-8175.2009.00956.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 519PI UT WOS:000271778900005 PM 19725855 ER PT J AU Phillips, TM Kalish, H Wellner, E AF Phillips, Terry M. Kalish, Heather Wellner, Edward TI Receptor affinity CE for measuring bioactive inflammatory cytokines in human skin biopsies SO ELECTROPHORESIS LA English DT Article DE Bioactivity; Chip-based CE; Clinical assessment; Inflammation; Receptor affinity ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; BODY-FLUIDS; BIOMARKERS; CONSTANTS; MIGRATION; PLASMA; ASSAYS AB A chip-based receptor affinity CE system has been employed to measure the concentrations of bioactive pro-inflammatory cytokines in biopsy materials obtained from human atopic skin lesions. The device employs a replaceable affinity disk to which recombinant cytokine receptors have been chemically immobilized. Homogenates obtained from micro-dissected human skin samples were injected into the system where the bioactive cytokines were captured in the receptor affinity port and labeled in situ with a laser dye. The captured cytokines were released and separated by CE, the resolved peaks being detected and measured by laser-induced fluorescence. When compared with conventional cell-based bioassays, the affinity receptor chip showed reasonable correlation with r(2) values of 0.998 for interferon gamma, 0.994 for IL-6 and 0.991 for tumor necrosis factor alpha. The complete process including cytokine capture, labeling, and analysis took approximately 12.5 min with intra- and inter-assay CVs below 5.3% and recoveries of 84.9-98.4% at the 100 pg/mL concentration in buffer solutions and 84.5-95% in normal human tissue extract. The system could indicate clear differences between the various clinical stages of atopic dermatitis in human patients and could run 4-6 samples per hour. This system, like previous chip-based systems designed in our laboratory, holds the potential for being modified to be a portable unit that could be used in clinics and other biomedical screening studies. C1 [Phillips, Terry M.] Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Sect, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Phillips, TM (reprint author), Natl Inst Biomed Imaging & Bioengn, Ultramicro Immunodiagnost Sect, Lab Bioengn & Phys Sci, NIH, 13-3N 15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM phillipt@mail.nih.gov FU National Institutes of Health, Bethesda, MD, USA FX This work was supported by the Intramural Program of the National Institutes of Health, Bethesda, MD, USA. NR 38 TC 6 Z9 6 U1 1 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD NOV PY 2009 VL 30 IS 22 BP 3947 EP 3954 DI 10.1002/elps.200900311 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 528VK UT WOS:000272474900020 PM 19938183 ER PT J AU Henley, DV Mueller, S Korach, KS AF Henley, Derek V. Mueller, Stephanie Korach, Kenneth S. TI The Short-Chain Fatty Acid Methoxyacetic Acid Disrupts Endogenous Estrogen Receptor-alpha-Mediated Signaling SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE estrogen receptor; estrogen; methoxyacetic acid; short-chain fatty acid ID ETHYLENE-GLYCOL MONOMETHYL; SODIUM-BUTYRATE; VALPROIC ACID; HISTONE DEACETYLASE; ETHER; CELLS; INHIBITION; ACTIVATION; TOXICITY; WOMEN AB BACKGROUND: Ethylene glycol monomethyl ether (EGME) exposure is associated with impaired reproductive function. The primary metabolite of EGME is methoxyacetic acid (MAA), a short-chain fatty acid that inhibits historic deacerylase activity and alters gene expression. OBJECTIVE: Because estrogen signaling is necessary for normal reproductive function and modulates gene expression, the estrogen-signaling pathway is a likely target for MAA; however, little is known about the effects of MAA in this regard. METHODS: We evaluated the mechanistic effects of MAA on estrogen receptor (ER) expression and estrogen signaling using in vitro and in vivo model systems. RESULTS: MAA potentiates 17 beta-estradiol (E(2)) stimulation of an estrogen-responsive reporter plasmid in HeLa cells transiently transfected with either a human ER alpha or ER beta expression vector containing a cytomegalovirus (CMV) promoter. This result is attributed to increased exogenous ER expression due to MAA-mediated activation of the CMV promoter. In contrast to its effects on exogenous ER, MAA decreases endogenous ER alpha expression and attenuates E(2)-stimulated endogenous gene expression in both MCF-7 cells and the mouse uterus. CONCLUSIONS: These results illustrate the importance of careful experimental design and analysis when assessing the potential endocrine-disrupting properties of a compound to ensure biological responses are in concordance with in vitro analyses. Given the established role of the ER in normal reproductive function, the effects of MAA on the endogenous ER reported here are consistent with the reproductive abnormalities observed after EGME exposure and suggest that these toxicities may be due, at least in part, to attenuation of endogenous ER-mediated signaling. C1 [Henley, Derek V.; Korach, Kenneth S.] NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Mueller, Stephanie] German Canc Res Ctr, D-6900 Heidelberg, Germany. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH,Dept Hlth & Human Serv, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS) [Z01 ES70065] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS), through grant Z01 ES70065 from the NIEHS. NR 32 TC 12 Z9 12 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2009 VL 117 IS 11 BP 1702 EP 1706 DI 10.1289/ehp.0900800 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 514MQ UT WOS:000271399300025 PM 20049119 ER PT J AU Birnbaum, LS AF Birnbaum, Linda S. TI Applying Research to Public Health Questions: Timing and the Environmentally Relevant Dose SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 [Birnbaum, Linda S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Birnbaum, Linda S.] NIH, NTP, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Birnbaum, LS (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbaumls@niehs.nih.gov NR 6 TC 8 Z9 9 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2009 VL 117 IS 11 BP A478 EP A478 DI 10.1289/ehp.0901417 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 514MQ UT WOS:000271399300001 PM 20049095 ER PT J AU Delinsky, AD Strynar, MJ Nakayama, SF Varns, JL Ye, XB McCann, PJ Lindstrom, AB AF Delinsky, Amy D. Strynar, Mark J. Nakayama, Shoji F. Varns, Jerry L. Ye, XiBiao McCann, Patricia J. Lindstrom, Andrew B. TI Determination of ten perfluorinated compounds in bluegill sunfish (Lepomis macrochirus) fillets SO ENVIRONMENTAL RESEARCH LA English DT Article DE LC/MS/MS; PFOS; PFOA; Fish; SPE; Perfluorinated compounds ID PERFLUOROOCTANE SULFONIC-ACID; PERFLUOROALKYL CONTAMINANTS; NORTH-CAROLINA; GREAT-LAKES; FOOD-WEB; WATER; FISH; CHAIN; USA; SURFACTANTS AB A rigorous solid phase extraction/liquid chromatography/tandem mass spectrometry method for the measurement of 10 perfluorinated compounds (PFCs) in fish fillets is described and applied to fillets of bluegill sunfish (Lepomis macrochirus) collected from selected areas of Minnesota and North Carolina. The 4 PFC analytes routinely detected in bluegill fillets were perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (C10), perfluoroundecanoic acid (C11), and perflurododecanoic acid (C12). Measures of method accuracy and precision for these compounds showed that calculated concentrations of PFCs in spiked samples differed by less than 20% from their theoretical values and that the %RSD for repeated measurements was less than 20%. Minnesota samples were collected from areas of the Mississippi River near historical PFC sources, from the St. Croix River as a background site, and from Lake Calhoun, which has no documented PFC sources. PFOS was the most prevalent PFC found in the Minnesota samples, with median concentrations of 47.0-102 ng/g at locations along the Mississippi River, 2.08 ng/g in the St. Croix River, and 275 ng/g in Lake Calhoun. North Carolina samples were collected from two rivers with no known historical PFC sources. PFOS was the predominant analyte in fish taken from the Haw and Deep Rivers, with median concentrations of 30.3 and 62.2 ng/g, respectively. Concentrations of C10, C11, and C12 in NC samples were among the highest reported in the literature, with respective median values of 9.08, 23.9, and 6.60 ng/g in fish from the Haw River and 2.90, 9.15, and 3.46 ng/g in fish from the Deep River. These results suggest that PFC contamination in freshwater fish may not be limited to areas with known historical PFC inputs. Published by Elsevier Inc. C1 [Delinsky, Amy D.; Strynar, Mark J.; Lindstrom, Andrew B.] US EPA, NERL, Res Triangle Pk, NC 27711 USA. [Nakayama, Shoji F.] US EPA, NRMRL, Cincinnati, OH 45268 USA. [Varns, Jerry L.] NCBA Inc, SEE Program, Durham, NC USA. [Ye, XiBiao] NIEHS, Res Triangle Pk, NC 27709 USA. [McCann, Patricia J.] Minnesota Dept Hlth, St Paul, MN USA. RP Lindstrom, AB (reprint author), US EPA, NERL, Res Triangle Pk, NC 27711 USA. EM lindstrom.andrew@epa.gov RI Nakayama, Shoji/B-9027-2008 FU Oak Ridge Institute for Science and Education (ORISE); US Department of Energy; US Environmental Protection Agency; Oasis WAX SPE cartridges [392-06] FX This research was supported in part by an appointment to the Research Participation Program at the National Exposure Research Laboratory administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the US Department of Energy and the US Environmental Protection Agency. We also acknowledge Waters Corporation for the donation of Oasis WAX SPE cartridges (Cooperative Research and Development Agreement # 392-06). The authors thank Scott Van Horn and Corey Oakley from the North Carolina Fish and Wildlife Commission and individuals at the Minnesota Pollution Control Agency and Minnesota Department of Natural Resources for their assistance in obtaining samples. We also thank Larry Helfant, Sissy Petropoulou, and Jessica Reiner for their assistance and technical expertise. The United States Environmental Protection Agency through its Office of Research and Development funded and managed the research described here. It has been subjected to Agency review and approved for publication. Mention of trade names or commercial products does not constitute endorsement or recommendation for use. NR 41 TC 23 Z9 23 U1 0 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2009 VL 109 IS 8 BP 975 EP 984 DI 10.1016/j.envres.2009.08.013 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 513BL UT WOS:000271296900005 PM 19775685 ER PT J AU Gee, GC Ro, A Shariff-Marco, S Chae, D AF Gee, Gilbert C. Ro, Annie Shariff-Marco, Salma Chae, David TI Racial Discrimination and Health Among Asian Americans: Evidence, Assessment, and Directions for Future Research SO EPIDEMIOLOGIC REVIEWS LA English DT Review DE Asian Americans; ethnic groups; health status disparities; minority health; population dynamics; prejudice; residence characteristics; stress; psychological ID COLLECTIVE SELF-ESTEEM; ETHNIC-MINORITY GROUPS; PERCEIVED UNFAIR TREATMENT; ISLANDER GAY MEN; RACIAL/ETHNIC DISCRIMINATION; RESIDENTIAL SEGREGATION; FILIPINO AMERICANS; AFRICAN-AMERICAN; BLOOD-PRESSURE; UNITED-STATES AB Research shows that racial discrimination is related to illness among diverse racial and ethnic populations. Studies of racial discrimination and health among Asian Americans, however, remain underdeveloped. In this paper, the authors review evidence on racial discrimination and health among Asian Americans, identify gaps in the literature, and provide suggestions for future research. They identified 62 empirical articles assessing the relation between discrimination and health among Asian Americans. The majority of articles focused on mental health problems, followed by physical and behavioral problems. Most studies find that discrimination was associated with poorer health, although the most consistent findings were for mental health problems. This review suggests that future studies should continue to investigate the following: 1) the measurement of discrimination among Asian Americans, whose experiences may be qualitatively different from those of other racial minority groups; 2) the heterogeneity among Asian Americans, including those factors that are particularly salient in this population, such as ethnic ancestry and immigration history; and 3) the health implications of discrimination at multiple ecologic levels, ranging from the individual level to the structural level. C1 [Gee, Gilbert C.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90095 USA. [Ro, Annie] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. [Shariff-Marco, Salma] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Chae, David] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Gee, GC (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, 650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM gilgee@ucla.edu FU NICHD NIH HHS [T32 HD007339] NR 181 TC 96 Z9 96 U1 6 U2 25 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0193-936X J9 EPIDEMIOL REV JI Epidemiol. Rev. PD NOV 1 PY 2009 VL 31 IS 1 BP 130 EP 151 DI 10.1093/epirev/mxp009 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 520BJ UT WOS:000271814500009 PM 19805401 ER PT J AU Longnecker, MP AF Longnecker, Matthew P. TI On Confounded Fishy Results Regarding Arsenic and Diabetes SO EPIDEMIOLOGY LA English DT Editorial Material ID HUMAN URINE; ASSOCIATION; ARSENOSUGAR; METABOLITES; PREVENTION; INGESTION; EXPOSURE; ADULTS C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnecl@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 14 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 BP 821 EP 823 DI 10.1097/EDE.0b013e3181b26bce PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SD UT WOS:000270874000007 PM 19730267 ER PT J AU Baris, D Vermeulen, R Purdue, M Wilson, W Pellizzari, E Hartge, P Rothman, N AF Baris, Dalsu Vermeulen, Roel Purdue, Mark Wilson, Wyndham Pellizzari, Edo Hartge, Patricia Rothman, Nathaniel TI Blood Levels of Organochlorines Before, During and After Chemotherapy Among Non-Hodgkin Lymphoma (NHL) Patients SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Baris, Dalsu; Purdue, Mark; Wilson, Wyndham; Hartge, Patricia; Rothman, Nathaniel] NCI, NIH, DHHS, Bethesda, MD 20892 USA. [Vermeulen, Roel] Univ Utrecht, Utrecht, Netherlands. [Pellizzari, Edo] RTI Int, Res Triangle Pk, NC USA. RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S235 EP S235 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101370 ER PT J AU Bloom, M Parsons, P Amy, S Coccaro, G Schisterman, E Browne, R Conti, G Narayan, N Fujimoto, V AF Bloom, Michael Parsons, Patrick Amy, Steuerwald Coccaro, Gregory Schisterman, Enrique Browne, Richard Conti, Giulia Narayan, Natasha Fujimoto, Victor TI Body Burdens of Mercury (Hg), Cadmium (Cd), and Lead (Pb) and Oocyte Fertilization among Women Undergoing a First Cycle of In Vitro Fertilization SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Bloom, Michael; Parsons, Patrick; Amy, Steuerwald] SUNY Buffalo, Dept Environm Hlth Sci, Rensselaer, NY 94143 USA. [Coccaro, Gregory] SUNY Buffalo, Dept Biomed Sci, Rensselaer, NY USA. [Parsons, Patrick; Amy, Steuerwald] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. [Schisterman, Enrique] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Browne, Richard] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY USA. [Conti, Giulia; Narayan, Natasha; Fujimoto, Victor] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. RI Parsons, Patrick/I-2985-2015 OI Parsons, Patrick/0000-0001-9133-875X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S121 EP S122 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101004 ER PT J AU Cao, Y Blount, B Valentin-Blasini, L Bernbaum, J Phillips, T Rogan, W AF Cao, Yang Blount, Ben Valentin-Blasini, Liza Bernbaum, Judy Phillips, Terry Rogan, Walter TI Pollutant Chemicals, Thyrotropin, and Thyroid Hormone in Infants SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Cao, Yang; Rogan, Walter] NIEHS, Res Triangle Pk, NC 27709 USA. [Blount, Ben; Valentin-Blasini, Liza] CDC, Atlanta, GA 30333 USA. [Bernbaum, Judy] Childrens Hosp, Philadelphia, PA 19104 USA. [Phillips, Terry] NIBIB, Bethesda, MD USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S160 EP S161 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101130 ER PT J AU Cao, Y Chen, AM Jones, R Peddada, S Radcliffe, J Dietrich, K Caldwell, K Rogan, W AF Cao, Yang Chen, Aimin Jones, Robert Peddada, Shyamal Radcliffe, Jerilynn Dietrich, Kim Caldwell, Kathleen Rogan, Walter TI Efficacy of Succimer Chelation of Mercury at Background Exposures in Toddlers: Randomised Trial SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Cao, Yang; Peddada, Shyamal; Rogan, Walter] NIEHS, Res Triangle Pk, NC 27709 USA. [Chen, Aimin] Creighton Univ, Omaha, NE 68178 USA. [Jones, Robert; Caldwell, Kathleen] CDC, Atlanta, GA 30333 USA. [Radcliffe, Jerilynn] Childrens Hosp, Philadelphia, PA 19104 USA. [Dietrich, Kim] Univ Cincinnati, Cincinnati, OH USA. RI Jones, Robert/E-1170-2011; Peddada, Shyamal/D-1278-2012; Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S159 EP S160 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101127 ER PT J AU Colt, J Karagas, M Schwenn, M Baris, D Johnson, A Stewart, P Verrill, C Moore, L Lubin, J Ward, M Samanic, C Rothman, N Cantor, K Freeman, LB Schned, A Cherala, S Silverman, D AF Colt, Joanne Karagas, Margaret Schwenn, Molly Baris, Dalsu Johnson, Alison Stewart, Patricia Verrill, Castine Moore, Lee Lubin, Jay Ward, Mary Samanic, Claudine Rothman, Nathaniel Cantor, Kenneth Freeman, Laura Beane Schned, Alan Cherala, Sai Silverman, Debra TI Occupation and Bladder Cancer in a Population Based Case-Control Study in Northern New England SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Colt, Joanne; Baris, Dalsu; Moore, Lee; Lubin, Jay; Ward, Mary; Samanic, Claudine; Rothman, Nathaniel; Cantor, Kenneth; Freeman, Laura Beane; Silverman, Debra] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Karagas, Margaret; Schned, Alan] Dartmouth Med Sch, Hanover, NH USA. [Schwenn, Molly; Verrill, Castine] Maine Canc Registry, Augusta, ME USA. [Johnson, Alison] Vermont Canc Registry, Burlington, VT USA. [Stewart, Patricia] Stewart Exposure Assessments LLC, Arlington, VA USA. [Cherala, Sai] New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA. RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S128 EP S128 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101025 ER PT J AU Cupul-Uicab, L Hernandez-Avila, M Longnecker, M AF Cupul-Uicab, Lea Hernandez-Avila, Mauricio Longnecker, Matthew TI Prenatal Exposure to the Major DDT Metabolite DDE and Longitudinal Measures of Body Mass Index in Boys from Southern Mexico SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Cupul-Uicab, Lea; Longnecker, Matthew] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. [Hernandez-Avila, Mauricio] Minist Hlth, Mexico City, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S234 EP S234 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101367 ER PT J AU Dilworth, C O'Fallon, L Gray, K AF Dilworth, Caroline O'Fallon, Liam Gray, Kimberly TI Community Engagement Benefits Environmental Health Research SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Dilworth, Caroline; O'Fallon, Liam; Gray, Kimberly] Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S45 EP S46 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100103 ER PT J AU Gohlke, JM Hales, S Portier, CJ Woodward, A Campbell-Lendrum, D Pruss-Ustun, A AF Gohlke, Julia M. Hales, Simon Portier, Christopher J. Woodward, Alistair Campbell-Lendrum, Diarmid Pruess-Ustun, Annette TI Building a Framework to Identify Global Health Impacts of Power Generation Systems SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Gohlke, Julia M.; Portier, Christopher J.] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. [Hales, Simon; Campbell-Lendrum, Diarmid; Pruess-Ustun, Annette] WHO, Dept Publ Hlth & Environm, CH-1211 Geneva, Switzerland. [Woodward, Alistair] Univ Auckland, Sch Populat Hlth, Auckland 1, New Zealand. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S263 EP S263 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101463 ER PT J AU Hernandez-Cadena, L Barraza-Villarreal, A Sever, M Zeldin, D Escamilla-Nunez, MC Sly, P Romieu, I AF Hernandez-Cadena, Leticia Barraza-Villarreal, Albino Sever, Michel Zeldin, Darryl Consuelo Escamilla-Nunez, Maria Sly, Peter Romieu, Isabelle TI Environmental Predictor of Allergen in Dust Samples and Its Relation to Total IgE Levels in Cord Blood in Cuernavaca, Morelos Mexico SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Hernandez-Cadena, Leticia; Barraza-Villarreal, Albino; Consuelo Escamilla-Nunez, Maria; Romieu, Isabelle] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. [Sever, Michel; Zeldin, Darryl] Natl Inst Environm Hlth Sci, NIH, Bethesda, MD 20892 USA. [Sly, Peter] WHO Collaborating Ctr Res Childrens Envrionm Hlth, W Pert, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S220 EP S220 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101321 ER PT J AU Huang, AT Cantor, K Batterman, S AF Huang, An-Tsun Cantor, Kenneth Batterman, Stuart TI Estimation for Reduced Trihalomethane Exposure Through Ingestion from Heated Tea and Drinking Water SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Huang, An-Tsun; Batterman, Stuart] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Huang, An-Tsun; Cantor, Kenneth] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S85 EP S86 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100226 ER PT J AU Kamel, F Bhudhikanok, G Blair, A Goldman, S Hoppin, J Korell, M Langston, JW Richards, M Ross, GW Sandler, D Umbach, D Tanner, C AF Kamel, Freya Bhudhikanok, Grace Blair, Aaron Goldman, Samuel Hoppin, Jane Korell, Monica Langston, J. William Richards, Marie Ross, G. Webster Sandler, Dale Umbach, David Tanner, Caroline TI Pesticide Exposure and Parkinson's Disease (PD) in the Agricultural Health Study (AHS) SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Kamel, Freya; Hoppin, Jane; Sandler, Dale; Umbach, David] NIEHS, Res Triangle Pk, NC 27709 USA. [Bhudhikanok, Grace; Goldman, Samuel; Korell, Monica; Langston, J. William; Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [Blair, Aaron] NCI, Rockville, MD USA. [Richards, Marie] Westat Corp, Durham, NC USA. [Ross, G. Webster] Pacific Hlth Res Inst, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S244 EP S244 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101399 ER PT J AU Lubin, J AF Lubin, Jay TI Toward a More Informative Approach for the Analysis of Environmental and Occupational Variables Based on Cumulative Exposure and Exposure Rate SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Lubin, Jay] US Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S86 EP S87 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100229 ER PT J AU Nuckols, J Airola, M Colt, J Johnson, A Schwenn, M Waddell, R Karagas, M Silverman, D Ward, MH AF Nuckols, John Airola, Matthew Colt, Joanne Johnson, Ali Schwenn, Molly Waddell, Richard Karagas, Margaret Silverman, Debra Ward, Mary H. TI The Impact of Residential Mobility on Exposure Assessment in Cancer Epidemiology SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Nuckols, John] Colorado State Univ, Ft Collins, CO 80523 USA. [Airola, Matthew] Westat Corp, Rockville, MD USA. [Nuckols, John; Colt, Joanne; Silverman, Debra; Ward, Mary H.] NCI, Rockville, MD USA. [Waddell, Richard; Karagas, Margaret] Dartmouth Coll, Hanover, NH 03755 USA. [Johnson, Ali] Vermont Dept Hlth, Burlington, VT 05402 USA. [Schwenn, Molly] Maine Dept Hlth & Human Serv, Augusta, ME USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S259 EP S260 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101450 ER PT J AU Pronk, A Nuckols, JR De Roos, AJ Airola, M Colt, JS Cerhan, JR Severson, R Blair, A Cleverly, D Ward, MH AF Pronk, Anjoeka Nuckols, John R. De Roos, Anneclaire J. Airola, Matthew Colt, Joanne S. Cerhan, James R. Severson, Richard Blair, Aaron Cleverly, David Ward, Mary H. TI Environmental Exposure to Dioxins from Living Near Industrial Combustion Sources and Risk of Non-Hodgkin Lymphoma SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Pronk, Anjoeka; Nuckols, John R.; Airola, Matthew; Colt, Joanne S.; Blair, Aaron; Ward, Mary H.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Nuckols, John R.] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [De Roos, Anneclaire J.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Airola, Matthew] Westat Corp, Rockville, MD USA. [Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA. [Cerhan, James R.] Univ Iowa, Iowa City, IA USA. [Severson, Richard] Wayne State Univ, Dept Family Med, Detroit, MI USA. [Severson, Richard] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Cleverly, David] US EPA, Off Res & Dev, Natl Ctr Environm Assessment, Washington, DC 20460 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S62 EP S63 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100155 ER PT J AU Purdue, M Engel, L Langseth, H Needham, L Andersen, A Barr, D Blair, A Rothman, N McGlynn, K AF Purdue, Mark Engel, Lawrence Langseth, Hilde Needham, Larry Andersen, Aage Barr, Dana Blair, Aaron Rothman, Nathaniel McGlynn, Katherine TI Pre-Diagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Purdue, Mark; Blair, Aaron; Rothman, Nathaniel; McGlynn, Katherine] NCI, Bethesda, MD 20892 USA. [Engel, Lawrence] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Langseth, Hilde; Andersen, Aage] Norwegian Canc Registry, Oslo, Norway. [Needham, Larry; Barr, Dana] Ctr Dis Control & Prevent, Atlanta, GA USA. RI Needham, Larry/E-4930-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S243 EP S243 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101396 ER PT J AU Romieu, I Barraza-Villarreal, A Escamilla-Nunez, C Hernandez-Cadena, L Li, HL Diaz-Sanchez, D Moreno-Macia, H London, S AF Romieu, Isabelle Barraza-Villarreal, Albino Escamilla-Nunez, Consuelo Hernandez-Cadena, Leticia Li Huiling Diaz-Sanchez, David Moreno-Macia, Hortensia London, Stephanie TI pH in Exhaled Breath and Ozone Exposure: Interaction with GSTM1 and GSTP1 SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Romieu, Isabelle; Barraza-Villarreal, Albino; Escamilla-Nunez, Consuelo; Hernandez-Cadena, Leticia; Moreno-Macia, Hortensia] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico. [Li Huiling; London, Stephanie] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Diaz-Sanchez, David] US EPA, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S63 EP S63 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874100156 ER PT J AU Savarath, V Kamin, R Punshon, T Rees, J Folt, C Zens, S Flanagan, V Baker, E Troisi, R Jackson, B Korrick, S Karagas, M AF Savarath, Vicki Kamin, Roxanne Punshon, Tracy Rees, Judy Folt, Carol Zens, Scot Flanagan, Victoria Baker, Emily Troisi, Rebecca Jackson, Brian Korrick, Susan Karagas, Margaret TI Contribution of Food Borne Exposure to Arsenic and to Biomarker Levels SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Savarath, Vicki; Rees, Judy; Zens, Scot; Troisi, Rebecca; Karagas, Margaret] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Kamin, Roxanne; Punshon, Tracy; Folt, Carol] Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. [Flanagan, Victoria; Baker, Emily] Dartmouth Hitchcock Med Ctr, Dept Obstet & Gynecol, Lebanon, NH 03766 USA. [Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Jackson, Brian] Dartmouth Coll, Dept Earth Sci, Hanover, NH 03755 USA. [Korrick, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S182 EP S182 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101197 ER PT J AU Ward, MH Colt, JS Metayer, C Gunter, RB Lubin, J Crouse, V Nishioka, MG Reynolds, P Buffler, PA AF Ward, Mary H. Colt, Joanne S. Metayer, Catherine Gunter, Robert B. Lubin, Jay Crouse, Vonda Nishioka, Marcia G. Reynolds, Peggy Buffler, Patricia A. TI Residential Exposure to Polychlorinated Biphenyls and Organochlorine Pesticides and Risk of Childhood Leukemia SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 21st Annual Conference of the International-Society-for-Environmental-Epidemiology CY AUG 25-29, 2009 CL Dublin, IRELAND C1 [Ward, Mary H.; Colt, Joanne S.; Lubin, Jay] NCI, Bethesda, MD 20892 USA. [Metayer, Catherine; Buffler, Patricia A.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Gunter, Robert B.; Reynolds, Peggy] No Calif Canc Ctr, Berkeley, CA USA. [Crouse, Vonda] Childrens Hosp Cent Calif, Madera, CA USA. [Nishioka, Marcia G.] Battelle Mem Inst, Columbus, OH 43201 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2009 VL 20 IS 6 SU S BP S244 EP S245 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507SE UT WOS:000270874101401 ER PT J AU Theodore, W Finegersh, A Cannon, D Musachio, J Herscovitch, P AF Theodore, William Finegersh, A. Cannon, D. Musachio, J. Herscovitch, P. TI REDUCED SEROTONIN TRANSPORT IN TEMPORAL LOBE EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Theodore, William] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. [Finegersh, A.; Cannon, D.] Natl Univ Ireland, Clin Neuroimaging Lab, Galway, Ireland. [Musachio, J.; Herscovitch, P.] NIH, PET Dept, Bethesda, MD USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 88 EP 89 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500178 ER PT J AU Bae, EH Theodore, WH Fregni, F Cantello, R Pascual-Leone, A Rotenberg, A AF Bae, Erica H. Theodore, W. H. Fregni, F. Cantello, R. Pascual-Leone, A. Rotenberg, A. TI AN ESTIMATE OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION PLACEBO EFFECT SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Bae, Erica H.; Rotenberg, A.] NYU, New York, NY USA. [Theodore, W. H.] NINDS, NIH, Bethesda, MD 20892 USA. [Fregni, F.; Pascual-Leone, A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, NY USA. [Cantello, R.] Amedeo Avogadro Univ, Dept Clin & Expt Med, Neurol Sect, Novara, Italy. [Bae, Erica H.] Harvard Univ, Sch Med, Childrens Hosp, Bethesda, MD USA. RI Cantello, Roberto/L-3786-2016 OI Cantello, Roberto/0000-0001-6999-5729 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 133 EP 133 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500274 ER PT J AU Trollinger, S Frazier, C Kunitz, S Miller, K Stout, A Fureman, B Jacobs, M Odenkirchen, J AF Trollinger, S. Frazier, C. Kunitz, S. Miller, K. Stout, A. Fureman, B. Jacobs, M. Odenkirchen, J. TI NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS), NATIONAL INSTITUTES OF HEALTH (NIH), COMMON DATA ELEMENT (CDE) PROJECT: EPILEPSY CDE UPDATE SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Trollinger, S.; Frazier, C.; Kunitz, S.; Miller, K.; Stout, A.] KAI Res Inc, Rockville, MD USA. [Fureman, B.; Jacobs, M.; Odenkirchen, J.] NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 158 EP 158 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500332 ER PT J AU Blackstone, K Mayo, J Moore, EN Vaidya, CJ Gaillard, WD Berl, MM AF Blackstone, Kaitlin Mayo, J. Moore, E. N. Vaidya, C. J. Gaillard, W. D. Berl, M. M. TI CHARACTERIZATION OF MEMORY IMPAIRMENT IN PEDIATRIC LOCALIZATION RELATED EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Blackstone, Kaitlin; Mayo, J.; Moore, E. N.; Gaillard, W. D.; Berl, M. M.] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Vaidya, C. J.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. [Gaillard, W. D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 284 EP 284 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500613 ER PT J AU Walkowiak, J Blackstone, K Duke, E Salpekar, J Gaillard, W Berl, M AF Walkowiak, Jenifer Blackstone, K. Duke, E. Salpekar, J. Gaillard, W. Berl, M. TI PATTERN OF ATTENTION DIFFICULTIES IN CHILDREN WITH LOCALIZATION RELATED EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Walkowiak, Jenifer; Blackstone, K.; Duke, E.; Salpekar, J.; Gaillard, W.; Berl, M.] Childrens Natl Med Ctr, Dept Psychiat, Washington Dc, DC USA. [Walkowiak, Jenifer; Blackstone, K.; Duke, E.; Salpekar, J.; Gaillard, W.; Berl, M.] Childrens Natl Med Ctr, Dept Behav Sci, Washington Dc, DC USA. [Duke, E.; Gaillard, W.] NINDS, Clin Epidemiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 289 EP 290 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500627 ER PT J AU Gaillard, WD You, X Bernal, B Guillen, MR Ayala, M Jayakar, P Barreto, A Rishe, N Sullivan, J Dlugos, D Berl, MM VanMeter, J Morris, D Donner, E Bjornson, B Smith, M Adjouadi, M AF Gaillard, W. D. You, X. Bernal, B. Guillen, M. R. Ayala, M. Jayakar, P. Barreto, A. Rishe, N. Sullivan, J. Dlugos, D. Berl, M. M. VanMeter, J. Morris, D. Donner, E. Bjornson, B. Smith, M. Adjouadi, M. TI PEDIATRIC FUNCTIONAL IMAGING CONSORTIUM: SUB-PATTERNS OF LANGUAGE DOMINANCE IN PEDIATRIC LOCALIZATION RELATED EPILEPSY IDENTIFIED BY DATA DRIVEN SEPARATION ANALYSIS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [You, X.; Guillen, M. R.; Ayala, M.; Barreto, A.; Rishe, N.; Adjouadi, M.] Florida Int Univ, Coll Engn & Comp, Miami, FL 33199 USA. [Sullivan, J.; Dlugos, D.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Bernal, B.; Jayakar, P.] Miami Childrens Hosp, Miami, FL USA. [Gaillard, W. D.; Berl, M. M.] George Washington Univ, Childrens Natl Med Ctr, Dept Neurosci, Washington, DC USA. [VanMeter, J.] Georgetown Univ, Dept Neurol, Washington, DC USA. [Morris, D.; Donner, E.; Smith, M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Smith, M.] Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. [Bjornson, B.] BC Childrens Hosp, Vancouver, BC, Canada. [Gaillard, W. D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RI Bjornson, Bruce/A-8616-2010 OI Bjornson, Bruce/0000-0002-1465-6196 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 437 EP 437 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500978 ER PT J AU Depositario-Cabacar, DF Fasano, R Yaun, A Pearl, P Conry, J Tsuchida, TN Heath, C Sato, S Gaillard, WD AF Depositario-Cabacar, Dewi Frances Fasano, R. Yaun, A. Pearl, P. Conry, J. Tsuchida, T. N. Heath, C. Sato, S. Gaillard, W. D. TI MEG FINDINGS AND ITS CONCORDANCE WITH VIDEO EEG AND SUBDURAL EEG AND SURGICAL OUTCOMES IN CHILDREN SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Depositario-Cabacar, Dewi Frances; Yaun, A.; Pearl, P.; Conry, J.; Tsuchida, T. N.; Heath, C.; Gaillard, W. D.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Depositario-Cabacar, Dewi Frances; Yaun, A.; Pearl, P.; Conry, J.; Tsuchida, T. N.; Heath, C.; Gaillard, W. D.] George Washington Univ, Sch Med, Washington, DC USA. [Fasano, R.; Sato, S.] NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 438 EP 438 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500980 ER PT J AU Duke, ES Berl, MM Rosenberger, LR Conry, JA Pearl, PL Tsuchida, T Depositario-Cabacar, D Heath, C Vezina, LG Sato, S Theodore, WH Gaillard, WD AF Duke, Elizabeth S. Berl, M. M. Rosenberger, L. R. Conry, J. A. Pearl, P. L. Tsuchida, T. Depositario-Cabacar, D. Heath, C. Vezina, L. G. Sato, S. Theodore, W. H. Gaillard, W. D. TI LANGUAGE REORGANIZATION IN PATIENTS WITH BRAIN LESIONS AND SHORT DURATION EPILEPSY SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Duke, Elizabeth S.; Berl, M. M.; Rosenberger, L. R.; Conry, J. A.; Pearl, P. L.; Tsuchida, T.; Depositario-Cabacar, D.; Heath, C.; Vezina, L. G.; Gaillard, W. D.] Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA. [Duke, Elizabeth S.; Rosenberger, L. R.; Sato, S.; Theodore, W. H.; Gaillard, W. D.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 440 EP 441 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500986 ER PT J AU Finegersh, A Avedissian, C Thompson, P Dustin, I Theodore, W AF Finegersh, A. Avedissian, C. Thompson, P. Dustin, I. Theodore, William TI THREE-DIMENSIONAL SURFACE MAPPING SHOWS HIPPOCAMPAL ATROPHY CONTRALATERAL AND IPSILATERAL TO SEIZURE FOCI IN TEMPORAL LOBE EPILEPSY PATIENTS WITH DEPRESSION, OR A HISTORY OF FEBRILE SEIZURES SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Finegersh, A.; Dustin, I.; Theodore, William] NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. [Avedissian, C.; Thompson, P.] Univ Calif Los Angeles, Lab Neuroimaging, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 441 EP 442 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550500988 ER PT J AU Pearl, PL AF Pearl, Phillip L. TI TREATABLE INHERITED METABOLIC EPILEPSIES: THE TOP TEN DIAGNOSES YOU CAN'T AFFORD TO MISS SO EPILEPSIA LA English DT Meeting Abstract CT 63rd Annual Meeting of the American-Epilepsy-Society CY DEC 04-08, 2009 CL Boston, MA SP Amer Epilepsy Soc C1 [Pearl, Phillip L.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pearl, Phillip L.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD NOV PY 2009 VL 50 BP 501 EP 501 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 503PP UT WOS:000270550501127 ER PT J AU Cabib, E AF Cabib, Enrico TI Two Novel Techniques for Determination of Polysaccharide Cross-Links Show that Crh1p and Crh2p Attach Chitin to both beta(1-6)- and beta(1-3)Glucan in the Saccharomyces cerevisiae Cell Wall SO EUKARYOTIC CELL LA English DT Article ID YEAST; ARCHITECTURE; DEACETYLATION; CONSTRUCTION; CHITOSAN AB Previous work, using solubilization of yeast cell walls by carboxymethylation, before or after digestion with beta(1-3)- or beta(1-6) glucanase, followed by size chromatography, showed that the transglycosylases Crh1p and Crh2p/Utr2p were redundantly required for the attachment of chitin to beta(1-6) glucan. With this technique, crh1 Delta crh2 Delta mutants still appeared to contain a substantial percentage of chitin linked to Delta(1-3) glucan. Two novel procedures have now been developed for the analysis of polysaccharide cross-links in the cell wall. One is based on the affinity of curdlan, a beta(1-3)glucan, for beta(1-3)glucan chains in carboxymethylated cell walls. The other consists of in situ deacetylation of cell wall chitin, generating chitosan, which can be extracted with acetic acid, either directly (free chitosan) or after digestion with different glucanases (bound chitosan). Both methodologies indicated that all of the chitin in crh1 Delta crh2 Delta strains is free. Reexamination of the previously used procedure revealed that the beta(1-3) glucanase preparation used (zymolyase) is contaminated with a small amount of endochitinase, which caused erroneous results with the double mutant. After removing the chitinase from the zymolyase, all three procedures gave coincident results. Therefore, Crh1p and Crh2p catalyze the transfer of chitin to both beta(1-3)- and beta(1-6) glucan, and the biosynthetic mechanism for all chitin cross-links in the cell wall has been established. C1 NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cabib, E (reprint author), NIDDK, Lab Biochem & Genet, NIH, Dept Hlth & Human Serv, Bldg 8,Room 403, Bethesda, MD 20892 USA. EM enricoc@bdg10.niddk.nih.gov FU National Institutes of Health FX I thank J. Arroyo, V. Farkas, and P. McPhie for useful discussions and a critical reading of the manuscript and V. Bouriotis for a sample of Cryptococcus chitin deacetylase. This study was supported by a National Institutes of Health grant (Intramural Research Program, NIDDK). NR 17 TC 28 Z9 28 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 EI 1535-9786 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2009 VL 8 IS 11 BP 1626 EP 1636 DI 10.1128/EC.00228-09 PG 11 WC Microbiology; Mycology SC Microbiology; Mycology GA 514BO UT WOS:000271368700002 PM 19734368 ER PT J AU Chang, YC Ingavale, SS Bien, C Espenshade, P Kwon-Chung, KJ AF Chang, Yun C. Ingavale, Susham S. Bien, Clara Espenshade, Peter Kwon-Chung, Kyung J. TI Conservation of the Sterol Regulatory Element-Binding Protein Pathway and Its Pathobiological Importance in Cryptococcus neoformans SO EUKARYOTIC CELL LA English DT Article ID FISSION YEAST; NUCLEAR IMPORT; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; COPII PROTEINS; SREBP PATHWAY; GENE; HYPOXIA; FAMILY; INSIG AB The mammalian sterol regulatory element-binding protein (SREBP) homolog, Sre1, is important for adaptation and growth of Cryptococcus neoformans in the mouse brain, where oxygen concentration and nutritional conditions are suboptimal for fungal growth. The extent of conservation of the SREBP pathway in C. neoformans or in any other fungi, however, has not been investigated. We generated mutants susceptible to low oxygen and identified six genes that play a role in the SREBP pathway. Three of these genes (SFB2, KAP123, and GSK3) are not known to be involved in the SREBP pathway in other fungi. Furthermore, we show that C. neoformans contains an additional gene, DAM1, which functions in the SREBP pathway but is yet to be described. Mutants associated with the steps prior to formation of the nuclear Sre1 form dramatically reduced accumulation of the nuclear form under low-oxygen conditions. Concurrently, two mutant strains, scp1 Delta and stp1 Delta, and the previously isolated sre1 Delta strain showed reduction in ergosterol levels, hypersensitivity to several chemical agents, including azole antifungals, CoCl(2), and compounds producing reactive oxygen or nitrogen species, and most importantly, reduced virulence in mice. Mutants affecting genes involved in later steps of the Sre1 pathway, such as those required for import and phosphorylation of proteins in the nucleus, showed less compelling phenotypes. These findings suggest that the SREBP pathway is highly conserved in C. neoformans and it serves as an important link between sterol biosynthesis, oxygen sensing, CoCl(2) sensitivity, and virulence in C. neoformans. C1 [Chang, Yun C.; Ingavale, Susham S.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Bien, Clara; Espenshade, Peter] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,Room 11C304, Bethesda, MD 20892 USA. EM June_Kwon-Chung@nih.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD; National Institutes of Health [AI072186]; Burroughs Wellcome Fund Investigator FX This study was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. This work was supported by grant AI072186 from the National Institutes of Health (to P. E.). P. E. is a Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease. NR 44 TC 24 Z9 26 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD NOV PY 2009 VL 8 IS 11 BP 1770 EP 1779 DI 10.1128/EC.00207-09 PG 10 WC Microbiology; Mycology SC Microbiology; Mycology GA 514BO UT WOS:000271368700015 PM 19749173 ER PT J AU Lang, IM Forman, SA Maggioni, AP Ruzyllo, W Renkin, J Vozzi, C Steg, PG Hernandez-Garcia, JM Zmudka, K Jimenez-Navarro, M Sopko, G Lamas, GA Hochman, JS AF Lang, Irene M. Forman, Sandra A. Maggioni, Aldo P. Ruzyllo, Witold Renkin, Jean Vozzi, Carlos Steg, P. Gabriel Hernandez-Garcia, Jose-Maria Zmudka, Krzysztof Jimenez-Navarro, Manuel Sopko, George Lamas, Gervasio A. Hochman, Judith S. TI Causes of death in early MI survivors with persistent infarct artery occlusion: results from the Occluded Artery Trial (OAT) SO EUROINTERVENTION LA English DT Article DE Myocardial infarction; causes of death; percutaneous coronary intervention; cardiac rupture AB Aims: OAT randomised patients with an occluded infarct artery three to 28 days after myocardial infarction (MI). The study demonstrated that PCI did not reduce the occurrence of the primary composite endpoint of death, re-MI, and New York Heart Association class IV heart failure in comparison with patients assigned to optimal medical therapy alone (MED). In view of prior literature in similar cohorts showing fewer sudden cardiac deaths and less left ventricular (LV) remodelling, but excess re-MI with PCI, causes of death were analysed in more detail. Methods and results: Stepwise Cox regression was used to examine baseline variables associated with causes of death. The immediate and primary cause of death did not differ between 1,101 PCI and 1,100 MED patients. One-year cardiovascular death rates were 3.8% for the PCI group, and 3.7% for the MED group, and 0.9% per year for the next four years in both groups. Five of six cases of cardiac rupture occurred in patients undergoing PCI. Conclusions: In stable post-MI patients with occlusion of the infarct-related artery, PCI did not change the rate or cause of death. The observation that the majority of cardiac ruptures occurred in patients undergoing PCI deserves further investigation. C1 [Lang, Irene M.] Med Univ Vienna, Dept Internal Med 2, Div Cardiol, A-1090 Vienna, Austria. [Forman, Sandra A.] Maryland Med Res Inst, Baltimore, MD USA. [Maggioni, Aldo P.] Italian Assoc Hosp Cardiologists ANMCO, Res Ctr, Florence, Italy. [Ruzyllo, Witold] Natl Inst Cardiol, Warsaw, Poland. [Renkin, Jean] Clin Univ St Luc, B-1200 Brussels, Belgium. [Vozzi, Carlos] Inst Intervenciones Cardiovasc SA, Rosario, Argentina. [Steg, P. Gabriel] Univ Paris 07, INSERM, U 698, AP HP, Paris, France. [Hernandez-Garcia, Jose-Maria; Jimenez-Navarro, Manuel] Hosp Univ Virgen Victoria Malaga, Malaga, Spain. [Zmudka, Krzysztof] Jan Pawel II Hosp, Int Cardiol Clin, Krakow, Poland. [Sopko, George] Natl Heart Lung & Blood Inst, Bethesda, MD USA. [Lamas, Gervasio A.] Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. [Hochman, Judith S.] NYU, Sch Med, New York, NY USA. RP Lang, IM (reprint author), Med Univ Vienna, Dept Internal Med 2, Div Cardiol, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM irene.lang@meduniwien.ac.at OI Jimenez Navarro, Manuel Francisco/0000-0002-6759-0514 FU National Heart, Lung, And Blood Institute [U01HL062509, U01HL062511] FX The project described was supported by Award Numbers U01HL062509 and U01HL062511 from the National Heart, Lung, And Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, And Blood Institute or the National Institutes of Health. NR 38 TC 1 Z9 1 U1 0 U2 9 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 5, RUE SAINT-PANTALEON, BP 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X J9 EUROINTERVENTION JI EuroIntervention PD NOV PY 2009 VL 5 IS 5 BP 610 EP 618 DI 10.4244/EIJV5I5A98 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V18ZB UT WOS:000208041600016 PM 20142183 ER PT J AU Calado, RT Regal, JA Kajigaya, S Young, NS AF Calado, R. T. Regal, J. A. Kajigaya, S. Young, N. S. TI Erosion of telomeric single-stranded overhang in patients with aplastic anaemia carrying telomerase complex mutations SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Aplastic anaemia; dyskeratosis congenita; mutation; telomerase; telomere; telomeric overhang ID RECESSIVE DYSKERATOSIS-CONGENITA; HOYERAAL-HREIDARSSON SYNDROME; FUNCTIONAL-CHARACTERIZATION; HEMATOLOGIC DISORDERS; REVERSE-TRANSCRIPTASE; HUMAN-CHROMOSOMES; RNA; GENE; DYSFUNCTION; SENESCENCE AB P>Background Loss-of-function mutations in telomerase complex genes reduce telomerase activity and shorten overall telomere length in leucocytes, and they can clinically manifest as bone marrow failure (aplastic anaemia and dyskeratosis congenita) and familial pulmonary fibrosis. Telomeres are constituted of double-stranded tandem TTAGGG repeats followed by a 3' G-rich single-stranded overhang, a crucial telomeric structural component responsible for the t-loop formation. Materials and methods We investigated the length of telomeric overhangs in 25 healthy individuals from 0 to 76 years of age, 16 patients with aplastic anaemia, and 13 immediate relatives using a non-denaturing in-gel method and the telomere-oligonucleotide ligation assay. Results Telomeric overhang lengths were constant from birth to eighth decade of life in healthy subjects, in contrast to overall telomere length, which shortened with ageing. Most patients with marrow failure and a telomerase gene mutation showed marked erosion of telomeric overhang associated with critically short telomeres; in other aplastic patients with normal genotypes, normal overall telomere lengths and who responded to immunosuppressive therapy, telomeric overhangs were maintained. Conclusions Telomeric overhang erosion does not participate in physiological ageing but support a role for eroded telomeric overhangs and abnormal telomere structure in pathological shortening of telomeres, especially caused by loss-of-function telomerase mutations. Disrupted telomere structure caused by short telomeric overhangs may contribute to the mechanisms of abnormal haematopoietic compartment senescence and chromosomal instability in human bone marrow failure. C1 [Calado, R. T.; Regal, J. A.; Kajigaya, S.; Young, N. S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Calado, RT (reprint author), 10 Ctr Dr,Bldg 10 CRC,Rm 3E-5140, Bethesda, MD 20892 USA. EM calador@mail.nih.gov RI Calado, Rodrigo/G-2619-2011 NR 33 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD NOV PY 2009 VL 39 IS 11 BP 1025 EP 1032 DI 10.1111/j.1365-2362.2009.02209.x PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 504WJ UT WOS:000270648300010 PM 19674077 ER PT J AU Kashaw, SK Kashaw, V Mishra, P Jain, NK Stables, JP AF Kashaw, Sushil K. Kashaw, Varsha Mishra, Pradeep Jain, N. K. Stables, J. P. TI Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-ure a SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE 4(3H)-Quinazolinones; MES; Subcutaneous pentylenetetrazole induced seizure; CNS depressants activity ID MAXIMAL ELECTROSHOCK; SEMICARBAZONES; QUINAZOLINE-4(3H)-ONES; AGENTS AB Several new 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyi/ethyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant and sedative-hypnotic activity in the mice. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight synthesized compounds were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. Compounds E1, E6, E9, E12, P3, P4 and P6 were found to be active in the MES screen whereas El, P4, P6 and P11 were found to be active in the scPTZ screen. All except E6, E11 and P6 showed more than 50% decrease in locomotor activity at 1 h of compound administration via actophotometer screen. CNS depressant activity screened with the help of the forced swim method resulted into some potent compounds. All the compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed promising CNS activities. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Kashaw, Sushil K.; Kashaw, Varsha; Mishra, Pradeep; Jain, N. K.] Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar 470003, India. [Stables, J. P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Kashaw, SK (reprint author), Dr Hari Singh Gour Vishwavidyalaya, Dept Pharmaceut Sci, Pharmaceut Chem Div, Sagar 470003, India. EM sushilkashaw@gmail.com NR 24 TC 59 Z9 59 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV PY 2009 VL 44 IS 11 BP 4335 EP 4343 DI 10.1016/j.ejmech.2009.05.008 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 512EE UT WOS:000271225800008 PM 19674817 ER PT J AU Kulandasamy, R Adhikari, AV Stables, JP AF Kulandasamy, Ravi Adhikari, Airody Vasudeva Stables, James P. TI A new class of anticonvulsants possessing 6 Hz activity: 3,4-Dialkyloxy thiophene bishydrazones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Thiophene bishydrazones; Synthesis; Anticonvulsants; 6 Hz test; Neurotoxicity ID MAXIMAL ELECTROSHOCK; PARTIAL EPILEPSY; DESIGN; SEMICARBAZONES; MODELS; AGENTS AB Thirty nine new 3,4-di(substituted)oxy-N(2),N(5)-bis(substituted)thiophene-2,5-dicarbohydrazides were synthesized starting from ethyl thiodiglycolate through multi-step reactions. In the synthetic sequence, 3,4-dihydroxythiophene-2,5-diester (1) was obtained by condensing the ethyl thiodiglycolate with diethyl oxalate. It was derivatized using different alkyl halides to give disubstituted thiophene esters (25), which were then converted to corresponding hydrazides (6-9) following usual methods. Finally, these hydrazides, on treatment with various substituted carbonyl compounds underwent smooth condensation to yield target hydrazones (10-13). The new compounds were characterized using FT-IR, (1)H NMR and (13)C NMR, mass spectral and elemental analyses. The anticonvulsant activity of the title compounds was established after intraperitoneal (ip) administration in three seizure models, which include maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and 6 Hz screens and their neurotoxicity was also evaluated. Compound 11f has emerged as an active compound with no neurotoxicity in this series. Also, the structure-activity relationship of the tested compounds was discussed. (C) 2009 Elsevier Masson SAS. All rights reserved. C1 [Kulandasamy, Ravi; Adhikari, Airody Vasudeva] Natl Inst Technol Karnataka, Dept Chem, Mangalore 575025, Karnataka, India. [Stables, James P.] NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Adhikari, AV (reprint author), Natl Inst Technol Karnataka, Dept Chem, Mangalore 575025, Karnataka, India. EM avchem@nitk.ac.in NR 25 TC 28 Z9 31 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD NOV PY 2009 VL 44 IS 11 BP 4376 EP 4384 DI 10.1016/j.ejmech.2009.05.026 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 512EE UT WOS:000271225800013 PM 19556038 ER PT J AU Pardini, M Garaci, FG Bonzano, L Roccatagliata, L Palmieri, MG Pompili, E Coniglione, F Krueger, F Ludovici, A Floris, R Benassi, F Gialloreti, LE AF Pardini, M. Garaci, F. G. Bonzano, L. Roccatagliata, L. Palmieri, M. G. Pompili, E. Coniglione, F. Krueger, F. Ludovici, A. Floris, R. Benassi, F. Gialloreti, L. Emberti TI White matter reduced streamline coherence in young men with autism and mental retardation SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE autism; diffusion tensor imaging; IQ; orbitofrontal cortex; white matter ID DIFFUSION ANISOTROPY; ORBITOFRONTAL CORTEX; ASPERGER-SYNDROME; CHILDHOOD AUTISM; SCHIZOPHRENIA; BRAIN; ABNORMALITIES; ACTIVATION; CHILDREN AB Background and purpose: It has been proposed that white matter alterations might play a role in autistic disorders; however, published data are mainly limited to high-functioning autism. The goal of this study was to apply diffusion tensor imaging (DTI) and fiber tractography (FT) to study white matter in low-functioning autism and the relationship between white matter and cognitive impairment. Methods: Ten low-functioning males with autism (mean age: 19.7 +/- 2.83 years) and 10 age-matched healthy males (mean age: 19.9 +/- 2.64 years) underwent DTI-MRI scanning. fractional anisotropy (FA) maps were analyzed with whole brain voxel-wise and tract-of-interest statistics. Using FT algorithms, white matter tracts connecting the orbitofrontal cortex (OFC) with other brain regions were identified and compared between the two groups. FA mean values of the autistic group were correlated with intelligence quotient (IQ) scores. Results: Low-functioning autistic subjects showed a reduced tract volume and lower mean FA values in the left OFC network compared with controls. In the autistic group, lower FA values were associated with lower IQ scores. Conclusions: We showed evidence of OFC white matter network abnormalities in low-functioning autistic individuals. Our results point to a relationship between the severity of the intellectual impairment and the extent of white matter alterations. C1 [Gialloreti, L. Emberti] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, I-00133 Rome, Italy. [Pardini, M.; Bonzano, L.; Roccatagliata, L.] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy. [Pardini, M.; Bonzano, L.; Roccatagliata, L.] Univ Genoa, Magnet Resonance Res Ctr Nervous Syst Dis, Genoa, Italy. [Garaci, F. G.; Ludovici, A.; Floris, R.] Univ Roma Tor Vergata, Dept Diagnost Imaging & Intervent Radiol, I-00133 Rome, Italy. [Palmieri, M. G.] Fdn S Lucia IRCCS, Rome, Italy. [Palmieri, M. G.] Tor Vergata Univ Hosp, Serv Neurophysiopathol, Rome, Italy. [Pompili, E.] ASL RMC, Territorial Neuropsychiat Serv, Rome, Italy. [Coniglione, F.] Univ Roma Tor Vergata, Dept Anaesthesiol & Intens Care Med, I-00133 Rome, Italy. [Krueger, F.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Benassi, F.] CNAPP, Ctr Commun & Neurorehabil Res, Rome, Italy. RP Gialloreti, LE (reprint author), Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Via Montpellier 1, I-00133 Rome, Italy. EM leonardo.emberti.gialloreti@uniroma2.it RI Pardini, Matteo/F-8414-2010; Emberti Gialloreti, Leonardo/H-4702-2012; OI Pardini, Matteo/0000-0002-4740-1982; Bonzano, Laura/0000-0001-8186-2566 NR 27 TC 38 Z9 40 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD NOV PY 2009 VL 16 IS 11 BP 1185 EP 1190 DI 10.1111/j.1468-1331.2009.02699.x PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 508BB UT WOS:000270900700006 PM 19538216 ER PT J AU Marin, MT Berkow, A Golden, SA Koya, E Planeta, CS Hope, BT AF Marin, Marcelo T. Berkow, Alexander Golden, Sam A. Koya, Eisuke Planeta, Cleopatra S. Hope, Bruce T. TI Context-specific modulation of cocaine-induced locomotor sensitization and ERK and CREB phosphorylation in the rat nucleus accumbens SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium; calmodulin-dependent kinase; CaMK; kinase; neuroadaptation; PKA ID ELEMENT-BINDING PROTEIN; C-FOS EXPRESSION; BEHAVIORAL SENSITIZATION; RESPONSE ELEMENT; GENE-EXPRESSION; KINASE-IV; PSYCHOMOTOR SENSITIZATION; AMPHETAMINE SENSITIZATION; ENVIRONMENTAL CONTEXT; SYNAPTIC PLASTICITY AB Learned associations are hypothesized to develop between drug effects and contextual stimuli during repeated drug administration to produce context-specific sensitization that is expressed only in the drug-associated environment and not in a non-drug-paired environment. The neuroadaptations that mediate such context-specific behavior are largely unknown. We investigated context-specific modulation of cAMP-response element-binding protein (CREB) phosphorylation and that of four upstream kinases in the nucleus accumbens that phosphorylate CREB, including extracellular signal-regulated kinase (ERK), cAMP-dependent protein kinase, calcium/calmodulin-dependent kinase (CaMK) II and CaMKIV. Rats received seven once-daily injections of cocaine or saline in one of two distinct environments outside their home cages. Seven days later, test injections of cocaine or saline were administered in either the paired or the non-paired environment. CREB and ERK phosphorylation were assessed with immunohistochemistry, and phosphorylation of the remaining kinases, as well as of CREB and ERK, was assessed by western blotting. Repeated cocaine administration produced context-specific sensitized locomotor responses accompanied by context-specific enhancement of the number of cocaine-induced phosphoCREB-immunoreactive and phosphoERK-immunoreactive nuclei in a minority of neurons. In contrast, CREB and CaMKIV phosphorylation in nucleus accumbens homogenates were decreased by cocaine test injections. We have recently shown that a small number of cocaine-activated accumbens neurons mediate the learned association between cocaine effects and the drug administration environment to produce context-specific sensitization. Context-specific phosphorylation of ERK and CREB in the present study suggests that this signal transduction pathway is selectively activated in the same set of cocaine-activated accumbens neurons that mediate this learned association. C1 [Berkow, Alexander; Golden, Sam A.; Koya, Eisuke; Hope, Bruce T.] NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. [Marin, Marcelo T.; Planeta, Cleopatra S.] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Pharmacol Lab, Araraquara, SP, Brazil. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; Marin, Marcelo/J-3026-2012; OI Hope, Bruce/0000-0001-5804-7061; Golden, Sam/0000-0002-2104-2272 FU NIH; NIDA; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP) FX This research was supported in part by the Intramural Research Program of the NIH, NIDA. M. T. Marin was supported by a grant from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) and Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP). C. S. Planeta was supported by a grant from FAPESP. NR 64 TC 26 Z9 26 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2009 VL 30 IS 10 BP 1931 EP 1940 DI 10.1111/j.1460-9568.2009.06982.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 521DH UT WOS:000271899600011 PM 19912338 ER PT J AU Vandersteen, A Turnbull, J Jan, W Simpson, J Lucas, S Anderson, D Lin, JP Stratakis, C Pichert, G Lim, M AF Vandersteen, Anthony Turnbull, Jess Jan, Wajanat Simpson, John Lucas, Sebastian Anderson, David Lin, Jean-Pierre Stratakis, Constantine Pichert, Gabriella Lim, Ming TI Cutaneous signs are important in the diagnosis of the rare neoplasia syndrome Carney complex SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Article DE Carney complex; Stroke; Atrial myxoma; Cutaneous lentiginosis ID PATIENT; MUTATION; GENETICS; MYXOMAS AB We describe a 15-year-old boy who presented with a stroke. Brain MRI imaging showed thalamic and multiple cerebral infarcts. An echocardiogram revealed multiple atrial masses, which were resected. Histological examination confirmed multiple atrial myxomas. Further clinical examination of the patient revealed subtle buccal and peri-oral lentigenes. The diagnosis of Carney complex was made clinically. The patient was subsequently diagnosed with testicular seminomas and a cutaneous angiomyxoma. Genetic investigation revealed a pathological mutation in the PRKAR1A gene. We review the reported manifestations and presentations of Carney complex, along with current diagnostic guidelines. We emphasise the importance of recognising the cutaneous manifestations of this rare autosomal dominantly inherited neoplasia syndrome. C1 [Lin, Jean-Pierre; Lim, Ming] Evelina Childrens Hosp, Guys & St Thomas NHS Fdn Trust, Dept Paediat Neurol, London SE1 7EH, England. [Anderson, David] Guys & St Thomas NHS Fdn Trust, Dept Cardiothorac Surg, London, England. [Stratakis, Constantine] NICHHD, Dept Pediat Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. [Vandersteen, Anthony; Pichert, Gabriella] Guys & St Thomas NHS Fdn Trust, Dept Clin Genet, London, England. [Turnbull, Jess] Lewisham Hosp NHS Trust, Dept Paediat, London, England. [Jan, Wajanat] Guys & St Thomas NHS Fdn Trust, Dept Radiol, London, England. [Simpson, John] Guys & St Thomas NHS Fdn Trust, Dept Paediat Cardiol, London, England. [Lucas, Sebastian] Guys & St Thomas NHS Fdn Trust, Dept Histol, London, England. RP Lim, M (reprint author), Evelina Childrens Hosp, Guys & St Thomas NHS Fdn Trust, Dept Paediat Neurol, Lambeth Palace Rd, London SE1 7EH, England. EM Ming.Lim@gstt.nhs.uk OI Lin, Jean-Pierre/0000-0001-9314-2259 FU National Institutes of Health, Eunie Kennedy Shriver National Institute of Child Health & Human Development [Z01-HD-000642-04] FX This work was supported in part by the National Institutes of Health, Eunie Kennedy Shriver National Institute of Child Health & Human Development intramural project Z01-HD-000642-04 to Dr. C. A. Stratakis. We thank the medical photographers at Guy's and St. Thomas' NHS Foundation Trust. NR 18 TC 6 Z9 7 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD NOV PY 2009 VL 168 IS 11 BP 1401 EP 1404 DI 10.1007/s00431-009-0935-y PG 4 WC Pediatrics SC Pediatrics GA 495RF UT WOS:000269912000017 PM 19219454 ER PT J AU Allik, J Realo, A Mottus, R Pullmann, H Trifonova, A McCrae, RR AF Allik, Jueri Realo, Anu Mottus, Rene Pullmann, Helle Trifonova, Anastasia McCrae, Robert R. CA 56 MEMBERS RUSSIAN CHARACTER PERSO TI Personality Traits of Russians from the Observer's Perspective SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article DE personality scales and inventories; development of personality; cross-cultural research ID LIFE-SPAN; CULTURES; ADULTHOOD; PROFILES; AGE; TEMPERAMENT; UNIVERSAL; PATTERNS; BIG-5 AB Data were collected by the members of the Russian character and personality survey from 39 samples in 33 administrative areas of the Russian Federation. Respondents (N = 7065) identified an ethnically Russian adult or college-aged man or woman whom they knew well and rated the target using the Russian observer rating version of the Revised NEO Personality Inventory, which measures neuroticism, extraversion, openness to experience, agreeableness and conscientiousness. Factor analyses within samples showed that the factor structure of an international sample combining data from 50 different cultures was well replicated in all 39 Russian samples. Sex differences replicated the known pattern in all samples, demonstrating that women scored higher than men on most of the neuroticism, openness, agreeableness and conscientiousness facet scales. Cross-sectional analyses demonstrated consistent age differences for four factors: Older individuals compared to younger ones were less extraverted and open but more agreeable and conscientious. The mean levels of traits were similar in all 39 samples. Although in general personality traits in Russians closely followed the universal pattern, some reliable culture-specific effects were also found that future studies can help interpret. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Allik, Jueri; Realo, Anu; Mottus, Rene; Pullmann, Helle; Trifonova, Anastasia] Univ Tartu, Dept Psychol, EE-50410 Tartu, Estonia. [Allik, Jueri; Realo, Anu; Mottus, Rene; Pullmann, Helle; Trifonova, Anastasia] Estonian Ctr Behav & Hlth Sci, Tartu, Estonia. [McCrae, Robert R.] NIA, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. RP Allik, J (reprint author), Univ Tartu, Dept Psychol, EE-50410 Tartu, Estonia. EM juri.allik@ut.ee RI Allik, Juri/D-5609-2009; Fadina, Angelina/D-8005-2014; Lopukhova, Olga/M-8997-2013; Realo, Anu/M-9524-2016 OI Allik, Juri/0000-0002-8358-4747; Lopukhova, Olga/0000-0003-1243-3594; NR 38 TC 16 Z9 16 U1 2 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD NOV PY 2009 VL 23 IS 7 BP 567 EP 588 DI 10.1002/per.721 PG 22 WC Psychology, Social SC Psychology GA 500ZU UT WOS:000270346700002 ER PT J AU Figueroa-Romero, C Iniguez-Lluhi, JA Stadler, J Chang, CR Arnoult, D Keller, PJ Hong, Y Blackstone, C Feldman, EL AF Figueroa-Romero, Claudia Iniguez-Lluhi, Jorge A. Stadler, Julia Chang, Chuang-Rung Arnoult, Damien Keller, Peter J. Hong, Yu Blackstone, Craig Feldman, Eva L. TI SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle SO FASEB JOURNAL LA English DT Article DE Ubc9; small ubiquitin-like modifier; post-translational modification ID DYNAMIN-RELATED PROTEIN; SUMO E3 LIGASE; COATED VESICLE FORMATION; DOMINANT OPTIC ATROPHY; MAMMALIAN-CELLS; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTORS; OUTER-MEMBRANE; GTPASE DRP1; MORPHOLOGY AB Dynamin-related protein (Drp) 1 is a key regulator of mitochondrial fission and is composed of GTP-binding, Middle, insert B, and C-terminal GTPase effector (GED) domains. Drp1 associates with mitochondrial fission sites and promotes membrane constriction through its intrinsic GTPase activity. The mechanisms that regulate Drp1 activity remain poorly understood but are likely to involve reversible post-translational modifications, such as conjugation of small ubiquitin-like modifier (SUMO) proteins. Through a detailed analysis, we find that Drp1 interacts with the SUMO-conjugating enzyme Ubc9 via multiple regions and demonstrate that Drp1 is a direct target of SUMO modification by all three SUMO isoforms. While Drp1 does not harbor consensus SUMOylation sequences, our analysis identified2 clusters of lysine residues within the B domain that serve as noncanonical conjugation sites. Although initial analysis indicates that mitochondrial recruitment of ectopically expressed Drp1 in response to staurosporine is unaffected by loss of SUMOylation, we find that Drp1 SUMOylation is enhanced in the context of the K38A mutation. This dominant-negative mutant, which is deficient in GTP binding and hydrolysis, does not associate with mitochondria and prevents normal mitochondrial fission. This finding suggests that SUMOylation of Drp1 is linked to its activity cycle and is influenced by Drp1 localization.-Figueroa-Romero, C., Iniguez-Lluhi, J. A., Stadler, J., Chang, C.-R., Arnoult, D., Keller, P. J., Hong, Y., Blackstone, C., Feldman, E. L. SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle. FASEB J. 23, 3917-3927 (2009). www.fasebj.org C1 [Figueroa-Romero, Claudia; Keller, Peter J.; Hong, Yu; Feldman, Eva L.] Univ Michigan, Dept Neurol, Sch Med, Ann Arbor, MI 48109 USA. [Iniguez-Lluhi, Jorge A.] Univ Michigan, Dept Pharmacol, Sch Med, Ann Arbor, MI 48109 USA. [Stadler, Julia; Chang, Chuang-Rung; Blackstone, Craig] Natl Inst Neurol Disorders & Stroke, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD USA. [Arnoult, Damien] INSERM, U542, Villejuif, France. [Arnoult, Damien] Univ Paris 11, Hop Paul Brousse, Villejuif, France. RP Feldman, EL (reprint author), Univ Michigan, Dept Neurol, Sch Med, 5017 BSRB,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM efeldman@umich.edu RI Chang, Chuang-Rung /C-1815-2012; OI Iniguez-Lluhi, Jorge/0000-0001-7010-089X FU U. S. Public Health Service [DK61656]; Program for Neurology Research and Discovery; A. Alfred Taubman Medical Research Institute; U. S. National Institutes of Health (NIH) [NIHU01 DK076160]; Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS); Agence Nationale de La Recherche sur le SIDA; Fondation pour La Recherche Medicale; Ligue contre le Cancer; Universite Paris Sud; National Institute of Diabetes and Digestive and Kidney Diseases [NIH5P60 DK20572] FX This work was supported by U. S. Public Health Service grant DK61656 (J. A. I.), the Program for Neurology Research and Discovery, the A. Alfred Taubman Medical Research Institute, U. S. National Institutes of Health (NIH) grant NIHU01 DK076160 (C. F.-R., E. L. F., Y. H., P. J. K.), and in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS), NIH (J. S., C.-R. C., C. B.) as well as the Agence Nationale de La Recherche sur le SIDA, Fondation pour La Recherche Medicale, the Ligue contre le Cancer, and the Universite Paris Sud (D. A.). This work utilized the sequencing core of the Michigan Diabetes Research and Training Center, funded by National Institute of Diabetes and Digestive and Kidney Diseases grant NIH5P60 DK20572. The authors also thank J. Nagle and D. Kauffman (NINDS DNA Sequencing Facility) for DNA sequencing. NR 83 TC 81 Z9 87 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2009 VL 23 IS 11 BP 3917 EP 3927 DI 10.1096/fj.09-136630 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 512TC UT WOS:000271272500027 PM 19638400 ER PT J AU Subramanian, M Gonzalez, RW Patil, H Ueda, T Lim, JH Kraemer, KH Bustin, M Bergel, M AF Subramanian, Mangalam Gonzalez, Rhiannon W. Patil, Hemangi Ueda, Takahiro Lim, Jae-Hwan Kraemer, Kenneth H. Bustin, Michael Bergel, Michael TI The nucleosome-binding protein HMGN2 modulates global genome repair SO FEBS JOURNAL LA English DT Article DE apoptosis; cell cycle; chromatin; DNA repair; UV irradiation ID NUCLEOTIDE EXCISION-REPAIR; CHROMATIN-REMODELING FACTOR; GROUP CHROMOSOMAL-PROTEINS; MOBILITY-GROUP PROTEINS; DNA-REPAIR; XERODERMA-PIGMENTOSUM; HMG-17 GENE; HISTONE H1; IN-VITRO; DAMAGE AB The HMGN family comprises nuclear proteins that bind to nucleosomes and alter the structure of chromatin. Here, we report that DT40 chicken cells lacking either HMGN2 or HMGN1a, or lacking both HMGN1a and HMGN2, are hypersensitive to killing by UV irradiation. Loss of both HMGN1a and HMGN2 or only HMGN2 increases the extent of UV-induced G(2)-M checkpoint arrest and the rate of apoptosis. HMGN null mutant cells showed slower removal of UV-induced DNA lesions from native chromatin, but the nucleotide excision repair remained intact, as measured by host cell reactivation assays. These results identify HMGN2 as a component of the global genome repair subpathway of the nucleotide excision repair pathway, and may indicate that HMGN2 facilitates the ability of the DNA repair proteins to access and repair UV-induced DNA lesions in chromatin. Our finding that HMGNs play a role in global DNA repair expands the role of these proteins in the maintenance of genome integrity. C1 [Subramanian, Mangalam; Gonzalez, Rhiannon W.; Patil, Hemangi; Bergel, Michael] Texas Womans Univ, Dept Biol, Denton, TX 76204 USA. [Ueda, Takahiro; Kraemer, Kenneth H.] NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lim, Jae-Hwan; Bustin, Michael; Bergel, Michael] NCI, Prot Sect, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Bergel, M (reprint author), Texas Womans Univ, Dept Biol, POB 425799, Denton, TX 76204 USA. EM MBergel@mail.twu.edu RI Bustin, Michael/G-6155-2015 FU Texas Woman's University (TWU) Research Enhancement Program; TWU Chancellor's Research Fellowship; NIH [GM 55380]; National Cancer Institute, Center for Cancer Research FX This work was supported by Texas Woman's University (TWU) Research Enhancement Program grants for the years 2004 and 2005 (to M. Bergel), TWU Chancellor's Research Fellowship for the year 2005-2006 and 2006-2007 (awarded to M. Bergel), and an MBRS program funded by NIH GM 55380. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. We thank J. B. Dodgson, who gave us the DT40-derived HMGN null cell lines. We thank T. Tadokoro for the gift of the monoclonal antibody TDM-2. We thank B. J. Taylor from the NCI, NIH, for technical assistance with the FACS analysis. We thank R. M. Paulson from TWU for help with the statistical analysis. We thank S. Dhanireddy from TWU for his technical assistance. We thank D. Hynds and M. Bergel for critical reading, editing and proofreading of the manuscript. NR 51 TC 5 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD NOV PY 2009 VL 276 IS 22 BP 6646 EP 6657 DI 10.1111/j.1742-4658.2009.07375.x PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 509ZG UT WOS:000271057200022 PM 19843163 ER PT J AU Seifer, DB Golub, ET Lambert-Messerlian, G Benning, L Anastos, K Watts, DH Cohen, MH Karim, R Young, MA Minkoff, H Greenblatt, RM AF Seifer, David B. Golub, Elizabeth T. Lambert-Messerlian, Geralyn Benning, Lorie Anastos, Kathryn Watts, D. Heather Cohen, Mardge H. Karim, Roksana Young, Mary A. Minkoff, Howard Greenblatt, Ruth M. TI Variations in serum mullerian inhibiting substance between white, black, and Hispanic women SO FERTILITY AND STERILITY LA English DT Article DE Mullerian inhibiting substance; antimullerian hormone; ovarian reserve; race; ethnicity ID ASSISTED REPRODUCTIVE TECHNOLOGY; ANTIMULLERIAN HORMONE-LEVELS; SPONTANEOUS MENSTRUAL-CYCLE; AFRICAN-AMERICAN; OVARIAN RESERVE; AGE; MENOPAUSE; OUTCOMES; HIV AB Objective: To compare serum mullerian inhibiting substance (MIS) levels between white, black, and Hispanic women to determine whether ovarian aging occurs at a different time course for women of different racial groups. Design: Longitudinal study of serum MIS levels in women of different race and ethnicity over two different time points. Setting: Women's Interagency HIV Study, a multicenter prospective cohort study. Patient(s): Serum samples obtained from 809 participants (122 white, 462 black, and 225 Hispanic women). Intervention(s): Comparison of serum MIS between women of different race and ethnicity at two time points (median age 37.5 years and 43.3 years). Main Outcome Measure(s): Variation in MIS by race and ethnicity over time, controlling for age, body mass index, HIV status, and smoking. Result(s): Compared with white women, average MIS values were lower among black (25.2% lower) and Hispanic (24.6% lower) women, adjusting for age, body mass index, smoking, and HIV status. Conclusion(s): There is an independent effect of race and ethnicity on the age-related decline in MIS over time. (Fertil Steril (R) 2009;92:1674-8. (C) 2009 by American Society for Reproductive Medicine.) C1 [Seifer, David B.; Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11228 USA. [Seifer, David B.] Mt Sinai Sch Med, New York, NY USA. [Golub, Elizabeth T.; Benning, Lorie] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Lambert-Messerlian, Geralyn] Brown Univ, Alpert Med Sch, Dept Pathol & Lab Med, Providence, RI 02912 USA. [Lambert-Messerlian, Geralyn] Brown Univ, Women & Infants Hosp, Providence, RI USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. [Anastos, Kathryn] Montefiore Med Ctr, Dept Epidemiol, Bronx, NY 10467 USA. [Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. [Cohen, Mardge H.] John H Stroger Jr Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge H.] Rush Med Coll, Chicago, IL 60612 USA. [Karim, Roksana] Univ So Calif, Keck Sch Med, Dept Pediat & Prevent Med, Los Angeles, CA 90033 USA. [Young, Mary A.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Minkoff, Howard] Suny Downstate Med Ctr, New York, NY USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Seifer, DB (reprint author), Maimonides Hosp, Dept Obstet & Gynecol, 1355 84th St, Brooklyn, NY 11228 USA. EM drseifer@genesisfertility.com OI Seifer, David/0000-0003-3950-9341; Messerlian, Geralyn/0000-0002-9440-3411 FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO1-HD-32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness and Other Communication Disorders; National Center for Research Resources [MO1-RR-00071, MO1-RR-00079, MO1-RR-00083] FX The Women's Interagency HIV Study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (MO1-RR-00071, MO1-RR-00079, MO1-RR-00083). NR 23 TC 61 Z9 62 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2009 VL 92 IS 5 BP 1674 EP 1678 DI 10.1016/j.fertnstert.2008.08.110 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 518RG UT WOS:000271710200027 PM 18930217 ER PT J AU Doroshow, JH Kummar, S AF Doroshow, James H. Kummar, Shivaani TI Role of Phase 0 trials in drug development SO FUTURE MEDICINAL CHEMISTRY LA English DT Editorial Material ID ADP-RIBOSE POLYMERASE; CLINICAL-TRIALS; POLY(ADP-RIBOSE) POLYMERASE; CANCER CHEMOPREVENTION; PARP INHIBITORS; PATHWAYS; THERAPY; ABT-888; PATIENT; FDA AB Phase 0 trials can provide proof of concept that an agent modulates its intended target without exposing patients to the drug-tolerability testing that precedes efficacy evaluation. Drugs that do not modulate their targets can be discarded, focusing development resources on the most clinically promising agents. However, wider uptake of Phase 0 trials may be hindered by ethical concerns over their lack of therapeutic intent, the substantial resources required to develop and validate target assays or skepticism that such trials save development time. C1 [Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.nih.gov NR 38 TC 1 Z9 1 U1 0 U2 1 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 J9 FUTURE MED CHEM JI Future Med. Chem. PD NOV PY 2009 VL 1 IS 8 BP 1375 EP 1380 DI 10.4155/FMC.09.117 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 575UJ UT WOS:000276094100002 PM 21426052 ER PT J AU Newman, DJ Cragg, GM AF Newman, David J. Cragg, Gordon M. TI Natural product scaffolds as leads-to drugs SO FUTURE MEDICINAL CHEMISTRY LA English DT Review ID 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITORS; MICROTUBULE-STABILIZING AGENTS; COENZYME-A REDUCTASE; HMG-COA REDUCTASE; RAPAMYCIN AY-22,989; LACTONE DERIVATIVES; HYPOCHOLESTEROLEMIC AGENT; CHOLESTEROL-BIOSYNTHESIS; TETRACYCLINE ANTIBIOTICS; STRUCTURAL MODIFICATION AB Numerous 'scaffolds' that have been identified in natural product structures have led to very significant numbers of approved drugs and drug candidates for a multiplicity of diseases over the years. In this mini-review, we discuss the base scaffolds (chemical skeletons) that we feel have produced very significant numbers of agents as drugs or drug leads and, in a number of cases, compounds that can be used as chemical synthons or that present activities in biological areas that were not obvious from their earlier history. C1 [Newman, David J.; Cragg, Gordon M.] NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Frederick, MD 21702 USA. EM dn22a@nih.gov NR 89 TC 55 Z9 55 U1 1 U2 27 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PD NOV PY 2009 VL 1 IS 8 BP 1415 EP 1427 DI 10.4155/FMC.09.113 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 575UJ UT WOS:000276094100012 PM 21426057 ER PT J AU Reynolds, SJ AF Reynolds, Steven J. TI Role of HSV-2 suppressive therapy for HIV prevention SO FUTURE MICROBIOLOGY LA English DT Editorial Material ID HERPES-SIMPLEX-VIRUS; TYPE-2 INFECTION; ACQUISITION; WOMEN; MEN; REACTIVATION; RECOVERY; LESIONS; CELLS; RISK C1 [Reynolds, Steven J.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Reynolds, SJ (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. EM sjr@jhmi.edu FU Intramural NIH HHS [ZIA AI000361-28] NR 16 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD NOV PY 2009 VL 4 IS 9 BP 1095 EP 1097 DI 10.2217/FMB.09.81 PG 3 WC Microbiology SC Microbiology GA 522JP UT WOS:000271994100001 PM 19895212 ER PT J AU Brody, JR Witkiewicz, AK Yeo, CJ Gorospe, M Keen, JC AF Brody, Jonathan R. Witkiewicz, Agnieszka K. Yeo, Charles J. Gorospe, Myriam Keen, Judith C. TI The 'RNA-binding ome': future implications for chemotherapeutic efficacy SO FUTURE ONCOLOGY LA English DT Editorial Material ID HUR; EXPRESSION C1 [Brody, Jonathan R.] Thomas Jefferson Univ, Jefferson Pancreas Biliary & Related Canc Ctr, Philadelphia, PA 19107 USA. [Yeo, Charles J.] Thomas Jefferson Univ, Dept Surg, Philadelphia, PA 19107 USA. [Gorospe, Myriam] NIA, LCMB, Intramural Res Program, NIH,Biomed Res Ctr, Baltimore, MD 21224 USA. [Keen, Judith C.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. [Witkiewicz, Agnieszka K.] Thomas Jefferson Univ, Dept Pathol, Philadelphia, PA 19107 USA. RP Brody, JR (reprint author), Thomas Jefferson Univ, Jefferson Pancreas Biliary & Related Canc Ctr, 1015 Walnut St,Curtis 611A, Philadelphia, PA 19107 USA. EM Jonathan.Brody@jefferson.edu NR 7 TC 5 Z9 5 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD NOV PY 2009 VL 5 IS 9 BP 1317 EP 1319 DI 10.2217/FON.09.114 PG 3 WC Oncology SC Oncology GA 523VT UT WOS:000272103400001 PM 19903059 ER PT J AU McGlynn, KA Cook, MB AF McGlynn, Katherine A. Cook, Michael B. TI Etiologic factors in testicular germ-cell tumors SO FUTURE ONCOLOGY LA English DT Review DE nonseminoma; perinatal etiology; seminoma; testicular germ-cell tumor ID FAMILY-CANCER DATABASE; CARCINOMA-IN-SITU; MATERNAL HORMONE-LEVELS; PERINATAL RISK-FACTORS; EPSTEIN-BARR-VIRUS; BODY-MASS INDEX; PHYSICAL-ACTIVITY; UNITED-STATES; SPERM COUNTS; SPERMATOCYTIC SEMINOMA AB Globally, testicular cancer incidence is highest among men of northern European ancestry and lowest among men of Asian and African descent. Incidence rates have been increasing around the world for at least 50 years, but mortality rates, at least in developed countries, have been declining. While reasons for the decreases in mortality are related to improvements in therapeutic regimens introduced in the late 1970s, reasons for the increase in incidence are less well understood. However, an accumulating body of evidence suggests that testicular cancer arises in fetal life, Perinatal factors, including exposure to endocrine-disrupting chemicals, have been suggested to be related to risk. C1 [McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. RP McGlynn, KA (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Suite 550,6120 Execut Blvd, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov RI Cook, Michael/A-5641-2009 OI Cook, Michael/0000-0002-0533-7302 FU Intramural NIH HHS [ZIA CP010126-15] NR 207 TC 53 Z9 54 U1 2 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD NOV PY 2009 VL 5 IS 9 BP 1389 EP 1402 DI 10.2217/FON.09.116 PG 14 WC Oncology SC Oncology GA 523VT UT WOS:000272103400012 PM 19903067 ER PT J AU Kosaka, N Ogawa, M Choyke, PL Kobayashi, H AF Kosaka, Nobuyuki Ogawa, Mikako Choyke, Peter L. Kobayashi, Hisataka TI Clinical implications of near-infrared fluorescence imaging in cancer SO FUTURE ONCOLOGY LA English DT Review DE activatable probe; cancer; fluorescence imaging; lymphatic imaging; near infrared ID DIFFUSE OPTICAL TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; LABELED MONOCLONAL-ANTIBODIES; SEMICONDUCTOR QUANTUM DOTS; IN-VIVO; INDOCYANINE-GREEN; BREAST-CANCER; INVISIBLE LIGHT; CONTRAST AGENTS; LUNG-CANCER AB Near-infrared (NIR) fluorescence cancer imaging is a growing field for both preclinical and clinical application to the clinical management for cancer patients due to its advantageous features, including a high spatial resolution, portability, real-time display and detailed molecular profiling with the multiplexed use of fluorescent probes. In this review, we present a basic concept of NIR fluorescence imaging and overview its potential clinical applications for in vivo cancer imaging, including cancer detection/characterization, lymphatic imaging (sentinel lymph node detection) and surgical/endoscopic guidance. NIR fluorescence imaging can compensate some limitations of conventional imaging modalities, and thus it could play an important role for cancer imaging combined with other modalities in clinical practice. C1 [Kosaka, Nobuyuki; Ogawa, Mikako; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov FU National Institutes of Health; National Cancer Institute; Center for Cancer Research FX No writing assistance was utilized in the production of this manuscript. NR 80 TC 43 Z9 43 U1 2 U2 36 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 J9 FUTURE ONCOL JI Future Oncol. PD NOV PY 2009 VL 5 IS 9 BP 1501 EP 1511 DI 10.2217/FON.09.109 PG 11 WC Oncology SC Oncology GA 523VT UT WOS:000272103400020 PM 19903075 ER PT J AU Camp, M Norcross, M Whittle, N Feyder, M D'Hanis, W Yilmazer-Hanke, D Singewald, N Holmes, A AF Camp, M. Norcross, M. Whittle, N. Feyder, M. D'Hanis, W. Yilmazer-Hanke, D. Singewald, N. Holmes, A. TI Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strain SO GENES BRAIN AND BEHAVIOR LA English DT Article DE Amygdala; anxiety; behavior; gene; genetics; incubation; prefrontal cortex; PTSD; rodent; sensitization ID CONDITIONED FEAR; BEHAVIORAL-DIFFERENCES; C57BL/6J MICE; KNOCKOUT MICE; MEMORY; EXPRESSION; ANXIETY; SUBSTRAINS; ESTABLISHMENT; MUTAGENESIS AB Fear extinction is impaired in psychiatric disorders such as post-traumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared with C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain's four different genetic lineages (parental, steel, teratoma and contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. On the basis of these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e. five x higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data show that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may reflect a pro-fear incubation-like process. C1 [Camp, M.; Norcross, M.; Feyder, M.; Holmes, A.] NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. [Whittle, N.; Singewald, N.] Univ Innsbruck, Inst Pharm, Dept Pharmacol & Toxicol, A-6020 Innsbruck, Austria. [Whittle, N.; Singewald, N.] Univ Innsbruck, Ctr Mol Biosci Innsbruck, A-6020 Innsbruck, Austria. [D'Hanis, W.; Yilmazer-Hanke, D.] Otto VonGuericke Univ Magdegurg, Fac Med, Inst Anat, D-39120 Magdeburg, Germany. [Yilmazer-Hanke, D.] Natl Univ Ireland Univ Coll Cork, Dept Anat, Cork, Ireland. [Yilmazer-Hanke, D.] Natl Univ Ireland Univ Coll Cork, Biosci Inst, Cork, Ireland. RP Camp, M (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, 5625 Fishers Lane Room 2N09, Bethesda, MD 20892 USA. EM campmc@mail.nih.gov FU National Institute on Alcohol Abuse and Alcoholism Intramural Research Program; Fonds zur Forderung der Wissenschaftlichen Forschung; NFN [S102]; German Academic Exchange Service (DAAD) FX Work supported by the National Institute on Alcohol Abuse and Alcoholism Intramural Research Program, the Fonds zur Forderung der Wissenschaftlichen Forschung, NFN-S102 and the German Academic Exchange Service (DAAD). NR 47 TC 36 Z9 36 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD NOV PY 2009 VL 8 IS 8 BP 744 EP 752 DI 10.1111/j.1601-183X.2009.00519.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 517QY UT WOS:000271633300002 PM 19674120 ER PT J AU Camps, J Nguyen, QT Padilla-Nash, HM Knutsen, T McNeil, NE Wangsa, D Hummon, AB Grade, M Ried, T Difilippantonio, MJ AF Camps, Jordi Nguyen, Quang Tri Padilla-Nash, Hesed M. Knutsen, Turid McNeil, Nicole E. Wangsa, Danny Hummon, Amanda B. Grade, Marian Ried, Thomas Difilippantonio, Michael J. TI Integrative Genomics Reveals Mechanisms of Copy Number Alterations Responsible for Transcriptional Deregulation in Colorectal Cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN BREAST-CANCER; CELL-LINES; GENE-EXPRESSION; HOMOZYGOUS DELETIONS; AMPLIFICATION; IDENTIFICATION; CARCINOMAS; PATTERN; TUMORS; FUSION AB To evaluate the mechanisms and consequences of chromosomal aberrations in colorectal cancer (CRC), we used a combination of spectral karyotyping, array comparative genomic hybridization (aCGH), and array-based global gene expression profiling on 31 primary carcinomas and 15 established cell lines. Importantly, aCGH showed that the genomic profiles of primary tumors are recapitulated in the cell lines. We revealed a preponderance of chromosome breakpoints at sites of copy number variants (CNVs) in the CRC cell lines, a novel mechanism of DNA breakage in cancer. The integration of gene expression and aCGH led to the identification of 157 genes localized within high-level copy number changes whose transcriptional deregulation was significantly affected across all of the samples, thereby suggesting that these genes play a functional role in CRC. Genomic amplification at 8q24 was the most recurrent event and led to the overexpression of MYC and FAM84B. Copy number dependent gene expression resulted in deregulation of known cancer genes such as APC, FGFR2, and ERBB2. The identification of only 36 genes whose localization near a breakpoint could account for their observed deregulated expression demonstrates that the major mechanism for transcriptional deregulation in CRC is genomic copy number changes resulting from chromosomal aberrations. (C) 2009 Wiley-Liss, Inc. C1 [Camps, Jordi; Nguyen, Quang Tri; Padilla-Nash, Hesed M.; Knutsen, Turid; McNeil, Nicole E.; Wangsa, Danny; Hummon, Amanda B.; Grade, Marian; Ried, Thomas; Difilippantonio, Michael J.] NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. [Grade, Marian] Univ Gottingen, Univ Med Ctr Groningen, Dept Gen & Visceral Surg, Gottingen, Germany. RP Difilippantonio, MJ (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, 50 S Dr,Bldg 50,Rm 1408, Bethesda, MD 20892 USA. EM difilipm@mail.nih.gov FU NIH; National Cancer Institute; Center for Cancer Research FX Supported by: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 42 TC 39 Z9 39 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2009 VL 48 IS 11 BP 1002 EP 1017 DI 10.1002/gcc.20699 PG 16 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 499BH UT WOS:000270191000007 PM 19691111 ER PT J AU Stine, ZE Huynh, JL Loftus, SK Gorkin, DU Salmasi, AH Novak, T Purves, T Miller, RA Antonellis, A Gearhart, JR Pavan, WJ McCallion, AS AF Stine, Zachary E. Huynh, Jimmy L. Loftus, Stacie K. Gorkin, David U. Salmasi, Amirali H. Novak, Thomas Purves, Todd Miller, Ronald A. Antonellis, Anthony Gearhart, John R. Pavan, William J. McCallion, Andrew S. TI Oligodendroglial and Pan-Neural Crest Expression of Cre Recombinase Directed by Sox10 Enhancer SO GENESIS LA English DT Article DE transgenic mouse; Cre recombinase; Sox10; oligodendroglia; neural crest ID STEM-CELLS; MOUSE; DIFFERENTIATION; ZEBRAFISH; FATE; MUTATIONS; GENE AB Utilizing a recently identified Sox10 distal enhancer directing Cre expression, we report S4F:Cre, a transgenic mouse line capable of inducing recombination in oligodendroglia and all examined neural crest derived tissues. Assayed using R26R:LacZ reporter mice expression was detected in neural crest derived tissues including the forming facial skeleton, dorsal root ganglia, sympathetic ganglia, enteric nervous system, aortae, and melanoblasts, consistent with Sox10 expression. LacZ reporter expression was also detected in non-neural crest derived tissues including the oligodendrocytes and the ventral neural tube. This line provides appreciable differences in Cre expression pattern from other transgenic mouse lines that mark neural crest populations, including additional populations defined by the expression of other SoxE proteins. The S4F:Cre transgenic line will thus serve as a powerful tool for lineage tracing, gene function characterization, and genome manipulation in these populations. genesis 47:765-770, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Stine, Zachary E.; Huynh, Jimmy L.; Gorkin, David U.; Miller, Ronald A.; McCallion, Andrew S.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21205 USA. [Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Salmasi, Amirali H.; Novak, Thomas; Purves, Todd; Gearhart, John R.] Johns Hopkins Univ, Dept Pediat Urol, Sch Med, Baltimore, MD 21205 USA. [Antonellis, Anthony] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [McCallion, Andrew S.] Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, Sch Med, Baltimore, MD 21205 USA. RP McCallion, AS (reprint author), Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, 733 N Broadway,BRB Room 407, Baltimore, MD 21205 USA. EM andy@jhmi.edu FU National Human Genome Research Institute's (NHGRI); National Institute of General Medical Sciences (NIGMS) [R01GM071648]; Johns Hopkins Department of Pediatric Urology FX Contract grant sponsors: National Human Genome Research Institute's (NHGRI) Intramural Research Program and the National Institute of General Medical Sciences (NIGMS), Contract grant number: R01GM071648; Contract grant sponsor: Institutional funds front Johns Hopkins Department of Pediatric Urology. NR 35 TC 13 Z9 13 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-954X J9 GENESIS JI Genesis PD NOV PY 2009 VL 47 IS 11 BP 765 EP 770 DI 10.1002/dvg.20559 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 525KS UT WOS:000272215400007 PM 19830815 ER PT J AU Lewin, HA Larkin, DM Pontius, J O'Brien, SJ AF Lewin, Harris A. Larkin, Denis M. Pontius, Joan O'Brien, Stephen J. TI Every genome sequence needs a good map SO GENOME RESEARCH LA English DT Article ID RADIATION HYBRID MAP; MAMMALIAN CHROMOSOME EVOLUTION; BREAKPOINT REUSE; INITIAL SEQUENCE; DOMESTIC DOG; CAT GENOME; PROVIDE; REGIONS; CANINE; GENES C1 [Lewin, Harris A.; Larkin, Denis M.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA. [Lewin, Harris A.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. [Pontius, Joan; O'Brien, Stephen J.] NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Lewin, HA (reprint author), Univ Illinois, Dept Anim Sci, 328 Mumford Hall, Urbana, IL 61801 USA. EM H-lewin@uiuc.edu FU USDA-CSREES [538 AG 2008-34480-19328]; National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded in whole or in part with federal funds from the USDA-CSREES under contract 538 AG 2008-34480-19328 ( H. A. L.) and the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400 ( J. P.). 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 37 TC 78 Z9 81 U1 1 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2009 VL 19 IS 11 BP 1925 EP 1928 DI 10.1101/gr.094557.109 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 514WK UT WOS:000271426600001 PM 19596977 ER PT J AU Irimia, M Roy, SW Neafsey, DE Abril, JF Garcia-Fernandez, J Koonin, EV AF Irimia, Manuel Roy, Scott William Neafsey, Daniel E. Abril, Josep F. Garcia-Fernandez, Jordi Koonin, Eugene V. TI Complex selection on 5 ' splice sites in intron-rich organisms SO GENOME RESEARCH LA English DT Article ID PRE-MESSENGER-RNA; POSITIVE SELECTION; 5'-SPLICE SITES; REPETITIVE DNA; CODON USAGE; U1 SNRNP; EVOLUTION; GENES; EUKARYOTES; SEQUENCES AB In contrast to the typically streamlined genomes of prokaryotes, many eukaryotic genomes are riddled with long intergenic regions, spliceosomal introns, and repetitive elements. What explains the persistence of these and other seemingly suboptimal structures? There are three general hypotheses: ( 1) the structures in question are not actually suboptimal but optimal, being favored by selection, for unknown reasons; ( 2) the structures are not suboptimal, but of ( essentially) equal fitness to "optimal'' ones; or ( 3) the structures are truly suboptimal, but selection is too weak to systematically eliminate them. The 5' splice sites of introns offer a rare opportunity to directly test these hypotheses. Intron-poor species show a clear consensus splice site; most introns begin with the same six nucleotide sequence ( typically GTAAGT or GTATGT), indicating efficient selection for this consensus sequence. In contrast, intron-rich species have much less pronounced boundary consensus sequences, and only small minorities of introns in intron-rich species share the same boundary sequence. We studied rates of evolutionary change of 5' splice sites in three groups of closely related intron-rich species-three primates, five Drosophila species, and four Cryptococcus fungi. Surprisingly, the results indicate that changes from consensus-to-variant nucleotides are generally disfavored by selection, but that changes from variant to consensus are neither favored nor disfavored. This evolutionary pattern is consistent with selective differences across introns, for instance, due to compensatory changes at other sites within the gene, which compensate for the otherwise suboptimal consensus-to-variant changes in splice boundaries. C1 [Roy, Scott William; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Irimia, Manuel; Abril, Josep F.; Garcia-Fernandez, Jordi] Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Spain. [Neafsey, Daniel E.] MIT & Harvard, Broad Inst, Microbial Anal Grp, Cambridge, MA 02142 USA. [Abril, Josep F.] Univ Barcelona, Inst Biomed IBUB, E-08028 Barcelona, Spain. RP Roy, SW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM royscott@ncbi.nlm.nih.gov RI Irimia, Manuel/E-3040-2010; Abril Ferrando, Josep/B-3877-2014; Garcia-Fernandez, Jordi/B-3839-2013; OI Abril Ferrando, Josep/0000-0001-7793-589X; Garcia-Fernandez, Jordi/0000-0001-5677-5970; Irimia, Manuel/0000-0002-2179-2567 FU Spanish Ministerio of Educacion y Ciencia [BFU2005-00252, BFU2005-00422]; Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS; National Institute of Allergy and Infectious Disease; National Science Foundation [0450812] FX M. I., J. G. F., and J. F. A. were funded by the Spanish Ministerio of Educacion y Ciencia, through the BFU2005-00252 and BFU2005-00422 grants, respectively, S. W. R. and E. V. K. were funded by the Intramural Research Program of the National Library of Medicine at National Institutes of Health/DHHS, and D.E.N. by funds from the National Institute of Allergy and Infectious Disease and a grant from the National Science Foundation (0450812). NR 54 TC 12 Z9 12 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 2009 VL 19 IS 11 BP 2021 EP 2027 DI 10.1101/gr.089276.108 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 514WK UT WOS:000271426600010 PM 19745111 ER PT J AU Mertz, E Rossi, A Facchini, M Gualeni, B Forlino, A AF Mertz, Edward Rossi, Antonio Facchini, Marcella Gualeni, Benedetta Forlino, Antonella TI Matrix Disruptions, Growth and Degradation of Diastrophic Dysplasia Cartilage with Impaired Sulfation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Mertz, Edward] NIH, Bethesda, MD 20892 USA. [Rossi, Antonio; Facchini, Marcella; Gualeni, Benedetta; Forlino, Antonella] Univ Pavia, I-27100 Pavia, Italy. RI Rossi, Antonio/E-9935-2012; Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 14 BP 1291 EP 1292 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700025 ER PT J AU Huizing, M Poling, J Ciccone, C Vincent, L Yardeni, T Dorward, H Darvish, D Gahl, WA AF Huizing, Marjan Poling, Justin Ciccone, Carla Vincent, Lisa Yardeni, Tal Dorward, Heidi Darvish, Daniel Gahl, William A. TI Hyposialylation of Various Glomerulopathies and Possible Rescue by N-Acetylmannosamine SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Huizing, Marjan; Poling, Justin; Ciccone, Carla; Vincent, Lisa; Yardeni, Tal; Dorward, Heidi; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Darvish, Daniel] HIBM Res Grp, Encino, CA USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 20 BP 1293 EP 1293 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700031 ER PT J AU Lewis, B Hart, G Sakabe, K AF Lewis, Brian Hart, Gerald Sakabe, Kaoru TI A Cycle of O-Glcnacylation Targeting the Human RNA Polymerase II CTD is Necessary for Transcription Initiation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Lewis, Brian] NCI, Metab Branch, CCR, NIH, Bethesda, MD USA. [Hart, Gerald; Sakabe, Kaoru] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 45 BP 1300 EP 1301 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700056 ER PT J AU Ishihara, M Chu, C Shiloach, J Azadi, P AF Ishihara, Mayumi Chu, Chia Shiloach, Joseph Azadi, Parastoo TI Elucidation of Glycan Expression on the ST6GalNAcV (Siat7e)-Transfected MDCK Cells by Mass Spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Ishihara, Mayumi; Azadi, Parastoo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Chu, Chia; Shiloach, Joseph] NIH, Biotechnol Core Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 127 BP 1325 EP 1325 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700138 ER PT J AU Liu, M Tran, D Lim, JM Wells, L Ten Hagen, K Live, D AF Liu, Mian Tran, Duy Lim, Jae-Min Wells, Lance Ten Hagen, Kelly Live, David TI Post-Translational Processing of Alpha-Dystroglycan SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Liu, Mian; Lim, Jae-Min; Wells, Lance; Live, David] Univ Georgia, CCRC, Athens, GA 30602 USA. [Tran, Duy; Ten Hagen, Kelly] NIDCR, NIH, Bethesda, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 137 BP 1328 EP 1328 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700147 ER PT J AU Rana, NA Xu, ML Moss, H Rab, A Nita-Lazar, A Caswell, D Tan, E Haltiwanger, RS AF Rana, Nadia A. Xu, Min Li Moss, Hillary Rab, Ahmed Nita-Lazar, Aleksandra Caswell, Devin Tan, Eugene Haltiwanger, Robert S. TI On the "Fringe" of Notch: Mapping Sites of O-Fucosylation and Fringe Elongation on Drosophila Notch Extracellular Domain using Mass Spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Rana, Nadia A.; Xu, Min Li; Moss, Hillary; Rab, Ahmed; Caswell, Devin; Tan, Eugene; Haltiwanger, Robert S.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Nita-Lazar, Aleksandra] NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 159 BP 1334 EP 1334 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700169 ER PT J AU Tran, D Tian, E Hagen, KT AF Tran, Duy Tian, E. Hagen, Kelly Ten TI Investigating the Role of Protein O-Glycosylation during Drosophila Development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Tran, Duy; Tian, E.; Hagen, Kelly Ten] NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 162 BP 1335 EP 1335 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700172 ER PT J AU Tharp, CA Srinivasan, A Kramer, KL AF Tharp, Charles A. Srinivasan, Ashok Kramer, Kenneth L. TI Glypicans Coordinately Regulate Zebrafish Dorsoventral Development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Tharp, Charles A.; Srinivasan, Ashok; Kramer, Kenneth L.] NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 169 BP 1337 EP 1337 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700179 ER PT J AU Pasek, M Boeggeman, E Ramakrishnan, B Qasba, P AF Pasek, Marta Boeggeman, Elizabeth Ramakrishnan, Boopathy Qasba, Pradman TI Galectin-1 as a Fusion Partner for the Production of Soluble and Folded Beta-1, 4-Galactosyltransferase-T7 in E. Coli SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Pasek, Marta; Qasba, Pradman] NCI, CCR, Nanobiol Program, Frederick, MD 21701 USA. [Boeggeman, Elizabeth; Ramakrishnan, Boopathy] SAIC, Frederick, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 182 BP 1341 EP 1341 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700192 ER PT J AU Gerken, TA Perrine, C Jamison, O Moinova, H Ravi, L Markowitz, S Patel, H Tabak, L AF Gerken, Thomas A. Perrine, Cynthia Jamison, Oliver Moinova, Helen Ravi, Lakshmeswari Markowitz, Sanford Patel, Himatkumar Tabak, Lawrence TI Paradigms for the Initiation of Mucin Type O-Glycosylation by the Ppgalnac-T Family of Glycosyltransferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Gerken, Thomas A.; Perrine, Cynthia; Jamison, Oliver; Moinova, Helen; Ravi, Lakshmeswari; Markowitz, Sanford] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Patel, Himatkumar; Tabak, Lawrence] NIDDK, NIH, Bethesda, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 208 BP 1349 EP 1349 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700218 ER PT J AU Tatsuta, T Kariya, Y Nitta, K Youle, RJ Handa, K Hakomori, SI AF Tatsuta, Takeo Kariya, Yukiko Nitta, Kazuo Youle, Richard J. Handa, Kazuko Hakomori, Sen-Itiroh TI Functional Interaction of Frog Egg Rnases as Sialic Acid-Binding Lectins, and Their Tumoricidal Effect SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol ID RANA-CATESBEIANA; RIBONUCLEASES C1 [Tatsuta, Takeo; Handa, Kazuko; Hakomori, Sen-Itiroh] Pacific NW Res Inst, Seattle, WA USA. [Kariya, Yukiko; Nitta, Kazuo] Tohoku Pharmaceut Univ, Inst Mol Biomemb Glycobiol, Sendai, Miyagi, Japan. [Youle, Richard J.] NINDS, Biochem Sec, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 210 BP 1350 EP 1350 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700220 ER PT J AU Ul Hussan, SS Bewley, C AF Ul Hussan, Syed Shahzad Bewley, Carole TI Structural Specificity for HIV-Fusion Blocking Cyanobacterial Lectins to Bind Gp120 Carbohydrates and Unusual Enzymatic Activity of Lectin Mvl SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Ul Hussan, Syed Shahzad; Bewley, Carole] NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 214 BP 1351 EP 1351 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700224 ER PT J AU Hashimoto, K Madej, T Bryant, S Panchenko, A AF Hashimoto, Kosuke Madej, Thomas Bryant, Stephen Panchenko, Anna TI Evolution of Quaternary Structures and Homooligomerization in Glycosyltransferases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Hashimoto, Kosuke; Madej, Thomas; Bryant, Stephen; Panchenko, Anna] NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 220 BP 1353 EP 1353 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700230 ER PT J AU Poulain, FE Kramer, K Chien, CB AF Poulain, Fabienne E. Kramer, Kenneth Chien, Chi-Bin TI Glypicans (Hspgs) Have Distinct and Specific Regulatory Roles in Retinal Axon Guidance in vivo SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Poulain, Fabienne E.; Chien, Chi-Bin] Univ Utah, Salt Lake City, UT USA. [Kramer, Kenneth] NHLBI, Dev Biol Lab, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 261 BP 1365 EP 1366 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700271 ER PT J AU Love, D Ghosh, S Wang, P Keembiyehetty, C Fukushige, T Krause, M Hanover, J AF Love, Dona Ghosh, Salil Wang, Peng Keembiyehetty, Chithra Fukushige, Tetsunari Krause, Michael Hanover, John TI Regulation of the Transcriptional Machinery by O-Glcnac Cycling SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Love, Dona; Ghosh, Salil; Wang, Peng; Keembiyehetty, Chithra; Fukushige, Tetsunari; Krause, Michael; Hanover, John] NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 279 BP 1371 EP 1371 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700289 ER PT J AU Ramakrishnan, B Qasba, P AF Ramakrishnan, Boopathy Qasba, Pradman TI Crystal Structure of the Catalytic Domain of Drosophila B-1,4-Galactosyltransferase-T7 SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2009 CL San Diego, CA SP Soc* Glycobiol C1 [Qasba, Pradman] NCI, Struct Glycobiol Sect, CCRNP, CCR, Frederick, MD 21701 USA. [Ramakrishnan, Boopathy] SAIC Frederick Inc, Frderick, MD USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2009 VL 19 IS 11 MA 282 BP 1372 EP 1372 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505PX UT WOS:000270707700292 ER PT J AU Mozos, A Royo, C Hartmann, E De Jong, D Baro, C Valera, A Fu, K Weisenburger, DD Delabie, J Chuang, SS Jaffe, ES Ruiz-Marcellan, C Dave, S Rimsza, L Braziel, R Gascoyne, RD Sole, F Lopez-Guillermo, A Colomer, D Staudt, LM Rosenwald, A Ott, G Jares, P Campo, E AF Mozos, Ana Royo, Cristina Hartmann, Elena De Jong, Daphne Baro, Cristina Valera, Alexandra Fu, Kai Weisenburger, Dennis D. Delabie, Jan Chuang, Shih-Sung Jaffe, Elaine S. Ruiz-Marcellan, Carmen Dave, Sandeep Rimsza, Lisa Braziel, Rita Gascoyne, Randy D. Sole, Francisco Lopez-Guillermo, Armando Colomer, Dolors Staudt, Louis M. Rosenwald, Andreas Ott, German Jares, Pedro Campo, Elias TI SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE mantle cell lymphoma; cyclin D1; SOX11 ID MOLECULAR PATHOGENESIS; ABERRANT EXPRESSION; GENE; OVEREXPRESSION; PERSPECTIVES; SIGNATURE; PROFILES; SURVIVAL; CCND2 AB Background Cyclin D1-negative mantle cell lymphoma is difficult to distinguish from other small B-cell lymphomas. The clinical and pathological characteristics of patients with this form of lymphoma have not been well defined. Overexpression of the transcription factor SOX11 has been observed in conventional mantle cell lymphoma. The aim of this study was to determine whether this gene is expressed in cyclin D1-negative mantle cell lymphoma and whether its detection may be useful to identify these tumors. Design and Methods The microarray database of 238 mature B-cell neoplasms was re-examined. SOX11 protein expression was investigated immunohistochemically in 12 cases of cyclin D1-negative mantle cell lymphoma, 54 cases of conventional mantle cell lymphoma, and 209 additional lymphoid neoplasms. Results SOX11 mRNA was highly expressed in conventional and cyclin D1-negative mantle cell lymphoma and in 33% of the cases of Burkitt's lymphoma but not in any other mature lymphoid neoplasm. SOX11 nuclear protein was detected in 50 cases (93%) of conventional mantle cell lymphoma and also in the 12 cyclin D1-negative cases of mantle cell lymphoma, the six cases of lymphoblastic lymphomas, in two of eight cases of Burkitt's lymphoma, and in two of three T-prolymphocytic leukemias but was negative in the remaining lymphoid neoplasms. Cyclin D2 and D3 mRNA levels were significantly higher in cyclin D1-negative mantle cell lymphoma than in conventional mantle cell lymphoma but the protein expression was not discriminative. The clinico-pathological features and outcomes of the patients with cyclin D1-negative mantle cell lymphoma identified by SOX11 expression were similar to those of patients with conventional mantle cell lymphoma. Conclusions SOX11 mRNA and nuclear protein expression is a highly specific marker for both cyclin D1-positive and negative mantle cell lymphoma. C1 [Mozos, Ana; Royo, Cristina; Valera, Alexandra; Lopez-Guillermo, Armando; Colomer, Dolors; Jares, Pedro; Campo, Elias] Univ Barcelona, Dept Pathol & Hematol, Hematopathol Sect, Hosp Clin,IDIBAPS, E-08007 Barcelona, Spain. [Hartmann, Elena] Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. [De Jong, Daphne] Antoni von Leevenhoek Hosp, Netherlands Canc Inst, Dept Pathol, Amsterdam, Netherlands. [Baro, Cristina; Sole, Francisco] Hosp del Mar, Dept Pathol, Lab Mol Cytogenet, Barcelona, Spain. [Fu, Kai; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [Delabie, Jan] Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. [Chuang, Shih-Sung] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan. [Jaffe, Elaine S.; Staudt, Louis M.] NCI, Sect Hematopathol & Lymphoma Clin Res, Ctr Canc Res, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. [Ruiz-Marcellan, Carmen] Autonomous Univ Barcelona, Vall Hebron Univ Hosp, Dept Pathol, E-08193 Barcelona, Spain. [Dave, Sandeep] Duke Univ, Duke Inst Genome Sci & Policy, Durham, NC USA. [Rimsza, Lisa] Univ Arizona, Coll Med, Dept Pathol, Tucson, AZ 85721 USA. [Braziel, Rita] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Gascoyne, Randy D.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Rosenwald, Andreas; Ott, German] Robert Bosch Krankenhaus, Inst Klin Pathol, Stuttgart, Germany. RP Campo, E (reprint author), Hosp Clin Barcelona, Dept Pathol, Villarroel 170, E-08036 Barcelona, Spain. EM ecampo@clinic.ub.es RI sole, francesc/A-2430-2011; Sole, Francesc/K-8373-2012; Royo, Cristina/H-3193-2015; OI Sole, Francesc/0000-0002-3251-2161; Royo, Cristina/0000-0002-1214-4656; Delabie, Jan/0000-0001-5023-0689; COLOMER, DOLORS/0000-0001-7486-8484; Campo, elias/0000-0001-9850-9793 FU Spanish Ministery of Science and Innovation [SAF 2008-03630]; Instituto de Salud Carlos III "Red Temdtica de Investigacion Cooperativa de Cancer" [2006RET2039]; Accion Transversal [V-2008-ISCIII01]; National of Health [5U01CA114778-03]; Interdisciplinary Center for Clinical Research (IZKF), University of Wurzburg, Germany FX Funding: this study was supported by the Spanish Ministery of Science and Innovation SAF 2008-03630, Instituto de Salud Carlos III "Red Temdtica de Investigacion Cooperativa de Cancer" (2006RET2039) and Accion Transversal (V-2008-ISCIII01) and the National of Health (5U01CA114778-03). AR and EMH are supported by the Interdisciplinary Center for Clinical Research (IZKF), University of Wurzburg, Germany. NR 26 TC 138 Z9 149 U1 2 U2 9 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2009 VL 94 IS 11 BP 1555 EP 1562 DI 10.3324/haematol.2009.010264 PG 8 WC Hematology SC Hematology GA 524TJ UT WOS:000272165800012 PM 19880778 ER PT J AU Kristinsson, SY Goldin, LR Bjorkholm, M Koshiol, J Turesson, I Landgren, O AF Kristinsson, Sigurdur Y. Goldin, Lynn R. Bjorkholm, Magnus Koshiol, Jill Turesson, Ingemar Landgren, Ola TI Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Review DE Hodgkin's lymphoma; non-Hodgkin's lymphoma; chronic lymphocytic leukemia; lymphoplasmacytic lymphoma; Waldenstrom's macroglobulinemia; lymphoma; MGUS; multiple myeloma; familial aggregation; susceptibility; immune-related; autoimmune disease; rheumatoid arthritis; monoclonal B-cell lymphocytosis ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; RESPIRATORY-TRACT INFECTIONS; FAMILY-CANCER DATABASE; HEPATITIS-C VIRUS; MULTIPLE-MYELOMA; RHEUMATOID-ARTHRITIS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; 1ST-DEGREE RELATIVES AB There are data to support a role for genetic and immune-related factors in the pathogenesis of lymphomas and plasma cell diseases. In this paper, we review our published large population-based studies and other relevant studies in Hodgkin's and non-Hodgkin's lymphomas, multiple myeloma, and the precursor condition monoclonal gammopathy of undetermined significance. We discuss the overlap in risk factors between related malignancies and explore the underlying mechanisms. Based on these studies, we provide clinical implications and discuss the relevance of these data for patient counseling and clinical follow-up. Finally, we suggest future directions for new studies designed to increase our current knowledge and to define underlying biological mechanisms of our findings. C1 [Landgren, Ola] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, Stockholm, Sweden. [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Inst, Stockholm, Sweden. [Goldin, Lynn R.; Koshiol, Jill] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. RP Landgren, O (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 10 Room 13N240F, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov RI Kristinsson, Sigurdur /M-2910-2015 OI Kristinsson, Sigurdur /0000-0002-4964-7476 FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations; NIH; NCI FX this research was supported by grants from the Swedish Cancer Society, Stockholm County Council, the Karolinska Institutet Foundations, and the Intramural Research Program of the NIH, NCI. NR 91 TC 21 Z9 21 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2009 VL 94 IS 11 BP 1581 EP 1589 DI 10.3324/haematol.2009.008979 PG 9 WC Hematology SC Hematology GA 524TJ UT WOS:000272165800015 PM 19586941 ER PT J AU Ritchie, D Piekarz, RL Blombery, P Karai, LJ Pittaluga, S Jaffe, ES Raffeld, M Janik, JE Prince, HM Bates, SE AF Ritchie, David Piekarz, Richard L. Blombery, Piers Karai, Laszlo J. Pittaluga, Stefania Jaffe, Elaine S. Raffeld, Mark Janik, John E. Prince, H. Miles Bates, Susan E. TI Reactivation of DNA viruses in association with histone deacetylase inhibitor therapy: a case series report SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE DNA virus; histone deacetylase inhibitor; therapy ID EPSTEIN-BARR-VIRUS; T-CELL LYMPHOMA; LYMPHOPROLIFERATIVE DISORDER; CANCER-THERAPY; DEPSIPEPTIDE; INFECTION; CHEMOTHERAPY; REPLICATION; PROPHYLAXIS; MODEL AB Histone deacetylase inhibitors are a class of anti-neoplastic agents that induce growth arrest, differentiation, and/or apoptotic cell death of transformed cells in vitro and in vivo. A phase II study exploring the efficacy of romidepsin, an histone deacetylase inhibitor, in patients with cutaneous or peripheral T-cell lymphomas was initiated at the National Cancer Institute. To date, over 120 patients with T-cell lymphoma have been treated on a multi-institutional phase II trial of romidepsin. Reactivation of latent DNA viruses including EBV, HBV, and VZV is well described as a consequence of the immune suppression associated with systemic chemotherapy. The incidence of viral reactivation in patients treated with histone deacetylase inhibitors is not yet known. We report the observation of EBV-associated illnesses in 2 patients and the reactivation of HBV in an additional patient treated with romidepsin. These cases may represent reactivation of DNA viruses due to histone deacetylase inhibitor induced immunosuppression, or direct promotion of viral replication via histone deacetylase inhibitor induced chromatin remodeling, or, alternatively, may be related to the underlying disease process. These observations suggest that vigilance for DNA virus reactivation is needed to quantify the risk in patients treated with histone deacetylase inhibitors. C1 [Ritchie, David; Blombery, Piers; Prince, H. Miles] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic 3002, Australia. [Ritchie, David; Blombery, Piers; Prince, H. Miles] Univ Melbourne, Melbourne, Vic 3002, Australia. [Piekarz, Richard L.; Bates, Susan E.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Karai, Laszlo J.; Pittaluga, Stefania; Jaffe, Elaine S.; Raffeld, Mark] NCI, Pathol Lab, Hematopathol Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Janik, John E.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Ritchie, D (reprint author), Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic 3002, Australia. EM david.ritchie@petermac.org FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX this research was supported, in part, by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 31 Z9 33 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2009 VL 94 IS 11 BP 1618 EP 1622 DI 10.3324/haematol.2009.008607 PG 5 WC Hematology SC Hematology GA 524TJ UT WOS:000272165800022 PM 19608677 ER PT J AU Fauci, AS Folkers, GK AF Fauci, Anthony S. Folkers, Gregory K. TI Investing To Meet The Scientific Challenges Of HIV/AIDS SO HEALTH AFFAIRS LA English DT Article ID ANTIRETROVIRAL THERAPY; EXTENDED PERIODS; HIV PREVENTION; UNITED-STATES; TRANSMISSION; ERADICATION; INFECTION; RESERVOIR; VACCINE; VIRUS AB Despite extraordinary scientific advances over more than twenty-five years, the human immunodeficiency virus (HIV) continues to exact an enormous toll worldwide. Given the limitations of current HIV treatment and prevention interventions and the financial and logistical impediments to delivering them, new and potentially transforming interventions are needed if the HIV/AIDS pandemic is to be significantly slowed. Serious scientific challenges remain in the realm of developing potentially curative therapies and a safe and effective HIV vaccine, and in developing, assessing, and validating other new prevention modalities. Substantial funding of the research enterprise must be maintained. [Health Aff (Millwood). 2009;28(6):1629-41] C1 [Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA. [Folkers, Gregory K.] NIAID, Immediate Off Director, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gfolkers@nih.gov NR 29 TC 13 Z9 13 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP 1629 EP 1641 DI 10.1377/hlthaff.28.6.1629 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300007 PM 19887404 ER PT J AU Greenberg, AE Hader, SL Masur, H Young, AT Skillicorn, J Dieffenbach, CW AF Greenberg, Alan E. Hader, Shannon L. Masur, Henry Young, A. Toni Skillicorn, Jennifer Dieffenbach, Carl W. TI Fighting HIV/AIDS In Washington, DC SO HEALTH AFFAIRS LA English DT Article AB Washington, D.C., is the capital of the United States and is a major center for public health and health policy expertise. Yet the District of Columbia has an HIV prevalence rate among adults of 3 percent, on par with some sub-Saharan African countries. To date, the local public health response has not controlled the epidemic. The ways in which that response has been galvanized in recent years-through collaboration among the capital's public health agencies, community and faith organizations, and research institutions-may be instructive to other jurisdictions combating HIV/AIDS. [Health Aff (Millwood). 2009;28(6):1677-87] C1 [Greenberg, Alan E.] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC 20052 USA. [Hader, Shannon L.] Dept Hlth, HIV AIDS Adm, Washington, DC USA. [Masur, Henry] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Young, A. Toni] Community Educ Grp, Washington, DC USA. [Skillicorn, Jennifer] GWU Med Ctr, HIV AIDS Inst, Washington, DC USA. [Dieffenbach, Carl W.] NIAID, Div Aids, NIH, Bethesda, MD USA. RP Greenberg, AE (reprint author), George Washington Univ, Dept Epidemiol & Biostat, Washington, DC 20052 USA. EM aeg1@gwu.edu NR 12 TC 38 Z9 39 U1 0 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP 1677 EP 1687 DI 10.1377/hlthaff.28.6.1677 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300011 PM 19887408 ER PT J AU Mahmoud, A Zerhouni, E AF Mahmoud, Adel Zerhouni, Elias TI Neglected Tropical Diseases: Moving Beyond Mass Drug Treatment To Understanding The Science SO HEALTH AFFAIRS LA English DT Article ID SCHISTOSOMIASIS-MANSONI; LYMPHATIC FILARIASIS; GENOME; VACCINE AB Neglected tropical diseases (NTDs) represent a major health burden in many developing countries. To date, global efforts to control thirteen parasitic and bacterial infections that affect more than 1.4 billion people have relied on mass drug administration. This singular approach should now be expanded to a more comprehensive suite of tools including coordinated community-based programs, vector control, local training, education, and environmental change. In addition, an intensive basic research agenda is urgently needed to develop effective diagnostic, preventive, and therapeutic interventions to stay one step ahead of the evolutionary adaptation tactics of disease-causing microbes and parasites. [Health Aff (Millwood). 2009;28(6):1726-33] C1 [Mahmoud, Adel] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. [Mahmoud, Adel] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA. [Zerhouni, Elias] NIH, Dept Radiol & Biomed Engn, Baltimore, MD USA. [Zerhouni, Elias] Johns Hopkins Med, Baltimore, MD USA. RP Mahmoud, A (reprint author), Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. EM amahmoud@princeton.edu RI Mahmoud, Azza/S-1502-2016 NR 31 TC 16 Z9 16 U1 0 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2009 VL 28 IS 6 BP 1726 EP 1733 DI 10.1377/hlthaff.28.6.1726 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 517NR UT WOS:000271622300016 PM 19887413 ER PT J AU Land, CE AF Land, Charles E. TI LOW-DOSE EXTRAPOLATION OF RADIATION HEALTH RISKS: SOME IMPLICATIONS OF UNCERTAINTY FOR RADIATION PROTECTION AT LOW DOSES SO HEALTH PHYSICS LA English DT Article DE cancer; epidemiology; linear hypothesis; National Council on Radiation Protection and Measurements ID ATOMIC-BOMB SURVIVORS; CANCER-RISKS AB Ionizing radiation is a known and well-quantified human cancer risk factor, based on a remarkably consistent body of information from epidemiological studies of exposed populations. Typical examples of risk estimation include use of Japanese atomic bomb survivor data to estimate future risk from radiation-related cancer among American patients receiving multiple computed tomography scans, persons affected by radioactive fallout, or persons whose livelihoods involve some radiation exposure, such as x-ray technicians, interventional radiologists, or shipyard workers. Our estimates of radiation-related risk are uncertain, reflecting statistical variation and our imperfect understanding of crucial assumptions that must be made if we are to apply existing epidemiological data to particular situations. Fortunately, that uncertainty is also highly quantifiable, and can be presented concisely and transparently. Radiation protection is ultimately a political process that involves consent by stakeholders, a diverse group that includes people who might be expected to be risk-averse and concerned with plausible upper limits on risk (how bad could it be?), cost-averse and concerned with lower limits on risk (can you prove there is a nontrivial risk at current dose levels?), or combining both points of view. How radiation-related risk is viewed by individuals and population subgroups also depends very much on perception of related benefit, which might be (for example) medical, economic, altruistic, or nonexistent The following presentation follows the lead of National Council on Radiation Protection and Measurements (NCRP) Commentary 14, NCRP Report 126, and later documents in treating radiation protection from the viewpoint of quantitative uncertainty analysis. Health Phys. 97(5):407-415; 2009 C1 NCI, NIH, Radiat Epidemiol Branch EPS 7046, Bethesda, MD 20892 USA. RP Land, CE (reprint author), NCI, NIH, Radiat Epidemiol Branch EPS 7046, 6120 Execut Blvd,MS7238, Bethesda, MD 20892 USA. EM landc@mail.nih.gov NR 30 TC 17 Z9 17 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2009 VL 97 IS 5 BP 407 EP 415 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 506UI UT WOS:000270801500005 PM 19820450 ER PT J AU Gilbert, ES AF Gilbert, Ethel S. TI THE IMPACT OF DOSIMETRY UNCERTAINTIES ON DOSE-RESPONSE ANALYSES SO HEALTH PHYSICS LA English DT Article DE analysis, statistical; dosimetry; epidemiology; National Council on Radiation Protection and Measurements ID EXPOSURE MEASUREMENT ERROR; LUNG-CANCER; RESIDENTIAL RADON; RADIATION WORKERS; NUCLEAR INDUSTRY; RISK; REANALYSIS; PLUTONIUM; COHORT; MODEL AB Radiation dose estimates. used in epidemiological studies are subject to many sources of uncertainty, and the error structure may be a complicated mixture of different types of error. Increasingly, efforts are being made to evaluate dosimetry uncertainties and to take account of them in statistical analyses. The impact of these uncertainties on dose-response analyses depends on the magnitude and type of error. Errors that are independent from subject to subject (random errors) reduce statistical power for detecting a dose-response relationship, increase uncertainties in estimated risk coefficients, and may lead to underestimation of risk coefficients. The specific effects of random errors depend on whether the errors are "classical" or "Berkson." Classical error can be thought of as error that arises from an imprecise measuring device, whereas Berkson error occurs when a single dose is used to represent a group of subjects (with varying true doses). Uncertainties in quantities that are common to some or all subjects are "shared" uncertainties. Such uncertainties increase the possibility of bias, and accounting for this possibility increases the length of confidence intervals. In studies that provide a direct evaluation of risk at low doses and dose rates, dosimetry errors are more likely to mask a true effect than to create a spurious one. In addition, classical errors and shared dosimetry uncertainties increase the potential for bias in estimated risks coefficients, but this potential may already be large due to the extreme vulnerability to confounding in studies involving very small relative risk. Health Phys. 97(5):487-492; 2009 C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gilbert, ES (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Room 7050, Bethesda, MD 20892 USA. EM gilberte@mail.nih.gov FU Intramural NIH HHS [ZIA CP010131-18] NR 28 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2009 VL 97 IS 5 BP 487 EP 492 PG 6 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 506UI UT WOS:000270801500013 PM 19820458 ER PT J AU Freedman, ND Everhart, JE Lindsay, KL Ghany, MG Curto, TM Shiffman, ML Lee, WM Lok, AS Di Bisceglie, AM Bonkovsky, HL Hoefs, JC Dienstag, JL Morishima, C Abnet, CC Sinha, R AF Freedman, Neal D. Everhart, James E. Lindsay, Karen L. Ghany, Marc G. Curto, Teresa M. Shiffman, Mitchell L. Lee, William M. Lok, Anna S. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Hoefs, John C. Dienstag, Jules L. Morishima, Chihiro Abnet, Christian C. Sinha, Rashmi CA HALT-C Trial Grp TI Coffee Intake Is Associated with Lower Rates of Liver Disease Progression in Chronic Hepatitis C SO HEPATOLOGY LA English DT Article ID ALANINE AMINOTRANSFERASE ACTIVITY; GAMMA-GLUTAMYL-TRANSFERASE; TEA CONSUMPTION; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; RISK; CAFFEINE; INHIBITION; CIRRHOSIS; PEGINTERFERON AB Higher coffee consumption has been associated inversely with the incidence of chronic liver disease in population studies. We examined the relationship of coffee consumption with liver disease progression in individuals with advanced hepatitis C-related liver disease. Baseline coffee and tea intake were assessed in 766 participants of the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial who had hepatitis C-related bridging fibrosis or cirrhosis on liver biopsy and failed to achieve a sustained virological response to peginterferon plus ribavirin treatment. Participants were followed for 3.8 years for clinical outcomes and, for those without cirrhosis, a 2-point increase in Ishak fibrosis score on protocol biopsies. At baseline, higher coffee consumption was associated with less severe steatosis on biopsy, lower serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, alpha-fetoprotein, insulin, and homeostatic model assessment (HOMA2) score, and higher albumin (P < 0.05 for all). Two hundred thirty patients had outcomes. Outcome rates declined with increasing coffee intake: 11.1/100 person-years for none, 12.1 for less than 1 cup/day, 8.2 for 1 to fewer than 3 cups/day, and 6.3 for 3 or more cups/day (P-trend = 0.0011). Relative risks (95% confidence intervals) were 1.11 (0.76-1.61) for less than I cup/day; 0.70 (0.48-1.02) for I to fewer than 3 cups/day; and 0.47 (0.27-0.85) for 3 or more cups/day (P-trend = 0.0003) versus not drinking. Risk estimates did not vary by treatment assignment or cirrhosis status at baseline. Tea intake was not associated with outcomes. Conclusion: In a large prospective study of participants with advanced hepatitis C-related liver disease, regular coffee consumption was associated with lower rates of disease progression. (HEPATOLOGY 2009;50:1360-1369.) C1 [Freedman, Neal D.; Abnet, Christian C.; Sinha, Rashmi] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Lindsay, Karen L.] Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Shiffman, Mitchell L.] Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Hoefs, John C.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Morishima, Chihiro] Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM freedmanne@mail.nih.gov RI Abnet, Christian/C-4111-2015; Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015; OI Abnet, Christian/0000-0002-3008-7843; Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098; Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; National Cancer Institute; National Center for Minority Health and Health Disparities; General Clinical Research Center; National Center for Research Resources, National Institutes of Health FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health. This research was also supported in part by the Intramural Research Program of the National Cancer Institute. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement with the National Institutes of Health. The funding organizations bad no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 42 TC 78 Z9 81 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2009 VL 50 IS 5 BP 1360 EP 1369 DI 10.1002/hep.23162 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516TK UT WOS:000271565600008 PM 19676128 ER PT J AU Ale-Agha, N Galban, S Sobieroy, C Abdelmohsen, K Gorospe, M Sies, H Klotz, LO AF Ale-Agha, Niloofar Galban, Stefanie Sobieroy, Christiane Abdelmohsen, Kotb Gorospe, Myriam Sies, Helmut Klotz, Lars-Oliver TI HuR Regulates Gap Junctional Intercellular Communication by Controlling beta-Catenin Levels and Adherens Junction Integrity SO HEPATOLOGY LA English DT Article ID LIVER EPITHELIAL-CELLS; BINDING PROTEIN HUR; HEPATIC STELLATE CELLS; STEM-LIKE CELLS; MESSENGER-RNA; RAT-LIVER; CONNEXIN PHOSPHORYLATION; GENE-EXPRESSION; RETINOIC ACID; DIFFERENTIATION AB Gap junctional intercellular communication (GJIC) plays a critical role in the regulation of tissue homeostasis and carcinogenesis and is modulated by the levels, subcellular localization, and posttranslational modification of gap junction proteins, the connexins (Cx). Here, using oval cell-like rat liver epithelial cells, we demonstrate that the RNA-binding protein HuR promotes GJIC through two mechanisms. First, HuR silencing lowered the levels of Cx43 protein and Cx43 messenger RNA (mRNA), and decreased Cx43 mRNA half-life. This regulation was likely due to the direct stabilization of Cx43 mRNA by HuR, because HuR associated directly with Cx43 mRNA, a transcript that bears signature adenylate-uridylate-rich (AU-rich) and uridylate-rich (U-rich) sequences in its 3'-untranslated region. Second, HuR silencing reduced both half-life and the levels of beta-catenin mRNA, also a target of HuR; accordingly, HuR silencing lowered the levels of whole-cell and membrane-associated beta-catenin. Coimmunoprecipitation experiments showed a direct interaction between beta-catenin and Cx43. Small interfering RNA (siRNA)-mediated depletion of beta-catenin recapitulated the effects of decreasing HuR levels: it attenuated GJIC, decreased Cx43 levels, and redistributed Cx43 to the cytoplasm, suggesting that depletion of beta-catenin in HuR-silenced cells contributed to lowering Cx43 levels at the membrane. Finally, HuR was demonstrated to support GJIC after exposure to a genotoxic agent, doxorubicin, or an inducer of differentiation processes, retinoic acid, thus pointing to a crucial role of HuR in the cellular response to stress and in physiological processes modulated by GJIC. Conclusion: HuR promotes gap junctional intercellular communication in rat liver epithelial cells through two related regulatory processes, by enhancing the expression of Cx43 and by increasing the expression of beta-catenin, which, in turn, interacts with Cx43 and is required for proper positioning of Cx43 at the plasma membrane. (HEPATOLOGY 2009;50:1567-1576.) C1 [Ale-Agha, Niloofar; Sies, Helmut; Klotz, Lars-Oliver] Univ Dusseldorf, Inst Umweltmed Forsch, D-40225 Dusseldorf, Germany. [Galban, Stefanie; Sobieroy, Christiane; Sies, Helmut; Klotz, Lars-Oliver] Univ Dusseldorf, Inst Biochem & Mol Biol 1, D-40225 Dusseldorf, Germany. [Galban, Stefanie; Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Klotz, LO (reprint author), Univ Dusseldorf, Inst Umweltmed Forsch, Aufm Hennekamp 50, D-40225 Dusseldorf, Germany. EM LarsOliver.Klotz@uni-duesseldorf.de RI Sies, Helmut/B-7266-2008 FU Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany) [SFB 575/B4]; NIA-IRP National Institutes of Health; National Foundation for Cancer Research, Bethesda, MD FX Supported by Deutsche Forschungsgemeinschaft (DFG, Bonn, Germany), SFB 575/B4. S G, K.A., and M. G. were supported by the NIA-IRP National Institutes of Health. H. S. is a Fellow of the National Foundation for Cancer Research, Bethesda, MD. NR 45 TC 22 Z9 23 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2009 VL 50 IS 5 BP 1567 EP 1576 DI 10.1002/hep.23146 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516TK UT WOS:000271565600028 PM 19676129 ER PT J AU Freedman, ND Curto, TM Everhart, JE AF Freedman, Neal D. Curto, Teresa M. Everhart, James E. TI Coffee Intake and Chronic Hepatitis C Reply SO HEPATOLOGY LA English DT Letter C1 [Freedman, Neal D.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human serv, Rockville, MD USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human serv, Bethesda, MD USA. RP Freedman, ND (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human serv, Rockville, MD USA. RI Freedman, Neal/B-9741-2015 OI Freedman, Neal/0000-0003-0074-1098 NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2009 VL 50 IS 5 BP 1673 EP 1673 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 516TK UT WOS:000271565600040 ER PT J AU Voruganti, VS Goring, HHH Mottl, A Franceschini, N Haack, K Laston, S Almasy, L Fabsitz, RR Lee, ET Best, LG Devereux, RB Howard, BV MacCluer, JW Comuzzie, AG Umans, JG Cole, SA AF Voruganti, V. Saroja Goering, Harald H. H. Mottl, Amy Franceschini, Nora Haack, Karin Laston, Sandra Almasy, Laura Fabsitz, Richard R. Lee, Elisa T. Best, Lyle G. Devereux, Richard B. Howard, Barbara V. MacCluer, Jean W. Comuzzie, Anthony G. Umans, Jason G. Cole, Shelley A. TI Genetic influence on variation in serum uric acid in American Indians: the strong heart family study SO HUMAN GENETICS LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; GENOME-WIDE ASSOCIATION; METABOLIC SYNDROME; LINKAGE ANALYSIS; RENAL HYPOURICEMIA; INSULIN SENSITIVITY; BARTTERS-SYNDROME; DISEASE; HYPERURICEMIA; HYPERTENSION AB Hyperuricemia is associated with the metabolic syndrome, gout, renal and cardiovascular disease (CVD). American Indians have high rates of CVD and 25% of individuals in the strong heart family study (SHFS) have high serum uric acid levels. The aim of this study was to investigate the genetic determinants of serum uric acid variation in American Indian participants of the SHFS. A variance component decomposition approach (implemented in SOLAR) was used to conduct univariate genetic analyses in each of three study centers and the combined sample. Serum uric acid was adjusted for age, sex, age x sex, BMI, estimated glomerular filtration rate, alcohol intake, diabetic status and medications. Overall mean +/- A SD serum uric acid for all individuals was 5.14 +/- A 1.5 mg/dl. Serum uric acid was found to be significantly heritable (0.46 +/- A 0.03 in all centers, and 0.39 +/- A 0.07, 0.51 +/- A 0.05, 0.44 +/- A 0.06 in Arizona, Dakotas and Oklahoma, respectively). Multipoint linkage analysis showed significant evidence of linkage for serum uric acid on chromosome 11 in the Dakotas center [logarithm of odds score (LOD) = 3.02] and in the combined sample (LOD = 3.56) and on chromosome 1 (LOD = 3.51) in the combined sample. A strong positional candidate gene in the chromosome 11 region is solute carrier family22, member 12 (SLC22A12) that encodes a major uric acid transporter URAT1. These results show a significant genetic influence and a possible role for one or more genes on chromosomes 1 and 11 on the variation in serum uric acid in American Indian populations. C1 [Voruganti, V. Saroja; Goering, Harald H. H.; Haack, Karin; Laston, Sandra; Almasy, Laura; MacCluer, Jean W.; Comuzzie, Anthony G.; Cole, Shelley A.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. [Mottl, Amy] Univ N Carolina, UNC Kidney Ctr, Chapel Hill, NC USA. [Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. [Fabsitz, Richard R.] NHLBI, NIH, Bethesda, MD 20892 USA. [Lee, Elisa T.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Best, Lyle G.] Missouri Breaks Ind Res Inc, Timber Lake, SD USA. [Devereux, Richard B.] Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. [Howard, Barbara V.; Umans, Jason G.] Medstar Res Inst, Washington, DC USA. RP Voruganti, VS (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM svorugan@sfbrgenetics.org OI Mottl, Amy/0000-0002-4258-1726 FU National Heart, Lung, and Blood Institute, Bethesda [U01-HL65520, U01-HL41642, U01-HL41652, U01-HL41654, U01-HL65521]; NIH [MH59490]; Research Facilities Improvement Program [C06 RR014578, C06 RR013556, C06 RR015456, C06 RR017515] FX We thank the SHFS participants, Indian Health Services facilities, and participating tribal communities for their extraordinary cooperation and involvement, and without whose assistance, this project would not have been possible. The opinions expressed in this paper are those of the author(s) and do not necessarily reflect the views of the Indian Health Service. This work was also supported by grants U01-HL65520, U01-HL41642, U01-HL41652, U01-HL41654 and U01-HL65521 from the National Heart, Lung, and Blood Institute, Bethesda, MD. Development of SOLAR was supported by NIH grant MH59490. This investigation was conducted in part in facilities constructed with support from the Research Facilities Improvement Program under grant numbered C06 RR014578, C06 RR013556, C06 RR015456, and C06 RR017515. NR 68 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2009 VL 126 IS 5 BP 667 EP 676 DI 10.1007/s00439-009-0716-8 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 514MU UT WOS:000271399700007 PM 19590895 ER PT J AU Li, YF Ni, R Song, W Shao, WS Shrestha, S Ahmad, S Cunningham, CK Flynn, PM Kapogiannis, BG Wilson, CM Tang, JM AF Li, Yufeng Ni, Rong Song, Wei Shao, Wenshuo Shrestha, Sadeep Ahmad, Sushma Cunningham, Coleen K. Flynn, Patricia M. Kapogiannis, Bill G. Wilson, Craig M. Tang, Jianming TI Clear and independent associations of several HLA-DRB1 alleles with differential antibody responses to hepatitis B vaccination in youth SO HUMAN GENETICS LA English DT Article ID HUMAN-LEUKOCYTE ANTIGEN; MAJOR HISTOCOMPATIBILITY COMPLEX; GENOME-WIDE ASSOCIATION; INFECTED ADULT PATIENTS; HIV-1 VIRAL LOAD; CLASS-II ALLELES; SURFACE-ANTIGEN; HLA-C; HEMODIALYSIS-PATIENTS; SEROLOGIC RESPONSE AB To confirm and refine associations of human leukocyte antigen (HLA) genotypes with variable antibody (Ab) responses to hepatitis B vaccination, we have analyzed 255 HIV-1 seropositive (HIV(+)) youth and 80 HIV-1 seronegatives (HIV(-)) enrolled into prospective studies. In univariate analyses that focused on HLA-DRB1, -DQA1, and -DQB1 alleles and haplotypes, the DRB1*03 allele group and DRB1*0701 were negatively associated with the responder phenotype (serum Ab concentration a parts per thousand yen 10 mIU/mL) (P = 0.026 and 0.043, respectively). Collectively, DRB1*03 and DRB1*0701 were found in 42 (53.8%) out of 78 non-responders (serum Ab < 10 mIU/mL), 65 (40.6%) out of 160 medium responders (serum Ab 10-1,000 mIU/mL), and 27 (27.8%) out of 97 high responders (serum Ab > 1,000 mIU/mL) (P < 0.001 for trend). Meanwhile, DRB1*08 was positively associated with the responder phenotype (P = 0.010), mostly due to DRB1*0804 (P = 0.008). These immunogenetic relationships were all independent of non-genetic factors, including HIV-1 infection status and immunodeficiency. Alternative analyses confined to HIV(+) youth or Hispanic youth led to similar findings. In contrast, analyses of more than 80 non-coding, single nucleotide polymorphisms within and beyond the three HLA class II genes revealed no clear associations. Overall, several HLA-DRB1 alleles were major predictors of differential Ab responses to hepatitis B vaccination in youth, suggesting that T-helper cell-dependent pathways mediated through HLA class II antigen presentation are critical to effective immune response to recombinant vaccines. C1 [Li, Yufeng; Ni, Rong; Tang, Jianming] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. [Song, Wei; Shao, Wenshuo; Shrestha, Sadeep; Wilson, Craig M.] Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. [Ahmad, Sushma] Westat Corp, Rockville, MD USA. [Cunningham, Coleen K.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Flynn, Patricia M.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Kapogiannis, Bill G.] NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. RP Tang, JM (reprint author), Univ Alabama, Dept Med, 1665 Univ Blvd, Birmingham, AL 35294 USA. EM jtang@uab.edu FU National Institute of Child Health and Human Development [U01 HD40474, U01 HD40533]; National Institute of Allergy and Infectious Diseases (Patrick Jean-Philippe); National Institute on Drug Abuse; National Institute of Mental Health; National Institute of Allergy and Infectious Diseases [K02 AI076123] FX This work was supported by the Adolescent Trials Network for HIV/AIDS Interventions (ATN), with primary funding through two grants (U01 HD40474 and U01 HD40533) from National Institute of Child Health and Human Development (B. Kapogiannis, L. Serchuck) and supplemental funding from the National Institute of Allergy and Infectious Diseases (Patrick Jean-Philippe), National Institute on Drug Abuse (N. Borek), as well as National Institute of Mental Health (P. Brouwers, S. Allison). J. T. is the recipient of an independent scientist award (K02 AI076123) from National Institute of Allergy and Infectious Diseases. The entire project was scientifically reviewed by ATN's Therapeutic Leadership Group. Network, scientific and logistical support was provided by the ATN Coordinating Center (C. Wilson, C. Partlow) at the University of Alabama at Birmingham. Network operations and analytic support came from the ATN Data and Operations Center at Westat Inc. (J. Korelitz, B. Driver). We sincerely thank members of the local youth Community Advisory Boards for their insight and counsel, the youth who participated in this study for their cooperation, Stephanie Crane (Adolescent Medicine Trials Unit) and Jenese Tucker (Westat) for valuable assistance with protocol implementation, Rick Mitchell (Westat) for data management, Richard A. Kaslow, Audrey Rogers, and Steven Spector for consultation and advice on protocol development, Karine Viaud (Illumina) for assistance with bioinformatics, Dale Isabelle and Mary Shirley for administrative assistance, Peter Havens, Sharon Nachman, Bret Rudy, Kathleen Squires, and John Sleasman for critical reading of an earlier version of this manuscript. NR 64 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2009 VL 126 IS 5 BP 685 EP 696 DI 10.1007/s00439-009-0720-z PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 514MU UT WOS:000271399700009 PM 19597844 ER PT J AU Yu, KJ Gao, XJ Chen, CJ Yang, XH Diehl, SR Goldstein, A Hsu, WL Liang, XY Marti, D Liu, MY Chen, JY Carrington, M Hildesheim, A AF Yu, Kelly J. Gao, Xiaojiang Chen, Chien-Jen Yang, Xiaohong (Rose) Diehl, Scott R. Goldstein, Alisa Hsu, Wan-Lun Liang, Xueying (Sharon) Marti, Darlene Liu, Mei-Ying Chen, Jen-Yang Carrington, Mary Hildesheim, Allan TI Association of human leukocyte antigens with nasopharyngeal carcinoma in high-risk multiplex families in Taiwan SO HUMAN IMMUNOLOGY LA English DT Article DE Human leukocyte antigens; Nasopharyngeal carcinoma; Epidemiology; Genetics ID EPSTEIN-BARR-VIRUS; GENETIC-VARIANTS; LINKAGE; ANTIBODIES; INFECTION; FREQUENCY; ETIOLOGY; MARKER; LOCUS; DNASE AB An association between specific human leukocyte antigens (HLA) alleles and nasopharyngeal carcinoma (NPC) has been reported for sporadic NPC, but studies of familial NPC are lacking. We evaluated this association with familial NPC in a study of 301 NPC cases and 1010 family and community controls from Taiwan. Class I HLA alleles were characterized using a sequence-based typing protocol. Allele frequencies between case and control groups were compared by chi(2) or exact tests. For alleles associated with NPC, oddsratios (OR) and 95% confidence intervals (CI) were calculated. Similar allelic frequency distribution and HLA associations were found as those previously reported for sporadic NPC: protective effect for HLA-A*1101 and increased risk for HLA-A*0207, HLA-A*3303, HLA-B*3802, and HLA-B*5801. Overall, the magnitude of observed associations was weakest when cases were compared with sibling controls and strongest when compared with unrelated community controls. Evaluating the joint effect of HLA-A*0207 and HLA-B*4601, individuals who were carriers of HLA-A*0207 with or without the presence of HLA-B*4601 had a 1.9-fold (95% CI = 1.0-3.4) and 2.1-fold (95% CI = 0.83-5.3) risk of NPC, respectively. Conversely, carriers of HLA-B*4601 in the absence of HLA-A*0207 had a 50% reduction in NPC risk (95% CI = 0.27-0.93). Comparable findings from our family study and those from previous sporadic studies were found with the notable exception of a lack of positive association between HLA-B*4601 and familial NPC in the absence of HLA-A*0207. This finding requires replication in larger studies. Published by Elsevier Inc. on behalf of American Society for Histocompatibility and Immunogenetics. C1 [Yu, Kelly J.; Yang, Xiaohong (Rose); Goldstein, Alisa; Liang, Xueying (Sharon); Hildesheim, Allan] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Gao, Xiaojiang; Marti, Darlene; Carrington, Mary] NCI, Canc & Inflammat Program, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Chen, Chien-Jen; Hsu, Wan-Lun] Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. [Chen, Chien-Jen; Hsu, Wan-Lun] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Diehl, Scott R.] Univ Med & Dent New Jersey, New Jersey Dent Sch, Ctr Pharmacogenom & Complex Dis Res, Newark, NJ 07103 USA. [Liu, Mei-Ying] Natl Taipei Coll Nursing, Ctr Gen Educ, Taipei, Taiwan. [Chen, Jen-Yang] Natl Hlth Res Inst, Natl Inst Canc Res, Chunan, Taiwan. [Chen, Jen-Yang] Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei 10764, Taiwan. RP Yu, KJ (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM yuke@mail.nih.gov RI Chen, Chien-Jen/C-6976-2008; Chen, Jen-Yang/D-2085-2010; Hildesheim, Allan/B-9760-2015 OI Hildesheim, Allan/0000-0003-0257-2363 FU National Cancer Institute; National Institutes of Health [HHSN261200800001E] FX We thank Brenda Sun, Beth Mittl, and Jeanne Rosenthal (Westat, Inc., Rockville, MD) for managing the result database, and Joseph Danny Carreon (NCI/DCEG/HREB) for assistance with data. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This Research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 30 TC 10 Z9 15 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 2009 VL 70 IS 11 BP 910 EP 914 DI 10.1016/j.humimm.2009.08.005 PG 5 WC Immunology SC Immunology GA 517KA UT WOS:000271611100006 PM 19683024 ER PT J AU Li, LL Biswas, K Habib, LA Kuznetsov, SG Hamel, N Kirchhoff, T Wong, N Armel, S Chong, G Narod, SA Claes, K Offit, K Robson, ME Stauffer, S Sharan, SK Foulkes, WD AF Li, Lili Biswas, Kajal Habib, Laura Anne Kuznetsov, Sergey G. Hamel, Nancy Kirchhoff, Tomas Wong, Nora Armel, Susan Chong, George Narod, Steven A. Claes, Kathleen Offit, Kenneth Robson, Mark E. Stauffer, Stacey Sharan, Shyam K. Foulkes, William D. TI Functional Redundancy of Exon 12 of BRCA2 Revealed by a Comprehensive Analysis of the c.6853A > G (p.I2285V) Variant SO HUMAN MUTATION LA English DT Article DE BRCA2; unclassified variants; VUS; exon splicing enhancer; ESE; ES cells ID BREAST-CANCER; MISSENSE SUBSTITUTIONS; CLINICAL-SIGNIFICANCE; MUTATIONS; CLASSIFICATION; GENES; NONSENSE; OVARIAN; REPAIR AB Variants of unknown significance (VUS) in BRCA1 and BRCA2 are common, and present significant challenges for genetic counseling. We observed that BRCA2: c.6853A>G (p.I2285V) (Breast Cancer Information Core [BIC] name: 7081A > G; http://research.nhgri.nih.gov/bic/) co-occurs in trans with the founder mutation c.5946delT (p.S1982RfsX22) (BIC name: 6174deIT), supporting the published classification of p.I2285V as a neutral variant. However, we also noted that when compared with wild,type BRCA2, p.I2285V resulted in increased exclusion of exon 12. Functional assay using allelic complementation in Brca2-null mouse embryonic stern cells revealed that p.I2285V, an allele with exon 12 deleted and wild-type BRCA2 were all phenotypically indistinguishable, as measured by sensitivity to DNA-damaging agents, effect on irradiation-induced Rad51. foci formation, homologous recombination, and overall genontic integrity. An allele frequency study showed the p.I2285V variant was identified in 15 out of 722 (2.1%) Ashkenazi Jewish cases and 10 out of 475 (2.1%) ethnically,matched controls (odds ratio, 0.99; 95% confidence interval: 0.44-2.21; P = 0.97). Thus the p.I2285V variant is not associated with an increased risk for breast cancer. Taken together, our clinical and functional studies strongly suggest that exon 12 is functionally redundant and therefore missense variants in this exon are likely to be neutral. Such comprehensive functional studies will be important adjuncts to genetic studies of variants. Hum Mutat 30:1543-1550, 2009. Published 2009 Wiley-Liss, Inc. C1 [Wong, Nora; Foulkes, William D.] SMBD Jewish Gen Hosp, Canc Prevent Ctr, Montreal, PQ H3T 1E2, Canada. [Wong, Nora; Foulkes, William D.] SMBD Jewish Gen Hosp, Dept Med Genet, Montreal, PQ H3T 1E2, Canada. [Li, Lili; Habib, Laura Anne; Foulkes, William D.] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Li, Lili; Habib, Laura Anne; Foulkes, William D.] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada. [Biswas, Kajal; Kuznetsov, Sergey G.; Stauffer, Stacey; Sharan, Shyam K.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. [Hamel, Nancy; Foulkes, William D.] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. [Kirchhoff, Tomas; Offit, Kenneth; Robson, Mark E.] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Armel, Susan] Univ Toronto, Princess Margaret Hosp, Familial Breast & Ovarian Canc Clin, Toronto, ON M5S 1A1, Canada. [Chong, George] SMBD Jewish Gen Hosp, Dept Pathol, Montreal, PQ H3T 1E2, Canada. [Narod, Steven A.] Univ Toronto, Womens Coll Hosp, Res Inst, Toronto, ON M5S 1A1, Canada. [Claes, Kathleen] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium. RP Foulkes, WD (reprint author), SMBD Jewish Gen Hosp, Canc Prevent Ctr, Room E-757,3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. EM william.foulkes@mcgill.ca OI Kuznetsov, Sergey/0000-0002-5662-9700; foulkes, william/0000-0001-7427-4651; Kirchhoff, Tomas/0000-0002-9055-2364; Robson, Mark/0000-0002-3109-1692 FU Department of Defense [W81XWH-08-1-0402]; National Cancer Institute; National Institutes of Health FX We thank Drs. Jun Zhu and Jacek Majewski and Mr. Kevin Ha for helpful discussions; Ms. Megan Harlan for her help with the New York families; and Ms. Sabrina Notte for help with manuscript preparation. Supported by grants from the Canadian Breast Cancer Research Alliance IDEA grant award, Department of Defense grant number W81XWH-08-1-0402 (both to W.D.F.), and National Cancer Institute, National Institutes of Health (to S.K.S.). NR 25 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD NOV PY 2009 VL 30 IS 11 BP 1543 EP 1550 DI 10.1002/humu.21101 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 516XL UT WOS:000271576600006 PM 19795481 ER PT J AU Langen, JS Ciribilli, Y Andreotti, V Menendez, D Resnick, MA Inga, A Schonfelder, G AF Langen, J. S. Ciribilli, Y. Andreotti, V Menendez, D. Resnick, M. A. Inga, A. Schonfelder, G. TI TRANSCRIPTIONAL REGULATION OF THE VEGF-RECEPTOR 1 (FLT1) SO HYPERTENSION LA English DT Meeting Abstract CT 14th Annual Meeting of the European-Council-for-Cardiovascular-Research CY OCT 09-11, 2009 CL Nice, FRANCE SP European Council Cardiovasc Res C1 [Langen, J. S.; Schonfelder, G.] Charite, Inst Clin Pharmacol & Toxicol, D-13353 Berlin, Germany. [Ciribilli, Y.; Andreotti, V; Inga, A.] IST, Natl Inst Canc Res, Unit Mol Mutagenesis & DNA Repair, Genoa, Italy. [Menendez, D.; Resnick, M. A.] NIEHS, Mol Genet Lab, NIH, RTP, Res Triangle Pk, NC USA. Univ Wurzburg, Inst Pharmacol & Toxicol, Wurzburg, Bavaria, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2009 VL 54 IS 5 BP 1181 EP 1182 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 509CW UT WOS:000270992100124 ER PT J AU Tolar, P Sohn, HW Liu, WL Pierce, SK AF Tolar, Pavel Sohn, Hae Won Liu, Wanli Pierce, Susan K. TI The molecular assembly and organization of signaling active B-cell receptor oligomers SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B-cell receptor; signaling; coreceptors; adapters ID RESONANCE ENERGY-TRANSFER; ANTIGEN RECEPTOR; SYNAPSE FORMATION; LIVING CELLS; LIPID RAFTS; LYMPH-NODE; SUBCAPSULAR SINUS; IMMUNE SYNAPSE; ACTIVATION; INITIATION AB In B cells, antigen drives the formation of B-cell receptor (BCR) clusters that initiate the formation of signaling complexes associated with the cytoplasmic domains of the BCRs. These signaling active complexes contain a number of protein and lipid kinases and phosphatases and adapter and scaffolding proteins that together function to trigger downstream signaling cascades leading to the activation of a variety of genes associated with B-cell activation. Although we are learning a considerable amount about the molecular details of the assembly of immune receptor signaling complexes, as reviewed in this volume, a fundamental question remains, namely how does antigen binding outside the cell initiate the assembly of signaling complexes inside the cell. For B cells, we do not yet understand how the information that the ectodomain of the BCR has bound to an antigen is translated across the membrane to induce changes in the cytoplasmic domains that trigger the assembly of signaling complexes. Here we describe what is known about the initiation of the antigen-driven BCR signal transduction in the newly emerging context of B-cell recognition of antigens presented by antigen-presenting cells in lymphoid tissues. We also discuss a recently proposed model for the initiation of BCR signaling termed the 'conformation-induced oligomerization model' and address the implications of this model for the mechanisms by which BCR signaling may be modulated by adapters and coreceptors. C1 [Tolar, Pavel; Sohn, Hae Won; Liu, Wanli; Pierce, Susan K.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Tolar, Pavel] Natl Inst Med Res, London NW7 1AA, England. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Room 200B,MSC 8180, Rockville, MD 20852 USA. EM spierce@nih.gov RI liu, wanli/H-5690-2011 OI liu, wanli/0000-0003-2624-6802 FU 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 35 TC 41 Z9 42 U1 0 U2 5 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2009 VL 232 BP 34 EP 41 PG 8 WC Immunology SC Immunology GA 509ZK UT WOS:000271057600004 PM 19909354 ER PT J AU Balagopalan, L Barr, VA Samelson, LE AF Balagopalan, Lakshmi Barr, Valarie A. Samelson, Lawrence E. TI Endocytic events in TCR signaling: focus on adapters in microclusters SO IMMUNOLOGICAL REVIEWS LA English DT Review DE endocytosis; ubiquitylation; linker for activation of T cells; SLP-76; microclusters; T-cell signaling ID T-CELL-RECEPTOR; CLATHRIN-INDEPENDENT ENDOCYTOSIS; PROTEIN-KINASE-C; SUPRAMOLECULAR ACTIVATION CLUSTER; GPI-ANCHORED PROTEINS; FC-EPSILON-RI; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECEPTOR; NEGATIVE REGULATION; UBIQUITIN LIGASES AB Although the critical role of T-cell receptor (TCR) microclusters in T-cell activation is now widely accepted, the mechanisms of regulation of these TCR-rich structures, which also contain enzymes, adapters, and effectors, remain poorly defined. Soon after microcluster formation, several signaling proteins rapidly dissociate from the TCR. Recent studies from our laboratory demonstrated that the movement of the adapters linker for activation of T cells (LAT) and Src homology 2 domain-containing leukocyte protein of 76 kDa (SLP-76) away from initial microcluster formation sites represents endocytic events. Ubiquitylation, Cbl proteins, and multiple endocytic pathways are involved in the internalization events that disassemble signaling microclusters. Several recent studies have indicated that microcluster movement and centralization plays an important role in signal termination. We suggest that microcluster movement is directly linked to endocytic events, thus implicating endocytosis of microclusters as a means to regulate signaling output of the T cell. C1 [Balagopalan, Lakshmi; Barr, Valarie A.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 2066, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU NIH; NCI; CCR FX We thank Dr. Roman Polishchuk for assistance with electron microscopy. This research was supported by the Intramural Research Program of the NIH, NCI, CCR. NR 135 TC 25 Z9 25 U1 3 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2009 VL 232 BP 84 EP 98 PG 15 WC Immunology SC Immunology GA 509ZK UT WOS:000271057600008 PM 19909358 ER PT J AU Alvarez-Errico, D Lessmann, E Rivera, J AF Alvarez-Errico, Damiana Lessmann, Eva Rivera, Juan TI Adapters in the organization of mast cell signaling SO IMMUNOLOGICAL REVIEWS LA English DT Review DE adapters; Fc epsilon RI; IgE; mast cells; signaling ID FC-EPSILON-RI; AFFINITY IGE RECEPTOR; PROTEIN-TYROSINE KINASE; IMMUNOGLOBULIN-E RECEPTOR; SRC-FAMILY KINASES; GLYCOSPHINGOLIPID-ENRICHED MICRODOMAINS; BASOPHILIC LEUKEMIA-CELLS; LEMLI-OPITZ-SYNDROME; NEGATIVE REGULATION; T-CELLS AB Mast cells are pivotal in innate immunity and play an important role in amplifying adaptive immunity. Nonetheless, they have long been known to be central to the initiation of allergic disorders. This results from the dysregulation of the immune response whereby normally innocuous substances are recognized as non-self, resulting in the production of IgE antibodies to these 'allergens'. Preformed and newly synthesized inflammatory (allergic) mediators are released from the mast cell following allergen-mediated aggregation of allergen-specific IgE bound to the high-affinity receptors for IgE (Fc epsilon RI). Thus, the process by which the mast cell is able to interpret the engagement of Fc epsilon RI into the molecular events necessary for release of their allergic mediators is of considerable therapeutic interest. Unraveling these molecular events has led to the discovery of a functional class of proteins that are essential in organizing activated signaling molecules and in coordinating and compartmentalizing their activity. These so-called 'adapters' bind multiple signaling proteins and localize them to specific cellular compartments, such as the plasma membrane. This organization is essential for normal mast cell responses. Here, we summarize the role of adapter proteins in mast cells focusing on the most recent advances toward understanding how these molecules work upon Fc epsilon RI engagement. C1 [Alvarez-Errico, Damiana; Lessmann, Eva; Rivera, Juan] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Rivera, J (reprint author), NIAMS, Immunogenet Mol Lab, NIH, Bldg 10,Room 13C103,MSC1930,10 Ctr Dr, Bethesda, MD 20892 USA. EM juan-rivera@nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases within the National Institutes of Health, USA FX Research in the authors' laboratory is supported by the Intramural Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases within the National Institutes of Health, USA. NR 197 TC 31 Z9 32 U1 1 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2009 VL 232 BP 195 EP 217 PG 23 WC Immunology SC Immunology GA 509ZK UT WOS:000271057600015 PM 19909365 ER PT J AU Kotlan, B Stroncek, DF Marincola, FM AF Kotlan, Beatrix Stroncek, David F. Marincola, Francesco M. TI Intravenous immunoglobulin-based immunotherapy: an arsenal of possibilities for patients and science SO IMMUNOTHERAPY LA English DT Review DE autoimmune disease; cancer; ganglioside; immunomodulatory effect immunotherapy; intravenous immunoglobulin; natural antibody; recurrent miscarriage; tumor-associated antigen ID RECURRENT PREGNANCY LOSS; IDIOPATHIC THROMBOCYTOPENIC PURPURA; ANTIIDIOTYPIC MONOCLONAL-ANTIBODY; MIMICS GD3 GANGLIOSIDE; ANTIGANGLIOSIDE IGM ANTIBODIES; ACTIVE SPECIFIC IMMUNOTHERAPY; MULTIFOCAL MOTOR NEUROPATHY; MELANOMA-ASSOCIATED ANTIGEN; IMMUNE GLOBULIN TREATMENT; CHRONIC-FATIGUE-SYNDROME AB The use of intravenous immunoglobulin (IVIG) concentrated from pooled healthy donors' plasma has gained increasing popularity. IVIG therapy has become important as a replacement therapy in primary and acquired humoral immunodeficiencies, and it has been extended to autoimmune, neurodegenerative and inflammatory conditions and transplantation therapy. Recurrent pregnancy failure and cancer are rather new platforms, where IVIG has shown its beneficial effects. This manuscript is focused on these two off-labelled usages. The immunomodulatory mechanisms of IVIG therapy appear as a coordinated orchestration of different functions, resulting in a synergistic effect. Treatment monitoring and detailed molecular analyses reveal how such treatments may interfere with disease pathogenesis. These finding may foster the development of novel therapeutic and/or preventive strategies. Studying this field with bidirectional bench-to-bedside and bedside-to-bench approaches fit well into 'the two-way road' paradigm of translational medicine. C1 [Kotlan, Beatrix] Natl Inst Oncol, Ctr Surg & Mol Tumorpathol, H-1122 Budapest, Hungary. [Stroncek, David F.; Marincola, Francesco M.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Kotlan, B (reprint author), Natl Inst Oncol, Ctr Surg & Mol Tumorpathol, Rath Gy St 7-9, H-1122 Budapest, Hungary. EM kotlanb@netscape.net FU International and Hungarian [120610, OTKA T048933]; ETT [17212000] FX International and Hungarian grants support this work: Fulbright Grant No: 120610, OTKA T048933, previous and present ETT grants (17212000). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NR 219 TC 9 Z9 9 U1 0 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X J9 IMMUNOTHERAPY JI Immunotherapy PD NOV PY 2009 VL 1 IS 6 BP 995 EP 1014 DI 10.2217/IMT.09.67 PG 20 WC Immunology SC Immunology GA 542UV UT WOS:000273524900018 PM 20635915 ER PT J AU Ravindra, PV Tiwari, AK Sharma, B Chauhan, RS AF Ravindra, P. V. Tiwari, Ashok K. Sharma, Bhaskar Chauhan, R. S. TI Newcastle disease virus as an oncolytic agent SO INDIAN JOURNAL OF MEDICAL RESEARCH LA English DT Review DE Cancer; newcastle disease virus; oncolytic virotherapy ID HUMAN TUMOR-CELLS; ACTIVE SPECIFIC IMMUNOTHERAPY; APOPTOSIS-INDUCING LIGAND; MALIGNANT-MELANOMA; INTERFERON-ALPHA; F-PROTEIN; IN-VITRO; PHASE-I; CANCER; INDUCTION AB Cancer is a major cause of deaths in humans. Though there has been significant progress in cancer therapy, the limited efficacy and toxicities of current chemo- and radiotherapics have provided an impetus for the search of new therapeutics. A therapeutic approach, which uses viruses for the treatment of cancer termed, oncolytic virotherapy has recently emerged. Newcastle disease virus (NDV) is one such virus with an inherent oncolytic property. NDV causes a highly infectious disease in poultry worldwide. In humans it is reported to have oncolytic and immuno-stimulatory effects. It specifically replicates in tumour cells while sparing normal cells and cause oncolysis. For many years different strains of the NDV have been investigated for treatment of various human cancers. Recent advances in reverse genetics provided investigators the tools to produce recombinant NDV with improved oncolytic property. C1 [Ravindra, P. V.; Tiwari, Ashok K.; Sharma, Bhaskar; Chauhan, R. S.] Indian Vet Res Inst, Mol Biol Lab, Div Anim Biotechnol, Izatnagar 243122, Uttar Pradesh, India. RP Ravindra, PV (reprint author), NCI, NIH, Bldg 10,Rm 6N 106, Bethesda, MD 20892 USA. EM raviravindra1@gmail.com OI Ravindra, P V/0000-0003-4228-1843 FU University Grants Commission, India FX The authors wish to thank the Director, Indian Veterinary Research Institute, Izatnagar, for providing necessary facilities to carry out the work. The first author (PVR) also acknowledges University Grants Commission, India, for providing financial support in the form of a Senior Research Fellowship. NR 69 TC 24 Z9 28 U1 2 U2 2 PU INDIAN COUNCIL MEDICAL RES PI NEW DELHI PA PO BOX 4911 ANSARI NAGAR, NEW DELHI 110029, INDIA SN 0971-5916 J9 INDIAN J MED RES JI Indian J. Med. Res. PD NOV PY 2009 VL 130 IS 5 BP 507 EP 513 PG 7 WC Immunology; Medicine, General & Internal; Medicine, Research & Experimental SC Immunology; General & Internal Medicine; Research & Experimental Medicine GA 539PA UT WOS:000273266800006 PM 20090097 ER PT J AU Peters, NC Kroeger, DR Mickelwright, S Bretscher, PA AF Peters, Nathan C. Kroeger, David R. Mickelwright, Steven Bretscher, Peter A. TI CD4 T cell cooperation is required for the in vivo activation of CD4 T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD4 T cell activation; CD4 T cell cooperation; peripheral tolerance ID PERIPHERAL TOLERANCE; DENDRITIC CELLS; IMMUNOLOGICAL-TOLERANCE; ANTIGEN PRESENTATION; SELF; INDUCTION; HELPER; DETERMINANTS; LYMPHOCYTES; RESPONSES AB We address here the role of CD4 T cell cooperation in the activation of CD4 T cells. Administration of aggregated hen egg lysozyme (HEL) without microbial adjuvant to BALB/c mice normally generates cytokine-producing CD4 T cells specific for the HEL major peptide, HEL(105-120), as well as CD4 T cells specific for HEL non-major peptides. The prior administration of HEL(105-120) ablates the generation of cytokine-secreting CD4 T cells specific for HEL(105-120), as well as the CD4 T cells specific for HEL non-major peptides, normally generated upon HEL challenge. Thus, the activation of HEL non-major peptide-specific CD4 T cells appears to depend upon the HEL(105-120)-specific CD4 T cell population. In contrast, when HEL(105-120) and saline-treated mice are challenged with HEL coupled to ovalbumin (OVA), CD4 T cell responses to HEL non-major peptides and to OVA are the same, whereas treated mice still do not generate cytokine-secreting cells specific for HEL(105-120). We infer that the administration of HEL(105-120) does not generate regulatory cells capable of down-regulating CD4 T cell responses to HEL and OVA peptides. OVA-specific CD4 T cells restore the generation of HEL non-major peptide-specific T cells in the absence of HEL major peptide-specific T cells. We conclude that the generation of CD4 T cells producing IL-2, IFN-gamma and IL-4 requires CD4 T cell cooperation and that this cooperation is not mediated simply by CD40-CD40L interactions. We also conclude from these observations that there is no requirement for a microbial or danger signal for CD4 T cell activation. C1 [Peters, Nathan C.; Kroeger, David R.; Mickelwright, Steven; Bretscher, Peter A.] Univ Saskatchewan, Coll Med, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada. RP Bretscher, PA (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room B1-12,4 Ctr Dr, Bethesda, MD 20892 USA. EM NPeters@niaid.nih.gov; peter.bretscher@usask.ca FU Canadian Institutes for Health Research [MOP-1412]; Natural Sciences and Engineering Research Council of Canada FX Canadian Institutes for Health Research (MOP-1412 to P.A.B.); Natural Sciences and Engineering Research Council of Canada (to P.A.B.). NR 48 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2009 VL 21 IS 11 BP 1213 EP 1224 DI 10.1093/intimm/dxp085 PG 12 WC Immunology SC Immunology GA 514GK UT WOS:000271382200003 PM 19736293 ER PT J AU Lazarus, BD Love, DC Hanover, JA AF Lazarus, Brooke D. Love, Dona C. Hanover, John A. TI O-GlcNAc cycling: Implications for neurodegenerative disorders SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE Glycosylation; O-GlcNAc transferase; O-GlcNAcase ID LINKED N-ACETYLGLUCOSAMINE; ACTIVATED PROTEIN-KINASE; PANCREATIC BETA-CELLS; COIL DOMAIN PROTEINS; RNA-POLYMERASE-II; INSULIN-RESISTANCE; TAU-PROTEIN; TRANSCRIPTION FACTOR; ALZHEIMERS-DISEASE; GENE-EXPRESSION AB The dynamic post-translational modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc), termed O-GlcNAcylation, is an important mechanism for modulating cellular signaling pathways. O-GlcNAcylation impacts transcription, translation, organelle trafficking, proteasomal degradation and apoptosis. O-GlcNAcylation has been implicated in the etiology of several human diseases including type-2 diabetes and neurodegeneration. This review describes the pair of enzymes responsible for the cycling of this post-translational modification: O-GlcNAc transferase (OGT) and beta-N-acetylglucosaminidase (OGA), with a focus on the function of their structural domains We will also highlight the important processes and substrates regulated by these enzymes, with an emphasis on the role of O-GlcNAc as a nutrient sensor impacting insulin signaling and the cellular stress response Finally, we will focus attention on the many ways by which O-GlcNAc cycling may affect the cellular machinery in the neuroendocrine and central nervous systems. Published by Elsevier Ltd. C1 [Lazarus, Brooke D.; Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biol & Biochem, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biol & Biochem, NIH, Bldg 8,Room 402,9000 Rockville Pike, Bethesda, MD 20897 USA. EM jah@helix.nih.gov FU Intramural NIH HHS [Z01 DK060001-13, Z01 DK060101-01, Z01 DK060102-01, Z01 DK060103-01] NR 142 TC 57 Z9 57 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD NOV PY 2009 VL 41 IS 11 BP 2134 EP 2146 DI 10.1016/j.biocel.2009.03.008 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 510WR UT WOS:000271124700010 PM 19782947 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 Patterns of hematologic malignancies and solid tumors among 37,838 first-degree relatives of 13,896 patients with multiple myeloma in Sweden SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE multiple myeloma; MGUS; solid tumors; bladder cancer; familial aggregation; susceptibility ID POPULATION-BASED SAMPLES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; HODGKIN-LYMPHOMA; FAMILIAL AGGREGATION; LONG-TERM; CANCER; RISK; AUTOIMMUNE; DISORDERS AB There are emerging data to suggest a role for genetic factors in the pathogenesis of multiple myeloma (MM). Based on small numbers, certain solid tumors have been reported to occur more frequently among blood relatives of patients with MM. Using population-based data, we assessed risks for hematologic malignancies, monoclonal gammopathy of undetermined significance (MGUS), and solid tumors among first-degree relatives of patients with MM. We included 13,896 patients with MM and 54,365 matched controls. Also we identified first-degree relatives of patients with MM (n = 37,838) and controls (n = 151,068). Using a marginal survival model, we estimated relative risks (RRs) and 95% confidence intervals (CIs) for hematologic and solid tumors among family members of patients with MM and controls as measures of familial aggregation. Compared with relatives of controls, relatives of patients with MM had an increased risk of developing MM (RR = 2.1; 95% CI 1.6-2.9), MGUS (2.1; 1.5-3.1), acute lymphoblastic leukemia (ALL) (2.1; 1.0-4.2), any solid tumor (1.1; 1.0-1.1) and bladder cancer (1.3; 1.0-1.5). No significantly increased risk was found for other hematologic or solid malignancies. Our findings support a role for a shared susceptibility (genetic, environmental or both) that predisposes to MM, MGUS, ALL and bladder cancer. (C) 2009 UICC C1 [Kristinsson, Sigurdur Y.; Bjorkholm, Magnus; Landgren, Ola] Karolinska Univ Hosp, Dept Med, Div Hematol, Solna & Karolinska Inst, Stockholm, Sweden. [Goldin, Lynn R.; Landgren, Ola] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. [Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, Gothenburg, Sweden. [Wahlin, Anders] Umea Univ, Sect Hematol, Dept Med, Umea, Sweden. [Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Dept Med, Div Hematol, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@karolinska.se RI Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015 OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur /0000-0002-4964-7476 FU Swedish Cancer Society; Stockholm County Council; Karolinska Institutet Foundations; NIH; NCI FX Grant sponsors: Swedish Cancer Society, Stockholm County Council, Karolinska Institutet Foundations, Intramural Research Program of the NIH, NCI. NR 30 TC 34 Z9 35 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 1 PY 2009 VL 125 IS 9 BP 2147 EP 2150 DI 10.1002/ijc.24514 PG 4 WC Oncology SC Oncology GA 506CE UT WOS:000270750000019 PM 19582882 ER PT J AU Wentzensen, N Schiffman, M Dunn, T Zuna, RE Gold, MA Allen, RA Zhang, R Sherman, ME Wacholder, S Walker, J Wang, SS AF Wentzensen, Nicolas Schiffman, Mark Dunn, Terence Zuna, Rosemary E. Gold, Michael A. Allen, Richard A. Zhang, Roy Sherman, Mark E. Wacholder, Sholom Walker, Joan Wang, Sophia S. TI Multiple human papillomavirus genotype infections in cervical cancer progression in the study to understand cervical cancer early endpoints and determinants SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cervical cancer; HPV; SUCCEED; epidemiology; molecular ID ATTRIBUTABLE RISK; HPV TYPES; WOMEN; LESIONS; PREVALENCE; NEOPLASIA; AGE; ACQUISITION; VACCINE; IMPACT AB Determining the causal attribution of human papillomavirus (HPV) genotypes to cervical disease is important to estimate the effect of HPV vaccination and to establish a type spectrum for HPV-based screening. We analyzed the prevalence of HPV infections and their attribution to cervical disease in a population of 1,670 women referred to colposcopy for abnormal cytology at the University of Oklahoma. HPV genotyping was performed from cytology specimens using the Linear Array assay that detects 37 HPV genotypes. We used different methods of type attribution to revised cervical disease categories. We found very high prevalence of multiple HPV infections with up to 14 genotypes detected in single specimens. In all disease categories except for cancers, there was a significant trend of having more infections at a younger age. We did not see type interactions in multiple genotype infections. HPV16 was the most frequent genotype at all disease categories. Based on different attribution strategies, the attribution of vaccine genotypes (6, 11, 16, 18) ranged from 50.5 to 67.3% in cancers (n = 107), from 25.6 to 74.8% in CIN3 (n = 305), from 15.2 to 52.2% in CIN2 (n = 427), and from 6.6 to 26.0% in 600 was 19.2%. Individuals who survived 7 years had a significantly higher frequency of HIV-1 subtype A (P < 0.05), but seroconverters infected with HIV-1A did not have a significantly higher probability of becoming an LTNP. Conclusions: The frequency of LTNPs appears to be relatively high in Uganda and it may be important to take this into account when designing studies of viral pathogenesis and performing HIV vaccine trials in sub-Saharan Africa. C1 [Laeyendecker, Oliver; Redd, Andrew D.; Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Laeyendecker, Oliver; Gamiel, Jordyn; Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21215 USA. [Gray, Ronald H.; Wawer, Maria; Ssempijja, Victor] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21215 USA. [Lutalo, Tom; Bwanika, John Baptist; Makumbi, Fred; Nalugoda, Fred; Opendi, Pius; Kigozi, Godfrey; Ndyanabo, Anthony; Iga, Boaz; Kiwanuka, Noah] Rakai Hlth Sci Program, Entebbe, Uganda. [Makumbi, Fred; Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Sewankambo, Nelson] Makerere Univ, Sch Med, Kampala, Uganda. RP Redd, AD (reprint author), Johns Hopkins Univ, Immunoregulat Lab, NIAID, NIH,Sch Med, Rangos Bldg Room 527,855 N Wolfe St, Baltimore, MD 21215 USA. EM aredd2@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; Redd, Andrew/D-1802-2010; OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760 FU US Army Medical Research and Material Command, Department of the Army [DAMD17-98-2-8007]; Fogarty Foundation, National Institutes of Health [5D43TW00010, 2DTW000010-19]; National Institute of Allergy and Infectious Diseases [R01 A134826]; National Institute of Child Health and Development [5P30HDS06826]; Fogarty Foundation [5D43W00010]; US National Institutes of Health; World Bank Uganda STI; Division of Intramural Research; National Institute of Allergy and Infectious Diseases; National Institutes of Health FX Supported by US Army Medical Research and Material Command, Department of the Army (cooperative agreement DAMD17-98-2-8007): Henry M. Jackson Foundation (grants 5D43TW00010 and 2DTW000010-19 from the Fogarty Foundation, National Institutes of Health. National Institute of Allergy and Infectious Diseases (grant R01 A134826); National Institute of Child Health and Development (grant 5P30HDS06826); Fogarty Foundation (grant 5D43W00010); US National Institutes of Health; World Bank Uganda STI Project. Additional support was provided by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 24 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2009 VL 52 IS 3 BP 316 EP 319 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 511WR UT WOS:000271202900003 PM 19726998 ER PT J AU Elliott-DeSorbo, DK Martin, S Wolters, PL AF Elliott-DeSorbo, Deborah K. Martin, Staci Wolters, Pamela L. TI Stressful Life Events and Their Relationship to Psychological and Medical Functioning in Children and Adolescents With HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE children; HIV disease; psychological functioning; stressful life events ID HUMAN-IMMUNODEFICIENCY-VIRUS; BEHAVIOR ASSESSMENT SYSTEM; SOCIAL SUPPORT; DEPRESSIVE SYMPTOMS; DISEASE PROGRESSION; RATING-SCALES; DISORDERS; VALIDITY; PARENT; YOUTH AB Objectives: To assess the relationship between number and type of stressful life events (SLEs) and psychological and medical functioning in HIV-infected children. Methods: For this cross-sectional study, caregivers of 55 vertically infected children aged 8-17 years completed a measure assessing SLEs occurring in the past 6 months. Children and caregivers both completed a questionnaire assessing the child's level of depression and anxiety. Concurrent demographic and medical data were gathered from chart review. Results: School-related SLEs were the most common type of event and predicted child-reported depressive symptoms. Children who had disclosed their diagnosis in the past 6 months were rated as more anxious by their caregivers than nondisclosers. Also, disclosers had lower CD4 percentages and absolute counts and higher viral load levels and were more likely to have been hospitalized recently. The total number of loss-related SLEs predicted viral load levels. Finally, children who experienced at least 1 financially related SLE had lower CD4 counts and were more likely to have been hospitalized than those experiencing no financial SLEs. Overall, children and caregivers reported nonsignificant levels of child depression and anxiety. Conclusions: Both the total number and type of SLEs experienced have important implications for psychological and medical functioning in HIV-infected youth. C1 [Elliott-DeSorbo, Deborah K.; Martin, Staci; Wolters, Pamela L.] NCI, Neuropsychol Grp, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Elliott-DeSorbo, Deborah K.; Martin, Staci; Wolters, Pamela L.] Med Illness Counseling Ctr, Chevy Chase, MD USA. [Elliott-DeSorbo, Deborah K.] George Washington Univ, Washington, DC USA. RP Martin, S (reprint author), 9030 Old Georgetown Rd,Bldg 82,Room 107, Bethesda, MD 20892 USA. EM martins@mail.nih.gov FU National Institutes of Health, National Cancer Institute [N01-SC-07006, HHSN261200477004C] FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and by federal contracts N01-SC-07006 and HHSN261200477004C. NR 38 TC 11 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2009 VL 52 IS 3 BP 364 EP 370 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 511WR UT WOS:000271202900010 PM 19668083 ER PT J AU Bingham, RJ AF Bingham, Raymond J. TI Annotated Bibliography of NINR Findings on Women's Health Across the Lifespan: 2009 Update SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article C1 NINR, Off Sci Policy & Publ Liaison, NIH, Bethesda, MD 20892 USA. RP Bingham, RJ (reprint author), NINR, Off Sci Policy & Publ Liaison, NIH, 31 Ctr Dr,MSC-2178,Bldg 31,Room 5B-10, Bethesda, MD 20892 USA. EM binghamr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD NOV-DEC PY 2009 VL 38 IS 6 BP 699 EP 702 DI 10.1111/j.1552-6909.2009.01070.x PG 4 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 516EZ UT WOS:000271526000008 PM 19930284 ER PT J AU Williams, LR Degnan, KA Perez-Edgar, KE Henderson, HA Rubin, KH Pine, DS Steinberg, L Fox, NA AF Williams, Lela Rankin Degnan, Kathryn A. Perez-Edgar, Koraly E. Henderson, Heather A. Rubin, Kenneth H. Pine, Daniel S. Steinberg, Laurence Fox, Nathan A. TI Impact of Behavioral Inhibition and Parenting Style on Internalizing and Externalizing Problems from Early Childhood through Adolescence SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Internalizing; Externalizing; Parenting; Temperament; Longitudinal ID CONDUCT PROBLEMS; MATERNAL-BEHAVIOR; CHILDREN; ANXIETY; AUTHORITARIAN; TRAJECTORIES; TEMPERAMENT; PATTERNS; SOCIALIZATION; ASSOCIATION AB Behavioral inhibition (BI) is characterized by a pattern of extreme social reticence, risk for internalizing behavior problems, and possible protection against externalizing behavior problems. Parenting style may also contribute to these associations between BI and behavior problems (BP). A sample of 113 children was assessed for BI in the laboratory at 14 and 24 months of age, self-report of maternal parenting style at 7 years of age, and maternal report of child internalizing and externalizing BP at 4, 7, and 15 years. Internalizing problems at age 4 were greatest among behaviorally inhibited children who also were exposed to permissive parenting. Furthermore, greater authoritative parenting was associated with less of an increase in internalizing behavior problems over time and greater authoritarian parenting was associated with a steeper decline in externalizing problems. Results highlight the importance of considering child and environmental factors in longitudinal patterns of BP across childhood and adolescence. C1 [Degnan, Kathryn A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Williams, Lela Rankin] Arizona State Univ, Sch Social Work, Phoenix, AZ 85004 USA. [Perez-Edgar, Koraly E.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Henderson, Heather A.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. [Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20895 USA. [Steinberg, Laurence] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Degnan, KA (reprint author), Univ Maryland, Dept Human Dev, 3304 Benjamin, College Pk, MD 20742 USA. EM kdegnan@umd.edu OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU Intramural NIH HHS [ZIA MH002781-08, ZIA MH002780-08, ZIA MH002782-08]; NICHD NIH HHS [R01 HD017899, R37 HD017899]; NIMH NIH HHS [R01 MH074454, U01 MH074454] NR 64 TC 66 Z9 67 U1 12 U2 83 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD NOV PY 2009 VL 37 IS 8 BP 1063 EP 1075 DI 10.1007/s10802-009-9331-3 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 510HJ UT WOS:000271078500003 PM 19521761 ER PT J AU Smoski, MJ Felder, J Bizzell, J Green, SR Ernst, M Lynch, TR Dichter, GS AF Smoski, Moria J. Felder, Jennifer Bizzell, Joshua Green, Steven R. Ernst, Monique Lynch, Thomas R. Dichter, Gabriel S. TI fMRI of alterations in reward selection, anticipation, and feedback in major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Unipolar depression; Ventral striatum; Dorsal striatum; Cingulate gyrus; fMRI; Functional magnetic resonance imaging ID ANTERIOR CINGULATE CORTEX; BEHAVIORAL ACTIVATION; NEURAL RESPONSES; DECISION-MAKING; SYSTEMS; ANHEDONIA; DOPAMINE; STIMULI AB The purpose of the present investigation was to evaluate reward processing ill unipolar major depressive disorder (MDD). Specifically, we investigated whether adults with MDD demonstrated hyporesponsivity in striatal brain regions and/or hyperresponsivity in cortical brain regions involved in conflict monitoring using a Wheel of Fortune task designed to probe responses during reward selection, reward anticipation, and reward feedback. Functional magnetic resonance imaging (fMRI) data indicated that the MDD group was characterized by reduced activation of striatal reward regions during reward selection, reward anticipation, and reward feedback, Supporting previous data indicating hyporesponsivity of reward systems in MDD. Support was not found for hyperresponsivity of cognitive control regions during reward selection or reward anticipation. Instead, MDD participants showed hyperresponsivity in orbitofrontal cortex, a region associated with assessment of risk and reward, during reward selection, as well as decreased activation of the middle frontal gyrus and the rostral cingulate gyrus during reward selection and anticipation. Finally, depression severity was predicted by activation in bilateral midfrontal gyrus during reward selection. Results indicate that MDD is characterized by striatal hyporesponsivity, and that future studies of MDD treatments that seek to improve responses to rewarding stimuli should assess striatal functioning. (C) 2009 Elsevier B.V. All rights reserved. C1 [Smoski, Moria J.; Lynch, Thomas R.; Dichter, Gabriel S.] Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. [Dichter, Gabriel S.] Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. [Felder, Jennifer; Bizzell, Joshua; Dichter, Gabriel S.] Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. [Bizzell, Joshua; Green, Steven R.; Dichter, Gabriel S.] Duke Univ, Med Ctr, Duke UNC Brain Imaging & Anal Ctr, Durham, NC 27710 USA. [Ernst, Monique] NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Smoski, MJ (reprint author), Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. EM moria.smoski@duke.edu RI Dichter, Gabriel/K-6726-2015; OI Dichter, Gabriel/0000-0003-3407-5417; Felder, Jennifer/0000-0002-4598-7836; Lynch, Thomas/0000-0003-1270-6097 FU NCRR NIH HHS [K12 RR023248, K12 RR023248-03]; NICHD NIH HHS [K12 HD043446-07, K12 HD043446, T32 HD040127, T32 HD040127-07]; NIMH NIH HHS [K23 MH081285, K23 MH081285-01A1, K23 MH087754, MH078145, R03 MH078145, R03 MH078145-01, R03 MH078145-02, T32 MH070448, T32 MH070448-04, T32-MH070448]; PHS HHS [NCRR K12 RR023248, NICHD K12 HD043446, NICHD T32-HD40127, NIMH K23 MH081285] NR 30 TC 125 Z9 128 U1 4 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 2009 VL 118 IS 1-3 BP 69 EP 78 DI 10.1016/j.jad.2009.01.034 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 506CI UT WOS:000270750500009 PM 19261334 ER PT J AU Fessler, MB Massing, MW Spruell, B Jaramillo, R Draper, DW Madenspacher, JH Arbes, SJ Calatroni, A Zeldin, DC AF Fessler, Michael B. Massing, Mark W. Spruell, Brian Jaramillo, Renee Draper, David W. Madenspacher, Jennifer H. Arbes, Samuel J. Calatroni, Agustin Zeldin, Darryl C. TI Novel relationship of serum cholesterol with asthma and wheeze in the United States SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Lung; asthma; wheeze; cholesterol; atopy; Hispanic ID LOW-DENSITY LIPOPROTEINS; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; RISK-FACTORS; ATHEROSCLEROSIS MESA; PUERTO-RICAN; CARDIOVASCULAR-DISEASE; PULMONARY INFLAMMATION; INSULIN-RESISTANCE; MEXICAN-AMERICANS AB Background: Cholesterol exerts complex effects on inflammation. There has been little investigation of whether serum cholesterol is associated with asthma, an inflammatory airways disease with great public health impact. Objective: To determine relationships between levels of 3 serum cholesterol measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], and non-HDL-C) and asthma/wheeze in a sample representative of the US population. Methods: Cross-sectional study of 7005 participants age; >= 6 years from the 2005 to 2006 National Health and Nutrition Examination Survey. Results: Serum TC and non-HDL-C were lower in patients with current asthma than in subjects without current asthma in the overall population (TC, 188.5 vs 192.2 mg/dL; non-HDL-C, 133.9 vs 137.7 mg/dL; P < .05 for both), whereas HDL-C was not different. Adjusted odds ratios (ORs) from multivariate logistic regression per 1-SD increase of TC and non-HDL-C for current asthma were 0.92 (95% CI, 0.86-0.98) and 0.91 (95% CI, 0.85-0.98), respectively. On racial/ethnic stratification, these relationships reflect marked reductions unique to Mexican Americans (MAs; TC, 171.4 vs 189.3 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.80; non-HDL-C, 119.8 vs 137.9 mg/dL; P < .001; OR, 0.62; 95% CI, 0.48-0.79). Among MAs, the adjusted OR for wheeze requiring medical attention was 0.57 (95% CI, 0.43-0.75) for TC and 0.53 (95% CI, 0.33-0.85) for non-HDL-C. Relationships between cholesterol and asthma/wheeze were independent of body mass index and serum C-reactive protein, and similar between atopic and nonatopic participants. Conclusion: Serum TC and non-HDL-C are inversely related to asthma in the US population, chiefly reflecting a relationship among MAs. (J Allergy Clin Immunol 2009;124:967-74.) C1 [Fessler, Michael B.; Draper, David W.; Madenspacher, Jennifer H.; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Massing, Mark W.; Spruell, Brian; Jaramillo, Renee] SRA Int, Durham, NC USA. [Arbes, Samuel J.; Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC USA. RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,Maildrop D2-01, Res Triangle Pk, NC 27709 USA. EM fesslerm@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 48 TC 23 Z9 23 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2009 VL 124 IS 5 BP 967 EP 974 DI 10.1016/j.jaci.2009.08.005 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 523XI UT WOS:000272108000014 PM 19800678 ER PT J AU Gold, DR Bloomberg, GR Cruikshank, WW Visness, CM Schwarz, J Kattan, M O'Connor, GT Wood, RA Burger, MS Wright, RJ Witter, F Lee-Parritz, A Sperling, R Sadovsky, Y Togias, A Gern, JE AF Gold, Diane R. Bloomberg, Gordon R. Cruikshank, William W. Visness, Cynthia M. Schwarz, John Kattan, Meyer O'Connor, George T. Wood, Robert A. Burger, Melissa S. Wright, Rosalind J. Witter, Frank Lee-Parritz, Aviva Sperling, Rhoda Sadovsky, Yoel Togias, Alkis Gern, James E. TI Parental characteristics, somatic fetal growth, and season of birth influence innate and adaptive cord blood cytokine responses SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Atopy; immune response; cord blood; birth cohort; gestational age; cytokines ID INTERFERON-GAMMA PRODUCTION; HUMAN IMMUNE-SYSTEM; ENVIRONMENTAL ALLERGENS; CHILDHOOD ASTHMA; POSTNATAL-DEVELOPMENT; NORMAL PREGNANCIES; MONONUCLEAR-CELLS; GESTATIONAL-AGE; ATOPIC DISEASE; UNITED-STATES AB Background: Immunologic responses at birth likely relate to subsequent risks for allergic diseases and wheezing in infancy; however, the influences of parental characteristics and prenatal factors on neonatal immune responses are incompletely understood. Objective: This study investigates potential correlations between urban parental, prenatal, and perinatal factors on innate and adaptive stimuli-induced cytokine responses. Methods: Five hundred sixty and 49 children of parents with and without allergic disease or asthma, respectively, were enrolled into a prospective birth cohort study (Urban Environment and Childhood Asthma). Cord blood mononuclear cells were incubated with innate and adaptive immune stimuli, and cytokine responses (ELISA) were compared with season of birth, parental characteristics, in utero stressors, and fetal growth. Results: Many cytokine responses varied by season of birth, including 2-fold to 3-fold fluctuations with specific IFN-alpha and IFN-gamma responses. Birth weight was inversely associated with IFN-gamma responses to respiratory syncytial virus.(R = -0.16), but positively associated with IL-8 responses to a variety of innate stimuli (R = 0.08-0.12). Respiratory syncytial virus-induced cytokine responses were 21% to 54% lower in children of mothers with asthma. Cytokine responses were generally lower in babies born to parents with allergy/asthma. Conclusions: Innate cytokine responses are associated with parental allergic or airway disease, somatic fetal growth, ethnicity, and season of birth. Collectively, these findings suggest that urban prenatal exposures and familial factors affect the development of the fetal immune system. (J Allergy Clin Immunol 2009;124:1078-87.) C1 [Gern, James E.] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Ctr Clin Sci, Madison, WI 53792 USA. [Gold, Diane R.; Wright, Rosalind J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO USA. [Cruikshank, William W.; O'Connor, George T.; Lee-Parritz, Aviva] Boston Univ, Sch Med, Boston, MA 02118 USA. [Visness, Cynthia M.; Schwarz, John] Rho Fed Syst Div Inc, Chapel Hill, NC USA. [Kattan, Meyer] Columbia Univ, Sch Med, New York, NY USA. [Wood, Robert A.; Witter, Frank] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Sperling, Rhoda] Mt Sinai Sch Med, New York, NY USA. [Sadovsky, Yoel] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Togias, Alkis] NIAID, Bethesda, MD 20892 USA. RP Gern, JE (reprint author), Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Ctr Clin Sci, K4-918,600 Highland Ave, Madison, WI 53792 USA. EM gern@medicine.wise.edu OI Lee-Parritz, Aviva/0000-0003-4655-7720; O'Connor, George/0000-0002-6476-3926 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health [NO1-AI-25496, NO1-AI-25482]; National Center for Research Resources, National Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02]; National Institutes of Health (NIH); Environmental Protection Agency; American Thoracic Society; Massachusetts Medical Society; Merck Inc; AstraZeneca FX Disclosure of potential conflict of interest: C. M. Visness is employed by Rho Federal Systems Division, Inc. D. R. Gold receives grant support from the National Institutes of Health (NIH) and the Environmental Protection Agency and is a member of the American Thoracic Society and the Massachusetts Medical Society. G. R. Bloomberg receives grant support from the NIH/National Institute of Allergy and Infectious Diseases. W. W. Cruikshank receives grant support from the NIH. J. Schwarz is employed by Rho. M. Kattan receives grant support from the NIH/National Institute of Allergy and Infectious Diseases. R. A. Wood is on the advisory board for Dey, receives grant support from Genentech and the NIH, and is on the advisory board for Food Allergy and Anaphylaxis Network (FAAN). Y. Sadovsky receives grant support from the NIH. J. E. Gem is on the speakers' bureau for Merck Inc and receives grant support from Merck Inc and AstraZeneca. The rest of the authors have declared that they have no conflict of interest. NR 60 TC 41 Z9 42 U1 2 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2009 VL 124 IS 5 BP 1078 EP 1087 DI 10.1016/j.jaci.2009.08.021 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 523XI UT WOS:000272108000031 PM 19895995 ER PT J AU Westin, AA Huestis, MA Aarstad, K Spigset, O AF Westin, Andreas A. Huestis, Marilyn A. Aarstad, Kjell Spigset, Olav TI Urinary Excretion of 11-Nor-9-Carboxy-Delta(9)-Tetrahydrocannabinol in a Pregnant Woman Following Heavy, Chronic Cannabis Use SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CREATININE RATIO; MARIJUANA USERS; HALF-LIFE; PHARMACOKINETICS; DELTA(9)-THC-COOH; IMMUNOASSAY; METABOLITES; ABSTINENCE; PROFILES C1 [Westin, Andreas A.; Aarstad, Kjell; Spigset, Olav] St Olavs Univ Hosp, Dept Clin Pharmacol, N-7006 Trondheim, Norway. [Huestis, Marilyn A.] NIDA, IRP, NIH, Baltimore, MD USA. [Spigset, Olav] Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway. RP Westin, AA (reprint author), St Olavs Univ Hosp, Dept Clin Pharmacol, Olav Kyrres Gate 17, N-7006 Trondheim, Norway. EM andreas.westin@legemidler.no FU National Institute on Drug Abuse, National Institutes of Health FX The authors gratefully acknowledge Cecilie Semmingsen for her skillful aid in the laboratory. Funding for MAH was from the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 21 TC 5 Z9 5 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 2009 VL 33 IS 9 BP 610 EP 614 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 524NM UT WOS:000272150000006 PM 20040136 ER PT J AU Beck, S Schubert, M Richardson, SP Hallett, M AF Beck, S. Schubert, M. Richardson, S. Pirio Hallett, M. TI Surround inhibition depends on the force exerted and is abnormal in focal hand dystonia SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE transcranial magnetic stimulation; short intracortical inhibition; fine finger movement; movement selection ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; INDIVIDUATED FINGER MOVEMENTS; INTRACORTICAL INHIBITION; WRITERS CRAMP; CORTICOSPINAL CONTROL; PRODUCTION TASKS; PREMOTOR CORTEX; PRECISION GRIP; MUSCLE AB Beck S, Schubert M, Pirio Richardson S, Hallett M. Surround inhibition depends on the force exerted and is abnormal in focal hand dystonia. J Appl Physiol 107: 1513-1518, 2009. First published August 27, 2009; doi: 10.1152/japplphysiol.91580.2008.-There is evidence that surround inhibition (SI), a neural mechanism to enhance contrast between signals, may play a role in primary motor cortex during movement initiation, while it is deficient in patients with focal hand dystonia (FHD). To further characterize SI with respect to different force levels, single- and paired-pulse transcranial magnetic stimulation was applied at rest and during index finger movement to evoke potentials in the nonsynergistic, abductor policis muscle. In Experiment 1, in 19 healthy volunteers, SI was tested using single-pulse transcranial magnetic stimulation. Motor-evoked potentials at rest were compared with those during contraction using four different force levels [5, 10, 20, and 40% of maximum force (F-max)]. In Experiments 2 and 3, SI and short intracortical inhibition (SICI) were tested, respectively, in 16 patients with FHD and 20 age-matched controls for the 10% and 20% F-max levels. SI was most pronounced for 10% F-max and abolished for the 40% F-max level in controls, whereas FHD patients had no SI at all. In contrast, a loss of SICI was observed in FHD patients, which was more pronounced for 10% F-max than for 20% F-max. Our results suggest that SI is involved in the generation of fine finger movements with low-force levels. The greater loss of SICI for the 10% F-max level in patients with FHD than for the 20% F-max level indicates that this inhibitory mechanism is more abnormal at lower levels of force. C1 [Beck, S.; Richardson, S. Pirio; Hallett, M.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. [Beck, S.] Univ Freiburg, Dept Clin Neurol & Neurophysiol, D-7800 Freiburg, Germany. [Schubert, M.] Univ Hosp Balgrist, Spinal Cord Injury Ctr, Zurich, Switzerland. [Richardson, S. Pirio] Univ New Mexico, Dept Neurol, Albuquerque, NM 87131 USA. RP Beck, S (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10-5N240,10 Ctr Dr, Bethesda, MD 20892 USA. EM sandra.beck@miklinik-freiburg.de FU Deutsche Forschungsgemeinschaft [BE-3792/1]; National Institute of Neurological Disorders and Stroke; National Institutes of Health FX This work was supported by the Deutsche Forschungsgemeinschaft (BE-3792/1) and by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health. NR 45 TC 30 Z9 30 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2009 VL 107 IS 5 BP 1513 EP 1518 DI 10.1152/japplphysiol.91580.2008 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 515KO UT WOS:000271468900020 PM 19713426 ER PT J AU Patri, A Umbreit, T Zheng, J Nagashima, K Goering, P Francke-Carroll, S Gordon, E Weaver, J Miller, T Sadrieh, N McNeil, S Stratmeyer, M AF Patri, Anil Umbreit, Thomas Zheng, J. Nagashima, K. Goering, Peter Francke-Carroll, Sabine Gordon, Edward Weaver, James Miller, Terry Sadrieh, Nakissa McNeil, Scott Stratmeyer, Mel TI Energy dispersive X-ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE EDS; electron microscopy; titanium dioxide; nanoparticles; mouse; TiO(2); distribution ID PARTICLES; TOXICITY; TISSUES; LUNGS; SIZE; EDX AB In an effort to understand the disposition and toxicokinetics of nanoscale materials, we used EDS (energy dispersive X-ray spectroscopy) to detect and map the distribution of titanium dioxide (TiO(2)) in tissue sections from mice following either subcutaneous (s.c.) or intravenous (i.v.) injection. TiO(2) nanoparticles were administered at a dose of 560 mg/kg (i.v.) or 5600 mg/kg (s.c.) to Balb/c female mice on two consecutive days. Tissues (liver, kidney, lung, heart, spleen, and brain) were examined by light microscopy, TEM (transmission electron microscopy), SEM (scanning electron microscopy), and EDS following necropsy one day after treatment. Particle agglomerates were detected by light microsopy in all tissues examined, EDS microanalysis was used to confirm that these tissues contained elemental titanium and oxygen. The TEM micrographs and EDS spectra of the aggregates were compared with in vitro measurements of TiO(2) nanoparticle injection solution (i.e., in water). The nanoparticles were also characterized using dynamic light scattering in water, 10 mM NaCl, and phosphate buffered saline (PBS). In low ionic strength solvents (water and 10 mM NaCl), the TiO(2) particles had average hydrodynamic diameters ranging from 114-122 nm. In PBS, however, the average diameter increases to 1-2 mu m, likely due to aggregation analogous to that observed in tissue by TEM and EDS. This investigation demonstrates the suitability of energy dispersive X-ray spectroscopy (EDS) for detection of nanoparticle aggregates in tissues and shows that disposition of TiO(2) nanoparticles depends on the route of administration (i.v. or s.c.). Published in 2009 by John Wiley and Sons, Ltd. C1 [Umbreit, Thomas; Goering, Peter; Gordon, Edward; Stratmeyer, Mel] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. [Patri, Anil; Zheng, J.; Nagashima, K.; McNeil, Scott] SAIC Frederick Inc, Nonotechnol Characterizat Lab, NCI Frederick, Frederick, MD 21702 USA. [Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Weaver, James; Miller, Terry; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, DAPR, Silver Spring, MD 20903 USA. RP Umbreit, T (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. EM thomos.umbreit@fda.hhs.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012 FU National Cancer Institute, National Institutes of Health [N01-CO-12400, HHSN261200800001E] FX This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contracts N01-CO-12400 and HHSN261200800001E. NR 11 TC 28 Z9 31 U1 3 U2 35 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV PY 2009 VL 29 IS 8 BP 662 EP 672 DI 10.1002/jat.1454 PG 11 WC Toxicology SC Toxicology GA 526SQ UT WOS:000272314300004 PM 19626582 ER PT J AU Black, DO Wallace, GL Sokoloff, JL Kenworthy, L AF Black, David O. Wallace, Gregory L. Sokoloff, Jennifer L. Kenworthy, Lauren TI IQ Split Predicts Social Symptoms and Communication Abilities in High-Functioning Children with Autism Spectrum Disorders SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Cognitive profiles; IQ; Symptomatology; Adaptive functioning; Asperger syndrome ID DEVELOPMENTAL DISORDERS; DIAGNOSTIC INTERVIEW; EXECUTIVE FUNCTION; INDIVIDUALS; PROFILES AB We investigated the relationship of discrepancies between VIQ and NVIQ (IQ split) to autism symptoms and adaptive behavior in a sample of high-functioning (mean FSIQ = 98.5) school-age children with autism spectrum disorders divided into three groups: discrepantly high VIQ (n = 18); discrepantly high NVIQ (n = 24); and equivalent VIQ and NVIQ (n = 36). Discrepantly high VIQ and NVIQ were associated with autism social symptoms but not communication symptoms or repetitive behaviors. Higher VIQ and NVIQ were associated with better adaptive communication but not socialization or Daily Living Skills. IQ discrepancy may be an important phenotypic marker in autism. Although better verbal abilities are associated with better functional outcomes in autism, discrepantly high VIQ in high-functioning children may also be associated with social difficulties. C1 [Black, David O.] NIMH, Pediat Dev Neurosci Branch, Bethesda, MD 20892 USA. [Wallace, Gregory L.] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. [Sokoloff, Jennifer L.; Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD USA. RP Black, DO (reprint author), NIMH, Pediat Dev Neurosci Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM blackdavid@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [U54 MH066417, U54 MH066417-05] NR 27 TC 36 Z9 36 U1 1 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD NOV PY 2009 VL 39 IS 11 BP 1613 EP 1619 DI 10.1007/s10803-009-0795-3 PG 7 WC Psychology, Developmental SC Psychology GA 505DO UT WOS:000270669300015 PM 19572193 ER PT J AU Chiorini, JA Cihakova, D Ouellette, CE Caturegli, P AF Chiorini, J. A. Cihakova, D. Ouellette, C. E. Caturegli, P. TI Sjogren syndrome: Advances in the pathogenesis from animal models SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Sjogren syndrome; Mouse models; Autoimmunity ID LYMPHOID-TISSUE LYMPHOMA; SYNDROME-LIKE DISEASE; SALIVARY-GLAND; CLASSIFICATION CRITERIA; AUTOIMMUNE-DISEASES; PULMONARY INVOLVEMENT; CARBONIC-ANHYDRASE; LUNG INVOLVEMENT; INTERFERON-GAMMA; AIRWAY DISEASE AB Sjogren syndrome is an autoimmune disease characterized by hyposecretion of the lacrimal and salivary glands, resulting in dryness of the eyes and mouth. Individuals may experience primary Sjogren syndrome or a secondary form accompanying another rheumatic autoimmune disease, such as rheumatoid arthritis or systemic lupus erythematosus. The pathogenic mechanisms of Sjogren syndrome remain largely unknown, in part a consequence of the heterogeneity of the disease. Animal models have shed light on the connections between specific pathways and symptoms, but an ideal system is wanting. Improved disease models will enable a better understanding of Sjogren syndrome, including how immune tolerance is lost and potential therapeutic interventions. Most importantly, an optimal model will enable detection of disease biomarkers, since injury to the salivary glands may precede lymphocytic infiltration. This review aims to characterize available mice models of Sjogren syndrome, including advantages and disadvantages, from the researcher's perspective. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Chiorini, J. A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD USA. [Cihakova, D.; Caturegli, P.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Ouellette, C. E.; Caturegli, P.] Johns Hopkins Bloomberg Sch Publ Hlth, Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Caturegli, P (reprint author), Johns Hopkins Pathol Ross 632,720 Rutland Ave, Baltimore, MD 21205 USA. EM pcat@jhmi.edu RI Cihakova, Daniela /A-9821-2017 OI Cihakova, Daniela /0000-0002-8713-2860 FU Sjogren Syndrome Foundation; NIH NIDCR intramural researc FX This manuscript was supported by a grant from the Sjogren Syndrome Foundation to PC, and an NIH NIDCR intramural research grant to JAC. NR 80 TC 48 Z9 50 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV-DEC PY 2009 VL 33 IS 3-4 BP 190 EP 196 DI 10.1016/j.jaut.2009.09.009 PG 7 WC Immunology SC Immunology GA 534KZ UT WOS:000272896800005 PM 19800762 ER PT J AU Subleski, JJ Wiltrout, RH Weiss, JM AF Subleski, Jeff J. Wiltrout, Robert H. Weiss, Jonathan M. TI Application of tissue-specific NK and NKT cell activity for tumor immunotherapy SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE NK cells; NKT cells; Liver microenvironment; Immunotherapy; Cancer ID NATURAL-KILLER-CELLS; APOPTOSIS-INDUCING LIGAND; IFN-GAMMA; IMMUNE-RESPONSE; T-CELLS; IN-VIVO; ALPHA-GALACTOSYLCERAMIDE; IMMUNOREGULATORY AXIS; RECEPTOR EXPRESSION; CRITICAL-APPRAISAL AB Natural killer (NK) and NKT cells are a first line of defense against pathogens and transformed cells. However, dysregulation of their function can lead to autoimmune disease. A better understanding of the mechanisms controlling NK and NKT effector function should lead to the development of improved strategies for the treatment of many diseases. The site in which NK and NKT cells reside should be taken into account, because accumulating evidence suggests that the tissue microenvironment strongly influences their function. In this regard, the liver represents a unique immunologic organ in which the balance between the need for tolerance and the ability to respond rapidly to pathogens and tissue injury is tightly regulated. NK cells in the liver have augmented cytolytic activity as compared to other organs, which is consistent with a role for liver-associated NK cells in being critical effector cells for inhibiting tumor metastasis in the liver. Several studies also suggest that hepatic NKT cells have different functions than those in other organs. Whereas splenic and thymic NKT cells have been shown to suppress diabetes development, facilitate the induction of systemic tolerance and are regulated by IL-4 and other Th2 cytokines, certain subsets of NKT cells in the liver are important sources of Th1 cytokines such as Interferon gamma, and are the primary mediators of anti-tumor responses. The unique properties and roles as critical effector cells make NK and NKT cells within the liver microenvironment attractive targets of immunotherapeutic approaches that have the goal of controlling tumor metastasis in the liver. Published by Elsevier Ltd. C1 [Subleski, Jeff J.; Wiltrout, Robert H.; Weiss, Jonathan M.] Natl Canc Inst, Canc & Inflammat Program, Ft Detrick, MD 21702 USA. RP Weiss, JM (reprint author), Natl Canc Inst, Canc & Inflammat Program, 1050 Boyles St, Ft Detrick, MD 21702 USA. EM jsubleski@mail.ncifcrf.gov; wiltrour@mail.nih.gov; weissj@ncifcrf.gov FU Intramural NIH HHS [Z99 CA999999] NR 75 TC 31 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV-DEC PY 2009 VL 33 IS 3-4 BP 275 EP 281 DI 10.1016/j.jaut.2009.07.010 PG 7 WC Immunology SC Immunology GA 534KZ UT WOS:000272896800016 PM 19682859 ER PT J AU Torchia, DA AF Torchia, Dennis A. TI Slight mistuning of a cryogenic probe significantly perturbs the water H-1 precession frequency SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE Probe; Tuning; Water; Proton; Precession; Frequency; Chemical shift; Reference ID NMR; ASSIGNMENT AB A shift of the water proton precession frequency is described that can introduce errors in chemical shifts derived using the water signal as the chemical shift reference. This shift, f(s), arises as a consequence of radiation damping when the water proton and detector circuit resonance frequencies differ. Herein it is shown that experimental values of f(s), measured as a function of detector circuit tuning offset for 500 and 900 MHz cryogenic probes, are in good agreement with theory. Of importance is the fact that even a small degree of mistuning, which does not significantly impact the performance of a pulse sequence, introduces chemical shift errors of +/- 0.03 ppm, that negatively impact many types of experiments. A simple remedy that attenuates the frequency shift is presented. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. EM dtorchia@mail.nih.gov FU Intramural AIDS Targeted Anti-Viral Program of the Office of the Director of the National Institutes of Health FX I am grateful to Ad Bax for encouragement and helpful discussions. I also thank Ad and Jinfa Ying for their help in measuring the 900 MHz data. This work was supported by the Intramural AIDS Targeted Anti-Viral Program of the Office of the Director of the National Institutes of Health. NR 13 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD NOV PY 2009 VL 45 IS 3 BP 241 EP 244 DI 10.1007/s10858-009-9363-6 PG 4 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 507RF UT WOS:000270871600001 PM 19669101 ER PT J AU Katz, SI AF Katz, Stephen I. TI Training at the NIAMS: Ensuring a Vibrant Future for Musculoskeletal Research SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material RP Katz, SI (reprint author), NIAMSD, NIH, 31 Ctr Dr,MSC 2350,Bldg 31,Room 4C32, Bethesda, MD 20892 USA. EM katzs@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2009 VL 91A IS 11 BP 2743 EP 2744 DI 10.2106/JBJS.I.01071 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 518DZ UT WOS:000271671800029 PM 19884452 ER PT J AU Szabova, L Yamada, SS Wimer, H Chrysovergis, K Ingvarsen, S Behrendt, N Engelholm, LH Holmbeck, K AF Szabova, Ludmila Yamada, Susan S. Wimer, Helen Chrysovergis, Kaliopi Ingvarsen, Signe Behrendt, Niels Engelholm, Lars H. Holmbeck, Kenn TI MT1-MMP and Type II Collagen Specify Skeletal Stem Cells and Their Bone and Cartilage Progeny SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE membrane-type 1 matrix metalloproteinase; type II collagen; bone cells; cartilage; bone marrow stromal cell; transgenic mouse ID MATRIX METALLOPROTEINASES; EXTRACELLULAR-MATRIX; IN-VIVO; TISSUE INHIBITOR; TRABECULAR BONE; MEMBRANE; MICE; CHONDROCYTES; DEGRADATION; ACTIVATION AB Skeletal formation is dependent on timely recruitment of skeletal stem cells and their ensuing synthesis and remodeling of the major fibrillar collagens, type I collagen and type II collagen, in bone and cartilage tissues during development and postnatal growth. Loss of the major collagenolytic activity associated with the membrane-type I matrix metalloproteinase (MT1-MMP) results in disrupted skeletal development and growth in both cartilage and bone, where MT1-MMP is required for pericellular collagen dissolution. We show here that reconstitution of MT1-MMP activity in the type It collagen-expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified in bone cells and skeletal stem/progenitor cells of wildtype mice. Moreover, bone marrow stromal cells isolated from mice expressing MT1-MMP under the control of the type II collagen promoter in an MTI-MMP-deficient background showed enhanced bone formation in vitro and in vivo compared with cells derived from nontransgenic MT1-MMP-deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic and osteogenic lineage progeny where collagenolytic activity is a requisite for proper cell and tissue function. J Bone Miner Res 2009;24:1905-1916. Published online on May 5, 2009; doi: 10.1359/JBMR.090510 C1 [Szabova, Ludmila; Yamada, Susan S.; Wimer, Helen; Chrysovergis, Kaliopi; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Ingvarsen, Signe; Behrendt, Niels; Engelholm, Lars H.] Rigshosp, Finsen Lab, DK-2100 Copenhagen N, Denmark. RP Holmbeck, K (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30,Room 125,30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. EM kenn.holmbeck@nih.gov OI Engelholm, Lars/0000-0002-6616-1232 FU DIR; NIDCR of the IRP; NIH; European Union [LSHC-CT-2003-50329]; European Union FP7; Danish Cancer Society; Danish Cancer Research Foundation; Lundbeck Foundation; Danish Medical Research Council; University of Copenhagen FX The authors thank Paniela Gehron Robey, PhD, for comments and critical reading of the manuscript. This study was supported by the DIR, NIDCR of the IRP, NIH, and by European Union contract LSHC-CT-2003-50329 (FP6), by the European Union FP7 program and by grants from the Danish Cancer Society, the Danish Cancer Research Foundation, the Lundbeck Foundation, and the Danish Medical Research Council. S.I. has a personal grant from the University of Copenhagen, the Faculty of Science. NR 40 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2009 VL 24 IS 11 BP 1905 EP 1916 DI 10.1359/JBMR.090510 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 518XU UT WOS:000271730200015 PM 19419317 ER PT J AU Bagorda, A Das, S Rericha, EC Chen, D Davidson, J Parent, CA AF Bagorda, Anna Das, Satarupa Rericha, Erin C. Chen, David Davidson, Jean Parent, Carole A. TI Real-time measurements of cAMP production in live Dictyostelium cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE Chemotaxis; cAMP; FRET; Dictyostelium discoideum ID DEPENDENT PROTEIN-KINASE; ADENYLYL-CYCLASE; MEDIATED ACTIVATION; SIGNALING NETWORKS; CYCLIC-AMP; DISCOIDEUM; DIFFERENTIATION; CHEMOTAXIS; EXPRESSION; OSCILLATIONS AB Cyclic AMP has a crucial role during the entire developmental program of the social amoebae Dictyostelium, acting both as an intracellular second messenger and, when secreted, as a directional cue that is relayed to neighboring cells during chemotaxis. Although significant knowledge about cAMP production in chemotaxing cells has been derived from studies performed on cell populations, cAMP dynamics at the single cell level have not been investigated. To examine this, we used a FRET-based cAMP sensor that possesses high cAMP sensitivity and great temporal resolution. We show the transient profile of cAMP accumulation in live Dictyostelium cells and establish that chemoattractants control intracellular cAMP dynamics by regulating synthesis via the adenylyl cyclase ACA. aca-cells show no significant change in FRET response following chemoattractant addition. Furthermore, cells lacking ACB, the other adenylyl cyclase expressed in chemotaxing cells, behave similarly to wild-type cells. We also establish that the RegA is the major phosphodiesterase that degrades intracellular cAMP in chemotaxis-competent cells. Interestingly, we failed to measure intracellular cAMP compartmentalization in actively chemotaxing cells. We conclude that cytosolic cAMP, which is destined to activate PKA, is regulated by ACA and RegA and does not compartmentalize during chemotaxis. C1 [Bagorda, Anna; Das, Satarupa; Chen, David; Davidson, Jean; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rericha, Erin C.] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20740 USA. RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM parentc@mail.nih.gov RI Davidson, Jean/G-7558-2012; OI Davidson, Jean/0000-0001-5951-5955; Das, Satarupa/0000-0002-4217-9972 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Italian Cancer Federation; Burroughs Wellcome fund FX We thank Manuela Zaccolo for providing the RII-CFP and C-YFP plasmids and the Dictyostelium Stock Center for providing the acb- and regA- cells. We also thank Michael Maurizi for allowing us to use his luminescence spectrometer and for his precious help to measure in vitro FRET as well as Alex Braiman and Valarie Barr for helping set up the in vivo FRET experiments and Gene Garcia for providing the partially purified PdsA. We would like to thank the Parent and Losert lab members as well as Paul Randazzo for excellent discussions and suggestions. This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. A. B. is a recipient of an Italian Cancer Federation Fellowship. E. C. R. is a recipient of a Career Award at the Scientific Interface from the Burroughs Wellcome fund. Deposited in PMC for release after 12 months. NR 39 TC 14 Z9 14 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2009 VL 122 IS 21 BP 3907 EP 3914 DI 10.1242/jcs.051987 PG 8 WC Cell Biology SC Cell Biology GA 515MK UT WOS:000271475600010 PM 19808889 ER PT J AU Chen, Y Veracini, L Benistant, C Jacobson, K AF Chen, Yun Veracini, Laurence Benistant, Christine Jacobson, Ken TI The transmembrane protein CBP plays a role in transiently anchoring small clusters of Thy-1, a GPI-anchored protein, to the cytoskeleton SO JOURNAL OF CELL SCIENCE LA English DT Article DE Lipid rafts; Signal transduction; Single-particle tracking; GPI-anchored proteins; CFTR; Thy-1; Cytoskeleton ID EXCHANGER REGULATORY FACTOR; T-CELL-ACTIVATION; LIPID RAFTS; CONDUCTANCE REGULATOR; ENRICHED MICRODOMAINS; SIGNAL-TRANSDUCTION; ADAPTER PROTEINS; PDZ INTERACTIONS; RECEPTOR; MEMBRANE AB It remains unclear how GPI-anchored proteins (GPIAPs), which lack cytoplasmic domains, transduce signals triggered by specific ligation. Such signal transduction has been speculated to require the ligated GPIAP to associate with membrane-spanning proteins that communicate with obligate cytoplasmic proteins. Transient anchorage of crosslinked proteins on the cell surface was previously characterized by single-particle tracking, and temporary association with the actin cytoskeleton was hypothesized to cause regulated anchorage. GPIAPs, such as Thy-1, require clustering, cholesterol and Src-family kinase (SFK) activity to become transiently anchored. By contrast, a transmembrane protein, the cystic fibrosis transmembrane conductance regulator (CFTR), which has a PDZ-binding motif in its cytoplasmic C-terminus that binds the ERM adaptor EBP50, exhibits anchorage that strictly requires EBP50 but has little dependence on cholesterol or SFK. We hypothesized that a transmembrane protein would be required to mediate the linkage between Thy-1 and the cytoskeleton. Here, we present evidence, obtained by shRNA knockdown, that the transmembrane protein Csk-binding protein (CBP) plays an obligatory role in the transient anchorage of Thy1. Furthermore, either a dominant-negative form of CBP that did not bind EBP50 or a dominant-negative EBP50 drastically reduced transient anchorage of Thy-1, indicating the involvement of this adaptor. Finally, we speculate on the role of phosphorylation in the regulation of transient anchorage. C1 [Chen, Yun; Jacobson, Ken] Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. [Jacobson, Ken] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Chen, Yun] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20815 USA. [Veracini, Laurence; Benistant, Christine] Univ Montpellier 1, CRBM, CNRS, UMR5237, F-34293 Montpellier, France. [Veracini, Laurence; Benistant, Christine] Univ Montpellier 2, F-34293 Montpellier, France. RP Jacobson, K (reprint author), Univ N Carolina, Sch Med, Dept Cell & Dev Biol, Chapel Hill, NC 27599 USA. EM frap@med.unc.edu OI Chen, Yun/0000-0001-6917-7814 FU NIH [GM 41402]; NIH Cell Migration Consortium (NIH) [GM 64346] FX This work was supported by NIH GM 41402 and the NIH Cell Migration Consortium (NIH GM 64346). We thank Bing Yang for excellent technical assistance. We also thank Vaclav Horejsi for CBP constructs and antibodies. Deposited in PMC for release after 12 months. NR 35 TC 31 Z9 31 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2009 VL 122 IS 21 BP 3966 EP 3972 DI 10.1242/jcs.049346 PG 7 WC Cell Biology SC Cell Biology GA 515MK UT WOS:000271475600016 PM 19825940 ER PT J AU Shi, SL Li, QF Liu, QR Xu, DH Tang, J Liang, Y Zhao, ZL Yang, LM AF Shi, Song-Lin Li, Qi-Fu Liu, Qing-Rong Xu, Dong-Hui Tang, Jian Liang, Ying Zhao, Zhen-Li Yang, Li-Ming TI Nuclear Matrix Protein, Prohibitin, Was Down-Regulated and Translocated From Nucleus to Cytoplasm During the Differentiation of Osteosarcoma MG-63 Cells Induced by Ginsenoside Rg1. Cinnamic acid, and Tanshinone IIA (RCT) SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE CELL DIFFERENTIATION; HUAMAN OSTEOSARCOMA MG-63 CELLS; NUCLEAR MATRIX; PROHIBITIN ID GENE; REPRESSION; IDENTIFICATION; COMPLEX; GROWTH; CANCER; RB AB Ginsenoside Rg1, cinnamic acid, and tanshinone IIA (RCT) are effective anticancer and antioxidant constituents of traditional Chinese herbal medicines of Ginseng, Xuanseng, and Danseng. The molecular mechanisms of anticancer effects of those constituents and their targets are unknown. Prohibitin, an inner membrane-bound chaperone in mitochondrion involved in the regulation of cell growth, proliferation, differentiation, aging, and apoptosis, was chosen as a candidate molecular target because of its frequent up-regulation in various cancer cells. We demonstrated that prohibitin existed in the filaments of the nuclear matrix of the MG-63 cell and its expression was down-regulated by the treatment of RCT using proteomic methodologies and Western blot analysis. Immunogold electro-microscopy also found that prohibitin was localized on nuclear matrix intermediate filaments (NM-IF) that had undergone restorational changes after RCT treatment. Prohibitin may function as a molecular chaperone that might interact with multiple oncogenes and tumor suppressor genes. We found that oncogenes c-myc and c-fos and tumor suppressor genes P53 and Rb were regulated by RCT as well and that these gene products co-localized with prohibitin. Our study identified prohibitin as a molecular target of the effective anticancer constituents of Ginseng, Xuanseng, and Danseng that downregulated prohibitin in nuclear matrix, changed prohibtin trafficking from nucleolus to cytoplasm, and regulated several oncogenes and tumor suppressor genes. Prohibitin downregulation and cellular trafficking from nucleolus to cytoplasm indicated RCT protective roles in cancer prevention and treatment. J. Cell. Biochem. 108: 926-934, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Shi, Song-Lin; Li, Qi-Fu; Tang, Jian; Liang, Ying; Zhao, Zhen-Li; Yang, Li-Ming] Xiamen Univ, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Sch Life Sci, Xiamen 361005, Peoples R China. [Liu, Qing-Rong] Natl Inst Drug Abuse, Mol Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. [Xu, Dong-Hui] Fujian Med Univ, Dept Hepatobiliary Pancreas Vasc Surg, Affiliated Xiamen Hosp 1, Xiamen 361003, Peoples R China. RP Li, QF (reprint author), Xiamen Univ, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Sch Life Sci, Xiamen 361005, Peoples R China. EM chifulee@xmu.edu.cn RI Li, QF/G-4604-2010; Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU National Natural Science Foundation of China [30871241]; Natural Science Foundation of Fujian Province of China [2008J0302]; China Postdoctoral Science Foundation [20070420754] FX Grant sponsor: National Natural Science Foundation of China; Grant number: 30871241; Grant sponsor: Natural Science Foundation of Fujian Province of China; Grant number: 2008J0302; Grant sponsor: China Postdoctoral Science Foundation; Grant number: 20070420754. NR 28 TC 20 Z9 23 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2009 VL 108 IS 4 BP 926 EP 934 DI 10.1002/jcb.22324 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 515TI UT WOS:000271495400021 PM 19725052 ER PT J AU Pillai, DR Dittmar, MS Baldaranov, D Heidemann, RM Henning, EC Schuierer, G Bogdahn, U Schlachetzki, F AF Pillai, Deepu R. Dittmar, Michael S. Baldaranov, Dobri Heidemann, Robin M. Henning, Erica C. Schuierer, Gerhard Bogdahn, Ulrich Schlachetzki, Felix TI Cerebral ischemia-reperfusion injury in rats-A 3 T MRI study on biphasic blood-brain barrier opening and the dynamics of edema formation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE blood-brain barrier; cerebral edema; magnetic resonance imaging; stroke ID ARTERY OCCLUSION; FOCAL ISCHEMIA; TIGHT JUNCTION; STROKE; PERMEABILITY; WATER; DISRUPTION; INFARCTION; PROTEINS; ALBUMIN AB Serial magnetic resonance imaging (MRI) was performed to investigate the temporal and spatial relationship between the biphasic nature of blood-brain barrier (BBB) opening and, in parallel, edema formation after ischemia-reperfusion (I/R) injury in rats. T(2)-weighted imaging combined with T(2)-relaxometry, mainly for edema assessment, was performed at 1 h after ischemia, after reperfusion, and at 4, 24 and 48 h after reperfusion. T(1)-weighted imaging was performed before and after gadolinium contrast at the last three time points to assess BBB integrity. The biphasic course of BBB opening with a significant reduction in BBB permeability at 24 h after reperfusion, associated with a progressive expansion of leaky BBB volume, was accompanied by a peak ipsilateral edema formation. In addition, at 4 h after reperfusion, edema formation could also be detected at the contralateral striatum as determined by the elevated T(2)-values that persisted to varying degrees, indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in the mechanisms responsible for biphasic BBB permeability changes, with complex relations to edema formation. Stroke therapy aimed at vasogenic edema and drug delivery for neuroprotection may also be guided according to the functional status of the BBB, and these findings have to be confirmed in human stroke. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 1846-1855; doi:10.1038/jcbfm.2009.106; published online 5 August 2009 C1 [Schlachetzki, Felix] Univ Regensburg, Med Ctr, Dept Neurol, Bezirksklinikum, D-93053 Regensburg, Germany. [Dittmar, Michael S.] Univ Regensburg, Med Ctr, Dept Anaesthesiol, D-93053 Regensburg, Germany. [Heidemann, Robin M.] Max Planck Inst Human Cognit & Brain Sci, Dept Neurophys, Leipzig, Germany. [Henning, Erica C.] NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA. [Schuierer, Gerhard] Univ Regensburg, Med Ctr, Ctr Neuroradiol, Bezirksklinikum, D-93053 Regensburg, Germany. RP Schlachetzki, F (reprint author), Univ Regensburg, Med Ctr, Dept Neurol, Bezirksklinikum, Univ Str 84, D-93053 Regensburg, Germany. EM felix.schlachetzki@klinik.uni-regensburg.de RI Henning, Erica/E-8542-2010 FU Bayerische Forschungsgemeinschaft; Bavarian State Ministry of Sciences, Research and the Arts, 'For-NeuroCell' FX DR Pillai was supported by a grant from 'Bayerische Forschungsgemeinschaft' and by the Bavarian State Ministry of Sciences, Research and the Arts, 'For-NeuroCell' grant. We thank the 'Achtzehn Medical Service' (Erlangen, Germany) for donation of anesthetic equipment. NR 39 TC 44 Z9 46 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2009 VL 29 IS 11 BP 1846 EP 1855 DI 10.1038/jcbfm.2009.106 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 514XK UT WOS:000271429500013 PM 19654585 ER PT J AU Reeb-Sutherland, BC Vanderwert, RE Degnan, KA Marshall, PJ Perez-Edgar, K Chronis-Tuscano, A Pine, DS Fox, NA AF Reeb-Sutherland, Bethany C. Vanderwert, Ross E. Degnan, Kathryn A. Marshall, Peter J. Perez-Edgar, Koraly Chronis-Tuscano, Andrea Pine, Daniel S. Fox, Nathan A. TI Attention to novelty in behaviorally inhibited adolescents moderates risk for anxiety SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Temperament; anxiety; adolescence; attention; risk factors ID EVENT-RELATED POTENTIALS; MISMATCH NEGATIVITY; YOUNG-CHILDREN; SOCIAL ANXIETY; DISORDERS; RESPONSES; TEMPERAMENT; ASSOCIATION; CHILDHOOD; SOLITUDE AB Background: Individual differences in specific components of attention contribute to behavioral reactivity and regulation. Children with the temperament of behavioral inhibition (BI) provide a good context for considering the manner in which certain components of attention shape behavior. Infants and children characterized as behaviorally inhibited manifest signs of heightened orienting to novelty. The current study considers whether this attention profile moderates risk for clinical anxiety disorders among adolescents with a history of BI. Methods: Participants were assessed at multiple time points for BI, beginning in early childhood. At adolescence, event-related potentials (ERPs) were recorded during a three-stimulus auditory novelty oddball task, which employed frequent standard and infrequent deviant tones as well as a set of complex, novel sounds. Clinical diagnosis was carried out using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). P3 and mismatch negativity (MMN) components were examined at midline frontal, central, and parietal electrode sites. Results: Individuals who displayed high levels of BI during childhood and increased P3 amplitude to novelty in adolescence were more likely to have a history of anxiety disorders compared to behaviorally inhibited adolescents with lower P3 amplitudes. Groups did not differ on measures of MMN. Conclusions: Increased neural responses to novelty moderate risk for anxiety disorders amongst individuals with a history of BI. C1 [Reeb-Sutherland, Bethany C.; Vanderwert, Ross E.; Degnan, Kathryn A.; Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA. [Marshall, Peter J.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA. [Chronis-Tuscano, Andrea] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Pine, Daniel S.] NIMH, Emot Dev & Affect Neurosci Branch, Bethesda, MD 20892 USA. RP Reeb-Sutherland, BC (reprint author), Univ Maryland, Dept Human Dev, 3304 Benjamin Bldg, College Pk, MD 20742 USA. EM breeb@umd.edu OI Vanderwert, Ross/0000-0002-2280-8401; Perez-Edgar, Koraly/0000-0003-4051-9563 FU National Institutes of Health [MH074454, HD 17899] FX This project was supported by grants from the National Institutes of Health (MH074454 and HD 17899) to Nathan A. Fox. The authors would like to thank children and their families for their continued participation in our studies. NR 40 TC 24 Z9 24 U1 2 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2009 VL 50 IS 11 BP 1365 EP 1372 DI 10.1111/j.1469-7610.2009.02170.x PG 8 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 507CS UT WOS:000270829100006 PM 19788588 ER PT J AU Manian, N Bornstein, MH AF Manian, Nanmathi Bornstein, Marc H. TI Dynamics of emotion regulation in infants of clinically depressed and nondepressed mothers SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE Emotion regulation; maternal depression; mother-infant interaction; still-face paradigm; sequential analysis ID STILL-FACE PARADIGM; MATERNAL DEPRESSION; VAGAL REGULATION; SYNCHRONY; SENSITIVITY; DISTRESS; BEHAVIOR AB Background: Emotion regulation (ER) has been conceptualized as an ongoing process of the individual's emotion patterns in relation to moment-to-moment contextual demands. In contrast to traditional approaches of descriptively quantizing ER, we employed a dynamic approach to ER by examining key transitions in infants of clinically depressed and nondepressed mothers in the context of maternal still-face (SF). Methods: Mothers with (n = 48) and without a clinical diagnosis of depression (n = 68) were seen in a modified SF paradigm with their 5-month-olds. Infant states and self-soothing behaviors were coded in 1-sec time intervals. Results: Infants of nondepressed mothers used attentional regulatory strategies, whereas infants of depressed mothers used internally directed strategies of self-soothing to reduce negativity and maintain engagement with mother. Conclusions: This study advances our understanding of processes underlying infant ER and points to possible mechanisms for the development of long-term maladaptive ER strategies in infants of depressed mothers. C1 [Manian, Nanmathi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Manian, N (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM maniann@mail.nih.gov FU NIH, NICHD FX We thank the parents and children who have repeatedly given their time and effort to participate in this research. We also thank Elizabeth Conradt, Jennifer Meeter, Alexandra Palchuk, Stephanie Shapiro, Sharon Smith, Joan Suwalsky, and Alice Winstanley for coding videorecords. This research was supported by the Intramural Research Program of the NIH, NICHD. NR 36 TC 25 Z9 25 U1 1 U2 17 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2009 VL 50 IS 11 BP 1410 EP 1418 DI 10.1111/j.1469-7610.2009.02166.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 507CS UT WOS:000270829100011 PM 19788549 ER PT J AU Shakleya, DM Huestis, MA AF Shakleya, Diaa M. Huestis, Marilyn A. TI Simultaneous and sensitive measurement of nicotine, cotinine, trans-3 '-hydroxycotinine and norcotinine in human plasma by liquid chromatography-tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Nicotine; Cotinine; trans-3 '-Hydroxycotinine; Norcotinine; Plasma; LC-MS/MS ID SOLID-PHASE EXTRACTION; GAS-CHROMATOGRAPHY; URINARY NICOTINE; METABOLITES; SMOKERS; RADIOIMMUNOASSAY; QUANTIFICATION; DISPOSITION; MECONIUM; CAFFEINE AB An LC-MS/MS method for the simultaneous quantification of nicotine, cotinine. trans-T-hydroxycotinine and norcotinine in human plasma was developed and fully validated. Potential endogenous and exogenous interferences were extensively evaluated and limits of quantification were determined by decreasing analyte concentration. Analytical ranges were 1-500 ng/mL for nicotine and cotinine, 5-500 ng/mL for trans-3'-hydroxycotinine and norcotinine. Mean intra- and inter-assay analytical recoveries were between 101.9 and 116.8%, and intra-and inter-assay imprecision were less than 11% RSD for all analytes: parameters were evaluated at three different concentrations across the linear range of the assay. Extraction efficiency was >= 70% for all analytes. This validated method is useful for the determination of nicotine and metabolites in human plasma to support research on the role of nicotine biomarkers on neuronal systems mediating cognitive and affective processes and to differentiate active, passive and environmental exposure. Published by Elsevier B.V. C1 [Huestis, Marilyn A.] NIDA, Intramural Res Program, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, Biomed Res Ctr, NIH, 251 Bayview Blvd,Suite 200,Room 05A-721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institutes of Health. NR 41 TC 34 Z9 35 U1 1 U2 15 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 1 PY 2009 VL 877 IS 29 BP 3537 EP 3542 DI 10.1016/j.jchromb.2009.08.033 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 511MA UT WOS:000271168100009 PM 19748838 ER PT J AU Resnick, SM Espeland, MA An, Y Maki, PM Coker, LH Jackson, R Stefanick, ML Wallace, R Rapp, SR AF Resnick, Susan M. Espeland, Mark A. An, Yang Maki, Pauline M. Coker, Laura H. Jackson, Rebecca Stefanick, Marcia L. Wallace, Robert Rapp, Stephen R. CA Womens Hlth Initiative Study Cogn TI Effects of Conjugated Equine Estrogens on Cognition and Affect in Postmenopausal Women with Prior Hysterectomy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; HORMONE-REPLACEMENT THERAPY; QUALITY-OF-LIFE; PLUS PROGESTIN; ELDERLY WOMEN; DEMENTIA; IMPAIRMENT; ESTRADIOL; DECLINE AB Context: Different menopausal hormone therapies may have varied effects on specific cognitive functions. We previously reported that conjugated equine estrogens (CEE) with medroxyprogesterone acetate had a negative impact on verbal memory but tended to impact figural memory positively over time in older postmenopausal women. Objective: The objective of the study was to determine the effects of unopposed CEE on changes in domain-specific cognitive function and affect in older postmenopausal women with prior hysterectomy. Design: This was a randomized, double blind, placebo-controlled clinical trial. Setting: The study was conducted at 14 of 40 Women's Health Initiative (WHI) clinical centers. Participants: Participants were 886 postmenopausal women with prior hysterectomy, aged 65 yr and older (mean 74 yr), free of probable dementia, and enrolled in the WHI and WHI Memory Study (WHIMS) CEE-Alone trial for a mean of 3 yr and followed up for a mean of 2.70 yr. Intervention: Intervention was 0.625 mg of CEE daily or placebo. Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured. Results: Compared with placebo, unopposed CEE was associated with lower spatial rotational ability (P < 0.01) at initial assessment (after 3 yr of treatment), a difference that diminished over 2.7 yr of continued treatment. CEE did not significantly influence change in other cognitive functions and affect. Conclusions: CEE did not improve cognitive functioning in postmenopausal women with prior hysterectomy. CEE was associated with lower spatial rotational performance after an average of 3 yr of treatment. Overall, CEE does not appear to have enduring effects on rates of domain-specific cognitive change in older postmenopausal women. (J Clin Endocrinol Metab 94: 4152-4161, 2009) C1 [Resnick, Susan M.] NIA, Lab Personal & Cognit, Biomed Res Ctr, Baltimore, MD 21224 USA. [Espeland, Mark A.; Coker, Laura H.; Rapp, Stephen R.] Wake Forest Univ Hlth Sci, Winston Salem, NC 27157 USA. [An, Yang] Medstar Res Inst, Hyattsville, MD 20785 USA. [Jackson, Rebecca] Ohio State Univ, Columbus, OH 43210 USA. [Stefanick, Marcia L.] Stanford Univ, Stanford, CA 94305 USA. [Wallace, Robert] Univ Iowa, Iowa City, IA 52242 USA. RP Resnick, SM (reprint author), NIA, Lab Personal & Cognit, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM susan.resnick@nih.gov FU National Institute on Aging [N01-AG-9-2115]; Intramural Research Program of the National Institutes of Health; National Heart, Lung, and Blood Institute, National Institutes of Health; U. S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; Wyeth Pharmaceuticals FX WHISCA is funded by the National Institute on Aging Contract N01-AG-9-2115 and is supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U. S. Department of Health and Human Services, through Contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. The WHIMS study was funded in part by Wyeth Pharmaceuticals. NR 29 TC 52 Z9 53 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2009 VL 94 IS 11 BP 4152 EP 4161 DI 10.1210/jc.2009-1340 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515LD UT WOS:000271470800006 PM 19850684 ER PT J AU Vlassara, H Cai, WJ Goodman, S Pyzik, R Yong, A Chen, X Zhu, L Neade, T Beeri, M Silverman, JM Ferrucci, L Tansman, L Striker, GE Uribarri, J AF Vlassara, Helen Cai, Weijing Goodman, Susan Pyzik, Renata Yong, Angie Chen, Xue Zhu, Li Neade, Tina Beeri, Michal Silverman, Jeremy M. Ferrucci, Luigi Tansman, Laurie Striker, Gary E. Uribarri, Jaime TI Protection against Loss of Innate Defenses in Adulthood by Low Advanced Glycation End Products (AGE) Intake: Role of the Antiinflammatory AGE Receptor-1 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHRONIC KIDNEY-DISEASE; OXIDATIVE STRESS; DIABETIC COMPLICATIONS; OXIDANT STRESS; INFLAMMATORY MEDIATORS; DIETARY GLYCOTOXINS; MAILLARD REACTION; RENAL-FAILURE; EGF RECEPTOR; SERUM-LEVELS AB Context: Increased oxidant stress and inflammation (OS/infl) are linked to both aging-related diseases and advanced glycation end products (AGEs). Whereas AGE receptor-1 (AGER1) reduces OS/infl in animals, this has not been assessed in normal humans. Objective: The objectives of the study were to determine whether AGER1 correlates with AGEs and OS/infl and a reduction of dietary AGEs (dAGEs) lowers OS/infl in healthy adults and chronic kidney disease (CKD-3) patients. Design: This study was cross-sectional with 2-yr follow-up studies of healthy adults and CKD-3 patients, a subset of which received a reduced AGE or regular diet. Setting: The study was conducted at general community and renal clinics. Participants: Participants included 325 healthy adults (18-45 and >60 yr old) and 66 CKD-3 patients. Intervention: An isocaloric low-AGE (30-50% reduction) or regular diet was given to 40 healthy subjects for 4 months and to nine CKD-3 patients for 4 wk. Main Outcome: Relationships between age, dAGEs, serum AGEs, peripheral mononuclear cell AGE-receptors, and OS/Infl before and after reduction of dAGE intake were measured. Results: AGEs, oxidant stress, receptor for AGE, and TNF alpha were reduced in normal and CKD-3 patients after the low-AGE diet, independently of age. AGER1 levels in CKD-3 patients on the low-AGE diet resembled 18- to 45-yr-old normal subjects. Dietary, serum, and urine AGEs correlated positively with peripheral mononuclear cell AGER1 levels in healthy participants. AGER1 was suppressed in CKD-3 subjects, whereas receptor for AGE and TNF alpha were increased. Conclusions: Reduction of AGEs in normal diets may lower oxidant stress/inflammation and restore levels of AGER1, an antioxidant, in healthy and aging subjects and CKD-3 patients. AGE intake has implications for health outcomes and costs and warrants further testing. (J Clin Endocrinol Metab 94: 4483-4491, 2009) C1 [Vlassara, Helen; Cai, Weijing; Goodman, Susan; Pyzik, Renata; Yong, Angie; Chen, Xue; Zhu, Li; Striker, Gary E.] Mt Sinai Sch Med, Div Expt Diabet & Aging, New York, NY 10029 USA. [Neade, Tina; Striker, Gary E.; Uribarri, Jaime] Mt Sinai Sch Med, Brookdale Dept Adult Dev & Geriatr, Dept Med, Div Nephrol, New York, NY 10029 USA. [Beeri, Michal; Silverman, Jeremy M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Tansman, Laurie] Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY 10029 USA. [Ferrucci, Luigi] NIA, NIH, Bethesda, MD 20892 USA. RP Vlassara, H (reprint author), Mt Sinai Sch Med, Div Expt Diabet & Aging, Box 1640,1 Gustave Levy Pl, New York, NY 10029 USA. EM helen.vlassara@mssm.edu FU National Institute on Aging [AG-23188, AG-09453]; National Institute of Research Resources [MO1-RR00071] FX This work was supported by MERIT Grants AG-23188 and AG-09453 from the National Institute on Aging (to H. V.) and the National Institute of Research Resources Grant MO1-RR00071 awarded to the General Clinical Research Center at Mount Sinai School of Medicine. NR 45 TC 72 Z9 75 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2009 VL 94 IS 11 BP 4483 EP 4491 DI 10.1210/jc.2009-0089 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515LD UT WOS:000271470800047 PM 19820033 ER PT J AU Ix, JH Wassel, CL Chertow, GM Koster, A Johnson, KC Tylavsky, FA Cauley, JA Cummings, SR Harris, TB Shlipak, MG AF Ix, Joachim H. Wassel, Christina L. Chertow, Glenn M. Koster, Annemarie Johnson, Karen C. Tylavsky, Frances A. Cauley, Jane A. Cummings, Steven R. Harris, Tamara B. Shlipak, Michael G. CA Hlth Aging Body Composition Study TI Fetuin-A and Change in Body Composition in Older Persons SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INCIDENT DIABETES-MELLITUS; TYROSINE KINASE INHIBITOR; INSULIN-RECEPTOR; MYOCARDIAL-INFARCTION; RESISTANCE; PLASMA; ADULTS; ADIPOCYTOKINES; GLYCOPROTEIN; ASSOCIATION AB Context: Fetuin-A inhibits the insulin receptor in vitro. Higher serum fetuin-A concentrations are associated with type 2 diabetes longitudinally and greater adiposity in cross-sectional analyses. Whether higher fetuin-A concentrations are associated with accumulation of adiposity over time is unknown. Objective: To determine the association of fetuin-A levels with changes in body composition over 5 yr. Study Design: Observational cohort study nested in the Health Aging and Body Composition Study. Predictor: Serum fetuin-A levels. Outcomes: Visceral adipose tissue (VAT), abdominal sc adipose tissue, and thigh muscle area by computed tomography, and waist circumference and body mass index were measured at baseline and again after 5 yr. Percent change and extreme change (>1.5 SDs) in each measure were calculated. Results: Over 5 yr, subjects lost body mass in each measure, including 6% decline in VAT. Yet each SD (0.42 g/liter) higher fetuin-A concentration was associated with a 5.5% increase in VAT over 5 yr (95% confidence interval 1.9-9.2%; P = 0.003) in models adjusted for age, sex, race, clinical site, diabetes, physical activity, triglycerides, kidney function, and the baseline VAT score. Similarly, higher fetuin-A concentrations were associated with extreme VAT gain (relative risk 1.70, 95% confidence interval 1.12-2.60, P = 0.01). Fetuin-A concentrations were not statistically significant associated with change in any other measures of body composition (P > 0.20). Conclusions: Higher fetuin-A concentrations are associated with the accumulation of VAT in well-functioning, community-living older persons. The mechanisms linking fetuin-A, VAT, and insulin resistance remain to be determined. (J Clin Endocrinol Metab 94: 4492-4498, 2009) C1 [Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, Dept Med, San Diego, CA 92161 USA. [Ix, Joachim H.; Wassel, Christina L.] Univ Calif San Diego, Div Prevent Med, Dept Family & Prevent Med, San Diego, CA 92161 USA. [Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA 92161 USA. [Chertow, Glenn M.] Stanford Univ, Dept Med, Div Nephrol, Stanford, CA 94305 USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Johnson, Karen C.; Tylavsky, Frances A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Cummings, Steven R.] Calif Pacific Med Ctr, Dept Med, San Francisco, CA 94120 USA. [Cummings, Steven R.] San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. [Cummings, Steven R.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. RP Ix, JH (reprint author), Univ Calif San Diego, Dept Med, Div Nephrol & Hypertens, 3350 La Jolla Village Dr,Mail Code 111-H, San Diego, CA 92161 USA. EM joeix@ucsd.edu RI Koster, Annemarie/E-7438-2010; Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU American Diabetes Association (ADA); Association of Subspecialty Professors (ASP); Atlantic Philanthropies; John A. Hartford Foundation; American Heart Association; National Institutes of Health, National Institute on Aging (NIA); [N01-AG-6-2101]; [N01-AG6-2103]; [N01-AG-6-2106] FX This study was supported by an American Diabetes Association (ADA) -Association of Subspecialty Professors (ASP) Young Investigator Innovation Award in Geriatric Endocrinology sponsored by the Atlantic Philanthropies, ADA, the John A. Hartford Foundation, and ASP, an American Heart Association Fellow to Faculty Transition Award (J. H. I.). The Health ABC study was supported by contracts N01-AG-6-2101, N01-AG6-2103, and N01-AG-6-2106 and by the Intramural Research Program of the National Institutes of Health, National Institute on Aging (NIA). The funding sources played no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data, nor in the preparation of the manuscript. The NIA reviewed and approved this manuscript prior to submission. NR 27 TC 25 Z9 25 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2009 VL 94 IS 11 BP 4492 EP 4498 DI 10.1210/jc.2009-0916 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 515LD UT WOS:000271470800048 PM 19820014 ER PT J AU Taylor, JG Cheuk, AT Tsang, PS Chung, JY Song, YK Desai, K Yu, YL Chen, QR Shah, K Youngblood, V Fang, J Kim, SY Yeung, C Helman, LJ Mendoza, A Ngo, V Staudt, LM Wei, JS Khanna, C Catchpoole, D Qualman, SJ Hewitt, SM Merlino, G Chanock, SJ Khan, J AF Taylor, James G. Cheuk, Adam T. Tsang, Patricia S. Chung, Joon-Yong Song, Young K. Desai, Krupa Yu, Yanlin Chen, Qing-Rong Shah, Kushal Youngblood, Victoria Fang, Jun Kim, Su Young Yeung, Choh Helman, Lee J. Mendoza, Arnulfo Ngo, Vu Staudt, Louis M. Wei, Jun S. Khanna, Chand Catchpoole, Daniel Qualman, Stephen J. Hewitt, Stephen M. Merlino, Glenn Chanock, Stephen J. Khan, Javed TI Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RECEPTOR TYROSINE KINASES; POLYMERASE-CHAIN-REACTION; GROWTH-FACTOR RECEPTOR-3; SOFT-TISSUE SARCOMA; BREAST-CANCER; ALVEOLAR RHABDOMYOSARCOMAS; ACTIVATING MUTATIONS; MUSCLE REGENERATION; SOMATIC MUTATIONS; SIGNAL TRANSDUCER AB Rhabdomyosarcoma (RMS) is a childhood cancer originating from skeletal muscle, and patient survival is poor in the presence of metastatic disease. Few determinants that regulate metastasis development have been identified. The receptor tyrosine kinase FGFR4 is highly expressed in RMS tissue, suggesting a role in tumorigenesis, although its functional importance has not been defined. Here, we report the identification of mutations in FGFR4 in human RMS tumors that lead to its activation and present evidence that it functions as an oncogene in RMS. Higher FGFR4 expression in RMS tumors was associated with advanced-stage cancer and poor survival, while FGFR4 knockdown in a human RMS cell line reduced tumor growth and experimental lung metastases when the cells were transplanted into mice. Moreover, 6 FGFR4 tyrosine kinase domain mutations were found among 7 of 94 (7.5%) primary human RMS tumors. The mutants K535 and E550 increased autophosphorylation, Stat3 signaling, tumor proliferation, and metastatic potential when expressed in a murine RMS cell fine. These mutants also transformed NIH 3T3 cells and led to an enhanced metastatic phenotype. Finally, murine RMS cell lines expressing the K535 and E550 FGFR4 mutants were substantially more susceptible to apoptosis in the presence of a pharmacologic FGFR inhibitor than the control cell lines expressing the empty vector or wild-type FGFR4. Together, our results demonstrate that mutationally activated FGFR4 acts as an oncogene, and these are what we believe to be the first known mutations in a receptor tyrosine kinase in RMS. These findings support the potential therapeutic targeting of FGFR4 in RMS. C1 [Taylor, James G.; Desai, Krupa; Shah, Kushal; Youngblood, Victoria] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA. [Cheuk, Adam T.; Tsang, Patricia S.; Song, Young K.; Chen, Qing-Rong; Wei, Jun S.; Khan, Javed] NCI, Oncogenom Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Yu, Yanlin; Merlino, Glenn] NCI, Canc Modeling Sect, Lab Canc Biol & Genet, CCR,NIH, Bethesda, MD 20892 USA. [Chen, Qing-Rong] NCI, Adv Biomed Comp Ctr, SAIC Frederick Inc, Frederick, MD 21701 USA. [Fang, Jun; Chanock, Stephen J.] NCI, Lab Translat Genorn, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kim, Su Young; Yeung, Choh; Helman, Lee J.] NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Mendoza, Arnulfo; Khanna, Chand] NCI, Tumor & Metastasis Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ngo, Vu; Staudt, Louis M.] NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. [Catchpoole, Daniel] Childrens Hosp Westmead, Oncol Res Unit, Westmead, NSW, Australia. [Qualman, Stephen J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH USA. [Qualman, Stephen J.] Nationwide Childrens Hosp, Childrens Res Inst, Columbus, OH USA. RP Khan, J (reprint author), Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014; OI Khan, Javed/0000-0002-5858-0488; Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982; Taylor, James/0000-0002-4421-1809 FU NIH FX The authors thank Bryan Clary for the pMSCVzeo retroviral luciferase gene construct and Kent Hunter (NCI) and Mauro Tiso (University of Pittsburgh, Pittsburgh, Pennsylvania, USA) for useful discussions. This work was supported in part by the Cooperative Human Tissue Network, which is funded by the NCI, and by the intramural programs of the NIH (NHLBI and NCI). NR 66 TC 131 Z9 138 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2009 VL 119 IS 11 BP 3395 EP 3407 DI 10.1172/JCI39703 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 517CC UT WOS:000271589400022 PM 19809159 ER PT J AU Bornstein, S White, R Malkoski, S Oka, M Han, GW Cleaver, T Reh, D Andersen, P Gross, N Olson, S Deng, CX Lu, SL Wang, XJ AF Bornstein, Sophia White, Ruth Malkoski, Stephen Oka, Masako Han, Gangwen Cleaver, Timothy Reh, Douglas Andersen, Peter Gross, Neil Olson, Susan Deng, Chuxia Lu, Shi-Long Wang, Xiao-Jing TI Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SQUAMOUS-CELL CARCINOMA; FANCONI ANEMIA/BRCA PATHWAY; TUMOR-SUPPRESSOR GENE; TGF-BETA; SIGNALING PATHWAY; EPITHELIAL-CELLS; KNOCKOUT MICE; T-CELLS; EXPRESSION; SKIN AB Smad4 is a central mediator of TGF-beta signaling, and its expression is downregulated or lost at the malignant stage in several cancer types. In this study, we found that Smad4 was frequently downregulated not only in human head and neck squamous cell carcinoma (HNSCC) malignant lesions, but also in grossly normal adjacent buccal mucosa. To gain insight into the importance of this observation, we generated mice in which Smad4 was deleted in head and neck epithelia (referred to herein as HN-Smad4(-/-) mice) and found that they developed spontaneous HNSCC. Interestingly, both normal head and neck tissue and HNSCC from HN-Smad4(-/-) mice exhibited increased genomic instability, which correlated with downregulated expression and function of genes encoding proteins in the Fanconi anemia/Brca (Fanc/Brca) DNA repair pathway linked to HNSCC susceptibility in humans. Consistent with this, further analysis revealed a correlation between downregulation of Smad4 protein and downregulation of the Brica1 and Rad51 proteins in human HNSCC. In addition to the above changes in tumor epithelia, both normal head and neck tissue and HNSCC from HN-Smad4(-/-) mice exhibited severe inflammation, which was associated with increased expression of TGF-beta 1 and activated Smad3. We present what we believe to be the first single gene-knockout model for HNSCC, in which both HNSCC formation and invasion occurred as a result of Smad4 deletion. Our results reveal an intriguing connection between Smad4 and the Fanc/Brca pathway and highlight the impact of epithelial Smad4 loss on inflammation. C1 [Lu, Shi-Long] Univ Colorado Denver, Dept Otolaryngol, Aurora, CO 80045 USA. [Bornstein, Sophia; White, Ruth; Reh, Douglas; Andersen, Peter; Gross, Neil; Wang, Xiao-Jing] Oregon Hlth & Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA. [White, Ruth; Oka, Masako; Han, Gangwen; Wang, Xiao-Jing] Univ Colorado Denver, Dept Pathol, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Malkoski, Stephen; Cleaver, Timothy] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO 80045 USA. [Olson, Susan] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. [Deng, Chuxia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD USA. RP Lu, SL (reprint author), Univ Colorado Denver, Dept Otolaryngol, Bldg RC-2,Rm P15-7112,Mail Stop 8116, Aurora, CO 80045 USA. EM shi-long.lu@ucdenver.edu; xj.wang@ucdenver.edu RI deng, chuxia/N-6713-2016 FU NIH; Oregon Medical Research Foundation FX The authors thank Yuexin Li and Donna Wang for their technical assistance. This work was supported by NIH grants to X-J. Wang and by an Oregon Medical Research Foundation grant to S.-L. Lu. S.-L. Lu is an investigator of the THANC (Thyroid, Head and Neck Cancer) Foundation. S. Bornstein and S. Malkoski are recipients of NIH training grants. NR 60 TC 84 Z9 85 U1 1 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2009 VL 119 IS 11 BP 3408 EP 3419 DI 10.1172/JCI38854 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 517CC UT WOS:000271589400023 PM 19841536 ER PT J AU Richardson-Harman, N Lackman-Smith, C Fletcher, PS Anton, PA Bremer, JW Dezzutti, CS Elliott, J Grivel, JC Guenthner, P Gupta, P Jones, M Lurain, NS Margolis, LB Mohan, S Ratner, D Reichelderfer, P Roberts, P Shattock, RJ Cummins, JE AF Richardson-Harman, Nicola Lackman-Smith, Carol Fletcher, Patricia S. Anton, Peter A. Bremer, James W. Dezzutti, Charlene S. Elliott, Julie Grivel, Jean-Charles Guenthner, Patricia Gupta, Phalguni Jones, Maureen Lurain, Nell S. Margolis, Leonid B. Mohan, Swarna Ratner, Deena Reichelderfer, Patricia Roberts, Paula Shattock, Robin J. Cummins, James E., Jr. TI Multisite Comparison of Anti-Human Immunodeficiency Virus Microbicide Activity in Explant Assays Using a Novel Endpoint Analysis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HUMAN CERVICAL TISSUE; ORGAN-CULTURE SYSTEM; TOPICAL MICROBICIDES; CANDIDATE MICROBICIDES; CXCR4-TROPIC HIV-1; TYPE-1 INFECTION; EX-VIVO; TRANSMISSION; CELLS; DISSEMINATION AB Microbicide candidates with promising in vitro activity are often advanced for evaluations using human primary tissue explants relevant to the in vivo mucosal transmission of human immunodeficiency virus type 1 (HIV-1), such as tonsil, cervical, or rectal tissue. To compare virus growth or the anti-HIV-1 efficacies of candidate microbicides in tissue explants, a novel soft-endpoint method was evaluated to provide a single, objective measurement of virus growth. The applicability of the soft endpoint is shown across several different ex vivo tissue types, with the method performed in different laboratories, and for a candidate microbicide (PRO 2000). The soft-endpoint method was compared to several other endpoint methods, including (i) the growth of virus on specific days after infection, (ii) the area under the virus growth curve, and (iii) the slope of the virus growth curve. Virus growth at the assay soft endpoint was compared between laboratories, methods, and experimental conditions, using nonparametric statistical analyses. Intra-assay variability determinations using the coefficient of variation demonstrated higher variability for virus growth in rectal explants. Significant virus inhibition by PRO 2000 and significant differences in the growth of certain primary HIV-1 isolates were observed by the majority of laboratories. These studies indicate that different laboratories can provide consistent measurements of anti-HIV-1 microbicide efficacy when (i) the soft endpoint or another standardized endpoint is used, (ii) drugs and/or virus reagents are centrally sourced, and (iii) the same explant tissue type and method are used. Application of the soft-endpoint method reduces the inherent variability in comparisons of preclinical assays used for microbicide development. C1 [Richardson-Harman, Nicola; Lackman-Smith, Carol; Jones, Maureen; Roberts, Paula; Cummins, James E., Jr.] So Res Inst, Microbicide Qual Assurance Program, Frederick, MD 21701 USA. [Fletcher, Patricia S.; Shattock, Robin J.] St Georges Univ London, Dept Cellular & Mol Med, Ctr Infect, London, England. [Anton, Peter A.; Elliott, Julie] Univ Calif Los Angeles, Ctr Prevent Res, Los Angeles, CA USA. [Bremer, James W.; Lurain, Nell S.] Rush Univ, Virol Qual Assurance Lab, Dept Immunol & Microbiol, Med Ctr, Chicago, IL 60612 USA. [Dezzutti, Charlene S.; Mohan, Swarna] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Grivel, Jean-Charles; Margolis, Leonid B.; Reichelderfer, Patricia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA. [Guenthner, Patricia] Ctr Dis Control, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30333 USA. [Gupta, Phalguni; Ratner, Deena] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. RP Lackman-Smith, C (reprint author), So Res Inst, Microbicide Qual Assurance Program, 431 Aviat Way, Frederick, MD 21701 USA. EM lackmansmith@southernresearch.org FU Microbicide Quality Assurance Program (MQAP); U. S. National Institutes of Health [NICHDN01-HD-3-3350]; NIAID [N01-AI-33350]; St. George's, University of London, London, United Kingdom (DFID/MRD); Magee-Womens Research Institute; University of Pittsburgh,; NIH [U01 AI068633-07]; NIH CFAR Mucosal Immunology Core [AI 28997]; NIH IP/CP U19 [AI 060614] FX Investigators using explant assays in their respective microbicide-related research were invited to participate in the design of the studies described in this paper. Technical staff participated in regular conference calls and discussions of the standardized procedures as the studies were implemented and data were acquired. The author list includes the principal investigators from the participating laboratories and their respective technical representatives. Since participation in the MQAP was voluntary, it should be noted that the explant studies described in this paper were facilitated by the infrastructure, resources, and microbicide-related grant support available at each of the following participating laboratories (this order does not correspond to the randomly assigned lab identification letters): National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (NIH Intramural Program); Rush University Medical Center, Department of Immunology/Microbiology, Chicago, IL (Virology Quality Assurance [VQA] Program supported by NIAID grant N01-AI-50044); St. George's, University of London, London, United Kingdom (DFID/MRD to R. J. S. as part of the Microbicide Development Programme); Magee-Womens Research Institute, University of Pittsburgh, School of Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, PA (NIH grant U01 AI068633-07 to C. S. D.); and Center for Prevention Research at David Geffen School of Medicine, University of California-Los Angeles AIDS Institute (NIH CFAR Mucosal Immunology Core grant AI 28997 and NIH IP/CP U19 grant AI 060614 to P. A. A.). NR 34 TC 24 Z9 25 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2009 VL 47 IS 11 BP 3530 EP 3539 DI 10.1128/JCM.00673-09 PG 10 WC Microbiology SC Microbiology GA 514CZ UT WOS:000271373000023 PM 19726602 ER PT J AU Huang, SW Hsu, YW Smith, DJ Kiang, D Tsai, HP Lin, KH Wang, SM Liu, CC Su, IJ Wang, JR AF Huang, Sheng-Wen Hsu, Yun-Wei Smith, Derek J. Kiang, David Tsai, Huey-Pin Lin, Kuei-Hsiang Wang, Shih-Min Liu, Ching-Chung Su, Ih-Jen Wang, Jen-Ren TI Reemergence of Enterovirus 71 in 2008 in Taiwan: Dynamics of Genetic and Antigenic Evolution from 1998 to 2008 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VACCINE-DERIVED POLIOVIRUS; MOUTH-DISEASE EPIDEMICS; A H3N2 VIRUSES; MOLECULAR EPIDEMIOLOGY; PACIFIC REGION; 2 DECADES; OUTBREAK; MALAYSIA; HAND; INFECTION AB In recent years, enterovirus 71 (EV71) has been a cause of numerous outbreaks of hand-foot-and-mouth disease, with severe neurological complications in the Asia-Pacific region. The reemergence in Taiwan of EV71 genotype B5 in 2008 resulted in the largest outbreak of EV71 in Taiwan in the past 11 years. Phylogenetic analyses indicated that dominant genotype changes from B to C or C to B occurred at least three times between 1986 and 2008. Furthermore, antigenic cartography of EV71 by using neutralization tests revealed that the reemerging EV71 genotype B5 strains formed a separate cluster which was antigenically distinct from the B4 and C genotypes. Moreover, analyses of full-length genomic sequences of EV71 circulating in Taiwan during this period showed the occurrence of intra-and interserotypic recombination. Therefore, continuous surveillance of EV71 including the monitoring of genetic evolution and antigenic changes is recommended and may contribute to the development of a vaccine for EV71. C1 [Wang, Jen-Ren] Natl Cheng Kung Univ, Dept Med Lab Sci & Biotechnol, Tainan 701, Taiwan. [Wang, Shih-Min; Liu, Ching-Chung] Natl Cheng Kung Univ, Dept Pediat, Tainan 701, Taiwan. [Huang, Sheng-Wen; Wang, Jen-Ren] Natl Cheng Kung Univ, Inst Basic Med Sci, Tainan 701, Taiwan. [Tsai, Huey-Pin; Wang, Jen-Ren] Natl Cheng Kung Univ Hosp, Dept Pathol, Tainan 70428, Taiwan. [Hsu, Yun-Wei; Su, Ih-Jen; Wang, Jen-Ren] Natl Hlth Res Inst, Div Infect Dis, Tainan, Taiwan. [Kiang, David] Calif Dept Hlth Serv, Viral & Rickettsial Dis Labs, Richmond, CA USA. [Lin, Kuei-Hsiang] Kaohsiung Med Univ, Dept Clin Lab, Kaohsiung, Taiwan. [Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge, England. [Smith, Derek J.] Erasmus MC, Dept Virol, Rotterdam, Netherlands. [Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Wang, JR (reprint author), Natl Cheng Kung Univ, Dept Med Lab Sci & Biotechnol, 1 Univ Rd, Tainan 701, Taiwan. EM jrwang@mail.ncku.edu.tw RI Lin, Kuei-Hsiang/A-1331-2010; Wang, Ren-Jen/F-5254-2011; Huang, Sheng Wen/H-6338-2013; Su, Ih-Jen/B-2655-2010; OI Wang, Jen-Ren/0000-0002-4127-4046 FU National Health Research Institutes; National Science Council [NSC 97-3112-B-006]; Department of Health, Taiwan Centers for Disease Control [CB097135]; U.S. NIH [DP1-OD000490-01] FX This study was supported by National Health Research Institutes grants, National Science Council grant NSC 97-3112-B-006, and Department of Health, Taiwan Centers for Disease Control grant CB097135. D.J.S. was supported by a Director's Pioneer Award from the U.S. NIH (grant DP1-OD000490-01). NR 55 TC 116 Z9 129 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2009 VL 47 IS 11 BP 3653 EP 3662 DI 10.1128/JCM.00630-09 PG 10 WC Microbiology SC Microbiology GA 514CZ UT WOS:000271373000040 PM 19776232 ER PT J AU Legault, C Maki, PM Resnick, SM Coker, L Hogan, P Bevers, TB Shumaker, SA AF Legault, Claudine Maki, Pauline M. Resnick, Susan M. Coker, Laura Hogan, Patricia Bevers, Therese B. Shumaker, Sally A. TI Effects of Tamoxifen and Raloxifene on Memory and Other Cognitive Abilities: Cognition in the Study of Tamoxifen and Raloxifene SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ESTROGEN-RECEPTOR MODULATOR; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; POSTMENOPAUSAL WOMEN; BRAIN ACTIVATION; DISEASE; TRIAL; DEPRESSION; DEMENTIA; OUTCOMES AB Purpose To compare the effects of two selective estrogen receptor modulators, tamoxifen and raloxifene, on global and domain-specific cognitive function. Patients and Methods The National Surgical Adjuvant Breast and Bowel Project's Study of Tamoxifen and Raloxifene (STAR) study was a randomized clinical trial of tamoxifen 20 mg/d or raloxifene 60 mg/d in healthy postmenopausal women at increased risk of breast cancer. The 1,498 women who were randomly assigned in STAR were age 65 years and older, were not diagnosed with dementia, and were enrolled onto the Cognition in the Study of Tamoxifen and Raloxifene (Co-STAR) trial, beginning 18 months after STAR enrollment started. A cognitive test battery modeled after the one used in the Women's Health Initiative Study of Cognitive Aging (WHISCA) was administered. Technicians were centrally trained to administer the battery and recertified every 6 months. Analyses were conducted on all participants and on 273 women who completed the first cognitive battery before they started taking their medications. Results Overall, there were no significant differences in adjusted mean cognitive scores between the two treatment groups across visits. There were significant time effects across the three visits for some of the cognitive measures. Similar results were obtained for the subset of women with true baseline measures. Conclusion Tamoxifen and raloxifene are associated with similar patterns of cognitive function in postmenopausal women at increased risk of breast cancer. Future comparisons between these findings and patterns of cognitive function in hormone therapy and placebo groups in WHISCA should provide additional insights into the effects of tamoxifen and raloxifene on cognitive function in older women. C1 [Legault, Claudine] Wake Forest Univ, Bowman Gray Sch Med, Med Ctr, Dept Biostat Sci,Div Publ Hlth, Winston Salem, NC 27157 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. RP Legault, C (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Med Ctr, Dept Biostat Sci,Div Publ Hlth, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM clegault@wfubmc.edu FU National Institute on Aging [NO1-AG-2106]; National Institutes of Health (Co-STAR); National Cancer Institute [U10-CA-37377, U10-CA-69974, U10CA-12027, U10CA-69651]; Department of Health and Human Services; AstraZeneca; Eli Lilly (STAR) FX Supported by the National Institute on Aging Grant No. NO1-AG-2106 and in part by the Intramural Research Program, National Institute on Aging, National Institutes of Health (Co-STAR); supported by Public Health Service Grants No. U10-CA-37377, U10-CA-69974, U10CA-12027, and U10CA-69651 from the National Cancer Institute, the Department of Health and Human Services, AstraZeneca, and Eli Lilly (STAR). NR 34 TC 21 Z9 22 U1 0 U2 1 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 1 PY 2009 VL 27 IS 31 BP 5144 EP 5152 DI 10.1200/JCO.2008.21.0716 PG 9 WC Oncology SC Oncology GA 512TS UT WOS:000271274300008 PM 19770382 ER PT J AU Balinska, MA AF Balinska, Marta A. TI Hepatitis B vaccination and French Society ten years after the suspension of the vaccination campaign: How should we raise infant immunization coverage rates? SO JOURNAL OF CLINICAL VIROLOGY LA English DT Review DE Hepatitis B vaccination; France; Attitudes towards immunization; Ethics ID MULTIPLE-SCLEROSIS; VACCINES; FRANCE; RISK AB In 1998, official concerns were first voiced over a possible association between hepatitis B virus (HBV) vaccination and multiple sclerosis (MS). Despite a number of studies that have demonstrated no such association, ten years on the French population's confidence in the vaccine remains shaken and immunization rates of infants have stagnated beneath 30%. With a chronic carriage of the virus estimated at 0.68%. it seems unlikely that France will be able to control the circulation of the virus. This article analyses attitudes towards HBV vaccination based on recent surveys: not only the public but also the vast majority of "vaccinators" (88%) questions the safety of the vaccine. Physicians opposed to vaccinating infants cite the possibility of adverse events occurring later in life and their lack of trust in the health authorities and the pharmaceutical industry. Both the general public and physicians feel more inclined to vaccinate adolescents and adults, even though it was for these age groups (especially the latter) that neurological adverse events were notified. It appears that above all, the usefulness of the vaccine and its safety profile for young children should be explained in understandable language by all those involved in public health, including the media. However, when opting for public health policies on the basis of statistical estimations, the importance of individual cases (e.g. MS in the family) should not be overlooked both for biological and ethical reasons. (C) 2009 Elsevier B.V. All rights reserved. C1 Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Balinska, MA (reprint author), Fogarty Int Ctr, 31 Ctr Dr, Bethesda, MD 20892 USA. EM balinskima@mail.nih.gov NR 23 TC 17 Z9 18 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD NOV PY 2009 VL 46 IS 3 BP 202 EP 205 DI 10.1016/j.jcv.2009.07.024 PG 4 WC Virology SC Virology GA 517FQ UT WOS:000271599000002 PM 19716764 ER PT J AU Roy, S Roy, S Neuenswander, B Hill, D Larock, RC AF Roy, Sudipta Roy, Sujata Neuenswander, Benjamin Hill, David Larock, Richard C. TI Palladium- and Copper-Catalyzed Solution Phase Synthesis of a Diverse Library of Isoquinolines SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID DECUMBENINE-B; INTRAARTERIAL PAPAVERINE; PARALLEL SYNTHESIS; DRUG DISCOVERY; ALKALOIDS; CHEMISTRY; ALKYNES; 2-(1-ALKYNYL)BENZALDIMINES; DERIVATIVES; CYCLIZATION AB The solution-phase synthesis of a 111 member isoquinoline library is described. The isoquinoline scaffold has been accessed through the palladium- and copper-catalyzed cyclization of iminoalkynes and the palladium-catalyzed iminoannulation of internal alkynes, followed by diversification of hydroxyl functionality where it is present. C1 [Roy, Sudipta; Roy, Sujata; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Neuenswander, Benjamin; Hill, David] Univ Kansas, NIH, Ctr Excellence Chem Methodol & Lib Dev, Lawrence, KS 66047 USA. RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM larock@iastate.edu FU National Institute of General Medical Sciences [GM070620, GM079593]; National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence [GM069663]; Johnson Matthey, Inc; Kawaken Fine Chemicals Co., Ltd FX We would like to thank Dr. Jesse P. Waldo of Iowa State University and Dr. Frank Schoenen of Kansas University for helpful discussions. We thank the National Institute of General Medical Sciences (GM070620 and GM079593) and the National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence (GM069663) for support of this research and Johnson Matthey, Inc. and Kawaken Fine Chemicals Co., Ltd. for donating the palladium catalysts. NR 52 TC 35 Z9 35 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD NOV-DEC PY 2009 VL 11 IS 6 BP 1061 EP 1065 DI 10.1021/cc9000949 PG 5 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 514XB UT WOS:000271428500014 PM 19728736 ER PT J AU Roy, S Roy, S Neuenswander, B Hill, D Larock, RC AF Roy, Sujata Roy, Sudipta Neuenswander, Benjamin Hill, David Larock, Richard C. TI Solution-Phase Synthesis of a Diverse Isocoumarin Library SO JOURNAL OF COMBINATORIAL CHEMISTRY LA English DT Article ID HYDRANGEAE-DULCIS FOLIUM; PALLADIUM-CATALYZED ANNULATION; MULTIPLE-MYELOMA CELLS; O-IODOBENZOIC ACID; 3-SUBSTITUTED ISOCOUMARINS; ALPHA-PYRONES; THUNBERGINOL-B; ARTEMISIA-CAPILLARIS; MEDICINAL CHEMISTRY; INTERNAL ALKYNES AB The solution-phase synthesis of a 167-member library of isocoumarins is described. The key intermediates for library generation, 4-iodoisocoumarins. are easily prepared by iodocyclization of the corresponding 2-(1-alkynyl)arenecarboxyl ate esters. The 4-iodoisocoumarins undergo palladium-catalyzed Sonogashira, Suzuki-Miyura, and Heck reactions to yield a diverse set of isocoumarins. Alternatively, isocoumarins, bearing hydroxyl or bromine functionalities, have been prepared by ZnCl(2)- and Pd(PPh(3))(4)-mediated cyclization of the corresponding o-iodobenzoic acid and appropriate terminal alkynes. The resulting isocoumarins were further diversified by derivatization of the hydroxyl or bromine groups. A small set of isoquinolinones were also prepared from the corresponding isocoumarins. C1 [Roy, Sujata; Roy, Sudipta; Larock, Richard C.