FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hazarika, M Jiang, XP Liu, Q Lee, SL Ramchandani, R Garnett, C Orr, MS Sridhara, R Booth, B Leighton, JK Timmer, W Harapanhalli, R Dagher, R Justice, R Pazdur, R AF Hazarika, Maitreyee Jiang, Xiaoping Liu, Qi Lee, Shwu-Luan Ramchandani, Roshni Garnett, Christine Orr, Micheal S. Sridhara, Rajeshwari Booth, Brian Leighton, John K. Timmer, William Harapanhalli, Ravi Dagher, Ramzi Justice, Robert Pazdur, Richard TI Tasigna for chronic and accelerated phase Philadelphia chromosome-positive chronic myelogenous leukemia resistant to or intolerant of imatinib SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; KINASE DOMAIN MUTATIONS; BCR-ABL; SELECTIVE INHIBITOR; MESYLATE CAPSULES; TYROSINE KINASE; APPROVAL; MECHANISMS; NILOTINIB; BIOLOGY AB Purpose: This Food and Drug Administration (FDA) approval report describes the data and analyses leading to the approval by the FDA of nilotinib (Tasigna, AMN-107; Novartis Pharmaceuticals Corporation), an inhibitor of Bcr-AbI tyrosine kinase, for the treatment of chronic-phase (CP) and accelerated-phase (AP) chronic myelogenous leukemia (CIVIL) resistant to or intolerant of imatinib. Experimental Design: The FDA approval of the efficacy and safety of nilotinib was based on the results of an ongoing single-arm, open-label, phase 2 clinical trial. The primary end point for CML-CP was unconfirmed major cytogenetic response. The efficacy end point for CML-AP was confirmed hematologic response. Results: The major cytogenetic response rate in 232 evaluable CP patients was 40% (95% confidence interval, 33%, 46%). The hematologic response rate in 105 evaluable AP patients was 26% (95% confidence interval, 18%, 35%). The median duration of response has not been reached for both CML-CP and CML-AP responding patients. In CML-CP patients, the common serious drug-related adverse reactions were thrombocytopenia and neutropenia. In CML-AP patients, the common serious drug-related adverse reactions were thrombocytopenia, neutropenia, pneumonia, febrile neutropenia, leukopenia, intracranial hemorrhage, elevated lipase, and pyrexia. Nilotinib prolongs the QT interval and sudden deaths have been reported; these risks and appropriate risk minimization strategies are described in a boxed warning on the labeling. Conclusions: On October 29, 2007, the U.S. FDA granted accelerated approval to nilotinib (Tasigna) for use in the treatment of CP and AP Philadelphia chromosome positive CML in adult patients resistant to or intolerant of prior therapy that included imatinib. C1 [Hazarika, Maitreyee; Lee, Shwu-Luan; Leighton, John K.; Dagher, Ramzi; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. [Jiang, Xiaoping; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. [Liu, Qi; Lee, Shwu-Luan; Ramchandani, Roshni; Garnett, Christine; Orr, Micheal S.; Booth, Brian] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Timmer, William; Harapanhalli, Ravi] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Dagher, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 2389, Silver Spring, MD 20993 USA. EM ramzi.dagher@fda.hhs.gov NR 15 TC 85 Z9 89 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 SEP 1 PY 2008 VL 14 IS 17 BP 5325 EP 5331 DI 10.1158/1078-0432.CCR-08-0308 PG 7 WC Oncology SC Oncology GA 347UG UT WOS:000259166000004 PM 18765523 ER PT J AU Huang, SM Temple, R AF Huang, S-M Temple, R. TI Is this the drug or dose for you? Impact and consideration of ethnic factors in global drug development, regulatory review, and clinical practice SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 [Huang, S-M] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Temple, R.] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM shiewmei.huang@fda.hhs.gov; robert.temple@fda.hhs.gov NR 24 TC 68 Z9 69 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2008 VL 84 IS 3 BP 287 EP 294 DI 10.1038/clpt.2008.144 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339MW UT WOS:000258582700001 PM 18714314 ER PT J AU Lesko, LJ AF Lesko, L. J. TI The critical path of warfarin dosing: Finding an optimal dosing strategy using pharmacogenetics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID BLEEDING COMPLICATIONS; ANTICOAGULATION; CYP2C9; GENOTYPE; THERAPY; VARIANTS; AMERICAN; RISK; CARE C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM lawrence.lesko@fda.hhs.gov NR 19 TC 47 Z9 50 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2008 VL 84 IS 3 BP 301 EP 303 DI 10.1038/clpt.2008.133 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339MW UT WOS:000258582700002 PM 18714317 ER PT J AU Li, JS Baker-Smith, CM Smith, PB Hasselblad, V Murphy, MD Califf, RM Benjamin, DK AF Li, J. S. Baker-Smith, C. M. Smith, P. B. Hasselblad, V. Murphy, M. D. Califf, R. M. Benjamin, D. K., Jr. TI Racial differences in blood pressure response to angiotensin-converting enzyme inhibitors in children: A meta-analysis SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HYPERTENSIVE CHILDREN; DOSE-RESPONSE; DOUBLE-BLIND; PHARMACOKINETICS; TRIAL; LISINOPRIL; FOSINOPRIL; ENALAPRIL; SAFETY AB Angiotensin-converting enzyme (ACE) inhibitors are frequently used to treat hypertension in children.(1) ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and cardiac hypertrophic properties of angiotensin II and the vasodilatory and natriuretic properties of bradykinin; they also alter the metabolism of other vasoactive substances.(2) Through these mechanisms, ACE inhibitors decrease systemic vascular resistance and promote natriuresis without increasing heart rate. This study evaluated the results of six trials of ACE inhibitors in children, using meta-analytic techniques to estimate the effect of race on blood pressure response. C1 [Li, J. S.; Smith, P. B.; Murphy, M. D.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. [Li, J. S.; Baker-Smith, C. M.; Smith, P. B.; Benjamin, D. K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Li, J. S.; Baker-Smith, C. M.; Smith, P. B.; Hasselblad, V.; Califf, R. M.; Benjamin, D. K., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Hasselblad, V.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Califf, R. M.] Duke Univ, Dept Med, Durham, NC USA. RP Li, JS (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. EM jennifer.li@duke.edu RI Smith, Phillip/I-5565-2014 FU National Institute of Child Health and Human Development [1U10-HD45962-04]; National Center for Research Resources and National Institutes of Health [1UL1RR024128-01] FX Norman Stockbridge of the Division of Cardiovascular and Renal Products, Center for Drug Evaluation and Research, FDA, provided access to study data. The views expressed are those of the authors. No official endorsement by the FDA is provided or should be inferred. The Duke Clinical Research Institute was the coordinating center for the fosinopril trial. J.S.L. and D.K.B. received support from National Institute of Child Health and Human Development grant 1U10-HD45962-04 and the FDA.J.S.L., P.B.S., R.M.C., and D.K.B. received support from the National Center for Research Resources and National Institutes of Health grant 1UL1RR024128-01. NR 17 TC 11 Z9 12 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2008 VL 84 IS 3 BP 315 EP 319 DI 10.1038/clpt.2008.113 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339MW UT WOS:000258582700009 PM 18548000 ER PT J AU Yasuda, SU Zhang, L Huang, SM AF Yasuda, S. U. Zhang, L. Huang, S-M TI The role of ethnicity in variability in response to drugs: Focus on clinical pharmacology studies SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID GENETIC POLYMORPHISMS; AFRICAN-AMERICAN; INTERETHNIC DIFFERENCES; HEALTHY-INDIVIDUALS; NICOTINE METABOLISM; EUROPEAN-AMERICAN; ASIAN SUBJECTS; POPULATIONS; FREQUENCIES; PHARMACOKINETICS AB Ethnicity is one factor that may account for the observed differences in both pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, resulting in variability in response to drug therapy. Given that the applicability of clinical study results to the treatment of an individual patient is a critical consideration in a physician's choice of drug therapy, drug development should seek to ensure that a clinical pharmacologic evaluation includes a population that is representative of the target therapeutic population. Ethnic diversity in drug response with respect to safety and efficacy and the resulting differences in recommended doses have been well described for some drugs. Some of these differential responses may be related to the pharmacogenomics of a particular drug. Pharmacogenomic techniques have recently enjoyed widespread use in studies of drug exposure and response. The clinical relevance of variability in drug response due to pharmacogenomics of drug-metabolizing enzymes was considered at a September 2004 workshop cosponsored by the US Food and Drug Administration (FDA), Johns Hopkins University, and the Pharmaceutical Research and Manufacturers of America (http://www.fda.gov/cder/Offices/OCPB/workshops.htm).(1). C1 [Yasuda, S. U.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zhang, L.; Huang, S-M] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Yasuda, SU (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM sally.yasuda@fda.hhs.gov NR 36 TC 118 Z9 123 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 2008 VL 84 IS 3 BP 417 EP 423 DI 10.1038/clpt.2008.141 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 339MW UT WOS:000258582700022 PM 18615002 ER PT J AU Burckart, GJ AF Burckart, Gilbert J. TI Pharmacogenomics: The Key to Improved Drug Therapy in Transplant Patients SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; PROTEIN-2 GENETIC POLYMORPHISMS; TACROLIMUS PHARMACOKINETICS; LIVER-TRANSPLANTATION; RENAL-TRANSPLANTATION; ORGAN-TRANSPLANTATION; ABCB1 POLYMORPHISMS; CYP3A5; RECIPIENTS; CYCLOSPORINE AB The current success in organ transplantation has been brought about by immunosuppressive therapy. Improvements in transplant outcome using these drugs have stalled, and an understanding of the pharmacogenomics of immunosuppressive dosing and response holds the greatest promise for advancing the use of these agents. C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bldg 51,Room 3184,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM gilbert.burckart@fda.hhs.gov NR 33 TC 3 Z9 4 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 2008 VL 28 IS 3 BP 411 EP + DI 10.1016/j.cll.2008.09.004 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 390QC UT WOS:000262177800005 PM 19028260 ER PT J AU Luecke, RH Pearce, BA Wosilait, WD Doerge, DR Slikker, W Young, JF AF Luecke, Richard H. Pearce, Bruce A. Wosilait, Walter D. Doerge, Daniel R. Slikker, William, Jr. Young, John F. TI Windows (R) based general PBPK/PD modeling software SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE PBPK/PD; pharmacokinetic model; pharmacodynamic model; Windows (R) software; postnatal growth; human; dog; rat; mouse ID PHARMACOKINETIC MODEL; METHOTREXATE PHARMACOKINETICS; METABOLITES; HUMANS; MICE; TRICHLOROETHYLENE; DISPOSITION; ACID; RATS AB A physiologically based pharmacokinetic (PBPK) model and program (called PostNatal) was developed which focuses on postnatal growth. Algorithms defining organ/tissue growth curves from birth through adulthood for male and female humans, dogs, rats, and mice are utilized to calculate the appropriate weight and blood flow for the internal organs/tissues. This Windows (R) based program is actually four linked PBPK models with each PBPK model acting independently or totally integrated with the others through metabolism by first order or Michaelis-Menten kinetics. Data fitting is accomplished by a weighted least square regression algorithm. The model includes linkages for the simulation of pharmacodynamic (PD) effects. Published by Elsevier Ltd. C1 [Young, John F.] US FDA, Natl Ctr Toxicol Res, DHHS, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Luecke, Richard H.] Univ Missouri, Dept Chem Engn, Columbia, MO 65231 USA. [Pearce, Bruce A.] US FDA, Natl Ctr Toxicol Res, DHHS, Off Informat Technol, Jefferson, AR 72079 USA. [Wosilait, Walter D.] Univ Missouri, Dept Pharmacol, Columbia, MO 65231 USA. [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, DHHS, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, DHHS, Off Director, Jefferson, AR 72079 USA. RP Young, JF (reprint author), US FDA, Natl Ctr Toxicol Res, DHHS, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM john.young@fda.hhs.gov NR 20 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD SEP PY 2008 VL 38 IS 9 BP 962 EP 978 DI 10.1016/j.compbiomed.2008.06.001 PG 17 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 357NF UT WOS:000259851800002 PM 18657803 ER PT J AU Kurkjian, C Kummar, S Murgo, AJ AF Kurkjian, Carlo Kummar, Shivaani Murgo, Anthony J. TI DNA Methylation: Its Role in Cancer Development and Therapy SO CURRENT PROBLEMS IN CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CPG ISLAND METHYLATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; ABERRANT PROMOTER METHYLATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENES; RENAL-CELL CARCINOMA; HELICOBACTER-PYLORI ERADICATION; LOW-DOSE 5-AZA-2'-DEOXYCYTIDINE C1 [Kurkjian, Carlo] NCI, Div Canc Treatment & Diagnosis, Adv Dev Therapeut Training Program, Bethesda, MD USA. [Kummar, Shivaani] Yale Univ, Ctr Canc, New Haven, CT USA. [Kummar, Shivaani] NCI, Med Oncol Branch, Ctr Clin Res, Bethesda, MD USA. [Kummar, Shivaani] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA. [Murgo, Anthony J.] Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. [Murgo, Anthony J.] W Virginia Univ, Sch Med, Morgantown, WV 26506 USA. [Murgo, Anthony J.] W Virginia Univ, Hematol Oncol Sect, Morgantown, WV 26506 USA. [Murgo, Anthony J.] US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Kurkjian, C (reprint author), NCI, Div Canc Treatment & Diagnosis, Adv Dev Therapeut Training Program, Bethesda, MD USA. NR 256 TC 28 Z9 35 U1 0 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-0272 EI 1535-6345 J9 CURR PROB CANCER JI Curr. Probl. Cancer PD SEP-OCT PY 2008 VL 32 IS 5 BP 185 EP 235 DI 10.1016/j.currproblcancer.2008.08.002 PG 51 WC Oncology SC Oncology GA 360ZL UT WOS:000260097200002 PM 18926281 ER PT J AU Mielke, LA Elkins, K Starr, R Hilton, DJ Tsichlis, P O'Shea, JJ Watford, WT AF Mielke, Lisa A. Elkins, Karen Starr, Robyn Hilton, Douglas J. Tsichlis, Philip O'Shea, John J. Watford, Wendy T. TI Receptor and cell-specific function of MAP3K8/TPL2 in innate immune signaling and cytokine production SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Mielke, Lisa A.; O'Shea, John J.; Watford, Wendy T.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Mielke, Lisa A.; Hilton, Douglas J.] Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic, Australia. [Mielke, Lisa A.] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia. [Elkins, Karen] US FDA, CEBR, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20857 USA. [Starr, Robyn] St Vincents Inst, Signal Transduct Lab, Melbourne, Vic, Australia. [Tsichlis, Philip] Tufts Univ New England Med Ctr, Mol Oncol Res Inst, Boston, MA USA. RI Hilton, Douglas/C-7250-2013 OI Hilton, Douglas/0000-0002-7698-2392 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 314 EP 314 DI 10.1016/j.cyto.2008.07.381 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900346 ER PT J AU Pedras-Vasconcelos, JA Puig, M Sauder, C Wolbert, C Ovanesov, M Verthelyi, D AF Pedras-Vasconcelos, Joao A. Puig, Montserrat Sauder, Christian Wolbert, Candie Ovanesov, Mikhail Verthelyi, Daniela TI Immunotherapy with CpG oligonucleotides and antibodies to TNF alpha rescue neonatal mice from lethal arena Virus-induced meningoencephalitis SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Pedras-Vasconcelos, Joao A.; Puig, Montserrat; Verthelyi, Daniela] US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. [Sauder, Christian; Wolbert, Candie] US FDA, Div Viral Prod, CBER, Bethesda, MD 20014 USA. [Ovanesov, Mikhail] JHU Sch Med, Div Neurobiol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 321 EP 321 DI 10.1016/j.cyto.2008.07.411 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900375 ER PT J AU Baron, S Poast, J Suzuki, F Kobayashi, M Clouse, K Bacot, S Tiffany, L Lankford, C Boekhoudt, G Morrow, A Fey, S Schmeisser, H Bekisz, J Zoon, K AF Baron, Samuel Poast, Joyce Suzuki, Fujio Kobayashi, Makiko Clouse, Kathleen Bacot, Sylvia Tiffany, Linda Lankford, Carla Boekhoudt, Gunther Morrow, Angel Fey, Samuel Schmeisser, Hana Bekisz, Joseph Zoon, Kathryn TI Innate immunity: Preclinical study of eradication of tumor cells by IFN-activated monocytes in vitro and in vivo SO CYTOKINE LA English DT Meeting Abstract CT 7th Joint Conference of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytoklin-Research CY OCT 12-16, 2008 CL Montreal, CANADA SP Int Cytokine Soc, Int Soc Interferon & Cytokin Res C1 [Baron, Samuel; Poast, Joyce] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX USA. [Baron, Samuel; Suzuki, Fujio; Kobayashi, Makiko] Univ Texas Med Branch, Dept Internal Med, Galveston, TX USA. [Clouse, Kathleen; Bacot, Sylvia; Tiffany, Linda; Lankford, Carla; Boekhoudt, Gunther] US FDA, Bethesda, MD 20014 USA. [Baron, Samuel; Morrow, Angel; Fey, Samuel; Schmeisser, Hana; Bekisz, Joseph; Zoon, Kathryn] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD SEP PY 2008 VL 43 IS 3 BP 322 EP 322 DI 10.1016/j.cyto.2008.07.415 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 362QT UT WOS:000260212900379 ER PT J AU Agresti, C Tu, ZG Ng, C Yang, YS Liang, JF AF Agresti, Ciara Tu, Zhigang Ng, Charlene Yang, Yongsheng Liang, Jun F. TI Specific interactions between diphenhydramine and alpha-helical poly(glutamic acid) - A new ion-pairing complex for taste masking and pH-controlled diphenhydramine release SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE peptide; formulation; nanoparticles; controlled release; pH-sensitivity; taste masking ID ELECTRONIC TONGUE; EXCHANGE FIBERS; DRUG-DELIVERY; STABILITY; MICROENCAPSULATION; MICROSPHERES; TECHNOLOGIES AB Formation of drug/excipient complex through ionic interactions has proven to be very effective for both controlled release and taste masking. Unfortunately, the ionic interactions between drugs and small molecule excipients are usually weak, and the stability of the formed complexes can be greatly influenced by solution ionic strength. In this study, we explored to formulate diphenhydramine (DPH), a very bitter tasting drug, using small molecular weight and carboxyl group containing polymers. Studies showed that DPH interacted with alpha-helical poly(glutamic acid) specifically to produce DPH/poly(glutamic acid) complexes, mostly spherical in shape with a diameter of around 1.0 mu m. Other drugs with similar chemical structures as DPH, such as phenylephrine and pseudoephedrine, could not form complexes with poly(glutamic acid) or other polymers under the same conditions. Although DPH in DPH/poly(glutamic acid) complexes existed amorphously, it showed increased stability. In vitro studies using electronic tongue demonstrated that poly(glutamic acid) might be as effective as sucralose for DPH bitter taste blocking. In addition, DPH/poly(glutamic acid) complexes were not stable in neutral or weak acidic (pH > 5) environments and dissolved rapidly and completely. Therefore, DPH/poly(glutamic acid) complex may serve as a new formulation for taste masking and controlled DPH release in gastrointestinal tract. This is the first report that small molecule drugs can interact with peptides of specific secondary structures to form stable complexes. In addition to greatly expanded ion-pairing excipient pool, application of peptides in drug formulation may also solve the selectivity and stability problems faced by current small molecule excipients. (c) 2008 Elsevier B.V. All rights reserved. C1 [Agresti, Ciara; Tu, Zhigang; Liang, Jun F.] Stevens Inst Technol, Dept Chem & Chem Biol, Hoboken, NJ 07030 USA. [Ng, Charlene] McNeil Consumer Healthcare, Morris Plains, NJ USA. [Yang, Yongsheng] US FDA, Off Testing & Res, Silver Spring, MD USA. RP Liang, JF (reprint author), Stevens Inst Technol, Dept Chem & Chem Biol, Hoboken, NJ 07030 USA. EM jliang2@stevens.edu NR 28 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD SEP PY 2008 VL 70 IS 1 BP 226 EP 233 DI 10.1016/j.ejpb.2008.04.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 355XL UT WOS:000259742600025 PM 18514496 ER PT J AU Jia, YP Alayash, AI AF Jia, Yiping Alayash, Abdu I. TI Effects of (-)-epigallocatechin gallate on the redox reactions of human hemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE (-)-epigallocatechin gallate; blood substitutes; hemoglobin ID CROSS-LINKED HEMOGLOBIN; GREEN TEA EXTRACT; CARRIERS BLOOD SUBSTITUTES; OXIDE PRODUCING REACTIONS; NITRIC-OXIDE; OXYGEN CARRIERS; EPIGALLOCATECHIN GALLATE; HYDROGEN-PEROXIDE; (-)-EPICATECHIN GALLATE; METABOLIC-ACIDOSIS AB The toxicity of a cellular hemoglobin (Hb)-based therapeutics has been attributed in part to the uncontrolled oxidative reactions. A variety of antioxidant Strategies to ameliorate potential oxidative damage in vivo have been suggested. We have examined the effects of (-)-epigallocatechin gallate (EGCG), a green tea polyphenol compound widely regarded as a chain-breaking antioxidant. on the oxidative stability of diaspirin crosslinked Hb (DBBF) and its cytotoxic ferryl intermediate. DBBF (ferrous) was rapidly oxidized to the ferric form in the presence of EGCG relative to the normal spontaneous oxidation of this Hb. The fast elimination of ferrous Hb is probably due to the ability of EGCG to produce hydrogen peroxide (H2O2) as these reactions were almost completely reversed by the addition of catalase and superoxide dismutase to the reaction medium. EGCG, however, effectively reduced ferryl back to ferric Hb in a biphasic kinetic reaction at physiological pH. At acidic pH where the autoreduction of protonated ferryl Hb is enhanced, a monophasic reduction process of the ferry] heme is achieved. A balance between pro and antioxidant properties of EGCG should be taken into account if EGCG is used in combination therapy with redox active acellular Hbs. Published by Elsevier Inc. C1 [Jia, Yiping; Alayash, Abdu I.] US FDA, LBVB, CBER, Div Hematol, Bethesda, MD 20892 USA. RP Jia, YP (reprint author), US FDA, LBVB, CBER, Div Hematol, NIH Campus,8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM yiping.jia@fda.hhs.gov NR 68 TC 13 Z9 14 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 EI 1873-4596 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD SEP 1 PY 2008 VL 45 IS 5 BP 659 EP 666 DI 10.1016/j.freeradbiomed.2008.05.010 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 345KK UT WOS:000258995200015 PM 18539156 ER PT J AU Lee, HC Kioi, M Han, J Puri, RK Goodman, JL AF Lee, Hin C. Kioi, Mitomu Han, Jing Puri, Raj K. Goodman, Jesse L. TI Anaplasma phagocytophilum-induced gene expression in both human neutrophils and HL-60 cells SO GENOMICS LA English DT Article DE Anaplasma phagocytophilum; human granulocytic anaplasmosis; apoptosis; gene expression; neutrophils; HL-60 cells ID HUMAN GRANULOCYTIC EHRLICHIOSIS; TUMOR-NECROSIS-FACTOR; POLYMORPHONUCLEAR NEUTROPHILS; ENDOTHELIAL-CELLS; SELECTIN LIGAND; PROTEIN-KINASE; IN-VITRO; T-CELLS; APOPTOSIS; ACTIVATION AB Anaplasma phagocytophilum (Ap), the etiologic agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. We define and compare the spectra of host gene expression in response to Ap infection of human neutrophils and of HL-60 cells using long (70-mer)-oligonucleotide array technology. In addition to apoptosis-related genes, genes involved in signaling pathways, transcriptional regulation, immune response, host defense, cell adhesion, and cytoskeleton were modulated in neutrophils infected with Ap. Ap infection affected the same pathways in HL-60 cells but transcriptional changes occurred more slowly and in a reduced spectrum of genes. Gene expression changes detected by microarray were confirmed for randomly selected genes by QRT-PCR and Western blot studies. These studies demonstrate for the first time that the ERK pathway is activated in Ap-infected neutrophils and also define multiple pathways that are activated during intracellular Ap infection, which together serve to prolong the cell survival that is needed to allow bacterial replication and survival in neutrophils, which otherwise would rapidly apoptose. Published by Elsevier Inc. C1 [Lee, Hin C.; Kioi, Mitomu; Han, Jing; Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Goodman, Jesse L.] US FDA, Off Ctr Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Goodman, JL (reprint author), Stanford Univ, Dept Radiat Oncol, CCSR S,Room 1250,269 Campus Dr W, Stanford, CA 94305 USA. EM jesse.goodman@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 58 TC 21 Z9 23 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2008 VL 92 IS 3 BP 144 EP 151 DI 10.1016/j.ygeno.2008.05.005 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 342VP UT WOS:000258812000003 PM 18603403 ER PT J AU De Pascalis, R Taylor, BC Elkins, KL AF De Pascalis, Roberto Taylor, Betsy C. Elkins, Karen L. TI Diverse myeloid and lymphoid cell subpopulations produce gamma interferon during early innate immune responses to Francisella tularensis live vaccine strain SO INFECTION AND IMMUNITY LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; NATURAL-KILLER-CELLS; ANTIGEN-PRESENTING CELLS; NECROSIS-FACTOR-ALPHA; CD8(+) T-CELLS; IFN-GAMMA; IN-VIVO; DENDRITIC CELLS; HOST-DEFENSE; NK CELLS AB Francisella tularensis, a small gram-negative intracellular bacterium responsible for causing tularemia, is highly pathogenic and classified as a category A agent of bioterrorism. As for other intracellular pathogens, successful protective immune responses to Francisella tularensis require rapid and efficient induction of gamma interferon (IFN-gamma) production. Studies using intracellular bacteria such as Listeria monocytogenes as well as Francisella suggest that natural killer (NK) and T cells are important sources of IFN-gamma. However, comprehensive characterization of specific sources of IFN-gamma produced during Francisella infection in vivo remains incomplete, and depletion of NK cells before infection of mice with the F. tularensis live vaccine strain (LVS) has little impact on the course or outcome of infection. In this study, we determined the cell subpopulations that respond quickly to intradermal F. tularensis LVS infection of mice by producing IFN-gamma within hours to a few days. Splenic and liver lymphocytes were obtained from LVS-infected mice and analyzed for IFN-gamma mRNA by reverse transcription-PCR, for intracellular cytokine expression by multiparameter flow cytometry, and for ex vivo production of IFN-gamma protein by enzyme-linked immunosorbent assay. Cells producing IFN-gamma were readily detectable by day 3 after infection, and numbers progressively increased through days 5 to 7. Importantly, the cell types responsible for IFN-gamma production were much more varied than expected: these included not only NK cells and T cells, which might be predicted, but also other cells, including dendritic cells (DCs), "NK DCs," NK T cells, and neutrophils. Most importantly, since RAG-1 knockout mice appeared to exhibit a frequency of IFN-gamma-producing cells comparable to that of intact wild-type mice, early IFN-gamma production by innate immune cells does not depend on the presence of T or B cells. C1 [De Pascalis, Roberto; Elkins, Karen L.] US FDA, Ctr Biol Res & Evaluat, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. [Taylor, Betsy C.] Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP De Pascalis, R (reprint author), US FDA, Ctr Biol Res & Evaluat, Lab Mycobacterial Dis & Cellular Immunol, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM roberto.depascalis@fda.hhs.gov; karen.elkins@fda.hhs.gov FU DMID/NIAID/NIH FX We thank our colleagues Siobhan Cowley and Ronald Rabin for critical reviews of the manuscript.; This work was supported in part by an interagency agreement with DMID/NIAID/NIH.; We declare no conflict of interest or financial interests in this study. NR 55 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2008 VL 76 IS 9 BP 4311 EP 4321 DI 10.1128/IAI.00514-08 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 340TI UT WOS:000258667500053 PM 18573901 ER PT J AU Jacobson, AP Hammack, TS Andrews, WH AF Jacobson, Andrew P. Hammack, Thomas S. Andrews, Wallace H. TI Evaluation of Sample Preparation Methods for the Isolation of Salmonella from Alfalfa and Mung Bean Seeds with the Bacteriological Analytical Manual's Salmonella Culture Method SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ESCHERICHIA-COLI O157-H7; SPROUTS; INFECTIONS; OUTBREAK; GROWTH; SURVIVAL; CHLORINE AB Five pre-enrichment methods were evaluated for effectiveness with the U.S. Food and Drug Administration's Bacteriological Analytical Manual Salmonella culture method in recovering S. Stanley, S. Poona, and S. Muenchen from artificially contaminated alfalfa seeds, and S. Saintpaul, S. Anatum, and S. Infantis from artificially contaminated mung bean seeds. The methods included: (1) Soak.-Test portions were inoculated into pre-enrichment media; (2) Rinse.-Test portions were rinsed with pre-enrichment media, and the media was decanted from the test portions; (3) Rinsed seed.-Pre-enrichment media was added to the test portions that were rinsed in the rinse method; (4) Wet blend.-Test portions were blended with the pre-enrichment media; and (5) Dry blend.-Test portions were blended prior to pre-enrichment. The methods of pre-enrichment were also evaluated for effectiveness in recovering Pantoea agglomerans from alfalfa and mung bean seeds with a modified culture method for the recovery of Enterobacteriaceae from foods. The purpose of these studies was to provide a model for the recovery of Salmonella that may occur in seeds as a natural contaminant. The relative effectiveness of the soak method was consistently superior to the rinse method in isolating the selected Salmonella serovars from both seed types. Statistically, the rinsed seed method was as effective as the soak method in all trials, except 1 of 3, with S. Muenchen and alfalfa seeds (P > 0.05). The relative effectiveness of the methods in isolating P agglomerans from alfalfa and mung bean seeds was similar to that observed with the artificially contaminated test portions. The soak method was consistently the most effective method and the rinse method was consistently the most ineffective method. The rinsed seed, wet blend, and dry blend methods were also as effective as the soak method in all 3 trials with each seed type (P > 0.05). C1 [Jacobson, Andrew P.; Hammack, Thomas S.; Andrews, Wallace H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Jacobson, AP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM andrew.jacobson@fda.hhs.gov NR 29 TC 4 Z9 4 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2008 VL 91 IS 5 BP 1083 EP 1089 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 362XB UT WOS:000260229400011 PM 18980122 ER PT J AU Sokol, G Krasnow, R Knudsen, J Biade, S Cantilena, L AF Sokol, Gerald Krasnow, Ross Knudsen, James Biade, Siham Cantilena, Louis TI Investigational drug research and testicular/spermatocytic function ethical considerations SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 14-16, 2008 CL Philadelphia, PA SP Amer Coll Clin Pharmacol C1 [Sokol, Gerald] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Cantilena, Louis] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Sokol, Gerald; Krasnow, Ross; Knudsen, James; Biade, Siham] US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2008 VL 48 IS 9 MA 31 BP 1105 EP 1105 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 341MT UT WOS:000258719300035 ER PT J AU Lathers, CM Schraeder, PL Bungo, MW AF Lathers, C. M. Schraeder, P. L. Bungo, Michael W. TI Mystery of sudden death: Risk mechanisms SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 14-16, 2008 CL Philadelphia, PA SP Amer Coll Clin Pharmacol C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19104 USA. Univ Texas Houston, Sch Med, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2008 VL 48 IS 9 MA 43 BP 1108 EP 1108 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 341MT UT WOS:000258719300047 ER PT J AU Garber, EAE Walker, JL O'Brien, TW AF Garber, Eric A. E. Walker, Jennifer L. O'Brien, Thomas W. TI Detection of abrin in food using enzyme-linked immunosorbent assay and electrochemiluminescence technologies SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ABRUS-PRECATORIUS AGGLUTININ; TOXIC LECTINS; A-CHAINS; RICIN; SITE; MUTAGENESIS; SELECTION; PLANT; CELLS AB Abrin is a toxic ribosome-inactivating protein present in beans of Abrus precatorius, also known as rosary peas. The possibility that abrin could be used to adulterate food has made the development of assays for the detection of abrin a priority. Rabbit-derived polyclonal antibodies and mouse monoclonal antibodies were prepared against a mixture of abrin isozymes. The specificity and cross-reactivity of the antibodies were evaluated against a challenge library of 40 grains, nuts. legumes, and foods. An enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescence (ECL)-based assay were assembled and optimized. Polyclonal (capture) and polyclonal (detection) ELISAs, polyclonal and monoclonal ELISAs, and polyclonal and monoclonal ECL assays had limits of detection (LODs) of 0.1 to 0.5 ng/ml for abrin in buffer. The LOD for abrin dissolved into juices, dairy products, soda. chocolate drink, and condiments and analyzed with the ECL assay ranged from 0.1 to 0.5 ng/ml in the analytical sample. In contrast, the LODs for the ELISAs ranged from 0.5 to 10 ng/ml in the analytical sample. C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Walker, Jennifer L.; O'Brien, Thomas W.] Tetracore Inc, Rockville, MD 20850 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM eric.garber@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX We thank George Sigal. Ph.D., and Pamela Bruce-Staskal (Meso Scale Discovery) for providing the instrument and plates used in the study and for helpful discussions. The authors also thank Jingshu Wang (Tetracore, Inc.) for technical assistance and Vickery A. Brewer (FDA) for providing the material used to prepare the samples for examining antibody specificity and cross-reactivities. Gratitude is also expressed to Lynn L-B. Rust, Ph.D. (National Institute of Allergy and Infectious Diseases, National Institutes of Health) for scientific support. NR 26 TC 25 Z9 30 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2008 VL 71 IS 9 BP 1868 EP 1874 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 349WY UT WOS:000259315200015 PM 18810871 ER PT J AU Garber, EAE AF Garber, Eric A. E. TI Toxicity and detection of ricin and abrin in beverages SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ABRUS-PRECATORIUS AGGLUTININ; A-CHAIN; ORAL TOXICITY; LECTINS; SITE; PURIFICATION; MECHANISM; PROTEINS; KINETICS; TOXINS AB The oral and intraperitoneal (i.p.) toxicities to female BALB/c mice of ricin and abrin in phosphate-buffered saline (PBS), spring water, apple juice, and half-and-half (only oral) were examined after brief (2 h) and prolonged (11 to 13 days) storage. The ricin and abrin samples prepared in PBS had oral toxicities consistent with those previous studies, indicating oral and i.p. 50% lethal doses of >1 mg/kg of body weight and between 2 and 20 mu g/kg of body weight, respectively. The toxicities of ricin and abrin in PBS were greater than those in apple juice and water. The oral toxicity of ricin and abrin in half-and-half appeared comparable to or less than that observed for the toxins in water. Spiked samples stored for a maximum of I I days (13 for the abrin samples) at 4 degrees C induced similar numbers of fatalities as did samples stored for only 2 h. Enzyme-linked immunosorbent assays of the samples administered by i.p. injection indicated a decrease in detectable toxin at 0.5 mu g/ml. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM eric.garber@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health FX Appreciation is expressed to Marc S. Boyer (FDA) for the CMH statistical analyses and Frank Klotz (Biocon, Inc., Rockville, Md.) for providing technical expertise in the handling, care, and administration of the samples to the BALB/c mice. Gratitude is also expressed to Palmer A. Orlandi, Ph.D. (FDA), and Lynn L. B. Rust, Ph.D. (National Institute of Allergy and Infectious Diseases, National Institutes of Health), for support, Michael A. McLaughlin, Ph.D., for coordinating the contract that resulted in the acquisition of abrin fraction II, and Raoul E Reiser, Ph.D. (Toxin Technology, Sarasota. Fla,), for providing commercial abrin. NR 39 TC 29 Z9 30 U1 0 U2 9 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2008 VL 71 IS 9 BP 1875 EP 1883 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 349WY UT WOS:000259315200016 PM 18810872 ER PT J AU De Jesus, AJ Whiting, RC AF De Jesus, Antonio J. Whiting, Richard C. TI Modeling the physiological state of the inoculum and CO(2) atmosphere on the lag phase and growth rate of Listeria monocytogenes SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PREDICTIVE MODEL; TEMPERATURE; PH AB In previous studies, the growth of L. monocytogenes has been modeled under different CO(2) headspace concentrations; however, the inoculum cells were always in the stationary phase. In this study, the growth of L. monocytogenes under different CO(2) concentrations as affected by the physiological state of the cells was investigated. Exponential-growth-phase, stationary-phase, dried, and starved cells were prepared and inoculated at 5 degrees C into brain heart infusion broths that had been preequilibrated under atmospheres of 0, 20, 40, 60, or 80% CO(2) (the balance was N(2)). Lag-phase duration times (LDTs) and exponential growth rates were determined by enumerating cells at appropriate time intervals and by fitting the data to a three-phase linear function that has a lag period before the initiation of exponential growth. Longer LDTs were observed as the CO(2) concentration increased, with no growth observed at 80% CO(2). For example, the LDTs for exponential-phase, stationary-phase, starved, and dried cells were 2.21, 8.277 9.17, and 9.67 days, respectively, under the 40% CO(2) atmosphere. In general, exponential-growth-phase cells had the shortest LDT followed by starved cells and stationary-phase cells. Dried cells had the longest LDT Exponential growth rates decreased as the CO(2) Concentrations increased. Once exponential growth was attained, no retained differences among the various initial physiological states of the cells for any of the atmospheres were observed in the exponential growth rates. The exponential growth rates under 0, 20, 40, 60, and 80% CO(2) averaged 0.39, 0.37, 0.23, 0.23, and 0.0 log CFU/day, respectively. Dimensionless factors were calculated that describe the inhibitory action of CO(2) on the LDTs and exponential growth rates for the various physiological states. C1 [De Jesus, Antonio J.; Whiting, Richard C.] US FDA, Ctr Safety & Appl Nutr, College Pk, MD 20740 USA. RP De Jesus, AJ (reprint author), US FDA, Ctr Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM antonio.dejesus@fda.hhs.gov NR 13 TC 1 Z9 1 U1 1 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2008 VL 71 IS 9 BP 1915 EP 1918 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 349WY UT WOS:000259315200022 PM 18810878 ER PT J AU McGrath, PJ Walco, GA Turk, DC Dworkin, RH Brown, MT Davidson, K Eccleston, C Finley, GA Goldschneider, K Haverkos, L Hertz, SH Ljungman, G Palermo, T Rappaport, BA Rhodes, T Schechter, N Scott, J Sethna, N Svensson, OK Stinson, J von Baeyer, CL Walker, L Weisman, S White, RE Zajicek, A Zeltzer, L AF McGrath, Patrick J. Walco, Gary A. Turk, Dennis C. Dworkin, Robert H. Brown, Mark T. Davidson, Karina Eccleston, Christopher Finley, G. Allen Goldschneider, Kenneth Haverkos, Lynne Hertz, Sharon H. Ljungman, Gustaf Palermo, Tonya Rappaport, Bob A. Rhodes, Thomas Schechter, Neil Scott, Jane Sethna, Navil Svensson, Ola K. Stinson, Jennifer von Baeyer, Carl L. Walker, Lynn Weisman, Steven White, Richard E. Zajicek, Anne Zeltzer, Lonnie TI Core outcome domains and measures for pediatric acute and chronic/recurrent pain clinical trials: PedIMMPACT recommendations SO JOURNAL OF PAIN LA English DT Article DE acute pain; chronic pain; children; adolescents; pediatric; clinical trials; randomized controlled trials; assessment; outcomes; health-related quality of life; physical functioning; emotional functioning; global ratings; adverse events; IMMPACT ID QUALITY-OF-LIFE; FUNCTIONAL DISABILITY INVENTORY; SCHOOL-AGED CHILDREN; SICKLE-CELL-DISEASE; POSTOPERATIVE PAIN; PSYCHOMETRIC PROPERTIES; SELF-REPORT; IMMPACT RECOMMENDATIONS; BEHAVIORAL DISTRESS; INITIAL VALIDATION AB Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 26 professionals from academia, governmental agencies, and the pharmaceutical industry participated in a 2-stage Delphi poll and a consensus meeting that identified core outcome domains and measures that should be considered in clinical trials of treatments for acute and chronic pain in children and adolescents. Consensus was refined by consultation with the international pediatric pain community through announcement of our recommendations on the Pediatric Pain List and inviting and incorporating comments from external sources. There was consensus that investigators conducting pediatric acute pain clinical trials should consider assessing outcomes in pain intensity; global judgment of satisfaction with treatment; symptoms and adverse events; physical recovery; emotional response; and economic factors. There was also agreement that investigators conducting pediatric clinical trials in chronic and recurrent pain should consider assessing outcomes in pain intensity; physical functioning; emotional functioning; role functioning; symptoms and adverse events; global judgment of satisfaction with treatment; sleep; and economic factors. Specific measures or measurement strategies were recommended for different age groups for each domain. Perspective: Based on systematic review and consensus of experts, core domains and measures for clinical trials to treat pain in children and adolescents were defined. This will assist in comparison and pooling of data and promote evidence-based treatment, encourage complete reporting of outcomes, simplify the review of proposals and manuscripts, and facilitate clinicians making informed decisions regarding treatment. (C) 2008 by the American Pain Society. C1 [Walco, Gary A.] Hackensack Univ, Joseph M Sanzari Childrens Hosp, Med Ctr, Hackensack, NJ 07601 USA. [McGrath, Patrick J.; Finley, G. Allen] Dalhousie Univ, Halifax, NS, Canada. [McGrath, Patrick J.; Finley, G. Allen] IWK Hlth Ctr, Halifax, NS, Canada. [Turk, Dennis C.] Univ Washington, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Brown, Mark T.] Pfizer Inc, Ann Arbor, MI USA. [Davidson, Karina] Columbia Univ, New York, NY USA. [Eccleston, Christopher] Univ Bath, Bath BA2 7AY, Avon, England. [Goldschneider, Kenneth] Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. [Haverkos, Lynne; Zajicek, Anne] NIH NICHD, Bethesda, MD USA. [Hertz, Sharon H.; Rappaport, Bob A.; Scott, Jane] US FDA, Rockville, MD 20857 USA. [Ljungman, Gustaf] Uppsala Univ, Childrens Hosp, Uppsala, Sweden. [Palermo, Tonya] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Rhodes, Thomas] Merck & Co Inc, Blue Bell, PA USA. [Schechter, Neil] St Francis Hosp & Med Ctr, Hartford, CT USA. [Sethna, Navil] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. [Svensson, Ola K.] AstraZeneca, Stockholm, Sweden. [Stinson, Jennifer] Univ Toronto, Toronto, ON, Canada. [Stinson, Jennifer] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [von Baeyer, Carl L.] Univ Saskatchewan, Saskatoon, SK, Canada. [Walker, Lynn] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Weisman, Steven] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Weisman, Steven] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [White, Richard E.] Endo Pharmaceut, Chadds Ford, PA USA. [White, Richard E.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Walco, GA (reprint author), Hackensack Univ, Joseph M Sanzari Childrens Hosp, Med Ctr, 30 Prospect Ave, Hackensack, NJ 07601 USA. EM gwalco@humed.com OI Ljungman, Gustaf/0000-0002-4949-2494; von Baeyer, Carl/0000-0002-6308-1966; Zeltzer, Lonnie/0000-0001-9306-9450; Eccleston, Christopher/0000-0003-0698-1543; McGrath, Patrick/0000-0002-9568-2571 NR 80 TC 271 Z9 274 U1 4 U2 17 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD SEP PY 2008 VL 9 IS 9 BP 771 EP 783 DI 10.1016/j.jpain.2008.04.007 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 347WN UT WOS:000259172200002 PM 18562251 ER PT J AU Gryniewicz, CM Kauffman, JF AF Gryniewicz, Connie M. Kauffman, John F. TI Multivariate calibration of covalent aggregate fraction to the Raman spectrum of regular human insulin SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE proteins; protein aggregation; Raman spectroscopy; multivariate analysis; spectroscopy ID PROTEIN SECONDARY STRUCTURE; PHARMACEUTICAL PREPARATIONS; PHYSICAL STABILITY; CHEMICAL-STABILITY; LIGHT-SCATTERING; MOLECULAR-WEIGHT; SPECTROSCOPY; DEGRADATION; THERAPEUTICS; MECHANISM AB Insulin aggregates were prepared by exposing samples of formulated regular human insulin to agitation at 60 degrees C. Aliquots were drawn from the samples periodically over a time range spanning 192 h, and their aggregate compositions were determined with size exclusion chromatography. The complete data set was composed of 39 separate aliquots. The Raman spectra of three separate 10 mu L volumes from each aliquot were measured using the drop-coat deposition Raman (DCDR) method. The spectra were calibrated to aggregate composition by partial least squares regression (PLS), resulting in linear calibration (R-2 = 0.997) with a root mean squared error of calibration (RMSEC) of 1.3% and a root mean squared error of cross validation (RMSECV) of 5.1% in aggregate composition. Though the time required for aggregates to form under stressed conditions showed substantial sample-to-sample variation, the correlation between aggregate composition and Raman spectrum was remarkably consistent, indicating that Raman spectroscopy may be a viable screening method for aggregation of protein drugs. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:3727-3734, 2008. C1 [Gryniewicz, Connie M.; Kauffman, John F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Kauffman, JF (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM john.kauffman@fda.hhs.gov NR 23 TC 5 Z9 5 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD SEP PY 2008 VL 97 IS 9 BP 3727 EP 3734 DI 10.1002/jps.21326 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 344OL UT WOS:000258937100012 PM 18240298 ER PT J AU Tabasi, SH Fahmy, R Bensley, D O'Brien, C Hoag, SW AF Tabasi, Simin Hassannejad Fahmy, Raafat Bensley, Dennis O'Brien, Charles Hoag, Stephen W. TI Quality by design, part I: Application of NIR spectroscopy to monitor tablet manufacturing process SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE near infrared spectroscopy; NIR; vibrational spectroscopy; chemometric modeling; quality by design; orbifloxacin; compression force; crushing strength; partial least square regression; PLS ID NEAR-INFRARED SPECTROSCOPY; REFLECTANCE SPECTROSCOPY; POLYMORPHIC ANALYSIS; CONTENT UNIFORMITY; SIZE DISTRIBUTION; DOSAGE FORMS; VALIDATION; PREDICTION; STRENGTH; HARDNESS AB To monitor tableting production using near infrared (NIR) spectroscopy, chemometric models were developed to analyze peak compression force, crushing strength and content uniformity. To measure tablet content uniformity, orbifloxacin tablets with drug content ranging from 60 to 90 mg were made and analyzed using ultraviolet (UV) and NIR spectroscopy. To assess the compression force and crushing strength, several batches of tablets were made on a Stokes B2 rotary tablet press and compression force was varied from 360 to 3500 lb. Principal component analysis (PCA) was used to identify tablets with regular and capped tablets breakage patterns. Comparison of statistical parameters showed that partial least squares (PLS) models gave better fit than the multiple linear regression (MLR) models. The best fit PLS models had a standard error of calibration (SEC) and a standard error of prediction (SEP) for content uniformity of 1.13 and 1.36 mg; for compression force of 69.86 and 59.48 lb and for crushing strength 0.55 kP and 0.57 kP, respectively. NIR spectroscopy in combination with multivariate modeling is a rapid and nondestructive technique that could reliably predict content uniformity, compression force and crushing strength for orbifloxacin tablets. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Tabasi, Simin Hassannejad; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Fahmy, Raafat; Bensley, Dennis; O'Brien, Charles] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu NR 24 TC 30 Z9 30 U1 1 U2 20 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD SEP PY 2008 VL 97 IS 9 BP 4040 EP 4051 DI 10.1002/jps.21303 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 344OL UT WOS:000258937100035 PM 18300297 ER PT J AU Tabasi, SH Fahmy, R Bensley, D O'Brien, C Hoag, SW AF Tabasi, Simin Hassannejad Fahmy, Raafat Bensley, Dennis O'Brien, Charles Hoag, Stephen W. TI Quality by design, part II: Application of NIR spectroscopy to monitor the coating process for a pharmaceutical sustained release product SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE multivariate calibration; coating; chemometrics; coating thickness; near infrared spectroscopy (NIRS); dissolution profile; prediction ID NEAR-INFRARED SPECTROSCOPY AB Ammonio methacrylate copolymers are commercially available as Eudragit RL/RS; they differ in the degree of quaternary ammonium group substitution, which gives them different permeabilities. These closely related polymers can be combined in various ratios to control release rate; consequently, release rate is controlled by the polymer composition and coating thickness. Therefore, predicting drug release from methacrylate copolymers using near infrared spectroscopy (NIRS) can be technically difficult. Thus, the objective of this study is to use NIRS to develop multivariate calibration models to predict tablet coat thickness and release rate for tablets coated with varying polymer ratios. A series of sustained release orbifloxacin formulations were developed with varying polymer ratios. Partial least squares (PLS) models were developed to predict coat thickness; samples from these formulations were pooled and a combined calibration was generated. To assess dissolution, tablets were coated using Eudragit RL and RS with ratios of 0:5, 1:4, 2:3, 3:2, 4: 1, and 5:0. The amount released at set time-points was used to build PLS models. For the first time, NIRS has been successfully used to monitor Eudragit polymer coat thickness and drug release from tablets coated with various RL:RS ratios, which demonstrates the potential of NIRS as tool for coating process. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Tabasi, Simin Hassannejad; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Fahmy, Raafat; Bensley, Dennis; O'Brien, Charles] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu FU Rohm America FX The authors would like to acknowledge Rohm America for their support of this study. NR 13 TC 25 Z9 26 U1 1 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD SEP PY 2008 VL 97 IS 9 BP 4052 EP 4066 DI 10.1002/jps.21307 PG 15 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 344OL UT WOS:000258937100036 PM 18481308 ER PT J AU Tabasi, SH Fahmy, R Bensley, D O'Brien, C Hoag, SW AF Tabasi, Simin Hassannejad Fahmy, Raafat Bensley, Dennis O'Brien, Charles Hoag, Stephen W. TI Quality by design, part III: Study of curing process of sustained release coated products using NIR spectroscopy SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE multivariate analysis; film coat curing; tablet coating; chemometrics; NIR spectroscopy; dissolution profile; prediction; standard error of calibration; standard error of prediction ID THEOPHYLLINE PELLETS; LATEX FILMS; POLYMER; DISPERSIONS; ADDITIVES; RATES AB This study investigated the potential of near infrared spectroscopy (NIRS) to assess film coat curing for tablets coated with methacrylate copolymers. The ability of NIRS to monitor film coat curing was studied and compared to conventional methods like differential scanning calorimetry (DSC) and hot-stage microscopy (HSOM). This study showed that variation in the curing temperature and duration affected the NIR spectra for all formulations. These results and the DSC and HSOM results showed that the spectral changes are due to polymer curing. In addition, glass beads, theophylline and orbifloxacin tablets were coated using Eudragit RL, RS, and L 30-D with varying ratios. Principal component analysis (PCA) was performed on the NIR spectra to investigate the effect of curing time and temperature on cast films, uncoated tablets, coated tablets and coated glass beads. Score plots showed that curing duration and temperature affected coated glass beads, uncoated and coated tablets significantly. The amount of drug released at 250 min, and the NIR spectra of cured tablets were used to develop and validate a 7-factor partial least square (PLS) regression calibration for theophylline tablets coated with Eudragit RL:RS 30-D (1:4). This study demonstrated the potential of NIRS in film coat curing and release monitoring. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Tabasi, Simin Hassannejad; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Fahmy, Raafat; Bensley, Dennis; O'Brien, Charles] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu FU Rohm America FX The author would like to acknowledge Rohm America for their support of this study. NR 19 TC 14 Z9 15 U1 0 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD SEP PY 2008 VL 97 IS 9 BP 4067 EP 4086 DI 10.1002/jps.21420 PG 20 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 344OL UT WOS:000258937100037 PM 18481309 ER PT J AU Getie-Kebtie, M Franke, P Aksamit, R Alterman, MA AF Getie-Kebtie, Melkamu Franke, Peter Aksamit, Robert Alterman, Michail A. TI Experimental evaluation of protein identification by an LC/MALDI/on-target digestion approach SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE protein identification; proteomics; tryptic digest; MALDI; mass spectrometry; on-target; membrane proteins ID LASER-DESORPTION/IONIZATION TIME; ON-PLATE DIGESTION; MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; PROTEOMIC APPROACH; MEMBRANE-PROTEINS; CYTOCHROME-P450 ISOZYMES; SAMPLE PREPARATION; ESCHERICHIA-COLI; LARGE-SCALE AB Tryptic digestion of proteins continues to be a workhorse of proteomics. Traditional tryptic digestion requires several hours to generate an adequate protein digest. A number of enhanced accelerated digestion protocols have been developed in recent years. Nonetheless, a need still exists for new digestion strategies that meet the demands of proteomics for high-throughput and rapid detection and identification of proteins. We performed an evaluation of direct tryptic digestion of proteins on a MALDI target plate and the potential for integrating RP HPLC separation of protein with on-target tryptic digestion in order to achieve a rapid and effective identification of proteins in complex biological samples. To this end, we used a Tempo HPLC/MALDI target plate deposition hybrid instrument (ABI). The technique was evaluated using a number of soluble and membrane proteins and an MRC5 cell lysate. We demonstrated that direct deposition of proteins on a MALDI target plate after reverse-phase HPLC separation and subsequent tryptic digestion of the proteins on the target followed by MALDI TOF/TOF analysis provided substantial data (intact protein mass, peptide mass and peptide fragment mass) that allowed a rapid and unambiguous identification of proteins. The rapid protein separation and direct deposition of fractions on a MALDI target plate provided by the RP HPLC combined with off-line interfacing with the MALDI MS is a unique platform for rapid protein identification with improved sequence coverage. This simple and robust approach significantly reduces the sample handling and potential loss in large-scale proteomics experiments. This approach allows combination of peptide mass fingerprinting (PMF), MS/MS peptide fragment fingerprinting (PPF) and whole protein MS for both protein identification and structural analysis of proteins. C1 [Getie-Kebtie, Melkamu; Franke, Peter; Aksamit, Robert; Alterman, Michail A.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 29A,Room 2D12,8800 Rochville Pike, Bethesda, MD 20892 USA. EM Michail.Alterman@fda.hhs.gov NR 38 TC 12 Z9 12 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD SEP PY 2008 VL 7 IS 9 BP 3697 EP 3707 DI 10.1021/pr800258k PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 345RZ UT WOS:000259015500008 PM 18597512 ER PT J AU Wear, KA Padilla, F Laugier, P AF Wear, Keith A. Padilla, Frederic Laugier, Pascal TI Comparison of the Faran Cylinder Model and the Weak Scattering Model for predicting the frequency dependence of backscatter from human cancellous femur in vitro (L) SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TRABECULAR BONE; ULTRASONIC BACKSCATTER; THICKNESS; MICROTOMOGRAPHY AB This letter presents the first side-by-side comparison of the Faran Cylinder Model and the Weak Scattering Model for predicting backscatter from human femur. Both models are applied to the same dataset of frequency-dependent backscatter coefficients from 26 human femur cancellous bone samples in vitro. The Faran Cylinder Model predicts a slightly slower rate of increase of backscatter with frequency than the Weak Scattering Model, but both models are in reasonable agreement with the data and with each other, given the uncertainty in the measurements. (C) 2008 Acoustical Society of America. C1 [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Padilla, Frederic; Laugier, Pascal] Univ Paris 06, UPMC, UMR 7623, LIP, F-75005 Paris, France. [Padilla, Frederic; Laugier, Pascal] CNRS, UMR 7623, Lab Imagerie Parametr, F-75006 Paris, France. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM kaw@fda.hhs.gov NR 13 TC 5 Z9 5 U1 0 U2 0 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2008 VL 124 IS 3 BP 1408 EP 1410 DI 10.1121/1.2956480 PN 1 PG 3 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 356PQ UT WOS:000259790500003 PM 19045632 ER PT J AU Anderson, CC Marutyan, KR Holland, MR Wear, KA Miller, JG AF Anderson, Christian C. Marutyan, Karen R. Holland, Mark R. Wear, Keith A. Miller, James G. TI Interference between wave modes may contribute to the apparent negative dispersion observed in cancellous bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID KRAMERS-KRONIG RELATIONSHIP; BIOT-ATTENBOROUGH MODEL; TRABECULAR BONE; PHASE-VELOCITY; ULTRASONIC-ATTENUATION; HUMAN CALCANEUS; ACOUSTIC ANISOTROPY; STRATIFIED MODEL; PROPAGATION; TORTUOSITY AB Previous work has shown that ultrasonic waves propagating through cancellous bone often exhibit a linear-with-frequency attenuation coefficient, but a decrease in phase velocity with frequency (negative dispersion) that is inconsistent with the causality-imposed Kramers-Kronig relations. In the current study, interfering wave modes similar to those observed in bone are shown to potentially contribute to the observed negative dispersion. Biot theory, the modified Biot-Attenborogh model, and experimental results are used to aid in simulating multiple-mode wave propagation through cancellous bone. Simulations entail constructing individual wave modes exhibiting a positive dispersion using plausible velocities and amplitudes, and then summing the individual modes to create mixed-mode output wave forms. Results of the simulations indicate that mixed-mode wave forms can exhibit negative dispersion when analyzed conventionally under the assumption that only one wave is present, even when the individual interfering waves exhibit positive dispersions in accordance with the Kramers-Kronig relations. Furthermore, negative dispersion is observed when little or no visual evidence of interference exists in the time-domain data. Understanding the mechanisms responsible for the observed negative dispersion could aid in determining the true material properties of cancellous bone, as opposed to the apparent properties measured using conventional data analysis techniques. (C) 2008 Acoustical Society of America. C1 [Anderson, Christian C.; Marutyan, Karen R.; Holland, Mark R.; Miller, James G.] Washington Univ, Dept Phys, St Louis, MO 63130 USA. [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Anderson, CC (reprint author), Washington Univ, Dept Phys, St Louis, MO 63130 USA. EM james.g.miller@wustl.edu FU NSF [CBET-0717830]; NIH [R37 HL40302] FX This work was supported in part by NSF Grant No. CBET-0717830 Scholar in Residence at the FDA and by NIH Grant No. R37 HL40302. NR 38 TC 42 Z9 43 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2008 VL 124 IS 3 BP 1781 EP 1789 DI 10.1121/1.2953309 PN 1 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 356PQ UT WOS:000259790500039 PM 19045668 ER PT J AU Myers, MR Hariharan, P Banerjee, RK AF Myers, Matthew R. Hariharan, Prasanna Banerjee, Rupak K. TI Direct methods for characterizing high-intensity focused ultrasound transducers using acoustic streaming SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article AB Two techniques are presented for noninvasively determining the intensity field of high-intensity focused ultrasound transducers in a liquid medium. The techniques are based upon the streaming velocity induced in the liquid by the absorbed ultrasound beam. The approaches are similar to an iterative streaming method previously reported, but the present approaches are "direct:" The differential operations of the Navier-Stokes equations are performed directly upon the experimentally measured streaming velocity, rather than through an iterative approach that minimizes the difference between a theoretical estimate of the streaming velocity and the one measured experimentally. As such, the direct methods are much faster than the iterative technique. The price paid for the increase in speed is smaller spatial coverage; the direct techniques are applicable only where accurate streaming velocity is available. Comparisons performed in the range 100-1000 W/cm(2) focal intensity showed differences between the direct methods and the iterative streaming technique to be less than 20%. Similar differences were observed in low-power comparisons with hydrophone measurements. C1 [Myers, Matthew R.; Hariharan, Prasanna; Banerjee, Rupak K.] US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Myers, MR (reprint author), US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 2231, Silver Spring, MD 20993 USA. EM matthew.myers@fda.hhs.gov NR 10 TC 8 Z9 8 U1 0 U2 6 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2008 VL 124 IS 3 BP 1790 EP 1802 DI 10.1121/1.2957937 PN 1 PG 13 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 356PQ UT WOS:000259790500040 PM 19045669 ER PT J AU Liu, YB Maruvada, S King, RL Herman, BA Wear, KA AF Liu, Yunbo Maruvada, Subha King, Randy L. Herman, Bruce A. Wear, Keith A. TI Development and characterization of a blood mimicking fluid for high intensity focused ultrasound SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID THERMAL ABLATION; TISSUE; BACKSCATTER; PERFUSION; PHANTOM; HIFU; NONLINEARITY; ATTENUATION; VALIDATION; DEPENDENCE AB A blood mimicking fluid (BMF) has been developed for the acoustic and thermal characterizations of high intensity focused ultrasound (HIFU) ablation devices. The BMF is based on a degassed and de-ionized water solution dispersed with low density polyethylene microspheres, nylon particles, gellan gum, and glycerol. A broad range of physical parameters, including attenuation coefficient, speed of sound, viscosity, thermal conductivity, and diffusivity, were characterized as a function of temperature (20-70 degrees C). The nonlinear parameter B/A and backscatter coefficient were also measured at room temperature. Importantly, the attenuation coefficient is linearly proportional to the frequency (2-8 MHz) with a slope of about 0.2 dB cm(-1) MHz(-1) in the 20-70 degrees C range as in the case of human blood. Furthermore, sound speed and bloodlike backscattering indicate the usefulness of the BMF for ultrasound flow imaging and ultrasound-guided HIFU applications. Most of the other temperature-dependent physical parameters are also close to the reported values in human blood. These properties make it a unique HIFU research tool for developing standardized exposimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU ablation devices. (C) 2008 Acoustical Society of America. C1 [Liu, Yunbo; Maruvada, Subha; Herman, Bruce A.; Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [King, Randy L.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. RP Liu, YB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. FU Defense Advanced Research Projects Agency (DARPA) [224-05-6016] FX This research was supported by Defense Advanced Research Projects Agency (DARPA) through IAG No. 224-05-6016. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the U.S. Department of Health and Human Services. NR 37 TC 4 Z9 4 U1 0 U2 7 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2008 VL 124 IS 3 BP 1803 EP 1810 DI 10.1121/1.2956469 PN 1 PG 8 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 356PQ UT WOS:000259790500041 PM 19045670 ER PT J AU Gopee, NV Leakey, J Carraway, J AF Gopee, N. V. Leakey, J. Carraway, J. TI Topically Administered Recombinant Leptin for the Treatment of Ulcerative Dermatitis in Zucker Lean Rats SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 [Gopee, N. V.; Leakey, J.; Carraway, J.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2008 VL 47 IS 5 BP 110 EP 111 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 361MJ UT WOS:000260131500122 ER PT J AU Ghosh, K Ghosh, P Tiwari, RC AF Ghosh, Kaushik Ghosh, Pulak Tiwari, Ram C. TI The Nested Dirichlet Process Comment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material C1 [Ghosh, Kaushik] Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. [Ghosh, Pulak] Emory Univ, Dept Biostat, Atlanta, GA 30322 USA. [Ghosh, Pulak] Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. [Tiwari, Ram C.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. RP Ghosh, K (reprint author), Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. EM kaushik.ghosh@unlv.edu; pulakghosh@gmail.com; ram.tiwari@fda.hhs.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD SEP PY 2008 VL 103 IS 483 BP 1147 EP 1149 DI 10.1198/016214508000000562 PG 3 WC Statistics & Probability SC Mathematics GA 362JJ UT WOS:000260193700022 ER PT J AU Nanda, S Jayan, G Voulgaropoulou, F Sierra-Honigmann, AM Uhlenhaut, C McWatters, BJP Patel, A Krause, PR AF Nanda, Santosh Jayan, Geetha Voulgaropoulou, Frosso Sierra-Honigmann, Ana Maria Uhlenhaut, Christine McWatters, Bernard J. P. Patel, Amita Krause, Philip R. TI Universal virus detection by degenerate-oligonucleotide primed polymerase chain reaction of purified viral nucleic acids SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE universal virus detection; non-specific virus detection; DOP-PCR; virus discovery; capsid preparation ID DNA; IDENTIFICATION; PCR; DISEASE; CLONING; SAMPLES AB This study describes a novel non-specific universal virus detection method that permits molecular detection of viruses in biological materials containing mixtures of cells and viruses. Samples are subjected to nuclease digestion and ultracentrifugation to separate encapsidated viral nucleic acids from cellular nucleic acids. A degenerate oligonucleotide primer PCR (DOP-PCR) that has been optimized for the non-specific amplification of virus sized genomes is then employed. Virus identification is performed by sequencing of cloned DOP-PCR products followed by sequence comparison to sequences published in GenBank. This method was used to detect a variety of DNA viruses (including HSV, VZV, SV40, AAV, and EBV) and RNA viruses (including HTLV-I, HTLV-II, influenza, and poliovirus), which were spiked into cells, constitutively expressed in cell culture, or detected in productively infected cultured cells. This novel approach was compared with a non-specific virus detection method used previously and found to be several logs more sensitive. This type of approach has potential utility in solving virus detection and discovery problems where other methods have failed. Published by Elsevier B.V. C1 [Nanda, Santosh; Jayan, Geetha; Voulgaropoulou, Frosso; Sierra-Honigmann, Ana Maria; Uhlenhaut, Christine; McWatters, Bernard J. P.; Patel, Amita; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, 29A-1C16,HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 FU National Vaccine Program Office; National Institutes of Allergy and Infectious Diseases FX The authors acknowledge the National Vaccine Program Office for its support of this work. Portions of this work were also supported by the National Institutes of Allergy and Infectious Diseases, via a grant to the Mid Atlantic Regional Center for Excellence in Biodefense and Emerging Infectious Diseases, and by the National Institutes of Allergy and Infectious Diseases, via an interagency agreement with FDA/CBER. Helpful comments are highly acknowledged from Dr. Jeffrey Cohen of the National Institutes of Allergy and Infectious Diseases and from Dr. Shuang Tang of FDA/CBER. NR 17 TC 16 Z9 16 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2008 VL 152 IS 1-2 BP 18 EP 24 DI 10.1016/j.jviromet.2008.06.007 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 344BR UT WOS:000258900800004 PM 18601953 ER PT J AU Friedman, MA Fleming, LE Fernandez, M Bienfang, P Schrank, K Dickey, R Bottein, MY Backer, L Ayyar, R Weisman, R Watkins, S Granade, R Reich, A AF Friedman, Melissa A. Fleming, Lora E. Fernandez, Mercedes Bienfang, Paul Schrank, Kathleen Dickey, Robert Bottein, Marie-Yasmine Backer, Lorraine Ayyar, Ram Weisman, Richard Watkins, Sharon Granade, Ray Reich, Andrew TI Ciguatera fish poisoning: Treatment, prevention and management SO MARINE DRUGS LA English DT Review DE ciguatera fish poisoning; ciguatoxin; harmful algal bloom (HAB); treatment human health; marine toxins ID COMMON-SOURCE OUTBREAK; STATES VIRGIN-ISLANDS; INDIAN-OCEAN; SYMPTOMATIC IMPROVEMENT; CARIBBEAN CIGUATOXINS; PACIFIC CIGUATOXIN-1; CLINICAL-FEATURES; BREVETOXINS; TOXINS; DISEASE AB Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world, and it causes substantial physical and functional impact. It produces a myriad of gastrointestinal, neurologic and/or cardiovascular symptoms which last days to weeks, or even months. Although there are reports of symptom amelioration with some interventions ( e. g. IV mannitol), the appropriate treatment for CFP remains unclear to many physicians. We review the literature on the treatments for CFP, including randomized controlled studies and anecdotal reports. The article is intended to clarify treatment options, and provide information about management and prevention of CFP, for emergency room physicians, poison control information providers, other health care providers, and patients. C1 [Friedman, Melissa A.] Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. [Friedman, Melissa A.; Fleming, Lora E.] NIEHS, NSF, Oceans & Human Hlth Ctr, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33136 USA. [Fernandez, Mercedes] Carlos Albizu Univ, Miami, FL 33172 USA. [Bienfang, Paul] Univ Hawaii, Honolulu, HI 96822 USA. [Schrank, Kathleen] Univ Miami, Dept Med, Jackson Mem Med Ctr, Miami, FL 33136 USA. [Dickey, Robert; Granade, Ray] US FDA, Div Seafood Sci & Technol, Ctr Food Safety & Nutr, Dauphin Isl, AL 36528 USA. [Bottein, Marie-Yasmine] NOAA, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. [Backer, Lorraine] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Ayyar, Ram] Univ Miami, Dept Neurol, Miami, FL 33136 USA. [Weisman, Richard] Florida Poison Informat Ctr, Miami, FL 33136 USA. [Watkins, Sharon; Reich, Andrew] Florida Dept Hlth, Div Environm Hlth, Aquat Toxins Program, Tallahassee, FL 32399 USA. RP Friedman, MA (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF, NIEHS,Oceans & Human Hlth Ctr, 4600 Rickenbacker Causeway,E Grosvenor Bldg,E211, Key Biscayne, FL 33149 USA. EM melissafried@yahoo.com FU National Science Foundation (NSF) [NSF 0CE0432368]; National Institute of Environmental Health Sciences [NIEHS P50 ES12736]; Florida Dept of Health Aquatic Toxins Program; Centers for Disease Control and Prevention (CDC) FX This publication was made possible through the National Science Foundation (NSF) National Institute of Environmental Health Sciences Center for Oceans and Human Health (COHH) program at the University of Miami (NSF 0CE0432368; NIEHS P50 ES12736), as well as with funding from the Florida Dept of Health Aquatic Toxins Program and the Centers for Disease Control and Prevention (CDC). NR 106 TC 86 Z9 91 U1 6 U2 35 PU MOLECULAR DIVERSITY PRESERVATION INT PI BASEL PA MATTHAEUSSTRASSE 11, CH-4057 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD SEP PY 2008 VL 6 IS 3 BP 456 EP 479 DI 10.3390/md20080022 PG 24 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 354RO UT WOS:000259656900004 PM 19005579 ER PT J AU Blimke, J Myklebust, J Volkmer, H Merrill, S AF Blimke, John Myklebust, Joel Volkmer, Hans Merrill, Stephen TI Four-shell ellipsoidal model employing multipole expansion in ellipsoidal coordinates SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE ellipsoidal models; ellipsoidal coordinates; multipole expansion; EEG; ECG; dipole model; forward problem; Lame functions ID EPIDURAL ELECTRICAL-STIMULATION; HUMAN BRAIN; DIPOLE LOCALIZATION; IMPLANTED SOURCES; INVERSE PROBLEM; VOLUME CONDUCTOR; HEAD MODELS; SPINAL-CORD; EEG; POTENTIALS AB Although the head is more closely represented as an ellipsoid than a sphere, calculation in ellipsoidal coordinates is difficult. This paper presents a four shell ellipsoidal model, employing multipole expansion in ellipsoidal coordinates, for EEG, MEG, and evoked potential applications. Computational detail and insight into efficient calculation of the Lame functions of the first and second kind are provided to demonstrate feasibilty. The Lame function of the second kind, derived from the Lame function of the first kind, can be computed at higher degrees by means of partial fraction expansion. C1 [Blimke, John] Med Coll Wisconsin, Max McGee Natl Res Ctr Juvenile Diabet, Milwaukee, WI 53226 USA. [Myklebust, Joel] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD USA. [Volkmer, Hans] Univ Wisconsin, Dept Math Sci, Milwaukee, WI 53201 USA. [Merrill, Stephen] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53233 USA. RP Blimke, J (reprint author), Med Coll Wisconsin, Max McGee Natl Res Ctr Juvenile Diabet, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM jblimke@mcw.edu OI Myklebust, Joel/0000-0002-8709-9706 NR 52 TC 3 Z9 3 U1 2 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD SEP PY 2008 VL 46 IS 9 BP 859 EP 869 DI 10.1007/s11517-008-0352-9 PG 11 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 343GY UT WOS:000258842700003 PM 18488262 ER PT J AU Miglioretti, DL Rutter, CM Bradford, SC Zauber, AG Kessler, LG Feuer, EJ Grossman, DC AF Miglioretti, Diana L. Mutter, Carolyn M. Bradford, Susan Carol Zauber, Ann G. Kessler, Larry G. Feuer, Eric J. Grossman, David C. TI Improvement in the Diagnostic Evaluation of a Positive Fecal Occult Blood Test in an Integrated Health Care Organization SO MEDICAL CARE LA English DT Article DE fecal occult blood test; colorectal cancer screening; diagnostic follow-up ID IMPROVING PRIMARY-CARE; COLORECTAL-CANCER; FOLLOW-UP; CLINICAL GUIDELINES; CHRONIC ILLNESS; UNITED-STATES; PREVENTION; RATIONALE; MORTALITY; TRIAL AB Background: Screening for fecal occult blood can be effective in reducing colorectal cancer mortality only if positive tests are appropriately followed up with complete diagnostic evaluation (ie, colonoscopy or flexible sigmoidoscopy with double contrast barium enema) and treatment. Objectives: To examine whether rates of complete diagnostic evaluation after a positive fecal occult blood test (FOBT) have improved over time after the implementation of tracking systems and physician guidelines within a large integrated health care organization. Research Design: From 1993 to 2005, 8513 positive FOBTs were identified on 8291 enrollees aged 50-79 of a large health care system. Automated records were used to identify repeat FOBTs, colonoscopy, flexible sigmoidoscopy, and double-contrast barium enema within 1 year after the positive FOBT. National rates of complete diagnostic evaluation were estimated from the 2005 National Health Interview Survey. Results: In this integrated health care organization, the percentage of positive FOBTs followed by complete diagnostic evaluation within 1 year increased from 57-64% in 1993-1996 to 82-86% from 2000-2005. Use of repeat FOBT after a positive FOBT decreased from 28-31% in 1993-1996 to 6-11% in 2000-2005. Based on the National Health Interview Survey, only 52% of positive FOBTs in 2000-2005 were followed by omplete diagnostic evaluation nationally. Conclusions: Adherence to recommendations for complete diagnostic evaluation after a positive FOBT has greatly improved over time in an integrated group medical practice. Through the use of tracking systems and screening guidelines, it may be possible to reach levels of follow-up that are comparable to those observed in randomized trials. C1 [Miglioretti, Diana L.; Mutter, Carolyn M.; Grossman, David C.] Grp Hlth Ctr Hlth Studies, Seattle, WA 98101 USA. [Bradford, Susan Carol; Grossman, David C.] Grp Hlth Cooperat Puget Sound, Dept Clin Improvement & Prevent, Seattle, WA USA. [Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. [Kessler, Larry G.] Ctr Devices & Radiol Hlth Food & Drug Adm, Off Sci & Engn Labs, Silver Spring, MD USA. [Feuer, Eric J.] Natl Canc Inst, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Miglioretti, DL (reprint author), Grp Hlth Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM miglioretti.d@ghc.org FU National Cancer Institute [U01 CA-97427, U01 CA-97426] FX Supported by the National Cancer Institute grants U01 CA-97427 and U01 CA-97426. NR 27 TC 28 Z9 28 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD SEP PY 2008 VL 46 IS 9 SU 1 BP S91 EP S96 DI 10.1097/MLR.0b013e31817946c8 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 344RR UT WOS:000258945500022 PM 18725839 ER PT J AU Chen, HZ Xu, HY Kweon, O Chen, SW Cerniglia, CE AF Chen, Huizhong Xu, Haiyan Kweon, Ohgew Chen, Siwei Cerniglia, Carl E. TI Functional role of Trp-105 of Enterococcus faecalis azoreductase (AzoA) as resolved by structural and mutational analysis SO MICROBIOLOGY-SGM LA English DT Article ID FMN-DEPENDENT AZOREDUCTASE; MOLECULAR-CLONING; BINDING; OVEREXPRESSION; OXIDOREDUCTASE; PROTEINS; FLAVIN; SERVER; DYES AB Enterococcus faecalis azoreductase (AzoA) is a very active enzyme with a broad spectrum of substrate specificity and is capable of degrading various azo dyes. The enzyme has an absolute requirement for reduced FMN, which delivers a total of four electrons from NADH to the substrate, resulting in the cleavage of the nitrogen double bond. In this study, we report the identification of amino acid residues critical for FMN binding in AzoA. FMN is stabilized by 22 amino acid residues, eight of which, Trp-105, Asn-106, Leu-107, Gly-150, Gly-151, Tyr-153, Asn-121 and Tyr-129, are involved in binding the FMN isoalloxazine ring. In silico analysis of the amino acid residues revealed that the Trp residue at position 105 of AzoA is the most likely significant contributor to the binding of FMN to the enzyme and is involved in FMN stabilization and destabilization. Site-directed mutagenesis analysis of Trp-105 was performed to determine the role of this amino acid residue in FMN binding and azo dye reductive activity. The mutant proteins were overexpressed in Escherichia coli and purified by anion-exchange and size-exclusion chromatography. The replacement of Trp-105 by the small side-chain amino acids Ala and Gly caused complete loss of both affinity for FMN and enzyme activity. Substitution of Tyr for Trp-105 did not significantly decrease the V-max of the enzyme (22% reduction). Substitutions with three bulky side-chain amino acids, Gln, Phe and His, produced enzymes with lower V-max values (decreases of 68.2, 30.6 and 8.2-fold, respectively). However, these mutated enzymes maintained K, values similar to the wild-type enzyme. This study provides an insight into the catalytic properties of AzoA in FMN stabilization and enzyme activity. C1 [Chen, Huizhong; Xu, Haiyan; Kweon, Ohgew; Chen, Siwei; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU United States Food and Drug Administration; National Center for Toxicological Research FX We thank Drs Fatemeh Rafii and Robin Stingley for their critical review of the manuscript. This study, was funded by the United States Food and Drug Administration and the National Center for Toxicological Research and supported in part by appointment's (Haiyan Xu and Ohgew Kweon) to the Postgraduate Research Fellowship Program and an appointment to the summer internship program (Siwei Chen) at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 25 TC 15 Z9 15 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD SEP PY 2008 VL 154 BP 2659 EP 2667 DI 10.1099/mic.0.2008/019877-0 PN 9 PG 9 WC Microbiology SC Microbiology GA 351KK UT WOS:000259423000013 PM 18757799 ER PT J AU Liang, XJ Finkel, T Shen, DW Yin, JJ Aszalos, A Gottesman, MM AF Liang, Xing-Jie Finkel, Toren Shen, Ding-Wu Yin, Jun-Jie Aszalos, Adorjan Gottesman, Michael M. TI SIRT1 contributes in part to cisplatin resistance in cancer cells by altering mitochondrial metabolism SO MOLECULAR CANCER RESEARCH LA English DT Article ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION; CELLULAR PHARMACOLOGY; MULTIDRUG-RESISTANCE; REDUCED EXPRESSION; CROSS-RESISTANCE; REGULATES SIRT1; LINES; DEACETYLASE; PROTEINS AB Tumors frequently develop resistance to cisplatin, a platinum drug used as a cornerstone of present-day chemotherapy regimens, significantly decreasing its usefulness in the clinic. Although it is known that cisplatin-resistant (CP-r) cancer cells commonly grow more slowly and exhibit reduced uptake of various compounds, including nutrients, the effect of tumor metabolism on cisplatin resistance is unclear. It was found that in CP-r cells, uptake of 2-deoxyglucose was reduced due to dysfunction and altered morphology of mitochondria compared with cisplatin-sensitive parental cancer cells. The CP-r cells overexpressed SIRT1, a histone deacetylase that plays a central role in DNA damage response and transcriptional silencing. Incubation of drug-sensitive cells in low glucose medium induced the expression of SIRT1 and increased cellular resistance to cisplatin. Reduced SIRT1 expression by a SIRT1 SMART small interfering RNA duplex sensitized the >20-fold resistant CP-r cells to cisplatin treatment 1.5- to 2-fold, and SIRT1 overexpression by SIRT1 cDNA transfection increased cisplatin resistance in cisplatin-sensitive cells by 2- to 3-fold. Our findings therefore suggest that reduced glucose use and altered mitochondrial metabolism mediated by SIRT1 is one of several alterations that contribute to cellular resistance to cisplatin. C1 [Liang, Xing-Jie] Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, Lab Nanobiomed & Nanosafety, Beijing 100190, Peoples R China. [Finkel, Toren] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. [Liang, Xing-Jie; Shen, Ding-Wu; Aszalos, Adorjan; Gottesman, Michael M.] NCI, Cell Biol Lab, Bethesda, MD 20892 USA. [Yin, Jun-Jie] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Liang, XJ (reprint author), Natl Ctr Nanosci & Technol China, Div Nanomed & Nanobiol, Lab Nanobiomed & Nanosafety, Beijing 100190, Peoples R China. EM liangxj@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU NIH; National Cancer Institute; Chinese Academy of Sciences [07165111ZX] FX Intramural Research Program of the NIH, National Cancer Institute and Chinese Academy of Sciences "Hundred Talents Program" (07165111ZX). NR 34 TC 51 Z9 52 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD SEP PY 2008 VL 6 IS 9 BP 1499 EP 1506 DI 10.1158/1541-7786.MCR-07-2130 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 359WB UT WOS:000260017800012 PM 18723829 ER PT J AU Allen, C Paraskevakou, G Iankov, I Giannini, C Schroeder, M Sarkaria, J Schroeder, M Puri, RK Russell, SJ Galanis, E AF Allen, Cory Paraskevakou, Georgia Iankov, Ianko Giannini, Caterina Schroeder, Mark Sarkaria, Jann Schroeder, Mark Puri, Raj K. Russell, Stephen J. Galanis, Evanthia TI Interleukin-13 displaying retargeted oncolytic measles virus strains have significant activity against gliomas with improved specificity SO MOLECULAR THERAPY LA English DT Article ID GENETICALLY-MODIFIED MICE; RECEPTOR ALPHA-2 CHAIN; COFACTOR PROTEIN CD46; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMA; IL-13-ALPHA-2 RECEPTOR; PSEUDOMONAS EXOTOXIN; THERAPEUTIC TARGET; ANTITUMOR-ACTIVITY; CELLULAR RECEPTOR AB The majority of glioblastoma multiforme (GBM) tumors (80%) overexpress interleukin-13 receptor alpha 2 (IL-13R alpha 2), but there is no expression of IL-13R alpha 2 in normal brain. Vaccine strains of measles virus have significant antitumor activity against gliomas. We tested the hypothesis that measles virus entry could be retargeted via the IL-13R alpha 2. MV-GFP-H-AA-IL-13 was generated from the Edmonston-NSe vaccine strain, by displaying human IL-13 at the C-terminus of the H protein, and introducing CD46 and signaling lymphocyte activation molecule (SLAM)-ablating mutations in H. The IL-13 retargeted virus showed significant cytopathic effect (CPE) against IL-13R alpha 2 overexpressing glioma lines, and lack of CPE/viral replication in normal human astrocytes and normal human fibroblasts not expressing IL-13R alpha 2. In vivo treatment of orthotopically implanted GBM12 xenografts demonstrated significant prolongation of survival in mice treated with the retargeted strain (P < 0.0001), and comparable activity between the IL-13R retargeted strain and MV-GFP (P = 0.6377). In contrast to MV-GFP-treated mice, administration of the retargeted strain in the central nervous system of measles replication-permissive Ifnar(ko) CD46 Ge mice resulted in lack of neurotoxicity. Strains of measles virus retargeted against the glioma-specific IL-13R alpha 2 receptor have comparable therapeutic efficacy, and improved specificity as compared with the unmodified measles virus strain MV-GFP in vitro and in vivo. C1 [Allen, Cory; Paraskevakou, Georgia; Iankov, Ianko; Russell, Stephen J.; Galanis, Evanthia] Mayo Clin, Coll Med, Div Med Oncol, Dept Mol Med, Rochester, MN 55905 USA. [Giannini, Caterina] Mayo Clin, Coll Med, Div Anat Pathol, Rochester, MN 55905 USA. [Puri, Raj K.] US FDA, Rockville, MD 20857 USA. [Galanis, Evanthia] Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA. RP Galanis, E (reprint author), Mayo Clin, Coll Med, Div Med Oncol, Dept Mol Med, 200 1st St SW, Rochester, MN 55905 USA. EM galanis.evanthia@mayo.edu FU [P50 CA 108961]; [R21 CA 123839] FX We thank R. Cattaneo for the measles anti-H and anti-N antibodies, T. Nakamura for the Vero-alpha His cells, and Raquel Ostby for her help in manuscript preparation. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. This work was supported by: P50 CA 108961 (to E. G., C. G., J.S.) and R21 CA 123839 (to E. G.). NR 44 TC 35 Z9 36 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD SEP PY 2008 VL 16 IS 9 BP 1556 EP 1564 DI 10.1038/mt.2008.152 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 342KG UT WOS:000258782400008 PM 18665158 ER PT J AU Valentine, CR Rainey, HF Farrell, JM Shaddock, JG Dobrovolsky, VN Delongchamp, RR AF Valentine, Carrie R. Rainey, Heather F. Farrell, Jessica M. Shaddock, Joseph G. Dobrovolsky, Vasily N. Delongchamp, Robert R. TI Frequency and spectrum of ENU-induced mutation in the Phi X174 transgene in mouse splenic lymphocytes and their significance to spontaneous transgenic rodent mutation frequencies SO MUTAGENESIS LA English DT Article ID ENDOGENOUS HPRT GENE; IN-VIVO MUTATION; MUTANT FREQUENCIES; ESCHERICHIA-COLI; T-LYMPHOCYTES; BASE-PAIR; MICE; CELLS; REPAIR; ASSAY AB A perceived disadvantage of transgenic rodent mutation assays is that spontaneous mutant frequencies are high compared to those of endogenous genes and may consequently reduce sensitivity to induced mutation. We have previously argued that unrepaired G:T mismatches from spontaneous deamination of 5-methylcytosine at CpG sites could be converted to apparent in vivo mutations in the bacterial recovery systems because of rapid, random, mismatch repair in Escherichia coli. In this study, we have measured mutation frequencies in spleen of male mice induced by N-ethyl-N-nitrosourea (ENU) using the Phi X174 transgene, which is not subject to mismatch repair in E.coli, using single-burst analysis, a unique method to identify in vivo mutation. In order to compare our results to those using the lacI and cII transgenes, we converted all mutant frequencies to base pair substitution (bps) mutation frequencies per nucleotide based on mutant spectra from this study and published literature. We found this frequency in control spleen to be similar for lacI (3.8 +/- 0.7 x 10(-8)) and Phi X174 (3.1 +/- 1.2 x 10(-8)) at 6 weeks of age. We found a strong age dependence for spontaneous lacI mutation that extrapolated to a value at conception (1.8 +/- 0.9 x 10(-8)) that was not significantly different from the human germ line bps mutation frequency per nucleotide of 1.7 +/- 0.2 x 10(-8). These two transgenes provided similar mutational responses to 40 mg/kg ENU, 7- to 9-fold. In contrast, the cII target gene in the same tissue produces both spontaneous and induced mutation frequencies similar to 10 times higher, for unknown reasons. We conclude that the spontaneous mutant frequencies measured by the lacI and Phi X174 transgenes in this moderately dividing tissue accurately measure in vivo mutation frequencies at early ages. For these two transgenes, seemingly high mutant frequencies may reflect the expected accumulation of somatic mutation with age. C1 [Delongchamp, Robert R.] Univ Arkansas Med, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Valentine, Carrie R.; Rainey, Heather F.; Farrell, Jessica M.; Shaddock, Joseph G.; Dobrovolsky, Vasily N.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Delongchamp, RR (reprint author), Univ Arkansas Med, Coll Publ Hlth, Dept Epidemiol, 4301 W Markham,820, Little Rock, AR 72205 USA. EM rdelongchamp@uams.edu FU US Food and Drug Adminstration FX US Food and Drug Adminstration. NR 50 TC 1 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 2008 VL 23 IS 5 BP 383 EP 397 DI 10.1093/mutage/gen026 PG 15 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 343OV UT WOS:000258864300009 PM 18504270 ER PT J AU Parsons, BL AF Parsons, Barbara L. TI Many different tumor types have polyclonal tumor origin: Evidence and implications SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE monoclonal; tumor clonality; somatic mutation; tumor development; tumor etiology; X chromosome inactivation ID X-CHROMOSOME INACTIVATION; K-RAS MUTATIONS; ABERRANT CRYPT FOCI; CHRONIC MYELOCYTIC LEUKEMIA; COLORECTAL-CANCER PATIENTS; PARAFFIN-EMBEDDED TISSUE; DOSE-RESPONSE ASSESSMENT; SQUAMOUS-CELL CARCINOMA; ACB-PCR MEASUREMENT; CLONAL ORIGIN AB Few ideas have gained such strong acceptance in the scientific community as the monoclonal origin of tumors; the idea that tumors start with a single mutated cell (or a single clone of cells) that go on to accumulate additional mutations as a tumor develops. The certainty with which this concept is held by the scientific community reflects the length of time it has been unchallenged and the experimental difficulty in obtaining direct evidence to the contrary. Yet, recent findings regarding X chromosome inactivation patch size indicate that the X-linked marker data previously interpreted as evidence of monoclonal tumor origin is actually more consistent with polyclonal tumor origin, a situation where two or more cells or clones of cells interact to initiate a tumor. Although most tumors show homotypy for X-linked markers (as expected given the bias conferred by X chromosome inactivation patch size), the literature contains numerous examples of tumors with X-linked marker heterotypy, examples of which encompass 24 different tumor types. Chimeric models have yielded direct unequivocal demonstrations of polyclonality in rodent and human tumors. Also, mutational data are consistent with polyclonal tumor origin. Methods that analyze levels of tumor-associated oncogene and tumor suppressor gene mutations demonstrate that initiated cells are much more common in normal tissues than previously realized. Also, while tumors have higher levels of mutation than normal tissues, oncogenic mutations frequently are present as subpopulations within tumors, rather than as the pure mutant populations expected to develop from a single initiated cell. Understanding the mutational basis of tumor etiology has important practical significance for assessing cancer risk, as well as in modeling and treating cancer. Therefore, the scientific community needs to re-examine this issue and consider the implications of polyclonal origin for, perhaps, a majority of tumors, encompassing many different tumor types. Published by Elsevier B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov NR 156 TC 43 Z9 46 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD SEP-OCT PY 2008 VL 659 IS 3 BP 232 EP 247 DI 10.1016/j.mrrev.2008.05.004 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 355PO UT WOS:000259721000005 PM 18614394 ER PT J AU Torti, F AF Torti, Frank TI Frank Torti SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Torti, F (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2008 VL 7 IS 9 BP 724 EP 724 DI 10.1038/nrd2680 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 344GV UT WOS:000258915800007 PM 19172686 ER PT J AU Lanthier, M Behrman, R Nardinelli, C AF Lanthier, Michael Behrman, Rachel Nardinelli, Clark TI Economic issues with follow-on protein products SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID BIOLOGICS AB The economic effects of the possible introduction of 'follow-on' protein products have been the subject of recent debate. Here, we aim to explore the economic issues surrounding this debate using three measures: total sales, product complexity and patent expiry. Our analysis shows that the sales of therapeutic protein products are concentrated in a relatively small number of branded products, which may be the most attractive targets for follow- on development. For the years 2013-2015, we estimate that products representing US$ 20 billion in annual sales-approximately half of all sales in 2006-can be expected to lose patent protection. C1 [Lanthier, Michael; Behrman, Rachel; Nardinelli, Clark] US FDA, Rockville, MD 20857 USA. RP Lanthier, M (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. EM michael.lanthier@fda.hhs.gov NR 12 TC 30 Z9 33 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2008 VL 7 IS 9 BP 733 EP 737 DI 10.1038/nrd2636 PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 344GV UT WOS:000258915800015 PM 18654570 ER PT J AU Cope, JU AF Cope, Judith U. TI Safety of insulin pumps, even in adolescent use, depends on thorough patient selection, evaluation, and education - Reply SO PEDIATRICS LA English DT Letter C1 Food & Drug Adm, Off Pediat Therapeut, Rockville, MD 20857 USA. RP Cope, JU (reprint author), Food & Drug Adm, Off Pediat Therapeut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2008 VL 122 IS 3 BP 682 EP 683 DI 10.1542/peds.2008-1896 PG 8 WC Pediatrics SC Pediatrics GA 342ZR UT WOS:000258822600041 ER PT J AU Smith, PB Benjamin, DK Murphy, MD Johann-Liang, R Iyasu, S Gould, B Califf, RM Li, JS Rodriguez, W AF Smith, P. Brian Benjamin, Daniel K., Jr. Murphy, M. Dianne Johann-Liang, Rosemary Iyasu, Solomon Gould, Barbara Califf, Robert M. Li, Jennifer S. Rodriguez, William TI Safety monitoring of drugs receiving pediatric marketing exclusivity SO PEDIATRICS LA English DT Article DE pediatric drug safety; Pediatric Advisory Committee; adverse event reporting; drug labeling ID POSTMARKETING SURVEILLANCE; WITHDRAWALS AB OBJECTIVES. The Food and Drug Administration Modernization Act provided for an additional 6-month period of marketing exclusivity to companies that perform pediatric drug trials in response to a Food and Drug Administration-issued written request. Because many safety concerns cannot be detected until after the introduction of a product to a larger and more diverse market, the Best Pharmaceuticals for Children Act required the Food and Drug Administration to report to the Pediatric Advisory Committee on adverse events occurring during the 1-year period after granting pediatric exclusivity. We sought to describe the Pediatric Advisory Committee's recommendations made in response to safety reviews informed by data from the Food and Drug Administration Adverse Event Reporting System in 67 drugs granted exclusivity. PATIENTS AND METHODS. Pediatric Advisory Committee meetings and data presented by the Food and Drug Administration for all drugs were reviewed from June 2003 through April 2007. We divided the drugs into 2 groups: those that were returned to routine adverse event monitoring and those that had specific Pediatric Advisory Committee recommendations. RESULTS. Forty-four (65.7%) drugs were returned to routine monitoring for adverse events. The Pediatric Advisory Committee, sometimes working with other advisory committees, recommended label changes for 12 (17.9%) drugs, continued monitoring for 10 (14.9%), production of MedGuides for 9 (13.4%), and an update on label changes resulting from discussions with the sponsor for 1 (1.5%) drug. Some drugs had >1 action. Several of the adverse events revealed during this process were rare and life-threatening. CONCLUSIONS. Safety monitoring during the early postmarketing period is crucial to detect rare, serious, or pediatric-specific adverse events. Fortunately, the majority of drugs given exclusivity had no adverse events of a frequency or severity that prevented a return to routine adverse event monitoring. C1 [Smith, P. Brian] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Smith, P. Brian; Benjamin, Daniel K., Jr.; Califf, Robert M.; Li, Jennifer S.] Duke Univ, Dept Med, Durham, NC 27710 USA. [Smith, P. Brian; Benjamin, Daniel K., Jr.; Califf, Robert M.; Li, Jennifer S.] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA. [Smith, P. Brian; Benjamin, Daniel K., Jr.; Murphy, M. Dianne; Johann-Liang, Rosemary; Iyasu, Solomon; Gould, Barbara; Li, Jennifer S.; Rodriguez, William] US FDA, Rockville, MD 20857 USA. RP Smith, PB (reprint author), Duke Univ, Med Ctr, Dept Pediat, Box 3179, Durham, NC 27710 USA. EM brian.smith@duke.edu RI Smith, Phillip/I-5565-2014 FU National Institute of Child Health and Human Development [1U10-HD45962-04]; FDA; National Center for Research Resources [1UL1RR024128-01] FX Drs Benjamin and Li received support from National Institute of Child Health and Human Development grant 1U10-HD45962-04 and the FDA. Drs Benjamin, Li, Smith, and Califf received support from National Center for Research Resources grant 1UL1RR024128-01. NR 31 TC 16 Z9 17 U1 0 U2 3 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 SEP PY 2008 VL 122 IS 3 BP E628 EP E633 DI 10.1542/peds.2008-0585 PG 6 WC Pediatrics SC Pediatrics GA 342ZR UT WOS:000258822600066 PM 18762496 ER PT J AU Schnackenberg, LK Kaput, J Beger, RD AF Schnackenberg, Laura K. Kaput, Jim Beger, Richard D. TI Metabolomics: a tool for personalizing medicine? SO PERSONALIZED MEDICINE LA English DT Review DE biomarkers; genetics; genomics; metabolomics; personalized medicine ID CISPLATIN-INDUCED NEPHROTOXICITY; ACUTE LIVER-FAILURE; SYSTEMS BIOLOGY; VITAMIN-K; BIOMARKER QUALIFICATION; DIETARY FLAVONOIDS; DRUG INTERACTIONS; NMR-SPECTROSCOPY; GRAPEFRUIT JUICE; INDUCED TOXICITY AB The concept of personalized medicine is based upon using personal genetic information to predict individual responses to drug therapy. However, environmental factors such as diet, energy status, gut microbiota, health status and age will influence the expression of one's genetic potential. Metabolomics data from biofluid and tissue sample analysis hold information regarding a patient's genotype and phenotype. Metabolomics data can be rapidly collected from biofluid samples over time, providing temporal metabolic analyses of patient samples. in addition to metabolic markers of a patient's phenotype, metabolomics can provide markers of drug efficacy, toxicity and clearance. C1 [Schnackenberg, Laura K.; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM richard.beger@fda.hhs.gov NR 104 TC 3 Z9 3 U1 1 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD SEP PY 2008 VL 5 IS 5 BP 495 EP 504 DI 10.2217/17410541.5.5.495 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 349JZ UT WOS:000259278400016 ER PT J AU McAdams, MA Governale, LA Swartz, L Hammad, TA Dal Pan, GJ AF McAdams, Mara A. Governale, Laura A. Swartz, Lynette Hammad, Tarek A. Dal Pan, Gerald J. TI Identifying patterns of adverse event reporting for four members of the angiotensin II receptor blockers class of drugs: revisiting the Weber effect SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse event reporting; angiotensin II receptor blockers; Weber effect; Food and Drug Administration AB Purpose To evaluate the evidence for temporal reporting patterns, such as the Weber effect, in spontaneous post-marketing adverse event (AE) reports submitted to the Food and Drug Administration (FDA), for four members of the angiotensin 11 receptor blockers drug class (ARBs). Methods For losartan, valsartan, irbesartan, and candesartan, we evaluated temporal trends in reporting for the total number of AE reports, serious AE reports, and direct reports from consumers or health care provider.,; (direct reports) to FDA. Reporting patterns were considered consistent with the Weber effect when the peak occurred 2 years after US marketing and the number of reports declined thereafter. We tabulated the number of reports by year since the first report. We adjusted the total number of reports, number of serious AE reports, and number of direct reports by the number of US dispensed prescriptions. Results There were no clear temporal reporting patterns for the total number of reports, direct reports, or serious AE reports. We observed a consistent trend for the adjusted number of direct and serious AE reports. The adjusted number was highest in the first year and continually decreased over time for all four ARBs. For the adjusted total number of reports, the decline was not constant over time. Conclusion A characteristic temporal pattern in the adjusted number of reports, in which the adjusted number was highest in the first year and declined thereafter, was identified. However. we did not observe a pattern consistent with the Weber effect for these four ARBs. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [McAdams, Mara A.; Governale, Laura A.; Swartz, Lynette; Hammad, Tarek A.; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP McAdams, MA (reprint author), US FDA, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM mara.mcadams@fda.hhs.gov OI McAdams-DeMarco, Mara/0000-0003-3013-925X FU Center for Drug Evaluation and Research at the US Food and Drug Administration FX The authors thank Toni Piazza-Hepp and Jean Chung for their help with obtaining information on waiver requests. We also thank the Center for Drug Evaluation and Research at the US Food and Drug Administration for sponsoring our research. NR 7 TC 13 Z9 13 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD SEP PY 2008 VL 17 IS 9 BP 882 EP 889 DI 10.1002/pds.1633 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 348NR UT WOS:000259217700005 PM 18636418 ER PT J AU Pope, SJ Holick, MF Mackin, S Godar, DE AF Pope, Stanley J. Holick, Michael F. Mackin, Steven Godar, Dianne E. TI Action spectrum conversion factors that change erythemally weighted to previtamin D(3)-weighted UV doses SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID VITAMIN-D; HUMAN-SKIN; PHOTOSYNTHESIS; EXPOSURE; SUNLIGHT AB Many solar UV measurements, either terrestrial or personal, weight the raw data by the erythemal action spectrum. However, a problem arises when one tries to estimate the benefit of vitamin D(3) production based on erythemally weighted outdoor doses, like those measured by calibrated R-B meters or polysulphone badges, because the differences between action spectra give dissimilar values. While both action spectra peak in the UVB region, the erythemal action spectrum continues throughout the UVA region while the previtamin D(3) action spectrum stops near that boundary. When one uses the previtamin D(3) action spectrum to weight the solar spectra (D(eff)), one gets a different contribution in W m(-2) than what the erythemally weighted data predicts (E(eff)). Thus, to do proper benefit assessments, one must incorporate action spectrum conversion factors (ASCF) into the calculations to change erythemally weighted to previtamin D(3)-weighted doses. To date, all benefit assessments for vitamin D(3) production in human skin from outdoor exposures are overestimates because they did not account for the different contributions of each action spectrum with changing solar zenith angle and ozone and they did not account for body geometry. Here we describe how to normalize the ratios of the effective irradiances (D(eff)/E(eff)) to get ASCF that change erythemally weighted to previtamin D(3)-weighted doses. We also give the ASCF for each season of the year in the northern hemisphere every 5 degrees from 30 degrees N to 60 degrees N, based on ozone values. These ASCF, along with geometry conversion factors and other information, can give better vitamin D(3) estimates from erythemally weighted outdoor doses. C1 [Godar, Dianne E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Mackin, Steven] Solartech Inc, Harrison Township, MI USA. [Holick, Michael F.] Boston Sch Med, Boston, MA USA. [Pope, Stanley J.] Sun Syst & Svc Inc, Oak Pk, MI USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM dianne.godar@fda.hhs.gov OI GODAR, DIANNE/0000-0002-7690-5223; Holick, Michael/0000-0001-6023-9062 NR 24 TC 19 Z9 20 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD SEP-OCT PY 2008 VL 84 IS 5 BP 1277 EP 1283 DI 10.1111/j.1751-1097.2008.00373.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 342LL UT WOS:000258785500030 PM 18513232 ER PT J AU Mettler, FA Bhargavan, M Thomadsen, BR Gilley, DB Lipoti, JA Mahesh, M McCrohan, J Yoshizumi, TT AF Mettler, Fred A., Jr. Bhargavan, Mythreyi Thomadsen, Bruce R. Gilley, Debbie B. Lipoti, Jill A. Mahesh, Mahadevappa McCrohan, John Yoshizumi, Terry T. TI Nuclear medicine exposure in the United States, 2005-2007: Preliminary results SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review AB Medical radiation exposure of the U.S. population has not been systematically evaluated for almost 25 years. In 1982, the per-capita dose was estimated to be 0.54 mSv and the collective dose 124,000 person-Sv. The preliminary estimates of the National Council on Radiation Protection and Measurements Scientific Committee 6-2 medical subgroup are that, in 2006, the per-capita dose from all medical exposure (not including radiotherapy) had increased almost 600% to 3.0 mSv and the collective dose had increased more than 700% to approximately 900,000 person-Sv. >Nuclear medicine accounted for only about 2% of all procedures but 26% of the total collective dose from diagnostic studies in medicine. In 1982, the estimated number of nuclear medicine procedures was about 7.5 million. The per-capita effective dose from nuclear medicine was 0.14 mSv and the collective dose was 32,000 person Sv. By 2005, the estimated number of procedures had increased to about 19.6 million. The per-caput effective dose increased to about 0.75 mSv and the collective dose to about 220,000 person Sv. There also has been a marked shift in the type of procedures being performed with cardiac scanning accounting for about 70% of procedures. C1 [Mettler, Fred A., Jr.] NMVAHCS, Radiol & Nucl Med Serv, Albuquerque, NM 87108 USA. [Bhargavan, Mythreyi] Amer Coll Radiol, Reston, VA USA. [Thomadsen, Bruce R.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Lipoti, Jill A.] New Jersey Dept Environm Protect, Radiat Protect Programs, Trenton, NJ USA. [Mahesh, Mahadevappa] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. [McCrohan, John] US FDA, CDRH FDA, Rockville, MD 20857 USA. [Yoshizumi, Terry T.] Duke Univ, Sch Med, Durham, NC USA. RP Mettler, FA (reprint author), NMVAHCS, Radiol & Nucl Med Serv, 1501 San Pedro Blvd SE, Albuquerque, NM 87108 USA. EM fmettler@salud.unm.edu NR 11 TC 26 Z9 26 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD SEP PY 2008 VL 38 IS 5 BP 384 EP 391 DI 10.1053/j.semnuclmed.2008.05.004 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 336UY UT WOS:000258391300009 PM 18662559 ER PT J AU Flynn, TJ Ferguson, MS AF Flynn, Thomas J. Ferguson, Martine S. TI Multiendpoint mechanistic profiling of hepatotoxicants in HepG2/C3A human hepatoma cells and novel statistical approaches for development of a prediction model for acute hepatotoxicity SO TOXICOLOGY IN VITRO LA English DT Article DE hepatotoxicity; HepG2/C3A cells; mechanistic profiling; prediction model; discriminant analysis ID TEST METHOD PERFORMANCE; IN-VITRO; RAT HEPATOCYTES; INDUCED APOPTOSIS; FUMONISIN B-1; TOXICITY; LIVER; INDUCTION; ASSAY; DRUG AB HepG2/C3A human hepatoma cells were exposed to serial concentrations of seven known hepatotoxicants for 48 h. Six endpoint assays were selected to model different mechanisms of acute hepatotoxicity. Each compound produced a unique concentration-response pattern across all endpoints. The endpoints did not correlate strongly, suggesting that each endpoint monitored an independent cellular process. Prediction models were developed using five statistical methods. The models used only known hepatotoxicants for the training set. The zero concentration (control) and all concentrations not significantly different from control were programmed as non-toxic levels and concentrations significantly different from control as toxic levels. So, rather than a binary classification of each compound (i.e., toxic or nontoxic), the models gave a prediction of the concentration, if any, at which a compound showed behavior similar to liver toxicants at their toxic concentrations. The discriminant analysis model gave the best overall performance with positive and negative predictive values of 1.00 and 0.83, respectively. Ten additional compounds were tested using this prediction model. The model predicted liver active concentrations for each compound that were consistent with their known biologically active concentrations. This model system may be useful for predicting concentration levels at which unknown compounds would display undesirable liver activity. Published by Elsevier Ltd. C1 [Flynn, Thomas J.] US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol, Labs MOD 1, Laurel, MD 20708 USA. [Ferguson, Martine S.] US FDA, Ctr Food Safety & Appl Nutr, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP Flynn, TJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol, Labs MOD 1, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM thomas.flynn@fda.hhs.gov; martine.ferguson@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 54 TC 24 Z9 25 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD SEP PY 2008 VL 22 IS 6 BP 1618 EP 1631 DI 10.1016/j.tiv.2008.04.016 PG 14 WC Toxicology SC Toxicology GA 353DW UT WOS:000259547300028 PM 18539427 ER PT J AU Deeds, JR White, KD Etheridge, SM Landsberg, JH AF Deeds, Jonathan R. White, Kevin D. Etheridge, Stacey M. Landsberg, Jan H. TI Concentrations of Saxitoxin and Tetrodotoxin in Three Species of Puffers from the Indian River Lagoon, Florida, the Location for Multiple Cases of Saxitoxin Puffer Poisoning from 2002 to 2004 SO TRANSACTIONS OF THE AMERICAN FISHERIES SOCIETY LA English DT Article ID FRESH-WATER PUFFERS; PYRODINIUM-BAHAMENSE; GENUS SPHOEROIDES; MARINE PUFFER; UNITED-STATES; FISH; TOXICITY; TOXINS; USA; RUBRIPES AB In response to multiple, unexpected cases of saxitoxin poisoning that started in January 2002, southern puffers Sphoeroides nephelus, checkered puffers S. testudineus, and bandtail puffers S. spengleri were collected from April to August 2002 from several locations in the Indian River Lagoon (IRL), Florida. Fish were analyzed for saxitoxin (STX) and tetrodotoxin (TTX) content in muscle, liver, and gonad tissues by means of the liquid chromatography-electrospray ionization-mass spectrometry method in multiple reactions monitoring mode. Spatial, species, and tissue-specific differences in toxin content and composition were found among these puffer species in the IRL. Southern puffers from the northern IRL had the highest concentrations of STX, muscle being the most contaminated tissue (1,770 +/- 159 mu g/100 g tissue [mean +/- SD]; n = 3). Southern puffers from the Banana River and central IRL had lower amounts of STX in all tissues tested. Nearly all southern puffer tissues tested had only trace amounts of TTX. Both checkered and bandtail puffers from the central and southern IRL had higher concentrations of TTX than of STX in all tissues, checkered puffer livers being the most toxic (6,075 +/- 3,283 mu g/100 g tissue; n = 3). For comparison, U.S. mid-Atlantic northern puffers S. maculatus (n = 10) were tested and found to contain no detectable amounts of STX or TTX. This research confirms that STX and not TTX was responsible for 28 poisoning cases in southern puffers from the northern IRL between 2002 and 2004, and it describes for the first time the relative distribution of STX and TTX in U.S. East Coast puffers. C1 [Deeds, Jonathan R.; White, Kevin D.; Etheridge, Stacey M.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20723 USA. [Landsberg, Jan H.] Fish & Wildlife Res Inst, Florida Fish & Wildlife Conservat Commiss, St Petersburg, FL 33712 USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, Laurel, MD 20723 USA. EM jonathan.deeds@fda.hhs.gov OI DeGrasse, Stacey/0000-0001-7808-4193 FU FDA; FWC; U.S. National Oceanic and Atmospheric Administration; Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) [NA03NOS4780196]; FWQ; ECOHAB program [233] FX The authors express sincere thanks to D. Tremain, L. Sebastian, R. Papemo, D. Adams, K. Davis, and C. Hamden, Florida Fish and Wildlife Conservation Commission (FWQ and S. Doctor, Maryland Department of Natural Resources, for specimen collection; and to S. Conrad and S. Hall, U.S. Food and Drug Administration (FDA), for technical assistance and manuscript review, respectively. All research was conducted in compliance with the Animal Welfare Act and other applicable federal statutes relating to experiments involving animals. All fish were treated humanely and with regard to the alleviation of suffering according to the principles stated by DeTolla et al. (1995). Funding or support for this research was provided by the FDA, FWC, and U.S. National Oceanic and Atmospheric Administration as part of its Ecology and Oceanography of Harmful Algal Blooms (ECOHAB) Program (award NA03NOS4780196 to the FWQ. This is contribution 233 from the ECOHAB program. NR 49 TC 17 Z9 17 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0002-8487 EI 1548-8659 J9 T AM FISH SOC JI Trans. Am. Fish. Soc. PD SEP PY 2008 VL 137 IS 5 BP 1317 EP 1326 DI 10.1577/T07-204.1 PG 10 WC Fisheries SC Fisheries GA 369OR UT WOS:000260704300005 ER PT J AU Grinev, A Daniel, S Akolkar, N Chancey, C Stramer, SL Ball, C Land, KJ Rios, M AF Grinev, A. Daniel, S. Akolkar, N. Chancey, C. Stramer, S. L. Ball, C. Land, K. J. Rios, M. TI New west nile virus subtype found in Idaho isolates from humans, mosquitoes and birds in 2006 and 2007 SO TRANSFUSION LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO CY OCT 04-07, 2008 CL Montreal, CANADA SP Amer Assoc Blood Banks C1 US FDA, CBER, OBRR, DETT,LMV, Bethesda, MD 20014 USA. [Stramer, S. L.] Amer Red Cross, Biomed Serv, Gaithersburg, MD USA. [Ball, C.] Idaho Bur Labs, Boise, ID USA. [Land, K. J.] Bonfils Blood Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 2 SU S BP 24A EP 25A PG 2 WC Hematology SC Hematology GA 347CO UT WOS:000259118400069 ER PT J AU Holloway, K Fearon, M Drebot, M Scalia, V Grinev, A Rios, M O'Brien, S AF Holloway, K. Fearon, M. Drebot, M. Scalia, V. Grinev, A. Rios, M. O'Brien, S. TI West nile viral load and genotype of viruses in Canadian blood donors during the 2006 and 2007 west Nile seasons SO TRANSFUSION LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO CY OCT 04-07, 2008 CL Montreal, CANADA SP Amer Assoc Blood Banks C1 [Holloway, K.; Drebot, M.] Publ Hlth Agcy Canada, Winnipeg, MB, Canada. [Grinev, A.] US FDA, CBER, OBRR, DETTD,LMV, Rockville, MD 20857 USA. [Fearon, M.; O'Brien, S.] Canadian Blood Serv, Ottawa, ON, Canada. EM sheila.obrien@blood.ca NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 2 SU S BP 24A EP 24A PG 1 WC Hematology SC Hematology GA 347CO UT WOS:000259118400068 ER PT J AU Menis, M Burwen, D Holness, L Anderson, S AF Menis, M. Burwen, D. Holness, L. Anderson, S. TI Blood use in the ambulatory setting among elderly in the United States SO TRANSFUSION LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO CY OCT 04-07, 2008 CL Montreal, CANADA SP Amer Assoc Blood Banks C1 [Menis, M.; Burwen, D.; Holness, L.; Anderson, S.] US FDA, CDER, Rockville, MD 20857 USA. EM steven.anderson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 2 SU S BP 76A EP 76A PG 1 WC Hematology SC Hematology GA 347CO UT WOS:000259118400221 ER PT J AU Gubemot, D Lucey, C Lee, K Conley, G Holness, L Wise, R AF Gubemot, D. Lucey, C. Lee, K. Conley, G. Holness, L. Wise, R. TI Babesiosis transmission through blood transfusion: Recent fatality reports received by FDA SO TRANSFUSION LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-of-Blood-Banks and TXPO CY OCT 04-07, 2008 CL Montreal, CANADA SP Amer Assoc Blood Banks C1 [Lucey, C.] US FDA, CBER, OBRR, DETTD, Rockville, MD 20857 USA. [Conley, G.] US FDA, CBER, Off Compliance & Biol Qual, Rockville, MD 20857 USA. EM robert.wise@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 2 SU S BP 121A EP 122A PG 2 WC Hematology SC Hematology GA 347CO UT WOS:000259118400358 ER PT J AU Selvapandiyan, A Duncan, R Mendez, J Kumar, R Salotra, P Cardo, LJ Nakhasi, HL AF Selvapandiyan, Angamuthu Duncan, Robert Mendez, Juan Kumar, Rajesh Salotra, Poonam Cardo, Lisa J. Nakhasi, Hira L. TI A Leishmania minicircle DNA footprint assay for sensitive detection and rapid speciation of clinical isolates SO TRANSFUSION LA English DT Article ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; AZAR DERMAL LEISHMANIASIS; KINETOPLAST DNA; CUTANEOUS-LEISHMANIASIS; VISCERAL LEISHMANIASIS; KALA-AZAR; BLOOD-DONORS; MUCOSAL LEISHMANIASIS; INFANTUM PARASITEMIA AB BACKGROUND: Diversity in clinical outcome, due to different species of Leishmania, and its presence in asymptomatic blood donors in endemic areas warrant development of methods that are sensitive and can rapidly identify infecting species. STUDY DESIGN AND METHODS: The kinetoplast minicircle DNA is known to have heterogeneity in sequence and is present in many thousands of copies in Leishmania. Fluorescence-based polymerase chain reaction (PCR) was used to amplify minicircle DNA from six Leishmania species from different geographic locations. The sequences were then used to construct a phylogenetic tree. Speciation of 46 blinded parasite clinical isolates from various geographic regions was validated using the assay. RESULTS: Analysis displayed a distinct cluster for each species or strain. Forty-three of 46 isolates were correctly assigned to the same species identified by isoenzyme electrophoresis. The three untyped isolates were all either new species or samples from a unique geographic region. The minicircles of the three isolates formed new clusters in the tree analysis. Using minicircle DNA as PCR target, the sensitivity of the parasite detection in the spiked blood samples was five parasites per mL. CONCLUSION: Increased sensitivity and speciation without the need for parasite culture will be useful for diagnosis and treatment in clinical settings. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD USA. Walter Reed Army Inst Res, Dept Blood Res, Transfus Med Branch, Silver Spring, MD USA. Safdarjang Hosp, Inst Pathol, Indian Council Med Res, New Delhi, India. RP Selvapandiyan, A (reprint author), Bldg 29,Room 425,8800 Rockville Pike, Bethesda, MD 20892 USA. EM angamuthu.selvapandiyan@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU CBER/OBRR; US Army Combat Casualty Care Research; Medical Research and Materiel Command FX Support for this study was provided by the CBER/OBRR intramural funds and by the US Army Combat Casualty Care Research Program, Medical Research and Materiel Command. NR 63 TC 15 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 9 BP 1787 EP 1798 DI 10.1111/j.1537-2995.2008.01798.x PG 12 WC Hematology SC Hematology GA 347CN UT WOS:000259118300005 PM 18564397 ER PT J AU McCullough, J Kahn, J Adamson, J Anderlini, P Benjamin, R Confer, D Eapen, M Hirsch, B Kuter, D Lazarus, E Pamphilon, D Stroncek, D Sugarman, J Wilson, R AF McCullough, Jeffrey Kahn, Jeffrey Adamson, John Anderlini, Paolo Benjamin, Richard Confer, Dennis Eapen, Mary Hirsch, Betsy Kuter, David Lazarus, Ellen Pamphilon, Derwood Stroncek, David Sugarman, Jeremy Wilson, Robert TI Hematopoietic growth factors - use in normal blood and stem cell donors: clinical and ethical issues SO TRANSFUSION LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; ACUTE MYOCARDIAL-INFARCTION; ENDOTHELIAL PROGENITOR CELLS; PLACEBO-CONTROLLED TRIAL; RECOMBINANT-HUMAN-ERYTHROPOIETIN; THROMBOPOIETIN RECEPTOR AGONIST; IMMUNE THROMBOCYTOPENIC PURPURA; HUMAN MEGAKARYOCYTE GROWTH; MESSENGER-RNA EXPRESSION; ACUTE MYELOID-LEUKEMIA C1 [McCullough, Jeffrey] Univ Minnesota, Minneapolis, MN 55455 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Blood Ctr Wisconsin, Milwaukee, WI USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. Amer Red Cross, Biomed Serv, Washington, DC 20006 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. US FDA, Rockville, MD 20857 USA. Univ Bristol, Bristol, Avon, England. Natl Inst Hlth, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. RP McCullough, J (reprint author), Univ Minnesota, Minneapolis, MN 55455 USA. EM mccu1001@umn.edu NR 139 TC 18 Z9 18 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2008 VL 48 IS 9 BP 2008 EP 2025 DI 10.1111/j.1537-2995.2008.01788.x PG 18 WC Hematology SC Hematology GA 347CN UT WOS:000259118300033 PM 18564401 ER PT J AU Jacobson-Kram, D AF Jacobson-Kram, D. TI Regulatory toxicology and the critical path: Predicting long-term outcomes from short-term studies SO VETERINARY PATHOLOGY LA English DT Editorial Material ID CARCINOGENICITY C1 US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jacobson-Kram, D (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 11 TC 3 Z9 3 U1 0 U2 0 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 SEP PY 2008 VL 45 IS 5 BP 707 EP 709 DI 10.1354/vp.45-5-707 PG 3 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 353AL UT WOS:000259538400017 PM 18725478 ER PT J AU Mindak, WR Cheng, J Canas, BJ Bolger, PM AF Mindak, William R. Cheng, John Canas, Benjamin J. Bolger, P. Michael TI Lead in women's and children's vitamins SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE dietary supplements; vitamins; cryogenic grinding; Pb; microwave digestion; ICP-MS ID DIETARY-SUPPLEMENTS; BIOLOGICAL SAMPLES; FOOD; HOMOGENIZATION; PRODUCTS AB A survey was conducted to determine the extent of lead (Pb) contamination in vitamins labeled for use by women and children. The Pb content of 324 multivitamin-mineral products was determined using microwave assisted nitric acid digestion and inductively coupled plasma mass spectrometry. Cryogenic grinding was used to composite soft samples such as oil filled capsules and candy-like products such as gummies and jelly beans. Estimates of Pb exposures from consumption of these products were derived for four population groups: young children (0-6 yrs), older children (7+ yrs), pregnant or lactating women, and adult women. The estimated median and maximum Pb exposures were 0.123 and 2.88 mu g/day for young children, 0.356 and 1.78 mu g/day for older children, 0.845 and 8.97 mu g/day for pregnant and lactating women, and 0.842 and 4.92 mu g/day for adult women. The overall median value for Pb exposure was 0.576 mu g/day. Five samples would have provided exposures that exceeded 4 mu g/day. Estimates of exposures were assessed with respect to safe/tolerable exposure levels that have been developed for the specific age and sex groups. These safe/tolerable levels are referred to as the provisional total tolerable intake levels (PTTI) and are 6, 15, 25, and 75 mu g Pb/day for young children, older children, pregnant or lactating women, and adult women, respectively. Estimates of Pb exposures were below the PTTI levels for the four population groups. Median and maximum values were used instead of the mean and standard deviation because of the skewed distribution of results toward lower mass fraction and exposure. C1 [Mindak, William R.; Cheng, John; Canas, Benjamin J.; Bolger, P. Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mindak, WR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Mail Stop HFS-716, College Pk, MD 20740 USA. EM william.mindak@fda.hhs.gov NR 26 TC 15 Z9 16 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 27 PY 2008 VL 56 IS 16 BP 6892 EP 6896 DI 10.1021/jf801236w PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 340GI UT WOS:000258633700017 PM 18646762 ER PT J AU Kubachka, KM Richardson, DD Heitkemper, DT Caruso, JA AF Kubachka, Kevin M. Richardson, Douglas D. Heitkemper, Douglas T. Caruso, Joseph A. TI Detection of chemical warfare agent degradation products in foods using liquid chromatography coupled to inductively coupled plasma mass spectrometry and electrospray ionization mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE chemical warfare agent degradation products; phosphate; food matrices; LC-ICP-MS; LC-ESI-MS ID FLAME PHOTOMETRIC DETECTION; CAPILLARY-ELECTROPHORESIS; ALKYLPHOSPHONIC ACIDS; ENVIRONMENTAL-SAMPLES; GAS-CHROMATOGRAPHY; PHOSPHONIC-ACIDS; ICP-MS; IDENTIFICATION; PHASE; SOIL AB The following work presents the exploration of three chromatographic separations in combination with inductively coupled plasma mass spectrometry (ICP-MS) for the analysis of chemical warfare agent degradation products (CWADPs). The robust ionization of ICP is virtually matrix independent thus enabling the examination of sample matrices generally considered too complicated for analysis by electrospray ionization (ESI) or atmospheric pressure chemical ionization MS with little to no sample preparation. The analysis was focused on detecting CWADPs in food matrices, as they present possible vehicles for terrorist contamination. Due to the specific detection of P-31 by ICP-MS, resolution of analytes of interest from other P-containing interferences (H3PO4) was a crucial part of each separation. Up to 10 CWADPs were separated in the presence of H3PO4 with detection limits in the low part per billion levels using the methods described. Additionally, one method was tailored to be compatible with both ICP-MS and ESI-MS making structural verification possible. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kubachka, Kevin M.; Richardson, Douglas D.; Caruso, Joseph A.] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. [Kubachka, Kevin M.] US FDA, Cincinnati, OH 45237 USA. [Heitkemper, Douglas T.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu FU US Food and Drug Administration (FDA); US Environmental Protection Agency; NIEHS [ES04908]; Metallomics Center at the University of Cincinnati FX This project was supported in part through an Interagency Agreement between the US Food and Drug Administration (FDA) and US Environmental Protection Agency and by an appointment to the Research Fellowship Program at the FDA administered by Oak Ridge Associated Universities through a contract with the US FDA. The authors would like to thank NIEHS grant number ES04908 for partial funding. We are also is grateful to Agilent Technologies for their continuing support vital to our studies at the Metallomics Center at the University of Cincinnati. NR 41 TC 15 Z9 15 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD AUG 22 PY 2008 VL 1202 IS 2 BP 124 EP 131 DI 10.1016/j.chroma.2008.04.028 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 341EK UT WOS:000258696800003 PM 18644601 ER PT J AU Harp, BP Scher, AL Yang, HH Brodie, D Sullivan, M Barrows, JN AF Harp, Bhakti Petigara Scher, Alan L. Yang, Huei-Hsuan Brodie, Darlene Sullivan, Michael Barrows, Julie N. TI ANYL 151-High-performance liquid chromatographic determination of two manufacturing intermediates and two subsidiary colors in D&C Red No. 6, D&C Red No. 7, and their lakes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Harp, Bhakti Petigara; Scher, Alan L.; Yang, Huei-Hsuan; Brodie, Darlene; Sullivan, Michael; Barrows, Julie N.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. EM bhakti.petigara@fda.hhs.gov; ascher@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 151-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256301352 ER PT J AU Jackson, LS AF Jackson, Lauren S. TI AGFD 73-Chemical food safety issues: Past, present and future SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Jackson, Lauren S.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 73-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256300225 ER PT J AU Kondragunta, B Drew, J Brorson, K Moreira, AR Rao, G AF Kondragunta, Bhargavi Drew, Jessica Brorson, Kurt Moreira, Antonio R. Rao, Govind TI BIOT 420-Advances in sub-cloning using high-throughput bioreactors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Kondragunta, Bhargavi; Drew, Jessica; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM bkondra1@umbc.edu; Kurt.Brorson@fda.hhs.gov; moreira@umbc.edu; grao@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 420-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302207 ER PT J AU Krantz, ZB Weisz, A AF Krantz, Zoe B. Weisz, Adrian TI ANYL 166-Determination of synthetic by-products and an intermediate in the color additives D&C Red Nos. 27 and 28 (phloxine B) using high-performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Krantz, Zoe B.; Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM zoe.krantz@fda.hhs.gov; adnan.weisz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 166-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256301240 ER PT J AU Lute, S Shen, H Brorson, K Frey, D AF Lute, Scott Shen, Hong Brorson, Kurt Frey, Douglas TI BIOT 424-Characterization and purification of bacteriophages using chromatofocusing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Shen, Hong; Frey, Douglas] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. EM lute@cber.fda.gov; kurt.brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 424-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302027 ER PT J AU Park, JT Fuchs, C Swann, P AF Park, Jun T. Fuchs, Chana Swann, Patrick TI BIOT 124-Regulatory aspects of antibody-based immunoconjugates SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Park, Jun T.; Fuchs, Chana; Swann, Patrick] US FDA, Div Monoclonal Antibodies, OBP, CDER, Bethesda, MD 20892 USA. EM jun.park@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 124-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302082 ER PT J AU Swann, PG AF Swann, Patrick G. TI BIOT 85-Quality by Design in biotechnology product development and manufacturing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Swann, Patrick G.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM patrick.swann@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 85-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302495 ER PT J AU Vallejos, J Brorson, K Moreira, AR Rao, G AF Vallejos, Jose Brorson, Kurt Moreira, Antonio R. Rao, Govind TI BIOT 391-Oxygen transfer characterization of process scouting devices using a noninvasive optical sensor SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Vallejos, Jose; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Bethesda, MD 20892 USA. EM jose7@umbc.edu; kurt.brorson@fda.hhs.gov; moreira@umbc.edu; grao@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 391-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302182 ER PT J AU Yang, HHW Weisz, A AF Yang, H-H. Wendy Weisz, Adrian TI ANYL 164-Determination of synthetic by-products and an intermediate in the color additive D&C Orange No. 5 using high-performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Yang, H-H. Wendy; Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM hueihsuan.yang@fda.hhs.gov; adrian.weisz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 164-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256301153 ER PT J AU Yin, JJ AF Yin, Jun-Jie TI AGFD 37-Studies on the oxygen diffusion-concentration products of conjugated linoleic acid (CLA) isomers in liposomes and phospholipid solutions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM jyin@cfsan.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 37-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256300175 ER PT J AU Zhang, M Lute, S Norling, L Korbe, D Padua, K Blank, G Chen, Q Brorson, K AF Zhang, Min Lute, Scott Norling, Lenore Korbe, Denise Padua, Kevin Blank, Greg Chen, Qi Brorson, Kurt TI BIOT 55-Robustness of retroviral clearance by capture protein A chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Zhang, Min; Norling, Lenore; Korbe, Denise; Padua, Kevin; Blank, Greg; Chen, Qi] Genentech Inc, Proc Res & Dev, San Francisco, CA 94080 USA. [Lute, Scott; Brorson, Kurt] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM zhang.min@gene.com; lute@cber.fda.gov; norling.lenore@gene.com; korbe.denise@gene.com; kurt.brorson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 17 PY 2008 VL 236 MA 55-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 499WD UT WOS:000270256302473 ER PT J AU Ye, HP Hill, J Kauffman, J Gryniewicz, C Han, XL AF Ye, Hongping Hill, John Kauffman, John Gryniewicz, Connie Han, Xianlin TI Detection of protein modifications and counterfeit protein pharmaceuticals using isotope tags for relative and absolute quantification and matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry: Studies of insulins SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE iTRAQ/MALDI; insulins; Glu-C; deamidation; aggregation; generic protein drugs; counterfeit ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DEGRADATION; PERSPECTIVE; PROTEOMICS; STABILITY; PRODUCTS; COMPLEX AB Isotope tags for relative and absolute quantification (iTRAQ) reagent coupled with matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) mass spectrometric analysis has been evaluated as both a qualitative and quantitative method for the detection of modifications to active pharmaceutical ingredients derived from recombinant DNA technologies and as a method to detect counterfeit drug products. Five types of insulin (human, bovine, porcine, Lispro, and Lantus) were used as model products in the study because of their minor variations in amino acid sequence. Several experiments were conducted in which each insulin variant was separately digested with Glu-C, and the digestate was labeled with one of four different iTRAQ reagents. All digestates were then combined for desalting and MALDI-TOF/TOF mass spectrometric analysis. When the digestion procedure was optimized, the insulin sequence coverage was 100%. Five different types of insulin were readily differentiated, including human insulin (P28K29) and Lispro insulin (K28P29), which differ only by the interchange of two contiguous residues. Moreover, quantitative analyses show that the results obtained from the iTRAQ method agree well with those determined by other conventional methods. Collectively, the iTRAQ method can be used as a qualitative and quantitative technique for the detection of protein modification and counterfeiting. Published by Elsevier Inc. C1 [Ye, Hongping; Kauffman, John; Gryniewicz, Connie] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Hill, John] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. [Han, Xianlin] Washington Univ, Sch Med, Dept Internal Med, Div Bioorgan Chem & Mol Pharmacol, St Louis, MO 63110 USA. RP Ye, HP (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM hongping.ye@fda.hhs.gov FU NIA NIH HHS [R01 AG031675]; NIDDK NIH HHS [P30 DK056341-08, P30 DK056341-07] NR 28 TC 8 Z9 9 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 15 PY 2008 VL 379 IS 2 BP 182 EP 191 DI 10.1016/j.ab.2008.04.037 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 324XH UT WOS:000257552200005 PM 18489896 ER PT J AU Lechleider, RJ Arlen, PM Tsang, KY Steinberg, SM Yokokawa, J Cereda, V Camphausen, K Schlom, J Dahut, WL Gulley, JL AF Lechleider, Robert J. Arlen, Philip M. Tsang, Kwong-Yok Steinberg, Seth M. Yokokawa, Junko Cereda, Vittore Camphausen, Kevin Schlom, Jeffrey Dahut, William L. Gulley, James L. TI Safety and immunologic response of a viral vaccine to prostate-specific antigen in combination with radiation therapy when metronomic-dose interleukin 2 is used as an adjuvant SO CLINICAL CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; RADICAL PROSTATECTOMY; IN-VIVO; RECOMBINANT INTERLEUKIN-2; DEFINITIVE RADIOTHERAPY; EXTERNAL RADIOTHERAPY; ANDROGEN SUPPRESSION; COMBINED ORCHIECTOMY; PHASE-II; CANCER AB Purpose: We have previously reported on the safety and immunologic response of a poxvirus-based vaccine encoding prostate-specific antigen (PSA) used in combination with radiation therapy in patients with localized prostate cancer. We hypothesized that a "metronomic" dose of interleukin 2 (IL-2) as a biological adjuvant would cause less toxicity while maintaining immunologic response. Experimental Design: Eighteen patients with localized prostate cancer were treated in a single-arm trial using previously established doses of vaccine and radiation therapy. The vaccine used was a recombinant vaccinia virus engineered to encode PSA admixed with a recombinant vaccinia encoding the costimulatory molecule B7.1, followed by booster vaccinations with a recombinant fowlpox vector expressing PSA. Patients received a total of eight planned vaccination cycles, once every 4 weeks, with granulocyte-macrophage colony-stimulating factor given on days 1 to 4 and interleukin 2 (IL-2) at a dose of 0.6 MIU/M-2 given from days 8 to 21 after each vaccination. Definitive external beam radiation therapy was initiated after the third vaccination cycle. Patients were evaluated for safety and immunologic response. Toxicity and immunologic activity were compared with the previously reported regimen containing a higher dose of IL-2. Results: Seventeen of 18 patients received all eight cycles of vaccine with IL-2. Five of eight HLA-A2(+) patients evaluated had an increase in PSA-specific T cells of >= 3-fold. Toxicities were generally mild, with only seven vaccination cycles of 140 given resulting in grade 3 toxicities possibly attributable to IL-2. Conclusions: Metronomic-dose IL-2 in combination with vaccine and radiation therapy is safe, can induce prostate-specific immune responses, and has immunologic activity similar to low-dose IL-2, with markedly reduced toxicities. C1 [Lechleider, Robert J.; Arlen, Philip M.; Tsang, Kwong-Yok; Steinberg, Seth M.; Yokokawa, Junko; Cereda, Vittore; Camphausen, Kevin; Schlom, Jeffrey; Gulley, James L.] NCI, NIH, Ctr Canc Res, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, NIH, Ctr Canc Res, Biostat & Data Management Sect,Off Clin Director, Bethesda, MD 20892 USA. [Dahut, William L.] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. [Lechleider, Robert J.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Oncol Drug Prod, Silver Spring, MD USA. RP Schlom, J (reprint author), NCI, NIH, Ctr Canc Res, Tumor Immunol & Biol Lab, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS [Z01 BC010425-09] NR 36 TC 60 Z9 61 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2008 VL 14 IS 16 BP 5284 EP 5291 DI 10.1158/1078-0432.CCR-07-5162 PG 8 WC Oncology SC Oncology GA 338QX UT WOS:000258523800035 PM 18698048 ER PT J AU Sun, J Schnackenberg, LK Holland, RD Schmitt, TC Cantor, GH Dragan, YR Beger, RD AF Sun, Jinchun Schnackenberg, Laura K. Holland, Ricky D. Schmitt, Thomas C. Cantor, Glenn H. Dragan, Yvonne R. Beger, Richard D. TI Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE acetaminophen; metabonomics; metabolomics ID INDUCED HEPATIC-NECROSIS; SPRAGUE-DAWLEY RATS; S-ADENOSYLMETHIONINE PROTECTS; ENDOGENOUS METABOLITES; INDUCED HEPATOTOXICITY; LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; COVALENT BINDING; N-ACETYLCYSTEINE; L-METHIONINE AB Urinary metabolic perturbations associated with acute and chronic acetaminophen-induced hepatotoxicity were investigated using nuclear magnetic resonance (NMR) spectroscopy and ultra performance liquid chromatography/mass spectrometry (UPLC/MS) metabonomics approaches to determine biomarkers of hepatotoxicity. Acute and chronic doses of acetaminophen (APAP) were administered to male Sprague-Dawley rats. NMR and UPLC/MS were able to detect both drug metabolites and endogenous metabolites simultaneously. The principal component analysis (PCA) of NMR or UPLC/MS spectra showed that metabolic changes observed in both acute and chronic dosing of acetaminophen were similar. Histopathology and clinical chemistry studies were performed and correlated well with the PCA analysis and magnitude of metabolite changes. Depletion of antioxidants (e.g. ferulic acid), trigonelline, S-adenosyl-L-methionine, and energy-related metabolites indicated that oxidative stress was caused by acute and chronic acetaminophen administration. Similar patterns of metabolic changes in response to acute or chronic dosing suggest similar detoxification and recovery mechanisms following APAP administration. Published by Elsevier B.V. C1 [Sun, Jinchun; Schnackenberg, Laura K.; Holland, Ricky D.; Schmitt, Thomas C.; Dragan, Yvonne R.; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Cantor, Glenn H.] Pharmacia Corp, Invest Toxicol, Kalamazoo, MI 49001 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov FU National Center for Toxicological Research; Oak Ridge Associated Universities FX Jinchun Sun was supported in part by appointment to the ORAU Research Program at the National Center for Toxicological Research administered by the Oak Ridge Associated Universities through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We thank John Wijsman (Pharmacia Corp.) for carrying out the in-life portion of the study and Mary Bollard, Olaf Beckonert, Hector Keun, Henrik Antti, Timothy Ebbels, Elaine Holmes, John Lindon, and Jeremy Nicholson (imperial College-London) for their key role in organizing the COMET effort. We would like to thank Imperial College and the other four COMET companies for allowing Don Robertson and Michael Reily of Pfizer to take the time and effort to provide the NCTR Center for Metabolomics with the acetaminophen urine samples through a material transfer agreement. ACD/Labs 1D NMR manager is part of "beta test" collaboration between the NCTR and ACD/Labs. Waters LCT-Premier, and MarkerLynx software was part of a "beta test" material transfer agreement between Waters and the NCTR. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 50 TC 84 Z9 93 U1 1 U2 28 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 AUG 15 PY 2008 VL 871 IS 2 BP 328 EP 340 DI 10.1016/j.jchromb.2008.04.008 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 347HE UT WOS:000259130400022 PM 18472313 ER PT J AU Rubin, SA Qi, L Audet, SA Sullivan, B Carbone, KM Bellini, WJ Rota, PA Sirota, L Beeler, J AF Rubin, Steven A. Qi, Li Audet, Susette A. Sullivan, Bradley Carbone, Kathryn M. Bellini, William J. Rota, Paul A. Sirota, Lev Beeler, Judy TI Antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralizes a heterologous wild-type mumps virus associated with a large outbreak SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1st Vaccine Congress CY DEC 09-11, 2007 CL Amsterdam, NETHERLANDS ID HYDROPHOBIC PROTEIN GENE; LIVE ATTENUATED MEASLES; UNITED-STATES; ANTIGENIC RELATEDNESS; RUBELLA VACCINATION; IMMUNE-RESPONSES; FIELD EVALUATION; YOUNG-ADULTS; FOLLOW-UP; GENOTYPE AB Recent mumps outbreaks in older vaccinated populations were caused primarily by genotype G viruses, which are phylogenetically distinct from the genotype A vaccine strains used in the countries affected by the outbreaks. This finding suggests that genotype A vaccine strains could have reduced efficacy against heterologous mumps viruses. The remote history of vaccination also suggests that waning immunity could have contributed to susceptibility. To examine these issues, we obtained consecutive serum samples from children at different intervals after vaccination and assayed the ability of these samples to neutralize the genotype A Jeryl Lynn mumps virus vaccine strain and a genotype G wild-type virus obtained during the mumps outbreak that occurred in the United States in 2006. Although the geometric mean neutralizing antibody titers against the genotype G virus were approximately one-half the titers measured against the vaccine strain, and although titers to both viruses decreased with time after vaccination, antibody induced by immunization with the Jeryl Lynn mumps vaccine strain effectively neutralized the outbreak-associated virus at all time points tested. C1 [Rubin, Steven A.; Qi, Li; Audet, Susette A.; Carbone, Kathryn M.; Sirota, Lev; Beeler, Judy] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, OVRR, Bethesda, MD 20892 USA. [Sullivan, Bradley] Marshfield Clin Fdn Med Res & Educ, Dept Pediat, Marshfield, WI USA. [Bellini, William J.; Rota, Paul A.] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA USA. RP Rubin, SA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, OVRR, Bldg 29A,Rm 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM steven.rubin@fda.hhs.gov NR 48 TC 45 Z9 48 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2008 VL 198 IS 4 BP 508 EP 515 DI 10.1086/590115 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 329TK UT WOS:000257893300009 PM 18558869 ER PT J AU Peters, NC Egen, JG Secundino, N Debrabant, A Kimblin, N Kamhawi, S Lawyer, P Fay, MP Germain, RN Sacks, D AF Peters, Nathan C. Egen, Jackson G. Secundino, Nagila Debrabant, Alain Kimblin, Nicola Kamhawi, Shaden Lawyer, Phillip Fay, Michael P. Germain, Ronald N. Sacks, David TI In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies SO SCIENCE LA English DT Article ID MAJOR INFECTION; MICE; CELLS; MACROPHAGE; APOPTOSIS; SKIN; GRANULOCYTES; RECRUITMENT; MODULATION; CLEARANCE AB Infection with the obligate intracellular protozoan Leishmania is thought to be initiated by direct parasitization of macrophages, but the early events following transmission to the skin by vector sand flies have been difficult to examine directly. Using dynamic intravital microscopy and flow cytometry, we observed a rapid and sustained neutrophilic infiltrate at localized sand fly bite sites. Invading neutrophils efficiently captured Leishmania major ( L. m.) parasites early after sand fly transmission or needle inoculation, but phagocytosed L. m. remained viable and infected neutrophils efficiently initiated infection. Furthermore, neutrophil depletion reduced, rather than enhanced, the ability of parasites to establish productive infections. Thus, L. m. appears to have evolved to both evade and exploit the innate host response to sand fly bite in order to establish and promote disease. C1 [Egen, Jackson G.; Germain, Ronald N.] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Peters, Nathan C.; Secundino, Nagila; Kimblin, Nicola; Kamhawi, Shaden; Lawyer, Phillip; Sacks, David] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Debrabant, Alain] US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. RP Egen, JG (reprint author), NIAID, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. EM jegen@niaid.nih.gov; dsacks@nih.gov RI Okpebholo, Love/A-8163-2010; OI Egen, Jackson/0000-0003-2053-0837; Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS [Z01 AI000256-26, Z01 AI000494-21] NR 26 TC 343 Z9 351 U1 5 U2 28 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 15 PY 2008 VL 321 IS 5891 BP 970 EP 974 DI 10.1126/science.1159194 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 337LD UT WOS:000258436700041 PM 18703742 ER PT J AU Yourick, JJ Jung, CT Bronaugh, RL AF Yourick, Jeffrey J. Jung, Connie T. Bronaugh, Robert L. TI In vitro and in vivo percutaneous absorption of retinol from cosmetic formulations: Significance of the skin reservoir and prediction of systemic absorption SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE skin; dermal; absorption; retinal; lipophilic ID VITAMIN-A; METABOLISM; ACID; 0.1-PERCENT; PHOTODAMAGE; PALMITATE; TRETINOIN AB The percutaneous absorption of retinol (Vitamin A) from cosmetic formulations was studied to predict systemic absorption and to understand the significance of the skin reservoir in in vitro absorption studies. Viable skin from fuzzy rat or human subjects was assembled in flow-through diffusion cells for in vitro absorption studies. In vivo absorption studies using fuzzy rats were performed in glass metabolism cages for collection of urine, feces, and body content. Retinol (0.3%) formulations (hydroalcoholic gel and oil-in-water emulsion) containing H-3-retinol were applied and absorption was measured at 24 or 72 h. All percentages reported are % of applied dose. In vitro studies using human skin and the gel and emulsion vehicles found 0.3 and 1.3% retinol, respectively, in receptor fluid at 24 h. Levels of absorption in the receptor fluid increased over 72 h with the gel and emulsion vehicles. Using the gel vehicle, in vitro rat skin studies found 23% in skin and 6% in receptor fluid at 24 h, while 72-h studies found 18% in skin and 13% in receptor fluid. Thus, significant amounts of retinol remained in rat skin at 24 h and decreased over 72 h, with proportional increases in receptor fluid. In vivo rat studies with the gel found 4% systemic absorption of retinol after 24 h and systemic absorption did not increase at 72 h. Retinol remaining in rat skin after in vivo application was 18% and 13% of the applied dermal dose after 24 and 72 h, respectively. Similar observations were made with the oil-in water emulsion vehicle in the rat. Retinol formed a reservoir in rat skin both in vivo and in vitro. Little additional retinol was bioavailable after 24 h. Comparison of these in vitro and in vivo results for absorption through rat skin indicates that the 24-h in vitro receptor fluid value accurately estimated 24-h in vivo systemic absorption. Therefore, the best single estimate of retinol systemic absorption from in vitro human skin studies is the 24-h receptor fluid value. However, the receptor fluid value from the 72-h extended study may be used in a worst-case exposure estimate. In conclusion, in vivo skin absorption studies can be useful in determining whether to include material in the in vitro skin reservoir as absorbable material in estimates of systemic absorption. Published by Elsevier Inc. C1 [Yourick, Jeffrey J.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Jung, Connie T.] US FDA, Off Commissioner, Off Policy, Rockville, MD 20857 USA. RP Yourick, JJ (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, Harvey Wiley Bldg,HFS 717,Room 4E-019,5100 Paint, College Pk, MD 20740 USA. EM jeffrey.yourick@fda.hhs.gov FU U.S. Food and Drug Administration's Office of Women's Health FX This research was supported by the U.S. Food and Drug Administration's Office of Women's Health. NR 32 TC 26 Z9 26 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 15 PY 2008 VL 231 IS 1 BP 117 EP 121 DI 10.1016/j.taap.2008.04.006 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 345CU UT WOS:000258974400015 PM 18511092 ER PT J AU de Breyne, S Bonderoff, JM Chumakov, KM Lloyd, RE Hellen, CUT AF de Breyne, Sylvain Bonderoff, Jennifer M. Chumakov, Konstantin M. Lloyd, Richard E. Hellen, Christopher U. T. TI Cleavage of eukaryotic initiation factor eIF5B by enterovirus 3C proteases SO VIROLOGY LA English DT Article DE coxsackievirus; eIF5B; poliovirus; protease; rhinovirus; translation shutoff ID BINDING-PROTEIN COMPLEX; INFECTED HELA-CELLS; POLIOVIRUS INFECTION; POLY(A)-BINDING PROTEIN; IN-VITRO; ANTIVIRAL ACTIVITY; MESSENGER-RNA; FACTOR-III; TRANSLATION; RIBOSOME AB The enteroviruses poliovirus (PV), Coxsackie B virus (CVB) and rhinovirus (HRV) are members of Picorna-viridae that inhibit host cell translation early in infection. Enterovirus translation soon predominates in infected cells, but eventually also shuts off. This complex pattern of modulation of translation suggests regulation by a multifactorial mechanism. We report here that eIF5B is proteolytically cleaved during PV and CVB infection of cultured cells, beginning at 3 hours post-infection and increasing thereafter. Recombinant PV, CVB and HRV 3C(pro) cleaved purified native rabbit eukaryotic initiation factor (eIF) 5B in vitro at a single site (VVEQ down arrow G, equivalent to VMEQ down arrow G(479) in human eIF5B) that is consistent with the cleavage specificity of enterovirus 3C proteases. Cleavage separates the N-terminal domain of eIF5B from its essential conserved central GTPase and C-terminal domains. 3C(pro)-mediated cleavage of eIF5B may thus play an accessory role in the shutoff of translation that occurs in enterovirus-infected cells. (c) 2008 Elsevier Inc. All rights reserved. C1 [de Breyne, Sylvain; Bonderoff, Jennifer M.; Lloyd, Richard E.; Hellen, Christopher U. T.] Suny Downstate Med Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. [Bonderoff, Jennifer M.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hellen, CUT (reprint author), Suny Downstate Med Ctr, Dept Microbiol & Immunol, 450 Clarkson Ave,Box 44, Brooklyn, NY 11203 USA. EM christopher.hellen@downstate.edu RI de Breyne, Sylvain/M-6489-2014 OI de Breyne, Sylvain/0000-0002-1632-3475 FU NIAID NIH HHS [AI-51340, AI-50237, R01 AI050237, R01 AI051340, R56 AI050237, R56 AI050237-06, R56 AI051340, R56 AI051340-06] NR 38 TC 31 Z9 31 U1 1 U2 5 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 AUG 15 PY 2008 VL 378 IS 1 BP 118 EP 122 DI 10.1016/j.virol.2008.05.019 PG 5 WC Virology SC Virology GA 335UI UT WOS:000258316100013 PM 18572216 ER PT J AU Tareke, E Lyn-Cook, B Robinson, B Ali, SF AF Tareke, Eden Lyn-Cook, Beverly Robinson, Bonnie Ali, Syed F. TI Acrylamide: A dietary carcinogen formed in vivo? SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; endogenous formation; oxidative stress; MPTP; METH ID HEMOGLOBIN ADDUCT FORMATION; FISCHER-344 RATS; FATTY-ACIDS; EXPOSURE; MICE; GLYCIDAMIDE; HUMANS; NEUROTOXICITY; ONCOGENICITY; METABOLISM AB Acrylamide, a chemical formed during heating of human foods, reacts with N-terminal valine in hemoglobin (Hb) and forms stable reaction products (adducts). These adducts to N-terminal valine in Hb have been used to estimate daily intake of acrylamide. Daily intake of acrylamide estimated from Hb adduct levels was higher than daily intake estimated from dietary questionnaires, possibly indicating other sources of exposures. Therefore, in this study the possible endogenous formation of acrylamide was investigated by treating mice with FeSO4, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloric acid (MPTP), or methamphetamine (METH). Acrylamide Hb adducts were determined, and a significant increase (p < 0.05) in acrylamide Hb adduct levels was observed 24 h following treatment with FeSO4 and 72 h following treatment with MPTP or METH. The results of this study show that acrylamide Hb adduct levels are increased in mice treated with compounds known to induce free radicals, thus suggesting the endogenous production of acrylamide. C1 [Tareke, Eden; Lyn-Cook, Beverly] Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Robinson, Bonnie] Toxicol Pathol Assoc Inc, Jefferson, AR 72079 USA. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Tareke, E (reprint author), Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM eden.tareke@fda.hhs.gov NR 31 TC 10 Z9 10 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 13 PY 2008 VL 56 IS 15 BP 6020 EP 6023 DI 10.1021/jf703749h PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 335DF UT WOS:000258270300007 PM 18624427 ER PT J AU Doerge, DR Young, JF Chen, JJ DiNovi, MJ Henry, SH AF Doerge, Daniel R. Young, John F. Chen, James J. DiNovi, Michael J. Henry, Sara H. TI Using dietary exposure and physiologically based pharmacokinetic/pharmacodynamic modeling in human risk extrapolations for acrylamide toxicity SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE acrylamide; glycidamide; risk assessment; cancer; neurotoxicity; PBPK modeling; DNA adducts ID TANDEM MASS-SPECTROMETRY; HEMOGLOBIN ADDUCTS; FISCHER-344 RATS; N-METHYLOLACRYLAMIDE; MERCAPTURIC ACIDS; DRINKING-WATER; B6C3F(1) MICE; CANCER-RISK; F344 RATS; GLYCIDAMIDE AB The discovery of acrylamide (AA) in many common cooked starchy foods has presented significant challenges to toxicologists, food scientists, and national regulatory and public health organizations because of the potential for producing neurotoxicity and cancer. This paper reviews some of the underlying experimental bases for AA toxicity and earlier risk assessments. Then, dietary exposure modeling is used to estimate probable AA intake in the U.S. population, and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling is used to integrate the findings of rodent neurotoxicity and cancer into estimates of risks from human AA exposure through the diet. The goal of these modeling techniques is to reduce the uncertainty inherent in extrapolating toxicological findings across species and dose by comparing common exposure biomarkers. PBPK/PD modeling estimated population-based lifetime excess cancer risks from average AA consumption in the diet in the range of 1-4 x 10(-4); however, modeling did not support a link between dietary AA exposure and human neurotoxicity because marginal exposure ratios were 50-300 lower than in rodents. In addition, dietary exposure modeling suggests that because AA is found in so many common foods, even big changes in concentration for single foods or groups of foods would probably have a small impact on overall population-based intake and risk. These results suggest that a more holistic analysis of dietary cancer risks may be appropriate, by which potential risks from AA should be considered in conjunction with other risks and benefits from foods. C1 [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [DiNovi, Michael J.; Henry, Sara H.] Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov NR 61 TC 26 Z9 28 U1 1 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD AUG 13 PY 2008 VL 56 IS 15 BP 6031 EP 6038 DI 10.1021/jf073042g PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 335DF UT WOS:000258270300009 PM 18624435 ER PT J AU Eichelberger, M Golding, H Hess, M Weir, J Subbarao, K Luke, CJ Friede, M Wood, D AF Eichelberger, Maryna Golding, Hana Hess, Maureen Weir, Jerry Subbarao, Kanta Luke, Catherine J. Friede, Martin Wood, David TI FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007 SO VACCINE LA English DT Editorial Material DE influenza type A; avian influenza; pandemic; correlated of protection AB The goals of the workshop were to identify gaps in our knowledge and abilities to address the unique challenges encountered in the development of vaccines intended to protect against pandemic influenza and to facilitate implementation of a global research agenda to improve efficacy assessment of pandemic influenza vaccines. This workshop included discussions on: (i) current knowledge regarding immune correlates of protection against seasonal influenza; (ii) human immune responses to avian influenza infection and vaccines for novel influenza viruses: (iii) limitations of currently available assays to evaluate vaccine immunogenicity; and (iv) potential insights from animal models for correlates of protection against avian influenza. C1 [Eichelberger, Maryna; Golding, Hana; Hess, Maureen; Weir, Jerry] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. [Subbarao, Kanta; Luke, Catherine J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Friede, Martin; Wood, David] WHO, CH-1211 Geneva, Switzerland. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov NR 5 TC 72 Z9 73 U1 0 U2 3 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 AUG 12 PY 2008 VL 26 IS 34 BP 4299 EP 4303 DI 10.1016/j.vaccine.2008.06.012 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 342WF UT WOS:000258813600001 PM 18582523 ER PT J AU Shah, RB Bryant, A Collier, J Habib, MJ Khan, MA AF Shah, R. B. Bryant, A. Collier, J. Habib, M. J. Khan, M. A. TI Stability indicating validated HPLC method for quantification of levothyroxine with eight degradation peaks in the presence of excipients SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE levothyroxine; impurities; degradation products; validation; excipients ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SODIUM LEVOTHYROXINE; CONTENT UNIFORMITY; TABLET FORMULATIONS; LIOTHYRONINE; ASSAY; DISSOLUTION AB A simple, sensitive, accurate, and robust stability indicating analytical method is presented for identification, separation, and quantitation Of L-thyroxine and eight degradation impurities with an internal standard. The method was used in the presence of commonly used formulation excipients such as butylated hydroxyanisole, povidone, crospovidone, croscarmellose sodium, mannitol, sucrose, acacia, lactose monohydrate, confectionary sugar, microcrystalline cellulose, sodium laurel sulfate, magnesium stearate, talc, and silicon dioxide. The two active thyroid hormones: 3,3',5,5'-tetra-iodO-L-thyronine (Lthyroxine-T4) and 3,3',5-tri-iodO-L-thyronine J3) and degradation products including di-iodothyronine J2), thyronine (TO), tyrosine (Tyr), di-iodotyrosine (DIT), mono-iodotyrosine (MIT), 3,3',5,5'-tetraiodothyroacetic acid J4AA) and 3,31,5-tri-iodothyroacetic acid (T3AA) were assayed by the current method. The separation Of L-thyroxine and eight metabolites along with theophylline (internal standard) was achieved using a C18 column (25oC) with a mobile phase of trifluoroacetic acid (0.1%, v/v, pH 3)-acetonitrile in gradient elution at 0.8 ml/min at 223 nnn. The sample diluent was 0.01 M methanolic NaOH. Method was validated according to FDA, USP, and ICH guidelines for inter-day accuracy, precision, and robustness after checking performance with system suitability. Tyr (4.97 min), theophylline (9.09 min), MIT (9.55 min), DIT (11.37 min), TO (11.63 min), T2 (14.47 min), T3 (16.29 min), T4 (17.60 min), T3AA (22.71 min), and T4AA (24.83 min) separated in a single chromatographic run. Linear relationship (r2 > 0.99) was observed between the peak area ratio and the concentrations for all of the compounds within the range of 2-20 I.Lg/ml. The total time for analysis, equilibration and recovery was 40 min. The method was shown to separate well from commonly employed formulation excipients. Accuracy ranged from 95 to 105% for T4 and 90 to 110% for all other compounds. Precision was <2% for all the compounds. The method was found to be robust with minor changes in injection volume, flow rate, column temperature, and gradient ratio. Validation results indicated that the method shows satisfactory linearity, precision, accuracy, and ruggedness and also stress degradation studies indicated that the method can be used as stability indicating method for L-thyroxine in the presence of excipients. Published by Elsevier B.V. C1 [Shah, R. B.; Bryant, A.; Collier, J.; Khan, M. A.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Collier, J.; Habib, M. J.] Howard Univ, Dept Pharmaceut Sci, Sch Pharm, Washington, DC 20059 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Mansoor.khan@fda.hhs.gov NR 18 TC 20 Z9 21 U1 4 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD AUG 6 PY 2008 VL 360 IS 1-2 BP 77 EP 82 DI 10.1016/j.ijpharm.2008.04.018 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 338BQ UT WOS:000258480300010 PM 18524511 ER PT J AU Tang, S Bertke, AS Patel, A Wang, K Cohen, JI Krause, PR AF Tang, Shuang Bertke, Andrea S. Patel, Amita Wang, Kening Cohen, Jeffrey I. Krause, Philip R. TI An acutely and latently expressed herpes simplex virus 2 viral microRNA inhibits expression of ICP34.5, a viral neurovirulence factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HSV; latency-associated transcript; latency; reactivation; human ID SIMPLEX-VIRUS TYPE-1; PROTEIN-SYNTHESIS; MALIGNANT GLIOMA; INFECTED NEURONS; HERPES; TRANSCRIPT; GENE; IDENTIFICATION; REACTIVATION; PROMOTER AB Latency-associated transcript (LAT) sequences regulate herpes simplex virus (HSV) latency and reactivation from sensory neurons. We found a HSV-2 LAT-related microRNA (miRNA) designated miR-I in transfected and infected cells in vitro and in acutely and latently infected ganglia of guinea pigs in vivo. miR-I is also expressed in human sacral dorsal root ganglia latently infected with HSV-2. miR-I is expressed under the LAT promoter in vivo in infected sensory ganglia. We also predicted and identified a HSV-1 LAT exon-2 viral miRNA in a location similar to miR-I, implying a conserved mechanism in these closely related viruses. In transfected and infected cells, miR-I reduces expression of ICP34.5, a key viral neurovirulence factor. We hypothesize that miR-I may modulate the outcome of viral infection in the peripheral nervous system by functioning as a molecular switch for ICP34.5 expression. C1 [Tang, Shuang; Bertke, Andrea S.; Patel, Amita; Krause, Philip R.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. [Wang, Kening; Cohen, Jeffrey I.] NIAID, Lab Clin Infect Dis, Med Virol Sect, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov RI Tang, Shuang/F-9115-2014; OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536 FU Intramural NIH HHS NR 29 TC 91 Z9 102 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 5 PY 2008 VL 105 IS 31 BP 10931 EP 10936 DI 10.1073/pnas.0801845105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 335RT UT WOS:000258308500056 PM 18678906 ER PT J AU Merrill, SJ Myklebust, B Myklebust, J Reynolds, N Duthie, E AF Merrill, Stephen J. Myklebust, Barbara Myklebust, Joel Reynolds, Norman Duthie, Edmund TI A Poisson-like model of sub-clinical signs from the examination of healthy aging subjects SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Aging index; geriatrics; logistic regression; neurological examination; Poisson model ID POPULATION; TRANSITIONS; FITNESS; PEOPLE AB Background and aims: Our studies of the standard neurological examination on 66 middle-aged (50-64 yrs) and elderly subjects (65-84 yrs) demonstrate that healthy elders have neurological deficits (or "signs") that are not associated with specific known neurological disease. The purpose of the current study is to describe this loss of neurological function in healthy aging subjects as seen through accumulated subclinical neurological signs present. Methods: Logistic regression is applied to the data on each of six signs. Parameters determined are used to describe the distribution of first occurrence times for each sign. The results are then used to construct a Poisson-like model that describes the accumulation in the number of signs present over time on average. This model is also used to simulate a longitudinal population to explore the variability in the number of signs present over time in an aging population. Results: As the rate of arrival of the signs is heterogeneous, as determined through logistic regression, and the number of signs detected is finite, the resulting distributions of the number of signs over time have a different nature than Poisson. Our results suggest that toe can expect to see on average one neurological deficit in healthy people by the age of 62, and that the expected number of deficits increases linearly at the rate of I additional sign every 12 years over a wide age range (age 70-90). The distribution of the number of deficits over time is also described. Conclusions: The linearity in the average rate at which signs appear in this population is somewhat of a surprise, in that on increasing (accelerating) rate might be anticipated. In addition to characterizing the neurological exam results in this group, we demonstrate a methodology that allows the comparison of groups and defines a rate of neurological aging. C1 [Merrill, Stephen J.] Marquette Univ, Dept Math Stat & Comp Sci, Milwaukee, WI 53201 USA. [Myklebust, Barbara] George Washington Univ, Sch Engn & Appl Sci, Washington, DC 20052 USA. [Myklebust, Joel] FDA CDRH, Off Sci, Silver Spring, MD USA. [Myklebust, Joel] FDA CDRH, Engn Labs, Silver Spring, MD USA. [Reynolds, Norman] Zablocki Vet Affairs Med Ctr, Dept Neurol, Milwaukee, WI USA. [Duthie, Edmund] Med Coll Wisconsin, Dept Med Geriatr & Gerontol, Milwaukee, WI 53226 USA. RP Merrill, SJ (reprint author), Marquette Univ, Dept Math Stat & Comp Sci, POB 1881, Milwaukee, WI 53201 USA. EM stephen.merrill@marquette.edu OI Myklebust, Joel/0000-0002-8709-9706 FU VA Rehabilitation FX This Study is Supported in part by funds from VA Rehabilitation R&D to B. Myklebust. NR 29 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1594-0667 EI 1720-8319 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD AUG PY 2008 VL 20 IS 4 BP 368 EP 375 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 365TD UT WOS:000260429800014 PM 18852552 ER PT J AU Rao, SV Califf, RM Kramer, JM Peterson, ED Gross, TP Pepine, CJ Williams, DO Donohoe, D Waksman, R Mehran, R Krucoff, MW AF Rao, Sunil V. Califf, Robert M. Kramer, Judith M. Peterson, Eric D. Gross, Thomas P. Pepine, Carl J. Williams, David O. Donohoe, Dennis Waksman, Ron Mehran, Roxana Krucoff, Mitchell W. TI Postmarket evaluation of breakthrough technologies SO AMERICAN HEART JOURNAL LA English DT Article ID ELUTING CORONARY STENTS; SIRIUS TRIAL; SAFETY NET; CARDIOLOGY; HOLES AB Cardiovascular procedures performed in the United States have more than tripled in the last decade, a trend that is expected to continue with the aging of the population, coupled with epidemics of obesity and diabetes mellitus. Helping to drive this increase are new medical devices that address conditions previously treated by medication alone. Many of these novel devices receive expedited reviews before Food and Drug Administration (FDA) approval and are rapidly adopted into clinical practice. However, recent high-profile cases involving potentially dangerous defects in widely used medical devices have increased concerns about the adequacy of premarket trials and postmarket surveillance in establishing the safety of these devices. In response to these concerns, the American College of Cardiology and the Duke Clinical Research Institute sponsored a "think tank" of experts representing the industry, regulatory authorities, academic medicine, and professional societies to examine these concerns and propose possible solutions. This group examined case studies including drug-eluting stents and implantable cardioverter-defibrillators. Challenges inherent in the current system, including the difficulty of establishing accurate event rates for medical devices and potential disincentives for the industry to conduct comprehensive monitoring, were discussed. Possible solutions to these problems included improving and enforcing current regulations, considering creative study design strategies that link pre- and postmarket data, declaring postmarket surveillance a public health issue, creating financial incentives for participation in postmarketing studies, using more relevant animal models, encouraging postmortem device retrieval, and aligning professional societies with the FDA to evaluate breakthrough technologies and communicate findings to patients and clinicians. C1 [Rao, Sunil V.] Durham VA Med Ctr, Div Cardiol, Durham, NC 27705 USA. [Rao, Sunil V.; Califf, Robert M.; Kramer, Judith M.; Peterson, Eric D.; Krucoff, Mitchell W.] Duke Clin Res Inst, Durham, NC USA. [Rao, Sunil V.; Califf, Robert M.; Kramer, Judith M.; Peterson, Eric D.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Durham, NC USA. [Califf, Robert M.] Duke Translat Med Inst, Durham, NC USA. [Califf, Robert M.; Kramer, Judith M.; Peterson, Eric D.] Duke Ctr Educ & Res Therapeut, Durham, NC USA. [Gross, Thomas P.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Pepine, Carl J.] Univ Florida, Div Cardiovasc Med, Gainesville, FL USA. [Williams, David O.] Rhode Isl Hosp, Div Cardiol, Providence, RI USA. [Donohoe, Dennis] Cordis Corp, Warren, NJ USA. [Waksman, Ron] Washington Hosp Ctr, Div Cardiol, Washington, DC 20010 USA. [Mehran, Roxana] Columbia Univ, Med Ctr, Cardiovasc Res Fdn, New York, NY USA. RP Rao, SV (reprint author), Durham VA Med Ctr, Div Cardiol, 508 Fulton St 111A, Durham, NC 27705 USA. EM sunil.rao@duke.edu FU Duke Clinical Research Institute (DCRI); Medtronic; Inc; Abbott Vascular Devices; Cordis Corporation; Guidant Corporation FX Funding for this manuscript was provided by the Duke Clinical Research Institute (DCRI). Additional funding for the DCRI/American College of Cardiology "think tank" meeting was provided by the following sponsors: Medtronic, Inc, Abbott Vascular Devices, Cordis Corporation, and Guidant Corporation. NR 36 TC 15 Z9 17 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2008 VL 156 IS 2 BP 201 EP 208 DI 10.1016/j.ahj.2008.01.036 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 335ZF UT WOS:000258333400001 PM 18657647 ER PT J AU Macias, E de Marval, PLM De Siervi, A Conti, CJ Senderowicz, AM Rodriguez-Puebla, ML AF Macias, Everardo de Marval, Paula L. Miliani De Siervi, Adriana Conti, Claudio J. Senderowicz, Adrian M. Rodriguez-Puebla, Marcelo L. TI CDK2 activation in mouse epidermis induces keratinocyte proliferation but does not affect skin tumor development SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-CYCLE CONTROL; BREAST-CANCER; GENE AMPLIFICATION; TRANSGENIC MICE; TUMORIGENESIS; EXPRESSION; P27(KIP1); PROGRESSION; HYPERPLASIA; KINASE AB It has been widely assumed that elevated CDK2 kinase activity plays a contributory role in tumorigenesis. We have previously shown that mice overexpressing CDK4 under control of the keratin 5 promoter (K5CDK4 mice) develop epidermal hyperplasia and increased susceptibility to squamous cell carcinomas. In this model, CDK4 overexpression results in increased CDK2 activity associated with the noncatalytic function of CDK4, sequestration of p21(Cip1) and p27(Kip1). Furthermore, we have shown that ablation of Cdk2 reduces Ras-Cdk4 tumorigenesis, suggesting that increased CDK2 activity plays an important role in Ras-mediated tumorigenesis. To investigate this hypothesis, we generated two transgenic mouse models of elevated CDK2 kinase activity, K5Cdk2 and K5CAk4(D158N) mice. The D158N mutation blocks CDK4 kinase activity without interfering with its binding capability. CDK2 activation via overexpression of CDK4(D158N), but not of CDK2, resulted in epidermal hyperplasia. We observed elevated levels of p21(Cip1) in K5Cdk2, but not in K5Cdk4(D158N), epidermis, suggesting that CDK2 overexpression elicits a p21(Cip1) response to maintain keratinocyte homeostasis. Surprisingly, we found that neither CDK2 overexpression nor the indirect activation of CDK2 enhanced skin tumor development. Thus, although the indirect activation of CDK2 is sufficient to induce keratinocyte hyperproliferation, activation of CDK2 alone does not induce malignant progression in Ras-mediated tumorigenesis. C1 [Rodriguez-Puebla, Marcelo L.] N Carolina State Univ, CVM MBS, Dept Mol Biomed Sci, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA. [de Marval, Paula L. Miliani] Duke Univ, Med Ctr, Div Dermatol, Durham, NC 27710 USA. [De Siervi, Adriana; Senderowicz, Adrian M.] Natl Inst Dent & Craniofacial Res, Mol Therapeut Unit, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Conti, Claudio J.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA. [Senderowicz, Adrian M.] Ctr Drug Evaluat, US FDA, Silver Spring, MD USA. US FDA, Off New Drugs, Off Oncol Drug Prod, Div Drug Oncol Prod, Silver Spring, MD USA. RP Rodriguez-Puebla, ML (reprint author), N Carolina State Univ, CVM MBS, Dept Mol Biomed Sci, Ctr Comparat Med & Translat Res, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM marcelo_rodriguez-puebla@ncsu.edu FU NCI NIH HHS [CA90864, R01 CA090864, CA116328, R01 CA116328] NR 51 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2008 VL 173 IS 2 BP 526 EP 535 DI 10.2353/ajpath.2008.071124 PG 10 WC Pathology SC Pathology GA 331LJ UT WOS:000258013400022 PM 18599613 ER PT J AU Kauffman, JF Gilliam, SJ Martin, RS AF Kauffman, John F. Gilliam, Sean J. Martin, R. Scott TI Chemical imaging of pharmaceutical materials: Fabrication of micropatterned resolution targets SO ANALYTICAL CHEMISTRY LA English DT Article ID PROCESS ANALYTICAL TECHNOLOGY; DOSAGE FORMS; RAMAN; SPECTROSCOPY; TABLETS; FORMULATIONS; DIFFUSION; IMAGES; MEDIA; LIGHT AB Resolution targets composed of thick poly(ethylene glycol) (PEG) lines on silicon substrates have been fabricated using the method of micromolding in capillaries (MiMIC). Patterns of three parallel lines with equal width and spacing have been prepared, with widths between 5 and 25 mu m. Raman chemical images of the PEG-on-silicon devices as well as the metal-on-glass masks used to prepare the devices were measured. The Raman images were used to determine the impulse response of the instrument by comparing the measured images to model functions prepared by convolution of a test impulse function with the object functions of the devices. Impulse widths for PEG-on-silicon targets were approximately two times greater than impulse widths for metal-on-glass targets. The results provide a quantitative measure of the influence of light-matter interactions on the spatial resolution achievable with chemical imaging instruments. This work shows that microfluidic channels can be used to produce robust patterns of PEG on silicon, and these patterns are realistic resolution targets for spectroscopic chemical imaging of pharmaceutical materials. C1 [Kauffman, John F.; Gilliam, Sean J.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Martin, R. Scott] St Louis Univ, Dept Chem, St Louis, MO 63103 USA. RP Kauffman, JF (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St, St Louis, MO 63101 USA. EM John.Kauffrnan@fda.hhs.gov OI Martin, R. Scott/0000-0002-6952-1408 NR 30 TC 7 Z9 7 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 1 PY 2008 VL 80 IS 15 BP 5706 EP 5712 DI 10.1021/ac800864x PG 7 WC Chemistry, Analytical SC Chemistry GA 332PX UT WOS:000258096700010 PM 18576670 ER PT J AU Buehler, PW Vallelian, F Mikolajczyk, MG Schoedon, G Schweizer, T Alayash, AI Schaer, DJ AF Buehler, Paul W. Vallelian, Florence Mikolajczyk, Malgorzata G. Schoedon, Gabriele Schweizer, Thomas Alayash, Abdu I. Schaer, Dominik J. TI Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathways SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID CARRIERS BLOOD SUBSTITUTES; HAPTOGLOBIN-BINDING-SITE; ALPHA-CHAIN; HEME UPTAKE; CD163; RECEPTOR; MACROPHAGES; IDENTIFICATION; OXYHEMOGLOBIN; LOCALIZATION AB Hemoglobin (Hb) released into the circulation during hemolysis and chemically modified Hb proposed for use as oxygen therapeutics exert toxic effects that are partially attributable to heme's oxidant activity. Native extracellular Hb is scavenged by haptoglobin (Hp) after alpha beta-subunit dimerization. In the absence of Hp, monocyte/macrophage cell-surface CD163 binds and clears Hb. We evaluated several chemically modified Hbs to establish the role of chemical cross-linking patterns and molecular sizes on binding and clearance by each pathway. We found that Hbs possessing beta-globin cross-linking, irrespective of polymerization, demonstrate increased Hp affinity compared with beta-globin-stabilized Hbs. These data suggest that Hb alpha-subunit accessibility is critical for Hp binding in the absence of dimerization. beta-Globin chain cross-linked tetramers/polymers displayed strong polyvalent Hp binding with increased viscosity and formation of visible gel matrices. Modified Hb interaction with CD163 and cellular uptake demonstrated an inverse relation with molecular size, irrespective of alpha and beta cross-linking. These findings were confirmed by HO-1 induction and intracellular ferritin accumulation in CD163-expressing HEK293 cells. Based on these results, a rational and systematic approach to HBOC design may be used to optimize interaction with endogenous Hb clearance and detoxification pathways. C1 [Buehler, Paul W.; Mikolajczyk, Malgorzata G.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Rockville, MD USA. [Schweizer, Thomas] ETH, Dept Mat, Zurich, Switzerland. [Vallelian, Florence; Schoedon, Gabriele; Schaer, Dominik J.] Univ Zurich, Med Clin Res Unit, CH-8006 Zurich, Switzerland. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Med Clin Res Unit, CH-8091 Zurich, Switzerland. EM dominik.schaer@usz.ch NR 39 TC 30 Z9 31 U1 0 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD AUG PY 2008 VL 10 IS 8 BP 1449 EP 1462 DI 10.1089/ars.2008.2028 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 311TU UT WOS:000256624100006 PM 18522492 ER PT J AU Zhang, Q Wu, J Nguyen, A Wang, BD He, P Laurent, GS Rennert, OM Su, YA AF Zhang, Qiuyang Wu, Jun Nguyen, AnhThu Wang, Bi-Dar He, Ping Laurent, Georges St. Rennert, Owen M. Su, Yan A. TI Molecular mechanism underlying differential apoptosis between human melanoma cell lines UACC903 and UACC903(+6) revealed by mitochondria-focused cDNA microarrays SO APOPTOSIS LA English DT Article DE melanoma; apoptosis; pathways; FAS; FASLG; BAK1 ID HUMAN-MALIGNANT MELANOMA; DNA-DAMAGE; EXONUCLEASE ACTIVITY; GENE-EXPRESSION; CONNEXIN GENES; IN-SITU; TUMORIGENICITY; CHROMOSOME-6; IDENTIFICATION; SUPPRESSION AB Human malignant melanoma cell line UACC903 is resistant to apoptosis while chromosome 6-mediated suppressed cell line UACC903(+6) is sensitive. Here, we describe identification of differential molecular pathways underlying this difference. Using our recently developed mitochondria-focused cDNA microarrays, we identified 154 differentially expressed genes including proapoptotic (BAK1 [6p21.3], BCAP31, BNIP1, CASP3, CASP6, FAS, FDX1, FDXR, TNFSF10 and VDAC1) and antiapoptotic (BCL2L1, CLN3 and MCL1) genes. Expression of these pro- and anti-apoptotic genes was higher in UACC903(+6) than in UACC903 before UV treatment and was altered after UV treatment. qRT-PCR and Western blots validated microarray results. Our bioinformatic analysis mapped these genes to differential molecular pathways that predict resistance and sensitivity of UACC903 and UACC903(+6) to apoptosis respectively. The pathways were functionally confirmed by the FAS ligand-induced cell death and by siRNA knockdown of BAK1 protein. These results demonstrated the differential molecular pathways underlying survival and apoptosis of UACC903 and UACC903(+6) cell lines. C1 [Zhang, Qiuyang; Wu, Jun; Nguyen, AnhThu; Wang, Bi-Dar; Laurent, Georges St.; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Zhang, Qiuyang; Wu, Jun; Nguyen, AnhThu; Wang, Bi-Dar; Laurent, Georges St.; Su, Yan A.] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [He, Ping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Cellular Hemostasis, Bethesda, MD 20892 USA. [Laurent, Georges St.] Univ Antioquia, Immunovirol Biogenesis Grp, Medellin, Colombia. [Rennert, Owen M.] NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. RP Su, YA (reprint author), George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Ross Hall,Room 555,2300 I St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU PHS HHS [06-925] NR 45 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD AUG PY 2008 VL 13 IS 8 BP 993 EP 1004 DI 10.1007/s10495-008-0231-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 325KL UT WOS:000257587700004 PM 18563568 ER PT J AU Kaldhone, P Nayak, R Lynne, AM David, DE McDermott, PF Logue, CM Foley, SL AF Kaldhone, Pravin Nayak, Rajesh Lynne, Aaron M. David, Donna E. McDermott, Patrick F. Logue, Catherine M. Foley, Steven L. TI Characterization of Salmonella enterica serovar Heidelberg from Turkey-associated sources SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; FOOD ANIMALS; ANTIMICROBIAL RESISTANCE; UNITED-STATES; PLASMID; IDENTIFICATION; INFECTIONS; SEQUENCE; GENES; CMY-2 AB Salmonella enterica serovar Heidelberg strains are frequently associated with food-borne illness, with recent isolates showing higher rates of resistance to multiple antimicrobial agents. One hundred eighty S. enterica serovar Heidelberg isolates, collected from turkey-associated production and processing sources, were tested for antimicrobial susceptibility and compared by pulsed-field gel electrophoresis (PFGE) and plasmid profile analysis. The potential for the transfer of resistance between strains was studied by conjugation experiments. PFGE analysis using XbaI digestion identified eight clusters (based on 90% similarity), with the largest containing 71% of the isolates. Forty-two percent of the isolates were resistant to at least I of the 15 antimicrobial agents tested, and 4% of the isolates were resistant to 8 or more antimicrobial agents. Resistances to streptomycin (32%), tetracycline (30%), and kanamycin (24%) were most commonly detected. Interestingly, the XbaI PFGE profiles of selective multidrug-resistant strains (n = 22) of S. enterica serovar Heidelberg from turkey-associated sources were indistinguishable from the predominant profile (JF6X01.0022) detected in isolates associated with human infections. These isolates were further differentiated into seven distinct profiles following digestion with the BlnI enzyme, with the largest cluster comprising 15 isolates from veterinary diagnostic and turkey processing environments. Conjugation experiments indicated that resistance to multiple antimicrobial agents was transferable among strains with diverse PFGE profiles. C1 [Kaldhone, Pravin; Lynne, Aaron M.; David, Donna E.; Foley, Steven L.] Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. [Kaldhone, Pravin; Foley, Steven L.] Univ Cent Arkansas, Dept Biol, Conway, AR USA. [Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [McDermott, Patrick F.] US FDA, Div Anim & Food Microbiol, Ctr Vet Med, Laurel, MD USA. [Logue, Catherine M.] N Dakota State Univ, Dept Vet & Microbiol Sci, Fargo, ND 58105 USA. RP Foley, SL (reprint author), Marshfield Clin Res Fdn, Natl Farm Med Ctr, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM foley.steven@mcrf.mfldclin.edu FU Marshfield Clinic Research Foundation (MCRF); National Institutes for Health FX We appreciate the financial support for this project that was provided by the Marshfield Clinic Research Foundation (MCRF) and the National Institutes for Health-funded Arkansas Biomedical Research Infrastructure Network.; We also thank Mary Stemper of the MCRF and David G. White of the FDA Center for Veterinary Medicine for their assistance with the project and Nehal Patel of the CDC PulseNet Program for providing us with information on the predominant PFGE profiles associated with human salmonellosis.; The use of trade names is for identification purposes only and does not imply endorsement by the U.S. Food and Drug Administration or the U.S. Department of Health and Human Services. The views presented in this article do not necessarily reflect those of the FDA. NR 29 TC 23 Z9 24 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2008 VL 74 IS 16 BP 5038 EP 5046 DI 10.1128/AEM.00409-08 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 339UF UT WOS:000258602100007 PM 18586966 ER PT J AU Chung, S Kong, H Buyer, JS Lakshman, DK Lydon, J Kim, SD Roberts, DP AF Chung, Soohee Kong, Hyesuk Buyer, Jeffrey S. Lakshman, Dilip K. Lydon, John Kim, Sang-Dal Roberts, Daniel P. TI Isolation and partial characterization of Bacillus subtilis ME488 for suppression of soilborne pathogens of cucumber and pepper SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Bacillus subtilis; bacilysin; biological control; Fusarium oxysporum f. sp.; cucumerinum; iturin; mersacidin; methyl bromide replacement; Phytophthora capsici ID SP RADICIS-CUCUMERINUM; FUSARIUM-OXYSPORUM; PHYTOPHTHORA-CAPSICI; BIOLOGICAL-CONTROL; BELL PEPPER; STEM ROT; SOIL; MANAGEMENT; BLIGHT; PLANT AB Environmentally friendly control measures are needed for suppression of soilborne pathogens of vegetable crops in the Republic of Korea. In vitro challenge assays were used to screen approximately 500 bacterial isolates from 20 Korean greenhouse soils for inhibition of diverse plant pathogens. One isolate, Bacillus subtilis ME488, suppressed the growth of 39 of 42 plant pathogens tested. Isolate ME488 also suppressed the disease caused by Fusarium oxysporum f. sp. cucumerinum on cucumber and Phytophthora capsici on pepper in pot assays. Polymerase chain reaction was used to screen isolate ME488 for genes involved in biosynthesis of 11 antibiotics produced by various isolates of B. subtilis. Amplicons of the expected sizes were detected for bacD and bacAB, ituC and ituD, and mrsA and mrsM involved in the biosynthesis of bacilysin, iturin, and mersacidin, respectively. The identity of these genes was confirmed by DNA sequence analysis of the amplicons. Bacilysin and iturin were detected in culture filtrates from isolate ME488 by gas chromatography coupled with mass spectroscopy and by thin layer chromatography, respectively. Detection of mersacidin in ME488 culture filtrates was not attempted. Experiments reported here indicate that B. subtilis ME488 has potential for biological control of pathogens of cucumber and pepper possibly due to the production of antibiotics. C1 [Buyer, Jeffrey S.; Lydon, John; Roberts, Daniel P.] USDA ARS, Beltsville Agr Res Serv, Sustainable Agr Syst Lab, Beltsville, MD 20705 USA. [Chung, Soohee; Kim, Sang-Dal] Yeungnam Univ, Dept Appl Microbiol, Kyongsan 712749, South Korea. [Kong, Hyesuk] FDA, CBER, Lab Methods Dev, Rockville, MD 20852 USA. [Lakshman, Dilip K.] USDA ARS, Florist & Nursery Plants Unit, Beltsville, MD 20705 USA. RP Roberts, DP (reprint author), USDA ARS, Beltsville Agr Res Serv, Sustainable Agr Syst Lab, Bldg 001,Room 140,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM dan.roberts@ars.usda.gov OI Buyer, Jeffrey/0000-0003-2098-0547 NR 35 TC 66 Z9 80 U1 3 U2 28 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD AUG PY 2008 VL 80 IS 1 BP 115 EP 123 DI 10.1007/s00253-008-1520-4 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 323YY UT WOS:000257485900013 PM 18542950 ER PT J AU Grajkowski, A Cieslak, J Kauffman, JS Duff, RJ Norris, S Freedberg, DI Beaucage, SL AF Grajkowski, Andrzej Cieslak, Jacek Kauffman, Jon S. Duff, Robert J. Norris, Scott Freedberg, Daron I. Beaucage, Serge L. TI Thermolytic release of covalently linked DNA oligonucleotides and their conjugates from controlled-pore glass at near neutral pH SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; SOLID-PHASE SYNTHESIS; SULFUR-TRANSFER REAGENT; AUTOMATED SYNTHESIS; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; POLYMER SUPPORT; LIGATION AB The functionalization of long chain alkylamine controlled-pore glass (CPG) with a 3-hydroxypropyl-(2-cyanoethyl)thiophosphoryl linker and its conversion to the support 7 has led to the synthesis of DNA oligonucleotides and their 3'- or (3',5')-conjugates. Indeed, CPG support 7 has been successfully employed in the synthesis of both native and fully phosphorothioated DNA 20-mers. Unlike conventional succinylated CPG supports, this distinctively functionalized support allows oligonucleotide deprotection and removal of the deprotection side products to proceed without releasing the oligonucleotide into the aqueous milieu. When freed from deprotection side products, the DNA oligonucleotide is thermolytically released from the support within 2 h under nearly neutral conditions (pH 7.2, 90 degrees C). The quality of these oligonucleotides is comparable to that of identical oligonucleotides synthesized from succinylated CPG supports in terms of shorter than full length oligonucleotide contaminants and overall yields. The versatility of the thermolytic CPG support 7 is further demonstrated by the synthesis of a DNA oligonucleotide (20-mer) and its conjugation with an azido and alkynyl groups at both 5'-and 3'-termini, respectively. The functionality of the (3',5')-heteroconjugated oligonucleotide 18 is verified by its circularization to the DNA oligonucleotide 19 under "click" chemistry conditions. C1 [Grajkowski, Andrzej; Cieslak, Jacek; Beaucage, Serge L.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Norris, Scott; Freedberg, Daron I.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kauffman, Jon S.; Duff, Robert J.] Lancaster Labs, Lancaster, PA 19605 USA. RP Beaucage, SL (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Serge.Beaucage@fda.hhs.gov NR 30 TC 12 Z9 12 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD AUG PY 2008 VL 19 IS 8 BP 1696 EP 1706 DI 10.1021/bc800189e PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 339TQ UT WOS:000258600600024 PM 18646834 ER PT J AU Chapin, R Augustine-Rauch, K Beyer, B Daston, G Finnell, R Flynn, T Hunter, S Mirkes, P O'Shea, KS Piersma, A Sandler, D Vanparys, P Van Maele-Fabry, G AF Chapin, Robert Augustine-Rauch, Karen Beyer, Bruce Daston, George Finnell, Richard Flynn, Thomas Hunter, Sidney Mirkes, Phillip O'Shea, K. Sue Piersma, Aldert Sandler, David Vanparys, Philippe Van Maele-Fabry, Genevieve TI State of the art in developmental toxicity screening methods and a way forward: A meeting report addressing embryonic stem cells, whole embryo culture, and zebrafish SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE in vitro screens; environmental issues; pharmaceuticals ID MORPHOLOGICAL SCORING SYSTEM; VITRO EMBRYOTOXICITY TESTS; INVITRO DEVELOPMENT; VALIDATION; TERATOGENS; PALATE; ASSAYS AB A meeting was convened so that users of three models for in vitro developmental toxicity (embryonic stem cells, whole embryo culture, and zebrafish) could share their experiences with each model, and explore the areas for improvement. We present a summary of this meeting and the recommendations of the group. C1 [Chapin, Robert] Pfizer Global R&D, Dev & Reprod Toxicol Grp, Groton, CT 06340 USA. [Augustine-Rauch, Karen] Bristol Myers Squibb Co, Reprod Toxicol, Hopewell, NJ USA. [Beyer, Bruce] Sanofi Aventis US, Drug Safety Evaluat, Malvern, PA USA. [Daston, George] Procter & Gamble, Cent Prod Safety, Cincinnati, OH USA. [Finnell, Richard] Texas A&M Univ HSC, Ctr Environm & Genet Med, Houston, TX USA. [Flynn, Thomas] US FDA, CFSAN, Off Appl Res & Safety Assessment, Laurel, MD USA. [Hunter, Sidney] US EPA, Off Res & Dev, NHEERL, Reprod Toxicol Div, Res Triangle Pk, NC 27711 USA. [Mirkes, Phillip] Texas A&M Univ, Ctr Environm & Rural Hlth, College Stn, TX USA. [O'Shea, K. Sue] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA. [Piersma, Aldert] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Sandler, David] Hlth & Environm Sci Inst, Washington, DC USA. [Vanparys, Philippe] Johnson & Johnson Pharmaceut Res & Dev, Mechanist Toxicol, Beerse, Belgium. [Van Maele-Fabry, Genevieve] Catholic Univ Louvain, Ind Toxicol & Occupat Med Unit, Brussels, Belgium. RP Chapin, R (reprint author), Pfizer Global R&D, Dev & Reprod Toxicol Grp, Eastern Point Rd,MS 8274-1336, Groton, CT 06340 USA. EM robert.e.chapin@pfizer.com OI Chapin, Robert/0000-0002-5997-1261; Flynn, Thomas/0000-0002-7248-0643 NR 23 TC 39 Z9 41 U1 1 U2 12 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2008 VL 83 IS 4 BP 446 EP 456 DI 10.1002/bdrb.20158 PG 11 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 344NT UT WOS:000258935300005 PM 18702117 ER PT J AU Bass, AS Darpo, B Breidenbach, A Bruse, K Feldman, HS Garnes, D Hammond, T Haverkamp, W January, C Koerner, J Lawrence, C Leishman, D Roden, D Valentin, JP Vos, MA Zhou, YY Karluss, T Sager, P AF Bass, A. S. Darpo, B. Breidenbach, A. Bruse, K. Feldman, H. S. Garnes, D. Hammond, T. Haverkamp, W. January, C. Koerner, J. Lawrence, C. Leishman, D. Roden, D. Valentin, J. P. Vos, M. A. Zhou, Y-Y Karluss, T. Sager, P. TI International life sciences institute (health and environmental sciences institute, HESI) initiative on moving towards better predictors of drug-induced torsades de pointes SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE torsades de pointes; I(Kr); QT prolongation; ventricular repolarization; cardiac toxicity; safety pharmacology; hERG; arrhythmia; long QT syndrome; electrocardiogram ID AUTONOMIC NERVOUS-SYSTEM; LONG QT SYNDROME; INTERVAL PROLONGATION; CONSCIOUS DOGS; PROLONGING DRUGS; SUDDEN-DEATH; HERG; RISK; REPOLARIZATION; CHANNEL AB Knowledge of the cardiac safety of emerging new drugs is an important aspect of assuring the expeditious advancement of the best candidates targeted at unmet medical needs while also assuring the safety of clinical trial subjects or patients. Present methodologies for assessing drug-induced torsades de pointes (TdP) are woefully inadequate in terms of their specificity to select pharmaceutical agents, which are human arrhythmia toxicants. Thus, the critical challenge in the pharmaceutical industry today is to identify experimental models, composite strategies, or biomarkers of cardiac risk that can distinguish a drug, which prolongs cardiac ventricular repolarization, but is not proarrhythmic, from one that prolongs the QT interval and leads to TdP. To that end, the HESI Proarrhythmia Models Project Committee recognized that there was little practical understanding of the relationship between drug effects on cardiac ventricular repolarization and the rare clinical event of TdP. It was on that basis that a workshop was convened in Virginia, USA at which four topics were introduced by invited subject matter experts in the following fields: Molecular and Cellular Biology Underlying TdP, Dynamics of Periodicity, Models of TdP Proarrhythmia, and Key Considerations for Demonstrating Utility of Pre-Clinical Models. Contained in this special issue of the British Journal of Pharmacology are reports from each of the presenters that set out the background and key areas of discussion in each of these topic areas. Based on this information, the scientific community is encouraged to consider the ideas advanced in this workshop and to contribute to these important areas of investigations over the next several years. C1 [Bass, A. S.] Schering Plough Res Inst, Drug Safety & Metab, Kenilworth, NJ 07033 USA. [Darpo, B.] Pharmaceut Consultant, Lidingo, Sweden. [Breidenbach, A.] F Hoffmann La Roche & Co Ltd, Safety Pharmacol, Div Pharmaceut, CH-4002 Basel, Switzerland. [Bruse, K.] Covance Labs Inc, Safety Pharmacol, Madison, WI USA. [Feldman, H. S.] Wyeth Res, Safety Pharmacol, Chazy, NY USA. [Garnes, D.] Novartis Pharmaceut Corp, Anim Welfare Compliance, E Hanover, NJ USA. [Hammond, T.; Lawrence, C.; Valentin, J. P.] Safety Assessment UK, AstraZeneca R&D Alderley Pk, Macclesfield, Cheshire, England. [Haverkamp, W.] Charite Univ Med Berlin, Campus Vircho Klinikum, Med Klin M S Kardiol, Berlin, Germany. [January, C.] Univ Wisconsin, Dept Med, Madison, WI USA. [Koerner, J.] US FDA, Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. [Leishman, D.] Greenfield Labs, Lilly Res Lab, Greenfield, IN USA. [Roden, D.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Vos, M. A.] Univ Utrecht, Univ Med Ctr Utrecht, Utrecht, Netherlands. [Zhou, Y-Y] Schering Plough Res Inst, Invest & Regulatory Safety Pharmacol, Lafayette, NJ USA. [Karluss, T.] Hlth & Enironm Sci Inst, Int Life Sci, Washington, DC USA. [Sager, P.] CV Res AstraZeneca LP, Wilmington, DE USA. RP Bass, AS (reprint author), Schering Plough Res Inst, Drug Safety & Metab, 2015 Galloping Hill Rd,K15-2-2770, Kenilworth, NJ 07033 USA. EM alan.bass@spcorp.com NR 71 TC 16 Z9 18 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD AUG PY 2008 VL 154 IS 7 BP 1491 EP 1501 DI 10.1038/bjp.2008.279 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 331AF UT WOS:000257984400012 PM 18663380 ER PT J AU Zhang, MD Huang, WY Andreotti, G Gao, YT Rashid, A Chen, JB Sakoda, LC Shen, MC Wang, BS Chanock, S Hsing, AW AF Zhang, Mingdong Huang, Wen-Yi Andreotti, Gabriella Gao, Yu-Tang Rashid, Asif Chen, Jinbo Sakoda, Lori C. Shen, Ming-Chang Wang, Bing-Sheng Chanock, Stephen Hsing, Ann W. TI Variants of DNA repair genes and the risk of biliary tract cancers and stones: A populaton-based study in China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; POLYMORPHISMS; METHYLTRANSFERASE; GALLSTONES; SHANGHAI; SUSCEPTIBILITY; ASSOCIATION; SMOKING; MGMT AB Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs1291.7) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95%) CI), 0.41-0.97; P = 0.021 and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required. C1 [Zhang, Mingdong; Huang, Wen-Yi; Andreotti, Gabriella; Chanock, Stephen; Hsing, Ann W.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Zhang, Mingdong] US FDA, Rockville, MD 20857 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Washington, DC USA. [Shen, Ming-Chang] Fudan Univ, Shanghai Tumor Hosp, Shanghai 200433, Peoples R China. [Wang, Bing-Sheng] Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Chanock, Stephen] NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7058,MSC 7324, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov FU NIH; National Cancer Institute FX Intramural Research Program of the NIH, National Cancer Institute. NR 26 TC 11 Z9 11 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2008 VL 17 IS 8 BP 2123 EP 2127 DI 10.1158/1055-9965.EPI-07-2735 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 342RI UT WOS:000258800800041 PM 18708406 ER PT J AU Hsing, AW Sakoda, LC Rashid, A Andreotti, G Chen, JB Wang, BS Shen, MC Chen, BE Rosenberg, PS Zhang, MD Niwa, S Chu, L Welch, R Yeager, M Fraumeni, JF Gao, YT Chanock, SJ AF Hsing, Ann W. Sakoda, Lori C. Rashid, Asif Andreotti, Gabriella Chen, Jinbo Wang, Bin-Shen Shen, Ming-Chang Chen, Bingshu E. Rosenberg, Philip S. Zhang, Mingdong Niwa, Shelley Chu, Lisa Welch, Robert Yeager, Meredith Fraumeni, Joseph F., Jr. Gao, Yu-Tang Chanock, Stephen J. TI Variants in inflammation genes and the risk of biliary tract cancers and stones: A population-based study in China SO CANCER RESEARCH LA English DT Article ID NECROSIS-FACTOR-ALPHA; NON-HODGKIN-LYMPHOMA; PROMOTER REGION; PROSTATE-CANCER; POLYMORPHISMS; SUSCEPTIBILITY; ASSOCIATION; SHANGHAI; TUMOR; TNF AB To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer. C1 [Hsing, Ann W.; Andreotti, Gabriella; Chen, Bingshu E.; Rosenberg, Philip S.; Chu, Lisa; Yeager, Meredith; Fraumeni, Joseph F., Jr.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Sakoda, Lori C.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Chu, Lisa] NCI, Off Prevent Oncol, NIH, Bethesda, MD 20892 USA. [Chen, Jinbo] Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Wang, Bin-Shen] Fudan Univ, Zhong Shan Hosp, Dept Surg, Shanghai, Peoples R China. [Shen, Ming-Chang] Shanghai Tumor Hosp, Shanghai, Peoples R China. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [Zhang, Mingdong] US FDA, Silver Spring, MD USA. [Niwa, Shelley] Westat Corp, Rockville, MD USA. [Chu, Lisa; Welch, Robert; Chanock, Stephen J.] Natl Canc Inst, Sci Applicat Int Corp Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5024,MSC 7234, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov FU Intramural NIH HHS [ZIA CP010158-09]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 38 TC 44 Z9 45 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2008 VL 68 IS 15 BP 6442 EP 6452 DI 10.1158/0008-5472.CAN-08-0444 PG 11 WC Oncology SC Oncology GA 333UI UT WOS:000258177600050 PM 18676870 ER PT J AU Soldin, OP Dahlin, JRB Gresham, EG King, J Soldin, SJ AF Soldin, Offie P. Dahlin, Julia R. B. Gresham, Eric G. King, Julia Soldin, Steven J. TI IMMULITE (R) 2000 age and sex-specific reference intervals for alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and intact parathyroid hormone SO CLINICAL BIOCHEMISTRY LA English DT Article DE pediatric; reference intervals; alpha fetoprotein; homocysteine; insulin; insulin-like growth factor-I; insulin-like growth factor binding protein-3; C-peptide; immunoglobulin E; parathyroid hormone ID PEDIATRIC REFERENCE INTERVALS; TANDEM-MASS-SPECTROMETRY; CLINICAL UTILITY; REFERENCE RANGES; CHILDREN; TRANSFERRIN; RESISTANCE; PREGNANCY; CORTISOL; IRON AB Objectives: To determine age and sex-specific pediatric reference intervals for serum alpha fetoprotein, homocysteine, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-3, C-peptide, immunoglobulin E and parathyroid hormone. Design and methods: The study was conducted at both Children's National Medical Center and Georgetown University, Washington D.C. Results for the above analytes were obtained from the Children's National Medical Center laboratory information system over the period of 1151 2001-3/8/2007. Patient results using the IMMULITE 2000(R) were accessed and used to establish reference intervals for the analytes studied. All patient identifiers were removed except age and sex. Analysis of the data was performed at Georgetown University in the Bioanalytical Core Laboratory. The data was analyzed using the Hoffmann approach, and was computer adapted. The number of patient samples studied varied with each analyte and were: Alpha fetoprotein (557), homocysteine (924), insulin-like growth factor-I (1352), insulin-like growth factor binding protein-3 (711), insulin (3239), C-peptide (267), immunoglobulin E (2691) and parathyroid hormone (513). Results and conclusions: This study provides pediatric reference intervals for the eight analytes for children from birth to 18 years of age. All the analytes exhibited at least some age dependence, Sex differences between early and late childhood and adolescence were also frequently found. (C) 2008 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Soldin, Offie P.; Soldin, Steven J.] Georgetown Univ, Bioanalyt Core Lab, Med Ctr, Dept Med, Washington, DC 20057 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Oncol Physiol, Washington, DC 20057 USA. [Soldin, Offie P.] US FDA, Ctr Drug Evaluat & Res, Obstet Pharmacol Res Network, Natl Inst Child Hlth & Dev, Rockville, MD 20857 USA. [Dahlin, Julia R. B.; Gresham, Eric G.; King, Julia; Soldin, Steven J.] George Washington Univ, Dept Pediat & Pathol, Washington, DC USA. [Dahlin, Julia R. B.; Gresham, Eric G.; King, Julia; Soldin, Steven J.] Childrens Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA. RP Soldin, SJ (reprint author), Georgetown Univ, Bioanalyt Core Lab, Med Ctr, Dept Med, 3800 Reservoir Rd, Washington, DC 20057 USA. EM sjs44@georgetown.edu FU NCRR NIH HHS [M01 RR020359, M01 RR023942, M01RR-023942]; NICHD NIH HHS [1 U10HD45993-02, U10 HD045993, U10 HD047890] NR 25 TC 23 Z9 23 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD AUG PY 2008 VL 41 IS 12 BP 937 EP 942 DI 10.1016/j.clinbiochem.2008.04.025 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 330ZF UT WOS:000257980700003 PM 18503765 ER PT J AU Burke, LB Kennedy, DL Miskala, PH Papadopoulos, EJ Trentacosti, AM AF Burke, L. B. Kennedy, D. L. Miskala, P. H. Papadopoulos, E. J. Trentacosti, A. M. TI The use of patient-reported outcome measures in the evaluation of medical products for regulatory approval SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Patient-reported outcome (PRO) measures provide an important perspective on how patients feel and function that cannot be adequately captured by clinical measures. A PRO is any report that comes directly from a patient about a health condition or its treatment without interpretation of the patient's response by a clinician or anyone else. C1 [Burke, L. B.; Kennedy, D. L.; Miskala, P. H.; Papadopoulos, E. J.; Trentacosti, A. M.] US FDA, Res, Ctr Drug Evaluat, Off New Drugs,Study Endpoints & Label Dev, Silver Spring, MD USA. RP Burke, LB (reprint author), US FDA, Res, Ctr Drug Evaluat, Off New Drugs,Study Endpoints & Label Dev, Silver Spring, MD USA. EM Laurie.burke@fda.hhs.gov NR 3 TC 41 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2008 VL 84 IS 2 BP 281 EP 283 DI 10.1038/clpt.2008.128 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 337OK UT WOS:000258445200029 PM 18580868 ER PT J AU Swann, PG Tolnay, M Muthukkumar, S Shapiro, MA Rellahan, BL Clouse, KA AF Swann, Patrick G. Tolnay, Mate Muthukkumar, Subramanian Shapiro, Marjorie A. Rellahan, Barbara L. Clouse, Kathleen A. TI Considerations for the development of therapeutic monoclonal antibodies SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID FC-GAMMA RECEPTORS; PHASE-I TRIAL; HUMAN IGG1; ANTIINFLAMMATORY ACTIVITY; BIOTECHNOLOGY PRODUCTS; ENGINEERED ANTIBODIES; ANTI-CD3 ANTIBODY; IMMUNE-RESPONSES; HALF-LIFE; IMMUNOGENICITY AB An increasing number of Investigational New Drug (IND) applications for therapeutic monoclonal antibodies (mAbs) have been submitted to US FDA over the past several years. Monoclonal antibodies and related products are under development for a wide range of indications. In addition, the diversity of anti body-related products is increasing including IgG2/IgG4 subclasses and engineered Fc regions to enhance or reduce antibody effector functionality. Recent findings highlight the need to more fully characterize these products and their activity. Advances in product characterization tools, immunogenicity assessments, and other bioanalytical assays can be used to better understand product performance and facilitate development. C1 [Swann, Patrick G.; Tolnay, Mate; Muthukkumar, Subramanian; Shapiro, Marjorie A.; Rellahan, Barbara L.; Clouse, Kathleen A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Swann, PG (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM patrick.swann@fda.hhs.gov NR 57 TC 49 Z9 52 U1 0 U2 10 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2008 VL 20 IS 4 BP 493 EP 499 DI 10.1016/j.coi.2008.05.013 PG 7 WC Immunology SC Immunology GA 343PK UT WOS:000258865800020 PM 18586093 ER PT J AU Manqanatha, MG Shelton, SD Dobrovolsky, VN Shaddock, JG McGarrity, LY Lin, CJ Chen, JJ Mattison, DR Morris, SM AF Manqanatha, M. G. Shelton, S. D. Dobrovolsky, V. N. Shaddock, J. G. McGarrity, L. Y. Lin, C. J. Chen, J. J. Mattison, D. R. Morris, S. M. TI Genotoxicity of methylphenidate hydrochloride in big blue mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Manqanatha, M. G.; Shelton, S. D.; Dobrovolsky, V. N.; Shaddock, J. G.; McGarrity, L. Y.; Morris, S. M.] US FDA, Natl Ctr Toxicol Res, Genet & Reprod Toxicol Div, Jefferson, AR 72079 USA. [Lin, C. J.; Chen, J. J.] US FDA, NCTR, Personalized Med & Nutr Div, Jefferson, AR USA. [Mattison, D. R.] NICHHD, Bethesda, MD 20892 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 529 EP 529 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800054 ER PT J AU Morris, SM Hotchkiss, CE Bishop, ME Dobrovolsky, V Doerge, D Twaddle, N Chen, JJ Lin, CJ Paule, M Slikker, W Petibone, DM Tucker, JD Manjanatha, MG Mattison, DR AF Morris, S. M. Hotchkiss, C. E. Bishop, M. E. Dobrovolsky, V Doerge, D. Twaddle, N. Chen, J. J. Lin, C. J. Paule, M. Slikker, W. Petibone, D. M. Tucker, J. D. Manjanatha, M. G. Mattison, D. R. TI The genetic toxicology of methiphenidate hydrochloride in non-human primates SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Morris, S. M.; Bishop, M. E.; Dobrovolsky, V; Manjanatha, M. G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, J. J.; Lin, C. J.] WANPRC, Seattle, WA USA. [Doerge, D.; Twaddle, N.] Wayne State Univ, Detroit, MI USA. [Manjanatha, M. G.] NICHD, CRMC, NIH, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 529 EP 529 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800053 ER PT J AU Rodriguez, WJ AF Rodriguez, W. J. TI Recent experience in pediatric drug development and safety issues with methylphenidate and other drugs SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Rodriguez, W. J.] US FDA, Off Pediat Therapeut, OC, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 529 EP 529 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800055 ER PT J AU Slikker, W Mattison, DR Patterson, TA Paule, MG Li, M Doerge, D Twaddle, N Hotchkiss, CE Chen, JJ Morris, SM AF Slikker, W. Mattison, D. R. Patterson, T. A. Paule, M. G. Li, M. Doerge, D. Twaddle, N. Hotchkiss, C. E. Chen, J. J. Morris, S. M. TI Pharmacological effects of methylphenidate in the developing primate SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Slikker, W.; Patterson, T. A.; Paule, M. G.; Li, M.; Doerge, D.; Twaddle, N.; Chen, J. J.; Morris, S. M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mattison, D. R.] NICHD, NIH, Bethesda, MD USA. [Hotchkiss, C. E.] Washington Natl Primate Res Ctr, Seattle, WA USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 529 EP 529 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800056 ER PT J AU Valentine, CR AF Valentine, C. R. TI What Phi X174 has taught us about the spontaneous mutation frequencies of transgenic mutation targets SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Valentine, C. R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 535 EP 535 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800078 ER PT J AU Pogribny, IP Beland, FA AF Pogribny, I. P. Beland, F. A. TI DNA damage, epigenetic alterations and liver carcinogenesis SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Pogribny, I. P.; Beland, F. A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 537 EP 537 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800085 ER PT J AU Miura, D Dobrovolsky, V Heflich, R AF Miura, D. Dobrovolsky, V Heflich, R. TI Molecular aspects and potential advantages of Pig-A gene high throughput assay in the rat SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Miura, D.] Teijin Pharma Ltd, Tokyo, Japan. [Dobrovolsky, V; Heflich, R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 539 EP 539 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800091 ER PT J AU Montgomery, BA Bagnyukova, TV Pogribny, IP AF Montgomery, B. A. Bagnyukova, T., V Pogribny, I. P. TI Oxidative stress, antioxidant defense system during hepatocarcinogenesis induced by dietary methyl deficiency in mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Montgomery, B. A.; Bagnyukova, T., V; Pogribny, I. P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 553 EP 553 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800145 ER PT J AU Fuscoe, JC Han, T Wang, J Sawyer, J Mei, N Honma, M Chen, T Moore, MM AF Fuscoe, J. C. Han, T. Wang, J. Sawyer, J. Mei, N. Honma, M. Chen, T. Moore, M. M. TI Development of a new array comparative genomic hybridization tool for high resolution analysis of mouse chromosome 11 SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Fuscoe, J. C.; Han, T.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Wang, J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Sawyer, J.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Mei, N.; Chen, T.; Moore, M. M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Honma, M.] Natl Inst Hlth Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 556 EP 556 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800154 ER PT J AU Mei, N Guo, L Fuscoe, JC Chen, T AF Mei, N. Guo, L. Fuscoe, J. C. Chen, T. TI Riddelliine induced rat liver mutagenicity and gene expression profile SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Mei, N.; Chen, T.