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Neuenswander, Benjamin; Hill, David] Univ Kansas, NIH, Ctr Excellence Chem Methodol & Lib Dev, Lawrence, KS 66047 USA. RP Larock, RC (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM larock@iastate.edu FU National Institute of General Medical Sciences [GM070620, GM079593]; National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence [GM069663]; Johnson Matthey, Inc; Kawaken Fine Chemicals Co., Ltd; Frontier Scientific and Synthonix FX We would like to thank Dr. Jesse P. Waldo and Dr. Yu Chen of Iowa State University and Dr. Frank Schoenen of Kansas University for helpful discussions. We thank the National Institute of General Medical Sciences (GM070620 and GM079593) and the National Institutes of Health Kansas University Chemical Methodologies and Library Development Center of Excellence (GM069663) for support of this research, Johnson Matthey, Inc., and Kawaken Fine Chemicals Co., Ltd., for donating the palladium catalysts, and Frontier Scientific and Synthonix for donating the boronic acids. NR 87 TC 49 Z9 50 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-4766 J9 J COMB CHEM JI J. Comb. Chem. PD NOV-DEC PY 2009 VL 11 IS 6 BP 1128 EP 1135 DI 10.1021/cc9001197 PG 8 WC Chemistry, Applied; Chemistry, Medicinal; Chemistry, Multidisciplinary SC Chemistry; Pharmacology & Pharmacy GA 514XB UT WOS:000271428500023 PM 19817453 ER PT J AU Costanzi, S Tikhonova, IG Harden, TK Jacobson, KA AF Costanzi, Stefano Tikhonova, Irina G. Harden, T. Kendall Jacobson, Kenneth A. TI Ligand and structure-based methodologies for the prediction of the activity of G protein-coupled receptor ligands SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE 3D-QSAR; G protein-coupled receptors (GPCR); Homology modeling; Molecular docking; Virtual screening (VS) ID MOLECULAR-FIELD ANALYSIS; A(3) ADENOSINE RECEPTOR; BINDING-AFFINITY PREDICTION; FREE-ENERGY CALCULATIONS; 3D QSAR ANALYSIS; DRUG DESIGN; CRYSTAL-STRUCTURE; SCORING FUNCTION; COMPUTATIONAL-EFFICIENCY; BIOLOGICAL-ACTIVITY AB Accurate in silico models for the quantitative prediction of the activity of G protein-coupled receptor (GPCR) ligands would greatly facilitate the process of drug discovery and development. Several methodologies have been developed based on the properties of the ligands, the direct study of the receptor-ligand interactions, or a combination of both approaches. Ligand-based three-dimensional quantitative structure-activity relationships (3D-QSAR) techniques, not requiring knowledge of the receptor structure, have been historically the first to be applied to the prediction of the activity of GPCR ligands. They are generally endowed with robustness and good ranking ability; however they are highly dependent on training sets. Structure-based techniques generally do not provide the level of accuracy necessary to yield meaningful rankings when applied to GPCR homology models. However, they are essentially independent from training sets and have a sufficient level of accuracy to allow an effective discrimination between binders and nonbinders, thus qualifying as viable lead discovery tools. The combination of ligand and structure-based methodologies in the form of receptor-based 3D-QSAR and ligand and structure-based consensus models results in robust and accurate quantitative predictions. The contribution of the structure-based component to these combined approaches is expected to become more substantial and effective in the future, as more sophisticated scoring functions are developed and more detailed structural information on GPCRs is gathered. C1 [Costanzi, Stefano; Tikhonova, Irina G.] NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. [Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Costanzi, S (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU NIH; NIDDK FX The authors thank Dr. Santiago Vilar Varela for the helpful discussions. This research was supported by the Intramural Research Program of the NIH, NIDDK. NR 91 TC 15 Z9 15 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD NOV PY 2009 VL 23 IS 11 BP 747 EP 754 DI 10.1007/s10822-008-9218-3 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 526OX UT WOS:000272301700001 PM 18483766 ER PT J AU Jain, S Yadav, H Sinha, PR AF Jain, Shalini Yadav, Hariom Sinha, Pushpalata Ravindra TI Antioxidant and cholesterol assimilation activities of selected lactobacilli and lactococci cultures SO JOURNAL OF DAIRY RESEARCH LA English DT Article DE Lactic acid bacteria; Lactobacillus; Antioxidant activity; Cholesterol assimilation ID LACTIC-ACID BACTERIA; LIPID-PEROXIDATION; MILK WHEY; VITAMIN-E; ACIDOPHILUS; RATS; PROBIOTICS; CASEI; DAHI; DIET AB In present study, three strains of lactic acid bacteria (LAB) viz. Lactobacillus casei, Lactobacillus acidophilus and Lactococcus lactis and milk fermented with these strains have been studied for antioxidant and cholesterol assimilation activities in-vitro and in-vivo, in addition to the effect on total lactobacilli, lactococci and coliform counts into the gut of mice fed with diets supplemented by fermented milk. All three selected strains exhibited potent 2,2-diphenyl-1-picrylhydrazyl, malonaldialdehyde and hydrogen peroxide radical scavenging abilities as well as inhibition of linoleic acid peroxidation activity. These activities were highest in Lb. casei as followed by Lb. acidophilus and Lc. lactis. In addition, these bacterial cultures also exhibited good in-vitro cholesterol assimilation potential. Oral administration to mice of milk fermented with selected LAB strains, slightly decreased blood cholesterol, increased colonization of total lactobacilli and lactococci, and decreased coliforms in the intestinal tissues as well as faecal samples. These results indicate that, selected LAB strains have good antioxidant, hypocholesterolemic and coliform removal activities. It may suggest that, a novel functional food can be obtained by supplementation of selected LAB in milk, which may have various health beneficial properties such as antioxidant and hypocholesterolemic activities. C1 [Jain, Shalini; Yadav, Hariom; Sinha, Pushpalata Ravindra] Natl Dairy Res Inst, Anim Biochem Div, Karnal 132001, Haryana, India. RP Yadav, H (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM yadavhariom@gmail.com OI Yadav, Hariom/0000-0003-4504-1597 NR 43 TC 14 Z9 16 U1 0 U2 13 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0022-0299 J9 J DAIRY RES JI J. Dairy Res. PD NOV PY 2009 VL 76 IS 4 BP 385 EP 391 DI 10.1017/S0022029909990094 PG 7 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 518GR UT WOS:000271679300001 PM 19638266 ER PT J AU Ramirez, NE Wang, P Lejeune, J Shipitalo, MJ Ward, LA Sreevatsan, S Dick, WA AF Ramirez, Norma E. Wang, Ping Lejeune, Jeff Shipitalo, Martin J. Ward, Lucy A. Sreevatsan, Srinand Dick, Warren A. TI Effect of Tillage and Rainfall on Transport of Manure-Applied Cryptosporidium parvum Oocysts Through Soil SO JOURNAL OF ENVIRONMENTAL QUALITY LA English DT Article ID GIARDIA SPP.; DAIRY FARMS; WATER; INACTIVATION; SURFACE; DISPERSION; CHEMICALS; OUTBREAKS; MOVEMENT; SURVIVAL AB Most waterborne outbreaks of cryptosporidiosis have been attributed to agricultural sources due to the high prevalence of Cryptosporidium oocysts in animal wastes and manure spreading on farmlands. No-till, an effective conservation practice, often results in soil having higher water infiltration and percolation rates than conventional tillage. We treated six undisturbed no-till and six tilled soil blocks (30 by 30 by 30 cm) with 1 L liquid dairy manure containing 10(5) C parvum oocysts per milliliter to test the effect of tillage and rainfall on oocyst transport. The blocks were subjected to rainfall treatments consisting of 5 mm or 30 mm in 30 min. Leachate was collected from the base of the blocks in 35-mL increments using a 64-cell grid lysimeter. Even before any rain was applied, approximately 300 mL of water from the liquid manure (30% of that applied) was transported through the no-till soil, bur none through the tilled blocks. After rain was applied, a greater number and percentage of first leachate samples from the no-till soil blocks compared to the tilled blocks tested positive for Cryptosporidium oocysts. In contrast to leachate, greater numbers of oocysts were recovered from the tilled soil, itself, than from the no-till soil. Although tillage was the most important factor affecting oocyst transport, rainfall timing and intensity were also important. To minimize transport of Cryptosporidium in no-till fields, manure should be applied at least 48 h before heavy rainfall is anticipated or methods of disrupting the direct linkage of surface soil to drains, via macropores, need to be used. C1 [Ramirez, Norma E.; Lejeune, Jeff] Ohio State Univ, Food Anim Hlth Res Program, Wooster, OH 44691 USA. [Dick, Warren A.] Ohio State Univ, Sch Environm & Nat Resources, Wooster, OH 44691 USA. [Shipitalo, Martin J.] USDA ARS, Coshocton, OH 43812 USA. [Ward, Lucy A.] NIAID, NIH, Bethesda, MD 20892 USA. [Wang, Ping; Sreevatsan, Srinand] Univ Minnesota, Ctr Anim Hlth & Food Safety, Vet Populat Med Dep, St Paul, MN 55108 USA. RP Dick, WA (reprint author), Ohio State Univ, Food Anim Hlth Res Program, Wooster, OH 44691 USA. EM dick.5@osu.edu OI Shipitalo, Martin/0000-0003-4775-7345; Sreevatsan, Srinand/0000-0002-5162-2403 NR 46 TC 11 Z9 11 U1 0 U2 7 PU AMER SOC AGRONOMY PI MADISON PA 677 S SEGOE RD, MADISON, WI 53711 USA SN 0047-2425 J9 J ENVIRON QUAL JI J. Environ. Qual. PD NOV-DEC PY 2009 VL 38 IS 6 BP 2394 EP 2401 DI 10.2134/jeq2008.0432 PG 8 WC Environmental Sciences SC Environmental Sciences & Ecology GA 519NU UT WOS:000271774400025 PM 19875795 ER PT J AU Haggstrom, DA Arora, NK Helft, P Clayman, ML Oakley-Girvan, I AF Haggstrom, David A. Arora, Neeraj K. Helft, Paul Clayman, Marla L. Oakley-Girvan, Ingrid TI Follow-up Care Delivery Among Colorectal Cancer Survivors Most Often Seen by Primary and Subspecialty Care Physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cancer survivorship; colorectal cancer; primary care; health services research; quality assessment; patient-centered care ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PREVENTIVE CARE; SPECIALIST CARE; BREAST-CANCER; COLON-CANCER; EXPERIENCES AB The Institute of Medicine has identified patients as a key source of information for assessing the quality of care. To evaluate the association of physician specialty with the content and quality of follow-up cancer care. Three hundred three colorectal cancer (CRC) survivors in Northern California were surveyed 2-5 years post-diagnosis. Specialty of physician seen most often [primary care physician (PCP), oncologist, surgeon, or gastroenterologist]; other physician specialties seen; patient characteristics; content of visits; patient-centered quality of follow-up care (communication, coordination, nursing, and staff interactions). A minority (16%) of CRC survivors reported that the doctor they most often saw for follow-up cancer care was a PCP, while 60% saw an oncologist. Many CRC survivors (40%) saw > 1 physician for follow-up cancer care. Survivors most often seen by PCPs were more likely to have three or more medical comorbidities (70% vs. 51%, p = 0.012) than survivors seen by subspecialty physicians. Survivors seen by PCPs were less likely to report seeing a doctor for medical tests and more likely to report discussing disease prevention (82% vs. 64%, p = 0.012) or diet (70% vs. 48%, p = 0.005) with their doctor. There were no significant specialty differences in patient-centered quality of follow-up cancer care. Cancer survivors' assessment of the quality of care was similar across specialties, while the content of follow-up cancer care varied by physician specialty. These findings provide important information about the potential value of primary care and the need for coordination when delivering care to CRC survivors. C1 [Haggstrom, David A.] Richard L Roudebush VA Med Ctr, CIEBP, VA Hlth Serv Res & Dev, Indianapolis, IN 46202 USA. [Haggstrom, David A.] Regenstrief Inst Inc, IU Ctr Hlth Serv & Outcomes Res, Indianapolis, IN USA. [Haggstrom, David A.] Indiana Univ, Sch Med, Dept Med, Div Gen Internal Med & Geriatr, Indianapolis, IN USA. [Haggstrom, David A.; Helft, Paul] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Arora, Neeraj K.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Helft, Paul] Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN USA. [Helft, Paul] Clarian Hlth Inc, Charles Warren Fairbanks Ctr Med Eth, Indianapolis, IN USA. [Helft, Paul] Indiana Univ, Ctr Bioeth, Indianapolis, IN 46204 USA. [Clayman, Marla L.] Northwestern Univ, Feinberg Sch Med, Div Gen Internal Med, Chicago, IL 60611 USA. [Clayman, Marla L.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Oakley-Girvan, Ingrid] No Calif Canc Ctr, Fremont, CA USA. RP Haggstrom, DA (reprint author), Richard L Roudebush VA Med Ctr, CIEBP, VA Hlth Serv Res & Dev, 1481 W 10th St,11H, Indianapolis, IN 46202 USA. EM dahaggst@iupui.edu OI Clayman, Marla/0000-0001-8491-3672 FU VA HSR&D Career Development Award [CD207016-2]; NCI [N01-PC-35136] FX Dr. Haggstrom is supported by VA HSR&D Career Development Award CD207016-2. This research was funded by NCI contract N01-PC-35136 at the NCCC. Preliminary results of the paper were presented at the American Society of Clinical Oncology Annual Meeting, May 2008. This work represents the opinion of the authors and cannot be construed to represent the opinion of the National Cancer Institute, the Department of Veterans Affairs, or the Federal Government. NR 20 TC 18 Z9 18 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2009 VL 24 BP 472 EP 479 DI 10.1007/s11606-009-1017-6 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 507ZB UT WOS:000270894400017 ER PT J AU Brandon, WP Sundaram, R Dunham, AA AF Brandon, William P. Sundaram, Rajeshwari Dunham, Ashley A. TI Multiple Switching in Medicaid Managed Care: A Proportional Hazards Model SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Health maintenance organization; insurance; Medicaid; managed care; health plan; switching; churning; enrollment; disenrollment; population ID HEALTH PLAN CHOICE; UNITED-STATES; INSURANCE-COVERAGE; CHILDREN; DISENROLLMENT; ENROLLMENT; PROGRAM; PATTERNS; PRICE; GAPS AB This case study (n=41,969) aims to discover managerially useful predictors of multiple switching among HMOs in a Medicaid managed care population observed over 33 months. Cox's proportional hazards model was used to analyze eligibility data for the entire population, claims data for Medicaid services received during six months prior to HMO enrollment (sample n=2,474) and telephone interviews (sample n=656). Each analytic stage involved four comparisons: (1) enrollees with one switch compared with enrollees with no switches; (2) enrollees with multiple switches compared with those having no switches; (3) in relation to making the first switch, enrollees with multiple switches compared with those having one switch; and (4) in relation to making the second switch, multiple compared with those having one switch. Interruptions (which were independent of switches) predicted switching versus non-switching. Medical claims and, weakly, greater age were associated with multiple switching. Managers can use these three predictors to reduce switching and multiple switching. The finding that switching was associated with greater utilization before HMO enrollment contradicts findings for employer-sponsored insurance, but a possible explanation is offered. C1 [Brandon, William P.] Univ N Carolina, Charlotte, NC 28223 USA. [Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Dunham, Ashley A.] Duke Translat Med Inst Kannapolis, Kannapolis, NC USA. RP Brandon, WP (reprint author), Univ N Carolina, 9201 Univ City Blvd, Charlotte, NC 28223 USA. OI Sundaram, Rajeshwari/0000-0002-6918-5002 FU Intramural NIH HHS NR 43 TC 2 Z9 2 U1 1 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2009 VL 20 IS 4 BP 1124 EP 1141 PG 18 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 519IK UT WOS:000271759100019 PM 20168023 ER PT J AU Yiu, WH Pan, CJ Mead, PA Starost, MF Mansfield, BC Chou, JY AF Yiu, Wai Han Pan, Chi-Jiunn Mead, Paul A. Starost, Matthew F. Mansfield, Brian C. Chou, Janice Y. TI Normoglycemia alone is insufficient to prevent long-term complications of hepatocellular adenoma in glycogen storage disease type Ib mice SO JOURNAL OF HEPATOLOGY LA English DT Article DE Glycogen storage disease type Ib; Glucose-6-phosphate transporter; Hepatocellular adenoma; Malignant transformation; Adeno-associated virus; Gene therapy ID RECOMBINANT ADENOASSOCIATED VIRUS; COLONY-STIMULATING FACTORS; HEMATOPOIETIC STEM-CELL; GLUCOSE-6-PHOSPHATE TRANSPORTER; GENE-THERAPY; LIVER TRANSDUCTION; VECTOR GENOMES; NEUTROPHIL; EXPRESSION; DELIVERY AB Background/Aims: Glycogen storage disease type Ib (GSD-Ib) patients deficient in a glucose-6-phosphate transporter (G6PT) manifest disturbed glucose homeostasis, myeloid dysfunctions, and hepatocellular adenoma (HCA). This study was conducted to evaluate whether maintaining normoglycemia in GSD-Ib could prevent HCA. Methods:We infused neonatal GSD-Ib mice with adeno-associated virus (AAV) carrying G6PT and examined their metabolic and myeloid phenotypes for the 72-week study. Results:The AAV vector delivered the G6PT transgene to the liver and bone marrow. Long-term metabolic correction was achieved alongside a transient myeloid correction. Hepatic G6PT activity was 50% of wild-type levels at 2 weeks post-infusion but declined rapidly thereafter to reach 31% of wild-type levels by age 6 to 72 weeks. Despite this, the infused mice maintained normoglycemia throughout the study, exhibited near normal growth and normalized serum metabolite profiles. However, all five AAV-treated GSD-Ib mice that lived over 50 weeks accumulated excessive hepatic glycogen and fat. Two mice developed steatohepatitis and multiple HCAs with one undergoing malignant transformation. Conclusions: Normoglycemia alone cannot prevent hepatic steatosis and glycogen accumulation or the development of HCAs in GSD-Ib, providing one explanation why GSD-Ib patients maintaining normoglycemia under intense dietary therapy continue at risk for this long-term complication. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver. C1 [Yiu, Wai Han; Pan, Chi-Jiunn; Mead, Paul A.; Mansfield, Brian C.; Chou, Janice Y.] NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA. [Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 FU NICHD, NIH FX This research was supported by the Intramural Research Programs of the NICHD, NIH. The authors gratefully acknowledge the University of Florida Powell Gene Therapy Center for producing the AAV vectors used in this study. NR 43 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2009 VL 51 IS 5 BP 909 EP 917 DI 10.1016/j.jhep.2008.11.026 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 519IY UT WOS:000271760800010 PM 19376605 ER PT J AU Haussler, D O'Brien, SJ Ryder, OA Barker, FK Clamp, M Crawford, AJ Hanner, R Hanotte, O Johnson, WE McGuire, JA Miller, W Murphy, RW Murphy, WJ Sheldon, FH Sinervo, B Venkatesh, B Wiley, EO Allendorf, FW Amato, G Baker, CS Bauer, A Beja-Pereira, A Bermingham, E Bernardi, G Bonvicino, CR Brenner, S Burke, T Cracraft, J Diekhans, M Edwards, S Ericson, PGP Estes, J Fjelsda, J Flesness, N Gamble, T Gaubert, P Graphodatsky, AS Graves, JAM Green, ED Green, RE Hackett, S Hebert, P Helgen, KM Joseph, L Kessing, B Kingsley, DM Lewin, HA Luikart, G Martelli, P Moreira, MAM Nguyen, N Orti, G Pike, BL Rawson, DM Schuster, SC Seuanez, HN Shaffer, HB Springer, MS Stuart, JM Sumner, J Teeling, E Vrijenhoek, RC Ward, RD Warren, WC Wayne, R Williams, TM Wolfe, ND Zhang, YP Graph-Odatsky, A Johnson, WE Felsenfeld, A Turner, S AF Haussler, David O'Brien, Stephen J. Ryder, Oliver A. Barker, F. Keith Clamp, Michele Crawford, Andrew J. Hanner, Robert Hanotte, Olivier Johnson, Warren E. McGuire, Jimmy A. Miller, Webb Murphy, Robert W. Murphy, William J. Sheldon, Frederick H. Sinervo, Barry Venkatesh, Byrappa Wiley, Edward O. Allendorf, Fred W. Amato, George Baker, C. Scott Bauer, Aaron Beja-Pereira, Albano Bermingham, Eldredge Bernardi, Giacomo Bonvicino, Cibele R. Brenner, Sydney Burke, Terry Cracraft, Joel Diekhans, Mark Edwards, Scott Ericson, Per G. P. Estes, James Fjelsda, Jon Flesness, Nate Gamble, Tony Gaubert, Philippe Graphodatsky, Alexander S. Graves, Jennifer A. Marshall Green, Eric D. Green, Richard E. Hackett, Shannon Hebert, Paul Helgen, Kristofer M. Joseph, Leo Kessing, Bailey Kingsley, David M. Lewin, Harris A. Luikart, Gordon Martelli, Paolo Moreira, Miguel A. M. Nguyen, Ngan Orti, Guillermo Pike, Brian L. Rawson, David Michael Schuster, Stephan C. Seuanez, Hector N. Shaffer, H. Bradley Springer, Mark S. Stuart, Joshua Michael Sumner, Joanna Teeling, Emma Vrijenhoek, Robert C. Ward, Robert D. Warren, Wesley C. Wayne, Robert Williams, Terrie M. Wolfe, Nathan D. Zhang, Ya-Ping Graph-Odatsky, Alexander Johnson, Warren E. Felsenfeld, Adam Turner, Steve CA Genome 10K Community Scientists Mammals Grp Birds Grp Amphibians Reptiles Grp Fishes Grp General Policy Grp Anal Grp TI Genome 10K: A Proposal to Obtain Whole-Genome Sequence for 10 000 Vertebrate Species SO JOURNAL OF HEREDITY LA English DT Article DE ancestral state reconstruction; comparative genomics; G10K; molecular evolution; species conservation; vertebrate biology ID PLURIPOTENT STEM-CELLS; ANTIMICROBIAL PEPTIDES; MOLECULAR PHYLOGENY; DIVERGENCE TIMES; POISON FROGS; EVOLUTION; GENERATION; CONSERVATION; GENETICS; ORIGINS AB The human genome project has been recently complemented by whole-genome assessment sequence of 32 mammals and 24 nonmammalian vertebrate species suitable for comparative genomic analyses. Here we anticipate a precipitous drop in costs and increase in sequencing efficiency, with concomitant development of improved annotation technology and, therefore, propose to create a collection of tissue and DNA specimens for 10 000 vertebrate species specifically designated for whole-genome sequencing in the very near future. For this purpose, we, the Genome 10K Community of Scientists (G10KCOS), will assemble and allocate a biospecimen collection of some 16 203 representative vertebrate species spanning evolutionary diversity across living mammals, birds, nonavian reptiles, amphibians, and fishes (ca. 60 000 living species). In this proposal, we present precise counts for these 16 203 individual species with specimens presently tagged and stipulated for DNA sequencing by the G10KCOS. DNA sequencing has ushered in a new era of investigation in the biological sciences, allowing us to embark for the first time on a truly comprehensive study of vertebrate evolution, the results of which will touch nearly every aspect of vertebrate biological enquiry. C1 [Haussler, David] Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. [O'Brien, Stephen J.; Johnson, Warren E.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Ryder, Oliver A.] San Diego Zoos Inst Conservat Res, Escondido, CA USA. [Barker, F. Keith] Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA. [Clamp, Michele] Broad Inst MIT & Harvard, Cambridge, MA USA. [Crawford, Andrew J.] Univ Los Andes, Dept Ciencias Biol, Bogota 4976, Colombia. [Hanner, Robert] Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada. [Hanotte, Olivier] Univ Nottingham, Sch Biol, Frozen Ark Project, Nottingham, Northants, England. [McGuire, Jimmy A.] Univ Calif Berkeley, Museum Vertebrate Zool, Berkeley, CA 94720 USA. [McGuire, Jimmy A.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Miller, Webb] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. [Murphy, Robert W.] Royal Ontario Museum, Dept Nat Hist, Toronto, ON M5S 2C6, Canada. [Murphy, William J.] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. [Sheldon, Frederick H.] Louisiana State Univ, Museum Nat Sci, Baton Rouge, LA 70803 USA. [Sheldon, Frederick H.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Williams, Terrie M.] Univ Calif Santa Cruz, Dept Ecol & Evolutionary Biol, Ctr Ocean Hlth, Santa Cruz, CA 95064 USA. [Venkatesh, Byrappa] Agcy Sci Technol & Res, Inst Mol & Cell Biol, Singapore, Singapore. [Wiley, Edward O.] Univ Kansas, Museum Nat Hist, Dept Ecol & Evolutionary Biol, Lawrence, KS 66045 USA. [Wiley, Edward O.] Univ Kansas, Biodivers Res Ctr, Dept Ecol & Evolutionary Biol, Lawrence, KS 66045 USA. [Allendorf, Fred W.] Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. [Amato, George] Amer Museum Nat Hist, Ctr Conservat Genet, New York, NY 10024 USA. [Baker, C. Scott] Oregon State Univ, Marine Mammal Inst, Newport, OR USA. [Baker, C. Scott] Oregon State Univ, Dept Fisheries & Wildlife, Newport, OR USA. [Bauer, Aaron] Villanova Univ, Dept Biol, Villanova, PA 19085 USA. [Beja-Pereira, Albano] CIBIO, Maonte Crasto, Vairao, Portugal. [Bermingham, Eldredge] Smithsonian Trop Res Inst, Balboa, Ancon, Panama. [Seuanez, Hector N.] Univ Fed Rio de Janeiro, Inst Nacl Canc, Div Genet, BR-20231050 Rio De Janeiro, Brazil. [Bonvicino, Cibele R.] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Biol & Parasitol Mamiferos Reservatorios Silv, Rio De Janeiro, Brazil. [Brenner, Sydney] Salk Inst Biol Studies, San Diego, CA USA. [Brenner, Sydney] Okinawa Inst Sci & Technol, Okinawa, Japan. [Burke, Terry] Univ Sheffield, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England. [Cracraft, Joel] Amer Museum Nat Hist, Dept Ornithol, New York, NY 10024 USA. [Edwards, Scott] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. [Ericson, Per G. P.] Swedish Museum Nat Hist, S-10405 Stockholm, Sweden. [Estes, James] Ctr Ocean Hlth, Dept Ecol & Evolut, Santa Cruz, CA USA. [Fjelsda, Jon] Univ Copenhagen, Zool Museum, DK-1168 Copenhagen, Denmark. [Flesness, Nate] ISIS, Minneapolis, MN USA. [Gamble, Tony] Univ Minnesota, Dept Genet & Cell Biol, Minneapolis, MN 55455 USA. [Gaubert, Philippe] Museum Natl Hist Nat, UMR BOREA IRD 207, F-75231 Paris, France. [Graphodatsky, Alexander S.] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk, Russia. [Graves, Jennifer A. Marshall] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia. [Green, Eric D.] NHGRI, NIH, Bethesda, MD 20892 USA. [Green, Richard E.] Max Planck Inst Evolutionary Anthropol, Leipzig, Germany. [Hackett, Shannon] Field Museum Nat Hist, Dept Zool, Div Birds, Chicago, IL 60605 USA. [Hebert, Paul] Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada. [Helgen, Kristofer M.] Smithsonian Inst, Natl Museum Nat Hist, Div Mammals, Washington, DC 20560 USA. [Joseph, Leo] CSIRO Sustainable Ecosyst Gungahlin Homestead, Canberra, ACT, Australia. [Kessing, Bailey] NCI, SAIC Frederick Inc, Lab Genom Div, Frederick, MD 21701 USA. [Kingsley, David M.] HHMI, Stanford, CA USA. [Kingsley, David M.] Stanford Univ, Beckman Ctr, Stanford, CA USA. [Lewin, Harris A.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA. [Lewin, Harris A.] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA. [Luikart, Gordon] Univ Porto, Ctr Investigacao Biodiversidade & Recursos Genet, Univ Montana, Div Biol Sci,CIBIO, Missoula, MT 59812 USA. [Orti, Guillermo] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. [Pike, Brian L.; Wolfe, Nathan D.] Global Viral Forecasting Initiat, San Francisco, CA USA. [Rawson, David Michael] Univ Bedfordshire, LIRANS Inst, Luton, Beds, England. [Seuanez, Hector N.] Univ Fed Rio de Janeiro, Dept Genet, BR-21949570 Rio De Janeiro, Brazil. [Shaffer, H. Bradley] Univ Calif Davis, Dept Ecol & Evolut, Davis, CA 95616 USA. [Shaffer, H. Bradley] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA. [Springer, Mark S.] Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. [Sumner, Joanna] Museum Victoria, Melbourne, Vic, Australia. [Teeling, Emma] Univ Coll Dublin, Sch Biol & Environm Sci, Sci Ctr W, Dublin 2, Ireland. [Vrijenhoek, Robert C.] Monterey Bay Aquarium Res Inst, Moss Landing, CA USA. [Ward, Robert D.] CSIRO Marine & Atmospher Res, Hobart, Tas, Australia. [Warren, Wesley C.] Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO USA. [Wayne, Robert] Univ Calif Los Angeles, Los Angeles, CA USA. [Wolfe, Nathan D.] Stanford Univ, Program Human Biol, Stanford, CA 94305 USA. [Zhang, Ya-Ping] Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Yunnan, Peoples R China. RP Haussler, D (reprint author), Univ Calif Santa Cruz, Howard Hughes Med Inst, CBSE ITI E2501, Santa Cruz, CA 95064 USA. EM haussler@soe.ucsc.edu; stephen.obrien@nih.gov; oryder@sandiegozoo.org RI Johnson, Warren/D-4149-2016; Graphodatsky, Alexander/B-4922-2010; Beja-Pereira, Albano/B-3681-2008; Joseph, Leo/F-9235-2010; Murphy, Robert/D-8586-2011; Bernardi, Giacomo/F-6346-2011; Gamble, Tony/A-5690-2011; Ward, Robert/A-2319-2012; ASTAR, IMCB/E-2320-2012; Barker, Keith/K-2795-2012; Hanotte, Olivier/B-4669-2013; Inca, Inct/K-2204-2013; Burke, Terry/B-3196-2011; Bonvicino, Cibele /O-3390-2014 OI Johnson, Warren/0000-0002-5954-186X; Luikart, Gordon/0000-0001-8697-0582; Rawson, David/0000-0002-0289-3856; Edwards, Scott/0000-0003-2535-6217; Venkatesh, Byrappa/0000-0003-3620-0277; Graphodatsky, Alexander/0000-0002-8282-1085; Beja-Pereira, Albano/0000-0002-1607-7382; Bernardi, Giacomo/0000-0002-8249-4678; Barker, Keith/0000-0001-7488-2470; Burke, Terry/0000-0003-3848-1244; FU American Genetic Association,; Gordon and Betty Moore Foundation; NHGRI Intramural Sequencing Center; UCSC Alumni Association; Howard Hughes Medical Institute; Euteleost Tree of Life; National Science Foundation [0732819, DEB-0640967, 0543556, 0817042, EF0629849, DEB-0443470, 30621092]; The Global Viral Forecasting Initiative; Biomedical Research Council of A*STAR, Singapore; Natural Sciences and Engineering Research Council Discovery Grant; National Basic Research Program of China [2007CB411600]; Bureau of Science and Technology of Yunnan Province; MCB; SB RAS Programs; Portuguese-American Foundation for Development, CIBIO, UP, University of Montana; Portuguese Science Foundation [PTDC/CVT/69438/2006, PTDC/BIA-BDE/65625/2006] FX American Genetic Association, Gordon and Betty Moore Foundation, NHGRI Intramural Sequencing Center, and UCSC Alumni Association to cost of the Genome 10K workshop; Howard Hughes Medical Institute to D. H.; Gordon and Betty Moore Foundation to S. C. S.; Assembling the Euteleost Tree of Life to E. W.; National Science Foundation (0732819 to E. W., DEB-0640967 and 0543556 to J. A. M., 0817042 to H. B. S., EF0629849 to W. J. M., DEB-0443470 to G. O.); The Global Viral Forecasting Initiative to N. W., B. P., and M. L.; Biomedical Research Council of A*STAR, Singapore to B. V.; Natural Sciences and Engineering Research Council Discovery Grant to R. W. M.; National Basic Research Program of China (973 Program, 2007CB411600), the National Natural Science Foundation of China (30621092), and Bureau of Science and Technology of Yunnan Province to Y. Z.; MCB and SB RAS Programs (A. S. G.); Portuguese-American Foundation for Development, CIBIO, UP, University of Montana [G. L.] and Portuguese Science Foundation [PTDC/CVT/69438/2006; PTDC/BIA-BDE/65625/2006 to G. L]. NR 94 TC 204 Z9 208 U1 5 U2 62 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 EI 1465-7333 J9 J HERED JI J. Hered. PD NOV-DEC PY 2009 VL 100 IS 6 BP 659 EP 674 DI 10.1093/jhered/esp086 PG 16 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 520CN UT WOS:000271817600001 ER PT J AU Zhao, YB Wang, QJ Yang, SC Kochenderfer, JN Zheng, ZL Zhong, XS Sadelain, M Eshhar, Z Rosenberg, SA Morgan, RA AF Zhao, Yangbing Wang, Qiong J. Yang, Shicheng Kochenderfer, James N. Zheng, Zhili Zhong, Xiaosong Sadelain, Michel Eshhar, Zelig Rosenberg, Steven A. Morgan, Richard A. TI A Herceptin-Based Chimeric Antigen Receptor with Modified Signaling Domains Leads to Enhanced Survival of Transduced T Lymphocytes and Antitumor Activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ADOPTIVE CELL TRANSFER; EX-VIVO EXPANSION; BREAST-CANCER; IN-VIVO; MONOCLONAL-ANTIBODY; 4-1BB LIGAND; GENE-THERAPY; CYTOTOXIC LYMPHOCYTES; METASTATIC MELANOMA; EFFECTOR FUNCTION AB To generate chimeric Ag receptors (CARs) for the adoptive immunotherapy of cancer patients with ErbB2-expressing tumors, a single-chain Ab derived from the humanized mAb 4D5 Herceptin (trastuzumab) was initially linked to T cell signaling domains derived from CD28 and the CD3 zeta to generate a CAR against ErbB2. Human PBLs expressing the 41015 CAR demonstrated Ag-specific activities against ErbB2(+) tumors. However, a gradual loss of transgene expression was noted for PBLs transduced with this 4D5 CAR. When the CD3 zeta signaling domain of the CAR was truncated or mutated, loss of CAR expression was not observed, suggesting that the CD3 zeta signaling caused the transgene decrease, which was supported by the finding that T cells expressing 4D5 CARs with CD3 zeta ITAM mutations were less prone to apoptosis. By adding 4-1BB cytoplasmic domains to the CD28-CD3 zeta signaling moieties, we found increased transgene persistence in 4D5 CAR-transduced PBLs. Furthermore, constructs with 4-1BB sequences demonstrated increased cytokine secretion and lytic activity in 4D5 CAR-transduced T cells. More importantly, PBLs expressing this new version of the 4D5 CAR could not only efficiently lyse the autologous fresh tumor digests, but they could strongly suppress tumor growth in a xenogenic mouse model. The Journal of Immunology, 2009, 183: 5563-5574. C1 [Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sadelain, Michel] Mem Sloan Kettering Canc Ctr, Ctr Cell Engn, Mol Pharmacol & Chem Program, New York, NY 10021 USA. [Eshhar, Zelig] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. RP Morgan, RA (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1201,Bldg 10,Room 3W5940, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; European Commission FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. Z.E. was supported in part by and the Sixth Framework Programme of the European Commission consortium ATTACK. NR 80 TC 115 Z9 123 U1 1 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 1 PY 2009 VL 183 IS 9 BP 5563 EP 5574 DI 10.4049/jimmunol.0900447 PG 12 WC Immunology SC Immunology GA 515QU UT WOS:000271488500018 PM 19843940 ER PT J AU Chinnasamy, N Waigo, JA Yu, ZY Frankel, TL Riley, JP Paikhuist, MR Restifo, NP Robbins, PF Rosenberg, SA Morgan, RA AF Chinnasamy, Nachimuthu Waigo, Jennifer A. Yu, Zhiya Frankel, Timothy L. Riley, John P. Paikhuist, Maria R. Restifo, Nicholas P. Robbins, Paul F. Rosenberg, Steven A. Morgan, Richard A. TI TCR Against Cancer Testis Antigen MAGE-A3 for Targeted Adoptive Immunotherapy of Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Chinnasamy, Nachimuthu; Waigo, Jennifer A.; Yu, Zhiya; Frankel, Timothy L.; Riley, John P.; Paikhuist, Maria R.; Restifo, Nicholas P.; Robbins, Paul F.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Waigo, Jennifer A.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 941 EP 942 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100011 ER PT J AU Chinnasamy, D Yu, ZY Theoret, MR Shrimali, RK Zhao, YB Restifo, NP Rosenberg, SA AF Chinnasamy, Dhanalakshmi Yu, Zhiya Theoret, Marc R. Shrimali, Rajeev K. Zhao, Yang Bing Restifo, Nicholas P. Rosenberg, Steven A. TI Adoptive Cell Therapy Using T Cells Expressing a Chimeric Antigen Receptor for Vascular Endothelial Growth Factor Receptor-2 Promotes Tumor Destruction and Enhances Immunotherapy in Mice SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Theoret, Marc R.; Restifo, Nicholas P.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Zhao, Yang Bing] Univ Penn, Sch Med, Dept Pathol, Lab Med,Abramson Canc Res Inst, Philadelphia, PA 19104 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 942 EP 942 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100012 ER PT J AU Davis, JL Theoret, M Zheng, ZL Rosenberg, SA Morgan, RA AF Davis, Jeremy L. Theoret, Marc Zheng, Zhili Rosenberg, Steven A. Morgan, Richard A. TI Immune Responses to Murine T-cell Receptors in Patients Enrolled in the TCR Gene Therapy Trials SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Davis, Jeremy L.; Theoret, Marc; Zheng, Zhili; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 943 EP 943 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100014 ER PT J AU Friedman, KM Yang, JC Prieto, P Devillier, LE Rosenberg, SA Dudley, ME AF Friedman, Kevin M. Yang, James C. Prieto, Peter Devillier, Laura E. Rosenberg, Steven A. Dudley, Maik E. TI Evidence for CD4 T-cell - mediated Tumor Regression, the Mechanism of the Subsequent Tumor Immune Escape SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Friedman, Kevin M.; Yang, James C.; Prieto, Peter; Devillier, Laura E.; Rosenberg, Steven A.; Dudley, Maik E.] NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 943 EP 944 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100016 ER PT J AU Klebanoff, CA Yu, ZY Hwang, LN Palmer, DC Gattinoni, L Restifo, NP AF Klebanoff, Christopher A. Yu, Zhiya Hwang, Leroy N. Palmer, Douglas C. Gattinoni, Luca Restifo, Nicholas P. TI Programming Tumor-reactive Effector Memory CD8(+) T Cells In Vitro Obviates the Requirement For In Vivo Vaccination SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Klebanoff, Christopher A.; Hwang, Leroy N.; Palmer, Douglas C.; Gattinoni, Luca] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Klebanoff, Christopher A.] NIH, Res Scholars Program, HHMI, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 946 EP 946 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100024 ER PT J AU Restifo, NP Klebanoff, CA Hinrichs, CS Muranski, P Gattinoni, L AF Restifo, Nicholas P. Klebanoff, Christopher A. Hinrichs, Christian S. Muranski, Pawel Gattinoni, Luca TI What are the Functional and Phenotypic Qualities of Therapeutically Successful Antitumor T Cells? SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Restifo, Nicholas P.; Klebanoff, Christopher A.; Hinrichs, Christian S.; Muranski, Pawel] NCI, Bethesda, MD 20892 USA. [Klebanoff, Christopher A.] Howard Hughes Med Inst, Bethesda, MD USA. RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010 NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 948 EP 949 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100031 ER PT J AU Rosenberg, SA AF Rosenberg, Steven A. TI Cell Transfer Therapy for Patients With Metastatic Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Rosenberg, Steven A.] NIH, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 949 EP 949 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100032 ER PT J AU Shanker, A De Kluyver, R Wine, JW Sayers, TJ AF Shanker, Anil De Kluyver, Rachel Wine, John W. Sayers, Thomas J. TI Impact of Bortezomib-induced Proteasome Inhibition on Antitumor T-cell Responses In Vivo SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Shanker, Anil; De Kluyver, Rachel; Wine, John W.; Sayers, Thomas J.] NCI, Frederick, MD 21701 USA. [Shanker, Anil; Sayers, Thomas J.] SAIC Frederick Inc, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA. RI Sayers, Thomas/G-4859-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 949 EP 950 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100033 ER PT J AU Shrinath, RK Theoret, MR Yu, ZY Chinnasamy, D Restifo, NP Rosenberg, SA AF Shrinath, Rajeev K. Theoret, Marc R. Yu, Zhiya Chinnasamy, Dhanalakshmi Restifo, Nicholas P. Rosenberg, Steven A. TI Combination Therapy With Antiangiogenic Agents and Adoptive Cell Therapy (ACT) in a Murine Tumor Model SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Shrinath, Rajeev K.; Theoret, Marc R.; Yu, Zhiya; Chinnasamy, Dhanalakshmi; Restifo, Nicholas P.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 950 EP 950 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100034 ER PT J AU Chan, T Back, TC Subleski, JJ Weiss, JM Ortaldo, JR Wiltrout, RH AF Chan, Tim Back, Timothy C. Subleski, Jeffrey J. Weiss, Jonathan M. Ortaldo, John R. Wiltrout, Robert H. TI Differential Modulation of Hepatic and Splenic Dendritic Cell Number and Functions With Systemic Interleukin-12 Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Chan, Tim; Back, Timothy C.; Subleski, Jeffrey J.; Weiss, Jonathan M.; Ortaldo, John R.; Wiltrout, Robert H.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 955 EP 955 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100049 ER PT J AU Lugli, E Goldman, CK Roederer, M Waldmann, TA AF Lugli, Enrico Goldman, Catolyn K. Roederer, Mario Waldmann, Thomas A. TI Interleukin-15 Administration to Rhesus Macaques Expands Natural Killer and Memory T Cells and Induces Long-lasting Changes in T-cell Homeostasis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Roederer, Mario] NIH, VRC, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 958 EP 958 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100060 ER PT J AU Pos, Z Selleri, S Spivey, TL Liu, H Worschech, A Sabatino, M Monaco, A Falus, A Wang, E Alter, HJ Marincola, F AF Pos, Zoltan Selleri, Silvia Spivey, Tara L. Liu, Hui Worschech, Andrea Sabatino, Marianna Monaco, Alessandro Falus, Andras Wang, Ena Alter, Harvey J. Marincola, Francesco TI Race Affects Clinical Responsiveness to Interferon-alpha in a Disease-dependent Fashion SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Genelux Corp, San Diego Sci Ctr, San Diego, CA USA. Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. RI Worschech, Andrea/I-3919-2012; Monaco, Alessandro/O-5338-2015 OI Worschech, Andrea/0000-0002-4303-8653; Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 960 EP 960 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100066 ER PT J AU Weiss, JM Back, TC Scarzello, A Subleski, JJ Hall, VL Stauffer, JK Micic, D Alderson, K Murphy, WJ Wiltrout, RH AF Weiss, Jonathan M. Back, Timothy C. Scarzello, Anthony Subleski, Jeffrey J. Hall, Veronica L. Stauffer, Jimmy K. Micic, Dejan Alderson, Kory Murphy, Wilham J. Wiltrout, Robert H. TI Successful Immunotherapy With IL-2/Anti-CD40 Directly Coincides With Specific Chemokine-mediated Mitigation of an Immunosuppressive Tumor Microenvironment SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Weiss, Jonathan M.; Back, Timothy C.; Scarzello, Anthony; Subleski, Jeffrey J.; Hall, Veronica L.; Stauffer, Jimmy K.; Micic, Dejan; Wiltrout, Robert H.] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Alderson, Kory; Murphy, Wilham J.] Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 964 EP 965 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100079 ER PT J AU Zaharoff, DA Hance, KW Rogers, CJ Schlom, J Greiner, JW AF Zaharoff, David A. Hance, Kenneth W. Rogers, Connie J. Schlom, Jeffrey Greiner, John W. TI Intratumoral Immunotherapy With Chitosan/IL-12 Eradicates Established Tumors and Elicits Durable, Tumor-specific Immune Responses SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Zaharoff, David A.] Univ Arkansas, Fayetteville, AR 72701 USA. [Hance, Kenneth W.; Rogers, Connie J.; Schlom, Jeffrey; Greiner, John W.] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 965 EP 966 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100082 ER PT J AU Schlom, J AF Schlom, Jeffrey TI Enhancing Cancer Vaccines as Monotherapy and in Combination Therapies SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Schlom, Jeffrey] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 976 EP 976 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100113 ER PT J AU Monsurio, V Beghelli, S Wang, R Barbi, S Com, S Di Pasquale, G Bersani, S Castellucci, M Sorio, C Eleuteri, S Worschech, A Chiorini, J Pederzoli, P Alter, H Marincola, F Scarpa, A AF Monsurio, Vladia Beghelli, S. Wang, Richard Barbi, S. Com, S. Di Pasquale, G. Bersani, S. Castellucci, M. Sorio, C. Eleuteri, S. Worschech, Andrea Chiorini, J. Pederzoli, P. Alter, H. Marincola, Francesco Scarpa, A. TI Antiviral State Segregates 2 Molecular Phenotypes of Pancreatic Adenocarcinoma: Potential Relevance for Adenoviral Gene Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Monsurio, Vladia; Bersani, S.; Sorio, C.; Eleuteri, S.] Univ Verona, Dept Pathol, Sch Med, I-37100 Verona, Italy. [Pederzoli, P.] Univ Verona, Dept Surg & Gastroenterol Sci, Sch Med, I-37100 Verona, Italy. [Wang, Richard; Worschech, Andrea; Alter, H.; Marincola, Francesco] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Wang, Richard; Worschech, Andrea; Alter, H.; Marincola, Francesco] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Di Pasquale, G.; Chiorini, J.] NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 990 EP 991 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100157 ER PT J AU Bedognetti, D Zoppoli, G Massucco, C Zupo, S Sertoli, MR Zanardt, H Messina, M Siffredi, G Bruzzone, A Ballean, E Ferranni, M Nencioni, A Caltabiano, G Provinciali, N Racchi, O Ferraris, AM Blandmi, P Boccardo, F Sticcehi, L Icardi, G Marincola, F Bacilieri, S Ansaldi, F De Maria, A AF Bedognetti, Davide Zoppoli, Gabriele Massucco, Carlotta Zupo, Simonetta Sertoli, Mario Roberto Zanardt, Hisa Messina, Marco Siffredi, Guido Bruzzone, Andrea Ballean, Enrico Ferranni, Manlio Nencioni, Alessio Caltabiano, Graziano Provinciali, Nicoletta Racchi, Omar Ferraris, Anna Maria Blandmi, Pietro Boccardo, Francesco Sticcehi, Laura Icardi, Giancarlo Marincola, Francesco Bacilieri, Sabrina Ansaldi, Filippo De Maria, Andrea TI Impaired Humoral Response to Influenza Vaccine and Prolonged B Memory Cell Depletion as a Consequence of Rituximab-based Immunochemotherapy in non-Hodgkin Lymphoma Patients SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Bedognetti, Davide; Zoppoli, Gabriele; Sertoli, Mario Roberto; Messina, Marco; Siffredi, Guido; Ballean, Enrico; Ferranni, Manlio; Nencioni, Alessio; Caltabiano, Graziano; Provinciali, Nicoletta; Racchi, Omar; Ferraris, Anna Maria; Blandmi, Pietro; Boccardo, Francesco; Sticcehi, Laura; Icardi, Giancarlo; Bacilieri, Sabrina; De Maria, Andrea] Univ Genoa, Genoa, Italy. [Massucco, Carlotta; Zupo, Simonetta; Sertoli, Mario Roberto; Ferranni, Manlio; Ferraris, Anna Maria; Boccardo, Francesco; De Maria, Andrea] Natl Canc Res Inst Genoa, Genoa, Italy. [Bedognetti, Davide; Zoppoli, Gabriele; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. RI Zoppoli, Gabriele/A-9540-2010; Bedognetti, Davide/A-9090-2012; de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 992 EP 993 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100163 ER PT J AU Soto-Pantoja, DR Maxhimer, JB Isenberg, JS Ridnour, LA Shih, HB DeGraff, WG Tsokos, M Wink, DA Roberts, DD AF Soto-Pantoja, David R. Maxhimer, Justin B. Isenberg, Jeff S. Ridnour, Lisa A. Shih, Hubert B. DeGraff, William G. Tsokos, Maria Wink, David A. Roberts, David D. TI Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Soto-Pantoja, David R.; Shih, Hubert B.; Tsokos, Maria; Roberts, David D.] CCR, Pathol Lab, Bethesda, MD USA. [Ridnour, Lisa A.; DeGraff, William G.; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 992 EP 992 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100162 ER PT J AU Gentilcore, G Ascierto, ML Napolitano, M Capone, M Simeone, E Da Ponte, A Caraco, C Wang, E Mozzillo, N Marincola, F Ascierto, PA AF Gentilcore, Gutsy Ascierto, Maria L. Napolitano, Maria Capone, Marilena Simeone, Ester Da Ponte, Antonio Caraco, Corrado Wang, Ena Mozzillo, Nicola Marincola, Francesco Ascierto, Paolo A. TI CTREGS (Circulating Regulatory T Cells) Reduction in Melanoma Patients Treated With Intravenous High-dose Interferon-alpha 2B SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Gentilcore, Gutsy; Ascierto, Maria L.; Napolitano, Maria; Capone, Marilena; Simeone, Ester; Da Ponte, Antonio; Caraco, Corrado; Mozzillo, Nicola; Ascierto, Paolo A.] Natl Canc Inst, Naples, Italy. [Ascierto, Maria L.; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. RI Ascierto, Maria Libera/A-9239-2012 NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 996 EP 997 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100175 ER PT J AU Kmtectak, M Worschech, A Gowda, M Depcrynski, A Wang, E Godder, K Holt, S Knutson, KL Marmcola, F Manjih, MH AF Kmtectak, Maciej Worschech, Andrea Gowda, Madhu Depcrynski, Amy Wang, Ena Godder, Kamar Holt, Shawn Knutson, Keith L. Marmcola, Francesco Manjih, Masoud H. TI Helpless CD8(+) T Cells are not Hopeless SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Kmtectak, Maciej; Gowda, Madhu; Depcrynski, Amy; Wang, Ena; Godder, Kamar; Holt, Shawn; Manjih, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Worschech, Andrea; Wang, Ena; Marmcola, Francesco] NIH, Bethesda, MD 20892 USA. [Worschech, Andrea] Genelux Corp, San Diego, CA USA. [Knutson, Keith L.] Mayo Clin, Coll Med, Rochester, MN USA. [Worschech, Andrea] Univ Wurzburg, Wurzburg, Germany. RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 997 EP 998 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100179 ER PT J AU Knneciak, M Gowdi, M Graham, L Godder, K Bear, HD Marincola, F Manjih, MH AF Knneciak, Maciej Gowdi, Madhu Graham, Laura Godder, Kamar Bear, Harry D. Marincola, Francesco Manjih, Masoud H. TI Human FoxP3+T Regulatory Cells: Facts or Technical Artifacts? SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Knneciak, Maciej; Gowdi, Madhu; Graham, Laura; Godder, Kamar; Bear, Harry D.; Manjih, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Marincola, Francesco] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 997 EP 997 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100178 ER PT J AU Subleski, JJ Hall, VL Scarzello, AJ Wolfe, TB Ortaldo, JR Hodge, DL Weiss, JM Chan, T Wiltrout, RH AF Subleski, Jeffrey J. Hall, Veronica L. Scarzello, Anthony J. Wolfe, Thomas B. Ortaldo, John R. Hodge, Deborah L. Weiss, Jonathan M. Chan, Tim Wiltrout, Robert H. TI Acute Inflammation With Interleukin-18/Interleukin-12 or alpha-GalCer Treatment Induces Liver iNKT Cell Apoptosis and Repopulation From Peripheral Tissues Whereas Chronic Inflammation Ablates Systemic iNKT Cells With Thymic-dependent Repopulation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Subleski, Jeffrey J.; Hall, Veronica L.; Scarzello, Anthony J.; Wolfe, Thomas B.; Ortaldo, John R.; Hodge, Deborah L.; Weiss, Jonathan M.; Chan, Tim; Wiltrout, Robert H.] NCI, CCR, LEI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 999 EP 999 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100184 ER PT J AU Frinchieri, G Cardone, M Salcedo, R Jones, Y Lyakh, L Cataisson, C Yuspa, S AF Frinchieri, Giorgio Cardone, Marco Salcedo, Rosalba Jones, Yava Lyakh, Lyudmila Cataisson, Christophe Yuspa, Stuart TI Interleukin-1 Role in Human Th17 Responses, Dendritic Cell Activation, and Epithelial Cell Transformation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Frinchieri, Giorgio; Cardone, Marco; Jones, Yava; Lyakh, Lyudmila] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Cataisson, Christophe; Yuspa, Stuart] NCI, Cell Biol & Genet Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1000 EP 1000 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100187 ER PT J AU Terabe, M AF Terabe, Masaki TI Regulation of Tumor Immunity by Natural Killer T-cell Subsets SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Terabe, Masaki] NCI, Vaccine Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1000 EP 1000 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100186 ER PT J AU Ascierto, ML Gentilcoie, G Gravina, C Worschech, A Pos, Z Wang, RY Natale, E Capone, M De Maio, A Pirozzi, G De Martino, S Wang, E Marincola, F Ascierto, PA AF Ascierto, Maria L. Gentilcoie, Giusy Gravina, Carmela Worschech, Andrea Pos, Zoltan Wang, Richard Y. Natale, Emiliana Capone, Marilena De Maio, Anna Pirozzi, Giuseppe De Martino, Silvana Wang, Ena Marincola, Francesco Ascierto, Paolo A. TI In Vitro Anticancer Property of NBD Peptide Through Inhibition of Nuclear Factor-kappa B Activation SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Ascierto, Maria L.; Worschech, Andrea; Pos, Zoltan; Wang, Richard Y.; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Ascierto, Maria L.; Gentilcoie, Giusy; Gravina, Carmela; Capone, Marilena; Pirozzi, Giuseppe; De Martino, Silvana; Ascierto, Paolo A.] NCI, Bethesda, MD 20892 USA. [Natale, Emiliana; De Maio, Anna] Univ Naples Federico 2, Naples, Italy. RI Ascierto, Maria Libera/A-9239-2012; Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1001 EP 1001 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100191 ER PT J AU Maccalli, C Wang, E Di Tomaso, T Mazzoleni, S Sovena, G Ferione, S Galli, R Marincola, F Parmiani, G AF Maccalli, Cristina Wang, Ena Di Tomaso, Tiziano Mazzoleni, Stefania Sovena, Gloria Ferione, Soldano Galli, Rossella Marincola, Francesco Parmiani, Girogio TI Definition of the Immunologic Properties of Cancer Stem Cells Isolated From Human Glioblastoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Maccalli, Cristina; Di Tomaso, Tiziano; Sovena, Gloria; Parmiani, Girogio] San Raffaele Fdn, Inst Sci, Unit Immunobiotherapy Melanoma & Solid Tumors, Milan, Italy. [Mazzoleni, Stefania; Galli, Rossella] San Raffaele Fdn, Inst Sci, Stem Cell Res Inst, Milan, Italy. [Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Ferione, Soldano] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1001 EP 1001 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100190 ER PT J AU Savers, TJ Jacobsen, K Shanker, A Brooks, AD AF Savers, Thomas J. Jacobsen, Kristen Shanker, Anil Brooks, Alan D. TI Bortezomib Sensitizes Renal Cancer Cells to TRAIL-mediated Apoptosis In Vitro and In Vivo SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Savers, Thomas J.; Brooks, Alan D.] SAIC Frederick, Frederick, MD USA. [Jacobsen, Kristen] NCI, CIP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1008 EP 1008 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100213 ER PT J AU Wang, E Bussom, S Chen, LG Quinn, C Wing, L Jiang, Z Xi, D Jia, LB White, J Marincola, F Cheng, YC AF Wang, Ena Bussom, Scott Chen, Linguo Quinn, Courtney Wing, Lam Jiang, Zaoh Xi, Dan Jia, Libin White, Jeffrey Marincola, Francesco Cheng, Yung-Chi TI Transcriptional Alteration Induced by Treatment of Traditional Chinese Medicine (PHY-906) in Colon Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Wang, Ena; Chen, Linguo; Quinn, Courtney; Marincola, Francesco] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Bussom, Scott; Chen, Linguo; Quinn, Courtney; Wing, Lam; Jiang, Zaoh; Cheng, Yung-Chi] NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA. [Xi, Dan; Jia, Libin; White, Jeffrey] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1009 EP 1010 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100217 ER PT J AU Worschech, A Ascierto, ML Chen, NH Yu, YA Zhang, Q DiPasquale, G Pos, Z Wang, E Szalay, AA Marincola, F AF Worschech, Andrea Ascierto, Maria L. Chen, Nanhai Yu, Yong A. Zhang, Qian DiPasquale, Giovanni Pos, Zoltan Wang, Ena Szalay, Aladar A. Marincola, Francesco TI Cross-talk Between Constitutive Antiviral State in Cancer Cell Lines and the Host's Immune Response During Oncolytic Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 NIH, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. [Chen, Nanhai; Yu, Yong A.; Zhang, Qian; DiPasquale, Giovanni; Szalay, Aladar A.] Genelux Corp, Res & Dev, San Diego, CA USA. [Szalay, Aladar A.] Univ Wurzburg, Vinchow Ctr Expt Biomed, Wurzburg, Germany. RI Ascierto, Maria Libera/A-9239-2012; Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 3 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1010 EP 1011 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100219 ER PT J AU Worschech, A Kmieciak, M Knutson, KL Bear, HD Szalay, AA Wang, E Marincola, F Manjib, MH AF Worschech, Andrea Kmieciak, Maciej Knutson, Keith L. Bear, Harry D. Szalay, Aladar A. Wang, Ena Marincola, Francesco Manjib, Masoud H. TI Signatures Associated With Rejection or Recurrence in HER-2/Neu-positive Mammary Tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Worschech, Andrea; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA. [Worschech, Andrea] Genelux Corp, San Diego, CA USA. [Kmieciak, Maciej; Bear, Harry D.; Manjib, Masoud H.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. [Knutson, Keith L.] Mayo Clin, Coll Med, Rochester, MN USA. [Worschech, Andrea; Szalay, Aladar A.] Univ Wurzburg, Wurzburg, Germany. RI Worschech, Andrea/I-3919-2012 OI Worschech, Andrea/0000-0002-4303-8653 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1011 EP 1011 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100220 ER PT J AU Lowy, DR Day, PM Kines, R Roberts, JN Thompson, CD Pang, S Buck, CB Roden, R Schiller, JT AF Lowy, Douglas R. Day, Patricia M. Kines, Rhonda Roberts, Jeffrey N. Thompson, Cynthia D. Pang, Susana Buck, Christopher B. Roden, Richard Schiller, John T. TI Current and Future Preventive Human Papillomavirus Vaccines SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 24th Annual Meeting of the International-Society-for-Biology-Therapy-of-Cancer CY OCT 29-31, 2009 CL Washington, DC SP Int Soc Biol Therapy Canc C1 [Lowy, Douglas R.; Kines, Rhonda; Roberts, Jeffrey N.; Thompson, Cynthia D.; Pang, Susana; Buck, Christopher B.; Schiller, John T.] NCI, Cellular Oncol Lab, CCR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2009 VL 32 IS 9 BP 1012 EP 1012 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 510RX UT WOS:000271110100224 ER PT J AU Yuan, LJ Honma, S Kim, I Kapikian, AZ Hoshino, Y AF Yuan, Lijuan Honma, Shinjiro Kim, Inyoung Kapikian, Albert Z. Hoshino, Yasutaka TI Resistance to Rotavirus Infection in Adult Volunteers Challenged with a Virulent G1P1A[8] Virus Correlated with Serum Immunoglobulin G Antibodies to Homotypic Viral Proteins 7 and 4 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NEUTRALIZING-ANTIBODY; IMMUNE-RESPONSES; YOUNG-CHILDREN; NATURAL INFECTIONS; VACCINE; VP7; PROTECTION; BOVINE; EPITOPES; SEROTYPE AB Background. In a study performed in 1983, 18 adult volunteers received oral challenge with the virulent human rotavirus strain D (G1P1A[8], NSP4[B]). To identify correlates of resistance to rotavirus infection, we analyzed levels of serum immunoglobulin (Ig) A and IgG antibodies to various rotaviral antigens in 16 of the 18 volunteers. Methods. We used immunocytochemical assays that involved a total of 16 different recombinant baculoviruses, with each baculovirus expressing one of the following major serotype/genotype rotavirus proteins for the serologic assays: (1) viral protein (VP) 4 with P1A[8], P1B[4], P2A[6], P3[9], or P4[10] specificity; (2) VP7 with G1-G4 or G9 specificity; and (3) nonstructural viral protein (NSP) 4 with genotype A, B, C, or D specificity. Results. The prechallenge titers of IgG antibody to VP7 types G1, G3, G4, and G9; VP4 types P1A[8], P1B[4], P2A[6], and P4[10]; and NSP4 type [A] in the group of noninfected volunteers (n = 11) were significantly higher than those in the group of infected volunteers (n = 5; of these 5 volunteers, 4 were symptomatically infected). Moreover, logistic regression analysis showed that resistance to rotavirus infection most closely correlated with higher prechallenge titers of IgG antibody to homotypic VP7 (G1) and VP4 (P1A[8]). Conclusions. These results suggest that protection against rotavirus infection and disease is primarily VP7/VP4 homotypic and, to a lesser degree, heterotypic. C1 [Yuan, Lijuan; Honma, Shinjiro; Kim, Inyoung; Kapikian, Albert Z.; Hoshino, Yasutaka] NIAID, Epidemiol Sect, Infect Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, Natl Inst Hlth, 50 S Dr,MSC 8026,Bldg 50,Rm 6308, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov RI Yuan, Lijuan/A-2468-2008 OI Yuan, Lijuan/0000-0003-0709-5228 FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX Financial support: Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 43 TC 7 Z9 7 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 IS 9 BP 1443 EP 1451 DI 10.1086/606116 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504XY UT WOS:000270652800012 PM 19785527 ER PT J AU Hoofnagle, JH Wahed, AS Belle, SH AF Hoofnagle, Jay H. Wahed, Abdus S. Belle, Steven H. CA Virahep-C Study Grp TI Age and Prediction of Sustained Virological Response to Hepatitis C Virus (HCV) Infection Treatment Based on 28-Day Decrease in HCV RNA Levels Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID RIBAVIRIN TREATMENT; PLUS RIBAVIRIN; PEGINTERFERON C1 [Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Wahed, Abdus S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Belle, Steven H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, Natl Inst Hlth, 31 Ctr Dr,Rm 9A27, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 IS 9 BP 1485 EP 1485 DI 10.1086/644508 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504XY UT WOS:000270652800019 ER PT J AU Arvay, ML Curns, AT Terp, S Armah, G Wontuo, P Parashar, UD Binka, F Glass, RI Widdowson, MA AF Arvay, Melissa L. Curns, Aaron T. Terp, Sophia Armah, George Wontuo, Peter Parashar, Umesh D. Binka, Fred Glass, Roger I. Widdowson, Marc-Alain TI How Much Could Rotavirus Vaccines Reduce Diarrhea-Associated Mortality in Northern Ghana? A Model to Assess Impact SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COST-EFFECTIVENESS; RISK-FACTORS; VACCINATION; EFFICACY; CHILDREN; SAFETY AB Background. Effective rotavirus vaccines could substantially reduce the similar to 500,000 deaths due to rotavirus disease per year worldwide, although the impact will depend on vaccine effectiveness, timing of administration, and coverage. We modeled vaccine impact on rotavirus-associated mortality in rural Ghana. Methods. All deaths due to acute diarrhea among children during 1998-2004 in the Kassena-Nankana District of Ghana were identified, and the number of deaths due to rotavirus disease was estimated using hospital laboratory surveillance data. Assuming rotavirus vaccine would be included in the current Expanded Program on Immunization schedule, we estimated the reduction in rotavirus-associated mortality with use of the current coverage and timing of diphtheria, tetanus, and pertussis vaccine administration and various age-restricted schedules. Results. Of the 381 deaths due to diarrhea, 131 (34%) were estimated to be caused by rotavirus infection. On the basis of current diphtheria, tetanus, and pertussis vaccine coverage and timing, a 90% efficacious 3-dose rotavirus vaccine would prevent 70% of deaths due to rotavirus infection if administered without age restrictions, 53% if only initiated among children <12 weeks of age, and 52% if the course also was completed by 32 weeks of age. Conclusions. Rotavirus vaccine has the potential to substantially reduce rotavirus-associated mortality in rural Ghana. Although timely vaccination should be encouraged, extending the current age recommendation for initiation of rotavirus vaccination could increase the coverage and impact of vaccination. C1 [Arvay, Melissa L.; Curns, Aaron T.; Parashar, Umesh D.; Widdowson, Marc-Alain] Natl Ctr Immunizat & Resp Dis, Ctr Dis Control & Prevent, Atlanta, GA 30030 USA. [Terp, Sophia] Ctr Dis Control & Prevent Fdn, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Binka, Fred] Univ Ghana, Sch Publ Hlth, Accra, Ghana. [Armah, George] Univ Ghana, Legon, Ghana. [Wontuo, Peter] Navrongo Hlth Res Ctr, Navrongo, Ghana. RP Arvay, ML (reprint author), Natl Ctr Immunizat & Resp Dis, Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS C-12, Atlanta, GA 30030 USA. EM MArvay@cdc.gov OI Widdowson, Marc-Alain/0000-0002-0682-6933 FU O. C. Hubert Fellowship; Centers for Disease Control and Prevention Foundation; GAVI Alliance FX Financial support: O. C. Hubert Fellowship, Centers for Disease Control and Prevention Foundation, and the GAVI Alliance (through PATH). NR 24 TC 11 Z9 12 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S85 EP S91 DI 10.1086/605062 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100011 PM 19817619 ER PT J AU Curns, AT Coffin, F Glasser, JW Glass, RI Parashar, UD AF Curns, Aaron T. Coffin, Fanny Glasser, John W. Glass, Roger I. Parashar, Umesh D. TI Projected Impact of the New Rotavirus Vaccination Program on Hospitalizations for Gastroenteritis and Rotavirus Disease among US Children < 5 Years of Age during 2006-2015 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNIZATION PRACTICES ACIP; UNITED-STATES; VARICELLA VACCINATION; ADVISORY-COMMITTEE; DIARRHEA; SURVEILLANCE; TRENDS; PREVENTION; MORBIDITY; MORTALITY AB Background. Rotavirus causes approximately one-third to one-half (55,000-70,000 hospitalizations per year) of hospitalizations for acute gastroenteritis (AGE) among US children <5 years of age. We forecasted the potential reduction in the number of hospitalizations for rotavirus disease and AGE in US children during 2006-2015 as a result of the new rotavirus vaccine introduced in 2006. Methods. The mean number of hospitalizations for AGE by calendar month among US children was determined using the National Hospital Discharge Survey from the period 1993-2005. From these baseline prevaccine estimates, we forecasted the effect of vaccine in reducing the number of hospitalizations for rotavirus disease and AGE during 2006-2015 with use of estimates of vaccine effectiveness and uptake. Results. During 2006-2015, similar to 313,000 (45%) of an estimated 703,190 hospitalizations for rotavirus disease would be directly prevented by vaccination. A significant reduction in the number of hospitalizations for AGE should be detectable among infants aged 0-11 months during the first quarter of 2009, followed by children aged 12-23 months during 2010, and all children <5 years of age during 2011. Conclusions. Vaccination is expected to substantially reduce the health burden of hospitalizations for rotavirus disease among US children during 2006-2015, and the impact of vaccination based on direct protective effects alone was expected to first occur for hospitalizations for AGE among infants during winter 2009. C1 [Curns, Aaron T.; Glasser, John W.; Glass, Roger I.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30329 USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Coffin, Fanny] Inst Curie, Paris, France. [Coffin, Fanny] Inst Natl Sante & Rech Med, U900, Paris, France. [Coffin, Fanny] ParisTech, Fontainebleau, France. RP Curns, AT (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd,MS A47, Atlanta, GA 30329 USA. EM agc8@cdc.gov FU Centers for Disease Control and Prevention FX Financial support: Centers for Disease Control and Prevention. NR 28 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S49 EP S56 DI 10.1086/605036 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100006 PM 19817614 ER PT J AU Flem, ET Musabaev, E Juraev, R Kerin, T Gentsch, J Glass, RI Bresee, JS AF Flem, Elmira T. Musabaev, Erkin Juraev, Rivojiddin Kerin, Tara Gentsch, Jon Glass, Roger I. Bresee, Joseph S. TI Rotavirus Gastroenteritis in Uzbekistan: Implications for Vaccine Policy in Central Asia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; STRAINS; DISEASE; IMPLEMENTATION; EFFICACY; SAFETY; PCR AB Background. To determine the value of rotavirus vaccines in Central Asia, we conducted surveillance of rotavirus in Uzbekistan, the country with the largest birth cohort in the region. Uzbekistan is eligible for international funds to introduce new vaccines. Methods. We screened stool samples for rotavirus that were collected from children aged <5 years with gastroenteritis in 2 hospitals during 2005-2006. Using surveillance information and other data, we estimated national numbers of rotavirus-associated events per year. Results. Of 3537 enrolled children, 1046 (30%) had rotavirus detected in stool specimens. Children aged <2 years accounted for 841 (80%) of all rotavirus infections. The G1P[8] genotype was identified in 27 (52%) of 52 typed samples collected in 2005. Rotavirus is estimated to cause 1174-1857 deaths and 6394-6558 hospitalizations among children aged <5 years annually. The cumulative risk of hospitalization for rotavirus by age 5 years is 1 in 94-96 children, and the risk of rotavirus-related death is 1 in 330-524 children. Conclusions. One-third of all hospitalizations for gastroenteritis and almost 5% of all deaths among children aged <5 years in Uzbekistan may be attributable to rotavirus. Introduction of rotavirus vaccines into the national immunization program at the current subsidized prices could be cost-effective. C1 [Flem, Elmira T.] Norwegian Inst Publ Hlth, Div Infect Dis Control, N-0403 Oslo, Norway. [Musabaev, Erkin; Juraev, Rivojiddin] Res Inst Virol, Tashkent, Uzbekistan. [Kerin, Tara; Gentsch, Jon; Bresee, Joseph S.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int, Bethesda, MD 20892 USA. RP Flem, ET (reprint author), Norwegian Inst Publ Hlth, Div Infect Dis Control, POB 4404, N-0403 Oslo, Norway. EM elmira.flem@fhi.no FU GAVI Alliance; US Centers for Disease Control and Prevention; Norwegian Institute of Public Health FX Financial support: GAVI Alliance, US Centers for Disease Control and Prevention, and Norwegian Institute of Public Health. NR 24 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S154 EP S159 DI 10.1086/605032 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100018 PM 19817594 ER PT J AU Gentsch, JR Hull, JJ Teel, EN Kerin, TK Freeman, MM Esona, MD Griffin, DD Bielfelt-Krall, BP Banyai, K Jiang, BM Cortese, MM Glass, RI Parashar, UD AF Gentsch, Jon R. Hull, Jennifer J. Teel, Elizabeth N. Kerin, Tara K. Freeman, Molly M. Esona, Mathew D. Griffin, Dixie D. Bielfelt-Krall, Brittany P. Banyai, Krisztian Jiang, Baoming Cortese, Margaret M. Glass, Roger I. Parashar, Umesh D. CA Natl Rotavirus Strain Surveillance TI G and P Types of Circulating Rotavirus Strains in the United States during 1996-2005: Nine Years of Prevaccine Data SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; G12 HUMAN ROTAVIRUSES; GROUP-A ROTAVIRUSES; MOLECULAR EPIDEMIOLOGY; VACCINATED POPULATION; SEROTYPE VARIATION; SOUTH-INDIA; CHILDREN; GASTROENTERITIS; IDENTIFICATION AB Background. Rotavirus vaccine was recommended for routine use among US infants in 2006. To provide prevaccine data, we conducted strain surveillance for 9 consecutive seasons during 1996-2005. Methods. Using reverse-transcriptase polymerase chain reaction genotyping and nucleotide sequencing, we determined P/G genotypes of >3100 rotavirus strains collected in up to 12 cities each year from different US regions. Results. The most prevalent strain globally, P[8] G1, was the most prevalent each year in the United States (overall, 78.5% of strains; range, 60.0%-93.9%), and 9.2% of the samples were P[4] G2, 3.6% were P[8] G9, 1.7% were P[8] G3, and 0.8% were P[8] G4. Genotype P[6] G9, which emerged in 1995, was detected continuously for several seasons (from 1996-1997 to 2000-2001, 0.2%-5.4%) but was not identified in the subsequent 4 seasons. Single or a few detections of rare genotypes (eg, P[6] G12, P[9] G6, and P[9] G3) were observed during several rotavirus seasons at frequencies of 0.5%-1.7% and, overall, comprised 0.6% of all the samples from the entire surveillance period. Several globally common strains in addition to G1, especially G2 and G9, circulated at high prevalence (33%-62%) in some cities during certain years. Conclusions. Almost 85% of strains during 1996-2005 had either a G or P antigen that is present in both RotaTeq (Merck) and Rotarix (GlaxoSmithKline). Monitoring of strains after introduction of rotavirus vaccines is important. C1 [Gentsch, Jon R.; Griffin, Dixie D.; Bielfelt-Krall, Brittany P.; Jiang, Baoming] Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, Atlanta, GA 30333 USA. [Cortese, Margaret M.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Freeman, Molly M.; Esona, Mathew D.] Med Staffing Network, Atlanta, GA USA. [Hull, Jennifer J.; Teel, Elizabeth N.; Kerin, Tara K.] Atlanta Res & Educ Fdn, Decatur, GA USA. [Banyai, Krisztian] Assoc Publ Hlth Labs, Washington, DC USA. [Glass, Roger I.] Fogarty Int Ctr, Bethesda, MD USA. RP Gentsch, JR (reprint author), Ctr Dis Control & Prevent, Gastroenteritis & Resp Viruses Lab Branch, MS G-04,1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM jrg4@cdc.gov OI Banyai, Krisztian/0000-0002-6270-1772 FU National Vaccine Program Office of the Department of Health and Human Services, Centers for Disease Control and Prevention FX Financial support: National Vaccine Program Office of the Department of Health and Human Services, Centers for Disease Control and Prevention. NR 52 TC 37 Z9 38 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S99 EP S105 DI 10.1086/605038 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100013 PM 19817622 ER PT J AU Kang, G Arora, R Chitambar, SD Deshpande, J Gupte, MD Kulkarni, M Naik, TN Mukherji, D Venkatasubramaniam, S Gentsch, JR Glass, RI Parashar, UD AF Kang, Gagandeep Arora, Rashmi Chitambar, Shobha D. Deshpande, Jagdish Gupte, M. D. Kulkarni, Madhuri Naik, Trilok N. Mukherji, Dipali Venkatasubramaniam, S. Gentsch, Jon R. Glass, Roger I. Parashar, Umesh D. CA Indian Rotavirus Strain Surveillan TI Multicenter, Hospital-Based Surveillance of Rotavirus Disease and Strains among Indian Children Aged < 5 Years SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ACUTE DIARRHEA; SOUTH-INDIA; MOLECULAR EPIDEMIOLOGY; G12 GENOTYPE; BACTERIAL; EMERGENCE; GASTROENTERITIS; SPECIFICITY; INFECTIONS; VACCINES AB Background. Current, nationally representative data on rotavirus disease burden and rotavirus strains in India are needed to understand the potential health benefits of rotavirus vaccination. Methods. The Indian Rotavirus Strain Surveillance Network was established with 4 laboratories and 10 hospitals in 7 different regions of India. At each hospital, children aged <5 years who presented with acute gastroenteritis and required hospitalization with rehydration for at least 6 h were enrolled. A fecal specimen was obtained and was tested for rotavirus with use of a commercial enzyme immunoassay, and strains were characterized using reverse-transcription polymerase chain reaction. Results. From December 2005 through November 2007, rotavirus was found in similar to 39% of 4243 enrolled patients. Rotavirus was markedly seasonal in northern temperate locations but was less seasonal in southern locations with a tropical climate. Rotavirus detection rates were greatest among children aged 6-23 months, and 13.3% of rotavirus infections involved children aged <6 months. The most common types of strains were G2P[4] (25.7% of strains), G1P[8] (22.1%), and G9P[8] (8.5%); G12 strains were seen in combination with types P[4], P[6], and P[8] and together comprised 6.5% of strains. Conclusions. These data highlight the need for development and implementation of effective prophylactic measures, such as vaccines, to prevent the large burden of rotavirus disease among Indian children. C1 [Arora, Rashmi] Indian Council Med Res, Epidemiol & Communicable Dis Div, New Delhi 110029, India. [Kang, Gagandeep] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Chitambar, Shobha D.] Natl Inst Virol, Pune, Maharashtra, India. [Kulkarni, Madhuri] Lokmanya Tilak Municipal Gen Hosp, Bombay, Maharashtra, India. [Gupte, M. D.; Venkatasubramaniam, S.] Natl Inst Epidemiol, Madras, Tamil Nadu, India. [Naik, Trilok N.] Natl Inst Cholera & Enter Dis, Kolkata, India. [Gentsch, Jon R.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Arora, R (reprint author), Indian Council Med Res, Epidemiol & Communicable Dis Div, New Delhi 110029, India. EM arorar@icmr.org.in OI Deshpande, Jagadish/0000-0001-5194-0375 FU Indian Council for Medical Research, New Delhi; US Centers for Disease Control and Prevention FX Financial support: Indian Council for Medical Research, New Delhi; and US Centers for Disease Control and Prevention. NR 26 TC 70 Z9 70 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S147 EP S153 DI 10.1086/605031 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100017 PM 19817593 ER PT J AU Patel, M Shane, AL Parashar, UD Jiang, BM Gentsch, JR Glass, RI AF Patel, Manish Shane, Andi L. Parashar, Umesh D. Jiang, Baoming Gentsch, Jon R. Glass, Roger I. TI Oral Rotavirus Vaccines: How Well Will They Work Where They Are Needed Most? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TETRAVALENT RHESUS-HUMAN; POLIOVIRUS VACCINE; CHILDHOOD DIARRHEA; GAMBIAN INFANTS; YOUNG-CHILDREN; WC3 VACCINE; HUMAN-MILK; EFFICACY; IMMUNOGENICITY; SAFETY AB Rotavirus vaccines hold promise to decrease the burden of severe diarrhea in the poorest countries, where 85% of deaths due to rotavirus occur. However, the potency of live oral vaccines is lower in these challenging settings than in middle- and upper-income countries. Many hypotheses have been suggested to explain these differences that could provide clues to improve the ultimate success of these novel vaccines. Although introduction today of even moderately effective vaccines will decrease the morbidity and mortality associated with rotavirus in low-income settings, research is urgently needed to understand why these differences in efficacy occur and what could be done to improve vaccine performance to maximize the life-saving benefits of vaccination. C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Patel, Manish; Parashar, Umesh D.; Jiang, Baoming; Gentsch, Jon R.; Glass, Roger I.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Shane, Andi L.] Emory Univ, Dept Pediat, Div Infect Dis, Atlanta, GA 30322 USA. RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. EM glassr@mail.nih.gov FU National Institutes of Health National Center for Research Resources [1KL2RR025009] FX Financial support: National Institutes of Health National Center for Research Resources (1KL2RR025009 to A.S.). NR 73 TC 106 Z9 106 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S39 EP S48 DI 10.1086/605035 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100005 PM 19817613 ER PT J AU Podkolzin, AT Fenske, EB Abramycheva, NY Shipulin, GA Sagalova, OI Mazepa, VN Ivanova, GN Semena, AV Tagirova, ZG Alekseeva, MN Molochny, VP Parashar, UD Vinje, J Maleev, VV Glass, RI Pokrovsky, VI AF Podkolzin, A. T. Fenske, E. B. Abramycheva, N. Yu Shipulin, G. A. Sagalova, O. I. Mazepa, V. N. Ivanova, G. N. Semena, A. V. Tagirova, Z. G. Alekseeva, M. N. Molochny, V. P. Parashar, U. D. Vinje, J. Maleev, V. V. Glass, R. I. Pokrovsky, V. I. TI Hospital-Based Surveillance of Rotavirus and Other Viral Agents of Diarrhea in Children and Adults in Russia, 2005-2007 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POLYMERASE CHAIN-REACTION; GROUP-A ROTAVIRUS; UNITED-STATES; INFECTION; DISEASE; DEATHS; SEASON; INDIA; DELHI AB During a 2-year period in 2005-2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P[8] (44.9%), G4P[8] (40.0%), G2P[4] (8.5%), and G3P[8] (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination. C1 [Podkolzin, A. T.; Fenske, E. B.; Abramycheva, N. Yu; Shipulin, G. A.; Maleev, V. V.; Pokrovsky, V. I.] Cent Res Inst Epidemiol, Moscow 111123, Russia. [Sagalova, O. I.] Chelyabinsk State Med Acad, Chelyabinsk, Russia. [Mazepa, V. N.] Inst Epidemiol & Microbiol, Nizhnii Novgorod, Russia. [Ivanova, G. N.] Reg Infect Clin Hosp, Tyumen, Russia. [Semena, A. V.] Russian Army Med Acad, St Petersburg, Russia. [Tagirova, Z. G.] Daghestan State Med Acad, Makhachkala, Russia. [Alekseeva, M. N.] Yakut State Univ, Yakutsk, Russia. [Molochny, V. P.] Far Eastern Med Univ, Khabarovsk, Russia. [Parashar, U. D.; Vinje, J.; Glass, R. I.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Glass, R. I.] Fogarty Int Ctr, Bethesda, MD USA. RP Podkolzin, AT (reprint author), Cent Res Inst Epidemiol, Novogireevskaya 3A, Moscow 111123, Russia. EM apodkolzin@pcr.ru OI Podkolzin, Alexandr/0000-0002-0044-3341; Vinje, Jan/0000-0002-1530-3675; Shipulin, German/0000-0002-3668-6601 FU International Science and Technology Center [2935] FX Financial support: International Science and Technology Center 2935/Biotechnology Engagement Program 58 grant. NR 18 TC 31 Z9 35 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2009 VL 200 SU 1 BP S228 EP S233 DI 10.1086/605054 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 504YT UT WOS:000270655100025 PM 19817602 ER PT J AU Hamasaki, R Kato, H Terayama, Y Iwata, H Valenzuela, JG AF Hamasaki, Ryoichi Kato, Hirotomo Terayama, Yoshimi Iwata, Hiroyuki Valenzuela, Jesus G. TI Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major SO JOURNAL OF INSECT PHYSIOLOGY LA English DT Article DE Apyrase; Sand fly; Saliva ID SITE-DIRECTED MUTAGENESIS; BLOOD-FEEDING ARTHROPODS; 5'-NUCLEOTIDASE FAMILY; LUTZOMYIA-LONGIPALPIS; TRIATOMA-INFESTANS; RHODNIUS-PROLIXUS; EXPRESSION; IDENTIFICATION; PROTEINS; SIALOME AB Two transcripts coding for proteins homologous to apyrases were identified by massive sequencing of a Phlebotomus (P.) duboscqi salivary gland cDNA library. The sequence analysis revealed that the amino acids important for enzymatic activity including nucleotidase activity and the binding of calcium and nucleotides were well conserved in these molecules. A recombinant P. duboscqi salivary apyrase was expressed in Escherichia coli and purified. The resulting protein efficiently hydrolyzed ADP and ATP, but not AMP, GDP, CDP or UDP, in a calcium-dependent manner. Further, the recombinant protein inhibited ADP- and collagen-induced platelet aggregation. The results indicated that this salivary protein plays an important role in the blood-feeding process in P. duboscqi. Its unique enzymatic activity makes the salivary apyrase an attractive candidate as a therapeutic agent for the treatment of thrombotic pathologies as well as a reagent for a wide variety of research purposes. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Hamasaki, Ryoichi; Kato, Hirotomo; Terayama, Yoshimi; Iwata, Hiroyuki] Yamaguchi Univ, Dept Vet Hyg, Fac Agr, Yamaguchi 7538515, Japan. [Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD USA. RP Kato, H (reprint author), Yamaguchi Univ, Dept Vet Hyg, Fac Agr, 1677-1 Yoshida, Yamaguchi 7538515, Japan. EM katoh@yamaguchi-u.ac.jp RI Kato, Hirotomo/A-4820-2012 OI Kato, Hirotomo/0000-0001-5429-9536 FU Intramural NIH HHS [Z01 AI000932-05] NR 35 TC 15 Z9 16 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-1910 J9 J INSECT PHYSIOL JI J. Insect Physiol. PD NOV PY 2009 VL 55 IS 11 BP 1044 EP 1049 DI 10.1016/j.jinsphys.2009.07.010 PG 6 WC Entomology; Physiology; Zoology SC Entomology; Physiology; Zoology GA 511LB UT WOS:000271165400012 PM 19651132 ER PT J AU Stout, RD Watkins, SK Suttles, J AF Stout, Robert D. Watkins, Stephanie K. Suttles, Jill TI Functional plasticity of macrophages: in situ reprogramming of tumor-associated macrophages SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE macrophage subsets; cancer; IL-12; inflammation ID TOLL-LIKE RECEPTOR; GROWTH-FACTOR-BETA; INFILTRATING MACROPHAGES; CANCER-IMMUNOTHERAPY; SUPPRESSOR-CELLS; GENE-EXPRESSION; DENDRITIC CELLS; EX-VIVO; ACTIVATION; CYTOKINE AB The extent to which the functional heterogeneity of M phi s is dependent on the differentiation of functional sublineages remains unresolved. One alternative hypothesis proposes that M phi s are functionally plastic cells, which are capable of altering their functional activities progressively in response to progressively changing signaling molecules generated in their microenvironment. This "functional plasticity" hypothesis predicts that the functionally polarized M phi s in chronic pathologies do not represent M phi sublineages but rather, are mutable phenotypes sustained by chronic signaling from the pathological environment. Solid TAM phi s are chronically polarized to provide activities that support tumor growth and metastasis and suppress adaptive immune responses. In support of the functional plasticity hypothesis, administration of slow-release microsphere-encapsulated IL-12 successfully reprogrammed TAM phi s in situ, reducing M phi support of tumor growth and metastasis and enhancing M phi proimmunogenic activities. Increased knowledge of how M phi function is regulated and how polarized M phi s can be reprogrammed in situ will increase our ability to control M phi function in a variety of pathological states, including cancer and chronic inflammatory disease. J. Leukoc. Biol. 86: 1105-1109; 2009. C1 [Stout, Robert D.; Suttles, Jill] Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. [Stout, Robert D.; Suttles, Jill] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Watkins, Stephanie K.] Natl Canc Inst, Mol Immunoregulat Lab, Tumor Immun & Tolerance Sect, Canc & Inflammat Program, Frederick, MD USA. RP Stout, RD (reprint author), Univ Louisville, Sch Med, Dept Microbiol & Immunol, Louisville, KY 40292 USA. EM bobstout@louisville.edu FU National Institutes of Health [AI048850]; Susan G. Komen Race for the Cure; Kentucky Lung Cancer Research Fund; The American Lung Association; Commonwealth of Kentucky Research Challenge Trust Fund FX The authors' research about macrophage biology and its application to tumor immunology was supported by grants from the National Institutes of Health (AI048850 to J. S.), the Susan G. Komen Race for the Cure (R. D. S.), the Kentucky Lung Cancer Research Fund (individually to J. S. and to R. D. S.), and The American Lung Association (S. K. W.) and in part by the Commonwealth of Kentucky Research Challenge Trust Fund (individually to J. S. and to R. D. S.). NR 64 TC 89 Z9 94 U1 3 U2 16 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2009 VL 86 IS 5 BP 1105 EP 1109 DI 10.1189/jlb.0209073 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 512SJ UT WOS:000271270600011 PM 19605698 ER PT J AU Kulka, M Fukuishi, N Metcalfe, DD AF Kulka, Marianna Fukuishi, Nobuyuki Metcalfe, Dean D. TI Human mast cells synthesize and release angiogenin, a member of the ribonuclease A (RNase A) superfamily SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE RNase 5; Fc epsilon R1; innate immunity ID AMYOTROPHIC-LATERAL-SCLEROSIS; FIMBRIATED ESCHERICHIA-COLI; ENDOTHELIAL GROWTH-FACTOR; ANTIMICROBIAL ACTIVITY; CYTOKINE PRODUCTION; ACTIVATION; EXPRESSION; CD48; PROLIFERATION; DEGRANULATION AB ANG is a plasma protein with angiogenic and ribonucleolytic activity implicated in tumor growth, heart failure, wound healing, asthma, and the composition of the adult gut microflora. Human mast cells (HuMC) are similarly associated with modulation of vascular permeability, angiogenic processes, wound healing, and asthma. We hypothesized that HuMC express and secrete ANG in response to divergent stimuli. ANG expression was evaluated in the LAD2 HMC, the HMC-1, and CD34(+)-derived HuMC, following exposure to live Escherichia coli, TLR ligands, or neuropeptides and following Fc epsilon RI aggregation. Expression and production of ANG were determined by microarray analysis, qRT-PCR, confocal microscopy, and ELISA. Microarray analysis showed that ANG is up-regulated by LAD2 cells exposed to live E. coli. qRT-PCR analysis revealed that LAD2, HMC-1, and HuMC constitutively expressed ANG mRNA and that it was up-regulated by exposure to E. coli. Activation of HuMC by Fc epsilon RI aggregation resulted in release of small amounts of ANG (<100 pg/mL), whereas compound 48/80, NGF, LPS, PGN, and flagellin activated HuMC to secrete >160 pg/mL ANG. These observations demonstrate that HuMC store and secrete ANG to a variety of stimuli and suggest that MC-derived ANG is available in the subsequent inflammatory response. J. Leukoc. Biol. 86: 1217-1226; 2009. C1 [Kulka, Marianna] CNR, Inst Nutrisci & Hlth, Charlottetown, PE, Canada. [Fukuishi, Nobuyuki; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Kulka, M (reprint author), CNR, Inst Nutrisci & Hlth, 550 Univ Ave, Charlottetown, PE, Canada. EM marianna.kulka@nrc.ca FU Division of Intramural Research, NIAID; American Academy of Allergy, Asthma and Immunology FX This work was funded by the Division of Intramural Research, NIAID, and an interest section grant from the American Academy of Allergy, Asthma and Immunology. We thank Victor Karpov and Adriana Catalli for their technical assistance. NR 34 TC 19 Z9 23 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2009 VL 86 IS 5 BP 1217 EP 1226 DI 10.1189/jlb.0908517 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 512SJ UT WOS:000271270600023 PM 19625371 ER PT J AU Lin, PC Reiter, DA Spencer, RG AF Lin, Ping-Chang Reiter, David A. Spencer, Richard G. TI Classification of degraded cartilage through multiparametric MRI analysis SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Multiparametric; Classification; Clustering; Osteoarthritis; Sensitivity; Specificity ID ARTICULAR-CARTILAGE; DISCRIMINANT-ANALYSIS; MODEL; MICROSCOPY; SELECTION; DENSITY; DISEASE; KNEE; T-2 AB MRI analysis of cartilage matrix may play an important role in early detection and development of therapeutic protocols for degenerative joint disease. Correlations between MRI parameters and matrix integrity have been established in many studies, but the substantial overlap in values observed for normal and for degraded cartilage greatly limits the specificity of these analyses. We implemented established multiparametric analysis methods to define data Clusters corresponding to control and degraded bovine nasal cartilage in two-, three-, and four-dimensional parameter spaces, and applied these results to discriminant analysis of a validation data set. Analyses were performed using the parameters (T(1), T(2), k(m), ADC), where k(m) is the magnetization transfer rate and ADC is the apparent diffusion coefficient. Results were compared to univariate analyses. Multiparametric k-means clustering led to no improvement over univariate analyses, with a maximum sensitivity and specificity in the range of 60-70% for the detection of degradation using T(1), and in the range of 80% sensitivity but only 36% specificity using the parameter pair (T(1), k(m)). In contrast, model-based analysis using more general Gaussian clusters resulted in markedly improved classification, with sensitivity and specificity reaching levels of 80-90% using the pair (T(1), k(m)). Finally, a fuzzy clustering technique was implemented which may be still more appropriate to the continuum of degradation seen in degenerative cartilage disease. In view of its success in identifying mild cartilage degradation, the formal multiparametric approach implemented here may be applicable to the nondestructive evaluation of other biomaterials using MRI. Published by Elsevier Inc. C1 [Lin, Ping-Chang; Reiter, David A.; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, GRC 4D-06, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov RI Lin, Ping-Chang/C-9811-2009; OI Lin, Ping-Chang/0000-0003-0918-4072 FU NIH; National Institute on Aging FX This work was supported by the Intramural Research Program of the NIH, National Institute on Aging. NR 26 TC 29 Z9 29 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2009 VL 201 IS 1 BP 61 EP 71 DI 10.1016/j.jmr.2009.08.001 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 510ES UT WOS:000271071400009 PM 19762258 ER PT J AU El Khouli, RH Macura, KJ Barker, PB Habba, MR Jacobs, MA Bluemke, DA AF El Khouli, Riham H. Macura, Katarzyna J. Barker, Peter B. Habba, Mohamed R. Jacobs, Michael A. Bluemke, David A. TI Relationship of Temporal Resolution to Diagnostic Performance for Dynamic Contrast Enhanced MRI of the Breast SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE dynamic contrast enhanced (DCE); magnetic resonance imaging (MRI); breast; kinetic curve; temporal resolution; wash-out; wash-in ID INTERPRETATION MODEL; LESIONS; PARAMETERS; DIFFERENTIATION; MULTICENTER; VARIABILITY; PERFUSION; FEATURES; BENIGN; TRACER AB Purpose: To investigate the relationship between temporal resolution of dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) and classification of breast lesions as benign versus malignant. Materials and Methods: Patients underwent T(1) weighted DCE MRI with 15 s/acquisition temporal, resolution using 15 Tesla (n = 48) and 3.0T (n = 33) MRI scanners. Seventy nine patients had pathologically proven diagnosis and 2 had 2 years follow up showing no change in lesion size. The temporal resolution of DCE MRI was systematically reduced as a postprocessing step from 15 to 30, 45, and 60 s/acquisition by eliminating intermediate time points. Average wash in and wash out slopes, wash-out percentage changes, and kinetic curve shape (persistently enhancing, plateau or wash out) were compared or each temporal resolution. Logistic regression and receiver, operating characeteristic (ROC) curve analysis were used to compare kinetic parameters and diagnostic accuracy. Results: Sixty patients (74%) had malignant lesions and 21 patients (26%) had benign lesions. All temporal resolution parameters significantly predicted benign versus malignant diagnosis (P < 0.05). However, 45 s/acquisition and higher temporal resolution datasets showed higher accuracy than the 60 s/acquisition dataset by ROC curve analysis (0.72 versus 0.69 for average wash in slope; 0.85 versus 0.82, for average wash-out slope; and 0.88 versus 0.80 for kinetic curve shape assessment, for 45 s/acquisition versus 60 s/acquisition temporal-resolution datasets, respectively (P = 0.027). Conclusion: DCE MRI data with at least 45-s temporal resolution maximized the agreement between the kinetic parameters and correct classification of benign versus malignant diagnosis. C1 [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. [El Khouli, Riham H.; Macura, Katarzyna J.; Barker, Peter B.; Jacobs, Michael A.] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA. [El Khouli, Riham H.; Habba, Mohamed R.] Suez Canal Univ, Sch Med, Dept Diagnost Radiol, Ismailia, Egypt. [Jacobs, Michael A.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Bluemke, DA (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA. EM bluemked@nih.gov RI Jacobs, Michael/G-2901-2010; OI Bluemke, David/0000-0002-8323-8086 FU NIH [R01CA125258, 1R01CA100184, P50CA103175]; Intramural Research Program of the NIH/Clinical Center FX Contract grant sponsor: NIH; Contract grant numbers: R01CA125258, NIH 1R01CA100184, P50CA103175; Contract grant sponsor: the Intramural Research Program of the NIH/Clinical Center. NR 27 TC 34 Z9 34 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2009 VL 30 IS 5 BP 999 EP 1004 DI 10.1002/jmri.21947 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512KP UT WOS:000271247900011 PM 19856413 ER PT J AU Resnik, DB AF Resnik, D. B. TI Re-consenting human subjects: ethical, legal and practical issues SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material ID GENETIC RESEARCH C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-02] NR 9 TC 7 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD NOV PY 2009 VL 35 IS 11 BP 656 EP 657 DI 10.1136/jme.2009.030338 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 514ES UT WOS:000271377700003 PM 19880699 ER PT J AU Pelser, C Vitale, F Whitby, D Graubard, BI Messina, A Gafa, L Brown, EE Anderson, LA Romano, N Lauria, C Goedert, JJ AF Pelser, Colleen Vitale, Francesco Whitby, Denise Graubard, Barry I. Messina, Angelo Gafa, Lorenzo Brown, Elizabeth E. Anderson, Lesley A. Romano, Nino Lauria, Carmela Goedert, James J. TI Socio-Economic and Other Correlates of Kaposi Sarcoma-Associated Herpesvirus Seroprevalence Among Older Adults in Sicily SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE herpesviridae; Kaposi sarcoma; Italy; socio-economic status; migration ID HUMAN-HERPESVIRUS-8 INFECTION; RISK-FACTORS; NATURAL-PRODUCTS; TRANSMISSION; TYPE-8; PERFORMANCE; CHILDREN; UGANDA; VIRUS; MEN AB The virus that causes Kaposi sarcoma, KS-associated herpesvirus (KSHV, also known as human herpesvirus 8) has an unusual distribution and poorly characterized modes of transmission. To clarify these issues, socio-demographic correlates of KSHV seroprevalence were examined in a population-based study. In 1,154 randomly sampled adults (aged 3292, mean 71 years) throughout Sicily, KSHV antibodies were detected with four assays and a conservative algorithm. Seroprevalence was re-weighted to the population. Odds ratios with 95% confidence intervals (OR, CI) from multivariate logistic regression were used to estimate associations of seroprevalence with interview data. KSHV seroprevalence was 8.5%, including 5.3% among men (N=848) and 11.5% among women (N=306, P=0.22). Seroprevalence was higher with residence in a smaller community during childhood (P(trend)=0.03) and working with plants/soil during adulthood (OR 2.9, CI 1.1-7.9); these were especially strong among women. Among men, seroprevalence was significantly associated with lower education (OR 2.6, CI 1.1-5.9) and migration to a larger community (OR 0.3, CI 0.1-0.9). Other demographic and household variables were unrelated to seroprevalence. From these data, KSHV in Sicily appears to be related to low socio-economic status, but micro-endemicity in small communities cannot be excluded. J. Med. Virol. 81:1938-1944, 2009. (C) 2009 Wiley-Liss, Inc.(+) C1 [Goedert, James J.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. [Pelser, Colleen] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Vitale, Francesco] Univ Palermo, Dept Sci Hlth Promot G Alessandro, Sect Hyg, Palermo, Italy. [Whitby, Denise] NCI, Viral Oncol Sect, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD 21701 USA. [Messina, Angelo] Univ Catania, Dipartimento Sci Biomed, Catania, Italy. [Gafa, Lorenzo; Lauria, Carmela] Lega Italiana Lotta Contro & Tumori Sez Ragusa, Ragusa, Italy. [Brown, Elizabeth E.] Univ Alabama, Dept Epidemiol Med & Microbiol, Birmingham, AL USA. [Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. RP Goedert, JJ (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7068, Rockville, MD 20892 USA. EM goedertj@mail.nih.gov OI Anderson, Lesley/0000-0002-1000-3649 FU National Cancer Institute [N02-CP-91027]; Science Applications International Corporation [N01-CO-12400] FX Contract sponsor: National Cancer Institute (Intramural Research Program, RTI International; partially supported); Contract number: N02-CP-91027; Contract sponsor: Science Applications International Corporation; Contract number: N01-CO-12400. NR 20 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD NOV PY 2009 VL 81 IS 11 BP 1938 EP 1944 DI 10.1002/jmv.21589 PG 7 WC Virology SC Virology GA 503GS UT WOS:000270522300013 PM 19777527 ER PT J AU Shaltiel, G Deutsch, J Rapoport, SI Basselin, M Belmaker, RH Agam, G AF Shaltiel, G. Deutsch, J. Rapoport, S. I. Basselin, M. Belmaker, R. H. Agam, G. TI Is phosphoadenosine phosphate phosphatase a target of lithium's therapeutic effect? SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article; Proceedings Paper CT Interacademic Symposium on Neurobiology of Neuro-Psychiatric Diseases CY NOV 02-05, 2008 CL Jerusalem, ISRAEL SP German Acad Sci, Leopoldina, Israel Acad Sci & Humanities DE Lithium; Bipolar; Rat; Brain; Adenosine 3 '(2 ')-phosphoadenosine-5 '-phosphate; Phosphatase; Microwaving ID POSTMORTEM FRONTAL-CORTEX; RAT-BRAIN; 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE; 5'-PHOSPHATE PHOSPHATASE; BIPOLAR DISORDER; MESSENGER-RNA; PHARMACOLOGY; METABOLISM; MECHANISM; SULFATE AB Lithium, which is approved for treating patients with bipolar disorder, is reported to inhibit 3'(2')-phosphoadenosine-5'-phosphate (PAP) phosphatase activity. In yeast, deletion of PAP phosphatase results in elevated PAP levels and in inhibition of sulfation and of growth. The effect of lithium on PAP phosphatase is remarkable for the low Ki (similar to 0.2 mM), suggesting that this system would be almost completely shut down in vivo with therapeutic levels of 1 mM lithium, thereby elevating PAP levels. To test the hypothesis that lithium inhibition of PAP phosphatase is pharmacologically relevant to bipolar disorder, we fed rats LiCl for 6 weeks, and assayed brain PAP levels after subjecting the brain to high-energy microwaving. We also measured PAP phosphatase mRNA and protein levels in frozen brain tissue of lithium-treated mice. Brain adenosine phosphates were extracted by trichloroacetic acid and assayed by HPLC with a gradient system of two phases. PAP phosphatase mRNA was measured by RT-PCR, and PAP phosphatase protein was measured by Western blotting. Brain PAP levels were below detection limit of 2 nmol/g wet weight, even following lithium treatment. Lithium treatment also did not significantly change brain PAP phosphatase mRNA or protein levels. These results question the relevance of PAP phosphatase to the therapeutic mechanism of lithium. A statistically significant 25% reduced brain ADP/ATP ratio was found following lithium treatment in line with lithium's suggested neuroprotective effects. C1 [Shaltiel, G.; Belmaker, R. H.; Agam, G.] Ben Gurion Univ Negev, Psychiat Res Unit, Mental Hlth Ctr, Beer Sheva, Israel. [Deutsch, J.] Hebrew Univ Jerusalem, Hadassah Med Sch, Sch Pharm, Dept Med Chem, IL-91010 Jerusalem, Israel. [Deutsch, J.; Rapoport, S. I.; Basselin, M.] NIA, Brain Physiol & Metab Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Belmaker, RH (reprint author), Ben Gurion Univ Negev, Psychiat Res Unit, Mental Hlth Ctr, POB 4600, Beer Sheva, Israel. EM belmaker@bgu.ac.il FU Intramural NIH HHS [Z01 AG000134-24] NR 27 TC 2 Z9 2 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD NOV PY 2009 VL 116 IS 11 BP 1543 EP 1549 DI 10.1007/s00702-009-0298-6 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 514TF UT WOS:000271417800024 PM 19756369 ER PT J AU Marinova, Z Ren, M Wendland, JR Leng, Y Liang, MH Yasuda, S Leeds, P Chuang, DM AF Marinova, Zoya Ren, Ming Wendland, Jens R. Leng, Yan Liang, Min-Huei Yasuda, Shigeru Leeds, Peter Chuang, De-Maw TI Valproic acid induces functional heat-shock protein 70 via Class I histone deacetylase inhibition in cortical neurons: a potential role of Sp1 acetylation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE heat-shock protein 70; histone deacetylase; phosphatidylinositol 3-kinase; Sp1; valproic acid ID HEAT-SHOCK-PROTEIN; GLYCOGEN-SYNTHASE KINASE-3-BETA; AMYOTROPHIC-LATERAL-SCLEROSIS; REDUCES BRAIN-DAMAGE; TRANSCRIPTION FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; EXPERIMENTAL STROKE; MUTANT HUNTINGTIN; MOOD STABILIZERS; STRESS-RESPONSE AB Neuroprotective properties of the mood stabilizer valproic acid (VPA) are implicated in its therapeutic efficacy. Heat-shock protein 70 (HSP70) is a molecular chaperone, neuroprotective and anti-inflammatory agent. This study aimed to investigate underlying mechanisms and functional significance of HSP70 induction by VPA in rat cortical neurons. VPA treatment markedly up-regulated HSP70 protein levels, and this was accompanied by increased HSP70 mRNA levels and promoter hyperacetylation and activity. Other HDAC inhibitors - sodium butyrate, trichostatin A, and Class I HDAC-specific inhibitors MS-275 and apicidin, - all mimicked the ability of VPA to induce HSP70. Pre-treatment with phosphatidylinositol 3-kinase inhibitors or an Akt inhibitor attenuated HSP70 induction by VPA and other HDAC inhibitors. VPA treatment increased Sp1 acetylation, and a Sp1 inhibitor, mithramycin, abolished the induction of HSP70 by HDAC inhibitors. Moreover, VPA promoted the association of Sp1 with the histone acetyltransferases p300 and recruitment of p300 to the HSP70 promoter. Further, VPA-induced neuroprotection against glutamate excitotoxicity was prevented by blocking HSP70 induction. Taken together, the data suggest that the phosphatidylinositol 3-kinase/Akt pathway and Sp1 are likely involved in HSP70 induction by HDAC inhibitors, and induction of HSP70 by VPA in cortical neurons may contribute to its neuroprotective and therapeutic effects. C1 [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Wendland, Jens R.] NIMH, Clin Sci Lab, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Mood & Anxiety Disorders Program, NIH, Bldg 10,Rm 3D-38,10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov RI Wendland, Jens/A-1809-2012 FU National Institute of Mental Health (NIMH); HSU Family Foundation FX This research was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH) and a gift fund from the HSU Family Foundation. We thank Ioline Henter of the NIMH for the critical reading and comments on the manuscript. NR 57 TC 81 Z9 86 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2009 VL 111 IS 4 BP 976 EP 987 DI 10.1111/j.1471-4159.2009.06385.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 508BK UT WOS:000270901600008 PM 19765194 ER PT J AU Pluta, RM Butman, JA Schatlo, B Johnson, DL Oldfield, EH AF Pluta, Ryszard M. Butman, John A. Schatlo, Bawarjan Johnson, Dennis L. Oldfield, Edward H. TI Subarachnoid hemorrhage and the distribution of drugs delivered into the cerebrospinal fluid SO JOURNAL OF NEUROSURGERY LA English DT Review DE subarachnoid hemorrhage; vasospasm; thrombolysis; intrathecal; cerebrospinal fluid ID TISSUE-PLASMINOGEN-ACTIVATOR; EXPERIMENTAL CEREBRAL VASOSPASM; NITRIC-OXIDE DONOR; INTRAVENTRICULAR SODIUM-NITROPRUSSIDE; INTRATHECAL FIBRINOLYTIC THERAPY; GENE-RELATED PEPTIDE; CONTROLLED-RELEASE POLYMER; BLOOD-CLOT RESOLUTION; DOUBLE-BLIND TRIAL; PRIMATE MODEL AB Object. Investigators in experimental and clinical studies have used the intrathecal route to deliver drugs to prevent or treat vasospasm. However, a clot near an artery or arteries after subarachnoid hemorrhage (SAH) may hamper distribution and limit the effects of intrathecally delivered compounds. In a primate model of right middle cerebral artery (MCA) SAH, the authors examined the distribution of Isovue-M 300 and 3% Evans blue after infusion into the cisterna magna CSF. Methods. Ten cynomolgus monkeys were assigned to SAH and sham SAH surgery groups ( 5 in each group). Monkeys received CSF injections as long as 28 days after SAH and were killed 3 hours after the contrast/Evans blue injection. The authors assessed the distribution of contrast material on serial CT within 2 hours after contrast injection and during autopsy within 3 hours after Evans blue staining. Results. Computed tomography cisternographies showed no contrast in the vicinity of the right MCA (p < 0.05 compared with left); the distribution of contrast surrounding the entire right cerebral hemisphere was substantially reduced. Postmortem analysis demonstrated much less Evans blue staining of the right hemisphere surface compared with the left. Furthermore, the Evans blue dye did not penetrate into the right sylvian fissure, which occurred surrounding the left MCA. The authors observed the same pattern of changes and differences in contrast distribution between SAH and sham SAH animals and between the right and the left hemispheres on Days 1, 3, 7, 14, 21, and 28 after SAH. Conclusions. Intrathecal drug distribution is substantially limited by SAH. Thus, when using intrathecal drug delivery after SAH, vasoactive drugs are unlikely to reach the arteries that are at the highest risk of delayed cerebral vasospasm. (DOI: 10.3171/2009.2.JNS081256) C1 [Pluta, Ryszard M.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Butman, John A.; Johnson, Dennis L.] Natl Inst Hlth, Neuroradiol Sect, Dept Diagnost Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD USA. [Schatlo, Bawarjan] Univ Hosp Geneva, Dept Neurosurg, Geneva, Switzerland. [Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA. RP Pluta, RM (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Natl Inst Hlth, 10 Ctr Dr,Room 5D39, Bethesda, MD 20892 USA. EM plutar@ninds.nih.gov RI SCHATLO, Bawarjan/F-4285-2010; Butman, John/A-2694-2008; Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 FU Intramural Research Program of the National Institutes of Health; National Institute of Neurological Disorders and Stroke; Boehringer Ingelheim Foundation FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Neurological Disorders and Stroke. Bawarjan Schatlo, M. D., was supported by a scholarship from the Boehringer Ingelheim Foundation. NR 119 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2009 VL 111 IS 5 BP 1001 EP U128 DI 10.3171/2009.2.JNS081256 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 514DW UT WOS:000271375500022 PM 19374502 ER PT J AU Sciubba, DM Petteys, RJ Shakur, SF Gokaslan, ZL McCarthy, EF Collins, MT McGirt, MJ Hsieh, PC Nelson, CS Wolinsky, JP AF Sciubba, Daniel M. Petteys, Rory J. Shakur, Sophia F. Gokaslan, Ziya L. McCarthy, Edward F. Collins, Michael T. McGirt, Matthew J. Hsieh, Patrick C. Nelson, Clarke S. Wolinsky, Jean-Paul TI En bloc spondylectomy for treatment of tumor-induced osteomalacia SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Article DE en bloc spondylectomy; tumor; parathyroid hormone; osteoporosis ID MESENCHYMAL TUMORS; SPINE; RICKETS; VERTEBRECTOMY; MANAGEMENT; METABOLISM; DIAGNOSIS; CHORDOMA; CANCER; FGF-23 AB En bloc spondylectomy represents a radical resection of a spinal segment most often reserved for patients presenting with a primary extradural spine tumor or a solitary metastasis in the setting of an indolent, well-controlled systemic malignancy. The authors report a case in which en bloc spondylectomy was conducted to control a metabolically active spine tumor. A 56-year-old woman, who Suffered from severe tumor-induced osteomalacia, was found to have a fibroblast growth factor-23-secreting phosphaturic mesenchymal tumor in the T-8 vertebral body. En bloc resection was conducted, leading to resolution of her tumor-induced osteomalacia. This case suggests that radical spondylectomy may be beneficial in the management of metabolically or endocrinologically active tumors of the spine. (DOI: 10.3171/2009.6.SPINE08120) C1 [Sciubba, Daniel M.; Petteys, Rory J.; Shakur, Sophia F.; Gokaslan, Ziya L.; McGirt, Matthew J.; Hsieh, Patrick C.; Nelson, Clarke S.; Wolinsky, Jean-Paul] Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. [McCarthy, Edward F.] Johns Hopkins Univ, Dept Pathol & Orthopaed, Baltimore, MD USA. [Collins, Michael T.] NIH, Dept Med, Bethesda, MD 20892 USA. RP Sciubba, DM (reprint author), 600 N Wolfe St,Meyer 8-161, Baltimore, MD 21287 USA. EM dsciubb1@jhmi.edu FU AANS Neurosurgery Research and Education Foundation FX Ziya L. Gokaslan, M.D.. owns stock in US Spine and Spinal Kinetics. has received clinical or research support from AO Spine North America and Depuy Spine, has received fellowship support from AO Spine North America, and is a Board Member of AO Spine North America. Daniel Sciubba, M.D., has received clinical or research support from the AANS Neurosurgery Research and Education Foundation for a research grant, and has received honoraria from AO Spine, Depuy Spine, Medtronic, and Life Cell. NR 23 TC 13 Z9 13 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD NOV PY 2009 VL 11 IS 5 BP 600 EP 604 DI 10.3171/2009.6.SPINE08120 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 512JM UT WOS:000271244200019 PM 19929364 ER PT J AU Giovacchini, G Conant, S Herscovitch, P Theodore, WH AF Giovacchini, Giampiero Conant, Shielah Herscovitch, Peter Theodore, William H. TI Using Cerebral White Matter for Estimation of Nondisplaceable Binding of 5-HT1A Receptors in Temporal Lobe Epilepsy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE epilepsy; white matter; PET; 5-HT1A receptors; F-18-FCWAY ID POSITRON-EMISSION-TOMOGRAPHY; PARTIAL-VOLUME CORRECTION; HUMAN BRAIN; REFERENCE REGION; RAT-BRAIN; PET; QUANTITATION; VALIDATION; CEREBELLUM; WAY-100635 AB The estimation of nondisplaceable binding from cerebellar white matter, rather than from whole cerebellum, was proposed for the PET tracer carbonyl-C-11-WAY-100635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridyl)cyclohexane-carboxamidel]) because of the heterogeneity of total ligand binding in this region. For the 5-hydroxytryptamine receptor 1A (5-HT1A) antagonist F-18-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}-N-2-pyridyl)trans-4-fluorocyclohexanecarboxamide (F-18-FCWAY), the estimation of nondisplaceable binding from cerebellum (V-ND) may be additionally biased by spillover of F-18-fluoride activity from skull. We aimed to assess the effect of using cerebral white matter as reference region on detection of group differences in 5-HT1A binding with PET and F-18-FCWAY. Methods: In 22 temporal lobe epilepsy patients (TLE) and 10 healthy controls, F-18-FCWAY distribution volume in cerebral white matter (V-WM) was computed using an extrapolation method as part of a partial-volume correction (PVC) algorithm. To assess the feasibility of applying this method to clinical studies in which PVC is not performed, V-WM was also calculated by placing circular, 6-mm-diameter regions of interest (ROIs) in the centrum semiovalis on parametric images. Binding potentials were BPF = (V-T-V-ND)/f(P) and BPF-WM = (V-T-V-WM)/f(P), where V-T is total distribution volume and f(P) = F-18-FCWAY plasma free fraction. Statistical analysis was performed using t tests and linear regression. Results: In the whole group, V-WM was 14% +/- 19% lower than V-ND (P < 0.05). V-WM/f(P) was significantly (P < 0.05) lower in patients than in controls. All significant (P < 0.05) reductions of 5-HT1A receptor availability in TLE patients detected by BPF were also detected using BPF-WM. Significant (P < 0.05) reductions of 5-HT1A specific binding were detected by BPF-WM, but not BPF, in ipsilateral inferior temporal cortex, contralateral fusiform gyrus, and contralateral amygdala. However, effect sizes were similar for BPF-WM and BPF. The value of V-WM calculated with the ROI approach did not significantly (P > 0.05) differ from that calculated with the extrapolation approach (0.67 +/- 0.32 mL/mL and 0.72 +/- 0.34 mL/mL, respectively). Conclusion: Cerebral white matter can be used for the quantification of nondisplaceable binding of 5-HT1A without loss of statistical power for detection of regional group differences. The ROI approach is a good compromise between computational complexity and sensitivity to spillover of activity, and it appears suitable to studies in which PVC is not performed. For F-18-FCWAY, this approach has the advantage of avoiding spillover of F-18-fluoride activity onto the reference region. C1 [Giovacchini, Giampiero] S Andrea Hosp, Dept Nucl Med, I-19124 La Spezia, Italy. [Giovacchini, Giampiero; Conant, Shielah; Herscovitch, Peter] NINDS, PET Dept, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Theodore, William H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Giovacchini, G (reprint author), S Andrea Hosp, Dept Nucl Med, I-19124 La Spezia, Italy. EM giampiero.giovacchini@asl5.liguria.it FU Intramural NIH HHS [Z01 NS002236-33] NR 37 TC 9 Z9 9 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2009 VL 50 IS 11 BP 1794 EP 1800 DI 10.2967/jnumed.109.063743 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 529YA UT WOS:000272554100011 PM 19837769 ER PT J AU Williams-Piehota, P Latimer, AE Katulak, NA Cox, A Silvera, SAN Mowad, L Salovey, P AF Williams-Piehota, Pamela Latimer, Amy E. Katulak, Nicole A. Cox, Ashley Silvera, Stephanie A. N. Mowad, Linda Salovey, Peter TI Tailoring Messages to Individual Differences in Monitoring-Blunting Styles to Increase Fruit and Vegetable Intake SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE persuasive communication; nutrition education; tailoring; monitor; coping styles ID CANCER INFORMATION-SERVICE; NUTRITION EDUCATION; SOCIAL DESIRABILITY; HEALTH MESSAGES; CALLERS; INTERVENTION; CONSUMPTION; QUESTIONNAIRE; BEHAVIOR; SEEKING AB Objective: To examine whether messages matched to individuals' monitoring-blunting coping styles (MBCS) ire more effective in increasing fruit and vegetable intake than mismatched messages. MBCS refers to the tendency to either attend to and amplify, or distract oneself from and minimize threatening information. Design/Setting: Randomly assigned messages were tailored to resonate with either monitors or blunters and delivered at baseline, I week, 2 months, and 3 months later. Surveys were conducted at baseline and 2 and 4 months later. Participants: 531 callers to a cancer information hotline who did not meet the 5 A Day guideline. Intervention: A brief telephone-delivered message and 3 mailings of booklets and promotional items encouraging fruit and vegetable intake, tailored for either monitors or blunters. Main Outcome Measure: Fruit and vegetable intake 2 and 4 months post-baseline. Analysis: Hierarchical regression modeling. Results: Messages matched to MBCS were more effective than mismatched messages, particularly for the monitor message, in increasing intake at 2 months but not at 4 months. Conclusions and Implications: These minimal interventions influenced fruit and vegetable intake. MBCS may be a promising target for developing tailored messages aimed at increasing intake, although additional research is needed to verify the robustness of these findings. C1 [Williams-Piehota, Pamela; Latimer, Amy E.; Katulak, Nicole A.; Cox, Ashley; Salovey, Peter] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Williams-Piehota, Pamela] RTI Int, Res Triangle Pk, NC USA. [Latimer, Amy E.] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON, Canada. [Silvera, Stephanie A. N.] Montclair State Univ, Dept Hlth & Nutr Sci, Montclair, NJ USA. [Mowad, Linda] NCI, Canc Informat Serv, Yale Canc Ctr, New Haven, CT USA. RP Salovey, P (reprint author), Yale Univ, Dept Psychol, POB 208205, New Haven, CT 06520 USA. EM peter.salovey@yale.edu FU National Cancer Institute [R01-CA68427]; Yale Cancer Center [N02-CO-01002-75] FX Research reported in this article was funded by the National Cancer Institute through a grant to Peter Salovey (R01-CA68427) and a contract to the Yale Cancer Center (N02-CO-01002-75). The research was conducted as a partnership between the National Cancer Institute's Cancer Information Service (CIS) Research Program and Yale University. Staff from the CIS were involved in implementing and monitoring administration of the screening survey. The intervention materials were developed and modified in collaboration with the CIS. Sincere thanks to the CIS New England Office for attending study-related training seminars and for their help with data collection. NR 35 TC 6 Z9 7 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD NOV-DEC PY 2009 VL 41 IS 6 BP 398 EP 405 DI 10.1016/j.jneb.2008.06.006 PG 8 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 519OI UT WOS:000271776000005 PM 19879495 ER PT J AU Williams, KM Agwu, AL Dabb, AA Higman, MA Loeb, DM Valsamakis, A Chen, AR AF Williams, Kirsten Marie Agwu, Allison L. Dabb, Alix A. Higman, Meghan A. Loeb, David M. Valsamakis, Alexandra Chen, Allen R. TI A Clinical Algorithm Identifies High Risk Pediatric Oncology and Bone Marrow Transplant Patients Likely to Benefit From Treatment of Adenoviral Infection SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE adenovirus algorithm; hematopoietic stem cell transplant; cidofovir; hemolytic-uremic syndrome ID STEM-CELL TRANSPLANTATION; IMMUNE RECONSTITUTION; HEMORRHAGIC CYSTITIS; DISSEMINATED DISEASE; EARLY-DIAGNOSIS; DNA LOAD; RECIPIENTS; CIDOFOVIR; CHILDREN; PCR AB Background: Adenoviral infections cause morbidity and mortality in blood and marrow transplantation and pediatric oncology patients. Cidofovir is active against adenovirus, but must be used judiciously because of its nephrotoxicity and unclear indications. Therefore, before introducing cidofovir use during an adenoviral outbreak, we developed a clinical algorithm to distinguish low risk patients from those who merited cidofovir therapy because of significant adenoviral disease and high risk for death. Objective: This study was conducted to determine whether the algorithm accurately predicted severe adenovirus disease and whether selective cidofovir treatment was beneficial, Study Design: A retrospective analysis of a pediatric oncology/blood and marrow transplantation cohort prealgorithm and postalgorithm implementation was performed. Results: Twenty patients with adenovirus infection were identified (14 high risk and 6 low risk). All low-risk patients cleared their infections without treatment. Before algorithun implementation, all untreated high-risk patients died, 4 out of 5 (80%), from adenoviral infection. In contrast, cidofovir reduced adenovirus-related mortality in the high-risk group postalgorithm implementation (9 patients treated, 1 patient died; RR 0.14, P < 0.05) and all treated high-risk patients cleared their virus. Conclusions: The clinical algorithm accurately identified patients at high risk for severe fatal adenoviral disease who would benefit from selective use of cidofovir. C1 [Williams, Kirsten Marie; Higman, Meghan A.; Loeb, David M.; Chen, Allen R.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Williams, Kirsten Marie; Agwu, Allison L.; Higman, Meghan A.; Loeb, David M.; Chen, Allen R.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD USA. [Agwu, Allison L.] Johns Hopkins Univ, Dept Infect Dis, Baltimore, MD USA. [Dabb, Alix A.] Johns Hopkins Univ, Dept Pharm, Baltimore, MD USA. [Valsamakis, Alexandra] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. RP Williams, KM (reprint author), NCI, NIH, Transplantat & Immunol Branch, 10 Ctr Dr,Bldg 10-CRC 3-3288, Bethesda, MD 20892 USA. EM williaki@mail.nih.gov FU NIH-NIAID/SSS [204VC004]; The HIV Prevention Trials Network (HPTN); NIAID; NIDA; NIMH; Office of AIDS Research of the NIH; DHHS [UOI-Al-068613] FX Supported by the funds from NIH-NIAID/SSS contract No. 204VC004 and The HIV Prevention Trials Network (HPTN) sponsored by NIAID, NIDA, NIMH, and the Office of AIDS Research of the NIH, DHHS (UOI-Al-068613) (AV). NR 34 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 2009 VL 31 IS 11 BP 825 EP 831 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 519JZ UT WOS:000271763900005 PM 19801951 ER PT J AU Hay, WW Raju, TNK Higgins, RD Kalhan, SC Devaskar, SU AF Hay, William W., Jr. Raju, Tonse N. K. Higgins, Rosemary D. Kalhan, Satish C. Devaskar, Sherin U. TI Knowledge Gaps and Research Needs for Understanding and Treating Neonatal Hypoglycemia: Workshop Report from Eunice Kennedy Shriver National Institute of Child Health and Human Development SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID NEWBORN-INFANTS; GLUCOSE-PRODUCTION; TERM INFANTS; BRAIN-INJURY; CEREBRAL INJURY; IMMATURE BRAIN; HYPERINSULINISM; PRETERM; MECHANISMS; MANAGEMENT C1 [Raju, Tonse N. K.; Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Hay, William W., Jr.] Univ Colorado, Dept Pediat, Sch Med, Aurora, CO USA. [Kalhan, Satish C.] Case Western Reserve Univ, Dept Med, Lerner Coll Med, Cleveland Clin, Cleveland, OH 44106 USA. [Devaskar, Sherin U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Devaskar, Sherin U.] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. RP Raju, TNK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd,Room 4B03, Bethesda, MD 20892 USA. EM rajut@mail.nih.gov OI Kalhan, Satish/0000-0002-8012-4171 FU NCRR NIH HHS [UL1 RR025780, UL1 RR025780-04] NR 57 TC 53 Z9 53 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2009 VL 155 IS 5 BP 612 EP 617 DI 10.1016/j.jpeds.2009.06.044 PG 6 WC Pediatrics SC Pediatrics GA 516VH UT WOS:000271570900006 PM 19840614 ER PT J AU Ross, JL Mazzocco, MMM Kushner, H Kowal, K Cutler, GB Roeltgen, D AF Ross, Judith L. Mazzocco, Michele M. M. Kushner, Harvey Kowal, Karen Cutler, Gordon B., Jr. Roeltgen, David TI Effects of Treatment with Oxandrolone for 4 Years on the Frequency of Severe Arithmetic Learning Disability in Girls with Turner Syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID VISUOSPATIAL WORKING-MEMORY; FRAGILE-X-SYNDROME; GROWTH-HORMONE; DEVELOPMENTAL DYSCALCULIA; CHROMOSOME ABNORMALITIES; COGNITIVE DEFICITS; SEX-DIFFERENCES; MOTOR FUNCTION; BRAIN; ESTROGEN AB Objectives To study androgen treatment effects on arithmetic performance in girls with Turner syndrome. Study design Forty-four girls, ages 10 to 14 years at baseline, completed 4 years of treatment with oxandrolone (Ox) or placebo (PI). All received growth hormone and estrogen replacement therapy. We assessed the number of girls with severe learning disability (LD, standard score <= 5(th) percentile) on measures of academic arithmetic and reading achievement (WRAT-3, arithmetic and reading), given yearly, and the WIAT numerical operations (NOS) and reading subtests, given at year 4. Results On the WRAT-3 arithmetic, the frequency of severe arithmetic LD was similar in the Ox and PI groups at baseline and at years 1 and 2. At years 3 and 4, fewer girls in the Ox than PI group had a severe arithmetic LD (year 4: 0/22 vs 5/21, P = .02). On the WIAT NOS (year 4), fewer girls in the Ox than PI groups had a severe arithmetic LD (3/21 vs 8/20, P = .09). WIAT NOS error analysis suggested that the improved performance in the Ox group was associated with better performance on multiplication and division (P < .01). The frequency of severe LD for the WRAT-3 reading was similar for the Ox and PI groups (all years) and for the WIAT reading subtest (year 4). Conclusions Androgen treatment for 4 years in girls with Turner syndrome resulted in a small decrease in frequency of severe arithmetic LD, with no effect on reading LD. (J Pediatr 2009; 155: 714-20). C1 [Ross, Judith L.] Thomas Jefferson Univ, Dept Pediat, Philadelphia, PA 19107 USA. [Ross, Judith L.] DuPont Hosp Children, Wilmington, DE USA. [Ross, Judith L.] Dept Pediat, Wilmington, DE USA. [Mazzocco, Michele M. M.] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA. [Kushner, Harvey] Biomed Comp Res Inst, Philadelphia, PA USA. [Cutler, Gordon B., Jr.] NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD USA. [Roeltgen, David] Georgetown Univ, Dept Neurol, Washington, DC USA. [Roeltgen, David] Georgetown Univ, Ctr Aphasia Res & Rehabil, Washington, DC USA. RP Ross, JL (reprint author), Thomas Jefferson Univ, Dept Pediat, Suite 726,1025 Walnut St, Philadelphia, PA 19107 USA. EM Judith.Ross@mail.tju.edu FU NIH [NS32531] FX Supported by NIH NS32531. NR 50 TC 14 Z9 14 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2009 VL 155 IS 5 BP 714 EP 720 DI 10.1016/j.jpeds.2009.05.031 PG 7 WC Pediatrics SC Pediatrics GA 516VH UT WOS:000271570900024 PM 19643440 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Erez, O Mittal, P Chaiworapongsa, T Kim, SK Pacora, P Yeo, L Gotsch, F Dong, Z Yoon, BH Hassan, SS Kusanovic, JP AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Erez, Offer Mittal, Pooja Chaiworapongsa, Tinnakorn Kim, Sun Kwon Pacora, Percy Yeo, Lami Gotsch, Francesca Dong, Zhong Yoon, Bo Hyun Hassan, Sonia S. Kusanovic, Juan Pedro TI Maternal serum adiponectin multimers in patients with a small-for-gestational-age newborn SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Adipokines; adipose tissue; body mass index (BMI); fetal growth; high-molecular-weight (HMW) adiponectin; low-molecular-weight (LMW) adiponectin; medium-molecular-weight (MMW) adiponectin; obesity; overweight; pregnancy; small-for-gestational-age (SGA) ID HIGH-MOLECULAR-WEIGHT; INTRAUTERINE GROWTH RESTRICTION; NECROSIS-FACTOR-ALPHA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ENDOTHELIAL-CELL APOPTOSIS; ADVERSE PREGNANCY OUTCOMES; HEALTHY NULLIPAROUS WOMEN; CONSERVED LYSINE RESIDUES; ACTIVATED PROTEIN-KINASE; INSULIN-RESISTANCE AB Objective: Several mechanisms of disease have been implicated in the pathophysiology of small-for-gestational-age (SGA) including an anti-angiogenic state, and an exaggerated intravascular pro-inflammatory response. Adiponectin plays a role in a wide range of biological activities including those that have been implicated in the pathophysiology SGA. Thus, the aim of this study was to determine if third trimester adiponectin concentrations differed between women with normal weight infants and those with an SGA neonate. Study design: This cross-sectional study included women with: 1) a normal pregnancy (n=234); and 2) an SGA neonate (n=78). SGA was defined as a birth weight below the 10(th) percentile for gestational age at birth. The study population was further stratified by first trimester body mass index (BMI) (normal weight <25 kg/m(2) vs. overweight/obese >= 25 kg/m(2)). Maternal serum adiponectin multimers [total, high-molecular-weight (HMW), medium-molecular-weight (MMW) and low-molecular-weight (LMW)] concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median maternal serum concentrations of total, HMW and MMW adiponectin were significantly lower in patients with an SGA neonate than in those with normal pregnancies; 2) patients with an SGA neonate had a significantly lower median HMW/total adiponectin ratio and higher median MMW/total adiponectin and LMW/total adiponectin ratios than those with a normal pregnancy; 3) among patients with an SGA neonate, neither maternal serum concentrations of adiponectin multimers, nor their relative distribution differ between normal weight and overweight/obese patients. Conclusion: 1) Pregnancies complicated by an SGA neonate are characterized by a alterations in the maternal serum adiponectin multimers concentrations and their relative abundance; 2) the findings reported herein suggest that maternal adipose tissue may play a role, in the pathogenesis of SGA. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Bethesda, MD USA. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 150 TC 20 Z9 20 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD NOV PY 2009 VL 37 IS 6 BP 623 EP 635 DI 10.1515/JPM.2009.128 PG 13 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 519IG UT WOS:000271758700006 PM 19530958 ER PT J AU Mazaki-Tovi, S Romero, R Vaisbuch, E Erez, O Mittal, P Chaiworapongsa, T Kim, SK Pacora, P Yeo, L Gotsch, F Dong, Z Yoon, BH Hassan, SS Kusanovic, JP AF Mazaki-Tovi, Shali Romero, Roberto Vaisbuch, Edi Erez, Offer Mittal, Pooja Chaiworapongsa, Tinnakorn Kim, Sun Kwon Pacora, Percy Yeo, Lami Gotsch, Francesca Dong, Zhong Yoon, Bo Hyun Hassan, Sonia S. Kusanovic, Juan Pedro TI Maternal serum adiponectin multimers in gestational diabetes SO JOURNAL OF PERINATAL MEDICINE LA English DT Review DE Adipokines; body mass index (BMI); diabetes; gestational diabetes; high-molecular-weight (HMW) adiponectin; low-molecular-weight (LMW) adiponectin; medium-molecular-weight (MMW) adiponectin; obesity; overweight; pregnancy ID MOLECULAR-WEIGHT ADIPONECTIN; LINKED-IMMUNOSORBENT-ASSAY; GLUCOSE-TOLERANCE TEST; INSULIN-RESISTANCE SYNDROME; COMPLEMENT-RELATED PROTEIN; ADIPOSE-SPECIFIC PROTEIN; NECROSIS-FACTOR-ALPHA; PLASMA ADIPONECTIN; RISK-FACTORS; BIRTH-WEIGHT AB Objective: Adiponectin, an adipokine with profound insulin-sensitizing effect, consists of heterogeneous species of multimers. These oligomeric complexes circulate as low-molecular-weight (LMW) trimers, medium-molecular-weight (MMW) hexamers and high-molecular-weight (HMW) isoforms and can exert differential biological effects. The aims of this study were to determine whether there is a change in circulating adiponectin multimers in the presence of gestational diabetes mellitus (GDM), overweight/obesity or with a treatment with sulfonylurea or insulin in patients with GDM. Study design: This cross-sectional study included women with: 1) normal pregnancy (n=149); and 2) patients with GDM (n=72). Thirty-three patients with GDM were managed with diet alone. Among the others 39 diabetic patients, 17 were treated with Glyburide and 22 with insulin. The study population was further stratified by first trimester body mass index (BMI) (normal weight <25 kg/m(2) vs. overweight/obese >= 25 kg/m(2)). Serum adiponectin multimers (total, HMW, MMW and LMW) concentrations were determined by ELISA. Results: 1) The median maternal serum of total, HMW, MMW and LMW were lower in patients with GDM than in those with normal pregnancies (P<0.001 for all comparisons); 2) patients with GDM had a lower HMW/total adiponectin ratio and a higher MMW/total and LMW/total adiponectin ratio than those with a normal pregnancy (P<0.001 for all comparisons); and 3) among GDM patients, there were no differences in the concentrations and relative distribution of adiponectin multimers between those who were managed with diet, and those who were treated with pharmacological agents. Conclusion: 1) GDM is characterized by a distinctive pattern of concentrations and relative distribution of adiponectin multimers akin to Type 2 diabetes mellitus; 2) dysregulation of adiponectin multimeres can provide a mechanistic basis for the association between adiposity and GDM. C1 [Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Hassan, Sonia S.; Kusanovic, Juan Pedro] Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Detroit, MI 48201 USA. [Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Yeo, Lami; Hassan, Sonia S.; Kusanovic, Juan Pedro] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Yoon, Bo Hyun] Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. RP Romero, R (reprint author), Hutzel Womens Hosp, Perinatol Res Branch, Intramural Div, NICHD,NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Yoon, Bo Hyun/H-6344-2011; OI Vaisbuch, Edi/0000-0002-8400-9031 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS FX Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 153 TC 40 Z9 42 U1 2 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0300-5577 J9 J PERINAT MED JI J. Perinat. Med. PD NOV PY 2009 VL 37 IS 6 BP 637 EP 650 DI 10.1515/JPM.2009.101 PG 14 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 519IG UT WOS:000271758700007 PM 19530957 ER PT J AU Wang, LY Martin, B Brenneman, R Luttrell, LM Maudsley, S AF Wang, Liyun Martin, Bronwen Brenneman, Randall Luttrell, Louis M. Maudsley, Stuart TI Allosteric Modulators of G Protein-Coupled Receptors: Future Therapeutics for Complex Physiological Disorders SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Review ID BETA(2) ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS; AGONIST-DIRECTED TRAFFICKING; DELTA-OPIOID RECEPTORS; SIGNAL-TRANSDUCTION; BETA(2)-ADRENERGIC RECEPTOR; DRUG DISCOVERY; IN-VIVO; FUNCTIONAL SELECTIVITY; MOLECULAR-MECHANISM AB G protein-coupled receptors (GPCRs) are one of the most important classes of proteins in the genome, not only because of their tremendous molecular diversity but because they are the targets of nearly 50% of current pharmacotherapeutics. The majority of these drugs affect GPCR activity by binding to a similar molecular site as the endogenous cognate ligand for the receptor. These "orthosterically" targeted drugs currently dominate the existing pharmacopeia. Over the past two decades, novel opportunities for drug discovery have risen from a greater understanding of the complexity of GPCR signaling. A striking example of this is the appreciation that many GPCRs possess functional allosteric binding sites. Allosteric modulator ligands bind receptor domains topographically distinct from the orthosteric site, altering the biological activity of the orthosteric ligand by changing its binding affinity, functional efficacy, or both. This additional receptor signaling complexity can be embraced and exploited for the next generation of GPCR-targeted therapies. Despite the challenges associated with detecting and quantifying the myriad of possible allosteric effects on GPCR activity, allosteric ligands offer the prospect of engendering a facile stimulus-bias in orthosteric ligand signaling, paving the way for not only receptor-selective but also signaling pathway-selective therapies. Allosteric modulators possess specific advantages when considering the treatment of multifactorial syndromes, such as metabolic diseases or age-related cognitive impairment, because they may not greatly affect neurotransmitter or hormone release patterns, thus maintaining the integrity of complex signaling networks that underlie perception, memory patterns, or neuroendocrinological axes while introducing therapeutically beneficial signal bias. C1 [Maudsley, Stuart] NIA, Biomed Res Ctr, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. [Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA. [Brenneman, Randall] Univ Miami, Miller Sch Med, Canc Biol Program, Miami, FL 33136 USA. [Luttrell, Louis M.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Luttrell, Louis M.] Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. RP Maudsley, S (reprint author), NIA, Biomed Res Ctr, Receptor Pharmacol Unit, NIH, Room 5C228,251 Bayview Blvd, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU National Institutes of Health National Institute on Aging; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK055524]; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center FX This research was supported in part by the Intramural Research Program of the National Institutes of Health National Institute on Aging; the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant R01-DK055524] (L. M. L.); and the Research Service of the Ralph H. Johnson Veterans Affairs Medical Center (L. M. L.). NR 109 TC 56 Z9 56 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2009 VL 331 IS 2 BP 340 EP 348 DI 10.1124/jpet.109.156380 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509HR UT WOS:000271006200001 PM 19667132 ER PT J AU Li, JX Unzeitig, A Javors, MA Rice, KC Koek, W France, CP AF Li, Jun-Xu Unzeitig, Alison Javors, Martin A. Rice, Kenner C. Koek, Wouter France, Charles P. TI Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane (DOM), Ketanserin, and (R)-(+)-alpha-(2,3-Dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidi nemethanol (MDL100907) in Rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SEROTONIN 5-HT2A RECEPTOR; INVERSE AGONISTS; IN-VIVO; CONSTITUTIVE ACTIVITY; ANTAGONISTS; QUIPAZINE; DEPLETION; RABBIT; ANTIPSYCHOTICS; MDL100,907 AB Very little is known about constitutive activity in vivo. This study examined whether constitutive activity and inverse agonism contribute to discriminative stimulus effects of drugs acting at serotonin (5-HT)(2A) receptors. Rats were trained to discriminate between saline and either 0.56 mg/kg 5-HT(2) receptor agonist 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), 1.0 mg/kg 5-HT(2A) receptor antagonist ketanserin, or 0.1 mg/kg purported 5-HT(2A) receptor inverse agonist (R)-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-pipidinemethanol (MDL100907). Discriminative control was established with each drug after 33 to 35 sessions. MDL100907 and ketanserin did not occasion DOM lever responding but attenuated the discriminative stimulus effects of DOM. DOM did not occasion responding on the drug-associated lever in rats discriminating MDL100907 or ketanserin, but attenuated the discriminative stimulus effects of both drugs. Ketanserin and ritanserin occasioned MDL100907-lever responding, whereas rats discriminating ketanserin responded only partially on the drug-associated lever after receiving MDL100907, ritanserin, or the alpha(1)-adrenergic antagonist prazosin. Combining prazosin with MDL100907 or ritanserin resulted in near-complete ketanserin-lever responding, indicating that the ketanserin stimulus involves both 5-HT(2A) and alpha(1)-adrenergic receptors. Administration of p-chlorophenylalanine methyl ester, then fenfluramine, significantly decreased cortical 5-HT, enhanced sensitivity to the discriminative stimulus effects of DOM, and occasioned partial MDL100907-lever responding. Collectively, these results show that DOM and MDL100907 discriminative stimulus effects are mediated by 5-HT(2A) receptors and that ketanserin discriminative stimulus effects involve both 5-HT(2A) and alpha(1)-adrenergic receptors. Results in 5-HT-depleted rats further suggest that the discriminative stimulus effects of MDL100907 might involve antagonism of endogenous 5-HT and/or inverse agonism at 5-HT(2A) receptors. C1 [Li, Jun-Xu; Unzeitig, Alison; Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Javors, Martin A.; Koek, Wouter; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Rice, Kenner C.] NIDA, Chem Biol Res Branch, Bethesda, MD 20892 USA. RP France, CP (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM france@uthscsa.edu RI Li, Jun-Xu/K-9192-2013 FU National Institutes of Health National Institute on Drug Abuse [DA17918] FX This work was supported in part by the Intramural Research Program of the National Institutes of Health National Institute on Drug Abuse; and by the National Institutes of Health National Institute on Drug Abuse [Grant K05-DA17918] (Senior Scientist Award to C.P.F.). NR 37 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2009 VL 331 IS 2 BP 671 EP 679 DI 10.1124/jpet.109.157560 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 509HR UT WOS:000271006200034 PM 19687292 ER PT J AU Campbell, R Cooper, GS Gilkeson, GS AF Campbell, Robert, Jr. Cooper, Glinda S. Gilkeson, Gary S. TI The Impact of Systemic Lupus Erythematosus on Employment SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE JOB LOSS; LOST WAGES; SYSTEMIC LUPUS ERYTHEMATOSUS; CAROLINA LUPUS STUDY; ARTHRITIS; PLEURITIS ID RHEUMATOID-ARTHRITIS PATIENTS; SOUTHEASTERN UNITED-STATES; WORK DISABILITY; REVISED CRITERIA; RISK-FACTORS; CLASSIFICATION; POPULATION; COSTS; RACE AB Objective. Our primary objective was to examine work status (e.g., job loss, changes in amount worked) and predictors of job loss in patients with systemic lupus erythematosus (SLE). Methods. Recently diagnosed SLE patients were enrolled in the Carolina Lupus Study between 1997 and 1999: ail age-, sex-, and state-matched control group selected through driver's license registries for the 60-county study area was also enrolled. In 2001, a followup study of both groups was conducted (median 4 yrs since diagnosis). Work history data were obtained in ail in-person interview at enrollment and a telephone interview at followup. Results. Fifty-one patients (26%) and 26 controls (9%) (p < 0.0001) who were working the year before diagnosis (or for controls, it corresponding reference year) were no longer working at followup; 92% of patients compared with 40% of controls who were no longer working indicated that they had stopped working because of their health (p < 0.0001). College graduates were less likely to quit their jobs due to health compared to non-college graduates (adjusted OR = 0.27, 95% CI 0.09, 0.84). SLE patients with arthritis were 3 times more likely to have left their jobs due to health reasons compared to those who didn't have arthritis (adjusted OR = 3.3. 95% CI 1.2, 8.8); ail association was also seen with pleuritis (adjusted OR 2.3, 95% CI 1.1, 4.6). Conclusion. The burden expressed as work cessation due to health, especially among lesser educated patients and those with arthritis or pleuritis, is significant even early in the disease process. (First Release Oct 1 2009; J Rheumatol 2009;36:2470-5, doi: 10.3899/jrheum.080586) C1 [Campbell, Robert, Jr.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. NIEHS, NIH, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Cooper, Glinda S.] US EPA, Washington, DC 20460 USA. [Gilkeson, Gary S.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Campbell, R (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA. EM campber@musc.edu FU Intramural NIH HHS; NIAMS NIH HHS [2R01-AR045476, 1T32-AR050958, P60-AR049459] NR 28 TC 12 Z9 12 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2009 VL 36 IS 11 BP 2470 EP 2475 DI 10.3899/jrheum.080586 PG 6 WC Rheumatology SC Rheumatology GA 517DP UT WOS:000271593700016 PM 19273454 ER PT J AU Baker, K Pope, J Silverman, E Cooper, G Fortin, P Zummer, M Smith, CD Petty, R Tucker, L Albert, L Huber, A Ramsey, S Arbillaga, H Chedeville, G Hudson, M Peschken, C AF Baker, Kim Pope, Janet Silverman, Earl Cooper, Glinda Fortin, Paul Zummer, Michel Smith, C. Douglas Petty, Ross Tucker, Lori Albert, Lori Huber, Adam Ramsey, Suzanne Arbillaga, Hector Chedeville, Gaelle Hudson, Marie Peschken, Christine CA Investigators 1000 Faces Lupus CaN TI Work Disability in Systemic Lupus Erythematosus Is Prevalent and Predicted by Socio-demographic and Disease Related Factors: Results from a Multi-ethnic Cohort SO JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting/17th Winter Workshop of the Canadian-Rheumatology-Association CY FEB 18-21, 2009 CL Kananaskis, CANADA SP Canadian Rheumatol Assoc C1 [Baker, Kim] Queens Univ, Kingston, ON K7L 3N6, Canada. [Pope, Janet] Univ Western Ontario, London, ON N6A 3K7, Canada. [Silverman, Earl; Fortin, Paul; Albert, Lori] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Cooper, Glinda] NIEHS, NIH, Bethesda, MD 20892 USA. [Zummer, Michel] Hop Maison Neuve Rosemont, Rosemont, PA USA. [Smith, C. Douglas] Ottawa Gen Hosp, Ottawa, ON, Canada. [Petty, Ross; Tucker, Lori] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Huber, Adam; Ramsey, Suzanne] Dalhousie Univ, Halifax, NS B3H 3J5, Canada. [Arbillaga, Hector] Univ Calgary, Calgary, AB T2N 1N4, Canada. [Chedeville, Gaelle; Hudson, Marie] McGill Univ, Montreal, PQ H3A 2T5, Canada. [Peschken, Christine] Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2009 VL 36 IS 11 MA 3 BP 2559 EP 2560 PG 2 WC Rheumatology SC Rheumatology GA 517DP UT WOS:000271593700035 ER PT J AU Barnard, DE Lewis, SM Teter, BB Thigpen, JE AF Barnard, Dennis E. Lewis, Sherry M. Teter, Beverly B. Thigpen, Julius E. TI Open- and Closed-Formula Laboratory Animal Diets and Their Importance to Research SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID PHYTOESTROGEN CONTENT; RODENT DIETS; CD-1 MICE; RATS; COMMITTEE; TIME AB Almost 40 y ago the scientific community was taking actions to control environmental factors that contribute to variation in the responses of laboratory animals to scientific manipulation. Laboratory animal diet was recognized as an important variable. During the 1970s, the American Institute of Nutrition, National Academy of Science, Institute of Laboratory Animal Resources, and Laboratory Animals Centre Diets Advisory Committee supported the use of 'standard reference diets' in biomedical research as a means to improve the ability to replicate research. As a result the AIN76 purified diet was formulated. During this same time, the laboratory animal nutritionist at the NIH was formulating open-formula, natural-ingredient diets to meet the need for standardized laboratory animal diets. Since the development of open-formula diets, fixed-formula and constant-nutrient-concentration closed-formula laboratory animal natural ingredient diets have been introduced to help reduce the potential variation diet can cause in research. C1 [Barnard, Dennis E.