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Guo, L.; Fuscoe, J. C.] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 556 EP 556 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800156 ER PT J AU Chen, T Pearce, M Mei, N Guo, L AF Chen, T. Pearce, M. Mei, N. Guo, L. TI Comparison of MicroRNA expression, genomic gene expression, DNA adducts, mutation induction, and tumor incidence for carcinogenesis of aristolochic acid in rat kidney SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Chen, T.; Pearce, M.; Mei, N.; Guo, L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 557 EP 557 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800159 ER PT J AU Chen, JJ Zou, W Chang, CW Morris, SM AF Chen, J. J. Zou, W. Chang, C-W Morris, S. M. TI Gene selection and gene identification in Microarray data analysis SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Chen, J. J.; Zou, W.; Chang, C-W; Morris, S. M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 558 EP 558 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800164 ER PT J AU Miura, D Mittelstaedt, RA Shaddock, JG Dobrovolsky, VN Heflich, RH AF Miura, D. Mittelstaedt, R. A. Shaddock, J. G. Dobrovolsky, V. N. Heflich, R. H. TI GPI-deficient rat lymphocytes have mutations in the Pig-a gene SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Miura, D.] Teijin Pharma Ltd, Tokyo, Japan. [Mittelstaedt, R. A.; Shaddock, J. G.; Dobrovolsky, V. N.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 560 EP 560 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800172 ER PT J AU Shelton, SD Manjanatha, MG Mattison, DR Morris, SM AF Shelton, S. D. Manjanatha, M. G. Mattison, D. R. Morris, S. M. TI Evaluation of cll mutations in Big Blue mice fed methylphenidate hydrochloride for up to 24 weeks SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Shelton, S. D.; Manjanatha, M. G.; Morris, S. M.] US FDA, Natl Ctr Toxicol Res, DGRT, Jefferson, AR 72079 USA. [Mattison, D. R.] NICHHD, Bethesda, MD 20892 USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 561 EP 561 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800176 ER PT J AU Bishop, ME Hotchkiss, CE Lin, CJ Chen, JJ Mattison, DR Morris, SM AF Bishop, M. E. Hotchkiss, C. E. Lin, C.-J. Chen, J. J. Mattison, D. R. Morris, S. M. TI Flow cytometric determination of the micronucleus frequency in juvenile rhesus monkeys chronically exposed to methylphenidate hydrochloride SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Bishop, M. E.; Morris, S. M.] US FDA, DGRT, NCTR, Jefferson, AR USA. [Lin, C.-J.; Chen, J. J.] US FDA, DPMN, NCTR, Jefferson, AR USA. [Hotchkiss, C. E.] WANPRC UWashington, Seattle, WA USA. [Mattison, D. R.] NICHD, OPP, NIH, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 564 EP 564 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800188 ER PT J AU Dobrovolsky, VN Shaddock, JG Manjanatha, MG Miura, D Mattison, DR Morris, SM AF Dobrovolsky, V. N. Shaddock, J. G. Manjanatha, M. G. Miura, D. Mattison, D. R. Morris, S. M. TI Genotoxicity of methylphenidate hydrochloride in the rhesus monkey SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Dobrovolsky, V. N.; Shaddock, J. G.; Manjanatha, M. G.; Miura, D.; Morris, S. M.] NCTR, Jefferson, AR USA. [Mattison, D. R.] NICHD, Bethesda, MD USA. [Miura, D.] Teijin, Tokyo, Japan. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 565 EP 565 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800191 ER PT J AU Desai, VG Moland, CL Lee, T Branham, WS Beland, FA VonTungeln, LS Fuscoe, JC AF Desai, V. G. Moland, C. L. Lee, T. Branham, W. S. Beland, F. A. VonTungeln, L. S. Fuscoe, J. C. TI Impaired mitochondrial function may cause liver toxicity in nevirapine-treated B6C3F1 mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Desai, V. G.; Moland, C. L.; Lee, T.; Branham, W. S.; Beland, F. A.; VonTungeln, L. S.; Fuscoe, J. C.] NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 568 EP 568 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800205 ER PT J AU Sampliner, DS Elespuru, RK AF Sampliner, D. S. Elespuru, R. K. TI Carcinogen exposure, mutant DNA biomarkers, and human cancer risk SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Sampliner, D. S.; Elespuru, R. K.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 571 EP 571 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800216 ER PT J AU Whittaker, P Begley, TH Clarke, JJ San, RH Dunkel, VC AF Whittaker, P. Begley, T. H. Clarke, J. J. San, R. H. Dunkel, V. C. TI Evaluation of the butter flavoring diacetyl and the fluorochemical paper additive Lodyne P-208 (R) for mutagenicity SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Clarke, J. J.] BioReliance, Rockville, MD USA. [Whittaker, P.; Begley, T. H.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 571 EP 571 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800215 ER PT J AU Azuma, M McDaniel, L Manjanatha, M Shelton, S Mei, N AF Azuma, M. McDaniel, L. Manjanatha, M. Shelton, S. Mei, N. TI Mutagenic effects of acrylamide and glycidamide in the testes of Big Blue mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [Azuma, M.; McDaniel, L.; Manjanatha, M.; Shelton, S.; Mei, N.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 572 EP 572 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800219 ER PT J AU McDaniel, LP Dobrovolsky, VN Shaddock, JG Mei, N McGarrity, LJ Miura, D Doerge, D Heflich, RH AF McDaniel, L. P. Dobrovolsky, V. N. Shaddock, J. G. Mei, N. McGarrity, L. J. Miura, D. Doerge, D. R. Heflich, R. H. TI Genotoxicity of acrylamide and glycidamide in Big Blue rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 39th Annual Meeting of the Environment-Mutagen-Society CY OCT 18-22, 2008 CL PR SP Environm Mutagen Soc C1 [McDaniel, L. P.; Dobrovolsky, V. N.; Shaddock, J. G.; Mei, N.; McGarrity, L. J.; Doerge, D. R.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Miura, D.] Teijin Pharma, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2008 VL 49 IS 7 BP 575 EP 575 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 341PG UT WOS:000258725800232 ER PT J AU Wu, KM Ghantous, H Birnkrant, DB AF Wu, Kuei-Meng Ghantous, Hanan Birnkrant, Debra B. TI Current regulatory toxicology perspectives on the development of herbal medicines to prescription drug products in the United States SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT 6th Annual Oxford International Conference on the Science of Botanicals CY APR 30-MAY 03, 2007 CL Oxford, MS DE herbal; botanical; carcinogenicity; genotoxicity; reproductive toxicity; regulatory toxicology ID DOG AB Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. The US food and drug administration (FDA) published a guidance to assist academic and industry sponsors in the development of this unique group of drug products, and has recently approved an new drug application (NDA) based on green tea extract (Veregen(R)) for topical treatment of genital and perianal warts. In this article, current regulatory views on issues related to requirements and recommendations on various types of nonclinical toxicity studies in support of clinical trials and filing an NDA for a herbal medicine, including pharm/tox aspects of green tea extract (Veregen(R)) NDA, are discussed. Topics include nonclinical pharmacology/toxicology perspectives on herbal nomenclature and its identification, previous human experience and initial clinical trial proposal, regulatory aspects of acute toxicity studies, chronic toxicity studies, mutagenicity studies, reproductive toxicity studies, and carcinogenicity studies on botanicals. Certain regulatory review-related issues are also presented. It is anticipated that through a proactive two-way communication between the Agency and the sponsor, toxicological development of botanical drug product can be significantly facilitated. Published by Elsevier Ltd. C1 [Wu, Kuei-Meng; Ghantous, Hanan; Birnkrant, Debra B.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wu, KM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kueimeng.wu@fda.hhs.gov NR 26 TC 24 Z9 27 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 2008 VL 46 IS 8 BP 2606 EP 2610 DI 10.1016/j.fct.2008.05.029 PG 5 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 337ML UT WOS:000258440100002 PM 18614266 ER PT J AU Whittaker, P Clarke, JJ San, RHC Begley, TH Dunkel, VC AF Whittaker, Paul Clarke, Jane J. San, Richard H. C. Begley, Timothy H. Dunkel, Virginia C. TI Evaluation of the butter flavoring chemical diacetyl and a fluorochemical paper additive for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE diacetyl; lodyne; mutagenicity; mouse lymphoma ID HUMAN LIVER-MICROSOMES; BRONCHIOLITIS OBLITERANS; WORKERS; SUBSTANCES; MIGRATION AB Diacetyl (2,3-butanedione) is a yellowish liquid that is usually mixed with other ingredients to produce butter flavor or other flavors in a variety of food products. Inhalation of butter flavoring vapors was first associated with clinical bronchiolitis obliterans among workers in microwave popcorn production. Recent findings have shown irreversible obstructive lung disease among workers not only in the microwave popcorn industry, but also in flavoring manufacture, and in chemical synthesis of diacetyl, a predominant chemical for butter flavoring. It has been reported that perfluorochemicals utilized in food packaging are migrating into foods and may be sources of oral exposure. Relatively small quantities of perfluorochemicals are used in the manufacturing of paper or paperboard that is in direct contact with food to repel oil or grease and water. Because of recent concerns about perfluorochemicals such as those found on microwave popcorn bags (e.g. Lodyne P208E (R)) and diacetyl in foods, we evaluated both compounds for mutagenicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells. Lodyne P208E (R) was less toxic than diacetyl and did not induce a mutagenic response. Diacetyl induced a highly mutagenic response in the L5178Y mouse lymphoma mutation assay in the presence of human liver S9 for activation. The increase in the frequency of small colonies in the assay with diacetyl indicates that diacetyl causes damage to Multiple loci on chromosome 11 in addition to functional loss of the thymidine kinase locus. Published by Elsevier Ltd. C1 [Whittaker, Paul; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Clarke, Jane J.] BioReliance, Rockville, MD 20850 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-717, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 25 TC 13 Z9 16 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 2008 VL 46 IS 8 BP 2928 EP 2933 DI 10.1016/j.fct.2008.06.001 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 337ML UT WOS:000258440100048 PM 18585428 ER PT J AU Rasooly, A Herold, KE AF Rasooly, Avraham Herold, Keith E. TI Food microbial pathogen detection and analysis using DNA microarray technologies SO FOODBORNE PATHOGENS AND DISEASE LA English DT Review ID WHOLE-GENOME AMPLIFICATION; ANTIMICROBIAL RESISTANCE GENES; HIGH-DENSITY MICROARRAY; OLIGONUCLEOTIDE MICROARRAY; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; RIBOSOMAL DNA; BACILLUS-ANTHRACIS; POINT MUTATIONS; FLOW-CYTOMETRY AB Culture-based methods used for microbial detection and identification are simple to use, relatively inexpensive, and sensitive. However, culture-based methods are too time-consuming for high-throughput testing and too tedious for analysis of samples with multiple organisms and provide little clinical information methods, such as polymerase chain reaction (PCR), overcome some these limitations since they are generally faster and can provide more information than culture-based methods. One limitation of traditional PCR-based methods is that they are normally limited to the analysis of a single pathogen, a small group of related pathogens, or a small number of relevant genes. Microarray technology enables a significant expansion of the capability of DNA-based methods in terms of the number of DNA sequences that can be analyzed simultaneously, enabling molecular identification and characterization of multiple pathogens and many genes in a single array assay. Microarray analysis of microbial pathogens has potential uses in research, food safety, medical, agricultural, regulatory, public health, and industrial settings. In this article, we describe the main technical elements of microarray technology and the application and potential use of DNA microarrays for food microbial analysis. C1 [Rasooly, Avraham] NCI, NIH, Rockville, MD 20852 USA. [Herold, Keith E.] Univ Maryland, College Pk, MD 20742 USA. [Rasooly, Avraham] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 100 TC 41 Z9 46 U1 2 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD AUG PY 2008 VL 5 IS 4 BP 531 EP 550 DI 10.1089/fpd.2008.0119 PG 20 WC Food Science & Technology SC Food Science & Technology GA 340ZT UT WOS:000258684200015 PM 18673074 ER PT J AU Garvin, LE Bash, MC Keys, C Warner, DM Ram, S Shafer, WM Jerse, AE AF Garvin, Lotisha E. Bash, Margaret C. Keys, Christine Warner, Douglas M. Ram, Sanjay Shafer, William M. Jerse, Ann E. TI Phenotypic and genotypic analyses of Neisseria gonorrhoeae isolates that express frequently recovered PorB PIA variable region types suggest that certain P1a porin sequences confer a selective advantage for urogenital tract infection SO INFECTION AND IMMUNITY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; SEROVAR-SPECIFIC IMMUNITY; MTRRCDE EFFLUX SYSTEM; NORMAL HUMAN SERUM; C4B-BINDING PROTEIN; GONOCOCCAL-INFECTION; MOLECULAR-MECHANISM; POPULATION-GENETICS; FACTOR-H; RESISTANCE AB Typing of the porB variable region (VR) is an epidemiological tool that classifies gonococcal strains based on sequence differences in regions of the porB gene that encode surface-exposed loops. The frequent isolation of certain porB VR types suggests that some porin sequences confer a selective advantage during infection and/or transmission. Alternatively, certain porin types may be markers of strains that are successful due to factors unrelated to porin. In support of the first hypothesis, here we show urogenital tract isolates representing the most common PIA VR types identified in an urban clinic in Baltimore, MD, over a 10-year period belonged to several different clonal types, as determined by pulsed-field gel electrophoresis (PFGE). Serum resistance, which was confirmed by factor H and C4b-binding protein binding studies, was more often associated with gonococcal the most common VR types. In contrast, three porin-independent phenotypes, namely, lactoferrin utilization, beta-lactamase production, and multiple transferable resistance (Mtr), were segregated with the PFGE cluster and not with the VR type. Data combined with another PIA strain collection showed a strong correlation between serum resistance and the most common VR types. A comparison of VR typing hybridization patterns and nucleotide sequences of 12 porB1a genes suggests that certain porin loop 1, 3, 6, and/or 7 sequences may play a role in the serum resistance phenotype. We conclude that some PorB PIA sequences confer a survival or transmission advantage in the urogenital tract, perhaps via increased resistance to complement-mediated killing. The capacity of some porin types to evade a porin-specific adaptive immune response must also be considered. C1 [Garvin, Lotisha E.; Warner, Douglas M.; Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20853 USA. [Bash, Margaret C.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pediat, Bethesda, MD 20853 USA. [Bash, Margaret C.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Bethesda, MD USA. [Keys, Christine] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, College Pk, MD USA. [Ram, Sanjay] Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA USA. [Shafer, William M.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA. [Shafer, William M.] Vet Affairs Med Ctr, VA Med Res Serv, Labs Microbial Pathogensis, Decatur, GA 30033 USA. RP Jerse, AE (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20853 USA. EM ajerse@usuhs.mil FU National Institutes of Health STI/TM CRC [U19 AI31496]; NIH [RO1-AI062755, AI54544, AI032725]; VA Medical Research Service FX This work was supported by National Institutes of Health STI/TM CRC grant U19 AI31496 (A.E.J.), NIH grant RO1-AI062755 (W.M.S.), and NIH grants AI54544 and AI032725 (S.R.). W.M.S. was supported in part by a senior research career scientist award from the VA Medical Research Service. NR 61 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2008 VL 76 IS 8 BP 3700 EP 3709 DI 10.1128/IAI.00265-08 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 338BW UT WOS:000258480900036 PM 18541655 ER PT J AU Bataller, N AF Bataller, Neal TI Extralabel use of cephalosporins prohibited in food animals SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Ctr Vet Med HFV 230, Rockville, MD 20857 USA. RP Bataller, N (reprint author), US FDA, Ctr Vet Med HFV 230, 7519 Standish Pl, Rockville, MD 20857 USA. EM neal.bataller@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD AUG 1 PY 2008 VL 233 IS 3 BP 372 EP + PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 330RV UT WOS:000257961400003 ER PT J AU Sahu, SC Garthoff, LH Robl, MG Chirtel, SJ Ruggles, DI Flynn, TJ Sobotka, TJ AF Sahu, Saura C. Garthoff, Larry H. Robl, Martin G. Chirtel, Stuart J. Ruggles, Dennis I. Flynn, Thomas J. Sobotka, Thomas J. TI Rat liver clone-9 cells in culture as a model for screening hepatotoxic potential of food-related products: hepatotoxicity of deoxynivalenol SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE hepatotoxicity; liver toxicity; hepatocytes; clone-9 cell line; deoxynivalenol; mycotoxin ID FUSARIUM-TOXIN DEOXYNIVALENOL; IN-VITRO; GENE-EXPRESSION; CEREAL-GRAINS; GRADED-LEVELS; T-2 TOXIN; LINE; CYTOTOXICITY; HEPATOCYTES; MYCOTOXINS AB Deoxynivalenol (DON) is a mycotoxin food contaminant found in several cereal grains. The literature on the liver toxicity of DON in vivo is conflicting and does not clearly characterize its hepatotoxic effects. Cultured rat liver clone-9 cells were used as a model to assess the hepatotoxic potential of DON. The cell cultures, seeded onto 96-well plates, were treated at confluence with varying concentrations of DON (0-100 mu g ml(-1)) for 48 h at 37 degrees C in 5% CO2. After the treatment period, the cells were assayed for a number of hepatotoxic endpoints that included cytotoxicity, double-stranded DNA (ds-DNA) content, oxidative stress and mitochondrial function. The concentration-dependent toxicity of DON, as measured by cytotoxicity and ds-DNA content, was observed over the entire concentration range studied beginning at 0.5 mu g ml(-1). DON also induced a significant concentration-dependent increase in oxidative stress at DON concentrations starting at 10 mu g ml(-1). The mitochondrial function of the treated cells decreased with the increasing concentration of DON exposure, but it was not statistically different from that of the control value. Liver histopathology observed at 3, 24 and 72 h following a single intraperitoneal administration dose of DON (10 mg kg(-1) BW) to adult male rats is consistent with early mild hepatotoxicity. The overall results of this study suggest that acute DON exposure has early mild cytotoxic effects on hepatocytes in vivo that are expressed as severe effects in rat liver clone-9 cells in vitro. Published in 2008 by John Wiley & Sons, Ltd. C1 [Sahu, Saura C.; Garthoff, Larry H.; Flynn, Thomas J.; Sobotka, Thomas J.] US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Robl, Martin G.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Chirtel, Stuart J.; Ruggles, Dennis I.] US FDA, Div Math, Off Sci Anal & Support, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM saura.sahu@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 55 TC 25 Z9 26 U1 0 U2 12 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 AUG PY 2008 VL 28 IS 6 BP 765 EP 772 DI 10.1002/jat.1337 PG 8 WC Toxicology SC Toxicology GA 345BN UT WOS:000258971100006 PM 18300328 ER PT J AU Jones, RC Deck, J Edmondson, RD Hart, ME AF Jones, Richard C. Deck, Joanna Edmondson, Ricky D. Hart, Mark E. TI Relative quantitative comparisons of the extracellular protein profiles of Staphylococcus aureus UAMS-1 and its sarA, agr, and sarA agr regulatory mutants using one-dimensional polyacrylamide gel electrophoresis and nanocapillary liquid chromatography coupled with tandem mass spectrometry SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYTIC TRANSGLYCOSYLASE HOMOLOG; GONOCOCCAL GROWTH INHIBITOR; AMINO-ACID-SEQUENCE; BINDING PROTEIN; VIRULENCE DETERMINANTS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; MOLECULAR CHARACTERIZATION; TRANSFERRIN-BINDING; SHOTGUN PROTEOMICS; CELL-SURFACE AB One-dimensional polyacrylamide gel electrophoresis followed by nanocapillary liquid chromatography coupled with mass spectrometry was used to analyze proteins isolated from Staphylococcus aureus UAMS-1 after 3, 6, 12, and 24 111 of in vitro growth. Protein abundance was determined using a quantitative value termed normalized peptide number, and overall, proteins known to be associated with the cell wall were more abundant early on in growth, while proteins known to be secreted into the surrounding milieu were more abundant late in growth. In addition, proteins from spent media and cell lysates of strain UAMS-1 and its isogenic sarA, agr, and sarA agr regulatory mutant strains during exponential growth were identified, and their relative abundances were compared. Extracellular proteins known to be regulated by the global regulators sarA and agr displayed protein levels in accordance with what is known regarding the effects of these regulators. For example, cysteine protease (SspB), endopeptidase (SspA), staphopain (ScpA), and aureolysin (Aur) were higher in abundance in the sarA and sarA agr mutants than in strain UAMS-1. The immunoglobulin G (IgG)-binding protein (Sbi), immunodominant staphylococcal antigen A (IsaA), IgG-binding protein A (Spa), and the heme-iron-binding protein (IsdA) were most abundant in the agr mutant background. Proteins whose abundance was decreased in the sarA mutant included fibrinogen-binding protein (Fib [Efb]), IsaA, lipase I and 2, and two proteins identified as putative leukocidin F and S subunits of the two-component leukotoxin family. Collectively, this approach identified 1,263 proteins (matches of two peptides or more) and provided a convenient and reliable way of identifying proteins and comparing their relative abundances. C1 [Deck, Joanna; Hart, Mark E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Jones, Richard C.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Hart, ME (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT 250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mark.hart@fda.hhs.gov RI Hart, Mark/B-8976-2013 NR 67 TC 43 Z9 45 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2008 VL 190 IS 15 BP 5265 EP 5278 DI 10.1128/JB.00383-08 PG 14 WC Microbiology SC Microbiology GA 332VV UT WOS:000258112100015 PM 18539737 ER PT J AU Forrest, SW Russek-Cohen, E Lewis, BE Ho, C Sapirstein, JS Eloff, BC Lappalainen, SK Mallis, E AF Forrest, S. W. Russek-Cohen, E. Lewis, B. E. Ho, C. Sapirstein, J. S. Eloff, B. C. Lappalainen, S. K. Mallis, E. TI Statistical comparison of cardiac output measurement methods: Advantages of an error grid representation SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 12th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 21-24, 2008 CL Toronto, CANADA SP Heart Failure Soc Amer C1 [Forrest, S. W.; Russek-Cohen, E.; Lewis, B. E.; Ho, C.; Sapirstein, J. S.; Eloff, B. C.; Lappalainen, S. K.; Mallis, E.] US FDA, Off Device Evaluat, Rockville, MD 20857 USA. RI green, sam/C-2608-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2008 VL 14 IS 6 SU 1 MA 176 BP S56 EP S56 DI 10.1016/j.cardfail.2008.06.176 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 339GC UT WOS:000258565100177 ER PT J AU Gianni, L Herman, EH Lipshultz, SE Minotti, G Sarvazyan, N Sawyer, DB AF Gianni, Luca Herman, Eugene H. Lipshultz, Steven E. Minotti, Giorgio Sarvazyan, Narine Sawyer, Douglas B. TI Anthracycline cardiotoxicity: From bench to bedside SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CONGESTIVE-HEART-FAILURE; BREAST-CANCER PATIENTS; LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; LEFT-VENTRICULAR DYSFUNCTION; DRUG-INDUCED CARDIOTOXICITY; HIGH-DOSE CHEMOTHERAPY; OF-CLINICAL-ONCOLOGY; CARDIAC TROPONIN-T; CHILDHOOD-CANCER AB Anthracyclines remain among the most widely prescribed and effective anticancer agents. Unfortunately, life-threatening cardiotoxicity continues to compromise their usefulness. Despite more than four decades of investigation, the pathogenic mechanisms responsible for anthracycline cardiotoxicity have not been completely elucidated. In addition, new drugs and combination therapies often exacerbate the toxicity. The First International Workshop on Anthracycline Cardiotoxicity, held in fall 2006, in Como, Italy, focused on the state-of-the-art knowledge and discussed the research needed to address the cardiotoxicity of these drugs. Here, we incorporate these discussions into the framework of a broader review of preclinical and clinical issues. C1 Inst Nazl Tumori, Div Med Oncol, Fdn Ist Ricovero & Cura Carattere Sci, Milan, Italy. Univ Campus Biomed Rome, Ctr Integrated Res & Drug Sci, Rome, Italy. US FDA, Div Appl Pharmacol Res, Silver Spring, MD USA. Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Miami, FL 33101 USA. Univ Miami, Holtz Childrens Hosp, Jackson Mem Med Ctr, Miami, FL 33101 USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33101 USA. George Washington Univ, Sch Med, Dept Physiol & Pharmacol, Washington, DC USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. RP Lipshultz, SE (reprint author), Univ Miami, Dept Pediat D820, Leonard M Miller Sch Med, POB 016820, Miami, FL 33101 USA. EM slipshultz@med.miami.edu OI Minotti, Giorgio/0000-0002-5678-6175 FU NHLBI NIH HHS [R01 HL062419-04, R01 HL062419, R01 HL062419-01, R01 HL062419-02, R01 HL062419-03]; Associazione Italiana per la Ricerca sul Cancro NR 108 TC 207 Z9 217 U1 4 U2 20 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2008 VL 26 IS 22 BP 3777 EP 3784 DI 10.1200/JCO.2007.14.9401 PG 8 WC Oncology SC Oncology GA 331ZV UT WOS:000258052100021 PM 18669466 ER PT J AU Malinowski, HJ Westelinck, A Sato, J Ong, T AF Malinowski, Henry J. Westelinck, Agnes Sato, Junko Ong, Ting TI Same drug, different dosing: Differences in dosing for drugs approved in the United States, Europe, and Japan SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE international; dosing; regulatory decisions; exposure response; drug safety ID IMPACT AB With globalization of the pharmaceutical industry, newly approved drugs nearly always become available worldwide, including the 3 major pharmaceutical regions: the United States, Europe, and Japan. One might think that these drugs would have the some recommended dosing throughout the world, but this appears not to be true in many instances. The objective of this study was to identify any patterns of differences in labeled dosing. Approved labeling, for the most widely prescribed proprietary drugs in the United States, was used as a basis for this study. Dosing was compared, for common indications, for the United States, Europe, and Japan. Overall, these data indicate that there are numerous differences in approved dosing for drugs approved in all 3 regions. For about half of the drugs studied, dosing in Japan is considerably lower than the United States or Europe. Some differences in dosing are also apparent between the United States and Europe. C1 [Malinowski, Henry J.] US FDA, Rockville, MD 20857 USA. [Sato, Junko] Pharmaceut & Med Devices Agcy, Tokyo, Japan. [Westelinck, Agnes] Hoffmann LaRoche, Nutley, NJ USA. RP Malinowski, HJ (reprint author), 1549 Arnold Palmer Dr, Haymarket, VA 20169 USA. EM h_malinowski@comcast.net NR 22 TC 31 Z9 31 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2008 VL 48 IS 8 BP 900 EP 908 DI 10.1177/0091270008319794 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 330AD UT WOS:000257910800002 PM 18524997 ER PT J AU Udey, MC Rosenberg, AS AF Udey, Mark C. Rosenberg, Amy S. TI Langerhans cell dogma: Another round of rejections SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID LANGERIN(+) DENDRITIC CELLS; T-CELLS; CONTACT HYPERSENSITIVITY; SKIN; DEVELOP AB Mice that are deficient in epidermal Langerhans cells allow the functions of these cells in vivo to be rigorously assessed. Experiments that have been carried out with these animals have yielded surprising results, leading to major changes in existing paradigms. In this issue, Obhrai and coworkers explore the involvement of Langerhans cells in skin graft rejection and describe fascinating results. C1 [Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Rosenberg, Amy S.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20014 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM udey@helix.nih.gov NR 14 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2008 VL 128 IS 8 BP 1881 EP 1883 DI 10.1038/jid.2008.167 PG 3 WC Dermatology SC Dermatology GA 331SA UT WOS:000258031700003 PM 18626480 ER PT J AU Becker, C Califano, JC Chang, J Napier, J Sachs, H Viswanath, S Pal, A Sheikh, A Tolle, J AF Becker, Calvin Califano, Jean-Christophe Chang, Jane Napier, James Sachs, Howard Viswanath, Shekhar Pal, Agnes Sheikh, Ahmad Tolle, John TI Purification of synthetic peptides by reverse osmosis and crystallization SO JOURNAL OF PEPTIDE SCIENCE LA English DT Meeting Abstract C1 [Becker, Calvin; Califano, Jean-Christophe; Napier, James; Sachs, Howard; Viswanath, Shekhar; Pal, Agnes; Sheikh, Ahmad; Tolle, John] Abbott Labs, Abbott Pk, IL 60064 USA. [Chang, Jane] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PD AUG PY 2008 VL 14 IS 8 SU S BP 11 EP 11 PG 1 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 345VZ UT WOS:000259026900025 ER PT J AU Guo, CN Gillespie, SR Kauffman, J Doub, WH AF Guo, Changning Gillespie, Stacey R. Kauffman, John Doub, William H. TI Comparison of delivery characteristics from a combination metered-dose inhaler using the Andersen Cascade Impactor and the Next Generation Pharmaceutical Impactor SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Andersen Cascade Impactor; Next Generation Pharmaceutical Impactor; Combivent (R); particle size distribution; dose delivery profile; flow rate; induction port; albuterol sulfate; ipratropium bromide ID HUMAN RESPIRATORY-TRACT; HUMAN ORAL AIRWAYS; REGIONAL DEPOSITION; AEROSOL-PARTICLES; IN-VITRO; EFFICIENCY; THROAT; MOUTH; SIZE; CAST AB The purpose of this research was to compare two cascade impaction devices for the aerodynamic particle size assessment of a combination metered-dose inhaler (MDI) product, Combivent (R). Particle size analysis was performed using an Anderson Mark II cascade impactor (ACI) and a Next Generation Pharmaceutical Impactor (NGI), both fitted with a preseparator and either a 1 L glass chamber or USP throat, and operated at various flow rates. Particle size distributions (PSDs) and dose delivery profiles were assessed by means of the mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle fraction <5 micron aerodynamic diameter (FPF<5 mu m), and induction port deposition fraction (IPF). Under their normal operating conditions, the ACI (28.3 L/min) and the NGI (30 L/min) yield similar PSDs and dose delivery profiles. However, this equivalent performance for the ACI and the NGI no longer exists at a higher flow rate of 60 L/min. Furthermore, changes in PSD results may also be obtained between different operators and/or when different induction port designs were employed. Thus, it is strongly recommended that special care be taken to eliminate variation in experimental parameters and/or selection of ancillary devices such as the preseparator, induction port or throat, to insure good repeatability and reproducibility when testing inhalation drugs. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Guo, Changning; Gillespie, Stacey R.; Kauffman, John; Doub, William H.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Guo, CN (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM changning.guo@fda.hhs.gov NR 34 TC 10 Z9 11 U1 2 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2008 VL 97 IS 8 BP 3321 EP 3334 DI 10.1002/jps.21203 PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 332KE UT WOS:000258081100032 PM 17932959 ER PT J AU Gao, ZM Moore, TW Doub, WH AF Gao, Zongming Moore, Terry W. Doub, William H. TI Vibration effects on dissolution tests with USP Apparatuses 1 and 2 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution testing; vibration effect; USP Apparatus 1; USP Apparatus 2; disintegrating tablet; nondisintegrating tablet ID VARIABILITY AB Dissolution testing is of primary importance for drug formulation and quality control. Many sources of variability are accounted for in the apparatus' mechanical calibration process; the effect of vibration on dissolution tests is not well understood in that the test's tolerance for environmental vibration with respect to magnitude or frequency is largely unknown. In this study, USP Apparatuses 1 and 2 were used. Dissolution profiles were obtained for both disintegrating and nondisintegrating tablets. In separate experiments, a lab vacuum pump or a lab mixer, both commonly used in laboratories, was used to generate vibration during dissolution runs with vibration parameters being recorded at a location close to the dissolution vessels. Disintegrating tablets were found to be sensitive to induced vibrations with both the paddle and basket methods. Average dissolution results for nondisintegrating tablets were not sensitive to the studied vibrations; however, variability of the results increased in some cases. The dissolution profiles suggest that the vibration effects on paddle and basket method occur through different mechanisms. The importance of vibration to dissolution test results depends on the vibration source, product being tested and the apparatus type. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Gao, Zongming; Moore, Terry W.; Doub, William H.] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 22 TC 7 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2008 VL 97 IS 8 BP 3335 EP 3343 DI 10.1002/jps.21242 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 332KE UT WOS:000258081100033 PM 18000813 ER PT J AU Zidan, AS Habib, MJ Khan, MA AF Zidan, Ahmed S. Habib, Muhammad J. Khan, Mansoor A. TI Process analytical technology: Nondestructive evaluation of cyclosporine A and phospholipid solid dispersions by near infrared spectroscopy and imaging SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE solid dispersion; cyclosporine; DMPC; near infrared; NIR imaging ID DISSOLUTION BEHAVIOR; DRUG; SYSTEMS; DIMYRISTOYLPHOSPHATIDYLCHOLINE; PHOSPHATIDYLCHOLINE; NANOPARTICLES; CARBAMAZEPINE; FORMULATIONS; VARIABILITY; QUALITY AB The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess phospholipid compartment within its solid dispersion with cyclosporine A (CyA). By varying dimyristoyl phosphatidylcholine (DMPC) to CyA weight ratio, five batches were prepared by the kneading technique and characterized by DSC and FTIR. A drug/DMPC ratio of 50:1 provided an enhanced dissolution of CyA. FTIR spectra and DSC thermograms revealed a significant interaction between the drug and DMPC which suggested incorporation of CyA within the formed DMPC liposomes. The developed NTR calibration model was able to assess DMPC concentrations within the kneaded products. The calibration and prediction linear plots showed slopes of 0.9711 and 0.9915, offsets of 0.1247 and 0.1080, correlation coefficients of 0.9854 and 0.9889 and root mean square standard errors of 0.43% and 0.42%, respectively. In contrast, NIR spectral imaging was capable of clearly distinguishing the kneaded products, both qualitatively and quantitatively. NIR imaging revealed the poor powder blending efficiency of the method used to prepare physical mixture compared to the efficient distribution of the kneaded products. In conclusion, NIR spectral imaging system provides a rapid approach for acquiring high-resolution spatial and spectral information on solid dispersions. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association. C1 [Khan, Mansoor A.] US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. [Habib, Muhammad J.] Howard Univ, Sch Pharm, Washington, DC 20059 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. EM mansoor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 26 TC 12 Z9 13 U1 0 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD AUG PY 2008 VL 97 IS 8 BP 3388 EP 3399 DI 10.1002/jps.21238 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 332KE UT WOS:000258081100038 PM 18064594 ER PT J AU Siegel, J AF Siegel, Jeffrey TI The mean overall index-RA: A new disease activity measure in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID ACTIVITY SCORE; RANDOMIZED-TRIAL; CLINICAL-TRIALS; VALIDATION; REMISSION; STRATEGY C1 [Siegel, Jeffrey] US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. RP Siegel, J (reprint author), FDA CDER OND ODE II DAARP, Div Anesthesia Analgesia & Rheumatol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Jeffrey.siegel@fda.hhs.gov NR 13 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 AUG PY 2008 VL 35 IS 8 BP 1480 EP 1481 PG 2 WC Rheumatology SC Rheumatology GA 332UL UT WOS:000258108500003 PM 18671319 ER PT J AU Argaw, T Figueroa, M Salomon, DR Wilson, CA AF Argaw, Takele Figueroa, Mariel Salomon, Daniel R. Wilson, Carolyn A. TI Identification of residues outside of the receptor binding domain that influence the infectivity and tropism of porcine endogenous retrovirus SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; MINIATURE SWINE; HUMAN-CELLS; HOST-RANGE; SURFACE GLYCOPROTEIN; ENVELOPE PROTEINS; ISLET XENOTRANSPLANTATION; PROTEOLYTIC CLEAVAGE; ENDOTHELIAL-CELLS; VIRAL ENTRY AB Identification of determinants of human tropism of porcine endogenous retrovirus (PERV) is critical to understanding the risk of transmission of PERV to recipients of porcine xenotransplantation products. Previously, we showed that a chimeric envelope cDNA encoding the 360 N-terminal residues of the human-tropic PERV envelope class A (PERV-A) SU and the 130 C-terminal residues of the pig-tropic PERV-C SU and all of TM (PERV-A/C) showed a 100-fold decrease in infectivity titer on human cells (M. Gemeniano, O. Mpanju, D. R. Salomon, M. V. Eiden, and C. A. Wilson, Virology 346:108-117, 2006). To identify residues important for human cell infection, we performed site-directed mutagenesis on each of the nine residues, singly or in combination, that distinguish the C-terminal region of PERV-C from PERV-A. Of the nine amino acids, two single-amino-acid substitutions, Q374R and I412V, restored the infectivity of human cells to the chimeric PERV-A/C to a titer equivalent to that of PERV-A. In contrast, PERV-A/C mutant envelope Q439P resulted in undetectable infection of human cells and an approximately 1,000-fold decrease in control pig cells. Mutation of K441R rescued mutants that carried Q439P, suggesting an incompatibility between the proline residue at this position and the presence of KK in the proteolytic cleavage signal. We confirmed this incompatibility with vectors carrying PERV-A envelope mutant R462K that were also rendered noninfectious. Finally, tropism of vectors carrying PERV-C envelope mutants with only four amino acid changes in the C terminus of PERV-C envelope, NHRQ436YNRP plus K441R, was shifted to one similar to that of PERV-A. Our results show an important and previously unrecognized role for infectivity and tropism for residues at the C terminus of SU. C1 [Argaw, Takele; Figueroa, Mariel; Wilson, Carolyn A.] US FDA, Ctr Biol Evaluat & Res, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. [Salomon, Daniel R.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 93037 USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Bldg 29B,Room 5NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carolyn.wilson@fda.hhs.gov RI Salomon, Daniel/E-9380-2012 FU PHS HHS [A152349-052A2] NR 55 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2008 VL 82 IS 15 BP 7483 EP 7491 DI 10.1128/JVI.00295-08 PG 9 WC Virology SC Virology GA 328AV UT WOS:000257770500023 PM 18508891 ER PT J AU Li, J Van Uitert, R Yao, JH Petrick, N Franaszek, M Huang, A Summers, RM AF Li, Jiang Van Uitert, Robert Yao, Jianhua Petrick, Nicholas Franaszek, Marek Huang, Adam Summers, Ronald M. TI Wavelet method for CT colonography computer-aided polyp detection SO MEDICAL PHYSICS LA English DT Article; Proceedings Paper CT 3rd IEEE International Symposium on Biomedical Imaging CY APR 06-09, 2006 CL Arlington, VA SP IEEE DE CT colonography; CAD; false positive reduction; wavelet; SVM committee ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONIC POLYPS; FALSE POSITIVES; CLASSIFICATION; NETWORK; REDUCTION; ALGORITHM; DIAGNOSIS; SELECTION; SEGMENTATION AB Computed tomographic colonography (CTC) computer aided detection (CAD) is a new method to detect colon polyps. Colonic polyps are abnormal growths that may become cancerous. Detection and removal of colonic polyps, particularly larger ones, has been shown to reduce the incidence of colorectal cancer. While high sensitivities and low false positive rates are consistently achieved for the detection of polyps sized 1 cm or larger, lower sensitivities and higher false positive rates occur when the goal of CAD is to identify "medium"-sized polyps, 6-9 mm in diameter. Such medium-sized polyps may be important for clinical patient management. We have developed a wavelet-based postprocessor to reduce false positives for this polyp size range. We applied the wavelet-based postprocessor to CTC CAD findings from 44 patients in whom 45 polyps with sizes of 6-9 mm were found at segmentally unblinded optical colonoscopy and visible on retrospective review of the CT colonography images. Prior to the application of the wavelet-based postprocessor, the CTC CAD system detected 33 of the polyps (sensitivity 73.33%) with 12.4 false positives per patient, a sensitivity comparable to that of expert radiologists. Fourfold cross validation with 5000 bootstraps showed that the wavelet-based postprocessor could reduce the false positives by 56.61% (p < 0.001), to 5.38 per patient (95% confidence interval [4.41, 6.34]), without significant sensitivity degradation (32/45, 71.11%, 95% confidence interval [66.39%, 75.74%], p=0.1713). We conclude that this wavelet-based postprocessor can substantially reduce the false positive rate of our CTC CAD for this important polyp size range. C1 [Li, Jiang; Van Uitert, Robert; Yao, Jianhua; Franaszek, Marek; Huang, Adam; Summers, Ronald M.] Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Petrick, Nicholas] NIBIB, Ctr Devices & Radiol Hlth, Joint Lab Assessment Med Imaging Syst, US FDA, Silver Spring, MD 20993 USA. RP Li, J (reprint author), Natl Inst Hlth, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. EM lijiang_ts@yahoo.com FU Intramural NIH HHS NR 58 TC 13 Z9 14 U1 1 U2 3 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 AUG PY 2008 VL 35 IS 8 BP 3527 EP 3538 DI 10.1118/1.2938517 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 331UU UT WOS:000258038900014 PM 18777913 ER PT J AU Verkler, TL Delongchamp, RR Miller, BJ Webb, PJ Howard, PC Parsons, BL AF Verkler, Tracie L. Delongchamp, Robert R. Miller, Barbara J. Webb, Peggy J. Howard, Paul C. Parsons, Barbara L. TI Simulated solar light-induced p53 mutagenesis in SKH-1 mouse skin: A dose-response assessment SO MOLECULAR CARCINOGENESIS LA English DT Article DE ACB-PCR; Mutation; allele-specific amplification; skin neoplasm; dose-response ID SQUAMOUS-CELL CARCINOMAS; HAIRLESS MICE; MUTATIONS; INDUCTION; CANCER; TUMORS; CARCINOGENESIS; IRRADIATION; KINETICS; SUNLIGHT AB Sunlight and ultraviolet-induced mutation of the p53 gene is a frequent, possibly obligate step in skin cancer development, making quantitative measurement of p53 mutation an ideal biomarker for sunlight-induced skin carcinogenesis. To understand how the appearance of p53 mutation relates to skin tumor development, SKH-1 hairless mice were exposed 5 d per week to one of four different doses of simulated solar light (SSL; 0, 6.85, 13.70, 20.55 mJ . CIE/cm(2)) previously characterized for their tumorigenic potential. Allele-specific competitive blocker-PCR (ACB-PCR) was used to measure levels of p53 codon 270 CGT to TGT mutation within DNA isolated from dorsal skin of exposed mice. For each dose, p53 mutant fraction (MF) was measured after 4, 16, and 28 wk of exposure. Significant dose- and time-dependent increases in p53 MF were identified. All p53 MF measurements were integrated by relating the observed p53 MF to the cumulative dose of SSL. The increase in the logarithm of p53 MF was described by the linear function: log(10) MF - alpha + 0.0016 . d, where alpha is the spontaneous log(10) MF after a particuiar time point and d is the dose of SSL in mJ - CIE/cm(2). The p53 MF induced in nontumor bearing skin by 28 wk of exposure at the high dose of SSL was significantly lower than that found in skin tumors induced by similar to 32 wk of exposure to the same dose of SSL. p53 MF showed a strong negative correlation with tumor latency, suggesting this quantitative biomarker has the potential to predict tumorigenicity. (c) 2008 Wiley-Liss, Inc. C1 [Verkler, Tracie L.; Parsons, Barbara L.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Miller, Barbara J.; Webb, Peggy J.; Howard, Paul C.] US FDA, Natl Ctr Toxicol Res, Natl Toxicol Program Ctr Phototoxicol, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 12 Z9 12 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2008 VL 47 IS 8 BP 599 EP 607 DI 10.1002/mc.20415 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 330XB UT WOS:000257975000004 PM 18314877 ER PT J AU Wang, JH Lozier, J Johnson, G Kirshner, S Verthelyi, D Pariser, A Shores, E Rosenberg, A AF Wang, Jinhai Lozier, Jay Johnson, Gibbes Kirshner, Susan Verthelyi, Daniela Pariser, Anne Shores, Elizabeth Rosenberg, Amy TI Neutralizing antibodies to therapeutic enzymes: considerations for testing, prevention and treatment SO NATURE BIOTECHNOLOGY LA English DT Article ID ACID ALPHA-GLUCOSIDASE; T-CELL TOLERANCE; FACTOR-VIII INHIBITORS; LONG-TERM ACCEPTANCE; HUMAN GROWTH-HORMONE; SEVERE HEMOPHILIA-A; DISEASE TYPE-II; REPLACEMENT THERAPY; IMMUNE TOLERANCE; FABRY-DISEASE AB Lysosomal storage diseases are characterized by deficiencies in lysosomal enzymes, allowing accumulation of target substrate in cells and eventually causing cell death. Enzyme replacement therapy is the principal treatment for most of these diseases. However, these therapies are often complicated by immune responses to the enzymes, blocking efficacy and causing severe adverse outcomes by neutralizing product activity. It is thus crucial to understand the relationships between genetic mutations, endogenous residual enzyme proteins (cross-reactive immunologic material), development of neutralizing antibodies and their impact on clinical outcomes of lysosomal storage diseases. For patients in whom neutralizing antibodies may cause severe adverse clinical outcomes, it is paramount to develop tolerance inducing protocols to preclude, where predictable, or treat such life-threatening responses. C1 [Wang, Jinhai; Johnson, Gibbes; Kirshner, Susan; Verthelyi, Daniela; Shores, Elizabeth; Rosenberg, Amy] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Off Biotechnol Prod, Bethesda, MD 20892 USA. [Lozier, Jay] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [Pariser, Anne] US FDA, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Off New Drugs, Silver Spring, MD 20993 USA. RP Rosenberg, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Off Biotechnol Prod, NIH Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.hhs.gov FU Intramural NIH HHS [Z01 SC003811-33] NR 88 TC 81 Z9 81 U1 0 U2 8 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 AUG PY 2008 VL 26 IS 8 BP 901 EP 908 DI 10.1038/nbt.1484 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 335WX UT WOS:000258325500024 PM 18688246 ER PT J AU Zhou, Z Feng, HQ Hansen, DF Kato, H Luk, E Freedberg, DI Kay, LE Wu, C Bai, YW AF Zhou, Zheng Feng, Hanqiao Hansen, D. Flemming Kato, Hidenori Luk, Ed Freedberg, Daron I. Kay, Lewis E. Wu, Carl Bai, Yawen TI NMR structure of chaperone Chz1 complexed with histones H2A.Z-H2B SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID NUCLEOSOME CORE PARTICLE; CRYSTAL-STRUCTURE; EXCHANGE; H2AZ AB The NMR structure of budding yeast chaperone Chz1 complexed with histones H2A.Z-H2B has been determined. Chz1 forms a long irregular chain capped by two short alpha-helices, and uses both positively and negatively charged residues to stabilize the histone dimer. A molecular model that docks Chz1 onto the nucleosome has implications for its potential functions. C1 [Zhou, Zheng; Feng, Hanqiao; Kato, Hidenori; Luk, Ed; Wu, Carl; Bai, Yawen] NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hansen, D. Flemming; Kay, Lewis E.] Univ Toronto, Dept Med Genet Biochem & Chem, Toronto, ON M5S 1A8, Canada. [Freedberg, Daron I.] US FDA, NMR Spect Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM yawen@helix.nih.gov OI Luk, Ed/0000-0002-6619-2258 FU Intramural NIH HHS [Z01 BC010808-01] NR 10 TC 54 Z9 55 U1 0 U2 14 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 AUG PY 2008 VL 15 IS 8 BP 868 EP 869 DI 10.1038/nsmb.1465 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 333ZC UT WOS:000258191100023 PM 18641662 ER PT J AU Brady, LS Giffin, RB Woodcock, J Cassell, GH Holmes, EW AF Brady, Linda S. Giffin, Robert B. Woodcock, Janet Cassell, Gail H. Holmes, Edward W. TI Grand challenges for psychiatric drug discovery: A perspective SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material C1 [Brady, Linda S.] NIMH, Div Neurosci & Basic Behav Sci, Natl Inst Hlth, Bethesda, MD 20892 USA. [Giffin, Robert B.] Natl Acad Sci, Inst Med, Washington, DC 20418 USA. [Woodcock, Janet] US FDA, Rockville, MD 20857 USA. [Cassell, Gail H.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Holmes, Edward W.] Univ Calif, Star Biomed Res Council, La Jolla, CA USA. RP Brady, LS (reprint author), NIMH, Div Neurosci & Basic Behav Sci, Natl Inst Hlth, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 MH999999] NR 3 TC 3 Z9 3 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2008 VL 33 IS 9 BP 2047 EP 2047 DI 10.1038/npp.2008.54 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 325XN UT WOS:000257622200001 PM 18626470 ER PT J AU Trumbo, PR AF Trumbo, Paula R. TI Challenges with using chronic disease endpoints in setting dietary reference intakes SO NUTRITION REVIEWS LA English DT Review DE chronic disease; dietary reference intakes ID BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; PROSPECTIVE COHORT; RISK; CHILDHOOD; METAANALYSIS; POTASSIUM; ADULTHOOD; TRACKING; CHILDREN AB Since 1941, the recommended dietary allowances (RDAs) in the United States have been based on the goal of maintaining health in the country's population. There has been a growing body of evidence to support the role of diet in reducing the risk of chronic diseases. For this reason, there has been recent emphasis on considering data on chronic disease endpoints for setting dietary reference intakes (DRIs). Despite this emphasis, none of the RDAs set during the DRI review were based on chronic disease risk. However, chronic disease risk was considered for determining adequate intakes and even some acceptable macronutrient distribution ranges. This article discusses the application of and challenges associated with using chronic disease endpoints in setting DRIs. (C) 2008 International Life Sciences Institute. C1 [Trumbo, Paula R.] US FDA, Div Nutr Programs & Labeling, College Pk, MD USA. RP Trumbo, PR (reprint author), HFS 830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paula.trumbo@fda.hhs.gov NR 26 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD AUG PY 2008 VL 66 IS 8 BP 459 EP 464 DI 10.1111/j.1753-4887.2008.00077.x PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 332JF UT WOS:000258078600004 PM 18667007 ER PT J AU Pogribny, IP Tryndyak, VP Ross, SA Beland, FA AF Pogribny, Igor P. Tryndyak, Volodymyr P. Ross, Sharon A. Beland, Frederick A. TI Differential expression of microRNAs during hepatocarcinogenesis induced by methyl deficiency in rats SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Symposium on Diet, Epigenetic Events, and Cancer Prevention CY SEP 26-27, 2007 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID HEPATOCELLULAR-CARCINOMA; CANCER; CELLS; CARCINOGENESIS; APOPTOSIS; PATHWAY; E2F3 C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 12 TC 9 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD AUG PY 2008 VL 66 IS 8 SU 1 BP S33 EP S35 DI 10.1111/j.1753-4887.2008.00064.x PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 332QW UT WOS:000258099200010 PM 18673486 ER PT J AU Cope, JU Morrison, AE Samuels-Reid, J AF Cope, Judith U. Morrison, Audrey E. Samuels-Reid, Joy TI Adolescent use of insulin and patient-controlled analgesia pump technology: A 10-year food and drug administration retrospective study of adverse events - Reply SO PEDIATRICS LA English DT Letter C1 [Samuels-Reid, Joy] Gen Hosp, Div Anesthesiol, Off Device Evaluat, Ctr Devices & Radiol Hlth Food & Drug Adm, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 AUG PY 2008 VL 122 IS 2 BP 474 EP 474 DI 10.1542/peds.2008-1566 PG 1 WC Pediatrics SC Pediatrics GA 333HB UT WOS:000258142500035 ER PT J AU Ahmad, SR McMahon, A AF Ahmad, Syed Rizwanuddin McMahon, Ann TI Exposures to cough and cold preparations in children reported to US Poison Control Centers SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ahmad, Syed Rizwanuddin] US FDA, Div Epidemiol, OSE, CDER, Silver Spring, MD USA. [McMahon, Ann] US FDA, Div Adverse Event Anal, OSE, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 421 BP S185 EP S185 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100421 ER PT J AU Ahmad, SR Graham, DJ AF Ahmad, Syed Rizwanuddin Graham, David J. TI Exenatide and acute pancreatitis: Time to event analysis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ahmad, Syed Rizwanuddin] US FDA, Div Epidemiol, OSE, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 301 BP S132 EP S133 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100302 ER PT J AU Coster, TS Fram, D DuMouchel, W Szarfman, A Dobardzic, A Xie, S AF Coster, Trinka S. Fram, David DuMouchel, William Szarfman, Ana Dobardzic, Azra Xie, Suji TI Empirical Bayesian data mining for discovering safety signals in military electronic health records SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Coster, Trinka S.; Dobardzic, Azra; Xie, Suji] USA, Off Surg Gen, Hlth Policy & Serv, Falls Church, VA USA. [Fram, David; DuMouchel, William] Lincoln Technol, Phase Forward, Waltham, MA USA. [Szarfman, Ana] US FDA, Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 396 BP S174 EP S174 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100396 ER PT J AU Devine, S Hammad, T Kaplan, S McCune, S Aly, H AF Devine, Scott Hammad, Tarek Kaplan, Sigal McCune, Susan Aly, Hany TI Identifying cases of persistent pulmonary hypertension in the newborn within the general practice research database using the clinical free-text entries SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Devine, Scott] Univ N Carolina, Chapel Hill, NC USA. [Aly, Hany] George Washington Univ, Washington, DC USA. [Hammad, Tarek; Kaplan, Sigal; McCune, Susan] US FDA, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 316 BP S139 EP S139 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100317 ER PT J AU Devine, ST Hammad, TA AF Devine, Scott T. Hammad, Tarek A. TI Last menstrual period estimation techniques compared to physician recorded last menstrual period dates in the general practice research database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Devine, Scott T.] Univ N Carolina, Chapel Hill, NC USA. [Hammad, Tarek A.] US FDA, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 519 BP S228 EP S228 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100519 ER PT J AU Devine, ST Hammad, TA Andrews, EB AF Devine, Scott T. Hammad, Tarek A. Andrews, Elizabeth B. TI Validation of pregnancy identification algorithm within the general practice research database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Devine, Scott T.] Univ N Carolina, Chapel Hill, NC USA. [Hammad, Tarek A.] US FDA, Silver Spring, MD USA. [Andrews, Elizabeth B.] RTI Hlth Solut, Res Triangle Pk, NC USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 286 BP S126 EP S126 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100287 ER PT J AU Hammad, TA McAdams, MA Feight, A Iyasu, S Dal Pan, GJ AF Hammad, Tarek A. McAdams, Mara A. Feight, Andrea Iyasu, Solomon Dal Pan, Gerald J. TI Determining the predictive value of read codes to identify incident acute myocardial infarction in the general practice research database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hammad, Tarek A.; McAdams, Mara A.; Feight, Andrea; Iyasu, Solomon; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 284 BP S125 EP S126 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100285 ER PT J AU Hua, W Izurieta, HS Slade, B Belay, E Haber, P Tiernan, R Woo, EJ Iskander, J Braun, MM Ball, R AF Hua, Wei Izurieta, Hector S. Slade, Barbara Belay, Ermias Haber, Penina Tiernan, Rosemary Woo, Emil Jane Iskander, John Braun, M. Miles Ball, Robert TI Kawasaki disease after vaccination: Reports to the vaccine adverse event reporting system (VAERS) 1990-2007 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hua, Wei; Izurieta, Hector S.; Tiernan, Rosemary; Woo, Emil Jane; Braun, M. Miles; Ball, Robert] US FDA, Rockville, MD 20857 USA. [Slade, Barbara; Belay, Ermias; Haber, Penina; Iskander, John] Ctr Dis Control & Prevent, Atlanta, GA USA. RI Belay, Ermias/A-8829-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 254 BP S112 EP S112 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100255 ER PT J AU Huang, WT Chang, S Miller, ER Woo, EJ Hoffmaster, AR Gee, JE Clark, T Iskander, J Ball, R Broder, K AF Huang, W. T. Chang, S. Miller, E. R. Woo, E. J. Hoffmaster, A. R. Gee, J. E. Clark, T. Iskander, J. Ball, R. Broder, K. TI Safety assessment after recall of haemophilus influenzae type B (Hib) vaccine - United States, 2007-2008 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Huang, W. T.; Miller, E. R.; Hoffmaster, A. R.; Gee, J. E.; Clark, T.; Iskander, J.; Broder, K.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Chang, S.; Woo, E. J.; Ball, R.] US FDA, Rockville, MD 20857 USA. RI Huang, Wan-Ting/E-3497-2010 OI Huang, Wan-Ting/0000-0002-4344-9567 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 264 BP S116 EP S116 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100265 ER PT J AU Izurieta, HS Tobler, SK Garman, PM Hua, W Haber, P Iskander, J Braun, MM Ball, R AF Izurieta, Hector S. Tobler, Steven K. Garman, Patrick M. Hua, Wei Haber, Penina Iskander, John Braun, M. Miles Ball, Robert TI Anaphylaxis after measles, mumps and rubella (MMR) vaccine during 2006-7 in the US SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Izurieta, Hector S.; Hua, Wei; Braun, M. Miles; Ball, Robert] US FDA, Rockville, MD 20857 USA. [Tobler, Steven K.] US Army Med Surveillance Activ, Silver Spring, MD USA. [Garman, Patrick M.] US Mil Vaccinat Agcy, Falls Church, VA USA. [Haber, Penina; Iskander, John] CDC, Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 258 BP S113 EP S114 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100259 ER PT J AU Kaplan, S Hammad, TA AF Kaplan, Sigal Hammad, Tarek A. TI Drug switching patterns among patients using ezetimibe: Claims data study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Hammad, Tarek A.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 167 BP S74 EP S74 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100168 ER PT J AU Lee, KC Fenis, MT Tiernan, R Wise, RP AF Lee, Karen C. Fenis, Meghan T. Tiernan, Rosemary Wise, Robert P. TI Diagnostic testing, treatment, and outcomes of adverse events after use of intravesical Bacillus Calmette-Guerin SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Lee, Karen C.; Wise, Robert P.] US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA. [Fenis, Meghan T.] Johns Hopkins Univ, Baltimore, MD USA. [Tiernan, Rosemary] US FDA, Off Vaccine Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 063 BP S28 EP S28 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100064 ER PT J AU Levine, KB West, SL Mease, M Olsen, AK AF Levine, Kristen B. West, Suzanne L. Mease, Mary Olsen, Axel K. TI Consumer perceptions on drug safety: results from a population-based survey SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Levine, Kristen B.] Univ N Carolina, Chapel Hill, NC USA. [West, Suzanne L.] RTI Int, Res Triangle Pk, NC USA. [Mease, Mary] US FDA, Silver Spring, MD USA. [Olsen, Axel K.] Pharmaceut Safety Inst, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 336 BP S148 EP S148 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100336 ER PT J AU M'ikanatha, NM Sandt, CH Localio, R Tewari, D Russo, A Altekruse, SF Tait, J Hydock, M Reynolds, S Chiller, TM Rankin, S Lautenbach, E McDermott, P AF M'ikanatha, Nkuchia M. Sandt, Carol H. Localio, Russell Tewari, Deepanker Russo, Anthony Altekruse, Sean F. Tait, James Hydock, Michael Reynolds, Stanley Chiller, Tom M. Rankin, Shelley Lautenbach, Ebbing McDermott, Patrick CA PA Antimicrobial Resistance TI Prevalence of drug-resistant Salmonella from retail chicken and comparison with human clinical isolates SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [M'ikanatha, Nkuchia M.] Penn Dept Hlth, Harrisburg, PA 17108 USA. [M'ikanatha, Nkuchia M.; Localio, Russell; Rankin, Shelley; Lautenbach, Ebbing] Univ Penn, Philadelphia, PA 19104 USA. [Tewari, Deepanker; Hydock, Michael] Penn Dept Agr, Harrisburg, PA USA. [Altekruse, Sean F.] NIH, Bethesda, MD 20892 USA. [Chiller, Tom M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [McDermott, Patrick] US FDA, Ctr Vet Med, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 512 BP S224 EP S225 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100512 ER PT J AU McAdams, MA Staffa, JA Iyasu, S Dal Pan, GI AF McAdams, Mara A. Staffa, Judy A. Iyasu, Solomon Dal Pan, Gerald I. TI Timing of safety-related labeling changes and marketing withdrawals for new molecular entities (1991-2007) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [McAdams, Mara A.; Staffa, Judy A.; Iyasu, Solomon; Dal Pan, Gerald I.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 467 BP S205 EP S205 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100467 ER PT J AU McAdams, MA Gelperin, K Governale, LA Swartz, L Hammad, TA Dal Pan, GJ AF McAdams, Mara A. Gelperin, Kate Governale, Laura A. Swartz, Lynette Hammad, Tarek A. Dal Pan, Gerald J. TI Patterns of adverse event reporting for four members of the angiotensin II receptor blockers class of drugs: Revisiting the weber effect SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [McAdams, Mara A.; Gelperin, Kate; Governale, Laura A.; Swartz, Lynette; Hammad, Tarek A.; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 035 BP S16 EP S16 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100036 ER PT J AU Moore, K Braun, MM Lee, G Kulldorff, M Ziyadeh, N Burwen, D Ball, R Sandhu, S Platt, R Brown, J AF Moore, Kristen Braun, M. Miles Lee, Grace Kulldorff, Martin Ziyadeh, Najat Burwen, Dale Ball, Robert Sandhu, Sukhminder Platt, Richard Brown, Jeffrey TI Active safety surveillance of influenza vaccines: Potential for using large insurers' claims SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Moore, Kristen; Lee, Grace; Kulldorff, Martin; Platt, Richard; Brown, Jeffrey] Harvard Univ, Sch Med, DACP, Boston, MA USA. [Braun, M. Miles; Burwen, Dale; Sandhu, Sukhminder] FDA, CBER, Rockville, MD USA. [Ziyadeh, Najat] I3 Drug Safety, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 002 BP S1 EP S1 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100003 ER PT J AU Pamer, C Kaplan, S Wu, YT Hammad, TA Mosholder, AD Rochester, G AF Pamer, Carol Kaplan, Sigal Wu, Yu-Te Hammad, Tarek A. Mosholder, Andrew D. Rochester, George TI Changes in US antidepressant and antipsychotic prescription patterns in the time period following FDA actions SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Pamer, Carol; Kaplan, Sigal; Hammad, Tarek A.; Mosholder, Andrew D.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Wu, Yu-Te; Rochester, George] US FDA, Off Biostat, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 217 BP S95 EP S96 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100218 ER PT J AU Rowan, CG Brinker, AD Nourjah, P Chang, J Moshholder, A Avigan, M AF Rowan, Christopher G. Brinker, Allen D. Nourjah, Parivash Chang, Jennie Moshholder, Andrew Avigan, Mark TI Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rowan, Christopher G.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Brinker, Allen D.; Nourjah, Parivash; Chang, Jennie; Moshholder, Andrew; Avigan, Mark] US FDA, Div Drug Risk Evaluat, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 526 BP S231 EP S231 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100526 ER PT J AU Sutherland, A Izurieta, HS Ball, R Vellozzi, C Leidel, L Huang, WT Woo, J Hua, W Iskander, J Miller, N Pratt, D Braun, MM AF Sutherland, Andrea Izurieta, Hector S. Ball, Robert Vellozzi, Claudia Leidel, Laura Huang, Wan-Tin Woo, Jane Hua, Wei Iskander, John Miller, Nancy Pratt, Douglas Braun, M. Miles TI Syncope, convulsive syncope and traumatic injury after human papillomavirus and other adolescent immunizations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Sutherland, Andrea; Izurieta, Hector S.; Ball, Robert; Woo, Jane; Hua, Wei; Miller, Nancy; Pratt, Douglas; Braun, M. Miles] US FDA, Rockville, MD 20857 USA. [Vellozzi, Claudia; Leidel, Laura; Huang, Wan-Tin; Iskander, John] Ctr Dis Control & Prevent, Atlanta, GA USA. RI Huang, Wan-Ting/E-3497-2010 OI Huang, Wan-Ting/0000-0002-4344-9567 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2008 VL 17 SU 1 MA 392 BP S172 EP S172 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 337FE UT WOS:000258420100392 ER PT J AU Frueh, FW Amur, S Mummaneni, P Epstein, RS Aubert, RE DeLuca, TM Verbrugge, RR Burckart, GJ Lesko, LJ AF Frueh, Felix W. Amur, Shashi Mummaneni, Padmaja Epstein, Robert S. Aubert, Ronald E. DeLuca, Teresa M. Verbrugge, Robert R. Burckart, Gilbert J. Lesko, Lawrence J. TI Pharmacogenomic biomarker information in drug labels approved by the United States Food and Drug Administration: Prevalence of related drug use SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT FDA Science Forum 2006 CY APR 18-20, 2006 CL Washington, DC SP FDA DE biomarkers; pharmacogenomics; US Food and Drug Administration; FDA; drug labels; pharmacy benefits manager ID PERSONALIZED MEDICINE; PRESCRIBING INFORMATION; AVAILABILITY; METABOLISM; INHIBITORS; TAMOXIFEN AB Study Objectives. To review the labels of United States Food and Drug Administration (FDA)-approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling. Design. Retrospective analysis. Data Sources. The Physicians' Desk Reference Web site, Drugs@FDA Web site, and manufacturers' Web sites were used to identify drug labels containing pharmacogenomic information, and the prescription claims database of a large pharmacy benefits manager (insuring > 55 million individuals in the United States) was used to obtain drug utilization data. Measurements and Main Results. Pharmacogenomic biomarkers were defined, FDA-approved drug labels containing this information were identified, and utilization of these drugs was determined. Of 1200 drug labels reviewed for the years 1945-2005, 121 drug labels contained pharmacogenomic information based on a key word search and follow-up screening. Of those, 69 labels referred to human genomic biomarkers, and 52 referred to microbial genomic biomarkers. Of the labels referring to human biomarkers, 43 (62%) pertained to polymorphisms in cytochrome P450 (CYP) enzyme metabolism, with CYP2D6 being most common. Of 36.1 million patients whose prescriptions were processed by a large pharmacy benefits manager in 2006, about 8.8 million (24.3%) received one or more drugs with human genomic biomarker information in the drug label. Conclusion. Nearly one fourth of all outpatients received one or more drugs that have pharmacogenomic information in the label for that drug. The incorporation and appropriate use of pharmacogenomic information in drug labels should be tested for its ability to improve drug use and safety in the United States. C1 [Frueh, Felix W.; Amur, Shashi; Mummaneni, Padmaja; Burckart, Gilbert J.; Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Epstein, Robert S.; Aubert, Ronald E.; DeLuca, Teresa M.; Verbrugge, Robert R.] Medco Hlth Solut Inc, Franklin Lakes, NJ USA. RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM gilbert.burckart@fda.hhs.gov NR 22 TC 146 Z9 150 U1 0 U2 15 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2008 VL 28 IS 8 BP 992 EP 998 DI 10.1592/phco.28.8.992 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 332OC UT WOS:000258091300006 PM 18657016 ER PT J AU Donthamsetty, S Bhave, VS Mitra, MS Latendresse, JR Mehendale, HM AF Donthamsetty, Shashikiran Bhave, Vishakha S. Mitra, Mayurranjan S. Latendresse, John R. Mehendale, Harihara M. TI Nonalcoholic steatohepatitic (NASH) mice are protected from higher hepatotoxicity of acetaminophen upon induction of PPAR alpha with clofibrate SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE nonalcoholic steatohepatitis; acetaminophen; tissue repair; hepatotoxicity; methionine and choline deficient diet ID FATTY LIVER-DISEASE; MITOCHONDRIAL PERMEABILITY TRANSITION; CARBON-TETRACHLORIDE HEPATOTOXICITY; PROLIFERATOR-ACTIVATED RECEPTORS; ANTIMITOTIC AGENT COLCHICINE; MEDIATES PROGRESSION; CCL4 HEPATOTOXICITY; PEROXISOME PROLIFERATORS; INSULIN-RESISTANCE; NUTRITIONAL MODEL AB The objective was to investigate if the hepatotoxic sensitivity in nonalcoholic steatohepatitic mice to acetaminophen (APAP) is due to downregulation of nuclear receptor PPAR alpha via lower cell division and tissue repair. Male Swiss Webster mice fed methionine and choline deficient diet for 31 days exhibited NASH. On the 32nd day, a marginally toxic dose of APAP (360 mg/kg, ip) yielded 70% mortality in steatohepatitic mice, while all non steatohepatitic mice receiving the same dose survived. C-14-APAP covalent binding, CYP2E1 protein, and enzyme activity did not differ from the controls, obviating increased APAP bioactivation as the cause of amplified APAP hepatotoxicity. Liver injury progressed only in steatohepatitic livers between 6 and 24 h. Cell division and tissue repair assessed by H-3-thymidine incorporation and PCNA were inhibited only in the steatohepatitic mice given APAP suggesting that higher sensitivity of NASH liver to APAP-induced hepatotoxicity was due to lower tissue repair. The hypothesis that impeded liver tissue repair in steatohepatitic mice was due to downregulation of PPAR alpha was tested. PPAR alpha was downregulated in NASH. To investigate whether downregulation of PPAR alpha in NASH is the critical mechanism of compromised liver tissue repair, PPAR alpha was induced in steatohepatitic mice with clofibrate (250 mg/kg for 3 days, ip) before injecting APAP. All clofibrate pretreated steatohepatitic mice receiving APAP exhibited lower liver injury, which did not progress and the mice survived. The protection was not due to lower bioactivation of APAP but due to higher liver tissue repair. These findings suggest that inadequate PPAR alpha expression in steatohepatitic mice sensitizes them to APAP hepatotoxicity. (C) 2008 Published by Elsevier Inc. C1 [Donthamsetty, Shashikiran; Bhave, Vishakha S.; Mitra, Mayurranjan S.; Mehendale, Harihara M.] Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. [Latendresse, John R.] Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, 700 Univ Ave,Sugar Hall 306 B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009; OI Bhave, Vishakha/0000-0003-0149-579X NR 55 TC 15 Z9 15 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 1 PY 2008 VL 230 IS 3 BP 327 EP 337 DI 10.1016/j.taap.2008.02.031 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 337CD UT WOS:000258412200009 PM 18501395 ER PT J AU Abraham, A Plakas, SM Flewelling, LJ El Said, KR Jester, ELE Granade, HR White, KD Dickey, RW AF Abraham, Ann Plakas, Steven M. Flewelling, Leanne J. El Said, Kathleen R. Jester, Edward L. E. Granade, Hudson R. White, Kevin D. Dickey, Robert W. TI Biomarkers of neurotoxic shellfish poisoning SO TOXICON LA English DT Article DE brevetoxins; neurotoxic shellfish poisoning; biomarkers ID OYSTER CRASSOSTREA-VIRGINICA; TANDEM MASS-SPECTROMETRY; KARENIA-BREVIS CULTURES; RED TIDE; GYMNODINIUM-BREVE; PTYCHODISCUS-BREVIS; BREVETOXINS; METABOLITES; TOXIN; FLORIDA AB Urine specimens from patients diagnosed with neurotoxic shellfish poisoning (NSP) were examined for biomarkers of brevetoxin intoxication. Brevetoxins were concentrated from urine by using solid-phase extraction (SPE), and analyzed by enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urine extracts were fractionated by LC, and fractions analyzed for brevetoxins by ELISA. In subsequent LC-MS/MS analyses, several brevetoxin metabolites of B-type backbone were identified, with elution profiles consistent with those of ELISA. The more abundant brevetoxin metabolites in urine were characterized structurally by LC-MS/MS. With the exception of BTX-3, brevetoxin metabolites in urine differed from those found in shellfish and in shellfish meal remnants. Proposed structures of these major urinary metabolites are methylsulfoxy BTX-3, 27-epoxy BTX-3, and reduced BTX-B5. BTX-3 was found in all specimens examined. BTX-3 concentrations in urine, as determined by LC-MS/MS, correlated well with composite toxin measurements by ELISA (r(2) = 0.96). BTX-3 is a useful biomarker for confirmation of clinical diagnosis of NSP. Published by Elsevier Ltd. C1 [Abraham, Ann; Plakas, Steven M.; El Said, Kathleen R.; Jester, Edward L. E.; Granade, Hudson R.; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Flewelling, Leanne J.] Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, St Petersburg, FL 33701 USA. [White, Kevin D.] US FDA, Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA. RP Abraham, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158,1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM ann.abraham@fda.hhs.gov NR 17 TC 9 Z9 9 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD AUG 1 PY 2008 VL 52 IS 2 BP 237 EP 245 DI 10.1016/j.toxicon.2008.04.175 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 351YH UT WOS:000259461400006 PM 18582487 ER PT J AU Sacks, LV Behrman, RE AF Sacks, Leonard V. Behrman, Rachel E. TI Developing new drugs for the treatment of drug-resistant tuberculosis: a regulatory perspective SO TUBERCULOSIS LA English DT Article DE drug development; multi-drug resistant; tuberculosis ID SHORT-COURSE CHEMOTHERAPY; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; SPREAD; CONVERSION; SETTINGS; RIFAMPIN; CULTURE; TRIAL; TIME AB Simplifying and shortening treatment for drug-sensitive tuberculosis and providing new treatment options for drug-resistant tuberculosis constitute two principal goals in the development of novel drugs for tuberculosis. Demonstration of clinical efficacy in drug-sensitive tuberculosis is challenging, given high success rates for existing regimens, concerns about substituting an investigational agent for the most effective agents in a regimen and difficulties in determining the effect size of the components of a combination regimen. Large and prolonged studies would be needed either to show superiority over existing regimens or statistically defensible non-inferiority compared to existing regimens. In contrast, exploring efficacy of novel treatments in the setting of drug-resistant disease may present certain opportunities. In drug-resistant disease, the efficacy of existing regimens is comparatively poor, and companion drugs used to treat drug-resistant disease are weak or ineffective, enabling demonstration of the effect of the new drug. Other advantages of this approach, which has been used successfully in the development of antiretroviral agents, include the possibility of demonstrating drug efficacy using smaller studies, the possibility of accelerated approval based on a surrogate endpoint and the opportunity to address an urgent public health need. Experience with the activity and the safety of new agents in drug-resistant disease may provide a platform from which their indication can be broadened to include drug-sensitive disease. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Sacks, Leonard V.; Behrman, Rachel E.] US FDA, Off Crit Path Programs, Rockville, MD 20857 USA. RP Sacks, LV (reprint author), US FDA, Off Crit Path Programs, Room 148 45,5600 Fishers Lane, Rockville, MD 20857 USA. EM Leonard.sacks@fda.hhs.gov NR 37 TC 26 Z9 27 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD AUG PY 2008 VL 88 SU 1 BP S93 EP S100 DI 10.1016/S1472-9792(08)70040-4 PG 8 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 354LL UT WOS:000259641000010 PM 18762157 ER PT J AU Berkower, I Patel, C Ni, YS Virnik, K Xiang, ZX Spadaccini, A AF Berkower, Ira Patel, Chiraag Ni, Yisheng Virnik, Konstantin Xiang, Zhexin Spadaccini, Angelo TI Targeted deletion in the beta 20-beta 21 loop of HIV envelope glycoprotein gp120 exposes the CD4 binding site for antibody binding SO VIROLOGY LA English DT Article DE HIV; envelope glycoprotein gp120; neutralizing antibodies; CD4 binding site; targeted deletion ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-BINDING; NEUTRALIZING ANTIBODIES; CD4-BOUND STATE; EPITOPE; IMMUNOGENICITY; RECOGNIZES; REGIONS; VACCINE AB Different isolates of HIV-1 are known to vary in antibody binding and sensitivity to neutralization. In response to selective pressure, the virus may conceal important neutralizing determinants, such as the CD4 binding site on gp120, through steric hindrance or conformational masking. The 3D structure of gp120 shows five loop structures that surround the CD4 binding site (CD4BS) and may restrict antibody access to the site. We have generated gp120 mutants lacking each of these loops and characterized them with a panel of monoclonal antibodies, including b12 and F105. A targeted deletion in the beta 20-beta 21 loop resulted in gp120 with enhanced binding of both monoclonals. Enhancement of b12 binding suggests reduced steric hindrance, since the antibody is relatively insensitive to conformation. Enhanced binding of F105, which depends strongly on the protein conformation, suggests that the mutation may allow gp120 to move more freely into the liganded form. The same viral strategies that limit antibody binding may also inhibit antibody induction. Modified forms of gp120, in which the CD4 binding site is more exposed and accessible to antibodies, could provide novel immunogens for eliciting antibodies to this broadly shared neutralizing determinant. Published by Elsevier Inc. C1 [Berkower, Ira; Patel, Chiraag; Ni, Yisheng; Virnik, Konstantin; Spadaccini, Angelo] US FDA, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol, Bethesda, MD 20892 USA. [Xiang, Zhexin] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol,DHHS, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, DVP, Off Vaccine Res & Review,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov FU Intramural NIH HHS NR 52 TC 12 Z9 13 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 1 PY 2008 VL 377 IS 2 BP 330 EP 338 DI 10.1016/j.virol.2008.0:3.040 PG 9 WC Virology SC Virology GA 320HE UT WOS:000257223500013 PM 18519142 ER PT J AU Dayan-Kenigsberg, J Bertocchi, A Garber, EAE AF Dayan-Kenigsberg, Jacqueline Bertocchi, Agnes Garber, Eric A. E. TI Rapid detection of ricin in cosmetics and elimination of artifacts associated with wheat lectin SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ricin; detection; lectin; cosmetics; lateral flow devices (LFDs) ID CASTOR-BEAN-MEAL; A-CHAIN VACCINE; IMMUNOTOXINS; TOXIN; MECHANISM; AGENTS; 2.5-A; SITE AB Ricin can be detected in cosmetics at 0.005 mu g/mL in the analytical sample using lateral flow devices (LFDs). Wheat germ, an ingredient used in skin care products is also a potential source of wheat lectin. False positives were observed when wheat lectin was added to LFDs from two manufacturers, irrespective of whether the LFD was specific for ricin, Staphylococcus enterotoxin B (SEB), or botulinum toxin. In contrast, pea and peanut lectins did not cause false positives. Substitution of the buffer supplied with the LFDs with a buffer containing 2.5% non-fat milk powder eliminated the occurrence of false positives. This substitution increased the LOD to 0.01 mu g/mL ricin, which is an acceptable level for screening cosmetics for contamination by ricin. Published by Elsevier B.V. C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Dayan-Kenigsberg, Jacqueline; Bertocchi, Agnes] Agence Francaise Secur Sanitaire Prod Sante, Unite Biotechnol Biochim Prot & Macromol, F-93285 St Denis, France. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-716, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 28 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL 31 PY 2008 VL 336 IS 2 BP 251 EP 254 DI 10.1016/j.jim.2008.05.007 PG 4 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 335RN UT WOS:000258307800022 PM 18561943 ER PT J AU Buenconsejo, J Fish, D Childs, JE Holford, TR AF Buenconsejo, Joan Fish, Durland Childs, James E. Holford, Theodore R. TI A Bayesian hierarchical model for the estimation of two incomplete surveillance data sets SO STATISTICS IN MEDICINE LA English DT Article DE Bayesian approach; spatial-capture-recapture model; Gibbs sampling; Markov chain Monte Carlo; disease incidence; Rocky Mountain spotted fever; vector-borne zoonoses ID MOUNTAIN-SPOTTED-FEVER; CAPTURE-RECAPTURE MODELS; RECORD-LINKAGE; UNITED-STATES; POPULATION-SIZE; STATISTICAL-ANALYSIS; LIST MISMATCHES; HEALTH DATA; DISEASE; CENSUS AB A model-based approach to analyze two incomplete disease surveillance datasets is described. Such data typically consist of case counts, each originating from a specific geographical area. A Bayesian hierarchical model is proposed for estimating the total number of cases with disease while simultaneously adjusting for spatial variation. This approach explicitly accounts for model uncertainty and can make use of covariates. The method is applied to two surveillance datasets maintained by the Centers for Disease Control and Prevention on Rocky Mountain spotted fever (RMSF). An inference is drawn using Markov Chain Monte Carlo simulation techniques in a fully Bayesian framework. The central feature of the model is the ability to calculate and estimate the total number of cases and disease incidence for geographical regions where RMSF is endemic. The information generated by this model could significantly reduce the public health impact of RMSF and other vector-borne zoonoses, as well as other infectious or chronic diseases, by improving knowledge of the spatial distribution of disease risk of public health officials and medical practitioners. More accurate information on populations at high risk would focus attention and resources on specific areas, thereby reducing the morbidity and mortality caused by some of the preventable and treatable diseases. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Buenconsejo, Joan] US FDA, Ctr Drugs Evaluat & Res, Silver Spring, MD 20993 USA. [Fish, Durland; Childs, James E.; Holford, Theodore R.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Buenconsejo, J (reprint author), US FDA, Ctr Drugs Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 3241, Silver Spring, MD 20993 USA. EM Joan.Buenconsejo@fda.hhs.gov RI Childs, James/B-4002-2012 NR 61 TC 1 Z9 1 U1 3 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 30 PY 2008 VL 27 IS 17 BP 3269 EP 3285 DI 10.1002/sim.3190 PG 17 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 332HS UT WOS:000258074700004 PM 18314934 ER PT J AU Niemann, RA Anderson, DL AF Niemann, Richard A. Anderson, David L. TI Determination of iodide and thiocyanate in powdered milk and infant formula by on-line enrichment ion chromatography with photodiode array detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE ion chromatography; iodide; thiocyanate; milk; infant forniula ID TANDEM MASS-SPECTROMETRY; SYMPORTER INHIBITORS; PERCHLORATE; FOODS; EXCRETION; URINE AB Thiocyanate ranks after perchlorate as a potent inhibitor of iodide uptake by the thyroid but may be more concentrated in some food items such as milk products as to supersede perchlorate as the goitrogen of concern. A column-switching anion-exchange chromatographic method with UV spectral detection was developed to measure and confirm iodide and thiocyanate in powders of dry milk and infant formula. An aqueous solution was subjected to centrifugal ultrafiltration, the ultrafiltrate was cleaned up on a carbon solid-phase extraction column, and an aliquot was transferred to a precolumn for enrichment and subsequent injection onto an analytical column. In infant formula samples, thiocyanate was found at 2.0-5.1 mg/kg in five of seven milk-based products and was not found in the other two nor in three soybased products tested (0.2 mg/kgLOQ); iodidewas found atO.3-1.3 mg/kg(O.04 mg/kgLOQ). In 13 dry milk samples, thiocyanate was found at 27-38 mg/kg (1 mg/kg LOQ), and iodide was found at 1.8-3.2 mg/kg (0.2 mg/kg LOQ). Published by Elsevier B.V. C1 [Niemann, Richard A.; Anderson, David L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Niemann, RA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM richard.niemann@fda.hhs.gov NR 22 TC 25 Z9 33 U1 4 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 25 PY 2008 VL 1200 IS 2 BP 193 EP 197 DI 10.1016/j.chroma.2008.05.064 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 330QX UT WOS:000257959000012 PM 18554603 ER PT J AU Kimblin, N Peters, N Debrabant, A Secundino, N Egen, J Lawyer, P Fay, MP Kamhawi, S Sacks, D AF Kimblin, Nicola Peters, Nathan Debrabant, Alain Secundino, Nagila Egen, Jackson Lawyer, Phillip Fay, Michael P. Kamhawi, Shaden Sacks, David TI Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE leishmaniasis; vectors; bites; parasites ID LUTZOMYIA-LONGIPALPIS; PARASITE TRANSMISSION; PHLEBOTOMUS-PAPATASI; VECTOR; BITE; PROMASTIGOTES; MECHANISM; MEXICANA; MODELS; MICE AB Leishmaniasis is transmitted between mammalian hosts by the bites of bloodsucking vector sand flies. The dose of parasites transmitted to the mammalian host has never been directly determined. We developed a real-time PCR-based method to determine the number of Leishmania major parasites inoculated into the ears of living mice during feeding by individual infected flies (Phlebotomus duboscqi). The number of parasites transmitted varied over a wide range in the 58 ears in which Leishmania were detected and demonstrated a clear bimodal distribution. Most of the infected mice were inoculated with a low dose of <600 parasites. One in four received a higher dose of >1,000 and up to 100,000 cells. High-dose transmission was associated with a heavy midgut infection of >30,000 parasites, incomplete blood feeding, and transmission of a high percentage of the parasite load in the fly. To test the impact of inoculum size on infection outcome, we compared representative high- (5,000) and low- (100) dose intradermal needle infections in the ears of C57BL/6 mice. To mimic natural transmission, we used sand fly-derived metacyclic forms of L. major and preexposed the injection site to the bites of uninfected flies. Large lesions developed rapidly in the ears of mice receiving the high-dose inoculum. The low dose resulted in only minor pathology but a higher parasite titer in the chronic phase, and it established the host as an efficient long-term reservoir of infection back to vector sand flies. C1 [Kimblin, Nicola; Peters, Nathan; Secundino, Nagila; Lawyer, Phillip; Kamhawi, Shaden; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Egen, Jackson] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM dsacks@nih.gov OI Egen, Jackson/0000-0003-2053-0837; Fay, Michael P./0000-0002-8643-9625 FU Intramural NIH HHS NR 27 TC 78 Z9 80 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 22 PY 2008 VL 105 IS 29 BP 10125 EP 10130 DI 10.1073/pnas.0802331105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 330BB UT WOS:000257913200051 PM 18626016 ER PT J AU Lechleider, RJ Kaminskas, E Jiang, XP Aziz, R Bullock, J Kasliwal, R Harapanhalli, R Pope, S Sridhara, R Leighton, J Booth, B Dagher, R Justice, R Pazdur, R AF Lechleider, Robert J. Kaminskas, Edvardas Jiang, Xiaoping Aziz, Robeena Bullock, Julie Kasliwal, Ravindra Harapanhalli, Ravi Pope, Sarah Sridhara, Rajeshwari Leighton, John Booth, Brian Dagher, Ramzi Justice, Robert Pazdur, Richard TI Ixabepilone in combination with capecitabine and as monotherapy for treatment of advanced breast cancer refractory to previous chemotherapies SO CLINICAL CANCER RESEARCH LA English DT Article ID BMS-247550 AB Purpose: To describe the considerations leading to marketing approval of ixabepilone in combination with capecitabine and as monotherapy for the treatment of advanced breast cancer that is refractory to other chemotherapies. Experimental Design: Data from one randomized multicenter trial comparing combination therapy with ixabepilone and capecitabine to capecitabine alone were analyzed for support of the combination therapy indication. For monotherapy, a single-arm trial of ixabepilone was analyzed. Supporting data came from an additional single-arm combination therapy study and two single-arm monotherapy studies. Results: In patients with metastatic or locally advanced breast cancer who had disease progression on or following an anthracycline and a taxane, ixabepilone plus capecitabine showed an improvement in progression-free survival compared with capecitabine alone {median progression-free survival, 5.7 [95% confidence interval (95% CI), 4.8-6.7] versus 4.1 (95% CI, 3.1-4.3) months, stratified log-rank P < 0.0001; hazard ratio, 0.69 (95% CI, 0.58-0.83)}. As monotherapy for patients who had disease progression on or following an anthracycline, a taxane, and capecitabine, ixabepilone as monotherapy showed a 12% objective response rate by independent blinded review and 18% by investigator assessment. The major toxicities from ixabepilone therapy were peripheral neuropathy and myelosuppression, particularly neutropenia. Conclusions: On October 16, 2007, the Food and Drug Administration approved ixabepilone for injection in combination with capecitabine or as monotherapy for the treatment of patients with advanced breast cancer who have experienced disease progression on previous chemotherapies. C1 [Lechleider, Robert J.; Kaminskas, Edvardas; Aziz, Robeena; Leighton, John; Dagher, Ramzi; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20903 USA. [Jiang, Xiaoping; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20903 USA. [Bullock, Julie; Booth, Brian] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20903 USA. [Kasliwal, Ravindra; Harapanhalli, Ravi; Pope, Sarah] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assurance, Silver Spring, MD 20903 USA. RP Kaminskas, E (reprint author), US FDA, Div Drug Oncol Prod, Bldg 22,Room 2181, Silver Spring, MD 20903 USA. EM edvardas.kaminskas@fda.hhs.gov NR 3 TC 36 Z9 36 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 JUL 15 PY 2008 VL 14 IS 14 BP 4378 EP 4384 DI 10.1158/1078-0432.CCR-08-0015 PG 7 WC Oncology SC Oncology GA 328GD UT WOS:000257785500004 PM 18628451 ER PT J AU Varadkar, PA Kraman, M McCright, B AF Varadkar, Prajakta A. Kraman, Mathew McCright, Brent TI Notch2 controlled molecular mechanisms underlying secondary heart field differentiation and proliferation SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Varadkar, Prajakta A.; Kraman, Mathew; McCright, Brent] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 241 BP 537 EP 537 DI 10.1016/j.ydbio.2008.05.257 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600265 ER PT J AU Sosnik, J Miranda, P Spiridonov, N Yoon, S Fissore, RA Johnson, G Visconti, PE AF Sosnik, Julian Miranda, P. Spiridonov, N. Yoon, S. Fissore, R. A. Johnson, G. Visconti, P. E. TI TSSK6, a member of the testis-specific serine kinase family, is required for sperm-egg fusion in the mouse SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Developmental-Biology CY JUL 25-30, 2008 CL Univ Penn, Philadelphia, PA SP Soc Dev Biol HO Univ Penn C1 [Sosnik, Julian; Miranda, P.; Yoon, S.; Fissore, R. A.] Univ Massachusetts, Amherst, MA 01003 USA. [Spiridonov, N.; Johnson, G.] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2008 VL 319 IS 2 MA 281 BP 551 EP 551 DI 10.1016/j.ydbio.2008.05.300 PG 1 WC Developmental Biology SC Developmental Biology GA 327NA UT WOS:000257734600304 ER PT J AU Kanswal, S Katsenelson, N Selvapandiyan, A Bram, RJ Akkoyunlu, M AF Kanswal, Sunita Katsenelson, Nora Selvapandiyan, Angamuthu Bram, Richard J. Akkoyunlu, Mustafa TI Deficient TACI expression on B lymphocytes of newborn mice leads to defective Ig secretion in response to BAFF or APRIL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMMON VARIABLE IMMUNODEFICIENCY; CELL-ACTIVATING FACTOR; SPLENIC MARGINAL ZONE; CPG OLIGODEOXYNUCLEOTIDES; TNF FAMILY; T-CELL; IMMUNOGLOBULIN SECRETION; POLYSACCHARIDE ANTIGENS; INTESTINAL BACTERIA; HUMORAL RESPONSE AB Capsular polysaccharides of encapsulated bacteria do not induce immune response in newborns and the mechanism for this unresponsiveness is not clear. In adults, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) is a TNFR family member molecule with a pivotal role in Ab responses against polysaccharide vaccines. We investigated the expression and the functions of the TNF family cytokines, B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), and their receptors in newborn mice and found that TACI expression on B lymphocytes was dramatically reduced (p < 0.0001) in newborns as compared with adults. More importantly, TACI ligands BAFF or APRIL were unable to induce IgA/IgG/IgM secretion from newborn B lymphocytes. Additionally, TACI expression seems to be important in plasma cell development. Indeed, in contrast to adults, stimulation of newborn B lymphocytes with BAFF or APRIL did not result in up-regulation of CD138 expression. In vitro or in vivo exposure of newborn B lymphocytes to oligodeoxynucleotides (CpG ODN) led to up-regulation of TACI expression on newly formed, follicular, and marginal zone as well as B1 B lymphocyte populations, and rendered them responsive to BAFF- or APRIL-mediated CD138 expression and IgA/IgG secretion. Finally, immunization of newborn BALB/c mice but not TACI knockout mice with CpG ODN containing (4-hydroxy-3-nitrophenyl)acetyl-Ficoll led to development of IgG Abs against (4-hydroxy-3-nitrophenyl)acetyl. These findings demonstrate that low TACI expression may be a critical factor that determines the susceptibility of newborns to infections with encapsulated bacteria and the impaired immunogenicity of polysaccharide vaccines. Finally, CpG ODNs may correct deficient newborn response to polysaccharide vaccines by up-regulating TACI. C1 [Kanswal, Sunita; Katsenelson, Nora; Akkoyunlu, Mustafa] Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. [Selvapandiyan, Angamuthu] US FDA, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. [Bram, Richard J.] Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Pediat & Adolescent Med, Mayo Clin, Rochester, MN 55905 USA. RP Akkoyunlu, M (reprint author), Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, 1410 Rockville Pike HFM-428, Rockville, MD 20852 USA. EM mustafa.akkoyunlu@fda.hhs.gov RI Akkoyunlu, Mustafa/I-5712-2012 NR 61 TC 38 Z9 38 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2008 VL 181 IS 2 BP 976 EP 990 PG 15 WC Immunology SC Immunology GA 330QV UT WOS:000257958800016 PM 18606649 ER PT J AU Cowley, SC Goldberg, MF Ho, JA Elkins, KL AF Cowley, Siobhan C. Goldberg, Michael F. Ho, J. Anthony Elkins, Karen L. TI The membrane form of tumor necrosis factor is sufficient to mediate partial innate immunity to Francisella tularensis live vaccine strain SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th International Conference on Tularemia CY NOV 01-04, 2006 CL Woods Hole, MA ID BACILLUS-CALMETTE-GUERIN; CD8(+) T-CELLS; FACTOR-KAPPA-B; FACTOR-ALPHA; IFN-GAMMA; MYCOBACTERIUM-TUBERCULOSIS; LISTERIA-MONOCYTOGENES; PROTECTIVE IMMUNITY; MURINE MACROPHAGES; FACTOR ANTAGONISTS AB Here we characterize Francisella tularensis live vaccine strain (LVS) infection in total tumor necrosis factor (TNF) knockout ( KO) mice and in transgenic mice expressing only the membrane form of TNF (memTNF). MemTNF mice, but not TNF KO mice, survived low-dose, sublethal LVS infections. Splenic nitric oxide production was impaired in infected memTNF mice and was absent in infected TNF KO mice. Spleen cell production of interferon-gamma, RANTES, and monocyte chemotactic protein-1 was elevated in TNF KO mice, compared with that in WT mice, by days 4-5 after infection, along with transiently increased numbers of CCR2(+) cells, whereas memTNF mice had an intermediate phenotype. By day 6 after infection, TNF KO mice, but not memTNF mice, exhibited massive apoptosis in spleens and livers, which shortly preceded their death. Thus, memTNFpartially functions to regulate chemokine expression, cell recruitment, and nitric oxide production during primary LVS infection and protects against the induction of apoptosis observed in TNF KO mice. C1 [Cowley, Siobhan C.; Goldberg, Michael F.; Ho, J. Anthony; Elkins, Karen L.] US FDA, Ctr Biol Res & Evaluat, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20857 USA. RP Cowley, SC (reprint author), CBER FDA, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM siobhan.cowley@fda.hhs.gov; karen.elkins@fda.hhs.gov NR 31 TC 11 Z9 12 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 JUL 15 PY 2008 VL 198 IS 2 BP 284 EP 292 DI 10.1086/589620 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 321QA UT WOS:000257320400019 PM 18593295 ER PT J AU Turk, DC Dworkin, RH Revicki, D Harding, G Burke, LB Cella, D Cleeland, CS Cowan, P Farrar, JT Hertz, S Max, MB Rappaport, BA AF Turk, Dennis C. Dworkin, Robert H. Revicki, Dennis Harding, Gale Burke, Laurie B. Cella, David Cleeland, Charles S. Cowan, Penney Farrar, John T. Hertz, Sharon Max, Mitchell B. Rappaport, Bob A. TI Identifying important outcome domains for chronic pain clinical trials: An IMMPACT survey of people with pain SO PAIN LA English DT Article DE chronic pain; patient-reported outcomes; domains; health-related quality of life ID PATIENTS PERSPECTIVE; PATIENT PERSPECTIVE; RECOMMENDATIONS; MODERATE; MILD; POINTS; SCALES; TASK AB This two-phase study was conducted to identify relevant domains of patient-reported outcomes from the perspective of people who experience chronic pain. In Phase 1, focus groups were conducted to generate a pool of patient outcome-related domains and their components. The results of the focus groups identified 19 aspects of their lives that were significantly impacted by the presence of their symptoms and for which improvements were important criteria they would use in evaluating the effectiveness of any treatment. Phase 2 was conducted to examine the importance and relevance of domains identified from a much larger and diverse sample of people with chronic pain. A survey was developed and posted on the American Chronic Pain Association website. Participants were asked to rate the importance of each item or domain identified by the focus groups on a scale of 0 to10 (i.e., 0 = "not at all important" and 10 = "extremely important"). The survey was completed by 959 individuals. The results indicate that all 19 aspects of daily life derived from the focus groups were considered important with a majority of respondents indicating a score of 8 or greater. In addition to pain reduction, the most important aspects were enjoyment of life, emotional well-being, fatigue, weakness, and sleep-related problems. Chronic pain clearly impacts health-related quality of life. The results of the two phases of the study indicate that people with chronic pain consider functioning and well-being as important areas affected by the presence of symptoms and as appropriate targets of treatment. These multiple outcomes should be considered when evaluating the efficacy and effectiveness of chronic pain treatments. (c) 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Dworkin, Robert H.] Univ Rochester, Rochester, NY USA. [Revicki, Dennis; Harding, Gale] United BioSource Corp, Bethesda, MD USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.] US FDA, Rockville, MD 20857 USA. [Cella, David] Northwestern Univ, Chicago, IL 60611 USA. [Cleeland, Charles S.] MD Anderson Canc Ctr, Houston, TX USA. [Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA. [Farrar, John T.] Univ Penn, Philadelphia, PA 19104 USA. [Max, Mitchell B.] Natl Inst Dent & Craniofacial Res, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Box 356540, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 28 TC 163 Z9 163 U1 3 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL 15 PY 2008 VL 137 IS 2 BP 276 EP 285 DI 10.1016/j.pain.2007.09.002 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 333UF UT WOS:000258177300007 PM 17937976 ER PT J AU Bowyer, JF Latendresse, JR Delongchamp, RR Muskhelishvili, L Warbritton, AR Thomas, M Tareke, E McDaniel, LP Doerge, DR AF Bowyer, J. F. Latendresse, J. R. Delongchamp, R. R. Muskhelishvili, L. Warbritton, A. R. Thomas, M. Tareke, E. McDaniel, L. P. Doerge, D. R. TI Effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE acrylamide; cancer; hypothalamus; pituitary; thyroid; dopamine ID TANDEM MASS-SPECTROMETRY; N-METHYLOLACRYLAMIDE; HEMOGLOBIN ADDUCTS; F344 RATS; CARCINOGENICITY; TOXICITY; REGIONS; BRAIN; NEUROTOXICITY; HYBRIDIZATION AB A(Tylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal clysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamicpituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that is neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic- pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-incluced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor alpha and beta, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxiclase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) doparninergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification ofthis mechanistic dichotomy may be useful in human cancer risk assessments for AA. (c) 2008 Elsevier Inc. All rights reserved. C1 [Doerge, D. R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Bowyer, J. F.; Thomas, M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Latendresse, J. R.; Muskhelishvili, L.; Warbritton, A. R.] US FDA, Natl Ctr Toxicol Res, Div Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Delongchamp, R. R.] Univ Arkansas Med Sci, Dept Epidemiol, Coll Publ Hlth, Little Rock, AR 72205 USA. [Tareke, E.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [McDaniel, L. P.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov RI Latendresse, John/A-9215-2009 NR 37 TC 22 Z9 25 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 15 PY 2008 VL 230 IS 2 BP 208 EP 215 DI 10.1016/j.taap.2008.02.028 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 325GR UT WOS:000257577500009 PM 18430446 ER PT J AU Martinez, M Rathbone, M Burgess, D Huynh, M AF Martinez, Marilyn Rathbone, Michael Burgess, Diane Huynh, Mai TI In vitro and in vivo considerations associated with parenteral sustained release products: A review based upon information presented and points expressed at the 2007 Controlled Release Society Annual Meeting SO JOURNAL OF CONTROLLED RELEASE LA English DT Review ID PLGA-BASED MICROPARTICLES; DRUGS FOLLOWING INJECTION; SUBCUTANEOUS ABSORPTION; GAMMA-STERILIZATION; DELIVERY SYSTEMS; OIL SUSPENSIONS; GENE DELIVERY; MICROSPHERES; LIPOSOMES; MODEL C1 [Martinez, Marilyn; Huynh, Mai] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. [Rathbone, Michael] InterAg, Hamilton 20055, New Zealand. [Burgess, Diane] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06268 USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 66 TC 53 Z9 53 U1 4 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD JUL 14 PY 2008 VL 129 IS 2 BP 79 EP 87 DI 10.1016/j.jconrel.2008.04.004 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 330RB UT WOS:000257959400003 PM 18514351 ER PT J AU Arikawa, E Sun, Y Wang, J Zhou, Q Ning, B Dial, SL Guo, L Yang, JP AF Arikawa, Emi Sun, Yanyang Wang, Jie Zhou, Qiong Ning, Baitang Dial, Stacey L. Guo, Lei Yang, Jingping TI Cross-platform comparison of SYBR (R) Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study SO BMC GENOMICS LA English DT Article ID QUANTITATIVE PCR; DNA MICROARRAY; PERFORMANCE; PROJECT; ARRAYS AB Background: The MicroArray Quality Control (MAQC) project evaluated the inter-and intra-platform reproducibility of seven microarray platforms and three quantitative gene expression assays in profiling the expression of two commercially available Reference RNA samples (Nat Biotechnol 24:1115-22, 2006). The tested microarrays were the platforms from Affymetrix, Agilent Technologies, Applied Biosystems, GE Healthcare, Illumina, Eppendorf and the National Cancer Institute, and quantitative gene expression assays included TaqMan (R) Gene Expression PCR Assay, Standardized (Sta) RT-PCR (TM) and QuantiGene (R). The data showed great consistency in gene expression measurements across different microarray platforms, different technologies and test sites. However, SYBR (R) Green real-time PCR, another common technique utilized by half of all real-time PCR users for gene expression measurement, was not addressed in the MAQC study. In the present study, we compared the performance of SYBR Green PCR with TaqMan PCR, microarrays and other quantitative technologies using the same two Reference RNA samples as the MAQC project. We assessed SYBR Green real-time PCR using commercially available RT2 Profiler (TM) PCR Arrays from SuperArray, containing primer pairs that have been experimentally validated to ensure gene-specificity and high amplification efficiency. Results: The SYBR Green PCR Arrays exhibit good reproducibility among different users, PCR instruments and test sites. In addition, the SYBR Green PCR Arrays have the highest concordance with TaqMan PCR, and a high level of concordance with other quantitative methods and microarrays that were evaluated in this study in terms of fold-change correlation and overlap of lists of differentially expressed genes. Conclusion: These data demonstrate that SYBR Green real-time PCR delivers highly comparable results in gene expression measurement with TaqMan PCR and other high-density microarrays. C1 [Arikawa, Emi; Sun, Yanyang; Wang, Jie; Zhou, Qiong; Yang, Jingping] SuperArray Biosci Corp, Frederick, MD 21704 USA. [Ning, Baitang; Dial, Stacey L.; Guo, Lei] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yang, JP (reprint author), SuperArray Biosci Corp, Frederick, MD 21704 USA. EM earikawa@superarray.net; ysun@superarray.net; jwang@superarray.net; qzhou257@hotmail.com; baitang.ning@fda.hhs.gov; stacey.dial@fda.hhs.gov; lei.guo@fda.hhs.gov; jpyang@superarray.net RI Guo, Lei/E-9232-2011 NR 23 TC 84 Z9 86 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUL 11 PY 2008 VL 9 AR 328 DI 10.1186/1471-2164-9-328 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 333FV UT WOS:000258139300001 PM 18620571 ER PT J AU Weisz, A Ito, Y AF Weisz, Adrian Ito, Yoichiro TI Preparative purification of 4-hydroxy-1-naphthalenesulfonic acid sodium salt by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; color additive intermediate; purification; 4-hydroxy-1-naphthalenesulfonic acid sodium salt AB Among the many applications of 4-hydroxy-1-naphthalenesulfonic acid sodium salt (HNSA, CAS No. 6099-57-6) is its use as a common intermediate in the manufacture of dyes used as color additives. In order to develop an HPLC method to analyze HNSA in such additives, it was necessary to obtain pure HNSA as a reference material. This compound is only commercially available in "technical" or "practical" grade (similar to 70-85% purity). Unsatisfactory results were encountered during the attempts to eliminate impurities using published preparative purification methods. The current work demonstrates the successful application of high-speed counter-current chromatography (HSCCC) to the preparative purification of "practical" grade HNSA. The purifications of 0.55 g and 1.00 g portions were achieved by using a solvent system that consisted of n-butanol/water (1: 1), acidified with 0.2% trifluoroacetic acid. In contrast to the procedure involved in previous HSCCC separations of aromatic sulfortates, it was not necessary to add a ligand and a retainer to the solvent system for these separations. The resulting yields were 320 mg and 485 mg of HNSA, respectively, of over 99% purity. Elemental analysis, HPLC (at 240 nm), UV and high-resolution MS analyses confirmed the identity and purity of the HNSA obtained. Published by Elsevier B.V. C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Bioseparat Technol Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [Z99 HL999999] NR 15 TC 7 Z9 7 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 11 PY 2008 VL 1198 BP 232 EP 234 DI 10.1016/j.chroma.2008.05.060 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 324UT UT WOS:000257545600033 PM 18541251 ER PT J AU Cheng, ZH Zhou, HP Luther, M Yin, JJ Yu, LL AF Cheng, Zhihong Zhou, Huiping Luther, Marla Yin, Junjie Yu, Liangli (Lucy) TI Effects of wheat antioxidants on oxygen diffusion - Concentration products in liposomes and mRNA levels of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase in primary rat hepatocytes SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE wheat antioxidants; ESR; liposomes; cholesterol; lipid peroxidation ID CONJUGATED LINOLEIC-ACID; LIPID-PEROXIDATION; BRAN EXTRACTS; ATHEROSCLEROSIS; METABOLISM; FRACTIONS; MEMBRANES; DISEASE; STRESS; GRAINS AB Three wheat antioxidant fractions were investigated for their potential effects on oxygen diffusion-concentration products in liposomes prepared with egg yolk phosphatidycholine (yolk PC) and rat liver PC (liver PC), using the electron spin resonance (ESR) oximetry method with 2,2'-azobis(2-aminopropane) dihydrochloride (AAPH) and 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) as radical generators. Both water-soluble wheat antioxidant (WWA) and the second lipophilic antioxidant (LWA2) fractions were able to inhibit oxygen diffusion-concentration product induced by either AAPH or AMVN. The first lipophilic wheat antioxidant (LWA1) fraction only showed antioxidant activity in yolk PC liposomes with AAPH as the radical initiator but had pro-oxidant activity under other testing conditions. Both liposome composition and radical initiator altered the antioxidative properties of WWA, LWA1, and LWA2. WWA also showed the strongest DPPH center dot scavenging capacity on a per grain weight basis. HPLC analysis showed that WWA had a much higher level of total phenolic acids, which may partially explain their antioxidant properties. In addition, wheat antioxidants significantly down-regulated the mRNA of HMG-CoA reductase, the key enzyme for cholesterol biosynthesis, and up-regulated the mRNA of cholesterol 7 alpha-hydroxylase (CYP7A1), the key enzyme for cholesterol metabolism, in primary rat hepatocytes. These data indicated the potential of wheat antioxidants in reducing the risk of atherosclerosis through multimechanisms. C1 [Cheng, Zhihong; Luther, Marla; Yu, Liangli (Lucy)] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zhou, Huiping] Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA. [Yin, Junjie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014 NR 25 TC 8 Z9 8 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 9 PY 2008 VL 56 IS 13 BP 5033 EP 5042 DI 10.1021/jf800308n PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 321VU UT WOS:000257335400022 PM 18540627 ER PT J AU Albillos, SM Jin, T Howard, A Zhang, Y Kothary, MH Fu, TJ AF Albillos, Silvia M. Jin, Tengchijan Howard, Andrew Zhang, Yuzhu Kothary, Mahendra H. Fu, Tong-Jen TI Purification, crystallization and preliminary x-ray characterization of prunin-1, a major component of the almond (Prunus dulcis) allergen amandin SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE almond (Prunus dulcis); prunin; amandin; food allergy; x-ray crystallography ID SEED STORAGE PROTEIN; IGE-BINDING EPITOPES; SOYBEAN 11S GLOBULIN; FOOD ALLERGY; MOLECULAR-WEIGHTS; CUPIN SUPERFAMILY; CRYSTAL-STRUCTURE; CROSS-REACTIVITY; 2S ALBUMIN; TREE NUTS AB The 11 S globulins from plant seeds account for a number of major food allergens. Because of the interest in the structural basis underlying the allergenicity of food allergens, we sought to crystallize the main 11 S seed storage protein from almond (Prunus dulcis). Prunin-1 (Pru1) was purified from defatted almond flour by water extraction, cryoprecipitation, followed by sequential anion exchange, hydrophobic interaction, and size exclusion chromatography. Single crystals of Pru1 were obtained in a screening with a crystal screen kit, using the hanging-drop vapor diffusion method. Diffraction quality crystals were grown after optimization. The Pru1 crystals diffracted to at least 3.0 angstrom and belong to the tetragonal space group P4(1)22, with unit cell parameters of a = b = 150.912 angstrom, c = 165.248 A. Self-rotation functions and molecular replacement calculations showed that there are three molecules in the asymmetry unit with water content of 51.41%. The three Pru1 protomers are related by a noncrystallographic 3-fold axis and they form a doughnut-shaped trimer. Two prunin trimers form a homohexamer. Elucidation of prunin structure will allow further characterization of the allergenic features of the 11 S protein allergens at the molecular level. C1 [Jin, Tengchijan; Howard, Andrew; Zhang, Yuzhu] IIT, Dept Biol, Chicago, IL 60616 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Albillos, Silvia M.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Zhang, Y (reprint author), IIT, Dept Biol, 3101 S Dearborn St, Chicago, IL 60616 USA. EM yuzhu.zhang@iit.edu; tong.fu@fda.hhs.gov RI Zhang, Yuzhu/A-7109-2009; Albillos, Silvia/D-1276-2016; OI Zhang, Yuzhu/0000-0001-7882-5692; Albillos, Silvia/0000-0002-3273-0126; jin, tengchuan/0000-0002-1395-188X FU FDA HHS [FD-0004331] NR 62 TC 17 Z9 17 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUL 9 PY 2008 VL 56 IS 13 BP 5352 EP 5358 DI 10.1021/jf800529k PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 321VU UT WOS:000257335400067 PM 18553996 ER PT J AU Schaefer, M Baker, DJ Gibbons, JH Groat, CG Kennedy, D Kennel, CF Rejeski, D AF Schaefer, Mark Baker, D. James Gibbons, John H. Groat, Charles G. Kennedy, Donald Kennel, Charles F. Rejeski, David TI Science and government - An Earth Systems Science Agency SO SCIENCE LA English DT Editorial Material C1 [Schaefer, Mark; Groat, Charles G.] US Geol Survey, Reston, VA 20192 USA. [Baker, D. James] NOAA, Washington, DC USA. [Gibbons, John H.] White House Off Sci & Technol Policy, Washington, DC USA. [Kennedy, Donald] US FDA, Rockville, MD 20857 USA. [Kennel, Charles F.] NASA, Mission Planet Earth, Washington, DC 20546 USA. RP Schaefer, M (reprint author), US Geol Survey, Reston, VA 20192 USA. EM markschaefer24@msn.com; djamesbaker@comcast.net; jackgibbons@hughes.net; cgroat@mail.utexas.edu; kennedyd@stanford.edu; ckennel@ucsd.edu; david.rejeski@wilsoncenter.org RI Wright, Dawn/A-4518-2011 OI Wright, Dawn/0000-0002-2997-7611 NR 2 TC 3 Z9 3 U1 0 U2 2 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 JUL 4 PY 2008 VL 321 IS 5885 BP 44 EP 45 DI 10.1126/science.1160192 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 321QE UT WOS:000257320800024 PM 18599760 ER PT J AU Schultz, DG AF Schultz, Daniel G. TI Medical-device safety and the FDA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Schultz, DG (reprint author), US FDA, Rockville, MD 20850 USA. EM execsec@fda.hhs.gov NR 1 TC 1 Z9 1 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 JUL 3 PY 2008 VL 359 IS 1 BP 88 EP 89 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 320PB UT WOS:000257246000014 PM 18596278 ER PT J AU Nardinelli, C Lanthier, M Temple, R AF Nardinelli, Clark Lanthier, Michael Temple, Robert TI Drug-review deadlines and safety problems SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Nardinelli, Clark; Lanthier, Michael; Temple, Robert] US FDA, Silver Spring, MD 20993 USA. RP Nardinelli, C (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 2 TC 10 Z9 10 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 JUL 3 PY 2008 VL 359 IS 1 BP 95 EP 96 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 320PB UT WOS:000257246000028 PM 18596282 ER PT J AU Sander, LC Putzbach, K Nelson, BC Rimmer, CA Bedner, M Thomas, JB Porter, BJ Wood, LJ Schantz, MM Murphy, KE Sharpless, KE Wise, SA Yen, JH Siitonen, PH Evans, RL Pho, AN Roman, MC Betz, JM AF Sander, L. C. Putzbach, K. Nelson, B. C. Rimmer, C. A. Bedner, M. Thomas, J. Brown Porter, B. J. Wood, L. J. Schantz, M. M. Murphy, K. E. Sharpless, K. E. Wise, S. A. Yen, J. H. Siitonen, P. H. Evans, R. L. Pho, A. Nguyen Roman, M. C. Betz, J. M. TI Certification of standard reference materials containing bitter orange SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 11th International Symposium on Biological and Environmental Reference Materials (BERM 11) CY OCT 29-NOV 02, 2007 CL Tsukuba, JAPAN DE reference materials; natural products; organic compounds; high-performance liquid chromatography; foods/beverages ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIETARY-SUPPLEMENTS; EPHEDRINE ALKALOIDS; MASS-SPECTROMETRY; ADRENERGIC AMINES; CITRUS-AURANTIUM; FLUORESCENCE DETECTION; ULTRAVIOLET DETECTION; STATIONARY-PHASE; SYNEPHRINE AB A suite of three dietary supplement standard reference materials (SRMs) containing bitter orange has been developed, and the levels of five alkaloids and caffeine have been measured by multiple analytical methods. Synephrine, octopamine, tyramine, N-methyltyramine, hordenine, total alkaloids, and caffeine were determined by as many as six analytical methods, with measurements performed at the National Institute of Standards and Technology and at two collaborating laboratories. The methods offer substantial independence, with two types of extractions, two separation methods, and four detection methods. Excellent agreement was obtained among the measurements, with data reproducibility for most methods and analytes better than 5% relative standard deviation. The bitter-orange-containing dietary supplement SRMs are intended primarily for use as measurement controls and for use in the development and validation of analytical methods. C1 [Sander, L. C.; Putzbach, K.; Nelson, B. C.; Rimmer, C. A.; Bedner, M.; Thomas, J. Brown; Porter, B. J.; Wood, L. J.; Schantz, M. M.; Murphy, K. E.; Sharpless, K. E.; Wise, S. A.] Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Yen, J. H.] Natl Inst Stand & Technol, Informat Technol Lab, Gaithersburg, MD 20899 USA. [Siitonen, P. H.; Evans, R. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Roman, M. C.] ChromaDex Inc, Res & Dev, Clearwater, FL 33760 USA. [Betz, J. M.] Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Sander, LC (reprint author), Natl Inst Stand & Technol, Chem Sci & Technol Lab, 100 Bur Dr,MS 8392, Gaithersburg, MD 20899 USA. EM lane.sander@nist.gov NR 24 TC 26 Z9 26 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JUL PY 2008 VL 391 IS 6 BP 2023 EP 2034 DI 10.1007/s00216-008-2074-0 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 319YF UT WOS:000257200200006 PM 18425642 ER PT J AU Keener, WK Rivera, VR Cho, CY Hale, ML Garber, EAE Poli, MA AF Keener, William K. Rivera, Victor R. Cho, Chung Y. Hale, Martha L. Garber, Eric A. E. Poli, Mark A. TI Identification of the RNA N-glycosidase activity of ricin in castor bean extracts by an electrochemiluminescence-based assay SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB A simple electrochemiluminescence-based assay for RNA N-glycosidase activity has been modified to permit its use with authentic extracts of Ricinus communis (castor beans) and Abrus precatorius (jequirity seeds)-the natural sources of ricin and abrin. Modifications include the addition of an RNase inactivator to the reaction mixture, elimination of a signal-enhancing monoclonal antibody, and optimization of the incubation temperature. Concurrent testing with two substrates provides a diagnostic too] enabling castor bean toxins to be differentiated from a larger selection of N-glycosidase toxins than was previously examined. (c) 2008 Published by Elsevier Inc. C1 [Keener, William K.; Rivera, Victor R.; Hale, Martha L.; Poli, Mark A.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Cho, Chung Y.; Garber, Eric A. E.] US FDA, College Pk, MD 20740 USA. RP Keener, WK (reprint author), USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. EM william.keener@us.army.mil; mark.poli@us.army.mil NR 4 TC 6 Z9 6 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 1 PY 2008 VL 378 IS 1 BP 87 EP 89 DI 10.1016/j.ab.2008.03.019 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 309LQ UT WOS:000256462300013 PM 18394420 ER PT J AU Mukhtyar, C Flossmann, O Hellmich, B Bacon, P Cid, M Cohen-Tervaert, JW Gross, WL Guillevin, L Jayne, D Mahr, A Merkel, PA Raspe, H Scott, D Witter, J Yazici, H Luqmani, RA AF Mukhtyar, C. Flossmann, O. Hellmich, B. Bacon, P. Cid, M. Cohen-Tervaert, J. W. Gross, W. L. Guillevin, L. Jayne, D. Mahr, A. Merkel, P. A. Raspe, H. Scott, D. Witter, J. Yazici, H. Luqmani, R. A. CA European Vasculitis Study Grp TI Outcomes from studies of antineutrophil cytoplasm antibody associated vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CHURG-STRAUSS-SYNDROME; TERM-FOLLOW-UP; ANCA-ASSOCIATED VASCULITIS; SMALL-VESSEL VASCULITIS; WEGENERS-GRANULOMATOSIS; MICROSCOPIC POLYANGIITIS; POLYARTERITIS-NODOSA; PROGNOSTIC-FACTORS; RENAL INVOLVEMENT; RANDOMIZED-TRIAL AB Objectives: We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. Methods: Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. Results: A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg-Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74-91%, 45-76% and 60-97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. Methods used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male gender. Conclusions: Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV. C1 [Mukhtyar, C.; Luqmani, R. A.] Univ Oxford, Botnar Res Ctr, Oxford OX3 7LD, England. [Flossmann, O.; Jayne, D.] Addenbrookes Hosp, Dept Nephrol, Cambridge, England. [Hellmich, B.; Gross, W. L.] Univ Hosp Schleswig Holstein, Dept Rheumatol, Lubeck, Germany. [Bacon, P.] Univ Birmingham, Dept Rheumatol, Birmingham, W Midlands, England. [Cid, M.] Hosp Clin Barcelona, Dept Internal Med, Barcelona, Spain. [Cohen-Tervaert, J. W.] Maastricht Univ, Div Clin & Expt Immunol, Maastricht, Netherlands. [Guillevin, L.] Univ Paris 05, Dept Internal Med, Paris, France. [Mahr, A.; Merkel, P. A.] Boston Univ, Sch Med, Vasculitis Ctr, Boston, MA 02118 USA. [Raspe, H.] Univ Hosp Schleswig Holstein, Inst Social Med, Lubeck, Germany. [Scott, D.] Norfolk & Norwich Hosp, Dept Rheumatol, Norwich, Norfolk, England. [Witter, J.] US FDA, Rockville, MD 20857 USA. [Yazici, H.] Univ Istanbul, Cerrahpasa Med Fac, Istanbul, Turkey. RP Luqmani, RA (reprint author), Univ Oxford, Botnar Res Ctr, Windmill Rd, Oxford OX3 7LD, England. EM raashid.luqmani@noc.anglox.nhs.uk RI Raspe, Heiner /E-3612-2010; Gross, Wolfgang Ludwig/C-8733-2011; OI Luqmani, Raashid/0000-0002-4446-5841; Cid Xutgla, Maria Cinta/0000-0002-4730-0938 NR 63 TC 153 Z9 168 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2008 VL 67 IS 7 BP 1004 EP 1010 DI 10.1136/ard.2007.071936 PG 7 WC Rheumatology SC Rheumatology GA 312TV UT WOS:000256694600017 PM 17911225 ER PT J AU Wagner, RD Johnson, SJ Cerniglia, CE AF Wagner, R. Doug Johnson, Shemedia J. Cerniglia, Carl E. TI In vitro model of colonization resistance by the enteric microbiota: Effects of antimicrobial agents used in food-producing animals (vol 52, pg 1230, 2008) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 [Wagner, R. Doug; Johnson, Shemedia J.; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 2008 VL 52 IS 7 BP 2697 EP 2697 DI 10.1128/AAC.00564-08 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 319SE UT WOS:000257183400064 ER PT J AU Pearman, WF Angel, SM Ferry, JL Hall, S AF Pearman, William F. Angel, S. Michael Ferry, John L. Hall, Sherwood TI Characterization of the ag mediated surface-enhanced Raman spectroscopy of saxitoxin SO APPLIED SPECTROSCOPY LA English DT Article DE surface-enhanced Raman spectroscopy; SERS; saxitoxin; STX; silver colloid; paralytic shellfish poison; PSP; harmful algal bloom toxin ID HARMFUL ALGAL BLOOMS; PSP TOXINS; SCATTERING; BACTERIA; SPECTRA; STATES AB The rapid detection and quantification of saxitoxin (STX) is reported using surface-enhanced Raman spectroscopy (SERS) with a colloidal hydrosol of silver nanoparticles. Under the conditions of our experiments, the limit of detection (L-D) for STX using SERS is 3 nM, with a limit of quantification (L-Q) of 20 nM. It is shown that the SERS method is rapid, with spectra being collected in as little as 5 seconds total integration time for a 40 nM STX sample. In order to improve the signal-to-noise ratio, SERS spectra were generally collected with a total integration time of I minute (6 accumulations of 10 seconds each), with no need for extensive sample work-up or substrate preparation. Based on these results, the SERS technique shows great promise for the future detection and quantification of STX molecules in aqueous solutions. C1 [Pearman, William F.; Angel, S. Michael; Ferry, John L.] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. [Hall, Sherwood] US FDA, CHCB DBC ORS CFSAN, College Pk, MD 20740 USA. RP Pearman, WF (reprint author), Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. EM pearman@us.army.mil RI Ferry, John/G-8646-2013; OI Angel, Stanley/0000-0002-0328-0568; Ferry, John/0000-0002-1420-8406 NR 38 TC 3 Z9 6 U1 2 U2 18 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD JUL PY 2008 VL 62 IS 7 BP 727 EP 732 DI 10.1366/000370208784909580 PG 6 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 326DC UT WOS:000257637200003 PM 18935820 ER PT J AU Hotchkiss, CE Weis, C Blaydes, B Newbold, R Delclos, KB AF Hotchkiss, Charlotte E. Weis, Connie Blaydes, Betty Newbold, Retha Delclos, K. Barry TI Multigenerational exposure to ethinyl estradiol affects bone geometry, but not bone mineral density in rats SO BONE LA English DT Article DE estrogen; bone development; bone mineral density; endocrine disruptors; rat ID ORAL-CONTRACEPTIVE USE; YOUNG-ADULT WOMEN; EPIGENETIC TRANSGENERATIONAL ACTIONS; DEPOT-MEDROXYPROGESTERONE ACETATE; BIRTH-CONTROL PILLS; 30 MU-G; FEMALE RATS; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; GROWING-RATS AB Estrogenic compounds are known to prevent bone loss in ovariectomized adult rats; however, their effects on bone in developing and reproductively-intact rats are less well-understood. In a large multigenerational experiment 0, 2, 10, or 50 ppb ethinyl estradiol (EE) in the diet was fed to intact male and female rats from conception until either weaning, postnatal day 140, or continuously for 2 years. Vertebrae (lumbar and caudal) and femurs were collected from subsets of these animals at necropsy at 48 days, 70 days, 140 days, or 2 years of age and subjected to dual-energy X-ray absorptiometry (DXA) scanning to measure bone mineral density (BMD), bone mineral content (BMC), and bone area. In addition, the length, cross-sectional area, marrow area, and cortical bone area of the femurs were measured directly in all animals at PND 140 and 2 years. Continuous dietary intake of 50 ppb EE decreased body weight by 8-27%. BMD adjusted for body weight was not affected by EE, with the exception of an increase in the caudal vertebrae in males treated with 50 ppb EE. In female rats, continuous treatment with 50 ppb EE decreased length and cross-sectional area of the femur. The length of the femur was decreased in the first two generations following institution of a phytoestrogen-free diet at the initiation of the study in all animals, including controls, but returned to the original length by the third or fourth generation. The cross-sectional area of the femur also varied by generation. In conclusion, a high dose of EE throughout the lifespan resulted in decreased bone size in females, which could reduce the force required to break the bone. Furthermore, dietary changes may have epigenetic effects which persist for multiple generations. (C) 2008 Elsevier Inc. All rights reserved. C1 [Hotchkiss, Charlotte E.; Weis, Connie; Blaydes, Betty; Delclos, K. Barry] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Newbold, Retha] Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. RP Hotchkiss, CE (reprint author), Univ Washington, Washington Natl Primate Res Ctr, Box 357330, Seattle, WA 98195 USA. EM chotchki@wanprc.org NR 89 TC 5 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 EI 1873-2763 J9 BONE JI Bone PD JUL PY 2008 VL 43 IS 1 BP 110 EP 118 DI 10.1016/j.bone.2008.03.016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 319GC UT WOS:000257151100014 PM 18467201 ER PT J AU Maher, SG Sheikh, F Scarzello, AJ Romero-Weaver, AL Baker, DP Donnelly, RP Gamero, AM AF Maher, Stephen G. Sheikh, Faruk Scarzello, Anthony J. Romero-Weaver, Ana L. Baker, Darren P. Donnelly, Raymond P. Gamero, Ana M. TI IFN alpha and IFN lambda differ in their antiproliferative effects and duration of JAK/STAT signaling activity SO CANCER BIOLOGY & THERAPY LA English DT Article DE interferon-alpha; interferon-lambda; STAT; antiproliferation; apoptosis ID POTENT ANTIVIRAL ACTIVITY; C VIRUS-REPLICATION; TRANSCRIPTIONAL ACTIVATION; CELL CARCINOMA; IN-VIVO; INTERFERON; EXPRESSION; INFECTION; INDUCE; STAT3 AB Interferon (IFN)lambda, also known as IL-28A, IL-28B or IL-29, is a new type III IFN, which like type I IFN(alpha/beta), activates common elements of the JAK/STAT signaling pathway and exhibits anti-proliferative activity. Currently, IFN alpha is used in the treatment of certain forms of cancer, but its antitumor effects are limited and associated with high toxicity. In this study, we determined whether IFN lambda induced the same level of cell growth inhibition relative to IFN alpha. To this effect HaCaT cells, which are typically growth inhibited by IFN alpha, underwent apoptosis in response to IFN lambda. Next, in contrast to IFN alpha stimulation, IFN lambda prolonged the duration of activated STAT1 and STAT2. Furthermore, the kinetics of IFN-stimulated genes was different as IFN lambda induced a delayed but stronger induction of IFN-responsive genes. Components of the JAK/STAT pathway remained essential for the antiproliferative effects of IFN alpha and IFN lambda. IFN lambda-induced persistence of STAT activation required de novo protein synthesis and was in part due to a delay in STAT2 inactivation. Thus our data demonstrate that the duration of IFN lambda signaling is different from that of IFN alpha, and that IFN lambda could be a suitable cytokine to evaluate for cancer therapy. C1 [Scarzello, Anthony J.; Gamero, Ana M.] NCI, Canc & Inflammat Program, Expt Immunol Lab, NIH, Frederick, MD USA. [Maher, Stephen G.] Univ Dublin Trinity Coll, Dept Surg, Dublin 2, Ireland. [Romero-Weaver, Ana L.] Thomas Jefferson Univ, Dept Canc Biol, Philadelphia, PA 19107 USA. [Baker, Darren P.] Biogen Idec Inc, Cambridge, MA USA. [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD USA. RP Gamero, AM (reprint author), Temple Univ, Sch Med, Dept Biochem, 3440 N Broad St, Philadelphia, PA 19140 USA. EM gameroa@mail.nih.gov OI Maher, Stephen/0000-0003-0126-7906 FU National Cancer Institute, National Institutes of Health [N01-CO-12400]; NIH FX We thank Dr. Howard Young for helpful discussions, Dr. Giorgio Trinchieri for critical reading of this manuscript and Dr. Veronica Hall for technical assistance with the quantitative RT-PCR system. 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 project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health under Contract No. N01-CO-12400. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 101 Z9 115 U1 1 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2008 VL 7 IS 7 BP 1109 EP 1115 DI 10.4161/cbt.7.7.6192 PG 7 WC Oncology SC Oncology GA 338RA UT WOS:000258524300024 PM 18698163 ER PT J AU King, KE Ponnamperuma, RM Allen, C Lu, H Duggal, P Chen, Z Van Waes, C Weinberg, WC AF King, Kathryn E. Ponnamperuma, Roshini M. Allen, Clint Lu, Hai Duggal, Praveen Chen, Zhong Van Waes, Carter Weinberg, Wendy C. TI The p53 homologue Delta Np63 alpha interacts with the nuclear factor-kappa B pathway to modulate epithelial cell growth SO CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR REL; CHICKEN SPLEEN-CELLS; C-REL; EPIDERMAL DEVELOPMENT; P63 ISOFORMS; ACTIVATION; EXPRESSION; CARCINOMA; DISTINCT; ALPHA AB The p53 homologue Delta Np63 alpha is overexpressed and inhibits apoptosis in a subset of human squamous cell carcinomas (SCC). Here, we report that in normal keratinocytes over-expressing Delta Np63 alpha and in human squamous carcinoma cells, Delta Np63 alpha physically associates with phosphorylated, transcriptionally active nuclear c-Rel, a nuclear factor-kappa B family member, resulting in increased c-Rel nuclear accumulation. This accumulation and the associated enhanced proliferation driven by elevated Delta Np63 alpha are attenuated by c-Rel small interfering RNA or overexpression of mutant I kappa B alpha M, indicating that c-Rel-containing complex formation is critical to the ability of elevated Delta Np63 alpha to maintain proliferation in the presence of growth arresting signals. Consistent with a role in growth regulation, Delta Np63 alpha-c-Rel complexes bind a promoter motif and repress the cyclin-dependent kinase inhibitor p21WAF1 in both human squamous carcinoma cells and normal keratinocytes overexpressing Delta Np63 alpha. The relationship between Delta Np63 alpha and activated c-Rel is reflected in their strong nuclear staining in the proliferating compartment of primary head and neck SCC. This is the first report indicating that high levels of Delta Np63 alpha interact with activated c-Rel in keratinocytes and SCC, thereby promoting uncontrolled proliferation, a key alteration in the pathogenesis of cancers. C1 [Weinberg, Wendy C.] US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Allen, Clint; Lu, Hai; Duggal, Praveen; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Weinberg, WC (reprint author), US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 29B Lincoln Dr,NIH Bldg 29B,Room 3NN04,HFD-123, Bethesda, MD 20892 USA. EM wendy.weinberg@fda.hhs.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS [Z01 DC000016-14]; NIDCD NIH HHS [Z01 DC000016] NR 50 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2008 VL 68 IS 13 BP 5122 EP 5131 DI 10.1158/0008-5472.CAN-07-6123 PG 10 WC Oncology SC Oncology GA 323AB UT WOS:000257415300023 PM 18593911 ER PT J AU Ha, LN Merlino, G Sviderskaya, EV AF Ha, Linan Merlino, Glenn Sviderskaya, Elena V. TI Melanomagenesis - Overcoming the barrier of melanocyte senescence SO CELL CYCLE LA English DT Review DE senecence; melanoma; Ink4-Arf; p53; E2F1 ID TUMOR-SUPPRESSOR LOCUS; CELLULAR SENESCENCE; HUMAN CANCER; INK4A LOCUS; HUMAN-CELLS; P53; P16(INK4A); MICE; ARF; IMMORTALIZATION AB Although melanoma ultimately progresses to a highly aggressive and metastatic disease that is typically resistant to currently available therapy, it often begins as a benign nevus consisting of a clonal population of hyperplastic melanocytes that cannot progress because they are locked in a state of cellular senescence. Once senescence is overcome, the nevus can exhibit dysplastic features and readily progress to more lethal stages. Recent advances have convincingly demonstrated that senescence represents a true barrier to the progression of many types of cancer, including melanoma. Thus, understanding the mechanism(s) by which melanoma evades senescence has become a priority in the melanoma research community. Senescence in most cells is regulated through some combination of activities within the RB and p53 pathways. However, differences discovered among various tumor types, some subtle and others quite profound, have revealed that senescence frequently operates in a context-dependent manner. Here we review what is known about melanocyte senescence, and how such knowledge may provide a much-needed edge in our struggles to contain or perhaps vanquish this often-fatal malignancy. C1 [Sviderskaya, Elena V.] St Georges Univ London, Ctr Mol & Metab Signalling, Div Basic Med Sci, London SW17 0RE, England. [Ha, Linan] US FDA, Div Monoclonal Antibody, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Sviderskaya, EV (reprint author), St Georges Univ London, Ctr Mol & Metab Signalling, Div Basic Med Sci, Cranmer Terrace, London SW17 0RE, England. EM esviders@sgul.ac.uk RI Sviderskaya, Elena/D-2419-2009 FU Intramural NIH HHS [Z01 BC008756-20]; Wellcome Trust [078327] NR 65 TC 33 Z9 34 U1 1 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD JUL 1 PY 2008 VL 7 IS 13 BP 1944 EP 1948 DI 10.4161/cc.7.13.6230 PG 5 WC Cell Biology SC Cell Biology GA 323OX UT WOS:000257457200010 PM 18604170 ER PT J AU Antunes, AMM Duarte, MP Santos, PP da Costa, GG Heinze, TM Beland, FA Marques, MM AF Antunes, Alexandra M. M. Duarte, Mariana P. Santos, Pedro P. da Costa, Gongalo Gamboa Heinze, Thomas M. Beland, Frederick A. Marques, M. Matilde TI Synthesis and characterization of DNA adducts from the HIV reverse transcriptase inhibitor nevirapine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MOTHER-TO-CHILD; C-O BOND; IMMUNODEFICIENCY-VIRUS TYPE-1; UNACTIVATED ARYL HALIDES; MODEL QUINONE METHIDE; ANTIRETROVIRAL THERAPY; IN-VITRO; BUTADIENE MONOXIDE; RANDOMIZED-TRIAL; STYRENE OXIDE AB Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against the human immunodeficiency virus type 1 (HIV-1), mostly to prevent mother-to-child HIV transmission in developing countries. One of the limitations of nevirapine use is severe hepatotoxicity, which raises concerns about its administration, particularly in the perinatal and pediatric settings. Nevirapine metabolism involves oxidation of the 4-methyl substituent to 12-hydroxy-NVP and the formation of phenolic derivatives. Further metabolism of 12-hydroxy-NVP by phase II esterification may produce electrophilic derivatives capable of reacting with DNA to yield covalent adducts, which could potentially be involved in the initiation of mutagenic and carcinogenic events. In the present study, we have investigated the reactivity of the synthetic model electrophile, 12-mesyloxy-NVP, toward 2'-deoxynucleosides and DNA. Parallel synthetic studies were conducted with 12-bromo-NVP and 3',5'-O-bis(tert-butyldimethylsilyl)-2'deoxynucleosides, using palladium(O) catalysis. Multiple adducts from deoxyguanosine, deoxyadenosine, and deoxycytidine were isolated in the reactions with 12-mesyloxy-NVP and characterized by NMR and MS. The adduct structures consistently involved binding through C12 of NVP and N7 or N9 of deoxyguanosine; N1, N3, or N9 of deoxyadenosine; and N3 of deoxycytidine. Reactions conducted under palladium(O) catalysis yielded adducts through O-6 and NI of deoxyguanosine, NI of deoxyadenosine, and N3 of deoxycytidine. At least seven deoxynucleoside-NVP adducts were present in DNA reacted with 12-mesyloxy-NVP and enzymatically hydrolyzed. Four of these adducts were identified as 12(deoxyadenosin-N1-yl)nevirapine, 12-(deoxycytidin-N3-yl)nevirapine, 12-(deoxyguanosin-O-6-yl)nevirapine, and 12-(deoxyadenosin-N-6-yl)nevirapine. One depurinating adduct, 12-(guanin-N7-yl)nevirapine, was identified in the thermal neutral DNA hydrolysate. If formed in vivo, some of these adducts would have considerable mutagenic potential. Our results thus suggest that NVP metabolism to 12-hydroxy-NVP, may be a factor in NVP hepatocarcinogenicity. C1 [Antunes, Alexandra M. M.] Univ Nova Lisboa, REQUIMTE CQFB, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal. [Duarte, Mariana P.; Santos, Pedro P.; Marques, M. Matilde] Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. [da Costa, Gongalo Gamboa; Heinze, Thomas M.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Antunes, AMM (reprint author), Univ Nova Lisboa, REQUIMTE CQFB, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal. EM amma@dq.fct.unl.pt; matilde.marques@ist.utl.pt RI Caparica, cqfb_staff/H-2611-2013; REQUIMTE, AL/H-9106-2013; Chaves, Pedro/K-1288-2013; Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; Santos, Pedro Paulo/P-1769-2016 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Santos, Pedro Paulo/0000-0003-3045-4591 NR 77 TC 20 Z9 20 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2008 VL 21 IS 7 BP 1443 EP 1456 DI 10.1021/tx8000972 PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 329IG UT WOS:000257860700019 PM 18597499 ER PT J AU Rabin, RL Levinson, AI AF Rabin, R. L. Levinson, A. I. TI The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review DE allergy; autoimmunity; multiple sclerosis; rheumatoid arthritis; T cell subsets; type I diabetes mellitus ID KILLER T-CELLS; INDUCED AIRWAY HYPERREACTIVITY; MULTIPLE-SCLEROSIS PATIENTS; RHEUMATOID-ARTHRITIS; INTERFERON-GAMMA; DIABETES-MELLITUS; DENDRITIC CELLS; IFN-GAMMA; INFLAMMATORY DISEASES; DECREASED PREVALENCE AB There has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease 'protected' from developing allergic (immunoglobulin E-mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune-based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co-prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases. C1 [Rabin, R. L.] US FDA, Off Vaccines Regulat & Res, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Levinson, A. I.] Univ Penn, Sch Med, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. RP Rabin, RL (reprint author), US FDA, Off Vaccines Regulat & Res, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Bldg 29,Room 203A, Bethesda, MD 20892 USA. EM rrabin@helix.nih.gov NR 129 TC 49 Z9 50 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 2008 VL 153 IS 1 BP 19 EP 30 DI 10.1111/j.1365-2249.2008.03679.x PG 12 WC Immunology SC Immunology GA 310NQ UT WOS:000256536700003 PM 18505431 ER PT J AU Uppoor, RS Mummaneni, P Cooper, E Pien, HH Sorensen, AG Collins, J Mehta, MU Yasuda, SU AF Uppoor, R. S. Mummaneni, P. Cooper, E. Pien, H. H. Sorensen, A. G. Collins, J. Mehta, M. U. Yasuda, S. U. TI The use of imaging in the early development of neuropharmacological drugs: A survey of approved NDAs SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; RECEPTOR OCCUPANCY; DOPAMINE-D-2; PHARMACOKINETICS; SCHIZOPHRENIA; PET AB The aim of the study was to evaluate the use of imaging in the development of neuropharmacological drugs. All New Drug Applications (NDAs) approved from 1995 through 2004 in the Division of Neuropharmacological Drug Products at the Food and Drug Administration were surveyed for imaging studies. Imaging literature was also reviewed with respect to antipsychotics and antidepressants. One hundred and six NDAs (35 new molecular entities (NMEs)) were approved; 15 of these NDAs (10 NMEs) had imaging studies. The primary imaging modality was positron emission tomography. Imaging was primarily conducted for drugs used in schizophrenia, depression, multiple sclerosis, and migraine. The majority evaluated receptor occupancy or proof of concept. Examples (including literature) are discussed as pertinent to dosage, efficacy, safety, or further development of a drug or class of drugs. Imaging contributes to optimal clinical development of central nervous system (CNS)-active drugs. Opportunities are available for its broader use, contributing to improved understanding of the clinical pharmacology of CNS-active drugs. C1 [Uppoor, R. S.; Mummaneni, P.; Mehta, M. U.; Yasuda, S. U.