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR USA. [Teter, Beverly B.] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. [Thigpen, Julius E.] NIEHS, Comparat Med Branch, Res Triangle Pk, NC USA. RP Barnard, DE (reprint author), NIH, Off Res Serv, Div Vet Resources, Bldg 10, Bethesda, MD 20892 USA. EM barnardd@mail.nih.gov NR 37 TC 20 Z9 20 U1 1 U2 6 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2009 VL 48 IS 6 BP 709 EP 713 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 522OR UT WOS:000272008100003 PM 19930817 ER PT J AU Cannon, CZ Godfrey, VL King-Herbert, A Nielsen, JN AF Cannon, Coralie Zegre Godfrey, Virginia L. King-Herbert, Angela Nielsen, Judith N. TI Metastatic Uterine Adenocarcinoma in an 8-year-old Gilt SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID ENDOMETRIAL ADENOCARCINOMA; SUS-SCROFA; TUMORS; PIGS; GENITALIA; SOW AB An 8-y-old gilt was evaluated after the onset of hemorrhagic perineal discharge. Uterine adenocarcinoma with metastases to the lungs and regional lymph nodes was diagnosed at necropsy. Tumor cells lacked expression of estrogen receptor a and progesterone receptor. This case represents the first reported uterine adenocarcinoma in a research pig and the first swine uterine neoplasia in which steroid hormone receptor expression was evaluated. C1 [Cannon, Coralie Zegre; Godfrey, Virginia L.; Nielsen, Judith N.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA. [Cannon, Coralie Zegre; King-Herbert, Angela] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA. RP Nielsen, JN (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27515 USA. EM Judith_Nielsen@med.unc.edu FU NHLBI [HL069364]; North Carolina Biotechnology Center [MRG1101]; Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences; Division of Laboratory Animal Medicine at the University of North Carolina FX We extend special thanks to Dr Timothy Nichols, Ms Robin Raymer, Mr Kent Passingham, and Mr Adam Bakowski for their research expertise, assistance, facility management, and the animal care they provide to the swine colony at UNC. We also thank Ms Tiwanda Masincle and Ms Natasha Clayton for their immunohistochernistry support at NIEHS. This work was supported in part by grant NHLBI HL069364, North Carolina Biotechnology Center grant MRG1101, the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, and by the Division of Laboratory Animal Medicine at the University of North Carolina. NR 21 TC 3 Z9 3 U1 1 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD NOV PY 2009 VL 48 IS 6 BP 795 EP 800 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 522OR UT WOS:000272008100016 PM 19930830 ER PT J AU Colon-Ramos, U Thompson, FE Yaroch, AL Moser, RP McNeel, TS Dodd, KW Atienza, AA Sugerman, SB Nebeling, L AF Colon-Ramos, Uriyoan Thompson, Frances E. Yaroch, Amy Lazarus Moser, Richard P. McNeel, Timothy S. Dodd, Kevin W. Atienza, Audie A. Sugerman, Sharon B. Nebeling, Linda TI Differences in Fruit and Vegetable Intake among Hispanic Subgroups in California: Results from the 2005 California Health Interview Survey SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID MEXICAN-AMERICANS; CUBAN-AMERICANS; NATIONAL-HEALTH; PUERTO-RICANS; UNITED-STATES; DIETARY PATTERNS; ACCULTURATION; ASSOCIATION; OBESITY; BEHAVIORS AB Objective To compare total fruit and vegetable intake in cup equivalents and its individual components among Hispanic subgroups in California. Methods Data are from the adult portion of the 2005 California Health Interview Survey. Hispanic/Latino subjects (n=7,954) were grouped into six subcategories (Mexican, Central American, Caribbean, Spanish American, South American, and >1 group). Total fruit and vegetable intake in cup equivalents was estimated from frequency responses about seven food categories. Both t test and chi(2) test were used to assess differences in sociodemographic characteristics across Hispanic subgroups. Multivariate linear regressions using SUDAAN software (Survey Data Analysis, version 9.0.1, 2005, Research Triangle Institute, Research Triangle Park, NC) were conducted to obtain means of total fruit and vegetable intake in cup equivalents and its components by Hispanic subgroups controlling for confounders. Results Hispanic subgroups did not differ in their intake of total fruit and vegetable intake in cup equivalents (mean 3.4 c and 2.9 c for men and women, respectively). Small but significant differences (P<0.01) were found across Hispanic subgroups in individual fruit and vegetable components (green salad [women only], cooked dried beans and nonfried white potatoes) after adjusting for potential sociodemographic and acculturation confounders. Conclusions Fruit and vegetable intake by Hispanic respondents did not meet the national recommendation, although their reported intake is higher compared to other race/ethnicity groups. The public, health message remains the same: Increase fruit and vegetable intake. Examination of intake for subgroups of Hispanics may enhance the utility of dietary information for surveillance, program and message design, and intervention and evaluation. J Am Diet Assoc. 2009;109:1878-1885. C1 [Thompson, Frances E.] NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Yaroch, Amy Lazarus; Moser, Richard P.; Atienza, Audie A.; Nebeling, Linda] NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Yaroch, Amy Lazarus] Ctr Human Nutr, Omaha, NE USA. [McNeel, Timothy S.] Informat Management Serv Inc, Silver Spring, MD USA. [Dodd, Kevin W.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. [Sugerman, Sharon B.] Calif Dept Hlth, Canc Prevent & Nutr Sect, Res & Evaluat Unit, Sacramento, CA USA. RP Thompson, FE (reprint author), NCI, Risk Factor Monitoring & Methods Branch, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4095A MSC 7344, Bethesda, MD 20892 USA. EM thompsof@mail.nih.gov FU Network for a Healthy California FX The authors thank Susan Foerster, MPH, RD, Network for a Healthy California, for providing assistance and support during this project. NR 35 TC 22 Z9 22 U1 2 U2 6 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2009 VL 109 IS 11 BP 1878 EP 1885 DI 10.1016/j.jada.2009.08.015 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 516JL UT WOS:000271538200009 PM 19857629 ER PT J AU Vereecken, CA Covents, M Haynie, D Maes, L AF Vereecken, Carine Anna Covents, Marc Haynie, Denise Maes, Lea TI Feasibility of the Young Children's Nutrition Assessment on the Web SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; CRITERION VALIDITY; GENDER-DIFFERENCES; BLACK-ADOLESCENTS; REPRODUCIBILITY; DIET; CALCIUM; IRON; TOOL AB Methods to assess detailed dietary data are cumbersome, expensive, and difficult to implement with large samples. The purpose of the present article was to evaluate the feasibility of collecting data from parents about their child's diet using an online dietary assessment tool. The Young Children's Nutrition Assessment on the Web was developed as part of a longitudinal study of familial influences on food intake of preschool children. A sample of 862 parents from 56 nursery schools completed a paper-and-pencil questionnaire containing sociodemographic variables and a food frequency questionnaire about their child's diet and psychosocial variables. Subsequently, a subset of parents was asked to either complete a paper-and-pencil food diary or the Young Children's Nutrition Assessment on the Web (n=88); those remaining who provided e-mail addresses were asked to complete the Young Children's Nutrition Assessment on the Web (n=467) and a user-acceptability questionnaire. This resulted in 39 useful paper-and-pencil diaries, 217 useful Young Children's Nutrition Assessments on the Web, and 164 user-acceptability questionnaires. Mann-Whitney U tests comparing nutrient (macronutrients, vitamin C, calcium, and fiber) and food group intakes from data collected with the Young Children's Nutrition Assessment on the Web vs paper-and-pencil diaries resulted in no substantial differences except for water. Attrition analyses indicated that dropout for the online assessment was associated with the sex of the respondent (father completing the questionnaire), lower social status, being a smoker, and lower nutrition knowledge. The online measure was well-received by respondents. The majority found it user-friendly (79%), attractive (68%), and clear (93%). The Young Children's Nutrition Assessment on the Web is a promising tool to collect online dietary data. in large-scale surveys. J Am Diet Assoc. 2009;109:1896-1902. C1 [Vereecken, Carine Anna] Univ Ghent, Dept Publ Hlth, FWO Flanders, B-9000 Ghent, Belgium. [Haynie, Denise] Eunice Kennedy Shriver Natl Inst Child Hlth, Prevent Res Branch, NIH, Bethesda, MD USA. RP Vereecken, CA (reprint author), Univ Ghent, Dept Publ Hlth, FWO Flanders, UH Bloc A,2nd Floor,Pintelaan 185, B-9000 Ghent, Belgium. EM Carine.Vereecken@UGent.be OI Haynie, Denise/0000-0002-8270-6079 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institutes of Health; Department of Health and Human Services FX C.A.V. is postdoctoral researcher supported by the Research Foundation-Flanders (FWO-Vlaanderen). D. H. is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 22 TC 19 Z9 19 U1 0 U2 8 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2009 VL 109 IS 11 BP 1896 EP 1902 DI 10.1016/j.jada.2009.08.013 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 516JL UT WOS:000271538200011 PM 19857631 ER PT J AU Strotmeyer, ES de Rekeneire, N Schwartz, AV Resnick, HE Goodpaster, BH Faulkner, KA Shorr, RI Vinik, AI Harris, TB Newman, AB AF Strotmeyer, Elsa S. de Rekeneire, Nathalie Schwartz, Ann V. Resnick, Helaine E. Goodpaster, Bret H. Faulkner, Kimberly A. Shorr, Ronald I. Vinik, Aaron I. Harris, Tamara B. Newman, Anne B. CA Hlth ABC Study TI Sensory and Motor Peripheral Nerve Function and Lower-Extremity Quadriceps Strength: The Health, Aging and Body Composition Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quadriceps strength; peripheral nerves; performance ID DEPENDENT DIABETES-MELLITUS; SKELETAL-MUSCLE STRENGTH; OLDER-ADULTS; WOMENS HEALTH; PHYSICAL PERFORMANCE; BLACK ADULTS; AGE; DISABILITY; NEUROPATHY; POPULATION AB OBJECTIVES To determine whether sensory and motor nerve function is associated cross-sectionally with quadriceps or ankle dorsiflexion strength in an older community-based population. DESIGN Cross-sectional analyses within a longitudinal cohort study. SETTING Two U.S. clinical sites. PARTICIPANTS Two thousand fifty-nine Health, Aging and Body Composition Study (Health ABC) participants (49.5% male, 36.7% black, aged 73-82) in 2000/01. MEASUREMENTS Quadriceps and ankle strength were measured using an isokinetic dynamometer. Sensory and motor peripheral nerve function in the legs and feet was assessed using 10-g and 1.4-g monofilaments, vibration threshold, and peroneal motor nerve conduction amplitude and velocity. RESULTS Monofilament insensitivity, poorest vibration threshold quartile (> 60 mu), and poorest motor nerve conduction amplitude quartile (< 1.7 mV) were associated with 11%, 7%, and 8% lower quadriceps strength (all P <.01), respectively, than in the best peripheral nerve function categories in adjusted linear regression models. Monofilament insensitivity and lowest amplitude quartile were both associated with 17% lower ankle strength (P <.01). Multivariate analyses were adjusted for demographic characteristics, diabetes mellitus, body composition, lifestyle factors, and chronic health conditions and included all peripheral nerve measures in the same model. Monofilament insensitivity (beta=-7.19), vibration threshold (beta=-0.097), and motor nerve conduction amplitude (beta=2.01) each contributed independently to lower quadriceps strength (all P <.01). Monofilament insensitivity (beta=-5.29) and amplitude (beta=1.17) each contributed independently to lower ankle strength (all P <.01). Neither diabetes mellitus status nor lean mass explained the associations between peripheral nerve function and strength. CONCLUSION Reduced sensory and motor peripheral nerve function is related to poorer lower extremity strength in older adults, suggesting a mechanism for the relationship with lower extremity disability. C1 [Strotmeyer, Elsa S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA 15213 USA. [Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Div Endocrinol & Metab, Pittsburgh, PA 15213 USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. [de Rekeneire, Nathalie] Epicentre, Paris, France. [Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Resnick, Helaine E.] Amer Assoc Homes & Serv Aging, Washington, DC USA. [Shorr, Ronald I.] N Florida S Georgia Vet Hlth Syst, Geriatr Res Educ & Clin Ctr, Gainesville, FL USA. [Shorr, Ronald I.] Univ Florida, Dept Aging & Geriatr, Gainesville, FL USA. [Vinik, Aaron I.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, 130 N Bellefield Ave,Room 515, Pittsburgh, PA 15213 USA. EM StrotmeyerE@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036 FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, 1-R01-AG 028050]; Intramural Research Program of the National Institutes of Health, NIA FX We thank the participants and staff for their efforts, Dr. Robert Boudreau for statistical insights, Ms. Mei Yang for performing analyses, and Ms. Michelle Utz-Kiley for assistance with manuscript preparation. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This work was funded by the National Institute on Aging (NIA) under Contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, and 1-R01-AG 028050 (to ESS) and supported in part by the Intramural Research Program of the National Institutes of Health, NIA; University of Pittsburgh Claude D. Pepper Older Americans Independence Center (P30-AG024827) Pilot Grant (to ESS) and the American Diabetes Association (1-04-JF-46 to ESS). Author Contributions: ESS, HER: study concept and design, data analysis and interpretation, and preparation of the manuscript. ND, AVS BHG, KAF, RIS, AIV: data analysis and interpretation and preparation of the manuscript. TBH, ABN: study concept and design, acquisition of subjects and data, analysis and interpretation of data, and preparation of the manuscript. Sponsor's Role: The funding institutes had no role in the design, methods, subject recruitment, data collection, analysis, and preparation of manuscript or in the decision to submit the manuscript for publication. NR 43 TC 35 Z9 36 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2009 VL 57 IS 11 BP 2004 EP 2010 DI 10.1111/j.1532-5415.2009.02487.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 512KU UT WOS:000271248500005 PM 19793163 ER PT J AU Bandinelli, S Milaneschi, Y Ferrucci, L AF Bandinelli, Stefania Milaneschi, Yuri Ferrucci, Luigi TI Chair Stands Test and Survival in the Older Population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Milaneschi, Yuri] Tuscany Hlth Reg Agcy, Florence, Italy. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Bandinelli, S (reprint author), Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. FU Intramural NIH HHS [ZIA AG000015-56]; NIA NIH HHS [N01-AG-5-0002]; NIMHD NIH HHS [R01 MD009164] NR 3 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2009 VL 57 IS 11 BP 2172 EP 2173 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 512KU UT WOS:000271248500042 PM 20121975 ER PT J AU Lloyd, JR Hess, S AF Lloyd, John R. Hess, Sonja TI A Corona Discharge Initiated Electrochemical Electrospray Ionization Technique SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID LIQUID CHROMATOGRAPHY/ELECTROCHEMISTRY/MASS SPECTROMETRY; MASS-SPECTROMETRY; ION-SOURCE; ATMOSPHERIC-PRESSURE; PROTEIN-STRUCTURE; EMITTER CELL; GAS-PHASE; DERIVATIZATION; FERROCENE; MECHANISMS AB We report here the development of a corona discharge (CD) initiated electrochemical (EC) electrospray ionization (EST) technique using a standard electrospray ion source. This is a new ionization technique distinct from EST, electrochemistry inherent to EST, APCI, and techniques using hydroxyl radicals produced under atmospheric pressure conditions. By maximizing the observable CID at the tip of a stainless steel EST capillary, efficient electrochemical oxidation of electrochemically active compounds is observed. For electrochemical oxidation to be observed, the ionization potential of the analyte must be lower than Fe. Ferrocene labeled compounds were chosen as the electrochemically active moiety. The electrochemical cell in the EST source was robust, and generated ions with selectivity according to the ionization potential of the analytes and up to zeptomolar sensitivity. Our results indicate that CID initiated electrochemical ionization has the potential to become a powerful technique to increase the dynamic range, sensitivity, and selectivity of EST experiments. (J Am Soc Mass Spectrom 2009, 20,1988-1996) (C) 2009 American Society for Mass Spectrometry C1 [Hess, Sonja] CALTECH, Beckman Inst, Proteome Explorat Lab, Pasadena, CA 91125 USA. [Lloyd, John R.] NIDDK, Prote & Mass Spectrometry Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Hess, S (reprint author), CALTECH, Beckman Inst, Proteome Explorat Lab, 1200 E Calif Blvd,MC 139-74, Pasadena, CA 91125 USA. EM shess@caltech.edu RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 FU Intramural Research Program of the NIH; National Institute of Diabetes and Digestive and Kidney Diseases; Betty and Gordon Moore Foundation; Beckman Institute FX The authors acknowledge support for this work by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases, the Betty and Gordon Moore Foundation, and the Beckman Institute. The authors thank Daniel Eikel for taking the photograph, Jenny TC He for discussion. NR 52 TC 9 Z9 9 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD NOV PY 2009 VL 20 IS 11 BP 1988 EP 1996 DI 10.1016/j.jasms.2009.07.021 PG 9 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 522RU UT WOS:000272016900006 PM 19747843 ER PT J AU Jeang, KT Huang, LM AF Jeang, Kuan-Teh Huang, Li-Min TI HIV-1 Vaccine-Many Miles to Go Before We Sleep SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Editorial Material ID INTENTION-TO-TREAT; DOUBLE-BLIND; TRIAL; INFECTION; CHINA C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Huang, Li-Min] Natl Taiwan Univ, Dept Pediat, Taipei 10764, Taiwan. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Huang, Li-Min/0000-0002-9291-260X NR 17 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2009 VL 108 IS 11 BP 827 EP 829 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 535HK UT WOS:000272957800001 PM 19933024 ER PT J AU Oramasionwu, CU Skinner, J Ryan, L Frei, CR AF Oramasionwu, Christine U. Skinner, Jeff Ryan, Laurajo Frei, Christopher R. TI Disparities in Antiretroviral Prescribing for Blacks and Whites in the United States SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE HIV/AIDS; health disparities ID IMMUNODEFICIENCY-VIRUS-INFECTION; INJECTION-DRUG USE; HEPATITIS-C-VIRUS; TREATMENT GUIDELINES; HIV; THERAPY; MORTALITY; GENDER; COHORT; AIDS AB Purpose: The health benefits for blacks on highly active antiretroviral therapy (HAART) logs behind that of whites. We therefore investigated whether this discrepancy in health outcomes is attributable to disparities in the receipt of appropriate HAART between black and white human immunodeficiency virus (HIV) patients. Methods: The 2000-2005 National Ambulatory Medical Care Surveys were used to identify patients receiving antiretrovirals. Regimens were evaluated for appropriateness according to national antiretroviral guideline recommendations. A multivariable logistic regression model was used to assess black race as a predictor for appropriate HAART. Results: An estimated 4.1 million HIV-related visits with antiretroviral therapy were identified. Eighty-six percent of visits were associated with appropriate therapy; inappropriate therapy was often due to antiretroviral monotherapy. Interestingly, blacks were more likely to receive appropriate therapy in comparison to white patients (94% vs 83%, P < .001). Multivariable analysis revealed black race as an independent predictor for an appropriate regimen (chi(2) likelihood ratio, 12.3, P < .001) when controlling for age, gender, insurance status, and geographic region. Conclusions: Health outcome disparities between black and white HIV patients do not appear to be attributable to differences in receipt of appropriate HAART. Further investigations are warranted to identify factors responsible for these outcome disparities. C1 [Frei, Christopher R.] Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, San Antonio, TX 78229 USA. [Oramasionwu, Christine U.; Ryan, Laurajo; Frei, Christopher R.] Univ Texas Austin, Austin Coll Pharm, Austin, TX 78712 USA. [Skinner, Jeff] NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Frei, CR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Pharmacotherapy Educ & Res Ctr, MSC 6220,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM freic@uthscsa.edu OI Skinner, Jeff/0000-0001-5697-0442 NR 20 TC 4 Z9 4 U1 0 U2 0 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 2009 VL 101 IS 11 BP 1140 EP 1144 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 529SC UT WOS:000272536500009 PM 19998643 ER PT J AU Park, S Clarkson, E AF Park, Subok Clarkson, Eric TI Efficient estimation of ideal-observer performance in classification tasks involving high-dimensional complex backgrounds SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID CHANNELS; MODEL AB The Bayesian ideal observer is optimal among all observers and sets an absolute upper bound for the performance of any observer in classification tasks [Van Trees, Detection, Estimation, and Modulation Theory, Part I (Academic, 1968).]. Therefore, the ideal observer should be used for objective image quality assessment whenever possible. However, computation of ideal-observer performance is difficult in practice because this observer requires the full description of unknown, statistical properties of high-dimensional, complex data arising in real life problems. Previously, Markov-chain Monte Carlo (MCMC) methods were developed by Kupinski et al. [J. Opt. Soc. Am. A 20, 430(2003)] and by Park et al. [J. Opt. Sec. Am. A 24, B136 (2007) and IEEE Trans. Med. Imaging 28, 657 (2009)] to estimate the performance of the ideal observer and the channelized ideal observer (CIO), respectively, in classification tasks involving non-Gaussian random backgrounds. However, both algorithms had the disadvantage of long computation times. We propose a fast MCMC for real-time estimation of the likelihood ratio for the CIO. Our simulation results show that our method has the potential to speed up ideal-observer performance in tasks involving complex data when efficient channels are used for the CIO. (C) 2009 Optical Society of America C1 [Park, Subok] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, DIAM, CDRH, Silver Spring, MD 20993 USA. [Clarkson, Eric] Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. [Clarkson, Eric] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Park, S (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, DIAM, CDRH, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering; Radiological Health, FDA FX The authors thank Drs. Laura Thompson and Frank Samuelson at the FDA for their comments on the manuscript. This work is supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health intramural grant to the Center for Devices and Radiological Health, FDA. NR 15 TC 5 Z9 5 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD NOV PY 2009 VL 26 IS 11 BP B59 EP B71 PG 13 WC Optics SC Optics GA 524LA UT WOS:000272143600006 PM 19884916 ER PT J AU Ujhazy, P Stewart, D AF Ujhazy, Peter Stewart, David TI DNA Repair SO JOURNAL OF THORACIC ONCOLOGY LA English DT Editorial Material ID CANCER; INHIBITORS C1 [Ujhazy, Peter; Stewart, David] NCI, Bethesda, MD 20892 USA. RP Ujhazy, P (reprint author), NCI, Bethesda, MD 20892 USA. EM ujhazyp@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2009 VL 4 IS 11 BP S1068 EP S1070 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 514KU UT WOS:000271394100008 PM 19861921 ER PT J AU Carneiro-Lobo, TC Konig, S Machado, DE Nasciutti, LE Forni, MF Francischetti, IMB Sogayar, MC Monteiro, RQ AF Carneiro-Lobo, T. C. Konig, S. Machado, D. E. Nasciutti, L. E. Forni, M. F. Francischetti, I. M. B. Sogayar, M. C. Monteiro, R. Q. TI Ixolaris, a tissue factor inhibitor, blocks primary tumor growth and angiogenesis in a glioblastoma model SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE angiogenesis; anticoagulant therapy; glioblastoma; Ixolaris; primary tumor growth; tissue factor ID FACTOR PATHWAY INHIBITOR; HEPARIN-BINDING EXOSITE; FACTOR EXPRESSION; BLOOD-COAGULATION; FACTOR-XA; MOLECULAR-MECHANISMS; COLORECTAL-CANCER; PANCREATIC-CANCER; POTENT INHIBITOR; HUMAN GLIOMAS AB Background: The expression levels of the clotting initiator protein Tissue Factor (TF) correlate with vessel density and the histological malignancy grade of glioma patients. Increased procoagulant tonus in high grade tumors (glioblastomas) also indicates a potential role for TF in progression of this disease, and suggests that anticoagulants could be used as adjuvants for its treatment. Objectives: We hypothesized that blocking of TF activity with the tick anticoagulant Ixolaris might interfere with glioblastoma progression. Methods and results: TF was identified in U87-MG cells by flow-cytometric and functional assays (extrinsic tenase). In addition, flow-cytometric analysis demonstrated the exposure of phosphatidylserine in the surface of U87-MG cells, which supported the assembly of intrinsic tenase (FIXa/FVIIIa/FX) and prothrombinase (FVa/FXa/prothrombin) complexes, accounting for the production of FXa and thrombin, respectively. Ixolaris effectively blocked the in vitro TF-dependent procoagulant activity of the U87-MG human glioblastoma cell line and attenuated multimolecular coagulation complexes assembly. Notably, Ixolaris inhibited the in vivo tumorigenic potential of U87-MG cells in nude mice, without observable bleeding. This inhibitory effect of Ixolaris on tumor growth was associated with downregulation of VEGF and reduced tumor vascularization. Conclusion: Our results suggest that Ixolaris might be a promising agent for anti-tumor therapy in humans. C1 [Monteiro, R. Q.] UFRJ, CCS, Inst Bioquim Med, BR-21941590 Rio De Janeiro, Brazil. [Konig, S.] UFRJ, Dept Anat, BR-21941590 Rio De Janeiro, Brazil. [Machado, D. E.; Nasciutti, L. E.] UFRJ, Dept Histol & Embriol, BR-21941590 Rio De Janeiro, Brazil. [Forni, M. F.; Sogayar, M. C.] Univ Sao Paulo, Inst Quim, Dept Bioquim, BR-01498 Sao Paulo, Brazil. [Francischetti, I. M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Monteiro, RQ (reprint author), UFRJ, CCS, Inst Bioquim Med, Ave Carlos Chagas Filho 373,Cidade Univ, BR-21941590 Rio De Janeiro, Brazil. EM robsonqm@bioqmed.ufrj.br RI PCM, PG/D-1034-2013; Inbeb, Inct/K-2317-2013; Monteiro, Robson/B-8007-2014; OI Forni, Maria Fernanda/0000-0002-3335-9023 FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq); Fundacao de Amparo Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ); Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP); Financiadora de Estudos e Projetos (FINEP) FX We thank L. G. Lima for helpful discussion and technical support; C. Nogueira (HUCFF/UFRJ, RJ, Brazil) for providing the human plasma samples; and A. L. O. Carvalho, A. Dutra de Oliveira, Z. de Mendonca, S. Regina de Souza, D. Cristina da Costa and R. Krett de Oliveira for technical assistance. This research was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ), Fundacao de Amparo Pesquisa do Estado de Sao Paulo (FAPESP) and Financiadora de Estudos e Projetos (FINEP). NR 52 TC 39 Z9 40 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD NOV PY 2009 VL 7 IS 11 BP 1855 EP 1864 DI 10.1111/j.1538-7836.2009.03553.x PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 509QJ UT WOS:000271032900015 PM 19624457 ER PT J AU Olden, K Ramos, RM Freudenberg, N AF Olden, Kenneth Ramos, Rose Marie Freudenberg, Nicholas TI To Reduce Urban Disparities in Health, Strengthen and Enforce Equitably Environmental and Consumer Laws SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE Health disparities; Urban health; Health policy; Environmental health; Consumer protection ID PARTICULATE AIR-POLLUTION; UNITED-STATES; PUBLIC-HEALTH; 8 AMERICA; MORTALITY; RACE; CHILDREN; SMOKING; DISEASE; CANCER AB While observers agree that reducing disparities in health is an important health priority for the USA, there is little agreement and no comprehensive plan to achieve this goal. In this commentary, we make the case for reducing the disproportionate exposure to environmental and consumer hazards as a promising strategy for reducing health disparities. Exposures to environmental risks such as air pollution, lead, and hazardous wastes and to consumer products such as tobacco, alcohol, and unhealthy food have been identified as significant threats to health and important contributors to disparities in health. Strengthening the regulations that prevent exposure to these harmful substances and enforcing these rules equitably could bring benefits to the population as a whole and especially to the disenfranchised, primarily urban, populations that are most exposed. The current policy environment may present a window of opportunity for pursuing this strategy. C1 [Olden, Kenneth; Freudenberg, Nicholas] CUNY Hunter Coll, Sch Hlth Sci, New York, NY 10021 USA. [Freudenberg, Nicholas] CUNY, Grad Ctr, New York, NY USA. [Olden, Kenneth; Ramos, Rose Marie] NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Freudenberg, N (reprint author), CUNY Hunter Coll, Sch Hlth Sci, New York, NY 10021 USA. EM nfreuden@hunter.cuny.edu NR 45 TC 2 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD NOV PY 2009 VL 86 IS 6 BP 819 EP 824 DI 10.1007/s11524-009-9380-5 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 531DU UT WOS:000272643700001 PM 19533364 ER PT J AU Kowalczyk, KJ Hooper, HB Linehan, WM Pinto, PA Wood, BJ Bratslavsky, G AF Kowalczyk, Keith J. Hooper, H. Brooks Linehan, W. Marston Pinto, Peter A. Wood, Bradford J. Bratslavsky, Gennady TI Partial Nephrectomy After Previous Radio Frequency Ablation: The National Cancer Institute Experience SO JOURNAL OF UROLOGY LA English DT Article DE nephrectomy; catheter ablation; treatment outcome ID RENAL-CELL CARCINOMA; PARENCHYMAL SPARING SURGERY; RADIOFREQUENCY ABLATION; TUMOR SIZE; FEASIBILITY; OUTCOMES; SALVAGE; MASSES AB Purpose: Development of new renal tumors or recurrence after radio frequency ablation not amendable for repeat ablation presents a difficult therapeutic dilemma. We report on the outcomes of partial nephrectomy on kidneys previously treated with radio frequency ablation. Materials and Methods: We performed a chart review of 13 patients who underwent 16 attempted partial nephrectomies following radio frequency ablation. Hospital records and operative reports were reviewed for demographic data, perioperative data and outcomes. The outcomes of the present series were compared to historical controls of published studies in similar patient populations. Results: No cases were converted to radical nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of severe fibrosis in the operative field in 12 of 16 cases (75%). There was a modest but statistically significant decrease in renal function. Partial nephrectomy after radio frequency ablation had a higher reoperation rate compared to other series of primary or repeat partial nephrectomies but had the lowest rate of vascular or visceral injuries. Conclusions: Partial nephrectomy on kidneys previously treated with radio frequency ablation is a technically challenging but feasible procedure. Residual or metachronous disease after radio frequency ablation may be salvaged with partial nephrectomy with a modest decrease in renal function. A trend toward a higher chance of reoperation and urine leak after partial nephrectomy after radio frequency ablation may be useful information for the planning and discussion of treatment decisions. C1 [Kowalczyk, Keith J.; Hooper, H. Brooks; Linehan, W. Marston; Pinto, Peter A.; Bratslavsky, Gennady] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Wood, Bradford J.] NIH, Ctr Clin, US Dept HHS, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM bratslag@mail.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX Supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 20 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2009 VL 182 IS 5 BP 2158 EP 2163 DI 10.1016/j.juro.2009.07.064 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 506EO UT WOS:000270756900019 PM 19758659 ER PT J AU Venkatesan, AM Locklin, J Lai, EW Adams, KT Fojo, AT Pacak, K Wood, BJ AF Venkatesan, Aradhana M. Locklin, Julia Lai, Edwin W. Adams, Karen T. Fojo, Antonio Tito Pacak, Karel Wood, Bradford J. TI Radiofrequency Ablation of Metastatic Pheochromocytoma SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID MALIGNANT PHEOCHROMOCYTOMA; METYROSINE; MANAGEMENT; TUMORS AB In the present report on the preliminary safety and effectiveness of radiofrequency (RF) ablation for pheochromocytoma metastases, seven metastases were treated in six patients (mean size, 3.4 cm; range, 2.2-6 cm). alpha- and beta-adrenergic and catecholamine synthesis inhibition and intraprocedural anesthesia monitoring were used. Safety was assessed by recording ablation-related complications. Complete ablation was defined as a lack of enhancement within the ablation zone on follow-up computed tomography. No serious adverse sequelae were observed. Complete ablation was achieved in six of seven metastases (mean follow-up, 12.3 months; range, 2.5-28 months). In conclusion, RF ablation may be safely performed for metastatic pheochromocytorna given careful attention to peri-procedural management. C1 [Venkatesan, Aradhana M.; Locklin, Julia; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Ctr Intervent Oncol, Bethesda, MD 20892 USA. [Lai, Edwin W.; Adams, Karen T.; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Bethesda, MD USA. [Fojo, Antonio Tito] NCI, Expt Therapeut Sect, Med Oncol Branch, Bethesda, MD 20892 USA. RP Venkatesan, AM (reprint author), NIH, Dept Radiol & Imaging Sci, Ctr Clin, Ctr Intervent Oncol, 10 Ctr Dr,Bldg 10,Room 1C369,MSC 1182, Bethesda, MD 20892 USA. EM venkatesana@cc.nih.gov FU National Institutes of Health; NIH Center for Interventional Oncology FX This work was supported in part by the Intramural Research Program of the National Institutes of Health and the NIH Center for Interventional Oncology. None of the authors have identified a conflict of interest. NR 22 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2009 VL 20 IS 11 BP 1483 EP 1490 DI 10.1016/j.jvir.2009.07.031 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 513YB UT WOS:000271359000012 PM 19875067 ER PT J AU Starost, MF AF Starost, Matthew F. TI Adenomyofibroma of the fimbria in a cynomolgus monkey (Macaca fascicularis) SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article DE Adenomyofibroma; cynomolgus monkey; Macaca fascicularis; neoplasm; uterine tube ID UTERINE TUBE; OVIDUCT; LESIONS; SYSTEM; TUMORS; BITCH; DOG AB A 20-year-old female cynomolgus monkey (Macaca fascicularis) was presented for an end-of-study necropsy. At necropsy, a 2 cm x 1.5 cm x 1 cm, butterfly-shaped, multilobulated mass extended off the right uterine tube fimbria. Microscopically, the mass was composed of large, plump, Finger-like projections lined primarily by simple columnar ciliated epithelium. The interstitium contained a proliferation of smooth muscle stromal cells admixed with varying amounts of collagen. A diagnosis of adenomyofibroma of the fimbria was made. This benign neoplasm should be considered as a differential diagnosis for masses arising from the fallopian tube in old-world macaques. C1 NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP Starost, MF (reprint author), NIH, Div Vet Resources, Bldg 28A,Room 106,9000 Rockville Pike, Bethesda, MD 20892 USA. EM starostm@mail.nih.gov FU National Institutes of Health, Office of Research Services FX The author would like to thank Jorge Chavez, Annie Merriweather, and Patricia Zerfas for technical assistance. This work was supported by the Intramural Research Programs of the National Institutes of Health, Office of Research Services. NR 14 TC 1 Z9 2 U1 0 U2 1 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD NOV PY 2009 VL 21 IS 6 BP 892 EP 894 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA 519SU UT WOS:000271789100024 PM 19901298 ER PT J AU Wu, XL Zhou, TQ O'Dell, S Wyatt, RT Kwong, PD Mascola, JR AF Wu, Xueling Zhou, Tongqing O'Dell, Sijy Wyatt, Richard T. Kwong, Peter D. Mascola, John R. TI Mechanism of Human Immunodeficiency Virus Type 1 Resistance to Monoclonal Antibody b12 That Effectively Targets the Site of CD4 Attachment SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; N-LINKED GLYCAN; NEUTRALIZING ANTIBODY; HIV-1 GP120; BINDING-SITE; CD4-BINDING SITE; FAB FRAGMENTS; ENV CLONES; SUBTYPE-B; IN-VITRO AB The region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 that engages its primary cellular receptor CD4 forms a site of vulnerability to neutralizing antibodies. The monoclonal antibody b12 exploits the conservation and accessibility of the CD4-binding site to neutralize many, though not all, HIV-1 isolates. To understand the basis of viral resistance to b12, we used the atomic-level definition of b12-gp120 contact sites to study a panel of diverse circulating viruses. A combination of sequence analysis, computational modeling, and site-directed mutagenesis was used to determine the influence of amino acid variants on binding and neutralization by b12. We found that several substitutions within the dominant b12 contact surface, called the CD4-binding loop, mediated b12 resistance, and that these substitutions resided just proximal to the known CD4 contact surface. Hence, viruses varied in key b12 contact residues that are proximal to, but not part of, the CD4 contact surface. This explained how viral isolates were able to evade b12 neutralization while maintaining functional binding to CD4. In addition, some viruses were resistant to b12 despite minimal sequence variation at b12 contact sites. Such neutralization resistance usually could be reversed by alterations at residues thought to influence the quaternary configuration of the viral envelope spike. To design immunogens that elicit neutralizing antibodies directed to the CD4-binding site, researchers need to address the antigenic variation within this region of gp120 and the restricted access to the CD4-binding site imposed by the native configuration of the trimeric viral envelope spike. C1 [Wu, Xueling; Zhou, Tongqing; O'Dell, Sijy; Wyatt, Richard T.; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM jmascola@nih.gov RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU Intramural Research Program of the Vaccine Research Center, NIAID, NIH FX We thank Gary Nabel for helpful advice, Diane Wycuff for technical support and helpful discussions, and the Structural Biology Section personnel for helpful comments. We thank Dennis Burton, Marshall Posner, James Robinson, and Dimiter Dimitrov for gp120- reactive antibodies and the NIH AIDS Research and Reference Reagent Program for sCD4. NR 62 TC 71 Z9 73 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2009 VL 83 IS 21 BP 10892 EP 10907 DI 10.1128/JVI.01142-09 PG 16 WC Virology SC Virology GA 504FW UT WOS:000270602300005 PM 19692465 ER PT J AU Fornek, JL Gillim-Ross, L Santos, C Carter, V Ward, JM Cheng, LI Proll, S Katze, MG Subbarao, K AF Fornek, Jamie L. Gillim-Ross, Laura Santos, Celia Carter, Victoria Ward, Jerrold M. Cheng, Lily I. Proll, Sean Katze, Michael G. Subbarao, Kanta TI A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice SO JOURNAL OF VIROLOGY LA English DT Article ID HONG-KONG; HIGH VIRULENCE; A VIRUSES; MOUSE MODEL; PATHOGENESIS; HUMANS; HOST; PATHOGENICITY; REPLICATION; PB1 AB The transmission of H5N1 influenza viruses from birds to humans poses a significant public health threat. A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant. We utilized the BALB/c mouse model of H5N1 infection to examine how this substitution affects virus-host interactions and leads to systemic infection. Mice infected with H5N1 viruses containing lysine at amino acid 627 in the PB2 protein exhibited an increased severity of lesions in the lung parenchyma and the spleen, increased apoptosis in the lungs, and a decrease in oxygen saturation. Gene expression profiling revealed that T-cell receptor activation was impaired at 2 days postinfection (dpi) in the lungs of mice infected with these viruses. The inflammatory response was highly activated in the lungs of mice infected with these viruses and was sustained at 4 dpi. In the spleen, immune-related processes including NK cell cytotoxicity and antigen presentation were highly activated by 2 dpi. These differences are not attributable solely to differences in viral replication in the lungs but to an inefficient immune response early in infection as well. The timing and magnitude of the immune response to highly pathogenic influenza viruses is critical in determining the outcome of infection. The disruption of these factors by a single-amino-acid substitution in a polymerase protein of an influenza virus is associated with severe disease and correlates with the spread of the virus to extrapulmonary sites. C1 [Fornek, Jamie L.; Carter, Victoria; Proll, Sean; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Gillim-Ross, Laura; Santos, Celia; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Ward, Jerrold M.; Cheng, Lily I.] NIAID, Comparat Med Branch, NIH, Rockville, MD 20852 USA. RP Katze, MG (reprint author), Univ Washington, Dept Microbiol, Box 358070, Seattle, WA 98195 USA. EM honey@u.washington.edu FU NIAID, NIH; NIH [AI058113-01]; [CA09229-28] FX We thank Lawrence J. Faucette and Elizabeth M. Williams for excellent histotechnology assistance, Jadon Jackson for assistance with the studies of mice, and Olivia Perwitasari, Kara Jensen, and Thomas Teal for help with the gene expression studies. NR 30 TC 50 Z9 53 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 NOV PY 2009 VL 83 IS 21 BP 11102 EP 11115 DI 10.1128/JVI.00994-09 PG 14 WC Virology SC Virology GA 504FW UT WOS:000270602300023 PM 19692471 ER PT J AU Pike, R Filby, A Ploquin, MJY Urszula, E Marques, R Antunes, I Hasenkrug, K Kassiotis, G AF Pike, Rebecca Filby, Andrew Ploquin, Mickael J. -Y. Urszula, Eksmond Marques, Rute Antunes, Ines Hasenkrug, Kim Kassiotis, George TI Race between Retroviral Spread and CD4(+) T-Cell Response Determines the Outcome of Acute Friend Virus Infection SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; PERSISTENT VIRAL-INFECTION; CD4-DEFICIENT MICE; MEDIATED PROTECTION; IMMUNE-RESPONSES; TUMOR REJECTION; GAMMA RECEPTOR; HIV-INFECTION; BONE-MARROW; IFN-GAMMA AB Retroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. We examine here the contribution of virus-specific CD4(+) T cells in resistance against Friend virus (FV) infection in the murine host. We show that the magnitude and duration of the FV-specific CD4(+) T-cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4(+) T cells in the absence of a virus-specific CD8(+) T-cell or B-cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or coinfection with Lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4(+) T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4(+) T-cell response. Conversely, an increased frequency or continuous supply of FV-specific CD4(+) T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection. Thus, these results suggest that FV-specific CD4(+) T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4(+) T cells. C1 [Pike, Rebecca; Filby, Andrew; Ploquin, Mickael J. -Y.; Urszula, Eksmond; Marques, Rute; Antunes, Ines; Kassiotis, George] Natl Inst Med Res, MRC, The Ridgeway, Div Immunoregulat, London NW7 1AA, England. [Hasenkrug, Kim] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kassiotis, G (reprint author), Natl Inst Med Res, MRC, The Ridgeway, Div Immunoregulat, Mill Hill, London NW7 1AA, England. EM gkassio@nimr.mrc.ac.uk FU UK Medical Research Council; National Institute of Allergy and Infectious Diseases Division of Intramural Research; National Institutes of Health FX This study was supported by the UK Medical Research Council and the National Institute of Allergy and Infectious Diseases Division of Intramural Research, National Institutes of Health. NR 62 TC 26 Z9 26 U1 0 U2 0 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 PY 2009 VL 83 IS 21 BP 11211 EP 11222 DI 10.1128/JVI.01225-09 PG 12 WC Virology SC Virology GA 504FW UT WOS:000270602300034 PM 19692462 ER PT J AU Tribouillard-Tanvier, D Striebel, JF Peterson, KE Chesebro, B AF Tribouillard-Tanvier, Deborah Striebel, James F. Peterson, Karin E. Chesebro, Bruce TI Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; ALZHEIMERS-DISEASE; MICROGLIAL ACTIVATION; IN-VITRO; POSTTRANSCRIPTIONAL REGULATION; SPONGIFORM ENCEPHALOPATHIES; CHEMOKINE RECEPTORS; MULTIPLE-SCLEROSIS AB Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage initiated by other processes. In the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected C57BL/10 mouse brains, we observed elevation of CCL2, CCL5, CXCL1, CXCL10, granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma interferon (IFN-gamma), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-6, and IL-12p40. Scrapie agent-infected wild-type mice and transgenic mice expressing anchorless prion protein (PrP) had similar cytokine responses in spite of extensive differences in neuropathology. Therefore, these responses may be primarily a reaction to brain damage induced by prion infection rather than specific inducers of a particular type of pathology. To study the roles of astroglia and microglia in these cytokine responses, primary glial cultures were exposed to scrapie agent-infected brain homogenates. Microglia produced only IL-12p40 and CXCL10, whereas astroglia produced these cytokines plus CCL2, CCL3, CCL5, CXCL1, G-CSF, IL-1 beta, IL-6, IL-12p70, and IL-13. Glial cytokine responses from wild-type mice and transgenic mice expressing anchorless PrP differed only slightly, but glia from PrP-null mice produced only IL-12p40, indicating that PrP expression was required for scrapie agent induction of other cytokines detected. The difference in cytokine response between microglia and astroglia correlated with 20-fold-higher levels of PrP expression in astroglia versus microglia, suggesting that high-level PrP expression on astroglia might be important for induction of certain cytokines. C1 [Tribouillard-Tanvier, Deborah; Striebel, James F.; Peterson, Karin E.; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM bchesebro@nih.gov RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 FU NIAID Division of Intramural Research at NIH FX This work was supported by the NIAID Division of Intramural Research at NIH. NR 69 TC 31 Z9 31 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2009 VL 83 IS 21 BP 11244 EP 11253 DI 10.1128/JVI.01413-09 PG 10 WC Virology SC Virology GA 504FW UT WOS:000270602300037 PM 19710140 ER PT J AU Gray, ES Madiga, MC Moore, PL Mlisana, K Karim, SSA Binley, JM Shaw, GM Mascola, JR Morris, L AF Gray, Elin S. Madiga, Maphuti C. Moore, Penny L. Mlisana, Koleka Karim, Salim S. Abdool Binley, James M. Shaw, George M. Mascola, John R. Morris, Lynn TI Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; HIV TYPE-1; GLYCOPROTEIN GP41; INFECTION; 2F5; EPITOPE; RESPONSES; 4E10; ECTODOMAIN; VARIANTS AB We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies. Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases, respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design. C1 [Gray, Elin S.; Madiga, Maphuti C.; Moore, Penny L.; Morris, Lynn] Natl Inst Communicable Dis, AIDS Virus Res Unit, ZA-2131 Johannesburg, South Africa. [Mlisana, Koleka; Karim, Salim S. Abdool] Univ KwaZulu Natal, CAPRISA, Durban, South Africa. [Binley, James M.] Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. [Shaw, George M.] Univ Alabama, Birmingham, AL 35294 USA. [Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Morris, L (reprint author), Natl Inst Communicable Dis, AIDS Virus Res Unit, Private Bag X4, ZA-2131 Johannesburg, South Africa. EM lynnm@nicd.ac.za RI Abdool Karim, Salim Safurdeen/N-5947-2013; OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Moore, Penny/0000-0001-8719-4028; , Lynn/0000-0003-3961-7828; Mlisana, Koleka/0000-0002-8436-3268; Gray, Elin/0000-0002-8613-3570 FU South African Vaccine Initiative (SAAVI); Bill and Melinda Gates CAVD-VIMC [38619]; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) [AI51794]; National Research Foundation; Fogarty International Center, NIH [D43TW00231]; LifeLab FX This work was funded by the South African Vaccine Initiative (SAAVI) and Bill and Melinda Gates CAVD-VIMC grant number 38619. CAPRISA is supported by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) (grant no. AI51794); the National Research Foundation (grant no. 67385); the Columbia University-Southern African Fogarty AIDS International Training and Research Programme (AITRP) funded by the Fogarty International Center, NIH (grant no. D43TW00231); and a training grant from LifeLab, a biotechnology center of the South African Government Department of Science and Technology. NR 38 TC 66 Z9 67 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2009 VL 83 IS 21 BP 11265 EP 11274 DI 10.1128/JVI.01359-09 PG 10 WC Virology SC Virology GA 504FW UT WOS:000270602300039 PM 19692477 ER PT J AU Nelson, W Moser, RP Gaffey, A Waldron, W AF Nelson, Wendy Moser, Richard P. Gaffey, Allison Waldron, William TI Adherence to Cervical Cancer Screening Guidelines for US Women Aged 25-64: Data from the 2005 Health Information National Trends Survey (HINTS) SO JOURNAL OF WOMENS HEALTH LA English DT Review ID PAP SMEAR HISTORIES; INTERVIEW SURVEY; UNITED-STATES; SELF-REPORTS; CIGARETTE-SMOKING; HISPANIC WOMEN; RISK-FACTORS; UNREALISTIC OPTIMISM; ALCOHOL-CONSUMPTION; COLORECTAL-CANCER AB Background: Although it is widely accepted that Papanicolaou (Pap) screening can reduce cervical cancer mortality, many women still do not maintain regular cervical cancer screenings. Objective: To describe the prevalence of cervical cancer screening and the demographic, behavioral, psychological, and cancer-related knowledge factors associated with adherence to U. S. Preventive Services Task Force (USPSTF) cervical cancer screening guidelines among women in the United States. Methods: Data for women aged 25-64 were obtained from the National Cancer Institute's (NCI) 2005 Health Information National Trends Survey (HINTS). Women were considered adherent to screening guidelines if they had two consecutive, on-schedule screenings and planned to have another within the next 3 years. The sample comprised 2070 women. Results: Ninety-eight percent of women reported ever having a Pap smear, 90% reported having had a recent Pap smear (within 3 years), and 84% were adherent to USPSTF screening guidelines. Maintaining regular cervical cancer screening was significantly associated with having health insurance, normal body mass index (BMI), smoking status (nonsmoker), mood (absence of a mood disturbance), and being knowledgeable about cervical cancer screening and human papillomavirus (HPV) infection. Conclusions: Based on the observation that women who were current smokers, obese, or experiencing a substantial degree of psychological distress were significantly less likely to adhere to recommended screening guidelines, we suggest that healthcare providers pay particular attention to the screening needs of these more vulnerable women. C1 [Nelson, Wendy] NCI, Basic & Biobehav Res Program, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Gaffey, Allison] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Waldron, William] Informat Management Serv Inc, Silver Spring, MD USA. RP Nelson, W (reprint author), NCI, Basic & Biobehav Res Program, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. EM nelsonw@mail.nih.gov NR 104 TC 48 Z9 53 U1 4 U2 8 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 NOV PY 2009 VL 18 IS 11 BP 1759 EP 1768 DI 10.1089/jwh.2009.1430 PG 10 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 525XH UT WOS:000272250500005 PM 19951209 ER PT J AU Danforth, KN Schairer, C Schatzkin, A Lacey, JV AF Danforth, Kim N. Schairer, Catherine Schatzkin, Arthur Lacey, James V., Jr. TI Bone Fractures and Incident Epithelial Ovarian Cancer in a Prospective Cohort Study SO JOURNAL OF WOMENS HEALTH LA English DT Article ID POSTMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; ELDERLY-WOMEN; OSTEOPOROTIC FRACTURES; VERTEBRAL FRACTURES; REPLACEMENT THERAPY; STEROID-HORMONES; MINERAL DENSITY; SAMPLE-SIZE; RISK AB Objective: Osteoporosis and osteoporotic fractures are hypothesized to reflect circulating hormone levels in older women and have been inversely associated with breast and endometrial cancers. However, associations between fractures and ovarian cancer, another hormonal cancer, have not been examined. Therefore, we conducted a prospective study among women in the Breast Cancer Detection Demonstration Project Follow-up Study. Methods: Fractures after age 45 were assessed using two questionnaires from 1987 to 1995. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models, adjusting for potential confounders. Fracture location was used to further evaluate the fractures most likely to be osteoporotic. Results: Among 36,115 women with up to 11 years of follow-up (average follow-up was 8.3 years), there were 151 cases of incident ovarian cancer. Fractures were reported by 19% (n=6,919) of women. Ovarian cancer risk was not associated with any (RR = 1.13, 95% CI 0.74-1.71) or likely osteoporotic (RR = 1.05, 95% CI 0.65-1.69) fractures. Among never users of postmenopausal hormones, the association between any fracture and ovarian cancer (RR = 1.21, 95% CI 0.55-2.65, n = 50 cases) also was statistically nonsignificant. Conclusions: Data from this large, prospective study do not support an association between fractures and ovarian cancer risk. C1 [Danforth, Kim N.; Schairer, Catherine; Schatzkin, Arthur; Lacey, James V., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Danforth, KN (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,Suite 550,MSC 7234, Rockville, MD 20852 USA. EM danfortk@mail.nih.gov FU National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the National Cancer Institute, NIH. K.N.D. was supported in part by the Sallie Rosen Kaplan Fellowship for Women Scientists in Cancer Research, National Cancer Institute, NIH. NR 29 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2009 VL 18 IS 11 BP 1777 EP 1782 DI 10.1089/jwh.2008.1341 PG 6 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 525XH UT WOS:000272250500007 PM 19951211 ER PT J AU D'Souza, T Sherman-Baust, CA Poosala, S Mullin, JM Morin, PJ AF D'Souza, Theresa Sherman-Baust, Cheryl A. Poosala, Suresh Mullin, James M. Morin, Patrice J. TI Age-Related Changes of Claudin Expression in Mouse Liver, Kidney, and Pancreas SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Claudin; Aging; Tight junction; Immunohistochemistry ID JUNCTION BARRIER FUNCTION; OVARIAN-CANCER CELLS; TIGHT JUNCTIONS; PROTEINS; MICE; PERMEABILITY; PHOSPHORYLATION; EPIDIDYMIS; OCCLUDIN; PATHWAY AB Tight junctions (TJs) play crucial roles in tissue homeostasis and inflammation through their roles in the control of paracellular transport and barrier function. There is evidence that these functions are compromised in older organisms, but the exact mechanisms leading to TJ deterioration are not well understood. Claudin proteins are a family of membrane proteins that constitute the structural barrier elements of TJs and therefore play a major role in their formation and function. Using immunohistochemistry and immunoblotting, we have Studied the expression of six different claudin proteins (claudin-1, -2, -3, -4, -5, and -7) in three tissues (liver, kidney, and pancreas) of aging male and female mice. In general, we find an age-dependent decrease in the expression of several claudin proteins in all three tissues observed, although the exact changes are tissue specific. Our findings provide a possible basis for the decrease in tissue barrier function in older organisms. C1 [Morin, Patrice J.] NIA, Cellular & Mol Biol Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Poosala, Suresh] NIA, Res Resource Branch, Baltimore, MD 21224 USA. [Mullin, James M.] Lankenau Inst Med Res, Wynnewood, PA USA. [Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100,Room 6C228, Baltimore, MD 21224 USA. EM morinp@mail.nih.gov OI Mullin, James/0000-0001-5285-7530 FU National Institutes of Health, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 41 TC 12 Z9 12 U1 1 U2 4 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 NOV PY 2009 VL 64 IS 11 BP 1146 EP 1153 DI 10.1093/gerona/glp118 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509UU UT WOS:000271044900006 PM 19692671 ER PT J AU Newman, AB Ferrucci, L AF Newman, Anne B. Ferrucci, Luigi TI Call for Papers: Aging Versus Disease SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material C1 [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Div Geriatr Med, Pittsburgh, PA 15260 USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Sch Med, Pittsburgh, PA 15260 USA. [Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Dept Epidemiol, Div Geriatr Med, Pittsburgh, PA 15260 USA. EM newmana@edc.pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 9 TC 7 Z9 7 U1 0 U2 1 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 NOV PY 2009 VL 64 IS 11 BP 1163 EP 1164 DI 10.1093/gerona/glp039 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509UU UT WOS:000271044900008 PM 19359442 ER PT J AU Guralnik, JM Ferrucci, L AF Guralnik, Jack M. Ferrucci, Luigi TI The Challenge of Understanding the Disablement Process in Older Persons SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID DISABILITY; ADULTS; ICF C1 [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM jack.guralnik@nih.gov FU Intramural NIH HHS NR 16 TC 14 Z9 14 U1 1 U2 7 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 NOV PY 2009 VL 64 IS 11 BP 1169 EP 1171 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509UU UT WOS:000271044900010 PM 19628636 ER PT J AU Thomas, K Rafiq, S Frayling, TM Ebrahim, S Kumari, M Gallacher, J Ferrucci, L Bandinelli, S Wallace, RB Melzer, D Martin, RM Ben-Shlomo, Y AF Thomas, Kate Rafiq, Sajjad Frayling, Timothy M. Ebrahim, Shah Kumari, Meena Gallacher, John Ferrucci, Luigi Bandinelli, Stefania Wallace, Robert B. Melzer, David Martin, Richard M. Ben-Shlomo, Yoav TI Interleukin-18 Polymorphism and Physical Functioning in Older People: A Replication Study and Meta-Analysis SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Interleukin-18 polymorphism; IL-18; Ageing; Physical function; Gait speed; Walk time ID EPIDEMIOLOGY; DISEASE AB Background. Levels of the proinflammatory cytokine interleukin-18 (IL-18) are raised in old age and are associated with reduced physical functioning. Previous studies have indicated that the C allele of the rs5744256 polymorphism in the IL-18 gene is strongly associated with reduced circulating IL-18 levels. This variant has previously been associated with improved locomotor performance in old age, but the finding requires independent replication. Methods. We examined the association between the IL-18 polymorphism rs5744256 and physical functioning in three cohorts with a total of 4,107 participants aged 60-85 years: the English Longitudinal Study of Ageing, Caerphilly, and Boyd Orr. We meta-analyzed (N = 6,141) the results with data from the original paper reporting this association: lowa-Established Populations for Epidemiological Study of the Elderly and InCHIANTI cohorts. Physical functioning was assessed by timed walks or the get up and go test. As locomotor performance tests differed between the cohorts and the distributions of times to complete the test (in seconds) were positively skewed, we used the reciprocal transformation and computed study-specific z scores. Results. Based on the three new studies, the estimated linear regression coefficient per C allele was 0.011 (95% confidence interval [95% CI]: -0.04 to 0.06). A meta-analysis that pooled the data from all Studies showed weak evidence of an effect, with it regression coefficient of 0.047 (95% Cl: 0.010 to 0.083). Conclusions. We did not replicate an association between the IL-18 rs5744256 polymorphism and the physical function in people aged 60-85 years. However, pooling data from all studies suggested a weak association of the C allele of the rs5744256 single nucleotide polymorphism on improving walking times in old age. C1 [Thomas, Kate; Martin, Richard M.; Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, Bristol BS8 2PS, Avon, England. [Rafiq, Sajjad; Frayling, Timothy M.; Melzer, David] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England. [Ebrahim, Shah] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London, England. [Kumari, Meena] UCL, Dept Epidemiol & Publ Hlth, London, England. [Gallacher, John] Cardiff Univ, Sch Med, Ctr Hlth Sci Res, Dept Publ Hlth & Primary Care, Cardiff, S Glam, Wales. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Gerontol Res Ctr, Baltimore, MD 21224 USA. [Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy. [Wallace, Robert B.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. [Martin, Richard M.; Ben-Shlomo, Yoav] Univ Bristol, Dept Social Med, MRC, Ctr Causal Anal Translat Epidemiol, Bristol BS8 1TH, Avon, England. RP Thomas, K (reprint author), Univ Bristol, Dept Social Med, Carynge Hall,39 Whatley Rd, Bristol BS8 2PS, Avon, England. EM kate.thomas@bristol.ac.uk OI Rafiq, Sajjad/0000-0003-4873-4540; Kumari, Meena/0000-0001-9716-1035; Melzer, David/0000-0002-0170-3838 FU Alzheimer's Society; Medical Research Council; World Cancer Research Fund; Research into Ageing; United Kingdom Survivors; Economic and Social Research Council; Wellcome Trust [GR068468MA]; British Heart Foundation; Wellcome Research Training Fellowship in Clinical Epidemiology [GR063779FR]; National Institutes of Aging [R01AG1764406S1]; Italian Ministry of Health [ICS 110.1\RS97.71] FX K.T. was a recipient of a Research into Ageing PhD studentship (reference: 302). CaPS was undertaken by the former MRC Epidemiology Unit (South Wales), and the Department of Social Medicine, University of Bristol, acts as the data custodian. Phase V of CaPS was funded by a grant from the Alzheimer's Society. The Boyd Orr cohort has received funding from the Medical Research Council, the World Cancer Research Fund, Research into Ageing, United Kingdom Survivors, the Economic and Social Research Council, the Wellcome Trust, and the British Heart Foundation. The Boyd Orr DNA bank was established with a grant from the Wellcome Trust (GR068468MA) and the follow-up clinics in 2002 were funded within a Wellcome Research Training Fellowship in Clinical Epidemiology to R.M.M. (GR063779FR). The funding for English Longitudinal Study of Ageing (ELSA) is provided by the National Institute of Aging in the United States, and a consortium of UK government departments coordinated by the Office for National Statistics. The ELSA DNA Repository was established with a grant from the National Institutes of Aging (R01AG1764406S1). The developers and funders of ELSA do not bear any responsibility for the analyses or interpretations presented here. The InCHIANTI study was supported as a "targeted project" (ICS 110.1\RS97.71) by the Italian Ministry of Health. NR 19 TC 2 Z9 2 U1 1 U2 1 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 NOV PY 2009 VL 64 IS 11 BP 1177 EP 1182 DI 10.1093/gerona/glp092 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509UU UT WOS:000271044900013 PM 19633236 ER PT J AU Schaap, LA Pluijm, SMF Deeg, DJH Harris, TB Kritchevsky, SB Newman, AB Colbert, LH Pahor, M Rubin, SM Tylavsky, FA Visser, M AF Schaap, Laura A. Pluijm, Saskia M. F. Deeg, Dorly J. H. Harris, Tamara B. Kritchevsky, Stephen B. Newman, Anne B. Colbert, Lisa H. Pahor, Marco Rubin, Susan M. Tylavsky, Frances A. Visser, Marjolein CA Hlth ABC Study TI Higher Inflammatory Marker Levels in Older Persons: Associations With 5-Year Change in Muscle Mass and Muscle Strength SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Muscle; Inflammatory markers; Aging; Weight ID TUMOR-NECROSIS-FACTOR; C-REACTIVE PROTEIN; FACTOR-ALPHA; SKELETAL-MUSCLE; HEART-FAILURE; PHYSICAL PERFORMANCE; BODY-COMPOSITION; SERUM LEVELS; WEIGHT-LOSS; HEALTH ABC AB Background. There is growing evidence that higher levels of inflammatory markets are associated with physical decline in older persons, possibly through the catabolic effects of inflammatory markers on muscle. The aim of this study was to investigate the association between serum levels of inflammatory markers and loss of muscle mass and strength in older persons. Methods. Using data on 2,177 men and women in the Health, Aging, and Body Composition Study, we examined 5-year change in thigh muscle area estimated by computed tomography and grip and knee extensor strength in relation to serum levels of interleukin-6 (IL-6), C-reactive protein, tumor necrosis factor-alpha (TNF-alpha), and soluble receptors (measured in a subsample) at baseline, Results. Higher levels of inflammatory markers were generally associated with greater 5-year decline in thigh muscle area. Most associations, with the exception of soluble receptors, were attenuated by adjustment for 5-year change in weight. Higher TNF-alpha and interleukin-6 Soluble receptor levels remained associated with greater decline in grip strength in men. Analyses in a subgroup of weight-stable persons showed that higher levels of TNF-alpha and its soluble receptors were associated with 5-year decline in thigh muscle area and that higher levels of TNF-alpha were associated with decline in grip strength. Conclusions. TNF-alpha and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia. C1 [Schaap, Laura A.; Deeg, Dorly J. H.; Visser, Marjolein] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, NL-1081 BT Amsterdam, Netherlands. [Pluijm, Saskia M. F.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Kritchevsky, Stephen B.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Colbert, Lisa H.] Univ Wisconsin, Dept Kinesiol, Madison, WI 53706 USA. [Pahor, Marco] Univ Florida, Inst Aging, Dept Aging & Geriatr Res, Gainesville, FL USA. [Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Tylavsky, Frances A.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. [Visser, Marjolein] Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Hlth Sci, Amsterdam, Netherlands. RP Schaap, LA (reprint author), Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM l.schaap@vumc.nl RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institutes of Health FX The Health, Aging, and Body Composition Study Was Supported by National Institute on Aging contract,; N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. NR 35 TC 178 Z9 183 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2009 VL 64 IS 11 BP 1183 EP 1189 DI 10.1093/gerona/glp097 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 509UU UT WOS:000271044900014 PM 19622801 ER PT J AU Cornwell, B Schumm, LP Laumann, EO Graber, J AF Cornwell, Benjamin Schumm, L. Philip Laumann, Edward O. Graber, Jessica TI Social Networks in the NSHAP Study: Rationale, Measurement, and Preliminary Findings SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article DE Aging; Health; Medical decision making; Social integration; Social networks ID NAME GENERATOR; PERSONAL NETWORKS; OLDER-ADULTS; LATER LIFE; SUPPORT; COMMUNITY; HEALTH; TIES; DETERMINANTS; EXPLORATION AB Objectives. This paper describes the rationale behind the National Social Life. Health, and Aging Project's (NSHAP) social networks module, data collection procedures. and the measurement of several egocentric network properties. This includes a discussion of network size, composition, volume of contact with network members, density, and bridging potential. Data on the extent to which older adults involve network members in personal health matters are also discussed. Methods. Descriptive statistics are presented for key network measures. Sociodemographic distributions of these measures are presented. Older adults' likelihood of discussing health with network members is also broken down by network member characteristics. Results. Older adults tended to have large, kin-centered, dense networks, with sonic bridging potential. Network characteristics were related to age, gender, race/ethnicity, education, and health. Older adults tended to be very likely to involve network members (especially close ties) in health discussions and medical decision making. Discussion. The data reiterate the relevance of social networks to older adults' health. We close by discussing how the NSHAP measures might be employed in future analyses of health. C1 [Cornwell, Benjamin] Cornell Univ, Dept Sociol, Ithaca, NY 14853 USA. [Schumm, L. Philip] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Laumann, Edward O.] Univ Chicago, Dept Sociol, Chicago, IL 60637 USA. [Graber, Jessica] NICHHD, Bethesda, MD 20892 USA. RP Cornwell, B (reprint author), Cornell Univ, Dept Sociol, 354 Uris Hall, Ithaca, NY 14853 USA. EM btc49@cornell.edu FU National Institutes of Health; National Institute on Aging; Office of Women's Health Research; Office of AIDS Research; Office of Behavioral and Social Sciences Research [5R01AG021487] FX The National Social Life, Health, and Aging Project is Supported by the National Institutes of Health, including the National Institute on Aging, the Office of Women's Health Research, the Office of AIDS Research, and the Office of Behavioral and Social Sciences Research (5R01AG021487). NR 51 TC 37 Z9 38 U1 6 U2 20 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 EI 1758-5368 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2009 VL 64 SU 1 BP I47 EP I55 DI 10.1093/geronb/gbp042 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 518TZ UT WOS:000271718300006 PM 19502574 ER PT J AU Suzman, R AF Suzman, Richard TI The National Social Life, Health, and Aging Project: An Introduction SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Editorial Material ID OLDER-ADULTS; UNITED-STATES; PREVALENCE; RISK C1 [Suzman, Richard] NIA, NIH, Bethesda, MD 20892 USA. RP Suzman, R (reprint author), Gateway Bldg,533,7201 Wisconsin Ave, Bethesda, MD 20814 USA. EM suzmanr@nia.nih.gov FU NIA NIH HHS [5R01AG021487] NR 15 TC 31 Z9 31 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2009 VL 64 SU 1 BP I5 EP I11 DI 10.1093/geronb/gbp078 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 518TZ UT WOS:000271718300001 PM 19837963 ER PT J AU Johansen, KL Zhang, R Huang, YJ Chen, SC Blagg, CR Goldfarb-Rumyantzev, AS Hoy, CD Lockridge, RS Miller, BW Eggers, PW Kutner, NG AF Johansen, Kirsten L. Zhang, Rebecca Huang, Yijian Chen, Shu-Cheng Blagg, Christopher R. Goldfarb-Rumyantzev, Alexander S. Hoy, Chistopher D. Lockridge, Robert S., Jr. Miller, Brent W. Eggers, Paul W. Kutner, Nancy G. TI Survival and hospitalization among patients using nocturnal and short daily compared to conventional hemodialysis: a USRDS study SO KIDNEY INTERNATIONAL LA English DT Article DE daily hemodialysis; hospitalization; survival; USRDS ID LEFT-VENTRICULAR HYPERTROPHY; QUALITY-OF-LIFE; IN-CENTER HEMODIALYSIS; VASCULAR ACCESS; HOME HEMODIALYSIS; DAILY DIALYSIS; LONG-TERM; COST; MORTALITY; TRIAL AB We estimated the survival and hospitalization among frequent hemodialysis users in comparison to those patients undergoing thrice-weekly conventional hemodialysis. All patients had similar characteristics and medical histories. In this cohort study of frequent hemodialysis users and propensity score-matched controls, the collaborating clinicians identified 94 patients who used nocturnal hermodialysis (NHD) and 43 patients who used short-duration daily hemodialysis (SDHD) for a minimum of 60 days. Ten propensity score-matched control patients for each NHD and SDHD patient were identified from the United States Renal Data System database. Primary outcomes were risk for all-cause mortality and risk for the composite outcome of mortality or major morbid event (acute myocardial infarction or stroke) estimated using Cox proportional hazards models. Risks for all-cause, cardiovascular-related, infection-related, and vascular access-related hospital admissions were also studied. Nocturnal hemodialysis was associated with significant reductions in mortality risk and risk for mortality or major morbid event when compared to conventional hemodialysis. There was a reduced but non-significant risk of death for patients using SDHD compared to controls. All-cause and specific hospitalizations did not differ significantly between NHD and SDHD patients and their matched control cohorts. Our study suggests that NHD may improve patient survival. Kidney International (2009) 76, 984-990; doi:10.1038/ki.2009.291; published online 19 August 2009 C1 [Kutner, Nancy G.] Emory Univ, Dept Rehabil Med, USRDS Rehabil QoL Special Studies Ctr, Atlanta, GA 30322 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Chen, Shu-Cheng] USRDS Coordinating Ctr, Minneapolis, MN USA. [Blagg, Christopher R.] NW Kidney Ctr, Seattle, WA USA. [Goldfarb-Rumyantzev, Alexander S.] Harvard Univ, Sch Med, Boston, MA USA. [Hoy, Chistopher D.] Rubin Dialysis Ctr, Saratoga Springs, NY USA. [Lockridge, Robert S., Jr.] Lynchburg Nephrol Dialysis, Lynchburg, VA USA. [Miller, Brent W.] Washington Univ, Sch Med, St Louis, MO USA. [Eggers, Paul W.] NIDDK, NIH, Bethesda, MD USA. RP Kutner, NG (reprint author), Emory Univ, Dept Rehabil Med, USRDS Rehabil QoL Special Studies Ctr, 1441 Clifton Rd NE, Atlanta, GA 30322 USA. EM nkutner@emory.edu FU National Institutes of Health [N01-DK-1-2471, HHSN267200715004C] FX This study was supported by the National Institutes of Health contracts N01-DK-1-2471 and HHSN267200715004C, ADB No. N01-DK-7-5004. The interpretation and reporting of the data presented here are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the United States government. An abstract was presented in poster form at the annual meeting of the American Society of Nephrology; 3 November 2007, San Francisco, CA, USA. NR 37 TC 101 Z9 101 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2009 VL 76 IS 9 BP 984 EP 990 DI 10.1038/ki.2009.291 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 507LC UT WOS:000270853800011 PM 19692997 ER PT J AU Amdur, RL Chawla, LS Amodeo, S Kimmel, PL Palant, CE AF Amdur, Richard L. Chawla, Lakhmir S. Amodeo, Susan Kimmel, Paul L. Palant, Carlos E. TI Outcomes following diagnosis of acute renal failure in US veterans: focus on acute tubular necrosis SO KIDNEY INTERNATIONAL LA English DT Article DE acute kidney injury; acute renal failure; acute tubular necrosis; chronic kidney disease; survival analysis ID ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; GLOMERULAR-FILTRATION-RATE; SERUM CREATININE; MYOCARDIAL-INFARCTION; HOSPITALIZED-PATIENTS; MORTALITY; EPIDEMIOLOGY; RECOVERY; DISEASE AB When patients develop acute kidney injury, a small fraction of them will develop end-stage renal disease later. The severity of renal impairment in the remaining patients is uncertain because studies have not carefully examined renal function over time or the precise timing of entry into a late stage of chronic kidney disease. To determine these factors, we used a United States Department of Veterans Affairs database to ascertain long-term renal function in 113,272 patients. Of these, 44,377 had established chronic kidney disease and were analyzed separately. A cohort of 63,491 patients was hospitalized for acute myocardial infarction or pneumonia and designated as controls. The remaining 5,404 patients had diagnostic codes indicating acute renal failure or acute tubular necrosis. Serum creatinine, estimated glomerular filtration rates, and dates of death over a 75-month period were followed. Renal function deteriorated over time in all groups, but with significantly greater severity in those who had acute renal failure and acute tubular necrosis compared to controls. Patients with acute kidney injury, especially those with acute tubular necrosis, were more likely than controls to enter stage 4 chronic kidney disease, but this entry time was similar to that of patients who initially had chronic kidney disease. The risk of death was elevated in those with acute kidney injury and chronic kidney disease compared to controls after accounting for covariates. We found that patients who had an episode of acute tubular necrosis were at high risk for the development of stage 4 disease and had a reduced survival time when compared to control patients. Kidney International (2009) 76, 1089-1097; doi: 10.1038/ki.2009.332; published online 9 September 2009 C1 [Chawla, Lakhmir S.; Kimmel, Paul L.; Palant, Carlos E.] George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. [Amdur, Richard L.; Amodeo, Susan; Palant, Carlos E.] Vet Affairs Med Ctr, Res & Med Serv, Washington, DC 20422 USA. [Amdur, Richard L.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Chawla, Lakhmir S.] George Washington Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Washington, DC 20037 USA. [Amodeo, Susan] Vet Affairs Med Ctr, Fiscal Serv, Washington, DC 20422 USA. [Kimmel, Paul L.] NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD USA. RP Chawla, LS (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 900 23rd St NW,Room G-105, Washington, DC 20037 USA. EM lchawla@mfa.gwu.edu FU Satellite Research: Norman S Coplon Extramural Research Grant FX The authors express their gratitude to Dr Paul Eggers (National Institutes of Health-NIDDK), to Mr David Lyle and Dr George J Busch (Clinical User Support, Veterans Health Administration Decision Support System), and to Mr Robert Williamson (Information Resource Management, Washington DC VA Medical Center) for their valuable assistance with data collection. Dr Chawla's effort is in part supported by Satellite Research: Norman S Coplon Extramural Research Grant. NR 40 TC 142 Z9 147 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2009 VL 76 IS 10 BP 1089 EP 1097 DI 10.1038/ki.2009.332 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 514GS UT WOS:000271383000011 PM 19741590 ER PT J AU Brown, P Gipson, C AF Brown, Patricia Gipson, Chester TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. [Gipson, Chester] USDA, APHIS, AC, Washington, DC USA. RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD NOV PY 2009 VL 38 IS 11 BP 347 EP 347 DI 10.1038/laban1109-347 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 517KL UT WOS:000271612200010 PM 19847176 ER PT J AU Ment, LR Hirtz, D Huppi, PS AF Ment, Laura R. Hirtz, Deborah Hueppi, Petra S. TI Imaging biomarkers of outcome in the developing preterm brain SO LANCET NEUROLOGY LA English DT Review ID LOW-BIRTH-WEIGHT; CEREBRAL WHITE-MATTER; TERM-EQUIVALENT AGE; VOXEL-BASED MORPHOMETRY; DIFFUSION TENSOR MRI; OLIGODENDROCYTE LINEAGE MATURATION; STATE FUNCTIONAL CONNECTIVITY; PREMATURELY BORN CHILDREN; NEURODEVELOPMENTAL OUTCOMES; INFANTS BORN AB The neurodevelopmental disabilities of those who were born prematurely have been well described, yet the underlying alterations in brain development that lead to these changes remain poorly understood. Processes that are vulnerable to injury in the developing brain include maturation of oligodendrocyte precursors and genetically programmed changes in cortical connectivity; recent data have indicated that diffuse injury of the white matter accompanied by neuronal and axonal disruption is common in prematurely born infants. Recent advances in MRI include diffusion tensor imaging and sophisticated image analysis tools, such as functional connectivity, voxel-based morphometry, and mathematical morphology-based cortical folding strategies. These advanced techniques have shown that white matter structure is dependent on gestational age and have started to provide important information about the dynamic interactions between development, injury, and functional recovery in the preterm brain. Identification of early biomarkers for outcome could enable physicians and scientists to develop targeted pharmacological and behavioural therapies to restore functional connectivity. C1 [Ment, Laura R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Ment, Laura R.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06520 USA. [Hirtz, Deborah] Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Hueppi, Petra S.] Univ Hosp Geneva, Childrens Hosp, Dept Pediat, Geneva, Switzerland. RP Ment, LR (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St, New Haven, CT 06520 USA. EM laura.ment@yale.edu RI Huppi, Petra/A-4079-2009 OI Huppi, Petra/0000-0002-7383-6648 FU National Institute of Neurological Disorders and Stroke, National Institutes of Health [NS 27116, NS 53865]; Swiss National Science Foundation SNF [32-102127, 32-113632]; Leenards Foundation; European Union FX This work was supported by grants NS 27116 and NS 53865 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health (LAM), the Swiss National Science Foundation SNF 32-102127; 32-113632 (PSH), the Leenards Foundation, and the European Union 6th Framework Programme NEOBRAIN (PSH). The authors are grateful to Cheryl Lacadie, Karol H Katz, and Jill Maller-Kesselman for technical, computer, and editorial support and to the children and families who participated in the studies we describe. NR 132 TC 181 Z9 184 U1 1 U2 13 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 NOV PY 2009 VL 8 IS 11 BP 1042 EP 1055 DI 10.1016/S1474-4422(09)70257-1 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 513GC UT WOS:000271309600016 PM 19800293 ER PT J AU Katki, HA Wacholder, S Solomon, D Castle, PE Schiffman, M AF Katki, Hormuzd A. Wacholder, Sholom Solomon, Diane Castle, Philip E. Schiffman, Mark TI Risk estimation for the next generation of prevention programmes for cervical cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID 2006 CONSENSUS GUIDELINES; HUMAN-PAPILLOMAVIRUS; INTRAEPITHELIAL NEOPLASIA; MANAGEMENT; WOMEN C1 [Katki, Hormuzd A.; Wacholder, Sholom; Castle, Philip E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Solomon, Diane] NCI, Canc Prevent Div, Bethesda, MD 20852 USA. RP Katki, HA (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. EM katkih@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 FU Intramural NIH HHS [ZIA CP010181-08, Z01 CP010181-05] NR 11 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2009 VL 10 IS 11 BP 1022 EP 1023 DI 10.1016/S1470-2045(09)70253-0 PG 2 WC Oncology SC Oncology GA 520NT UT WOS:000271852800002 PM 19767237 ER PT J AU Farag, SS Zhang, SH Jansak, BS Wang, XJ Kraut, E Chan, K Dancey, JE Grever, MR AF Farag, Sherif S. Zhang, Shuhong Jansak, Buffy S. Wang, Xiaojing Kraut, Eric Chan, Kenneth Dancey, Janet E. Grever, Michael R. TI Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma SO LEUKEMIA RESEARCH LA English DT Article DE Multiple myeloma; mTOR; Temsirolimus; Pharmacokinetics ID RECURRENT GLIOBLASTOMA-MULTIFORME; MTOR INHIBITOR; CCI-779; CANCER; CELLS; RAPAMYCIN; PHARMACOKINETICS; DEXAMETHASONE; CHEMOTHERAPY; THALIDOMIDE AB In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25 mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3-4 toxicity included fatigue (n = 3), neutropenia (n = 2), thrombocytopenia (n = 2), interstitial pneumonitis(n = 1), stomatitis (n = 1) and diarrhea (n = 1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70(S6)K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. investigation of alternate dosing schedules and use in combinations is indicated. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Farag, Sherif S.] Indiana Univ Sch Med, Div Hematol & Oncol, Dept Internal Med, Indianapolis, IN 46202 USA. [Farag, Sherif S.; Zhang, Shuhong; Wang, Xiaojing] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Jansak, Buffy S.; Kraut, Eric; Grever, Michael R.] Ohio State Univ, Dept Internal Med, Div Hematol & Oncol, Columbus, OH 43210 USA. [Chan, Kenneth] Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. [Dancey, Janet E.] NCI, Bethesda, MD 20892 USA. RP Farag, SS (reprint author), Indiana Univ Sch Med, Div Hematol & Oncol, Dept Internal Med, 635 Barnhill Dr,Room 224G, Indianapolis, IN 46202 USA. EM ssfarag@iupui.edu FU National Cancer Institute of the United States [R21 CA11289, UO1 CA76576] FX This work was supported by the following grants from the National Cancer Institute of the United States: R21 CA11289 (SSF) and UO1 CA76576 (MRG). NR 33 TC 44 Z9 45 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 NOV PY 2009 VL 33 IS 11 BP 1475 EP 1480 DI 10.1016/j.leukres.2009.01.039 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 495DM UT WOS:000269870400010 PM 19261329 ER PT J AU Shami, PJ Maciag, AE Eddington, JK Udupi, V Kosak, KM Saavedra, JE Keefer, LK AF Shami, Paul J. Maciag, Anna E. Eddington, Jordan K. Udupi, Vidya Kosak, Ken M. Saavedra, Joseph E. Keefer, Larry K. TI JS-K, an arylating nitric oxide (NO) donor, has synergistic anti-leukemic activity with cytarabine (ARA-C) SO LEUKEMIA RESEARCH LA English DT Article DE Acute myeloid leukemia; Nitric oxide; JS-K; Cytarabine; Synergy ID DNA-DAMAGE; IN-VITRO; LEUKEMIA-CELLS; VIVO; DIFFERENTIATION; INHIBITION; MODULATION; ACTIVATION; RESISTANCE; APOPTOSIS AB We have designed prodrugs; that release nitric oxide (NO) on metabolism by glutathione S-transferases (GST). This design exploits the upregulation of GST in acute myeloid leukemia (AML) cells. O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K, a member of this class) has potent anti-leukemic activity. HL-60 myeloid leukemia cells were used for in vitro studies of the combination of JS-K with daunorubicin (DAUNO), cytarabine (ARA-C) or etoposide (ETOP) using the median effect method to determine synergistic, antagonistic, or additive effects. Combinations of JS-K added simultaneously, 2 h before or 2 h after the other compounds were used. JS-K and DAUNO were antagonistic in all three drug sequences. JS-K and ETOP were also antagonistic but to a lesser degree. JS-K and ARA-C showed strong synergy. The combination index at the 50% fraction affected was 0.37 +/- 0.23, 0.24 +/- 0.27, and 0.15 +/- 0.11 for simultaneous,JS-K first and ARA-C first additions, respectively. JS-K by itself induced DNA strand breaks at relatively high concentrations. However, at submicromolar concentrations, it significantly augmented ARA-C-induced DNA strand breaks. NMR spectroscopy revealed no evidence of chemical interaction between JS-K and the other chemotherapeutic agents. We conclude that ARA-C and JS-K have synergistic anti-leukemic activity and warrant further exploration in combination. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Shami, Paul J.; Eddington, Jordan K.; Udupi, Vidya; Kosak, Ken M.] Univ Utah, Salt Lake City, UT USA. [Maciag, Anna E.; Saavedra, Joseph E.] SAIC Frederick Inc, Frederick, MD USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Shami, PJ (reprint author), Huntsman Canc Inst, Suite 2100,2000 Circle Hope, Salt Lake City, UT 84112 USA. EM paul.shami@utah.edu RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Leukemia and Lymphoma Society; NIH [R01 CA84496, R01 CA129611]; National Cancer Institute [N01-CO-12400]; Intramural Research Program of the NIH; National Cancer Institute, Center for Cancer Research FX Contributions. Paul J. Shami designed research, analyzed and interpreted data, and wrote manuscript. Anna E. Maciag performed research, reviewed and edited manuscript. Jordan K. Eddington performed research. Vidya Udupi performed research. Ken M. Kosak performed research. Joseph E. Saavedra designed, synthesized and provided JS-K, performed research, reviewed and edited manuscript. Larry K. Keefer designed JS-K, reviewed and edited manuscript. NR 20 TC 12 Z9 13 U1 0 U2 1 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 NOV PY 2009 VL 33 IS 11 BP 1525 EP 1529 DI 10.1016/j.leukres.2009.01.002 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 495DM UT WOS:000269870400018 PM 19193435 ER PT J AU Hosgood, HD Cawthon, R He, XZ Chanock, S Lan, Q AF Hosgood, H. Dean, III Cawthon, Richard He, Xingzhou Chanock, Stephen Lan, Qing TI Genetic variation in telomere maintenance genes, telomere length, and lung cancer susceptibility SO LUNG CANCER LA English DT Article DE POT1; TERT; TERF2; Lung cancer; Telomore length; Risk ID INDOOR AIR-POLLUTION; XUAN-WEI; EXPRESSION; CHINA; RISK; MARKERS; EPIDEMIOLOGY; DYSFUNCTION; SUGGEST; PROTEIN AB Telomeres are responsible for the protection of the chromosome ends and shortened telomere length has been associated with risk of multiple cancers. Genetic variation in telomere-related genes may alter cancer risk associated with telomere length. Using lung cancer cases (n=120) and population-based controls (n = 110) from Xuanwei, China, we analyzed telomere length separately and in conjunction with single nucleotide polymorphisms in the telomere maintenance genes POT1, TERT, and TERF2, which we have previously reported were associated with risk of lung cancer in this study. POT1 rs10244817, TERT rs2075786, and TERF2 rs251796 were significantly associated with lung cancer (P(trend)<= 0.05). The shortest tertile of telomere length was not significantly associated with risk of lung cancer (OR = 1.58; 95% CI = 0.79-3.18) when compared to the longest tertile of telomere length. When stratified by genotype, there was a suggestion of a dose-response relationship between tertiles of telomere length and risk of lung cancer among the POT1 rs10244817 common variant carriers (OR (95%CI) = 1.33 (0.47-3.75), 3.30 (1.14-9.56), respectively) but not among variant genotype carriers (p(interaction) = 0.05). Our findings provide evidence that telomere length and genetic variation in telomere maintenance genes may be associated with risk of lung cancer susceptibility and warrant replication in larger studies. Published by Elsevier Ireland Ltd. C1 [Hosgood, H. Dean, III] NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Cawthon, Richard] Univ Utah, Eccles Inst Human Genet, Salt Lake City, UT USA. [He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. [Chanock, Stephen] NCI, Ctr Canc Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hosgood, HD (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8118,MCS 7240, Bethesda, MD 20892 USA. EM hosgoodd@mail.nih.gov FU Intramural National Cancer Institute [N01-CO-12400] FX This project was funded in by the Intramural National Cancer Institute (N01-CO-12400) program. NR 38 TC 34 Z9 35 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD NOV PY 2009 VL 66 IS 2 BP 157 EP 161 DI 10.1016/j.lungcan.2009.02.005 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 527ME UT WOS:000272370400003 PM 19285750 ER PT J AU Berger, JR Houff, SA Major, EO AF Berger, Joseph R. Houff, Sidney A. Major, Eugene O. TI Monoclonal antibodies and progressive multifocal leukoencephalopathy SO MABS LA English DT Article DE progressive multifocal leukoencephalopathy; JC virus; natalizumab; efalizumab; rituximab; alemtuzumab; multiple sclerosis; crohn disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTIPLE-SCLEROSIS PATIENTS; IMMUNE-DEFICIENCY SYNDROME; CYTOTOXIC T-LYMPHOCYTES; JC VIRUS; B-CELLS; HUMAN POLYOMAVIRUS; PLAQUE PSORIASIS; BONE-MARROW; LYMPHOPROLIFERATIVE DISORDERS AB Since their introduction, monoclonal antibodies have found an ever expanding role in the treatment of a wide number of disorders. However, the perturbation of the immune system that attends their use may also increase the risk for the development of disorders that arise in the setting of immunosuppressive conditions, such as, opportunistic infection and malignancy. In this paper, we address the association between some monoclonal antibodies and the development of a rare demyelinating disease of the brain, progressive multifocal leukoencephalopathy (PML). PML results from infection with a ubiquitous polyoma virus, JC virus, and typically occurs in the setting of impaired immunity, most commonly, AIDS. It was first recognized as a potential complication of monoclonal antibody therapy in patients with multiple sclerosis and Crohn disease being treated with natalizumab, an alpha 4 beta 1 and alpha 4 beta 7 integrin inhibitor. Subsequently, efalizumab, a monoclonal antibody used in the treatment of psoriasis, was also demonstrated to be associated with PML. An increased risk has been suggested for rituximab, although most of the patients developing PML with that monoclonal antibody have been treated for B-cell disorders that predispose to the development of PML. Based on our Current understanding of the biology of JC virus and the pathogenesis of PML, we propose an explanation for the increased risk for PML that is observed with natalizumab and certain other monoclonal antibodies. C1 [Berger, Joseph R.; Houff, Sidney A.] Univ Kentucky, Dept Neurol, Coll Med, Lexington, KY 40536 USA. [Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. RP Berger, JR (reprint author), Univ Kentucky, Dept Neurol, Coll Med, Lexington, KY 40536 USA. EM jrbneuro@uky.edu NR 84 TC 40 Z9 42 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1942-0862 EI 1942-0870 J9 MABS-AUSTIN JI mAbs PD NOV-DEC PY 2009 VL 1 IS 6 BP 583 EP 589 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 564OG UT WOS:000275224000009 PM 20073129 ER PT J AU Lin, PC Reiter, DA Spencer, RG AF Lin, Ping-Chang Reiter, David A. Spencer, Richard G. TI Sensitivity and Specificity of Univariate MRI Analysis of Experimentally Degraded Cartilage SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cartilage; degradation; sensitivity; specificity; osteoarthritis ID ARTICULAR-CARTILAGE; MAGNETIZATION-TRANSFER; CLUSTERING-ALGORITHM; COLLAGEN; DESIGN; T-2; PROTEOGLYCAN; DEGRADATION; DISEASE AB MRI is increasingly used to evaluate cartilage in tissue constructs, explants, and animal and patient studies. However, while mean values of MR parameters, including T(1), T(2), magnetization transfer rate k(m), apparent diffusion coefficient (ADC), and the dGEMRIC-derived fixed charge density, correlate with tissue status, the ability to classify tissue according to these parameters has not been explored. Therefore, the sensitivity and specificity with which each of these parameters was able to distinguish between normal and trypsin-degraded, and between normal and collagenase-degraded, cartilage explants were determined. Initial analysis was performed using a training set to determine simple group means to which parameters obtained from a validation set were compared. T(1) and apparent diffusion coefficient showed the greatest ability to discriminate between normal and degraded cartilage. Further analysis with k-means clustering, which eliminates the need for a priori identification of sample status, generally performed comparably. Use of fuzzy c-means (FCM) clustering to define centroids like-wise did not result in improvement in discrimination. Finally, an FCM clustering approach in which validation samples were assigned in a probabilistic fashion to control and degraded groups was implemented, reflecting the range of tissue characteristics seen with cartilage degradation. Magn Reson Med 62:1311-1318, 2009. (C) 2009 Wiley-Liss, Inc. C1 [Lin, Ping-Chang; Reiter, David A.; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, Magnet Resonance Imaging & Spect Sect, NIH, GRC 4D-06, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov OI Lin, Ping-Chang/0000-0003-0918-4072 FU 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. NR 22 TC 22 Z9 22 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2009 VL 62 IS 5 BP 1311 EP 1318 DI 10.1002/mrm.22110 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 514XX UT WOS:000271431200026 PM 19705467 ER PT J AU Lee, JH Shahram, M Pauly, JM AF Lee, Jongho Shahram, Morteza Pauly, John M. TI Combining Complex Signal Change in Functional MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Letter ID HIGH-RESOLUTION FMRI; SSFP C1 [Lee, Jongho] Natl Inst Neurol Disorders & Stroke, Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. [Shahram, Morteza] Stanford Univ, Dept Stat, Stanford, CA 94305 USA. [Pauly, John M.] Stanford Univ, Magnet Resonance Syst Res Lab, Dept Elect Engn, Stanford, CA 94305 USA. RP Lee, JH (reprint author), 9000 Rockville Pike,Bldg 10,Room B1D723A, Bethesda, MD 20892 USA. EM jonghoyi@mail.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2009 VL 62 IS 5 BP 1358 EP 1360 DI 10.1002/mrm.22104 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 514XX UT WOS:000271431200034 ER PT J AU Wright, ME Solo-Gabriele, HM Elmir, S Fleming, LE AF Wright, Mary E. Solo-Gabriele, Helena M. Elmir, Samir Fleming, Lora E. TI Microbial load from animal feces at a recreational beach SO MARINE POLLUTION BULLETIN LA English DT Article DE Enterococci; Animal feces; Enumeration; Recreational water; Bacteria indicators; Non-point pollution sources ID FECAL-COLIFORM BACTERIA; WATER-QUALITY; INDICATOR BACTERIA; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; MICROBIOLOGICAL QUALITY; LARUS-DELAWARENSIS; BATHING WATERS; GULL DROPPINGS; WHITE IBIS AB The goal of this study was to quantify the microbial load (enterococci) contributed by the different animals that frequent a beach site. The highest enterococci concentrations were observed in dog feces with average levels of 3.9 x 10(7) CFU/g; the next highest enterococci levels were observed in birds averaging 3.3 x 10(5) CFU/g. The lowest measured levels of enterococci were observed in material collected from shrimp fecal mounds (2.0 CFU/g). A comparison of the microbial loads showed that 1 dog fecal event was equivalent to 6940 bird fecal events or 3.2 x 10(8) shrimp fecal mounds. Comparing animal contributions to previously published numbers for human bather shedding indicates that one adult human swimmer contributes approximately the same microbial load as one bird fecal event. Given the abundance of animals observed on the beach, this study suggests that dogs are the largest contributing animal source of enterococci to the beach site. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Wright, Mary E.; Solo-Gabriele, Helena M.; Elmir, Samir; Fleming, Lora E.] Univ Miami, Oceans & Human Hlth Ctr, NIEHS, Rosenstiel Sch Marine & Atmospher Sci,NSF, Miami, FL 33136 USA. [Wright, Mary E.; Solo-Gabriele, Helena M.; Elmir, Samir] Univ Miami, Dept Civil Architectural & Environm Engn, Coral Gables, FL 33124 USA. [Elmir, Samir] Miami Dade Cty Hlth Dept, Miami, FL 33056 USA. [Fleming, Lora E.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Fleming, Lora E.] Marine Biol & Fisheries Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA. RP Solo-Gabriele, HM (reprint author), Univ Miami, Dept Civil Architectural & Environm Engn, POB 248294, Coral Gables, FL 33124 USA. FU NSF-NIEHS [NSF OCE0432368/0911373, NIEHS P50 ES12736-01]; NSF-REU [OCE 0432368] FX This work was funded by NSF-NIEHS Oceans and Human Health Program (NSF OCE0432368/0911373 and NIEHS P50 ES12736-01) and the NSF-REU Program (OCE 0432368). We would like to thank all the students, scientists and professionals, including the individuals from the bird rehabilitation center, Miami Metro Zoo, and Miami Seaquarium who participated in the logistics and sample collection for this project. Environmental Specialists, Gary Miller and Sudhir Oberoi, from the Miami-Dade County Health Department assisted considerably. We thank John D. Wang for insightful comments on the manuscript and we would like to thank Amir Abdelzaher, Cristina Ortega, Colleen Block, Kelly Jackson, Eduardo Lam, Karina Vega, Jonathan Fernandes, Adrianne Vargas, and Freddy Nava for assistance with data collection. NR 52 TC 55 Z9 55 U1 2 U2 28 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0025-326X EI 1879-3363 J9 MAR POLLUT BULL JI Mar. Pollut. Bull. PD NOV PY 2009 VL 58 IS 11 BP 1649 EP 1656 DI 10.1016/j.marpolbul.2009.07.003 PG 8 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 520MB UT WOS:000271847500019 PM 19664785 ER PT J AU Freed, M Miller, S Tang, K Badano, A AF Freed, Melanie Miller, Stuart Tang, Katherine Badano, Aldo TI Experimental validation of Monte Carlo (MANTIS) simulated x-ray response of columnar CsI scintillator screens SO MEDICAL PHYSICS LA English DT Article DE Cesium Iodide; Monte Carlo simulation; experimental validation; scintillator blur ID IMAGING PERFORMANCE; BREAST TOMOSYNTHESIS; MEGAVOLTAGE CT; FLAT-PANEL; DETECTOR; RADIOGRAPHY; EFFICIENCY; IMAGER AB Purpose: MANTIS is a Monte Carlo code developed for the detailed simulation of columnar CsI scintillator screens in x-ray imaging systems. Validation of this code is needed to provide a reliable and valuable tool for system optimization and accurate reconstructions for a variety of x-ray applications. Whereas previous validation efforts have focused on matching of summary statistics, in this work the authors examine the complete point response function (PRF) of the detector system in addition to relative light output values. Methods: Relative light output values and high-resolution PRFs have been experimentally measured with a custom setup. A corresponding set of simulated light output values and PRFs have also been produced, where detailed knowledge of the experimental setup and CsI:Tl screen structures are accounted for in the simulations. Four different screens were investigated with different thicknesses, column tilt angles, and substrate types. A quantitative comparison between the experimental and simulated PRFs was performed for four different incidence angles (0 degrees, 15 degrees, 30 degrees, and 45 degrees) and two different x-ray spectra (40 and 70 kVp). The figure of merit (FOM) used measures the normalized differences between the simulated and experimental data averaged over a region of interest. Results: Experimental relative light output values ranged from 1.456 to 1.650 and were in approximate agreement for aluminum substrates, but poor agreement for graphite substrates. The FOMs for all screen types, incidence angles, and energies ranged from 0.1929 to 0.4775. To put these FOMs in context, the same FOM was computed for 2D symmetric Gaussians fit to the same experimental data. These FOMs ranged from 0.2068 to 0.8029. Our analysis demonstrates that MANTIS reproduces experimental PRFs with higher accuracy than a symmetric 2D Gaussian fit to the experimental data in the majority of cases. Examination of the spatial distribution of differences between the PRFs shows that the main reason for errors between MANTIS and the experimental data is that MANTIS-generated PRFs are sharper than the experimental PRFs. Conclusions: The experimental validation of MANTIS performed in this study demonstrates that MANTIS is able to reliably predict experimental PRFs, especially for thinner screens, and can reproduce the highly asymmetric shape seen in the experimental data. As a result, optimizations and reconstructions carried out using MANTIS should yield results indicative of actual detector performance. Better characterization of screen properties is necessary to reconcile the simulated light output values with experimental data. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3233683] C1 [Freed, Melanie; Tang, Katherine; Badano, Aldo] US FDA, CDRH NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, College Pk, MD 20742 USA. [Miller, Stuart] RMD Inc, Watertown, MA 02472 USA. RP Freed, M (reprint author), US FDA, CDRH NIBIB Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU intramural program at NIBIB; FDA's Office of Women Health; Research Participation Program at the Center for Devices and Radiological Health FX The authors thank Eugene O'Bryan for invaluable help with the high voltage power supply triggering, Ilko Ilev, Erik Gorman, and Boris Vassilev for help in taking the digital optical microscopy images, Glenn Link for help with the electronic components, Mary Walker for help with the x-ray tube and polaroid camera, Bob Jennings for discussions of film and x-ray beam measurements, Annie Saha for initial experimental measurements, Kyle J. Myers and Brandon D. Gallas (CDRH, FDA) for support and discussions, Frank Samuelson (CDRH, FDA) for providing PERL scripts that allow parallel execution of MANTIS, Samta Thacker (RMD Inc.) for useful discussions regarding the details about the microscopic structures in CsI columnar screens, and the anonymous reviewers for their comments. The authors also acknowledge funding from the intramural program at NIBIB and from FDA's Office of Women Health. This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 25 TC 15 Z9 15 U1 0 U2 2 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 NOV PY 2009 VL 36 IS 11 BP 4944 EP 4956 DI 10.1118/1.3233683 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 512BR UT WOS:000271217900013 PM 19994503 ER PT J AU Geller, SE Shulman, LP van Breemen, RB Banuvar, S Zhou, Y Epstein, G Hedayat, S Nikolic, D Krause, EC Piersen, CE Bolton, JL Pauli, GF Farnsworth, NR AF Geller, Stacie E. Shulman, Lee P. van Breemen, Richard B. Banuvar, Suzanne Zhou, Ying Epstein, Geena Hedayat, Samad Nikolic, Dejan Krause, Elizabeth C. Piersen, Colleen E. Bolton, Judy L. Pauli, Guido F. Farnsworth, Norman R. TI Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Botanicals; Hot flashes ID ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL HORMONE-THERAPY; CONTROLLED CLINICAL-TRIAL; DIETARY-SUPPLEMENTS; CIMICIFUGA-RACEMOSA; MENOPAUSAL SYMPTOMS; HOT FLASHES; CLIMACTERIC SYMPTOMS; DOUBLE-BLIND; COGNITIVE FUNCTION AB Objective: The aim of this study was to evaluate the safety and efficacy of black cohosh and red clover compared with placebo for the relief of menopausal vasomotor symptoms. Methods: This study was a randomized, four-ann, double-blind clinical trial of standardized black cohosh, red clover, placebo, and 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA; n = 89). Primary outcome measures were reduction in vasomotor symptoms (hot flashes and night sweats) by black cohosh and red clover compared with placebo; secondary outcomes included safety evaluation, reduction of somatic symptoms, relief of sexual dysfunction, and overall improvement in quality of life. Results: Reductions in number of vasomotor symptoms after a 12-month intervention were as follows: black cohosh (34%), red clover (57%), placebo (63%), and CEE/MPA (94%), with only CEE/MPA differing significantly from placebo. Black cohosh and red clover did not significantly reduce the frequency of vasomotor symptoms as compared with placebo. Secondary measures indicated that both botanicals were safe as administered. In general, there were no improvements in other menopausal symptoms. Conclusions: Compared with placebo, black cohosh and red clover did not reduce the number of vasomotor symptoms. Safety monitoring indicated that chemically and biologically standardized extracts of black cohosh and red clover were safe during daily administration for 12 months. C1 [Geller, Stacie E.] Univ Illinois, Dept Obstet & Gynecol, Ctr Res Women & Gender, Coll Med, Chicago, IL 60612 USA. [Shulman, Lee P.; Banuvar, Suzanne; Epstein, Geena] Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA. [van Breemen, Richard B.; Nikolic, Dejan; Krause, Elizabeth C.; Piersen, Colleen E.; Bolton, Judy L.; Pauli, Guido F.; Farnsworth, Norman R.] Univ Illinois, NIH, Ctr Bot Dietary Supplements Res, Coll Pharm, Chicago, IL 60612 USA. [Zhou, Ying; Hedayat, Samad] Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60612 USA. RP Geller, SE (reprint author), Univ Illinois, Dept Obstet & Gynecol, Ctr Res Women & Gender, Coll Med, 820 S Wood St,M-C 808, Chicago, IL 60612 USA. EM sgeller@uic.edu OI Pauli, Guido/0000-0003-1022-4326 FU National Institutes of Health [P50 AT000155]; Office of Dietary Supplements; National Center for Complementary and Alternative Medicine; National Institute for General Medical Sciences; Office for Research on Women's Health FX This study by the University of Illinois at Chicago/National Institutes of Health Center for Botanical Dietary Supplements Research was supported by National Institutes of Health Grant P50 AT000155 funded jointly by the Office of Dietary Supplements, the National Center for Complementary and Alternative Medicine, the National Institute for General Medical Sciences, and the Office for Research on Women's Health. NR 65 TC 83 Z9 87 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2009 VL 16 IS 6 BP 1156 EP 1166 DI 10.1097/gme.0b013e3181ace49b PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 518ZB UT WOS:000271733700016 PM 19609225 ER PT J AU Levin, HL AF Levin, Henry L. TI Transposon Technology - Introduction SO METHODS LA English DT Editorial Material C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. EM henry_levin@nih.gov NR 3 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 2009 VL 49 IS 3 BP 217 EP 218 DI 10.1016/j.ymeth.2009.09.004 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518NA UT WOS:000271698200001 PM 19835786 ER PT J AU Park, JM Evertts, AG Levin, HL AF Park, Jung M. Evertts, Adam G. Levin, Henry L. TI The Hermes transposon of Musca domestica and its use as a mutagen of Schizosaccharomyces pombe SO METHODS LA English DT Review DE Transposon; Hermes; Mutagenesis; Schizosaccharomyces pombe ID INTEGRATION; YEAST; TOOL AB Transposon mutagenesis allows for the discovery and characterization of genes by creating mutations that can be easily mapped and sequenced. Moreover, this method allows for a relatively unbiased approach to isolating genes of interest. Recently, a system of transposon based mutagenesis for Schizosaccharomyces pombe became available. This mutagenesis relies on Hermes, a DNA transposon from the house fly that readily integrates into the chromosomes of S. pombe. The Hermes system is distinct from the retrotransposons of S. pombe because it efficiently integrates into open reading frames. To mutagenize S. pombe, cells are transformed with a plasmid that contains a drug resistance marker flanked by the terminal inverted repeats of Hermes. The Hermes transposase expressed from a second plasmid excises the resistance marker with the inverted repeats and inserts this DNA into chromosomal sites. After S. pombe with these two plasmids grow 25 generations, approximately 2% of the cells contain insertions. Of the cells with insertions, 68% contain single integration events. The protocols listed here provide the detailed information necessary to mutagenize a strain of interest, screen for specific phenotypes, and sequence the positions of insertion. Published by Elsevier Inc. C1 [Park, Jung M.; Evertts, Adam G.; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bldg 18T Ctr Dr,Room 106,MSC 5431, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This research was supported by the Intramural Research Program of the NIH from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 11 TC 9 Z9 9 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 2009 VL 49 IS 3 BP 243 EP 247 DI 10.1016/j.ymeth.2009.05.004 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 518NA UT WOS:000271698200005 PM 19450689 ER PT J AU Claborn, DM Rowton, ED Lawyer, PG Brown, GC Keep, LW AF Claborn, David M. Rowton, Edgar D. Lawyer, Phillip G. Brown, Grayson C. Keep, Lisa W. TI Species Diversity and Relative Abundance of Phlebotomine Sand Flies (Diptera: Psychodidae) on Three Army Installations in the Southern United States and Susceptibility of a Domestic Sand Fly to Infection With Old World Leishmania major SO MILITARY MEDICINE LA English DT Article ID US MILITARY OPERATIONS; TALLIL-AIR-BASE; CUTANEOUS LEISHMANIASIS; TRANSMISSION; IMPACT; TEXAS; IRAQ AB Leishmania infections in American veterans of Iraq and Afghanistan have raised concern that veterans could serve as reservoirs of Old World parasites for domestic vector populations. A survey of sand flies on three U.S. Army facilities in the southern United States was conducted to identify potential vectors. Five species, including two new state records, are reported for Fort Hood, TX. Very few flies were detected in Fort Bragg, NC. Large numbers of a man-biting species, Lutzomyia shannoni, were trapped on Fort Campbell, KY. Weekly activity patterns for dominant species are presented. In addition, an infection experiment was conducted to determine if a domestic sand fly is susceptible to infection with Old World Leishmania major. Lt. shannoni became infected and supported Le. major up to 6 days postprandial. Metacyclogenesis and actual transmission of Le. major to an uninfected mouse did not occur because infected flies did not take subsequent blood meals. C1 [Claborn, David M.] Missouri State Univ, Dept Nursing, Springfield, MO 65897 USA. [Rowton, Edgar D.] Walter Reed Army Inst Hlth, Dept Entomol, Silver Spring, MD 20910 USA. [Lawyer, Phillip G.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Brown, Grayson C.] Univ Kentucky, Dept Entomol, Lexington, KY 40546 USA. [Keep, Lisa W.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20851 USA. RP Claborn, DM (reprint author), Missouri State Univ, Dept Nursing, 901 S Natl Ave, Springfield, MO 65897 USA. RI Rowton, Edgar/A-1975-2011 OI Rowton, Edgar/0000-0002-1979-1485 FU Uniformed Services University of Health Sciences, School of Medicine [RO87WB] FX The authors thank Brian Kovacik, Logan Minter, Jeffrey Clark, Heather Ferguson, and Juan Mendez for their invaluable assistance during this study. This research was funded by internal grant number RO87WB from the Uniformed Services University of Health Sciences, School of Medicine. NR 17 TC 4 Z9 4 U1 0 U2 3 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD NOV PY 2009 VL 174 IS 11 BP 1203 EP 1208 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 601LL UT WOS:000278060900014 PM 19960830 ER PT J AU Jiang, LB Duriseti, S Sun, P Miller, LH AF Jiang, Lubin Duriseti, Sai Sun, Peter Miller, Louis H. TI Molecular basis of binding of the Plasmodium falciparum receptor BAEBL to erythrocyte receptor glycophorin C SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Mutations; BAEBL; Glycophorin C; Sialic acid; Erythrocyte receptors ID SIALIC-ACID; BLOOD-GROUP; NEW-GUINEA; LIGAND; POLYMORPHISM; INVASION; MALARIA; VIVAX; SPECIFICITY; PARASITES AB Plasmodium falciparum invades human erythrocytes by redundant pathways. Unlike Plasmodium vivax that has one Duffy Binding-Like (DBL) receptor, P. falciparum has four members of the DBL receptor family. Furthermore, one of these DBL genes, BAEBL, has polymorphisms at four amino acids in region 11; each polymorphism binds to a different erythrocyte receptor. One BAEBL variant (VSTK) binds specifically to erythrocyte glycophorin C and binds poorly to neuraminidase-treated erythrocytes. When the amino acid threonine (T121) in BAEBL (VSTK) is changed to a lysine (VSKK), it no longer requires sialic acid as a receptor. To explore the molecular basis of sialic acid binding, we modeled the structure of region 11 of BAEBL (VSTK) on the crystal structure of a related DBL receptor, region 11 of erythrocyte binding antigen-175 (EBA-175). Four charged amino acids, R52, R114, E54 and D125, are predicted to surround T121 in BAEBL (VSTK). They were individually mutated to alanine (R52A, R114A, E54A, and D125A) or lysine (R52K, R114K) and expressed on the surface of Chinese hamster ovary (CHO-K1) cells. BAEBL (VSTK) with mutations in R52 or R114 of BAEBL (VSTK) bound neuraminidase-treated erythrocytes. Unlike the arginine mutations, E54A and D125A still bound poorly to neuraminidase-treated erythrocytes. These findings suggest that the two arginine residues surrounding T121 are critical for the binding specificity of BAEBL (VSTK) to sialic acid and suggest a role for arginine in sialic acid binding independent of its negative charge. Published by Elsevier B.V. C1 [Jiang, Lubin; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Duriseti, Sai; Sun, Peter] NIAID, Struct Immunol Sect, NIH, Rockville, MD 20852 USA. RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Twinbrook 3,Room 3E-32, Bethesda, MD 20892 USA. EM lomiller@mail.nih.gov FU NIH, NIAID FX We thank Dr. Susan Pierce for reviewing paper, Dr. Michael Fay for statistic analysis of data, Dr. Jianbing Mu for sequencing of some plasmids. This research was supported by the Intramural Research Program of the NIH, NIAID. NR 22 TC 18 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV PY 2009 VL 168 IS 1 BP 49 EP 54 DI 10.1016/j.molbiopara.2009.06.006 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 496ZN UT WOS:000270019800007 PM 19563830 ER PT J AU Yedjou, CG Tchounwou, PB AF Yedjou, Clement G. Tchounwou, Paul B. TI Modulation of p53, c-fos, RARE, cyclin A, and cyclin D1 expression in human leukemia (HL-60) cells exposed to arsenic trioxide SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE As(2)O(3); HL-60 cells; Cyclin A; Cyclin D1; RARE; c-fos; p53; APL ID ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID; MOLECULAR-MECHANISMS; DEPENDENT KINASES; BREAST-CANCER; IN-VITRO; APOPTOSIS; TRANSCRIPTION; ACTIVATION; INDUCTION AB Arsenic trioxide (As(2)O(3)) has recently been successfully used to treat all trans retinoic acid (ATRA) resistant relapsing acute promyelocytic leukemia. However, its molecular mechanisms of action are poorly understood. In the present study, we used the human leukemia (HL-60) cell line as a test model to study the cellular and molecular mechanisms of anti-cancer properties of As(2)O(3). We hypothesized that As(2)O(3)-induced expression of stress genes and related proteins may play a role in the cellular and molecular events leading to cell cycle modulation in leukemic cells. To test this hypothesis, we performed Western blot analysis to assess the expression of specific cellular response proteins including p53, c-fos, RARE, Cyclin A, and Cyclin D1. Densitometric analysis was performed to determine the relative abundance of these proteins. Western Blot and densitometric analyses demonstrated a strong dose-response relationship with regard to p53 and RARE expression within the dose-range of 0-8 mu g/ml. Expression of c-fos was slightly up-regulated at 2 mu g/ml, and down-regulated within the dose-range of 4-8 mu g/ml. A statistically significant down-regulation of this protein was detected at the 6 and 8 mu g/ml dose levels. No statistically significant differences (p > 0.05) in Cyclin D1 expression was found between As(2)O(3)-treated cells and the control. Cyclin A expression in As(2)O(3)-treated HL-60 cells was up-regulated at 6 mu g/ml, suggesting that it is required for S phase and passage through G(2) phase in cell cycle progression. Taken together, these results indicate that As(2)O(3) has the potential to induce cell cycle arrest through activation of the 53-kDa tumor suppressor protein and repression of the c-fos transcription factor. Up-regulation of RARE by As(2)O(3) indicates that its cytotoxicity may be mediated through interaction/binding with the retinoic acid receptor, and subsequent inhibition of growth and differentiation. C1 [Yedjou, Clement G.; Tchounwou, Paul B.] Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Cell & Toxicogenom Res Lab,Coll Sci Engn & Techno, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, NIH, RCMI Ctr Environm Hlth, Cell & Toxicogenom Res Lab,Coll Sci Engn & Techno, 1400 Lynch St,Box 18540, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU National Institutes of Health [2G12RR13459-11] FX This research was financially supported by a grant from the National Institutes of Health (Grant No. 2G12RR13459-11), through the RCMI- Center for Environmental Health at Jackson State University. The authors thank Dr. Ronald Mason: President and Dr. Abdul Mohamed: Dean Emeritus of College of Science, Engineering & Technology at Jackson State University, for their technical support of this research. NR 57 TC 10 Z9 16 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2009 VL 331 IS 1-2 BP 207 EP 214 DI 10.1007/s11010-009-0160-z PG 8 WC Cell Biology SC Cell Biology GA 513FN UT WOS:000271308000024 PM 19444595 ER PT J AU Saydam, O Shen, YP Wurdinger, T Senol, O Boke, E James, MF Tannous, BA Stemmer-Rachamimov, AO Yi, M Stephens, RM Fraefel, C Gusella, JF Krichevsky, AM Breakefield, XO AF Saydam, Okay Shen, Yiping Wuerdinger, Thomas Senol, Ozlem Boke, Elvan James, Marianne F. Tannous, Bakhos A. Stemmer-Rachamimov, Anat O. Yi, Ming Stephens, Robert M. Fraefel, Cornel Gusella, James F. Krichevsky, Anna M. Breakefield, Xandra O. TI Downregulated MicroRNA-200a in Meningiomas Promotes Tumor Growth by Reducing E-Cadherin and Activating the Wnt/beta-Catenin Signaling Pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MIR-200 FAMILY; MESENCHYMAL TRANSITION; COLORECTAL-CANCER; REPRESSORS ZEB1; GENETIC MODEL; BETA-CATENIN; IN-VIVO; CELLS; EXPRESSION; NF2 AB Meningiomas, one of the most common human brain tumors, are derived from arachnoidal cells associated with brain meninges, are usually benign, and are frequently associated with neurofibromatosis type 2. Here, we define a typical human meningioma microRNA (miRNA) profile and characterize the effects of one downregulated miRNA, miR-200a, on tumor growth. Elevated levels of miR-200a inhibited meningioma cell growth in culture and in a tumor model in vivo. Upregulation of miR-200a decreased the expression of transcription factors ZEB1 and SIP1, with consequent increased expression of E-cadherin, an adhesion protein associated with cell differentiation. Downregulation of miR-200a in meningiomas and arachnoidal cells resulted in increased expression of beta-catenin and cyclin D1 involved in cell proliferation. miR-200a was found to directly target beta-catenin mRNA, thereby inhibiting its translation and blocking Wnt/beta-catenin signaling, which is frequently involved in cancer. A direct correlation was found between the downregulation of miR-200a and the upregulation of beta-catenin in human meningioma samples. Thus, miR-200a appears to act as a multifunctional tumor suppressor miRNA in meningiomas through effects on the E-cadherin and Wnt/beta-catenin signaling pathways. This reveals a previously unrecognized signaling cascade involved in meningioma tumor development and highlights a novel molecular interaction between miR-200a and Wnt signaling, thereby providing insights into novel therapies for meningiomas. C1 [Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. [Saydam, Okay; Wuerdinger, Thomas; Senol, Ozlem; Boke, Elvan; Tannous, Bakhos A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. [Shen, Yiping; James, Marianne F.; Gusella, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Mol Neurogenet Unit, Boston, MA 02114 USA. [Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Amsterdam, Netherlands. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. [Stemmer-Rachamimov, Anat O.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02129 USA. [Yi, Ming; Stephens, Robert M.] NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Fraefel, Cornel] Univ Zurich, Inst Virol, CH-8057 Zurich, Switzerland. [Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Mol Neurogenet Unit, Sch Med, E 13th St,Bldg 149, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI huang, nqi/F-7238-2011 FU Children's Tumor Foundation [2007-01-043, 2005-01-004, NINDS NS24279, NCI CA69246, CA86355]; Brain Tumor Society; American Brain Tumor Society; Cancer League of Canton Zurich; Neurofibromatosis Inc.-New England; S. Sydney De Young Foundation FX We thank Anita Lal for meningioma cell lines SF4433 and SF4068. We also thank Casey A. Maguire for critical reading of the manuscript, Arda Mizrak for assistance, Suzanne McDavitt for skilled editorial assistance, and Applied Biosystems for supplying the miRNA qRT-PCR primers. NR 46 TC 126 Z9 144 U1 1 U2 19 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 1 PY 2009 VL 29 IS 21 BP 5923 EP 5940 DI 10.1128/MCB.00332-09 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 505SV UT WOS:000270716800024 PM 19703993 ER PT J AU Hall, BG Pikis, A Thompson, J AF Hall, Barry G. Pikis, Andreas Thompson, John TI Evolution and Biochemistry of Family 4 Glycosidases: Implications for Assigning Enzyme Function in Sequence Annotations SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE glycosyl hydrolases; family GH4; phylogenetics; genomic annotation; enzyme specificity ID PHOSPHO-ALPHA-GLUCOSIDASE; THERMOTOGA-MARITIMA MSB8; GLUCOSYL-D-FRUCTOSES; RED-BLOOD-CELLS; KLEBSIELLA-PNEUMONIAE; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; FUSOBACTERIUM-MORTIFERUM; HYDROLASE FAMILY-4; METABOLISM AB Glycosyl hydrolase Family 4 (GH4) is exceptional among the 114 families in this enzyme superfamily. Members of GH4 exhibit unusual cofactor requirements for activity, and an essential cysteine residue is present at the active site. Of greatest significance is the fact that members of GH4 employ a unique catalytic mechanism for cleavage of the glycosidic bond. By phylogenetic analysis, and from available substrate specificities, we have assigned a majority of the enzymes of GH4 to five subgroups. Our classification revealed an unexpected relationship between substrate specificity and the presence, in each subgroup, of a motif of four amino acids that includes the active-site Cys residue: a-glucosidase, CHE(I/V); alpha-galactosidase, CHSV; alpha-glucuronidase, CHGx; 6-phospho-alpha-glucosidase, CDMP; and 6-phospho-beta-glucosidase, CN(V/I)P. The question arises: Does the presence of a particular Motif sufficiently predict the catalytic function of an unassigned GH4 protein? To test this hypothesis, we have purified and characterized the a-glucoside -specific GH4 enzyme (PalH) from the phytopathogen, Erwinia rhapontici. The CHEI motif in this protein has been changed by site-dirceted mutagenesis, and the effects upon Substrate specificity have been determined. The change to CHSV caused the loss of all a-glucosidase activity, but the mutant protein exhibited none of the anticipated alpha-galactosidase activity. The Cys-containing motif may be suggestive of enzyme specificity, but phylogenetic placement is required for confidence in that specificity. The Acholeplasma laidlawii GH4 protein is phylogenetically a phospho-beta-glucosidase but has a unique SSSP motif. Lacking the initial Cys in that motif it cannot hydrolyze glycosides by the normal GH4 mechanism because the Cys is required to position the metal ion for hydrolysis, nor can it use the more common single or double-displacement mechanism of Koshland. Several considerations suggest that the protein has acquired a new function as the consequence of positive selection. This study emphasizes the importance of automatic annotation systems that by integrating phylogenetic analysis, functional motifs, and bioinformatics data, may lead to innovative experiments that further our understanding of biological systems. C1 [Hall, Barry G.] Bellingham Res Inst, Bellingham, WA USA. [Pikis, Andreas; Thompson, John] Natl Inst Dent & Craniofacial Res, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Hall, BG (reprint author), Bellingham Res Inst, Bellingham, WA USA. EM barryhall@zeninternet.com FU NIDCR; National Institutes of Health FX This work was supported by the Intramural Research Program of the NIDCR, National Institutes of Health, Bethesda, MD. We thank Frederik Boernke for kindly providing plasmid pPALI lcontaining the palH gene from E. rhapontici. NR 37 TC 9 Z9 10 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 2009 VL 26 IS 11 BP 2487 EP 2497 DI 10.1093/molbev/msp162 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 514UX UT WOS:000271422300008 PM 19625389 ER PT J AU Jacobs, DT Weigert, R Grode, KD Donaldson, JG Cheney, RE AF Jacobs, Damon T. Weigert, Roberto Grode, Kyle D. Donaldson, Julie G. Cheney, Richard E. TI Myosin Vc Is a Molecular Motor That Functions in Secretory Granule Trafficking SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PANCREATIC ACINAR-CELLS; GREEN FLUORESCENT PROTEIN; HEAD-TO-TAIL; EPITHELIAL-CELLS; UNCONVENTIONAL MYOSIN; PLASMA-MEMBRANE; CHROMOGRANIN-A; COMPENSATORY ENDOCYTOSIS; SACCHAROMYCES-CEREVISIAE; MIGRATING FIBROBLASTS AB Class V myosins are actin-based motor proteins that have critical functions in organelle trafficking. Of the three class V myosins expressed in mammals, relatively little is known about Myo5c except that it is abundant in exocrine tissues. Here we use MCF-7 cells to identify the organelles that Myo5c associates with, image the dynamics of Myo5c in living cells, and test the functions of Myo5c. Endogenous Myo5c localizes to two distinct compartments: small puncta and slender tubules. Myo5c often exhibits a highly polarized distribution toward the leading edge in migrating cells and is clearly distinct from the Myo5a or Myo5b compartments. Imaging with GFP-Myo5c reveals that Myo5c puncta move slowly (similar to 30 nm/s) and microtubule independently, whereas tubules move rapidly (similar to 440 nm/s) and microtubule dependently. Myo5c puncta colocalize with secretory granule markers such as chromogranin A and Rab27b, whereas Myo5c tubules are labeled by Rab8a. TIRF imaging indicates that the granules can be triggered to undergo secretion. To test if Myo5c functions in granule trafficking, we used the Myo5c tail as a dominant negative and found that it dramatically perturbs the distribution of granule markers. These results provide the first live-cell imaging of Myo5c and indicate that Myo5c functions in secretory granule trafficking. C1 [Jacobs, Damon T.; Grode, Kyle D.; Cheney, Richard E.] Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. [Weigert, Roberto] NHLBI, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. [Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cheney, RE (reprint author), Univ N Carolina, Sch Med, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. EM CheneyR@med.UNC.edu FU American Physiological Society; UNC Sequoyah Dissertation Completion Fellowship; National Institutes of Health, National Institute on Deafness and Other Communicative Disorders [DC03299] FX The authors thank Marvin Lai for assistance in generating GFP-Myo5c globular tail, Chi W. Pak for assistance with image analysis, and Drs. Sarah Hamm-Alvarez and Ron Marchelletta (University of Southern California) for helpful comments and suggestions. We also acknowledge the University of North Carolina (UNC) Neuroscience Center Confocal and Multi-Photon Imaging Facility for confocal imaging, the assistance of Kirk McNaughton of the UNC Cell and Molecular Physiology Histology Facility, and the University of Kansas Microscopy and Analytical Imaging Facility. D. T. J. was supported by a Porter Fellowship from the American Physiological Society and a UNC Sequoyah Dissertation Completion Fellowship. This research was supported by National Institutes of Health, National Institute on Deafness and Other Communicative Disorders Grant DC03299 to R. E. C. NR 88 TC 30 Z9 30 U1 0 U2 3 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 NOV 1 PY 2009 VL 20 IS 21 BP 4471 EP 4488 DI 10.1091/mbc.E08-08-0865 PG 18 WC Cell Biology SC Cell Biology GA 514DL UT WOS:000271374400001 PM 19741097 ER PT J AU Gundry, RL Raginski, K Tarasova, Y Tchernyshyov, I Bausch-Fluck, D Elliott, ST Boheler, KR Van Eyk, JE Wollscheid, B AF Gundry, Rebekah L. Raginski, Kimberly Tarasova, Yelena Tchernyshyov, Irina Bausch-Fluck, Damaris Elliott, Steven T. Boheler, Kenneth R. Van Eyk, Jennifer E. Wollscheid, Bernd TI The Mouse C2C12 Myoblast Cell Surface N-Linked Glycoproteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Review ID INTEGRAL MEMBRANE-PROTEINS; COMPREHENSIVE PROTEOMIC ANALYSIS; SKELETAL-MUSCLE DIFFERENTIATION; EMBRYONIC STEM-CELLS; MASS-SPECTROMETRY; PLASMA-MEMBRANE; SATELLITE CELLS; M-CADHERIN; ADHESION MOLECULE; FIBROBLAST-GROWTH-FACTOR-2 RESPONSIVENESS AB Endogenous regeneration and repair mechanisms are responsible for replacing dead and damaged cells to maintain or enhance tissue and organ function, and one of the best examples of endogenous repair mechanisms involves skeletal muscle. Although the molecular mechanisms that regulate the differentiation of satellite cells and myoblasts toward myofibers are not fully understood, cell surface proteins that sense and respond to their environment play an important role. The cell surface capturing technology was used here to uncover the cell surface N-linked glycoprotein subproteome of myoblasts and to identify potential markers of myoblast differentiation. 128 bona fide cell surface-exposed N-linked glycoproteins, including 117 transmembrane, four glycosylphosphatidylinositol-anchored, five extracellular matrix, and two membrane-associated proteins were identified from mouse C2C12 myoblasts. The data set revealed 36 cluster of differentiation-annotated proteins and confirmed the occupancy for 235 N-linked glycosylation sites. The identification of the N-glycosylation sites on the extracellular domain of the proteins allowed for the determination of the orientation of the identified proteins within the plasma membrane. One glycoprotein transmembrane orientation was found to be inconsistent with Swiss-Prot annotations, whereas ambiguous annotations for 14 other proteins were resolved. Several of the identified N-linked glycoproteins, including aquaporin-1 and beta-sarcoglycan, were found in validation experiments to change in overall abundance as the myoblasts differentiate toward myotubes. Therefore, the strategy and data presented shed new light on the complexity of the myoblast cell surface subproteome and reveal new targets for the clinically important characterization of cell intermediates during myoblast differentiation into myotubes. Molecular & Cellular Proteomics 8: 2555-2569, 2009. C1 [Gundry, Rebekah L.; Tarasova, Yelena; Tchernyshyov, Irina; Elliott, Steven T.; Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Med, Sch Med, Baltimore, MD 21224 USA. [Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Biol Chem, Sch Med, Baltimore, MD 21224 USA. [Van Eyk, Jennifer E.] Johns Hopkins Univ, Dept Biomed Engn, Sch Med, Baltimore, MD 21224 USA. [Gundry, Rebekah L.; Raginski, Kimberly; Tarasova, Yelena; Boheler, Kenneth R.] NIA, NIH, Baltimore, MD 21224 USA. [Bausch-Fluck, Damaris; Wollscheid, Bernd] ETH, Inst Mol Syst Biol, NCCR Neuro Ctr Prote, CH-8093 Zurich, Switzerland. RP Van Eyk, JE (reprint author), Johns Hopkins Univ, Dept Med, Sch Med, Rm 602,Mason F Lord Bldg,Ctr Tower, Baltimore, MD 21224 USA. EM jvaneyk1@jhmi.edu RI Wollscheid, Bernd/E-8909-2010 OI Wollscheid, Bernd/0000-0002-3923-1610 FU NHLBI NIH HHS [K99 HL094708, K99 HL094708-01, K99 HL094708-02, N01 HV028180, N01-HV-28180, N01HV28180, P50 HL084946, P50 HL084946-019003, P50 HL084946-029003, P50 HL084946-039003, P50-HL-084946-01, R00 HL094708, R01 HL085434, R01 HL085434-01A2]; PHS HHS [K99-L094708-01] NR 120 TC 44 Z9 132 U1 4 U2 30 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2009 VL 8 IS 11 BP 2555 EP 2569 DI 10.1074/mcp.M900195-MCP200 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 517LL UT WOS:000271615200012 PM 19656770 ER PT J AU Mishra, PJ Menon, LG Mishra, PJ Mayer-Kuckuk, P Bertino, JR Banerjee, D AF Mishra, Prasun J. Menon, Lata G. Mishra, Pravin J. Mayer-Kuckuk, Philipp Bertino, Joseph R. Banerjee, Debabrata TI Translational Modulation of Proteins Expressed from Bicistronic Vectors SO MOLECULAR IMAGING LA English DT Article ID RIBOSOME ENTRY SEGMENT; DIHYDROFOLATE-REDUCTASE PROTEIN; 2ND GENE-EXPRESSION; 5'-UNTRANSLATED REGION; THYMIDYLATE SYNTHASE; REPORTER GENE; SITE; IRES; RESISTANCE; CELLS AB Bicistronic vectors are useful tools for exogenous expression of two gene products from a single promoter element; however, reduced expression of protein from the second cistron compared with the first cistron is a common limitation to this approach. To overcome this limitation, we explored use of dihydrofolate reductase (DHFR) complementary DNA encoded in bicistronic vectors to induce a second protein of interest by methotrexate (MTX) treatment. Previous studies have demonstrated that levels of DHFR protein and DHFR fusion protein can be induced translationally following MTX treatment of cells. We demonstrated that in response to MTX treatment, DHFR partner protein in a bicistronic construct is induced for longer periods of time when compared with endogenous DHFR and DHFR fusion protein, in vitro and in vivo. Using rapamycin pretreatment followed by MTX treatment, we also devised a strategy to modulate levels of two proteins expressed from a bicistronic construct in a cap-independent manner. To our knowledge, this is the first report demonstrating that levels of proteins in DHFR-based bicistronic constructs can be induced and modulated using MTX and rapamycin treatment. C1 [Banerjee, Debabrata] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Pharmacol, New Brunswick, NJ 08903 USA. NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Med, New Brunswick, NJ 08903 USA. Hosp Special Surg, Bone Cell Biol & Imaging Lab, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. RP Banerjee, D (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Pharmacol, 195 Little Albany St,Room 3035, New Brunswick, NJ 08903 USA. EM banerjed@umdnj.edu FU National Institutes of Health and National Cancer Institute (NIH/NCI) [CA 86438, CA 08010] FX This work was Supported by grants, National Institutes of Health and National Cancer Institute (NIH/NCI), CA 86438 and CA 08010. NR 31 TC 2 Z9 2 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD NOV-DEC PY 2009 VL 8 IS 6 BP 305 EP 318 DI 10.2310/7290.2009.00028 PG 14 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 545HH UT WOS:000273722600003 PM 20003889 ER PT J AU Alford, R Simpson, HM Duberman, J Hill, GC Ogawa, M Regino, C Kobayashi, H Choyke, PL AF Alford, Raphael Simpson, Haley M. Duberman, Josh Hill, G. Craig Ogawa, Mikako Regino, Celeste Kobayashi, Hisataka Choyke, Peter L. TI Toxicity of Organic Fluorophores Used in Molecular Imaging: Literature Review SO MOLECULAR IMAGING LA English DT Review ID RETINAL-PIGMENT EPITHELIUM; INDOCYANINE GREEN-DYE; MACULAR HOLE SURGERY; NEAR-INFRARED LIGHT; FLUORESCEIN ANGIOGRAPHY; IN-VIVO; ADVERSE REACTIONS; RHODAMINE DYES; SODIUM FLUORESCEIN; CELLS AB Fluorophores are potentially useful for in vivo cancer diagnosis. Using relatively inexpensive and portable equipment, optical imaging with fluorophores permits real-time detection of cancer. However, fluorophores can be toxic and must be investigated before they can be administered safely to patients. A review of published literature on the toxicity of 19 widely used fluorophores was conducted by searching 26 comprehensive biomedical and chemical literature databases and analyzing the retrieved material. These fluorophores included Alexa Fluor 488 and 514, BODIPY FL, BODIPY R6G, Cy 5.5, Cy 7, cypate, fluorescein, indocyanine green, Oregon green, 8-phenyl BODIPY, rhodamine 110, rhodamine 6G, rhodamine X, rhodol, TAMRA, Texas red, and Tokyo green. Information regarding cytotoxicity, tissue toxicity, in vivo toxicity, and mutagenicity was included. Considerable toxicity-related information was available for the Food and Drug Administration (FDA)-approved compounds indocyanine green and fluorescein, but published information on many of the non-FDA-approved fluorophores was limited. The information located was encouraging because the amounts of fluorophore used in molecular imaging probes are typically much lower than the toxic doses described in the literature. Ultimately, the most effective and appropriate probes for use in patients will be determined by their fluorescent characteristics and the safety of the conjugates. C1 [Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, NIH Lib, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. Univ N Carolina, Chapel Hill, NC USA. NCI, Clin Res Program Directorate, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM pchoyke@mail.nih.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This project was funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 70 TC 134 Z9 135 U1 26 U2 131 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD NOV-DEC PY 2009 VL 8 IS 6 BP 341 EP 354 DI 10.2310/7290.2009.00031 PG 14 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 545HH UT WOS:000273722600006 PM 20003892 ER PT J AU Bien, CM Chang, YC Nes, WD Kwon-Chung, KJ Espenshade, PJ AF Bien, Clara M. Chang, Yun C. Nes, W. David Kwon-Chung, Kyung J. Espenshade, Peter J. TI Cryptococcus neoformans Site-2 protease is required for virulence and survival in the presence of azole drugs SO MOLECULAR MICROBIOLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; INTRAMEMBRANE PROTEOLYSIS; STEROL SYNTHESIS; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; ANTIFUNGAL AGENTS; GENE; CLEAVAGE; OXYGEN; METALLOPROTEASE AB P>In the human fungal pathogen Cryptococcus neoformans, the SREBP orthologue Sre1 is important for adaptation and growth in nutrient-limiting host tissues. In this study, we characterize the C. neoformans serotype A Sre1 and its activating protease, Stp1. We demonstrate that Stp1 is a functionally conserved orthologue of the mammalian Site-2 protease and that Stp1 cleaves Sre1 within its predicted first transmembrane segment. Gene expression analysis revealed that Stp1 is required for both Sre1-dependent and Sre1-independent gene transcription, indicating that other substrates of Stp1 may exist. Using gas chromatography, we showed that Sre1 and Stp1 are required for both normoxic and hypoxic ergosterol biosynthesis, and therefore cells lacking SRE1 or STP1 are defective for growth in the presence of low levels of the ergosterol biosynthesis inhibitors, itraconazole and 25-thialanosterol. Importantly, our studies demonstrated fungicidal effects of itraconazole and 25-thialanosterol towards sre1 Delta and stp1 Delta cells, demonstrating that the Sre1 pathway is required for both growth and survival in the presence of sterol biosynthesis-inhibiting antifungal drugs. Given the need for fungicidal drugs, we propose that inhibitors of Stp1, Sre1, or other regulators of Sre1 function administered in combination with a sterol synthesis inhibitor could prove an effective anticryptococcal therapy. C1 [Bien, Clara M.; Espenshade, Peter J.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. [Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Nes, W. David] Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USA. RP Espenshade, PJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. EM peter.espenshade@jhmi.edu FU National Institutes of Health [HL077588, AI72186]; National Science Foundation [MCB-0417436]; Welch Foundation [D-1276]; National Institutes of Allergy and Infectious Diseases FX This work was supported by grants from the National Institutes of Health HL077588 and AI72186 (to P.J.E.), grants from the National Science Foundation MCB-0417436 and the Welch Foundation D-1276 (to W.D.N.), and funds from the intramural programme of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health (to K.J.K.-C.). P.J.E. is a Burroughs Wellcome Fund Investigator in the Pathogenesis of Infectious Disease. We thank J. Burg for compiling and assigning GO terms for C. neoformans H99 genes, and S. Zhao for outstanding technical assistance. NR 37 TC 34 Z9 34 U1 1 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2009 VL 74 IS 3 BP 672 EP 690 DI 10.1111/j.1365-2958.2009.06895.x PG 19 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 509VM UT WOS:000271047100012 PM 19818023 ER PT J AU Weecharangsan, W Yu, B Zheng, Y Liu, SJ Pang, JX Lee, LJ Marcucci, G Lee, RJ AF Weecharangsan, Wanlop Yu, Bo Zheng, Yu Liu, Shujun Pang, Jiu Xia Lee, L. James Marcucci, Guido Lee, Robert J. TI Efficient Delivery of Antisense Oligodeoxyribonucleotide G3139 by Human Serum Albumin-Coated Liposomes SO MOLECULAR PHARMACEUTICS LA English DT Article DE Liposomes; antisense oligonucleotide; G3139; Bcl-2; lipoplex; human serum albumin; drug delivery; cancer ID CATIONIC LIPOSOMES; BCL-2 ANTISENSE; GENE DELIVERY; SECONDARY STRUCTURE; OLIGONUCLEOTIDES; COMPLEXES; CELLS; OLIGODEOXYNUCLEOTIDES; TRANSFECTION; ENHANCEMENT AB Human serum albumin (HSA)-coated liposomal formulations were synthesized and evaluated for the delivery of antisense oligodeoxyribonucleotide (ODN) 63139 in KB human oral carcinoma cells. Liposomes composed of dimethyldioctadecylammonium bromide/egg phosphatidylcholine/alpha-tocopheryl polyethylene glycol 1000 succinate (58:40:2 molar ratio) complexed with G3139 and coated with HSA were investigated for Bcl-2 downregulating activity. Cellular uptake of HSA-coated liposome-ODN complexes was more efficient than the uncoated liposome-ODN complexes. Treatment of the cells with HSA-coated liposome-ODN complexes resulted in efficient Bcl-2 mRNA downregulation that was approximately 3-fold greater than with uncoated liposomes (p < 0.05) and 6-fold greater than with free ODN. The transfection efficiency of liposome-ODN complexes coated with HSA was dependent on the concentration of HSA used and on the contents of alpha-helix and beta-strand in HSA. HSA-coated liposomes are effective delivery vehicles for antisense ODN. C1 [Weecharangsan, Wanlop; Zheng, Yu; Lee, Robert J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. [Weecharangsan, Wanlop] Srinakharinwirot Univ, Fac Pharm, Dept Pharmaceut Technol, Nakhon Nayok, Thailand. [Yu, Bo; Lee, L. James] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Liu, Shujun; Pang, Jiu Xia; Marcucci, Guido; Lee, Robert J.] Ohio State Univ, NCI, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Marcucci, Guido] Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. [Yu, Bo; Lee, L. James; Lee, Robert J.] Ohio State Univ, NSF NSEC Affordable Nanoengn Polymer Biomed Devic, CANPBD, Columbus, OH 43210 USA. RP Weecharangsan, W (reprint author), Ohio State Univ, Coll Pharm, Div Pharmaceut, 542 LM Parks Hall,500 W 12th Ave, Columbus, OH 43210 USA. EM wanlop@swu.ac.th; lee.1339@osu.edu FU NIH [CA-135243]; NSF [EEC-0425626] FX This work was supported in part by NIH Grant CA-135243 and NSF Grant EEC-0425626. We are grateful to Prof. Rumiana Koynova for helpful advice in revising the manuscript. NR 24 TC 11 Z9 13 U1 6 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD NOV-DEC PY 2009 VL 6 IS 6 BP 1848 EP 1855 DI 10.1021/mp900150g PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 528QJ UT WOS:000272461300018 PM 19725564 ER PT J AU Deeken, JF Robey, RW Shukla, S Steadman, K Chakraborty, AR Poonkuzhali, B Schuetz, EG Holbeck, S Ambudkar, SV Bates, SE AF Deeken, John F. Robey, Robert W. Shukla, Suneet Steadman, Kenneth Chakraborty, Arup R. Poonkuzhali, Balasubramanian Schuetz, Erin G. Holbeck, Susan Ambudkar, Suresh V. Bates, Susan E. TI Identification of Compounds that Correlate with ABCG2 Transporter Function in the National Cancer Institute Anticancer Drug Screen SO MOLECULAR PHARMACOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; RESISTANCE PROTEIN; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CELL-LINES; HALF-TRANSPORTER; BRAIN PENETRATION; GENE-EXPRESSION; POLYMORPHISMS; LOCALIZATION AB ABCG2 is an ATP-binding cassette transporter that counts multiple anticancer compounds among its substrates and is believed to regulate oral bioavailability as well as serve a protective role in the blood-brain barrier, the maternal-fetal barrier, and hematopoietic stem cells. We sought to determine whether novel compounds that interact with the transporter could be identified through analysis of cytotoxicity profiles recorded in the NCI Anticancer Drug Screen database. A flow cytometric assay was used to measure ABCG2 function in the 60 cell lines and generate a molecular profile for COMPARE analysis. This strategy identified >70 compounds with Pearson correlation coefficients (PCCs) >0.4, where reduced drug sensitivity correlated with ABCG2 expression, as well as >120 compounds with PCCs < -0.4, indicating compounds to which ABCG2 expression conferred greater sensitivity. Despite identification of known single nucleotide polymorphisms in the ABCG2 gene in a number of the cell lines, omission of these lines from the COMPARE analysis did not affect PCCs. Available compounds were subjected to validation studies to confirm interaction with the transporter, including flow cytometry, [(125)I]IAAP binding, and cytotoxicity assays, and interaction was documented in 20 of the 27 compounds studied. Although known substrates of ABCG2 such as mitoxantrone or topotecan were not identified, we characterized three novel substrates-5-hydroxypicolinaldehyde thiosemicarbazone (NSC107392), (E)-N-(1-decylsulfanyl-3-hydroxypropan-2-yl)-3-(6-methyl-2,4-dioxo-1H-pyrimidin-5-yl)prop-2-enamide (NSC265473), and 1,2,3,4,7-pentahydroxy-1,3,4,4a,5,11b-hexahydro[1,3]dioxolo[4,5-j]phenanthridin-6(2H)-one [NSC349156 (pancratistatin)]-and four compounds that inhibited transporter function-2-[methyl(2-pyridin-2-ylethyl)amino]fluoren-9-one hydroiodide (NSC24048), 5-amino-6-(7-amino-5,8-dihydro-6-methoxy-5,8-dioxo-2-quinolinyl)-4-(2-hydroxy-3,4-dimethoxyphenyl)-3-methyl-2-pyridinecarboxylic acid, methyl ester (NSC45384), (17 beta)-2,4-dibromo-estra-1,3,5(10)-triene-3,17-diol (NSC103054), and methyl N-(pyridine-4-carbonylamino) carbamodithioate (NSC636795). In summary, COMPARE analysis of the NCI drug screen database using the ABCG2 functional profile was able to identify novel substrates and transporter-interacting compounds. C1 [Deeken, John F.; Steadman, Kenneth] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. [Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Shukla, Suneet; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Holbeck, Susan] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Holbeck, Susan] NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. [Poonkuzhali, Balasubramanian] Christian Med Coll & Hosp, Dept Hematol, Vellore, Tamil Nadu, India. [Schuetz, Erin G.] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. [Chakraborty, Arup R.] Texas Tech Univ, Dept Biol Sci, Lubbock, TX 79409 USA. RP Deeken, JF (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd,NW, Washington, DC 20007 USA. EM deekenj@georgetown.edu RI shukla, suneet/B-4626-2012; Steadman, Kenneth/J-3883-2013 FU National Institutes of Health National Cancer Institute; National Institutes of Health National Institute of General Medical Sciences [U01-GM61374, U01-GM61393]; National Institutes of Health National Cancer Institute [P30-CA21765]; American Lebanese Syrian Associated Charities FX This work was supported in part by the Intramural Research Program of the National Institutes of Health National Cancer Institute; by the National Institutes of Health National Institute of General Medical Sciences [Grants U01-GM61374, U01-GM61393], by the National Institutes of Health National Cancer Institute [Grant P30-CA21765]; and by the American Lebanese Syrian Associated Charities. NR 38 TC 14 Z9 15 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2009 VL 76 IS 5 BP 946 EP 956 DI 10.1124/mol.109.056192 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507VM UT WOS:000270883300003 PM 19633067 ER PT J AU Chapuis, J Hot, D Hansmannel, F Kerdraon, O Ferreira, S Hubans, C Maurage, CA Huot, L Bensemain, F Laumet, G Ayral, AM Fievet, N Hauw, JJ DeKosky, ST Lemoine, Y Iwatsubo, T Wavrant-Devrieze, F Dartigues, JF Tzourio, C Buee, L Pasquier, F Berr, C Mann, D Lendon, C Alperovitch, A Kamboh, MI Amouyel, P Lambert, JC AF Chapuis, J. Hot, D. Hansmannel, F. Kerdraon, O. Ferreira, S. Hubans, C. Maurage, C. A. Huot, L. Bensemain, F. Laumet, G. Ayral, A. M. Fievet, N. Hauw, J. J. DeKosky, S. T. Lemoine, Y. Iwatsubo, T. Wavrant-Devrieze, F. Dartigues, J. F. Tzourio, C. Buee, L. Pasquier, F. Berr, C. Mann, D. Lendon, C. Alperovitch, A. Kamboh, M. I. Amouyel, P. Lambert, J. C. TI Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease SO MOLECULAR PSYCHIATRY LA English DT Article DE Alzheimer; IL-33; brain expression; polymorphism; CAA ID CEREBRAL AMYLOID ANGIOPATHY; APOLIPOPROTEIN-E GENOTYPE; SMOOTH-MUSCLE-CELLS; A-BETA; VASCULAR DEMENTIA; IMMUNE CELLS; MAST-CELLS; ASSOCIATION; PROTEIN; RISK AB The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n = 945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation. Molecular Psychiatry (2009) 14, 1004-1016; doi:10.1038/mp.2009.10; published online 10 February 2009 C1 [Chapuis, J.; Hansmannel, F.; Bensemain, F.; Laumet, G.; Ayral, A. M.; Fievet, N.; Amouyel, P.; Lambert, J. C.] Univ Lille 2, INSERM, U744, Inst Pasteur Lille, F-59019 Lille, France. [Hot, D.; Huot, L.; Lemoine, Y.] Inst Pasteur, Lab Biopuces, Lille, France. [Kerdraon, O.; Maurage, C. A.; Buee, L.] Univ Lille 2, INSERM, U837, F-59019 Lille, France. [Ferreira, S.; Hubans, C.] Genoscreen, Lille, France. [Hauw, J. J.] Hop La Pitie Salpetriere, INSERM, IFR70, Neuropathol Lab, Paris, France. [DeKosky, S. T.; Kamboh, M. I.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. [DeKosky, S. T.; Kamboh, M. I.] Univ Pittsburgh, Alzheimers Dis Res Ctr, Pittsburgh, PA USA. [Iwatsubo, T.] Univ Tokyo, Dept Neuropathol & Neurosci, Bunkyo Ku, Tokyo, Japan. [Wavrant-Devrieze, F.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Dartigues, J. F.] Univ Victor Segalen, INSERM, U593, Bordeaux, France. [Pasquier, F.] CHU Hop Roger Salengro, Univ Hosp Lille, Memory Clin, Dept Neurol,EA2391, Lille, France. [Berr, C.] Univ Montpellier 1, INSERM, U888, Hop La Colombiere, F-34493 Montpellier, France. [Mann, D.] Univ Manchester, Hope Hosp, Sch Translat Med, Salford M6 8HD, Lancs, England. [Lendon, C.] PO Royal Brisbane Hosp Queensland, Queensland Inst Med Res, Mol Psychiat Grp, Brisbane, Qld, Australia. RP Lambert, JC (reprint author), Univ Lille 2, INSERM, U744, Inst Pasteur Lille, BP 245,1 Rue Prof Calmette, F-59019 Lille, France. EM jean-charles.lambert@pasteur-lille.fr RI Tzourio, christophe/B-4015-2009; berr, Claudine/D-5238-2014; lambert, jean-charles/F-8787-2013; BUEE, Luc/B-3126-2010; LICEND, CEMND/F-1296-2015; Lambert, jean-charles/A-9553-2014; OI Tzourio, christophe/0000-0002-6517-2984; berr, Claudine/0000-0001-5254-7655; BUEE, Luc/0000-0002-6261-4230; Lambert, jean-charles/0000-0003-0829-7817; Kamboh, M. Ilyas/0000-0002-3453-1438 FU Ministere de l'enseignement superieur et de la Recherche (MESR); Alzheimer's association [IIRG-06-25487]; France Alzheimer Association; Pasteur Institute of Lille; Nord-Pas de Calais; Genoscreen; INSERM; genopole of Lille; CPER-neuroscience; US National Institute on Aging [AG13672, AG05133]; Fondation pour la Recherche Medicale; Caisse Nationale Maladie des Travailleurs Salaries; Direction Generale de la Sante; MGEN; Institut de la Longevite; Agence Francaise de Securite Sanitaire des Produits de Sante; Aquitaine and Bourgogne Regional Councils; jont French Ministry of Research/INSERM; Eisai FX We thank Jo Ann Cahn for her helpful contribution in writing of the manuscript and Dr Morisada Hayakawa for providing us the monoclonal ST2 antibody and Ryan Minster for technical support. Julien Chapuis was supported by the Ministere de l'enseignement superieur et de la Recherche (MESR). Franck Hansmannel was supported by the Alzheimer's association (Grant IIRG-06-25487). Faiza Bensemain was supported by the France Alzheimer Association. Geoffroy Laumet was supported by the Pasteur Institute of Lille and the region Nord-Pas de Calais. This study was funded by Genoscreen, INSERM (ATC-vieillissement), the Pasteur Institute of Lille, the genopole of Lille, the CPER-neuroscience and the US National Institute on Aging Grants AG13672 and AG05133 (I. K. and S. T. D.). The Three-City Study was performed as part of a collaboration between the Institut National de la Sante et de la Recherche Medicale (INSERM), the Victor Segalen-Bordeaux II University and Sanofi-Synthelabo. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C-Study was also funded by the Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Agence Francaise de Securite Sanitaire des Produits de Sante, the Aquitaine and Bourgogne Regional Councils, Fondation de France and the jont French Ministry of Research/INSERM 'Cohortes et collections de donnees biologiques' programme. Lille Genopole received an unconditional grant from Eisai. NR 44 TC 79 Z9 83 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2009 VL 14 IS 11 BP 1004 EP 1016 DI 10.1038/mp.2009.10 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 509MO UT WOS:000271022100004 PM 19204726 ER PT J AU Grant, BF Goldstein, RB Chou, SP Huang, B Stinson, FS Dawson, DA Saha, TD Smith, SM Pulay, AJ Pickering, RP Ruan, WJ Compton, WM AF Grant, B. F. Goldstein, R. B. Chou, S. P. Huang, B. Stinson, F. S. Dawson, D. A. Saha, T. D. Smith, S. M. Pulay, A. J. Pickering, R. P. Ruan, W. J. Compton, W. M. TI Sociodemographic and psychopathologic predictors of first incidence of DSM-IV substance use, mood and anxiety disorders: results from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions SO MOLECULAR PSYCHIATRY LA English DT Review DE incidence; epidemiology; prospective study; substance use disorders; mood disorders; anxiety disorders ID MENTAL-HEALTH SURVEY; INTERVIEW SCHEDULE AUDADIS; ENVIRONMENTAL RISK-FACTORS; GENERAL-POPULATION SAMPLE; R PSYCHIATRIC-DISORDERS; AREA FOLLOW-UP; PARTLY DIFFERENT ENVIRONMENTS; MAJOR DEPRESSIVE DISORDER; UNITED-STATES; DRUG-USE AB The objective of this study was to present nationally representative findings on sociodemographic and psychopathologic predictors of first incidence of Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV) substance, mood and anxiety disorders using the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions. One-year incidence rates of DSM-IV substance, mood and anxiety disorders were highest for alcohol abuse (1.02), alcohol dependence (1.70), major depressive disorder (MDD; 1.51) and generalized anxiety disorder (GAD; 1.12). Incidence rates were significantly greater (P < 0.01) among men for substance use disorders and greater among women for mood and anxiety disorders except bipolar disorders and social phobia. Age was inversely related to all disorders. Black individuals were at decreased risk of incident alcohol abuse and Hispanic individuals were at decreased risk of GAD. Anxiety disorders at baseline more often predicted incidence of other anxiety disorders than mood disorders. Reciprocal temporal relationships were found between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. Borderline and schizotypal personality disorders predicted most incident disorders. Incidence rates of substance, mood and anxiety disorders were comparable to or greater than rates of lung cancer, stroke and cardiovascular disease. The greater incidence of all disorders in the youngest cohort underscores the need for increased vigilance in identifying and treating these disorders among young adults. Strong common factors and unique factors appear to underlie associations between alcohol abuse and dependence, MDD and GAD, and GAD and panic disorder. The major results of this study are discussed with regard to prevention and treatment implications. Molecular Psychiatry (2009) 14, 1051-1066; doi:10.1038/mp.2008.41; published online 22 April 2008 C1 [Grant, B. F.; Goldstein, R. B.; Chou, S. P.; Huang, B.; Stinson, F. S.; Dawson, D. A.; Saha, T. D.; Smith, S. M.; Pulay, A. J.; Pickering, R. P.; Ruan, W. J.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. [Compton, W. M.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, MS 9304,Room 3077,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Pulay, Attila/B-6155-2011; OI Goldstein, Rise/0000-0002-9603-9473 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National Institute on Drug Abuse (NIDA); National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism FX The National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with supplemental support from the National Institute on Drug Abuse (NIDA). This research was supported in part by the Intramural Program of the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism. Dr Bridget Grant had full access to all of the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 102 TC 94 Z9 97 U1 7 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2009 VL 14 IS 11 BP 1051 EP 1066 DI 10.1038/mp.2008.41 PG 16 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 509MO UT WOS:000271022100009 ER PT J AU Smith, RH Levy, JR Kotin, RM AF Smith, Richard H. Levy, Justin R. Kotin, Robert M. TI A Simplified Baculovirus-AAV Expression Vector System Coupled With One-step Affinity Purification Yields High-titer rAAV Stocks From Insect Cells SO MOLECULAR THERAPY LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; ION-EXCHANGE CHROMATOGRAPHY; TYPE-2 VECTORS; MESSENGER-RNAS; TRANSLATION; EUKARYOTES; BIOREACTOR; INITIATION; SEQUENCES; COLUMN AB Scalable methods of recombinant adeno-associated virus (rAAV) production have gained much recent interest as the field of rAAV-mediated gene therapy approaches the clinic. In particular, the production of rAAV vectors in insect cells via the use of recombinant baculovirus technology has proven to be an efficient and scalable means of rAAV production. Here, we describe a method for the production of rAAV serotypes 1 and 2 in insect cells using a simplified baculovirus-AAV expression-vector system coupled with particle purification via affinity chromatography. The number of separate baculovirus constructs required for rAAV production was reduced by genetically modifying the AAV rep gene to allow expression of the AAV-encoded replication enzymes, Rep78 and Rep52, from a single mRNA species and combining the modified rep gene with an AAV cap gene expression cassette in a single baculovirus construct. Additionally, we describe lysis, binding, and elution conditions compatible with a commercially available affinity medium (AVB Sepharose High Performance) used to purify rAAV particles to near homogeneity in a single chromatography step. Using the described method, we obtained an average yield of 7 x 10(4) purified rAAV particles per cell (range: 3.7 x 10(4) to 9.6 x 10(4)) from suspension cultures of recombinant baculovirus-infected insect cells. C1 [Smith, Richard H.; Levy, Justin R.; Kotin, Robert M.] NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. RP Kotin, RM (reprint author), NHLBI, Lab Biochem Genet, Bldg 10,Room 7N260, Bethesda, MD 20892 USA. EM kotinr@nhlbi.nih.gov RI kotin, robert/B-8954-2008 FU National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health FX We thank Loy Volkman for providing the anti-VP39 monoclonal-antibody. We also thank Mathew P. Daniels and the National Heart, Lung, and Blood Institute (NHLBI) Electron Microscopy Core Facility for assistance with the transmission electron microscopy procedure. This work was supported by the Intramural Research Program of the NHLBI, National Institutes of Health. The authors declare no conflict of interest. NR 30 TC 85 Z9 87 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2009 VL 17 IS 11 BP 1888 EP 1896 DI 10.1038/mt.2009.128 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 520HT UT WOS:000271835000009 PM 19532142 ER PT J AU Bosticardo, M Ghosh, A Du, Y Jenkins, NA Copeland, NG Candotti, F AF Bosticardo, Marita Ghosh, Amrita Du, Yang Jenkins, Nancy A. Copeland, Neal G. Candotti, Fabio TI Self-inactivating Retroviral Vector-mediated Gene Transfer Induces Oncogene Activation and Immortalization of Primary Murine Bone Marrow Cells SO MOLECULAR THERAPY LA English DT Article ID BIDIRECTIONAL TRANSCRIPTIONAL ACTIVITY; SEVERE COMBINED IMMUNODEFICIENCY; INSERTIONAL MUTAGENESIS; MOUSE MODEL; THERAPY; INTEGRATION; SCID-X1; MARKING; GENOTOXICITY; PROMOTER AB Insertional mutagenesis leading to insurgence of leukemia has been shown as a consequence of retroviral (RV)-mediated gene transfer in animal models and in clinical trials of gene therapy for X-linked severe combined immunodeficiency. Aberrant expression of oncogenes neighboring the gamma-RV vector insertion site via induction by the enhancer element of the viral long terminal repeats (LTRs) is thought to have played a role in leukemogenesis. Consequently, RV vectors devoid of LTR enhancer elements could prove as safer tools for gene transfer. To test this hypothesis, we evaluated the immortalization ability of two RV vectors: one carrying the full-length Moloney leukemia virus (MLV) LTR and one with the same LTR in which the enhancer element was deleted [MLV self-inactivating (SIN)]. Unexpectedly, transduction with MLV SIN resulted in an only slightly and not significant decreased immortalization frequency of primary bone marrow (BM) cultures (about 37%) compared to transduction with MLV (about 48%). Similar to MLV, immortalization by MLV SIN is likely caused by insertional activation of oncogenes including Evi1, Mds1, Mef2c, and Hoxa7. Our results indicate that the MLV SIN, devoid of the LTR enhancer element, was still able to immortalize BM cells by activating nearby gene expression, indicating the need of an accurate selection of the internal promoter to obtain safer SIN RV vectors. C1 [Candotti, Fabio] NHGRI, Disorders Immun Sect, GMBB, Bethesda, MD 20892 USA. [Du, Yang; Jenkins, Nancy A.; Copeland, Neal G.] NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21701 USA. [Du, Yang] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, GMBB, 49 Convent Dr,Bldg 49,Room 3A04, Bethesda, MD 20892 USA. EM fabio@mail.nih.gov FU NIH/NHGRI; NIH/NCI FX This work was funded in part by NIH/NHGRI and NIH/NCI, Center for Cancer Research, intramural funds. The authors have no conflicting financial interests. NR 32 TC 20 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2009 VL 17 IS 11 BP 1910 EP 1918 DI 10.1038/mt.2009.172 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 520HT UT WOS:000271835000012 PM 19638958 ER PT J AU Shamir, L AF Shamir, Lior TI Automatic morphological classification of galaxy images SO MONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY LA English DT Article DE methods: data analysis; techniques: image processing ID DIGITAL-SKY-SURVEY; FEATURES; ZOO AB We describe an image analysis supervised learning algorithm that can automatically classify galaxy images. The algorithm is first trained using manually classified images of elliptical, spiral and edge-on galaxies. A large set of image features is extracted from each image, and the most informative features are selected using Fisher scores. Test images can then be classified using a simple Weighted Nearest Neighbour rule such that the Fisher scores are used as the feature weights. Experimental results show that galaxy images from Galaxy Zoo can be classified automatically to spiral, elliptical and edge-on galaxies with an accuracy of similar to 90 per cent compared to classifications carried out by the author. Full compilable source code of the algorithm is available for free download, and its general-purpose nature makes it suitable for other uses that involve automatic image analysis of celestial objects. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Shamir, L (reprint author), NIA, Genet Lab, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM shamirl@mail.nih.gov FU Intramural Research Program of the NIH; National Institute on Aging; Alfred P. Sloan Foundation; National Science Foundation; US Department of Energy; National Aeronautics and Space Administration; Japanese Monbukagakusho; Max Planck Society; Higher Education Funding Council for England FX The SDSS is managed by the Astrophysical Research Consortium for the Participating Institutions. The Participating Institutions are the American Museum of Natural History, Astrophysical Institute Potsdam, University of Basel, University of Cambridge, Case Western Reserve University, University of Chicago, Drexel University, Fermilab, the Institute for Advanced Study, the Japan Participation Group, Johns Hopkins University, the Joint Institute for Nuclear Astrophysics, the Kavli Institute for Particle Astrophysics and Cosmology, the Korean Scientist Group, the Chinese Academy of Sciences (LAMOST), Los Alamos National Laboratory, the Max Planck Institute for Astronomy, the Max Planck Institute for Astrophysics, New Mexico State University, Ohio State University, University of Pittsburgh, University of Portsmouth, Princeton University, the United States Naval Observatory and the University of Washington. NR 15 TC 23 Z9 23 U1 1 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-8711 J9 MON NOT R ASTRON SOC JI Mon. Not. Roy. Astron. Soc. PD NOV 1 PY 2009 VL 399 IS 3 BP 1367 EP 1372 DI 10.1111/j.1365-2966.2009.15366.x PG 6 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 508BP UT WOS:000270902100021 PM 20161594 ER PT J AU Jacobson, S AF Jacobson, Steven TI Role of human herpesviruses in multiple sclerosis SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 14th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/Cons ortium-for-Multiple-Sclerosis-Centers CY MAY 27-30, 2009 CL Atlanta, GA SP Amer Comm Treatment & Res Multiple Sclerosis, Consortium Multiple Sclerosis Ctr C1 [Jacobson, Steven] NIH, Viral Immunol Sect, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD NOV PY 2009 VL 15 IS 11 BP 1388 EP 1389 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 516IU UT WOS:000271536400025 ER PT J AU Nelson, F Cofield, SS Conwit, R Narayana, PA Cutter, GR Lublin, FD Wolinsky, JS AF Nelson, Flavia Cofield, Stacey S. Conwit, Robin Narayana, Ponnada A. Cutter, Gary R. Lublin, Fred D. Wolinsky, Jerry S. CA CombiRx Investigators TI Magnetic resonance imaging characteristics of the CombiRx cohort at baseline SO MULTIPLE SCLEROSIS LA English DT Meeting Abstract CT 14th Annual Meeting of the Americas-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis/Cons ortium-for-Multiple-Sclerosis-Centers CY MAY 27-30, 2009 CL Atlanta, GA SP Amer Comm Treatment & Res Multiple Sclerosis, Consortium Multiple Sclerosis Ctr C1 [Nelson, Flavia; Narayana, Ponnada A.] Univ Texas Med Sch Houston, Houston, TX USA. [Cofield, Stacey S.; Cutter, Gary R.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Conwit, Robin] NINDS, Bethesda, MD 20892 USA. [Lublin, Fred D.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Wolinsky, Jerry S.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD NOV PY 2009 VL 15 IS 11 BP 1405 EP 1405 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 516IU UT WOS:000271536400066 ER PT J AU Lehky, TJ Chen, CJ Di Prospero, NA Rhodes, LE Fischbeck, K Floeter, MK AF Lehky, Tanya J. Chen, Cheun Ju Di Prospero, Nicholas A. Rhodes, Lindsay E. Fischbeck, Kenneth Floeter, Mary Kay TI STANDARD AND MODIFIED STATISTICAL MUNE EVALUATIONS IN SPINAL-BULBAR MUSCULAR ATROPHY SO MUSCLE & NERVE LA English DT Article DE Spinal bulbar muscular atrophy; motor unit number estimations; motor neuron disease ID UNIT NUMBER ESTIMATION; TRIAL AB Motor unit number estimation (MUNE), a technique used in amyotrophic lateral sclerosis (ALS) clinical trials to quantitatively assess motor neuron loss, should also be valuable in assessing progression in spinal bulbar muscular atrophy (SBMA), an x-linked neuronopathy. In ALS, instability of single motor units (SMUP) prompted Shefner et al.(6) to modify the statistical MUNE method to exclude SMUPs <= 40 mu V. It is unknown if there is similar SMUP instability in the more chronic degenerative disease of SBMA. In this study the standard parameter of excluding SMUP < 10 mu V was compared with the exclusion of SMUP < 40 mu V in the calculation of the statistical MUNE. The mean statistical MUNE, using the standard method and the Shefner et al. method, was 60 +/- 21 to 47 +/- 23, respectively. Similar to ALS, SBMA showed an increased proportion (17%) of individual SMUPs <= 40 mu V compared to normal controls. In conclusion, excluding SMUPs <= 40 mu V from the statistical MUNE calculations is appropriate for SBMA subjects because their SMUP, characteristics are similar to ALS. Exclusion of the low-amplitude SMUPs reduces the calculated MUNE. Muscle Nerve 40: 809-814, 2009 C1 [Lehky, Tanya J.; Floeter, Mary Kay] NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. [Chen, Cheun Ju; Di Prospero, Nicholas A.; Rhodes, Lindsay E.; Fischbeck, Kenneth] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Lehky, TJ (reprint author), NINDS, EMG Sect, NIH, Bldg 10 Room 7-5680,10 Ctr Dr, Bethesda, MD 20892 USA. EM lehkyt@ninds.nih.gov FU Intramural Research Program of the NINDS; NIH FX Supported by the Intramural Research Program of the NINDS, NIH. We thank Barbara Lear for technical assistance. NR 11 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 2009 VL 40 IS 5 BP 809 EP 814 DI 10.1002/mus.21399 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 511OF UT WOS:000271174400007 PM 19670325 ER PT J AU Manjanatha, MG Shelton, SD Dobrovolsky, VN Shaddock, JG McGarrity, LG Twaddle, NW Moore, MM Mattison, DR Slikker, W Morris, SM AF Manjanatha, Mugimane G. Shelton, Sharon D. Dobrovolsky, Vasily N. Shaddock, Joseph G. McGarrity, Lynda G. Twaddle, Nathan W. Moore, Martha M. Mattison, Donald R. Slikker, William, Jr. Morris, Suzanne M. TI Evaluation of mutagenic mode of action in Big Blue mice fed methylphenidate for 24 weeks SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Methylphenidate hydrochloride; Big Blue mice; cII mutant frequency; Micronucleus frequency; Hprt mutations ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TRANSGENIC MICE; CHILDREN; HYDROCHLORIDE; MUTATIONS; PHARMACOKINETICS; LYMPHOCYTES; SPECTRA; MONKEY; DAMAGE AB Methylphenidate hydrochloride (MPH), a widely prescribed pediatric drug for attention deficit hyperactivity disorder, induced liver adenocarcinomas in B6C3F1 mice exposed to 500 ppm in feed for 2 years (Dunnick and Hailey (1995) [14]). In order to determine if the induction of liver tumors was by a mutagenic mode of action, groups of male Big Blue (BB) mice (B6C3F1 background) were fed diets containing 50-4000 ppm MPH for 4, 12, or 24 weeks. At sacrifice, the livers were removed and the cII mutant frequency (MF) and spectrum of cII mutations were determined. In addition, the frequencies of micronucleated reticulocytes (MN-RETs) and normochromatic erythrocytes (MN-NCEs) were measured in peripheral blood erythrocytes as was the Hprt MF in splenic lymphocytes. Food consumption and body weight gain/loss were recorded weekly for each animal. The levels of MPH and RA were determined immediately before sacrifice in the serum of mice fed MPH for 24 weeks. A significant loss in body weights (p <= 0.01) was found in mice fed the 2000 and 4000 ppm doses of MPH; however, there was no significant difference in the food consumption by any of the MPH-treated groups. The average liver cII MF in control animals was 20 +/- 4.5 x 10(-6) where as in MPH-treated animals, the average cII MFs ranged between 20 +/- 2.5 and 32 +/- 6.7 x 10(-6). None of the cII MFs in livers from any of the MPH treatment was significantly higher than the concurrent controls at either 4, 12 or 24 weeks. Further, there was no significant increase in either the Hprt MF or the micronucleus frequency at any time point in the treated animals. These results suggest that MPH is not mutagenic in mice and that the induction of tumors as previously reported in the liver is probably through a nongenotoxic mode of action. Published by Elsevier B.V. C1 [Manjanatha, Mugimane G.; Shelton, Sharon D.; Dobrovolsky, Vasily N.; Shaddock, Joseph G.; McGarrity, Lynda G.; Moore, Martha M.; Morris, Suzanne M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Twaddle, Nathan W.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. [Mattison, Donald R.] NICHD, NIH, Bethesda, MD 20892 USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Mugimane.manjanatha@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU InterAgency Agreement between NICHD/NIH; NCTR/FDA FX All work was funded by an InterAgency Agreement between NICHD/NIH and NCTR/FDA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD NOV-DEC PY 2009 VL 680 IS 1-2 BP 43 EP 48 DI 10.1016/j.mrgentox.2009.09.004 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 534DK UT WOS:000272875500007 PM 19778631 ER PT J AU Fuller, CW Middendorf, LR Benner, SA Church, GM Harris, T Huang, XH Jovanovich, SB Nelson, JR Schloss, JA Schwartz, DC Vezenov, DV AF Fuller, Carl W. Middendorf, Lyle R. Benner, Steven A. Church, George M. Harris, Timothy Huang, Xiaohua Jovanovich, Stevan B. Nelson, John R. Schloss, Jeffery A. Schwartz, David C. Vezenov, Dmitri V. TI The challenges of sequencing by synthesis SO NATURE BIOTECHNOLOGY LA English DT Review ID PHOSPHATE-LABELED NUCLEOTIDES; ESTIMATING DETECTION LIMITS; ROLLING-CIRCLE AMPLIFICATION; SINGLE DNA-MOLECULES; REVERSIBLE TERMINATORS; ULTRATRACE ANALYSIS; REAL-TIME; FLUORESCENT NUCLEOTIDES; POLYMERASE MOLECULES; PHYSICAL LIMITS AB DNA sequencing-by-synthesis (SBS) technology, using a polymerase or ligase enzyme as its core biochemistry, has already been incorporated in several second-generation DNA sequencing systems with significant performance. Notwithstanding the substantial success of these SBS platforms, challenges continue to limit the ability to reduce the cost of sequencing a human genome to $ 100,000 or less. Achieving dramatically reduced cost with enhanced throughput and quality will require the seamless integration of scientific and technological effort across disciplines within biochemistry, chemistry, physics and engineering. The challenges include sample preparation, surface chemistry, fluorescent labels, optimizing the enzyme-substrate system, optics, instrumentation, understanding tradeoffs of throughput versus accuracy, and read-length/phasing limitations. By framing these challenges in a manner accessible to a broad community of scientists and engineers, we hope to solicit input from the broader research community on means of accelerating the advancement of genome sequencing technology. C1 [Fuller, Carl W.] GE Healthcare Life Sci, Piscataway, NJ USA. [Middendorf, Lyle R.] LI COR, Lincoln, NE USA. [Benner, Steven A.] Fdn Appl Mol Evolut, Alachua, FL USA. [Church, George M.] Harvard Univ, Sch Med, Boston, MA USA. [Harris, Timothy] Howard Hughes Med Inst, Ashburn, VA USA. [Huang, Xiaohua] Univ Calif San Diego, La Jolla, CA 92093 USA. [Jovanovich, Stevan B.] Microchip Biotechnol Inc, Dublin, CA USA. [Nelson, John R.] Gen Elect Global Res Ctr, Niskayuna, NY USA. [Schloss, Jeffery A.] NHGRI, NIH, Bethesda, MD 20892 USA. [Schwartz, David C.] Univ Wisconsin, Madison, WI USA. [Vezenov, Dmitri V.] Lehigh Univ, Bethlehem, PA 18015 USA. RP Fuller, CW (reprint author), GE Healthcare Life Sci, Piscataway, NJ USA. EM carl.fuller@alumni.upenn.edu RI xu, tao/K-6631-2016 FU National Human Genome Research Institute; National Institutes of Health FX This work was supported in part by the National Human Genome Research Institute, National Institutes of Health. NR 110 TC 101 Z9 106 U1 6 U2 78 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2009 VL 27 IS 11 BP 1013 EP 1023 DI 10.1038/nbt.1585 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 516EM UT WOS:000271524700022 PM 19898456 ER PT J AU Pechhold, S Stouffer, M Walker, G Martel, R Seligmann, B Hang, Y Stein, R Harlan, DM Pechhold, K AF Pechhold, Susanne Stouffer, Melissa Walker, Gregory Martel, Ralph Seligmann, Bruce Hang, Yan Stein, Roland Harlan, David M. Pechhold, Klaus TI Transcriptional analysis of intracytoplasmically stained, FACS-purified cells by high-throughput, quantitative nuclease protection SO NATURE BIOTECHNOLOGY LA English DT Article ID BETA-CELLS; ALPHA-CELLS; INSULIN-SECRETION; GENE-EXPRESSION; MOUSE; PANCREAS; ISLETS; MAFA; DIFFERENTIATION; PROLIFERATION AB Analyzing specialized cells in heterogeneous tissues is crucial for understanding organ function in health and disease. Thus far, however, there has been no convenient method for studying gene expression in cells purified by fluorescence-activated cell sorting (FACS) using intracellular markers. Here we show that the quantitative nuclease protection assay (qNPA) enables transcriptional analysis of intracytoplasmically stained cells sorted by FACS. Applying the method to mouse pancreatic islet-cell subsets, we detected both expected and unknown lineage-specific gene expression patterns. Some beta cells from pregnant animals were found to express Mafb, previously observed only in immature beta cells during embryonic development. The four 'housekeeping' genes tested were expressed in purified islet-cell subpopulations with a notable variability, dependent on both cell lineage and developmental stage. Application of qNPA to intracellularly stained, FACS-sorted cells should be broadly applicable to the analysis of gene expression in subpopulations of any heterogeneous tissue, including tumors. C1 [Pechhold, Susanne; Walker, Gregory; Harlan, David M.; Pechhold, Klaus] NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. [Stouffer, Melissa; Martel, Ralph; Seligmann, Bruce] High Throughput Genom Inc, Tucson, AZ USA. [Hang, Yan; Stein, Roland] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. RP Pechhold, K (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. EM KlausP@intra.NIDDK.NIH.gov FU US National Institutes of Health (NIH); National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK); NIH [DK042502]; Juvenile Diabetes Research Foundation [1-2008-595] FX The authors like to thank A. Franks for mouse colony management and S. Wank, O. Gavrilova and L. Weinstein for critically reading the manuscript and making helpful suggestions. This research was supported in part by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), and NIH DK042502, Juvenile Diabetes Research Foundation 1-2008-595 to R. NR 30 TC 24 Z9 24 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2009 VL 27 IS 11 BP 1038 EP U106 DI 10.1038/nbt.1579 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 516EM UT WOS:000271524700025 PM 19838197 ER PT J AU Veith, H Southall, N Huang, RL James, T Fayne, D Artemenko, N Shen, M Inglese, J Austin, CP Lloyd, DG Auld, DS AF Veith, Henrike Southall, Noel Huang, Ruili James, Tim Fayne, Darren Artemenko, Natalia Shen, Min Inglese, James Austin, Christopher P. Lloyd, David G. Auld, Douglas S. TI Comprehensive characterization of cytochrome P450 isozyme selectivity across chemical libraries SO NATURE BIOTECHNOLOGY LA English DT Article ID IN-VITRO INHIBITION; DRUG-LIKE PROPERTIES; LIVER-MICROSOMES; STATISTICAL PARAMETER; PROBE SELECTION; CYP ENZYMES; ASSAYS; DISCOVERY; P450; IDENTIFICATION AB The cytochrome P450 (CYP) gene family catalyzes drug metabolism and bioactivation and is therefore relevant to drug development. We determined potency values for 17,143 compounds against five recombinant CYP isozymes (1A2, 2C9, 2C19, 2D6 and 3A4) using an in vitro bioluminescent assay. The compounds included libraries of US Food and Drug Administration (FDA)-approved drugs and screening libraries. We observed cross-library isozyme inhibition (30-78%) with important differences between libraries. Whereas only 7% of the typical screening library was inactive against all five isozymes, 33% of FDA-approved drugs were inactive, reflecting the optimized pharmacological properties of the latter. Our results suggest that low CYP 2C isozyme activity is a common property of drugs, whereas other isozymes, such as CYP 2D6, show little discrimination between drugs and unoptimized compounds found in screening libraries. We also identified chemical substructures that differentiated between the five isozymes. The pharmacological compendium described here should further the understanding of CYP isozymes. C1 [Veith, Henrike; Southall, Noel; Huang, Ruili; Shen, Min; Inglese, James; Austin, Christopher P.; Auld, Douglas S.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [James, Tim; Fayne, Darren; Artemenko, Natalia; Lloyd, David G.] Trinity Coll Dublin, Sch Biochem & Immunol, Mol Design Grp, Dublin, Ireland. RP Auld, DS (reprint author), NIH, Chem Genom Ctr, Bldg 10, Bethesda, MD 20892 USA. EM dauld@mail.nih.gov RI Southall, Noel/H-8991-2012; Lloyd, David/E-9152-2013; OI Southall, Noel/0000-0003-4500-880X; Lloyd, David/0000-0003-0658-8995; Fayne, Darren/0000-0003-2417-5406 FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; National Human Genome Research Institute; Enterprise Ireland; Chemical Computing Group; OpenEye Scientific; Accelrys FX This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research and the Intramural Research Program of the National Human Genome Research Institute. Work in Trinity College Dublin was supported by Enterprise Ireland, the Chemical Computing Group, OpenEye Scientific and Accelrys. We thank S. Jefferies and G. Carta for helpful discussions, S. Michael and C. Klumpp for help with robotic automation of the assays and P. Shinn for preparation of compound dilutions and library plates. NR 50 TC 52 Z9 53 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2009 VL 27 IS 11 BP 1050 EP U123 DI 10.1038/nbt.1581 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 516EM UT WOS:000271524700027 PM 19855396 ER PT J AU Tuduri, S Crabbe, L Conti, C Tourriere, H Holtgreve-Grez, H Jauch, A Pantesco, V De Vos, J Thomas, A Theillet, C Pommier, Y Tazi, J Coquelle, A Pasero, P AF Tuduri, Sandie Crabbe, Laure Conti, Chiara Tourriere, Helene Holtgreve-Grez, Heidi Jauch, Anna Pantesco, Veronique De Vos, John Thomas, Aubin Theillet, Charles Pommier, Yves Tazi, Jamal Coquelle, Arnaud Pasero, Philippe TI Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription SO NATURE CELL BIOLOGY LA English DT Article ID SPLICING FACTOR ASF/SF2; MAMMALIAN-CELLS; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; FORK PROGRESSION; FRAGILE SITES; SR PROTEINS; ORIGIN CHOICE; PHOSPHORYLATION; DAMAGE AB Topoisomerase I (Top1) is a key enzyme in functioning at the interface between DNA replication, transcription and mRNA maturation. Here, we show that Top1 suppresses genomic instability in mammalian cells by preventing a conflict between transcription and DNA replication. Using DNA combing and ChIP (chromatin immunoprecipitation)-on-chip, we found that Top1-deficient cells accumulate stalled replication forks and chromosome breaks in S phase, and that breaks occur preferentially at gene-rich regions of the genome. Notably, these phenotypes were suppressed by preventing the formation of RNA-DNA hybrids (R-loops) during transcription. Moreover, these defects could be mimicked by depletion of the splicing factor ASF/SF2 (alternative splicing factor/splicing factor 2), which interacts functionally with Top1. Taken together, these data indicate that Top1 prevents replication fork collapse by suppressing the formation of R-loops in an ASF/SF2-dependent manner. We propose that interference between replication and transcription represents a major source of spontaneous replication stress, which could drive genomic instability during the early stages of tumorigenesis. C1 [Tuduri, Sandie; Theillet, Charles; Coquelle, Arnaud] Univ Montpellier 1, IRCM, INSERM, CRLC Val Aurelle Paul Lamarque,U896, F-34298 Montpellier, France. [Tuduri, Sandie; Crabbe, Laure; Tourriere, Helene; Thomas, Aubin; Pasero, Philippe] CNRS, Inst Human Genet, UPR1142, F-34396 Montpellier, France. [Conti, Chiara; Pommier, Yves] NIH, Mol Pharmacol Lab, Bethesda, MD 20892 USA. [Holtgreve-Grez, Heidi; Jauch, Anna] Univ Heidelberg Hosp, Inst Human Genet, D-69120 Heidelberg, Germany. [Pantesco, Veronique; De Vos, John] INSERM, U847, F-34000 Montpellier, France. [Pantesco, Veronique; De Vos, John] CHU Montpellier, Inst Rech Biotherapie, Hop St Eloi, F-34000 Montpellier, France. [Pantesco, Veronique; De Vos, John] Univ Montpellier 1, F-34000 Montpellier, France. [Tazi, Jamal] CNRS, Inst Mol Genet, UMR5535, F-34293 Montpellier, France. RP Coquelle, A (reprint author), Univ Montpellier 1, IRCM, INSERM, CRLC Val Aurelle Paul Lamarque,U896, F-34298 Montpellier, France. EM arnaud.coquelle@inserm.fr; philippe.pasero@igh.cnrs.fr RI Crabbe, Laure/P-8955-2014; OI Tazi, Jamal/0000-0002-1949-8748; DE VOS, John/0000-0003-1880-4130 FU FRM (Equipe FRM); ANR; INCa; EMBO Young Investigator Programme; Ligue contre le cancer (Comite de l'Herault); ARC (Association pour la Recherche contre le Cancer); EMBO; CNRS FX We thank M. Debatisse and M. Mechali for discussions and critical comments on the manuscript, D. Durocher for communicating data before publication, J. Piette for his initial contribution to this project and E. Schwob and the DNA combing facility of Montpellier for providing silanized coverslips. Work in the P. P. laboratory is supported by FRM (Equipe FRM), ANR, INCa and the EMBO Young Investigator Programme. Work in the J. T. laboratory is supported by ANR. A. C. is supported by the Ligue contre le cancer (Comite de l'Herault), ARC (Association pour la Recherche contre le Cancer) and INCa. S. T., L. C. and H. T. were recipients of fellowships from ARC, EMBO and CNRS, respectively. NR 54 TC 157 Z9 160 U1 0 U2 31 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2009 VL 11 IS 11 BP 1315 EP U125 DI 10.1038/ncb1984 PG 23 WC Cell Biology SC Cell Biology GA 514WC UT WOS:000271425800011 PM 19838172 ER PT J AU Boehr, DD Nussinov, R Wright, PE AF Boehr, David D. Nussinov, Ruth Wright, Peter E. TI The role of dynamic conformational ensembles in biomolecular recognition SO NATURE CHEMICAL BIOLOGY LA English DT Article ID DIHYDROFOLATE-REDUCTASE CATALYSIS; RESIDUAL DIPOLAR COUPLINGS; PROTEIN-PROTEIN DOCKING; MOLECULAR RECOGNITION; ASPARTATE TRANSCARBAMOYLASE; LIGAND-BINDING; CONFORMER SELECTION; ENERGY LANDSCAPES; INTRINSIC MOTIONS; FOLDING FUNNELS AB Molecular recognition is central to all biological processes. For the past 50 years, Koshland's 'induced fit' hypothesis has been the textbook explanation for molecular recognition events. However, recent experimental evidence supports an alternative mechanism. 'Conformational selection' postulates that all protein conformations pre-exist, and the ligand selects the most favored conformation. Following binding the ensemble undergoes a population shift, redistributing the conformational states. Both conformational selection and induced fit appear to play roles. Following binding by a primary conformational selection event, optimization of side chain and backbone interactions is likely to proceed by an induced fit mechanism. Conformational selection has been observed for protein-ligand, protein-protein, protein-DNA, protein-RNA and RNA-ligand interactions. These data support a new molecular recognition paradigm for processes as diverse as signaling, catalysis, gene regulation and protein aggregation in disease, which has the potential to significantly impact our views and strategies in drug design, biomolecular engineering and molecular evolution. C1 [Wright, Peter E.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Wright, Peter E.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Boehr, David D.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA. [Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Wright, PE (reprint author), Scripps Res Inst, Dept Mol Biol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM ddb12@psu.edu; wright@scripps.edu RI Boehr, David/A-2068-2010; OI Wright, Peter/0000-0002-1368-0223 FU US National Institutes of Health (NIH) [GM75995, CA96865, N01-CO-12400]; Skaggs Institute for Chemical Biology; National Cancer Institute; Center for Cancer Research FX This work was supported by the US National Institutes of Health (NIH grants GM75995 and CA96865 to P.E.W.) and by the Skaggs Institute for Chemical Biology. This project has been funded in whole or in part with federal funds from the National Cancer Institute, NIH, under contract number 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. This research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 98 TC 805 Z9 810 U1 21 U2 254 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD NOV PY 2009 VL 5 IS 11 BP 789 EP 796 DI 10.1038/nchembio.232 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 508FQ UT WOS:000270915000007 PM 19841628 ER PT J AU Yang, XHR Ng, D Alcorta, DA Liebsch, NJ Sheridan, E Li, SF Goldstein, AM Parry, DM Kelley, MJ AF Yang, Xiaohong R. Ng, David Alcorta, David A. Liebsch, Norbert J. Sheridan, Eamonn Li, Sufeng Goldstein, Alisa M. Parry, Dilys M. Kelley, Michael J. TI T (brachyury) gene duplication confers major susceptibility to familial chordoma SO NATURE GENETICS LA English DT Article ID COPY-NUMBER VARIATION; GENOMIC REARRANGEMENTS; DISORDERS; PROTEIN; DISEASE; LOCUS AB Using high-resolution array-CGH, we identified unique duplications of a region on 6q27 in four multiplex families with at least three cases of chordoma, a cancer of presumed notochordal origin. The duplicated region contains only the T (brachyury) gene, which is important in notochord development and is expressed in most sporadic chordomas. Our findings highlight the value of screening for complex genomic rearrangements in searches for cancer-susceptibility genes. C1 [Yang, Xiaohong R.; Ng, David; Goldstein, Alisa M.; Parry, Dilys M.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Alcorta, David A.; Li, Sufeng; Kelley, Michael J.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Liebsch, Norbert J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sheridan, Eamonn] St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. [Li, Sufeng; Kelley, Michael J.] Durham Vet Affairs Med Ctr, Durham, NC USA. RP Parry, DM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM parryd@mail.nih.gov OI Kelley, Michael/0000-0001-9523-6080 FU US National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institutes of Health; Department of Veterans Affairs, Veterans Health Administration; Office of Research and Development, Biomedical Laboratory Research and Development program; Chordoma Foundation FX We thank D. Zametkin for her outstanding skills as a research nurse; G. M. Glenn and M. L. McMaster for their careful clinical evaluations of affected individuals and family members; N. J. Patronas for reviewing the MRIs; A. Bergen and S. Chanock for SNP genotyping; K. Haque and D. Maeder for technical assistance; and, especially, the affected individuals and their families for their participation. This work was supported by the intramural research program of the US National Cancer Institute, Division of Cancer Epidemiology and Genetics, National Institutes of Health; by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development program; and by a grant from the Chordoma Foundation (M. J. K.). NR 13 TC 104 Z9 111 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2009 VL 41 IS 11 BP 1176 EP 1178 DI 10.1038/ng.454 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 512KM UT WOS:000271247600008 PM 19801981 ER PT J AU Ganesh, SK Zakai, NA van Rooij, FJA Soranzo, N Smith, AV Nalls, MA Chen, MH Kottgen, A Glazer, NL Dehghan, A Kuhnel, B Aspelund, T Yang, Q Tanaka, T Jaffe, A Bis, JCM Verwoert, GC Teumer, A Fox, CS Guralnik, JM Ehret, GB Rice, K Felix, JF Rendon, A Eiriksdottir, G Levy, D Patel, KV Boerwinkle, E Rotter, JI Hofman, A Sambrook, JG Hernandez, DG Zheng, G Bandinelli, S Singleton, AB Coresh, J Lumley, T Uitterlinden, AG vanGils, JM Launer, LJ Cupples, LA Oostra, BA Zwaginga, JJ Ouwehand, WH Thein, SL Meisinger, C Deloukas, P Nauck, M Spector, TD Gieger, C Gudnason, V van Duijn, CM Psaty, BM Ferrucci, L Chakravarti, A Greinacher, A O'Donnell, CJ Witteman, JCM Furth, S Cushman, M Harris, TB Lin, JP AF Ganesh, Santhi K. Zakai, Neil A. van Rooij, Frank J. A. Soranzo, Nicole Smith, Albert V. Nalls, Michael A. Chen, Ming-Huei Kottgen, Anna Glazer, Nicole L. Dehghan, Abbas Kuhnel, Brigitte Aspelund, Thor Yang, Qiong Tanaka, Toshiko Jaffe, Andrew Bis, Joshua C. M. Verwoert, Germaine C. Teumer, Alexander Fox, Caroline S. Guralnik, Jack M. Ehret, Georg B. Rice, Kenneth Felix, Janine F. Rendon, Augusto Eiriksdottir, Gudny Levy, Daniel Patel, Kushang V. Boerwinkle, Eric Rotter, Jerome I. Hofman, Albert Sambrook, Jennifer G. Hernandez, Dena G. Zheng, Gang Bandinelli, Stefania Singleton, Andrew B. Coresh, Josef Lumley, Thomas Uitterlinden, Andre G. vanGils, Janine M. Launer, Lenore J. Cupples, L. Adrienne Oostra, Ben A. Zwaginga, Jaap-Jan Ouwehand, Willem H. Thein, Swee-Lay Meisinger, Christa Deloukas, Panos Nauck, Matthias Spector, Tim D. Gieger, Christian Gudnason, Vilmundur van Duijn, Cornelia M. Psaty, Bruce M. Ferrucci, Luigi Chakravarti, Aravinda Greinacher, Andreas O'Donnell, Christopher J. Witteman, Jacqueline C. M. Furth, Susan Cushman, Mary Harris, Tamara B. Lin, Jing-Ping TI Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; HEMOGLOBIN CONCENTRATION; HEMOCHROMATOSIS GENE; HEREDITARY HEMOCHROMATOSIS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; FETAL-HEMOGLOBIN; CELIAC-DISEASE; C-MYB AB Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell count (RBC). We performed an initial GWAS in cohorts of the CHARGE Consortium totaling 24,167 individuals of European ancestry and replication in additional independent cohorts of the HaemGen Consortium totaling 9,456 individuals. We identified 23 loci significantly associated with these traits in a meta-analysis of the discovery and replication cohorts (combined P values ranging from 5 x 10(-8) to 7 x 10(-86)). Our findings include loci previously associated with these traits (HBS1L-MYB, HFE, TMPRSS6, TFR2, SPTA1) as well as new associations (EPO, TFRC, SH2B3 and 15 other loci). This study has identified new determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures. C1 [Ganesh, Santhi K.] NHGRI, Div Intramural Res, Bethesda, MD 20892 USA. [Ganesh, Santhi K.; Fox, Caroline S.; Levy, Daniel] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Ganesh, Santhi K.; Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Zakai, Neil A.; Cushman, Mary] Univ Vermont, Dept Med, Burlington, VT USA. [Zakai, Neil A.; Cushman, Mary] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. [van Rooij, Frank J. A.; Dehghan, Abbas; Verwoert, Germaine C.; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Rooij, Frank J. A.; Dehghan, Abbas; Verwoert, Germaine C.; Felix, Janine F.; Hofman, Albert; Uitterlinden, Andre G.; Oostra, Ben A.; van Duijn, Cornelia M.; Witteman, Jacqueline C. M.] NCHA, NGI, Leiden, Netherlands. [Soranzo, Nicole; Ouwehand, Willem H.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England. [Soranzo, Nicole; Cupples, L. Adrienne; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Hernandez, Dena G.] NIA, Intramural Res Program, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Chen, Ming-Huei; Yang, Qiong; Fox, Caroline S.; Levy, Daniel; Cupples, L. Adrienne; O'Donnell, Christopher J.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Kottgen, Anna; Jaffe, Andrew; Coresh, Josef] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Glazer, Nicole L.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA. [Glazer, Nicole L.; Bis, Joshua C. M.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Kuhnel, Brigitte; Meisinger, Christa; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. [Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Tanaka, Toshiko] MedStar Res Inst, Hyattsville, MD USA. [Verwoert, Germaine C.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Guralnik, Jack M.; Patel, Kushang V.; Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Ehret, Georg B.] Univ Hosp Geneva, Ctr Cardiol, Geneva, Switzerland. [Rice, Kenneth; Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Rendon, Augusto; Sambrook, Jennifer G.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Rendon, Augusto; Sambrook, Jennifer G.; Ouwehand, Willem H.] Natl Hlth Serv Blood & Transplant, Cambridge, England. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Zheng, Gang; Lin, Jing-Ping] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Bandinelli, Stefania] Geriatr Unit ASF, Florence, Italy. [Uitterlinden, Andre G.] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands. [Zwaginga, Jaap-Jan] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Zwaginga, Jaap-Jan] Sanquin Res, Dept Expt Immunohematol, Amsterdam, Netherlands. [Thein, Swee-Lay] Kings Coll London, Dept Haematol, London WC2R 2LS, England. [Nauck, Matthias] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem & Lab Med, Greifswald, Germany. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Greinacher, Andreas] Ernst Moritz Arndt Univ Greifswald, Inst Immunol & Transfus Med, Greifswald, Germany. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Furth, Susan] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. RP Ganesh, SK (reprint author), NHGRI, Div Intramural Res, Bethesda, MD 20892 USA. EM ganeshs@mail.nih.gov; odonnellc@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; EHRET, Georg/A-9532-2009; Kottgen, Anna/D-2920-2012; Spector, Tim/F-6533-2012; Rice, Kenneth/A-4150-2013; Deloukas, Panos/B-2922-2013; Meisinger, Christine/B-5358-2014; Yang, Qiong/G-5438-2014; Gudnason, Vilmundur/K-6885-2015; Smith, Albert/K-5150-2015; OI Felix, Janine/0000-0002-9801-5774; Rendon, Augusto/0000-0001-8994-0039; Soranzo, Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554; Meisinger, Christa/0000-0002-9026-6544; Dehghan, Abbas/0000-0001-6403-016X; Aspelund, Thor/0000-0002-7998-5433; EHRET, Georg/0000-0002-5730-0675; Rice, Kenneth/0000-0001-5779-4495; Deloukas, Panos/0000-0001-9251-070X; Gudnason, Vilmundur/0000-0001-5696-0084; Smith, Albert/0000-0003-1942-5845; Cupples, L. Adrienne/0000-0003-0273-7965 FU Medical Research Council [G0000111]; NHLBI NIH HHS [R01 HL086694, R01 HL086694-01A1, R01 HL086694-02, R01 HL086694-03]; NIDDK NIH HHS [K24 DK078737, P30 DK063491, P30 DK063491-019004, P30 DK063491-029004, P30 DK063491-039004, P30 DK063491-049004, P30 DK063491-05, U01 DK066174] NR 65 TC 190 Z9 196 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2009 VL 41 IS 11 BP 1191 EP U48 DI 10.1038/ng.466 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 512KM UT WOS:000271247600011 PM 19862010 ER PT J AU McCarthy, SE Makarov, V Kirov, G Addington, AM McClellan, J Yoon, S Perkins, DO Dickel, DE Kusenda, M Krastoshevsky, O Krause, V Kumar, RA Grozeva, D Malhotra, D Walsh, T Zackai, EH Kaplan, P Ganesh, J Krantz, ID Spinner, NB Roccanova, P Bhandari, A Pavon, K Lakshmi, B Leotta, A Kendall, J Lee, YH Vacic, V Gary, S Iakoucheva, LM Crow, TJ Christian, SL Lieberman, JA Stroup, TS Lehtimaki, T Puura, K Haldeman-Englert, C Pearl, J Goodell, M Willour, VL DeRosse, P Steele, J Kassem, L Wolff, J Chitkara, N McMahon, FJ Malhotra, AK Potash, JB Schulze, TG Nothen, MM Cichon, S Rietschel, M Leibenluft, E Kustanovich, V Lajonchere, CM Sutcliffe, JS Skuse, D Gill, M Gallagher, L Mendell, NR Craddock, N Owen, MJ O'Donovan, MC Shaikh, TH Susser, E DeLisi, LE Sullivan, PF Deutsch, CK Rapoport, J Levy, DL King, MC Sebat, J AF McCarthy, Shane E. Makarov, Vladimir Kirov, George Addington, Anjene M. McClellan, Jon Yoon, Seungtai Perkins, Diana O. Dickel, Diane E. Kusenda, Mary Krastoshevsky, Olga Krause, Verena Kumar, Ravinesh A. Grozeva, Detelina Malhotra, Dheeraj Walsh, Tom Zackai, Elaine H. Kaplan, Paige Ganesh, Jaya Krantz, Ian D. Spinner, Nancy B. Roccanova, Patricia Bhandari, Abhishek Pavon, Kevin Lakshmi, B. Leotta, Anthony Kendall, Jude Lee, Yoon-ha Vacic, Vladimir Gary, Sydney Iakoucheva, Lilia M. Crow, Timothy J. Christian, Susan L. Lieberman, Jeffrey A. Stroup, T. Scott Lehtimaki, Terho Puura, Kaija Haldeman-Englert, Chad Pearl, Justin Goodell, Meredith Willour, Virginia L. DeRosse, Pamela Steele, Jo Kassem, Layla Wolff, Jessica Chitkara, Nisha McMahon, Francis J. Malhotra, Anil K. Potash, James B. Schulze, Thomas G. Noethen, Markus M. Cichon, Sven Rietschel, Marcella Leibenluft, Ellen Kustanovich, Vlad Lajonchere, Clara M. Sutcliffe, James S. Skuse, David Gill, Michael Gallagher, Louise Mendell, Nancy R. Craddock, Nick Owen, Michael J. O'Donovan, Michael C. Shaikh, Tamim H. Susser, Ezra DeLisi, Lynn E. Sullivan, Patrick F. Deutsch, Curtis K. Rapoport, Judith Levy, Deborah L. King, Mary-Claire Sebat, Jonathan CA Wellcome Trust Case Control Consor TI Microduplications of 16p11.2 are associated with schizophrenia SO NATURE GENETICS LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; AUTISM SPECTRUM DISORDER; HEAD CIRCUMFERENCE; RECURRENT REARRANGEMENTS; HUMAN GENOME; 1ST YEAR; INDIVIDUALS; DISRUPTION; DELETIONS; GENES AB Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders(1-3). We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 x 10(-5), OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 x 10(-7)), bipolar disorder (P = 0.017) and autism (P = 1.9 x 10(-7)). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 x 10(-13)). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007). C1 [McCarthy, Shane E.; Makarov, Vladimir; Yoon, Seungtai; Kusenda, Mary; Malhotra, Dheeraj; Roccanova, Patricia; Bhandari, Abhishek; Pavon, Kevin; Lakshmi, B.; Leotta, Anthony; Kendall, Jude; Lee, Yoon-ha; Vacic, Vladimir; Gary, Sydney; Sebat, Jonathan] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Kirov, George; Grozeva, Detelina; Craddock, Nick; Owen, Michael J.; O'Donovan, Michael C.] Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales. [Addington, Anjene M.; Rapoport, Judith] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [McClellan, Jon] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Dickel, Diane E.; Walsh, Tom; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Kusenda, Mary] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA. [Krastoshevsky, Olga; Krause, Verena; Levy, Deborah L.] McLean Hosp, Psychol Res Lab, Belmont, MA 02178 USA. [Kumar, Ravinesh A.; Christian, Susan L.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Zackai, Elaine H.; Krantz, Ian D.; Spinner, Nancy B.; Haldeman-Englert, Chad; Shaikh, Tamim H.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [Kaplan, Paige; Ganesh, Jaya] Childrens Hosp Philadelphia, Sect Biochem Genet, Philadelphia, PA 19104 USA. [Lakshmi, B.] Ontario Inst Canc Res, Toronto, ON, Canada. [Iakoucheva, Lilia M.] Rockefeller Univ, Lab Stat Genet, New York, NY 10021 USA. [Crow, Timothy J.] Warneford Hosp, Prince Wales Int Ctr SANE Res, Oxford OX3 7JX, England. [Lieberman, Jeffrey A.; Stroup, T. Scott; Susser, Ezra] Columbia Univ, Columbia Univ Coll Phys & Surg, New York, NY USA. [Lieberman, Jeffrey A.] New York State Psychiat Hosp, New York, NY USA. [Lehtimaki, Terho] Tampere Univ, Dept Clin Chem, FIN-33101 Tampere, Finland. [Puura, Kaija] Tampere Univ, Dept Child Psychiat, FIN-33101 Tampere, Finland. [Puura, Kaija] Univ Hosp, Tampere, Finland. [Pearl, Justin; Steele, Jo; Kassem, Layla; Wolff, Jessica; McMahon, Francis J.; Schulze, Thomas G.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, NIH, Bethesda, MD 20892 USA. [Goodell, Meredith; Willour, Virginia L.; Potash, James B.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. [DeRosse, Pamela; Chitkara, Nisha; Malhotra, Anil K.] Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY USA. [Schulze, Thomas G.; Rietschel, Marcella] Heidelberg Univ, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-6800 Mannheim, Germany. [Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany. [Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany. [Rietschel, Marcella] Univ Bonn, Dept Psychiat & Psychotherapy, D-5300 Bonn, Germany. [Leibenluft, Ellen] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Kustanovich, Vlad; Lajonchere, Clara M.] Autism Speaks, Autism Genet Resource Exchange, Los Angeles, CA USA. [Sutcliffe, James S.] Vanderbilt Univ, Ctr Mol Neurosci, Nashville, TN USA. [Skuse, David] UCL, Behav Sci Unit, Inst Child Hlth, London, England. [Gill, Michael; Gallagher, Louise] Trinity Coll Dublin, Sch Med, Dept Psychiat, Dublin, Ireland. [Mendell, Nancy R.] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [DeLisi, Lynn E.; Deutsch, Curtis K.; Levy, Deborah L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [DeLisi, Lynn E.] VA Boston Healthcare Syst, Brockton, MA USA. [Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Deutsch, Curtis K.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Waltham, MA USA. RP Sebat, J (reprint author), Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA. EM sebat@cshl.edu RI Stroup, Thomas/F-9188-2014; turton, miranda/F-4682-2011; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Sutcliffe, James/C-1348-2012; OI Gallagher, Louise/0000-0001-9462-2836; Stroup, Thomas/0000-0002-3123-0672; Gill, Michael/0000-0003-0206-5337; Vacic, Vladimir/0000-0001-6571-2293; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Sutcliffe, James/0000-0001-5200-6007; Sebat, Jonathan/0000-0002-9087-526X; Walsh, Tom/0000-0002-8875-0310; O'Donovan, Michael/0000-0001-7073-2379; Iakoucheva, Lilia/0000-0002-4542-5219; McMahon, Francis/0000-0002-9469-305X; Dickel, Diane/0000-0001-5497-6824; Nothen, Markus/0000-0002-8770-2464 FU National Institute of Mental Health (NIMH) [R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469, U01 MH79470] FX Funding support for the genome-wide association of schizophrenia study was provided by the National Institute of Mental Health (NIMH) (R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800, U01 MH46276, U01 MH46289, U01 MH46318, U01 MH79469 and U01 MH79470), and the genotyping of samples was provided through the genetic association information network (GAIN). The datasets used for the analyses described in this manuscript were obtained from the database of genotype and phenotype (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000021.v2.p1. Samples and associated phenotype data for the genome-wide association of schizophrenia study were provided by the Molecular Genetics of Schizophrenia Collaboration (PI: P. V. Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, Illinois, USA). NR 41 TC 345 Z9 352 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 2009 VL 41 IS 11 BP 1223 EP U85 DI 10.1038/ng.474 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 512KM UT WOS:000271247600015 PM 19855392 ER PT J AU Mullighan, CG Collins-Underwood, JR Phillips, LAA Loudin, MG Liu, W Zhang, JH Ma, J Coustan-Smith, E Harvey, RC Willman, CL Mikhail, FM Meyer, J Carroll, AJ Williams, RT Cheng, JJ Heerema, NA Basso, G Pession, A Pui, CH Raimondi, SC Hunger, SP Downing, JR Carroll, WL Rabin, KR AF Mullighan, Charles G. Collins-Underwood, J. Racquel Phillips, Letha A. A. Loudin, Michael G. Liu, Wei Zhang, Jinghui Ma, Jing Coustan-Smith, Elaine Harvey, Richard C. Willman, Cheryl L. Mikhail, Fady M. Meyer, Julia Carroll, Andrew J. Williams, Richard T. Cheng, Jinjun Heerema, Nyla A. Basso, Giuseppe Pession, Andrea Pui, Ching-Hon Raimondi, Susana C. Hunger, Stephen P. Downing, James R. Carroll, William L. Rabin, Karen R. TI Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia SO NATURE GENETICS LA English DT Article ID THYMIC STROMAL LYMPHOPOIETIN; DOWN-SYNDROME; CELL DEVELOPMENT; COMPETING RISK; MUTATIONS; RECEPTOR; GENE; JAK2; EXPRESSION; CYTOKINE AB Aneuploidy and translocations are hallmarks of B-progenitor acute lymphoblastic leukemia (ALL), but many individuals with this cancer lack recurring chromosomal alterations. Here we report a recurring interstitial deletion of the pseudoautosomal region 1 of chromosomes X and Y in B-progenitor ALL that juxtaposes the first, noncoding exon of P2RY8 with the coding region of CRLF2. We identified the P2RY8-CRLF2 fusion in 7% of individuals with B-progenitor ALL and 53% of individuals with ALL associated with Down syndrome. CRLF2 alteration was associated with activating JAK mutations, and expression of human P2RY8-CRLF2 together with mutated mouse Jak2 resulted in constitutive Jak-Stat activation and cytokine-independent growth of Ba/F3 cells overexpressing interleukin-7 receptor alpha. Our findings indicate that these two genetic lesions together contribute to leukemogenesis in B-progenitor ALL. C1 [Mullighan, Charles G.; Collins-Underwood, J. Racquel; Phillips, Letha A. A.; Cheng, Jinjun; Raimondi, Susana C.; Downing, James R.] St Jude Childrens Hosp, Dept Pathol, Memphis, TN 38105 USA. [Loudin, Michael G.; Rabin, Karen R.] Baylor Coll Med, Dept Pediat, Hematol Oncol Sect, Houston, TX 77030 USA. [Liu, Wei] St Jude Childrens Hosp, Dept Biostat, Memphis, TN 38105 USA. [Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, NIH, Rockville, MD USA. [Ma, Jing] St Jude Childrens Hosp, Hartwell Ctr Bioinformat & Biotechnol, Memphis, TN 38105 USA. [Coustan-Smith, Elaine; Williams, Richard T.; Pui, Ching-Hon] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Harvey, Richard C.; Willman, Cheryl L.] Univ New Mexico, Canc Res Facil, Univ New Mexico Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. [Mikhail, Fady M.; Carroll, Andrew J.] Univ Alabama, Dept Genet, Birmingham, AL USA. [Meyer, Julia; Carroll, William L.] NYU, New York Univ Canc Inst, Langone Med Ctr, New York, NY USA. [Heerema, Nyla A.] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Dept Pathol, Columbus, OH 43210 USA. [Basso, Giuseppe] Univ Padua, Dept Pediat, Padua, Italy. [Pession, Andrea] Univ Bologna, Dept Pediat, Hematol & Oncol Unit Lalla Seragnoli, Bologna, Italy. [Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Childrens Hosp, Sect Pediat Hematol Oncol & Bone Marrow Transplan, Aurora, CO USA. [Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Childrens Hosp, Ctr Canc & Blood Disorders, Aurora, CO USA. RP Mullighan, CG (reprint author), St Jude Childrens Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM charles.mullighan@stjude.org OI Harvey, Richard/0000-0002-4904-9767; BASSO, GIUSEPPE/0000-0002-2634-9302; Mullighan, Charles/0000-0002-1871-1850 FU National Cancer Institute Cancer Center [P30 CA021765]; American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital; a Bear Necessities Pediatric Research Foundation; Children's Cancer Research Foundation; National Institutes of Health [CA90433-06] FX We thank M. Wang and D. Naeve (Functional Genomics Laboratory, Hartwell Center, St. Jude Children's Research Hospital) for conducting array-CGH analysis; E. Walker and J. Morris (CACT Laboratory, Hartwell Center) for conducting SNP microarrays; S. Tate, J. Armstrong and K. Rakestraw (St. Jude Hartwell Center Sequencing Core) for conducting sequencing; the St. Jude Flow Cytometry Core; John Gray and the St. Jude Vector Core for lentiviral reagents and methods; the St. Jude Tissue Resources Laboratory for providing primary patient samples; S. Nutt for providing the MSCV-mIL7R-IRES-hCD4 retroviral vector; G. P. Nolan, Stanford University, for the Eco Phoenix packaging cells (http://www.stanford.edu/group/nolan); and M. Smith and K. Dobbin for gene expression studies of CRLF2. This work was supported by National Cancer Institute Cancer Center Support Grant P30 CA021765, the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital, a Bear Necessities Pediatric Research Foundation grant (to K. R. R.), a Children's Cancer Research Foundation grant (to K. R. R.) and National Institutes of Health Pediatric Oncology Clinical Research Training Grant CA90433-06 (to K. R. R.). NR 33 TC 252 Z9 257 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2009 VL 41 IS 11 BP 1243 EP U111 DI 10.1038/ng.469 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 512KM UT WOS:000271247600019 PM 19838194 ER PT J AU Jacobs, KB Yeager, M Wacholder, S Craig, D Kraft, P Hunter, DJ Paschal, J Manolio, TA Tucker, M Hoover, RN Thomas, GD Chanock, SJ Chatterjee, N AF Jacobs, Kevin B. Yeager, Meredith Wacholder, Sholom Craig, David Kraft, Peter Hunter, David J. Paschal, Justin Manolio, Teri A. Tucker, Margaret Hoover, Robert N. Thomas, Gilles D. Chanock, Stephen J. Chatterjee, Nilanjan TI A new statistic and its power to infer membership in a genome-wide association study using genotype frequencies SO NATURE GENETICS LA English DT Article AB Aggregate results from genome-wide association studies (GWAS)(1-3), such as genotype frequencies for cases and controls, were until recently often made available on public websites(4,5) because they were thought to disclose negligible information concerning an individual's participation in a study. Homer et al.(6) recently suggested that a method for forensic detection of an individual's contribution to an admixed DNA sample could be applied to aggregate GWAS data. Using a likelihood-based statistical framework, we developed an improved statistic that uses genotype frequencies and individual genotypes to infer whether a specific individual or any close relatives participated in the GWAS and, if so, what the participant's phenotype status is. Our statistic compares the logarithm of genotype frequencies, in contrast to that of Homer et al.(6), which is based on differences in either SNP probe intensity or allele frequencies. We derive the theoretical power of our test statistics and explore the empirical performance in scenarios with varying numbers of randomly chosen or top-associated SNPs. C1 [Jacobs, Kevin B.; Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Jacobs, Kevin B.; Yeager, Meredith; Wacholder, Sholom; Tucker, Margaret; Hoover, Robert N.; Thomas, Gilles D.; Chanock, Stephen J.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Jacobs, Kevin B.] BioInformed LLC, Gaithersburg, MD USA. [Craig, David] Translat Genom Res Inst, Neurogenom Div, Phoenix, AZ USA. [Kraft, Peter; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. [Paschal, Justin] NHGRI, Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. [Manolio, Teri A.] NHGRI, Off Populat Genom, NIH, Bethesda, MD 20892 USA. RP Jacobs, KB (reprint author), NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. EM jacobske@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS [ZIC CP010178-08, ZIA CP010187-05] NR 6 TC 44 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2009 VL 41 IS 11 BP 1253 EP U126 DI 10.1038/ng.455 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 512KM UT WOS:000271247600021 PM 19801980 ER PT J AU Delker, RK Fugmann, SD Papavasiliou, FN AF Delker, Rebecca K. Fugmann, Sebastian D. Papavasiliou, F. Nina TI A coming-of-age story: activation-induced cytidine deaminase turns 10 SO NATURE IMMUNOLOGY LA English DT Review ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; ANTIBODY DIVERSIFICATION ENZYME; INDUCED CYTOSINE DEAMINASE; RNA EDITING ENZYME; HEAVY-CHAIN LOCUS; PROTEIN-KINASE-A; SOMATIC HYPERMUTATION; B-CELLS; IMMUNOGLOBULIN GENES AB The discovery and characterization of activation-induced cytidine deaminase (AID) 10 years ago provided the basis for a mechanistic understanding of secondary antibody diversification and the subsequent generation and maintenance of cellular memory in B lymphocytes, which signified a major advance in the field of B cell immunology. Here we celebrate and review the triumphs in the mission to understand the mechanisms through which AID influences antibody diversification, as well as the implications of AID function on human physiology. We also take time to point out important ongoing controversies and outstanding questions in the field and highlight key experiments and techniques that hold the potential to elucidate the remaining mysteries surrounding this vital protein. C1 [Delker, Rebecca K.; Papavasiliou, F. Nina] Rockefeller Univ, Lab Lymphocyte Biol, New York, NY 10021 USA. [Fugmann, Sebastian D.] NIA, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Papavasiliou, FN (reprint author), Rockefeller Univ, Lab Lymphocyte Biol, 1230 York Ave, New York, NY 10021 USA. EM papavasiliou@rockefeller.edu FU Department of Defense; US National Institutes of Health [CA098495]; National Institute on Aging of the National Institutes of Health FX Supported by the Department of Defense (R. K. D.), the US National Institutes of Health (CA098495 for AID-related work in the F. N. P. laboratory) and the Intramural Program of the National Institute on Aging of the National Institutes of Health (S. D. F.). NR 104 TC 68 Z9 72 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2009 VL 10 IS 11 BP 1147 EP 1153 DI 10.1038/ni.1799 PG 7 WC Immunology SC Immunology GA 508SO UT WOS:000270955900006 PM 19841648 ER PT J AU Chen, GL Subbarao, K AF Chen, Grace L. Subbarao, Kanta TI Attacking the flu Neutralizing antibodies may lead to 'universal' vaccine SO NATURE MEDICINE LA English DT Editorial Material ID INFLUENZA-A VIRUS; AVIAN INFLUENZA; UNITED-STATES; H5N1; EPITOPE; CELLS; HEMAGGLUTININS; H1; H2 AB Flu remains a major killer because of imperfect vaccines and widespread resistance to existing antivirals-problems particularly acute during a pandemic. New findings at the bedside and at the bench could lead to improvements on both fronts. Grace Chen and Kanta Subbarao discuss the implications of research identifying human antibodies than can neutralize a range of viral subtypes. The findings may help lead to a 'universal' vaccine against these diverse and rapidly evolving viruses. Estanislao Nistal-Villan and Adolfo Garcia-Sastre examine two recent studies that reveal the crystal structure of a promising viral drug target, the unique endonuclease domain of the viral polymerase. The findings open the door to the rational design of new influenza virus inhibitors. C1 [Chen, Grace L.; Subbarao, Kanta] NIAID, Infect Dis Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Chen, GL (reprint author), NIAID, Infect Dis Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000933-06] NR 13 TC 22 Z9 23 U1 0 U2 6 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 NOV PY 2009 VL 15 IS 11 BP 1251 EP 1252 DI 10.1038/nm1109-1251 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 516LM UT WOS:000271543700011 PM 19893556 ER PT J AU Liang, Y Vogel, JL Narayanan, A Peng, H Kristie, TM AF Liang, Yu Vogel, Jodi L. Narayanan, Aarthi Peng, Hua Kristie, Thomas M. TI Inhibition of the histone demethylase LSD1 blocks alpha-herpesvirus lytic replication and reactivation from latency SO NATURE MEDICINE LA English DT Article ID SIMPLEX-VIRUS TYPE-1; HOST-CELL FACTOR; GENE-EXPRESSION; ANDROGEN-RECEPTOR; DNA METHYLATION; SENSORY NEURONS; H3 LYSINE-4; EARLY TIMES; IN-VIVO; INFECTION AB Reversible methylation of histone tails serves as either a positive signal recognized by transcriptional assemblies or a negative signal that result in repression(1-4). Invading viral pathogens that depend upon the host cell's transcriptional apparatus are also subject to the regulatory impact of chromatin assembly and modifications(5-8). Here we show that infection by the alpha-herpesviruses, herpes simplex virus (HSV) and varicella zoster virus (VZV), results in the rapid accumulation of chromatin bearing repressive histone H3 Lys9 methylation. To enable expression of viral immediate early (IE) genes, both viruses use the cellular transcriptional coactivator host cell factor-1 (HCF-1) to recruit the lysine-specific demethylase-1 (LSD1) to the viral immediate early promoters. Depletion of LSD1 or inhibition of its activity with monoamine oxidase inhibitors (MAOIs) results in the accumulation of repressive chromatin and a block to viral gene expression. As HCF-1 is a component of the Set1 and MLL1 histone H3 Lys4 methyltransferase complexes(9,10), it thus coordinates modulation of repressive H3 Lys9 methylation levels with addition of activating H3 Lys4 trimethylation marks. Strikingly, MAOIs also block the reactivation of HSV from latency in sensory neurons, indicating that the HCF-1 complex is a crucial component of the reactivation mechanism. The results support pharmaceutical control of histone modifying enzymes as a strategy for controlling herpesvirus infections. C1 [Liang, Yu; Vogel, Jodi L.; Narayanan, Aarthi; Peng, Hua; Kristie, Thomas M.] NIAID, Mol Genet Sect, Viral Dis Lab, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kristie, TM (reprint author), NIAID, Mol Genet Sect, Viral Dis Lab, US Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM thomas_kristie@nih.gov FU Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health FX We thank J. Skinner for expert statistical analysis of the experimental data; B. Moss, J. Yewdell, T. Pierson, J. Bennink and A. McBride for critical discussions and comments on this manuscript; members of the Molecular Genetics Section of the Laboratory of Viral Diseases for discussion, advice and technical assistance; the US National Institute of Allergy and Infectious Diseases Bld33 Animal Care Facility staff; N. Fraser (University of Pennsylvania School of Medicine) for HSV-1 strain 17, W. Ruyechan (University at Buffalo, State University of New York) for ICP8-specific sera and X. Chen (University of California at Davis) for MCF7 inducible LSD shRNA cells. These studies were supported by the Laboratory of Viral Diseases, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health. NR 40 TC 124 Z9 127 U1 1 U2 10 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 NOV PY 2009 VL 15 IS 11 BP 1312 EP U112 DI 10.1038/nm.2051 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 516LM UT WOS:000271543700020 PM 19855399 ER PT J AU Wang, Y Cheong, CG Hall, TMT Wang, ZF AF Wang, Yang Cheong, Cheom-Gil Hall, Traci M. Tanaka Wang, Zefeng TI Engineering splicing factors with designed specificities SO NATURE METHODS LA English DT Article ID PRE-MESSENGER-RNA; BCL-X; HNRNP A1; IN-VIVO; ANTISENSE OLIGONUCLEOTIDES; REGULATORY ELEMENTS; GENE-EXPRESSION; CELL-DEATH; PROTEINS; SELECTION AB Alternative splicing is generally regulated by trans-acting factors that specifically bind pre-mRN A to activate or inhibit the splicing reaction. This regulation is critical for normal gene expression, and dysregulation of splicing is closely associated with human diseases. Here we engineered artificial splicing factors by combining sequence-specific RN A-binding domains of human Pumilio1 with functional domains that regulate splicing. We applied these factors to modulate different types of alternative splicing in selected targets, to examine the activity of effector domains from natural splicing factors and to modulate splicing of an endogenous human gene, Bcl-X, an anticancer target. The designer factor targeted to Bcl-X increased the amount of pro-apoptotic Bcl-xS splice isoform, thus promoting apoptosis and increasing chemosensitivity of cancer cells to common antitumor drugs. Our approach permitted the creation of artificial factors to target virtually any pre-mRN A, providing a strategy to study splicing regulation and to manipulate disease-associated splicing events. C1 [Wang, Yang; Wang, Zefeng] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. [Cheong, Cheom-Gil; Hall, Traci M. Tanaka] Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC USA. RP Wang, ZF (reprint author), Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27515 USA. EM zefeng@med.unc.edu RI Wang, Yang /A-1849-2010; OI Wang, Zefeng/0000-0002-6605-3637 FU Beckman Foundation; National Institutes of Health, National Institute of Environmental Health Sciences FX We thank C. Burge and our colleagues for critical reading of our manuscript. This work was supported by a grant from the Beckman Foundation (Z.W.) and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (T. M. T. H). NR 31 TC 66 Z9 67 U1 1 U2 9 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 NOV PY 2009 VL 6 IS 11 BP 825 EP U63 DI 10.1038/NMETH.1379 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 512KI UT WOS:000271247200016 PM 19801992 ER PT J AU Ryman-Rasmussen, JP Cesta, MF Brody, AR Shipley-Phillips, JK Everitt, JI Tewksbury, EW Moss, OR Wong, BA Dodd, DE Andersen, ME Bonner, JC AF Ryman-Rasmussen, Jessica P. Cesta, Mark F. Brody, Arnold R. Shipley-Phillips, Jeanette K. Everitt, Jeffrey I. Tewksbury, Earl W. Moss, Owen R. Wong, Brian A. Dodd, Darol E. Andersen, Melvin E. Bonner, James C. TI Inhaled carbon nanotubes reach the subpleural tissue in mice SO NATURE NANOTECHNOLOGY LA English DT Article ID INTRATRACHEAL INSTILLATION; DEPOSITION PATTERN; PULMONARY TOXICITY; ASBESTOS FIBERS; RAT LUNG; MESOTHELIOMA; INHALATION; EXPRESSION AB Carbon nanotubes are shaped like fibres(1) and can stimulate inflammation at the surface of the peritoneum when injected into the abdominal cavity of mice(2), raising concerns that inhaled nanotubes(3) may cause pleural fibrosis and/or mesothelioma(4). Here, we show that multiwalled carbon nanotubes reach the subpleura in mice after a single inhalation exposure of 30 mg m(-3) for 6 h. Nanotubes were embedded in the subpleural wall and within subpleural macrophages. Mononuclear cell aggregates on the pleural surface increased in number and size after 1 day and nanotube-containing macrophages were observed within these foci. Subpleural fibrosis unique to this form of nanotubes increased after 2 and 6 weeks following inhalation. None of these effects was seen in mice that inhaled carbon black nanoparticles or a lower dose of nanotubes (1 mg m(-3)). This work suggests that minimizing inhalation of nanotubes during handling is prudent until further long-term assessments are conducted. C1 [Ryman-Rasmussen, Jessica P.; Cesta, Mark F.; Bonner, James C.] N Carolina State Univ, Dept Environm & Mol Toxicol, Coll Agr & Life Sci, Raleigh, NC 27695 USA. [Ryman-Rasmussen, Jessica P.; Cesta, Mark F.; Tewksbury, Earl W.; Moss, Owen R.; Wong, Brian A.; Dodd, Darol E.; Andersen, Melvin E.] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA. [Cesta, Mark F.] NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. [Brody, Arnold R.] N Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27695 USA. [Shipley-Phillips, Jeanette K.; Everitt, Jeffrey I.] N Carolina State Univ, Dept Populat Hlth & Pathobiol, Coll Vet Med, Raleigh, NC 27695 USA. RP Bonner, JC (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Coll Agr & Life Sci, Raleigh, NC 27695 USA. EM james_bonner@ncsu.edu OI Andersen, Melvin/0000-0002-3894-4811; Everitt, Jeffrey/0000-0003-0273-6284 FU Hamner Institutes for Health Sciences; National Institutes of Environmental Health Sciences [R21-ES015801-01]; North Carolina State University College of Agricultural and Life Sciences; National Institutes of Health, National Institute of Environmental Health Sciences; ACS/LRRI FX This study was funded by the American Chemistry Council's Long Range Research Initiative provided to The Hamner Institutes for Health Sciences, The National Institutes of Environmental Health Sciences grant no. R21-ES015801-01, North Carolina State University College of Agricultural and Life Sciences, and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. ACS/LRRI provided funds only and played no role in study design, data gathering and interpretation, authoring of the manuscript, or decision to publish. Special thanks go to Betsy Gross-Bermudez and the pathology staff at The Hamner Institutes for excellent technical assistance, and to A. Taylor at NCSU for critical reading of the manuscript, NR 26 TC 223 Z9 227 U1 2 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 EI 1748-3395 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD NOV PY 2009 VL 4 IS 11 BP 747 EP 751 DI 10.1038/NNANO.2009.305 PG 5 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 528AW UT WOS:000272413500017 PM 19893520 ER PT J AU Bluestone, JA Mackay, CR O'Shea, JJ Stockinger, B AF Bluestone, Jeffrey A. Mackay, Charles R. O'Shea, John J. Stockinger, Brigitta TI The functional plasticity of T cell subsets SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID FOLLICULAR-HELPER-CELLS; ARYL-HYDROCARBON RECEPTOR; TH17 CELLS; IN-VIVO; INTERLEUKIN 22; CUTTING EDGE; TGF-BETA; DIFFERENTIATION; LINEAGE; GENERATION AB In 1986, Robert Coffman and Timothy Mossman first described the division of CD4(+) T cells into functional subsets, termed T helper 1 (T(H)1) and T(H)2, based on cytokine production, and in doing so unwittingly opened a Pandora's box of complexity and controversy. Although the mechanisms that regulate T(H)1 and T(H)2 cells are now well known, recent descriptions of other CD4(+) T cell subsets-such as regulatory T cells, T follicular helper cells, T(H)17, T(H)22 and most recently T(H)9 and T(H)22 cells-have questioned how we think of T cell subsets and what commitment to a functional T cell subset means. Here, Nature Reviews Immunology asks four leaders in the field their thoughts on the functional plasticity of T cell subsets. C1 [Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Bluestone, Jeffrey A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Mackay, Charles R.] Monash Univ, Fac Med, Nursing & Hlth Serv, Clayton, Vic 3800, Australia. [Mackay, Charles R.] Univ New S Wales, St Vincents Clin Sch, Sydney, NSW 2010, Australia. [Mackay, Charles R.] Univ New S Wales, Garvan Inst Med Res, Sydney, NSW 2010, Australia. [O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Stockinger, Brigitta] Natl Inst Med Res, MRC, Div Mol Immunol, London NW7 1AA, England. RP Bluestone, JA (reprint author), Univ Calif San Francisco, Ctr Diabet, 513 Parnassus Ave,Box 0540 HSW 1114, San Francisco, CA 94143 USA. EM jbluest@diabetes.ucsf.edu; charles.mackay@med.monash.edu.au; osheaj@arb.niams.nih.gov; bstocki@nimr.mrc.ac.uk RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU US National Institute of Health; Juvenile Diabetes Research Foundation; University of California; San Francisco Diabetes Center; National Health and Medical Research Council of Australia. FX J. J. O'S. would like to thank A. Laurence, L. Wei, V. Sartorelli, M. Gadina, R. Siegel and Y. e Belkaid for their lively discussion of this issue; however, I also wish to apologize to the members of my laboratory for taking so much time in lab meetings and journal clubs for endlessly debating this topic. NR 49 TC 125 Z9 132 U1 1 U2 16 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 NOV PY 2009 VL 9 IS 11 BP 811 EP 816 DI 10.1038/nri2654 PG 6 WC Immunology SC Immunology GA 510GG UT WOS:000271075500014 PM 19809471 ER PT J AU Ye, YH Rape, M AF Ye, Yihong Rape, Michael TI Building ubiquitin chains: E2 enzymes at work SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID ANAPHASE-PROMOTING COMPLEX; KAPPA-B ACTIVATION; CONJUGATING ENZYME; POLYUBIQUITIN CHAINS; IN-VITRO; DNA-REPAIR; YEAST RAD6; BRCA1/BARD1 HETERODIMER; MOLECULAR DETERMINANTS; ALLOSTERIC ACTIVATION AB The modification of proteins with ubiquitin chains can change their localization, activity and/or stability. Although ubiquitylation requires the concerted action of ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s), it is the E2s that have recently emerged as key mediators of chain assembly. These enzymes are able to govern the switch from ubiquitin chain initiation to elongation, regulate the processivity of chain formation and establish the topology of assembled chains, thereby determining the consequences of ubiquitylation for the modified proteins. C1 [Ye, Yihong] NIDDK, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Rape, Michael] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Ye, YH (reprint author), NIDDK, Mol Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM yihongy@mail.nih.gov; mrape@berkeley.edu FU Intramural NIH HHS [ZIA DK036137-03]; NIGMS NIH HHS [R01 GM083064, 5 R01 GM083064-02] NR 95 TC 371 Z9 386 U1 11 U2 51 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2009 VL 10 IS 11 BP 755 EP 764 DI 10.1038/nrm2780 PG 10 WC Cell Biology SC Cell Biology GA 510EQ UT WOS:000271071200010 PM 19851334 ER PT J AU Vicente-Manzanares, M Ma, XF Adelstein, RS Horwitz, AR AF Vicente-Manzanares, Miguel Ma, Xuefei Adelstein, Robert S. Horwitz, Alan Rick TI Non-muscle myosin II takes centre stage in cell adhesion and migration SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID LIGHT-CHAIN KINASE; MUSCLE HEAVY-MEROMYOSIN; F-ACTIN FLOW; SMOOTH-MUSCLE; FOCAL ADHESIONS; FIBROBLAST MIGRATION; MYH9-RELATED DISEASE; NASCENT ADHESIONS; SIGNALING PATHWAY; FILAMENT BUNDLES AB Non-muscle myosin II (NM II) is an actin-binding protein that has actin cross-linking and contractile properties and is regulated by the phosphorylation of its light and heavy chains. The three mammalian NM II isoforms have both overlapping and unique properties. Owing to its position downstream of convergent signalling pathways, NM II is central in the control of cell adhesion, cell migration and tissue architecture. Recent insight into the role of NM II in these processes has been gained from loss-of-function and mutant approaches, methods that quantitatively measure actin and adhesion dynamics and the discovery of NM II mutations that cause monogenic diseases. C1 [Vicente-Manzanares, Miguel; Horwitz, Alan Rick] Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA. [Ma, Xuefei; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Vicente-Manzanares, M (reprint author), Univ Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA 22908 USA. EM miguelvix@virginia.edu OI Vicente-Manzanares, Miguel/0000-0001-5943-3220; Adelstein, Robert/0000-0002-8683-2144 FU US National Institutes of Health (NIH) [GM23244]; Cell Migration Consortium [U54-GM064346]; Division of Intramural Research, NHLBI, NIH FX The authors apologize for the numerous studies left out owing to journal limits on the number of references. We thank M. A. Conti and J. R. Sellers (National Heart, Lung and Blood Institute (NHLBI)) for helpful suggestions and critical reading of the manuscript. This work was supported by the US National Institutes of Health (NIH) grant GM23244, the Cell Migration Consortium grant U54-GM064346 (A.R.H.), and the Division of Intramural Research, NHLBI, NIH (R.S.A.). NR 155 TC 660 Z9 674 U1 8 U2 103 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD NOV PY 2009 VL 10 IS 11 BP 778 EP 790 DI 10.1038/nrm2786 PG 13 WC Cell Biology SC Cell Biology GA 510EQ UT WOS:000271071200012 PM 19851336 ER PT J AU Hladunewich, MA Steinberg, G Karumanchi, SA Levine, RJ Keating, S Kingdom, J Keunen, J AF Hladunewich, Michelle A. Steinberg, Guy Karumanchi, S. Ananth Levine, Richard J. Keating, Sarah Kingdom, John Keunen, Johannes TI Angiogenic factor abnormalities and fetal demise in a twin pregnancy SO NATURE REVIEWS NEPHROLOGY LA English DT Article ID FETOCIDE REVERSES PREECLAMPSIA; MORPHOMETRIC-ANALYSIS; INTRAUTERINE DEATH; DISCORDANT TWINS; SOLUBLE ENDOGLIN; RESOLUTION; SFLT1; WOMEN AB Background. An otherwise healthy 31-year-old gravida 2 para 1 woman with a spontaneous dichorionic, diamniotic twin pregnancy presented with hypertension, nephrotic syndrome and renal insufficiency at 19 weeks' gestation. Fetal ultrasound revealed severe intrauterine growth restriction of one fetus and measurement of serum anti-angiogenic and angiogenic factors were consistent with a profound anti-angiogenic state. After one fetus died and the placenta became increasingly echogenic, the patient improved clinically, and weekly ultrasound assessments of the intact co-twin from 22 weeks onwards demonstrated symmetrical fetal growth along the 10th centile. Repeat serum angiogenic factors at 24 weeks' gestation revealed considerable improvement of the anti-angiogenic state and paralleled resolution of the clinical syndrome. Investigations. Physical examination, laboratory evaluations including full blood count, liver function tests, electrolytes, renal function tests, screening for glomerular-based disease, 24-h urine collection for total protein, analysis of serum anti-angiogenic and angiogenic factors, fetal ultrasonography and placental Doppler examination. Diagnosis. Spontaneous resolution of early-onset pre-eclampsia after single fetal demise in a twin pregnancy. Management. Labetalol was given to treat hypertension and furosemide was given as needed for edema. The patient was closely followed up throughout pregnancy in a combined nephrology/obstetrics outpatient clinic. C1 [Hladunewich, Michelle A.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Hladunewich, Michelle A.] Mt Sinai Hosp, Dept Med, Div Nephrol, Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Steinberg, Guy; Karumanchi, S. Ananth] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Cambridge, MA 02138 USA. [Levine, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Keating, Sarah] Univ Toronto, Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 1X5, Canada. [Kingdom, John; Keunen, Johannes] Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynecol, Toronto, ON M5G 1X5, Canada. RP Hladunewich, MA (reprint author), Mt Sinai Hosp, Dept Med, Div Nephrol, Sunnybrook Hlth Sci Ctr, 2075 Bayview Ave,Room A139, Toronto, ON M4N 3M5, Canada. EM michelle.hladunewich@sunnybrook.ca RI Kingdom, John/A-3247-2013 FU Bayer/Canadian Hypertension Society; Canadian Institutes of Health Research; Clinical Scholarship Research Award; Physicians' Services Incorporated Foundation; National Institute of Child Health and Human Development (NICHD) FX M. A. Hladunewich's salary is supported by the Bayer/Canadian Hypertension Society, Canadian Institutes of Health Research, Clinical Scholarship Research Award and her research is supported by the Physicians' Services Incorporated Foundation. S. A. Karumanchi is an investigator at the Howard Hughes Medical Institute. R. J. Levine receives salary support from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). NR 19 TC 10 Z9 10 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5061 J9 NAT REV NEPHROL JI Nat. Rev. Nephrol. PD NOV PY 2009 VL 5 IS 11 BP 658 EP 662 DI 10.1038/nrneph.2009.154 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 511UQ UT WOS:000271196000012 PM 19855426 ER PT J AU Pan, YP Tsai, CJ Ma, BY Nussinov, R AF Pan, Yongping Tsai, Chung-Jung Ma, Buyong Nussinov, Ruth TI How do transcription factors select specific binding sites in the genome? SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID ENERGY LANDSCAPES; DNA; PROTEINS; P53; RECOGNITION; MODULATION; MECHANISMS; ALLOSTERY; ENSEMBLES; CASCADES AB How does a transcription factor select a specific DNA response element given the presence of degenerate sequences? To date, this question has largely been viewed from the standpoint of DNA sequence variability and transcription factor binding affinity under steady-state conditions. Here we propose that to address this problem, it is also necessary to account for fluctuating cellular conditions. These lead to dynamic changes in the ensemble of protein (and DNA) conformational states via allosteric effects. C1 [Pan, Yongping; Tsai, Chung-Jung; Ma, Buyong; Nussinov, Ruth] NCI, Basic Sci Program, SAIC Frederick Inc, Canc Res Nanobiol Program, Frederick, MD 21701 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Pan, YP (reprint author), NCI, Basic Sci Program, SAIC Frederick Inc, Canc Res Nanobiol Program, Frederick, MD 21701 USA. EM ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; PHS HHS [HHSN261200800001E] NR 26 TC 31 Z9 31 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2009 VL 16 IS 11 BP 1118 EP 1120 DI 10.1038/nsmb1109-1118 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 515LM UT WOS:000271472300002 PM 19888307 ER PT J AU Tsutsumi, S Mollapour, M Graf, C Lee, CT Scroggins, BT Xu, WP Haslerova, L Hessling, M Konstantinova, AA Trepel, JB Panaretou, B Buchner, J Mayer, MP Prodromou, C Neckers, L AF Tsutsumi, Shinji Mollapour, Mehdi Graf, Christian Lee, Chung-Tien Scroggins, Bradley T. Xu, Wanping Haslerova, Lenka Hessling, Martin Konstantinova, Anna A. Trepel, Jane B. Panaretou, Barry Buchner, Johannes Mayer, Matthias P. Prodromou, Chrisostomos Neckers, Len TI Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID MOLECULAR CHAPERONE HSP90; AMIDE HYDROGEN-EXCHANGE; CONFORMATIONAL-CHANGES; SIGNAL-TRANSDUCTION; MASS-SPECTROMETRY; ATPASE ACTIVITY; GROWTH-FACTOR; PROTEIN; HYDROLYSIS; MACHINERY AB Heat shock protein 90 (Hsp90) is an essential molecular chaperone in eukaryotes, as it regulates diverse signal transduction nodes that integrate numerous environmental cues to maintain cellular homeostasis. Hsp90 also is secreted from normal and transformed cells and regulates cell motility. Here, we have identified a conserved hydrophobic motif in a beta-strand at the boundary between the N domain and charged linker of Hsp90, whose mutation not only abrogated Hsp90 secretion but also inhibited its function. These Hsp90 mutants lacked chaperone activity in vitro and failed to support yeast viability. Notably, truncation of the charged linker reduced solvent accessibility of this beta-strand and restored chaperone activity to these mutants. These data underscore the importance of beta-strand 8 for Hsp90 function and demonstrate that the functional consequences of weakened hydrophobic contacts in this region are reversed by charged-linker truncation. C1 [Tsutsumi, Shinji; Mollapour, Mehdi; Scroggins, Bradley T.; Xu, Wanping; Konstantinova, Anna A.; Neckers, Len] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Graf, Christian; Lee, Chung-Tien; Mayer, Matthias P.] Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany. [Haslerova, Lenka; Panaretou, Barry] Kings Coll London, Div Life Sci, London W8 7AH, England. [Hessling, Martin; Buchner, Johannes] Tech Univ Munich, Dept Chem, Munich, Germany. [Trepel, Jane B.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Prodromou, Chrisostomos] Inst Canc Res, Chester Beatty Labs, Sect Struct Biol, London SW3 6JB, England. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. EM len@helix.nih.gov RI Buchner, Johannes/A-2651-2010; OI Mayer, Matthias/0000-0002-7859-3112; Prodromou, Chrisostomos/0000-0003-4320-1147 FU US National Cancer Institute; Japanese Society of the Promotion of Science FX We are indebted to K. Beebe for comments on the manuscript. This work is supported by US National Cancer Institute intramural research funds. S. T. is partially supported by a fellowship from the Japanese Society of the Promotion of Science. NR 42 TC 38 Z9 39 U1 0 U2 7 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 NOV PY 2009 VL 16 IS 11 BP 1141 EP U3 DI 10.1038/nsmb.1682 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 515LM UT WOS:000271472300008 PM 19838189 ER PT J AU Freedman, BI Hicks, PJ Bostrom, MA Comeau, ME Divers, J Bleyer, AJ Kopp, JB Winkler, CA Nelson, GW Langefeld, CD Bowden, DW AF Freedman, Barry I. Hicks, Pamela J. Bostrom, Meredith A. Comeau, Mary E. Divers, Jasmin Bleyer, Anthony J. Kopp, Jeffrey B. Winkler, Cheryl A. Nelson, George W. Langefeld, Carl D. Bowden, Donald W. TI Non-muscle myosin heavy chain 9 gene MYH9 associations in African Americans with clinically diagnosed type 2 diabetes mellitus-associated ESRD SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE African American; diabetic nephropathy; kidney; MYH9; type 2 diabetes mellitus ID STAGE RENAL-DISEASE; KIDNEY-DISEASE; NEPHROPATHY; HYPERTENSION; GLOMERULOSCLEROSIS; MUTATIONS; DESIGN; RISK AB Background. Although MYH9 is strongly associated with biopsy-proven idiopathic and HIV-associated focal segmental glomerulosclerosis (FSGS) and clinically diagnosed 'hypertension-associated' end-stage renal disease (ESRD) in African Americans, its role in type 2 diabetes mellitus (T2DM)-associated ESRD is unclear. Methods. To assess whether MYH9 was associated with T2DM-ESRD, 751 African Americans with T2DM-ESRD, 227 with T2DM lacking nephropathy and 925 nondiabetic non-nephropathy controls were genotyped for 14 MYH9 SNPs. Association analyses used SNPGWA and Dandelion. Results. Comparing T2DM-ESRD cases with non-diabetic controls, single SNP associations were detected with 8 of 14 SNPs, gender- and admixture-adjusted P-values 0.047-0.005 [recessive model, odds ratio (OR) range 1.30-1.55]. The previously associated MYH9 E1 and L1 haplotypes were associated with T2DM-ESRD (E1: OR 1.27, 95% CI 1.04-1.56, P = 0.021 recessive and L1: OR 1.43, 95% CI 1.09-1.87, P = 0.009 dominant). Contrasting the 751 T2DM-ESRD cases with 227 T2DM non-nephropathy controls revealed that El haplotype SNPs rs4821480, rs2032487 and rs4821481 were associated with kidney failure (OR 1.38-1.40 recessive, all P < 0.048). Among E1 and L1 risk homozygotes, respectively, mean (SD) diabetes duration prior to renal replacement therapy was 16.6 (9.7) and 16.4 (10.0) years, and 65% had diabetic retinopathy. Conclusions. Genetic dissection of T2DM-associated ESRD reveals that MYH9 underlies a portion of this clinically diagnosed disorder in African Americans. It is likely that a subset of African Americans with T2DM and coincident nephropathy have primary MYH9-related kidney disease (e.g. FSGS or global glomerulosclerosis), although renal biopsy studies need to be performed. C1 [Freedman, Barry I.; Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA. [Winkler, Cheryl A.; Nelson, George W.] NCI, SAIC, Frederick, MD 21701 USA. RP Freedman, BI (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. EM bfreedma@wfubmc.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU NIH [R01 DK 070941, R01 DK53591]; NIDDK; NCI Intramural Research Programs; National Cancer Institute [N01-CO-12400, HHSN26120080000] FX This work was supported in part by NIH grants R01 DK 070941 (BIF) and R01 DK53591 (DWB), and the NIDDK and NCI Intramural Research Programs. The authors are indebted to the local nephrology community, including all physicians and their patients who participated, as well as to our study coordinators Joyce Byers, Carrie Smith, Mitzie Spainhour, Cassandra Bethea and Sharon Warren. 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 HHSN26120080000 I E. 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 Programs of the NIH, National Cancer Institute, Center for Cancer Research. NR 23 TC 53 Z9 59 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD NOV PY 2009 VL 24 IS 11 BP 3366 EP 3371 DI 10.1093/ndt/gfp316 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 518UD UT WOS:000271718900022 PM 19567477 ER PT J AU Laurin, D Curb, JD Masaki, KH White, LR Launer, LJ AF Laurin, Danielle Curb, J. David Masaki, Kamal H. White, Lon R. Launer, Lenore J. TI Midlife C-reactive protein and risk of cognitive decline: A 31-year follow-up SO NEUROBIOLOGY OF AGING LA English DT Article DE C-reactive protein; Cognition; Longitudinal studies ID ALZHEIMERS-DISEASE; DEMENTIA; INFLAMMATION; DIAGNOSIS; AMERICAN; MEN AB There is evidence for a relationship between raised inflammatory markers, including high sensitivity C-reactive protein (hs-CRP), measured late in life, and an increased risk of cognitive decline and dementia. This study evaluates the association of midlife hs-CRP concentrations with late-life longitudinal trends in cognitive function. Data are from the Honolulu-Asia Aging Study (HAAS), a longitudinal community-based study of Japanese American men. hs-CRP levels were measured on average 25 years before cognitive testing began in 1991. Subjects were followed from up to three follow-up examinations (mean of 6.1 years). At each exam, cognitive function was measured with the Cognitive Abilities Screening Instrument (CASI). This analysis includes a sub-sample of 691 subjects dementia-free in 1991. With incident dementia cases included, those with the highest quartile of hs-CRP had significantly more cognitive decline than those in the lowest quartile, after adjustment for baseline CASI score, demographic and cardiovascular risk factors. When cases were removed, there was no difference in cognitive decline by CRP quartile. This relationship was not modified by the presence of apolipoprotein E epsilon 4. These findings suggest that inflammatory mechanisms during midlife may reflect underlying processes contributing to dementia-related cognitive decline late in life. (C) 2008 Elsevier Inc. All rights reserved. C1 [Laurin, Danielle; Launer, Lenore J.] NIA, Lab Epidemiol Dermog & Biometry, NIH, Bethesda, MD 20892 USA. [Laurin, Danielle] Univ Laval, Fac Pharm, Quebec City, PQ G1S 4L8, Canada. [Laurin, Danielle] Univ Laval, Geriatr Res Unit, Ctr Rech, CHA, Quebec City, PQ G1S 4L8, Canada. [Curb, J. David; Masaki, Kamal H.; White, Lon R.] Pacific Hlth Res Inst, Honolulu, HI 96813 USA. [Curb, J. David; Masaki, Kamal H.; White, Lon R.] Kuakini Med Ctr, Honolulu, HI 96813 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Dermog & Biometry, NIH, 7201 Wisconsin Ave,Gateway Bldg,Room 3C309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU NIH, the National Institute on Aging [U01 AG019349, R01 AG0-17155 S1] FX The Honolulu-Asia Aging Study is supported by the Intramural Research Program of the NIH, the National Institute on Aging (grants U01 AG019349 and R01 AG0-17155 S1), NR 16 TC 40 Z9 40 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV PY 2009 VL 30 IS 11 BP 1724 EP 1727 DI 10.1016/j.neurobiolaging.2008.01.008 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 501ID UT WOS:000270374000002 PM 18316138 ER PT J AU Terry, GE Liow, JS Zoghbi, SS Hirvonen, J Farris, AG Lerner, A Tauscher, JT Schaus, JM Phebus, L Felder, CC Morse, CL Hong, JS Pike, VW Halldin, C Innis, RB AF Terry, Garth E. Liow, Jeih-San Zoghbi, Sami S. Hirvonen, Jussi Farris, Amanda G. Lerner, Alicja Tauscher, Johannes T. Schaus, John M. Phebus, Lee Felder, Christian C. Morse, Cheryl L. Hong, Jinsoo S. Pike, Victor W. Halldin, Christer Innis, Robert B. TI Quantitation of cannabinoid CB1 receptors in healthy human brain using positron emission tomography and an inverse agonist radioligand SO NEUROIMAGE LA English DT Article DE Positron emission tomography; Brain imaging; Neuroimaging ID IN-VIVO; MOUSE-BRAIN; PET; BINDING; EXPRESSION; MODEL AB [C-11]MePPEP is a high affinity, CB1 receptor-selective, inverse agonist that has been studied in rodents and monkeys. We examined the ability of [C-11]MePPEP to quantify CB1 receptors in human brain as distribution volume calculated with the "gold standard" method of compartmental modeling and compared results with the simple measure of brain uptake. A total of 17 healthy subjects participated in 26 positron emission tomography (PET) scans, with 8 having two PET scans to assess retest variability. After injection of [C-11]MePPEP, brain uptake of radioactivity was high (e.g., 3.6 SUV in putamen at similar to 60 min) and washed out very slowly. A two-tissue compartment model yielded values of distribution volume (which is proportional to receptor density) that were both well identified (SE 5%) and stable between 60 and 210 min. The simple measure of brain uptake (average concentration of radioactivity between 40 and 80 min) had good retest variability (similar to 8%) and moderate intersubject variability (16%, coefficient of variation). In contrast, distribution volume had two-fold greater retest variability (similar to 15%) and, thus, less precision. In addition, distribution volume had three-fold greater intersubject variability (similar to 52%). The decreased precision of distribution volume compared to brain uptake was likely due to the slow washout of radioactivity from brain and to noise in measurements of the low concentrations of [C-11]MePPEP in plasma. These results suggest that brain uptake can be used for within subject studies (e. g., to measure receptor occupancy by medications) but that distribution volume remains the gold standard for accurate measurements between groups. Published by Elsevier Inc. C1 [Terry, Garth E.; Liow, Jeih-San; Zoghbi, Sami S.; Hirvonen, Jussi; Farris, Amanda G.; Lerner, Alicja; Morse, Cheryl L.; Hong, Jinsoo S.; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Tauscher, Johannes T.; Schaus, John M.; Phebus, Lee; Felder, Christian C.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Terry, Garth E.; Halldin, Christer] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Eli Lilly [Z01-MH-002852-04, Z01-MH-002793-04]; NIMH [Z01-MH-002852-04, Z01-MH-002793-04]; Academy of Finland; Finnish Cultural Foundation; Finnish Foundation for Alcohol Studies; Finnish Medical Foundation; Instrumentarium Foundation; Jalmari and Rauha Ahokas Foundation; Paulo Foundation; Research Foundation of Orion Corporation; Yrj Jahnsson Foundation FX We thank Ed Tuan, Pavitra Kannan, Kimberly Jenko, and Kacey Anderson for measurements of radioligand in plasma; Yi Zhang for preparation of [11C]MePPEP; Desiree Araneta, William C. Kreisl, Barbara Prewitt, and the NIH PET Department for imaging; and PMOD Technologies for providing its image analysis and modeling software. This research was supported by a Cooperative Research and Development Agreement with Eli Lilly and by the Intramural Program of NIMH (projects # Z01-MH-002852-04 and # Z01-MH-002793-04). Jussi Hirvonenwas supported by personal grants from The Academy of Finland, The Finnish Cultural Foundation, The Finnish Foundation for Alcohol Studies, The Finnish Medical Foundation, The Instrumentarium Foundation, The Jalmari and Rauha Ahokas Foundation, The Paulo Foundation, The Research Foundation of Orion Corporation, and The Yrj Jahnsson Foundation. NR 26 TC 52 Z9 52 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2009 VL 48 IS 2 BP 362 EP 370 DI 10.1016/j.neuroimage.2009.06.059 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 558EP UT WOS:000274723900006 PM 19573609 ER PT J AU Goel, V Stollstorff, M Nakic, M Knutson, K Grafman, J AF Goel, Vinod Stollstorff, Melanie Nakic, Marina Knutson, Kris Grafman, Jordan TI A role for right ventrolateral prefrontal cortex in reasoning about indeterminate relations SO NEUROPSYCHOLOGIA LA English DT Article DE Reasoning; Hemispheric asymmetry; Neuroimaging; Frontal lobes; Uncertainty ID TRANSITIVE INFERENCE; RIGHT-HEMISPHERE; ACTIVATION; FMRI; PARIETAL; SPECIALIZATION; UNCERTAINTY; INVOLVEMENT; CORTICES; SYSTEMS AB While the role of left prefrontal cortex in reasoning tasks has long been recognized, the role of right prefrontal cortex remains unclear. One patient study [Goel, V., Tierney, M., Sheesley, L, Bartolo, A., Vartanian, O., & Grafman, J. (2007). Hemispheric specialization in human prefrontal cortex for resolving certain and uncertain inferences. Cerebral Cortex, 17(10), 2245-2250] has suggested that right prefrontal cortex plays an essential role in resolving indeterminate relations. To test this hypothesis, and to identify the involvement of specific regions within right prefrontal cortex we scanned 17 normal volunteers with fMRI while they engaged in a transitive inference task involving determinate and indeterminate relations. The results show a nice crossover interaction such that, right ventrolateral prefrontal cortex (BA 47) is selectively activated by the processing of indeterminate trials with no belief-bias cues, while left lateral prefrontal cortex (BA 45) is selectively activated by the processing of indeterminate trials containing belief-bias cues. These results are not only consistent with, but also amplify, the lesion data by identifying specific regions within right and left prefrontal cortex. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Goel, Vinod; Stollstorff, Melanie] York Univ, Dept Psychol, Toronto, ON M3J 1P3, Canada. [Goel, Vinod] Univ Hull, Dept Psychol, Kingston Upon Hull HU6 7RX, N Humberside, England. [Nakic, Marina; Knutson, Kris; Grafman, Jordan] NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. RP Goel, V (reprint author), York Univ, Dept Psychol, 4700 Keele St, Toronto, ON M3J 1P3, Canada. EM vgoel@yorku.ca OI Knutson, Kristine/0000-0003-4626-4514; Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS [Z01 NS002792-19] NR 42 TC 28 Z9 28 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD NOV PY 2009 VL 47 IS 13 BP 2790 EP 2797 DI 10.1016/j.neuropsychologia.2009.06.002 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 510DB UT WOS:000271067100013 PM 19523967 ER PT J AU Kreibich, AS Briand, L Cleck, JN Ecke, L Rice, KC Blendy, JA AF Kreibich, Arati S. Briand, Lisa Cleck, Jessica N. Ecke, Laurel Rice, Kenner C. Blendy, Julie A. TI Stress-Induced Potentiation of Cocaine Reward: A Role for CRFR1 and CREB SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE CREB; CRFR1; cocaine; forced swim stress; CPP ID ELEMENT-BINDING PROTEIN; CORTICOTROPIN-RELEASING-FACTOR; CONDITIONED PLACE PREFERENCE; INDUCED BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS SHELL; FORCED SWIM TEST; RECEPTOR ANTAGONIST; UNCONTROLLABLE STRESS; PAIRED ENVIRONMENT; RESTRAINT STRESS AB Both clinical and preclinical research have shown that stress can potentiate drug use; however, the underlying mechanisms of this interaction are unknown. Previously, we have shown that a single exposure to forced swim (FS) reinstates extinguished conditioned place preference (CPP) to cocaine and that cAMP response element binding protein (CREB) is necessary for this response. CREB can be activated by corticotropin releasing factor (CRF) receptor type 1 (CRFR1) binding, which mediates neuroendocrine and behavioral responses to stress as well as to drugs of abuse. The present experiments investigate whether changes in cocaine reward elicited by previous exposure to stress are mediated by CREB and/or CRFR1. Chronic exposure to FS in advance of conditioning enhances cocaine CPP in wild-type mice, but this is blocked in CREB-deficient mice. In addition, pretreatment with the CRFR1 antagonist, antalarmin, before FS exposure blocks this stress-induced enhancement of cocaine CPP. Furthermore, FS-induced increase in phosphorylated CREB (pCREB), specifically in the lateral septum (LS) and nucleus accumbens (NAc) is also blocked by antalarmin. Taken together, these studies suggest that both CREB and CRFR1 activation are necessary for stress-induced potentiation of drug reward. Neuropsychopharmacology (2009) 34, 2609-2617; doi:10.1038/npp.2009.91; published online 12 August 2009 C1 [Blendy, Julie A.] Univ Penn, Dept Pharmacol, Translat Res Lab, Philadelphia, PA 19104 USA. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, Rockville, MD USA. [Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA. RP Blendy, JA (reprint author), Univ Penn, Dept Pharmacol, Translat Res Lab, 125 S 31st St, Philadelphia, PA 19104 USA. EM blendy@mail.med.upenn.edu FU National Institute on Drug Abuse NIDA [DA116-49-01A2]; NIH Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases; National Institute on Alcohol Abuse and Alcoholism FX This work was supported by the National Institute on Drug Abuse NIDA Grant DA116-49-01A2 (J.A.B.). A portion of this work was supported by the NIH Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. NR 60 TC 37 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2009 VL 34 IS 12 BP 2609 EP 2617 DI 10.1038/npp.2009.91 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 506UW UT WOS:000270802900012 PM 19675537 ER PT J AU Vidrine, JI Vidrine, DJ Costello, TJ Mazas, C Cofta-Woerpel, L Mejia, LM Wetter, DW AF Vidrine, Jennifer Irvin Vidrine, Damon J. Costello, Tracy J. Mazas, Carlos Cofta-Woerpel, Ludmila Mejia, Luz Maria Wetter, David W. TI The Smoking Consequences Questionnaire: Factor structure and predictive validity among Spanish-speaking Latino smokers in the United States SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID OUTCOME EXPECTANCIES; NICOTINE DEPENDENCE; TOBACCO WITHDRAWAL; FAGERSTROM TEST; RELAPSE; CESSATION; DEPRESSION; CIGARETTE; WOMEN; TIME AB Introduction: Much of the existing research on smoking outcome expectancies has been guided by the Smoking Consequences Questionnaire (SCQ). Although the original version of the SCQ has been modified over time for use in different populations, none of the existing versions have been evaluated for use among Span ish-speaking Latino smokers in the United States. Methods: The present study evaluated the factor structure and predictive validity of the 3 previously validated versions of the SCQ-the original, the SCQ-Adult, and the SCQ Spanish, which was developed with Spanish-speaking smokers in Spain-among Spanish-speaking Latino smokers in Texas. Results: The SCQ-Spanish represented the least complex solution. Each of the SCQ-Spanish scales had good internal consistency, and the predictive validity of the SCQ-Spanish was partially supported. Nearly all the SCQ-Spanish scales predicted withdrawal severity even after controlling for demographics and dependence. Boredom Reduction predicted smoking relapse across the 5- and 12-week follow-up assessments in a multivariate model that also controlled for demographics and dependence. Discussion: Our results support use of the SCQ-Spanish with Spanish-speaking Latino smokers in the United States. C1 [Vidrine, Jennifer Irvin] Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440, Houston, TX 77230 USA. [Vidrine, Damon J.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77230 USA. [Cofta-Woerpel, Ludmila] NCI, Dept Behav Sci, Canc Informat Serv, Houston, TX USA. RP Vidrine, JI (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hlth Dispar Res, Unit 1440, POB 301402, Houston, TX 77230 USA. EM jirvinvidrine@mdanderson.org OI Costello, Tracy/0000-0001-6138-2450; Wetter, David/0000-0002-6366-0108 FU Texas Higher Education Coordinating Board; National Cancer Institute [R01CA125413, R01CA94826, R01CA89350, R01CA097893, R01CA132636, K07CA121037]; Centers for Disease Control and Prevention [K01DP000086] FX This research was supported by grants from the Minority Health Research and Education Program of the Texas Higher Education Coordinating Board, the National Cancer Institute (R01CA125413, R01CA94826, R01CA89350, R01CA097893, R01CA132636, K07CA121037), and the Centers for Disease Control and Prevention (K01DP000086). NR 52 TC 9 Z9 9 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2009 VL 11 IS 11 BP 1280 EP 1288 DI 10.1093/ntr/ntp128 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 518UI UT WOS:000271719400004 PM 19696309 ER PT J AU Covo, S de Villartay, JP Jeggo, PA Livneh, Z AF Covo, Shay de Villartay, Jean-Pierre Jeggo, Penny A. Livneh, Zvi TI Translesion DNA synthesis-assisted non-homologous end-joining of complex double-strand breaks prevents loss of DNA sequences in mammalian cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN NUCLEAR EXTRACTS; POLYMERASE-LAMBDA; IONIZING-RADIATION; ABASIC SITES; IV COMPLEX; LIGASE-IV; A-RULE; REPAIR; BYPASS; DAMAGE AB Double strand breaks (DSB) are severe DNA lesions, and if not properly repaired, may lead to cell death or cancer. While there is considerable data on the repair of simple DSB (sDSB) by non-homologous end-joining (NHEJ), little is known about the repair of complex DSBs (cDSB), namely breaks with a nearby modification, which precludes ligation without prior processing. To study the mechanism of cDSB repair we developed a plasmid-based shuttle assay for the repair of a defined site-specific cDSB in cultured mammalian cells. Using this assay we found that repair efficiency and accuracy of a cDSB with an abasic site in a 5' overhang was reduced compared with a sDSB. Translesion DNA synthesis (TLS) across the abasic site located at the break prevented loss of DNA sequences, but was highly mutagenic also at the template base next to the abasic site. Similar to sDSB repair, cDSB repair was totally dependent on XrccIV, and altered in the absence of Ku80. In contrast, Artemis appears to be specifically involved in cDSB repair. These results may indicate that mammalian cells have a damage control strategy, whereby severe deletions are prevented at the expense of the less deleterious point mutations during NHEJ. C1 [Covo, Shay; Livneh, Zvi] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel. [de Villartay, Jean-Pierre] Hop Necker Enfants Malad, INSERM, U768, Paris, France. [Jeggo, Penny A.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. RP Livneh, Z (reprint author), NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. EM zvi.livneh@weizmann.ac.il FU Flight Attendant Medical Research Institute, Florida, USA; Israel Science Foundation [564/04, 1136/08] FX Flight Attendant Medical Research Institute, Florida, USA grant; and the Israel Science Foundation grant (no 564/04 and 1136/08). Funding for open access charge: Flight Attendant Medical Research Institute, Florida, USA. NR 48 TC 20 Z9 20 U1 0 U2 0 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 NOV PY 2009 VL 37 IS 20 BP 6737 EP 6745 DI 10.1093/nar/gkp703 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 520DJ UT WOS:000271819900009 PM 19762482 ER PT J AU Huang, Y Koonin, EV Lipman, DJ Przytycka, TM AF Huang, Yang Koonin, Eugene V. Lipman, David J. Przytycka, Teresa M. TI Selection for minimization of translational frameshifting errors as a factor in the evolution of codon usage SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSFER-RNA GENES; READING FRAME MAINTENANCE; ESCHERICHIA-COLI GENES; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; SECONDARY STRUCTURE; SEQUENCE EVOLUTION; BACILLUS-SUBTILIS; WOBBLE HYPOTHESIS; EXPRESSION LEVEL AB In a wide range of genomes, it was observed that the usage of synonymous codons is biased toward specific codons and codon patterns. Factors that are implicated in the selection for codon usage include facilitation of fast and accurate translation. There are two types of translational errors: missense errors and processivity errors. There is considerable evidence in support of the hypothesis that codon usage is optimized to minimize missense errors. In contrast, little is known about the relationship between codon usage and frameshifting errors, an important form of processivity errors, which appear to occur at frequencies comparable to the frequencies of missense errors. Based on the recently proposed pause-and-slip model of frameshifting, we developed Frameshifting Robustness Score (FRS). We used this measure to test if the pattern of codon usage indicates optimization against frameshifting errors. We found that the FRS values of protein-coding sequences from four analyzed genomes (the bacteria Bacillus subtilis and Escherichia coli, and the yeasts Saccharomyces cerevisiae and Schizosaccharomyce pombe) were typically higher than expected by chance. Other properties of FRS patterns observed in B. subtilis, S. cerevisiae and S. pombe, such as the tendency of FRS to increase from the 5'- to 3'-end of protein-coding sequences, were also consistent with the hypothesis of optimization against frameshifting errors in translation. For E. coli, the results of different tests were less consistent, suggestive of a much weaker optimization, if any. Collectively, the results fit the concept of selection against mistranslation-induced protein misfolding being one of the factors shaping the evolution of both coding and non-coding sequences. C1 [Huang, Yang; Koonin, Eugene V.; Lipman, David J.; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Intramural Research Program of the National Institutes of Health, National Library of Medicine. Funding for open access charge: Intramural research program for the National Institutes of Health, National Library of Medicine. NR 50 TC 16 Z9 19 U1 1 U2 7 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 NOV PY 2009 VL 37 IS 20 BP 6799 EP 6810 DI 10.1093/nar/gkp712 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 520DJ UT WOS:000271819900014 PM 19745054 ER PT J AU van den Born, E Bekkelund, A Moen, MN Omelchenko, MV Klungland, A Falnes, PO AF van den Born, Erwin Bekkelund, Anders Moen, Marivi N. Omelchenko, Marina V. Klungland, Arne Falnes, Pal O. TI Bioinformatics and functional analysis define four distinct groups of AlkB DNA-dioxygenases in bacteria SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; REPAIR ENZYME ALKB; ESCHERICHIA-COLI; ALKYLATION DAMAGE; OXIDATIVE DEMETHYLATION; METHYLATION DAMAGE; CRYSTAL-STRUCTURES; VINYL-CHLORIDE; RNA; PROTEINS AB The iron(II)- and 2-oxoglutarate (2OG)-dependent dioxygenase AlkB from Escherichia coli (EcAlkB) repairs alkylation damage in DNA by direct reversal. EcAlkB substrates include methylated bases, such as 1-methyladenine (m(1)A) and 3-methylcytosine (m(3)C), as well as certain bulkier lesions, for example the exocyclic adduct 1,N-6-ethenoadenine (epsilon A). EcAlkB is the only bacterial AlkB protein characterized to date, and we here present an extensive bioinformatics and functional analysis of bacterial AlkB proteins. Based on sequence phylogeny, we show that these proteins can be subdivided into four groups: denoted 1A, 1B, 2A and 2B; each characterized by the presence of specific conserved amino acid residues in the putative nucleotide-recognizing domain. A scattered distribution of AlkB proteins from the four different groups across the bacterial kingdom indicates a substantial degree of horizontal transfer of AlkB genes. DNA repair activity was associated with all tested recombinant AlkB proteins. Notably, both a group 2B protein from Xanthomonas campestris and a group 2A protein from Rhizobium etli repaired etheno adducts, but had negligible activity on methylated bases. Our data indicate that the majority, if not all, of the bacterial AlkB proteins are DNA repair enzymes, and that some of these proteins do not primarily target methylated bases. C1 [van den Born, Erwin; Bekkelund, Anders; Falnes, Pal O.] Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. [Moen, Marivi N.; Klungland, Arne; Falnes, Pal O.] Oslo Univ Hosp, Inst Med Microbiol, Ctr Mol Biol & Neurosci, N-0027 Oslo, Norway. [Moen, Marivi N.; Klungland, Arne; Falnes, Pal O.] Univ Oslo, N-0027 Oslo, Norway. [Omelchenko, Marina V.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Klungland, Arne] Univ Oslo, Inst Basic Med Sci, N-0315 Oslo, Norway. RP Falnes, PO (reprint author), Univ Oslo, Dept Mol Biosci, POB 1041 Blindern, N-0316 Oslo, Norway. EM pal.falnes@imbv.uio.no FU Research Council of Norway; National Library of Medicine at the National Institutes of Health; National Institutes of Health Intramural Funds FX FRIBIOMOL and FUGE programs of the Research Council of Norway and the Intramural Research Program of the National Library of Medicine at the National Institutes of Health. Funding for open access charge: National Institutes of Health Intramural Funds. NR 55 TC 15 Z9 15 U1 0 U2 13 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 NOV PY 2009 VL 37 IS 21 BP 7124 EP 7136 DI 10.1093/nar/gkp774 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 531SK UT WOS:000272688400019 PM 19786499 ER PT J AU Zolotukhin, AS Uranishi, H Lindtner, S Bear, J Pavlakis, GN Felber, BK AF Zolotukhin, Andrei S. Uranishi, Hiroaki Lindtner, Susan Bear, Jenifer Pavlakis, George N. Felber, Barbara K. TI Nuclear export factor RBM15 facilitates the access of DBP5 to mRNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEAD-BOX PROTEINS; TRANSPORT ELEMENT RTE; HNRNP-LIKE PROTEINS; SPLICING FACTORS; PORE COMPLEX; MOTONEURON DISEASE; GENE-EXPRESSION; TAP NXF1; FAMILY; BINDING AB The conserved mRNA export receptor NXF1 (Mex67 in yeast) assembles with messenger ribonucleoproteins (mRNP) in the nucleus and guides them through the nuclear pore complex into the cytoplasm. The DEAD family RNA helicase Dbp5 is essential for nuclear export of mRNA and is thought to dissociate Mex67 from mRNP upon translocation, thereby generating directional passage. However, the molecular mechanism by which Dbp5 recognizes Mex67-containing mRNP is not clear. Here we report that the human NXF1-binding protein RBM15 binds specifically to human DBP5 and facilitates its direct contact with mRNA in vivo. We found that RBM15 is targeted to the nuclear envelope, where it colocalizes extensively with DBP5 and NXF1. Gene silencing of RBM15 leads to cytoplasmic depletion and nuclear accumulation of general mRNA as well as individual endogenous transcripts, indicating that RBM15 is required for efficient mRNA export. We propose a model in which RBM15 acts locally at the nuclear pore complex, by facilitating the recognition of NXF1-mRNP complexes by DBP5 during translocation, thereby contributing to efficient mRNA export. C1 [Zolotukhin, Andrei S.; Bear, Jenifer; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. [Uranishi, Hiroaki; Lindtner, Susan; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. EM felber@ncifcrf.gov FU NIH; National Cancer Institute; Center for Cancer Research FX Funding for open access charge: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 79 TC 19 Z9 20 U1 0 U2 3 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 NOV PY 2009 VL 37 IS 21 BP 7151 EP 7162 DI 10.1093/nar/gkp782 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 531SK UT WOS:000272688400021 PM 19786495 ER PT J AU Gardner, D AF Gardner, Deborah TI Health Care Reform: Through the Lens of Change SO NURSING ECONOMICS LA English DT Article AB Change theory concepts - drivers, vision, current and future states, and social buy-in - provide some analytical leverage in understanding current reform challenges. Various contentious issues in the health care reform battle have long serveo to polarize stakeholders and differentiate conservative and liberal positions. Successful change efforts are led by the development of a compelling vision, which has certain attributes. Change theory postulates that if there is not strong dissatisfaction with the current state, the future state is less feasible. Social systems change theory is another way to conceptualize and broaden our understanding of health policy as a form of social change, how environmental or external forces influence policy design, and how the ongoing media presentation of a policy influences direction of the outcome. C1 NIH, Off Org Dev, Ctr Clin, Bethesda, MD 20892 USA. RP Gardner, D (reprint author), NIH, Off Org Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD NOV-DEC PY 2009 VL 27 IS 6 BP 419 EP 421 PG 3 WC Nursing SC Nursing GA 531KJ UT WOS:000272664600011 PM 20050495 ER PT J AU Das, SK Saltzman, E Gilhooly, CH DeLany, JP Golden, JK Pittas, AG Dallal, GE Bhapkar, MV Fuss, PJ Dutta, C McCrory, MA Roberts, SB AF Das, Sai Krupa Saltzman, Edward Gilhooly, Cheryl H. DeLany, James P. Golden, Julie K. Pittas, Anastassios G. Dallal, Gerard E. Bhapkar, Manjushri V. Fuss, Paul J. Dutta, Chhanda McCrory, Megan A. Roberts, Susan B. TI Low or Moderate Dietary Energy Restriction for Long-term Weight Loss: What Works Best? SO OBESITY LA English DT Article ID LOW-FAT DIET; RANDOMIZED CONTROLLED-TRIAL; LOW-CARBOHYDRATE-DIET; DOUBLY LABELED WATER; BODY-COMPOSITION; GLYCEMIC LOAD; EXPENDITURE; OBESITY; DISINHIBITION; RESTRAINT AB Theoretical calculations suggest that small daily reductions in energy intake can cumulatively lead to substantial weight loss, but experimental data to support these calculations are lacking. We conducted a 1-year randomized controlled pilot study of low (10%) or moderate (30%) energy restriction (ER) with diets differing in glycemic load in 38 overweight adults (mean +/- s.d., age 35 +/- 6 years; BMI 27.6 +/- 1.4 kg/m(2)). Food was provided for 6 months and self-selected for 6 additional months. Measurements included body weight, resting metabolic rate (RMR), adherence to the ER prescription assessed using (2)H(2)(18)O, satiety, and eating behavior variables. The 10% ER group consumed significantly less energy (by (2)H(2)(18)O) than prescribed over 12 months (18.1 +/- 9.8%ER, P = 0.04), while the 30%ER group consumed significantly more (23.1 +/- 8.7%ER, P < 0.001). Changes in body weight, satiety, and other variables were not significantly different between groups. However, during self-selected eating (6-12 months) variability in % weight change was significantly greater in the 10%ER group (P < 0.001) and poorer weight outcome on 10%ER was predicted by higher baseline BMI and greater disinhibition (P < 0.0001; adj R(2) = 0.71). Weight loss at 12 months was not significantly different between groups prescribed 10 or 30%ER, supporting the efficacy of low ER recommendations. However, long-term weight change was more variable on 10%ER and weight change in this group was predicted by body size and eating behavior. These preliminary results indicate beneficial effects of low-level ER for some but not all individuals in a weight control program, and suggest testable approaches for optimizing dieting success based on individualizing prescribed level of ER. C1 [Das, Sai Krupa; Saltzman, Edward; Gilhooly, Cheryl H.; Golden, Julie K.; Dallal, Gerard E.; Fuss, Paul J.; Roberts, Susan B.] Tufts Univ, Human Nutr Res Ctr Aging, Energy Metab Lab, Jean Mayer USDA, Boston, MA 02111 USA. [DeLany, James P.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Pittas, Anastassios G.] Tufts Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA USA. [Bhapkar, Manjushri V.] Duke Clin Res Inst, Durham, NC USA. [Dutta, Chhanda] NIA, Clin Gerontol Branch, NIH, Bethesda, MD 20892 USA. [McCrory, Megan A.] Purdue Univ, Dept Foods & Nutr, Dept Psychol Sci, W Lafayette, IN 47907 USA. RP Roberts, SB (reprint author), Tufts Univ, Human Nutr Res Ctr Aging, Energy Metab Lab, Jean Mayer USDA, Boston, MA 02111 USA. RI Biguzzi, Felipe/E-4724-2015 FU National Institutes of Health [AG20480, H150001]; U.S Department of Agriculture [58-1950-4-401] FX We thank the subjects for their committed participation in this study, and the staff of the Metabolic Research Unit for their expert assistance This project work was supported by National Institutes of Health grants AG20480 and H150001, and by the U.S Department of Agriculture under agreement no 58-1950-4-401 Any opinions, findings, conclusion, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U S Department of Agriculture NR 37 TC 14 Z9 14 U1 4 U2 12 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 NOV PY 2009 VL 17 IS 11 BP 2019 EP 2024 DI 10.1038/oby.2009.120 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 512HT UT WOS:000271237700010 PM 19390525 ER PT J AU Parikh, NI Keyes, MJ Larson, MG Pou, KA Hamburg, NA Vita, JA O'Donnell, CJ Vasan, RS Mitchell, GF Hoffmann, U Fox, CS Benjamin, EJ AF Parikh, Nisha I. Keyes, Michelle J. Larson, Martin G. Pou, Karla A. Hamburg, Naomi A. Vita, Joseph A. O'Donnell, Christopher J. Vasan, Ramachandran S. Mitchell, Gary F. Hoffmann, Udo Fox, Caroline S. Benjamin, Emelia J. TI Visceral and Subcutaneous Adiposity and Brachial Artery Vasodilator Function SO OBESITY LA English DT Article ID FLOW-MEDIATED DILATION; CORONARY-HEART-DISEASE; METABOLIC RISK-FACTORS; BODY-FAT DISTRIBUTION; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; ENDOTHELIAL DYSFUNCTION; JAPANESE-AMERICANS; TISSUE; WOMEN AB Endothelial dysfunction may link obesity to cardiovascular disease (CVD). We tested the hypothesis that visceral abdominal tissue (VAT) as compared with subcutaneous adipose tissue (SAT) is more related to endothelium-dependent vasodilation. Among Framingham Offspring and Third Generation cohorts (n = 3,020, mean age 50 years, 47% women), we used multivariable linear regression adjusted for CVD and its risk factors to relate computed tomography (CT)-assessed VAT and SAT, BMI, and waist circumference (WC), with brachial artery measures. In multivariable-adjusted models, Bill WC, VAT, and SAT were positively related to baseline artery diameter and baseline mean flow velocity (all P < 0.001), but not hyperemic mean flow velocity. In multivariable-adjusted models, BMI (P = 0.002), WC (P = 0.001), and VAT (P = 0.01), but not SAT (P = 0.24) were inversely associated with percentage of flow-mediated dilation (FMD%). However, there was little incremental increase in the proportion of variability explained by VAT (R(2) = 0.266) as compared to SAT (R(2) = 0.265), above and beyond traditional risk factors. VAT, but not SAT was associated with FMD% after adjusting for clinical covariates. Nevertheless, the differential association with VAT as compared to SAT was minimal. C1 [Parikh, Nisha I.; Keyes, Michelle J.; Larson, Martin G.