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. [Cooper, E.; Pien, H. H.; Sorensen, A. G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Collins, J.] Food & Drug Adm, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD USA. RP Uppoor, RS (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. EM ramana.uppoor@fda.hhs.gov NR 12 TC 17 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2008 VL 84 IS 1 BP 69 EP 74 DI 10.1038/sj.clpt.6100422 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 314VN UT WOS:000256837400013 PM 18563070 ER PT J AU Humphrey, BD Kirsch, S Morris, D AF Humphrey, Brooke D. Kirsch, Sandra Morris, Diane TI Molecular cloning and characterization of the chicken cationic amino acid transporter-2 gene SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE arginine; chicken; lysine; nitric oxide; pectoralis; system y; transport ID GALLUS-GALLUS-DOMESTICUS; MESSENGER-RNA DECAY; GROWING CHICKENS; LYSINE OXIDATION; MAMMALIAN-CELLS; PLASMA-MEMBRANE; L-ARGININE; EXPRESSION; IDENTIFICATION; PROTEINS AB The system y(+) cationic amino acid transporters (CATs) play an important role in the regulation of lysine and arginine utilization. We have characterized the genomic organization and tissue transcription of the chicken CAT-2 (cCAT-2) isoforms from pectoralis muscle. The primary cCAT-2 transcript is alternatively spliced within the same position of the mRNA to produce cCAT-2A and cCAT-2B isoforms that share high nucleotide homology with their mammalian counterparts. We also identified a novel third CAT-2 isoform, cCAT-2C. This isoform contains a premature termination codon and studies in the chicken LMH cell line show that cCAT-2C mRNA is degraded by the nonsense-mediated mRNA decay pathway. All three cCAT-2 isoforms are transcribed in liver, pectoralis, gastrocnemius and heart. Chicken cCAT-2A was the predominant cCAT-2 isoform, in liver, pectoralis and gastrocnemius. Analysis of the 5'-untranslated region of cCAT-2 identified multiple cCAT-2 promoters. Chicken CAT-2 promoter usage was tissue dependent and was not responsible for cCAT-2 isoform production. Analysis of genomic sequence upstream cCAT-2 promoter regions revealed binding sites for transcription factors involved in amino acid sensing, hormone signaling and immune function. These results provide insight into the role of the cCAT-2 gene and its regulation of lysine and arginine utilization in aves. (C) 2008 Elsevier Inc. All rights reserved. C1 [Humphrey, Brooke D.] Calif Polytech State Univ San Luis Obispo, Dept Anim Sci, San Luis Obispo, CA 93407 USA. [Humphrey, Brooke D.; Kirsch, Sandra; Morris, Diane] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Morris, Diane] US FDA, Rockville, MD 20857 USA. RP Humphrey, BD (reprint author), Calif Polytech State Univ San Luis Obispo, Dept Anim Sci, 1 Grand Ave, San Luis Obispo, CA 93407 USA. EM bdhumphr@calpoly.edu NR 37 TC 4 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JUL PY 2008 VL 150 IS 3 BP 301 EP 311 DI 10.1016/j.cbpb.2008.03.018 PG 11 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 317JB UT WOS:000257014900008 PM 18495509 ER PT J AU Ahmad, E Steinberg, SM Goldin, L Hess, CJ Caporaso, N Kreitman, RJ Wiestner, A Wilson, W White, T Marti, G Stetler-Stevenson, M AF Ahmad, Ejaz Steinberg, Seth M. Goldin, Lynn Hess, Christopher J. Caporaso, Neil Kreitman, Robert J. Wiestner, Adrian Wilson, Wyndham White, Therese Marti, Gerald Stetler-Stevenson, Maryalice TI Immunophenotypic features distinguishing familial chronic lymphocytic leukemia from sporadic chronic lymphocytic leukemia SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE familial chronic lymphocytic leukemia; sporadic chronic lymphocytic leukemia; immunophenotype; flow cytometry; survival; CD38 ID CD38 EXPRESSION; B-CLL; CLINICAL-COURSE; MUTATION STATUS; ANTICIPATION; PROFILES; NEOPLASMS; DIAGNOSIS; CELLS AB Background: Familial chronic lymphocytic leukemia (CLL) has the most frequent familial aggregation among hematological malignancies. Familial C LL families have been studied to identify susceptibility genes and other factors that contribute in the etiology of CLL. To date no study has been conducted to evaluate and compare patterns of cell surface antigen expression in familial CLL and sporadic CLL. Methods: The pattern of cell surface antigen expression was studied in familial and sporadic CLL to determine if unique identifiers of familial CLL could be detected. Survival in familial CLL verses sporadic CLL was compared and the association between prognosis and CD38 expression studied. Results: Familial and sporadic CLL demonstrated the same characteristic immunophenotype (positive for surface immunoglobulin, CD5, CD19, and CD23 with dim CD20, and CD22). CD2 and CD13 expression, however, were more frequent (30% of cases) in familial CLL (P = 0.0003 for CD2, P = 0.006 for CD13) than in sporadic CLL (2-6%). There was no significant difference in survival in the two groups studied. Although the incidence of CD38 expression was similar in familial and sporadic CLL (47% and 44% respectively) the association with prognosis differed. There was a trend to decreased survival in CD38 positive sporadic (P = 0.06) but not familial CLL patients. Conclusions: We conclude that detection of CD2 or CD13 expression in CLL suggests familial CLL and examination of family history for additional affected members is warranted. Furthermore, CD38 expression does not carry the negative prognosis observed in sporadic CLL. Published 2008 Wiley-Liss, Inc. C1 [Hess, Christopher J.; Stetler-Stevenson, Maryalice] NCI, Chief Flow Cytometry Unit, LP, CCR,NIH, Bethesda, MD 20892 USA. [Ahmad, Ejaz] Good Samaritan Hosp, Dayton, OH USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. [Goldin, Lynn; Caporaso, Neil] NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Mol Biol Lab, CCR, NIH, Bethesda, MD 20892 USA. [Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Wilson, Wyndham; White, Therese] NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. [Marti, Gerald] US FDA, Ctr Biol & Res Evaluat, Off Cellular Tissues & Gene Therapies, Div Cell & Gene Therapies,Cellular & Tissue Branc, Bethesda, MD 20014 USA. RP Stetler-Stevenson, M (reprint author), NCI, Chief Flow Cytometry Unit, LP, CCR,NIH, Bldg 10,Room 2A33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov NR 29 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 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JUL PY 2008 VL 74B IS 4 BP 221 EP 226 DI 10.1002/cyto.b.20423 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 315HX UT WOS:000256870500003 PM 18431797 ER PT J AU Collier, RJ Miller, MA McLaughlin, CL Johnson, HD Baile, CA AF Collier, Robert J. Miller, M. A. McLaughlin, C. L. Johnson, H. D. Baile, C. A. TI Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows SO DOMESTIC ANIMAL ENDOCRINOLOGY LA English DT Article DE rbST; season; IGF-I; IGF-II; cattle ID LONG DAILY PHOTOPERIOD; HOLSTEIN COWS; ENVIRONMENTAL-TEMPERATURE; PHYSIOLOGICAL-RESPONSES; THERMAL STATUS; HEAT-STRESS; HORMONE; PROLACTIN; YIELD; EXPRESSION AB During two studies, effects of recombinant bovine somatotropin (rbST) on plasma and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows) conditions were evaluated. Each study consisted of on-farm periods (30 days) followed by climatology chamber periods (CC; 30 days). Cows were given daily injections of rbST, Sometribove, USAN (25 mg/day; 6 cows each study) or saline (control; 6 cows each study). During on-farm periods, blood and milk (am and pm) samples were collected once weekly. During CC periods, blood samples were collected every 2 days and milk samples (am and pm) were collected daily. Plasma IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected. Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II was not affected by rbST treatment or season. Although milk IGF-I and IGF-II concentrations were unaffected by rbST treatment, total IGF-output increased due to increased milk yield. The observed seasonal patterns in plasma IGF-I may be indicative of seasonal differences in the coupling of the somatotropin-IGF axis. In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis in S despite an induced negative energy balance during thermal stress. (C) 2008 Elsevier Inc. All rights reserved. C1 [Collier, Robert J.] Univ Arizona, Dept Anim Sci, Tucson, AZ 85721 USA. [Miller, M. A.] US FDA, Rockville, MD 20857 USA. [McLaughlin, C. L.] Pfizer Co, Kalamazoo, MI USA. [Johnson, H. D.] Univ Missouri, Columbia, MO USA. Univ Georgia, Athens, GA 30602 USA. RP Collier, RJ (reprint author), Univ Arizona, Dept Anim Sci, 204 Shantz Bldg,POB 210038, Tucson, AZ 85721 USA. EM rcollier@ag.arizona.edu NR 26 TC 17 Z9 18 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0739-7240 J9 DOMEST ANIM ENDOCRIN JI Domest. Anim. Endocrinol. PD JUL PY 2008 VL 35 IS 1 BP 16 EP 23 DI 10.1016/j.domaniend.2008.01.003 PG 8 WC Agriculture, Dairy & Animal Science; Endocrinology & Metabolism SC Agriculture; Endocrinology & Metabolism GA 316GR UT WOS:000256938000003 PM 18325721 ER PT J AU Wang, JH Norcross, M AF Wang, Jinhai Norcross, Michael TI Dimerization of chemokine receptors in living cells: key to receptor function and novel targets for therapy SO DRUG DISCOVERY TODAY LA English DT Review ID PROTEIN-COUPLED RECEPTOR; RESONANCE ENERGY-TRANSFER; BREAST-CANCER METASTASIS; FORM CONSTITUTIVE HOMODIMERS; CRYSTAL-STRUCTURE; SURFACE ASSOCIATION; HIV-1 INFECTION; PLASMA-MEMBRANE; CCR5 RECEPTOR; CXCR4 AB Chemokine receptors control and mediate a diverse array of physiological and pathogenic processes. Many seven transmembrane (TM) G-protein-coupled receptors (GPCRs), including chemokine receptors, exist as homo- or heterodimers. Growing evidence indicates that the dimeric form is the basic functional structure of these receptors. Hetero-dimerization may allow for enhanced or specific functions of receptors and may be essential for receptor activity. Thus, dimers may provide new targets for chemokine receptor-based therapies. Synthetic peptides of TM regions of chemokine receptors may interfere with homologous interactions and inhibit functional activity of the receptors. Therefore, TM peptides and possibly compounds that target dimers and/or signaling of chemokine receptors may have therapeutic applications. C1 [Wang, Jinhai; Norcross, Michael] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Bethesda, MD 20892 USA. EM jinhai.wang@fda.hhs.gov NR 77 TC 31 Z9 33 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL PY 2008 VL 13 IS 13-14 BP 625 EP 632 DI 10.1016/j.drudis.2008.04.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 330YD UT WOS:000257977800012 PM 18598920 ER PT J AU Lathers, CM Schraeder, PL Bungo, MW AF Lathers, Claire M. Schraeder, Paul L. Bungo, Michael W. TI Preventive measures for sudden cardiac death in epilepsy beyond therapies - rEPLY SO EPILEPSY & BEHAVIOR LA English DT Letter ID PENTYLENETETRAZOL-INDUCED SEIZURES; AUTONOMIC DYSFUNCTION; EPILEPTOGENIC ACTIVITY; NEURAL DISCHARGE; INDUCED ARRHYTHMIA; ANIMAL-MODEL; MECHANISMS; INCREASES; HEART C1 [Lathers, Claire M.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Schraeder, Paul L.] Drexel Univ, Coll Med, Dept Neurol, Philadelphia, PA 19102 USA. [Bungo, Michael W.] Univ Texas Houston, Sch Med, Houston, TX 77030 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM lathers@attglobal.net NR 42 TC 2 Z9 2 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD JUL PY 2008 VL 13 IS 1 BP 265 EP 269 DI 10.1016/j.yebeh.2008.01.005 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 317HA UT WOS:000257009400047 ER PT J AU Malinauskas, RA AF Malinauskas, Richard A. TI Decreased hemodialysis circuit pressures indicating postpump tubing kinks: A retrospective investigation of hemolysis in five patients SO HEMODIALYSIS INTERNATIONAL LA English DT Article DE hemolysis; circuit pressures; tubing kink; hemodialysis; adverse event; blood lines ID INTRAVASCULAR HEMOLYSIS; BLOOD LINES; FLOW AB The source of hemolysis during hemodialysis must be quickly identified to avoid life-threatening complications. At a single clinic, over a 10-day period in which 550 treatments were performed, 5 case-patients were retrospectively identified for experiencing acute hemolysis (4 deaths) from an unknown origin. The investigation focused on the postpump arterial tubing as the pressure was not monitored in this region, and the segment was shorter than required and could kink if overly stressed at bend points (i.e., tubing support clips, dialyzer inlet). To determine whether the circuit pressures indicated kinked tubing, a relative comparison between each case-patient's recorded arterial (prepump) and venous circuit pressures throughout their adverse event treatment and their immediately preceding treatment was conducted. Treatment pressure-time traces showed that sustained, significant decreases (> 25 mmHg) in both of the circuit pressures occurred only on the hemolytic event dates. While direct observations of kinked tubing were not reported, the circuit pressure decreases could only be explained by severe postpump tube kinking causing a decrease in the blood flow rate. While postpump obstructions and hemolysis can occur without causing noticeable changes to the prepump arterial and venous blood line pressures (due to the highly occlusive setting of the roller blood pump), recognizing sudden and/or sustained decreases in the circuit pressures during treatment may help to prevent adverse patient events. This analysis reinforces the importance of regularly checking the blood tubing set for kinks and for monitoring the circuit pressures for atypical trends within and between treatments. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Malinauskas, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave,Bldg 62,Room 2108, Silver Spring, MD 20993 USA. EM richard.malinauskas@fda.hhs.gov NR 29 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1492-7535 J9 HEMODIAL INT JI Hemodial. Int. PD JUL PY 2008 VL 12 IS 3 BP 383 EP 393 DI 10.1111/j.1542-4758.2008.00285.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 327DU UT WOS:000257710600018 PM 18638097 ER PT J AU Wang, C Wang, S Yin, JJ AF Wang, Chien Wang, Shiow Yin, Junjie TI Reducing decay and enhancing free radical scavenging capacity in blueberries by eugenol, thymol, and menthol SO HORTSCIENCE LA English DT Meeting Abstract CT 105th Annual Conference of the American-Society-for-Horticultural-Science CY JUL 21-24, 2008 CL Orlando, FL SP Amer Soc Horticultural Sci C1 [Wang, Chien; Wang, Shiow] USDA, Beltsville, MD 20705 USA. [Yin, Junjie] US FDA, College Pk, MD USA. EM chienyi.wang@ars.usda.gov; Shiow.Wang@ars.usda.gov; junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HORTICULTURAL SCIENCE PI ALEXANDRIA PA 113 S WEST ST, STE 200, ALEXANDRIA, VA 22314-2851 USA SN 0018-5345 J9 HORTSCIENCE JI Hortscience PD JUL PY 2008 VL 43 IS 4 BP 1202 EP 1202 PG 1 WC Horticulture SC Agriculture GA 323AN UT WOS:000257416500505 ER PT J AU Laugier, P Wear, KA Waters, KR AF Laugier, Pascal Wear, Keith A. Waters, Kendall R. TI Introduction to the Special Issue on diagnostic and therapeutic applications of ultrasound in bone - Part II SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Editorial Material C1 [Laugier, Pascal] Univ Paris 06, French Natl Sci Res Ctr, CNRS, Lab Parametr Imaging, Paris, France. [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Waters, Kendall R.] Lab Ondes & Acoust, Paris, France. [Waters, Kendall R.] Natl Inst Stand & Technol, Boulder, CO USA. RP Laugier, P (reprint author), Univ Paris 06, French Natl Sci Res Ctr, CNRS, Lab Parametr Imaging, Paris, France. NR 0 TC 1 Z9 2 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2008 VL 55 IS 7 BP 1415 EP 1416 DI 10.1109/TUFFC.2008.816 PG 2 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 322OU UT WOS:000257386000002 ER PT J AU Wear, KA AF Wear, Keith A. TI Ultrasonic scattering from cancellous bone: A review SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article; Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 28-31, 2007 CL New York, NY SP IEEE ID BOVINE TRABECULAR BONE; FREQUENCY-DEPENDENT ATTENUATION; QUANTITATIVE HEEL ULTRASOUND; HUMAN FEMUR SPECIMENS; IN-VITRO; MINERAL DENSITY; HUMAN CALCANEUS; HIP FRACTURE; MECHANICAL-PROPERTIES; ACOUSTIC PROPERTIES AB This paper reviews theory, measurements, and computer simulations of scattering from cancellous bone reported by many laboratories. Three theoretical models (binary mixture, Faran cylinder, and weak scattering) for scattering from cancellous bone have demonstrated some consistency with measurements of backscatter. Backscatter is moderately correlated with bone mineral density in human calcaneus in vitro (r(2) = 0.66-0.68). Backscatter varies approximately as frequency cubed and trabecular thickness cubed in human calcaneus and femur in vitro. Backscatter from human calcaneus and bovine tibia exhibits substantial anisotropy. So far, backscatter has demonstrated only modest clinical utility. Computer simulation models have helped to elucidate mechanisms underlying scattering from cancellous bones. C1 [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Wear, Keith A.] Georgetown Univ, Washington, DC 20057 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM keith.wear@fda.hhs.gov RI CHEN, Jiangang/A-1549-2011 NR 116 TC 70 Z9 83 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2008 VL 55 IS 7 BP 1432 EP 1441 DI 10.1109/TUFFC.2008.818 PG 10 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 322OU UT WOS:000257386000004 PM 18986932 ER PT J AU Wear, KA AF Wear, Keith A. TI A method for improved standardization of in vivo calcaneal time-domain speed-of-sound measurements SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article; Proceedings Paper CT IEEE Ultrasonics Symposium CY OCT 28-31, 2007 CL New York, NY SP IEEE ID BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND DEVICES; FREQUENCY-DEPENDENT ATTENUATION; HUMAN TRABECULAR BONE; HUMAN FEMUR SPECIMENS; HIP FRACTURE; ELDERLY-WOMEN; MECHANICAL-PROPERTIES; VELOCITY DISPERSION; ACOUSTIC PROPERTIES AB Although calcaneal speed of sound (SOS) is an effective predictor of osteoporotic fracture risk, clinical SOS measurements exhibit a high degree of inter-system variability. Calcaneal SOS is usually computed from time-of-flight measurements of broadband ultrasound pulses that propagate through the foot. In order to minimize the effects of multi-path interference, many investigators measure time-of-flight from markers near the leading edge of the pulse. The calcaneus is a highly attenuating, highly inhomogeneous bone that distorts propagating ultrasound pulses via frequency-dependent attenuation, reverberation, dispersion, multiple scattering, and refraction. This pulse distortion can produce errors in leading-edge transit-time marker-based SOS measurements. In this paper, an equation to predict dependence of time-domain SOS measurements on system parameters (center frequency and bandwidth), transit-time marker location, and bone properties (attenuation coefficient and thickness) is validated with through-transmission measurements in a bone-mimicking phantom and in 73 women in vivo, using a clinical bone sonometer. In order to test the utility of the formula for suppressing system dependence of SOS measurements, a wideband laboratory data acquisition system was used to make a second set of through-transmission measurements on the phantom. The compensation formula reduced system-dependent leading-edge transit-time marker-based SOS measurements in the phantom from 41 m/s to 5 m/s and reduced average transit-time marker-related SOS variability in 73 women from 40 m/s to 10 m/s. The compensation formula can be used to improve standardization in bone sonometry. C1 [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. [Wear, Keith A.] Georgetown Univ, Washington, DC 20057 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM keith.wear@fda.hhs.gov NR 52 TC 5 Z9 5 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2008 VL 55 IS 7 BP 1473 EP 1479 DI 10.1109/TUFFC.2008.822 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 322OU UT WOS:000257386000008 PM 18986936 ER PT J AU Sommers, CL Gurson, JM Surana, R Barda-Saad, M Lee, J Kishor, A Li, W Gasser, AJ Barr, VA Miyaji, M Love, PE Samelson, LE AF Sommers, Connie L. Gurson, Jordan M. Surana, Rishi Barda-Saad, Mira Lee, Jan Kishor, Aparna Li, WenMei Gasser, Adam J. Barr, Valarie A. Miyaji, Michihiko Love, Paul E. Samelson, Lawrence E. TI Bam32: a novel mediator of Erk activation in T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE Erk; IL-4; proliferation; TCR; T lymphocyte ID ANTIGEN RECEPTOR; ADAPTER PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; THYMOCYTE SELECTION; TYROSINE RESIDUES; LAT; IDENTIFICATION; DOWNSTREAM; MUTATION; TARGETS AB Bam32 (B lymphocyte adapter molecule of 32 kDa) is an adapter protein expressed in some hematopoietic cells including B and T lymphocytes. It was previously shown that Bam32-deficient mice have defects in various aspects of B cell activation including B cell receptor (BCR)-induced Erk activation, BCR-induced proliferation and T-independent antibody responses. In this study, we have examined the role of Bam32 in T cell activation using Bam32-deficient mice. By comparing CD4(+) T cells from lymph nodes of wild-type and Bam32-deficient mice, we found that Bam32 was required for optimal TCR-induced Erk activation, cytokine production, proliferation and actin-mediated spreading of CD4(+) T cells. These results indicate a novel pathway to Erk activation in T cells involving the adapter protein Bam32. C1 [Sommers, Connie L.; Gurson, Jordan M.; Surana, Rishi; Barda-Saad, Mira; Kishor, Aparna; Li, WenMei; Gasser, Adam J.; Barr, Valarie A.; Miyaji, Michihiko; Samelson, Lawrence E.] Natl Canc Inst, Natl Inst Hlth, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. [Lee, Jan] US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Love, Paul E.] NICHHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), Natl Canc Inst, Natl Inst Hlth, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 21 TC 11 Z9 11 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 JUL PY 2008 VL 20 IS 7 BP 811 EP 818 DI 10.1093/intimm/dxn039 PG 8 WC Immunology SC Immunology GA 316VT UT WOS:000256978500002 PM 18448454 ER PT J AU Espandiari, P Zhang, J Schnackenberg, LK Miller, TJ Knapton, A Herman, EH Beger, RD Hanig, JP AF Espandiari, Parvaneh Zhang, Jun Schnackenberg, Laura K. Miller, Terry J. Knapton, Alan Herman, Eugene H. Beger, Richard D. Hanig, Joseph P. TI Age-related differences in susceptibility to toxic effects of valproic acid in rats SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE valproic acid; age-related toxicity; stages of development; biomarkers ID ADVERSE DRUG-REACTIONS; CHILDRENS SUSCEPTIBILITY; HEPATIC FATALITIES; LIVER; HEPATOTOXICITY; METABOLISM; ADULTS; CYTOCHROMES-P-450; PHARMACOKINETICS; INHIBITION AB A multi-age rat model was evaluated as a means to identify a potential age-related difference in liver injury following exposure to valproic acid (VPA), a known pediatric hepatotoxic agent. Different age groups of Sprague-Dawley (SD) rats (10-, 25-, 40-, 80-day-old) were administered VPA at doses of 160, 320, 500 or 650 mg kg(-1) (i.p.) for 4 days. Animals from all age groups developed toxicity after treatment with VPA; however, the patterns of toxicity were dissimilar within each age group. The high dose of VPA caused significant lethality in 10- and 25-day-old rats. All doses of VPA caused decrease in the platelet counts (10-, 25-day-old rats) and the rate of growth (40-day-old rats) and increases in the urine creatine concentration (high dose, 80-day-old rats). VPA induced hepatic and splenic alterations in all age groups. The most severe lesions were found mostly in 10- and 80-day-old rats. Significant changes in blood urea nitrogen, alanine aminotransferase and alkaline phosphatase were observed in 10-day-old pups after treatment with low doses of VPA. The highest VPA dose caused significant decreases in the levels of serum total protein (40- and 80-day-old rats). Principal component analysis of spectra derived from terminal urine samples of all age groups showed that each age group clusters separately. In conclusion, this study showed that the vulnerability profile of each age group was different indicating that a multi-age pediatric animal model is appropriate to assess more completely age-dependent changes in drug toxicity. Published in 2007 by John Wiley & Sons, Ltd. C1 [Espandiari, Parvaneh; Zhang, Jun; Miller, Terry J.; Knapton, Alan; Herman, Eugene H.; Hanig, Joseph P.] US FDA, CDER, OPS, DAPR, Silver Spring, MD 20993 USA. [Schnackenberg, Laura K.; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Espandiari, P (reprint author), US FDA, CDER, OPS, DAPR, 10903 New Hampshire Ave,Life Sci Bldg 64,Room 208, Silver Spring, MD 20993 USA. EM parvaneh.espandiari@fda.hhs.gov NR 46 TC 10 Z9 10 U1 1 U2 2 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 JUL PY 2008 VL 28 IS 5 BP 628 EP 637 DI 10.1002/jat.1314 PG 10 WC Toxicology SC Toxicology GA 332KK UT WOS:000258081700007 PM 17994530 ER PT J AU Sahu, SC Wiesenfeld, PL Kim, CS Ross, IA Sapienza, PP Newell, R O'Donnell, MW Flynn, TJ AF Sahu, Saura C. Wiesenfeld, Paddy L. Kim, Chung S. Ross, Ivan A. Sapienza, Philip P. Newell, Richard O'Donnell, Michael W. Flynn, Thomas J. TI Validation of an in vitro model for assessment of androstenedione hepatotoxicity using the rat liver cell line clone-9 SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE androstenedione; hepatotoxicity; rat; liver; clone-9 cells ID NONPREGNANT FEMALE RATS; LIPID-PEROXIDATION; ORAL ANDROSTENEDIONE; PRIMARY HEPATOCYTES; ENZYME-INDUCTION; GENE-EXPRESSION; PROTEIN; ACID; METABOLISM; CYTOTOXICITY AB Androstenectione, a naturally occurring steroid hormone, has been used to enhance athletic performance. Little is known, however, about its hepatotoxicity. Clone-9 cells, a non-transformed epithelial cell line that was originally isolated from normal liver of a 4-week old Sprague-Dawley rat, were used as an in vitro model to assess the hepatotoxic potential of androstenedione. The cultures were treated with androstenedione for 24 h at 37 degrees C in 5% CO2 at concentrations of 0-100 mu g ml(-1). After the treatment period, the cells and the culture supernatants were assayed for markers of cytotoxicity which included: release of liver enzymes, cell viability, cellular double-stranded DNA content, oxidative stress, steatosis, cellular ATP content, caspase-3 activity, the mitochondrial permeability transition and induction of cytochrome P450 activity. Significant concentration-dependent differences from control were observed in some endpoints at medium concentrations of 10 mu g ml(-1) and above. These in vitro findings were compared with comparable endpoints obtained from an in vivo study of androstenedione toxicity in female Sprague-Dawley rats. Of the eight endpoints that could be compared between the two studies, only three (lipid accumulation, ATP depletion and P450 activity) appeared to be concordant. This suggests that, under the experimental conditions used, the clone-9 cells were not a good model for androstenedione hepatotoxicity. Published in 2007 by John Wiley & Sons, Ltd. C1 [Sahu, Saura C.; Wiesenfeld, Paddy L.; Kim, Chung S.; Ross, Ivan A.; Sapienza, Philip P.; Flynn, Thomas J.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. [Newell, Richard; O'Donnell, Michael W.] US FDA, Div Math, Off Sci Anal & Support, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM saura.sahu@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 69 TC 1 Z9 1 U1 0 U2 0 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 JUL PY 2008 VL 28 IS 5 BP 703 EP 709 DI 10.1002/jat.1325 PG 7 WC Toxicology SC Toxicology GA 332KK UT WOS:000258081700016 PM 18059068 ER PT J AU Ludu, JS de Bruin, OM Duplantis, BN Schmerk, CL Chou, AY Elkins, KL Nano, FE AF Ludu, Jagjit S. de Bruin, Olle M. Duplantis, Barry N. Schmerk, Crystal L. Chou, Alicia Y. Elkins, Karen L. Nano, Francis E. TI The Francisella pathogenicity island protein PdpD is required for full virulence and associates with homologues of the type VI secretion system SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TULARENSIS SUBSP TULARENSIS; PSEUDOMONAS-AERUGINOSA; INTRAMACROPHAGE GROWTH; INTRACELLULAR GROWTH; ALLELIC REPLACEMENT; ESCHERICHIA-COLI; IDENTIFICATION; TULAREMIA; NOVICIDA; CELLS AB Francisella tularensis is a highly infectious, facultative intracellular bacterial pathogen that is the causative agent of tularemia. Nearly a century ago, researchers observed that tularemia was often fatal in North America but almost never fatal in Europe and Asia. The chromosomes of F. tularensis strains carry two identical copies of the Francisella pathogenicity island (FPI), and the FPIs of North America-specific biotypes contain two genes, amnK and pdpD, that are not found in biotypes that are distributed over the entire Northern Hemisphere. In this work, we studied the contribution of anmK and pdpD to virulence by using F. novicida, which is very closely related to F. tularensis but which carries only one copy of the FPI. We showed that anmK and pdpD are necessary for full virulence but not for intracellular growth. This is in sharp contrast to most other FPI genes that have been studied to date, which are required for intracellular growth. We also showed that PdpD is localized to the outer membrane. Further, overexpression of PdpD affects the cellular distribution of FPI-encoded proteins IgIA, IgIB, and IgIC. Finally, deletions of FPI genes encoding proteins that are homologues of known components of type VI secretion systems abolished the altered distribution of IgIC and the outer membrane localization of PdpD. C1 [Ludu, Jagjit S.; de Bruin, Olle M.; Duplantis, Barry N.; Schmerk, Crystal L.; Nano, Francis E.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC V8W 3P6, Canada. [Chou, Alicia Y.; Elkins, Karen L.; Nano, Francis E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Nano, FE (reprint author), Univ Victoria, Dept Biochem & Microbiol, POB 3055 STN CSC, Victoria, BC V8W 3P6, Canada. EM fnano@uvic.ca FU NIAID NIH HHS [5R01 AI056212-02, K08 AI056212] NR 44 TC 72 Z9 72 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2008 VL 190 IS 13 BP 4584 EP 4595 DI 10.1128/JB.00198-08 PG 12 WC Microbiology SC Microbiology GA 319OW UT WOS:000257174400024 PM 18469101 ER PT J AU Hong, HX Xie, Q Ge, WG Qian, F Fang, H Shi, LM Su, ZQ Perkins, R Tong, WD AF Hong, Huixiao Xie, Qian Ge, Weigong Qian, Feng Fang, Hong Shi, Leming Su, Zhenqiang Perkins, Roger Tong, Weida TI Mold(2), molecular descriptors from 2D structures for chemoinformatics and toxicoinformatics SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID ESTROGEN-RECEPTOR BINDING; PARTITION-COEFFICIENTS; DECISION FOREST; STRUCTURE ELUCIDATION; TOPOLOGICAL INDEXES; BIOLOGICAL-ACTIVITY; EXPERT-SYSTEM; QSAR; PREDICTION; DIVERSITY AB Research applications in chemoinformatics and toxicoinformatics increasingly use representations of molecules in the form of numerical descriptors that capture the structural characteristics and properties of molecules. These representations are useful for ADME/toxicity prediction, diversity analysis, library design, QSAR/QSPR, virtual screening, and other purposes. Molecular descriptors have ranged from relatively simple forms calculated from simple two-dimensional (2D) chemical structures to more complex forms representing three-dimensional (3D) chemical structures or complex molecular fingerprints consisting of numerous bit positions to represent specific chemical information. The Mold(2) software was developed to enable the rapid calculation of a large and diverse set of descriptors encoding two-dimensional chemical structure information. Comparative analysis of Mold(2) descriptors with those calculated by Cerius(2), Dragon, and Molconn-Z oil several data sets using Shannon entropy analysis demonstrated that Mold(2) descriptors convey a similar amount of information. In addition, using the same classification method, slightly better models were generated C, using Mold(2) descriptors compared to those generated using descriptors from the compared commercial software packages. The low computing cost for Mold(2) makes it suitable not only for small data sets, such as in QSAR, but also for large databases in virtual screening. High reproducibility and reliability are expected because Mold(2) does not require 3D structures. Mold(2) is freely available to the public (http://www.fda.gov/nctr/science/centers/toxicoinformatics/index.htm). C1 [Hong, Huixiao; Ge, Weigong; Shi, Leming; Su, Zhenqiang; Tong, Weida] Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, Jefferson, AR 72079 USA. [Xie, Qian; Qian, Feng; Fang, Hong; Perkins, Roger] US FDA, Natl Ctr Toxicol Res, Div Bioinformat, ZTech,ICF Int Co, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 57 TC 68 Z9 71 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JUL PY 2008 VL 48 IS 7 BP 1337 EP 1344 DI 10.1021/ci800038f PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 331HW UT WOS:000258004300005 PM 18564836 ER PT J AU Kauffman, JF Tumuluri, V Guo, C Spencer, JA Doub, WH Nichols, GA Randle, SR Wu, S AF Kauffman, John F. Tumuluri, Venkat Guo, Changning Spencer, John A. Doub, William H. Nichols, Gary A. Randle, Scot R. Wu, Stephen TI Near infrared spectroscopy of magnesium stearate hydrates and multivariate calibration of pseudopolymorph composition SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE hydrate; near infrared spectroscopy; partial least squares regression; multivariate calibration; pseudopolymorphs; thermogravimetric analysis ID SCATTER-CORRECTION; MIXTURES; TABLETS AB Samples of magnesium stearate monohydrate and dihydrate were used to prepare standard mixtures of known pseudopolymorphic composition. Near infrared spectra (NIR) of the standard mixtures were measured to develop multivariate calibration models for the pseudopolymorphic composition of magnesium stearate by partial least squares (PLS) regression. Magnesium stearate hydrate compositions of the standard mixtures were compared against the hydrate composition based on thermogravimetric analysis (TGA). The mixture compositions determined from TGA mass loss on drying (LOD) measurements were found to be inaccurate. PLS regression was applied to the TGA thermograms of the standard mixtures to generate more accurate reference values, and this model was then applied to a set of validation samples. Application of the NIR PLS model to the validation sample set resulted in precise estimates of sample pseudopolymorphic composition when compared to the TGA PLS reference values. The NIR PLS model was found to be more sensitive than TGA LOD to small quantities of hydrates, and the TGA PLS model was also found to be more sensitive that TGA LOD. The results demonstrate the challenges and opportunities that arise when rapid, nondestructive spectroscopic methods depend on insensitive or inaccurate reference methods for development of multivariate calibration models. (C) 2007 Wiley-Liss, Inc. C1 [Kauffman, John F.; Tumuluri, Venkat; Guo, Changning; Spencer, John A.; Doub, William H.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Nichols, Gary A.; Randle, Scot R.; Wu, Stephen] Mallinckrodt Div, Tyco Healthcare Grp, Pharmaceut R&D, St Louis, MO 63119 USA. RP Kauffman, JF (reprint author), US FDA, CDER, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM John.Kauffman@fda.hhs.gov NR 15 TC 5 Z9 5 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2008 VL 97 IS 7 BP 2757 EP 2767 DI 10.1002/jps.21006 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 323JY UT WOS:000257443600024 PM 17546666 ER PT J AU Gozalo, AS Maximova, OA StClaire, MC Montali, RJ Ward, JM Cheng, LI Elkins, WR Kazacos, KR AF Gozalo, Alfonso S. Maximova, Olga A. StClaire, Marisa C. Montali, Richard J. Ward, Jerrold M. Cheng, Lily I. Elkins, William R. Kazacos, Kevin R. TI Visceral and neural larva migrans in rhesus macaques SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID BAYLISASCARIS-PROCYONIS; CEREBROSPINAL NEMATODIASIS; TOXASCARIS; COLONY AB Large ascarid larvae within granulomas were noted histologically in the mesenteric and pancreatic lymph nodes of 13 of 21 rhesus macaques (Macaca mulatta) euthanized as part of an experimental viral pathogenesis study. In addition, 7 of the 13 monkeys had cerebral granulomas, which in 4 animals contained nematode larvae similar to those within the lymph nodes. Despite the lesions, the animals did not show clinical signs associated with the parasitic infections. Characteristics of the larvae included, on cross-section, a midbody diameter of approximately 60 to 80 pm, a centrally located and slightly compressed intestine flanked on either side by large triangular excretory columns, and prominent single lateral cuticular alae. The morphology of the larvae was compatible with Baylisascaris spp. Baylisascariasis is a well-described infection of animals and humans that is caused by migrating larvae of the raccoon roundworm, Baylisascaris procyonis. A similar species, B. columnaris, is found in skunks and can cause cerebrospinal nematodiasis, but most reported cases of baylisascariasis have been due to B. procyonis. Our macaques were born free-ranging on an island in the southeastern United States where raccoons, but not skunks, were found to be common inhabitants, indicating that B. procyonis m as the most likely parasite involved. These cases are similar to the low-level or covert cases of Baylisascaris infection described to occur in humans and provide further evidence of the existence of this parasite in the southeastern United States. C1 [Gozalo, Alfonso S.; Montali, Richard J.; Ward, Jerrold M.; Cheng, Lily I.; Elkins, William R.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Gozalo, Alfonso S.; Montali, Richard J.; Ward, Jerrold M.; Cheng, Lily I.] Sobran Incorp, Bethesda, MD USA. [Maximova, Olga A.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [StClaire, Marisa C.] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Kazacos, Kevin R.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gozaloa@niaid.nih.gov FU Intramural NIH HHS NR 18 TC 5 Z9 7 U1 0 U2 3 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 JUL PY 2008 VL 47 IS 4 BP 64 EP 67 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 334CH UT WOS:000258199400009 PM 18702454 ER PT J AU Lee, LY Kortepeter, CM Willy, ME Nourjah, P AF Lee, Lauren Y. Kortepeter, Cindy M. Willy, Mary E. Nourjah, Parivash TI Drug-risk communication to pharmacists: Assessing the impact of risk-minimization strategies on the practice of pharmacy SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE risk management; pharmacists; medication safety; Food and Drug Administration; adverse drug effects; black box warnings ID DEAR DOCTOR LETTERS; INFORMATION AB Objectives: To gain insight on the knowledge, opinions, barriers, and practices of pharmacists regarding drug risk-minimization tools. Design: Descriptive, nonexperimental, cross-sectional survey. Setting: 20 states in the United States, fall 2004. Participants: 2,052 randomly selected licensed pharmacists employed in a position requiring an active pharmacist license at the time of the survey and who responded to the survey. Intervention: Participants completed a four-page survey regarding their experience with different types of risk-minimization tools. Main outcome measure: Univariate distributions for each question were analyzed. Results: 50% of survey recipients responded to the mailing; 88% of respondents had an active pharmacist license. Of respondents, 18% reported never having received a Dear Healthcare Professional letter and 29% stated that they were not familiar with Medication Guides. Patient package inserts were thought to be somewhat effective by 53% of respondents. Of pharmacists who dispensed a drug with programs for special stickers to be affixed on prescriptions to indicate that the labeled risk had been addressed by the prescriber, 41% reported receiving a prescription without a sticker; 45% dispensed the prescription when stickers were missing. Sixty percent of pharmacists stated that risk-minimization programs have a negative impact on the daily practice of pharmacy; nevertheless, many acknowledged that it was a necessary duty. Conclusion: Pharmacists might benefit from additional training on risk-minimization strategies. The successful implementation and impact of risk-minimization programs on the practice of pharmacy should be carefully considered by drug manufacturers and regulators. C1 [Lee, Lauren Y.; Kortepeter, Cindy M.; Willy, Mary E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Nourjah, Parivash] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Lee, LY (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 3432, Silver Spring, MD 20993 USA. EM lauren.lee@fda.hhs.gov NR 7 TC 5 Z9 6 U1 1 U2 3 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD JUL-AUG PY 2008 VL 48 IS 4 BP 494 EP 500 DI 10.1331/JAPhA.2008.07045 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 336BW UT WOS:000258340300016 PM 18653425 ER PT J AU Yustein, AS Schultz, D Neuland, C Buckles, DS Nipper, JC Stephenson, RA Gonzalez, G AF Yustein, Aron S. Schultz, Daniel Neuland, Carolyn Buckles, David S. Nipper, Joshua C. Stephenson, Rebecca A. Gonzalez, Gema TI US food and drug administration and off-label use of expandable metal biliary Stents within the peripheral vasculature SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article AB Expandable metal stents are used to maintain the patency of compromised ducts, lumens, and vessels. As medical devices, these products are regulated by the Center for Devices and Radiological Health of the U.S. Food and Drug Administration (FDA). During the past several years, the FDA has become aware of the increasing prevalence of off-label use of expandable metal stents cleared for biliary use within the peripheral vasculature. The authors provide an overview of how the FDA regulates medical devices and expandable stents and summarize safety issues reported to the Agency with regard to the off-label use of these biliary stents. C1 [Yustein, Aron S.; Schultz, Daniel; Neuland, Carolyn; Buckles, David S.; Nipper, Joshua C.; Stephenson, Rebecca A.; Gonzalez, Gema] US FDA, Ctr Devices & Radiol Hlth, HFZ 400, Rockville, MD 20850 USA. RP Yustein, AS (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 400, 9200 Corp Blvd, Rockville, MD 20850 USA. EM aron.yustein@fda.hhs.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUL PY 2008 VL 19 IS 7 BP 965 EP 969 DI 10.1016/j.jvir.2008.02.010 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 324FV UT WOS:000257504000001 PM 18672491 ER PT J AU Kovalchuk, O Filkowski, J Meservy, J IInytskyy, Y Tryndyak, VP Chekhun, VF Pogribny, IP AF Kovalchuk, Olga Filkowski, Jody Meservy, James IInytskyy, Yaroslav Tryndyak, Volodymyr P. Chekhun, Vasyl' F. Pogribny, Igor P. TI Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MULTIDRUG-RESISTANCE; TUMOR-SUPPRESSOR; GENE-EXPRESSION; DOWN-REGULATION; MESSENGER-RNA; TARGETS; OVEREXPRESSION; METHYLATION; METASTASIS; PHENOTYPE AB Many chemotherapy regiments are successfully used to treat breast cancer; however, often breast cancer cells develop drug resistance that usually leads to a relapse and worsening of prognosis. We have shown recently that epigenetic changes such as DNA methylation and histone modifications play an important role in breast cancer cell resistance to chemotherapeutic agents. Another mechanism of gene expression control is mediated via the function of small regulatory RNA, particularly microRNA (miRNA); its role in cancer cell drug resistance still remains unexplored. In the present study, we investigated the role of miRNA in the resistance of human MCF-7 breast adenocarcinoma cells to doxorubicin (DOX). Here, we for the first time show that DOX-resistant MCF-7 cells (MCF-7/DOX) exhibit a considerable dysregulation of the miRNAome profile and altered expression of miRNA processing enzymes Dicer and Argonaute 2. The mechanistic link of miRNAome deregulation and the multidrug-resistant phenotype of MCF-7/DOX cells was evidenced by a remarkable correlation between specific miRNA expression and corresponding changes in protein levels of their targets, specifically those ones that have a documented role in cancer drug resistance. Furthermore, we show that microRNA-451 regulates the expression of multidrug resistance 1 gene. More importantly, transfection of the MCF-7/DOX-resistant cells with microRNA-451 resulted in the increased sensitivity of cells to DOX, indicating that correction of altered expression of miRNA may have significant implications for therapeutic strategies aiming to overcome cancer cell resistance. C1 [Kovalchuk, Olga; Filkowski, Jody; Meservy, James; IInytskyy, Yaroslav] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Tryndyak, Volodymyr P.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Chekhun, Vasyl' F.] RE Kavetsky Inst Expt Pathol,Oncol & Radiobiol, Dept Mechanisms Anticanc Therapy, Kiev, Ukraine. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca; igor.pogribny@fda.hhs.gov NR 50 TC 320 Z9 368 U1 4 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2008 VL 7 IS 7 BP 2152 EP 2159 DI 10.1158/1535-7163.MCT-08-0021 PG 8 WC Oncology SC Oncology GA 330SW UT WOS:000257964100042 PM 18645025 ER PT J AU Wang, C Sadovova, N Patterson, TA Zou, XJ Fu, X Hanig, JP Paule, MG Ali, SF Zhang, X Slikker, W AF Wang, Cheng Sadovova, Natalya Patterson, Tucker A. Zou, Xiaoju Fu, Xin Hanig, Joseph P. Paule, Merle G. Ali, Syed F. Zhang, Xuan Slikker, William, Jr. TI Protective effects of 7-nitroindazole on ketamine-induced neurotoxicity in rat forebrain culture SO NEUROTOXICOLOGY LA English DT Article DE apoptosis; nitric oxide; neurodegeneration; N-methyl-D-aspartate; nNOS; neuroprotection ID CELL-ADHESION MOLECULE; INDUCED DOPAMINERGIC NEUROTOXICITY; D-ASPARTATE RECEPTORS; NITRIC-OXIDE; CHRONIC PHENCYCLIDINE; INDUCED APOPTOSIS; BLOCKADE; EXPRESSION; NEURONS; MICE AB Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, is used as a pediatric anesthetic for surgical procedures. Recent data suggest that anesthetic drugs may cause neurodegeneration during development. The purpose of this study was to determine the dose and temporal response of ketamine using newborn rat forebrain cultures and also to determine if co-administration of 7-nitroindazole, a nitric oxide synthase (NOS) inhibitor, could protect or reverse ketamine-induced cell death. Neural cells collected from the rat forebrain were incubated for 24 h with 1, 10 or 20 mu M ketamine alone or with ketamine plus 1, 5, 10 or 20 mu M 7-nitroindazole. Ketamine (10 mu M) caused an increase in DNA fragmentation and elevated immunoreactivity to nitrotyrosine, a marked reduction in the expression of the neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and in mitochondrial metabolism, as well as an increased Bax/BCL-XL ratio. No significant effect was observed in the release of lactate dehydrogenase (LDH). Ketamine-induced neurotoxic effects were effectively blocked by 7-nitroindazole (10 mu M). These data indicate a role for nitric oxide in the enhanced degeneration induced by ketamine in vitro and also suggest that blocking neuronal nitric oxide synthase (nNOS) may help reduce the risk of ketamine in pediatrics. Published by Elsevier Inc. C1 [Wang, Cheng; Patterson, Tucker A.; Zou, Xiaoju; Paule, Merle G.; Ali, Syed F.; Zhang, Xuan; Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Sadovova, Natalya] Toxicol Pathol Associates, Jefferson, AR USA. [Fu, Xin] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132 Jefferson, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov NR 30 TC 24 Z9 26 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JUL PY 2008 VL 29 IS 4 BP 613 EP 620 DI 10.1016/j.neuro.2008.03.007 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 328TA UT WOS:000257819500007 PM 18456338 ER PT J AU Raffaele, KC Fisher, JE Hancock, S Hazelden, K Sobrian, SK AF Raffaele, Kathleen C. Fisher, J. Edward, Jr. Hancock, Scott Hazelden, Keith Sobrian, Sonya K. TI Determining normal variability in a developmental neurotoxicity test - A report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Review DE developmental neurotoxicity testing; DNT; variability in DNT testing; regulatory testing ID ACOUSTIC STARTLE RESPONSE; FUNCTIONAL OBSERVATIONAL BATTERY; ELEVATED PLUS-MAZE; COLLABORATIVE BEHAVIORAL TERATOLOGY; PRENATAL COCAINE EXPOSURE; SPRAGUE-DAWLEY RATS; ENVIRONMENTAL ENRICHMENT; LITTER SIZE; LONG-EVANS; WATER MAZE AB With the implementation of the Food Quality Protection Act in 1996, more detailed evaluations of possible health effects of pesticides on developing organisms have been required. As a result, considerable developmental neurotoxicity (DNT) data have been generated on a variety of endpoints, including developmental changes in motor activity, auditory startle habituation, and various learning and memory parameters. One issue in interpreting these data is the level of variability for the measures used in these studies: excessive variability can obscure treatment-related effects, or conversely, small but statistically significant changes could be viewed as treatment related, when they might in fact be within the normal range. To aid laboratories in designing useful DNT studies for regulatory consideration, an operational framework for evaluating observed variability in study data has been developed. Elements of the framework suggest how an investigator might approach characterization of variability in the dataset; identification of appropriate datasets for comparison; evaluation of similarities and differences in variability between these datasets, and of possible sources of the variability, including those related to test conduct and test design. A case study using auditory startle habituation data is then presented, employing the elements of this proposed approach. (C) 2008 Elsevier Inc. All rights reserved. C1 [Raffaele, Kathleen C.] US EPA, Off Pesticide Programs, Washington, DC 20460 USA. [Fisher, J. Edward, Jr.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hancock, Scott] Hlth Canada, PMRA, Ottawa, ON K1A 0L2, Canada. [Hazelden, Keith] Huntingdon Life Sci, Dept Safety Assessment, Huntingdon, NJ USA. [Sobrian, Sonya K.] Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. RP Raffaele, KC (reprint author), US EPA, Off Pesticide Programs, Washington, DC 20460 USA. EM raffaele.kathleen@epa.gov NR 128 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2008 VL 30 IS 4 BP 288 EP 325 DI 10.1016/j.ntt.2007.12.009 PG 38 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 336LY UT WOS:000258366500003 PM 18280700 ER PT J AU Tyl, RW Crofton, K Moretto, A Moser, V Sheets, LP Sobotka, TJ AF Tyl, Rochelle W. Crofton, Kevin Moretto, Angelo Moser, Virginia Sheets, Larry P. Sobotka, Thomas J. TI Identification and interpretation of developmental neurotoxicity effects - A report from the ILSI Research Foundation/Risk Science Institute expert working group on neurodevelopmental endpoints SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Review DE developmental neurotoxicity testing; DNT; DNT treatment-related effects; interpretation of treatment-related effects ID HEALTH RISK ASSESSMENT; COLLABORATIVE BEHAVIORAL TERATOLOGY; ACOUSTIC STARTLE RESPONSE; HISTORICAL CONTROL DATA; NERVOUS-SYSTEM DEVELOPMENT; GENDER-BASED DIFFERENCES; SPRAGUE-DAWLEY RATS; REFLEX MODIFICATION; MOTOR-ACTIVITY; ENVIRONMENTAL-FACTORS AB The reliable detection, measurement, and interpretation of treatment-related developmental neurotoxicity (DNT) effects depend on appropriate study design and execution, using scientifically established methodologies, with appropriate controls to minimize confounding factors. Appropriate statistical approaches should lie optimized for the specific endpoints in advance, analyzing effects across time and functional domains as far as possible. If available, biomarkers of exposure are useful to assess the bioavailabitity of toxicants to the dam and offspring in utero and after birth. Finally, "weight of evidence" principles are used to aid assessment of the biological significance of differences from concurrent controls. These effects should be interpreted in light of available information from historical controls, positive controls, maternal and offspring systemic toxicity, and other relevant toxicological data. This review provides a framework for the integration of all these types of information in the interpretation of DNT studies. (C) 2007 Elsevier Inc. All rights reserved. C1 [Moretto, Angelo] Univ Padua, Dept Environm Med & Publ Hlth, I-35100 Padua, Italy. [Sobotka, Thomas J.] US FDA, CFSAN, Rockville, MD 20857 USA. EM rwt@rti.org RI Crofton, Kevin/J-4798-2015; OI Crofton, Kevin/0000-0003-1749-9971; Moretto, Angelo/0000-0003-4386-5736 NR 131 TC 18 Z9 18 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2008 VL 30 IS 4 BP 349 EP 381 DI 10.1016/j.ntt.2007.07.008 PG 33 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 336LY UT WOS:000258366500005 PM 17826946 ER PT J AU Ognibene, E Adriani, W Caprioli, A Ghirardi, O Ali, SF Aloe, L Laviola, G AF Ognibene, Elisa Adriani, Walter Caprioli, Antonio Ghirardi, Orlando Ali, Syed F. Aloe, Luigi Laviola, Giovanni TI The effect of early maternal separation on brain derived neurotrophic factor and monoamine levels in adult heterozygous reeler mice SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE early adversity; genetic vulnerability; mice; psychiatric disorder; reelin; social behavior ID ANTIPSYCHOTIC-DRUGS; MESSENGER-RNA; RAT-BRAIN; BEHAVIORAL-PHENOTYPE; SYNAPTIC PLASTICITY; HIPPOCAMPAL-NEURONS; STRESS REACTIVITY; FACTOR EXPRESSION; DOWN-REGULATION; CAJAL-RETZIUS AB Objective and methods: The reeler heterozygous (HZ) mice have provided a model for studying the relationship between reelin (a protein of extracellular matrix) haploinsufficiency and the emergence of neuropsychiatric diseases. In a neurodevelopmental framework, the enduring consequences of early maternal separation (5 h/day during the first postnatal week, or handling controls, H) were studied in reeler HZ and wild type (WT) mice at adulthood. The modulatory effects of a chronic treatment with the atypical antipsychotic olanzapine (OLZ, 1.5 mg/kg for 40 days) were also investigated. Results: Early maternal separation had long-term effects on brain plasticity, with a reduction of brain- and glial- derived neurotrophic factor (BDNF and GDNF) in several brain areas of mice, but such a consequence was less marked in the HZ genotype. On the other hand, treatment with OLZ did not affect at all the GDNF but led to an increase of BDNF levels in maternally separated (SEP) mice, an effect which was far more marked in the HZ genotype. Brain levels of serotonin (5-HT) were markedly increased, striatal dopamine (DA) was increased, whereas metabolites and turnover were decreased, in SEP mice of both genotypes. The spontaneous home-cage activity was generally lower in HZ than WT mice, and OLZ treatment contrasted this hypoactivity profile. Maternal separation also decreased the interest toward an unknown mouse proposed as a social stimulus, but only in WT mice. Conclusion: We investigated the interplay between genetic vulnerability (reelin haploinsufficiency), the outcome of early stressful experiences, and the efficacy of the antipsychotic drug therapy. The reeler HZ genotype exhibited a slightly lower sensitivity to the environmental insult as well as an enhanced response to the atypical antipsychotic treatment. (C) 2008 Elsevier Inc. All rights reserved. C1 [Ognibene, Elisa; Adriani, Walter; Laviola, Giovanni] Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. [Ognibene, Elisa; Caprioli, Antonio; Ghirardi, Orlando] Sigma Tau Pharmaceut Co, Cent & Peripheral Nervous Syst, Pomezia, Italy. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol,HFT 132, Jefferson, AR 72079 USA. [Aloe, Luigi] CNR, Inst Neurobiol & Mol Med, Rome, Italy. RP Laviola, G (reprint author), Ist Super Sanita, Sect Behav Neurosci, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM laviola@iss.it RI Laviola, Giovanni/K-4392-2016 OI Laviola, Giovanni/0000-0003-0388-0835 NR 60 TC 34 Z9 36 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JUL 1 PY 2008 VL 32 IS 5 BP 1269 EP 1276 DI 10.1016/j.pnpbp.2008.03.023 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 334HP UT WOS:000258213200025 PM 18501492 ER PT J AU Lutter, R McConagha, WA AF Lutter, Randall McConagha, William A. TI Prevention of deep vein thrombosis and pulmonary embolism - The FDA responds SO PUBLIC HEALTH REPORTS LA English DT Letter C1 [Lutter, Randall; McConagha, William A.] US FDA, Dept Hlth & Human Serv, Washington, DC 20204 USA. RP Lutter, R (reprint author), US FDA, Dept Hlth & Human Serv, Washington, DC 20204 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 2008 VL 123 IS 4 BP 422 EP 423 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 310ZX UT WOS:000256570700003 PM 18763403 ER PT J AU Moore, MM Heflich, RH Haber, LT Allen, BC Shipp, AM Kodell, RL AF Moore, Martha M. Heflich, Robert H. Haber, Lynne T. Allen, Bruce C. Shipp, Annette M. Kodell, Ralph L. TI Analysis of in vivo mutation data can inform cancer risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE cancer risk assessment; mode-of-action; mutagenic carcinogen; nonmutagenic carcinogen ID BIG BLUE RATS; DICHLOROACETIC ACID; CARCINOGENIC MODES; TRANSGENIC MICE; HUMAN RELEVANCE; MUTAGENICITY; MOUSE; TOXICITY; ASSAYS; LIVER AB Under the new U.S. Environmental Protection Agency (EPA) Cancer Risk Assessment Guidelines [U.S. EPA, 200.5. Guidelines for Carcinogen Risk Assessment. EPA/630/P-03/001B, March 2005], the quantitative model chosen for cancer risk assessment is based on the mode-of-action (MOA) of the chemical under consideration. In particular, the risk assessment model depends on whether or not the chemical causes tumors through a direct DNA-reactive mechanism. It is assumed that direct DNA-reactive carcinogens initiate carcinogenesis by inducing mutations and have low-dose linear dose-response curves, whereas carcinogens that operate through a nonmutagenic MOA may have nonlinear dose-responses. We are currently evaluating whether the analysis of in vivo gene mutation data can inform the risk assessment process by better defining the MOA for cancer and thus influencing the choice of the low-dose extrapolation model. This assessment includes both a temporal analysis of mutation induction and a dose-response concordance analysis of mutation with tumor incidence. Our analysis of published data on riddelliine in rats and dichloroacetic acid in mice indicates that our approach has merit. We propose an experimental design and graphical analysis that allow for assessing time-to-mutation and dose-response concordance, thereby optimizing the potential for in vivo mutation data to inform the choice of the quantitative model used in cancer risk assessment. (C) 2008 Published by Elsevier Inc. C1 [Moore, Martha M.; Heflich, Robert H.; Kodell, Ralph L.] US FDA, Natl Ctr Toxicol Res, Div Genet Reprod Toxicol, Jefferson, AR 72079 USA. [Haber, Lynne T.] Toxicol Excellence Risk Assessment, Cincinnati, OH USA. [Allen, Bruce C.] Bruce Allen Consulting, Chapel Hill, NC USA. [Shipp, Annette M.] ENVIRON Hlth Sci Inst, Ruston, LA USA. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet Reprod Toxicol, 3900 NCTR Road, Jefferson, AR 72079 USA. EM martha.moore@fda.hhs.gov NR 40 TC 15 Z9 15 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2008 VL 51 IS 2 BP 151 EP 161 DI 10.1016/j.yrtph.2008.01.015 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 317RE UT WOS:000257036500004 PM 18321622 ER PT J AU Starlard-Davenport, A Lyn-Cook, B Radominska-Pandya, A AF Starlard-Davenport, Athena Lyn-Cook, Beverly Radominska-Pandya, Anna TI Identification of UDP-glucuronosyltransferase 1A10 in non-malignant and malignant human breast tissues SO STEROIDS LA English DT Article DE UGTs; UGT1A10; breast cancer; African Americans; Caucasians ID GENETIC POLYMORPHISMS; CONJUGATION REACTIONS; HUMAN COLON; EXPRESSION; CANCER; ESTROGENS; GLUCURONIDATION; METABOLISM; ENZYMES; CLONING AB UGT1A10 was recently identified as the major isoform that conjugates estrogens. In this study, real-time PCR revealed high levels of UGT1A10 and UGT2B7 mRNA in human breast tissues. The expression of UGT1A10 in breast was a novel finding. UGT1A10 and UGT2B7 mRNAs were differentially expressed among normal and malignant specimens. Their overall expression was significantly decreased in breast carcinomas as compared to normal breast specimens (UGT1A10: 68 +/- 26 vs. 252 +/- 86, respectively; p < 0.05) and (UGT2B7: 1.4 +/- 0.7 vs. 12 +/- 4, respectively; p < 0.05). Interestingly, in African American women, UGT1A10 expression was significantly decreased in breast carcinomas in comparison to normals (57 +/- 35 vs. 397 +/- 152, respectively; p < 0.05). Among Caucasian women, UGT2B7 was significantly decreased in breast carcinomas in comparison to normals (1.1 +/- 0.5 vs. 13.5 +/- 6, respectively; p < 0.05). Glucuronidation of 4-hydroxylated estrone (4-OHE1) was significantly reduced in breast carcinomas compared to normals (30 +/- 15 vs. 106 +/- 31, respectively; p < 0.05). Differential down-regulation of UGT1A10 and UGT2B7 mRNAs, protein, and activity in breast carcinomas compared to the adjacent normal breast specimens from the same donor were also found. These data illustrate the novel finding of UGT1A10 in human breast and confirm the expression of UGT2B7. Significant individual variation and down-regulation of expression in breast carcinomas of both isoforms were also demonstrated. These findings provide evidence that decreased UGT expression and activity could result in the promotion of carcinogenesis. (C) 2008 Elsevier Inc. All rights reserved. C1 [Starlard-Davenport, Athena; Radominska-Pandya, Anna] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Lyn-Cook, Beverly] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Radominska-Pandya, A (reprint author), Univ Arkansas Med Sci, Dept Biochem & Mol Biol, 4301 W Markham,Slot 516, Little Rock, AR 72205 USA. EM radominskaanna@uams.edu FU NIDDK NIH HHS [DK60109, R01 DK060109, R01 DK060109-02, R01 DK060109-02S1, R01 DK060109-03, R01 DK060109-03S1] NR 44 TC 21 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD JUL PY 2008 VL 73 IS 6 BP 611 EP 620 DI 10.1016/j.steroids.2008.01.019 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 300II UT WOS:000255817100005 PM 18374377 ER PT J AU Kerlin, R Hutto, D Silverman, L Francke-Carroll, S Vahle, J AF Kerlin, Roy Hutto, David Silverman, Lee Francke-Carroll, Sabine Vahle, John TI Regulatory Forum for Toxicologic Pathology: An Update SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material C1 [Kerlin, Roy] Pfizer Global Res & Dev, Drug Safety Res & Dev, Groton, CT USA. [Hutto, David] Biogen Idec Inc, Comparat Pathol, Cambridge, MA USA. [Silverman, Lee] Drug Safety Evaluat Millennium Pharmaceut Inc, Cambridge, MA USA. [Francke-Carroll, Sabine] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Vahle, John] Lilly Res Labs, Greenfield, IN 46140 USA. RP Kerlin, R (reprint author), Pfizer Global Res & Dev, Drug Safety Res & Dev, MS 8274-1210, Groton, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUL PY 2008 VL 36 IS 5 BP 760 EP 760 DI 10.1177/0192623308322009 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463VC UT WOS:000267459500015 PM 18701425 ER PT J AU Plakas, SM Jester, ELE El Said, KR Granade, HR Abraham, A Dickey, RW Scott, PS Flewelling, LJ Henry, M Blum, P Pierce, R AF Plakas, Steven M. Jester, Edward L. E. El Said, Kathleen R. Granade, Hudson R. Abraham, Ann Dickey, Robert W. Scott, Paula S. Flewelling, Leanne J. Henry, Michael Blum, Patricia Pierce, Richard TI Monitoring of brevetoxins in the Karenia brevis bloom-exposed Eastern oyster (Crassostrea virginica) SO TOXICON LA English DT Article DE Karenia brevis; brevetoxins; Eastern oyster; monitoring ID CONTROLLED EXPOSURES; GYMNODINIUM-BREVE; METABOLITES; SHELLFISH; CULTURES; TOXINS AB Brevetoxin uptake and elimination were examined in Eastern oyster (Crassostrea virginica) exposed to recurring blooms of the marine alga Karenia brevis in Sarasota Bay, FL, over a three-year period. Brevetoxins were monitored by in vitro assays (ELISA, cytotoxicity assay, and receptor binding assay) and LC-MS, with in vivo toxicity of shellfish extracts assessed by the traditional mouse bioassay. Measurements by all methods reflected well the progression and magnitude of the blooms. Highest levels recorded by mouse bioassay at bloom peak were 157 MU/100 g. Oysters were toxic by Mouse bioassay at levels 20 MU/100 g for up to two weeks after bloom dissipation, whereas brevetoxins were measurable by in vitro assays and LC-MS for several months afterwards. For the structure-based methods, summed values for the principal brevetoxin metabolites of PbTx-2 (cysteine and cysteine sulfoxide conjugates), as determined by LC-MS, were highly correlated (r(2) = 0.90) with composite toxin measurements by ELISA. ELISA and LC-MS values also correlated well (r(2) = 0.74 and 0.73, respectively) with those of mouse bioassay. Pharmacology-based cytotoxicity and receptor binding assays did not correlate as well (r(2) = 0.65), and were weakly correlated with mouse bioassay (r(2) = 0.48 and 0.50, respectively). ELISA and LC-MS methods offer rapid screening and confirmation, respectively, of brevetoxin contamination in the oyster, and are excellent alternatives to mouse bioassay for assessing oyster toxicity following K. brevis blooms. Published by Elsevier Ltd. C1 [Plakas, Steven M.; Jester, Edward L. E.; El Said, Kathleen R.; Granade, Hudson R.; Abraham, Ann; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Scott, Paula S.; Flewelling, Leanne J.] Fish & Wildlife Res Inst, St Petersburg, FL 33701 USA. [Henry, Michael; Blum, Patricia; Pierce, Richard] Mote Marine Lab, Sarasota, FL 34236 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM steven.plakas@fda.hhs.gov FU NOAA-ECOHAB [NA03NOS4780197]; Florida Fish and Wildlife Conservation Commission [99013]; U.S. FDA; Gulf Coast Seafood Laboratory FX This project was funded by NOAA-ECOHAB Award No. NA03NOS4780197, and in part by the Florida Fish and Wildlife Conservation Commission Contract #99013, with in-kind support from the U.S. FDA, Gulf Coast Seafood Laboratory. NR 12 TC 24 Z9 25 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUL PY 2008 VL 52 IS 1 BP 32 EP 38 DI 10.1016/j.toxicon.2008.04.174 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 342XI UT WOS:000258816500004 PM 18582486 ER PT J AU Pornmanee, P Sanchez, EE Lopez, G Petsom, A Khow, O Pakmanee, N Chanhome, L Sangvanich, P Perez, JC AF Pornmanee, Piboon Sanchez, Elda E. Lopez, Gonzalo Petsom, Amorn Khow, Orawan Pakmanee, Narumol Chanhome, Lawan Sangvanich, Polkit Perez, John C. TI Neutralization of lethality and proteolytic activities of Malayan pit viper (Calloselasma rhodostoma) venom with North American Virginia opossum (Didelphis virginiana) serum SO TOXICON LA English DT Article DE snake; venom; Malayan pit viper; Calloselasma rhodostoma; Virginia opossum; Didelphis virginiana; antifibrinolytic; antihemorrhagic; antigelatinase; LD(50); ED(50) ID CROTALUS-ATROX VENOM; WARM-BLOODED ANIMALS; SNAKE-VENOM; HEMORRHAGIC METALLOPROTEINASE; ANTIHEMORRHAGIC FACTOR; MARSUPIALIS SERUM; BOTHROPS-ASPER; INHIBITOR; PURIFICATION; HEMOSTASIS AB Malayan pit viper (Calloselasma rhodostoma) envenomation is a major health problem in South East Asia. During envenomation, venom components mainly affect the hemostatic system. The sera from the North American Virginia opossums (Didelphis virginiana) were able to neutralize the venom of the Malayan pit viper. These natural inhibitors Could be explored as potential therapeutics against envenomations of a variety of venomous snake species in different geographical habitats. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Sanchez, Elda E.; Lopez, Gonzalo; Perez, John C.] Texas A&M Univ, Natl Ctr Toxicol Res, Kingsville, TX 78363 USA. [Pornmanee, Piboon] Chulalongkorn Univ, Fac Sci, Program Biotechnol, Bangkok 10330, Thailand. [Petsom, Amorn; Sangvanich, Polkit] Chulalongkorn Univ, Inst Biotechnol & Genet Engn, Bangkok 10330, Thailand. [Khow, Orawan; Pakmanee, Narumol; Chanhome, Lawan] Thai Red Cross Soc, Queen Saovabha Mem Inst, Bangkok 10330, Thailand. RP Perez, JC (reprint author), Texas A&M Univ, Natl Ctr Toxicol Res, MSC 158,975 W Ave B, Kingsville, TX 78363 USA. EM kfjcp00@tamuk.edu RI Sangvanich, Polkit/A-1921-2009; OI Sangvanich, Polkit/0000-0002-2766-7505; Petsom, Amorn/0000-0001-6969-4790 FU Natural Toxins Research Center (NTRC); Texas A&M University-Kingsville:; NIH/NCRR [1 P40 RR018300-01]; NIH/RIMI [5 PMD000216-02]; NIH/SCORE [5 S06 GM008107-29] FX This research was supported in part by the Natural Toxins Research Center (NTRC), Texas A&M University-Kingsville: NIH/NCRR #1 P40 RR018300-01, NIH/RIMI #5 PMD000216-02, and NIH/SCORE #5 S06 GM008107-29. We are grateful to Nora Diaz De Leon, NTRC administrative officer for technical assistance, Mark Hockmuller and Lucy Arispe, and we gratefully acknowledge all of the NTRC staff. Thanks to Thai Red Cross Society for their venom and special thanks to the Graduate School, Chulalongkorn University. NR 28 TC 2 Z9 2 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUL PY 2008 VL 52 IS 1 BP 186 EP 189 DI 10.1016/j.toxicon.2008.04.163 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 342XI UT WOS:000258816500022 PM 18617212 ER PT J AU Wang, J Figurski, M Shaw, LM Burckart, GJ AF Wang, Jian Figurski, Michael Shaw, Leslie M. Burckart, Gilbert J. TI The impact of P-glycoprotein and Mrp2 on mycophenolic acid levels in mice SO TRANSPLANT IMMUNOLOGY LA English DT Article DE mycophenolic acid; P-glycoprotein; mdr1; Mrp2; cyclosporine; knockout mouse ID MULTIDRUG-RESISTANCE PROTEIN-2; RENAL-ALLOGRAFT RECIPIENTS; GENETIC POLYMORPHISMS; TRANSPLANT RECIPIENTS; DRUG TRANSPORT; CYCLOSPORINE-A; RAT-LIVER; PHARMACOKINETICS; MOFETIL; TACROLIMUS AB Considerable variability has been observed in the exposure to mycophenolic acid (MPA) in transplant patients. The objective of this study was to clarify the roles of two important transporters, P-gp and Mrp2, in MPA absorption using an in vivo model. FVB strain wild-type, Mdr1a/1b(-/-) and Mrp2(-/-) mice were subjected to the administration of mycophenolate mofetil (MMF) alone or MMF in combination with cyclosporine (CsA), an immunosuppressive inhibitor of P-gp and Mrp2. At 30 min following treatment, the MPA levels in Mdr1a/1b(-/-) and Mrp2(-/-) mice were markedly increased as compared to wild-type mice. In contrast to the reduced MPA concentrations observed at 60 and 120 min in the CsA-treated groups, CsA produced increased mycophenolate glucuronide (MPAG) plasma levels in CsA-treated mice at each sampling time. Brain concentrations of MPA were elevated in the Mdr1a/1b(-/-) mice at 30 min after MMF in conjunction with increased plasma MPA concentrations, but not in the wild-type or the Mrp2(-/-) mice. This study demonstrated that: a) MPA appears to be a substrate for P-gp, and b) MPA plasma concentrations are influenced by multiple membrane transporters. Drug-transporter interactions must be considered in patients receiving mycophenolic acid products. (C) 2008 Published by Elsevier B.V. C1 [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Jian] Univ So Calif, Dept Biomed Engn, Los Angeles, CA 90089 USA. [Figurski, Michael; Shaw, Leslie M.] Hosp Univ Penn, Xenobiot Toxicokinet Res Lab, Philadelphia, PA 19104 USA. RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bldg 51,Rm 3184,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM gilbert.burckart@fda.hhs.gov NR 35 TC 19 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0966-3274 J9 TRANSPL IMMUNOL JI Transpl. Immunol. PD JUL PY 2008 VL 19 IS 3-4 BP 192 EP 196 DI 10.1016/j.trim.2008.05.009 PG 5 WC Immunology; Transplantation SC Immunology; Transplantation GA 346HW UT WOS:000259060400006 PM 18586494 ER PT J AU Talarico, S Zhang, LX Marrs, CF Foxman, B Cave, MD Brennan, MJ Yang, ZH AF Talarico, Sarah Zhang, Lixin Marrs, Carl F. Foxman, Betsy Cave, M. Donald Brennan, Michael J. Yang, Zhenhua TI Mycobacterium tuberculosis PE_PGRS16 and PE_PGRS26 genetic polymorphism among clinical isolates SO TUBERCULOSIS LA English DT Article DE mycobacterium tuberculosis; genetic diversity; PE_PGRS gene family ID PE-PGRS PROTEINS; ANTIGENS AB The Mycobacterium tuberculosis PE-PGRS multigene family is thought to be involved in antigenic variation, which can be generated by differential regulation of expression and a high frequency of genetic polymorphism. PE_PGRS16 and PE_PGRS26 are inversely regulated during persistent M. tuberculosis infection, suggesting that differential regulation of the expression of these two PE-PGRS genes may have a role in latency. To understand how genetic diversity, in addition to differential regulation, contributes to antigenic variability, we investigated the sequence variations in the PE_PGRS16 and PE_PGRS26 genes among 200 clinical M. tuberculosis strains, in comparison to the sequenced laboratory strain H37Rv, using PCR and DNA sequencing. Among the 200 strains, 102 (51%) and 100 (50%) had sequence variations within the PE_PGRS16 gene and the PE_PGRS26 gene, respectively. In-frame insertions and deletions, frameshifts, and SNPs were observed in both the PE_PGRS16 gene and the PE_PGRS26 gene. However, the frequency of frameshifts and in-frame deletions differed between the two PE-PGRS genes. Examining the profile of the PE_PGRS16, PE_PGRS26, and the previously investigated PE_PGRS33 amino acid sequences for each of the 200 strains, 72 different profiles were observed with frequencies ranging from 0.5% to 13%. In conclusion, a remarkable level of genetic diversity exists in the PE_PGRS16 and PE_PGRS26 genes of A tuberculosis clinical strains. The significant sequence variations in the two PE-PGRS genes observed in this study could impact the function of these two PE-PGRS proteins and be associated with differences in the ability of the tubercle bacilli to remain persistent within the host. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Talarico, Sarah; Zhang, Lixin; Marrs, Carl F.; Foxman, Betsy; Yang, Zhenhua] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Cave, M. Donald] Cent Arkansas Vet Healthcare Ctr, Little Rock, AR 72205 USA. [Cave, M. Donald] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Coll Med, Little Rock, AR 72205 USA. [Brennan, Michael J.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yang, ZH (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 S Observ St,4648 SPH 1, Ann Arbor, MI 48109 USA. EM zhenhua@umich.edu OI Foxman, Betsy/0000-0001-6682-238X FU NIAID NIH HHS [R01 AI051975-05, R01-AI151975] NR 15 TC 31 Z9 33 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD JUL PY 2008 VL 88 IS 4 BP 283 EP 294 DI 10.1016/j.tube.2008.01.001 PG 12 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 331JG UT WOS:000258007900002 PM 18313360 ER PT J AU Anderson, S Yang, H Walderhaug, M AF Anderson, S. Yang, H. Walderhaug, M. TI Evaluation of the potential risks and benefits of us blood donor deferral scenarios SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Anderson, S.; Yang, H.; Walderhaug, M.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 10 EP 10 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700019 ER PT J AU Rios, M Grinev, A Chancey, C Daniel, S Rios, M AF Rios, M. Grinev, A. Chancey, C. Daniel, S. Rios, M. TI Genetic variability of west nile virus (WNV) in clinical isolates from SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Rios, M.; Grinev, A.; Chancey, C.; Daniel, S.; Rios, M.] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 39 EP 40 PG 2 WC Hematology SC Hematology GA 298DD UT WOS:000255665700073 ER PT J AU Walderhaug, M Menis, M AF Walderhaug, M. Menis, M. TI Simulating the impact of pandemic influenza on the us blood supply SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Walderhaug, M.; Menis, M.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2008 VL 95 SU 1 BP 40 EP 40 PG 1 WC Hematology SC Hematology GA 298DD UT WOS:000255665700075 ER PT J AU Sharma, P Parekh, A Uhl, K AF Sharma, Pellavi Parekh, Ameeta Uhl, Kathleen TI An innovative approach to determine fetal risk - The FDA Office of Women's Health pregnancy exposure registry web listing SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID TERATOGENIC RISK C1 [Sharma, Pellavi; Parekh, Ameeta; Uhl, Kathleen] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Sharma, P (reprint author), 5600 Fishers Lane,Parklawn Bldg,Room 16-6 HF-8, Rockville, MD 20857 USA. EM pellavi.sharma@fda.hhs.gov NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2008 VL 18 IS 4 BP 226 EP 228 DI 10.1016/j.whi.2008.02.006 PG 3 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 325IB UT WOS:000257581500001 PM 18468921 ER PT J AU Boucher, RM Gilbert-McClain, L Chowdhury, B AF Boucher, Robert M. Gilbert-McClain, Lydia Chowdhury, Badrul TI Hypereosinophilic syndrome and mepolizumab SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Boucher, Robert M.; Gilbert-McClain, Lydia; Chowdhury, Badrul] US FDA, Silver Spring, MD 20993 USA. RP Boucher, RM (reprint author), US FDA, Silver Spring, MD 20993 USA. EM robert.boucher@fda.hhs.gov NR 1 TC 4 Z9 4 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 JUN 26 PY 2008 VL 358 IS 26 BP 2838 EP 2839 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 317UO UT WOS:000257045900016 PM 18579821 ER PT J AU Andersen, WC Turnipseed, SB Karbiwnyk, CM Clark, SB Madson, MR Gieseker, CA Miller, RA Rummel, NG Reimschuessel, R AF Andersen, Wendy C. Turnipseed, Sherri B. Karbiwnyk, Christine M. Clark, Susan B. Madson, Mark R. Gieseker, Charles A. Miller, Ron A. Rummel, Nathan G. Reimschuessel, Renate TI Determination and confirmation of melamine residues in catfish, trout, tilapia, salmon, and shrimp by liquid chromatography with tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE melamine; cyanuric acid; fish; shrimp; LC-MS/MS; incurred muscle ID CYANURIC ACID; MUSCLE-TISSUE; PET FOOD; CYROMAZINE; CATS AB Pet and food animal (hogs, chicken, and fish) feeds were recently found to be contaminated with melamine (MEL). A quantitative and confirmatory method is presented to determine MEL residues in edible tissues from fish fed this contaminant. Edible tissues were extracted with acidic acetonitrile, defatted with dichloromethane, and cleaned up using mixed-mode cation exchange solid-phase extraction cartridges. Extracts were analyzed by liquid chromatography with tandem mass spectrometry with hydrophilic interaction chromatography and electrospray ionization in positive ion mode. Fish and shrimp tissues were fortified with 10-500 mu g/kg (ppb) of MEL with an average recovery of 63.8% (21.5% relative standard deviation, n = 121). Incurred fish tissues were generated by feeding fish up to 400 mg/kg of MEL or a combination of MEL and the related triazine cyanuric acid (CYA). MEL and CYA are known to form an insoluble complex in the kidneys, which may lead to renal failure. Fifty-five treated catfish, trout, tilapia, and salmon were analyzed after withdrawal times of 1-14 days. MEL residues were found in edible tissues from all of the fish with concentrations ranging from 0.011 to 210 mg/kg (ppm). Incurred shrimp and a survey of market seafood products were also analyzed as part of this study. C1 [Andersen, Wendy C.; Turnipseed, Sherri B.; Karbiwnyk, Christine M.] US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Clark, Susan B.; Madson, Mark R.] US FDA, Denver Fed Ctr, Denver Dist Lab, Denver, CO 80225 USA. [Gieseker, Charles A.; Miller, Ron A.; Rummel, Nathan G.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Andersen, WC (reprint author), US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. NR 31 TC 180 Z9 201 U1 6 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 25 PY 2008 VL 56 IS 12 BP 4340 EP 4347 DI 10.1021/jf800295z PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 315PZ UT WOS:000256893200009 PM 18494486 ER PT J AU DiFrancesco, C AF DiFrancesco, Christopher TI Detecting drug danger SO NEW SCIENTIST LA English DT Letter C1 US FDA, Washington, DC 20204 USA. RP DiFrancesco, C (reprint author), US FDA, Washington, DC 20204 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD JUN 21 PY 2008 VL 198 IS 2661 BP 26 EP 26 DI 10.1016/S0262-4079(08)61536-5 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 317EZ UT WOS:000257004000026 ER PT J AU FitzGerald, GA AF FitzGerald, Garret A. TI Drugs, industry, and academia SO SCIENCE LA English DT Editorial Material C1 Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. US FDA, Inst Med Forum Drug Discovery Dev & Translat, Rockville, MD 20857 USA. US FDA, Sci Board, Rockville, MD 20857 USA. RP FitzGerald, GA (reprint author), Univ Penn, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. EM garret@spirit.gcrc.upenn.edu RI FitzGerald, Garret/A-4222-2010 NR 0 TC 15 Z9 15 U1 0 U2 6 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 JUN 20 PY 2008 VL 320 IS 5883 BP 1563 EP 1563 DI 10.1126/science.1161006 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 315NM UT WOS:000256886700001 PM 18566251 ER PT J AU Sharma, A Bhattacharya, B Puri, RK Maheshwari, RK AF Sharma, Anuj Bhattacharya, Bhaskar Puri, Raj K. Maheshwari, Radha K. TI Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain SO BMC GENOMICS LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MIGRATION INHIBITORY FACTOR; NF-KAPPA-B; INDUCED DISEASE; NERVOUS-SYSTEM; EXPRESSION; MICE; ENCEPHALOMYELITIS; NEUROINVASION; PATHOGENESIS AB Background: Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied. Results: Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxc110, CxC111, Cc15, Ifr7, Ifi27 Oaslb, Fcergl, Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (> 1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively). Conclusion: Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration. C1 [Sharma, Anuj; Maheshwari, Radha K.] Uniformed Serv Univ Hlth Sci, Ctr Combat Casulaty & Life Sustainment Res, Dept Pathol, Bethesda, MD 20814 USA. [Sharma, Anuj] Birla Inst Technol & Sci, Biol Sci Grp, Pilani, Rajasthan, India. [Bhattacharya, Bhaskar; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Maheshwari, RK (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Combat Casulaty & Life Sustainment Res, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM asharma@usuhs.mil; bhaskar.bhattacharya@fda.hhs.gov; raj.puri@fda.hhs.gov; rmaheshwari@usuhs.mil NR 37 TC 22 Z9 22 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 16 PY 2008 VL 9 AR 289 DI 10.1186/1471-2164-9-289 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 322FG UT WOS:000257360000001 PM 18558011 ER PT J AU Jacobson-Kram, D Mills, G AF Jacobson-Kram, David Mills, George TI Leveraging exploratory investigational new drug studies to accelerate drug development SO CLINICAL CANCER RESEARCH LA English DT Article AB In 2006, the U.S. Food and Drug Administration published its guide on exploratory investigational new drug (IND) studies with the goal of making the approach to early-stage, pilot clinical trials more flexible within the context of current regulations, The exploratory IND allows sponsors to initiate clinical trials of limited scale with reduced preclinical requirements. These studies may be important vehicles for the conduct of proof-of-principle pharmacodynamic investigations of highly potent molecules, for bioavailability studies that require only a single drug dose to be administered, and for imaging trials that permit critical dosimetry and biodistribution investigations of new molecules. These trials were done with no therapeutic intent and must be followed by traditional dose-escalation investigations that are supported by standard preclinical toxicologic and pharmacologic studies. To the extent that they allow early evaluations of essential drug characteristics that can only be obtained in humans, exploratory IND trials have the potential to limit the cost and improve the development times of new agents. C1 [Jacobson-Kram, David] CDER, Off New Drugs, US FDA, Silver Spring, MD 20993 USA. [Mills, George] Percept Informat, Waltham, MA USA. RP Jacobson-Kram, D (reprint author), CDER, Off New Drugs, US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov NR 9 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2008 VL 14 IS 12 BP 3670 EP 3674 DI 10.1158/1078-0432.CCR-07-4558 PG 5 WC Oncology SC Oncology GA 313ZS UT WOS:000256779100007 PM 18559581 ER PT J AU Miller, HI AF Miller, Henry I. TI No member of Congress left behind SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] NIH, Bethesda, MD 20892 USA. [Miller, Henry I.] US FDA, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. EM miller@boover.stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1935-472X EI 1937-8661 J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD JUN 15 PY 2008 VL 28 IS 12 BP 6 EP 7 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 315JB UT WOS:000256873600003 ER PT J AU Pedras-Vasconcelos, JA Puig, M Sauder, C Wolbert, C Ovanesov, M Goucher, D Verthelyi, D AF Pedras-Vasconcelos, Joao A. Puig, Montserrat Sauder, Christian Wolbert, Candie Ovanesov, Mikhail Goucher, David Verthelyi, Daniela TI Immunotherapy with CpG oligonucleotides and antibodies to TNF-alpha rescues neonatal mice from lethal arenavirus-induced meningoencephalitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ARGENTINE HEMORRHAGIC-FEVER; DISEASE VIRUS-INFECTION; CENTRAL-NERVOUS-SYSTEM; PROINFLAMMATORY CYTOKINES; INTERFERON-GAMMA; GENE-EXPRESSION; TACARIBE VIRUS; ENCEPHALITIS VIRUSES; LASSA-VIRUS; BRAIN AB Viral encephalitides are life-threatening diseases in neonates partly due to the irreversible damage inflammation causes to the CNS. This study explored the role of proinflammatory cytokines in the balance between controlling viral replication and eliciting pathologic immune responses in nonlytic viral encephalitis. We show that neonatal mice challenged with arenavirus Tacaribe (TCRV) develop a meningoencephalitis characterized by high IFN-gamma and TNF-alpha levels and mild T cell infiltration. Neutralization of the TNF-alpha using mAb was associated with lower chemokine expression, reduced T cell infiltration, and lower levels of IFN-gamma, and TNF-alpha in the CNS and led to 100% survival. Moreover, treatment with Abs to TNF-alpha improved mobility and increased survival even after the mice developed bilateral hind limb paralysis. Of note, animals treated with anti-TNF-alpha Abs alone did not clear the virus despite generating Abs to TCRV. Direct activation of the innate immune response using CpG oligodeoxynucleotides in combination with anti-TNF-alpha Abs resulted in 100% survival and complete viral clearance. To our knowledge, this is the first demonstration of the use of innate immune modulators plus Abs to TNF-alpha as therapeutics for a lethal neurotropic viral infection. C1 [Pedras-Vasconcelos, Joao A.; Puig, Montserrat; Goucher, David; Verthelyi, Daniela] Ctr Drug Evaluat & Review, Off Biotechnol, Div Therapeut Proteins, Immunol Lab, Bethesda, MD 20892 USA. [Sauder, Christian; Wolbert, Candie] US FDA, Ctr Biol Evaluat & Review, Div Viral Prod, Lab Methods Dev, Bethesda, MD 20892 USA. [Ovanesov, Mikhail] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21287 USA. RP Verthelyi, D (reprint author), Bldg 29A Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Verthelyi@fda.hhs.gov NR 46 TC 8 Z9 8 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2008 VL 180 IS 12 BP 8231 EP 8240 PG 10 WC Immunology SC Immunology GA 322VY UT WOS:000257404600050 PM 18523289 ER PT J AU Date, AA Kyaw, MH Rue, AM Klahn, J Obrecht, L Krohn, T Rowland, J Rubin, S Safranek, TJ Bellini, WJ Dayan, GH AF Date, Anand A. Kyaw, Moe H. Rue, Alison M. Klahn, Julie Obrecht, LeAnn Krohn, Terry Rowland, Josh Rubin, Steve Safranek, Thomas J. Bellini, William J. Dayan, Gustavo H. TI Long-term persistence of mumps antibody after receipt of 2 measles-mumps-rubella (MMR) vaccinations and antibody response after a third MMR vaccination among a University population SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT, 2007 CL San Diego, CA SP Infect Dis Soc Amer ID UNITED-STATES; ENZYME IMMUNOASSAYS; IMMUNOGLOBULIN-G; OUTBREAK; VIRUS; FAILURE; SCHOOL; IMMUNITY; ENGLAND; UPDATE AB Background. High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure. Methods. Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for <= 5 years and >= 15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration. Results. Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 ( P = .568). The geometric mean titer ( GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 ( 95% CI, 64-148), whereas, among those vaccinated >= 15 years before blood collection, the GMT was 58 ( 95% CI, 44-76) ( P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively. Conclusions. Lower levels of NA observed among persons who received MMR2 >= 15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response. C1 [Date, Anand A.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Kyaw, Moe H.; Rue, Alison M.; Dayan, Gustavo H.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Atlanta, GA 30333 USA. [Klahn, Julie; Obrecht, LeAnn] Univ Nebraska, Kearney, NE USA. [Krohn, Terry] Two Rivers Publ Hlth Dept, Kearney, NE USA. [Rowland, Josh] Univ Nebraska Med Ctr, Nebraska Publ Hlth Lab, Omaha, NE USA. [Safranek, Thomas J.] Nebraska Hlth & Human Serv Syst, Lincoln, NE USA. [Rubin, Steve] US FDA, Bethesda, MD 20014 USA. RP Date, AA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Epidem Intelligence Serv, 1600 Clifton Rd,MS E-04, Atlanta, GA 30333 USA. EM adate@cdc.gov NR 39 TC 54 Z9 58 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 JUN 15 PY 2008 VL 197 IS 12 BP 1662 EP 1668 DI 10.1086/588197 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 307JN UT WOS:000256315300005 PM 18419346 ER PT J AU Chen, J Zhong, JL Nie, L AF Chen, Jie Zhong, Jinglin Nie, Lei TI Bayesian hierarchical modeling of drug stability data SO STATISTICS IN MEDICINE LA English DT Article DE Bayesian hierarchical model; drug stability; shelf-life ID POOLING BATCHES; SHELF-LIFE; FREQUENTIST; HYPOTHESIS AB Stability data are commonly analyzed using linear fixed or random effect model. The linear fixed effect model does not take into account the batch-to-batch variation, whereas the random effect model may suffer from the unreliable shelf-life estimates due to small sample size. Moreover, both methods do not utilize any prior information that might have been available. In this article, we propose a Bayesian hierarchical approach to modeling drug stability data. Under this hierarchical structure, we first use Bayes factor to test the poolability of batches. Given the decision on poolability of batches, we then estimate the shelf-life that applies to all batches. The approach is illustrated with two example data sets and its performance is compared in simulation studies with that of the commonly used frequentist methods. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Chen, Jie] Merck Res Labs, N Wales, PA 19454 USA. [Zhong, Jinglin; Nie, Lei] US FDA, Div Biometr, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, J (reprint author), Merck Res Labs, POB 1000,UGID-88, N Wales, PA 19454 USA. EM jie_chen@merck.com NR 23 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2008 VL 27 IS 13 BP 2361 EP 2380 DI 10.1002/sim.3220 PG 20 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 309ZR UT WOS:000256499200006 PM 18338325 ER PT J AU Haffner, ME Torrent-Farnell, J Maher, PD AF Haffner, Marlene E. Torrent-Farnell, Josep Maher, Paul D. TI Does orphan drug legislation really answer the needs of patients? SO LANCET LA English DT Article ID PHARMACOGENOMICS; DEFICIENCY; WORLD C1 [Haffner, Marlene E.] Amgen Corp, Washington, DC 20004 USA. [Torrent-Farnell, Josep; Maher, Paul D.] US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), Amgen Corp, 555 13th St NW,Suite 600 W, Washington, DC 20004 USA. EM marlene.haffner@amgen.com NR 32 TC 37 Z9 40 U1 0 U2 0 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 JUN 14 PY 2008 VL 371 IS 9629 BP 2041 EP 2044 DI 10.1016/S0140-6736(08)60873-9 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 312YY UT WOS:000256709500032 PM 18555916 ER PT J AU Boedigheimer, MJ Wolfinger, RD Bass, MB Bushel, PR Chou, JW Cooper, M Corton, JC Fostel, J Hester, S Lee, JS Liu, FL Liu, J Qian, HR Quackenbush, J Pettit, S Thompson, KL AF Boedigheimer, Michael J. Wolfinger, Russell D. Bass, Michael B. Bushel, Pierre R. Chou, Jeff W. Cooper, Matthew Corton, J. Christopher Fostel, Jennifer Hester, Susan Lee, Janice S. Liu, Fenglong Liu, Jie Qian, Hui-Rong Quackenbush, John Pettit, Syril Thompson, Karol L. TI Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories SO BMC GENOMICS LA English DT Article ID RAT-LIVER; KIDNEY; TRANSCRIPTOME; PROFILES; PATTERNS; ARRAYS; BLOOD; MODEL AB Background: The use of gene expression profiling in both clinical and laboratory settings would be enhanced by better characterization of variance due to individual, environmental, and technical factors. Meta-analysis of microarray data from untreated or vehicle-treated animals within the control arm of toxicogenomics studies could yield useful information on baseline fluctuations in gene expression, although control animal data has not been available on a scale and in a form best served for data-mining. Results: A dataset of control animal microarray expression data was assembled by a working group of the Health and Environmental Sciences Institute's Technical Committee on the Application of Genomics in Mechanism Based Risk Assessment in order to provide a public resource for assessments of variability in baseline gene expression. Data from over 500 Affymetrix microarrays from control rat liver and kidney were collected from 16 different institutions. Thirty-five biological and technical factors were obtained for each animal, describing a wide range of study characteristics, and a subset were evaluated in detail for their contribution to total variability using multivariate statistical and graphical techniques. Conclusion: The study factors that emerged as key sources of variability included gender, organ section, strain, and fasting state. These and other study factors were identified as key descriptors that should be included in the minimal information about a toxicogenomics study needed for interpretation of results by an independent source. Genes that are the most and least variable, gender-selective, or altered by fasting were also identified and functionally categorized. Better characterization of gene expression variability in control animals will aid in the design of toxicogenomics studies and in the interpretation of their results. C1 [Thompson, Karol L.] US FDA, CDER, Silver Spring, MD 20993 USA. [Boedigheimer, Michael J.; Bass, Michael B.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Bushel, Pierre R.; Chou, Jeff W.; Fostel, Jennifer] NIEHS, Res Triangle Pk, NC 27709 USA. [Cooper, Matthew] Roche Palo Alto LLC, Palo Alto, CA 94304 USA. [Corton, J. Christopher; Hester, Susan; Lee, Janice S.] US EPA, Res Triangle Pk, NC 27711 USA. [Liu, Fenglong; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liu, Jie] NIEHS, NCI, ICS, Res Triangle Pk, NC 27709 USA. [Qian, Hui-Rong] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Pettit, Syril] ILSI HESI, Washington, DC 20005 USA. RP Thompson, KL (reprint author), US FDA, CDER, Silver Spring, MD 20993 USA. EM mboedigh@amgen.com; Russ.Wolfinger@jmp.com; mbass@amgen.com; bushel@niehs.nih.gov; chou@niehs.nih.gov; matthew.cooper.mc1@roche.com; Corton.Chris@epamail.epa.gov; fostel@niehs.nih.gov; hester.susan@epa.gov; lee.janices@epa.gov; fliu@jimmy.harvard.edu; liu6@niehs.nih.gov; QIAN_HUI-RONG@LILLY.COM; johnq@jimmy.harvard.edu; spettit@ilsi.org; karol.thompson@fda.hhs.gov NR 32 TC 32 Z9 32 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 12 PY 2008 VL 9 AR 285 DI 10.1186/1471-2164-9-285 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 327PR UT WOS:000257741500001 PM 18549499 ER PT J AU MohamedMohaideen, NN Palaninathan, SK Morin, PM Williams, BJ Braunstein, M Tichy, SE Locker, J Russell, DH Jacobs, WR Sacchettini, JC AF MohamedMohaideen, Nilofar N. Palaninathan, Satheesh K. Morin, Paul M. Williams, Brad J. Braunstein, Miriam Tichy, Shane E. Locker, Joseph Russell, David H. Jacobs, William R., Jr. Sacchettini, James C. TI Structure and function of the virulence-associated high-temperature requirement a of mycobacterium tuberculosis SO BIOCHEMISTRY LA English DT Article ID HEAT-SHOCK-PROTEIN; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; SERINE-PROTEASE; PERIPLASMIC PROTEASE; SIGNAL-TRANSDUCTION; ALPHA-CHYMOTRYPSIN; MACROMOLECULAR STRUCTURES; ANOMALOUS DIFFRACTION; GAMMA-CHYMOTRYPSIN AB The high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis (Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 angstrom resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb. C1 [MohamedMohaideen, Nilofar N.; Palaninathan, Satheesh K.; Sacchettini, James C.] Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. [Williams, Brad J.; Tichy, Shane E.; Russell, David H.] Texas A&M Univ, Dept Chem, College Stn, TX 77842 USA. [Jacobs, William R., Jr.] Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10461 USA. [Morin, Paul M.] US FDA, Microbiol Sci Branch, Jamaica, NY 11433 USA. [Braunstein, Miriam] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Locker, Joseph] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. RP Sacchettini, JC (reprint author), Texas A&M Univ, Dept Biochem & Biophys, College Stn, TX 77843 USA. EM sacchett@tamu.edu RI Russell, David/C-3618-2015 OI Russell, David/0000-0003-0830-3914 FU Howard Hughes Medical Institute; NIAID NIH HHS [AI26170, F32-AI149675, R01 AI026170]; PHS HHS [AIO68135] NR 60 TC 41 Z9 42 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 10 PY 2008 VL 47 IS 23 BP 6092 EP 6102 DI 10.1021/bi701929m PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 308QT UT WOS:000256405800002 PM 18479146 ER PT J AU Wang, QZ Yang, HZ Agrawal, A Wang, NS Pfefer, TJ AF Wang, Quanzeng Yang, Huizhong Agrawal, Anant Wang, Nam Sun Pfefer, T. Joshua TI Measurement of internal tissue optical properties at ultraviolet and visible wavelengths: Development and implementation of a fiberoptic-based system SO OPTICS EXPRESS LA English DT Article ID DIFFUSE-REFLECTANCE MEASUREMENTS; HIGHLY SCATTERING TISSUES; MONTE-CARLO SIMULATIONS; HUMAN COLON TISSUE; EPITHELIAL TISSUE; ABSORPTION-COEFFICIENTS; LIGHT-PROPAGATION; TURBID MEDIA; FLUORESCENCE; SPECTROSCOPY AB A novel, multi-wavelength, fiberoptic system was constructed, evaluated and implemented to determine internal tissue optical properties at ultraviolet A (UVA) and visible ( VIS) wavelengths. Inverse modeling was performed with a neural network to estimate absorption and reduced scattering coefficients based on spatially-resolved reflectance distributions. The model was calibrated with simulated reflectance datasets generated using a condensed Monte Carlo approach with absorption coefficients up to 85 cm(-1) and reduced scattering coefficients up to 118 cm(-1). After theoretical and experimental evaluations of the system, optical properties of porcine bladder, colon, esophagus, oral mucosa, and liver were measured at 325, 375, 405, 445 and 532 nm. These data provide evidence that as wavelengths decrease into the UVA, the dominant tissue chromophore shifts from hemoglobin to structural proteins such as collagen. This system provides a high level of accuracy over a wide range of optical properties, and should be particularly useful for in situ characterization of highly attenuating biological tissues in the UVA-VIS. (c) 2008 Optical Society of America. C1 [Wang, Quanzeng; Agrawal, Anant; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Wang, Quanzeng; Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Yang, Huizhong] Jiangnan Univ, Sch Commun & Control Engn, Jiangsu 214122, Peoples R China. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov RI Pfefer, Josh/I-9055-2012; Wang, Nam Sun/E-4253-2016 NR 45 TC 22 Z9 22 U1 0 U2 15 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JUN 9 PY 2008 VL 16 IS 12 BP 8685 EP 8703 DI 10.1364/OE.16.008685 PG 19 WC Optics SC Optics GA 315ED UT WOS:000256859900037 PM 18545582 ER PT J AU Tumuluri, VS Kemper, MS Lewis, IR Prodduturi, S Majumdar, S Avery, BA Repka, MA AF Tumuluri, Venkat S. Kemper, Mark S. Lewis, Ian R. Prodduturi, Suneela Majumdar, Soumyajit Avery, Bonnie A. Repka, Michael A. TI Off-line and on-line measurements of drug-loaded hot-melt extruded films using Raman spectroscopy SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Raman spectroscopy; hot-melt extrusion; on-line monitoring; PAT; process analysis ID NEAR-INFRARED SPECTROSCOPY; EXTRUSION; RELEASE; PELLETS AB The objective of this study was to investigate the use of Raman spectroscopy for the quantitative and qualitative analysis of an active ingredient in hot-melt extruded film formulations. Clotrimazole and ketoprofen were used as the active pharmaceutical ingredients (APIs) in the subject formulations. Films were prepared with contents varying from 1 to 20% of the respective ARI. Raman spectroscopy was used to quantify these APIs, both off-line and on-line. The spectral data were also used to ascertain the physical status of these APIs in the formulations. For off-line analysis, the films were cut into small rectangles, and the amount of the API was measured using a fiber optic probe equipped with a non-contact optic (NCO). For on-line analysis, real-time measurements were accomplished by fixing the probe over the extruded film for continuous data collection. Raman spectroscopy can be a convenient alternative to HPLC and other techniques currently employed for the quantification of the API in these formulations. Because Raman is also sensitive to changes in crystallinity, employment of the technique provided additional information to deduce the crystalline status of the API. The results reported in this paper suggest the suitability of Raman for PAT applications because of the on-line capability. (C) 2008 Elsevier B.V. All rights reserved. C1 [Tumuluri, Venkat S.; Majumdar, Soumyajit; Avery, Bonnie A.; Repka, Michael A.] Univ Mississippi, Sch Pharm, Dept Pharmaceut, University, MS 38677 USA. [Kemper, Mark S.; Lewis, Ian R.] Kaiser Opt Syst, Ann Arbor, MI USA. [Prodduturi, Suneela] US FDA, St Louis, MO USA. RP Repka, MA (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmaceut, POB 1848, University, MS 38677 USA. EM marepka@olemiss.edu FU NCRR NIH HHS [P20RR021929, P20 RR021929, P20 RR021929-027759] NR 24 TC 33 Z9 34 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD JUN 5 PY 2008 VL 357 IS 1-2 BP 77 EP 84 DI 10.1016/j.ijpharm.2008.01.036 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 310NW UT WOS:000256537300011 PM 18316165 ER PT J AU Kishimoto, TK Viswanathan, K Ganguly, T Elankumaran, S Smith, S Pelzer, K Lansing, JC Sriranganathan, N Zhao, GL Galcheva-Gargova, Z Al-Hakim, A Bailey, GS Fraser, B Roy, S Rogers-Cotrone, T Buhse, L Whary, M Fox, J Nasr, M Dal Pan, GJ Shriver, Z Langer, RS Venkataraman, G Austen, KF Woodcock, J Sasisekharan, R AF Kishimoto, Takashi Kei Viswanathan, Karthik Ganguly, Tanmoy Elankumaran, Subbiah Smith, Sean Pelzer, Kevin Lansing, Jonathan C. Sriranganathan, Nammalwar Zhao, Ganlin Galcheva-Gargova, Zoya Al-Hakim, Ali Bailey, Gregory Scott Fraser, Blair Roy, Sucharita Rogers-Cotrone, Thomas Buhse, Lucinda Whary, Mark Fox, James Nasr, Moheb Dal Pan, Gerald J. Shriver, Zachary Langer, Robert S. Venkataraman, Ganesh Austen, K. Frank Woodcock, Janet Sasisekharan, Ram TI Contaminated heparin associated with adverse clinical events and activation of the contact system SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HAGEMAN-FACTOR; PLASMA KALLIKREIN; DEXTRAN SULFATE; FACTOR-XII; ALTERNATIVE PATHWAY; COMPLEMENT; ANTITHROMBIN; INHIBITION; COFACTOR; RABBIT AB Background: There is an urgent need to determine whether oversulfated chondroitin sulfate (OSCS), a compound contaminating heparin supplies worldwide, is the cause of the severe anaphylactoid reactions that have occurred after intravenous heparin administration in the United States and Germany. Methods: Heparin procured from the Food and Drug Administration, consisting of suspect lots of heparin associated with the clinical events as well as control lots of heparin, were screened in a blinded fashion both for the presence of OSCS and for any biologic activity that could potentially link the contaminant to the observed clinical adverse events. In vitro assays for the activation of the contact system and the complement cascade were performed. In addition, the ability of OSCS to recapitulate key clinical manifestations in vivo was tested in swine. Results: The OSCS found in contaminated lots of unfractionated heparin, as well as a synthetically generated OSCS reference standard, directly activated the kinin-kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins. Activation of these two pathways was unexpectedly linked and dependent on fluid-phase activation of factor XII. Screening of plasma samples from various species indicated that swine and humans are sensitive to the effects of OSCS in a similar manner. OSCS-containing heparin and synthetically derived OSCS induced hypotension associated with kallikrein activation when administered by intravenous infusion in swine. Conclusions: Our results provide a scientific rationale for a potential biologic link between the presence of OSCS in suspect lots of heparin and the observed clinical adverse events. An assay to assess the amidolytic activity of kallikrein can supplement analytic tests to protect the heparin supply chain by screening for OSCS and other highly sulfated polysaccharide contaminants of heparin that can activate the contact system. C1 [Viswanathan, Karthik; Whary, Mark; Fox, James; Shriver, Zachary; Langer, Robert S.; Venkataraman, Ganesh; Sasisekharan, Ram] MIT, Dept Biol Engn, Harvard Mit Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kishimoto, Takashi Kei; Ganguly, Tanmoy; Smith, Sean; Lansing, Jonathan C.; Zhao, Ganlin; Galcheva-Gargova, Zoya; Bailey, Gregory Scott; Roy, Sucharita; Shriver, Zachary; Venkataraman, Ganesh] Momenta Pharmaceut, Cambridge, MA USA. [Elankumaran, Subbiah; Pelzer, Kevin; Sriranganathan, Nammalwar; Rogers-Cotrone, Thomas] Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Blacksburg, VA 24061 USA. [Al-Hakim, Ali; Fraser, Blair; Buhse, Lucinda; Nasr, Moheb; Dal Pan, Gerald J.; Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Austen, K. Frank] Brigham & Womens Hosp, Boston, MA 02115 USA. [Austen, K. Frank] Harvard Univ, Sch Med, Boston, MA USA. RP Sasisekharan, R (reprint author), MIT, Dept Biol Engn, Harvard Mit Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, 77 Massachusetts Ave,16-561, Cambridge, MA 02139 USA. EM rams@mit.edu RI Subbiah, Elankumaran/E-9277-2010; Pelzer, Kevin/S-3556-2016 OI Subbiah, Elankumaran/0000-0003-4135-9477; Pelzer, Kevin/0000-0001-6688-4986 FU NHLBI NIH HHS [R01 HL080278, HL080278-01]; NIGMS NIH HHS [GM57073, R01 GM057073, R37 GM057073] NR 20 TC 337 Z9 347 U1 3 U2 32 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 JUN 5 PY 2008 VL 358 IS 23 BP 2457 EP 2467 DI 10.1056/NEJMoa0803200 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 308HY UT WOS:000256380700005 PM 18434646 ER PT J AU Marcucci, KT Martina, Y Harrison, F Wilson, CA Salomon, DR AF Marcucci, Katherine T. Martina, Yuri Harrison, Frank Wilson, Carolyn A. Salomon, Daniel R. TI Functional hierarchy of two L domains in porcine endogenous retrovirus (PERV) that influence release and infectivity SO VIROLOGY LA English DT Article DE porcine endogenous retrovirus (PERV); late (L) domains; viral assembly; infectivity ID LEUKEMIA-VIRUS TYPE-1; ROUS-SARCOMA-VIRUS; LATE ASSEMBLY DOMAIN; PARTICLE RELEASE; GAG PROTEIN; IN-VITRO; TSG101; MOTIF; PPPY; MUTATIONS AB The porcine endogenous retrovirus (PERV) Gag protein contains two late (L) domain motifs, PPPY and P(F/S)AP. Using viral release assays we demonstrate that PPPY is the dominant L domain involved in PERV release. PFAP represents a novel retroviral L domain variant and is defined by abnormal viral assembly phenotypes visualized by electron microscopy and attenuation of early PERV release as measured by viral genomes. PSAP is functionally dominant over PFAP in early PERV release. PSAP virions are 3.5-fold more infectious in vitro by TCID(50) and in vivo results in more RNA positive tissues and higher levels of proviral DNA using our human PERV-A receptor (HuPAR-2) transgetric mouse model [Martina, Y., Marcucci, K.T., Cherqui, S., Szabo, A., Drysdale, T., Srinivisan, U., Wilson, C.A., Patience, C., Salomon, D.R., 2006. Mice transgenic for a human porcine endogenous retrovirus receptor are susceptible to productive viral infection. J. Virol. 80 (7), 3135-3146]. The functional hierarchies displayed by PERV L domains, demonstrates that L domain selection in viral evolution exists to promote efficient viral assembly, release and infectivity in the virus-host context. (c) 2008 Elsevier Inc. All rights reserved. C1 [Marcucci, Katherine T.; Martina, Yuri; Harrison, Frank; Salomon, Daniel R.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Marcucci, Katherine T.] Scripps Res Inst, Kellogg Sch Sci & Technol, La Jolla, CA 92037 USA. [Wilson, Carolyn A.] US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Salomon, DR (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM katiem@scripps.edu; yuri.martina@adaltis.com; harrison@scripps.edu; carolyn.wilson@fda.hhs.gov; dsalomon@scripps.edu RI Salomon, Daniel/E-9380-2012 FU NIAID NIH HHS [R01 AI 52349, R01 AI052349, R56 AI052349, R56 AI052349-05A2] NR 46 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 5 PY 2008 VL 375 IS 2 BP 637 EP 645 DI 10.1016/j.virol.2008.02.017 PG 9 WC Virology SC Virology GA 304JQ UT WOS:000256106200031 PM 18355887 ER PT J AU Sutherland, A Izurieta, H Ball, R Braun, MM Miller, ER Broder, KR Slade, BA Iskander, JK Kroger, AT Markowitz, LE Huang, WT AF Sutherland, A. Izurieta, H. Ball, R. Braun, M. M. Miller, E. R. Broder, K. R. Slade, B. A. Iskander, J. K. Kroger, A. T. Markowitz, L. E. Huang, W. T. TI Syncope after vaccination - United States, January 2005 to July 2007 (Reprinted from MMWR, vol 57, pg 457-460, 2008) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID IMMUNIZATION; SAFETY C1 [Sutherland, A.; Izurieta, H.; Ball, R.; Braun, M. M.] US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Miller, E. R.; Broder, K. R.; Slade, B. A.; Iskander, J. K.] CDC, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA 30333 USA. [Kroger, A. T.] CDC, Immunizat Svcs Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Markowitz, L. E.] CDC, Div STD Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA 30333 USA. [Huang, W. T.] CDC, EIS Officer, Atlanta, GA 30333 USA. RP Sutherland, A (reprint author), US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RI Huang, Wan-Ting/E-3497-2010 OI Huang, Wan-Ting/0000-0002-4344-9567 NR 10 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 4 PY 2008 VL 299 IS 21 BP 2502 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 308AR UT WOS:000256361200011 ER PT J AU Lionberger, RA Lee, SL Lee, L Raw, A Yu, LX AF Lionberger, Robert A. Lee, Sau Lawrence Lee, LaiMing Raw, Andre Yu, Lawrence X. TI Quality by design: Concepts for ANDAs SO AAPS JOURNAL LA English DT Review DE control strategy; critical material attributes; critical process parameters; design space; quality by design AB Quality by design is an essential part of the modern approach to pharmaceutical quality. There is much confusion among pharmaceutical scientists in generic drug industry about the appropriate element and terminology of quality by design. This paper discusses quality by design for generic drugs and presents a summary of the key terminology. The elements of quality by design are examined and a consistent nomenclature for quality by design, critical quality attribute, critical process parameter, critical material attribute, and control strategy is proposed. Agreement on these key concepts will allow discussion of the application of these concepts to abbreviated new drug applications to progress. C1 [Lionberger, Robert A.; Lee, Sau Lawrence; Lee, LaiMing; Raw, Andre; Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yu, LX (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM lawrence.yu@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 24 TC 89 Z9 91 U1 2 U2 39 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD JUN PY 2008 VL 10 IS 2 BP 268 EP 276 DI 10.1208/s12248-008-9026-7 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347IK UT WOS:000259133600005 PM 18465252 ER PT J AU Volpe, DA Asafu-Adjaye, EB Ellison, CD Doddapaneni, S Uppoor, RS Khan, MA AF Volpe, Donna A. Asafu-Adjaye, Ebenezer B. Ellison, Christopher D. Doddapaneni, Suresh Uppoor, Ramana S. Khan, Mansoor A. TI Effect of ethanol on opioid drug permeability through Caco-2 cell monolayers SO AAPS JOURNAL LA English DT Article DE Caco-2; ethanol; hydromorphone; oxycodone; oxymorphone; permeability ID ALCOHOL; HYDROMORPHONE; BIOAVAILABILITY C1 [Volpe, Donna A.; Asafu-Adjaye, Ebenezer B.; Ellison, Christopher D.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Doddapaneni, Suresh; Uppoor, Ramana S.] US FDA, Ctr Drug Evaluat & Res, Div Clin Pharmacol, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Div Prod Qual Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.volpe@fda.hhs.gov NR 18 TC 12 Z9 12 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD JUN PY 2008 VL 10 IS 2 BP 360 EP 362 DI 10.1208/s12248-008-9046-3 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347IK UT WOS:000259133600016 PM 18592381 ER PT J AU Polli, JE Abrahamsson, BSI Yu, LX Amidon, GL Baldoni, JM Cook, JA Fackler, P Hartauer, K Johnston, G Krill, SL Lipper, RA Malick, WA Shah, VP Sun, DX Winkle, HN Wu, YH Zhang, H AF Polli, James E. Abrahamsson, Bertil S. I. Yu, Lawrence X. Amidon, Gordon L. Baldoni, John M. Cook, Jack A. Fackler, Paul Hartauer, Kerry Johnston, Gordon Krill, Steve L. Lipper, Robert A. Malick, Waseem A. Shah, Vinod P. Sun, Duxin Winkle, Helen N. Wu, Yunhui Zhang, Hua TI Summary workshop report: Bioequivalence, biopharmaceutics classification system, and beyond SO AAPS JOURNAL LA English DT Editorial Material DE bioavailability; bioequivalence; biopharmaceutics classification system (BCS); oral absorption; permeability; regulatory science; solubility AB The workshop "Bioequivalence, Biopharmaceutics Classification System, and Beyond" was held May 21-23, 2007 in North Bethesda, MD, USA. This workshop provided an opportunity for pharmaceutical scientists to discuss the FDA guidance on the Biopharmaceutics Classification System (BCS), bioequivalence of oral products, and related FDA initiatives such as the FDA Critical Path Initiative. The objective of this Summary Workshop Report is to document the main points from this workshop. Key highlights of the workshop were (a) the described granting of over a dozen BCS-based biowaivers by the FDA for Class I drugs whose formulations exhibit rapid dissolution, (b) continued scientific support for biowaivers for Class III compounds whose formulations exhibit very rapid dissolution, (c) scientific support for a number of permeability methodologies to assess BCS permeability class, (d) utilization of BCS in pharmaceutical research and development, and (e) scientific progress in in vitro dissolution methods to predict dosage form performance. C1 [Polli, James E.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Abrahamsson, Bertil S. I.] AstraZeneca R&D, Molndal, Sweden. [Yu, Lawrence X.; Winkle, Helen N.] US FDA, Ctr Drug Evaluat, Rockville, MD 20857 USA. [Amidon, Gordon L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Baldoni, John M.] Glaxo SmithKline, Raleigh, NC 27709 USA. [Cook, Jack A.] Pfizer Global Res & Dev, New London, CT 06324 USA. [Fackler, Paul] Teva Pharmaceut USA, N Wales, PA 19454 USA. [Hartauer, Kerry] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Johnston, Gordon] Gener Pharmaceut Assoc, Arlington, VA 22201 USA. [Krill, Steve L.] Boehringer Ingelheim Pharmaceut, Ridgefield, CT 06877 USA. [Lipper, Robert A.] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. [Malick, Waseem A.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Shah, Vinod P.] North Potomac, Montgomery, MD 20878 USA. [Sun, Duxin] Ohio State Univ, Columbus, OH 43210 USA. [Wu, Yunhui] Merck & Co Inc, West Point, PA 19486 USA. [Zhang, Hua] AstraZeneca Pharmaceut LP, Wilmington, DE 19850 USA. RP Polli, JE (reprint author), Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. EM jpolli@rx.umaryland.edu NR 19 TC 33 Z9 36 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD JUN PY 2008 VL 10 IS 2 BP 373 EP 379 DI 10.1208/s12248-008-9040-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 347IK UT WOS:000259133600018 PM 18679807 ER PT J AU Wang, C Slikker, W AF Wang, Cheng Slikker, William TI Strategies and experimental models for evaluating anesthetics: Effects on the developing nervous system SO ANESTHESIA AND ANALGESIA LA English DT Article ID METHYL-D-ASPARTATE; CELL-ADHESION MOLECULE; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; INDUCED CORTICAL APOPTOSIS; DEVELOPING RAT-BRAIN; NMDA RECEPTOR; UP-REGULATION; CHRONIC PHENCYCLIDINE; PROCEDURAL PAIN; BASAL GANGLIA AB Advances in pediatric and obstetric surgery have resulted in an increase in the duration and complexity of procedures requiring anesthesia. It has been reported that anesthetic drugs cause widespread and dose-dependent apoptosis in the developing rat brain. The similarity of the physiology, pharmacology, metabolism, and reproductive systems of the nonhuman primate to that of the human especially during pregnancy, make the monkey an exceptionally good animal model for assessing potential neurotoxic effects of anesthetics. The window of vulnerability to these neuronal effects of pediatric anesthetics is restricted to the period of rapid synaptogenesis, also known as the brain growth spurt period. To minimize the risks to children resulting from the use of anesthesia, the following questions should be addressed: 1. What is the relationship between exposure and brain cell loss for drugs commonly used in the practice of pediatric anesthesia (inhaled anesthetics, midazolam, ketamine, and nitrous oxide)? 2. Are there "class effects," or does each drug need to be considered independently? 3. Are there important interactions among the drugs used as anesthetics contributing to the risk of brain cell death? 4. What is the likely period of human vulnerability? Pharmacogeneomic/system biology approaches have great potential for helping to advance the understanding of brain-related biological processes, including neuronal plasticity and neurotoxicity. Because of the complexity and temporal features of how developmental neurotoxicity is manifested, pharmacogenomic/systems biology approaches may prove to be useful tools for enhancing our understanding of the biological processes induced by anesthetics. Therefore, the main purpose of this review is to describe the application of these approaches and models, as well as protection strategies, especially as regards the issue of anesthetic-induced neuronal cell death during development. Much of the discussion that follows is based on experiments conducted with ketamine. This is due in part to the use of ketamine in the early studies and the volume of preclinical experimental work performed with this drug, as well as its use in anesthetic studies in developing rodents and nonhuman primates. Although ketamine use in pediatric anesthesia is relatively limited, the findings of the studies are sufficiently strong to merit concern about the N-methyl-D-aspartate antagonist drugs as a class. Our focus on ketamine should not be construed as implying that the risk of neurodegeneration with ketamine is greater, or less, than with other anesthetics. We are simply describing the effects where we have the most preclinical data. C1 [Wang, Cheng; Slikker, William] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov NR 100 TC 49 Z9 53 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2008 VL 106 IS 6 BP 1643 EP 1658 DI 10.1213/ane.0b013e3181732c01 PG 16 WC Anesthesiology SC Anesthesiology GA 303XU UT WOS:000256075200010 PM 18499593 ER PT J AU Amur, S Frueh, FW Lesko, LJ Huang, SM AF Amur, Shashi Frueh, Felix W. Lesko, Lawrence J. Huang, Shiew-Mei TI Integration and use of biomarkers in drug development, regulation and clinical practice: a US regulatory perspective SO BIOMARKERS IN MEDICINE LA English DT Review DE biomarker; clinical practice; drug development; FDA; genetic test; genomic test; voluntary submission ID HER-2/NEU GENE AMPLIFICATION; IN-SITU HYBRIDIZATION; PERSONALIZED MEDICINE; HYPERSENSITIVITY; QUALIFICATION; CARCINOMA; WARFARIN; ABACAVIR; REALITY; VISION AB The US FDA encourages the integration of biomarkers in drug development and their appropriate use in clinical practice. It is believed that this approach will help alleviate stagnation and foster innovation in the development of new medical products, and, ultimately, lead to more personalized medicine. To facilitate the use of biomarkers in drug development and clinical practice, the FDA organized workshops, issued guidances, established a voluntary submission process, developed online educational tools and, most importantly, strives to ensure the integration of this information into drug labels, for example, via the update of existing labels, or the inclusion of appropriate language in new drug labels. A pilot process has been set up to qualify novel biomarkers that are not associated with specific drug products, but are of more common use (e.g., biomarkers for drug safety). In addition, the FDA has initiated the creation of various consortia that are working towards the identification and characterization of exploratory biomarkers in order to qualify them for a specific use. C1 [Amur, Shashi; Frueh, Felix W.; Lesko, Lawrence J.; Huang, Shiew-Mei] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 32 TC 51 Z9 53 U1 2 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD JUN PY 2008 VL 2 IS 3 BP 305 EP 311 DI 10.2217/17520363.2.3.305 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344IZ UT WOS:000258921400012 PM 20477416 ER PT J AU Xiao, YM Word, B Starlard-Davenport, A Haefele, A Lyn-Cook, BD Hammons, G AF Xiao, Yongmei Word, Beverly Starlard-Davenport, Atena Haefele, Aaron Lyn-Cook, Beverly D. Hammons, George TI Age and gender affect DNMT3a and DNMT3b expression in human liver SO CELL BIOLOGY AND TOXICOLOGY LA English DT Article DE ageing; DNMT3a; DNMT3b; gender; human liver ID METHYLTRANSFERASE GENE-EXPRESSION; CPG ISLAND HYPERMETHYLATION; ZINC-FINGER PROTEINS; DE-NOVO METHYLATION; DNA-METHYLTRANSFERASE; HUMAN FIBROBLASTS; CANCER-CELLS; HEPATOCELLULAR CARCINOMAS; MAINTENANCE METHYLATION; SIGNALING PATHWAY AB DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b. Elevated levels of DNMTs have been found in cancer cells and in several types of human tumors. A polymorphism found in DNMT3b has been associated with increased risk for several cancers. The factors influencing DNMT expression in human tissues have not been clearly determined. he present study examined TDNMT3a and DNMT3b levels in human liver tissue samples and compared the effect of ageing, cigarette smoking, and gender. DNMT3a and DNMT3b expression levels in the samples from older individuals (56-78 years, n = 28) were both significantly higher than those of the younger group (16-48 years, n = 27) (73.2 +/- 3.4 vs 8.3 +/- 2.8 and 56.1 +/- 1.9 vs 17.5 +/- 5.7, respectively; p < 0.05). Levels of DNMT3b in females were significantly higher than those in males (75.4 +/- 2.2 vs 16.3 +/- 4.7; p < 0.05); however, DNMT3a levels were similar for females and males (52.7 +/- 2.7 vs 48.4 +/- 2.0). Expression levels of DNMT3a and DNMT3b were similar in smokers and nonsmokers (58.1 +/- 3.5 vs 60.8 +/- 3.1 and 54.5 +/- 2.3 vs 48.3 +/- 1.8, respectively). Genotyping for DNMT3b (C -> T) variant in this sample pool showed a frequency distribution of CC (41%), CT (50%), and TT (9%). The findings from this study suggest that ageing and gender may be important factors influencing DNA methylation status. C1 [Hammons, George] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Xiao, Yongmei; Word, Beverly; Starlard-Davenport, Atena; Haefele, Aaron; Lyn-Cook, Beverly D.; Hammons, George] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Hammons, G (reprint author), Natl Ctr Toxicol Res, HFT-100, Jefferson, AR 72079 USA. EM ghammons@nctr.fda.gov NR 58 TC 23 Z9 23 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0742-2091 J9 CELL BIOL TOXICOL JI Cell Biol. Toxicol. PD JUN PY 2008 VL 24 IS 3 BP 265 EP 272 DI 10.1007/s10565-007-9035-9 PG 8 WC Cell Biology; Toxicology SC Cell Biology; Toxicology GA 291IO UT WOS:000255190400007 PM 17929180 ER PT J AU Juneja, V Keegan, P Gootenberg, JE Rothmann, MD Shen, YL Lee, KY Weiss, KD Pazdur, R AF Juneja, Vinni Keegan, Patricia Gootenberg, Joseph E. Rothmann, Mark D. Shen, Yuan Li Lee, Kyung Y. Weiss, Karen D. Pazdur, Richard TI Continuing reassessment of the risks of erythropoiesis-stimulating agents in patients with cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PLACEBO-CONTROLLED TRIAL; TRANSFUSION-TRANSMITTED INFECTIONS; CELL LUNG-CANCER; DOUBLE-BLIND; RESIDUAL RISK; EPOETIN-ALPHA; DISEASE; SAFETY; ANEMIA AB Purpose: Erythropoiesis-stimulating agents (ESA) are approved for the treatment of anemia in patients with nonmyeloid malignancies whose anemia is due to the effect of concomitantly administered chemotherapy. Since the 1993 approval of epoetin alfa in patients with cancer, the risk of thrombovascular events, decreased survival, and poorer tumor control have been increasingly recognized. The risks of ESAs in patients with cancer and the design of trials to assess these risks have been the topic of discussion at two Oncologic Drugs Advisory Committees in 2004 and 2007. Experimental Design: Evaluation of randomized clinical trials comparing use of ESAs to transfusion support alone in patients with active cancer. Results: Six studies (Breast Cancer Erythropoeitin Survival Trial, Evaluation of NeoRecormon on outcome in Head And Neck Cancer in Europe, Danish Head and Neck Cancer, Lymphoid Malignancy, CAN-20, and Anemia of Cancer) investigating ESAs in oncology patients showed decreased survival, decreased duration of locoregional tumor control, and/or increased risk of thrombovascular events. In these six studies, ESA dosing was targeted to achieve and maintain hemoglobin values in excess of current recommendations, and in three of the six studies, ESAs were administered to patients not receiving chemotherapy. Conclusions: ESAs increase the risk of thrombovascular events and result in decreased survival and poorer tumor control when administered to achieve hemoglobin levels of >= 12 g/dL in patients with nonmyeloid malignancies. No completed or ongoing randomized, controlled trial has addressed safety issues of ESAs in patients with chemotherapy-associated anemia using currently approved dosing regimens in an epidermal tumor type. Additional studies are needed to better characterize these risks. C1 [Juneja, Vinni; Keegan, Patricia; Gootenberg, Joseph E.; Rothmann, Mark D.; Shen, Yuan Li; Lee, Kyung Y.; Weiss, Karen D.; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Juneja, V (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, White Oak Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM vinni.juneja@fda.hhs.gov NR 14 TC 31 Z9 33 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 JUN 1 PY 2008 VL 14 IS 11 BP 3242 EP 3247 DI 10.1158/1078-0432.CCR-07-1872 PG 6 WC Oncology SC Oncology GA 308RY UT WOS:000256408900002 PM 18519748 ER PT J AU Roberts, R McCune, SK AF Roberts, R. McCune, S. K. TI Animal studies in the development of medical countermeasures SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB The mission of the US Food and Drug Administration (FDA) is to protect public health by ensuring the safety, efficacy, and quality of drugs. In drug development, animal studies play a key role in assessing the safety (toxicology), pharmacokinetics (PK), and proof-of-concept efficacy of a new product. When clinical studies are neither ethical nor feasible to conduct, the Animal Rule (67 FR 37988, 2002) introduces the potential for drug (e. g., countermeasure) approval based on efficacy studies in animals, and appropriate human safety and pharmacokinetic information. The Center for Drug Evaluation and Research is responsible for the review of drug and therapeutic biologic applications. The use of the word "drugs" in this paper will henceforth refer to both drugs and therapeutic biologics (e. g., monoclonal antibodies and small protein molecules). Information about vaccines and other biologics, such as antisera and blood products, should be obtained from the Center for Biologic Evaluation and Research. C1 [Roberts, R.; McCune, S. K.] US FDA, Silver Spring, MD USA. RP Roberts, R (reprint author), US FDA, Silver Spring, MD USA. EM rosemary.roberts@fda.hhs.gov NR 3 TC 16 Z9 16 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2008 VL 83 IS 6 BP 918 EP 920 DI 10.1038/clpt.2008.23 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 303YU UT WOS:000256078000022 PM 18323860 ER PT J AU Hodges, GS Hodges, AC Unruh, CM AF Hodges, G. S. Hodges, A. C. Unruh, C. M. TI A new exotic pest for Florida's natural areas: Crypticerya genistae (Hemiptera : Monophlebidae) SO FLORIDA ENTOMOLOGIST LA English DT Editorial Material C1 FDACS, Div Plant Ind, Gainesville, FL 32608 USA. Univ Florida, Dept Entomol & Nematol, Gainesville, FL 32611 USA. Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. RP Hodges, GS (reprint author), FDACS, Div Plant Ind, 1911 SW 34th St, Gainesville, FL 32608 USA. NR 3 TC 5 Z9 6 U1 1 U2 1 PU FLORIDA ENTOMOLOGICAL SOC PI LUTZ PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA SN 0015-4040 J9 FLA ENTOMOL JI Fla. Entomol. PD JUN PY 2008 VL 91 IS 2 BP 335 EP 337 DI 10.1653/0015-4040(2008)91[335:ANEPFF]2.0.CO;2 PG 3 WC Entomology SC Entomology GA 308LI UT WOS:000256391200030 ER PT J AU Blodgett, RJ AF Blodgett, Robert J. TI Mathematical treatment of plates with colony counts outside the acceptable range (vol 25, pg 92, 2008) SO FOOD MICROBIOLOGY LA English DT Correction C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Room 2D-011,HFS-012,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM robert.blodgett@fda.hhs.gov NR 1 TC 1 Z9 1 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2008 VL 25 IS 4 BP 633 EP 633 DI 10.1016/j.fm.2008.01.006 PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 306CJ UT WOS:000256225600012 ER PT J AU Senior, JR AF Senior, John R. TI What is idiosyncratic hepatotoxicity? What is it not? SO HEPATOLOGY LA English DT Editorial Material ID INDUCED LIVER-INJURY; DRUG-REACTIONS C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Senior, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, 10903 New Hampshire Ave 22 3482, Silver Spring, MD 20993 USA. EM john.senior@fda.hhs.gov NR 20 TC 20 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2008 VL 47 IS 6 BP 1813 EP 1815 DI 10.1002/hep.22332 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 308LL UT WOS:000256391500007 PM 18508312 ER PT J AU Barrett, HH Furenlid, LR Freed, M Hesterman, JY Kupinski, MA Clarkson, E Whitaker, MK AF Barrett, Harrison H. Furenlid, Lars R. Freed, Melanie Hesterman, Jacob Y. Kupinski, Matthew A. Clarkson, Eric Whitaker, Meredith K. TI Adaptive SPECT SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE adaptive imaging; Hotelling observer; image quality; single-photon emission computed tomography (SPECT); Wiener estimator ID HOTELLING TRACE CRITERION; SMALL ANIMAL SPECT; IMAGE QUALITY; OBSERVER PERFORMANCE; OBJECTIVE ASSESSMENT; QUANTUM-NOISE; RESOLUTION; OPTICS; SYSTEM; MRI AB Adaptive imaging systems alter their data-acquisition configuration or protocol in response to the image information received. An adaptive pinhole single-photon emission computed tomography (SPECT) system might acquire an initial scout image to obtain preliminary information about the radiotracer distribution and then adjust the configuration or sizes of the pinholes, the magnifications, or the projection angles in order to improve performance. This paper briefly describes two small-animal SPECT systems that allow this flexibility and then presents a framework for evaluating adaptive systems in general, and adaptive SPECT systems in particular. The evaluation is in terms of the performance of linear observers on detection or estimation tasks. Expressions are derived for the ideal linear (Hotelling) observer and the ideal linear (Wiener) estimator with adaptive imaging. Detailed expressions for the performance figures of merit are given, and possible adaptation rules are discussed. C1 [Barrett, Harrison H.; Furenlid, Lars R.; Freed, Melanie; Hesterman, Jacob Y.; Kupinski, Matthew A.; Clarkson, Eric; Whitaker, Meredith K.] Univ Arizona, Ctr Gamma Ray Imaging, Tucson, AZ 85724 USA. [Barrett, Harrison H.; Furenlid, Lars R.; Freed, Melanie; Hesterman, Jacob Y.; Kupinski, Matthew A.; Clarkson, Eric; Whitaker, Meredith K.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. [Barrett, Harrison H.; Furenlid, Lars R.; Freed, Melanie; Hesterman, Jacob Y.; Kupinski, Matthew A.; Clarkson, Eric; Whitaker, Meredith K.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. [Freed, Melanie] US FDA, Silver Spring, MD 20993 USA. RP Barrett, HH (reprint author), Univ Arizona, Ctr Gamma Ray Imaging, Tucson, AZ 85724 USA. EM barrett@radiology.arizona.edu FU NIBIB NIH HHS [P41 EB 002035, P41 EB002035, P41 EB002035-09, R37 EB 000803, R37 EB000803, R37 EB000803-18] NR 61 TC 52 Z9 52 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUN PY 2008 VL 27 IS 6 BP 775 EP 788 DI 10.1109/TMI.2007.913241 PG 14 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 307YD UT WOS:000256354600005 PM 18541485 ER PT J AU Laugier, P Wear, KA Waters, KR AF Laugier, Pascal Wear, Keith A. Waters, Kendall R. TI Introduction to the special issue on diagnostic and therapeutic applications of ultrasound in bone - Part I SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Editorial Material C1 [Laugier, Pascal] Univ Paris 06, Lab Imagerie Parametr, Paris, France. [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Waters, Kendall R.] Volcano Corp, Cleveland, OH USA. RP Laugier, P (reprint author), Univ Paris 06, Lab Imagerie Parametr, Paris, France. NR 0 TC 2 Z9 3 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUN PY 2008 VL 55 IS 6 BP 1177 EP 1178 DI 10.1109/TUFFC.2008.781 PG 2 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 303FI UT WOS:000256026000002 ER PT J AU Sung, K Khan, SA Nawaz, MS AF Sung, Kidon Khan, Saeed A. Nawaz, Mohamed S. TI Genetic diversity of Tn1546-like elements in clinical isolates of vancomycin-resistant enterococci SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE van operon; hybridisation; insertion element; transposon ID VANA GLYCOPEPTIDE RESISTANCE; DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSORS; FAECIUM BM4147; CLUSTER AB We have investigated the genetic diversity of Tn1546 among 17 vancomycin-resistant enterococci (VRE) isolates of Enterococcus faecium. Most of these multidrug-resistant strains harboured plasmids of 2 kb to > 300 kb in size. The vancomycin resistance marker vanA was located on both the plasmid and the chromosomal DNA. VRE isolates 18 and 22 failed to amplify the orf1-IR(R) and orf2-IR(R) but contained the orf1 and orf2. VRE3 failed to amplify the orf1, orf2, vanR and vanS, but still yielded a larger than expected (4.4 kb vs. 2.3 kb) vanSH amplicon. VRE9, 10, 21 and 22 also yielded larger (5.5 kb) vanSH amplicons; all others yielded 4.0 kb vanSH amplicons. Sequence analysis of the vanSH amplicons from VRE9, 10, 21 and 22 revealed the presence of IS1251 between the vanS and vanH genes in these isolates. The observed vanSH amplicon from VRE3 contained orf31, orf30 and orf29 of the plasmid pRUM followed by the vanHAXYZ region of Tn1546. Translocation of Tn1546 to a pRUM-like plasmid in VRE3 resulted in the loss of its orf1, orf2, vanR and vanS elements and a loss of the orf32 of pRUM, leading to a unique structural arrangement of vanA elements that is hitherto unknown. Published by Elsevier B. V. on behalf of International Society of Chemotherapy. C1 [Sung, Kidon; Khan, Saeed A.; Nawaz, Mohamed S.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM saeed.khan@fda.hhs.gov NR 16 TC 9 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD JUN PY 2008 VL 31 IS 6 BP 549 EP 554 DI 10.1016/j.ijantimicag.2008.01.030 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 301PK UT WOS:000255907900010 PM 18462926 ER PT J AU Shah, S Kapoor, A Ding, J Guion, P Petrisor, D Karanian, J Pritchard, WF Stoianovici, D Wood, BJ Cleary, K AF Shah, S. Kapoor, A. Ding, J. Guion, P. Petrisor, D. Karanian, J. Pritchard, W. F. Stoianovici, D. Wood, B. J. Cleary, K. TI Robotically assisted needle driver: evaluation of safety release, force profiles, and needle spin in a swine abdominal model SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Robotics/instrumentation; Safety; Minimally invasive; Rotating needle driver AB Objective The objective of this study was to evaluate two features of a new rotating needle driver in a domestic swine model: (1) a quick release safety mechanism and (2) the impact of spinning the needle on the force profile. Materials and methods The experiments were conducted in a multi-modality interventional suite. An initial CT scan was obtained to determine the location of the target, in the liver or lung. The robotic arm was positioned directly over the marked skin entry point. Control parameters were set to rotation speeds of 0, 90, or 180 rpm. The breakaway force magnitude was also preset to a predetermined force. The physician used the joystick to drive the needle towards the target while the system recorded needle insertion depth and forces. Results Sixteen insertions were completed (14 in liver and 2 in lung) and 12 released the needle upon the desired set force. The mean response time of the quick release mechanism was 202 +/- 39 ms. Needle rotation resulted in reduced insertion force. Conclusion The robot-assisted needle insertion system was shown to be functional in a multimodality imaging clinical environment on a swine model. The system has potential future applications in precision minimally invasive procedures including biopsy and radiofrequency ablation. C1 [Shah, S.; Kapoor, A.; Guion, P.; Wood, B. J.] Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Ding, J.; Cleary, K.] Georgetown Univ, Dept Radiol, Imaging Sci & Informat Syst ISIS Ctr, Washington, DC USA. [Petrisor, D.; Stoianovici, D.] Johns Hopkins Med, Dept Urol, URobot Lab, Baltimore, MD USA. [Karanian, J.; Pritchard, W. F.] US FDA, Lab Cardiovasc & Intervent Therapeut, Laurel, MD USA. RP Shah, S (reprint author), Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM shahsap@cc.nih.gov; cleary@georgetown.edu FU NIH/NCI [5R33CA094274]; U.S. Army [W81XWH-04-1-007]; NIH FX Portions of this work were funded under NIH/NCI grant 5R33CA094274 and U.S. Army grant W81XWH-04-1-007, administered by the Telemedicine and Advanced Technology Research Center (TATRC), Fort Detrick, MD, USA. This research was also supported in part by the Intramural Research Program of the NIH. NR 25 TC 14 Z9 14 U1 1 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUN PY 2008 VL 3 IS 1-2 BP 173 EP 179 DI 10.1007/s11548-008-0164-2 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA V32ZZ UT WOS:000208990400020 ER PT J AU Iversen, C Mullane, N McCardel, B Tal, BD Lehner, A Fannin, S Stephan, R Joosten, H AF Iversen, Carol Mullane, Niall McCardel, Barbara Tal, Ben D. Lehner, Angelika Fannin, Seamus Stephan, Roger Joosten, Han TI Cronobacter gen nov, a new genus to accommodate the biogroups of Enterobacter sakazakii, and proposal of Cronobacter sakazakii gen nov, comb nov, Cronobacter malonaticus sp nov, Cronobacter turicensis sp nov, Cronobacter muytjensii sp nov, Cronobacter dublinensis sp nov, Cronobacter genomospecies 1, and of three subspecies, Cronobacter dublinensis subsp dublinensis subsp nov, Cronobacter dublinensis subsp lausannensis subsp nov and Cronobacter dublinensis subsp lactaridi subsp nov SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID RENATURATION RATES; DNA HYBRIDIZATION AB [Enterobacter] sakazakii is an opportunistic pathogen that can cause infections in neonates. This study further clarifies the taxonomy of isolates described as [E] sakazakii and completes the formal description of the proposed reclassification of these organisms as novel species and subspecies within a proposed novel genus, Cronobacter gen. nov. [E] sakazakii was first defined in 1980, however recent polyphasic taxonomic analysis has determined that this group of organisms consists of several genomospecies. In this study, the phenotypic descriptions of the proposed novel species are expanded using Biotype 100 and Biolog Phenotype MicroArray data. Further DNA-DNA hybridization experiments showed that malonate-positive strains within the [E] sakazakii genomospecies represent a distinct species, not a subspecies. DNA-DNA hybridizations also determined that phenotypically different strains within the proposed species, Cronobacter dublinensis sp. nov., belong to the same species and can be considered as novel subspecies. Based on these analyses, the following alternative classifications are proposed: Cronobacter sakazakii gen. nov., comb. nov. [type strain ATCC 29544(T) (=NCTC 11467(T))]; Cronobacter malonaticus sp. nov. [type strain CDC 1058-77(T) (=LMG 23826(T) =DSM 18702(T))] Cronobacter turicensis sp. nov. [type strain z3032(T) (=LMG 23827(T) =DSM 18703(T))]; Cronobacter muytjensii sp. nov. [type strain ATCC 51329(T) (=Clp 103581(T))]; Cronobacter dublinensis sp. nov. [type strain DES187(T) (=LMG 23823(T) =DSM 18705(T))]; Cronobacter dublinensis subsp. dublinensis subsp. nov. [type strain DES187(T) (=LMG 23823(T) =DSM 18705(T))]; Cronobacter dublinensis subsp. lausannensis subsp. nov. [type strain E515(T) (= LMG 23824=DSM 18706(T))], and Cronobacter dublinensis subsp. lactaridi subsp. nov. [type strain E464(T) (=LMG 23825(T)=DSM 18707(T))]. C1 [Iversen, Carol; Lehner, Angelika; Stephan, Roger] Univ Zurich, Inst Food Safety & Hyg, Vetsuisse Fac, CH-8057 Zurich, Switzerland. [Mullane, Niall; Fannin, Seamus] Univ Coll Dublin, Vet Sci Ctr, Ctr Food Safety & Food Borne Zoon, Dublin 4, Ireland. [McCardel, Barbara; Tal, Ben D.] US FDA, Laurel, MD 20708 USA. [Joosten, Han] Nestle Res Ctr, Qual & Safety Dept, CH-1000 Lausanne, Switzerland. RP Stephan, R (reprint author), Univ Zurich, Inst Food Safety & Hyg, Vetsuisse Fac, CH-8057 Zurich, Switzerland. EM stephanr@fsafety.unizh.ch NR 8 TC 286 Z9 315 U1 2 U2 36 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUN PY 2008 VL 58 BP 1442 EP 1447 DI 10.1099/ijs.0.65577-0 PN 6 PG 6 WC Microbiology SC Microbiology GA 321AT UT WOS:000257277200029 PM 18523192 ER PT J AU Okelo, PO Joseph, SW Wagner, DD Wheaton, FW Douglass, LW Carr, LE AF Okelo, P. O. Joseph, S. W. Wagner, D. D. Wheaton, F. W. Douglass, L. W. Carr, L. E. TI Improvements in Reduction of Feed Contamination: An Alternative Monitor of Bacterial Killing During Feed Extrusion SO JOURNAL OF APPLIED POULTRY RESEARCH LA English DT Article DE Bacillus stearothermophilus; Salmonella Typhimurium; spore; surrogate; feed; extrusion; sterilization; animal feed ID BACILLUS-STEAROTHERMOPHILUS SPORES; HEAT-RESISTANCE AB Although numerous studies have documented the use of surrogate organisms for the evaluation of pathogens in human food, reports on the use of such organisms for similar studies in animal feed are limited. In the current study, dry feed inocula of Salmonella Typhimurium cells or Bacillus stearothermophilus spores were prepared and used to evaluate the efficiency of sterilization during feed extrusion. The inocula were placed in sealed stomacher bags and kept under 4 degrees C refrigerated storage, where they remained stable for the 8-wk study period. Test feed batches were inoculated with the dry feed inocula of Salmonella Typhimurium or B. stearothermophilus spores, and the batches were then extruded by using a single-screw extruder set to various processing stringencies according to a designed experimental protocol. Only thermophilic B. stearothermophilus could be recovered from the test feed samples over the entire range of extrusion processing stringencies used (245 to 345 g of moisture/kg of feed; 3 to 11 s of feed retention time in the extruder barrel; and 77 to 110 degrees C extruder barrel exit temperature). It was concluded that B. stearothermophilus is a suitable surrogate organism for evaluating the sterilization efficiency of feed extrusion and for identifying the optimal processing conditions to use during feed extrusion to eliminate, or at least minimize, the incidence of mesophilic and thermotolerant pathogens in feed. C1 [Okelo, P. O.; Wagner, D. D.; Wheaton, F. W.; Carr, L. E.