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Fox, Caroline S.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Keyes, Michelle J.; Larson, Martin G.] Boston Univ, Sch Med, Math & Stat Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Pou, Karla A.; Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hamburg, Naomi A.; Vita, Joseph A.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Cardiol Sect, Boston, MA 02118 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Holiston, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA. OI Hamburg, Naomi/0000-0001-5504-5589; Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195, RO1 HL70100, 1 RO1 HL60040]; NHLBI/NIH [2K24HL04334] FX This work was supported by the National Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195, RO1 HL70100, 1 RO1 HL60040) Dr Vasan is supported in part by 2K24HL04334 (NHLBI/NIH). NR 38 TC 33 Z9 34 U1 0 U2 1 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 NOV PY 2009 VL 17 IS 11 BP 2054 EP 2059 DI 10.1038/oby.2009.60 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 512HT UT WOS:000271237700015 PM 19282819 ER PT J AU Liu, A McLaughlin, T Liu, T Sherman, A Yee, G Abbasi, F Lamendola, C Morton, J Cushman, SW Reaven, GM Tsao, PS AF Liu, Alice McLaughlin, Tracey Liu, Teresa Sherman, Arthur Yee, Gail Abbasi, Fahim Lamendola, Cindy Morton, John Cushman, Samuel W. Reaven, Gerald M. Tsao, Philip S. TI Differential Intra-abdominal Adipose Tissue Profiling in Obese, Insulin-resistant Women SO OBESITY SURGERY LA English DT Article DE Adipose cell size; Inflammation; Obesity; Visceral adipose tissue ID COLONY-ENHANCING FACTOR; MEDIATED GLUCOSE DISPOSAL; CARDIOVASCULAR-DISEASE; REGIONAL DIFFERENCES; SUPPRESSION TEST; FAT DISTRIBUTION; INFLAMMATION; METABOLISM; MEN; VISFATIN AB We recently identified differences in abdominal subcutaneous adipose tissue (SAT) from insulin-resistant (IR) as compared to obesity-matched insulin sensitive individuals, including accumulation of small adipose cells, decreased expression of cell differentiation markers, and increased inflammatory activity. This study was initiated to see if these changes in SAT of IR individuals were present in omental visceral adipose tissue (VAT); in this instance, individuals were chosen to be IR but varied in degree of adiposity. We compared cell size distribution and genetic markers in SAT and VAT of IR individuals undergoing bariatric surgery. Eleven obese/morbidly obese women were IR by the insulin suppression test. Adipose tissue surgical samples were fixed in osmium tetroxide for cell size analysis via Beckman Coulter Multisizer. Quantitative real-time polymerase chain reaction for genes related to adipocyte differentiation and inflammation was performed. While proportion of small cells and expression of adipocyte differentiation genes did not differ between depots, inflammatory genes were upregulated in VAT. Diameter of SAT large cells correlated highly with increasing proportion of small cells in both SAT and VAT (r = 0.85, p = 0.001; r = 0.72, p = 0.01, respectively). No associations were observed between VAT large cells and cell size variables in either depot. The effect of body mass index (BMI) on any variables in both depots was negligible. The major differential property of VAT of IR women is increased inflammatory activity, independent of BMI. The association of SAT adipocyte hypertrophy with hyperplasia in both depots suggests a primary role SAT may have in regulating regional fat storage. C1 [Liu, Alice; McLaughlin, Tracey] Stanford Univ, Med Ctr, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. [Liu, Teresa; Sherman, Arthur; Cushman, Samuel W.] NIDDK, NIH, Bethesda, MD USA. [Yee, Gail; Abbasi, Fahim; Lamendola, Cindy; Reaven, Gerald M.; Tsao, Philip S.] Stanford Univ, Div Cardiol, Dept Med, Stanford, CA 94305 USA. [Morton, John] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. RP Liu, A (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Endocrinol, 300 Pasteur Dr,Rm S-025, Stanford, CA 94305 USA. EM aliceliu@stanford.edu FU NIH/NIDDK [1 R01 DK071309-01, 5 R01 DK071333-04, 5 F32 DK079578-02]; NIDDK Intramural Research Program and supported by Human Health Service [M01-RR00070] FX Funding for this study was provided by study grants NIH/NIDDK 1 R01 DK071309-01, 5 R01 DK071333-04, and 5 F32 DK079578-02, by the NIDDK Intramural Research Program and supported by Human Health Service grant M01-RR00070. NR 42 TC 22 Z9 22 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD NOV PY 2009 VL 19 IS 11 BP 1564 EP 1573 DI 10.1007/s11695-009-9949-9 PG 10 WC Surgery SC Surgery GA 512WQ UT WOS:000271282900016 PM 19711137 ER PT J AU Molloy, AM Quadros, EV Sequeira, JM Troendle, JF Scott, JM Kirke, PN Mills, JL AF Molloy, Anne M. Quadros, Edward V. Sequeira, Jeffrey M. Troendle, James F. Scott, Jolm M. Kirke, Peadar N. Mills, James L. TI Lack of Association Between Folate-Receptor Autoantibodies and Neural-Tube Defects EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dublin, Ireland. Trinity Coll Dublin, Sch Biochem & Immunol, Dublin, Ireland. Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland. SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Molloy, AM (reprint author), Trinity Coll Dublin, Sch Med, Dublin, Ireland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD NOV PY 2009 VL 64 IS 11 BP 716 EP 718 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 515QO UT WOS:000271487800010 ER PT J AU Scher, AI Gudmundsson, LS Sigurdsson, S Ghambaryan, A Aspelund, T Eiriksdottir, G van Buchein, MA Gudnason, V Lanner, LJ AF Scher, Ann I. Gudmundsson, Larus S. Sigurdsson, Sigurdur Ghambaryan, Anna Aspelund, Thor Eiriksdottir, Gudny van Buchein, Mark A. Gudnason, Vilmundur Lanner, Lenore J. TI Migraine Headache in Middle Age and Late-Life Brain Infarcts EDITORIAL COMMENT SO OBSTETRICAL & GYNECOLOGICAL SURVEY LA English DT Editorial Material C1 [Scher, Ann I.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Iceland, Reykjavik, Iceland. Iceland Heart Assoc, Kopavogur, Iceland. Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. NIA, Bethesda, MD 20892 USA. RP Scher, AI (reprint author), Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7828 J9 OBSTET GYNECOL SURV JI Obstet. Gynecol. Surv. PD NOV PY 2009 VL 64 IS 11 BP 734 EP 735 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 515QO UT WOS:000271487800019 ER PT J AU Alexander, JM Leveno, KJ Hauth, JC Landon, MB Gilbert, S Spong, CY Varner, MW Caritis, SN Meis, P Wapner, RJ Sorokin, Y Miodovnik, M O'Sullivan, MJ Sibai, BM Langer, O Gabbe, SG AF Alexander, James M. Leveno, Kenneth J. Hauth, John C. Landon, Mark B. Gilbert, Sharon Spong, Catherine Y. Varner, Michael W. Caritis, Steve N. Meis, Paul Wapner, Ronald J. Sorokin, Yoram Miodovnik, Menachem O'Sullivan, Mary J. Sibai, Baha M. Langer, Oded Gabbe, Steven G. CA NICHD MFMU TI Failed Operative Vaginal Delivery SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CESAREAN DELIVERY; FORCEPS; LABOR; OUTCOMES; TRIAL AB OBJECTIVE: To compare maternal and neonatal outcomes in women undergoing second-stage cesarean delivery after a trial of operative vaginal delivery with those in women undergoing second-stage cesarean delivery without such an attempt. METHODS: This study is a secondary analysis of the women who underwent second-stage cesarean delivery. The maternal outcomes examined included blood transfusion, endometritis, wound complication, anesthesia use, and maternal death. Neonatal outcomes examined included umbilical artery pH less than 7.0, Apgar score of 3 or less at 5 minutes, seizures within 24 hours of birth, hypoxic ischemic encephalopathy, stillbirth, skull fracture, and neonatal death. RESULTS: Of 3,189 women who underwent second-stage cesarean delivery, operative vaginal delivery was attempted in 640. Labor characteristics were similar in the two groups, with the exception of the admission-to-delivery time and cesarean indication. Those with an attempted operative vaginal delivery were more likely to undergo cesarean delivery for a nonreassuring fetal heart rate tracing (18.0% compared with 13.9%, P=.01), have a wound complication (2.7% compared with 1.0%, odds ratio [OR] 2.65, 95% confidence interval [CI] 1.43-4.91), and require general anesthesia (8.0% compared with 4.1%, OR 2.05, 95% CI 1.44-2.91). Neonatal outcomes, including umbilical artery pH less than 7.0, Apgar score of 3 or less at 5 minutes, and hypoxic ischemic encephalopathy, were more common for those with an attempted operative vaginal delivery. This was not significant when cases with a nonreassuring fetal heart rate tracing were removed. CONCLUSION: Cesarean delivery after an attempt at operative vaginal delivery was not associated with adverse neonatal outcomes in the absence of a nonreassuring fetal heart rate tracing. (Obstet Gynecol 2009;114:1017-22) C1 Univ Texas SW Med Ctr Dallas, Dept Obstet, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Gynecol, Dallas, TX 75390 USA. Univ Alabama, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Utah, Salt Lake City, UT USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Univ Miami, Miami, FL USA. Univ Tennessee, Memphis, TN USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Vanderbilt Univ, Nashville, TN USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Alexander, JM (reprint author), Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. EM james.alexander@utsouthwestern.edu RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD21410, HD21414, HD27860, HD27867, HD27869, HD27905, HD27915, HD27977, HD34116, HD34122, HD34136, HD34208, HD34210, HD36801] FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD21410, HD21414, HD27860, HD27867, HD27869, HD27905, HD27915, HD27977, HD34116, HD34122, HD34136, HD34208, HD34210, and HD36801). NR 11 TC 15 Z9 15 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 NOV PY 2009 VL 114 IS 5 BP 1017 EP 1022 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 513AH UT WOS:000271293500008 PM 20168101 ER PT J AU Castle, PE Wentzensen, N Wheeler, CM Rydzak, G Schiffman, M AF Castle, Philip E. Wentzensen, Nicolas Wheeler, Cosette M. Rydzak, Greg Schiffman, Mark TI Effect of the Number of Biopsies on the Subsequent Acquisition of New Human Papillomavirus Infections SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ATYPICAL SQUAMOUS-CELLS; RANDOMIZED-TRIAL; UNDETERMINED SIGNIFICANCE; CYTOLOGY INTERPRETATIONS; MANAGEMENT; CANCER; WOMEN; PERSISTENCE; DIAGNOSIS AB OBJECTIVE: To analyze the effect of number of biopsies taken at enrollment with incident human papillomavirus (HPV) infections detected at the next 6-month visit. METHODS: Using data from the Atypical Squamous Cells of Undetermined Significance (ASCUS) and Low-Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), we compared the 6-month acquisition of new HPV infections among 988 women who underwent colposcopy, were not diagnosed and treated for cervical intraepithelial neoplasia grade 2 or more severe lesions, and had polymerase chain reaction results for 38 HPV genotypes at enrollment and follow-up. Our analysis considered each woman's possible acquisition of each of these HPV genotypes. RESULTS: The average 6-month acquisition of any HPV genotype for women with zero, one, and two or more biopsies was 1.82%, 1.74%, and 1.97%, respectively (P(trend)=.7). In a logistic regression model that controlled for age, baseline HPV status, and having a new sexual partner during the 6-month follow-up, two or more biopsies (compared with one biopsy) was not associated with acquiring HPV (odds ratio 1.0, 95% confidence interval 0.75-1.3). CONCLUSION: Multiple biopsies compared with a single biopsy did not increase the likelihood of acquiring new HPV infections. (Obstet Gynecol 2009;114:1057-62) C1 [Castle, Philip E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Obstet & Gynecol, Hlth Sci Ctr, Albuquerque, NM 87131 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 5004,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU National Cancer Institute; National Institutes of Health Department of Health and Human Services [CN-55153, CN-55754, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159, CN-55705]; NIH FX ALTS was supported by the National Cancer Institute, National Institutes of Health Department of Health and Human Services contracts CN-55153, CN-55754, CN-55155, CN-55156, CN-55157, CN-55158, CN-55159 and CN-55705. Some of the equipment and supplies used in these studies were donated or provided at reduced cost by Digene Corporation, Gaithersburg, MD; Cytyc Corporation, Marlborough, AM; National Testing Laboratories, Fenton, MO; Den Yu, Tucson, AZ; TriRath Imaging, Inc., Burlington, NC; and Roche Molecular Systems Inc., Alameda, CA. Supported in part by the Intramural Research Program of the NIH, National Cancer Institute. NR 20 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2009 VL 114 IS 5 BP 1057 EP 1062 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 513AH UT WOS:000271293500014 PM 20168107 ER PT J AU Massad, LS Xie, XH Darragh, TM Minkoff, H Levine, AM D'Souza, G Cajigas, A Colie, C Watts, DH Strickler, HD AF Massad, L. Stewart Xie, Xianhong Darragh, Teresa M. Minkoff, Howard Levine, Alexandra M. D'Souza, Gypsyamber Cajigas, Anthony Colie, Christine Watts, D. Heather Strickler, Howard D. TI Histologic Correlates of Glandular Abnormalities in Cervical Cytology Among Women With Human Immunodeficiency Virus SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; HIV-INFECTED WOMEN; TERM-FOLLOW-UP; HUMAN-PAPILLOMAVIRUS; INTERAGENCY HIV; UNITED-STATES; CANCER; RISK; POPULATION; PREVALENCE AB OBJECTIVE: To estimate the frequency and histologic correlates of glandular abnormalities in cervical cytology among women with the human immunodeficiency virus (HIV) and to compare findings with those of women without HIV. METHODS: In a cohort study of HIV-infected and uninfected women followed between 1994 and 2007, Pap tests were obtained every 6 months. Glandular abnormalities, including atypical glandular cells (AGC), adenocarcinoma in situ (AIS), and adenocarcinoma, were identified and correlated with biopsy histology. Multivariate models to summarize data across visits used generalized estimating equations. The association of Pap and histology results was assessed using chi(2) tests. RESULTS: Of 48,362 Pap tests from 3,766 women, glandular abnormalities were found in 341 (0.7%) tests from 244 (6%) women, including 93 (1.0%) of 9,564 Pap tests among HIV-seropositive women with CD4 lymphocyte counts less than 250/mm(3), 103 (0.8%) of 13,023 tests among those with counts 250-500/mm(3), 68 (0.6%) of 12,470 tests among women with counts greater than 500/mm(3), and 70 (0.6%) of 11,769 tests among HIV-seronegative women (P for trend=.006). Colposcopy was documented for only 148 (61%) of 244 index Pap tests in women with glandular abnormalities. After index abnormal tests, endocervical curettings were obtained from 106 (43%) women, cervical biopsies from 76 (38%), and endometrial biopsies from 19 (8%). Squamous lesions predominated among histologic findings and histology results did not differ by HIV serostatus (P=.16). CONCLUSION: Although immunosuppression increased the risk of glandular Pap test abnormalities in women with HIV, these remained uncommon. Compliance with management guidelines can improved. (Obstet Gynecol 2009,114:1063-8) C1 Washington Univ, Sch Med, Springfield, IL USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Georgetown Univ, Washington, DC USA. Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Massad, LS (reprint author), Washington Univ, Sch Med, Div Gynecol Oncol, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA. EM massadl@wudosis.wustl.edu FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004, UO1-AI-31834, U07-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Institute of Child Health and Human Development [UO7-HD32632]; National Cancer Institute; National Institute on Drug Abuse; National Institute on Deafness; National Center for Research Resources [UL7 RR024137]; [R07-CA-085778] FX The Women's Interagency HIV study is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, U07-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the National Institute of Child Health and Human Development (UO7-HD32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL7 RR024137). Analysis was funded through R07-CA-085778. NR 20 TC 4 Z9 5 U1 0 U2 0 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 NOV PY 2009 VL 114 IS 5 BP 1063 EP 1068 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 513AH UT WOS:000271293500015 PM 20168108 ER PT J AU Slager, RE Poole, JA LeVan, TD Sandler, DP Alavanja, MCR Hoppin, JA AF Slager, R. E. Poole, J. A. LeVan, T. D. Sandler, D. P. Alavanja, M. C. R. Hoppin, J. A. TI Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID OCCUPATIONAL RHINITIS; RESPIRATORY SYMPTOMS; ALLERGIC RHINITIS; FARMERS; WHEEZE; ONSET; IOWA AB Objectives: Rhinitis is common, but the risk factors are not well described. To investigate the association between current rhinitis and pesticide use, we used data from 2245 Iowa commercial pesticide applicators in the Agricultural Health Study. Methods: Using logistic regression models adjusted for age, education and growing up on a farm, we evaluated the association between current rhinitis and 34 pesticides used in the past year. Results: 74% of commercial pesticide applicators reported at least one episode of rhinitis in the past year (current rhinitis). Five pesticides used in the past year were significantly positively associated with current rhinitis: the herbicides 2,4-D, glyphosate and petroleum oil, the insecticide diazinon and the fungicide benomyl. The association for 2,4-D and glyphosate was limited to individuals who used both in the past year (OR 1.42, 95% CI 1.14 to 1.77). Both petroleum oil and diazinon showed consistent evidence of an association with rhinitis, based on both current use and exposure-response models. We saw no evidence of confounding by common agricultural rhinitis triggers such as handling grain or hay. Conclusions: Exposure to pesticides may increase the risk of rhinitis. C1 [Sandler, D. P.; Hoppin, J. A.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Slager, R. E.] Wake Forest Univ Hlth Sci, Dept Pediat, Ctr Human Genom, Winston Salem, NC USA. [Poole, J. A.; LeVan, T. D.] Univ Nebraska Med Ctr, Dept Internal Med, Pulm Crit Care Sleep & Allergy Med Sect, Omaha, NE USA. [LeVan, T. D.] Univ Nebraska Med Ctr, Dept Epidemiol, Coll Publ Hlth, Omaha, NE USA. [Alavanja, M. C. R.] NCI, Occupat Epidemiol Branch, NIH, DHHS, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU National Cancer Institute; National Institute of Environmental Health Sciences; National Institutes of Health; US Department of Health and Human Services; National Institute of Alcohol Abuse and Alcoholism FX This work was supported by intramural research funds from the National Cancer Institute and the National Institute of Environmental Health Sciences, National Institutes of Health, US Department of Health and Human Services. RES was supported by a National Institute of Alcohol Abuse and Alcoholism R01 to principal investigator Joseph H Sisson, MD at the University of Nebraska Medical Center. NR 19 TC 20 Z9 20 U1 2 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 2009 VL 66 IS 11 BP 718 EP 724 DI 10.1136/oem.2008.041798 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 507YR UT WOS:000270892900004 PM 19289390 ER PT J AU Murthy, GVS Vashist, P John, N Pokharel, G Ellwein, LB AF Murthy, Gudlavalleti V. S. Vashist, Praveen John, Neena Pokharel, Gopal Ellwein, Leon B. CA SEWA-Rural Cataract Study Grp TI Prevalence and vision-related outcomes of cataract surgery in Gujarat, India SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE Blindness; Cataract surgery; India; Surgical complications; Visual outcome ID QUALITY-OF-LIFE; ARAVIND COMPREHENSIVE EYE; SURGICAL SERVICES; VISUAL IMPAIRMENT; RAPID ASSESSMENT; OLDER-ADULTS; AVOIDABLE BLINDNESS; RURAL-POPULATION; SOUTHERN INDIA; SHUNYI COUNTY AB Purpose: Investigate the prevalence and vision-related outcomes of cataract surgery in an area of high cataract surgical rate. Methods: Cluster sampling was used in randomly selecting individuals >= 50 years of age in 2007. Participants were queried regarding year and place of previous cataract surgery. Cataract surgical procedures and evidence of surgical complications were recorded. The principal cause was identified for eyes presenting with visual acuity (VA) <= 20/40. Results: A total of 4,738 persons were examined and 834 (17.6%) had cataract surgery. Intra-ocular lenses (IOLs) were used in 84.1% of the 1,299 cataract-operated eyes, with more than half of these having manual small incision surgery. Surgical coverage among the cataract blind (visual acuity [VA] < 20/200) was estimated as 72.2%. Coverage was associated with older age, literacy, and urban residence; gender was not significant. Among cataract-operated eyes, 18.7% presented with VA >= 20/32 and 18.0% were < 20/200. With best-corrected acuity, the corresponding percentages were 55.7% and 11.0%. Presenting and best-corrected VA >= 20/63 were associated with young age, literacy, and IOL surgery; urban residence and surgery in non-governmental organizations (NGO)/private facilities were also significant for presenting VA; and recent surgery was significant for best-corrected VA. Refractive error was the main cause of vision impairment/blindness in cataract-operated eyes. Conclusions: Refractive error and posterior capsule opacification, easily treatable causes of visual impairment, are common among the operated. A greater emphasis on the quality of visual acuity outcomes along with sustained efforts to provide access to affordable surgery is needed. C1 [Murthy, Gudlavalleti V. S.] Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, London WC1E 7HT, England. [Vashist, Praveen; John, Neena] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Community Ophthalmol Unit, New Delhi 110029, India. [Pokharel, Gopal] NEI, NIH, Bethesda, MD 20892 USA. [Ellwein, Leon B.] SEWA Rural, Bharuch, Gujarat, India. RP Murthy, GVS (reprint author), Univ London London Sch Hyg & Trop Med, Int Ctr Eye Hlth, Keppel St, London WC1E 7HT, England. EM gvsmurthy2000@yahoo.com FU World Health Organization, Geneva, Switzerland [N01-EY-2103] FX We thank Mr. Tara Dutt Pant and Mr. Hira Ballabh Pant, SEWA-Rural, for assisting with the training of field workers and analysis of pilot data.; Supported by World Health Organization, Geneva, Switzerland (Under Natural Institute of Health, Bethesde, Maryland) Contract no. N01-EY-2103. NR 46 TC 23 Z9 23 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD NOV-DEC PY 2009 VL 16 IS 6 BP 400 EP 409 DI 10.3109/09286580903315809 PG 10 WC Ophthalmology SC Ophthalmology GA 554SD UT WOS:000274453800011 PM 19995206 ER PT J AU Forooghian, F Agron, E Clemons, TE Ferris, FL Chew, EY AF Forooghian, Farzin Agron, Elvira Clemons, Traci E. Ferris, Frederick L., III Chew, Emily Y. CA AREDS Res Grp TI Visual Acuity Outcomes after Cataract Surgery in Patients with Age-Related Macular Degeneration: Age-Related Eye Disease Study Report No. 27 SO OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; HIGH-DOSE SUPPLEMENTATION; BLUE MOUNTAINS EYE; BEAVER DAM EYE; VISION LOSS; CLINICAL-TRIAL; BETA-CAROTENE; VITAMIN-C; AREDS; MACULOPATHY AB Objective: To evaluate visual acuity outcomes after cataract surgery in patients with varying degrees of age-related macular degeneration (AMD). Design: Cohort study. Participants: A total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD and a randomized controlled trial of antioxidants and minerals. Methods: Standardized lens and fundus photographs, performed at baseline and annual visits, were graded by a centralized reading center using standardized protocols for severity of AMD and lens opacities. History of cataract surgery was obtained every 6 months. Analyses were conducted using multivariate logistic regression. Main Outcome Measure: The change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Results: Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean time from cataract surgery to measurement of postoperative BCVA was 6.9 months. After adjustment for age at surgery, gender, type, and severity of cataract, the mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery. Conclusions: On average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2009; 116:2093-2100 (C) 2009 by the American Academy of Ophthalmology. C1 [Forooghian, Farzin; Agron, Elvira; Ferris, Frederick L., III; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. [Clemons, Traci E.] EMMES Corp, Rockville, MD USA. RP Chew, EY (reprint author), NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU National Eye Institute/National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland FX Supported by the intramural program funds and contracts from the National Eye Institute/National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. NR 36 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2009 VL 116 IS 11 BP 2093 EP 2100 DI 10.1016/j.ophtha.2009.04.033 PG 8 WC Ophthalmology SC Ophthalmology GA 512ZQ UT WOS:000271291600009 PM 19700198 ER PT J AU Gangaputra, S Newcomb, CW Liesegang, TL Kacmaz, RO Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Kempen, JH AF Gangaputra, Sapna Newcomb, Craig W. Liesegang, Teresa L. Kacmaz, R. Oktay Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Kempen, John H. CA Systemic Immunosuppressive Therapy TI Methotrexate for Ocular Inflammatory Diseases SO OPHTHALMOLOGY LA English DT Article ID LOW-DOSE METHOTREXATE; JUVENILE RHEUMATOID-ARTHRITIS; CORTICOSTEROID-SPARING THERAPY; IDIOPATHIC ARTHRITIS; IMMUNOSUPPRESSIVE THERAPY; INDUCED PNEUMONITIS; INTRAOCULAR LEVELS; OPTIC NEUROPATHY; CHRONIC UVEITIS; TOXICITY AB Purpose: To evaluate the outcome of treatment with methotrexate for noninfectious ocular inflammation. Design: Retrospective cohort study. Participants: Patients with noninfectious ocular inflammation managed at 4 tertiary ocular inflammation clinics in the United States observed to add methotrexate as a single, noncorticosteroid immunosuppressive agent to their treatment regimen, between 1979 and 2007, inclusive. Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Demographic and clinical characteristics, including dosage, route of administration of methotrexate, and main outcome measures, were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Control of inflammation, corticosteroid-sparing effects, and incidence of and reason for discontinuation of therapy. Results: Among 384 patients (639 eyes) observed from the point of addition of methotrexate to an anti-inflammatory regimen, 32.8%, 9.9%, 21.4%, 14.6%, 15.1%, and 6.3%, respectively, had anterior uveitis, intermediate uveitis, posterior or panuveitis, scleritis, ocular mucous membrane pemphigoid, and other forms of ocular inflammation. In these groups, complete suppression of inflammation sustained for 28 days was achieved within 6 months in 55.6%, 47.4%, 38.6%, 56.4%, 39.5%, and 76.7%, respectively. Corticosteroid-sparing success (sustained suppression of inflammation with prednisone <= 10 mg/d) was achieved within 6 months among 46.1%, 41.3%, 20.7%, 37.3%, 36.5%, and 50.9%, respectively. Overall, success within 12 months was 66% and 58.4% for sustained control and corticosteroid sparing (<= 10 mg), respectively. Methotrexate was discontinued within 1 year by 42% of patients. It was discontinued owing to ineffectiveness in 50 patients (13%); 60 patients (16%) discontinued because of side effects, which typically were reversible with dose reduction or discontinuation. Remission was seen in 43 patients, with 7.7% remitting within 1 year of treatment. Conclusions: Our data suggest that adding methotrexate to an anti-inflammatory regimen not involving other noncorticosteroid immunosuppressive drugs is moderately effective for management of inflammatory activity and for achieving corticosteroid-sparing objectives, although many months may be required for therapeutic success. Methotrexate was well tolerated by most patients, and seems to convey little risk of serious side effects during treatment. Financial Disclosure(s): The authors have no proprietary or commercial interests in any of the materials discussed in this article. Ophthalmology 2009,116:2188-2198 (C) 2009 by the American Academy of Ophthalmology. C1 [Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA. [Gangaputra, Sapna; Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Newcomb, Craig W.; Kempen, John H.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Liesegang, Teresa L.; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Kacmaz, R. Oktay; Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu FU National Eye Institute [EY014943]; Paul and Evanina Mackall Foundation; Research to Prevent Blindness James S. Adams Special Scholar Award; Senior Scientific Investigator Award; Prevent Blindness Harrington Special Scholar Award FX Supported primarily by National Eye Institute Grant EY014943 (JHK). Additional support was provided by Research to Prevent Blindness and the Paul and Evanina Mackall Foundation. Dr Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Drs Jabs and Rosenbaum are Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Dr Levy-Clarke was previously supported by and Dr Nussenblatt continues to be supported by intramural funds of the National Eye Institute. NR 49 TC 80 Z9 82 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2009 VL 116 IS 11 BP 2188 EP 2198 DI 10.1016/j.ophtha.2009.04.020 PG 11 WC Ophthalmology SC Ophthalmology GA 512ZQ UT WOS:000271291600022 PM 19748676 ER PT J AU Roescher, N Tak, PP Illei, GG AF Roescher, N. Tak, P. P. Illei, G. G. TI Cytokines in Sjogren's syndrome SO ORAL DISEASES LA English DT Review DE salivary glands; cytokines; autoimmune diseases; pathogenesis; immunology ID NECROSIS-FACTOR-ALPHA; LABIAL SALIVARY-GLANDS; GROWTH-FACTOR-BETA; CELL-LINE; AUTOIMMUNE-DISEASE; PERIPHERAL-BLOOD; INTERFERON-GAMMA; B-LYMPHOCYTES; CIRCULATING LEVELS; DENDRITIC CELLS AB Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjogren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the current knowledge of the expression and the function of pro- and anti-inflammatory cytokines both locally and systemically in Sjogren's syndrome patients. In the salivary glands, saliva and serum of these patients, many pro-inflammatory cytokines are upregulated. Concomitantly, most anti-inflammatory cytokines are not detectable or are expressed at low levels. Besides a role in inflammation, cytokines are also thought to be involved in salivary gland dysfunction by directly interfering with the epithelial cells in the glands. Future research on the role of novel cytokines in Sjogren's syndrome in combination with a better understanding of the effect of cytokines on exocrine dysfunction will aide the identification of the best therapeutic targets for Sjogren's syndrome. C1 [Roescher, N.; Illei, G. G.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Roescher, N.; Tak, P. P.] Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. RP Roescher, N (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM roeschern@mail.nih.gov FU NIH, NIDCR FX This research was supported by the intramural research program of the NIH, NIDCR. NR 87 TC 48 Z9 52 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1354-523X J9 ORAL DIS JI Oral Dis. PD NOV PY 2009 VL 15 IS 8 BP 519 EP 526 DI 10.1111/j.1601-0825.2009.01582.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 505CP UT WOS:000270666200001 PM 19519622 ER PT J AU Zhang, YQ Guo, N Peng, GD Han, M Raincrow, J Chiu, CH Coolen, LM Wenthold, RJ Zhao, ZQ Jing, NH Yu, L AF Zhang, Yu-Qiu Guo, Ning Peng, Guangdun Han, Mei Raincrow, Jeremy Chiu, Chi-hua Coolen, Lique M. Wenthold, Robert J. Zhao, Zhi-Qi Jing, Naihe Yu, Lei TI Role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain SO PAIN LA English DT Article DE SIP30; Neuropathic pain; Chronic constriction injury; Spinal cord; Intrathecal; Dorsal horn ID CA2+-DEPENDENT EXOCYTOSIS; GENE-EXPRESSION; FUNCTIONAL INVOLVEMENT; C57BL/6 MICE; PROTEIN; SNAP-25; SYNTAXIN; RAT; SNARE; IDENTIFICATION AB Using the chronic constriction injury (CCI) model of neuropathic pain, we profiled gene expression in the rat spinal cord, and identified SIP30 as a gene whose expression was elevated after CCI. SIP30 was previously shown to interact with SNAP25, but whose function was otherwise unknown. We now show that in the spinal cord, SIP30 was present in the dorsal horn laminae where the peripheral nociceptive inputs first synapse, co-localizing with nociception-related neuropeptides CGRP and substance P. With the onset of neuropathic pain after CCI surgery, SIP30 mRNA and protein levels increased in the ipsilateral side of the spinal cord, suggesting a potential association between SIP30 and neuropathic pain. When CCI-upregulated SIP30 was inhibited by intrathecal antisense oligonucleotide administration, neuropathic pain was attenuated. This neuropathic pain-reducing effect was observed both during neuropathic pain onset following CCI, and after neuropathic pain was fully established, implicating SIP30 involvement in the development and maintenance phases of neuropathic pain. Using a secretion assay in PC12 cells, anti-SIP30 siRNA decreased the total pool of synaptic vesicles available for exocytosis, pointing to a potential function for SIP30. These results suggest a role of SIP30 in the development and maintenance of peripheral nerve injury-induced neuropathic pain. (C) 2009 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Zhang, Yu-Qiu; Han, Mei; Zhao, Zhi-Qi] Fudan Univ, Inst Neurobiol, Inst Brain Sci, Shanghai 200433, Peoples R China. [Zhang, Yu-Qiu; Han, Mei; Zhao, Zhi-Qi] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Peng, Guangdun; Jing, Naihe] Chinese Acad Sci, Shanghai Inst Biol Sci, Mol Cell Biol Lab, Inst Biochem & Cell Biol, Shanghai, Peoples R China. [Wenthold, Robert J.] NIDCD, Neurochem Lab, NIH, Bethesda, MD USA. [Guo, Ning; Raincrow, Jeremy; Chiu, Chi-hua; Yu, Lei] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. [Guo, Ning; Raincrow, Jeremy; Chiu, Chi-hua; Yu, Lei] Rutgers State Univ, Ctr Alcohol Studies, Piscataway, NJ 08854 USA. [Zhang, Yu-Qiu; Guo, Ning; Coolen, Lique M.; Yu, Lei] Univ Cincinnati, Coll Med, Dept Cell Biol Neurobiol & Anat, Cincinnati, OH USA. RP Yu, L (reprint author), Rutgers State Univ, Dept Genet, 607 Allison Rd, Piscataway, NJ 08854 USA. EM lei.yu@rutgers.edu OI Peng, Guangdun/0000-0002-8586-0637 FU National Institutes of Health of the United States [DA013471, DA020555]; Life Science Special Fund of the Chinese Academy of Sciences for Human Genome Research [KJ95T-06, KSCX1-Y02]; National Natural Science Foundation of China [30821002, 30870338, 30623003, 30721065, 30830034]; National Key Basic Research and Development Program of China [2007CB512303, 2007CB512502, 2006CB500807, 2005CB522704, 2006CB943902, 2007CB947101, 2008KR0695, 2009CB941100]; Shanghai Key Project of Basic Science Research [06DJ14001, 06DZ22032, 08DJ1400501]; Council of the Shanghai Municipal for Science and Technology [088014199] FX We thank Dr. Thomas Sudhof and Dr. Mary Bittner for generously providing human growth hormone plasmids. This work was supported in part by grants from the National Institutes of Health of the United States (DA013471 and DA020555), the Life Science Special Fund of the Chinese Academy of Sciences for Human Genome Research (KJ95T-06 and KSCX1-Y02), the National Natural Science Foundation of China (30821002, 30870338, 30623003, 30721065, and 30830034), the National Key Basic Research and Development Program of China (2007CB512303, 2007CB512502, 2006CB500807, 2005CB522704, 2006CB943902,' 2007CB947101, 2008KR0695 and 2009CB941100), the Shanghai Key Project of Basic Science Research (06DJ14001, 06DZ22032 and 08DJ1400501), and the Council of the Shanghai Municipal for Science and Technology (088014199). The authors have no conflict of interest regarding this manuscript. NR 41 TC 12 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2009 VL 146 IS 1-2 BP 130 EP 140 DI 10.1016/j.pain.2009.07.011 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 519QH UT WOS:000271781600023 PM 19748740 ER PT J AU Kaphingst, KA Persky, S McCall, C Lachance, C Loewenstein, J Beall, AC Blascovich, J AF Kaphingst, Kimberly A. Persky, Susan McCall, Cade Lachance, Christina Loewenstein, Johanna Beall, Andrew C. Blascovich, Jim TI Testing the effects of educational strategies on comprehension of a genomic concept using virtual reality technology SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Patient education; Learning approaches; Genetics; Genetic communication ID ENVIRONMENT TECHNOLOGY; CONFOUNDER-SELECTION; CONTROLLED-TRIAL; INFORMATION; MEDIA; PSYCHOLOGY; PHYSIOLOGY; KNOWLEDGE; FRAMEWORK; EXPOSURE AB Objective: Applying genetic susceptibility information to improve health will likely require educating patients about abstract concepts, for which there is little existing research. This experimental study examined the effect of learning mode on comprehension of a genomic concept. Methods: 156 individuals aged 18-40 without specialized knowledge were randomly assigned to either a virtual reality active learning or didactic learning condition. The outcome was comprehension (recall, transfer, mental models). Results: Change in recall was greater for didactic learning than for active learning (p < 0.001). Mean transfer and change in mental models were also higher for didactic learning (p < 0.0001 and p < 0.05, respectively). Believability was higher for didactic learning (p < 0.05), while ratings for motivation (p < 0.05), interest (p < 0.0001), and enjoyment (p < 0.0001) were higher for active learning, but these variables did not mediate the association between learning mode and comprehension. Conclusion: These results show that learning mode affects comprehension, but additional research is needed regarding how and in what contexts different approaches are best for educating patients about abstract concepts. Practice implications: Didactic, interpersonal health education approaches may be more effective than interactive games in educating patients about abstract, unfamiliar concepts. These findings indicate the importance of traditional health education approaches in emerging areas like genomics. Published by Elsevier Ireland Ltd. C1 [Kaphingst, Kimberly A.; Persky, Susan; Lachance, Christina; Loewenstein, Johanna] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. [McCall, Cade; Beall, Andrew C.; Blascovich, Jim] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. RP Kaphingst, KA (reprint author), NHGRI, Social & Behav Res Branch, Bldg 31,Room B1B37E,31 Ctr Dr,MSC 2073, Bethesda, MD 20892 USA. EM kkaphing@mail.nih.gov FU Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. We thank Rajiv Rimal, Celeste Condit, Colleen McBride, and Beth Ford for their comments on a previous draft of this manuscript and Ibrahim Senay for assistance with data collection. NR 43 TC 6 Z9 6 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD NOV PY 2009 VL 77 IS 2 BP 224 EP 230 DI 10.1016/j.pec.2009.03.029 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 522UO UT WOS:000272024700013 PM 19409749 ER PT J AU London, WB Sondel, P Gilman, AL Ozkaynak, F Kreissman, S Buxton, A Chen, H Matthay, KK Cohn, SL Maris, JM Yu, AL AF London, Wendy B. Sondel, Paul Gilman, Andrew L. Ozkaynak, Fevzi Kreissman, Susan Buxton, Allen Chen, Helen Matthay, Katherine K. Cohn, Susan L. Maris, John M. Yu, Alice L. TI SUCCESS OF CHIMERIC ANTI-GD2 ANTIBODY+GM-CSF+IL2 IMMUNOTHERAPY IN HIGH-RISK NEUROBLASTOMA (NB) IN FIRST RESPONSE: A CRITICAL APPRAISAL SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [London, Wendy B.] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Gainesville, FL USA. [Sondel, Paul] Univ Wisconsin, AFCH, Madison, WI USA. [Gilman, Andrew L.] Levine Childrens Hosp, Carolinas Med Ctr, Div Ped Blood & Marrow Transplantat, Charlotte, NC USA. [Ozkaynak, Fevzi] New York Med Coll, Pediat Sect Hematol Oncol, Valhalla, NY 10595 USA. [Kreissman, Susan] Duke Univ, Med Ctr, Durham, NC USA. [Buxton, Allen] Stat & Data Ctr, Childrens Oncol Grp, Arcadia, CA USA. [Chen, Helen] NCI, NIH, Clin Trials Evaluat Program, Bethesda, MD 20892 USA. [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Cohn, Susan L.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Yu, Alice L.] Univ Calif San Diego, Rady Childrens Hosp San Diego, Div Hematol Oncol, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2009 VL 53 IS 5 BP 708 EP 708 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 499XS UT WOS:000270260700022 ER PT J AU Stephen, H Mullighan, C Downing, J Relling, M Willman, C Devidas, M Reaman, G Carroll, W Smith, M Zhang, JH Gerhard, D AF Stephen, Hunger Mullighan, Charles Downing, James Relling, Mary Willman, Cheryl Devidas, Meenakshi Reaman, Greg Carroll, William Smith, Malcolm Zhang, Jinghui Gerhard, Daniela TI THE SPECTRUM OF MUTATIONS IN CHILDHOOD ALL SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Stephen, Hunger] Childrens Hosp, Pediat Hematol Oncol BMT, Aurora, CO USA. [Mullighan, Charles; Downing, James; Relling, Mary] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Willman, Cheryl] Univ New Mexico, Albuquerque, NM 87131 USA. [Devidas, Meenakshi] Univ Florida, Coll Med, Gainesville, FL USA. [Reaman, Greg] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Carroll, William] NYU, New York, NY USA. [Zhang, Jinghui] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA. [Gerhard, Daniela] NCI, Off Canc Genom, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2009 VL 53 IS 5 BP 730 EP 730 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 499XS UT WOS:000270260700099 ER PT J AU Kovar, H Kauer, M Ban, J Walker, B Davis, S Meltzer, P AF Kovar, Heinrich Kauer, Max Ban, Jozef Walker, Bob Davis, Sean Meltzer, Paul TI THE EWING'S SARCOMA ONCOGENE EWS-FLII COMBINES IN A SINGLE MOLECULE PROLIFERATION AND DIFFERENTIATION CONTROL BY DISTINCT TRANSCRIPTIONAL MECHANISMS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kovar, Heinrich; Kauer, Max; Ban, Jozef] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Walker, Bob; Davis, Sean; Meltzer, Paul] NCI, NIH, Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2009 VL 53 IS 5 BP 790 EP 791 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 499XS UT WOS:000270260700313 ER PT J AU Cogulu, D Becerik, S Emingil, G Hart, PS Hart, TC AF Cogulu, Dilsah Becerik, Sema Emingil, Gulnur Hart, P. Suzanne Hart, Thomas C. TI Oral Rehabilitation of a Patient with Amelogenesis lmperfecta SO PEDIATRIC DENTISTRY LA English DT Article DE GENETICS; GROWTH AND DEVELOPMENT; ORAL PATHOLOGY; AMELOGENESIS IMPERFECTA ID RESTORING FUNCTION; CLINICAL REPORT; INTERDISCIPLINARY APPROACH; FAM83H MUTATIONS; IMPERFECTA; CLASSIFICATION; AESTHETICS; FAMILIES; ENAMELIN; GENE AB Amelogenesis imperfecta is a hereditary disorder that causes defective enamel development in the primary and permanent teeth. Clinical treatment is important to address the esthetic appearance of affected teeth, reduce dentinal sensitivity, preserve tooth structure, and optimize masticatory function. The purpose of this case report was to describe the diagnosis, treatment planning, and dental rehabilitation of a patient with autosomal recessive amelogenesis imperfecta. The patient was followed for 5 years, and evaluation 3 years after restorations revealed no pathology associated with the rehabilitation. The patient's esthetic and functional expectations were satisfied. (Pediatr Dent 2009;31:523-7) Received August 5, 2008 vertical bar Lost Revision October 5, 2008 vertical bar Revision Accepted December 5, 2008 C1 [Cogulu, Dilsah] Ege Univ, Sch Dent, Dept Pediat Dent, Izmir, Turkey. [Becerik, Sema; Emingil, Gulnur] Ege Univ, Sch Dent, Dept Periodontol, Izmir, Turkey. [Hart, P. Suzanne] Natl Human Genome Inst, Bethesda, MD USA. [Hart, Thomas C.] Natl Inst Dent & Craniofacial Res, Human & Craniofacial Genet Sect, Bethesda, MD USA. RP Cogulu, D (reprint author), Ege Univ, Sch Dent, Dept Pediat Dent, Izmir, Turkey. EM dilash.cogulu@ege.edu.tr FU Intramural NIH HHS [Z99 HG999999] NR 41 TC 2 Z9 2 U1 1 U2 2 PU AMER ACAD PEDIATRIC DENTISTRY PI CHICAGO PA 211 E CHICAGO AVENUE SUITE 1036, CHICAGO, IL 60611-2616 USA SN 0164-1263 J9 PEDIATR DENT JI Pediatr. Dent. PD NOV-DEC PY 2009 VL 31 IS 7 BP 523 EP 527 PG 5 WC Dentistry, Oral Surgery & Medicine; Pediatrics SC Dentistry, Oral Surgery & Medicine; Pediatrics GA 668SK UT WOS:000283289900012 PM 20108745 ER PT J AU Freeman, AF Olivier, KN Rubio, TT Bartlett, G Ochi, JW Claypool, RJ Ding, L Kuhns, DB Holland, SM AF Freeman, Alexandra F. Olivier, Kenneth N. Rubio, Thomas T. Bartlett, Glen Ochi, James W. Claypool, Reginald J. Ding, Li Kuhns, Douglas B. Holland, Steven M. TI Intrathoracic Nontuberculous Mycobacterial Infections in Otherwise Healthy Children SO PEDIATRIC PULMONOLOGY LA English DT Article DE nontuberculous mycobacteria; intrathoracic infection; hilar lymphadenopathy; endobronchial granuloma ID AVIUM COMPLEX; CYSTIC-FIBROSIS; BRONCHIECTASIS; LYMPHADENITIS; IMMUNITY AB Background: Nontuberculous mycobacterial (NTM) infection is typically associated with lymphadenitis in immune competent children, and disseminated disease in children with immune deficiencies. Isolated pulmonary NTM disease is seen in cystic fibrosis, and is increasingly recognized in immunocompetent elderly women, where it is associated with an increased incidence of cystic fibrosis transmembrane regulator (CFTR) mutations. Thoracic NTM infection has been reported rarely in otherwise healthy children. We aimed to determine whether otherwise healthy children with pulmonary NTM disease had immunologic abnormalities or CFTR mutations. Clinical presentations of five otherwise healthy children with pulmonary NTM were reviewed. Immunologic studies were performed including a complete blood cell count (CBC), flow cytometric lymphocyte phenotyping and IFN-gamma receptor expression, in vitro cytokine stimulation, and serum immunoglobulin levels. Mutational analysis was performed for CFTR. The children ranged in age from 12 months to 2.5 years at diagnosis. Four presented with new onset wheezing or stridor failing bronchodilator therapy One child was asymptomatic. Endobronchial lesions and/or hilar lymph nodes causing bronchial obstruction were identified in all patients. Mycobacterium avium complex was cultured from four patients, and Mycobacterium abscessus from one patient. All patients were successfully treated with anti-mycobacterial therapy with or without surgery. No definitive immunologic abnormalities were identified. No clinically significant mutations were found in CFTR. Pulmonary NTM infection should be considered in otherwise healthy young children presenting with refractory stridor or wheezing with endobronchial lesions or hilar lymphadenopathy. It does not appear to be associated with recognized underlying immune deficiency or CFTR mutations. Pediatr Pulmonol. 2009; 44:1051-1056. (C) 2009 Wiley-Liss, Inc. C1 [Freeman, Alexandra F.; Kuhns, Douglas B.] SAIC Frederick Inc, NCI Frederick, Frederick, MD 21702 USA. [Olivier, Kenneth N.; Claypool, Reginald J.; Ding, Li; Holland, Steven M.] NIAID, NIH, Bethesda, MD 20892 USA. [Rubio, Thomas T.] Georgetown Univ Hosp, Dept Pediat, Washington, DC 20007 USA. [Ochi, James W.] Univ Calif San Diego, San Diego, CA 92103 USA. [Bartlett, Glen] Hershey Pediat Ctr, Hershey, PA USA. RP Freeman, AF (reprint author), Bldg 10,Room 11N234,10 Ctr Dr, Bethesda, MD 20892 USA. EM freemaal@mail.nih.gov FU National Cancer Institute; National Institutes of Health [N01-CO-12400, HHSN261200800001E]; NIAID FX Grant sponsor: National Cancer Institute; Grant sponsor: National Institutes of Health: Grant numbers: N01-CO-12400, HHSN261200800001E; Grant sponsor: Intramural Program of NIAID; Grant sponsor: National Institute of Allergy and Infectious Diseases. NR 17 TC 7 Z9 7 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-6863 J9 PEDIATR PULM JI Pediatr. Pulmonol. PD NOV PY 2009 VL 44 IS 11 BP 1051 EP 1056 DI 10.1002/ppul.21069 PG 6 WC Pediatrics; Respiratory System SC Pediatrics; Respiratory System GA 517GV UT WOS:000271602200001 PM 19824053 ER PT J AU Lester, BM Bagner, DM Liu, J LaGasse, LL Seifer, R Bauer, CR Shankaran, S Bada, H Higgins, RD Das, A AF Lester, Barry M. Bagner, Daniel M. Liu, Jing LaGasse, Linda L. Seifer, Ronald Bauer, Charles R. Shankaran, Seetha Bada, Henrietta Higgins, Rosemary D. Das, Abhik TI Infant Neurobehavioral Dysregulation: Behavior Problems in Children With Prenatal Substance Exposure SO PEDIATRICS LA English DT Article DE prenatal substance exposure; cocaine; neurobehavioral dysregulation; behavior problems ID MATERNAL LIFE-STYLE; COCAINE EXPOSURE; USE DISORDER; ENVIRONMENTAL RISK; YOUNG ADULTHOOD; DISINHIBITION; AGE; PREGNANCY; GENDER AB OBJECTIVE: The objective of this study was to test a developmental model of neurobehavioral dysregulation relating prenatal substance exposure to behavior problems at age 7. METHODS: The sample included 360 cocaine-exposed and 480 unexposed children from lower to lower middle class families of which 78% were black. Structural equation modeling was used to test models whereby prenatal exposure to cocaine and other substances would result in neurobehavioral dysregulation in infancy, which would predict externalizing and internalizing behavior problems in early childhood. Structural equation models were developed for individual and combined parent and teacher report for externalizing, internalizing, and total problem scores on the Child Behavior Checklist. RESULTS: The goodness-of-fit statistics indicated that all of the models met criteria for adequate fit with 7 of the 9 models explaining 18% to 60% of the variance in behavior problems at age 7. The paths in the models indicate that there are direct effects of prenatal substance exposure on 7-year behavior problems as well as indirect effects, including neurobehavioral dysregulation. CONCLUSIONS: Prenatal substance exposure affects behavior problems at age 7 through 2 mechanisms. The direct pathway is consistent with a teratogenic effect. Indirect pathways suggest cascading effects whereby prenatal substance exposure results in neurobehavioral dysregulation manifesting as deviations in later behavioral expression. Developmental models provide an understanding of pathways that describe how prenatal substance exposure affects child outcome and have significant implications for early identification and prevention. Pediatrics 2009; 124: 1355-1362 C1 [Lester, Barry M.; Bagner, Daniel M.; Liu, Jing; LaGasse, Linda L.] Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Dept Pediat, Providence, RI 02905 USA. [Seifer, Ronald] Brown Univ, Warren Alpert Med Sch, Bradley Hosp, Dept Psychiat & Human Behav, Providence, RI 02905 USA. [Bauer, Charles R.] Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. [Shankaran, Seetha] Wayne State Univ Detroit, Sch Med, Dept Pediat, Detroit, MI USA. [Bada, Henrietta] Univ Kentucky Hosp, Lexington, KY USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Bethesda, MD USA. [Das, Abhik] Res Triangle Inst, Div Stat Res, Res Triangle Pk, NC 27709 USA. RP Lester, BM (reprint author), Brown Univ, Women & Infants Hosp, Brown Ctr Study Children Risk, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA. EM blester@wihri.org OI Seifer, Ronald/0000-0003-4879-2839 FU NICHD NIH HHS [U01 HD 36790, N01-HD-2-3159, U10 HD027904, U01 HD036790, U10 HD021385, U10 HD021397, U10HD 21397, U10 HD 27904, U10 HD 21415, U10 HD 21385]; NIDA NIH HHS [U10 DA024119-04, U10 DA024119, U10 DA024119-03, U10 DA024128-09, U10 DA024117-01, U10 DA024117-04, U10 DA024118-03, U10 DA024119-02, U10 DA024119-02S2, U10 DA024128-08, U10 DA024117-02, U10 DA024118-01, U10 DA024118-04, U10 DA024128-06, U10 DA024128-07, U10 DA024119-02S1, U10 DA024119-01, U10 DA024118-02, U10 DA024117-03, U10 DA024117] NR 31 TC 25 Z9 25 U1 3 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2009 VL 124 IS 5 BP 1355 EP 1362 DI 10.1542/peds.2008-2898 PG 8 WC Pediatrics SC Pediatrics GA 510MH UT WOS:000271092100014 PM 19822596 ER PT J AU Binns, HJ Forman, JA Karr, CJ Paulson, JA Osterhoudt, KC Roberts, JR Sandel, MT Seltzer, JM Wright, RO Best, D Blackburn, E Anderson, M Savage, S Rogan, WJ Spire, P Williams, JF Behnke, M Kokotailo, PK Levy, SJ Sims, TH Wunsch, MJ Simkin, D Smith, KS Blythe, MJ Barratt, MS Braverman, PK Murray, PJ Rosen, DS Seigel, WM Wibbelsman, CJ Breech, LL Pinzon, JL Shain, B Smith, KS Moore, KR Bell, JT Etzel, RA Hoffman, BD Ponder, SW Redding, MM Waldron, D Dubray, KL Lund, KJ Saylor, K Storck, MG Holve, SA Thierry, JK Kim, S Kim, S AF Binns, Helen J. Forman, Joel A. Karr, Catherine J. Paulson, Jerome A. Osterhoudt, Kevin C. Roberts, James R. Sandel, Megan T. Seltzer, James M. Wright, Robert O. Best, Dana Blackburn, Elizabeth Anderson, Mark Savage, Sharon Rogan, Walter J. Spire, Paul Williams, Janet F. Behnke, Marylou Kokotailo, Patricia K. Levy, Sharon J. Sims, Tammy H. Wunsch, Martha J. Simkin, Deborah Smith, Karen S. Blythe, Margaret J. Barratt, Michelle S. Braverman, Paula K. Murray, Pamela J. Rosen, David S. Seigel, Warren M. Wibbelsman, Charles J. Breech, Lesley L. Pinzon, Jorge L. Shain, Benjamin Smith, Karen S. Moore, Kelly R. Bell, Joseph T. Etzel, Ruth A. Hoffman, Benjamin D. Ponder, Stephen W. Redding, Mark M. Waldron, Debra Dubray, Kansas L. Lund, Kirsten J. Saylor, Kent Storck, Michael G. Holve, Stephen A. Thierry, Judith K. Kim, Sunnah Kim, Sunnah CA Comm Environm Hlth Comm Subst Abuse Comm Adolescence Comm Native Amer Child Hlth TI Policy Statement-Tobacco Use: A Pediatric Disease SO PEDIATRICS LA English DT Review DE tobacco; smoke; cigarette; environmental tobacco; nicotine; secondhand; smoke free; cigar; smokeless ID CLINICAL PREVENTIVE SERVICES; NICOTINE DEPENDENCE; SMOKING-CESSATION; CIGARETTE-SMOKING; COST-EFFECTIVENESS; UNITED-STATES; MENTAL-HEALTH; ADOLESCENTS; INITIATION; CHILDREN AB Tobacco use and secondhand tobacco-smoke (SHS) exposure are major national and international health concerns. Pediatricians and other clinicians who care for children are uniquely positioned to assist patients and families with tobacco-use prevention and treatment. Understanding the nature and extent of tobacco use and SHS exposure is an essential first step toward the goal of eliminating tobacco use and its consequences in the pediatric population. The next steps include counseling patients and family members to avoid SHS exposures or cease tobacco use; advocacy for policies that protect children from SHS exposure; and elimination of tobacco use in the media, public places, and homes. Three overarching principles of this policy can be identified: (1) there is no safe way to use tobacco; (2) there is no safe level or duration of exposure to SHS; and (3) the financial and political power of individuals, organizations, and government should be used to support tobacco control. Pediatricians are advised not to smoke or use tobacco; to make their homes, cars, and workplaces tobacco free; to consider tobacco control when making personal and professional decisions; to support and advocate for comprehensive tobacco control; and to advise parents and patients not to start using tobacco or to quit if they are already using tobacco. Prohibiting both tobacco advertising and the use of tobacco products in the media is recommended. Recommendations for eliminating SHS exposure and reducing tobacco use include attaining universal (1) smoke-free home, car, school, work, and play environments, both inside and outside, (2) treatment of tobacco use and dependence through employer, insurance, state, and federal supports, (3) implementation and enforcement of evidence-based tobacco-control measures in local, state, national, and international jurisdictions, and (4) financial and systems support for training in and research of effective ways to prevent and treat tobacco use and SHS exposure. Pediatricians, their staff and colleagues, and the American Academy of Pediatrics have key responsibilities in tobacco control to promote the health of children, adolescents, and young adults. Pediatrics 2009; 124: 1474-1487 C1 [Blackburn, Elizabeth] US EPA, Washington, DC 20460 USA. [Anderson, Mark] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. [Savage, Sharon] NCI, Bethesda, MD 20892 USA. [Rogan, Walter J.] NIEHS, Res Triangle Pk, NC 27709 USA. OI Savage, Sharon/0000-0001-6006-0740 NR 100 TC 66 Z9 68 U1 4 U2 12 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2009 VL 124 IS 5 BP 1474 EP 1487 DI 10.1542/peds.2009-2114 PG 14 WC Pediatrics SC Pediatrics GA 510MH UT WOS:000271092100028 ER PT J AU Lambert, LM Minich, LL Newburger, JW Lu, M Pemberton, VL McGrath, EA Atz, AM Xu, MF Radojewski, E Servedio, D McCrindle, BW AF Lambert, Linda M. Minich, L. LuAnn Newburger, Jane W. Lu, Minmin Pemberton, Victoria L. McGrath, Ellen A. Atz, Andrew M. Xu, Mingfen Radojewski, Elizabeth Servedio, Darlene McCrindle, Brian W. CA Pediat Heart Network Investigators TI Parent-Versus Child-Reported Functional Health Status After the Fontan Procedure SO PEDIATRICS LA English DT Article DE Fontan procedure; congenital heart disease; single ventricle; functional health status; quality of life ID QUALITY-OF-LIFE; CONGENITAL HEART-DISEASE; CYSTIC-FIBROSIS; AGREEMENT; ADOLESCENTS; OPERATION; FAMILIES; OUTCOMES AB OBJECTIVE: We sought to compare perceptions of functional health status between children who had undergone a Fontan procedure and their parents. METHODS: Fontan procedure survivors 10 to 18 years of age were included in the study if the child completed the Child Health Questionnaire (CHQ) and the parent completed the parent form to assess the child's functional health status. Comparisons were made between raw domain scores for the parent- and child-completed CHQs. RESULTS: Between March 2003 and April 2004, 1078 Fontan survivors were screened. Of the 546 eligible and consented patients, 354 were 10-18 years of age and 328 parent/child pairs completed the CHQs. Parents reported significantly lower scores (worse functioning) for their children than the children reported for themselves in the domains of physical functioning (P < .01), impact on school or activities from emotional and behavioral problems (P < .01), impact on school or activities from physical health issues (P < .01), general behavior (P < .01), mental health (P < .01), self-esteem (P < .01), and general health perceptions (P < .01). No significant differences were noted for the domains of bodily pain, family cohesiveness, or family activities. For the physical functioning domain, factors contributing to lower scores for parent versus child reports included pulmonary artery anomalies and fenestration at the time of the Fontan operation. Lower parent-reported scores also were associated with more noncardiac health problems in the child. CONCLUSIONS: Parents' perceptions of the functional health status of their children after the Fontan procedure were worse than the children's perceptions. Pediatrics 2009; 124: e942-e949 C1 [Lambert, Linda M.; Minich, L. LuAnn] Primary Childrens Med Ctr, Dept Pediat, Salt Lake City, UT 84113 USA. [Lambert, Linda M.] Primary Childrens Med Ctr, Dept Cardiothorac, Salt Lake City, UT 84113 USA. Univ Utah, Salt Lake City, UT USA. [Newburger, Jane W.; McGrath, Ellen A.] Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. [Lu, Minmin] New England Res Inst, Watertown, MA 02172 USA. [Pemberton, Victoria L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Atz, Andrew M.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Xu, Mingfen] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Radojewski, Elizabeth; McCrindle, Brian W.] Univ Toronto, Dept Pediat, Toronto, ON, Canada. [Radojewski, Elizabeth; McCrindle, Brian W.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Servedio, Darlene] Columbia Univ, Med Ctr, Dept Pediat, New York, NY USA. RP Lambert, LM (reprint author), Primary Childrens Med Ctr, Dept Pediat, 100 N Mario Capecchi Dr,Suite 2800, Salt Lake City, UT 84113 USA. EM linda.lambert@imail.org RI Hurwitz Koweek, lynne/N-1351-2015 OI Hurwitz Koweek, lynne/0000-0001-9990-3397 FU NHLBI NIH HHS [HL068292, HL068269, HL068270, HL068279, HL068281, HL068285, HL068288, HL068290, U01 HL068269, U01 HL068270, U01 HL068279, U01 HL068281, U01 HL068285, U01 HL068288, U01 HL068288-09, U01 HL068290, U01 HL068292, U10 HL068270, U10 HL109778] NR 30 TC 27 Z9 27 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2009 VL 124 IS 5 BP E942 EP E949 DI 10.1542/peds.2008-1697 PG 8 WC Pediatrics SC Pediatrics GA 510MH UT WOS:000271092100047 PM 19841109 ER PT J AU Thomas, FC Taskar, K Rudraraju, V Goda, S Thorsheim, HR Gaasch, JA Mittapalli, RK Palmieri, D Steeg, PS Lockman, PR Smith, QR AF Thomas, Fancy C. Taskar, Kunal Rudraraju, Vinay Goda, Satyanarayana Thorsheim, Helen R. Gaasch, Julie A. Mittapalli, Rajendar K. Palmieri, Diane Steeg, Patricia S. Lockman, Paul R. Smith, Quentin R. TI Uptake of ANG1005, A Novel Paclitaxel Derivative, Through the Blood-Brain Barrier into Brain and Experimental Brain Metastases of Breast Cancer SO PHARMACEUTICAL RESEARCH LA English DT Article DE ANG1005; blood-brain barrier; brain tumor; paclitaxel ID CENTRAL-NERVOUS-SYSTEM; CELL LUNG-CANCER; PROPHYLACTIC CRANIAL IRRADIATION; DELIVERY VECTOR ANGIOPEP-2; RECEPTOR-RELATED PROTEIN; IN-VITRO; P-GLYCOPROTEIN; MEDIATED ENDOCYTOSIS; TISSUE DISTRIBUTION; PERFUSION TECHNIQUE AB We evaluated the uptake of angiopep-2 paclitaxel conjugate, ANG1005, into brain and brain metastases of breast cancer in rodents. Most anticancer drugs show poor delivery to brain tumors due to limited transport across the blood-brain barrier (BBB). To overcome this, a 19-amino acid peptide (angiopep-2) was developed that binds to low density lipoprotein receptor-related protein (LRP) receptors at the BBB and has the potential to deliver drugs to brain by receptor-mediated transport. The transfer coefficient (K(in)) for brain influx was measured by in situ rat brain perfusion. Drug distribution was determined at 30 min after i.v. injection in mice bearing intracerebral MDA-MB-231BR metastases of breast cancer. The BBB K(in) for (125)I-ANG1005 uptake (7.3 +/- 0.2 x 10(-3) mL/s/g) exceeded that for (3)H-paclitaxel (8.5 +/- 0.5 x 10(-5)) by 86-fold. Over 70% of (125)I-ANG1005 tracer stayed in brain after capillary depletion or vascular washout. Brain (125)I-ANG1005 uptake was reduced by unlabeled angiopep-2 vector and by LRP ligands, consistent with receptor transport. In vivo uptake of (125)I-ANG1005 into vascularly corrected brain and brain metastases exceeded that of (14)C-paclitaxel by 4-54-fold. The results demonstrate that ANG1005 shows significantly improved delivery to brain and brain metastases of breast cancer compared to free paclitaxel. C1 [Thomas, Fancy C.; Taskar, Kunal; Rudraraju, Vinay; Goda, Satyanarayana; Thorsheim, Helen R.; Gaasch, Julie A.; Mittapalli, Rajendar K.; Lockman, Paul R.; Smith, Quentin R.] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. [Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Cancers Sect, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Gaasch, Julie A.] W Texas A&M Univ, Dept Life Earth & Environm Sci, Canyon, TX 79016 USA. RP Smith, QR (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Pharmaceut Sci, 1300 S Coulter Dr, Amarillo, TX 79106 USA. EM Quentin.Smith@ttuhsc.edu RI Palmieri, Diane/B-4258-2015 FU Department of Defense Breast Cancer Program [W81XWH-062-0033]; NIH/NINDS [R01 NS052484]; AngioChem, Inc. FX This work was supported by grants from the Department of Defense Breast Cancer Program (W81XWH-062-0033), NIH/NINDS (R01 NS052484), and from AngioChem, Inc. NR 54 TC 87 Z9 93 U1 2 U2 15 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD NOV PY 2009 VL 26 IS 11 BP 2486 EP 2494 DI 10.1007/s11095-009-9964-5 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 507ZP UT WOS:000270896000011 PM 19774344 ER PT J AU Maurice, T Su, TP AF Maurice, Tangui Su, Tsung-Ping TI The pharmacology of sigma-1 receptors SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Sigma-1 receptor; Cocaine; Cancer; Pain; Stroke; Depression ID LONG-TERM POTENTIATION; CONDITIONED PLACE PREFERENCE; TUMOR-CELL-LINES; AMINOTETRAHYDROFURAN DERIVATIVE ANAVEX1-41; INDUCED BEHAVIORAL SENSITIZATION; HIPPOCAMPAL CA1 SYNAPSES; NITRIC-OXIDE SYNTHASE; DORSAL RAPHE NUCLEUS; FORCED SWIMMING TEST; HUMAN BREAST-CANCER AB Originally considered an enigmatic protein, the sigma-1 receptor has recently been identified as a unique ligand-regulated molecular chaperone in the endoplasmic reticulum of cells. This discovery causes us to look back at the many proposed roles of this receptor, even before its molecular function was identified, in many diseases such as methamphetamine or cocaine addiction, amnesia, pain, depression, Alzheimer's disease, stroke, retinal neuroprotection, HIV infection, and cancer. In this review, we examine the reports that have clearly shown an agonist-antagonist relationship regarding sigma-1 receptors in models of those diseases and also review the relatively known mechanisms of action of sigma-1 receptors in an attempt to spur the speculation of readers on how the sigma-1 receptor at the endoplasmic reticulum might relate to so many diseases. We found that the most prominent action of sigma-1 receptors in biological systems including cell lines, primary cultures, and animals is the regulation and modulation of voltage-regulated and ligand-gated ion channels, including Ca2+-, K+-, Na+, Cl-, and SK channels, and NMDA and IP3 receptors. We found that the final output of the action of sigma-1 receptor agonists is to inhibit all above-mentioned voltage-gated ion channels, while they potentiate ligand-gated channels. The inhibition or potentiation induced by agonists is blocked by sigma-1 receptor antagonists. Other mechanisms of action of sigma-1 receptors, and to some extent those of sigma-2 receptors, were also considered. We conclude that the sigma-1 and sigma-2 receptors represent potential fruitful targets for therapeutic developments in combating many human diseases. Published by Elsevier Inc. C1 [Maurice, Tangui] INSERM, U710, Team Endogenous Neuroprotect Neurodegenerat Dis 2, F-34095 Montpellier 5, France. [Maurice, Tangui] Univ Montpellier 2, EPHE, CC 105, F-34095 Montpellier 5, France. [Maurice, Tangui] EPHE, F-75017 Paris, France. [Su, Tsung-Ping] NIDA, Cellular Pathobiol Sect, Cellular Neurobiol Res Branch, IRP,NIH, Baltimore, MD 21224 USA. RP Maurice, T (reprint author), INSERM, U710, Team Endogenous Neuroprotect Neurodegenerat Dis 2, F-34095 Montpellier 5, France. EM Tangui.Maurice@univ-montp2.fr; TSU@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000206-22, Z99 DA999999] NR 172 TC 311 Z9 316 U1 8 U2 51 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD NOV PY 2009 VL 124 IS 2 BP 195 EP 206 DI 10.1016/j.pharmthera.2009.07.001 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 506LW UT WOS:000270777300005 PM 19619582 ER PT J AU Casado, V Cortes, A Mallol, J Perez-Capote, K Ferre, S Lluis, C Franco, R Canela, EI AF Casado, Vicent Cortes, Antoni Mallol, Josefa Perez-Capote, Kamil Ferre, Sergi Lluis, Carmen Franco, Rafael Canela, Enric I. TI GPCR homomers and heteromers: A better choice as targets for drug development than GPCR monomers? SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Equilibrium constants; Binding assays; Cooperativity; G protein-coupled receptors; Receptor heteromers; Receptor dimers ID PROTEIN-COUPLED RECEPTORS; DELTA-OPIOID RECEPTORS; A(1) ADENOSINE RECEPTORS; TERNARY COMPLEX MODEL; ALLOSTERIC MODULATION; NEGATIVE COOPERATIVITY; DOPAMINE-D-2 RECEPTORS; MOLECULAR-MECHANISMS; MORPHINE-TOLERANCE; BINDING-PROPERTIES AB G protein-coupled receptors (GPCR) are targeted by many therapeutic drugs marketed to fight against a variety of diseases. Selection of novel lead compounds are based on pharmacological parameters obtained assuming that GPCR are monomers. However, many GPCR are expressed as dimers/oligomers. Therefore, drug development may consider GPCR as homo- and hetero-oligomers. A two-state dimer receptor model is now available to understand GPCR operation and to interpret data obtained from drugs interacting with dimers, and even from mixtures of monomers and dimers. Heteromers are distinct entities and therefore a given drug is expected to have different affinities and different efficacies depending on the heteromer. All these concepts would lead to broaden the therapeutic potential of drugs targeting GPCRs, including receptor heteromer-selective drugs with a lower incidence of side effects, or to identify novel pharmacological profiles using cell models expressing receptor heteromers. (C) 2009 Elsevier Inc. All rights reserved. C1 [Casado, Vicent; Cortes, Antoni; Mallol, Josefa; Perez-Capote, Kamil; Lluis, Carmen; Franco, Rafael; Canela, Enric I.] Univ Barcelona, Dept Bioquim & Biol Mol, CIBERNED, Ctr Invest Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain. [Casado, Vicent; Cortes, Antoni; Mallol, Josefa; Perez-Capote, Kamil; Lluis, Carmen; Franco, Rafael; Canela, Enric I.] Univ Barcelona, IDIBAPS, E-08028 Barcelona, Spain. [Ferre, Sergi] Natl Inst Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224 USA. RP Franco, R (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, CIBERNED, Ctr Invest Red Enfermedades Neurodegenerat, Diagonal 645,Av Diagonal 645, E-08028 Barcelona, Spain. EM rfranco@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Franco, Rafael/0000-0003-2549-4919; Casado, Vicent/0000-0002-1764-3825 FU Intramural NIH HHS NR 80 TC 46 Z9 46 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD NOV PY 2009 VL 124 IS 2 BP 248 EP 257 DI 10.1016/j.pharmthera.2009.07.005 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 506LW UT WOS:000270777300009 PM 19664655 ER PT J AU Han, SK Sik, RH Motten, AG Chignell, CF Bilski, PJ AF Han, Sang-Kuk Sik, Robert H. Motten, Ann G. Chignell, Colin F. Bilski, Piotr J. TI Photosensitized Oxidation of Tetrabromobisphenol A by Humic Acid in Aqueous Solution SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID BROMINATED FLAME RETARDANTS; DISSOLVED ORGANIC-MATTER; POLYCYCLIC AROMATIC-HYDROCARBONS; SINGLET OXYGEN; HYDROGEN-PEROXIDE; MOLECULAR-OXYGEN; INTRAHUMIC DECHLORINATION; OPTICAL-PROPERTIES; FREE-RADICALS; FULVIC-ACIDS AB The brominated flame retardant 3,3',5,5'-tetrabromobisphenol A (TBBPA) may accumulate in the environment, including surface waters, and degrade there to potentially toxic products. We have previously shown that singlet oxygen ((1)O(2)), produced by irradiation of rose bengal with visible light, oxidizes Triton X-100-solubilized TBBPA to yield the 2,6-dibromo-p-benzosemiquinone anion radical while consuming oxygen (Environ. Sci. Technol. 42, 166, 2008). Here, we report that a similar (1)O(2)-induced oxidation can be initiated in aqueous solutions by the irradiation of TBBPA dissolved in a humic acid (HA) solution. HA is a known weak (1)O(2) photosensitizer and we indeed detected the infrared (1)O(2) phosphorescence from HA preparations in D(2)O. When an aqueous preparation of HA was irradiated (k > 400 nm) in the presence of TBBPA, oxygen was consumed, and the 2,6-dibromo-p-benzosemiquinone anion radical was generated and detected using electron paramagnetic resonance. Radical formation and oxygen consumption were inhibited by sodium azide, a singlet oxygen quencher. Our results suggest that solar radiation, in the presence of HA, may play an important role in the photodegradation of TBBPA in the aquatic environment. C1 [Han, Sang-Kuk; Sik, Robert H.; Motten, Ann G.; Chignell, Colin F.; Bilski, Piotr J.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Han, Sang-Kuk] Mokpo Natl Maritime Univ, Dept Marine Environm Engn, Mokpo, South Korea. RP Bilski, PJ (reprint author), NIEHS, Pharmacol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM piobil@gmail.com FU NIH; National Institute of Environmental Health Sciences; Mokpo National Maritime University Fund FX This research was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences and the Mokpo National Maritime University Fund. NR 45 TC 19 Z9 24 U1 6 U2 41 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2009 VL 85 IS 6 BP 1299 EP 1305 DI 10.1111/j.1751-1097.2009.00608.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 509UX UT WOS:000271045200003 PM 19769581 ER PT J AU Bilski, PJ Wolak, MA Zhang, V Moore, DE Chignell, CF AF Bilski, Piotr J. Wolak, M. A. Zhang, V. Moore, D. E. Chignell, C. F. TI Photochemical Reactions Involved in the Phototoxicity of the Anticonvulsant and Antidepressant Drug Lamotrigine (Lamictal (R)) SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MOLECULAR-OXYGEN O-1(2); SINGLET OXYGEN; HYPERSENSITIVITY SYNDROME; ANTIEPILEPTIC DRUGS; SOLVENT MIXTURES; BIPOLAR DISORDER; LONG-TERM; PHOTOSENSITIZATION; CHILDREN; MONOTHERAPY AB Lamotrigine (LTG) [3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine], an anticonvulsant and antidepressant drug Lamictal(R), produces a (photo) toxic response in some patients. LTG absorbs UV light, generating singlet oxygen ((1)O(2)) with a quantum yield of 0.22 in CH(2)Cl(2), 0.11 in MeCN and 0.01 in D(2)O. A small production of superoxide radical anion was also detected in acetonitrile. Thus, LTG is a moderate photosensitizer producing phototoxicity and oxidizing linoleic acid. LTG is a weak (1)O(2) quencher (k(q) = 3.2 x 10(5) M(-1) s(-1) in MeCN), but its photodecomposition products in dimethyl sulfoxide (DMSO) quenched (1)O(2) very efficiently. Upon intense UV irradiation from a xenon lamp, LTG was photobleached rapidly in DMSO and slowly in acetonitrile, alcohol and water. The rate increased significantly when laser pulses at 266 nm were employed. The photobleaching products generated (1)O(2) twice as strongly as LTG. Photobleaching was usually accompanied by the release of chloride anions, which increased in the presence of ascorbic acid. This suggests the formation of aryl radicals via dechlorination, a process which may be responsible for the photoallergic response observed in some patients. Our results demonstrate that LTG is a moderate generator of (1)O(2) prone to photodechlorination, especially in a reducing environment, which can contribute to the reported phototoxicity of LTG. C1 [Bilski, Piotr J.; Wolak, M. A.; Chignell, C. F.] NIEHS, Pharmacol Lab, RTP, Res Triangle Pk, NC 27709 USA. [Zhang, V.; Moore, D. E.] Univ Sydney, Dept Pharm, Sydney, NSW 2006, Australia. RP Bilski, PJ (reprint author), NIEHS, Pharmacol Lab, RTP, Res Triangle Pk, NC 27709 USA. EM Bilski@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. The authors thank Mr. R. Sik, NIEHS for the photoproduct separation and Dr. K. Tomer, Dr. L. Deterding and Mr. F. Bjorn, NIEHS for the MS analysis. NR 64 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2009 VL 85 IS 6 BP 1327 EP 1335 DI 10.1111/j.1751-1097.2009.00590.x PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 509UX UT WOS:000271045200007 PM 19659919 ER PT J AU Straszewski-Chavez, SL Abrahams, VM Alvero, AB Aldo, PB Ma, Y Guller, S Romero, R Mor, G AF Straszewski-Chavez, S. L. Abrahams, V. M. Alvero, A. B. Aldo, P. B. Ma, Y. Guller, S. Romero, R. Mor, G. TI The Isolation and Characterization of a Novel Telomerase Immortalized First Trimester Trophoblast Cell Line, Swan 71 SO PLACENTA LA English DT Article DE Apoptosis; hTERT; Placenta; Pregnancy; Telomerase; Trophoblast ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; X-LINKED INHIBITOR; HLA-G EXPRESSION; HUMAN-PLACENTA; LIFE-SPAN; WORKSHOP REPORT; TERMINAL TRANSFERASE; HUMAN FIBROBLASTS; EPITHELIAL-CELLS AB Studies using first trimester trophoblast cells may be limited by the inability to obtain patient samples and/or adequate cell numbers. First trimester trophoblast cell lines have been generated by SV40 transformation or similar methods, however, this approach is known to induce phenotypic and karyotypic abnormalities. The introduction of telomerase has been proposed to be a viable alternative for the immortalization of primary human cells. To investigate whether telomerase-induced immortalization might be a more feasible approach for the generation of first trimester trophoblast cell lines, we isolated primary trophoblast cells from a 7-week normal placenta and infected the cells with human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Although this hTERT-infected first trimester trophoblast cell line, which we have named Swan 71, has been propagated for more than 100 passages, it still has attributes that are characteristic of primary first trimester trophoblast cells. The Swan 71 cells are positive for the expression of cytokeratin 7, vimentin and HLA-G, but do not express CD45, CD68 or the Fibroblast Specific Antigen (FSA), CD90/Thy-1. In addition, we also demonstrated that the Swan 71 cells secrete fetal fibronectin (FFN) as well as low levels of human Chorionic Gonadotrophin (hCG). Moreover, the Swan 71 cells exhibit a cytokine and growth factor profile that is similar to primary trophoblast cells and are resistant to Fas, but not TNF-alpha-induced apoptosis. This suggests that the Swan 71 cells may represent a valuable model for future in vitro trophoblast studies. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Abrahams, V. M.; Alvero, A. B.; Aldo, P. B.; Ma, Y.; Guller, S.; Mor, G.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. [Straszewski-Chavez, S. L.] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Romero, R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,LSOG 305A, New Haven, CT 06520 USA. EM Gil.Mor@yale.edu FU Perinatology Research Branch, Division of Intramural Research; NICHD; NIH; DHHS FX This work was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, NICHD, NIH, DHHS. NR 68 TC 62 Z9 62 U1 0 U2 6 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0143-4004 EI 1532-3102 J9 PLACENTA JI Placenta PD NOV PY 2009 VL 30 IS 11 BP 939 EP 948 DI 10.1016/j.placenta.2009.08.007 PG 10 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 523KQ UT WOS:000272072500003 PM 19766308 ER PT J AU de Graaf, AA Freidig, AP De Roos, B Jamshidi, N Heinemann, M Rullmann, JAC Hall, KD Adiels, M van Ommen, B AF de Graaf, Albert A. Freidig, Andreas P. De Roos, Baukje Jamshidi, Neema Heinemann, Matthias Rullmann, Johan A. C. Hall, Kevin D. Adiels, Martin van Ommen, Ben TI Nutritional Systems Biology Modeling: From Molecular Mechanisms to Physiology SO PLOS COMPUTATIONAL BIOLOGY LA English DT Review ID DENSITY LIPOPROTEIN-TRIGLYCERIDE; BIDIRECTIONAL REACTION STEPS; METABOLIC NETWORK; APOLIPOPROTEIN B-100; MATHEMATICAL-MODEL; WEIGHT-LOSS; DIABETIC DYSLIPIDEMIA; LABELING EXPERIMENTS; INSULIN-RESISTANCE; ENERGY-METABOLISM AB The use of computational modeling and simulation has increased in many biological fields, but despite their potential these techniques are only marginally applied in nutritional sciences. Nevertheless, recent applications of modeling have been instrumental in answering important nutritional questions from the cellular up to the physiological levels. Capturing the complexity of today's important nutritional research questions poses a challenge for modeling to become truly integrative in the consideration and interpretation of experimental data at widely differing scales of space and time. In this review, we discuss a selection of available modeling approaches and applications relevant for nutrition. We then put these models into perspective by categorizing them according to their space and time domain. Through this categorization process, we identified a dearth of models that consider processes occurring between the microscopic and macroscopic scale. We propose a "middle-out'' strategy to develop the required full-scale, multilevel computational models. Exhaustive and accurate phenotyping, the use of the virtual patient concept, and the development of biomarkers from "-omics'' signatures are identified as key elements of a successful systems biology modeling approach in nutrition research-one that integrates physiological mechanisms and data at multiple space and time scales. C1 [de Graaf, Albert A.; Freidig, Andreas P.; van Ommen, Ben] TNO Qual Life, Biosci, Zeist, Netherlands. [Freidig, Andreas P.] Amsterdam Mol Therapeut, Amsterdam, Netherlands. [De Roos, Baukje] Rowett Res Inst, Aberdeen, Scotland. [Jamshidi, Neema] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Heinemann, Matthias] ETH, Inst Mol Syst Biol, Zurich, Switzerland. [Rullmann, Johan A. C.] NV Organon, Dept Mol Design & Informat, NL-5340 BH Oss, Netherlands. [Hall, Kevin D.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Adiels, Martin] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. RP de Graaf, AA (reprint author), TNO Qual Life, Biosci, Zeist, Netherlands. EM albert.degraaf@tno.nl RI Hall, Kevin/F-2383-2010; Adiels, Martin/C-9278-2011; Heinemann, Matthias/B-9421-2008; OI Heinemann, Matthias/0000-0002-5512-9077; de Graaf, Albert/0000-0002-1067-3570 NR 89 TC 37 Z9 37 U1 2 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD NOV PY 2009 VL 5 IS 11 AR e1000554 DI 10.1371/journal.pcbi.1000554 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 551SA UT WOS:000274228500002 PM 19956660 ER PT J AU Dallosso, AR Hancock, AL Szemes, M Moorwood, K Chilukamarri, L Tsai, HH Sarkar, A Barasch, J Vuononvirta, R Jones, C Pritchard-Jones, K Royer-Pokora, B Lee, SB Owen, C Malik, S Feng, Y Frank, M Ward, A Brown, KW Malik, K AF Dallosso, Anthony R. Hancock, Anne L. Szemes, Marianna Moorwood, Kim Chilukamarri, Laxmi Tsai, Hsin-Hao Sarkar, Abby Barasch, Jonathan Vuononvirta, Raisa Jones, Chris Pritchard-Jones, Kathy Royer-Pokora, Brigitte Lee, Sean Bong Owen, Ceris Malik, Sally Feng, Yi Frank, Marcus Ward, Andrew Brown, Keith W. Malik, Karim TI Frequent Long-Range Epigenetic Silencing of Protocadherin Gene Clusters on Chromosome 5q31 in Wilms' Tumor SO PLOS GENETICS LA English DT Article ID GAMMA-PROTOCADHERINS; BREAST-CANCER; COLORECTAL-CANCER; SUPPRESSOR GENE; KIDNEY DEVELOPMENT; NEPHROGENIC RESTS; DNA METHYLATION; COMMON EVENT; LUNG-CANCER; CELL-LINE AB Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to alpha-, beta-, and gamma-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA-induced reduction of PCDHG@ encoded proteins leads to elevated beta-catenin protein, increased beta-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses beta-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling. C1 [Dallosso, Anthony R.; Hancock, Anne L.; Szemes, Marianna; Chilukamarri, Laxmi; Tsai, Hsin-Hao; Owen, Ceris; Malik, Sally; Brown, Keith W.; Malik, Karim] Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Canc & Leukaemia Childhood Sargent Res Unit, Bristol BS8 1TD, Avon, England. [Moorwood, Kim; Ward, Andrew] Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. [Sarkar, Abby; Barasch, Jonathan] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. [Vuononvirta, Raisa; Jones, Chris; Pritchard-Jones, Kathy] Royal Marsden NHS Trust, Inst Canc Res, Sutton, Surrey, England. [Royer-Pokora, Brigitte] Univ Dusseldorf, Inst Human Genet & Anthropol, Dusseldorf, Germany. [Lee, Sean Bong] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Feng, Yi] Univ Bristol, Sch Med Sci, Dept Biochem, Bristol BS8 1TD, Avon, England. [Frank, Marcus] Univ Freiburg, Inst Biol 1, D-7800 Freiburg, Germany. RP Dallosso, AR (reprint author), Univ Bristol, Sch Med Sci, Dept Cellular & Mol Med, Canc & Leukaemia Childhood Sargent Res Unit, Bristol BS8 1TD, Avon, England. EM Keith.Brown@bristol.ac.uk; k.t.a.malik@bristol.ac.uk RI Pritchard-Jones, Kathy/F-4286-2014; Brown, Keith/C-3355-2009; OI Pritchard-Jones, Kathy/0000-0002-2384-9475; Brown, Keith/0000-0002-4258-5129; Dallosso, Anthony/0000-0002-1460-2550; Moorwood, Kim/0000-0003-0943-6161 FU Cancer and Leukaemia in Childhood - Sargent; Children's Leukaemia Trust; Kidney Research UK FX This work was supported by Cancer and Leukaemia in Childhood - Sargent, the Children's Leukaemia Trust, and Kidney Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 70 Z9 71 U1 0 U2 8 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 NOV PY 2009 VL 5 IS 11 AR e1000745 DI 10.1371/journal.pgen.1000745 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 528CW UT WOS:000272419500040 PM 19956686 ER PT J AU Won, S Wilk, JB Mathias, RA O'Donnell, CJ Silverman, EK Barnes, K O'Connor, GT Weiss, ST Lange, C AF Won, Sungho Wilk, Jemma B. Mathias, Rasika A. O'Donnell, Christopher J. Silverman, Edwin K. Barnes, Kathleen O'Connor, George T. Weiss, Scott T. Lange, Christoph TI On the Analysis of Genome-Wide Association Studies in Family-Based Designs: A Universal, Robust Analysis Approach and an Application to Four Genome-Wide Association Studies SO PLOS GENETICS LA English DT Article ID QUANTITATIVE TRAITS; UNIFIED APPROACH; GENERAL-CLASS; TESTS; POWER; STRATIFICATION; REGRESSION; LINKAGE; ASTHMA AB For genome-wide association studies in family-based designs, we propose a new, universally applicable approach. The new test statistic exploits all available information about the association, while, by virtue of its design, it maintains the same robustness against population admixture as traditional family-based approaches that are based exclusively on the within-family information. The approach is suitable for the analysis of almost any trait type, e. g. binary, continuous, time-to-onset, multivariate, etc., and combinations of those. We use simulation studies to verify all theoretically derived properties of the approach, estimate its power, and compare it with other standard approaches. We illustrate the practical implications of the new analysis method by an application to a lung-function phenotype, forced expiratory volume in one second (FEV1) in 4 genome-wide association studies. C1 [Won, Sungho] Chung Ang Univ, Dept Stat, Seoul 156756, South Korea. [Won, Sungho] Chung Ang Univ, Res Ctr Data Sci, Seoul 156756, South Korea. [Wilk, Jemma B.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Mathias, Rasika A.] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Framingham Heart Dis Epidemiol Study, Bethesda, MD USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Silverman, Edwin K.; Weiss, Scott T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Silverman, Edwin K.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Barnes, Kathleen] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [O'Connor, George T.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. [Weiss, Scott T.; Lange, Christoph] Brigham & Womens Hosp, Ctr Genom Med, Boston, MA 02115 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Won, S (reprint author), Chung Ang Univ, Dept Stat, Seoul 156756, South Korea. EM clange@hsph.harvard.edu OI O'Connor, George/0000-0002-6476-3926 FU National Heart, Lung, and Blood Institute, National Institutes of Health [U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601, T32 HL07427]; National Institutes of Health [R01MH081862]; Medic Research Council [G00000934]; Wellcome Trust [068545/Z/02] FX The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, P01 HL083069, R01 HL086601, and T32 HL07427 from the National Heart, Lung, and Blood Institute, National Institutes of Health. CL is supported by the National Institutes of Health grant R01MH081862. Framingham Heart Study genotype and phenotype data are publicly available through the NHLBI's SNP Health Association Resource (SHARe) initiative (http://public.nhlbi.nih.gov/GeneticsGenomics/home/share.aspx). The British 1958 Birth Cohort DNA collection is funded by the Medic Research Council grant G00000934 and the Wellcome Trust grant 068545/Z/02. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 26 Z9 27 U1 0 U2 5 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 NOV PY 2009 VL 5 IS 11 AR e1000741 DI 10.1371/journal.pgen.1000741 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 528CW UT WOS:000272419500036 PM 19956679 ER PT J AU Gray, RH Serwadda, D Tobian, AAR Chen, MZ Makumbi, F Suntoke, T Kigozi, G Nalugoda, F Iga, B Quinn, TC Moulton, LH Laeyendecker, O Reynolds, SJ Kong, XR Wawer, MJ AF Gray, Ronald H. Serwadda, David Tobian, Aaron A. R. Chen, Michael Z. Makumbi, Frederick Suntoke, Tara Kigozi, Godfrey Nalugoda, Fred Iga, Boaz Quinn, Thomas C. Moulton, Lawrence H. Laeyendecker, Oliver Reynolds, Steven J. Kong, Xiangrong Wawer, Maria J. TI Effects of Genital Ulcer Disease and Herpes Simplex Virus Type 2 on the Efficacy of Male Circumcision for HIV Prevention: Analyses from the Rakai Trials SO PLOS MEDICINE LA English DT Article ID TARGET-CELLS; INFECTION; RISK; MEN; METAANALYSIS; HSV-2; ACQUISITION; SYPHILIS; UGANDA; WOMEN AB Background: Randomized trials show that male circumcision (MC) reduces the incidence of HIV and herpes simplex virus type 2 (HSV-2) infections, and symptomatic genital ulcer disease (GUD). We assessed the role of GUD and HSV-2 in the protection against HIV afforded by MC. Methods and Findings: HIV-uninfected men were randomized to immediate (n = 2,756) or delayed MC (n = 2,775) in two randomized trials in Rakai, Uganda. GUD symptoms, HSV-2 status, and HIV acquisition were determined at enrollment and at 6, 12, and 24 mo of follow up. Ulcer etiology was assessed by PCR. We estimated the prevalence and prevalence risk ratios (PRRs) of GUD in circumcised versus uncircumcised men and assessed the effects of HSV-2 serostatus as a risk-modifying factor for GUD. We estimated the proportion of the effect of MC on HIV acquisition that was mediated by symptomatic GUD, and by HSV-2 infection. Circumcision significantly reduced symptomatic GUD in HSV-2-seronegative men (PRR = 0.51, 95% [confidence interval] CI 0.43-0.74), HSV-2-seropositive men (PRR = 0.66, 95% CI 0.51-0.69), and in HSV-2 seroconverters (PRR = 0.48, 95% CI 0.30-0.79). The proportion of acute ulcers due to HSV-2 detected by PCR was 48.0% in circumcised men and 39.3% in uncircumcised men (chi(2) p = 0.62). Circumcision reduced the risk of HIV acquisition in HSV-2 seronegative men (incidence rate ratio [IRR] = 0.34, 95% CI 0.15-0.81), and potentially in HSV-2 seroconverters (IRR = 0.56, 95% CI 0.19-1.57; not significant), but not in men with prevalent HSV-2 at enrollment (IRR = 0.89, 95% CI 0.49-1.60). The proportion of reduced HIV acquisition in circumcised men mediated by reductions in symptomatic GUD was 11.2% (95% CI 5.0-38.0), and the proportion mediated by reduced HSV-2 incidence was 8.6% (95% CI -1.2 to 77.1). Conclusions: Circumcision reduced GUD irrespective of HSV-2 status, but this reduction played only a modest role in the protective effect of circumcision on HIV acquisition. C1 [Gray, Ronald H.; Chen, Michael Z.; Suntoke, Tara; Moulton, Lawrence H.; Kong, Xiangrong; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Serwadda, David; Makumbi, Frederick] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Serwadda, David; Makumbi, Frederick; Kigozi, Godfrey; Nalugoda, Fred; Iga, Boaz] Rakai Hlth Sci Program, Entebbe, Uganda. [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Quinn, Thomas C.; Laeyendecker, Oliver; Reynolds, Steven J.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Quinn, Thomas C.; Laeyendecker, Oliver; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. EM rgray@jhsph.edu RI Laeyendecker, Oliver/B-9331-2009; Kong, Xiangrong/B-5098-2010; OI Laeyendecker, Oliver/0000-0002-6429-4760; Moulton, Lawrence/0000-0001-7041-7387 FU US National Institutes of Health [U1AI51171]; Bill & Melinda Gates Foundation [22006.02]; Fogarty International Center [5D43TW001508, D43TW00015]; National Institute of Allergy and Infectious Diseases, NIH FX The trials were funded by the US National Institutes of Health (#U1AI51171), the Bill & Melinda Gates Foundation (#22006.02), and the Fogarty International Center (# 5D43TW001508 and # D43TW00015). This study was also supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of this manuscript. NR 24 TC 27 Z9 27 U1 0 U2 0 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 NOV PY 2009 VL 6 IS 11 AR e1000187 DI 10.1371/journal.pmed.1000187 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 522XC UT WOS:000272032500014 PM 19936044 ER PT J AU Chan, L Wang, H Terdiman, J Hoffman, J Ciol, MA Lattimore, BF Sidney, S Quesenberry, C Lu, Q Sandel, ME AF Chan, Leighton Wang, Hua Terdiman, Joe Hoffman, Jeanne Ciol, Marcia A. Lattimore, Bernadette Ford Sidney, Steven Quesenberry, Charles Lu, Qi Sandel, M. Elizabeth TI Disparities in Outpatient and Home Health Service Utilization Following Stroke: Results of a 9-Year Cohort Study in Northern California SO PM&R LA English DT Article AB Objective: To examine whether there are disparities in utilization of outpatient and home care services after stroke. Design: Retrospective cohort study. Setting: The Kaiser Permanente of Northern California health care system, which provides health care for approximately 3.3 million members. Participants: A total of 11,119 patients hospitalized for a stroke between 1996 and 2003 and followed for 1 year. Main Outcome Measures: Receipt of outpatient rehabilitation (physical therapy, occupational therapy, speech pathology, or physical medicine and rehabilitation/physiatry visits), and/or home health care. Results: There were significant differences in outpatient rehabilitation visits and home health enrollment during the year after acute care discharge for all the parameters under study. Older age and female gender were associated with less outpatient rehabilitation treatment, but these subpopulations were more likely to be enrolled in home health care. Non-whites, patients from urban areas, those with ischemic strokes, and those with longer acute care hospital stays had relatively more outpatient rehabilitation and were also more likely to be enrolled in the home health program. In addition, patients living in geographic areas with a median household income of $80,000 or more had significantly more outpatient rehabilitation visits than did patients living in lower income areas. Conclusions: Variations in outpatient rehabilitation visits and in home health care exist in this large integrated health system in terms of age, gender, race/ethnicity, residence area, type of stroke, and length of stay in an acute care hospital. The Kaiser Permanente integrated health care system seems to have outpatient stroke rehabilitation and home health programs that are providing care without disparities in relation to non-white populations, but other disparities appear to exist that may be related to socioeconomic factors, referral patterns, family support systems, or other cultural factors that have not been identified. C1 [Chan, Leighton] NIH Clin Ctr, Dept Rehabil Med, Bethesda, MD 20892 USA. [Wang, Hua; Sandel, M. Elizabeth] Kaiser Fdn Rehabil Ctr, Dept Phys Med & Rehabil, Vallejo, CA USA. [Terdiman, Joe; Sidney, Steven] Kaiser Permanente Div Res, Oakland, CA USA. [Hoffman, Jeanne; Ciol, Marcia A.] Univ Washington, Seattle, WA 98195 USA. [Lattimore, Bernadette Ford] Ctr Dis Control & Prevent, Atlanta, GA USA. [Lu, Qi] Kaiser Fdn Rehabil Ctr, Kaiser Permanente Div Res, Vallejo, CA USA. RP Chan, L (reprint author), NIH Clin Ctr, Dept Rehabil Med, Bldg 10,CRC,Room 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM chanle@cc.nih.gov FU Centers for Disease Control and Prevention FX This study supported by funding from the Centers for Disease Control and Prevention. Additional resources were provided by the Intramural Research Program of (Clinical Research Center) the National Institutes of Health, the Centers for Medicare and Medicaid Services, and Kaiser Permanente. NR 28 TC 16 Z9 16 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD NOV PY 2009 VL 1 IS 11 BP 997 EP 1003 DI 10.1016/j.pmrj.2009.09.019 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LO UT WOS:000208412100003 PM 19942185 ER PT J AU Curcio, CA Johnson, M Huang, JD Rudolf, M AF Curcio, Christine A. Johnson, Mark Huang, Jiahn-Dar Rudolf, Martin TI Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review DE Age-related macular degeneration; Retinal pigment epithelium; Bruch's membrane; Drusen; Basal deposits; Lipoproteins; Cholesterol; Retinyl ester; Apolipoprotein B ID RETINAL-PIGMENT EPITHELIUM; TRIGLYCERIDE TRANSFER PROTEIN; LOW-DENSITY-LIPOPROTEIN; HUMAN BRUCHS MEMBRANE; BASAL LAMINAR DEPOSIT; HUMAN ATHEROSCLEROTIC LESIONS; ENDOTHELIAL GROWTH-FACTOR; ROD OUTER SEGMENTS; LIPID-RICH CORE; MONOCYTE-DERIVED MACROPHAGES AB The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch's membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely-accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. (C) 2009 Published by Elsevier Ltd. C1 [Curcio, Christine A.] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA. [Johnson, Mark] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Huang, Jiahn-Dar] NEI, NIH, Bethesda, MD 20892 USA. [Rudolf, Martin] Univ Klinikum Schleswig Holstein, Univ Eye Hosp Lubeck, D-23538 Lubeck, Germany. RP Curcio, CA (reprint author), Univ Alabama Birmingham, Dept Ophthalmol, Callahan Eye Fdn Hosp, Sch Med, 700 S 18th St,Room H020, Birmingham, AL 35294 USA. EM curcio@uab.edu RI Johnson, Mark/B-6921-2009 FU NIH [EY06109, EY014662]; International Retinal Research Foundation; American Health Assistance Foundation; EyeSight Foundation of Alabama; Research to Prevent Blindness, Inc.; Macula Vision Research Foundation; Roger Johnson Prize in Macular Degeneration Research; Deutsche Forschungsgemeinschaft FX We are grateful for support from NIH grants EY06109 and EY014662, International Retinal Research Foundation, American Health Assistance Foundation, EyeSight Foundation of Alabama, Research to Prevent Blindness, Inc., Macula Vision Research Foundation, Roger Johnson Prize in Macular Degeneration Research, and Deutsche Forschungsgemeinschaft. CAC thanks especially the Alabama Eye Bank, members of Lipid Breakfast (Atherosclerosis Research Unit, J.P. Segrest, MD, Phl), Director, Department of Medicine, UAB), Lanning B. Kline, MD, Peter A. Dudley, Phl), John Guyton, MD, Howard Kruth, MD, and Clyde Guidry, Phl). David Fisher provided graphical design. NR 339 TC 103 Z9 108 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD NOV PY 2009 VL 28 IS 6 BP 393 EP 422 DI 10.1016/j.preteyeres.2009.08.001 PG 30 WC Ophthalmology SC Ophthalmology GA 527LV UT WOS:000272369500001 PM 19698799 ER PT J AU Saade, E Mechold, U Kulyyassov, A Vertut, D Lipinski, M Ogryzko, V AF Saade, Evelyne Mechold, Undine Kulyyassov, Arman Vertut, Damien Lipinski, Marc Ogryzko, Vasily TI Analysis of interaction partners of H4 histone by a new proteomics approach SO PROTEOMICS LA English DT Article DE Acetylation; Cell biology; Chaperones; Chromatin; Fractionation; Tandem affinity purification ID ACETYLTRANSFERASE; CHROMATIN; PROTEINS; BINDING; YEAST; HAT1; REPLICATION; CHAPERONES; COMPLEXES AB We describe a modification of the tandem affinity purification method for purification and analysis of multiprotein complexes, termed here DEF-TAP (for differential elution fractionation after tandem affinity purification). Its essential new feature is the use for last purification step of 6 x His-Ni(++) interaction, which is resistant to a variety of harsh washing conditions, including high ionic strength and the presence of organic solvents. This allows us to use various fractionation schemes before the protease digestion, which is expected to improve the coverage of the analyzed protein mixture and also to provide an additional insight into the structure of the purified macromolecular complex and the nature of protein-protein interactions involved. We illustrate our new approach by analysis of soluble nuclear complexes containing histone H4 purified from HeLa cells. In particular, we observed different fractionation patterns of HAT1 and RbAp46 proteins as compared with RbAp48 protein, all identified as interaction partners of H4 histone. In addition, we report all components of the licensing MCM2-7 complex and the apoptosis-related DAXX protein among the interaction partners of the soluble H4. Finally, we show that HAT1 requires N-terminal tail of H4 for its stable association with this histone. C1 [Saade, Evelyne] Inst Gustave Roussy, PRI, F-94805 Villejuif, France. [Mechold, Undine] Inst Pasteur, URA, Unite Genet Genomes Bacteriens, Paris, France. [Kulyyassov, Arman] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Ogryzko, V (reprint author), Inst Gustave Roussy, PRI, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. EM vogryzko@gmail.com RI Ogryzko, Vasily/M-6665-2015; OI Ogryzko, Vasily/0000-0002-8548-1389; Kulyyassov, Arman/0000-0002-7932-5689 FU La Ligue Contre le Cancer [9ADO1217/1B1-BIOCE]; Institut National du Cancer [247343/1B1-BIOCE]; National Center for Biotechnology (Kazakhstan) FX We thank Dr. W Knippers (Department of Biology, Universitat Konstanz, Germany) for his generous gift of anti-MCM antibodies. The work was supported by grants from "La Ligue Contre le Cancer" (9ADO1217/1B1-BIOCE), the "Institut National du Cancer" (247343/1B1-BIOCE) and the National Center for Biotechnology (Kazakhstan) to V. O. NR 25 TC 13 Z9 16 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD NOV PY 2009 VL 9 IS 21 BP 4934 EP 4943 DI 10.1002/pmic.200900206 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 524DS UT WOS:000272124600010 PM 19862764 ER PT J AU Ernst, M Pine, DS Hardin, M AF Ernst, M. Pine, D. -S. Hardin, M. TI Triadic model of the neurobiology of motivated behavior in adolescence SO PSN-PSYCHIATRIE SCIENCES HUMAINES NEUROSCIENCES LA French DT Review DE Choice selection; Motivation; Anticipation; Development; Anxiety; Schizophrenia ID NUCLEUS-ACCUMBENS DOPAMINE; ANTERIOR CINGULATE CORTEX; EMOTIONAL FACIAL EXPRESSIONS; INCREASING MONETARY REWARD; EVENT-RELATED POTENTIALS; PREFRONTAL CORTEX; DECISION-MAKING; HUMAN AMYGDALA; ORBITOFRONTAL CORTEX; BRAIN-DEVELOPMENT AB Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems based model of adolescent decision-making. We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e., amygdala, nucleus accumbens and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed. The propensity during adolescence for reward-novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm avoidant system (amygdala) and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety. A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior. C1 [Ernst, M.; Pine, D. -S.; Hardin, M.] NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov NR 151 TC 1 Z9 1 U1 10 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1639-8319 J9 PSN-PSYCHIATR SCI HU JI PSN-Psychiatr. Sci. Hum. Neurosc. PD NOV PY 2009 VL 7 IS 3-4 BP 127 EP 139 DI 10.1007/s11836-009-0094-2 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 519ZQ UT WOS:000271809900005 ER PT J AU Laje, G Perlis, RH Rush, AJ McMahon, FJ AF Laje, Gonzalo Perlis, Roy H. Rush, A. John McMahon, Francis J. TI Pharmacogenetics Studies in STAR*D: Strengths, Limitations, and Results SO PSYCHIATRIC SERVICES LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; FACTOR GENETIC-POLYMORPHISM; EMERGENT SUICIDAL IDEATION; MAJOR DEPRESSIVE DISORDER; GENOME-WIDE ASSOCIATION; ELEMENT-BINDING PROTEIN; ANTIDEPRESSANT TREATMENT; NEUROTROPHIC-FACTOR; D COHORT; SEROTONIN TRANSPORTER AB Several lines of evidence support an important genetic contribution to the wide individual variation in therapeutic response to antidepressant medications. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provided the largest cohort assembled to date of DNA from patients with nonpsychotic major depressive disorder, uniformly treated with citalopram and followed prospectively for up to 12 weeks. This pivotal study changed the face of pharmacogenetics research by increasing the sample size by an order of magnitude as well as by providing detailed prospective information about antidepressant response and tolerability. Several groups have identified markers in genes and tested the replication of previous findings of genes associated with outcome and side effects of antidepressant treatment. Variants in HTR2A, GRIK4, and KCNK2 were associated with citalopram treatment outcome. Replication was achieved in markers in the FKBP5 gene. Other findings in PDE11A and BDNF were not successfully replicated, and reports of potential confounders in previous associations with serotonin transporter variation (SLC6A4) were identified. Polymorphisms in pharmacokinetic genes involved in metabolism and transmembrane transport were also not associated with antidepressant response. Adverse events were also tested. Treatment-emergent suicidal ideation was associated with GRIK2, GRIA3, PAPLN, IL28RA, and CREB1. Sexual dysfunction was linked with variation in GRIN3A, GRIA1 GRIA3, and GRIK2. Reported and future findings of pharmacogenetics studies in STAR*D could help elucidate pathways involved in major depression and those pertinent to antidepressant outcome and side effects. Replication of these findings in independent samples could lead to the development of new treatments and to optimization of available treatments. (Psychiatric Services 60: 1446-1457, 2009) C1 [Laje, Gonzalo; McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Bethesda, MD 20892 USA. [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rush, A. John] Duke Natl Univ Singapore, Singapore, Singapore. RP Laje, G (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Unit, 35 Convent Dr,MSC 3719,Bldg 35-1A207, Bethesda, MD 20892 USA. EM gonzalo.laje@nih.gov RI Laje, Gonzalo/L-2654-2014; OI Laje, Gonzalo/0000-0003-2763-3329; Rush, Augustus/0000-0003-2004-2382; McMahon, Francis/0000-0002-9469-305X FU NIMH [N01 MH-90003, K23MH67060]; National Institutes of Health (NIH); U.S. Department of Health and Human Services (DHHS); NARSAD Young Investigator/Sidney R. Baer Jr. Foundation; Bowman Family Foundation FX STAR*D is supported by federal funds from NIMH under contract N01 MH-90003 to the University of Texas-Southwestern Medical Center at Dallas (Dr. Rush, principal investigator). This study was funded by the Intramural Research Program of NIMH, National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS), NIMH grant K23MH67060, a NARSAD Young Investigator/Sidney R. Baer Jr. Foundation Award, and a Bowman Family Foundation award. The content of this publication does not necessarily reflect the views or policies of DHHS nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 67 TC 51 Z9 52 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2009 VL 60 IS 11 BP 1446 EP 1457 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 514KM UT WOS:000271393200007 PM 19880459 ER PT J AU Insel, TR Wang, PS AF Insel, Thomas R. Wang, Philip S. TI The STAR*D Trial: Revealing the Need for Better Treatments SO PSYCHIATRIC SERVICES LA English DT Editorial Material ID COMORBIDITY SURVEY REPLICATION; MAJOR DEPRESSION; UNITED-STATES; IDEATION AB STAR*D (Sequenced Treatment Alternatives to Relieve Depression) continues to stimulate debate. The landmark trial demonstrated the feasibility of large-scale, community-based studies conducted without pharmaceutical company support. The results provided insight into nonresponse to initial treatment with selective serotonin reuptake inhibitors and alternatives for second-and third-line treatment options and suggested opportunities for personalized approaches to depression care. However, initial and one-year remission rates (28% and 70%, respectively) suggest that important goals for treatment of this disabling disease remain out of reach and that the bar for antidepressants has been set far too low. (Psychiatric Services 60: 1466-1467, 2009) C1 [Insel, Thomas R.; Wang, Philip S.] NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd,Rm 8235,MSC 9669, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 12 TC 41 Z9 41 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2009 VL 60 IS 11 BP 1466 EP 1467 PG 2 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 514KM UT WOS:000271393200011 PM 19880463 ER PT J AU Reyna, VF Nelson, WL Han, PK Dieckmann, NF AF Reyna, Valerie F. Nelson, Wendy L. Han, Paul K. Dieckmann, Nathan F. TI How Numeracy Influences Risk Comprehension and Medical Decision Making SO PSYCHOLOGICAL BULLETIN LA English DT Review DE risk perception; risk communication; mathematical cognition; intuition; dual processes ID FUNCTIONAL HEALTH LITERACY; FUZZY-TRACE THEORY; BREAST-CANCER RISK; MANAGED CARE ORGANIZATION; I CLINICAL-TRIALS; DUAL-PROCESSES; INDIVIDUAL-DIFFERENCES; SCREENING MAMMOGRAPHY; NUMERICAL ESTIMATION; QUALITY INFORMATION AB We review the growing literature oil health numeracy. the ability to understand and use numerical information, and its relation to cognition, health behaviors, and medical Outcome;. Despite the surfeit of health information from commercial and noncommercial sources. national and International surveys show that many people lack basic numerical skills that are essential to maintain their health and make informed medical decisions. Low numeracy distorts perceptions of risks and benefits of screening. reduces medication compliance impedes access to treatments. Impairs risk communication (limiting prevention efforts among the Most vulnerable). and. based oil the scant research conducted on outcomes, appears to adversely affect medical outcomes Low numeracy is also associated with greater susceptibility to extraneous factors (i.e., factors that do not change the objective numerical information) That is. low numeracy increases susceptibility to effects of mood or how information presented (e g. as frequencies vs percentages) and to biases In Judgment and decision making (e g framing and ratio bias effects) Much of this research is not grounded in empirically supported theories of numeracy or mathematical cognition. which are crucial for designing evidence-based policies and intervention, that are effective in reducing risk and improving medical decision making To address this gap, we outline four theoretical approaches (psychophysical, computational, standard dual-process, and fuzzy trace theory), review their implications for numeracy. and point to avenues for future research C1 [Reyna, Valerie F.] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. [Reyna, Valerie F.] Cornell Univ, Dept Psychol, Ithaca, NY 14853 USA. [Nelson, Wendy L.; Han, Paul K.] NCI, Bethesda, MD 20892 USA. [Dieckmann, Nathan F.] Decis Res, Eugene, OR USA. [Dieckmann, Nathan F.] Univ Oregon, Eugene, OR 97403 USA. RP Reyna, VF (reprint author), Cornell Univ, Dept Human Dev, B44 Martha Van Rensselaer Hall, Ithaca, NY 14853 USA. OI Han, Paul/0000-0003-0165-1940 FU Intramural NIH HHS [Z99 HG999999]; NCI NIH HHS [R13 CA126359-01, R13CA126359, R13 CA126359]; NIMH NIH HHS [R01 MH061211, R01 MH061211-02, R01 MH061211-07, R01-MH-061211] NR 227 TC 320 Z9 326 U1 27 U2 113 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0033-2909 EI 1939-1455 J9 PSYCHOL BULL JI Psychol. Bull. PD NOV PY 2009 VL 135 IS 6 BP 943 EP 973 DI 10.1037/a0017327 PG 31 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 512MS UT WOS:000271254200007 PM 19883143 ER PT J AU Worley, LLM Levenson, JL Stern, TA Epstein, SA Rundell, JR Crone, CC Wise, TN Rummans, TA Muskin, PR Bourgeois, JA Saravay, SM Pao, M Alter, C Steinberg, M Wulsin, L Breitbart, W Fricchione, GL Boland, R Epstein, LA Winstead, D Gitlin, DF AF Worley, Linda L. M. Levenson, James L. Stern, Theodore A. Epstein, Steven A. Rundell, James R. Crone, Catherine C. Wise, Thomas N. Rummans, Teresa A. Muskin, Philip R. Bourgeois, James A. Saravay, Stephen M. Pao, Maryland Alter, Carol Steinberg, Maurice Wulsin, Lawson Breitbart, William Fricchione, Gregory L. Boland, Robert Epstein, Lucy A. Winstead, Daniel Gitlin, David F. TI Core Competencies for Fellowship Training in Psychosomatic Medicine: A Collaborative Effort by the APA Council on Psychosomatic Medicine, the ABPN Psychosomatic Committee, and The Academy of Psychosomatic Medicine SO PSYCHOSOMATICS LA English DT Article ID CONSULTATION-LIAISON PSYCHIATRY; GUIDELINES C1 [Worley, Linda L. M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Virginia Commonwealth Univ, Med Coll Virginia, Sch Med, Richmond, VA 23298 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Georgetown Univ, Sch Med, Washington, DC USA. Mayo Clin, Rochester, MN USA. INOVA Fairfax Hosp, Falls Church, VA USA. Columbia Univ, Med Ctr, New York, NY USA. McMaster Univ, Hamilton, ON, Canada. Long Isl Jewish Med Ctr, Hyde Pk, NY USA. NIMH, Bethesda, MD 20892 USA. Univ Cincinnati, Cincinnati, OH USA. Sloan Kettering Inst, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Tulane Univ, New Orleans, LA 70118 USA. Harvard Univ, Sch Med, Faulkner Hosp, Boston, MA USA. RP Worley, LLM (reprint author), Univ Arkansas Med Sci, 4301 W Markham,789, Little Rock, AR 72205 USA. EM WorleyLindaL@uams.edu NR 13 TC 9 Z9 9 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2009 VL 50 IS 6 BP 557 EP 562 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 529AU UT WOS:000272488900002 PM 19996225 ER PT J AU Kaiser, K AF Kaiser, Karen TI Protecting Respondent Confidentiality in Qualitative Research SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE breast cancer; confidentiality, participant; interviews; qualitative methods, general; research, design; research, dissemination and utilization ID INFORMED-CONSENT; PARTICIPANTS; IDENTITY; ETHICS; WOMEN AB For qualitative researchers, maintaining respondent confidentiality while presenting rich, detailed accounts of social life presents unique challenges. These challenges are not adequately addressed in the literature on research ethics and research methods. Using an example from a study of breast cancer survivors, I argue that by carefully considering the audience for one's research and by reenvisioning the informed consent process, qualitative researchers can avoid confidentiality dilemmas that might otherwise lead them not to report rich, detailed data. C1 [Kaiser, Karen] Univ Illinois, Chicago Canc Ctr, NCI, Canc Educ & Career Dev Program, Chicago, IL USA. RP Kaiser, K (reprint author), Inst Hlth Res & Policy, 1747 W Roosevelt Rd,Room 558,MC275, Chicago, IL 60608 USA. EM kkaiser1@uic.edu FU NCI NIH HHS [R25 CA057699, R25 CA057699-16]; PHS HHS [R25TCA57699-14] NR 39 TC 41 Z9 41 U1 1 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD NOV PY 2009 VL 19 IS 11 BP 1632 EP 1641 DI 10.1177/1049732309350879 PG 10 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 508OI UT WOS:000270942300012 PM 19843971 ER PT J AU Watanabe, KH Djordjevic, MV Stellman, SD Toccalino, PL Austin, DF Pankow, JF AF Watanabe, Karen H. Djordjevic, Mirjana V. Stellman, Steven D. Toccalino, Patricia L. Austin, Donald F. Pankow, James F. TI Incremental lifetime cancer risks computed for benzo[a]pyrene and two tobacco-specific N-nitrosamines in mainstream cigarette smoke compared with lung cancer risks derived from epidemiologic data SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Tobacco; Cigarette smoking topography; Lifetime cancer risk; Lung cancer; Cancer Prevention Study; Monte Carlo simulation ID PHARMACOKINETIC MODELS; GENDER-DIFFERENCES; MORTALITY; WOMEN; CARCINOGENESIS; PREVENTION; EXPOSURE; SCIENCE; HUMANS; IMPACT AB The manner in which humans smoke cigarettes is an important determinant of smoking risks. Of the few investigators that have predicted cancer risks from smoking on a chemical-specific basis, most used mainstream cigarette smoke (MCS) carcinogen emissions obtained via machine smoking protocols that only approximate human smoking conditions. Here we use data of Djordjevic et al. [Djordjevic, M.V., Stellman, S.D., Zang, E., 2000. Doses of nicotine and lung carcinogens delivered to cigarette smokers. J. Natl. Cancer Inst. 92, 106-111] for MCS emissions of three carcinogens measured under human smoking conditions to compute probability distributions of incremental lifetime cancer risk (ILCR) values using Monte Carlo simulations. The three carcinogens considered are benzo[a]pyrene, N'-nitrosonornicotine (NNN), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Computed NNK ILCR values were compared with lifetime risks of lung cancer (ILCR(CMD)(obs Sigma-lung))derived from American Cancer Society Cancer Prevention Studies (CPS) I and II. Within the Monte Carlo simulation results, NNK was responsible for the greatest ILCR values for all cancer endpoints: median ILCR values for NNK were similar to 18-fold and 120-fold higher than medians for NNN and benzo[a]pyrene, respectively. For "regular" cigarettes, the NNK median ILCR for lung cancer was lower than ILCR(CMD)(obs Sigma-lung)from CPS-I and II by >90-fold for men and >4-fold for women. Given what is known about chemical carcinogens in MCS, this study shows that there is a higher incidence of lung cancer from exposure to MCS than can be predicted with current risk assessment methods using available toxicity and emission data. (C) 2009 Elsevier Inc. All rights reserved. C1 [Watanabe, Karen H.; Toccalino, Patricia L.] Oregon Hlth & Sci Univ, Div Environm & Biomol Syst, Sch Med, Beaverton, OR 97006 USA. [Djordjevic, Mirjana V.] NCI, Div Canc Control & Populat Sci, Tobacco Control Res Branch, Bethesda, MD 20892 USA. [Stellman, Steven D.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Austin, Donald F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Pankow, James F.] Portland State Univ, Dept Chem, Portland, OR 97207 USA. [Pankow, James F.] Portland State Univ, Dept Civil & Environm Engn, Portland, OR 97207 USA. RP Watanabe, KH (reprint author), Oregon Hlth & Sci Univ, Div Environm & Biomol Syst, Sch Med, W Campus,20000 NW Walker Rd, Beaverton, OR 97006 USA. EM watanabe@ebs.ogi.edu FU OHSU Oregon Opportunity Program; Public Health Service [CA-68384, CA-17613]; Cooley Family Fund for Critical Research of the Oregon Community Foundation FX This study was funded in part by the OHSU Oregon Opportunity Program (to K.H.W.), Public Health Service Grants CA-68384 and CA-17613 (to S.D.S. and M.V.D.), and the Cooley Family Fund for Critical Research of the Oregon Community Foundation (to J.F.P.). NR 73 TC 7 Z9 11 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD NOV PY 2009 VL 55 IS 2 BP 123 EP 133 DI 10.1016/j.yrtph.2009.06.007 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 507OF UT WOS:000270863300002 PM 19540296 ER PT J AU Gohlke, JM Stockton, PS Sieber, S Foley, J Portier, CJ AF Gohlke, Julia M. Stockton, Pat S. Sieber, Stella Foley, Julie Portier, Christopher J. TI AhR-mediated gene expression in the developing mouse telencephalon SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Neurodevelopment; Gene expression; Bioinformatics; TCDD; Dioxin; Neurotoxicity ID ARYL-HYDROCARBON RECEPTOR; ABNORMAL LIVER DEVELOPMENT; POLYCHLORINATED-BIPHENYLS; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; NUCLEAR TRANSLOCATOR; PERINATAL EXPOSURE; PRENATAL EXPOSURE; TRANSCRIPTION FACTORS; RAT CEREBELLUM; RETINOIC ACID AB We hypothesize that TCDD-induced developmental neurotoxicity is modulated through an AhR-dependent interaction with key regulatory neuronal differentiation pathways during telencephalon development. To test this hypothesis we examined global gene expression in both dorsal and ventral telencephalon tissues in E13.5 AhR-/- and wildtype mice exposed to TCDD or vehicle. Consistent with previous biochemical, pathological and behavioral studies, our results suggest TCDD initiated changes in gene expression in the developing telencephalon are primarily AhR-dependent, as no statistically significant gene expression changes are evident after TCDD exposure in AhR-/- mice. Based on a gene regulatory network for neuronal specification in the developing telencephalon, the present analysis suggests differentiation of GABAergic neurons in the ventral telencephalon is compromised in TCDD exposed and AhR-/- mice. In addition, our analysis suggests Sox11 may be directly regulated by AhR based on gene expression and comparative genomics analyses. In conclusion, this analysis supports the hypothesis that AhR has a specific role in the normal development of the telencephalon and provides a mechanistic framework for neurodevelopmental toxicity of chemicals that perturb AhR signaling. Published by Elsevier Inc. C1 [Gohlke, Julia M.; Portier, Christopher J.] Natl Inst Environm Hlth Sci, Environm Syst Biol Grp, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Stockton, Pat S.; Foley, Julie] Natl Inst Environm Hlth Sci, Lab Environm Pathol, Res Triangle Pk, NC 27709 USA. RP Portier, CJ (reprint author), Natl Inst Environm Hlth Sci, Environm Syst Biol Grp, Mol Toxicol Lab, 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; Gohlke, Julia/0000-0002-6984-2893 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. NR 70 TC 13 Z9 13 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD NOV PY 2009 VL 28 IS 3 BP 321 EP 328 DI 10.1016/j.reprotox.2009.05.067 PG 8 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 514YS UT WOS:000271433400004 PM 19465110 ER PT J AU Latendresse, JR Bucci, TJ Olson, G Mellick, P Weis, CC Thorn, B Newbold, RR Delclos, KB AF Latendresse, John R. Bucci, Thomas J. Olson, Greg Mellick, Paul Weis, Constance C. Thorn, Brett Newbold, Retha R. Delclos, K. Barry TI Genistein and ethinyl estradiol dietary exposure in multigenerational and chronic studies induce similar proliferative lesions in mammary gland of male Sprague-Dawley rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE Genistein; Ethinyl estradiol; Rat; Multigenerational; Reproductive toxicity; Mammary gland toxicity; Soy-free diet; Endocrine disrupter ID GUIDELINE NO. 407; CD BR RATS; REPRODUCTIVE-SYSTEM; CELL HYPERPLASIA; SOY ISOFLAVONES; DRAFT PROTOCOL; ORAL TOXICITY; MICE; ESTROGENS; ETHINYLESTRADIOL AB Genistein and ethinyl estradiol (EE2) were examined in multigenerational reproductive and 2-yr chronic toxicity studies with different exposure durations across generations F-0 through F-4. Sprague-Dawley rats were exposed to genistein (0, 5, 100, or 500ppm) or EE2 (0, 2, 10, or 50ppb). Effects in the male mammary gland are described here. In the multigeneration studies, mammary hyperplasia was induced by both compounds; the chronic studies had a lower incidence, without proportionate neoplasia. Sexual dimorphism (predominant tubuloalveolar growth in females and lobuloalveolar in males) was retained without feminization in high dose genistein or EE2. In the continuously exposed generations, mammary hyperplasia was sustained but not amplified, appeared morphologically similar across all generations, and was not carried over into unexposed offspring of previously exposed generations. The hyperplasia in male rats was similar whether induced by genistein or EE2. Results substantiate and extend previous reports that mammary gland hyperplasia in the male rat is one of the most sensitive markers of estrogenic endocrine disruption. Published by Elsevier Inc. C1 [Latendresse, John R.; Bucci, Thomas J.; Olson, Greg; Mellick, Paul] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Weis, Constance C.; Thorn, Brett; Delclos, K. Barry] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Newbold, Retha R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Latendresse, JR (reprint author), Toxicol Pathol Associates, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.latendresse@fda.hhs.gov RI Olson, Gregory/B-7529-2009 FU Interagency Agreement IAG [224-07-007]; U.S. Food and Drug Administration; National Institute for Environmental Health Sciences FX This work was supported by Interagency Agreement IAG 224-07-007 between the U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences. The extensive and expert technical assistance of the NCTR support staff in providing diet preparation, chemical analysis, animal care, computer support, and pathology services for these studies is gratefully acknowledged. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 59 TC 41 Z9 42 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD NOV PY 2009 VL 28 IS 3 BP 342 EP 353 DI 10.1016/j.reprotox.2009.04.006 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 514YS UT WOS:000271433400007 PM 19383540 ER PT J AU Miller, KM Browning, DJ Aiello, LP Beck, RW Bressler, NM Davis, MD DiLoreto, DA Ferris, FL Friedman, SM Glassman, AR Glazer, LC Kollman, C Lauer, AK Marcus, DM Starr, J AF Miller, Kellee M. Browning, David J. Aiello, Lloyd Paul Beck, Roy W. Bressler, Neil M. Davis, Matthew D. DiLoreto, David A. Ferris, Frederick L., III Friedman, Scott M. Glassman, Adam R. Glazer, Louis C. Kollman, Craig Lauer, Andreas K. Marcus, Dennis M. Starr, JoAnn CA Diabetic Retinopathy Clinical Res TI THE COURSE OF RESPONSE TO FOCAL/GRID PHOTOCOAGULATION FOR DIABETIC MACULAR EDEMA SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE focal/grid photocoagulation; diabetic macular edema; optical coherence tomography ID GRID LASER PHOTOCOAGULATION; OPTICAL COHERENCE TOMOGRAPHY; VISUAL-ACUITY; RETINOPATHY; FIBROSIS AB Purpose: The purpose of this study was to determine whether eyes with center-involved diabetic macular edema, treated with focal/grid photocoagulation, in which there is a reduction in central subfield thickness (CST) measured with optical coherence tomography after 16 weeks, will continue to improve if retreatment is deferred. Methods: This is a prospective, multicenter, observational, single-group focal/grid photocoagulation study of 122 eyes with center-involved diabetic macular edema (optical coherence tomography CST >= 250 mu m). At the 16-week visit and continuing every 8 weeks, eyes were assessed for retreatment and additional laser treatment was deferred if the visual acuity letter score improved >= 5 letters or optical coherence tomography CST decreased >= 10% compared with the visit 16 weeks prior. Results: Of the 115 eyes that completed the 16-week visit, 54 (47%) had a decrease in CST by >= 10% compared with baseline. Of these, 26 (48%) had a CST >= 250 mu m at 16 weeks and were evaluable at 32 weeks. Eleven (42%; 95% confidence interval, 23-63%) of the 26 eyes had a further decrease in CST >= 10% from 16 weeks to 32 weeks without further treatment. Conclusion: Sixteen weeks after focal/grid laser for diabetic macular edema in eyes with a definite reduction, but not resolution, of central edema, 23% to 63% likely will continue to improve without additional treatment. RETINA 29:1436-1443, 2009 C1 [Davis, Matthew D.; DiLoreto, David A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. [Lauer, Andreas K.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Miller, KM (reprint author), 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat4@jaeb.org FU National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health, Department of Health and Human Services [EY14231, EY14269, EY14229] FX Supported by a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services EY14231, EY14269, and EY14229. NR 14 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X EI 1539-2864 J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD NOV-DEC PY 2009 VL 29 IS 10 BP 1436 EP 1443 PG 8 WC Ophthalmology SC Ophthalmology GA 519SH UT WOS:000271787600008 ER PT J AU Kiene, SM Bateganya, M Wanyenze, R Lule, H Mayer, K Stein, M AF Kiene, Susan M. Bateganya, Moses Wanyenze, Rhoda Lule, Haruna Mayer, Kenneth Stein, Michael TI Provider-initiated HIV testing in health care settings: Should it include client-centered counselling? SO SAHARA J-JOURNAL OF SOCIAL ASPECTS OF HIV-AIDS LA English DT Article DE Provider-initiated HIV testing; client-centered counselling; HIV prevention; developing countries ID UNPROTECTED SEXUAL-BEHAVIOR; INFECTED PATIENTS; SOUTH-AFRICA; UGANDA; INTERVENTION; METAANALYSIS; BOTSWANA; KAMPALA; WOMEN AB To increase access to HIV testing, the WHO and CDC have recommended implementing provider-initiated HIV testing (PITC). To address the resource limitations of the PITC setting, WHO and CDC suggest that patient-provider interactions during PITC may need to focus on providing information and referrals, instead of engaging patients in client-centered counselling, as is recommended during client-initiated HIV testing. Providing HIV prevention information has been shown to be less effective than client-centered counselling in reducing HIV-risk behaviour and STI incidence. Therefore, concerns exist about the efficacy of PITC as an HIV prevention approach. However, reductions in HIV incidence may be greater if more people know their HIV status through expanded availability of PITC, even if PITC is a less effective prevention intervention than is client-initiated HIV testing for individual patients. In the absence of an answer to this public health question, adaptation of effective brief client-centered counselling approaches to PITC should be explored along with research assessing the efficacy of PITC. C1 [Mayer, Kenneth] Brown Univ, AIDS Int Training & Res Programme, Providence, RI 02912 USA. [Stein, Michael] Rhode Isl Hosp, HIV Serv, Providence, RI 02903 USA. [Kiene, Susan M.; Wanyenze, Rhoda] Makerere Univ, Sch Publ Hlth, CDC HIV Fellowship Programme, Kampala, Uganda. [Mayer, Kenneth] Miriam Hosp Rhode Isl, Providence, RI USA. [Mayer, Kenneth] Ctr Dis Control, Atlanta, GA 30333 USA. [Mayer, Kenneth] NIH, New England Vaccine Preparedness Cohort Studies, Bethesda, MD USA. [Mayer, Kenneth] Natl Inst Hlth, Data Safety & Monitoring Board, AIDS Clin Trials Grp, Bethesda, MD 20892 USA. RP Kiene, SM (reprint author), Makerere Univ, Sch Publ Hlth, CDC HIV Fellowship Programme, Kampala, Uganda. EM susan_kiene@brown.edu FU NIDA NIH HHS [K24 DA00512]; NIMH NIH HHS [K01 MH083536] NR 27 TC 6 Z9 6 U1 4 U2 4 PU SA MEDICAL ASSOC HEALTH & MEDICAL PUBL GROUP PI CLAREMONT PA 21 DREYER ST, 4TH FLOOR, SANCLARE BLDG, CLAREMONT, 7700, SOUTH AFRICA SN 1729-0376 J9 SAHARA J-J SOC ASP H JI Sahara J-J. Soc. Asp. HIV/AIDS PD NOV PY 2009 VL 6 IS 3 BP 115 EP 119 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 534PR UT WOS:000272910100003 PM 20485851 ER PT J AU Bakalar, JL Greenstein, DK Clasen, L Tossell, JW Miller, R Evans, AC Mattai, AA Rapoport, JL Gogtay, N AF Bakalar, Jennifer L. Greenstein, Deanna K. Clasen, Liv Tossell, Julia W. Miller, Rachel Evans, Alan C. Mattai, Anand A. Rapoport, Judith L. Gogtay, Nitin TI General absence of abnormal cortical asymmetry in childhood-onset schizophrenia: A longitudinal study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Magnetic resonance imaging; Children; Cortical asymmetry; Development; Longitudinal ID TEMPORAL-LOBE; MAGNETIC-RESONANCE; BRAIN-DEVELOPMENT; PLANUM TEMPORALE; HEMISPHERIC DOMINANCE; VOLUME ASYMMETRIES; MRI; DISORDER; ADOLESCENCE; MORPHOMETRY AB Background: Childhood-onset schizophrenia (COS) is a rare, severe form of the adult-onset illness, with more salient neurobiological causes. Previous cross-sectional structural neuroimaging research has suggested that normal cortical asymmetry patterns [(R - L/(R + L)] may be altered in adult schizophrenia, although these findings were not well replicated. Recent studies show dynamic changes in brain asymmetry during childhood and adolescence. We hypothesized that COS patients would show a lack of normal development of asymmetry and decreased overall asymmetry. Methods: Prospective structural magnetic resonance scans were obtained at baseline and at two-year follow-up visits in 49 right-handed COS patients (mean baseline age: 14.72 +/- 2.63, 117 scans) and 50 age and sex-matched, right-handed healthy controls (mean baseline age: 15.15 +/- 3.37, 125 scans). Cortical thickness was calculated at 40,962 homologous points across each cerebral hemisphere using a fully automated, validated method. Differences in developmental asymmetry patterns across the cortical surface were analyzed using a linear mixed effects regression model. Results: No significant asymmetry differences were found either for cross-sectional comparisons of COS and healthy controls across the lateral and medial cortical surfaces or with respect to timing of developmental changes in asymmetry. Conclusions: The present findings do not support asymmetry differences for this severe, early form of schizophrenia. Published by Elsevier B.V. C1 [Bakalar, Jennifer L.; Greenstein, Deanna K.; Clasen, Liv; Tossell, Julia W.; Miller, Rachel; Mattai, Anand A.; Rapoport, Judith L.; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Evans, Alan C.] McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada. RP Bakalar, JL (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,3 N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM bakalarj@mail.nih.gov RI Gogtay, Nitin/A-3035-2008 FU Intramural NIH HHS [Z01 MH002581-17] NR 41 TC 7 Z9 7 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2009 VL 115 IS 1 BP 12 EP 16 DI 10.1016/j.schres.2009.07.026 PG 5 WC Psychiatry SC Psychiatry GA 518JD UT WOS:000271686400003 PM 19734017 ER PT J AU Walker, EF Cornblatt, BA Addington, J Cadenhead, KS Cannon, TD McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Woods, SW Heinssen, R AF Walker, Elaine F. Cornblatt, Barbara A. Addington, Jean Cadenhead, Kristin S. Cannon, Tyrone D. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Woods, Scott W. Heinssen, Robert TI The relation of antipsychotic and antidepressant medication with baseline symptoms and symptom progression: A naturalistic study of the North American Prodrome Longitudinal Sample SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Psychosis; Prodrome; Medication ID RANDOMIZED CONTROLLED-TRIAL; ULTRA-HIGH RISK; SCHIZOPHRENIA PRODROME; FOLLOW-UP; PSYCHOSIS; PEOPLE; PHASE; NEURODEVELOPMENT; INTERVENTIONS; OLANZAPINE AB A substantial number of patients who meet criteria for a prodromal syndrome for first psychosis are treated with antipsychotic and/or antidepressant medications. There is suggestive evidence that both classes of medication may reduce prodromal symptoms. This longitudinal study examined the relation of antipsychotic and antidepressant medication with prodromal symptom severity at baseline and 6-month follow-up. Participants met Structured Interview for Prodromal Syndromes (SIPS) criteria for the prodrome, and were evaluated at eight centers as part of the North American Prodrome Longitudinal Study (NAPLS). Symptom ratings (positive, negative, disorganized and general) and data on antipsychotics, SSRIs, and other antidepressant medications were obtained at baseline and 6-month follow-up. Analyses revealed that all symptom dimensions declined in severity over time, but there were differences in the magnitude of the decline as a function of antipsychotic medication. Those never on antipsychotics showed less reduction in positive and disorganized symptoms over time. SSRIs and other antidepressants were not linked with declines in symptom severity. Consistent with findings from small-sample, clinical trials, the present results suggest that atypical antipsychotics may be effective in reducing the severity of attenuated positive symptoms associated with the prodrome to psychotic disorders. Limitations of the present study are noted, including the fact that it is not a randomized trial, and data on duration and dosage of medication and 2-year follow-up were not available for most participants. The results are discussed in light of the relative risks and benefits of preventive interventions, both medication and cognitive therapies, and the importance of future clinical trials. (C) 2009 Elsevier B.V. All rights reserved. C1 [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cannon, Tyrone D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.; Tsuang, Ming T.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Seidman, Larry J.; Tsuang, Ming T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Heinssen, Robert] NIMH, Schizophrenia Spectrum Res Program, Div Adult Translat Res, Bethesda, MD 20892 USA. RP Walker, EF (reprint author), Emory Univ, Dept Psychol, 36 Eagle Row, Atlanta, GA 30322 USA. EM psyefw@emory.edu FU NCATS NIH HHS [UL1 TR000454]; NIMH NIH HHS [U01 MH081988-01A1, K23 MH001905, K24 MH076191, K24 MH076191-05, R01 MH060720, R01 MH060720-10, U01 MH081944, U01 MH081944-05, U01 MH081988, U01 MH081988-02] NR 22 TC 33 Z9 34 U1 5 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2009 VL 115 IS 1 BP 50 EP 57 DI 10.1016/j.schres.2009.07.023 PG 8 WC Psychiatry SC Psychiatry GA 518JD UT WOS:000271686400008 PM 19709859 ER PT J AU Schaffer, W Rockey, S AF Schaffer, Walter Rockey, Sally TI NIH Continues to Support the Best Science through RO1s SO SCIENTIST LA English DT Editorial Material C1 [Schaffer, Walter; Rockey, Sally] NIH, Bethesda, MD 20892 USA. RP Schaffer, W (reprint author), NIH, Bethesda, MD 20892 USA. RI Schaffer, Walter/E-5982-2010 OI Schaffer, Walter/0000-0002-2276-4656 NR 0 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 NOV PY 2009 VL 23 IS 11 BP 25 EP 25 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 510KK UT WOS:000271087200014 ER PT J AU Kleiner, DE AF Kleiner, David E. TI The Pathology of Drug-Induced Liver Injury SO SEMINARS IN LIVER DISEASE LA English DT Review DE Liver biopsy; pathology pattern; differential diagnosis ID NONALCOHOLIC STEATOHEPATITIS; GRANULOMATOUS HEPATITIS; ANTIRETROVIRAL THERAPY; VENOOCCLUSIVE DISEASE; LACTIC-ACIDOSIS; III PROCOLLAGEN; FAILURE; METHOTREXATE; FIALURIDINE; STEATOSIS AB The liver biopsy is frequently used as an adjunct diagnostic test in the evaluation of drug-induced liver injury (DILI). A biopsy may be performed to confirm the diagnosis, especially when there is a complex clinical differential diagnosis that includes DILI. A biopsy can also be used to stage the severity of hepatotoxicity so that a necessary agent may be continued. Alternatively, a drug or toxin may only be implicated after a biopsy is performed, particularly in the case of subacute or chronic liver injury. The pathologist should approach the biopsy systematically by first classifying the disease and then working with the clinician to include or exclude etiologies in the pathological differential diagnosis. This article outlines a practical approach to the diagnosis of DILI on liver biopsy, including the common patterns of injury observed in drug- and toxin-induced liver pathology and prognostic pathological features that may be associated with the outcome of patients with DILI. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Kleiner, DE (reprint author), NCI, Pathol Lab, NCI,Bldg 10,Room 2B50,MSC 1500,10 Ctr Dr, Bethesda, MD 20892 USA. EM kleinerd@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU National Institutes of Health (NIH); National Cancer Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute. NR 53 TC 46 Z9 51 U1 0 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD NOV PY 2009 VL 29 IS 4 BP 364 EP 372 DI 10.1055/s-0029-1240005 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 508DE UT WOS:000270907000005 PM 19826970 ER PT J AU Striker, GE Vlassara, H Ferrucci, L AF Striker, Gary E. Vlassara, Helen Ferrucci, Luigi TI Aging and the Kidney: Introduction SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material C1 [Striker, Gary E.; Vlassara, Helen] Mt Sinai Sch Med, New York, NY 10029 USA. [Ferrucci, Luigi] NIH, Baltimore, MD USA. RP Striker, GE (reprint author), Mt Sinai Sch Med, New York, NY 10029 USA. FU Intramural NIH HHS [Z01 AG000015-49] NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2009 VL 29 IS 6 BP 549 EP 550 DI 10.1016/j.semnephrol.2009.07.014 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 617CD UT WOS:000279257500001 PM 20006785 ER PT J AU Eggers, PW AF Eggers, Paul W. TI The Aging Pandemic: Demographic Changes in the General and End-Stage Renal Disease Populations SO SEMINARS IN NEPHROLOGY LA English DT Review DE ESRD; epidemiology; aging; renal disease; populations ID CHRONIC KIDNEY-DISEASE; UNITED-STATES; DIABETES BURDEN; US; IMPACT; AGE; PROGRESSION; PREVALENCE; TRENDS; EXPENDITURE C1 NIDDK, Div Kidney Urol & Hematol, Bethesda, MD 20892 USA. RP Eggers, PW (reprint author), NIDDK, Div Kidney Urol & Hematol, 6707 Democracy Blvd,Room 615, Bethesda, MD 20892 USA. EM eggersp@extra.niddk.nih.gov NR 35 TC 6 Z9 7 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2009 VL 29 IS 6 BP 551 EP 554 DI 10.1016/j.semnephrol.2009.07.001 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 617CD UT WOS:000279257500002 PM 20006786 ER PT J AU Vlassara, H Uribarri, J Ferrucci, L Cai, WJ Torreggiani, M Post, JB Zheng, F Striker, GE AF Vlassara, Helen Uribarri, Jaime Ferrucci, Luigi Cai, Weijing Torreggiani, Massimo Post, James B. Zheng, Feng Striker, Gary E. TI Identifying Advanced Glycation End Products as a Major Source of Oxidants in Aging: Implications for the Management and/or Prevention of Reduced Renal Function in Elderly Persons SO SEMINARS IN NEPHROLOGY LA English DT Review DE AGEs; aging; diet; CKD ID CHRONIC KIDNEY-DISEASE; GLOMERULOSCLEROSIS-PRONE MICE; MESANGIAL CELLS; DIABETIC COMPLICATIONS; DIETARY GLYCOTOXINS; OXIDATIVE STRESS; RISK-FACTOR; DB/DB MICE; INFLAMMATORY RESPONSE; CALORIE RESTRICTION C1 [Vlassara, Helen; Cai, Weijing; Torreggiani, Massimo; Zheng, Feng; Striker, Gary E.] Mt Sinai Sch Med, Div Diabet & Aging, Dept Geriatr, New York, NY 10029 USA. [Uribarri, Jaime; Post, James B.; Striker, Gary E.] Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Torreggiani, Massimo] Univ Pavia, Unit Nephrol Dialysis & Transplantat, I-27100 Pavia, Italy. RP Vlassara, H (reprint author), Mt Sinai Sch Med, Div Diabet & Aging, Dept Geriatr, Box 1640,1 Gustave Levy Pl, New York, NY 10029 USA. EM helen.vlassara@mssm.edu FU Intramural NIH HHS [Z01 AG000015-49] NR 65 TC 29 Z9 29 U1 0 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2009 VL 29 IS 6 BP 594 EP 603 DI 10.1016/j.semnephrol.2009.07.013 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 617CD UT WOS:000279257500007 PM 20006791 ER PT J AU Schiffman, M Safaeian, M Wentzensen, N AF Schiffman, Mark Safaeian, Mahboobeh Wentzensen, Nicolas TI The Use of Human Papillomavirus Seroepidemiology to Inform Vaccine Policy SO SEXUALLY TRANSMITTED DISEASES LA English DT Editorial Material ID CERVICAL LESIONS; COSTA-RICA; ANTIBODIES; TYPE-16; NEUTRALIZATION; REACTIVITY; INFECTION; COHORT; WOMEN; ELISA C1 [Schiffman, Mark; Safaeian, Mahboobeh; Wentzensen, Nicolas] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Execut Plaza S,Room 5026, Bethesda, MD 20892 USA. EM schiffmm@mail.nih.gov FU Intramural NIH HHS [ZIA CP010124-18] NR 18 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV PY 2009 VL 36 IS 11 BP 675 EP 679 DI 10.1097/OLQ.0b013e3181bce102 PG 5 WC Infectious Diseases SC Infectious Diseases GA 511OA UT WOS:000271173900002 PM 19773679 ER PT J AU Lack, CW Storch, EA Keeley, ML Geffken, GR Ricketts, ED Murphy, TK Goodman, WK AF Lack, Caleb W. Storch, Eric A. Keeley, Mary L. Geffken, Gary R. Ricketts, Emily D. Murphy, Tanya K. Goodman, Wayne K. TI Quality of life in children and adolescents with obsessive-compulsive disorder: base rates, parent-child agreement, and clinical correlates SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Obsessive-compulsive disorder; Quality of Life; Children; Impairment ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COGNITIVE-BEHAVIORAL THERAPY; FUNCTIONAL IMPAIRMENT; TOURETTES-SYNDROME; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; COMORBIDITY; DEPRESSION; IMPACT; SCALE AB The presence of obsessive-compulsive disorder (OCD) has been linked to decreased quality of life (QoL) among adults, yet little is known about the impact of OCD on QoL in pediatric patients. Sixty-two youth with OCD and their parent(s) were administered the Children's Yale-Brown Obsessive Compulsive Scale following a clinical interview. Children completed the Pediatric Quality of Life Inventory and parents completed the Pediatric Quality of Life Parent Proxy Inventory and Child Behavior Checklist. QoL scores for OCD patients were significantly lower than for healthy controls, but similar to QoL in a general psychiatric sample on the majority of domains. Parent-child agreement on QoL was moderate to strong across age groups. Results indicate that, in youth with OCD, QoL is reduced relative to healthy controls, related to OCD symptom severity per parent-report, and are strongly predicted by the presence of comorbid externalizing and internalizing symptoms. C1 [Lack, Caleb W.] Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA. [Storch, Eric A.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat, Tampa, FL USA. [Storch, Eric A.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Keeley, Mary L.; Geffken, Gary R.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. [Ricketts, Emily D.] Univ Wisconsin, Milwaukee, WI 53201 USA. [Goodman, Wayne K.] NIH, Bethesda, MD 20892 USA. RP Lack, CW (reprint author), Arkansas Tech Univ, Dept Behav Sci, Russellville, AR 72801 USA. EM clack@atu.edu RI Storch, Eric/I-4935-2012 NR 42 TC 49 Z9 50 U1 5 U2 12 PU DR DIETRICH STEINKOPFF VERLAG PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD NOV PY 2009 VL 44 IS 11 BP 935 EP 942 DI 10.1007/s00127-009-0013-9 PG 8 WC Psychiatry SC Psychiatry GA 508ZG UT WOS:000270978800006 PM 19255701 ER PT J AU Zheng, G Marchini, J Geller, NL AF Zheng, Gang Marchini, Jonathan Geller, Nancy L. TI Introduction to the Special Issue: Genome-Wide Association Studies SO STATISTICAL SCIENCE LA English DT Editorial Material C1 [Zheng, Gang; Geller, Nancy L.] NHLBI, Off Biostat Res, Div Cardiovasc Dis, Bethesda, MD 20892 USA. [Marchini, Jonathan] Univ Oxford, Dept Stat, Math Genet Grp, Oxford OX1 3TG, England. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Dis, 6701 Rockledge Dr, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov; marchini@stats.ox.ac.uk; gellern@nhlbi.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2009 VL 24 IS 4 SI SI BP 387 EP 387 DI 10.1214/09-STS310 PG 1 WC Statistics & Probability SC Mathematics GA 590VS UT WOS:000277257000001 ER PT J AU Chatterjee, N Chen, YH Luo, S Carroll, RJ AF Chatterjee, Nilanjan Chen, Yi-Hau Luo, Sheng Carroll, Raymond J. TI Analysis of Case-Control Association Studies: SNPs, Imputation and Haplotypes SO STATISTICAL SCIENCE LA English DT Article DE Case-control studies; Empirical-Bayes; genetic epidemiology; haplotypes; model averaging; model robustness; model selection; retrospective studies; shrinkage ID GENOME-WIDE ASSOCIATION; GENE-ENVIRONMENT INDEPENDENCE; LIKELIHOOD-BASED INFERENCE; DISEASE ASSOCIATIONS; PROSTATE-CANCER; GENOTYPE DATA; ESTIMATORS; ALLELES; MODELS; TESTS AB Although prospective logistic regression is the standard method of analysis for case-control data, it has been recently noted that in genetic epidemiologic studies one can use the "retrospective" likelihood to gain major power by incorporating various population genetics model assumptions such as Hardy-Weinberg-Equilibrium (HWE), gene gene and gene environment independence. In this article we review these modern methods and contrast them with the more classical approaches through two types of applications (i) association tests for typed and untyped single nucleotide polymorphisms (SNPs) and (ii) estimation of haplotype effects and haplotype environment interactions in the presence of haplotype-phase ambiguity. We provide novel insights to existing methods by construction of various score-tests and pseudo-likelihoods. In addition, we describe a novel two-stage method for analysis of untyped SNPs that can use any flexible external algorithm for genotype imputation followed by a powerful association test based on the retrospective likelihood. We illustrate applications of the methods using simulated and real data. C1 [Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. [Chen, Yi-Hau] Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. [Luo, Sheng] Univ Texas Sch Publ Hlth, Div Biostat, Houston, TX 77030 USA. [Carroll, Raymond J.] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. EM chattern@mail.nih.gov; yhchen@stat.sinica.edu.tw; Sheng.T.Luo@uth.tmc.edu; carroll@stat.tamu.edu FU National Heart Lung and Blood Institute [RO1HL091172-01]; National Cancer Institute [CA57030]; National Science Council of ROC [NSC 95-2118-M-001-022-MY3]; King Abdullah University of Science and Technology (KAUST) [KUS-CI-016-04] FX Chatterjee's research was supported by a gene environment initiative grant from the National Heart Lung and Blood Institute (RO1HL091172-01) and by the Intramural Research Program of the National Cancer Institute. Chen's research was supported by the National Science Council of ROC (NSC 95-2118-M-001-022-MY3). Carroll's research was supported by a grant from the National Cancer Institute (CA57030) and by Award Number KUS-CI-016-04, made by King Abdullah University of Science and Technology (KAUST). NR 32 TC 9 Z9 9 U1 1 U2 2 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2009 VL 24 IS 4 SI SI BP 489 EP 502 DI 10.1214/09-STS297 PG 14 WC Statistics & Probability SC Mathematics GA 590VS UT WOS:000277257000008 PM 20543902 ER PT J AU Zheng, G Joo, J Zaykin, D Wu, C Geller, N AF Zheng, Gang Joo, Jungnam Zaykin, Dmitri Wu, Colin Geller, Nancy TI Robust Tests in Genome-Wide Scans under Incomplete Linkage Disequilibrium SO STATISTICAL SCIENCE LA English DT Article DE Efficiency robustness; genetic models; genomewide association studies; linkage disequilibrium; ranking and selection; incomplete LD model ID CASE-CONTROL ASSOCIATION; HARDY-WEINBERG DISEQUILIBRIUM; CONTROL GENETIC ASSOCIATION; SAMPLE-SIZE; QUANTITATIVE TRAITS; NUISANCE PARAMETER; CORRELATED TESTS; TREND TESTS; DISEASE; POWER AB Under complete linkage disequilibrium (LD), robust tests often have greater power than Pearson's chi-square test and trend tests for the analysis of case-control genetic association studies. Robust statistics have been used in candidate-gene and genome-wide association studies (GWAS) when the genetic model is unknown. We consider here a more general incomplete LD model, and examine the impact of penetrances at the marker locus when the genetic models are defined at the disease locus. Robust statistics are then reviewed and their efficiency and robustness are compared through simulations in GWAS of 300,000 markers under the incomplete LID model. Applications of several robust tests to the Wellcome Trust Case-Control Consortium [Nature 447 (2007) 661-678] are presented. C1 [Zheng, Gang; Joo, Jungnam; Wu, Colin; Geller, Nancy] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. [Zaykin, Dmitri] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov; jooj@nhlbi.nih.gov; zaykind@niehs.nih.gov; wuc@nhlbi.nih.gov; gellern@nhlbi.nih.gov FU NIH, National Institute of Environmental Health Sciences FX The research of Dmitri Zaykin was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. We would like to thank three reviewers for their helpful suggestions and comments. NR 46 TC 18 Z9 18 U1 1 U2 4 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2009 VL 24 IS 4 SI SI BP 503 EP 516 DI 10.1214/09-STS314 PG 14 WC Statistics & Probability SC Mathematics GA 590VS UT WOS:000277257000009 ER PT J AU Pfeiffer, RM Gail, MH Pee, D AF Pfeiffer, Ruth M. Gail, Mitchell H. Pee, David TI On Combining Data From Genome-Wide Association Studies to Discover Disease-Associated SNPs SO STATISTICAL SCIENCE LA English DT Article DE Whole genome scans; hypothesis testing; random effects; Wald test; multiple comparison ID SUSCEPTIBILITY LOCI; SAMPLE-SIZE; METAANALYSIS; PROBABILITY; GENOTYPES; DESIGNS; TRIALS; TESTS AB Combining data from several case-control genome-wide association (GWA) studies can yield greater efficiency for detecting associations of disease with single nucleotide polymorphisms (SNPs) than separate analyses of the component studies. We compared several procedures to combine GWA study data both in terms of the power to detect a disease-associated SNP while controlling the genome-wide significance level, and in terms of the detection probability (DP). The DP is the probability that a particular disease-associated SNP will be among the T most promising SNPs selected on the basis of low p-values. We studied both fixed effects and random effects models in which associations varied across studies. In settings of practical relevance, meta-analytic approaches that focus on a single degree of freedom had higher power and DP than global tests such as summing chi-square test-statistics across studies, Fisher's combination of p-values, and forming a combined list of the best SNPs from within each study. C1 [Pfeiffer, Ruth M.; Gail, Mitchell H.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Pee, David] Informat Management Serv Inc, Silver Spring, MD 20904 USA. RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. EM pfeiffer@mail.nih.gov; gailm@mail.nih.gov; PeeD@imsweb.com NR 18 TC 14 Z9 14 U1 1 U2 1 PU INST MATHEMATICAL STATISTICS PI CLEVELAND PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2009 VL 24 IS 4 SI SI BP 547 EP 560 DI 10.1214/09-STS286 PG 14 WC Statistics & Probability SC Mathematics GA 590VS UT WOS:000277257000012 ER PT J AU Xi, SC Geiman, TM Briones, V Tao, YG Xu, H Muegge, K AF Xi, Sichuan Geiman, Theresa M. Briones, Victorino Tao, Yong Guang Xu, Hong Muegge, Kathrin TI Lsh Participates in DNA Methylation and Silencing of Stem Cell Genes SO STEM CELLS LA English DT Article DE DNA methylation; Chromatin; Epigenetics; Differentiation; Stem cell genes ID DE-NOVO METHYLATION; EMBRYONAL CARCINOMA-CELLS; NEURONAL DIFFERENTIATION; REPRESS TRANSCRIPTION; RETINOIC ACID; FAMILY-MEMBER; SNF2 FAMILY; PLURIPOTENCY; EXPRESSION; NANOG AB Transcriptional control of stem cell genes is a critical step in differentiation of embryonic stem cells and in reprogramming of somatic cells into stem cells. Here we report that Lsh, a regulator of repressive chromatin at retrotransposons, also plays an important role in silencing of stem cell-specific genes such as Oct4. We found that CpG methylation is gained during in vitro differentiation of several stem cell-specific genes (in 11 of 12 promoter regions) and thus appears to be a common epigenetic mark. Lsh depletion prevents complete silencing of stem cell gene expression and moreover promotes the maintenance of stem cell characteristics in culture. Lsh is required for establishment of DNA methylation patterns at stem cell genes during differentiation, in part by regulating access of Dnmt3b to its genomic targets. Our results indicate that Lsh is involved in the control of stem cell genes and suggest that Lsh is an important epigenetic modulator during early stem cell differentiation. STEM CELLS 2009; 27: 2691-2702 C1 [Xi, Sichuan; Geiman, Theresa M.; Briones, Victorino; Tao, Yong Guang; Xu, Hong; Muegge, Kathrin] NCI, Lab Canc Prevent, SAIC Frederick, Frederick, MD 21701 USA. RP Muegge, K (reprint author), NCI, Lab Canc Prevent, SAIC Frederick, Frederick, MD 21701 USA. EM muegge@ncifcrf.gov FU National Cancer Institute (NCI); National Institutes of Health [N01-C0-12400] FX This project has been funded in whole or part with federal funds from the National Cancer Institute (NCI), National Institutes of Health, under contract N01-C0-12400. NCI-Frederick is accredited by Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International and follows the Public Health Service Policy for the Care and Use of Laboratory Animals in accordance with the "Guide for the Care and Use of Laboratory Animals.'' 58 NR 58 TC 32 Z9 34 U1 0 U2 4 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2009 VL 27 IS 11 BP 2691 EP 2702 DI 10.1002/stem.183 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 520GS UT WOS:000271830700007 PM 19650037 ER PT J AU Wilson, LM Wong, SHK Yu, NP Geras-Raaka, E Raaka, BM Gershengorn, MC AF Wilson, Leah M. Wong, Stephen H. K. Yu, Ningpu Geras-Raaka, Elizabeth Raaka, Bruce M. Gershengorn, Marvin C. TI Insulin but Not Glucagon Gene is Silenced in Human Pancreas-Derived Mesenchymal Stem Cells SO STEM CELLS LA English DT Article DE Epigenetics; Gene silencing; Glucagon; Insulin; Mesenchymal stem cells; Pancreatic precursor cells; Transcription factors ID TRANSCRIPTION FACTOR; BETA-CELLS; PRECURSOR CELLS; ISLET TRANSPLANTATION; EXPRESSING CELLS; HISTONE H4; IN-VITRO; DIFFERENTIATION; MAFA; METHYLATION AB We previously characterized human islet-derived precursor cells (hIPCs) as a specific type of mesenchymal stem cell capable of differentiating to insulin (INS)- and glucagon (GCG)-expressing cells. However, during proliferative expansion, INS transcript becomes undetectable and then cannot be induced, a phenomenon consistent with silencing of the INS gene. We explored this possibility by determining whether ectopic expression of transcription factors known to induce transcription of this gene in beta cells, pancreatic and duodenal homeobox factor 1 (Pdx1), V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa), and neurogenic differentiation 1 (Neurod1), would activate INS gene expression in long-term hIPC cultures. Coexpression of all three transcription factors had little effect on INS mRNA levels but unexpectedly increased GCG mRNA at least 100,000-fold. In contrast to the endogenous promoter, an exogenous rat INS promoter was activated by expression of Pdx1 and Mafa in hIPCs. Chromatin immunoprecipitation (ChIP) assays using antibodies directed at posttranslationally modified histones show that regions of the INS and GCG genes have similar levels of activation-associated modifications but the INS gene has higher levels of repression-associated modifications. Furthermore, the INS gene was found to be less accessible to micrococcal nuclease digestion than the GCG gene. Lastly, ChIP assays show that exogenously expressed Pdx1 and Mafa bind at very low levels to the INS promoter and at 20- to 25-fold higher levels to the GCG promoter in hIPCs. We conclude that the INS gene in hIPCs is modified epigenetically ("silenced'') so that it is resistant to activation by transcription factors. STEM CELLS 2009; 27: 2703-2711 C1 [Wilson, Leah M.; Wong, Stephen H. K.; Yu, Ningpu; Geras-Raaka, Elizabeth; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 50 S Dr, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov RI Yu, Ningpu/D-4266-2009 FU NIDDK [Z01DK047046CEB, Z01DK047047CEB]; NIH FX We thank Dr. Vesco Mutskov, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), for critical reading of the manuscript and for helpful suggestions concerning ChIP methodology. This research was supported by the Intramural Research Program of the NIDDK, Project numbers Z01DK047046CEB and Z01DK047047CEB, NIH. L.M.W. and S.H.K.W. contributed equally to this work. NR 51 TC 9 Z9 9 U1 1 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV PY 2009 VL 27 IS 11 BP 2703 EP 2711 DI 10.1002/stem.229 PG 9 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 520GS UT WOS:000271830700008 PM 19785038 ER PT J AU Matarin, M Brown, WM Dena, H Britton, A De Vrieze, FW Brott, TG Brown, RD Worrall, BB Case, LD Chanock, SJ Metter, EJ Ferruci, L Gamble, D Hardy, JA Rich, SS Singleton, A Meschia, JF AF Matarin, Mar Brown, W. Mark Dena, Hernandez Britton, Angela De Vrieze, Fabienne Wavrant Brott, Thomas G. Brown, Robert D., Jr. Worrall, Bradford B. Case, L. Douglas Chanock, Stephen J. Metter, E. Jeffrey Ferruci, Luigi Gamble, Dale Hardy, John A. Rich, Stephen S. Singleton, Andrew Meschia, James F. TI Candidate Gene Polymorphisms for Ischemic Stroke SO STROKE LA English DT Article DE candidate genes; genetics; ischemic stroke ID RISK; METAANALYSIS; ASSOCIATION; EPIDEMIOLOGY; DISEASE AB Background and Purpose-Ischemic stroke (IS) is a multifactorial disorder with strong evidence from twin, family, and animal model studies suggesting a genetic influence on risk and prognosis. Several candidate genes for IS have been proposed, but few have been replicated. We investigated the contribution of 67 candidate genes (369 single nucleotide polymorphisms [SNPs]) on the risk of IS in a North American population of European descent. Methods-Two independent studies were performed. In the first, 342 SNPs from 52 candidate genes were genotyped in 307 IS cases and 324 control subjects. The SNPs significantly associated with IS were tested for replication in another cohort of 583 IS cases and 270 control subjects. In the second study, 212 SNPs from 62 candidate genes were analyzed in 710 IS cases with subtyping available and 3751 control subjects. Results-None of the candidate genes (SNPs) were significantly associated with IS risk independent of known stroke risk factors after correction for multiple hypotheses testing. Conclusion-These results are consistent with previous meta-analyses that demonstrate an absence of genetic association of variants in plausible candidate genes with IS risk. Our study suggests that the effect of the investigated SNPs may be weak or restricted to specific populations or IS subtypes. (Stroke. 2009; 40: 3436-3442.) C1 [Brott, Thomas G.; Gamble, Dale; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Matarin, Mar; Britton, Angela; Singleton, Andrew] NIA, Mol Genet Sect, NIH, Bethesda, MD 20892 USA. [Dena, Hernandez; De Vrieze, Fabienne Wavrant; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Brown, W. Mark; Case, L. Douglas] Wake Forest Univ, Med Ctr, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Chanock, Stephen J.] NCI, Adv Technol Ctr, Gaithersburg, MD USA. [Metter, E. Jeffrey; Ferruci, Luigi] NIA, Longitudinal Studies Sect, Intramural Res Program, Bethesda, MD USA. [Hardy, John A.] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. EM Meschia.James@mayo.edu RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Matarin, Mar/F-1771-2016 OI Matarin, Mar/0000-0002-4717-5735 FU National Institute on Aging, National Institutes of Health, Department of Health and Human Services [Z01 AG00095406]; National Institute of Neurological Disorders and Stroke [R01 NS39987] FX This work was supported in part by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Department of Health and Human Services, project Z01 AG00095406. SWISS is supported by a grant from the National Institute of Neurological Disorders and Stroke (R01 NS39987). NR 24 TC 31 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2009 VL 40 IS 11 BP 3436 EP 3442 DI 10.1161/STROKEAHA.109.558015 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 511JM UT WOS:000271160300006 PM 19729601 ER PT J AU Huang, AH Stein, A Tuan, RS Mauck, RL AF Huang, Alice H. Stein, Ashley Tuan, Rocky S. Mauck, Robert L. TI Transient Exposure to Transforming Growth Factor Beta 3 Improves the Mechanical Properties of Mesenchymal Stem Cell-Laden Cartilage Constructs in a Density-Dependent Manner SO TISSUE ENGINEERING PART A LA English DT Article ID TISSUE-ENGINEERED CARTILAGE; BOVINE ARTICULAR-CARTILAGE; IN-VITRO CHONDROGENESIS; HYALURONIC-ACID HYDROGELS; AGAROSE CULTURE; OSTEOGENIC DIFFERENTIATION; EXTRACELLULAR-MATRIX; PROGENITOR CELLS; SEEDING DENSITY; N-CADHERIN AB Mesenchymal stem cells (MSCs) are an attractive cell source for cartilage tissue engineering and regenerative medicine. However, the use of these cells has been limited by their reduced ability to form functional tissue compared to chondrocytes when placed in three-dimensional culture systems. To optimize MSC functional chondrogenesis, we examined the effects of increasing seeding density and transient application of transforming growth factor beta 3 (TGF-beta 3), two factors previously shown to improve growth of chondrocyte-based constructs. Chondrocytes seeded in agarose at 20 million cells/mL and MSCs seeded at 20 or 60 million cells/mL agarose were cultured for 7 weeks under continuous or transient application of TGF-beta 3. In the transient group, cell-laden constructs were exposed to TGF-beta 3 for the initial 3 weeks, followed by 4 weeks of culture in medium without TGF-beta 3. Compressive properties, biochemical content, and gene expression were assessed at 3, 5, and 7 weeks. Matrix distribution and collagen type was determined using histology and immunohistochemistry, and chondrogenic and osteogenic markers were assessed using real-time polymerase chain reaction. When maintained continuously with TGF-beta 3, chondrocyte-seeded constructs achieved a higher equilibrium compressive modulus than MSCs similarly maintained. Although properties of both groups increased with respect to starting values, there was no difference in bulk mechanical or biochemical properties with higher seeding density when MSCs were cultured with constant TGF-beta 3. Findings also showed that while transient application of TGF-beta 3 elicited robust growth from chondrocyte-laden gels, MSCs seeded at the same density failed to respond, although constructs maintained their previously accrued properties and continued to express cartilaginous genes after TGF-beta 3 removal. Conversely, MSCs seeded at 60 million cells/mL exhibited a strong anabolic response with transient TGF-beta 3 exposure, achieving an equilibrium modulus of approximately 200 kPa. Although this represents the highest modulus we have been able to achieve with MSC-seeded constructs using our culture system, further work remains to optimize MSC chondrogenesis for cartilage tissue engineering, particularly in terms of collagen content and dynamic mechanical properties. C1 [Huang, Alice H.; Stein, Ashley; Mauck, Robert L.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA. [Huang, Alice H.; Stein, Ashley; Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Mauck, RL (reprint author), Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, 36th St & Hamilton Walk, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu RI Huang, Alice/L-2256-2015 OI Huang, Alice/0000-0002-5037-6829 FU National Institutes of Health [RO3 AR053668]; National Science Foundation (AHH) FX This work was supported by the National Institutes of Health (RO3 AR053668) and a Graduate Research Fellowship from the National Science Foundation (AHH). Additional support was provided by the Penn Center for Musculoskeletal Disorders. The type II collagen and type X collagen antibodies developed by Thomas F. Linsenmayer were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by the Department of Biology, University of Iowa, Iowa City, Iowa. NR 58 TC 85 Z9 86 U1 1 U2 14 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 NOV PY 2009 VL 15 IS 11 BP 3461 EP 3472 DI 10.1089/ten.tea.2009.0198 PG 12 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 519EC UT WOS:000271746800023 PM 19432533 ER PT J AU Xia, MH Huang, RL Sun, Y Semenza, GL Aldred, SF Witt, KL Inglese, J Tice, RR Austin, CP AF Xia, Menghang Huang, Ruili Sun, Yi Semenza, Gregg L. Aldred, Shelley Force Witt, Kristine L. Inglese, James Tice, Raymond R. Austin, Christopher P. TI Identification of Chemical Compounds that Induce HIF-1 alpha Activity SO TOXICOLOGICAL SCIENCES LA English DT Article DE cobalt sulfate heptahydrate; 7-diethylamino-4-methylcoumarin; 7; 12-dimethylbenz(a)anthracence; HIF-1 alpha; inducers; iodochlorohydroxyquinoline; NTP 1408 compound library; o-phenanthroline; qHTS ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-I; TRANSCRIPTIONAL ACTIVATION; ASPARAGINE HYDROXYLATION; LACTATE-DEHYDROGENASE; RESPONSE ELEMENTS; FACTOR 1-ALPHA; LOW-OXYGEN; HIF-ALPHA; HYPOXIA AB Cellular metabolism depends on the availability of oxygen and the major regulator of oxygen homeostasis is hypoxia-inducible factor 1 (HIF-1), a highly conserved transcription factor that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF-1 is a heterodimeric transcription factor composed of hypoxia-inducible HIF-1 alpha and constitutively expressed HIF-1 beta. Under hypoxic conditions, the two subunits dimerize, allowing translocation of the HIF-1 complex to the nucleus where it binds to hypoxia-response elements (HREs) and activates expression of target genes implicated in angiogenesis, cell growth, and survival. The HIF-1 pathway is essential to normal growth and development, and is involved in the pathophysiology of cancer, inflammation, and ischemia. Thus, there is considerable interest in identifying compounds that modulate the HIF-1 signaling pathway. To assess the ability of environmental chemicals to stimulate the HIF-1 signaling pathway, we screened a National Toxicology Program collection of 1408 compounds using a cell-based beta-lactamase HRE reporter gene assay in a quantitative high-throughput screening (qHTS) format. Twelve active compounds were identified. These compounds were tested in a confirmatory assay for induction of vascular endothelial growth factor, a known hypoxia target gene, and confirmed compounds were further tested for their ability to mimic the effect of a reduced-oxygen environment on hypoxia-regulated promoter activity. Based on this testing strategy, three compounds (o-phenanthroline, iodochlorohydroxyquinoline, cobalt sulfate heptahydrate) were confirmed as hypoxia mimetics, whereas two compounds (7-diethylamino-4-methylcoumarin and 7,12-dimethylbenz(a)anthracence) were found to interact with HIF-1 in a manner different from hypoxia. These results demonstrate the effectiveness of qHTS in combination with secondary assays for identification of HIF-1 alpha inducers and for distinguishing among inducers based on their pattern of activated hypoxic target genes. Identification of environmental compounds having HIF-1 alpha activation activity in cell-based assays may be useful for prioritizing chemicals for further testing as hypoxia-response inducers in vivo. C1 [Xia, Menghang; Huang, Ruili; Inglese, James; Austin, Christopher P.] NIH, Chem Genom Ctr, Bethesda, MD 20892 USA. [Sun, Yi] Univ Michigan, Ctr Comprehens Canc, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Vasc Biol Program,Inst Cell Engn,Dept Pediat, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Vasc Biol Program,Inst Cell Engn,Dept Med, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Vasc Biol Program,Inst Cell Engn,Dept Oncol, Baltimore, MD 21205 USA. [Semenza, Gregg L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Vasc Biol Program,Inst Cell Engn,Dept Radiat Onco, Baltimore, MD 21205 USA. [Aldred, Shelley Force] SwitchGear Genom, Menlo Pk, CA 94025 USA. [Witt, Kristine L.; Tice, Raymond R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Xia, MH (reprint author), NIH, Chem Genom Ctr, 9800 Med Ctr Dr, Bethesda, MD 20892 USA. EM mxia@mail.nih.gov FU National Toxicology Program [Y2-ES-7020-01]; National Institute of Environmental Health Sciences and the National Human Genome Research Institute; National Institutes of Health (NIH); NIH Roadmap for Medical Research Molecular Libraries Program [U54MH084681] FX Intramural Research Programs (NIH Interagency agreement # Y2-ES-7020-01) of the National Toxicology Program; National Institute of Environmental Health Sciences and the National Human Genome Research Institute; National Institutes of Health (NIH); and the NIH Roadmap for Medical Research Molecular Libraries Program (U54MH084681). NR 43 TC 31 Z9 32 U1 0 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2009 VL 112 IS 1 BP 153 EP 163 DI 10.1093/toxsci/kfp123 PG 11 WC Toxicology SC Toxicology GA 514IO UT WOS:000271387900015 PM 19502547 ER PT J AU Hosking, CR Schwartz, JL AF Hosking, C. Rose Schwartz, Jennifer Lippincott TI The future's bright: Imaging cell biology in the 21st century SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material C1 [Schwartz, Jennifer Lippincott] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD USA. EM R.Hosking@elsevier.com NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 2009 VL 19 IS 11 BP 553 EP 554 DI 10.1016/j.tcb.2009.09.005 PG 2 WC Cell Biology SC Cell Biology GA 523FM UT WOS:000272057500001 PM 19833517 ER PT J AU Lippincott-Schwartz, J Patterson, GH AF Lippincott-Schwartz, Jennifer Patterson, George H. TI Photoactivatable fluorescent proteins for diffraction-limited and super-resolution imaging SO TRENDS IN CELL BIOLOGY LA English DT Review ID OPTICAL RECONSTRUCTION MICROSCOPY; TO-RED CONVERSION; LOCALIZATION MICROSCOPY; MONOMERIC RED; GREEN; CELLS; COLOR; NANOSCOPY; EOSFP; GFP AB Photoactivatable fluorescent proteins (PA-FPs) are molecules that switch to a new fluorescent state in response to activation to generate a high level of contrast. Over the past eight years, several types of PA-FPs have been developed. The PA-FPs fluoresce green or red, or convert from green to red in response to activating light. Others reversibly switch between 'off' and 'on' in response to light. The optical "highlighting" capability of PA-FPs has led to the rise of novel imaging techniques providing important new biological insights. These range from in cellulo pulse-chase labeling for tracking subpopulations of cells, organelles or proteins under physiological settings, to super-resolution imaging of single molecules for determining intracellular protein distributions at nanometer precision. This review surveys the expanding array of PA-FPs, including their advantages and disadvantages, and highlights their use in novel imaging methodologies. C1 [Lippincott-Schwartz, Jennifer; Patterson, George H.] NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHD, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov FU Intramural NIH HHS [Z01 HD008850-02] NR 64 TC 173 Z9 176 U1 8 U2 68 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 2009 VL 19 IS 11 BP 555 EP 565 DI 10.1016/j.tcb.2009.09.003 PG 11 WC Cell Biology SC Cell Biology GA 523FM UT WOS:000272057500002 PM 19836954 ER PT J AU Balla, T AF Balla, Tamas TI Green light to illuminate signal transduction events SO TRENDS IN CELL BIOLOGY LA English DT Review ID RESONANCE ENERGY-TRANSFER; PROTEIN-KINASE-C; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; ENCODED FLUORESCENT REPORTER; HETEROTRIMERIC G-PROTEINS; SINGLE LIVING CELLS; SPATIOTEMPORAL DYNAMICS; PHOSPHATIDIC-ACID; COUPLED RECEPTORS; PLASMA-MEMBRANE AB When cells are exposed to hormones that act on cell surface receptors, information is processed through the plasma membrane into the cell interior via second messengers generated in the inner leaflet of the plasma membrane. Individual biochemical steps along this cascade have been characterized from ligand binding to receptors through to activation of guanine nucleotide binding proteins and their downstream effectors such as adenylate cyclase or phospholipase C. However, the complexity of temporal and spatial integration of these molecular events requires that they are studied in intact cells. The great expansion of fluorescent techniques and improved imaging technologies such as confocal and TIRF microscopy combined with genetically-engineered protein modules has provided a completely new approach to signal transduction research. Spatial definition of biochemical events followed with real-time temporal resolution has become a standard goal, and several new techniques are now breaking the resolution barrier of light microscopy. C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transcluct, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transcluct, Program Dev Neurosci, Natl Inst Hlth, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health FX The research of TB is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. NR 128 TC 19 Z9 19 U1 0 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 2009 VL 19 IS 11 BP 575 EP 586 DI 10.1016/j.tcb.2009.08.001 PG 12 WC Cell Biology SC Cell Biology GA 523FM UT WOS:000272057500004 PM 19818623 ER PT J AU Stojilkovic, SS AF Stojilkovic, Stanko S. TI Purinergic regulation of hypothalamopituitary functions SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ISOLATED NEUROHYPOPHYSEAL TERMINALS; PITUITARY FOLLICULOSTELLATE CELLS; RAT SUPRAOPTIC NUCLEUS; P2X RECEPTORS; EXTRACELLULAR NUCLEOTIDES; VASOPRESSIN RELEASE; ADENOSINE RECEPTOR; PEPTIDE RELEASE; CA2+ CURRENTS; ATP AB The hypothalamus controls the release of hormones by the pituitary and is involved in control of food and water intake, sexual behavior, reproduction and daily cycles in physiological state and behavior, temperature regulation and emotional responses. Aden osine-5'-triphosphate (ATP) and its metabolic products contribute to these functions, acting as agonists; for adenosine and P2Y receptors and two-transmembrane domain P2X receptor channels. This review summarizes the recent findings on purinergic receptor expression and their roles in signaling and cellular function in secretory and supporting cells of the hypothalamopituitary system. ATP secretion by these tissues, the enzymes involved in ATP hydrolysis, and the relevance of this pathway for sequential activation of receptors and termination of signaling are also discussed. C1 NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov FU NICHD; NIH FX This study was supported by the Intramural Research Program of the NICHD, NIH. NR 62 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2009 VL 20 IS 9 BP 460 EP 468 DI 10.1016/j.tem.2009.05.005 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 519OT UT WOS:000271777200007 PM 19800813 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI The Origin at 150: is a new evolutionary synthesis in sight? SO TRENDS IN GENETICS LA English DT Article ID GENOMICS; WORLD AB The 200th anniversary of Charles Darwin and the 150th jubilee of the On the Origin of Species could prompt a new look at evolutionary biology. The 1959 Origin centennial was marked by the consolidation of the modern synthesis. The edifice of the modern synthesis has crumbled, apparently, beyond repair. The hallmark of the Darwinian discourse of 2009 is the plurality of evolutionary processes and patterns. Nevertheless, glimpses of a new synthesis might be discernible in emerging universals of evolution. C1 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 FU DHHS (NIH, National Library of Medicine) FX The author is supported by the DHHS (NIH, National Library of Medicine) intramural funds. NR 23 TC 11 Z9 14 U1 0 U2 10 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD NOV PY 2009 VL 25 IS 11 BP 473 EP 475 DI 10.1016/j.tig.2009.09.007 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 518TW UT WOS:000271717800001 PM 19836100 ER PT J AU Yang, D de la Rosa, G Tewary, P Oppenheim, JJ AF Yang, De de la Rosa, Gonzalo Tewary, Poonam Oppenheim, Joost J. TI Alarmins link neutrophils and dendritic cells SO TRENDS IN IMMUNOLOGY LA English DT Review ID HEPARIN-BINDING PROTEIN; NECROSIS-FACTOR-ALPHA; ANTIMICROBIAL PEPTIDE LL-37; ADAPTIVE IMMUNE-RESPONSES; PAPILLON-LEFEVRE-SYNDROME; CHEDIAK-HIGASHI-SYNDROME; INFLAMMATORY MONOCYTES; SECRETORY VESICLES; GRANULE DEFICIENCY; ENDOTHELIAL-CELLS AB Neutrophils are the first major population of leukocyte to infiltrate infected or injured tissues and are crucial for initiating host innate defense and adaptive immunity. Although the contribution of neutrophils to innate immune defense is mediated predominantly by phagocytosis and killing of microorganisms, neutrophils also participate in the induction of adaptive immune responses. At sites of infection and/or injury, neutrophils release numerous mediators upon degranulation or death, among these are alarmins which have a characteristic dual capacity to mobilize and activate antigen-presenting cells. We describe here how alarmins released by neutrophil degranulation and/or death can link neutrophils to dendritic cells by promoting their recruitment and activation, resulting in the augmentation of innate and adaptive immune responses. C1 [Yang, De; de la Rosa, Gonzalo; Tewary, Poonam; Oppenheim, Joost J.] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Yang, De] SAIC Frederick Inc, Basic Sci Program, Frederick, MD 21702 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. EM oppenhei@ncifcrf.gov FU Deutsche Forschungsgemeinschaft [SO876/3-1, FOR809, WE1913/10-1]; Swedish Research Council; Swedish Heart-Lung Foundation; Lars Hierta Memorial Fund; Karolinska Institute; Interdisciplinary Center for Clinical Research "BIOMAT" within the Faculty of Medicine at the RWTH Aachen University [VV-B113] FX This work was supported by the Deutsche Forschungsgemeinschaft (SO876/3-1, FOR809, WE1913/10-1), the Swedish Research Council, the Swedish Heart-Lung Foundation, the Lars Hierta Memorial Fund, the Karolinska Institute and the Interdisciplinary Center for Clinical Research "BIOMAT" within the Faculty of Medicine at the RWTH Aachen University (VV-B113). NR 104 TC 108 Z9 114 U1 2 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2009 VL 30 IS 11 BP 531 EP 538 DI 10.1016/j.it.2009.07.004 PG 8 WC Immunology SC Immunology GA 521LS UT WOS:000271923500004 PM 19699678 ER PT J AU Kwon-Chung, KJ Sugui, JA AF Kwon-Chung, Kyung J. Sugui, Janyce A. TI Sexual reproduction in Aspergillus species of medical or economical importance: why so fastidious? SO TRENDS IN MICROBIOLOGY LA English DT Review ID INVASIVE ASPERGILLOSIS; EVOLUTIONARY ADVANTAGE; ECOLOGICAL SPECIATION; CRYPTIC SPECIATION; FUMIGATUS; RECOMBINATION; PARASITICUS; PATHOGEN; NEOSARTORYA; FLAVUS AB Heterothallism is dependent upon the obligatory cross-mating between self-sterile homokaryotic individuals and represents a common pattern of sexuality in yeasts and molds. Heterothallic reproductive cycles have recently been discovered in three Aspergillus species of medical and economic importance, namely Aspergillus fumigatus, A. parasiticus and A. flavus. Together with Aspergillus udagawae (Neosartorya udagawae), heterothallism has now been discovered in a total of four aspergilli that affect human health or economy. These fungi appear to express relatively low levels of fertility compared to other heterothallic or homothallic aspergilli and require unusually fastidious environmental parameters to complete the sexual cycle. Because the purpose of sex is to reproduce, we favor the hypothesis that while fertility of these species is on the decline this is compensated by their proficiency to reproduce asexually in a wider range of environmental conditions. Heterothallism in these species could provide an invaluable tool for the recombinational analysis of factors relevant to pathogenicity or toxin production. There is concern, however, whether extensive recombinational analysis can be very practical in light of the fact that formation of ascospores in these species requires a long period of time and the construction of genetically marked C1 [Kwon-Chung, Kyung J.; Sugui, Janyce A.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. EM june_kwon-chung@nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by funds from the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 57 TC 17 Z9 19 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD NOV PY 2009 VL 17 IS 11 BP 481 EP 487 DI 10.1016/j.tim.2009.08.004 PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 522MD UT WOS:000272001200002 PM 19783441 ER PT J AU Zhang, PS Lathia, JD Flavahan, WA Riche, JN Mattson, MP AF Zhang, Peisu Lathia, Justin D. Flavahan, William A. Riche, Jeremy N. Mattson, Mark P. TI Squelching glioblastoma stem cells by targeting REST for proteasomal degradation SO TRENDS IN NEUROSCIENCES LA English DT Review ID TUMOR-INITIATING CELLS; ACUTE MYELOID-LEUKEMIA; DNA-DAMAGE; BRAIN-TUMORS; SELF-RENEWAL; NEURONAL GENES; PROTEIN TRF2; CANCER CELLS; BETA-TRCP; TELOMERE AB Glioblastoma brain tumors harbor a small population of cancer stem cells that are resistant to conventional chemotherapeutic and radiation treatments, and are believed responsible for tumor recurrence and mortality. The identification of the epigenetic molecular mechanisms that control self-renewal of glioblastoma stem cells will foster development of targeted therapeutic approaches. The transcriptional repressor REST, best known for its role in controlling cell fate decisions in neural progenitor cells, may also be crucial for cancer stem cell self-renewal. Two novel mechanisms for regulating the stability of REST have recently been revealed: these involve the telomere-binding protein TRF2 and the ubiquitin E3 ligase SCF beta-TrCP. Reduced TRF2 binding to REST, and increased SCF beta-TrCP activity, target REST for proteasomal degradation and thereby inhibit cancer stem cell proliferation. Neurological side effects of treatments that target REST and TRF2 may be less severe than conventional brain tumor treatments because post-mitotic neurons do not express REST and have relatively stable telomeres. C1 [Zhang, Peisu; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Lathia, Justin D.; Flavahan, William A.; Riche, Jeremy N.] Cleveland Clin Fdn, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, Cleveland, OH 44195 USA. RP Zhang, PS (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM zhangpe@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU National Institute on Aging Intramural Research Program; Childhood Brain Tumor Foundation; Pediatric Brain Tumor Foundation of the United States; Accelerate Brain Cancer Cure; Alexander and Margaret Stewart Trust; Brain Tumor Society; Goldhirsh Foundation; Duke Comprehensive Cancer Center Stem Cell Initiative Grant; NIH [NS047409, NS054276, CA116659]; Damon Runyon Cancer Research Foundation; Sidney Mmmel Foundation for Cancer Research Scholar FX The work was supported by the National Institute on Aging Intramural Research Program (M.P.M.) and by grants to J.N.R. from the Childhood Brain Tumor Foundation, the Pediatric Brain Tumor Foundation of the United States, Accelerate Brain Cancer Cure, Alexander and Margaret Stewart Trust, Brain Tumor Society, Goldhirsh Foundation, Duke Comprehensive Cancer Center Stem Cell Initiative Grant, NIH grants NS047409, NS054276, and CA116659. J.N.R. is a Damon Runyon-Lilly Clinical Investigator supported by the Damon Runyon Cancer Research Foundation and a Sidney Mmmel Foundation for Cancer Research Scholar. NR 72 TC 18 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2009 VL 32 IS 11 BP 559 EP 565 DI 10.1016/j.tins.2009.07.005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 520VG UT WOS:000271877000001 PM 19748686 ER PT J AU Chuang, DM Leng, Y Marinova, Z Kim, HJ Chiu, CT AF Chuang, De-Maw Leng, Yan Marinova, Zoya Kim, Hyeon-Ju Chiu, Chi-Tso TI Multiple roles of HDAC inhibition in neurodegenerative conditions SO TRENDS IN NEUROSCIENCES LA English DT Review ID HISTONE DEACETYLASE INHIBITORS; SPINAL MUSCULAR-ATROPHY; AMYOTROPHIC-LATERAL-SCLEROSIS; SUBEROYLANILIDE HYDROXAMIC ACID; PROTECTS DOPAMINERGIC-NEURONS; INCREASES SMN EXPRESSION; DISEASE TRANSGENIC MICE; BDNF GENE-TRANSCRIPTION; HEAT-SHOCK-PROTEIN; VALPROIC ACID AB Histone deacetylases (HDACs) play a key role in homeostasis of protein acetylation in histones and other proteins and in regulating fundamental cellular activities such as transcription. A wide range of brain disorders are associated with imbalances in protein acetylation levels and transcriptional dysfunctions. Treatment with various HDAC inhibitors can correct these deficiencies and has emerged as a promising new strategy for therapeutic intervention in neurodegenerative disease. Here, we review and discuss intriguing recent developments in the use of HDAC inhibitors to combat neurodegenerative conditions in cellular and disease models. HDAC inhibitors have neuroprotective, neurotrophic and anti-inflammatory properties; improvements in neurological performance, learning/memory and other disease phenotypes are frequently seen in these models. We discuss the targets and mechanisms underlying these effects of HDAC inhibition and comment on the potential for some HDAC inhibitors to prove clinically effective in the treatment of neurodegenerative disorders. C1 [Chuang, De-Maw; Leng, Yan; Marinova, Zoya; Kim, Hyeon-Ju; Chiu, Chi-Tso] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA. EM chuang@mail.nih.gov FU Intramural Research Program of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Mental Health (NIMH) at the National Institutes of Health (NIH). We thank Jau-Shyong Hong and his colleagues at the National Institute of Environmental Health Sciences (NIEHS), NIH, for their collaboration. The critical comments of Li-Kai Tsai and Zhifei Wang (Molecular Neurobiology Section, NIMH, NIH) and the editorial assistance of Peter Leeds (NIMH) and Ioline Heater (NIMH) are appreciated. We also wish to apologize to investigators whose related papers are not cited in this review due to space constraints. NR 104 TC 283 Z9 294 U1 5 U2 52 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 2009 VL 32 IS 11 BP 591 EP 601 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 520VG UT WOS:000271877000005 PM 19775759 ER PT J AU Watkins, LR Hutchinson, MR Rice, KC Maier, SF AF Watkins, Linda R. Hutchinson, Mark R. Rice, Kenner C. Maier, Steven F. TI The "Toll" of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID PERIPHERAL-NERVE INJURY; MORPHINE ANTINOCICEPTIVE TOLERANCE; REGIONAL-PAIN-SYNDROME; PROINFLAMMATORY CYTOKINE EXPRESSION; RECEPTOR NR-1 SUBUNIT; NECROSIS-FACTOR-ALPHA; SPINAL-CORD-INJURY; NEUROPATHIC PAIN; RAT MODEL; ANTIINFLAMMATORY CYTOKINE AB Glial activation participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products. Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression. Such effects can occur, not via classical opioid receptors, but rather via non-stereoselective activation of toll-like receptor 4 (TLR4), a recently recognized key glial receptor participating in neuropathic pain as well. This discovery identifies a means for separating the beneficial actions of opioids (opioid receptor mediated) from the unwanted side-effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug should be a stand-alone therapeutic for treating neuropathic pain as well. Excitingly, with newly-established clinical trials of two glial modulators for treating neuropathic pain and improving the utility of opioids, translation from rats-to-humans now begins with the promise of improved clinical pain control. C1 [Watkins, Linda R.; Hutchinson, Mark R.; Maier, Steven F.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. [Watkins, Linda R.; Hutchinson, Mark R.; Maier, Steven F.] Univ Colorado, Ctr Neurosci, Boulder, CO 80309 USA. [Hutchinson, Mark R.] Univ Adelaide, Discipline Pharmacol, Adelaide, SA, Australia. [Rice, Kenner C.] Natl Inst Drug Abuse, Chem Biol Res Branch, NIH, Rockville, MD USA. [Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA. RP Watkins, LR (reprint author), Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA. EM Linda.Watkins@colorado.edu RI Hutchinson, Mark/G-4147-2014 OI Hutchinson, Mark/0000-0003-2154-5950 FU American Australian Association Merck Company Foundation Fellowship; National Health and Medical Research Council CJ Martin Fellowship [ID 465423]; NIH [DA015642, DA017670, DA024044, DE017782]; National Institute on Drug Abuse; National Institute on Alcohol Abuse and Alcoholism FX International Association for the Study of Pain International Collaborative grant, American Australian Association Merck Company Foundation Fellowship, National Health and Medical Research Council CJ Martin Fellowship (ID 465423; M.R.H.) and NIH Grants DA015642, DA017670, DA024044, and DE017782. This work was partially supported by the by the NIH Intramural Research Programs of the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. We thank Avigen for permission to use their images in Figure 1 and Mitesh Shridhar for the photographs and graphs of Figure 4. NR 114 TC 154 Z9 157 U1 0 U2 10 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 NOV PY 2009 VL 30 IS 11 BP 581 EP 591 DI 10.1016/j.tips.2009.08.002 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 523TH UT WOS:000272096900004 PM 19762094 ER PT J AU Lee, W Balasubramaniam, M Deter, RL Yeo, L Hassan, SS Gotsch, F Kusanovic, JP Goncalves, LF Romero, R AF Lee, W. Balasubramaniam, M. Deter, R. L. Yeo, L. Hassan, S. S. Gotsch, F. Kusanovic, J. P. Goncalves, L. F. Romero, R. TI New fetal weight estimation models using fractional limb volume SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE birth weight; body composition; estimated fetal weight; fetal growth; fetal soft tissue; fetal weight; fractional arm volume; fractional limb volume; fractional thigh volume ID SUBCUTANEOUS TISSUE THICKNESS; NEONATAL BODY-COMPOSITION; PREDICTING BIRTH-WEIGHT; TO-CHEEK DIAMETER; MENSTRUAL AGE; SOFT-TISSUE; 3-DIMENSIONAL ULTRASONOGRAPHY; SONOGRAPHIC ESTIMATION; NORMAL FETUSES; FEMUR LENGTH AB Objectives The main goal of this study was to determine the accuracy and precision of new fetal weight estimation Models, based on fractional limb volume and conventional two-dimensional (2D) sonographic measurements during the second and third trimesters of pregnancy. Methods A prospective cross-sectional study of 271 fetuses was performed using three-dimensional ultrasonography to extract standard measurements - biparietal diameter (BPD), abdominal circumference (AC) and femoral diaphysis length (FDL) - plus fractional arm volume (AVol) and fractional thigh volume (TVol) within 4 days of delivery. Weighted multiple linear regression analysis was used to develop 'modified Hadlock' models and new models using transformed predictors that included soft tissue parameters for estimating birth weight. Estimated and observed birth weights were compared using mean percent difference (systematic weight estimation error) and the SD of the percent differences (random weight estimation error). The proportion of newborns with estimated birth weight within 5 or 10% of actual birth weight were compared using McNemar's test. Results Birth weights in the study group ranged from 235 to 5790 g, with equal proportions of male and female infants. Six new fetal weight estimation models were compared with the results for modified Hadlock models with sample-specific coefficients. All the new models were very accurate, with mean percent differences that were not significantly different from zero. Model 3 (which used the natural logarithms of BPD, AC and AVol) and Model 6 (which used the natural logarithms of BPD, AC and TVol) provided the most precise weight estimations (random error = 6.6% of actual birth weight) as compared with 8.5% for the best original Hadlock model and 7.6% for a modified Hadlock model using sample-specific coefficients. Model 5 (which used the natural logarithms of A C and TVol) classified an additional 9.1% and 8.3% of the fetuses within 5% and 10% of actual birth weight and Model 6 classified an additional 7.3% and 4.1% of infants within 5% and 10% of actual birth weight. Conclusion The precision of fetal weight estimation can be improved by adding fractional limb volume measurements to conventional 2D biometry. New models that consider fractional limb volume may offer novel insight into the contribution of soft tissue development to weight estimation. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd. C1 [Lee, W.] Oakland Univ, William Beaumont Sch Med, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI USA. [Balasubramaniam, M.] William Beaumont Hosp, Res Inst, Div Biostat, Royal Oak, MI 48072 USA. [Lee, W.; Yeo, L.; Hassan, S. S.; Kusanovic, J. P.; Goncalves, L. F.; Romero, R.] Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. [Romero, R.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Lee, W.; Yeo, L.; Hassan, S. S.; Gotsch, F.; Kusanovic, J. P.; Goncalves, L. F.; Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Deter, R. L.] Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu FU Perinatology Research Branch; Division of Intramural Research; Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH; DHHS FX The authors wish to acknowledge the technical assistance of Melissa Powell, RDMS and Beverley McNie, BS, CCRP. This research was supported (in part) by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, DHHS. NR 59 TC 28 Z9 30 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD NOV PY 2009 VL 34 IS 5 BP 556 EP 565 DI 10.1002/uog.7327 PG 10 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 519XB UT WOS:000271801700013 PM 19725080 ER PT J AU Osswald, M Harlan, LC Penson, D Stevens, JL Clegg, LX AF Osswald, Michael Harlan, Linda C. Penson, David Stevens, Jennifer L. Clegg, Limin X. TI Treatment of a population based sample of men diagnosed with testicular cancer in the United States SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Testicular cancer; Treatment; Surgery; Radiotherapy; Guideline adherence ID GERM-CELL CANCER; RANDOMIZED-TRIAL; CHEMOTHERAPY; TUMORS; SURVEILLANCE; CARBOPLATIN; ETOPOSIDE; BLEOMYCIN; TESTIS; UPDATE AB Objectives: Testicular cancer is the most common cancer in men age 25 to 35 years. We examined therapy, compliance with guidelines, and survival in a population based sample of men newly diagnosed with testicular cancer. Materials and Methods: We analyzed the National Cancer Institute's (NCI) patterns of care data on 702 men diagnosed with testicular cancer in 1999. These studies supplement routine data collection by verifying therapy with the patients' treating physicians. Follow-up for vital status was available through December 31, 2004. Results: The majority of the men with seminoma were diagnosed while their cancer was localized and more than 80% of received orchiectomy with radiation. For men with seminoma and nonseminoma germ cell tumors (NSGCT), the percent receiving chemotherapy increased markedly as stage increased. More than 90% of men with regional and distant NSGCT received chemotherapy. Less than 25% of men with localized NSGCT received orchiectomy and retroperitoneal lymph node dissection (RPLND), about 40% had surveillance following an orchiectomy alone, and 30% received orchiectomy and chemotherapy. Conclusions: The majority of these patients received therapy consistent with guidelines. While there was no significant difference in the use of RPLND in men with localized NSGCT by geographic region, chemotherapy use varied widely. Over 90% of men with localized or regional disease diagnosed in 1999 were alive at the end of 2004. The excellent survival rates point to the need to monitor for late effects of therapy. Published by Elsevier Inc. C1 [Harlan, Linda C.] NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. [Osswald, Michael] Dept Med, San Antonio, TX 78236 USA. [Penson, David] Univ So Calif, Dept Urol & Prevent Med, Los Angeles, CA 90089 USA. [Stevens, Jennifer L.] Informat Management Serv Inc, Silver Spring, MD 20904 USA. [Clegg, Limin X.] Dept Vet Affairs, Off Inspector Gen, Off Healthcare Inspect, Washington, DC 20001 USA. RP Harlan, LC (reprint author), NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. EM lh50w@nih.gov FU National Cancer Institute [N01-PC-35133, N01-PC35135, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01-PC-35139, N01-PC-35141, N01-PC-35142, N01-PC-35143, N01-PC-35145, N02-PC-15105, N02-PC-15106, N02-PC-15107] FX Funded by National Cancer Institute N01-PC-35133, N01-PC35135, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01-PC-35139 N01-PC-35141, N01-PC-35142, N01-PC-35143, N01-PC-35145, N02-PC-15105, N02-PC-15106, N02-PC-15107. NR 17 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD NOV-DEC PY 2009 VL 27 IS 6 BP 604 EP 610 DI 10.1016/j.urolonc.2008.06.004 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 519WX UT WOS:000271801200005 PM 18799329 ER PT J AU Clemens, JQ Calhoun, EA Litwin, MS McNaughton-Collins, M Kusek, JW Crowley, EM Landis, JR AF Clemens, J. Quentin Calhoun, Elizabeth A. Litwin, Mark S. McNaughton-Collins, Mary Kusek, John W. Crowley, Evelyn M. Landis, J. Richard CA Urologic Pelvic Pain Collaborative TI Validation of a Modified National Institutes of Health Chronic Prostatitis Symptom Index to Assess Genitourinary Pain in Both Men and Women SO UROLOGY LA English DT Article ID MANAGED CARE POPULATION; INTERSTITIAL CYSTITIS; BLADDER SYNDROME; PREVALENCE; TRIAL AB OBJECTIVES To date, separate condition-specific instruments have been used to assess severity of symptoms, in men and women with urological pain conditions. We developed a single instrument that can be used to assess treatment response in clinical trials and cohort Studies that involve both genders. METHODS We developed the Genitourinary Pain Index (GUPI) by modifying and adding questions to the National Institutes of Health-Chronic Prostatitis Symptom Index. To assess discriminant validity, concurrent validity, and reliability, we administered the GUPI to 1653 men and 1403 women in a large managed care Population. To assess responsiveness, we administered the GUPI to 47 men and women who completed a National Institutes of Health-sponsored trial of pelvic floor physical therapy. RESULTS The GUPI discriminated between men with chronic prostatitis or interstitial cystitis, those with other symptomatic conditions (dysuria, frequency, chronic cystitis), and those with none of these diagnoses (P < .05). It also discriminated between women with interstitial cystitis, those with incontinence, and those with none of these diagnoses (P < .05). The GUPI demonstrated good internal consistency within subscale domains, and GUPI scores correlated highly with scores on the Interstitial Cystitis Symptom Index and Problem Index. The GUPI was highly responsive to change, and the change in score was similar in both male and female responders. A reduction of 7 points robustly predicted being a treatment responder (sensitivity 100%, specificity 76%). CONCLUSIONS The GUN is a valid, reliable, and responsive instrument that can be used to assess the degree of symptoms in both men and women with genitourinary pain complaints. UROLOGY 74: 983-988, 2009. (C) 2009 Elsevier Inc. C1 [Clemens, J. Quentin] Univ Michigan, Med Ctr, Dept Urol, Ann Arbor, MI 48109 USA. Univ Illinois, Sch Publ Hlth, Dept Hlth Policy & Adm, Chicago, IL USA. Univ Calif Los Angeles, Sch Med & Publ Hlth, Dept Urol, Los Angeles, CA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NIDDK, Bethesda, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Clemens, JQ (reprint author), Univ Michigan, Med Ctr, Dept Urol, 1500 E Med Ctr Dr,Taubman Ctr 3875, Ann Arbor, MI 48109 USA. EM qclemens@umich.edu RI Landis, J. Richard/A-9330-2010; OI Landis, J Richard/0000-0001-8099-0988 FU NIDDK [5U01DK065257] FX This study was supported by grant number NIDDK 5U01DK065257. NR 15 TC 28 Z9 28 U1 0 U2 1 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 NOV PY 2009 VL 74 IS 5 BP 983 EP 987 DI 10.1016/j.urology.2009.06.078 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 522IZ UT WOS:000271992400005 PM 19800663 ER PT J AU Bronas, UG Hirsch, AT Murphy, T Badenhop, D Collins, TC Ehrman, JK Ershow, AG Lewis, B Treat-Jacobson, DJ Walsh, ME Oldenburg, N Regensteiner, JG AF Bronas, Ulf G. Hirsch, Alan T. Murphy, Timothy Badenhop, Dalynn Collins, Tracie C. Ehrman, Jonathan K. Ershow, Abby G. Lewis, Beth Treat-Jacobson, Diane J. Walsh, M. Eileen Oldenburg, Niki Regensteiner, Judith G. TI Design of the multicenter standardized supervised exercise training intervention for the 'CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study' SO VASCULAR MEDICINE LA English DT Article DE clinical trials; exercise; intermittent claudication; peripheral arterial disease ID PERIPHERAL ARTERIAL-DISEASE; CARDIAC REHABILITATION; HEART-FAILURE; TRIAL; RATIONALE; PROGRAM; MORTALITY; SYMPTOMS; OUTCOMES; THERAPY AB The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice. C1 [Bronas, Ulf G.; Treat-Jacobson, Diane J.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Hirsch, Alan T.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Murphy, Timothy] Rhode Isl Hosp, Vasc Dis Res Ctr, Providence, RI 02903 USA. [Murphy, Timothy] Brown Med Sch, Dept Diagnost Imaging, Providence, RI USA. [Badenhop, Dalynn] Univ Toledo, Med Ctr, Div Cardiovasc Med, Toledo, OH USA. [Collins, Tracie C.] Univ Minnesota, Dept Med, Div Gen Internal Med, Minneapolis, MN 55455 USA. [Ehrman, Jonathan K.] Henry Ford Hosp, Div Cardiol, Detroit, MI USA. [Ershow, Abby G.] NHLBI, NIH, Bethesda, MD USA. [Lewis, Beth] Univ Minnesota, Dept Kinesiol, Minneapolis, MN 55455 USA. [Oldenburg, Niki] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. [Regensteiner, Judith G.] Univ Colorado, Denver Sch Med, CLEVER Res Grp, Ctr Womens Hlth Res,Div Gen Internal Med,Dept Med, Boulder, CO 80309 USA. [Regensteiner, Judith G.] Univ Colorado, Denver Sch Med, CLEVER Res Grp, Ctr Womens Hlth Res,Div Cardiol,Dept Med, Boulder, CO 80309 USA. RP Bronas, UG (reprint author), Univ Minnesota, Sch Nursing, 5-140 Weaver Densford Hall,308 Harvard St SE, Minneapolis, MN 55455 USA. EM brona001@umn.edu FU National Heart Lung and Blood Institute [U01 HL077221]; National Institutes of Health Office for Research on Women's Health; Boston Scientific; Cordis/Johnson Johnson; Guidant Corporation FX This study is funded by the National Heart Lung and Blood Institute (# U01 HL077221, PI: Timothy Murphy), the National Institutes of Health Office for Research on Women's Health, and research grants from Boston Scientific, Cordis/Johnson & Johnson, and Guidant Corporation. NR 33 TC 14 Z9 16 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD NOV PY 2009 VL 14 IS 4 BP 313 EP 321 DI 10.1177/1358863X09102295 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 503NZ UT WOS:000270544900004 PM 19808716 ER PT J AU Hard, GC Flake, GP Sills, RC AF Hard, G. C. Flake, G. P. Sills, R. C. TI Re-evaluation of Kidney Histopathology from 13-Week Toxicity and Two-Year Carcinogenicity Studies of Melamine in the F344 Rat: Morphologic Evidence of Retrograde Nephropathy SO VETERINARY PATHOLOGY LA English DT Article DE Ascending nephropathy; melamine; pyelonephritis; rat kidney; reflux nephropathy; retrograde nephropathy ID EXPERIMENTAL PYELONEPHRITIS; VESICOURETERAL REFLUX; URINARY-INFECTION; URETERAL REFLUX; RISK-ASSESSMENT; CYANURIC ACID; RENAL-FAILURE; PATHOGENESIS; CATS; DOGS AB The histopathologic changes induced in F344 rat kidney by oral administration of melamine for 13-week and 2-year periods in studies conducted by the National Toxicology Program, NIH,(25) from 1976 to 1983 have been re-evaluated and described in detail. A constellation of tubule changes extending from papilla to cortex consistently included tubule dilatation and tubule basophilia as salient features at the subchronic time point. By 2 years, these lesions had usually resolved into fibrotic scars, in which tubule loss and collagen deposition were prominent, running from superficial cortex into the medulla. These fibrotic lesions required discrimination from chronic scars resulting from infarcts and foci of chronic progressive nephropathy (CPN). A case is presented here for interpreting the constellation of histologic changes induced in rats by melamine as representing an ascending form of nephropathy. The term retrograde nephropathy is considered to be the appropriate nomenclature for both the acute and chronic lesions. The cause for the reflux, emanating from the lower urinary tract, appeared not to be infection as an inflammatory response was not prominent. It can be speculated that melamine precipitation in the lower urinary tract created pressure effects through transient obstruction leading to the renal changes. These changes were different from those involved in a major US outbreak of renal disease and death in cats and dogs associated with triazine-contaminated pet food, in which crystalluria from insoluble melamine/cyanuric acid complexes occurred in the kidney. However, the rat findings may be relevant to melamine-associated kidney disease recently reported in infants in China. C1 [Flake, G. P.; Sills, R. C.] Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. RP Hard, GC (reprint author), 203 Paku Dr, Tairua 3508, New Zealand. EM gordonhard@msn.com FU National Institute of Environmental Health Sciences (NIEHS), NIH [NO1-ES-95435] FX The preparation of this manuscript was supported by Federal funds from the National Institute of Environmental Health Sciences (NIEHS), NIH, under contract NO1-ES-95435 to Experimental Pathology Laboratories (EPL) Inc., Research Triangle Park, North Carolina. One author (GCH) is very grateful to Drs. Jerry Hardisty and Mel Hamlin of EPL, and to Dr. Ron Herbert, NIEHS, for the opportunity to work on this project. The authors acknowledge Maureen Puccini and Emily Singletary of EPL for their expert assistance with photography, and Nancy Harris (EPL) for special histologic staining of kidney tissue. NR 36 TC 20 Z9 20 U1 0 U2 3 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD NOV PY 2009 VL 46 IS 6 BP 1248 EP 1257 DI 10.1354/vp.08-VP-0317-F-FL PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 519XA UT WOS:000271801600026 PM 19605901 ER PT J AU Ravizzini, G Turkbey, B Barrett, T Kobayashi, H Choyke, PL AF Ravizzini, Gregory Turkbey, Bans Barrett, Tristan Kobayashi, Hisataka Choyke, Peter L. TI Nanoparticles in sentinel lymph node mapping SO WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY LA English DT Review ID AMERICAN-JOINT-COMMITTEE; BREAST-CANCER PATIENTS; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; NEPHROGENIC SYSTEMIC FIBROSIS; EARLY-STAGE MELANOMA; QUANTUM DOTS; RANDOMIZED-TRIALS; GAMMA-PROBE; 15-YEAR SURVIVAL; INVISIBLE LIGHT AB The lymph nodes and lymphatic vessels are more difficult to access than most vascular structures. Interstitial injection of imaging agents is often necessary to opacify the lymphatics. Traditionally, radionuclide methods of sentinel node imaging have dominated this field, however, limitations in resolution and exposure to radiation have encouraged the development of newer imaging methods. Among these are magnetic resonance lymphography in which a Gadolinium labeled nanoparticle is injected and imaged providing superior anatomic resolution and assessment of lymphatic dynamics. Optical imaging employing various nanoparticles including quantum dots also provide the capability of mapping each lymphatic basin in another "color". Taken together this "toolbox" of lymphatic imaging agents is poised to improve our understanding of the lymphatic system. (C) 2009 John Wiley & Sons, Inc. WIREs Nanomed Nanobiotechnol 2009 1 610-623 C1 [Ravizzini, Gregory; Turkbey, Bans; Barrett, Tristan; Kobayashi, Hisataka; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 100 TC 29 Z9 29 U1 3 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5116 J9 WIRES NANOMED NANOBI JI Wiley Interdiscip. Rev.-Nanomed. Nanobiotechnol. PD NOV-DEC PY 2009 VL 1 IS 6 BP 610 EP 623 DI 10.1002/wnan.48 PG 14 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 585PW UT WOS:000276839900002 PM 20049820 ER PT J AU Kobayashi, SD DeLeo, FR AF Kobayashi, Scott D. DeLeo, Frank R. TI Role of neutrophils in innate immunity: a systems biology-level approach SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Review ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CHRONIC GRANULOMATOUS-DISEASE; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; APOPTOSIS-DIFFERENTIATION PROGRAM; EARLY TRANSCRIPTIONAL RESPONSE; RESPIRATORY BURST OXIDASE; GENE-EXPRESSION PATTERNS; BINDING-PROTEIN-EPSILON; HYPER-IGE SYNDROME AB The innate immune system is the first line of host defense against invading microorganisms. Polymorphonuclear leukocytes (PMNs or neutrophils) are the most abundant leukocyte in humans and essential to the innate immune response against invading pathogens. Compared with the acquired immune response, which requires time to develop and is dependent on previous interaction with specific microbes, the ability of neutrophils to kill microorganisms is immediate, nonspecific, and not dependent on previous exposure to microorganisms. Historically, studies on PMN-pathogen interaction focused on the events leading to killing of microorganisms, such as recruitment/chemotaxis, transmigration, phagocytosis, and activation, whereas post-phagocytosis sequelae were infrequently considered. In addition, it was widely accepted that human neutrophils possessed limited capacity for new gene transcription and thus, relatively little biosynthetic capacity. This notion has changed dramatically within the past decade. Further, there is now more effort directed to understand the events occurring in PMNs after killing of microbes. Herein we review the systems biology-level approaches that have been used to gain an enhanced view of the role of neutrophils during host-pathogen interaction. We anticipate that these and future systems-level studies will ultimately provide information critical to our understanding, treatment, and control of diseases caused by pathogenic microorganisms. (C) 2009 John Wiley & Sons, Inc. WIREs Syst Biol Med 2009 1 309-333 C1 [Kobayashi, Scott D.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This article was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank Christopher Burlak and David W. Dorward for their help in generating the transmission electron micrographs. NR 204 TC 68 Z9 70 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5094 J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD NOV-DEC PY 2009 VL 1 IS 3 BP 309 EP 333 DI 10.1002/wsbm.032 PG 25 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 674CF UT WOS:000283710600004 PM 20836000 ER PT J AU Baxter, LL Loftus, SK Pavan, WJ AF Baxter, Laura L. Loftus, Stacie K. Pavan, William J. TI Networks and pathways in pigmentation, health, and disease SO WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE LA English DT Article ID TRANSCRIPTION FACTOR MITF; WAARDENBURG-SYNDROME; NEURAL CREST; MELANOCYTE DEVELOPMENT; GENE-EXPRESSION; MALIGNANT-MELANOMA; DARK SKIN; MOLECULAR CLASSIFICATION; MELANOCORTIN-1 RECEPTOR; ULTRAVIOLET-RADIATION AB Extensive studies of the biology of the pigment-producing cell (melanocyte) have resulted in a wealth of knowledge regarding the genetics and developmental mechanisms governing skin and hair pigmentation. The ease of identification of altered pigment phenotypes, particularly in mouse coat color mutants, facilitated early use of the pigmentary system in mammalian genetics and development. In addition to the large collection of developmental genetics data, melanocytes are of interest because their malignancy results in melanoma, a highly aggressive and frequently fatal cancer that is increasing in Caucasian populations worldwide. The genetic programs regulating melanocyte development, function, and malignancy are highly complex and only partially understood. Current research in melanocyte development and pigmentation is revealing new genes important in these processes and additional functions for previously known individual components. A detailed understanding of all the components involved in melanocyte development and function, including interactions with neighboring cells and response to environmental stimuli, will be necessary to fully comprehend this complex system. The inherent characteristics of pigmentation biology as well as the resources available to researchers in the pigment cell community make melanocytes an ideal cell type for analysis using systems biology approaches. In this review, the study of melanocyte development and pigmentation is considered as a candidate for systems biology-based analyses. (C) 2009 John Wiley & Sons, Inc. WIREs Syst Biol Med 2009 1 359-371 C1 [Baxter, Laura L.; Loftus, Stacie K.; Pavan, William J.] NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Pavan, WJ (reprint author), NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM bpavan@nhgri.nih.gov FU National Human Genome Research Institute, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. NR 119 TC 11 Z9 14 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1939-5094 J9 WIRES SYST BIOL MED JI Wiley Interdiscip. Rev.-Syst. Biol PD NOV-DEC PY 2009 VL 1 IS 3 BP 359 EP 371 DI 10.1002/wsbm.020 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 674CF UT WOS:000283710600007 PM 20161540 ER PT J AU Sayenko, EM Bogatov, VV Zaykin, DV AF Sayenko, E. M. Bogatov, V. V. Zaykin, D. V. TI ON THE SYSTEMATIC POSITION OF THE FAR EASTERN KUNASHIRIA AND ARSENIEVINAIA GENERA (BIVALVIA, UNIONIDAE) SO ZOOLOGICHESKY ZHURNAL LA Russian DT Article ID UNIONIFORMES; ANODONTINAE; PRIMORYE AB Based on the analysis of anodontin shells, soft parts and glochidia morphology, the synonymy is proved: Kunashiria Starobogatov in Zatrawkin 1983 = Arsenievinaia Zatrawkin et Bogatov 1987; Kunashiria haconensis (Ihering 1893) = Arsenievinaia sihotealinica (Zatrawkin et Starobogatov 1984). Five species were transferred from the genus Arsenievinaia to the genus Kunashiria: K. taranetzi (Shadin 1938), K. zimini (Zatrawkin et Bogatov 1987), K. coptzevi (Zatrawkin et Bogatov 1987), K. zarjaensis (Bogatov et Zatrawkin 1988), K. compressa (Bogatov et Starobogatov 1996). The data on the Kunashiria distribution were generalized. C1 [Sayenko, E. M.; Bogatov, V. V.] Russian Acad Sci, Inst Biol & Soil Sci, Far E Branch, Vladivostok 690022, Russia. [Zaykin, D. V.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Sayenko, EM (reprint author), Russian Acad Sci, Inst Biol & Soil Sci, Far E Branch, Vladivostok 690022, Russia. EM sayenko@ibss.dvo.ru; bogatov@ibss.dvo.ru; zaykind@niehs.nih.gov NR 34 TC 1 Z9 1 U1 0 U2 1 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0044-5134 J9 ZOOL ZH JI Zool. Zhurnal PD NOV PY 2009 VL 88 IS 11 BP 1298 EP 1310 PG 13 WC Zoology SC Zoology GA 538OY UT WOS:000273195000003 ER PT J AU Zhou, Z Fan, JB Zhu, HL Shewmaker, F Yan, X Chen, X Chen, J Xiao, GF Guo, L Liang, Y AF Zhou, Zheng Fan, Jun-Bao Zhu, Hai-Li Shewmaker, Frank Yan, Xu Chen, Xi Chen, Jie Xiao, Geng-Fu Guo, Lin Liang, Yi TI Crowded Cell-like Environment Accelerates the Nucleation Step of Amyloidogenic Protein Misfolding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; CREUTZFELDT-JAKOB-DISEASE; MAMMALIAN PRION PROTEIN; MUSCLE CREATINE-KINASE; IN-VITRO CONVERSION; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; SACCHAROMYCES-CEREVISIAE; NEURODEGENERATIVE DISEASES; PHYSIOLOGICAL CONSEQUENCES AB To understand the role of a crowded physiological environment in the pathogenesis of neurodegenerative diseases, we report the following. 1) The formation of fibrous aggregates of the human Tau fragment Tau-(244-441), when hyperphosphorylated by glycogen synthase kinase-3 beta, is dramatically facilitated by the addition of crowding agents. 2) Fibril formation of nonphosphorylated Tau-(244 -441) is only promoted moderately by macromolecular crowding. 3) Macromolecular crowding dramatically accelerates amyloid formation by human prion protein. A sigmoidal equation has been used to fit these kinetic data, including published data of human alpha-synuclein, yielding lag times and apparent rate constants for the growth of fibrils for these amyloidogenic proteins. These biochemical data indicate that crowded cell-like environments significantly accelerate the nucleation step of fibril formation of human Tau fragment/human prion protein/human alpha-synuclein (a significant decrease in the lag time). These results can in principle be predicted based on some known data concerning protein concentration effects on fibril formation both in vitro and in vivo. Furthermore, macromolecular crowding causes human prion protein to form short fibrils and nonfibrillar particles with lower conformational stability and higher protease resistance activity, compared with those formed in dilute solutions. Our data demonstrate that a crowded physiological environment could play an important role in the pathogenesis of neurodegenerative diseases by accelerating amyloidogenic protein misfolding and inducing human prion fibril fragmentation, which is considered to be an essential step in prion replication. C1 [Zhou, Zheng; Fan, Jun-Bao; Zhu, Hai-Li; Yan, Xu; Chen, Xi; Chen, Jie; Xiao, Geng-Fu; Guo, Lin; Liang, Yi] Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China. [Shewmaker, Frank] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Liang, Y (reprint author), Wuhan Univ, Coll Life Sci, State Key Lab Virol, Wuhan 430072, Peoples R China. EM liangyi@whu.edu.cn RI Fan, Jun-bao/E-7155-2012 FU National Key Basic Research Foundation of China [2006CB910301]; National Natural Science Foundation of China [30770421, 30970599] FX This work was authored, in part, by National Institutes of Health staff. This work was supported by National Key Basic Research Foundation of China Grant 2006CB910301 and National Natural Science Foundation of China Grants 30770421 and 30970599. NR 78 TC 48 Z9 48 U1 3 U2 25 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 OCT 30 PY 2009 VL 284 IS 44 BP 30148 EP 30158 DI 10.1074/jbc.M109.002832 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 510LM UT WOS:000271090000018 PM 19748895 ER PT J AU Richter, K Brar, S Ray, M Pisitkun, P Bolland, S Verkoczy, L Diaz, M AF Richter, Kathleen Brar, Sukhdev Ray, Madhumita Pisitkun, Prapaporn Bolland, Silvia Verkoczy, Laurent Diaz, Marilyn TI Speckled-like Pattern in the Germinal Center (SLIP-GC), a Nuclear GTPase Expressed in Activation-induced Deaminase-expressing Lymphomas and Germinal Center B Cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LUPUS NEPHRITIS; MRL/LPR MICE; AID; LINES; HYPERMUTATION; PROTEIN; BURKITTS; GROWTH; BLAST AB We identified a novel GTPase, SLIP-GC, with expression limited to a few tissues, in particular germinal center B cells. It lacks homology to any known proteins, indicating that it may belong to a novel family of GTPases. SLIP-GC is expressed in germinal center B cells and in lymphomas derived from germinal center B cells such as large diffuse B cell lymphomas. In cell lines, SLIP-GC is expressed in lymphomas that express activation-induced deaminase ( AID) and that likely undergo somatic hypermutation. SLIP-GC is a nuclear protein, and it localizes to replication factories. Reduction of SLIP-GC levels in the Burkitt lymphoma cell line Raji and in non-Hodgkin lymphoma cell lines resulted in an increase in DNA breaks and apoptosis that was AID-dependent, as simultaneous reduction of AID abrogated the deleterious effects of SLIP-GC reduction. These results strongly suggest that SLIP-GC is a replication-related protein in germinal center B cells whose reduction is toxic to cells through an AID-dependent mechanism. C1 [Richter, Kathleen; Brar, Sukhdev; Ray, Madhumita; Diaz, Marilyn] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. [Pisitkun, Prapaporn; Bolland, Silvia] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Verkoczy, Laurent] Duke Univ, Duke Human Vaccine Inst, Med Ctr, Durham, NC 27710 USA. RP Diaz, M (reprint author), NIEHS, Mol Genet Lab, NIH, D3-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM diaz@niehs.nih.gov FU National Institutes of Health Grant (Intramural Research Program, NIEHS) [1Z01ES101603-2008] FX This work was supported, in whole or in part, by National Institutes of Health Grant (Intramural Research Program, NIEHS) 1Z01ES101603-2008. NR 31 TC 6 Z9 7 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 OCT 30 PY 2009 VL 284 IS 44 BP 30652 EP 30661 DI 10.1074/jbc.M109.014506 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 510LM UT WOS:000271090000067 PM 19734146 ER PT J AU Wang, JB Zuo, XB Yu, P Xu, H Starich, MR Tiede, DM Shapiro, BA Schwieters, CD Wang, YX AF Wang, Jinbu Zuo, Xiaobing Yu, Ping Xu, Huan Starich, Mary R. Tiede, David M. Shapiro, Bruce A. Schwieters, Charles D. Wang, Yun-Xing TI A Method for Helical RNA Global Structure Determination in Solution Using Small-Angle X-Ray Scattering and NMR Measurements SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RNA structure; SAXS; NMR; duplex orientation; RDC waves ID RESIDUAL DIPOLAR COUPLINGS; MOLECULAR-STRUCTURE; GENE-EXPRESSION; BASE-PAIRS; DYNAMICS; RIBOSWITCHES; RESOLUTION; REFINEMENT; TRNA(VAL); PROTEINS AB We report a "top-down" method that uses mainly duplexes' global orientations and overall molecular dimension and shape restraints, which were extracted from experimental NMR and small-angle X-ray scattering data, respectively, to determine global architectures of RNA molecules consisting of mostly A-form-like duplexes. The method is implemented in the G2G (from global measurement to global structure) toolkit of programs. We demonstrate the efficiency and accuracy of the method by determining the global structure of a 71-nt RNA using experimental data. The backbone root-mean-square deviation of the ensemble of the calculated global structures relative to the X-ray crystal structure is 3.0 +/- 0.3 angstrom using the experimental data and is only 2.5 +/- 0.2 angstrom for the three duplexes that were orientation restrained during the calculation. The global structure simplifies interpretation of multidimensional nuclear Overhauser spectra for high-resolution structure determination. The potential general application of the method for RNA structure determination is discussed. Published by Elsevier Ltd. C1 [Wang, Jinbu; Zuo, Xiaobing; Yu, Ping; Xu, Huan; Wang, Yun-Xing] NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. [Yu, Ping] SAIC Frederick Inc, NCI, NIH, Frederick, MD 21702 USA. [Starich, Mary R.] NCI, Off Chief, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. [Tiede, David M.] Argonne Natl Lab, Chem Sci & Engn Div, Argonne, IL 60439 USA. [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, NIH, Frederick, MD 21702 USA. [Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Wang, YX (reprint author), NCI, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. EM wangyu@ncifcrf.gov RI Zuo, Xiaobing/F-1469-2010; ID, BioCAT/D-2459-2012 FU National Institutes of Health National Cancer Institute; National Institutes of Health Center for Information Technology Intramural Research Program; U.S. Department of Energy [DE-AC02-06CH11357, W-31-109-ENG-38]; National Institutes of Health [RR-08630]; Argonne National Laboratory FX This research was supported [in part] by the Intramural Research Program of the National Institutes of Health National Cancer Institute (Y.-X.W. and B.A.S.) and by the National Institutes of Health Center for Information Technology Intramural Research Program (C.D.S.). Work at Argonne National Laboratory (D.M.T.) and that at the Advanced Photon Source were supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under contract no. DE-AC02-06CH11357. Use of the Advanced Photon Source was supported by the U.S. Department of Energy, Basic Energy Sciences, Office of Science, under contract no. W-31-109-ENG-38. We thank Professor D. E. Draper for providing us with the plasmid template for in vitro transcription of the riboA RNA, for helpful discussions, and for reviewing the manuscript. We also thank Dr. L. Guo (BioCAT, Sector 18-ID) [BioCAT is a National Institutes of Health-supported research center (RR-08630)] and Dr. S. Seifert (BESSRC, Sector 12-ID) of the Argonne National Laboratory for their support for synchrotron experiments. The content of this article is solely the responsibility of the authors and does not necessarily reflect the official views of the National Center for Research Resources or the National Institutes of Health. NR 41 TC 34 Z9 34 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 OCT 30 PY 2009 VL 393 IS 3 BP 717 EP 734 DI 10.1016/j.jmb.2009.08.001 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 511LT UT WOS:000271167400013 PM 19666030 ER PT J AU Yin, H Vistica, BP Chan, CC Strominger, JL Gery, I AF Yin, Hongen Vistica, Barbara P. Chan, Chi-Chao Strominger, Jack L. Gery, Igal TI Inhibition of experimental autoimmune uveitis by amino acid copolymers SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE Autoimmunity; Copolymers; Cytokines; EAU; Glatiramer acetate ID CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; REGULATORY T-CELLS; HLA-DR MOLECULES; MULTIPLE-SCLEROSIS; GLATIRAMER ACETATE; DENDRITIC CELLS; MICE; ENCEPHALOMYELITIS; BINDING AB Glatiramer acetate (GA), a synthetic random amino acid copolymer, poly(Y, E, A, K)n, is widely used for treatment of multiple sclerosis. It inhibits experimental autoimmune encephalomyelitis (EAE) in mice by competition with the antigen and by induction of regulatory T cells. A novel copolymer, poly (F, Y, A, K)n, designated FYAK, was more effective than GA in its immunomodulatory activity in EAE. Here, FYAK and GA were compared in the amelioration of another disease model in mice, experimental autoimmune uveoretinitis (EAU). When tested by co-immunization with an uveitogenic antigen, FYAK was superior to GA in its capacity to inhibit EAU induction, as well as immune processes related to this condition. Further, regulatory T-cell lines specific to FYAK were more immunosuppressive than GA-specific lines in the EAU model. The superiority of FYAK-specific lines was accompanied by higher production of Th2 cytokines. These data thus demonstrate that FYAK, a novel copolymer, is superior to GA in its capacity to inhibit immunopathogenic processes in a non-central nervous system tissue. Published by Elsevier B.V. C1 [Yin, Hongen; Vistica, Barbara P.; Chan, Chi-Chao; Gery, Igal] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Strominger, Jack L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM geryi@nei.nih.gov FU Intramural Research Program of the National Eye Institute; NIH; NMSS [RG3796A3]; NIH [RO1 A149524] FX This study was supported by the Intramural Research Program of the National Eye Institute, NIH, and by grants NMSS RG3796A3 and NIH RO1 A149524 to JLS. We thank Peptimmune Inc. for generously providing the FYAK copolymer. We are also grateful to Drs. G. Shi, C.E. Egwuagu and C.-R. Yu for helpful advice. NR 30 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT 30 PY 2009 VL 215 IS 1-2 BP 43 EP 48 DI 10.1016/j.jneuroim.2009.08.002 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 518BX UT WOS:000271666200006 PM 19748134 ER PT J AU Ravina, B Tanner, C DiEuliis, D Eberly, S Flagg, E Galpern, WR Fahn, S Goetz, CG Grate, S Kurlan, R Lang, AE Marek, K Kieburtz, K Oakes, D Elliott, R Shoulson, I AF Ravina, Bernard Tanner, Caroline DiEuliis, Diane Eberly, Shirley Flagg, Emily Galpern, Wendy R. Fahn, Stanley Goetz, Christopher G. Grate, Stephen Kurlan, Roger Lang, Anthony E. Marek, Kenneth Kieburtz, Karl Oakes, David Elliott, Robin Shoulson, Ira CA Parkinson Study Grp LABS-PD Invest TI A Longitudinal Program for Biomarker Development in Parkinson's Disease: A Feasibility Study SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; progression; biomarker ID MONTREAL COGNITIVE ASSESSMENT; RATING-SCALE; CLINICAL-DIAGNOSIS; OLFACTORY FUNCTION; SCREENING TOOL; HUMAN PLASMA; IMPAIRMENT; ACCURACY; DEMENTIA; RELIABILITY AB Long-term follow up is necessary to understand the natural history of treated Parkinson's disease (PD). The Longitudinal and Biomarker Study in PD (LABS-PD) is an observational study designed to prospectively measure the evolution of motor and non-motor features of PD and sample promising biomarkers from early to late stage illness. LABS-PD is organized on the premise that cohorts from completed clinical trials can be re-recruited for long-term follow up. LABS-PD will eventually contain multiple cohorts, but to test the feasibility of the strategy, we examined enrollment and biomarker sampling in the initial cohorts. The first PD cohort (PostCEPT) comes from the de novo clinical trial of a mixed lineage kinase inhibitor (PRECEPT). We assessed the recruitment from PRECEPT to PostCEPT, the ability to link data from the two studies, and sample collection for a variety of biomarkers. A total of 537 of 709 eligible PRECEPT subjects (76%) enrolled in PostCEPT; 509 (95%) had repeat dopamine transporter imaging. PRECEPT clinical and imaging data were successfully linked to PostCEPT, to provide 3 to 4 year follow-up. A biomarker sub-study enrolled over 100 PD cases from PostCEPT and 100 controls to measure olfaction and blood markers of gene expression, alpha-synuclein, and proteomic profiles. We were also successful in linking clinical and biomarker data to DNA samples that have been collected in the publicly accessible Coriell repository. The PostCEPT cohort and associated studies strongly Support the feasibility of the LABS-PD approach of retaining and repurposing clinical trial cohorts to collect longitudinal clinical and biomarker data. (C) 2009 Movement Disorder Society C1 [Ravina, Bernard; Eberly, Shirley; Flagg, Emily; Kurlan, Roger; Kieburtz, Karl; Oakes, David; Shoulson, Ira] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Tanner, Caroline] Parkinsons Inst, Sunnyvale, CA USA. [DiEuliis, Diane; Galpern, Wendy R.] NINDS, Bethesda, MD 20892 USA. [Fahn, Stanley] Columbia Univ, Dept Neurol, New York, NY USA. [Goetz, Christopher G.] Rush Univ, Med Ctr, Dept Neurosci, Chicago, IL 60612 USA. [Grate, Stephen] Telemed & Adv Technol Res Ctr, Ft Detrick, MD USA. [Lang, Anthony E.] Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. [Marek, Kenneth] Inst Neurodegenerat Disorders, New Haven, CT USA. [Elliott, Robin] Parkinsons Dis Fdn, New York, NY USA. RP Ravina, B (reprint author), 1351 Mt Hope Ave,Suite 223, Rochester, NY 14620 USA. EM bernard.ravina@ctcc.rochester.edu OI Espay, Alberto/0000-0002-3389-136X FU NINDS NIH HHS [5U01NS050095-05] NR 39 TC 23 Z9 23 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 30 PY 2009 VL 24 IS 14 BP 2081 EP 2090 DI 10.1002/mds.22690 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 518MJ UT WOS:000271696400007 PM 19691116 ER PT J AU Mouton, PR Chachich, ME Quigley, C Spangler, E Ingram, DK AF Mouton, Peter R. Chachich, Mark E. Quigley, Christopher Spangler, Edward Ingram, Donald K. TI Caloric restriction attenuates amyloid deposition in middle-aged dtg APP/PS1 mice SO NEUROSCIENCE LETTERS LA English DT Article DE Caloric restriction; Unbiased stereology; Stereologer; APP; PS1 ID ALZHEIMERS TRANSGENIC MICE; PRECURSOR-PROTEIN; MOUSE MODEL; PRESENILIN-1 TRANSGENES; MUTANT PRESENILIN-1; COGNITIVE DECLINE; DENTATE GYRUS; LIFE-SPAN; DISEASE; BRAIN AB Caloric restriction (CR) mitigates neurological damage arising from aging and a variety of other sources, including neuropathology in young adult mice that express single and double transgenic (tg) mutations associated with Alzheimer disease (AD). To evaluate the potential of CR to protect against relatively heavy AD-type pathology, middle-aged (13-14-month-old) mice that co-express two mutations related to familial AD, amyloid precursor protein (APP) and presenilin 1 (PS1), were fed balanced diets with 40% fewer calories than ad libitum-fed controls. Following 18 weeks of treatment, mice were killed and brains were processed for quantification of total volume of amyloid-beta (A beta) in the hippocampal formation and the overlying neocortex. Computerized stereology confirmed that CR reduced the total A beta volume by about one-third compared to that in age-matched controls. Thus, CR appears to attenuate the accumulation of AD-type neuropathology in two cortical brain regions of middle-aged dtg APP/PS1 mice. These findings support the view that CR could be a potentially effective, non-pharmacology strategy for reducing relatively heavy A beta deposition in older adult dtg APP/PS1 mice, and possibly afford similar protection against the onset and progression of AD in older adult humans. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Mouton, Peter R.] NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Chachich, Mark E.] Towson Univ, Dept Psychol, Towson, MD USA. [Mouton, Peter R.] Stereol Res Ctr, Chester, MD USA. [Ingram, Donald K.] Louisiana State Univ Syst, Nutr Neurosci & Aging Lab, Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Mouton, PR (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Room 9C223,251 Bayview Blvd, Baltimore, MD 21224 USA. EM Moutonpe@mail.nih.gov FU Intramural Research Program (NIA/NIH); U.S. Public Health Service NIH [MH076541] FX This research was supported in part by the Intramural Research Program (NIA/NIH) and extramural grants from the U.S. Public Health Service (NIH grant MH076541). NR 49 TC 48 Z9 49 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 30 PY 2009 VL 464 IS 3 BP 184 EP 187 DI 10.1016/j.neulet.2009.08.038 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 505AJ UT WOS:000270659500008 PM 19699265 ER PT J AU Wei, BR Hoover, SB Ross, MM Zhou, WD Meani, F Edwards, JB Spehalski, EI Risinger, JI Alvord, WG Quinones, OA Belluco, C Martella, L Campagnutta, E Ravaggi, A Dai, RM Goldsmith, PK Woolard, KD Pecorelli, S Liotta, LA Petricoin, EF Simpson, RM AF Wei, Bih-Rong Hoover, Shelley B. Ross, Mark M. Zhou, Weidong Meani, Francesco Edwards, Jennifer B. Spehalski, Elizabeth I. Risinger, John I. Alvord, W. Gregory Quinones, Octavio A. Belluco, Claudio Martella, Luca Campagnutta, Elio Ravaggi, Antonella Dai, Ren-Ming Goldsmith, Paul K. Woolard, Kevin D. Pecorelli, Sergio Liotta, Lance A. Petricoin, Emanuel F., III Simpson, R. Mark TI Serum S100A6 Concentration Predicts Peritoneal Tumor Burden in Mice with Epithelial Ovarian Cancer and Is Associated with Advanced Stage in Patients SO PLOS ONE LA English DT Article ID PHASE PROTEIN MICROARRAYS; CALCIUM-BINDING PROTEINS; EF-HAND TYPE; BIOMARKER DISCOVERY; PANCREATIC-CANCER; ALBUMIN-BINDING; INCREASED EXPRESSION; SAMPLE PREPARATION; MASS-SPECTROMETRY; FUNCTIONAL ROLES AB Background: Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival. Methodology and Principal Findings: Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease. Conclusions: S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers. RP Wei, BR (reprint author), NCI, Mol Pathol Unit, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA. EM ms43b@nih.gov RI Ravaggi, Antonella/K-5585-2016; OI Ravaggi, Antonella/0000-0003-4661-9979; belluco, claudio/0000-0001-5972-9574 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 56 TC 24 Z9 26 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 30 PY 2009 VL 4 IS 10 AR e7670 DI 10.1371/journal.pone.0007670 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514RW UT WOS:000271414300015 PM 19888321 ER PT J AU Rouault, TA AF Rouault, Tracey A. TI An Ancient Gauge for Iron SO SCIENCE LA English DT Editorial Material ID REGULATORY PROTEINS; HOMEOSTASIS; DIOXYGEN C1 NICHHD, Program Mol Med, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Program Mol Med, Bethesda, MD 20892 USA. EM trou@helix.nih.gov FU Intramural NIH HHS [ZIA HD001602-25] NR 12 TC 15 Z9 16 U1 0 U2 4 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 OCT 30 PY 2009 VL 326 IS 5953 BP 676 EP 677 DI 10.1126/science.1181938 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 512GB UT WOS:000271233200022 PM 19900922 ER PT J AU Park, AW Daly, JM Lewis, NS Smith, DJ Wood, JLN Grenfell, BT AF Park, Andrew W. Daly, Janet M. Lewis, Nicola S. Smith, Derek J. Wood, James L. N. Grenfell, Bryan T. TI Quantifying the Impact of Immune Escape on Transmission Dynamics of Influenza SO SCIENCE LA English DT Article ID PANDEMIC INFLUENZA; EQUINE INFLUENZA; VIRUS; INFECTION; EVOLUTION; VACCINES; STRATEGIES AB Influenza virus evades prevailing natural and vaccine-induced immunity by accumulating antigenic change in the haemagglutinin surface protein. Linking amino acid substitutions in haemagglutinin epitopes to epidemiology has been problematic because of the scarcity of data connecting these scales. We use experiments on equine influenza virus to address this issue, quantifying how key parameters of viral establishment and shedding increase the probability of transmission with genetic distance between previously immunizing virus and challenge virus. Qualitatively similar patterns emerge from analyses based on antigenic distance and from a published human influenza study. Combination of the equine data and epidemiological models allows us to calculate the effective reproductive number of transmission as a function of relevant genetic change in the virus, illuminating the probability of influenza epidemics as a function of immunity. C1 [Park, Andrew W.] Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. [Park, Andrew W.] Univ Georgia, Dept Infect Dis, Coll Vet Med, Athens, GA 30602 USA. [Daly, Janet M.; Lewis, Nicola S.] Anim Hlth Trust, Newmarket CB8 7UU, Suffolk, England. [Daly, Janet M.] Univ Nottingham, Sch Vet Med & Sci, Loughborough LE12 5RD, Leics, England. [Lewis, Nicola S.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. [Lewis, Nicola S.; Wood, James L. N.] Cambridge Infect Dis Consortium, Dept Vet Med, Cambridge CB3 0ES, England. [Smith, Derek J.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Smith, Derek J.] Erasmus MC, Dept Virol, Rotterdam, Netherlands. [Grenfell, Bryan T.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. [Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. [Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08540 USA. RP Park, AW (reprint author), Univ Georgia, Odum Sch Ecol, Athens, GA 30602 USA. EM awpark@uga.edu RI Wood, James/A-1626-2008; Daly, Janet/G-9797-2011; OI Wood, James/0000-0002-0258-3188; Daly, Janet/0000-0002-1912-4500 FU Horserace Betting Levy Board; University of Georgia; Cambridge Infectious Diseases Consortium; NIH [DP1-OD000490-01, R01GM083983-02]; European Union [223498]; Human Frontiers Science Program; Defra [VT0105]; Alborada Trust; Department of Homeland Security; NSF [0742373]; Fogarty International Center FX We are grateful to R. Pyhala, National Public Health Institute, Finland, for providing the HA1 sequence for A/Finland/74 (H3N2) and L. Yipu, National Institute for Medical Research, UK, for providing a sample of A/Scotland/74 (H3N2) from which we obtained the HA1 sequence. We also thank J. Gog, S. Gandon, J. Drake, P. Rohani, and Y. Michalakis for helpful discussions. Financial support came from Horserace Betting Levy Board (A. P. and J. D.), University of Georgia (A. P.), Cambridge Infectious Diseases Consortium (N. L.), NIH Director's pioneer award DP1-OD000490-01 (D. S.), European Union 223498 (D. S.), Human Frontiers Science Program (D. S.), Defra grant VT0105 (J. W.), Alborada Trust (J. W.), Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate, Department of Homeland Security (J. W. and B. G.), NIH grant R01GM083983-02 (B. G.), NSF grant 0742373 (B. G.), Fogarty International Center, and NIH (B. G., D. S., J. W.). The authors declare no competing financial interests. NR 24 TC 43 Z9 43 U1 3 U2 18 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 OCT 30 PY 2009 VL 326 IS 5953 BP 726 EP 728 DI 10.1126/science.1175980 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 512GB UT WOS:000271233200037 PM 19900931 ER PT J AU Hensley, SE Das, SR Bailey, AL Schmidt, LM Hickman, HD Jayaraman, A Viswanathan, K Raman, R Sasisekharan, R Bennink, JR Yewdell, JW AF Hensley, Scott E. Das, Suman R. Bailey, Adam L. Schmidt, Loren M. Hickman, Heather D. Jayaraman, Akila Viswanathan, Karthik Raman, Rahul Sasisekharan, Ram Bennink, Jack R. Yewdell, Jonathan W. TI Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift SO SCIENCE LA English DT Article ID VARIANTS; NEUTRALIZATION; RECOGNITION; ANTIBODIES AB Rapid antigenic evolution in the influenza A virus hemagglutinin precludes effective vaccination with existing vaccines. To understand this phenomenon, we passaged virus in mice immunized with influenza vaccine. Neutralizing antibodies selected mutants with single-amino acid hemagglutinin substitutions that increased virus binding to cell surface glycan receptors. Passaging these high-avidity binding mutants in naive mice, but not immune mice, selected for additional hemagglutinin substitutions that decreased cellular receptor binding avidity. Analyzing a panel of monoclonal antibody hemagglutinin escape mutants revealed a positive correlation between receptor binding avidity and escape from polyclonal antibodies. We propose that in response to variation in neutralizing antibody pressure between individuals, influenza A virus evolves by adjusting receptor binding avidity via amino acid substitutions throughout the hemagglutinin globular domain, many of which simultaneously alter antigenicity. C1 [Hensley, Scott E.; Das, Suman R.; Bailey, Adam L.; Schmidt, Loren M.; Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Jayaraman, Akila; Viswanathan, Karthik; Raman, Rahul; Sasisekharan, Ram] MIT, Harvard Mit Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jayaraman, Akila; Viswanathan, Karthik; Raman, Rahul; Sasisekharan, Ram] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM jyewdell@mail.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Das, Suman/C-8760-2009 FU Division of Intramural Research, NIAID; Singapore-Massachusetts Institute of Technology Alliance for Research and Technology; National Institute of General Medical Sciences [GM 57073, U54 GM62116] FX We thank the staff of the National Institute of Allergy and Infectious Diseases (NIAID) Comparative Medical Branch for assistance with animal studies, G. Reynoso for technical assistance, the Consortium for Functional Glycomics for glycan standards, and S. Epstein (U. S. Food and Drug Administration) for insightful reading of the manuscript. This work was supported by Division of Intramural Research, NIAID (J.R.B. and J.W.Y.), the Singapore-Massachusetts Institute of Technology Alliance for Research and Technology (R. S.), and the National Institute of General Medical Sciences (GM 57073 and U54 GM62116) (R. S.). NR 18 TC 199 Z9 201 U1 4 U2 42 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 OCT 30 PY 2009 VL 326 IS 5953 BP 734 EP 736 DI 10.1126/science.1178258 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 512GB UT WOS:000271233200039 PM 19900932 ER PT J AU Klion, AD AF Klion, Amy D. TI How I treat hypereosinophilic syndromes SO BLOOD LA English DT Review ID CHRONIC EOSINOPHILIC LEUKEMIA; T-CELL-CLONES; IMATINIB MESYLATE; MYELOPROLIFERATIVE VARIANT; SYSTEMIC MASTOCYTOSIS; ALPHA; DISEASE; FUSION; INHIBITOR; REMISSION AB Hypereosinophilic syndromes (HESs) are a heterogeneous group of uncommon disorders characterized by marked peripheral eosinophilia and end organ manifestations attributable to the eosinophilia or unexplained in the clinical setting. Whereas corticosteroids remain the main-stay of treatment for most patients, recent diagnostic advances and the development of novel targeted therapies, including tyrosine kinase inhibitors and humanized monoclonal antibodies, have increased the complexity of therapeutic decisions in HESs. This review presents a treatment-based approach to the diagnosis and classification of patients with peripheral blood eosinophilia of 1.5 x 10(9)/L (1500/mm(3)) or higher and discusses the role of currently available therapeutic agents in the treatment of these patients. (Blood. 2009; 114: 3736-3741) C1 NIAID, Parasit Dis Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Klion, AD (reprint author), NIAID, Parasit Dis Lab, Natl Inst Hlth, 9000 Rockville Pike,Bldg 50,Rm 6351, Bethesda, MD 20892 USA. EM aklion@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 FU National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID). NR 38 TC 23 Z9 28 U1 0 U2 7 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 OCT 29 PY 2009 VL 114 IS 18 BP 3736 EP 3741 DI 10.1182/blood-2009-07-143552 PG 6 WC Hematology SC Hematology GA 512RO UT WOS:000271268100006 PM 19692700 ER PT J AU Brunetta, E Fogli, M Varchetta, S Bozzo, L Hudspeth, KL Marcenaro, E Moretta, A Mavilio, D AF Brunetta, Enrico Fogli, Manuela Varchetta, Stefania Bozzo, Luisa Hudspeth, Kelly L. Marcenaro, Emanuela Moretta, Alessandro Mavilio, Domenico TI The decreased expression of Siglec-7 represents an early marker of dysfunctional natural killer-cell subsets associated with high levels of HIV-1 viremia SO BLOOD LA English DT Article ID NK CELLS; ACTIVATING RECEPTORS; DENDRITIC CELLS; INFECTION; SIALOADHESIN; RESPONSES; IMMUNODEFICIENCY; IDENTIFICATION; RECOGNITION; SPECIFICITY AB HIV-1 has developed several strategies to evade natural killer (NK)-cell antiviral functions. One of these mechanisms is the HIV-1-induced expansion of highly dysfunctional NK-cell subsets. Here, we analyze a large cohort of HIV-1-infected patients in early or chronic phases of infection, both cross-sectionally and longitudinally. We demonstrate that a striking decrease in the surface expression of sialic acid-binding immunoglobulin-like lectin 7 (Siglec-7) represents the earliest marker of the aberrant NK-cell dysregulation, which precedes the down-modulation of CD56 mostly occurring in patients with chronic HIV-1 viremia. The combined detection of Siglec-7 and CD56 allows the identification of 2 new pathologic NK-cell subsets expanded preferentially in early (Siglec-7(-)/CD56(+)) or chronic (Siglec-7(-)/CD56(+)) stages of HIV-1 infection. Remarkably, these phenotypic abnormalities were directly associated with progressive and distinct impairments of NK-cell functions. The aforementioned NK-cell aberrancies could be observed only in the presence of high levels of viral replication and not in patients with low or undetectable HIV-1 viremia, such as long-term nonprogressors or patients having undergone anti-retroviral therapy. High frequencies of Siglec-7(-)/CD56(+) and Siglec-7(-)/CD56(+) pathologic NK cells reflect the immune and clinical status of HIV-1 infection and can also track the effectiveness of therapy. (Blood. 2009; 114: 3822-3830) C1 [Brunetta, Enrico; Bozzo, Luisa; Mavilio, Domenico] Ist Clin Humanitas, Clin & Expt Immunol Lab, Ist Ricovero & Cura Carattere Sci, Milan, Italy. [Brunetta, Enrico; Fogli, Manuela] NIAID, Immunoregulat Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Varchetta, Stefania] Univ Pavia, I-27100 Pavia, Italy. [Varchetta, Stefania] Policlin San Matteo, Ctr Hepatol & Infect Dis, I-27100 Pavia, Italy. [Hudspeth, Kelly L.] Rush Univ, Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. [Marcenaro, Emanuela; Moretta, Alessandro] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy. RP Mavilio, D (reprint author), Ist Clin Humanitas, Clin & Expt Immunol Lab, Ist Ricovero & Cura Carattere Sci, Via Alessandro Manzoni 113, Milan, Italy. EM mavilio@humanitas.it OI Varchetta, Stefania/0000-0002-0289-2896; Mavilio, Domenico/0000-0001-6147-0952 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Istituto Clinico Humanitas FX This work was supported by the intramural research program of National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by intramural program of Istituto Clinico Humanitas. NR 42 TC 50 Z9 50 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 OCT 29 PY 2009 VL 114 IS 18 BP 3822 EP 3830 DI 10.1182/blood-2009-06-226332 PG 9 WC Hematology SC Hematology GA 512RO UT WOS:000271268100017 PM 19710502 ER PT J AU Cui, YZ Zhang, H Meadors, J Poon, R Guimond, M Mackall, CL AF Cui, Yongzhi Zhang, Hua Meadors, Joanna Poon, Rita Guimond, Martin Mackall, Crystal L. TI Harnessing the physiology of lymphopenia to support adoptive immunotherapy in lymphoreplete hosts SO BLOOD LA English DT Article ID CD8(+) T-CELLS; CHRONIC VIRAL-INFECTION; METASTATIC MELANOMA; HOMEOSTATIC PROLIFERATION; IN-VIVO; PARTIAL REDUCTION; CANCER-THERAPY; ANTIGEN; EXPANSION; MEMORY AB Lymphopenia enhances the effectiveness of adoptive immunotherapy by facilitating expansion of transferred T cells but also limits the T-cell repertoire available to mediate immune responses and, in humans, is associated with chronic immune dysfunction. Previous studies concluded that lymphopenia augments adoptive immunotherapy by diminishing Tregs and increasing homeostatic cytokines. We sought to determine whether targeted therapies that replicate the physiology of lymphopenia in lymphoreplete hosts could provide a similarly supportive milieu. Pmel-1 T cells were transferred to B16-bearing lymphopenic versus lymphoreplete mice receiving alpha CD25 and/or recombinant human interleukin-7. Although CD25-based Treg depletion was inefficient because of peripheral expansion of CD4(+) CD25(-) FOXP3(+) cells, outcomes were better in alpha CD25-treated lymphoreplete hosts than in lymphopenic hosts, and adoptive immunotherapy was most effective in lymphoreplete hosts receiving alpha CD25 plus recombinant human interleukin-7. Lymphopenic hosts supported increased proliferation of adoptively transferred antigen-specific T cells, but cells transferred to lymphoreplete recipients receiving targeted therapies showed superior function. Further, determinant spreading was substantial in lymphoreplete hosts but absent in lymphopenic hosts. These results demonstrate that targeted therapies delivered to mimic the "physiology of lymphopenia" enhance the efficacy of adoptive immunotherapy in lymphoreplete hosts and provide a potentially superior alternative to the induction of lymphopenia. (Blood. 2009; 114: 3831-3840) C1 [Cui, Yongzhi; Zhang, Hua; Meadors, Joanna; Poon, Rita; Guimond, Martin; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 10CRC 1W-3750,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU National Cancer Institute FX This work was supported by the Intramural Research Program of the National Cancer Institute. NR 50 TC 31 Z9 32 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 OCT 29 PY 2009 VL 114 IS 18 BP 3831 EP 3840 DI 10.1182/blood-2009-03-212134 PG 10 WC Hematology SC Hematology GA 512RO UT WOS:000271268100018 PM 19704119 ER PT J AU O'Brien, EP Okamoto, Y Straub, JE Brooks, BR Thirumalai, D AF O'Brien, Edward P. Okamoto, Yuko Straub, John E. Brooks, Bernard R. Thirumalai, D. TI Thermodynamic Perspective on the Dock-Lock Growth Mechanism of Amyloid Fibrils SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY CALCULATIONS; PROTEIN DENATURATION; UREA SOLUTIONS; BETA-PROTEIN; PEPTIDE; AGGREGATION; DISEASE; ELONGATION; KINETICS AB The mechanism of addition of a soluble unstructured monomer to a preformed ordered amyloid fibril is a complex process. On the basis of the kinetics of monomer disassociation of A beta(1-40) from the amyloid fibril, it has been suggested that deposition is a multistep process involving a rapid reversible association of the unstructured monomer to the fibril surface (docking) followed by a slower conformational rearrangement leading to the incorporation onto the underlying fibril lattice (locking). By exploiting the vast time scale separation between the dock and lock processes and using molecular dynamics simulation of deposition of the disordered peptide fragment (35)MVGGVV(40) from the A beta peptide onto the fibril with known crystal structure, we provide a thermodynamic basis for the dock-lock mechanism of fibril growth. Free energy profiles, computed using implicit solvent model and enhanced sampling methods with the distance (delta(C)) between the center of mass of the peptide and the fibril surface as the order parameter, show three distinct basins of attraction. When delta(C) is large, the monomer is compact and unstructured and the favorable interactions with the fibril results in stretching of the peptide at delta(C) approximate to 13 angstrom. As delta(C) is further decreased, the peptide docks onto the fibril surface with a structure that is determined by a balance between intrapeptide and peptide fibril interactions. At delta(C) approximate to 4 angstrom, a value that is commensurate with the spacing between beta-strands in the fibril, the monomer expands and locks onto the fibril. Using simulations with implicit solvent model and all atom molecular dynamics in explicit water, we show that the locked monomer, which interacts with the underlying fibril, undergoes substantial conformational fluctuations and is not stable. The cosolutes urea and TMAO destabilize the unbound phase and stabilize the docked phase. Interestingly, small crowding particles enhance the stability of the fibril-bound monomer only marginally. We predict that the experimentally measurable critical monomer concentration, C-R, at which the soluble unbound monomer is in equilibrium with the ordered fibril, increases sharply as temperature is increased under all solution conditions. C1 [O'Brien, Edward P.; Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. [Thirumalai, D.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [O'Brien, Edward P.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. [Okamoto, Yuko] Nagoya Univ, Dept Phys, Nagoya, Aichi 464, Japan. [Straub, John E.] Boston Univ, Dept Chem, Boston, MA 02215 USA. RP Thirumalai, D (reprint author), Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. EM thirum@umd.edu RI O'Brien, Edward/C-3587-2015 FU NIH [RO1GM076688-05]; NSF-East Asia and Pacific Summer Institutes Fellowship; NHLBI FX We are grateful to Govardhan Reddy for useful discussions. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). This work was supported in part by grants from the NIH to J.E.S. and D.T. (RO1GM076688-05), a NIH GPP Biophysics Fellowship and a NSF-East Asia and Pacific Summer Institutes Fellowship to E.O., and by the Intramural Research Program of the NIH, NHLBI. NR 52 TC 40 Z9 40 U1 0 U2 27 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 OCT 29 PY 2009 VL 113 IS 43 BP 14421 EP 14430 DI 10.1021/jp9050098 PG 10 WC Chemistry, Physical SC Chemistry GA 508EM UT WOS:000270911100045 PM 19813700 ER PT J AU Glocker, EO Hennigs, A Nabavi, M Schaffer, AA Woellner, C Salzer, U Pfeifer, D Veelken, H Warnatz, K Tahami, F Jamal, S Manguiat, A Rezaei, N Amirzargar, AA Plebani, A Hannesschlager, N Gross, O Ruland, J Grimbacher, B AF Glocker, Erik-Oliver Hennigs, Andre Nabavi, Mohammad Schaeffer, Alejandro A. Woellner, Cristina Salzer, Ulrich Pfeifer, Dietmar Veelken, Hendrik Warnatz, Klaus Tahami, Fariba Jamal, Sarah Manguiat, Annabelle Rezaei, Nima Amirzargar, Ali Akbar Plebani, Alessandro Hannesschlaeger, Nicole Gross, Olaf Ruland, Juergen Grimbacher, Bodo TI A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HYPER-IGE SYNDROME; COMMON VARIABLE IMMUNODEFICIENCY; PATTERN-RECOGNITION RECEPTOR; INNATE IMMUNE-RESPONSES; LINKAGE ANALYSIS; TH17 CELLS; ANTIFUNGAL IMMUNITY; SINGLE-FAMILY; HOST-DEFENSE AB BACKGROUND Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. METHODS We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. RESULTS We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin- 17). Functional studies based on genetic reconstitution of myeloid cells from Card9(-/-) mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. CONCLUSIONS An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. C1 [Glocker, Erik-Oliver; Woellner, Cristina; Tahami, Fariba; Jamal, Sarah; Manguiat, Annabelle; Grimbacher, Bodo] Royal Free Hosp, Dept Immunol & Mol Pathol, London NW3 2QG, England. [Glocker, Erik-Oliver; Woellner, Cristina; Tahami, Fariba; Jamal, Sarah; Manguiat, Annabelle; Grimbacher, Bodo] UCL, London, England. [Hennigs, Andre; Salzer, Ulrich; Warnatz, Klaus] Univ Hosp Freiburg, Dept Rheumatol & Clin Immunol, Freiburg, Germany. [Pfeifer, Dietmar; Veelken, Hendrik] Univ Hosp Freiburg, Dept Hematol & Oncol, Freiburg, Germany. [Nabavi, Mohammad] Semnan Univ Med Sci, Semnan, Iran. [Schaeffer, Alejandro A.] NIH, Natl Ctr Biotechnol Informat, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Rezaei, Nima] Univ Tehran Med Sci, Sch Med, Childrens Med Ctr, Growth & Dev Res Ctr,Ctr Excellence Pediat, Tehran, Iran. [Amirzargar, Ali Akbar] Univ Tehran Med Sci, Sch Med, Dept Immunol, Immunogenet Lab, Tehran, Iran. [Plebani, Alessandro] Univ Brescia, Pediat Clin, Brescia, Italy. [Plebani, Alessandro] Spedali Civil Brescia, Ist Med Mol Angelo Nocivelli, I-25125 Brescia, Italy. [Hannesschlaeger, Nicole; Gross, Olaf; Ruland, Juergen] Tech Univ Munich, Klinikum Rechts Isar, Med Klin 3, D-8000 Munich, Germany. [Ruland, Juergen] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Lab Signaling Immune Syst, Neuherberg, Germany. RP Grimbacher, B (reprint author), Royal Free Hosp, Dept Immunol & Mol Pathol, Pond St, London NW3 2QG, England. EM b.grimbacher@ucl.ac.uk RI Plebani, Alessandro/C-8593-2011; Rezaei, Nima/B-4245-2008; Schaffer, Alejandro/F-2902-2012; Gross, Olaf/E-4570-2010; OI Rezaei, Nima/0000-0002-3836-1827; Veelken, Hendrik/0000-0002-9108-3125 FU European Commission [MEXT-CT-2006-042316]; European Society for Immunodeficiencies; National Institutes of Health (NIH), National Library of Medicine; Deutsche Krebshilfe; Deutsche Forschungsgemeinschaft FX Supported in part by a European Commission Marie Curie Excellence Grant (MEXT-CT-2006-042316); the young investigator award of 2008 from the European Society for Immunodeficiencies; the Intramural Research Program of the National Institutes of Health (NIH), National Library of Medicine; a Max Eder Program Grant from Deutsche Krebshilfe (to Dr. Ruland); and Sonderforschungsbereich grants from the Deutsche Forschungsgemeinschaft (to Dr. Ruland). NR 59 TC 326 Z9 333 U1 2 U2 20 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 OCT 29 PY 2009 VL 361 IS 18 BP 1727 EP 1735 DI 10.1056/NEJMoa0810719 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 511RY UT WOS:000271185600005 PM 19864672 ER PT J AU Glass, RI Parashar, UD Estes, MK AF Glass, Roger I. Parashar, Umesh D. Estes, Mary K. TI CURRENT CONCEPTS Norovirus Gastroenteritis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID NORWALK VIRUS-INFECTION; BLOOD GROUP ANTIGENS; REVERSE TRANSCRIPTION-PCR; HUMAN CALICIVIRUS; IMMUNE-RESPONSES; SPORADIC GASTROENTERITIS; VIRAL GASTROENTERITIS; UNITED-STATES; FECAL SAMPLES; CHILDREN C1 [Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Glass, Roger I.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Estes, Mary K.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,Rm 31 B2 C02, Bethesda, MD 20892 USA. FU National Institutes of Health FX Supported by grants from the National Institutes of Health (to Dr. Estes). NR 67 TC 460 Z9 478 U1 15 U2 133 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 OCT 29 PY 2009 VL 361 IS 18 BP 1776 EP 1785 DI 10.1056/NEJMra0804575 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 511RY UT WOS:000271185600010 PM 19864676 ER PT J AU Holland, SM Vinh, DC AF Holland, Steven M. Vinh, Donald C. TI Yeast Infections - Human Genetics on the Rise SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Holland, Steven M.; Vinh, Donald C.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI VINH, DONALD/0000-0003-1347-7767 NR 5 TC 14 Z9 14 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 29 PY 2009 VL 361 IS 18 BP 1798 EP 1801 DI 10.1056/NEJMe0907186 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 511RY UT WOS:000271185600014 PM 19864679 ER PT J AU Carlson, BA Yoo, MH Sano, Y Sengupta, A Kim, JY Irons, R Gladyshev, VN Hatfield, DL Park, JM AF Carlson, Bradley A. Yoo, Min-Hyuk Sano, Yasuyo Sengupta, Aniruddha Kim, Jin Young Irons, Robert Gladyshev, Vadim N. Hatfield, Dolph L. Park, Jin Mo TI Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression SO BMC IMMUNOLOGY LA English DT Article ID SELENOCYSTEINE TRANSFER-RNA; SIGNAL-TRANSDUCTION; INNATE IMMUNITY; KAPPA-B; ACTIVATION; SELENIUM; MICE; INHIBITION; TRSP AB Background: Selenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA([Ser]Sec). Results: To define macrophage-specific selenoprotein functions, we generated mice with the Sec tRNA([Ser]Sec) gene specifically deleted in myeloid cells. These mutant mice were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration of macrophages in a protein gel matrix. Conclusion: Selenium status may affect immune defense and tissue homeostasis through its effect on selenoprotein expression and the trafficking of tissue macrophages. C1 [Carlson, Bradley A.; Yoo, Min-Hyuk; Sengupta, Aniruddha; Kim, Jin Young; Irons, Robert; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Sano, Yasuyo; Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Sano, Yasuyo; Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Gladyshev, Vadim N.] Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RP Hatfield, DL (reprint author), NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM carlsonb@mail.nih.gov; yoom@mail.nih.gov; yasuyo.sano@cbrc2.mgh.harvard.edu; sengupta@mail.nih.gov; glory80@snu.ac.kr; robert@veirons.com; vgladysh@unlnotes.unl.edu; hatfield@mail.nih.gov; jmpark@cbrc2.mgh.harvard.edu RI Gladyshev, Vadim/A-9894-2013 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research, and in addition, a specific grant from the Office of Dietary Supplements, NCI, NIH and the Cutaneous Biology Research Center through the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement to JMP and NIH grants awarded to VNG. NR 26 TC 35 Z9 36 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD OCT 28 PY 2009 VL 10 AR 57 DI 10.1186/1471-2172-10-57 PG 12 WC Immunology SC Immunology GA 521LY UT WOS:000271924100001 PM 19863805 ER PT J AU Schiffman, M Solomon, D AF Schiffman, Mark Solomon, Diane TI Screening and Prevention Methods for Cervical Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HUMAN-PAPILLOMAVIRUS; CYTOLOGY; TRIAGE C1 [Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Solomon, Diane] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Schiffman, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM schiffmm@mail.nih.gov NR 12 TC 10 Z9 11 U1 0 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 OCT 28 PY 2009 VL 302 IS 16 BP 1809 EP 1810 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 511FW UT WOS:000271150300027 PM 19861676 ER PT J AU Liu, SB Schauer, CK Pedersen, LG AF Liu, Shubin Schauer, Cynthia K. Pedersen, Lee G. TI Molecular acidity: A quantitative conceptual density functional theory description SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HUNDS MULTIPLICITY RULE; PKA VALUES; ELECTROPHILICITY INDEX; THERMODYNAMIC CYCLES; IONIZABLE RESIDUES; ORGANIC-COMPOUNDS; CARBOXYLIC-ACIDS; PK(A) PREDICTION; AQUEOUS-SOLUTION; ENERGIES AB Accurate predictions of molecular acidity using ab initio and density functional approaches are still a daunting task. Using electronic and reactivity properties, one can quantitatively estimate pKa values of acids. In a recent paper [S. B. Liu and L. G. Pedersen, J. Phys. Chem. A 113, 3648 (2009)], we employed the molecular electrostatic potential (MEP) on the nucleus and the sum of valence natural atomic orbital (NAO) energies for the purpose. In this work, we reformulate these relationships on the basis of conceptual density functional theory and compare the results with those from the thermodynamic cycle method. We show that MEP and NAO properties of the dissociating proton of an acid should satisfy the same relationships with experimental pKa data. We employ 27 main groups and first to third row transition metal-water complexes as illustrative examples to numerically verify the validity of these strong linear correlations. Results also show that the accuracy of our approach and that of the conventional method through the thermodynamic cycle are statistically similar. (C) 2009 American Institute of Physics. [doi: 10.1063/1.3251124] C1 [Liu, Shubin] Univ N Carolina, Ctr Res Comp, Chapel Hill, NC 27599 USA. [Schauer, Cynthia K.; Pedersen, Lee G.] Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. [Pedersen, Lee G.] Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Liu, SB (reprint author), Univ N Carolina, Ctr Res Comp, Chapel Hill, NC 27599 USA. EM shubin@email.unc.edu RI Liu, Shubin/B-1502-2009; Pedersen, Lee/E-3405-2013 OI Liu, Shubin/0000-0001-9331-0427; Pedersen, Lee/0000-0003-1262-9861 FU National Institutes of Health [HL-06350]; NSF [DMR-0804549]; NIEHS FX Helpful discussions with Robert G. Parr of University of North Carolina and Andy Maynard are gratefully acknowledged. This work was supported in part by the National Institutes of Health (Grant No. HL-06350), the NSF (FRG Grant No. DMR-0804549), and the Intramural Research Program of NIH, NIEHS. We acknowledge the use of the computational resources provided by the Research Computing Center at University of North Carolina at Chapel Hill and the Biomedical Unit of the Pittsburgh Supercomputer Center. NR 54 TC 22 Z9 23 U1 2 U2 14 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 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 28 PY 2009 VL 131 IS 16 AR 164107 DI 10.1063/1.3251124 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 513XV UT WOS:000271358400015 PM 19894927 ER PT J AU Rosta, E Hummer, G AF Rosta, Edina Hummer, Gerhard TI Error and efficiency of replica exchange molecular dynamics simulations SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FLUORESCENCE SPECTROSCOPY; SYSTEMS; MODEL AB We derive simple analytical expressions for the error and computational efficiency of replica exchange molecular dynamics (REMD) simulations (and by analogy replica exchange Monte Carlo simulations). The theory applies to the important case of systems whose dynamics at long times is dominated by the slow interconversion between two metastable states. As a specific example, we consider the folding and unfolding of a protein. The efficiency is defined as the rate with which the error in an estimated equilibrium property, as measured by the variance of the estimator over repeated simulations, decreases with simulation time. For two-state systems, this rate is in general independent of the particular property. Our main result is that, with comparable computational resources used, the relative efficiency of REMD and molecular dynamics (MD) simulations is given by the ratio of the number of transitions between the two states averaged over all replicas at the different temperatures, and the number of transitions at the single temperature of the MD run. This formula applies if replica exchange is frequent, as compared to the transition times. High efficiency of REMD is thus achieved by including replica temperatures in which the frequency of transitions is higher than that at the temperature of interest. In tests of the expressions for the error in the estimator, computational efficiency, and the rate of equilibration we find quantitative agreement with the results both from kinetic models of REMD and from actual all-atom simulations of the folding of a peptide in water. [doi:10.1063/1.3249608] C1 [Rosta, Edina; Hummer, Gerhard] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Rosta, E (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; OI Hummer, Gerhard/0000-0001-7768-746X; Rosta, Edina/0000-0002-9823-4766 FU NIH; Intramural Research Program of the NIDDK FX We thank Dr. A. Szabo, Dr. N.-V. Buchete, Dr. A. M. Berezhkovskii, Dr. A. B. Adib, and Dr. Y.-C. Kim for many helpful and stimulating discussions. This research used the Biowulf Linux cluster at the NIH and was supported by the Intramural Research Program of the NIDDK, NIH. NR 30 TC 37 Z9 37 U1 1 U2 18 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 OCT 28 PY 2009 VL 131 IS 16 AR 165102 DI 10.1063/1.3249608 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 513XV UT WOS:000271358400065 PM 19894977 ER PT J AU Won, YJ Puhl, HL Ikeda, SR AF Won, Yu-Jin Puhl, Henry L., III Ikeda, Stephen R. TI Molecular Reconstruction of mGluR5a-Mediated Endocannabinoid Signaling Cascade in Single Rat Sympathetic Neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article ID N-TYPE CALCIUM; METABOTROPIC GLUTAMATE RECEPTORS; DIACYLGLYCEROL-LIPASE-ALPHA; G-PROTEIN SUBUNITS; CA2+ CHANNELS; POTASSIUM CHANNELS; NEOCORTICAL INTERNEURONS; CANNABINOID RECEPTORS; SYNAPTIC PLASTICITY; MAMMALIAN NEURONS AB Endocannabinoids (eCB) such as 2-arachidonylglycerol (2-AG) are lipid metabolites that are synthesized in a postsynaptic neurons and act upon CB(1) cannabinoid receptors (CB(1)R) in presynaptic nerve terminals. This retrograde transmission underlies several forms of short and long term synaptic plasticity within the CNS. Here, we constructed a model system based on isolated rat sympathetic neurons, in which an eCB signaling cascade could be studied in a reduced, spatially compact, and genetically malleable system. We constructed a complete eCB production/mobilization pathway by sequential addition of molecular components. Heterologous expression of four components was required for eCB production and detection: metabotropic glutamate receptor 5a (mGluR5a), Homer 2b, diacylglycerol lipase alpha, and CB(1)R. In these neurons, application of L-glutamate produced voltage-dependent modulation of N-type Ca(2+) channels mediated by activation of CB(1)R. Using both molecular dissection and pharmacological agents, we provide evidence that activation of mGluR5a results in rapid enzymatic production of 2-AG followed by activation of CB(1)R. These experiments define the critical elements required to recapitulate retrograde eCB production and signaling in a single peripheral neuron. Moreover, production/mobilization of eCB can be detected on a physiologically relevant time scale using electrophysiological techniques. The system provides a platform for testing candidate molecules underlying facilitation of eCB transport across the plasma membrane. C1 [Won, Yu-Jin; Puhl, Henry L., III; Ikeda, Stephen R.] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Fishers Lane 5625,Room TS-11,MSC 9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508; Puhl, Henry/0000-0003-3095-7201 FU National Institutes of Health-National Institute on Alcohol Abuse and Alcoholism FX This research was supported by the Intramural Research Program of the National Institutes of Health-National Institute on Alcohol Abuse and Alcoholism. We are grateful to Dr. David M. Lovinger for many helpful discussions and reading an earlier draft of this manuscript. NR 50 TC 20 Z9 20 U1 4 U2 24 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 OCT 28 PY 2009 VL 29 IS 43 BP 13603 EP 13612 DI 10.1523/JNEUROSCI.2244-09.2009 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 512RA UT WOS:000271266600019 PM 19864572 ER PT J AU Kato, H Gruschus, J Ghirlando, R Tjandra, N Bai, YW AF Kato, Hidenori Gruschus, James Ghirlando, Rodolfo Tjandra, Nico Bai, Yawen TI Characterization of the N-Terminal Tail Domain of Histone H3 in Condensed Nucleosome Arrays by Hydrogen Exchange and NMR SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CHROMATIN FIBER; RESOLUTION; PROTEINS; DYNAMICS; PARTICLE AB The N-terminal tail domains (NTDs) of histones play important roles in the formation of higher-order structures of chromatin and the regulation of gene functions. Although the structure of the nucleosome core particle has been determined by X-ray crystallography at near-atomic resolution, the histone tails are not observed in this structure. Here, we demonstrate that large quantities of nucleosome arrays with well-defined DNA positioning can be reconstituted using specific DNA sequences and recombinant isotope-labeled histones, allowing for the investigation of NTD conformations by amide hydrogen exchange and multidimensional nuclear magnetic resonance (NMR) methods. We examined the NTD of Drosophila melanogaster histones H3 in condensed nucleosome arrays. The results reveal that the majority of the amide protons in the NTD of H3 are protected from exchange, consistent with the NTDs having formed folded structures. Our study demonstrates hydrogen exchange coupled with NMR can provide residue-by-residue characterization of NTDs of histones in condensed nucleosome arrays, a technique that may be used to study NTDs of other histones and those with post-translational modifications. C1 [Kato, Hidenori; Bai, Yawen] NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Gruschus, James; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. [Ghirlando, Rodolfo] NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU National Cancer Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung and Blood Institute, National Institutes of Health FX We thank Drs. Carl Wu and Karolin Luger for the expression vectors of histones and DNA. This work is supported by the intramural research programs of the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute, National Institutes of Health. NR 13 TC 21 Z9 22 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 28 PY 2009 VL 131 IS 42 BP 15104 EP + DI 10.1021/ja9070078 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 512SX UT WOS:000271272000015 PM 19795894 ER PT J AU Adams, JP Robinson, RA Hudgins, ED Wissink, EM Dudek, SM AF Adams, J. Paige Robinson, Rachel A. Hudgins, Eric D. Wissink, Erin M. Dudek, Serena M. TI NMDA receptor-independent control of transcription factors and gene expression SO NEUROREPORT LA English DT Article DE action potential; arc/Arg3.1; calcium; CREB; long-term potentiation; hippocampus ID LONG-TERM POTENTIATION; REGULATED KINASE ACTIVATION; LATE-PHASE; HIPPOCAMPAL-NEURONS; MESSENGER-RNA; CONSOLIDATION; ARC/ARG3.1; INDUCTION; ARC; LTP AB Consolidation of synaptic plasticity seems to require transcription, but how the nucleus is informed in this context remains unknown. As NMDA receptor antagonists have been shown to interfere with action potential generation, the issue of whether or not a synaptically generated signal is required for nuclear signaling is currently unresolved. Here, we show that pharmacological maintenance of action potentials during NMDA receptor blockade allows for NMDA receptor-independent transcription factor binding and arc gene expression, both of which were previously thought to be NMDA receptor dependent. These data suggest that types of signaling in the nucleus previously attributed to NMDA-receptor-dependent synapse-to-nucleus signals can be initiated in the absence of NMDA receptor-dependent synaptic plasticity. NeuroReport 20:1429-1433 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Adams, J. Paige; Robinson, Rachel A.; Hudgins, Eric D.; Wissink, Erin M.; Dudek, Serena M.] NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Dudek, SM (reprint author), NIEHS, Neurobiol Lab, NIH, POB 12233,MD F2-04, Res Triangle Pk, NC 27709 USA. EM dudek@niehs.nih.gov OI Dudek, Serena M./0000-0003-4094-8368; Wissink, Erin/0000-0003-1054-4899 FU National Institutes of Health; National Institute of Environmental Health Sciences FX The authors thank Dr Mineyoshl Aoyama for help with the qPCR and Dr G. Jean Harry for advice on the data analysis. This study was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. NR 26 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD OCT 28 PY 2009 VL 20 IS 16 BP 1429 EP 1433 DI 10.1097/WNR.0b013e3283311db6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 512ZY UT WOS:000271292400007 PM 19794318 ER PT J AU Bohle, DS Keefer, LK Saavedra, JE AF Bohle, D. Scott Keefer, Larry K. Saavedra, Joseph E. TI Primary amine diazeniumdiolate ions of structure {RNN(O)NOR '}(-) as ambident nucleophiles SO TETRAHEDRON LETTERS LA English DT Article DE Nitric oxide; Nitroxyl; Diazeniumdiolate; Bidentate anion ID CHEMISTRY AB An O-2-substituted primary amine diazeniumdiolate RHN-N(O)=NOR' is ionized to an anion that attacks an electrophile R '' X via either of two nitrogens to form both RR '' N-N(O)=NOR' and R-N=N(O)-N(R '')OR'. The bidentate character of such anions should be kept in mind when planning or evaluating drug discovery efforts involving diazeniumdiolates of structure RHN-N(O)=NOR'. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Bohle, D. Scott] McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada. [Keefer, Larry K.] NCI, Frederick, MD 21702 USA. [Saavedra, Joseph E.] NCI, Basic Sci Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bohle, DS (reprint author), McGill Univ, Dept Chem, 801 Sherbrooke St W, Montreal, PQ H3A 2K6, Canada. EM david.bohle@mcgill.ca RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU National Cancer Institute; National Institutes of Health [NO1CO-2008-00001]; Center for Cancer Research; National Science and Engineering Council in Canada FX This project has been funded by the National Cancer Institute, National Institutes of Health, under contract NO1CO-2008-00001, by the Intramural Program of the NIH, National Cancer Institute, Center for Cancer Research, by the National Science and Engineering Council in Canada, in the form of a Discovery grant to D.S.B., and by the CRC and CH for infrastructure support. NR 5 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD OCT 28 PY 2009 VL 50 IS 43 BP 5917 EP 5919 DI 10.1016/j.tetlet.2009.08.012 PG 3 WC Chemistry, Organic SC Chemistry GA 501YX UT WOS:000270421700010 ER PT J AU Tabakoff, B Saba, L Printz, M Flodman, P Hodgkinson, C Goldman, D Koob, G Richardson, HN Kechris, K Bell, RL Hubner, N Heinig, M Pravenec, M Mangion, J Legault, L Dongier, M Conigrave, KM Whitfield, JB Saunders, J Grant, B Hoffman, PL AF Tabakoff, Boris Saba, Laura Printz, Morton Flodman, Pam Hodgkinson, Colin Goldman, David Koob, George Richardson, Heather N. Kechris, Katerina Bell, Richard L. Huebner, Norbert Heinig, Matthias Pravenec, Michal Mangion, Jonathan Legault, Lucie Dongier, Maurice Conigrave, Katherine M. Whitfield, John B. Saunders, John Grant, Bridget Hoffman, Paula L. CA WHO ISBRA Study State Trait Marker TI Genetical genomic determinants of alcohol consumption in rats and humans SO BMC BIOLOGY LA English DT Review ID VENTRAL TEGMENTAL AREA; PROTEASE-ACTIVATED RECEPTORS; HIPPOCAMPAL DENTATE GYRUS; CENTRAL-NERVOUS-SYSTEM; GABAERGIC TRANSMISSION; ETHANOL INTAKE; MELANOCORTIN-4 RECEPTOR; NUCLEUS-ACCUMBENS; CANDIDATE GENES; FOOD-INTAKE AB Background: We have used a genetical genomic approach, in conjunction with phenotypic analysis of alcohol consumption, to identify candidate genes that predispose to varying levels of alcohol intake by HXB/BXH recombinant inbred rat strains. In addition, in two populations of humans, we assessed genetic polymorphisms associated with alcohol consumption using a custom genotyping array for 1,350 single nucleotide polymorphisms (SNPs). Our goal was to ascertain whether our approach, which relies on statistical and informatics techniques, and non-human animal models of alcohol drinking behavior, could inform interpretation of genetic association studies with human populations. Results: In the HXB/BXH recombinant inbred (RI) rats, correlation analysis of brain gene expression levels with alcohol consumption in a two-bottle choice paradigm, and filtering based on behavioral and gene expression quantitative trait locus (QTL) analyses, generated a list of candidate genes. A literature-based, functional analysis of the interactions of the products of these candidate genes defined pathways linked to presynaptic GABA release, activation of dopamine neurons, and postsynaptic GABA receptor trafficking, in brain regions including the hypothalamus, ventral tegmentum and amygdala. The analysis also implicated energy metabolism and caloric intake control as potential influences on alcohol consumption by the recombinant inbred rats. In the human populations, polymorphisms in genes associated with GABA synthesis and GABA receptors, as well as genes related to dopaminergic transmission, were associated with alcohol consumption. Conclusion: Our results emphasize the importance of the signaling pathways identified using the non-human animal models, rather than single gene products, in identifying factors responsible for complex traits such as alcohol consumption. The results suggest cross-species similarities in pathways that influence predisposition to consume alcohol by rats and humans. The importance of a well-defined phenotype is also illustrated. Our results also suggest that different genetic factors predispose alcohol dependence versus the phenotype of alcohol consumption. C1 [Tabakoff, Boris; Saba, Laura; Hoffman, Paula L.] Univ Colorado, Dept Pharmacol, Aurora, CO USA. [Printz, Morton] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Flodman, Pam] Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. [Hodgkinson, Colin; Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA. [Koob, George; Richardson, Heather N.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA USA. [Kechris, Katerina] Univ Colorado, Dept Biostat & Informat, Colorado Sch Publ Hlth, Aurora, CO USA. [Bell, Richard L.] Indiana Univ Sch Med, Inst Psychiat Res, Indianapolis, IN USA. [Huebner, Norbert; Heinig, Matthias] Max Delbruck Ctr Mol Med, Berlin, Germany. [Pravenec, Michal] Acad Sci Czech Republic, Inst Physiol, Prague, Czech Republic. [Mangion, Jonathan] MRC Clin Sci Ctr, London, England. [Legault, Lucie; Dongier, Maurice] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Conigrave, Katherine M.] Univ Sydney, Drug Hlth Serv, Royal Prince Alfred Hosp, Sydney Med Sch, Sydney, NSW 2006, Australia. [Whitfield, John B.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Saunders, John] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Grant, Bridget] NIAAA, Div Epidemiol, Rockville, MD 20852 USA. [Richardson, Heather N.] Univ Massachusetts, Dept Psychol Neurosci, Amherst, MA 01003 USA. [Mangion, Jonathan] Appl Biosyst Inc, Warrington WA3 7QH, Cheshire, England. RP Tabakoff, B (reprint author), Univ Colorado, Dept Pharmacol, Aurora, CO USA. EM boris.tabakoff@ucdenver.edu; laura.saba@ucdenver.edu; mprintz@ucsd.edu; pflodman@uci.edu; ch32z@nih.gov; davidgoldman@mail.nih.gov; gkoob@scripps.edu; hrichardson@cns.umass.edu; katerina.kechris@ucdenver.edu; ribell@iupui.edu; nhuebner@mdc-berlin.de; m.heinig@mdc-berlin.de; pravenec@biomed.cas.cz; jonathan.mangion@eur.appliedbiosystems.com; lucie.legault@douglas.mcgill.ca; maurice.dongier@douglas.mcgill.ca; katec@med.usyd.edu.au; John.Whitfield@qimr.edu.au; mail@jbsaunders.net; bgrant@mail.nih.gov; paula.hoffman@ucdenver.edu RI Goldman, David/F-9772-2010; Hodgkinson, Colin/F-9899-2010; Souza-Formigoni, Maria Lucia/B-5736-2011; koob, george/P-8791-2016; Pravenec, Michal/B-1666-2012 OI Goldman, David/0000-0002-1724-5405; Souza-Formigoni, Maria Lucia/0000-0002-6361-5630; Saba, Laura/0000-0001-9649-1294; Conigrave, Katherine/0000-0002-6428-1441; Richardson, Heather/0000-0001-7659-1212; FU NIAAA; NIH [AA013162, AA006420, AA016649-INIA, AA016663-INIA, AA013522-INIA, AA013517-INIA, AA-U01, AA16922]; NHLBI, NIH [HL35018]; Banbury Fund; Pearson Center for Alcoholism and Addiction Research; National Health and Medical Research Council of Australia ( WHO/ ISBRA Sydney); La Fondation Jean Lapointe ( WHO/ ISBRA Montreal); National Health Research Development Program, Canada ( WHO/ ISBRA Montreal); Wellcome Trust Program for Cardiovascular Functional Genomics ( JM); Ministry of Education of the Czech Republic [1M6837805002]; Howard Hughes Medical Institute FX The authors thank Janet Hopkins for performance of assays for measuring mRNA levels; Ron Smith, Laura Breen and Joseph Gatewood for technical assistance with behavioral data collection and Dr. Samuel P. Hazen for expert advice on database management. WHO/ ISBRA Study on State and Trait Markers of Alcoholism is an abbreviation for World Health Organization/ International Society for Biomedical Research on Alcoholism Study on State and Trait Markers of Alcohol Use and Dependence Investigators. This work was supported in part by NIAAA, NIH ( AA013162 ( BT); AA006420 ( GK); AA016649-INIA Project ( PH); AA016663-INIA Project ( BT); AA013522-INIA Project ( RLB); AA013517-INIA Project ( GK); AA-U01-Developmental Grant - INIA Project ( M Printz); AA16922 ( KK)); NHLBI, NIH ( HL35018 ( M Printz)); Banbury Fund ( BT); Pearson Center for Alcoholism and Addiction Research ( GK); National Health and Medical Research Council of Australia ( WHO/ ISBRA Sydney); La Fondation Jean Lapointe ( WHO/ ISBRA Montreal); National Health Research Development Program, Canada ( WHO/ ISBRA Montreal); Wellcome Trust Program for Cardiovascular Functional Genomics ( JM); Ministry of Education of the Czech Republic ( 1M6837805002( M Pravenec)) and Howard Hughes Medical Institute ( M Pravenec). NR 118 TC 95 Z9 95 U1 1 U2 15 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7007 J9 BMC BIOL JI BMC Biol. PD OCT 27 PY 2009 VL 7 AR 70 DI 10.1186/1741-7007-7-70 PG 23 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 520JG UT WOS:000271839600001 PM 19874574 ER PT J AU Sherman, KJ Hawkes, RJ Ichikawa, L Cherkin, DC Deyo, RA Avins, AL Khalsa, PS AF Sherman, Karen J. Hawkes, Rene J. Ichikawa, Laura Cherkin, Daniel C. Deyo, Richard A. Avins, Andrew L. Khalsa, Partap S. TI Comparing recruitment strategies in a study of acupuncture for chronic back pain SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID PRIMARY-CARE; TRIAL AB Background: Meeting recruitment goals is challenging for many clinical trials conducted in primary care populations. Little is known about how the use of different recruitment strategies affects the types of individuals choosing to participate or the conclusions of the study. Methods: A secondary analysis was performed using data from participants recruited to a clinical trial evaluating acupuncture for chronic back pain among primary care patients in a large integrated health care organization. We used two recruitment methods: mailed letters of invitation and an advertisement in the health plan's magazine. For these two recruitment methods, we compared recruitment success (% randomized, treatment completers, drop outs and losses to follow-up), participant characteristics, and primary clinical outcomes. A linear regression model was used to test for interaction between treatment group and recruitment method. Results: Participants recruited via mailed letters closely resembled those responding to the advertisement in terms of demographic characteristics, most aspects of their back pain history and current episode and beliefs and expectations about acupuncture. No interaction between method of recruitment and treatment group was seen, suggesting that study outcomes were not affected by recruitment strategy. Conclusion: In this trial, the two recruitment strategies yielded similar estimates of treatment effectiveness. However, because this finding may not apply to other recruitment strategies or trial circumstances, trials employing multiple recruitment strategies should evaluate the effect of recruitment strategy on outcome. C1 [Sherman, Karen J.; Hawkes, Rene J.; Ichikawa, Laura; Cherkin, Daniel C.] Grp Hlth Res Inst, Seattle, WA 98101 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97239 USA. [Deyo, Richard A.] Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97239 USA. [Avins, Andrew L.] No Calif Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Khalsa, Partap S.] NIH, Div Extramural Res & Training, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Sherman, KJ (reprint author), Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM sherman.k@ghc.org; hawkes.r@ghc.org; ichikawa.l@ghc.org; cherkin.d@ghc.org; deyor@ohsu.edu; Andrew.Avins@ucsf.edu; khalsap@mail.nih.gov FU National Center for Complementary and Alternative Medicine (NCCAM) [U01 AT 001110] FX The National Center for Complementary and Alternative Medicine (NCCAM) funded this study through a Cooperative Agreement (U01 AT 001110). Dr. Partap Khalsa, Project Officer for NCCAM, was involved in the analysis and interpretation of data and review and approval of the manuscript. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of NCCAM. NR 10 TC 3 Z9 3 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD OCT 27 PY 2009 VL 9 AR 69 DI 10.1186/1471-2288-9-69 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 523AJ UT WOS:000272041800001 PM 19860906 ER PT J AU Meinhold, CL Park, Y Stolzenberg-Solomon, RZ Hollenbeck, AR Schatzkin, A de Gonzalez, AB AF Meinhold, C. L. Park, Y. Stolzenberg-Solomon, R. Z. Hollenbeck, A. R. Schatzkin, A. de Gonzalez, A. Berrington TI Alcohol intake and risk of thyroid cancer in the NIH-AARP Diet and Health Study SO BRITISH JOURNAL OF CANCER LA English DT Article DE thyroid cancer; alcohol drinking; cohort study; epidemiology ID COHORT; CONSUMPTION; TRENDS; SMOKING; WOMEN AB BACKGROUND: Certain studies suggest that alcohol may reduce the risk of thyroid cancer in women, but the effect in men remains unclear. METHODS: We analysed the association between alcohol and thyroid cancer in a large (n = 490 159) prospective NIH-AARP Diet and Health Study with self-reported beer, wine, and liquor intakes. RESULTS: Over 7.5 years of follow-up ( median), 170 men and 200 women developed thyroid cancer. Overall, the thyroid cancer risk decreased with greater alcohol consumption (>= 2 drinks per day vs none, relative risk 0.57, 95% CI 0.36-0.89, P-trend = 0.01). CONCLUSIONS: These results suggest a potential protective role for alcohol consumption in thyroid cancer. British Journal of Cancer ( 2009) 101, 1630-1634. doi: 10.1038/sj.bjc.6605337 www.bjcancer.com Published online 29 September 2009 (C) 2009 Cancer Research UK C1 [Meinhold, C. L.; Park, Y.; Stolzenberg-Solomon, R. Z.; Schatzkin, A.; de Gonzalez, A. Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Hollenbeck, A. R.] AARP, Washington, DC USA. RP Meinhold, CL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. EM meinholdc@mail.nih.gov RI Kitahara, Cari/R-8267-2016; OI Park, Yikyung/0000-0002-6281-489X FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; Georgia Center for Cancer Statistics; Department of Epidemiology; Rollins School of Public Health; Emory University; California Department of Health Services; Cancer Surveillance Section FX We are indebted to the participants in the NIH-AARP Diet and Health Study for their outstanding cooperation. We also thank Sigurd Hermansen and Kerry Grace Morrissey from Westat for study outcome ascertainment and management and Leslie Carroll at the Information Management Services for data support and analysis. NR 17 TC 16 Z9 16 U1 0 U2 0 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 OCT 27 PY 2009 VL 101 IS 9 BP 1630 EP 1634 DI 10.1038/sj.bjc.6605337 PG 5 WC Oncology SC Oncology GA 512KO UT WOS:000271247800020 PM 19862001 ER PT J AU Islami, F Ren, JS Taylor, PR Kamangar, F AF Islami, F. Ren, J-S Taylor, P. R. Kamangar, F. TI Pickled vegetables and the risk of oesophageal cancer: a meta-analysis SO BRITISH JOURNAL OF CANCER LA English DT Article DE pickled vegetable; oesophageal cancer; case-control; cohort; meta-analysis ID SQUAMOUS-CELL CARCINOMA; HIGH-EPIDEMIC AREA; REPUBLIC-OF-CHINA; JIANGSU PROVINCE; STOMACH CANCERS; LINXIAN; REGION; PUBLICATION; COUNTY; COHORT AB BACKGROUND: Ecological and experimental studies have suggested a relationship between Asian pickled vegetable consumption and oesophageal squamous cell carcinoma (OSCC), but the results of epidemiological studies investigating the association have been inconsistent. We conducted a meta-analysis of observational studies of this association to evaluate the existing evidence. METHODS: We searched the PubMed, ISI-Web of Science, J-EAST, IndMed, Vip Chinese Periodical, and China National Knowledge Infrastructure databases for all studies published in English or Chinese languages. Pooled results for all studies combined and for several study subgroups were computed. RESULTS: A total of 34 studies were included in this analysis. The overall random effects odds ratio ( OR) and 95% confidence interval (CI) for pickled vegetable consumption was 2.08 (1.66-2.60), but the results were heterogeneous across studies. After excluding the three most influential studies, the respective numbers were 2.32 (1.92-2.81). Similar to the overall association, the majority of subgroup analyses showed a statistically significant association between consuming pickled vegetables and OSCC risk. There were only three prospective studies. CONCLUSIONS: Our results suggest a potential two-fold increased risk of oesophageal cancer associated with the intake of pickled vegetables. However, because the majority of data was from retrospective studies and there was a high heterogeneity in the results, further well-designed prospective studies are warranted. British Journal of Cancer ( 2009) 101, 1641-1647. doi: 10.1038/sj.bjc.6605372 www.bjcancer.com (C) 2009 Cancer Research UK C1 [Islami, F.; Kamangar, F.] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran 14117, Iran. [Islami, F.] Int Agcy Res Canc, F-69008 Lyon, France. [Islami, F.] Kings Coll London, Thames Canc Registry, London SE1 3QD, England. [Ren, J-S; Taylor, P. R.; Kamangar, F.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Kamangar, F.] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Hlth Anal, Baltimore, MD 21251 USA. RP Kamangar, F (reprint author), Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran 14117, Iran. EM farin.kamangar@morgan.edu FU Intramural Research Program of the National Cancer Institute; National Institutes of Health FX This study was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. NR 76 TC 20 Z9 21 U1 2 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 OCT 27 PY 2009 VL 101 IS 9 BP 1641 EP 1647 DI 10.1038/sj.bjc.6605372 PG 7 WC Oncology SC Oncology GA 512KO UT WOS:000271247800022 PM 19862003 ER PT J AU Drazen, JM Van der Weyden, MB Sahni, P Rosenberg, J Marusic, A Laine, C Kotzin, S Horton, R Hebert, PC Haug, C Godlee, F Frizelle, FA de Leeuw, PW DeAngelis, CD AF Drazen, Jeffrey M. Van der Weyden, Martin B. Sahni, Peush Rosenberg, Jacob Marusic, Ana Laine, Christine Kotzin, Sheldon Horton, Richard Hebert, Paul C. Haug, Charlotte Godlee, Fiona Frizelle, Frank A. de Leeuw, Peter W. DeAngelis, Catherine D. TI Uniform format for disclosure of competing interests in ICMJE journals SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 [Kotzin, Sheldon] Natl Lib Med, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013 OI Marusic, Ana/0000-0001-6272-0917 NR 0 TC 5 Z9 5 U1 0 U2 2 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD OCT 27 PY 2009 VL 181 IS 9 BP 565 EP 565 DI 10.1503/cmaj.091691 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 507PI UT WOS:000270866300001 PM 19825925 ER PT J AU Gottlieb, JD Schwartz, AR Marshall, J Ouyang, P Kern, L Shetty, V Trois, M Punjabi, NM Brown, C Najjar, SS Gottlieb, SS AF Gottlieb, Joshua D. Schwartz, Alan R. Marshall, Joanne Ouyang, Pamela Kern, Linda Shetty, Veena Trois, Maria Punjabi, Naresh M. Brown, Cynthia Najjar, Samer S. Gottlieb, Stephen S. TI Hypoxia, Not the Frequency of Sleep Apnea, Induces Acute Hemodynamic Stress in Patients With Chronic Heart Failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE brain natriuretic peptide; sleep apnea; hypoxia ID POSITIVE AIRWAY PRESSURE; CHEYNE-STOKES RESPIRATION; BRAIN NATRIURETIC PEPTIDE; NT-PRO-BNP; BLOOD-PRESSURE; CONTRACTILE FAILURE; OXYGEN; THERAPY; RELEASE; SYSTEM AB Objectives This study was conducted to evaluate whether brain (B-type) natriuretic peptide (BNP) changes during sleep are associated with the frequency and severity of apneic/hypopneic episodes, intermittent arousals, and hypoxia. Background Sleep apnea is strongly associated with heart failure (HF) and could conceivably worsen HF through increased sympathetic activity, hemodynamic stress, hypoxemia, and oxidative stress. If apneic activity does cause acute stress in HF, it should increase BNP. Methods Sixty-four HF patients with New York Heart Association functional class II and III HF and ejection fraction <40% underwent a baseline sleep study. Five patients with no sleep apnea and 12 with severe sleep apnea underwent repeat sleep studies, during which blood was collected every 20 min for the measurement of BNP. Patients with severe sleep apnea also underwent a third sleep study with frequent BNP measurements while they were administered oxygen. This provided 643 observations with which to relate apnea to BNP. The association of log BNP with each of 6 markers of apnea severity was evaluated with repeated measures regression models. Results There was no relationship between BNP and the number of apneic/hypopneic episodes or the number of arousals. However, the burden of hypoxemia (the time spent with oxygen saturation <90%) significantly predicted BNP concentrations; each 10% increase in duration of hypoxemia increased BNP by 9.6% (95% confidence interval: 1.5% to 17.7%, p = 0.02). Conclusions Hypoxemia appears to be an important factor that underlies the impact of sleep abnormalities on hemodynamic stress in patients with HF. Prevention of hypoxia might be especially important for these patients. (J Am Coll Cardiol 2009; 54: 1706-12) (c) 2009 by the American College of Cardiology Foundation C1 [Marshall, Joanne; Gottlieb, Stephen S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Gottlieb, Joshua D.] Harvard Univ, Cambridge, MA 02138 USA. [Schwartz, Alan R.; Ouyang, Pamela; Kern, Linda; Trois, Maria; Punjabi, Naresh M.] Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. [Shetty, Veena] Medstar Res Inst, Baltimore, MD USA. [Brown, Cynthia] Univ Virginia, Charlottesville, VA USA. [Najjar, Samer S.] NIA, NIH, Baltimore, MD 21224 USA. RP Gottlieb, SS (reprint author), Univ Maryland, Sch Med, 22 S Greene St, Baltimore, MD 21201 USA. EM sgottlie@medicine.umaryland.edu OI Gottlieb, Joshua/0000-0001-8730-0468 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR002719, M01 RR002719-18, M01-RR02719]; NHLBI NIH HHS [R01 HL071506-01, R01 HL071506] NR 35 TC 28 Z9 31 U1 0 U2 2 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 OCT 27 PY 2009 VL 54 IS 18 BP 1706 EP 1712 DI 10.1016/j.jacc.2009.08.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 508XJ UT WOS:000270971400008 PM 19850211 ER PT J AU Adelman, K Kennedy, MA Nechaev, S Gilchrist, DA Muse, GW Chinenov, Y Rogatsky, I AF Adelman, Karen Kennedy, Megan A. Nechaev, Sergei Gilchrist, Daniel A. Muse, Ginger W. Chinenov, Yurii Rogatsky, Inez TI Immediate mediators of the inflammatory response are poised for gene activation through RNA polymerase II stalling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokine gene expression; inflammation; TNF alpha; transcription initiation and elongation; NELF ID NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; TRANSCRIPTION INITIATION; MACROPHAGE ACTIVATION; FEEDBACK INHIBITION; TNF SUPERFAMILY; P-TEFB; RECEPTOR; ELONGATION; PROMOTER AB The kinetics and magnitude of cytokine gene expression are tightly regulated to elicit a balanced response to pathogens and result from integrated changes in transcription and mRNA stability. Yet, how a single microbial stimulus induces peak transcription of some genes (TNF alpha) within minutes whereas others (IP-10) require hours remains unclear. Here, we dissect activation of several lipopolysaccharide (LPS)-inducible genes in macrophages, an essential cell type mediating inflammatory response in mammals. We show that a key difference between the genes is the step of the transcription cycle at which they are regulated. Specifically, at TNF alpha, RNA Polymerase II initiates transcription in resting macrophages, but stalls near the promoter until LPS triggers rapid and transient release of the negative elongation factor (NELF) complex and productive elongation. In contrast, no NELF or polymerase is detectible near the IP-10 promoter before induction, and LPS-dependent polymerase recruitment is rate limiting for transcription. We further demonstrate that this strategy is shared by other immune mediators and is independent of the inducer and signaling pathway responsible for gene activation. Finally, as a striking example of evolutionary conservation, the Drosophila homolog of the TNF alpha gene, eiger, displayed all of the hallmarks of NELF-dependent polymerase stalling. We propose that polymerase stalling ensures the coordinated, timely activation the inflammatory gene expression program from Drosophila to mammals. C1 [Adelman, Karen; Nechaev, Sergei; Gilchrist, Daniel A.; Muse, Ginger W.] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. [Kennedy, Megan A.; Chinenov, Yurii; Rogatsky, Inez] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. [Kennedy, Megan A.; Chinenov, Yurii; Rogatsky, Inez] Cornell Univ, Hosp Special Surg, New York, NY 10021 USA. RP Adelman, K (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. EM adelmank@niehs.nih.gov; rogatskyi@hss.edu OI Gilchrist, Daniel/0000-0003-1668-2790 FU National Institutes of Health; National Institute of Environmental Health Sciences [Z01 ES101987]; National Institutes of Health [T32 AR07517]; National Institutes of Health National Institute of Allergy and Infectious Diseases [R01 AI068820]; Lupus Research Institute; Mary Kirkland Center FX We thank the members of the immunohistochemistry core at the National Institute of Environmental Health Sciences and Drs. Lionel Ivashkiv and Perry Blackshear for critical comments on the manuscript. This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences Grant Z01 ES101987 (to K. A.); by the National Institutes of Health Grant T32 AR07517 (to Y. C.); and by grants (to I. R.) from the National Institutes of Health National Institute of Allergy and Infectious Diseases (R01 AI068820), the Lupus Research Institute, and the Mary Kirkland Center. NR 42 TC 66 Z9 67 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 27 PY 2009 VL 106 IS 43 BP 18207 EP 18212 DI 10.1073/pnas.0910177106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 512DB UT WOS:000271222500032 PM 19820169 ER PT J AU Marasa, BS Srikantan, S Masuda, K Abdelmohsen, K Kuwano, Y Yang, XL Martindale, JL Rinker-Schaeffer, CW Gorospe, M AF Marasa, Bernard S. Srikantan, Subramanya Masuda, Kiyoshi Abdelmohsen, Kotb Kuwano, Yuki Yang, Xiaoling Martindale, Jennifer L. Rinker-Schaeffer, Carrie W. Gorospe, Myriam TI Increased MKK4 Abundance with Replicative Senescence Is Linked to the Joint Reduction of Multiple MicroRNAs SO SCIENCE SIGNALING LA English DT Article ID KINASE KINASE 4; TUMOR SUPPRESSION; CELLULAR SENESCENCE; SIGNAL-TRANSDUCTION; IN-VIVO; RNA; PROTEINS; CELLS; TRANSLATION; STRESS AB MKK4 (mitogen-activated protein kinase kinase 4) is a pivotal upstream activator of c-Jun N-terminal kinase and p38. Here, we report that the abundance of MKK4 increases in senescent human diploid fibroblasts through enhanced translation. We identified four microRNAs (miR-15b, miR-24, miR-25, and miR-141) that target the MKK4 messenger RNA (mRNA); the abundance of these microRNAs decreased during replicative senescence. Individually modulating the amount of each microRNA did not modify MKK4 abundance, but their concomitant overexpression decreased and their joint reduction increased MKK4 abundance. Reporter analyses indicated that these microRNAs acted through the MKK4 5' and 3' untranslated regions. Elevated MKK4 abundance inhibited cell proliferation and increased the phosphorylation and activity of p38 and PRAK (p38-regulated/activated protein kinase). Thus, multiple microRNAs acting on a single target, the MKK4 mRNA, collectively influence MKK4 abundance during replicative senescence. C1 [Marasa, Bernard S.; Srikantan, Subramanya; Masuda, Kiyoshi; Abdelmohsen, Kotb; Kuwano, Yuki; Yang, Xiaoling; Martindale, Jennifer L.; Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Rinker-Schaeffer, Carrie W.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. RP Gorospe, M (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov OI srikantan, subramanya/0000-0003-1810-6519; abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS [Z01 AG000394-02] NR 27 TC 47 Z9 52 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD OCT 27 PY 2009 VL 2 IS 94 AR ra69 DI 10.1126/scisignal.2000442 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570AM UT WOS:000275644000007 PM 19861690 ER PT J AU VanHook, AM Gorospe, M AF VanHook, Annalisa M. Gorospe, Myriam TI Science Signaling Podcast: 27 October 2009 SO SCIENCE SIGNALING LA English DT Editorial Material AB This is a conversation with Myriam Gorospe about a Research Article published in the 27 October 2009 issue of Science Signaling. C1 [VanHook, Annalisa M.] Amer Assoc Advancement Sci, Washington, DC 20005 USA. [Gorospe, Myriam] NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. RP VanHook, AM (reprint author), Amer Assoc Advancement Sci, 1200 New York Ave NW, Washington, DC 20005 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD OCT 27 PY 2009 VL 2 IS 94 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 570AM UT WOS:000275644000003 ER PT J AU Gambhira, R Jagu, S Karanam, B Day, PM Roden, R AF Gambhira, Ratish Jagu, Subhashini Karanam, Balasubramanyam Day, Patricia M. Roden, Richard TI Role of L2 cysteines in papillomavirus infection and neutralization SO VIROLOGY JOURNAL LA English DT Article ID MINOR CAPSID PROTEIN; HEPARAN-SULFATE; CERVICAL-CANCER; VACCINES; BINDING; EPITOPE; HPV16; L1 AB Vaccination of mice with minor capsid protein L2 or passive transfer with the L2-specific neutralizing monoclonal antibody RG-1 protects against human papillomavirus type 16 (HPV16) challenge. Here we explored the nature of the RG-1 epitope and its contribution to viral infectivity. RG-1 bound equivalently HPV16 L2 residues 17-36 with or without an intact C22-C28 disulphide bridge. HPV16 L2 mutations K20A, C22A, C22S, C28A, C28S, or P29A prevented RG-1 binding, whereas Y19A, K23A or Q24A had no impact. Mutation of either C22 or C28 to alanine or serine compromises HPV16 pseudoviral infectivity both in vitro and in the murine vaginal tract, but does not impact pseudovirion assembly. Despite their lack of infectivity, HPV16 pseudovirions containing C22S or C28S mutant L2 bind to cell surfaces, are taken up, and expose the 17-36 region on the virion surface as for wild type HPV16 pseudovirions suggesting normal furin cleavage of L2. Mutation of the second cysteine residue in Bovine papillomavirus type 1 (BPV1) L2 to serine (C25S) dramatically reduced the infectivity of BPV1 pseudovirions. Surprisingly, in contrast to the double mutation in HPV16 L2, the BPV1 L2 C19S, C25S double mutation reduced BPV1 pseudovirion infectivity of 293TT cells by only half. C1 [Gambhira, Ratish; Jagu, Subhashini; Karanam, Balasubramanyam; Roden, Richard] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. [Roden, Richard] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21231 USA. [Roden, Richard] Johns Hopkins Univ, Dept Obstet & Gynecol, Baltimore, MD 21231 USA. [Gambhira, Ratish] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. [Day, Patricia M.] NCI, Bethesda, MD 20892 USA. RP Roden, R (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. EM rgambhir@tulane.edu; sjagu1@jhmi.edu; bkarana1@jhmi.edu; dayp@dc37a.nci.nih.gov; roden@jhmi.edu FU National Institutes of Health [P50 CA098252, CA118790]; American Cancer Society [RSG-08-116-01-CCE]; Prevent Cancer Foundation, Alexandria, VA FX Funding for this study was provided by the National Institutes of Health (National Cancer Institute, SPORE in Cervical Cancer, P50 CA098252 and CA118790 to RBSR), the American Cancer Society (RSG-08-116-01-CCE to RBSR) and the Prevent Cancer Foundation, Alexandria, VA (fellowship to SJ) and the intramural program (PMD). We are grateful for the helpful comments and numerous clones kindly provided by Christopher Buck (NCI, NIH). We thank Philip Cole and Tatania Boronina of the Johns Hopkins University Proteomics Core for performing the mass spectrometry analysis and Martin Muller (Deutsches Krebsforschungszentrum, Germany) for codon-modified HPV16 L1 and L2. NR 17 TC 13 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD OCT 27 PY 2009 VL 6 AR 176 DI 10.1186/1743-422X-6-176 PG 6 WC Virology SC Virology GA 518GX UT WOS:000271679900005 PM 19860897 ER PT J AU Largent, EA Miller, FG Pearson, SD AF Largent, Emily A. Miller, Franklin G. Pearson, Steven D. TI Going Off-label Without Venturing Off-Course Evidence and Ethical Off-label Prescribing SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Pearson, Steven D.] NIH, Ctr Clin, Dept Eth, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), NIH, Ctr Clin, Dept Eth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM pearsonsd@cc.nih.gov NR 14 TC 30 Z9 30 U1 0 U2 4 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 OCT 26 PY 2009 VL 169 IS 19 BP 1745 EP 1747 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 511KS UT WOS:000271163800004 PM 19858430 ER PT J AU Nagatake, T Fukuyama, S Kim, DY Goda, K Igarashi, O Sato, S Nochi, T Sagara, H Yokota, Y Jetten, AM Kaisho, T Akira, S Mimuro, H Sasakawa, C Fukui, Y Fujihashi, K Akiyama, T Inoue, J Penninger, JM Kunisawa, J Kiyono, H AF Nagatake, Takahiro Fukuyama, Satoshi Kim, Dong-Young Goda, Kaoru Igarashi, Osamu Sato, Shintaro Nochi, Tomonori Sagara, Hiroshi Yokota, Yoshifumi Jetten, Anton M. Kaisho, Tsuneyasu Akira, Shizuo Mimuro, Hitomi Sasakawa, Chihiro Fukui, Yoshinori Fujihashi, Kohtaro Akiyama, Taishin Inoue, Jun-ichiro Penninger, Josef M. Kunisawa, Jun Kiyono, Hiroshi TI Id2-, ROR gamma t-, and LT beta R-independent initiation of lymphoid organogenesis in ocular immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TISSUE-INDUCER CELLS; HIGH ENDOTHELIAL VENULES; ORPHAN RECEPTOR-GAMMA; CUTTING EDGE; LYMPHOTOXIN-ALPHA; PSEUDOMONAS-AERUGINOSA; NODE ORGANOGENESIS; ORGAN DEVELOPMENT; GERMINAL-CENTERS; LACRIMAL GLANDS AB The eye is protected by the ocular immunosurveillance system. We show that tear duct associated lymphoid tissue (TALT) is located in the mouse lacrimal sac and shares immunological characteristics with mucosa-associated lymphoid tissues (MALTs), including the presence of M cells and immunocompetent cells for antigen uptake and subsequent generation of mucosal immune responses against ocularly encountered antigens and bacteria such as Pseudomonas aeruginosa. Initiation of TALT genesis began postnatally; it occurred even in germ-free conditions and was independent of signaling through organogenesis regulators, including inhibitor of DNA binding/ differentiation 2, retinoic acid-related orphan receptor gamma t, lymphotoxin (LT) alpha 1 beta 2-LT beta R, and lymphoid chemokines (CCL19, CCL21, and CXCL13). Thus, TALT shares immunological features with MALT but has a distinct tissue genesis mechanism and plays a key role in ocular immunity. C1 [Nagatake, Takahiro; Fukuyama, Satoshi; Kim, Dong-Young; Goda, Kaoru; Igarashi, Osamu; Sato, Shintaro; Nochi, Tomonori; Kunisawa, Jun; Kiyono, Hiroshi] Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Dept Microbiol & Immunol,Minato Ku, Tokyo 1088639, Japan. [Sagara, Hiroshi] Univ Tokyo, Med Prote Lab, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. [Mimuro, Hitomi; Sasakawa, Chihiro] Univ Tokyo, Inst Med Sci, Div Bacterial Infect, Dept Microbiol & Immunol,Minato Ku, Tokyo 1088639, Japan. [Akiyama, Taishin; Inoue, Jun-ichiro] Univ Tokyo, Inst Med Sci, Div Cellular & Mol Biol, Minato Ku, Tokyo 1088639, Japan. [Nagatake, Takahiro; Kiyono, Hiroshi] Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan. [Nagatake, Takahiro; Kiyono, Hiroshi] Univ Tokyo, Fac Med, Bunkyo Ku, Tokyo 1130033, Japan. [Kim, Dong-Young] Seoul Natl Univ, Coll Med, Dept Otorhinolaryngol, Seoul 110744, South Korea. [Yokota, Yoshifumi] Univ Fukui, Sch Med, Dept Mol Genet, Eiheiji, Fukui 9101193, Japan. [Jetten, Anton M.] NIEHS, Cell Biol Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. [Kaisho, Tsuneyasu] Inst Phys & Chem Res, Res Ctr Allergy & Immunol, Host Def Lab, Tsurumi Ku, Kanagawa 2300045, Japan. [Akira, Shizuo] Osaka Univ, Host Def Lab, World Premier Int Res Ctr, Immunol Frontier Res Ctr, Suita, Osaka 5650871, Japan. [Fukui, Yoshinori] Kyushu Univ, Div Immunogenet, Dept Immunobiol & Neurosci, Med Inst Bioregulat, Fukuoka 8128582, Japan. [Fujihashi, Kohtaro; Kiyono, Hiroshi] Univ Alabama, Dept Pediat Dent, Immunobiol Vaccine Ctr, Birmingham, AL 35294 USA. [Penninger, Josef M.] Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria. [Kunisawa, Jun; Kiyono, Hiroshi] Univ Tokyo, Grad Sch Frontier Sci, Chiba 2778561, Japan. RP Kiyono, H (reprint author), Univ Tokyo, Inst Med Sci, Div Mucosal Immunol, Dept Microbiol & Immunol,Minato Ku, Tokyo 1088639, Japan. EM kiyono@ims.u-tokyo.ac.jp RI Akira, Shizuo/C-3134-2009; Kaisho, Tsuneyasu/B-4130-2012; Kim, Dong-Young/J-2737-2012; Penninger, Josef/I-6860-2013; OI Penninger, Josef/0000-0002-8194-3777; Jetten, Anton/0000-0003-0954-4445; Nagatake, Takahiro/0000-0003-3022-9626 FU Ministry of Education, Culture, Sports, Science, and Technology (MEXT); Japan Society for the Promotion of Science for Graduate Students; National Institute of Environmental Health Sciences [Z01-ES-101586] FX This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), the Ministry of Health and Welfare of Japan and the Global Center of Excellence Program "Center of Education and Research for the Advanced Genome-Based Medicine For Personalized Medicine and the Control of Worldwide Infectious Diseases," and an "Academic Frontier" project for private universities matching-fund subsidy from MEXT. T. Nagatake, S. Fukuyama, and D.- Y. Kim were supported by research fellowships from the Japan Society for the Promotion of Science for Graduate Students, Young Scientists, and Foreign Researchers, respectively. A. M. Jetten was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences ( grant Z01-ES-101586). NR 69 TC 34 Z9 34 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 OCT 26 PY 2009 VL 206 IS 11 BP 2351 EP 2364 DI 10.1084/jem.20091436 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 511KU UT WOS:000271164000007 PM 19822644 ER PT J AU Erdag, G Brosky, K Fetsch, P Moss, J Filie, AC AF Erdag, Gulsun Brosky, Keith Fetsch, Patricia Moss, Joel Filie, Armando C. TI Effusion Cytology in Lymphangioleiomyomatosis SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Erdag, Gulsun; Brosky, Keith; Fetsch, Patricia; Filie, Armando C.] NCI, LP, NIH, Bethesda, MD 20892 USA. [Moss, Joel] NHLBI, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2009 VL 117 IS 5 BP 362 EP 363 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 510HM UT WOS:000271078800022 ER PT J AU Mernoli, MJ Tumpey, TM Jagger, BW Dugan, VG Sheng, ZM Qi, L Kash, JC Taubenberger, JK AF Mernoli, Matthew J. Tumpey, Terrence M. Jagger, Brett W. Dugan, Vivien G. Sheng, Zong-Mei Qi, Li Kash, John C. Taubenberger, Jeffery K. TI An early 'classical' swine H1N1 influenza virus shows similar pathogenicity to the 1918 pandemic virus in ferrets and mice SO VIROLOGY LA English DT Article DE Viruses; Influenza; Pandemic; Ferrets; Viral pathogenesis; Animal models; Swine influenza ID A VIRUSES; EUROPEAN PIGS; ORIGIN; HEMAGGLUTININ; EVOLUTION; VIRULENCE; PATHOGENESIS; INFECTIONS; EPIDEMIC; HUMANS AB The 1918 pandemic influenza virus has demonstrated significant pathogenicity in animal models and is the progenitor of 'classical' swine and modern seasonal human H1N1 lineages. Here we characterize the pathogenicity of an early 'classical' swine H1N1 influenza A virus isolated in 1931 compared to the pathogenicity of the 1918 pandemic virus and a seasonal H1N1 virus in mice and ferrets. A/Swine/Iowa/31 (Sw31) and the 1918 influenza viruses were uniformly lethal in mice at low doses and produced severe lung pathology. In ferrets, Sw31 and 1918 influenza viruses caused severe clinical disease and lung pathology with necrotizing bronchiolitis and alveolitis. The modern H I NI virus Caused little disease in either animal model. These findings revealed that in these models the virulence factors of the 1918 influenza virus are likely preserved in the Sw31 virus and suggest that early swine viruses may be a good surrogate model to study 1918 virulence and pathogenesis. Published by Elsevier Inc. C1 [Mernoli, Matthew J.; Jagger, Brett W.; Dugan, Vivien G.; Sheng, Zong-Mei; Qi, Li; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Tumpey, Terrence M.] Ctr Dis Control & Prevent, Immunol & Pathogenesis Branch, Influenza Div, Natl Ctr Immunizat & Resp Dis,Collaborating Ctr I, Atlanta, GA USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 N Dr,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU NIH; MAID FX The Intramural Research Program of the NIH and the MAID supported this work. NR 42 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2009 VL 393 IS 2 BP 338 EP 345 DI 10.1016/j.virol.2009.08.021 PG 8 WC Virology SC Virology GA 511FC UT WOS:000271148300017 ER PT J AU Drazen, JM Van der Weyden, MB Sahni, P Rosenberg, J Marusic, A Laine, C Kotzin, S Horton, R Hebert, PC Haug, C Godlee, F Frizelle, FA de Leeuw, PW DeAngelis, CD AF Drazen, Jeffrey M. Van der Weyden, Martin B. Sahni, Peush Rosenberg, Jacob Marusic, Ana Laine, Christine Kotzin, Sheldon Horton, Richard Hebert, Paul C. Haug, Charlotte Godlee, Fiona Frizelle, Frank A. de Leeuw, Peter W. DeAngelis, Catherine D. TI Uniform format for disclosure of competing interests in ICMJE journals SO LANCET LA English DT Editorial Material C1 [Kotzin, Sheldon] Natl Lib Med, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Sahni, Peush/0000-0002-6910-062X NR 0 TC 10 Z9 10 U1 0 U2 3 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 OCT 24 PY 2009 VL 374 IS 9699 BP 1395 EP 1396 DI 10.1016/S0140-6736(09)61796-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 512MZ UT WOS:000271255000004 PM 19836071 ER PT J AU Kanda, A Swaroop, A AF Kanda, Atsuhiro Swaroop, Anand TI A comprehensive analysis of sequence variants and putative disease-causing mutations in photoreceptor-specific nuclear receptor NR2E3 SO MOLECULAR VISION LA English DT Article ID S-CONE-SYNDROME; DOMINANT RETINITIS-PIGMENTOSA; LIGAND-BINDING DOMAIN; GOLDMANN-FAVRE-SYNDROME; RETINAL DEGENERATION; COMPOUND HETEROZYGOSITY; ROD PHOTORECEPTORS; CRYSTAL-STRUCTURE; GENE; TRANSCRIPTION AB Purpose: The photoreceptor-specific orphan nuclear receptor NR2E3 is a key regulator of transcriptional events during photoreceptor differentiation in mammalian retina. Mutations in NR2E3 are associated with enhanced S-cone syndrome and related retinal phenotypes that reveal characteristic excess of S-cone function. This study was undertaken to determine biochemical as well as functional consequences of reported sequence variants and disease-causing mutations in NR2E3. Methods: Twenty-five different mutations in the wild-type NR2E3 expression construct were generated by site-directed mutagenesis and performed nuclear localization, gel-shift, rhodopsin promoter activity assays, and co-immunoprecipitation in cultured mammalian cells. Results: Of the 25 mutant proteins, 15 mislocalize at least partially to the cytoplasm. Eight of the nine changes in the DNA-binding domain (DBD) and 12 of the 14 mutations in the ligand-binding domain (LBD) of NR2E3 exhibited reduced DNA-binding and transcriptional activation of the rhodopsin promoter. Moreover, these mutations dramatically altered the interaction of NR2E3 with NRL as well as with CRX. Two NR2E3 variants between DBD and LBD showed no effect on any biochemical or functional parameter tested. Conclusions: These data provide a better understanding of sequence variants, validate disease-causing mutations, and demonstrate the significance of DBD and LBD in mediating NR2E3 function. These studies contribute to molecular mechanisms underlying retinal phenotypes caused by NR2E3 mutations. C1 [Kanda, Atsuhiro] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Kanda, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bldg 6-308,MSC0610,6 Ctr Dr, Bethesda, MD 20892 USA. EM kandaa@nei.nih.gov OI Swaroop, Anand/0000-0002-1975-1141 FU National Eye Institute; National Institutes of Health [EY011115, EY007003]; Foundation Fighting Blindness; Suntory Institute FX We thank James Friedman, Jerome Roger, Hong Cheng, Edwin Oh, and other members of Swaroop laboratory for comments and discussion, and Sharyn Ferrara and Lucia Lawrence for administrative assistance. This work was supported by the intramural program of the National Eye Institute and by grants from the National Institutes of Health (EY011115 and EY007003), The Foundation Fighting Blindness, and Research to Prevent Blindness. A. K. was supported in part by the Suntory Institute for Bioorganic Research (Osaka, Japan). NR 48 TC 17 Z9 17 U1 1 U2 1 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 OCT 24 PY 2009 VL 15 IS 234 BP 2174 EP 2184 PG 11 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 528ES UT WOS:000272425200001 PM 19898638 ER PT J AU Kigozi, G Wawer, M Ssettuba, A Kagaayi, J Nalugoda, F Watya, S Mangen, FW Kiwanuka, N Bacon, MC Lutalo, T Serwadda, D Gray, RH AF Kigozi, Godfrey Wawer, Maria Ssettuba, Absalom Kagaayi, Joseph Nalugoda, Fred Watya, Stephen Mangen, Fred Wabwire Kiwanuka, Noah Bacon, Melanie C. Lutalo, Tom Serwadda, David Gray, Ronald H. TI Foreskin surface area and HIV acquisition in Rakai, Uganda (size matters) SO AIDS LA English DT Article DE foreskin surface area; HIV acquisition; HIV target cells; male circumcision ID SEXUALLY-TRANSMITTED INFECTIONS; RANDOMIZED CONTROLLED-TRIAL; MALE CIRCUMCISION; TARGET-CELLS; MEN; RISK; TRANSMISSION; METAANALYSIS; PREVENTION; COHORT AB Introduction: Male circumcision reduces HIV acquisition in men. We assessed whether foreskin surface area was associated with HIV acquisition prior to circumcision. Methods: In two randomized trials of male circumcision, the surface area of the foreskin was measured after surgery using standardized procedures. Nine hundred and sixty-five initially HIV-negative men were enrolled in a community cohort who subsequently enrolled in the male circumcision trials, provided 3920.8 person-years of observation prior to circumcision. We estimated HIV incidence per 100 person-years prior to circumcision, associated with foreskin surface area categorized into quartiles. Results: Mean foreskin surface area was significantly higher among men who acquired HIV (43.3 cm(2), standard error 2.1) compared with men who remained uninfected (36.8 cm(2), standard error 0.5, P=0.01). HIV incidence was 0.80/100 person-years (8/994.9 person-years) for men with foreskin surface areas in the lowest quartile (<= 26.3 cm(2)), 0.92/100 person-years (9/975.3 person-years) with foreskin areas in the second quartile (26.4-35.0 cm(2)), 0.90/100 person-years (8/888.5 person-years) with foreskin area in the third quartile (35.2-45.5 cm(2)) and 2.48/100 person-years (23/926.8 person-years) in men with foreskin surfaces areas in the highest quartile (>45.6 cm(2)). Compared with men with foreskin surface areas in the lowest quartile, the adjusted incidence rate ratio of HIV acquisition was 2.37 (95% confidence interval 1.05-5.31) in men with the largest quartile of foreskin surface area. Conclusion: The risk of male HIV acquisition is increased among men with larger foreskin surface areas. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Kigozi, Godfrey; Ssettuba, Absalom; Kagaayi, Joseph; Nalugoda, Fred] Rakai Hlth Sci Program, Entebbe, Uganda. [Wawer, Maria; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Mangen, Fred Wabwire; Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda. [Bacon, Melanie C.] NIAID, NIH, Bethesda, MD 20892 USA. [Lutalo, Tom] Uganda Virus Res Inst, Entebbe, Uganda. RP Kigozi, G (reprint author), Rakai Hlth Sci Program, POB 279, Kalisizo, Uganda. EM gkigozi@rhsp.org FU Fogarty AIDS International Training and Research Program (AITRP); National Institutes of Health [U1AI51171]; Bill and Melinda Gates Foundation [22006.02] FX The trials were funded by the National Institutes of Health (#U1AI51171) and the Bill and Melinda Gates Foundation (#22006.02). NR 16 TC 37 Z9 37 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 23 PY 2009 VL 23 IS 16 BP 2209 EP 2213 DI 10.1097/QAD.0b013e328330eda8 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 517FS UT WOS:000271599200017 PM 19770623 ER PT J AU Chu, AY Parekh, RS Astor, BC Coresh, J Berthier-Schaad, Y Smith, MW Shuldiner, AR Kao, WHL AF Chu, Audrey Y. Parekh, Rulan S. Astor, Brad C. Coresh, Josef Berthier-Schaad, Yvette Smith, Michael W. Shuldiner, Alan R. Kao, Wen Hong L. TI Association of APOE polymorphism with chronic kidney disease in a nationally representative sample: a Third National Health and Nutrition Examination Survey (NHANES III) Genetic Study SO BMC MEDICAL GENETICS LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; GLOMERULAR-FILTRATION-RATE; TYPE-2 DIABETIC-PATIENTS; SERUM CREATININE; RENAL-DISEASE; LIPOPROTEIN METABOLISM; AFRICAN-AMERICANS; ALZHEIMER-DISEASE; NEPHROPATHY; ALLELE AB Background: Apolipoprotein E polymorphisms (APOE) have been associated with lowered glomerular filtration rate (GFR) and chronic kidney disease (CKD) with e2 allele conferring risk and e4 providing protection. However, few data are available in non-European ethnic groups or in a population-based cohort. Methods: The authors analyzed 5,583 individuals from the Third National Health and Nutrition Examination Survey (NHANES III) to determine association with estimated GFR by the Modification of Diet in Renal Disease (MDRD) equation and low-GFR cases. Low-GFR cases were defined as GFR <75 ml/min/1.73 m(2); additionally, GFR was analyzed continuously. Results: In univariate analysis, the e4 allele was negatively associated with low-GFR cases in non-Hispanic whites, odds ratio (OR): 0.76, 95% confidence interval (CI): 0.60, 0.97. In whites, there was a significant association between increasing APOE score (indicating greater number of e2 alleles) and higher prevalence of low-GFR cases (OR: 1.21, 95% CI: 1.01, 1.45). Analysis of continuous GFR in whites found the e4 allele was associated with higher levels of continuous GFR (beta-coefficient: 2.57 ml/min/ 1.73 m2, 95% CI: 0.005, 5.14); in non-Hispanic blacks the e2 allele was associated with lower levels of continuous GFR (beta coefficient: -3.73 ml/min/1.73 m(2), 95% CI: -6.61, -0.84). APOE e2 and e4 alleles were rare and not associated with low-GFR cases or continuous GFR in Mexican Americans. Conclusion: In conclusion, the authors observed a weak association between the APOE e4 allele and low-GFR cases and continuous GFR in non-Hispanic whites, and the APOE e2 allele and continuous GFR in non-Hispanic blacks, but found no association with either measure of kidney function in Mexican Americans. Larger studies including multiethnic groups are needed to determine the significance of this association. C1 [Chu, Audrey Y.; Parekh, Rulan S.; Astor, Brad C.; Coresh, Josef; Berthier-Schaad, Yvette; Kao, Wen Hong L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. [Parekh, Rulan S.] Univ Hlth Network, Sick Kids Res Inst, Hosp Sick Children, Toronto, ON, Canada. [Parekh, Rulan S.] Univ Toronto, Toronto, ON, Canada. [Berthier-Schaad, Yvette; Smith, Michael W.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. [Smith, Michael W.] NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21701 USA. [Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. RP Kao, WHL (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. EM achu@jhsph.edu; rsparekh@jhmi.edu; bastor@jhsph.edu; coresh@jhu.edu; yberthier@ncifcrf.gov; smith@ncifcrf.gov; Ashuldin@medicine.umaryland.edu; wkao@jhsph.edu RI Smith, Michael/B-5341-2012 FU National Heart, Lung and Blood Institute [5T32HL007024]; National Institute of Diabetes and Digestive and Kidney Diseases [K01DK067607] FX This work was supported by the National Heart, Lung and Blood Institute (grant number 5T32HL007024 to AC), the National Institute of Diabetes and Digestive and Kidney Diseases (grant number K01DK067607 to LK) and an education gift from Merck. None of the funding bodies played a role in study design; in the collection, analysis, and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. NR 56 TC 17 Z9 17 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD OCT 23 PY 2009 VL 10 AR 108 DI 10.1186/1471-2350-10-108 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 523AC UT WOS:000272041000001 PM 19852818 ER PT J AU Lu, ZP Scott, I Webster, BR Sack, MN AF Lu, Zhongping Scott, Iain Webster, Bradley R. Sack, Michael N. TI The Emerging Characterization of Lysine Residue Deacetylation on the Modulation of Mitochondrial Function and Cardiovascular Biology SO CIRCULATION RESEARCH LA English DT Review DE sirtuins; mitochondrial metabolism; apoptosis; redox stress; heart; vascular biology ID STRESS-RESPONSIVE DEACETYLASE; ACTIVATED PROTEIN-KINASE; HYPOXIA-INDUCIBLE FACTOR; NITRIC-OXIDE SYNTHASE; CALORIE RESTRICTION; DEPENDENT DEACETYLASE; ISCHEMIA-REPERFUSION; CARDIAC MYOCYTES; CELL-SURVIVAL; SIR2 HOMOLOG AB There is emerging recognition of a novel fuel and redox sensing regulatory program that controls cellular adaptation via nonhistone protein lysine residue acetyl posttranslation modifications. This program functions in tissues with high energy demand and oxidative capacity and is highly enriched in the heart. Deacetylation is regulated by NAD(+)-dependent activation of the sirtuin family of proteins, whereas acetyltransferase modifications are controlled by less clearly delineated acetyltransferases. Subcellular localization specific protein targets of lysine-acetyl modification have been identified in the nucleus, cytoplasm, and mitochondria. Despite distinct subcellular localizations, these modifications appear, in large part, to modify mitochondrial properties including respiration, energy production, apoptosis, and antioxidant defenses. These mitochondrial regulatory programs are important in cardiovascular biology, although how protein acetyl modifications effects cardiovascular pathophysiology has not been extensively explored. This review will introduce the role of nonhistone protein lysine residue acetyl modifications, discuss their regulation and biochemistry and present the direct and indirect data implicating their involvement in the heart and vasculature. (Circ Res. 2009; 105: 830-841.) C1 [Lu, Zhongping; Scott, Iain; Webster, Bradley R.; Sack, Michael N.] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), Bld 10 CRC,Room 5-3150,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov FU NIH FX This work was funded by the NIH, Divisions of Intramural Research of the National Heart, Lung, and Blood Institute. NR 130 TC 35 Z9 35 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 23 PY 2009 VL 105 IS 9 BP 830 EP 841 DI 10.1161/CIRCRESAHA.109.204974 PG 12 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 509QE UT WOS:000271032300002 PM 19850949 ER PT J AU Rafikova, ER Melikov, K Ramos, C Dye, L Chernomordik, LV AF Rafikova, Elvira R. Melikov, Kamran Ramos, Corinne Dye, Louis Chernomordik, Leonid V. TI Transmembrane Protein-free Membranes Fuse into Xenopus Nuclear Envelope and Promote Assembly of Functional Pores SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; CELL-CYCLE; EGG EXTRACTS; FORMATION INVITRO; FUSION; COMPLEXES; SNARE; CHROMATIN; DYNAMICS; ROLES AB Post-mitotic reassembly of nuclear envelope (NE) and the endoplasmic reticulum (ER) has been reconstituted in a cell-free system based on interphase Xenopus egg extract. To evaluate the relative contributions of cytosolic and transmembrane proteins in NE and ER assembly, we replaced a part of native membrane vesicles with ones either functionally impaired by trypsin or N-ethylmaleimide treatments or with protein-free liposomes. Although neither impaired membrane vesicles nor liposomes formed ER and nuclear membrane, they both supported assembly reactions by fusing with native membrane vesicles. At membrane concentrations insufficient to generate full-sized functional nuclei, addition of liposomes and their fusion with membrane vesicles resulted in an extensive expansion of NE, further chromatin decondensation, restoration of the functionality, and spatial distribution of the nuclear pore complexes (NPCs), and, absent newly delivered transmembrane proteins, an increase in NPC numbers. This rescue of the nuclear assembly by liposomes was inhibited by wheat germ agglutinin and thus required active nuclear transport, similarly to the assembly of full-sized functional NE with membrane vesicles. Mechanism of fusion between liposomes and between liposomes and membrane vesicles was investigated using lipid mixing assay. This fusion required interphase cytosol and, like fusion between native membrane vesicles, was inhibited by guanosine 5'-3-O-(thio) triphosphate, soluble N-ethylmaleimide-sensitive factor attachment protein, and N-ethylmaleimide. Our findings suggest that interphase cytosol contains proteins that mediate the fusion stage of ER and NE reassembly, emphasize an unexpected tolerance of nucleus assembly to changes in concentrations of transmembrane proteins, and reveal the existence of a feedback mechanism that couples NE expansion with NPC assembly. C1 [Rafikova, Elvira R.; Melikov, Kamran; Chernomordik, Leonid V.] Eunice Kennedy Shriver NICHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. [Ramos, Corinne] Univ Calif San Diego, Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. RP Chernomordik, LV (reprint author), Bldg 10,Rm 10D04A,10 Ctr Dr, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov FU National Institutes of Health Intramural Research Program of the Eunice Kennedy Shriver NICHD FX This work was supported, in whole or in part, by National Institutes of Health Intramural Research Program of the Eunice Kennedy Shriver NICHD (to L. V. C.). NR 78 TC 7 Z9 7 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 OCT 23 PY 2009 VL 284 IS 43 BP 29847 EP 29859 DI 10.1074/jbc.M109.044453 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 507ZW UT WOS:000270896800065 PM 19696024 ER PT J AU Farrell, KB Tusnady, GE Eiden, MV AF Farrell, Karen B. Tusnady, Gabor E. Eiden, Maribeth V. TI New Structural Arrangement of the Extracellular Regions of the Phosphate Transporter SLC20A1, the Receptor for Gibbon Ape Leukemia Virus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE PROTEIN TOPOLOGY; CELL-SURFACE RECEPTORS; RETROVIRUS RECEPTOR; PREDICTION; INFECTION; FAMILY; DOMAIN; ENTRY; IDENTIFICATION; REVEALS AB Infection of a host cell by a retrovirus requires an initial interaction with a cellular receptor. For numerous gammaretroviruses, such as the gibbon ape leukemia virus, woolly monkey virus, feline leukemia virus subgroup B, feline leukemia virus subgroup T, and 10A1 murine leukemia virus, this receptor is the human type III sodium-dependent inorganic phosphate transporter, SLC20A1, formerly known as PiT1. Understanding the critical receptor functionalities and interactions with the virus that lead to successful infection requires that we first know the surface structure of the cellular receptor. Previous molecular modeling from the protein sequence, and limited empirical data, predicted a protein with 10 transmembrane helices. Here we undertake the biochemical approach of substituted cysteine accessibility mutagenesis to resolve the topology of this receptor in live cells. We discover that there are segments of the protein that are unexpectedly exposed to the outside milieu. By using information determined by substituted cysteine accessibility mutagenesis to set constraints in HMMTOP, a hidden Markov model-based transmembrane topology prediction method, we now propose a comprehensive topological model for SLC20A1, a transmembrane protein with 12 transmembrane helices and 7 extracellular regions, that varies from previous models and should permit approaches that define both virus interaction and transport function. C1 [Farrell, Karen B.; Eiden, Maribeth V.] NIH, Sect Mol Virol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Tusnady, Gabor E.] Hungarian Acad Sci, Biol Res Ctr, Inst Enzymol, H-1113 Budapest, Hungary. RP Eiden, MV (reprint author), 49 Convent Dr,MSC 4483,Bldg 49,Rm 5A60, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov RI Tusnady, Gabor/A-3207-2009 OI Tusnady, Gabor/0000-0001-8105-0285 FU National Institutes of Health; Bolyai Janos scholarship; Hungarian Research and Development Funds [OTKA K75460] FX This work was authored, in whole or in part, by National Institutes of Health staff. This work was supported by a Bolyai Janos scholarship and Hungarian Research and Development Funds OTKA K75460 ( to G. E. T.). NR 30 TC 13 Z9 13 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 OCT 23 PY 2009 VL 284 IS 43 BP 29979 EP 29987 DI 10.1074/jbc.M109.022566 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 507ZW UT WOS:000270896800076 PM 19717569 ER PT J AU Modi, HR Katyare, SS AF Modi, Hiren R. Katyare, Surendra S. TI Cadmium exposure-induced alterations in the lipid/phospholipids composition of rat brain microsomes and mitochondria SO NEUROSCIENCE LETTERS LA English DT Article DE Cd neurotoxicity; Cd and Brain microsomal lipids; Cd and brain mitochondrial lipids ID MEMBRANE PHOSPHOLIPIDS; INDUCED HEPATOTOXICITY; LIPID-PEROXIDATION; OXIDATIVE STRESS; FLUIDITY; PRETREATMENT; TOLERANCE; TRANSPORT; TISSUES; ATPASE AB Effects of treatment with a single intra-peritoneal (i.p.) injection (0.84 mg Cd/kg body weight) of cadmium (Cd) on lipid/phospholipids profiles of rat brain microsomes and mitochondria were examined. At the end of one-week following treatment with Cd the microsomal total phospholipids (TPL) content was unchanged but the cholesterol (CHL) content increased. In one-month Cd-treated group both TPL and CHL contents increased. In one-week Cd-treated group the content of phosphatidylinositol (PI) decreased whereas that of lysophospholipid and phosphatidic acid (PA) increased. In one-month Cd-treated group the sphinghomyelin (SPM) and phosphatidycholine (PC) components increased whereas phosphatidyethanolamine (PE) and PA decreased. In mitochondria, CHL content increased in both Cd-treated groups. The content of TPL decreased only in one-month Cd-treated group. In one-week Cd-treated group the lysophospholipids increased whereas PI and phosphatidylserine (PS) decreased. In one-month group the lysophospholipids, PI and diphosphatidylglycerol (DPG) components decreased whereas PS and PE component increased. The results suggest that exposure to a single dose of Cd has differential and long-lasting effects on lipid/phospholipids profiles of rat brain microsomes and mitochondria. (C) 2009 Elsevier Ireland Ltd. All rights reserved. C1 [Modi, Hiren R.; Katyare, Surendra S.] Maharaja Sayajirao Univ Baroda, Fac Sci, Dept Biochem, Vadodara 390002, Gujarat, India. RP Modi, HR (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S126, Bethesda, MD 20892 USA. EM modi_hiren@yahoo.co.in NR 35 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 23 PY 2009 VL 464 IS 2 BP 108 EP 112 DI 10.1016/j.neulet.2009.08.003 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 501YC UT WOS:000270419400007 PM 19664684 ER PT J AU Lombardi, VC Ruscetti, FW Das Gupta, J Pfost, MA Hagen, KS Peterson, DL Ruscetti, SK Bagni, RK Petrow-Sadowski, C Gold, B Dean, M Silverman, RH Mikovits, JA AF Lombardi, Vincent C. Ruscetti, Francis W. Das Gupta, Jaydip Pfost, Max A. Hagen, Kathryn S. Peterson, Daniel L. Ruscetti, Sandra K. Bagni, Rachel K. Petrow-Sadowski, Cari Gold, Bert Dean, Michael Silverman, Robert H. Mikovits, Judy A. TI Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome SO SCIENCE LA English DT Article ID MURINE LEUKEMIA-VIRUS; FOCUS-FORMING VIRUS; CENTRIFUGAL ENHANCEMENT; GROWTH-FACTOR; RNASE-L; GENE; LYMPHOMA; REGION AB Chronic fatigue syndrome (CFS) is a debilitating disease of unknown etiology that is estimated to affect 17 million people worldwide. Studying peripheral blood mononuclear cells (PBMCs) from CFS patients, we identified DNA from a human gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), in 68 of 101 patients (67%) as compared to 8 of 218 (3.7%) healthy controls. Cell culture experiments revealed that patient-derived XMRV is infectious and that both cell-associated and cell-free transmission of the virus are possible. Secondary viral infections were established in uninfected primary lymphocytes and indicator cell lines after their exposure to activated PBMCs, B cells, T cells, or plasma derived from CFS patients. These findings raise the possibility that XMRV may be a contributing factor in the pathogenesis of CFS. C1 [Lombardi, Vincent C.; Pfost, Max A.; Hagen, Kathryn S.; Peterson, Daniel L.; Mikovits, Judy A.] Whittemore Peterson Inst, Reno, NV 89557 USA. [Ruscetti, Francis W.; Gold, Bert; Dean, Michael] NCI, Expt Immunol Lab, Frederick, MD 21701 USA. [Das Gupta, Jaydip; Silverman, Robert H.] Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. [Ruscetti, Sandra K.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA. [Bagni, Rachel K.] NCI, Adv Technol Program, Frederick, MD 21701 USA. [Petrow-Sadowski, Cari] NCI, Basic Res Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Mikovits, JA (reprint author), Whittemore Peterson Inst, Reno, NV 89557 USA. EM judym@wpinstitute.org FU Whittemore Peterson Institute; Whittemore Family foundation; National Cancer Institute (NCI); NIH [HHSN26120080001E]; NCI/ NIH [CA104943]; U. S. DoD Prostate Cancer Research Program [W81XWH-07-1338]; V Foundation for Cancer Research; Charlotte Geyer Foundation; Mal and Lea Bank FX We thank D. Bertolette, Y. Huang, C. Hanson, and J. Troxler for technical assistance; K. Nagashima for EM; and C. Ware and K. Hunter for discussions. Funded by the Whittemore Peterson Institute and the Whittemore Family foundation; the National Cancer Institute (NCI); NIH (under contract HHSN26120080001E); and grants to R. H. S. from NCI/ NIH (CA104943), the U. S. DoD Prostate Cancer Research Program (W81XWH-07-1338), the V Foundation for Cancer Research, the Charlotte Geyer Foundation, and Mal and Lea Bank. The content of this publication does not reflect the views or policies of the U. S. DHHS, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government. R. H. S. may receive royalty payments in the future from Abbott Laboratories. GenBank accession numbers are as follows: WPI-1130, GQ483508; WPI-1138, GQ483509; WPI-1169,GQ483510; WPI-1178, GQ497343; WPI-1106, GQ497344; and WPI-1104, GQ497345.; Note added in proof: V. C. L. is operations manager of Viral Immune Pathologies Laboratory, which is in negotiations with the Whittemore Peterson Institute to offer a diagnostic test for XMRV. NR 20 TC 347 Z9 356 U1 0 U2 33 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 OCT 23 PY 2009 VL 326 IS 5952 BP 585 EP 589 DI 10.1126/science.1179052 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 509LN UT WOS:000271019400045 PM 19815723 ER PT J AU Simonsen, L Viboud, C Taylor, RJ Miller, MA Jackson, L AF Simonsen, Lone Viboud, Cecile Taylor, Robert J. Miller, Mark A. Jackson, Lisa TI Influenza vaccination and mortality benefits: New insights, new opportunities SO VACCINE LA English DT Article; Proceedings Paper CT 3rd European Influenza Conference CY SEP 14-17, 2008 CL Vilamoura, PORTUGAL SP European Sci Working Grp Influenza DE Influenza; Vaccine effectiveness; Seniors ID RESPIRATORY SYNCYTIAL VIRUS; ELDERLY-PEOPLE; UNITED-STATES; COMMUNITY; RISK; POPULATION; EFFICACY; SENIORS AB Influenza vaccination control strategies in most countries rely on vaccination of seniors and other high risk groups. Although placebo-controlled randomized trials show influenza vaccine is effective in younger age groups, few seniors >70 years were studied even though they suffer >90% of influenza-related deaths. Excess mortality studies could not confirm a national decline in influenza-related mortality while vaccine coverage quadrupled. Cohort studies have consistently reported that vaccination reduces all-cause winter mortality by similar to 50%, an astonishing claim given only similar to 5% of all winter deaths are attributable to influenza. This VE overestimation has now been attributed to profound confounding frailty selection bias. A way forward includes a new generation of unbiased studies with laboratory endpoints, and requires an agreement that the evidence base was flawed. The latter may clear the way for more immunogenic vaccines for seniors and exploration of other influenza control strategies. (C) 2009 Elsevier Ltd. All rights reserved. C1 [Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. [Viboud, Cecile] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Taylor, Robert J.; Miller, Mark A.] SAGE Analyt LLC, Bethesda, MD USA. [Jackson, Lisa] Ctr Hlth Studies, Grp Hlth, Seattle, WA USA. RP Simonsen, L (reprint author), George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Global Hlth, Washington, DC USA. EM lone@gwu.edu OI Simonsen, Lone/0000-0003-1535-8526 NR 24 TC 41 Z9 41 U1 1 U2 5 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 OCT 23 PY 2009 VL 27 IS 45 BP 6300 EP 6304 DI 10.1016/j.vaccine.2009.07.008 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 518SC UT WOS:000271712400008 PM 19840664 ER PT J AU Klein, HG AF Klein, Harvey G. TI Transfused B19V: B-nign, B-ware, B-gone? SO BLOOD LA English DT Editorial Material ID PARVOVIRUS-B19; INFECTION C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Klein, HG (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 7 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 OCT 22 PY 2009 VL 114 IS 17 BP 3509 EP 3511 DI 10.1182/blood-2009-09-239939 PG 5 WC Hematology SC Hematology GA 509NK UT WOS:000271024500003 PM 19850749 ER PT J AU Gaspar, HB Aiuti, A Porta, F Candotti, F Hershfield, MS Notarangelo, LD AF Gaspar, H. Bobby Aiuti, Alessandro Porta, Fulvio Candotti, Fabio Hershfield, Michael S. Notarangelo, Luigi D. TI How I treat ADA deficiency SO BLOOD LA English DT Review ID ADENOSINE-DEAMINASE DEFICIENCY; SEVERE COMBINED IMMUNODEFICIENCY; CELL GENE-THERAPY; BONE-MARROW-TRANSPLANTATION; COMBINED IMMUNE-DEFICIENCY; ENZYME REPLACEMENT; IMMUNOLOGICAL RECONSTITUTION; BEHAVIORAL ABNORMALITIES; CD34(+) CELLS; SCID PATIENTS AB Adenosine deaminase deficiency is a disorder of purine metabolism leading to severe combined immunodeficiency (ADA-SCID). Without treatment, the condition is fatal and requires early intervention. Haematopoietic stem cell transplantation is the major treatment for ADA-SCID, although survival following different donor sources varies considerably. Unlike other SCID forms, 2 other options are available for ADA-SCID: enzyme replacement therapy (ERT) with pegylated bovine ADA, and autologous haematopoietic stem cell gene therapy (GT). Due to the rarity of the condition, the lack of large scale outcome studies, and availability of different treatments, guidance on treatment strategies is limited. We have reviewed the currently available evidence and together with our experience of managing this condition propose a consensus management strategy. Matched sibling donor transplants represent a successful treatment option with high survival rates and excellent immune recovery. Mismatched parental donor transplants have a poor survival outcome and should be avoided unless other treatments are unavailable. ERT and GT both show excellent survival, and therefore the choice between ERT, MUD transplant, or GT is difficult and dependent on several factors, including accessibility to the different modalities, response of patients to long-term ERT, and the attitudes of physicians and parents to the short- and potential long-term risks associated with different treatments. (Blood. 2009;114:3524-3532) C1 [Gaspar, H. Bobby] UCL Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, London WC1N 1EH, England. [Aiuti, Alessandro] San Raffaele Telethon Inst Gene Therapy, Milan, Italy. [Aiuti, Alessandro] Univ Roma Tor Vergata, Rome, Italy. [Porta, Fulvio] Osped Bambini Spedali Civili, Oncol Haematol & BMT Unit, Brescia, Italy. [Candotti, Fabio] NHGRI, Disorders Immun Sect, Natl Inst Hlth, Bethesda, MD 20892 USA. [Hershfield, Michael S.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Hershfield, Michael S.] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Notarangelo, Luigi D.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Notarangelo, Luigi D.] Childrens Hosp Boston, Manton Ctr Orphan Dis Res, Boston, MA USA. RP Gaspar, HB (reprint author), UCL Inst Child Hlth, Mol Immunol Unit, Ctr Immunodeficiency, 30 Guilford St, London WC1N 1EH, England. EM h.gaspar@ich.ucl.ac.uk RI Notarangelo, Luigi/F-9718-2016; AIUTI, ALESSANDRO/K-3918-2016 OI Notarangelo, Luigi/0000-0002-8335-0262; AIUTI, ALESSANDRO/0000-0002-5398-1717 FU National Human Genome Research Institute; National Institutes of Health; Fondazione Telethon; Great Ormond Street Hospital Biomedical Research Center FX F. C. was supported in part by funding from the National Human Genome Research Institute/National Institutes of Health intramural research program. A. A. has received grant support from the Fondazione Telethon. H. B. G is supported in part from the Great Ormond Street Hospital Biomedical Research Center. NR 51 TC 107 Z9 110 U1 2 U2 13 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 OCT 22 PY 2009 VL 114 IS 17 BP 3524 EP 3532 DI 10.1182/blood-2009-06-189209 PG 9 WC Hematology SC Hematology GA 509NK UT WOS:000271024500005 PM 19638621 ER PT J AU Kleinman, SH Glynn, SA Lee, TH Tobler, LH Schlumpf, KS Todd, DS Qiao, H Yu, MYW Busch, MP AF Kleinman, Steven H. Glynn, Simone A. Lee, Tzong-Hae Tobler, Leslie H. Schlumpf, Karen S. Todd, Deborah S. Qiao, Hannah Yu, Mei-ying W. Busch, Michael P. CA NHLBI REDS II TI A linked donor-recipient study to evaluate parvovirus B19 transmission by blood component transfusion SO BLOOD LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN ERYTHROVIRUS B19; HIGH-PURITY; INFECTION; DNA; PREVALENCE; INDIVIDUALS; EXPOSURE; PATIENT; VIRUS AB Parvovirus B19V infection can be a serious infection for hematology patients with underlying hemolysis or compromised erythropoiesis syndromes. Although case reports of B19V transmission by blood component transfusion (as contrasted to manufactured plasma derivatives) are rare, no studies have systematically determined a rate of transmission to recipients transfused with B19V DNA-positive components. We used a linked donor and recipient repository and a sensitive, quantitative B19V DNA polymerase chain reaction (PCR) assay to assess such transmission in B19V-susceptible (ie, anti-B19V immunoglobulin G [IgG] negative) recipients. We assessed 112 B19V DNA-positive components from 105 donors (of 12 529 tested donations) transfused into a population of surgical patients with a pretransfusion B19V IgG seroprevalence of 78%. We found no transmission to 24 susceptible recipients from transfusion of components with B19V DNA at concentrations less than 10(6) IU/mL (upper 95% confidence interval, 11.7%). We found an anamnestic IgG response in one pretransfusion seropositive recipient transfused with a component containing greater than 10(10) IU/mL B19V DNA. These findings show either that transmission from components with less than 10(6) IU/mL does not occur, or, if it does, it is an uncommon event. These data do not support the need to routinely screen blood donations with a sensitive B19V DNA nucleic acid assay. (Blood. 2009114:3677-3683) C1 [Kleinman, Steven H.; Schlumpf, Karen S.; Todd, Deborah S.; Qiao, Hannah] Westat Corp, Rockville, MD USA. [Kleinman, Steven H.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. [Glynn, Simone A.] NHLBI, Rockville, MD USA. [Lee, Tzong-Hae; Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. [Yu, Mei-ying W.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Kleinman, SH (reprint author), 1281 Rockcrest Ave, Victoria, BC V9A 4W4, Canada. EM skleinman@shaw.ca FU NHLBI REDS-II [N01-HB-47175, N01-HB-57181] FX This work was supported by NHLBI REDS-II (contracts N01-HB-47175 and N01-HB-57181). NR 37 TC 36 Z9 39 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 22 PY 2009 VL 114 IS 17 BP 3677 EP 3683 DI 10.1182/blood-2009-06-225706 PG 7 WC Hematology SC Hematology GA 509NK UT WOS:000271024500024 PM 19687508 ER PT J AU Tong, YX Melara, RD Rao, A AF Tong, Yunxia Melara, Robert D. Rao, Aparna TI P2 enhancement from auditory discrimination training is associated with improved reaction times SO BRAIN RESEARCH LA English DT Article DE ERPs; Auditory; P2; MMN; Reaction times; P3; Discrimination training; Oddball task ID MISMATCH NEGATIVITY; RECEPTIVE-FIELDS; EVOKED POTENTIALS; SPEECH SOUNDS; HUMAN BRAIN; CORTEX; PLASTICITY; FREQUENCY; SLEEP; COMPLEXITY AB This study examined the effects of training in a pure tone discrimination task on relations between behavioral performance and the magnitude of auditory event-related potentials (ERPs). Participants performed both passive (listening) and active (detecting) oddball tasks in a pretest and two posttests (1 and 9 weeks after training). Training produced a long-term benefit in both perceptual sensitivity and reaction times (RT). Training enhanced the amplitude of the P2 ERP component to both standards and deviants at both early and delayed posttests. importantly, P2 enhancement was strongly associated with discrimination RT, suggesting that experience facilitates rapid, preattentive access to perceptual representations. Training also elevated the mismatch negativity, possibly due to the strengthening of acoustic traces. Finally, training enhanced the amplitude of the P3 component to deviants across posttests, indicating a long-lasting effect of discrimination training on stimulus salience. Published by Elsevier B.V. C1 [Melara, Robert D.] CUNY City Coll, Dept Psychol, New York, NY 10031 USA. [Tong, Yunxia] NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. [Rao, Aparna] Univ Minnesota, Dept Speech Language Hearing Sci, Minneapolis, MN 55455 USA. RP Melara, RD (reprint author), CUNY City Coll, Dept Psychol, 138th St & Convent Ave,NAC 7-120, New York, NY 10031 USA. EM melara@ccny.ccny.edu FU American Speech-Language-Hearing Association FX The authors thank all three anonymous reviewers who provided excellent suggestions to improve this manuscript. This work was completed when all three authors were associated with Purdue University. Portions of this work were presented at the 12th annual meeting of the Cognitive Neuroscience Society in 2005. The third author gratefully acknowledges financial support received from the American Speech-Language-Hearing Association. NR 48 TC 28 Z9 28 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 22 PY 2009 VL 1297 BP 80 EP 88 DI 10.1016/j.brainres.2009.07.089 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 511NT UT WOS:000271173200009 PM 19651109 ER PT J AU Kwong, PD Mascola, JR Nabel, GJ AF Kwong, Peter D. Mascola, John R. Nabel, Gary J. TI Mining the B Cell Repertoire for Broadly Neutralizing Monoclonal Antibodies to HIV-1 SO CELL HOST & MICROBE LA English DT Editorial Material ID INDIVIDUALS AB Monoclonal antibodies that effectively neutralize HIV-1 have been widely sought, yet few have been isolated. Now, technological advances in sera evaluation, B cell stimulation, microneutralization, and antibody cloning have allowed Burton and colleagues to identify two broadly neutralizing monoclonal antibodies, PG9 and PG16, which provide insights for HIV vaccine design. C1 [Kwong, Peter D.; Mascola, John R.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM gary.nabel@nih.gov NR 10 TC 15 Z9 16 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD OCT 22 PY 2009 VL 6 IS 4 BP 292 EP 294 DI 10.1016/j.chom.2009.09.008 PG 3 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 512EQ UT WOS:000271227700002 PM 19837366 ER PT J AU Shelburne, CP Nakano, H St John, AL Chan, C McLachlan, JB Gunn, MD Staats, HF Abraham, SN AF Shelburne, Christopher P. Nakano, Hideki St John, Ashley L. Chan, Cheryl McLachlan, James B. Gunn, Michael D. Staats, Herman F. Abraham, Soman N. TI Mast Cells Augment Adaptive Immunity by Orchestrating Dendritic Cell Trafficking through Infected Tissues SO CELL HOST & MICROBE LA English DT Article ID LYMPH-NODES; BACTERIAL CLEARANCE; ESCHERICHIA-COLI; LANGERHANS CELLS; TNF-ALPHA; IN-VIVO; RESPONSES; MIGRATION; MICE; HYPERTROPHY AB Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the serum antibody response is significantly diminished and less protective following passive immunization in a urinary tract infection (UTI) model in wild-type mice. MCs were found to recruit large numbers of dendritic cells (DCs) into the infected tissue site, which eventually migrated into draining lymph nodes (DLNs) during a prolonged time course. This pattern of trafficking was facilitated by MC-generated TNF, which increased the expression of E-selectin on local blood vessels. Antibody blockade of E-selectin inhibited DC recruitment into the site of infection and DLNs and consequently impaired the primary humoral immune response. Thus, during infection, resident MCs contribute to the primary protective adaptive response through recruitment of DCs from the circulation into infected sites. C1 [Shelburne, Christopher P.; Chan, Cheryl; McLachlan, James B.; Staats, Herman F.; Abraham, Soman N.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [St John, Ashley L.; Gunn, Michael D.; Staats, Herman F.; Abraham, Soman N.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Gunn, Michael D.; Staats, Herman F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Abraham, Soman N.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. [Abraham, Soman N.] Duke Natl Univ Singapore, Grad Sch Med, Program Emerging Infect Dis, Singapore 169547, Singapore. [Nakano, Hideki] Natl Inst Environm Hlth Sci, Biol Res Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Shelburne, CP (reprint author), Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. EM cps4@duke.edu OI Gunn, Michael/0000-0003-4602-0667; Staats, Herman/0000-0003-1039-1087 FU National Institutes of Health [RO1-DK077159, R37-DK050814, R21-DK077307, R01-AI 50021]; Sandier Foundation for Asthma Research; NCRR/NIH [UL1RR024128] FX This work was supported by funds from the National Institutes of Health RO1-DK077159, R37-DK050814, R21-DK077307, and R01-AI 50021; the Sandier Foundation for Asthma Research; and the Duke University CTSA grant UL1RR024128 from NCRR/NIH. C.P.S. conducted most of the experiments and wrote most of the paper. M.D.G., H.F.S., H.N., J.B.M., and S.N.A. provided suggestions and discussion. A.L.S.J. and C.C. assisted with studies associated with DC trafficking to the lymph nodes. H.F.S., A.L.S.J., and S.N.A. helped with portions of the writing and editing of the manuscript. NR 31 TC 57 Z9 57 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD OCT 22 PY 2009 VL 6 IS 4 BP 331 EP 342 DI 10.1016/j.chom.2009.09.004 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 512EQ UT WOS:000271227700009 PM 19837373 ER PT J AU Mehlhop, E Nelson, S Jost, CA Gorlatov, S Johnson, S Fremont, DH Diamond, MS Pierson, TC AF Mehlhop, Erin Nelson, Steevenson Jost, Christiane A. Gorlatov, Sergey Johnson, Syd Fremont, Daved H. Diamond, Michael S. Pierson, Theodore C. TI Complement Protein C1q Reduces the Stoichiometric Threshold for Antibody-Mediated Neutralization of West Nile Virus SO CELL HOST & MICROBE LA English DT Article ID HUMANIZED MONOCLONAL-ANTIBODY; FC-GAMMA RECEPTORS; YELLOW-FEVER VIRUS; DENGUE VIRUS; DEPENDENT ENHANCEMENT; ENVELOPE GLYCOPROTEIN; FLAVIVIRUS INFECTION; ADAPTIVE IMMUNITY; CRYSTAL-STRUCTURE; ENCEPHALITIS-VIRUS AB Virus neutralization is governed by the number of antibodies that bind a virion during the cellular entry process. Cellular and serum factors that interact with antibodies have the potential to modulate neutralization potency. Although the addition of serum complement can increase the neutralizing activity of antiviral antibodies in vitro, the mechanism and significance of this augmented potency in vivo remain uncertain. Herein, we show that the complement component C1q increases the potency of antibodies against West Nile virus by modulating the stoichiometric requirements for neutralization. The addition of C1q does not result in virolysis but instead reduces the number of antibodies that must bind the virion to neutralize infectivity. For IgG subclasses that bind C1q avidly, this reduced stoichiometric threshold falls below the minimal number of antibodies required for antibody-dependent enhancement (ADE) of infection of cells expressing Fc-gamma receptors (CD32) and explains how C1q restricts the ADE of flavivirus infection. C1 [Mehlhop, Erin; Fremont, Daved H.; Diamond, Michael S.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Diamond, Michael S.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Nelson, Steevenson; Jost, Christiane A.; Pierson, Theodore C.] NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. [Gorlatov, Sergey; Johnson, Syd] MacroGenics Inc, Rockville, MD 20850 USA. RP Diamond, MS (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM diamond@borcim.wustl.edu; piersontc@mail.nih.gov FU Intramural Research Program of the National Institutes of Allergy and Infectious Diseases (NIAID); Pediatric Dengue Vaccine Initiative; National Institutes of Health (NIH) [U01 A1061373, R01 A1073755]; Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research [U54 AI057160] FX We thank J. Atkinson and members of our laboratories for helpful discussions; H. Hickman, H. Virgin, T. Kristie, and B. Moss for critical comments on the manuscript; and J. Bramson and M. Loeb for the convalescent human WNV sera. This work was supported by the Intramural Research Program of the National Institutes of Allergy and Infectious Diseases (NIAID) and grants from the Pediatric Dengue Vaccine Initiative (T.C.P. and M.S.D.), the National Institutes of Health (NIH) (grants U01 A1061373 and R01 A1073755 to M.S.D. and D.H.F.), and the Midwest Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research (U54 AI057160). S.J. generated huE16 IgG subclass-switch variants and characterized antibody affinity; E.M., C.A.J., and S.N. analyzed neutralization of mouse and human mAbs; S.N. performed the stoichiometry studies; S.J. and S.G. characterized antibody-affinity measurements by SPR; E.M. analyzed the in vivo protective capacity of E16 variants; E.M., S.N., D.H.F., M.S.D., and T.C.P. designed the studies, analyzed the data, and wrote the paper; all authors discussed the data and commented on the manuscript. S.G. and S.J. are employees of MacroGenics, a company that has licensed the E16 antibody from Washington University for commercial use. M.S.D. is a consultant for MacroGenics. NR 76 TC 42 Z9 42 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD OCT 22 PY 2009 VL 6 IS 4 BP 381 EP 391 DI 10.1016/j.chom.2009.09.003 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 512EQ UT WOS:000271227700013 PM 19837377 ER PT J AU Gomez, J Munayco, CV Arrasco, JC Suarez, L Laguna-Torres, VA Aguilar, PV Chowell, G Kochel, TJ AF Gomez, J. Munayco, C. V. Arrasco, J. C. Suarez, L. Laguna-Torres, V. A. Aguilar, P. V. Chowell, G. Kochel, T. J. TI PANDEMIC INFLUENZA IN A SOUTHERN HEMISPHERE SETTING: THE EXPERIENCE IN PERU FROM MAY TO SEPTEMBER, 2009 SO EUROSURVEILLANCE LA English DT Article ID A H1N1 AB This paper presents a description of Peru's experience with pandemic H1N1 influenza 2009. It is based on data from four main surveillance systems: a) ongoing sentinel surveillance of influenza-like illness cases with virological surveillance of influenza and other respiratory viruses; b) sentinel surveillance of severe acute respiratory infections and associated deaths; c) surveillance of acute respiratory infections in children under the age of five years and pneumonia in all age groups; and d) case and cluster surveillance. On 9 May 2009, the first confirmed case of pandemic H1N1 influenza in Peru was diagnosed in a Peruvian citizen returning from New York with a respiratory illness. By July, community transmission of influenza had been identified and until 27 September 2009, a total of 8,381 cases were confirmed. The incidence rate per 10,000 persons was 4.4 (in the 0-9 year-olds) and 4.1 (in the 10-19 year-olds). During epidemiological weeks (EW)* 26 to 37, a total of 143 fatal cases were notified (a case fatality of 1.71%, based on confirmed cases). The maximum peak in the number of cases was reached in EW 30 with 37 deaths. Currently, the impact of the pandemic in the Peruvian population has not been too severe, and fortunately, healthcare centres have not been overwhelmed. However, the future of this pandemic is uncertain and despite the fact that our country has not been seriously affected, we should be prepared for upcoming pandemic waves. C1 [Gomez, J.; Munayco, C. V.; Arrasco, J. C.; Suarez, L.] Peru Minist Hlth, Gen Directorate Epidemiol, Lima, Peru. [Laguna-Torres, V. A.; Aguilar, P. V.; Kochel, T. J.] US Naval Med Res Ctr Detachment, Lima, Peru. [Chowell, G.] Arizona State Univ, Sch Human Evolut & Social Change, Math & Computat Modeling Sci Ctr, Tempe, AZ USA. [Chowell, G.] NIH, Div Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Gomez, J (reprint author), Peru Minist Hlth, Gen Directorate Epidemiol, Lima, Peru. EM jgomez@dge.gob.pe RI Munayco, Cesar/G-9990-2013; Chowell, Gerardo/F-5038-2012; Valle, Ruben/A-7512-2013 OI Munayco, Cesar/0000-0001-7872-8913; Chowell, Gerardo/0000-0003-2194-2251; NR 17 TC 5 Z9 6 U1 1 U2 1 PU EUR CENTRE DIS PREVENTION & CONTROL PI STOCKHOLM PA TOMTEBODAVAGEN 11A, STOCKHOLM, 171 83, SWEDEN SN 1560-7917 J9 EUROSURVEILLANCE JI Eurosurveillance PD OCT 22 PY 2009 VL 14 IS 42 BP 22 EP 27 AR 19371 PG 6 WC Infectious Diseases SC Infectious Diseases GA 515IQ UT WOS:000271463800005 ER PT J AU Chi, YH Chen, ZJ Jeang, KT AF Chi, Ya-Hui Chen, Zi-Jie Jeang, Kuan-Teh TI The nuclear envelopathies and human diseases SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Review ID DREIFUSS MUSCULAR-DYSTROPHY; SPINDLE ASSEMBLY CHECKPOINT; GILFORD-PROGERIA-SYNDROME; ENCODING LAMIN A/C; FAMILIAL PARTIAL LIPODYSTROPHY; A-TYPE LAMINS; MEMBRANE PROTEIN; GENE-REGULATION; MISSENSE MUTATIONS; MAMMALIAN-CELLS AB The nuclear envelope (NE) consists of two membrane layers that segregate the nuclear from the cytoplasmic contents. Recent progress in our understanding of nuclear-lamina associated diseases has revealed intriguing connections between the envelope components and nuclear processes. Here, we review the functions of the nuclear envelope in chromosome organization, gene expression, DNA repair and cell cycle progression, and correlate deficiencies in envelope function with human pathologies. C1 [Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Chi, Ya-Hui; Chen, Zi-Jie] Natl Hlth Res Inst, Inst Cellular & Syst Med, Zhunan 35053, Taiwan. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ychi@nhri.org.tw; zchen@nhri.org.tw; kjeang@niaid.nih.gov RI Chi, Ya-Hui/B-1080-2010; Jeang, Kuan-Teh/A-2424-2008 FU NIAID/NIH; Intramural AIDS Targeted Anti-viral Program (IATAP); National Health Research Institutes, Taiwan [NHRI 98A1-CSPP14-014]; National Science Council, Taiwan [NSC 98-2320-B-400-009-MY3] FX Work in the authors' laboratories was supported in part by NIAID/NIH intramural funds, by the Intramural AIDS Targeted Anti-viral Program (IATAP), and by intramural grants to Y.-H.C. from the National Health Research Institutes, Taiwan (NHRI 98A1-CSPP14-014), and National Science Council, Taiwan (NSC 98-2320-B-400-009-MY3). NR 75 TC 17 Z9 17 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD OCT 22 PY 2009 VL 16 AR 96 DI 10.1186/1423-0127-16-96 PG 8 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 515GU UT WOS:000271456800001 PM 19849840 ER PT J AU Rai, G Sayed, AA Lea, WA Luecke, HF Chakrapani, H Prast-Nielsen, S Jadhav, A Leister, W Shen, M Inglese, J Austin, CP Keefer, L Arner, ESJ Simeonov, A Maloney, DJ Williams, DL Thomas, CJ AF Rai, Ganesha Sayed, Ahmed A. Lea, Wendy A. Luecke, Hans F. Chakrapani, Harinath Prast-Nielsen, Stefanie Jadhav, Ajit Leister, William Shen, Min Inglese, James Austin, Christopher P. Keefer, Larry Arner, Elias S. J. Simeonov, Anton Maloney, David J. Williams, David L. Thomas, Craig J. TI Structure Mechanism Insights and the Role of Nitric Oxide Donation Guide the Development of Oxadiazole-2-Oxides as Therapeutic Agents against Schistosomiasis SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID THIOREDOXIN GLUTATHIONE-REDUCTASE; MANSONI THIOREDOXIN; FUROXAN DERIVATIVES; S-NITROSYLATION; TROPICAL DISEASES; NO; SELENOCYSTEINE; PRAZIQUANTEL; RESISTANCE; INHIBITORS AB Schistosomiasis is a chronic parasitic disease affecting hundreds of millions of individuals worldwide. Current treatment depends on a single agent, praziquantel, raising concerns of emergence of resistant parasites. Here, we continue our explorations of an oxadiazole-2-oxide class of compounds we recently identified as inhibitors of thioredoxin glutathione reductase (TGR), a selenocysteine-containing flavoenzyme required by the parasite to maintain proper cellular redox balance. Through systematic evaluation of the core molecular structure of this chemotype, we define the essential pharmacophore, establish a link between the nitric oxide donation and TGR inhibition, determine the selectivity for this chemotype versus related reductase enzymes, and present evidence that these agents can be modified to possess appropriate drug metabolism and pharmacokinetic properties. The mechanistic link between exogenous NO donation and parasite injury is expanded and better defined. The results of these studies verify the utility of oxadiazole-2-oxides as novel inhibitors of TGR and as efficacious antischistosomal agents. C1 [Sayed, Ahmed A.; Williams, David L.] Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. [Rai, Ganesha; Lea, Wendy A.; Jadhav, Ajit; Leister, William; Shen, Min; Inglese, James; Austin, Christopher P.; Simeonov, Anton; Maloney, David J.; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. [Sayed, Ahmed A.] Ain Shams Univ, Dept Biochem, Cairo, Egypt. [Luecke, Hans F.] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Chakrapani, Harinath; Keefer, Larry] NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21702 USA. [Prast-Nielsen, Stefanie; Arner, Elias S. J.] Karolinska Inst, Dept Med Biochem & Biophys, Div Biochem, SE-17177 Stockholm, Sweden. [Williams, David L.] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. RP Williams, DL (reprint author), Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. EM david_l_williams@rush.edu; craigt@nhgri.nih.gov RI Arner, Elias/J-5832-2012; OI Arner, Elias/0000-0002-4807-6114; Prast-Nielsen, Stefanie/0000-0001-5877-7988 FU Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research; Intramural Research Program of the National Human Genome Research Institute; National Cancer Institute, and Center for Cancer Research; National Institute of Allergy and Infectious Diseases Schistosomiasis Resource Center at the Biomedical Research Institute (Rockville, Maryland) through NIAID [N01-AI-30026]; [AI065622] FX We thank Allison Peck for critical reading of this manuscript. This research was supported by the Molecular Libraries Initiative of the National Institutes of Health Roadmap for Medical Research, the Intramural Research Program of the National Human Genome Research Institute, National Cancer Institute, and Center for Cancer Research. Schistosome life stages used in this research were supplied in part by the National Institute of Allergy and Infectious Diseases Schistosomiasis Resource Center at the Biomedical Research Institute (Rockville, Maryland) through NIAID contract N01-AI-30026. This work was partially supported by grant AI065622. NR 64 TC 45 Z9 48 U1 2 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD OCT 22 PY 2009 VL 52 IS 20 BP 6474 EP 6483 DI 10.1021/jm901021k PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 505EE UT WOS:000270671200031 PM 19761212 ER PT J AU Mittal, J AF Mittal, Jeetain TI Using Compressibility Factor as a Predictor of Confined Hard-Sphere Fluid Dynamics SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID MOLECULAR-DYNAMICS; BEHAVIOR; LIQUIDS; SIMULATION; DIFFUSION; TRANSPORT; ENTROPY; SYSTEMS; ENERGY; PORES AB We Study the correlations between the diffusivity (or viscosity) and the compressibility factor of. bulk hard-sphere fluid as predicted by the ultralocal limit of the barrier hopping theory. Our specific aim is to determine if these correlations observed in the bulk equilibrium hard-sphere fluid call be used to predict the self-diffusivity of fluid confined between a slit-pore or a rectangular channel. In this work, we consider a single-component and a binary Mixture of hard spheres. To represent confining walls, we use purely reflecting hard walls and interacting square-well walls. Our results clearly show that the correspondence between the diffusivity and the compressibility factor can be used along, with the knowledge or the confined fluid's compressibility factor to predict its diffusivity with quantitative accuracy. Our analysis also suggests that a simple measure, the average fluid density, can be ail accurate predictor of confined fluid diffusivity for very tight confinements 2-3 particle diameters wide) at low to intermediate density conditions. Together, these results provide Further support for the idea that one call use robust connections between thermodynamic and dynamic quantities to predict dynamics of confined fluids from their thermodynamics, C1 [Mittal, Jeetain] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. [Mittal, Jeetain] Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. RP Mittal, J (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM jeetain@helix.nih.gov FU NIH, NIDDK FX It is my great pleasure to contribute this paper for an issue honoring Prof. Ted Davis as his work oil confined fluids has been a great source of inspiration for me. I also acknowledge the kind hospitality of Dr. Robert Best and the Department of Chemistry during, my stay at the University of Cambridge where a part of this paper was written. I thank Dr. Artur Adib for Supporting a postdoctoral fellowship. This research was supported by the Intramural Research Program of the NIH, NIDDK. This Study utilized the high-performance computational capabilities of the Biowulf PC/Linux Cluster at the National Institutes of Health, Bethesda, MD (http:H biowulf.nih.gov), and the NSF TeraGrid resources provided by TACC. NR 35 TC 6 Z9 7 U1 1 U2 9 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 OCT 22 PY 2009 VL 113 IS 42 BP 13800 EP 13804 DI 10.1021/jp902934x PG 5 WC Chemistry, Physical SC Chemistry GA 505EB UT WOS:000270670800017 PM 19702285 ER PT J AU Kmieciak, M Gowda, M Graham, L Godder, K Bear, HD Marincola, FM Manjili, MH AF Kmieciak, Maciej Gowda, Madhu Graham, Laura Godder, Kamar Bear, Harry D. Marincola, Francesco M. Manjili, Masoud H. TI Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID PERIPHERAL-BLOOD; BREAST-CANCER; PROTEIN; PROLIFERATION; INDUCTION; FREQUENCY; SCURFY; MOUSE AB Background: Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation. Methods: T cell activation was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte reaction ( MLR), and CD3/CD28 activation. T cell proliferation was performed using BrdU and CFSE staining. Flow cytometry was performed to determine Foxp3 expression, cell proliferation, viabilities and phenotype analyses of T cells. Results: Both CD4+ and CD8+ T cells expressed Foxp3 upon activation in vitro. Expression of Foxp3 remained more stable in CD4+CD25+ T cells compared to that in CD8+CD25+ T cells. The CD4+CD25+Foxp3+ T cells expressed CD44 and CD62L, showing their effector and memory phenotypes. Both FoxP3-responder T cells and CD4+FoxP3+ T cells underwent proliferation upon CD3/CD28 activation. Conclusion: Expression of Foxp3 does not necessarily convey regulatory function in human CD4+CD25+ T cells. Increased FoxP3 on CD44+ effector and CD44+CD62L+ memory T cells upon stimulation suggest the activation-induced regulation of FoxP3 expression. C1 [Kmieciak, Maciej; Manjili, Masoud H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Massey Canc Ctr, Richmond, VA 23284 USA. [Gowda, Madhu; Godder, Kamar] Virginia Commonwealth Univ, Dept Pediat, Massey Canc Ctr, Richmond, VA USA. [Graham, Laura; Bear, Harry D.] Virginia Commonwealth Univ, Dept Surg, Massey Canc Ctr, Richmond, VA USA. [Kmieciak, Maciej; Gowda, Madhu; Graham, Laura; Godder, Kamar; Bear, Harry D.; Marincola, Francesco M.; Manjili, Masoud H.] Virginia Commonwealth Univ, Dept Pathol, Massey Canc Ctr, Richmond, VA USA. [Marincola, Francesco M.] NIH, Dept Transfus Med, IDIS, Ctr Clin, Bethesda, MD 20892 USA. [Marincola, Francesco M.] NIH, CHI, Bethesda, MD 20892 USA. RP Manjili, MH (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Massey Canc Ctr, Richmond, VA 23284 USA. EM mkmieciak@vcu.edu; MSGowda@mcvh-vcu.edu; lgraham2@mcvh-vcu.edu; kgodder@mcvh-vcu.edu; hdbear@vcu.edu; FMarincola@cc.nih.gov; mmanjili@vcu.edu FU NIH [R01 CA104757]; Massey Cancer Center Pilot Project Program [646564]; VCU Massey Cancer Centre; Commonwealth Foundation for Cancer Research FX This work was supported by NIH R01 CA104757 grant ( M. H. Manjili) and Massey Cancer Center Pilot Project Program, 646564. We gratefully acknowledge the support of VCU Massey Cancer Centre and the Commonwealth Foundation for Cancer Research. NR 27 TC 59 Z9 60 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD OCT 22 PY 2009 VL 7 AR 89 DI 10.1186/1479-5876-7-89 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 516HD UT WOS:000271531900001 PM 19849846 ER PT J AU Sidransky, E Nalls, MA Aasly, JO Aharon-Peretz, J Annesi, G Barbosa, ER Bar-Shira, A Berg, D Bras, J Brice, A Chen, CM Clark, LN Condroyer, C De Marco, EV Durr, A Eblan, MJ Fahn, S Farrer, MJ Fung, HC Gan-Or, Z Gasser, T Gershoni-Baruch, R Giladi, N Griffith, A Gurevich, T Januario, C Kropp, P Lang, AE Lee-Chen, GJ Lesage, S Marder, K Mata, IF Mirelman, A Mitsui, J Mizuta, I Nicoletti, G Oliveira, C Ottman, R Orr-Urtreger, A Pereira, LV Quattrone, A Rogaeva, E Rolfs, A Rosenbaum, H Rozenberg, R Samii, A Samaddar, T Schulte, C Sharma, M Singleton, A Spitz, M Tan, EK Tayebi, N Toda, T Troiano, AR Tsuji, S Wittstock, M Wolfsberg, TG Wu, YR Zabetian, CP Zhao, Y Ziegler, SG AF Sidransky, E. Nalls, M. A. Aasly, J. O. Aharon-Peretz, J. Annesi, G. Barbosa, E. R. Bar-Shira, A. Berg, D. Bras, J. Brice, A. Chen, C. -M. Clark, L. N. Condroyer, C. De Marco, E. V. Duerr, A. Eblan, M. J. Fahn, S. Farrer, M. J. Fung, H. -C. Gan-Or, Z. Gasser, T. Gershoni-Baruch, R. Giladi, N. Griffith, A. Gurevich, T. Januario, C. Kropp, P. Lang, A. E. Lee-Chen, G. -J. Lesage, S. Marder, K. Mata, I. F. Mirelman, A. Mitsui, J. Mizuta, I. Nicoletti, G. Oliveira, C. Ottman, R. Orr-Urtreger, A. Pereira, L. V. Quattrone, A. Rogaeva, E. Rolfs, A. Rosenbaum, H. Rozenberg, R. Samii, A. Samaddar, T. Schulte, C. Sharma, M. Singleton, A. Spitz, M. Tan, E. -K. Tayebi, N. Toda, T. Troiano, A. R. Tsuji, S. Wittstock, M. Wolfsberg, T. G. Wu, Y. -R. Zabetian, C. P. Zhao, Y. Ziegler, S. G. TI Multicenter Analysis of Glucocerebrosidase Mutations in Parkinson's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LEWY BODY DISORDERS; GAUCHER-DISEASE; GENE-MUTATIONS; EARLY-ONSET; RISK-FACTOR; GBA; SUSCEPTIBILITY; MANIFESTATIONS; POLYMORPHISM; ASSOCIATION AB Background Recent studies indicate an increased frequency of mutations in the gene encoding glucocerebrosidase (GBA), a deficiency of which causes Gaucher's disease, among patients with Parkinson's disease. We aimed to ascertain the frequency of GBA mutations in an ethnically diverse group of patients with Parkinson's disease. Methods Sixteen centers participated in our international, collaborative study: five from the Americas, six from Europe, two from Israel, and three from Asia. Each center genotyped a standard DNA panel to permit comparison of the genotyping results across centers. Genotypes and phenotypic data from a total of 5691 patients with Parkinson's disease (780 Ashkenazi Jews) and 4898 controls (387 Ashkenazi Jews) were analyzed, with multivariate logistic-regression models and the Mantel-Haenszel procedure used to estimate odds ratios across centers. Results All 16 centers could detect two GBA mutations, L444P and N370S. Among Ashkenazi Jewish subjects, either mutation was found in 15% of patients and 3% of controls, and among non-Ashkenazi Jewish subjects, either mutation was found in 3% of patients and less than 1% of controls. GBA was fully sequenced for 1883 non-Ashkenazi Jewish patients, and mutations were identified in 7%, showing that limited mutation screening can miss half the mutant alleles. The odds ratio for any GBA mutation in patients versus controls was 5.43 across centers. As compared with patients who did not carry a GBA mutation, those with a GBA mutation presented earlier with the disease, were more likely to have affected relatives, and were more likely to have atypical clinical manifestations. Conclusions Data collected from 16 centers demonstrate that there is a strong association between GBA mutations and Parkinson's disease. C1 [Sidransky, E.; Eblan, M. J.; Samaddar, T.; Tayebi, N.; Ziegler, S. G.] NHGRI, Sect Mol Neurogenet, Med Genet Branch, Bethesda, MD 20892 USA. [Nalls, M. A.; Bras, J.; Samii, A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Wolfsberg, T. G.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Aasly, J. O.] St Olavs Hosp, Dept Neurol, Trondheim, Norway. [Aasly, J. O.] Norwegian Univ Sci & Technol, Dept Neurosci, N-7034 Trondheim, Norway. [Aharon-Peretz, J.] Technion Israel Inst Technol, Cognit Neurol & Movement Disorder Unit, Haifa, Israel. [Gershoni-Baruch, R.] Technion Israel Inst Technol, Human Genet Rambam Med Ctr, Haifa, Israel. [Gershoni-Baruch, R.] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. [Rosenbaum, H.] Technion Israel Inst Technol, Dept Hematol, IL-31096 Haifa, Israel. [Rosenbaum, H.] Technion Israel Inst Technol, Dept Bone Marrow Transplant, IL-31096 Haifa, Israel. [Nicoletti, G.; Quattrone, A.] Magna Graecia Univ Catanzaro, Dept Med Sci, Inst Neurol, Catanzaro, Italy. [Annesi, G.; De Marco, E. V.; Nicoletti, G.; Quattrone, A.] CNR, Inst Neurol Sci, Cosenza, Italy. [Barbosa, E. R.; Spitz, M.] Univ Sao Paulo, Sch Med, Dept Neurol, Movement Disorders Unit, Sao Paulo, Brazil. [Pereira, L. V.; Rozenberg, R.] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Mol Genet Lab, Sao Paulo, Brazil. [Bar-Shira, A.; Gan-Or, Z.; Orr-Urtreger, A.] Tel Aviv Univ, Genet Inst, IL-69978 Tel Aviv, Israel. [Giladi, N.; Gurevich, T.; Mirelman, A.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, Movement Disorders Unit,Parkinson Ctr, IL-69978 Tel Aviv, Israel. [Gan-Or, Z.; Giladi, N.; Gurevich, T.; Orr-Urtreger, A.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Berg, D.; Gasser, T.; Schulte, C.; Sharma, M.] Univ Tubingen, Dept Neurodegenerat Dis, Hertie Inst Clin Brain Res, Tubingen, Germany. [Bras, J.; Oliveira, C.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal. [Januario, C.; Oliveira, C.] Univ Coimbra Hosp, Neurol Serv, Coimbra, Portugal. [Brice, A.; Condroyer, C.; Duerr, A.; Lesage, S.] Univ Paris 06, INSERM, Ctr Rech,Inst Cerveau & Moelle Epiniere, Unite Mixte Rech S679, Paris, France. [Brice, A.; Duerr, A.] Grp Hosp Pitie Salpetriere, AP HP, F-75634 Paris, France. [Brice, A.; Duerr, A.] Grp Hosp Pitie Salpetriere, Dept Genet & Cytogenet, F-75634 Paris, France. [Chen, C. -M.; Fung, H. -C.; Wu, Y. -R.] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Neurol, Taipei, Taiwan. [Clark, L. N.; Marder, K.] Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA. [Clark, L. N.] Columbia Univ Coll Phys & Surg, Ctr Human Genet, New York, NY 10032 USA. [Clark, L. N.] Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. [Fahn, S.; Marder, K.; Ottman, R.] Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. [Marder, K.] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Marder, K.; Ottman, R.] Columbia Univ Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. [Ottman, R.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Ottman, R.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Farrer, M. J.] Mayo Clin, Coll Med, Dept Neurosci, Neurogenet Lab, Jacksonville, FL 32224 USA. [Griffith, A.] Evergreen Hosp Med Ctr, Booth Gardner Parkinsons Care Ctr, Kirkland, WA USA. [Kropp, P.] Univ Rostock, Inst Med Psychol, Rostock, Germany. [Rolfs, A.] Univ Rostock, Albrecht Kossel Inst Neuroregenerat, Rostock, Germany. [Wittstock, M.] Univ Rostock, Dept Neurol, Rostock, Germany. [Lang, A. E.] Toronto Western Hosp, Movement Disorders Ctr, Div Neurol, Dept Med, Toronto, ON M5T 2S8, Canada. [Rogaeva, E.] Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON, Canada. [Lee-Chen, G. -J.] Natl Taiwan Normal Univ, Dept Life Sci, Taipei, Taiwan. [Mata, I. F.; Samii, A.; Zabetian, C. P.] VA Puget Sound Hlth Care Syst, Parkinsons Dis & Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Mata, I. F.; Samii, A.; Zabetian, C. P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Mitsui, J.; Tsuji, S.] Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo, Japan. [Mizuta, I.; Toda, T.] Kobe Univ, Grad Sch Med, Div Neurol & Mol Brain Sci, Kobe, Hyogo 657, Japan. [Tan, E. -K.] Singapore Gen Hosp, Natl Inst Neurosci, Singapore 0316, Singapore. [Tan, E. -K.] Duke NUS Grada Med Sch, Singapore, Singapore. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, Rm 1A213,35 Convent Dr, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov RI Bras, Jose/D-3366-2009; Bras, Jose/A-1428-2011; Singleton, Andrew/C-3010-2009; Mitsui, Jun/B-5455-2012; Pereira, Lygia/C-1049-2012; Kropp, Peter/B-8132-2012; Barbosa, Egberto/G-7763-2012; Ottman, Ruth/O-2371-2013; QUATTRONE, Aldo/A-6734-2016; OI Gan-Or, Ziv/0000-0003-0332-234X; Zabetian, Cyrus/0000-0002-7739-4306; Mitsui, Jun/0000-0001-7425-4765; Pereira, Lygia/0000-0002-0002-725X; QUATTRONE, Aldo/0000-0003-2001-957X; Schulte, Claudia/0000-0003-4006-1265; Oliveira, Catarina/0000-0001-6942-4328; DEMARCO, ELVIRAVALERIA/0000-0002-4947-8481 FU National Institutes of Health [Z01AG000957-05]; National Institute of Neurological Disorders and Stroke and the National Center for Research Resources [NS050487, NS060113, NS40256]; Parkinson's Disease Foundation; Department of Veterans Affairs, Seattle; German National Genome Network, German Ministry for Education and Research [01GS08134]; French Parkinson's Disease Genetics Study Group; Duke-National University of Singapore (NUS) Graduate Medical School, National Medical Research Council, Biomedical Research Council, Singapore Millennium Foundation; SingHealth, Singapore General Hospital, National Neuroscience Institute; Tel Aviv Sourasky Medical Center Grant of Excellence; Wolfson and Kahn Foundations; Portuguese Fundacao para a Ciencia e a Tecnologia; National Science Council, Executive Yuan, Taiwan [NSC-95-2314-B-182A-061]; Ministry of Education, Culture, Sports, Science and Technology of Japan FX Supported in part by the Intramural Research Programs of NHGRI and the National Institute on Aging (project Z01AG000957-05), National Institutes of Health; grants from the National Institute of Neurological Disorders and Stroke and the National Center for Research Resources (NS050487, NS060113, and NS40256); grants from the Parkinson's Disease Foundation; a Merit Review Award from the Department of Veterans Affairs, Seattle; a grant from the German National Genome Network, German Ministry for Education and Research (01GS08134); a grant from the French Parkinson's Disease Genetics Study Group; a grant from the Duke-National University of Singapore (NUS) Graduate Medical School, National Medical Research Council, Biomedical Research Council, Singapore Millennium Foundation; a grant from SingHealth, Singapore General Hospital, National Neuroscience Institute; the Tel Aviv Sourasky Medical Center Grant of Excellence; grants from the Wolfson and Kahn Foundations; a grant from the Portuguese Fundacao para a Ciencia e a Tecnologia; a grant from the National Science Council, Executive Yuan, Taiwan (NSC-95-2314-B-182A-061); and a Grant-in-Aid for Scientific Research on Priority Areas, Applied Genomics, and Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. NR 44 TC 550 Z9 558 U1 4 U2 29 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 OCT 22 PY 2009 VL 361 IS 17 BP 1651 EP 1661 DI 10.1056/NEJMoa0901281 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 508YW UT WOS:000270977400007 PM 19846850 ER PT J AU Abu-Arish, A Kalab, P Ng-Kamstra, J Weis, K Fradin, C AF Abu-Arish, Asmahan Kalab, Petr Ng-Kamstra, Josh Weis, Karsten Fradin, Cecile TI Spatial Distribution and Mobility of the Ran GTPase in Live Interphase Cells SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE CORRELATION SPECTROSCOPY; LASER-SCANNING MICROSCOPE; NUCLEAR-PORE COMPLEXES; LIVING CELLS; NUCLEOCYTOPLASMIC TRANSPORT; CONFOCAL MICROSCOPE; BINDING PROTEIN; IMPORT; RCC1; TRANSLOCATION AB The GTPase Ran is a key regulator of molecular transport through nuclear pore complex (NPC) channels. To analyze the role of Ran in its nuclear transport function, we used several quantitative fluorescence techniques to follow the distribution and dynamics of an enhanced yellow fluorescent protein (EYFP)-Ran in HeLa cells. The diffusion coefficient of the majority of EYFP-Ran molecules throughout the cells corresponded to an unbound state, revealing the remarkably dynamic Ran regulation. Although we observed no significant immobile Ran populations in cells, similar to 10% of the cytoplasmic EYFP-Ran and 30% of the nuclear EYFP-Ran exhibited low mobility indicative of molecular interactions. The high fraction of slow nuclear EYFP-Ran reflects the expected numerous interactions of nuclear RanGTP with nuclear transport receptors. However, it is not high enough to support retention mechanisms as the main cause for the observed nuclear accumulation of Ran. The highest cellular concentration of EYFP-Ran was detected at the nuclear envelope, corresponding to similar to 200 endogenous Ran molecules for each NPC, and exceeding the currently estimated NPC channel transport capacity. Together with the relatively long residence time of EYFP-Ran at the nuclear envelope (33 +/- 14 ms), these observations suggest that only a fraction of the Ran concentrated at NPCs transits through NPC channels. C1 [Abu-Arish, Asmahan; Fradin, Cecile] McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada. [Ng-Kamstra, Josh; Fradin, Cecile] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8S 4M1, Canada. [Kalab, Petr] NCI, NIH, Bethesda, MD 20892 USA. [Kalab, Petr; Weis, Karsten] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Fradin, C (reprint author), McMaster Univ, Dept Phys & Astron, Hamilton, ON L8S 4M1, Canada. EM fradin@physics.mcmaster.ca RI Fradin, Cecile/D-9302-2011; Weis, Karsten/F-5719-2011; Kalab, Petr/B-2478-2009 OI Weis, Karsten/0000-0001-7224-925X; FU Natural Sciences and Engineering Research Council of Canada FX This work was funded by the Natural Sciences and Engineering Research Council of Canada. C. F. is the recipient of a Canada Research Chair. NR 56 TC 11 Z9 11 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT 21 PY 2009 VL 97 IS 8 BP 2164 EP 2178 DI 10.1016/j.bpj.2009.07.055 PG 15 WC Biophysics SC Biophysics GA 507YM UT WOS:000270892000007 PM 19843449 ER PT J AU Reider, A Barker, SL Mishra, SK Im, YJ Maldonado-Baez, L Hurley, JH Traub, LM Wendland, B AF Reider, Amanda Barker, Sarah L. Mishra, Sanjay K. Im, Young Jun Maldonado-Baez, Lymarie Hurley, James H. Traub, Linton M. Wendland, Beverly TI Syp1 is a conserved endocytic adaptor that contains domains involved in cargo selection and membrane tubulation SO EMBO JOURNAL LA English DT Article DE adaptor; endocytosis; F-BAR; mu HD; Syp1 ID CLATHRIN-COATED PITS; SACCHAROMYCES-CEREVISIAE; MEDIATED ENDOCYTOSIS; ACTIN CYTOSKELETON; SIGNALING PATHWAY; BINDING SEQUENCE; BAR PROTEINS; IN-VITRO; YEAST; CURVATURE AB Internalization of diverse transmembrane cargos from the plasma membrane requires a similarly diverse array of specialized adaptors, yet only a few adaptors have been characterized. We report the identification of the muniscin family of endocytic adaptors that is conserved from yeast to human beings. Solving the structures of yeast muniscin domains confirmed the unique combination of an N-terminal domain homologous to the crescent-shaped membrane-tubulating EFC/F-BAR domains and a C-terminal domain homologous to cargo-binding mu homology domains (mu HDs). In vitro and in vivo assays confirmed membrane-tubulation activity for muniscin EFC/F-BAR domains. The mu HD domain has conserved interactions with the endocytic adaptor/scaffold Ede1/eps15, which influences muniscin localization. The transmembrane protein Mid2, earlier implicated in polarized Rho1 signalling, was identified as a cargo of the yeast adaptor protein. These and other data suggest a model in which the muniscins provide a combined adaptor/membrane-tubulation activity that is important for regulating endocytosis. The EMBO Journal (2009) 28, 3103-3116. doi: 10.1038/emboj. 2009.248; Published online 27 August 2009 C1 [Reider, Amanda; Barker, Sarah L.; Maldonado-Baez, Lymarie; Wendland, Beverly] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Mishra, Sanjay K.; Traub, Linton M.] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. [Im, Young Jun; Hurley, James H.] NIH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Wendland, B (reprint author), Johns Hopkins Univ, Dept Biol, 144 Mudd Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM bwendland@jhu.edu FU U. S. DOE, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]; NIH [R01 GM60979, R01 DK53249, GM07231]; Ford Foundation Diversity Fellowship FX We thank Rejji Kuruvilla, Mark Van Doren, Trina Schroer, Marnie Halpern, and members of the Wendland laboratory for comments on the paper, Nathan Wright for technical support, members of the Hurley laboratory for advice and support during BW sabbatical, and J Michael McCaffery for the electron microscopy experiments. We also thank Daniel Kloer for helping with the Syp1 mu HD density map and R Blake Hill for helping with early attempts to generate an Syp1 mHD threaded structure model. The JHU Integrated Imaging Center was instrumental for all of the microscopy work. Use of the APS was supported by the U. S. DOE, Basic Energy Sciences, Office of Science, under Contract No. W-31-109-Eng-38. Crystallographic coordinates have been deposited in the RCSB protein data bank with accession numbers 3G9G and 3G9H. We also acknowledge our funding sources (BW, NIH R01 GM60979; LT, NIH R01 DK53249; JHH, Intramural Program of the NIH (NIDDK); AR, NIH Training Grant GM07231; LMB, Ford Foundation Diversity Fellowship). NR 62 TC 86 Z9 89 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 21 PY 2009 VL 28 IS 20 BP 3103 EP 3116 DI 10.1038/emboj.2009.248 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509II UT WOS:000271008200005 PM 19713939 ER PT J AU Minneci, PC Deans, KJ Natanson, C AF Minneci, Peter C. Deans, Katherine J. Natanson, Charles TI Corticosteroid Therapy for Severe Sepsis and Septic Shock SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID METAANALYSIS C1 [Minneci, Peter C.; Deans, Katherine J.] Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. [Natanson, Charles] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Minneci, PC (reprint author), Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. EM minneci@email.chop.edu NR 5 TC 5 Z9 6 U1 0 U2 3 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 OCT 21 PY 2009 VL 302 IS 15 BP 1643 EP 1643 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 508NX UT WOS:000270941200010 PM 19843895 ER PT J AU Chew, EY AF Chew, Emily Y. TI Laser Photocoagulation and Intravitreal Injection of Triamcinolone for Retinal Vein Occlusions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MACULAR EDEMA SECONDARY; STANDARD-CARE; EFFICACY; SAFETY; EYE AB Objective: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). Methods: Multicenter, randomized, clinical trial of 271 participants. Main Outcome Measure: Gain in visual acuity letter score of 15 or more from baseline to month 12. Results: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.8-14.1; P=.001) and 5.0 times greater in 4-mg group than the observation group (OR, 5.0; 95% CI, 1.8-14.4; P=.001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0, 95% CI, 0.5-2.1; P=.97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. Conclusions: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice: Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. C1 NEI, NIH, CRC, Bethesda, MD 20892 USA. RP Chew, EY (reprint author), NEI, NIH, CRC, Bldg 10,Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 10 TC 2 Z9 2 U1 0 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 OCT 21 PY 2009 VL 302 IS 15 BP 1693 EP 1695 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 508NX UT WOS:000270941200025 PM 19856489 ER PT J AU Mustata, M Capone, R Jang, H Arce, FT Ramachandran, S Lal, R Nussinov, R AF Mustata, Mirela Capone, Ricardo Jang, Hyunbum Arce, Fernando Teran Ramachandran, Srinivasan Lal, Ratnesh Nussinov, Ruth TI K3 Fragment of Amyloidogenic beta(2)-Microglobulin Forms Ion Channels: Implication for Dialysis Related Amyloidosis SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; FORMATION IN-VITRO; SOLID-STATE NMR; FIBRIL FORMATION; BETA-PROTEIN; 3D STRUCTURE; MEMBRANE DISRUPTION; ALZHEIMERS-DISEASE; LIPID-BILAYERS; PORE FORMATION AB beta(2)-microglobulin (beta(2)m) amyloid deposits are linked to dialysis-related amyloidosis (DRA) in hemodialysis patients The mechanism by which beta(2)m causes DRA is not understood. It is also unclear whether only the full-length beta(2)m induces pathophysiology or if proteolytic fragments are sufficient for inducing this effect. Ser20-Lys41 (K3) is a digestion fragment of full-length beta(2)m Solid state NMR (ssNMR) combined with X-ray diffraction and atomic force microscopy (AFM) revealed the characteristic oligomeric amyloid conformation of the U-turn beta-strand-turn-beta-strand motif stacked in parallel and stabilized by intermolecular interactions also shown by A beta(9) (40)/A beta(17) (42) and the CA150 WW domain. Here we use the K3 U-turn atomic coordinates and molecular dynamic (MID) simulations to model K3 channels in the membrane Consistent with previous AFM imaging of other amyloids that show channel-like structures in the membrane, in the simulations K3 also forms ion channels with 3-6 loosely attached mobile subunits. We carry out AFM, single channel electrical recording, and fluorescence imaging experiments, AFM images display 3D ion channel topography with shapes, morphologies, and dimensions consistent with the theoretical model Electrical conductance measurements indicate multiple single channel conductances, suggesting that various K3 oligomer sizes can constitute the channel structure Fluorescence measurements in kidney cells show channel-mediated cell calcium uptake These results suggest that the beta(2)m-induced DRA can be mediated by ion channels formed by its K3 fragment Because the beta-strand-turn-beta-strand motif appears to be a universal amyloid feature, its ability to form ion channels further suggests that the motif may play a generic role in toxicity C1 [Mustata, Mirela; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. [Mustata, Mirela; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Jang, Hyunbum; Nussinov, Ruth] SAIC Frederick Inc, Ctr Canc Res Nanobiol, NCI Frederick, Frederick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Lal, R (reprint author), Univ Chicago, Ctr Nanomed, Chicago, IL 60637 USA. RI Capone, Ricardo/D-1943-2010; Ramachandran, Srinivasan/G-5300-2010 OI Capone, Ricardo/0000-0002-7327-9837; Ramachandran, Srinivasan/0000-0002-4912-0279 FU National Cancer Institute; National Institutes of Health [N01-CO-12400] FX This project has been funded by the National Cancer Institute, National Institutes of Health, Under contract No N01-CO-12400, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research R L. acknowledges support from (lie NIH (NIA) extra-mural program H J did the modeling, M M and F T A contributed to AFM experiments. R C. did the electrophysiology. S R and M M contributed to cell work This study utilized the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health. Bethesda, MD (http Hbiowult'nih.gov) NR 73 TC 33 Z9 33 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 21 PY 2009 VL 131 IS 41 BP 14938 EP 14945 DI 10.1021/ja9049299 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 512SV UT WOS:000271271800068 PM 19824733 ER PT J AU Brown, LM Devesa, SS Chow, WH AF Brown, Linda Morris Devesa, Susan S. Chow, Wong-Ho TI Response: Re: Incidence of Adenocarcinoma of the Esophagus Among White Americans by Sex, Stage, and Age SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 [Brown, Linda Morris] RTI Int, Stat & Epidemiol Div, Rockville, MD 20852 USA. [Brown, Linda Morris; Devesa, Susan S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brown, LM (reprint author), RTI Int, Stat & Epidemiol Div, 6110 Execut Blvd,Ste 902, Rockville, MD 20852 USA. EM lindabrown@rti.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 21 PY 2009 VL 101 IS 20 BP 1429 EP 1429 DI 10.1093/jnci/djp305 PG 1 WC Oncology SC Oncology GA 510RJ UT WOS:000271108300013 ER PT J AU Mai, V McCrary, QM Sinha, R Glei, M AF Mai, Volker McCrary, Quintece M. Sinha, Rashmi Glei, Michael TI Associations between dietary habits and body mass index with gut microbiota composition and fecal water genotoxicity: an observational study in African American and Caucasian American volunteers SO NUTRITION JOURNAL LA English DT Article ID 16S RIBOSOMAL-RNA; COLON-CANCER RISK; IN-SITU HYBRIDIZATION; INTESTINAL MICROBIOTA; HUMAN FECES; DNA-DAMAGE; OLIGONUCLEOTIDE PROBES; EXTENSIVE SET; COMET ASSAY; OBESITY AB Background: African Americans (AA) suffer from an increased incidence and mortality of colorectal cancer (CRC). Environmental exposures including dietary habits likely contribute to a high burden of CRC, however, data on the dietary habits of AA is sparse. Diet might change the composition and the activities of the intestinal microbiota, in turn affecting fecal genotoxicity/mutagenicity that is thought to be associated with carcinogenesis. Methods: We assessed dietary habits by food frequency questionnaire and by food records in 52 AA and 46 CA residents of the Eastern Shore of MD. Fecal microbiota composition was determined using 16S rRNA based methods and fecal genotoxicity measured using the Comet assay. Results: AA reported an increased intake of heterocyclic amines and a decreased dietary intake of vitamins including vitamin D (p < 0.05) that correlated with differences in fecal microbiota composition but not fecal genotoxicity. Intake of dietary fiber, calcium, total fat and heterocyclic amines correlated with differences in microbiota composition. Total bacterial counts/g of stool and raw counts of Bacteroides were increased in AA. In contrast to a previous study, BMI was not associated with proportions of Bacteroides. Conclusion: Dietary habits of African Americans, including increased HCA intake and decreased vitamin D intake might at least partially contribute to CRC through modifications of gut microbiota composition that result in changes of the intestinal milieu. C1 [Mai, Volker] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. [McCrary, Quintece M.] Univ Maryland Eastern Shore, Princess Anne, MD USA. [Sinha, Rashmi] NCI, DCEG, Bethesda, MD 20892 USA. [Glei, Michael] Univ Jena, Inst Nutr, Dept Nutr Toxicol, Jena, Germany. RP Mai, V (reprint author), Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32611 USA. EM vmai@ufl.edu; qmmccrary@umes.edu; sinhar@exchange.nih.gov; Michael.Glei@uni-jena.de FU Maryland Special Population Network; ACS [MRSGT CCE-107301] FX This work was supported by a pilot grant from the Maryland Special Population Network. Work in the lab of Dr. Mai is supported by ACS grant MRSGT CCE-107301. We thank B. L. Zobel (deceased 2008) for discussion regarding study design and interpretation of the findings. We thank Dr. C. Boushey for help with the food record data. NR 51 TC 60 Z9 65 U1 3 U2 22 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2891 J9 NUTR J JI Nutr. J. PD OCT 21 PY 2009 VL 8 AR 49 DI 10.1186/1475-2891-8-49 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 517QV UT WOS:000271632900001 PM 19845958 ER PT J AU Zach, L Stall, B Ning, H Ondos, J Arora, B Uma, S Miller, RW Citrin, D Camphausen, K AF Zach, Leor Stall, Bronwyn Ning, Holly Ondos, John Arora, Barbara Uma, Shankavaram Miller, Robert W. Citrin, Deborah Camphausen, Kevin TI A dosimetric comparison of four treatment planning methods for high grade glioma SO RADIATION ONCOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; NEURAL STEM-CELLS; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; NERVOUS-SYSTEM MALIGNANCIES; GLIOBLASTOMA-MULTIFORME; INTEGRATED BOOST; CONVENTIONAL RADIOTHERAPY; SUBVENTRICULAR ZONE; BRAIN; IMRT AB Background: High grade gliomas (HGG) are typically treated with a combination of surgery, radiotherapy and chemotherapy. Three dimensional (3D) conformal radiotherapy treatment planning is still the main stay of treatment for these patients. New treatment planning methods suggest better dose distributions and organ sparing but their clinical benefit is unclear. The purpose of the current study was to compare normal tissue sparing and tumor coverage using four different radiotherapy planning methods in patients with high grade glioma. Methods: Three dimensional conformal (3D), sequential boost IMRT, integrated boost (IB) IMRT and Tomotherapy (TOMO) treatment plans were generated for 20 high grade glioma patients. T1 and T2 MRI abnormalities were used to define GTV and CTV with 2 and 2.5 cm margins to define PTV1 and PTV2 respectively. Results: The mean dose to PTV2 but not to PTV1 was less then 95% of the prescribed dose with IB and IMRT plans. The mean doses to the optic chiasm and the ipsilateral globe were highest with 3D plans and least with IB plans. The mean dose to the contralateral globe was highest with TOMO plans. The mean of the integral dose (ID) to the brain was least with the IB plan and was lower with IMRT compared to 3D plans. The TOMO plans had the least mean D10 to the normal brain but higher mean D50 and D90 compared to IB and IMRT plans. The mean D10 and D50 but not D90 were significantly lower with the IMRT plans compared to the 3D plans. Conclusion: No single treatment planning method was found to be superior to all others and a personalized approach is advised for planning and treating high-grade glioma patients with radiotherapy. Integral dose did not reflect accurately the dose volume histogram (DVH) of the normal brain and may not be a good indicator of delayed radiation toxicity. C1 [Zach, Leor; Stall, Bronwyn; Ning, Holly; Ondos, John; Arora, Barbara; Uma, Shankavaram; Miller, Robert W.; Citrin, Deborah; Camphausen, Kevin] NCI, Radiat Oncol Branch, CRC, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, CRC, 10 Ctr Dr Bldg 10, Bethesda, MD 20892 USA. EM zachl@mail.nih.gov; stallb@mail.nih.gov; hning@mail.nih.gov; ondosj@mail.nih.gov; arorab@mail.nih.gov; uma@mail.nih.gov; rwmiller@mail.nih.gov; citrind@mail.nih.gov; camphauk@mail.nih.gov NR 22 TC 15 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PD OCT 21 PY 2009 VL 4 AR 45 DI 10.1186/1748-717X-4-45 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 517RW UT WOS:000271636000001 PM 19845946 ER PT J AU Maxhimer, JB Soto-Pantoja, DR Ridnour, LA Shih, HB DeGraff, WG Tsokos, M Wink, DA Isenberg, JS Roberts, DD AF Maxhimer, Justin B. Soto-Pantoja, David R. Ridnour, Lisa A. Shih, Hubert B. DeGraff, William G. Tsokos, Maria Wink, David A. Isenberg, Jeff S. Roberts, David D. TI Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of CD47 Signaling SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID NITRIC-OXIDE; ISCHEMIC TISSUE; CELL RESPONSES; IN-VIVO; RADIATION ONCOLOGY; IONIZING-RADIATION; BREAST-CANCER; THROMBOSPONDIN-1; RADIOTHERAPY; PHAGOCYTOSIS AB Radiation-induced damage of normal tissues restricts the therapeutic doses of ionizing radiation that can be delivered to tumors and thereby limits the effectiveness of radiotherapy. Thrombospondin-1 signaling through its cell surface receptor CD47 limits recovery from several types of stress, and mice lacking either gene are profoundly resistant to radiation injury. We describe strategies to protect normal tissues from radiation damage with antibodies to CD47 or thrombospondin-1, a CD47-binding peptide, or antisense suppression of CD47. A morpholino oligonucleotide targeting CD47 confers radioresistance to human endothelial cells in vitro and protects soft tissue, bone marrow, and tumor-associated leukocytes in irradiated mice. In contrast, CD47 suppression in mice bearing melanoma or squamous lung tumors before irradiation results in 89% and 71% smaller tumors, respectively. Thus, inhibition of CD47 signaling maintains the viability of normal tissues after irradiation while increasing the radiosensitivity of tumors. C1 [Maxhimer, Justin B.; Soto-Pantoja, David R.; Shih, Hubert B.; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Maxhimer, Justin B.] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21287 USA. [Ridnour, Lisa A.; DeGraff, William G.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Shih, Hubert B.] Howard Hughes Med Inst, Natl Inst Hlth Res Scholars Program, Bethesda, MD 20814 USA. [Isenberg, Jeff S.] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA 15261 USA. [Isenberg, Jeff S.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15261 USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU Intramural NIH HHS [ZIA SC009174-21, ZIA SC009172-21] NR 62 TC 44 Z9 44 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD OCT 21 PY 2009 VL 1 IS 3 AR 3ra7 DI 10.1126/scitranslmed.3000139 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 590AW UT WOS:000277196700003 PM 20161613 ER PT J AU Rebustini, IT Myers, C Lassiter, KS Surmak, A Szabova, L Holmbeck, K Pedchenko, V Hudson, BG Hoffman, MP AF Rebustini, Ivan T. Myers, Christopher Lassiter, Keyonica S. Surmak, Andrew Szabova, Ludmila Holmbeck, Kenn Pedchenko, Vadim Hudson, Billy G. Hoffman, Matthew P. TI MT2-MMP-Dependent Release of Collagen IV NC1 Domains Regulates Submandibular Gland Branching Morphogenesis SO DEVELOPMENTAL CELL LA English DT Article ID TYPE-1 MATRIX-METALLOPROTEINASE; GROWTH IN-VIVO; BASEMENT-MEMBRANE; EPITHELIAL MORPHOGENESIS; NONCOLLAGENOUS DOMAINS; CELL-PROLIFERATION; EGF; EXPRESSION; MICE; ANGIOGENESIS AB Proteolysis is essential during branching morphogenesis, but the roles of MT-MMPs and their proteolytic products are not clearly understood. Here, we discover that decreasing MT-MMP activity during submandibular gland branching morphogenesis decreases proliferation and increases collagen IV and MT-MMP expression. Specifically, reducing epithelial MT2-MMP profoundly decreases proliferation and morphogenesis, increases Col4a2 and intracellular accumulation of collagen IV, and decreases the proteolytic release of collagen IV NC1 domains. Importantly, we demonstrate the presence of collagen IV NC1 domains in developing tissue. Furthermore, recombinant collagen IV NC1 domains rescue branching morphogenesis after MT2-siRNA treatment, increasing MT-MMP and proproliferative gene expression via beta 1 integrin and PI3K-AKT signaling. Additionally, HBEGF also rescues MT2-siRNA treatment, increasing NC1 domain release, proliferation, and MT2-MMP and Hbegf expression. Our studies provide mechanistic insight into how MT2-MMP-dependent release of bioactive NC1 domains from collagen IV is critical for integrating collagen IV synthesis and proteolysis with epithelial proliferation during branching morphogenesis. C1 [Rebustini, Ivan T.; Myers, Christopher; Lassiter, Keyonica S.; Hoffman, Matthew P.] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Surmak, Andrew; Szabova, Ludmila; Holmbeck, Kenn] Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. [Pedchenko, Vadim; Hudson, Billy G.] Vanderbilt Univ, Med Ctr, Ctr Matrix Biol, Dept Med, Nashville, TN 37232 USA. [Pedchenko, Vadim; Hudson, Billy G.] Vanderbilt Univ, Med Ctr, Ctr Matrix Biol, Dept Pathol, Nashville, TN 37232 USA. [Pedchenko, Vadim; Hudson, Billy G.] Vanderbilt Univ, Med Ctr, Ctr Matrix Biol, Dept Biochem, Nashville, TN 37232 USA. RP Hoffman, MP (reprint author), Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Lab Cell & Dev Biol, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM mhoffman@mail.nih.gov FU National Institute of Dental and Craniofacial Research at the National Institutes of Health; National Institutes of Health [DK 18381] FX The authors would like to thank Harry Grant, Shelagh Powers, Hynda Kleinman, Sarah Knox, Vaishali Patel, and Thomas Bugge for the critical reading of this manuscript, and E Tian and Roberto Weigert for helpful discussions and the gifts of antibodies. The study was supported by the Intramural Research Program of the National Institute of Dental and Craniofacial Research at the National Institutes of Health and by the National Institutes of Health Grant DK 18381 (to B.G.H.). NR 57 TC 62 Z9 62 U1 0 U2 9 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 OCT 20 PY 2009 VL 17 IS 4 BP 482 EP 493 DI 10.1016/j.devcel.2009.07.016 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 511QL UT WOS:000271181400008 PM 19853562 ER PT J AU Kulldorff, M Huang, L Konty, K AF Kulldorff, Martin Huang, Lan Konty, Kevin TI A scan statistic for continuous data based on the normal probability model SO INTERNATIONAL JOURNAL OF HEALTH GEOGRAPHICS LA English DT Article ID NEW-YORK-CITY; INFANT-MORTALITY; SPATIAL-ANALYSIS; CLUSTER DETECTION; DISEASE; SURVEILLANCE; CANCER; SEGREGATION; OUTBREAK; RISK AB Temporal, spatial and space-time scan statistics are commonly used to detect and evaluate the statistical significance of temporal and/or geographical disease clusters, without any prior assumptions on the location, time period or size of those clusters. Scan statistics are mostly used for count data, such as disease incidence or mortality. Sometimes there is an interest in looking for clusters with respect to a continuous variable, such as lead levels in children or low birth weight. For such continuous data, we present a scan statistic where the likelihood is calculated using the the normal probability model. It may also be used for other distributions, while still maintaining the correct alpha level. In an application of the new method, we look for geographical clusters of low birth weight in New York City. C1 [Kulldorff, Martin] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Kulldorff, Martin] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Huang, Lan] NCI, Bethesda, MD 20892 USA. [Konty, Kevin] New York City Dept Hlth & Mental Hyg, New York, NY USA. RP Kulldorff, M (reprint author), Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. EM martin_kulldorff@hms.harvard.edu; lan.huang@fda.hhs.gov; kkonty@health.nyc.gov RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 FU NICHD NIH HHS [R01 HD048852, R01HD048852] NR 35 TC 55 Z9 56 U1 3 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-072X J9 INT J HEALTH GEOGR JI Int. J. Health Geogr. PD OCT 20 PY 2009 VL 8 AR 58 DI 10.1186/1476-072X-8-58 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 515GH UT WOS:000271455400001 PM 19843331 ER PT J AU Antonarakis, ES Heath, EI Walczak, JR Nelson, WG Fedor, H De Marzo, AM Zahurak, ML Piantadosi, S Dannenberg, AJ Gurganus, RT Baker, SD Parnes, HL DeWeese, TL Partin, AW Carducci, MA AF Antonarakis, Emmanuel S. Heath, Elisabeth I. Walczak, Janet R. Nelson, William G. Fedor, Helen De Marzo, Angelo M. Zahurak, Marianna L. Piantadosi, Steven Dannenberg, Andrew J. Gurganus, Robin T. Baker, Sharyn D. Parnes, Howard L. DeWeese, Theodore L. Partin, Alan W. Carducci, Michael A. TI Phase II, Randomized, Placebo-Controlled Trial of Neoadjuvant Celecoxib in Men With Clinically Localized Prostate Cancer: Evaluation of Drug-Specific Biomarkers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROLIFERATIVE INFLAMMATORY ATROPHY; CYCLOOXYGENASE-2 COX-2 INHIBITORS; FAMILIAL ADENOMATOUS POLYPOSIS; RADICAL PROSTATECTOMY; RADIATION-THERAPY; OXIDATIVE STRESS; CELLS; RISK; CARCINOMA AB Purpose Cyclooxygenase-2 (COX-2) is a potential pharmacologic target for the prevention of various malignancies, including prostate cancer. We conducted a randomized, double-blind trial to examine the effect of celecoxib on drug-specific biomarkers from prostate tissue obtained at prostatectomy. Patients and Methods Patients with localized prostate cancer and Gleason sum >= 7, prostate-specific antigen (PSA) >= 15 ng/mL, clinical stage T2b or greater, or any combination with greater than 45% risk of capsular penetration were randomly assigned to celecoxib 400 mg by mouth twice daily or placebo for 4 to 6 weeks before prostatectomy. The primary end point was the difference in prostatic prostaglandin levels between the two groups. Secondary end points were differences in COX-1 and -2 expressions; oxidized DNA bases; and markers of proliferation, apoptosis and angiogenesis. Tissue celecoxib concentrations also were measured. Tertiary end points were drug safety and compliance. Results Seventy-three patients consented, and 64 were randomly assigned and included in the intention-to-treat analysis. There were no treatment differences in any of the primary or secondary outcomes. Multivariable regression revealed that tumor tissue had significantly lower COX-2 expression than benign prostatic tissue (P = .01) and significantly higher levels of the proliferation marker Ki-67 (P < .0001). Celecoxib was measurable in prostate tissue of patients on treatment, demonstrating that celecoxib reached its target. Celecoxib was safe and resulted in only grade 1 toxicities. Conclusion Treatment with 4 to 6 weeks of celecoxib had no effect on intermediate biomarkers of prostate carcinogenesis, despite the achievement of measurable tissue levels. We caution against using celecoxib 400 mg twice daily as a preventive agent for prostate cancer in additional studies. C1 Johns Hopkins, James Buchanan Brady Urol Inst, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Samuel Oschin Comprehens Canc Inst, Los Angeles, CA USA. Weill Cornell Med Coll, New York, NY USA. RP Carducci, MA (reprint author), Johns Hopkins Sch Med, Prostate Canc Res Program, Sidney Kimmel Comprehens Canc Ctr, CRB1 1M59,1650 Orleans St, Baltimore, MD 21231 USA. EM carducci@jhmi.edu RI Antonarakis, Emmanuel/E-4550-2011 FU National Cancer Institute [N01-CN-95000-46] FX Supported by National Cancer Institute Grant No. N01-CN-95000-46 (M.A.C.) and by Pfizer (M.A.C). NR 52 TC 37 Z9 37 U1 0 U2 1 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 OCT 20 PY 2009 VL 27 IS 30 BP 4986 EP 4993 DI 10.1200/JCO.2009.21.9410 PG 8 WC Oncology SC Oncology GA 507SN UT WOS:000270875100013 PM 19720908 ER PT J AU Chadburn, A Chiu, A Lee, JY Chen, X Hyjek, E Banham, AH Noy, A Kaplan, LD Sparano, JA Bhatia, K Cesarman, E AF Chadburn, Amy Chiu, April Lee, Jeannette Y. Chen, Xia Hyjek, Elizabeth Banham, Alison H. Noy, Ariela Kaplan, Lawrence D. Sparano, Joseph A. Bhatia, Kishor Cesarman, Ethel TI Immunophenotypic Analysis of AIDS-Related Diffuse Large B-Cell Lymphoma and Clinical Implications in Patients From AIDS Malignancies Consortium Clinical Trials 010 and 034 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; DOSE-ADJUSTED EPOCH; GERMINAL CENTER; GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; INFERIOR SURVIVAL; PREDICT SURVIVAL; ACTIVATION AB Purpose Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis. Patients and Methods We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts. Results The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL. Conclusion These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates. C1 [Cesarman, Ethel] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10065 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Albert Einstein Comprehens Canc Ctr, New York, NY USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Oxford, Dept Clin Lab Sci, Oxford, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. NCI, NIH, Washington, DC USA. RP Cesarman, E (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 1300 York Ave, New York, NY 10065 USA. EM ecesarm@med.cornell.edu RI Banham, Alison/B-2966-2009; OI Banham, Alison/0000-0002-3197-273X FU National Cancer Institute [CA-121947]; Leukaemia Research Fund, United Kingdom FX Supported by Grant No. CA-121947 from the National Cancer Institute to the AIDS Malignancy Consortium. A. H. B. is supported by the Leukaemia Research Fund, United Kingdom. NR 46 TC 39 Z9 39 U1 0 U2 0 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 OCT 20 PY 2009 VL 27 IS 30 BP 5039 EP 5048 DI 10.1200/JCO.2008.20.5450 PG 10 WC Oncology SC Oncology GA 507SN UT WOS:000270875100020 PM 19752343 ER EF