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Douglass, L. W.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20740 USA. [Okelo, P. O.; Wheaton, F. W.; Carr, L. E.] Univ Maryland, Dept Environm Sci & Technol, College Pk, MD 20740 USA. [Joseph, S. W.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20740 USA. RP Okelo, PO (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM Phares.Okelo@fda.hhs.gov NR 20 TC 6 Z9 6 U1 2 U2 8 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 1056-6171 J9 J APPL POULTRY RES JI J. Appl. Poult. Res. PD SUM PY 2008 VL 17 IS 2 BP 219 EP 228 DI 10.3382/japr.2007-00060 PG 10 WC Agriculture, Dairy & Animal Science SC Agriculture GA 357XL UT WOS:000259880400004 ER PT J AU Huang, SM Strong, JM Zhang, L Reynolds, KS Nallani, S Temple, R Abraham, S Al Habet, S Baweja, RK Burckart, GJ Chung, S Colangelo, P Frucht, D Green, MD Hepp, P Karnaukhova, E Ko, HS Lee, JI Marroum, PJ Norden, JM Qiu, W Rahman, A Sobel, S Stifano, T Thummel, K Wei, XX Yasuda, S Zheng, JH Zhao, H Lesko, LJ AF Huang, Shiew-Mei Strong, John M. Zhang, Lei Reynolds, Kellie S. Nallani, Srikanth Temple, Robert Abraham, Sophia Al Habet, Sayed Baweja, Raman K. Burckart, Gilbert J. Chung, Sang Colangelo, Philip Frucht, David Green, Martin D. Hepp, Paul Karnaukhova, Elena Ko, Hon-Sum Lee, Jang-Ik Marroum, Patrick J. Norden, Janet M. Qiu, Wei Rahman, Atiqur Sobel, Solomon Stifano, Toni Thummel, Kenneth Wei, Xiao-Xiong Yasuda, Sally Zheng, Jenny H. Zhao, Hong Lesko, Lawrence J. TI New era in drug interaction evaluation: US Food and Drug Administration update on CYP enzymes, transporters, and the guidance process SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review DE drug interactions; transporter proteins; P-glycoprotein; cytochrome P450 enzymes; inhibition; induction; pharmacogenetics ID ST-JOHNS-WORT; PHARMACEUTICAL-INDUSTRY; PLASMA-CONCENTRATIONS; METABOLIZING-ENZYMES; P-GLYCOPROTEIN; CYTOCHROME-P450; PHARMACOKINETICS; EXPRESSION; GEMFIBROZIL; DIGOXIN AB Predicting clinically significant drug interactions during drug development is a challenge for the pharmaceutical industry and regulatory agencies. Since the publication of the US Food and Drug Administration's (FDA's) first in vitro and in vivo drug interaction guidance documents in 1997 and 1999, researchers and clinicians have gained a better understanding of drug interactions. This knowledge has enabled the FDA and the industry to progress and begin to overcome these challenges. The FDA has continued its efforts to evaluate methodologies to study drug interactions and communicate recommendations regarding the conduct of drug interaction studies, particularly for CYP-based and transporter-based drug interactions, to the pharmaceutical industry. A drug interaction Web site was established to document the FDA's current understanding of drug interactions (http://www.fda.gov/cder/drug/drugInteractions/default.htm). This report provides an overview of the evolution of the drug interaction guidances, includes a synopsis of the steps taken by the FDA to revise the original drug interaction guidance documents, and summarizes and highlights updated sections in the current guidance document, Drug Interaction Studies-Study Design, Data Analysis, and Implications for Dosing and Labeling. C1 [Huang, Shiew-Mei; Zhang, Lei; Reynolds, Kellie S.; Nallani, Srikanth; Abraham, Sophia; Al Habet, Sayed; Baweja, Raman K.; Chung, Sang; Colangelo, Philip; Hepp, Paul; Lee, Jang-Ik; Marroum, Patrick J.; Qiu, Wei; Rahman, Atiqur; Wei, Xiao-Xiong; Yasuda, Sally; Zheng, Jenny H.; Zhao, Hong; Lesko, Lawrence J.] US FDA, CDER, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Strong, John M.; Frucht, David] US FDA, CDER, Off Pharmaceut Sci, Silver Spring, MD USA. [Temple, Robert; Norden, Janet M.] US FDA, CDER, Off Med Policy, Silver Spring, MD USA. [Karnaukhova, Elena; Ko, Hon-Sum] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Bethesda, MD USA. [Green, Martin D.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Bethesda, MD USA. [Burckart, Gilbert J.] Univ So Calif, Dept Pharm, Los Angeles, CA USA. [Thummel, Kenneth] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. RP Huang, SM (reprint author), US FDA, CDER, Off Clin Pharmacol, New Hampshire Ave, Silver Spring, MD 20993 USA. NR 58 TC 150 Z9 157 U1 4 U2 25 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 2008 VL 48 IS 6 BP 662 EP 670 DI 10.1177/0091270007312153 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 305CZ UT WOS:000256156700001 PM 18378963 ER PT J AU Kadegowda, AKG Piperova, LS Delmonte, P Erdman, RA AF Kadegowda, A. K. G. Piperova, L. S. Delmonte, P. Erdman, R. A. TI Abomasal infusion of butterfat increases milk fat in lactating dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE lactating dairy cow; milk fat synthesis; de novo fatty acid ID LINOLEIC-ACID ISOMERS; MEDIUM-CHAIN TRIGLYCERIDES; COCONUT OIL; SECRETION; DIET; YIELD; IDENTIFICATION; SEPARATION; MIXTURES; TRANS-10 AB The objective of this study was to compare the effects of abomasal infusion of butterfat containing all fatty acids (FA) present in milk, including the short- and medium-chain FA, with infusion of only the long-chain FA (LCFA) present in milk, on the FA composition and milk fat yield in lactating dairy cows. Eight rumen-fistulated Holstein cows, in early lactation (49 +/- 20 days in milk) were used in a replicated 4 x 4 Latin square design. Treatments were abomasal infusion of the following: 1) no infusion (control), 2) 400 g/d of butterfat (butterfat), 3) 245 g/d of LCFA (blend of 59% cocoa butter, 36% olive oil, and 5% palm oil) providing 50% of the 16: 0 and equivalent amounts of C18 FA as found in 400 g of butterfat, and 4) 100 g/d of conjugated linoleic acid (CLA, negative control), providing 10 g of trans-10, cis-12 CLA. Fat supplements were infused in equal portions 3 times daily at 0800, 1400, and 1800 h during the last 2 wk of each 3-wk experimental period. Daily dry matter intake and milk production were unaffected by the infusion treatments. Butterfat infusion increased milk fat percentage by 14% to 4.26% and milk fat yield by 21% to 1,421 g/d compared with controls (3.74% and 1,178 g/d). Milk fat percentage and fat yield were decreased by 43% by CLA. Milk protein percentage was higher (3.70%) in CLA-infused cows than in control (3.30%), butterfat (3.28%), or LCFA (3.27%) treatments. Although LCFA had no effect on fat synthesis, abomasal infusion of butterfat increased milk fat percentage and yield, suggesting that the availability of short- and medium-chain FA may be a limiting factor for milk fat synthesis. C1 [Kadegowda, A. K. G.; Piperova, L. S.; Erdman, R. A.] Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. [Delmonte, P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Erdman, RA (reprint author), Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. EM erdman@umd.edu RI Erdman, Richard/F-6195-2010 OI Erdman, Richard/0000-0001-6954-4282 NR 36 TC 17 Z9 24 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD JUN PY 2008 VL 91 IS 6 BP 2370 EP 2379 DI 10.3168/jds.2007-0894 PG 10 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 302CG UT WOS:000255945800022 PM 18487659 ER PT J AU Klontz, KC McCarthy, PV Datta, AR Lee, JO Acheson, DWK Brackett, RE AF Klontz, Karl C. McCarthy, Patrick V. Datta, Atin R. Lee, Judy O. Acheson, David W. K. Brackett, Robert E. TI Role of the US Food and Drug Administration in the regulatory management of human listeriosis in the United States SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MEXICAN-STYLE CHEESE; PASTEURIZED MILK; SPORADIC LISTERIOSIS; EPIDEMIC LISTERIOSIS; MONOCYTOGENES; OUTBREAK; PATHOGENICITY; CONSUMPTION; POSITION AB From 1986 to 2006, the incidence of listeriosis in the United States dropped from approximately seven to three cases per million population, a reduction that most likely reflects the joint efforts of industry, government, consumers, and academia. Herein, we describe the U.S. Food and Drug Administration (FDA) strategy over the past three decades to combat listeriosis. Specifically, we discuss early actions taken to address outbreaks during the 1980s, policy decisions regarding the presence of Listeria monocytogenes in. FDA-regulated foods, FDA compliance programs with L. monocytogenes components, enforcement actions to remove L. monocytogenes-contaminated products from the market (i.e., recalls) or to prevent entry of such products into the market (i.e., import detentions and refusals), research milestones, outreach and education efforts, and selected special projects. Evolving demographic trends in the United States may pose a challenge to further reduction of the incidence of listeriosis. C1 [Klontz, Karl C.; McCarthy, Patrick V.; Datta, Atin R.; Lee, Judy O.; Brackett, Robert E.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Acheson, David W. K.] US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Klontz, KC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM karl.klontz@fda.hhs.gov NR 43 TC 15 Z9 15 U1 2 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2008 VL 71 IS 6 BP 1277 EP 1286 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 309XW UT WOS:000256494500028 PM 18592761 ER PT J AU Warfel, JM D'Agnillo, F AF Warfel, Jason M. D'Agnillo, Felice TI Anthrax lethal toxin enhances TNF-induced endothelial VCAM-1 expression via an IFN regulatory factor-1-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; CELL-ADHESION MOLECULE-1; NECROSIS-FACTOR-ALPHA; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; INHALATIONAL ANTHRAX; FACTOR-I; INFLAMMATORY CYTOKINES; MURINE MACROPHAGES; SIGNALING PATHWAYS AB Impaired host defenses and vascular dysfunction are hallmarks of the late, antibiotic-refractory stages of systemic anthrax infection. Anthrax lethal toxin (LT), a key virulence factor of Bacillus anthracis, was previously shown to enhance VCAM-I expression on primary human endothelial cells suggesting a causative link between dysregulated adhesion molecule expression and the poor immune response and vasculitis associated with anthrax. In this study, we report that LT amplification of TNF-induced VCAM-1 expression is driven transcriptionally by the cooperative activation of NF-kappa B and IFN regulatory factor-1 (UM-1). LT enhancement of NF-kappa B phosphorylation and nuclear translocation correlated temporally with a delayed reaccumulation of I kappa B alpha, while increased induction of IRF-1 was linked to STAT1 activation. LT failed to augment TNF-induced ICAM-1 or E-selectin expression, two adhesion molecules regulated by NF-kappa B, but not IRF-1. These results suggest that LT can differentially modulate NF-kappa B target genes and highlight the importance of IRF-1 in VCAM-1 enhancement. Altering the activity of key transcription factors involved in host response to infection may be a critical mechanism by which LT contributes to anthrax pathogenesis. C1 [Warfel, Jason M.; D'Agnillo, Felice] US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Bethesda, MD 20892 USA. [Warfel, Jason M.] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA. RP D'Agnillo, F (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, 29 Lincoln Dr,Bldg 29,Room 129, Bethesda, MD 20892 USA. EM felice.dagnillo@fda.hhs.gov RI Warfel, Jason/D-2557-2011 NR 67 TC 19 Z9 21 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2008 VL 180 IS 11 BP 7516 EP 7524 PG 9 WC Immunology SC Immunology GA 324GX UT WOS:000257507300049 PM 18490752 ER PT J AU Walsh, DL Schroeder, RJ Stewart, SFC AF Walsh, Donna L. Schroeder, R. Jason Stewart, Sandy F. C. TI Mechanical Performance of Generic and Proprietary Enema Bottles SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article DE inflammatory bowel disease; enema bottle; compression testing; stiffness ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; ARTICLE; THERAPY AB Enemas containing the anti-inflammatory drug mesalamine are an effective treatment for a distal form of inflammatory bowel disease (IBD). An IBD patient discovered that a generic mesalamine enema was more difficult and painful to use than the proprietary version. A study was initiated to determine whether these differences were measurable in the laboratory using conventional mechanical test equipment. Differences among three bottle types (the proprietary brand and two generic versions) were quantified by mechanical testing. The compressive force required to squeeze the drug from each bottle was measured, tensile testing was performed on the bottle wall, and stiffness of the nozzle tips was studied via bend testing. The thickness of the bottle walls and the inner diameter (ID) of the nozzles were also recorded. The work required to expel the drug from the generic versions during bottle compression was significantly greater than for the proprietary (p < 0.01). This was likely due to the wall thickness being greater in the generics; the elastic moduli of the three bottles were similar. The ID of the nozzles was smaller for the generic bottles, suggesting additional resistance to flow. Increased flow resistance was also observed for bottles in which lubricant obstructed the nozzle opening. The work required to bend the nozzle was greater in the generics than in the proprietary (p < 0.01). These differences between the generic and proprietary bottles are consistent with the patient's subjective experience. Poor bottle performance may adversely affect patient compliance with this treatment. Improved bottle design (such as tighter tolerances for wall thickness, nozzle ID, and nozzle stiffness) and manufacturing controls (e.g., preventing the nozzle lubricant from impeding delivery of the drug) could be achieved through the development of a standard specification for enema bottles. An optimal bottle design is suggested. [DOI: 10.1115/1.2902856] C1 [Walsh, Donna L.; Stewart, Sandy F. C.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Schroeder, R. Jason] US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Walsh, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.walsh@fda.hhs.gov NR 21 TC 0 Z9 0 U1 1 U2 1 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 J9 J MED DEVICES JI J. Med. Devices PD JUN PY 2008 VL 2 IS 2 AR 025001 DI 10.1115/1.2902856 PG 7 WC Engineering, Biomedical SC Engineering GA V18SW UT WOS:000208025500005 ER PT J AU Naum, M Brown, EW Mason-Gamer, RJ AF Naum, Marianna Brown, Eric W. Mason-Gamer, Roberta J. TI Is 16S rDNA a reliable phylogenetic marker to characterize relationships below the family level in the Enterobacteriaceae? SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE Erwinia; 16S rDNA; housekeeping genes; phylogenetic analysis; Enterobacteriaceae; GARLI ID RIBOSOMAL-RNA GENE; BACTERIAL TAXONOMY; EVOLUTION; POSITION; DIVERSITY; SEQUENCES; REGIONS AB The phylogenetic relationships of multiple enterobacterial species were reconstructed based on 16S rDNA gene sequences to evaluate the robustness of this housekeeping gene in the taxonomic placement of the enteric plant pathogens Erwinia, Brenneria, Pectobacterium, and Pantoea. Four data sets were compiled, two of which consisted of previously published data. The data sets were designed in order to evaluate how 16S rDNA gene phylogenies are affected by the use of different plant pathogen accessions and varying numbers of animal pathogen and outgroup sequences. DNA data matrices were analyzed using maximum likelihood (ML) algorithms, and character support was determined by ML bootstrap and Bayesian analyses. As additional animal pathogen sequences were added to the phylogenetic analyses, taxon placement changed. Further, the phylogenies varied in their placement of the plant pathogen species, and only the genus Pantoea was monophyletic in all four trees. Finally, bootstrap and Bayesian support values were low for most of the nodes, and all nonterminal branches collapsed in strict consensus trees. Inspection of 16S rDNA nucleotide alignments revealed several highly variable blocks punctuated by regions of conserved sequence. These data suggest that 16S rDNA, while effective for both species-level and family-level phylogenetic reconstruction, may underperform for genus-level phylogenetic analyses in the Enterobacteriaceae. C1 [Naum, Marianna; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, College Pk, MD 20740 USA. [Naum, Marianna; Mason-Gamer, Roberta J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60607 USA. RP Naum, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, 5100 Paint Branch Pkwy,HFS-712, College Pk, MD 20740 USA. EM marianna.naum@fda.hhs.gov NR 34 TC 36 Z9 37 U1 2 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JUN PY 2008 VL 66 IS 6 BP 630 EP 642 DI 10.1007/s00239-008-9115-3 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 322RK UT WOS:000257392800010 PM 18504519 ER PT J AU Dobretsova, A Johnson, JW Jones, RC Edmondson, RD Wight, PA AF Dobretsova, Anna Johnson, Jennifer W. Jones, Richard C. Edmondson, Ricky D. Wight, Patricia A. TI Proteomic analysis of nuclear factors binding to an intronic enhancer in the myelin proteolipid protein gene SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dNA affinity chromatography; DNA-binding proteins; enhanceosome; intronic enhancer; mass spectrometry; multi-protein complex; myelin proteolipid protein gene; proteomics ID FORKHEAD TRANSCRIPTION FACTORS; OLIGODENDROCYTE DEVELOPMENT; RAT-BRAIN; PUR-ALPHA; MASS-SPECTROMETRY; EXPRESSION; DNA; MICE; MOUSE; PROMOTER AB The myelin proteolipid protein gene (Plp1) encodes the most abundant protein found in CNS myelin, accounting for nearly one-half of the total protein. Its expression in oligodendrocytes is developmentally regulated - peaking during the active myelination period of CNS development. Previously, we have identified a novel enhancer (designated ASE) in intron 1 DNA that appears to be important in mediating the surge of Plp1 gene activity during the active myelination period. Evidence suggests that the ASE participates in the formation of a specialized multi-protein/DNA complex called an enhanceosome. The current study describes an optimized, five-step, DNA affinity chromatography purification procedure to purify nuclear proteins from mouse brain that bind to the 85-bp ASE sequence, specifically. Electrophoretic mobility shift assay analysis demonstrated that specific DNA-binding activity was retained throughout the purification procedure, resulting in concomitant enrichment of nucleoprotein complexes. Identification of the purported regulatory factors was achieved through mass spectrometry analysis and included over 20 sequence-specific DNA-binding proteins. Supplementary western blot analyses to determine which of these sequence-specific factors are present in oligodendrocytes, and their developmental and regional expression in whole brain, suggest that Pur alpha and Pur beta rank highest among the candidate factors as constituents of the multi-protein complex formed on the ASE. C1 [Dobretsova, Anna; Wight, Patricia A.] Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. [Johnson, Jennifer W.] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wight, PA (reprint author), Univ Arkansas Med Sci, Dept Physiol & Biophys, Slot 750,4301 W Markham St, Little Rock, AR 72205 USA. EM pwight@uams.edu FU NINDS NIH HHS [NS037821, NS047546, P30 NS047546, R01 NS037821] NR 57 TC 13 Z9 13 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2008 VL 105 IS 5 BP 1979 EP 1995 DI 10.1111/j.1471-4159.2008.05288.x PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 300OQ UT WOS:000255835000035 PM 18266931 ER PT J AU Sanhai, W AF Sanhai, Wendy TI Strategies to engage industry SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Sanhai, W (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 JUN PY 2008 VL 49 IS 6 BP 32N EP 34N PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309WN UT WOS:000256491000006 PM 18511818 ER PT J AU Sanhai, WR AF Sanhai, Wendy R. TI Working together to enhance the efficiency of medical product development SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Sanhai, WR (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 JUN PY 2008 VL 49 IS 6 BP 43N EP 45N PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 309WN UT WOS:000256491000011 PM 18511823 ER PT J AU Maccabe, AT Matchett, KF Hueston, WD AF Maccabe, Andrew T. Matchett, Karin F. Hueston, William D. TI The need for public-health veterinarians as seen by future employers SO JOURNAL OF VETERINARY MEDICAL EDUCATION LA English DT Article DE public health; zoonotic medicine; structure of academic programs; public practice; global issues in veterinary medicine; biodefense; curriculum structure ID INSPECTION SERVICE; FOOD SAFETY; EDUCATION AB Future employers of veterinarians working in public health see a fast-growing demand. Emerging zoonotic diseases, bio-security threats, and food-safety problems all require the expertise of veterinarians with a focus on complex, global problems that span both human and animal health. The Public Health Task Force of the Association of American Veterinary Medical Colleges convened a group of stakeholders representing various branches of the US federal government, state and local governments, and professional societies to discuss their needs for public-health veterinarians. This article discusses those needs, the broader societal needs that require veterinarians with public-health expertise, and the implications of these for educational programs to train DVMs in public-health issues. C1 [Maccabe, Andrew T.] Ctr Dis Control & Prevent, US FDA, Natl Ctr Zoonot Vectorborne & Enter Dis CDC CCID, Atlanta, GA 30039 USA. [Matchett, Karin F.] Univ Minnesota, Coll Vet Med, St Paul, MN 55108 USA. [Matchett, Karin F.] Univ Minnesota, Ctr Anim Hlth & Food Safety, St Paul, MN 55108 USA. [Hueston, William D.] Univ Minnesota, Global Food Syst Endowed Chair, Coll Vet Med, St Paul, MN 55108 USA. [Hueston, William D.] Univ Minnesota, Sch Publ Hlth, St Paul, MN 55108 USA. RP Maccabe, AT (reprint author), Ctr Dis Control & Prevent, US FDA, Natl Ctr Zoonot Vectorborne & Enter Dis CDC CCID, 1600 Clifton Rd,Mailstop C-09, Atlanta, GA 30039 USA. EM amaccabe@comcast.net NR 16 TC 4 Z9 6 U1 0 U2 0 PU UNIV TORONTO PRESS INC PI TORONTO PA JOURNALS DIVISION, 5201 DUFFERIN ST, DOWNSVIEW, TORONTO, ON M3H 5T8, CANADA SN 0748-321X J9 J VET MED EDUC JI J. Vet. Med. Educ. PD SUM PY 2008 VL 35 IS 2 BP 269 EP 274 PG 6 WC Education, Scientific Disciplines; Veterinary Sciences SC Education & Educational Research; Veterinary Sciences GA 340TO UT WOS:000258668100026 PM 18723814 ER PT J AU Hunter, RP Mahmood, I Martinez, MN AF Hunter, R. P. Mahmood, I. Martinez, M. N. TI Prediction of xenobiotic clearance in avian species using mammalian or avian data: how accurate is the prediction? SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material ID COMPARATIVE PHARMACOKINETICS; METABOLITE CIPROFLOXACIN; FLUNIXIN MEGLUMINE; ENROFLOXACIN; GENTAMICIN; DRUGS; BIRDS; DOGS; CHLORAMPHENICOL; SULFADIMIDINE C1 [Hunter, R. P.] Eli Lilly & Co, Elanco Anim Hlth, Div A, Greenfield, IN 46140 USA. [Mahmood, I.] US FDA, Ctr Biol Evaluat & Res, OBRR, Rockville, MD 20857 USA. [Martinez, M. N.] US FDA, Ctr Vet Med, Div Therapeut Drugs Food Anim HFV 130, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. RP Hunter, RP (reprint author), Eli Lilly & Co, Elanco Anim Hlth, Div A, 2001 W Main St, Greenfield, IN 46140 USA. EM hunter_robert_p@lilly.com RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 36 TC 19 Z9 19 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD JUN PY 2008 VL 31 IS 3 BP 281 EP 284 DI 10.1111/j.1365-2885.2008.00956.x PG 4 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 298WE UT WOS:000255717000015 PM 18471153 ER PT J AU Maximova, OA Ward, JM Asher, DM Claire, MS Finneyfrock, BW Speicher, JM Murphy, BR Pletnev, AG AF Maximova, Olga A. Ward, Jerrold M. Asher, David M. Claire, Marisa St. Finneyfrock, Brad W. Speicher, James M. Murphy, Brian R. Pletnev, Alexander G. TI Comparative neuropathogenesis and neurovirulence of attenuated flaviviruses in nonhuman primates SO JOURNAL OF VIROLOGY LA English DT Article ID TICK-BORNE ENCEPHALITIS; GROUP-B ARBOVIRUSES; CENTRAL NERVOUS-SYSTEM; DENGUE TYPE-4 VIRUSES; MONKEY NEUROVIRULENCE; VACCINE CANDIDATE; RHESUS-MONKEYS; MONOCLONAL-ANTIBODIES; LANGAT VIRUS; LIVE AB Based on previous preclinical evaluation in mice and monkeys, the chimeric TBEV/DEN4 Delta 30 virus, carrying the prM and E protein genes from a highly virulent Far Eastern strain of tick-borne encephalitis virus (TBEV) on the backbone of a nonneuroinvasive dengue type 4 virus (DEN4), has been identified as a promising live attenuated virus vaccine candidate against disease caused by TBEV. However, prior to use of this vaccine candidate in humans, its neurovirulence in nonhuman primates needed to be evaluated. In the present study, we compared the neuropathogeneses of the chimeric TBEV/DEN4 Delta 30 virus; Langat virus (LGTV), a former live TBEV vaccine; and yellow fever 17D virus vaccine (YF 17D) in rhesus monkeys inoculated intracerebrally. TBEV/DEN4 Delta 30 and YF 17D demonstrated remarkably similar spatiotemporal profiles of virus replication and virus-associated histopathology in the central nervous system (CNS) that were high in cerebral hemispheres but progressively decreased toward the spinal cord. In contrast, the neurovirullence of LGTV exhibited the reverse profile, progressing from the site of inoculation toward the cerebellum and spinal cord. Analysis of the spatiotemporal distribution of viral antigens in the CNS of monkeys revealed a prominent neurotropism associated with all three attenuated viruses. Nevertheless, TBEV/DEN4 Delta 30 virus exhibited higher neurovirulence in monkeys than either LGTV or YF 17D, suggesting insufficient attenuation. These results provide insight into the neuropathogenesis associated with attenuated flaviviruses that may guide the design of safe vaccines. C1 [Speicher, James M.; Murphy, Brian R.; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Maximova, Olga A.; Asher, David M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ward, Jerrold M.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. [Claire, Marisa St.; Finneyfrock, Brad W.] Bioqual Inc, Rockville, MD 20850 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, 33 N Dr,Room 3W10A,MSC 3203, Bethesda, MD 20892 USA. EM apletnev@niaid.nih.gov FU Intramural NIH HHS NR 48 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2008 VL 82 IS 11 BP 5255 EP 5268 DI 10.1128/JVI.00172-08 PG 14 WC Virology SC Virology GA 301FN UT WOS:000255881900015 PM 18353947 ER PT J AU Deeds, JR Landsberg, JH Etheridge, SM Pitcher, GC Longan, SW AF Deeds, Jonathan R. Landsberg, Jan H. Etheridge, Stacey M. Pitcher, Grant C. Longan, Sara Watt TI Non-traditional vectors for paralytic shellfish poisoning SO MARINE DRUGS LA English DT Review DE saxitoxins; STXs; paralytic shellfish poisoning; PSP; saxitoxin puffer fish poisoning; SPFP; non traditional vectors; gastropods; crustaceans; puffer fish; public health ID APHANIZOMENON-FLOS-AQUAE; BLUE-GREEN-ALGA; CYANOBACTERIUM CYLINDROSPERMOPSIS-RACIBORSKII; DINOFLAGELLATE ALEXANDRIUM-OSTENFELDII; CRABS TELMESSUS-ACUTIDENS; BAHAMENSE VAR COMPRESSA; FRESH-WATER PUFFERS; CORAL-REEF CRABS; XANTHID CRAB; PYRODINIUM-BAHAMENSE AB Paralytic shellfish poisoning (PSP), due to saxitoxin and related compounds, typically results from the consumption of filter-feeding molluscan shellfish that concentrate toxins from marine dinoflagellates. In addition to these microalgal sources, saxitoxin and related compounds, referred to in this review as STXs, are also produced in freshwater cyanobacteria and have been associated with calcareous red macroalgae. STXs are transferred and bioaccumulate throughout aquatic food webs, and can be vectored to terrestrial biota, including humans. Fisheries closures and human intoxications due to STXs have been documented in several non-traditional (i.e. non-filter-feeding) vectors. These include, but are not limited to, marine gastropods, both carnivorous and grazing, crustacea, and fish that acquire STXs through toxin transfer. Often due to spatial, temporal, or a species disconnection from the primary source of STXs (bloom forming dinoflagellates), monitoring and management of such non-traditional PSP vectors has been challenging. A brief literature review is provided for filter feeding (traditional) and non-filter feeding (non-traditional) vectors of STXs with specific reference to human effects. We include several case studies pertaining to management actions to prevent PSP, as well as food poisoning incidents from STX(s) accumulation in non- traditional PSP vectors. C1 [Deeds, Jonathan R.; Etheridge, Stacey M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20723 USA. [Landsberg, Jan H.] Florida Fish & Wildlife Conservat Commiss, Fish & Wildlife Res Inst, St Petersburg, FL 33712 USA. [Pitcher, Grant C.] Marine & Coastal Management, Cape Town, South Africa. [Longan, Sara Watt] State Alaska Dept Environm Conservat, Anchorage, AK USA. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20723 USA. EM jonathan.deeds@fda.hhs.gov; jan.landsberg@myfwc.com OI DeGrasse, Stacey/0000-0001-7808-4193 NR 218 TC 81 Z9 86 U1 9 U2 44 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-3397 J9 MAR DRUGS JI Mar. Drugs PD JUN PY 2008 VL 6 IS 2 BP 308 EP 348 DI 10.3390/md20080015 PG 41 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 319YY UT WOS:000257202100012 PM 18728730 ER PT J AU Kioi, M Seetharam, S Puri, RK AF Kioi, Mitomu Seetharam, Saraswathy Puri, Rai K. TI Targeting IL-13R alpha 2-positive cancer with a novel recombinant immunotoxin composed of a single-chain antibody and mutated Pseudomonas exotoxin SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID RECEPTOR ALPHA-2 CHAIN; T-CELL LYMPHOMA; INTERLEUKIN-13 RECEPTOR; MALIGNANT GLIOMA; DENILEUKIN DIFTITOX; CYTOTOXIN; THERAPY; ANTAGONIST; DELIVERY; PROTEIN AB We have shown previously that high-affinity receptors for interleukin-13 (IL-11R alpha 2) are overexpressed on a variety of solid cancer cells, diseased fibroblasts, and other cells, and a chimeric fusion protein composed of human IL-13 and mutated Pseudomonas exotoxin (IL-13-PE38) is highly and specifically cytotoxic to these cells in vitro and in vivo. To improve the specificity for the target, we isolated specific antibodies against IL-13R alpha 2 from human single-chain Fv (scFv) antibody phage library and developed immunotoxin by selecting two high-affinity clones of scFv and fused to PE. The fusion chimeric gene was expressed in Escherichia coli, and highly purified IL-13R-specific immunotoxin, termed anti-IL-13R alpha 2(scFv)-PE38, was tested for its cytotoxicity. This molecule was highly cytotoxic to U251 glioma and PM-RCC renal cell carcinoma cell lines in vitro. The cytotoxic activity was neutralized by purified extracellular domain of IL-13R alpha 2 but not by IL-13, indicating that cytotoxic activity is specific. Anti-IL-13R alpha 2(scFv)-PE38 showed significant antitumor activity in immuno-deficient mice with s.c. glioma tumors. Both i.p. and i.t. routes of administration showed antitumor activity in a dose-dependent manner. The maximum tolerated dose of anti-IL-13R alpha 2(scFv)-PE38 was 200 mu g/kg i.p. twice daily for 5 days. These results indicate that anti-IL13R alpha 2(scFv)-PE38 is a highly selective therapeutic agent for cancer therapy and should be further tested in animal models of human cancer. C1 [Kioi, Mitomu; Seetharam, Saraswathy; Puri, Rai K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 27 TC 40 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2008 VL 7 IS 6 BP 1579 EP 1587 DI 10.1158/1535-7163.MCT-07-2131 PG 9 WC Oncology SC Oncology GA 316NF UT WOS:000256955900025 PM 18566228 ER PT J AU Cott, JM AF Cott, Jerry M. TI Herb-drug interactions: Theory versus practice SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Editorial Material C1 US FDA, Silver Spring, MD USA. RP Cott, JM (reprint author), US FDA, Silver Spring, MD USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUN PY 2008 VL 52 IS 7 BP 745 EP 746 DI 10.1002/mnfr.200890030 PG 2 WC Food Science & Technology SC Food Science & Technology GA 333NM UT WOS:000258159200001 PM 18624348 ER PT J AU Guerrini, M Beccati, D Shriver, Z Naggi, A Viswanathan, K Bisio, A Capila, I Lansing, JC Guglieri, S Fraser, B Al-Hakim, A Gunay, NS Zhang, ZQ Robinson, L Buhse, L Nasr, M Woodcock, J Langer, R Venkataraman, G Linhardt, RJ Casu, B Torri, G Sasisekharan, R AF Guerrini, Marco Beccati, Daniela Shriver, Zachary Naggi, Annamaria Viswanathan, Karthik Bisio, Antonella Capila, Ishan Lansing, Jonathan C. Guglieri, Sara Fraser, Blair Al-Hakim, Ali Gunay, Nur Sibel Zhang, Zhenqing Robinson, Luke Buhse, Lucinda Nasr, Moheb Woodcock, Janet Langer, Robert Venkataraman, Ganesh Linhardt, Robert J. Casu, Benito Torri, Giangiacomo Sasisekharan, Ram TI Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events SO NATURE BIOTECHNOLOGY LA English DT Article ID DEXTRAN SULFATE; FLAVOBACTERIUM-HEPARINUM; RECOMBINANT EXPRESSION; MOLECULAR-CLONING; THROMBOCYTOPENIA; ACTIVATION; SYSTEM; C-13; H-1 AB Recently, certain lots of heparin have been associated with an acute, rapid onset of serious side effects indicative of an allergic-type reaction. To identify potential causes for this sudden rise in side effects, we examined lots of heparin that correlated with adverse events using orthogonal high-resolution analytical techniques. Through detailed structural analysis, the contaminant was found to contain a disaccharide repeat unit of glucuronic acid linked beta 1 -> 3 to a beta-N-acetylgalactosamine. The disaccharide unit has an unusual sulfation pattern and is sulfated at the 2-O and 3-O positions of the glucuronic acid as well as at the 4-O and 6-O positions of the galactosamine. Given the nature of this contaminant, traditional screening tests cannot differentiate between affected and unaffected lots. Our analysis suggests effective screening methods that can be used to determine whether or not heparin lots contain the contaminant reported here. C1 [Shriver, Zachary; Viswanathan, Karthik; Robinson, Luke; Langer, Robert; Venkataraman, Ganesh; Sasisekharan, Ram] Harvard MIT Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA 02139 USA. [Guerrini, Marco; Naggi, Annamaria; Bisio, Antonella; Guglieri, Sara; Casu, Benito; Torri, Giangiacomo] Ist Ric Chim & Biochim G Ronzoni, I-20133 Milan, Italy. [Beccati, Daniela; Shriver, Zachary; Capila, Ishan; Lansing, Jonathan C.; Gunay, Nur Sibel; Venkataraman, Ganesh] Momenta Pharmaceut Inc, Cambridge, MA 02142 USA. [Fraser, Blair; Al-Hakim, Ali; Buhse, Lucinda; Nasr, Moheb; Woodcock, Janet] Ctr Drug Evaluat & Res, US FDA, Silver Spring, MD 20993 USA. [Zhang, Zhenqing; Linhardt, Robert J.] Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Troy, NY 12180 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Sasisekharan, R (reprint author), Harvard MIT Div Hlth Sci & Technol, Koch Inst Integrat Canc Res, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rams@mit.edu OI Lansing, Jonathan/0000-0003-2041-190X FU NHLBI NIH HHS [R01 HL052622, R01 HL052622-09]; NIGMS NIH HHS [T32 GM008334, GM38060, GM57073, R01 GM038060, R01 GM038060-19, R01 GM057073, R37 GM057073] NR 29 TC 329 Z9 336 U1 5 U2 43 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 JUN PY 2008 VL 26 IS 6 BP 669 EP 675 DI 10.1038/nbt1407 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 311PK UT WOS:000256611900026 PM 18437154 ER PT J AU Joshi, BH Puri, RA Leland, P Varricchio, F Gupta, G Kocak, M Gilbertson, RJ Puri, RK AF Joshi, Bharat H. Puri, Rada A. Leland, Pamela Varricchio, Frederick Gupta, Ghanshyam Kocak, Mehmet Gilbertson, Richard J. Puri, Raj K. CA US Pediat Brain Tumor Consortium TI Identification of interleukin-13 receptor alpha 2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma SO NEURO-ONCOLOGY LA English DT Article DE brainstem glioma; IL-13 receptor alpha 2; immunohistochemical analysis (IHC); in situ hybridization (ISH); pediatric tumors ID CIRCULARLY PERMUTED INTERLEUKIN-4; CONVECTION-ENHANCED DELIVERY; CHILDRENS CANCER GROUP; KAPOSIS-SARCOMA CELLS; PSEUDOMONAS EXOTOXIN; MALIGNANT GLIOMA; IL-13 RECEPTOR; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; TARGETED CYTOTOXIN AB Human malignant glioma cell lines and adult brain tumors overexpress high levels of interleukin-13 receptor alpha 2 chain (IL-13R alpha 2). Because the IL-13R alpha 2 chain is an important target for cancer therapy and prognosis for patients with brainstem glioma (BSG) remains dismal, we investigated the expression of this receptor in specimens of diffusely infiltrative pediatric BSG relative to normal brain tissue. Twenty-eight BSG specimens and 15 normal brain specimens were investigated for IL-13R alpha 2 protein expression by immunohistochemical analysis (IHC) using two different antibodies in two different laboratories. Highly sensitive Q-dot-based IHC and in situ hybridization (ISH) assays were also developed to identify IL-13R alpha 2 protein and RNA in these specimens. The results were evaluated independently in two laboratories in a blinded fashion. By Q-dot IHC or a standard IHC assay, 17 of 28 (61%) tumor specimens showed modest to strong staining for IL-13R alpha 2, while 15 normal brain tissue samples showed weak expression for IL-13R alpha 2 protein. Significant interrater agreement between the two laboratories was seen in the assessment of IL-13R alpha 2 intensity. High-level IL-13R alpha 2 RNA expression was detected in tumor samples by Q-dot ISH, but only weak RNA expression was observed in normal brain. Significant agreement between ISH and IHC assays was observed (simple kappa [kappa] estimate = 0.358, weighted kappa = 0.89, p = 0.001). IL-13R alpha 2 protein and mRNA arc expressed to significantly higher levels in BSG than in normal brain tissue. Both IHC and ISH represent robust methods to detect expression of the IL-13R alpha 2 receptor in BSG that could represent an important new drug target for treatment of this disease. C1 [Kocak, Mehmet; Gilbertson, Richard J.] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Brain Tumor Program, Memphis, TN 38105 USA. [Joshi, Bharat H.; Puri, Rada A.; Leland, Pamela; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Bethesda, MD 20014 USA. [Varricchio, Frederick; Gupta, Ghanshyam] US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Puri, RK (reprint author), St Jude Childrens Res Hosp, Dept Dev Neurobiol, Brain Tumor Program, 332 N Lauderdale St, Memphis, TN 38105 USA. EM richard.gilbertson@stjude.org; raj.puri@fda.hhs.gov FU NCI NIH HHS [U01 CA81457, U01 CA081457] NR 60 TC 16 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUN PY 2008 VL 10 IS 3 BP 265 EP 274 DI 10.1215/15228517-2007-066 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 316UJ UT WOS:000256974900005 PM 18430795 ER PT J AU Sansone, SA Rocca-Serra, P Brandizi, M Brazma, A Field, D Fostel, J Garrow, AG Gilbert, J Goodsaid, F Hardy, N Jones, P Lister, A Miller, M Morrison, N Rayner, T Sklyar, N Taylor, C Tong, W Warner, G Wiemann, S AF Sansone, Susanna-Assunta Rocca-Serra, Philippe Brandizi, Marco Brazma, Alvis Field, Dawn Fostel, Jennifer Garrow, Andrew G. Gilbert, Jack Goodsaid, Federico Hardy, Nigel Jones, Phil Lister, Allyson Miller, Michael Morrison, Norman Rayner, Tim Sklyar, Nataliya Taylor, Chris Tong, Weida Warner, Guy Wiemann, Stefan CA RSBI Working Grp TI The first RSBI (ISA-TAB) workshop: "Can a Simple Format Work for Complex Studies?" SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 4th Genomic Standards Consortium Workshop CY JUN 06-08, 2007 CL Cambridge, ENGLAND ID MINIMUM INFORMATION; MICROARRAY DATA; DATA STANDARDS; GENOMICS AB This article summarizes the motivation for, and the proceedings of, the first ISA-TAB workshop held December 6-8, 2007, at the EBI, Cambridge, UK. This exploratory workshop, organized by members of the Microarray Gene Expression Data (MGED) Society's Reporting Structure for Biological Investigations (RSBI) working group, brought together a group of developers of a range of collaborative systems to discuss the use of a common format to address the pressing need of reporting and communicating data and metadata from biological, biomedical, and environmental studies employing combinations of genomics, transcriptomics, proteomics, and metabolomics technologies along with more conventional methodologies. The expertise of the participants comprised database development, data management, and hands-on experience in the development of data communication standards. The workshop's outcomes are set to help formalize the proposed Investigation, Study, Assay (ISA)-TAB tab-delimited format for representing and communicating experimental metadata. This article is part of the special issue of OMICS on the activities of the Genomics Standards Consortium (GSC). C1 [Sansone, Susanna-Assunta; Rocca-Serra, Philippe; Brandizi, Marco; Brazma, Alvis; Jones, Phil; Rayner, Tim; Sklyar, Nataliya; Taylor, Chris] EMBL EBI, Cambridge CB10 1SD, England. [Field, Dawn; Morrison, Norman] NERC, Ctr Ecol & Hydrol, Oxford OX1 3SR, England. [Fostel, Jennifer] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Garrow, Andrew G.; Warner, Guy] Unilever Safety & Environm Assurance Ctr, Bedford, England. [Gilbert, Jack] Plymouth Marine Lab, Plymouth, Devon, England. [Goodsaid, Federico] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hardy, Nigel] Aberystwyth Univ, Dept Comp Sci, Ceredigion, Wales. [Lister, Allyson] Univ Newcastle, CISBAN, Newcastle Upon Tyne, Tyne & Wear, England. [Lister, Allyson] Univ Newcastle, Sch Comp Sci, Newcastle Upon Tyne, Tyne & Wear, England. [Miller, Michael] Rosetta Biosoftware, Seattle, WA USA. [Morrison, Norman] NERC, Bioinformat Ctr NEBC, Ctr Ecol & Hydrol, Oxford OX1 3SR, England. [Morrison, Norman] Univ Manchester, Sch Comp Sci, Manchester, Lancs, England. [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. [Wiemann, Stefan] German Canc Res Ctr, D-6900 Heidelberg, Germany. RP Sansone, SA (reprint author), EMBL EBI, Wellcome Trust Genome Campus, Cambridge CB10 1SD, England. EM sansone@ebi.ac.uk; rocca@ebi.ac.uk RI Field, Dawn/C-1653-2010; Wiemann, Stefan/E-4424-2013; OI Wiemann, Stefan/0000-0003-4683-3174; Lister, Allyson/0000-0002-7702-4495; Brazma, Alvis/0000-0001-5988-7409; Sansone, Susanna-Assunta/0000-0001-5306-5690; Brandizi, Marco/0000-0002-5427-2496; Rayner, Tim/0000-0002-6992-5592 FU Biotechnology and Biological Sciences Research Council [BB/E025080/1] NR 28 TC 53 Z9 53 U1 0 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD JUN PY 2008 VL 12 IS 2 BP 143 EP 149 DI 10.1089/omi.2008.0019 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 321PT UT WOS:000257319700006 PM 18447634 ER PT J AU Beger, RD Holland, RD Sun, J Schnackenberg, LK Moore, PC Dent, CL Devarajan, P Portilla, D AF Beger, Richard D. Holland, Ricky D. Sun, Jinchun Schnackenberg, Laura K. Moore, Page C. Dent, Catherine L. Devarajan, Prasad Portilla, Didier TI Metabonomics of acute kidney injury in children after cardiac surgery SO PEDIATRIC NEPHROLOGY LA English DT Article DE metabonomics; acute renal failure; acute kidney injury; biomarkers; homovanillic acid sulfate ID GELATINASE-ASSOCIATED LIPOCALIN; ISCHEMIC RENAL INJURY; GENE-EXPRESSION; BIOMARKER; DOPAMINE; FAILURE; METABOLOMICS; IL-18; RAT AB Acute kidney injury (AKI) is a major complication in children who undergo cardiopulmonary bypass surgery. We performed metabonomic analyses of urine samples obtained from 40 children that underwent cardiac surgery for correction of congenital cardiac defects. Serial urine samples were obtained from each patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50% or greater rise in baseline level of serum creatinine, was noted in 21 children at 48-72 h after cardiac surgery. The principal component analysis of liquid chromatography/mass spectrometry (LC/MS) negative ionization data of the urine samples obtained 4 h and 12 h after surgery from patients who develop AKI clustered away from patients who did not develop AKI. The LC/MS peak with mass-to-charge ratio (m/z) 261.01 and retention time (t(R)) 4.92 min was further analyzed by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/mu l for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac surgery. C1 [Beger, Richard D.; Holland, Ricky D.; Sun, Jinchun; Schnackenberg, Laura K.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Moore, Page C.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Dent, Catherine L.; Devarajan, Prasad] Univ Cincinnati, Sch Med, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Portilla, Didier] Univ Arkansas Med Sci, Div Nephrol, Dept Internal Med, Little Rock, AR 72205 USA. [Portilla, Didier] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov FU NIDDK NIH HHS [R01 DK075976, R21-DK070163] NR 27 TC 46 Z9 52 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUN PY 2008 VL 23 IS 6 BP 977 EP 984 DI 10.1007/s00467-008-0756-7 PG 8 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 294NV UT WOS:000255413700017 PM 18320237 ER PT J AU Haber, P Patel, M Izurieta, HS Baggs, J Gargiullo, P Weintraub, E Cortese, M Braun, MM Belongia, EA Miller, E Ball, R Iskander, J Parashar, UD AF Haber, Penina Patel, Manish Izurieta, Hector S. Baggs, James Gargiullo, Paul Weintraub, Eric Cortese, Margaret Braun, M. Miles Belongia, Edward A. Miller, Elaine Ball, Robert Iskander, John Parashar, Umesh D. TI Postlicensure monitoring of intussusception after RotaTeq vaccination in the United States, February 1, 2006, to September 25, 2007 SO PEDIATRICS LA English DT Article DE rotavirus vaccine; intussusception; vaccine safety; adverse event ID EVENT REPORTING SYSTEM; ORAL ROTAVIRUS VACCINE; ADVERSE EVENTS; SAFETY; IMMUNIZATION; SURVEILLANCE; INFANTS; CHILDREN; VAERS AB BACKGROUND. In 1999, a previous rotavirus vaccine (RotaShield; Wyeth Laboratories, Marietta, PA) was withdrawn from the US market after postlicensure monitoring identified an association with intussusception. Although the new rotavirus vaccine (RotaTeq; Merck, West Point, PA) introduced in 2006 was not associated with intussusception in prelicensure trials, additional monitoring is important to ensure a complete safety profile. METHODS. We assessed intussusception reports after RotaTeq vaccination by using data from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink, a cohort of children enrolled in managed care. Observed versus expected rate ratios were determined by using vaccine dose distribution data and Vaccine Safety Datalink background intussusception rates. RESULTS. Between February 1, 2006, and September 25, 2007, the Vaccine Adverse Event Reporting System received 160 intussusception reports after RotaTeq vaccination. With the assumptions that reporting completeness was 75% and that 75% of the distributed doses of RotaTeq were administered, the observed versus expected rate ratios were 0.53 and 0.91 for the 1-21 and 1-7 day interval after vaccination, respectively. In the Vaccine Safety Datalink, 3 intussusception cases occurred within 30 days after 111 521 RotaTeq vaccinations, compared with 6 cases after 186 722 non-RotaTeq vaccinations during the same period. If, like RotaShield, RotaTeq had a 37-fold increased risk of intussusception within 3 to 7 days after vaccination, then 8 intussusception cases would be expected within 3 to 7 days among the similar to 84 000 infants vaccinated with the first dose of RotaTeq in the Vaccine Safety Datalink (N = 49 902) and the prelicensure trial (N = 34 035) combined, whereas no cases have been observed. CONCLUSIONS. Available data do not indicate that RotaTeq is associated with intussusception. Although an intussusception risk similar in magnitude to that of RotaShield can be excluded, continued monitoring is necessary for complete assessment of the safety profile of RotaTeq. C1 [Patel, Manish; Cortese, Margaret; Parashar, Umesh D.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Haber, Penina; Baggs, James; Gargiullo, Paul; Weintraub, Eric; Miller, Elaine; Iskander, John] Off Chief Sci Officer, Immunizat Safety Off, Atlanta, GA USA. [Izurieta, Hector S.; Braun, M. Miles; Ball, Robert] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Belongia, Edward A.] Marshfield Clin Fdn Med Res & Educ, Epidemiol Res Ctr, Marshfield, WI 54449 USA. RP Patel, M (reprint author), Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd,MS A-47, Atlanta, GA 30333 USA. EM aul3@cdc.gov OI Baggs, James/0000-0003-0757-4683 NR 21 TC 79 Z9 82 U1 0 U2 2 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 JUN PY 2008 VL 121 IS 6 BP 1206 EP 1212 DI 10.1542/peds.2007-3793 PG 7 WC Pediatrics SC Pediatrics GA 307IX UT WOS:000256313700052 PM 18519491 ER PT J AU Wang, Q Smith, RE Luchtefeld, R Sun, AY Simonyi, A Luo, RS Sun, GY AF Wang, Qun Smith, Robert E. Luchtefeld, Ron Sun, Albert Y. Simonyi, Agnes Luo, Rensheng Sun, Grace Y. TI Bioavailability of apocynin through its conversion to glycoconjugate but not to diapocynin SO PHYTOMEDICINE LA English DT Article DE apocynin; NADPH oxidase inhibitor; bioavailability; glycoconjugates; plasma; brain ID NADPH OXIDASE INHIBITION; OXIDATIVE STRESS; CEREBRAL-ISCHEMIA; NAD(P)H OXIDASE; MECHANISMS; EXPRESSION; PROTECTS; INJURY; BRAIN; RATS AB Apocynin (4-hydroxy-3-methoxyacetophen one) is a major active ingredient from the rhizomes of Picrorhiza kurroa, a botanical plant used as an herbal medicine for treatment of a number of inflammatory diseases. Recently, apocynin is regarded as a specific inhibitor for NADPH oxidase in cell and animal models. In vitro studies indicated conversion of apocynin to diapocynin in the presence of peroxidases, e.g., myloperoxidase, posing the possibility that diapocynin also contributes to the anti-oxidative action of apocynin. The objectives of this study are to examine the bioavailability of apocynin to plasma, liver and brain tissue after intraperitoneal (i.p.) injection, and to examine whether apocynin is converted to diapocynin in vivo. Diapocynin was chemically synthetized and characterized by NMR and IR. Apocynin (5 mg/kg body wt) was injected i.p. to adult male Sprague-Dawley rats and plasma, liver and brain were collected at different times (30 min, 1 and 2 h) after injection. Samples were treated with beta-glucuronidase to hydrolyze the glycosyl linkage and analyzed by HPLC/M S. At 30 min and 1 h after injection, approximately 50% of apocynin was converted to its glycosyl derivative and was distributed in plasma, liver and brain. No diapocynin was detected in any samples. These results indicate rapid glycosylation of apocynin and its transport to blood and other organs but no apparent conversion to diapocynin in vivo. (c) 2007 Elsevier GmbH. All rights reserved. C1 [Wang, Qun; Simonyi, Agnes; Sun, Grace Y.] Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. [Sun, Albert Y.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA. [Smith, Robert E.; Luchtefeld, Ron] US Dept Food & Drug Adm, Lenexa, KS 66214 USA. [Luo, Rensheng] Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. RP Sun, GY (reprint author), Univ Missouri, Dept Biochem, M743 Med Sci Bldg, Columbia, MO 65212 USA. EM wangqu@missouri.edu; sung@missouri.edu FU NIH [P01 AG18357] FX This work was supported in part by P01 AG18357 from NIH. This work should not be taken as having an impact on FDA policy or regulations. NR 24 TC 27 Z9 27 U1 1 U2 6 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PD JUN PY 2008 VL 15 IS 6-7 BP 496 EP 503 DI 10.1016/j.phymed.2007.09.019 PG 8 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 339EU UT WOS:000258561700014 PM 17977702 ER PT J AU Levy, AS Choiniere, CJ Fein, SB AF Levy, Alan S. Choiniere, Conrad J. Fein, Sara B. TI Practice-specific risk perceptions and self-reported food safety practices SO RISK ANALYSIS LA English DT Article DE endogeneity; food safety practices; response bias; risk perception ID CONSUMPTION; PREVALENCE; FREQUENCY; BEHAVIORS; ILLNESS; RECORDS; DISEASE; DEATH; BIAS AB The relationship between risk perception and risk avoidance is typically analyzed using self-reported measures. However, in domains such as driving or food handling, the validity of responses about usual behavior is threatened because people think about the situations in which they are self-aware, such as when they encounter a hazard. Indeed, researchers have often noted a divergence between what people say about their behavior and how they actually behave. Thus, in order to draw conclusions about risk perceptions and risk avoidance from survey data, it is important to identify particular cognitive elements, such as those measured by questions about risk and safety knowledge, risk perceptions, or information search behavior, which may be effective antecedents of self-reported safety behavior. It is also important to identify and correct for potential sources of bias that may exist in the data. The authors analyze the Food and Drug Administration's 1998 Food Safety Survey to determine whether there are consistent cognitive antecedents for three types of safe food practices: preparation, eating, and cooling of foods. An assessment of measurement biases shows that endogeneity of food choices affects reports of food preparation. In addition, response bias affects reports of cooling practices as evidenced by its relation to knowledge and information search, a pattern of cognitive effects unique to cooling practices. After correcting for these biases, results show that practice-specific risk perceptions are the primary cognitive antecedents of safe food behavior, which has implications for the design of effective education messages about food safety. C1 [Levy, Alan S.; Choiniere, Conrad J.; Fein, Sara B.] US FDA, Off Regulat Policy & Social Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Choiniere, CJ (reprint author), US FDA, Off Regulat Policy & Social Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM conrad.choiniere@fda.hhs.gov NR 37 TC 17 Z9 17 U1 15 U2 29 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 2008 VL 28 IS 3 BP 749 EP 761 DI 10.1111/j.1539-6924.2008.01051.x PG 13 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 315DT UT WOS:000256858800015 PM 18643830 ER PT J AU Raghunandan, R Ruiz-Hidalgo, M Jia, Y Ettinger, R Rudikoff, E Riggins, P Farnsworth, R Tesfaye, A Laborda, J Bauer, SR AF Raghunandan, Ramadevi Ruiz-Hidalgo, Maria Jia, Yifeng Ettinger, Rachael Rudikoff, Eva Riggins, Patrick Farnsworth, Richard Tesfaye, Abeba Laborda, Jorge Bauer, Steven R. TI Dlk1 influences differentiation and function of B lymphocytes SO STEM CELLS AND DEVELOPMENT LA English DT Article ID BONE-MARROW CULTURES; ADIPOCYTE DIFFERENTIATION; CELL-DIFFERENTIATION; STROMAL CELLS; PROTEIN DLK; DELTA-LIKE; EXPRESSION; GROWTH; LYMPHOPOIESIS; ANTIGEN AB The Dlk1 (delta-like-1) gene is a member of the epidermal growth factor (EGF)-like homeotic gene family. It influences cell-cell interactions between stromal cells and pro-B cells in vitro. To define the in vivo role of the dlk protein in B cell development, we established a Dlk1(-/-) mouse model. In spleens of Dlk1(-/-) mice, transitional B cell numbers were increased and the ratio between transitional B cell subsets was altered. Numbers of follicular B cells decreased, while the number of marginal zone B cells and the size of the marginal zone were increased. Loss of dlk resulted in increased immunoglobulin G1 (IgG(1)) and IgG(3) in preimmune sera. Furthermore, there was an exaggerated primary T-dependent antigen-specific humoral immune response. In bone marrow, the lack of dlk led to increased numbers of the earliest B lineage cells in young mice without affecting numbers of later B lineage cells. In vitro experiments showed that lack of dlk on either stromal cells or pro-B cells caused changes in differentiation and proliferation of pro-B cells, suggesting that lack of dlk leads to changes in cell-cell interactions in the bone marrow microenvironment. These results show that dlk expression is essential for normal B cell development. C1 [Raghunandan, Ramadevi; Jia, Yifeng; Rudikoff, Eva; Riggins, Patrick; Farnsworth, Richard; Tesfaye, Abeba; Bauer, Steven R.] US FDA, Ctr Biol Evaluat & Res, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. [Ruiz-Hidalgo, Maria; Laborda, Jorge] Univ Castilla La Mancha, Biochem & Mol Biol Branch, Med Sch Reg Ctr Biomed Invest CRIB, Albacete, Spain. [Ettinger, Rachael] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Bauer, SR (reprint author), FDA Ctr Biol Evaluat & Res, Cell & Tissue Therapy Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, NIH Bldg 29B Room 2NN10,HFM-740,1401 Rockville Pi, Rockville, MD 20852 USA. EM Steven.Bauer@fda.hhs.gov RI Bauer, Steven/G-5559-2012; Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; OI Laborda, Jorge/0000-0002-9210-838X; Bauer, Steven/0000-0003-2831-846X FU Intramural NIH HHS NR 50 TC 46 Z9 47 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD JUN PY 2008 VL 17 IS 3 BP 495 EP 507 DI 10.1089/scd.2007.0102 PG 13 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 318TL UT WOS:000257115600011 PM 18513163 ER PT J AU Petibone, DM Morris, SM Hotchkiss, CE Mattison, DR Tucker, JD AF Petibone, D. M. Morris, S. M. Hotchkiss, C. E. Mattison, D. R. Tucker, J. D. TI Technique for culturing Macaca mulatta peripheral blood lymphocytes for fluorescence in situ hybridization of whole chromosome paints SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Macaca mulatta; whole chromosome painting; chromosome translocations; baseline; methods ID DOSE RECONSTRUCTION; IONIZING-RADIATION; NONHUMAN-PRIMATES; RHESUS-MONKEYS; ABERRATIONS; FREQUENCY; TRANSLOCATIONS; FASCICULARIS; PERSISTENCE; CLONING AB The rhesus monkey (Macaca mulatto) has long been an important model in biomedical and behavioral research. The biomedical importance of M. mulatto is due to its 93% genetic similarity with humans and its complex social behavior. The recent sequencing of the M. mulatto genome has enhanced its role in biological research. However, the use of the macaque as an experimental model in cytogenetic assays has been problematic due to difficulties in obtaining large numbers of well-spread cells in metaphase without the use of extremely toxic mitogens such as staphylococcal enterotoxin A (SEA). Here we describe a technique for culturing and producing sufficient numbers of cells in metaphase using the common mitogens phytohemagglutinin (PHA), concanavalin A (ConA), and T-cell growth factor (TCGF) which act synergistically to induce M. mulatto T-lymphocyte division. Using this method we have obtained a mitotic index in 48 h cultures of 12.0 +/- 2.2 metaphase cells/100cells (n =5 animals). Fluorescence in situ hybridization with whole chromosome painting of M. mulatto cells was performed with human whole-chromosome probes that labeled the following chromosomes for human (M. mulatto): 1(1), 2q(12), 2p(13), 4(5) pairs in red, and 3(2), 5(6) and 6(4) pairs in green. In humans this probe combination simultaneously paints 3 chromosome pairs in red and 3 in green, whereas in M. mulatto 4 chromosome pairs are labeled in red and 3 pairs are labeled in green. Using this method we show a baseline frequency of 0.026 translocations per 100 whole-genome cell equivalents in peripheral blood lymphocytes obtained from unexposed adolescent non-human primates. This method will add to the usefulness of M. mulatto as an animal model in biomedical research. (C) 2008 Elsevier B.V. All rights reserved. C1 [Petibone, D. M.; Tucker, J. D.] Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. [Morris, S. M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Hotchkiss, C. E.] Bionetics Corp, Jefferson, AR 72079 USA. [Mattison, D. R.] NIH, HHS, Bethesda, MD 20892 USA. RP Tucker, JD (reprint author), Wayne State Univ, Dept Biol Sci, 1370 Biol Sci Bldg,5047 Gullen Mall, Detroit, MI 48202 USA. EM jtucker@biology.biosci.wayne.edu RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 28 TC 2 Z9 3 U1 1 U2 2 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 MAY 31 PY 2008 VL 653 IS 1-2 BP 76 EP 81 DI 10.1016/j.mrgentox.2008.03.012 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 326DQ UT WOS:000257638700011 PM 18499509 ER PT J AU Reepmeyer, JC Ye, W Ritschel, WA AF Reepmeyer, John C. Ye, Wei Ritschel, Wolfgang A. TI Modifications and insights into a method for the analysis of the nitrogen mustard mechlorethamine by high-performance liquid chromatography SO ANALYTICA CHIMICA ACTA LA English DT Article DE nitrogen mustard; mechlorethamine; analysis; derivatization; high-performance liquid; chromatography ID MASS-SPECTROMETRY; ALKYLATING AGENTS; MYCOSIS-FUNGOIDES; PRODUCTS AB Previously, method was presented for the analysis of mechlorethamine by derivatization of this unstable nitrogen mustard to bis(2-phenylthioethyl)methylamine (PTEMA), a stable compound suitable for analysis by HPLC with UV detection [J.C. Reepmeyer, J. Chromatogr. A, 1085 (2005) 262]. Mechlorethamine HCl served as a reference standard and it was derivatized in situ simultaneously with samples of mechlorethamine HCl in ointment preparations. This paper presents the synthesis of PTEMA on a gram scale, synthesis of its picrate salt, bis(2-phenylthioethyl)methylamine picrate (PTEMAP), and isolation of the picrate as a crystalline solid. PTEMAP may serve as a reference standard replacing the toxic mechlorethamine HCl. insights into the handling, storage, drying, and hygroscopic properties of mechlorethamine HCl and PTEMAP are discussed. In addition, one step following the derivatization procedure in the original method is recognized as a potential for error, and a procedure relating to the order of addition of reagents is presented to avoid this error. The method has been extended to the analysis of mechlorethamine in aqueous solutions.. (C) 2008 Elsevier B.V. All rights reserved. C1 [Reepmeyer, John C.; Ye, Wei] US FDA, Ctr Drug Evaluat & Res, Off Phamaceut Sci, Div Pharmaceut Anal,FDA, St Louis, MO 63101 USA. [Ritschel, Wolfgang A.] Univ Cincinnati, Med Ctr, James L Winkle Coll Pharm, Cincinnati, OH 45267 USA. RP Reepmeyer, JC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Phamaceut Sci, Div Pharmaceut Anal,FDA, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.reepmeyer@fda.hhs.gov NR 21 TC 3 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD MAY 26 PY 2008 VL 616 IS 1 BP 78 EP 84 DI 10.1016/j.aca.2008.04.020 PG 7 WC Chemistry, Analytical SC Chemistry GA 307JJ UT WOS:000256314900010 PM 18471487 ER PT J AU De Jager, LS Perfetti, GA Diachenko, GW AF De Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Analysis of tetramethylene disulfotetramine in foods using solid-phase microextraction-gas chromatography-mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE tetramine; SPME; food analysis; food defense; TETS ID TETRAMINE AB An automated solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) method for the determination of tetramethylene disulfotetramine in foods was developed. A comparison of direct immersion (DI) and headspace (HS) extraction techniques using a 70 mu m carbowax/divinylbenzene (CW/DVB) fiber is presented. The optimized DI-SPME method provided an aqueous extraction limit of detection (LOD) of 9.0 ng/g while the HS-SPME LOD was 2.7 ng/g. In both SPME modes, recovery was highly matrix dependent and quantification requires standard addition calibrations. Analysis of foods using DI-SPME encountered many obstacles including fiber fouling, low recovery and poor reproducibility. HS-SPME was successfully applied to food analysis with minimal interferences. Standard addition calibration curves for foods gave high linearity (R-2 > 0.98), reproducibility (RSD < 12%) and sensitivity with LODs ranging from 0.9 to 4.3 ng/g. Published by Elsevier B.V. C1 [De Jager, Lowri S.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP De Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Point Branch Pkwy, College Pk, MD USA. EM lowri.dejager@fda.hhs.gov NR 13 TC 23 Z9 23 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 23 PY 2008 VL 1192 IS 1 BP 36 EP 40 DI 10.1016/j.chroma.2008.03.042 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 305TM UT WOS:000256200700005 PM 18378250 ER PT J AU Cortazar, P Johnson, JR Justice, R Pazdur, R AF Cortazar, P. Johnson, J. R. Justice, R. Pazdur, R. TI Metastatic breast cancer (MBC): FDA approval overview SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Potomac, MD USA. US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 1 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 MAY 20 PY 2008 VL 26 IS 15 SU S MA 1013 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400322 ER PT J AU Liu, Q Madabushi, R Garnett, C Booth, B AF Liu, Q. Madabushi, R. Garnett, C. Booth, B. TI Experience in QT evaluation of oncology drug products since ICH E14 guidance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Liu, Q.; Madabushi, R.; Garnett, C.; Booth, B.] US FDA, Silver Spring, MD USA. NR 0 TC 4 Z9 4 U1 1 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 MAY 20 PY 2008 VL 26 IS 15 SU S MA 2554 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400658 ER PT J AU Mann, BS Cortazar, P Johnson, JR He, K Sridhara, R Farrell, AT Justice, R Pazdur, R AF Mann, B. S. Cortazar, P. Johnson, J. R. He, K. Sridhara, R. Farrell, A. T. Justice, R. Pazdur, R. TI Differences in prior estrogen exposure may explain the difference in magnitude of breast cancer risk reduction observed in raloxifene breast cancer prevention trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Mann, B. S.; Cortazar, P.; Johnson, J. R.; He, K.; Sridhara, R.; Farrell, A. T.; Justice, R.; Pazdur, R.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 MAY 20 PY 2008 VL 26 IS 15 SU S MA 1519 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400425 ER PT J AU Men, YA Mummaneni, P Zhao, H Amur, S Lee, J Kenna, L Frueh, F Rahman, NA Huang, S AF Men, Y. A. Mummaneni, P. Zhao, H. Amur, S. Lee, J. Kenna, L. Frueh, F. Rahman, N. A. Huang, S. TI Can skin/eye toxicity be used as a biomarker for dose selection of FDA approved Anti-EGFR agents? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Men, Y. A.; Mummaneni, P.; Zhao, H.; Amur, S.; Lee, J.; Kenna, L.; Frueh, F.; Rahman, N. A.; Huang, S.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 14696 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400903 ER PT J AU Ning, YM Arlen, PM Gulley, JL Stein, WD Fojo, AT Latham, L Wright, JJ Parnes, H Figg, WD Dahut, WL AF Ning, Y. M. Arlen, P. M. Gulley, J. L. Stein, W. D. Fojo, A. T. Latham, L. Wright, J. J. Parnes, H. Figg, W. D. Dahut, W. L. TI Phase II trial of thalidomide (T), bevacizumab (Bv), and docetaxel (Doc) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Silver Spring, MD USA. NCI, Bethesda, MD 20892 USA. Med Oncol Branch, Bethesda, MD USA. Canc Therapy Evaluat Program, Rockville, MD USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 5000 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457401900 ER PT J AU Roy, A Zhu, H Cohen, M Zhang, L Pfister, M AF Roy, A. Zhu, H. Cohen, M. Zhang, L. Pfister, M. TI Analysis of ixabepilone exposure-response for neutropenia in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 Bristol Myers Squibb Co, Princeton, NJ USA. US FDA, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2008 VL 26 IS 15 SU S MA 2511 PG 1 WC Oncology SC Oncology GA V25CZ UT WOS:000208457400668 ER PT J AU Chandler, C Gryniewicz, CM Pringle, T Cunningham, F AF Chandler, Chris Gryniewicz, Connie M. Pringle, Tom Cunningham, Fran TI Insulin temperature and stability under simulated transit conditions SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE control, quality; insulin human isophane; insulin human; insulins; packaging; stability; storage; temperature; transportation AB Purpose. The transit temperature profiles, mean kinetic temperatures (MKTs), and stability of insulin samples in both insulated and noninsulated containers exposed to summer and winter temperatures were evaluated. Methods. Regular insulin, isophane insulin human (NPH) insulin, and 70% isophane-30% regular (70/30) insulin were packaged in the most commonly dispensed quantity of four vials in noninsulated mailers and insulated containers with frozen gel packs. After packaging, sealed containers and mailers were placed in an environmental chamber for 24-120 hours and exposed to summer and winter transit conditions. Temperatures inside the environmental chamber were recorded every 15 minutes and maintained within 3 degrees C of the specified transit temperature. After exposure to the transit conditions, insulin cartons were removed from their packaging, visually inspected for changes in physical appearance, and stored at 4 degrees C until analysis. The MKT of each package was calculated. High-performance liquid chromatography was performed to determine sample stability, and size-exclusion chromatography was conducted to detect aggregate products of insulin. Results. Regardless of shipping conditions or packaging, all samples met the United States Pharmacopeia's (USP's) specified limits and retained product stability. Visual inspection of the physical appearance of insulin samples before and after temperature exposure revealed results similar to those described in the product inserts. Microscopic analysis of the injectable suspensions confirmed similar crystal morphologies before and after temperature exposure. Conclusion. Regular, NPH, and 70/30 insulin maintained potency within USP limits when stored in programmable environmental chambers simulating summer and winter overnight or three- to five-day ground delivery conditions, regardless of packaging material. C1 [Chandler, Chris] Dept Vet Affairs Great Lakes Consolidated Mail Ou, Hines, IL 60141 USA. [Gryniewicz, Connie M.] US FDA, Div Pharmaceut Anal, St Louis, MO USA. [Pringle, Tom] Tegrant Diversified Brands Inc, ThermoSafe Brands, Phoenix, AZ USA. [Cunningham, Fran] Patient Safety Ctr Inquiry, Ctr Medicat Safety, Hines, IL USA. [Cunningham, Fran] US Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Hines, IL 60141 USA. RP Chandler, C (reprint author), Dept Vet Affairs Great Lakes Consolidated Mail Ou, 5th & Roosevelt Rd,Bldg 37 NW, Hines, IL 60141 USA. EM chris.chandler@va.gov NR 6 TC 8 Z9 9 U1 1 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 15 PY 2008 VL 65 IS 10 BP 953 EP 963 DI 10.2146/ajhp070347 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 300RF UT WOS:000255842200016 PM 18463345 ER PT J AU Vora, S Damon, I Fulginiti, V Weber, SG Kahana, M Stein, SL Gerber, SI Garcia-Houchins, S Lederman, E Hruby, D Collins, L Scott, D Thompson, K Barson, JV Regnery, R Hughes, C Daum, RS Li, Y Zhao, H Smith, S Braden, Z Karem, K Olson, V Davidson, W Trindade, G Bolken, T Jordan, R Tien, D Marcinak, J AF Vora, Surabhi Damon, Inger Fulginiti, Vincent Weber, Stephen G. Kahana, Madelyn Stein, Sarah L. Gerber, Susan I. Garcia-Houchins, Sylvia Lederman, Edith Hruby, Dennis Collins, Limone Scott, Dorothy Thompson, Kenneth Barson, John V. Regnery, Russell Hughes, Christine Daum, Robert S. Li, Yu Zhao, Hui Smith, Scott Braden, Zach Karem, Kevin Olson, Victoria Davidson, Whitni Trindade, Giliane Bolken, Tove Jordan, Robert Tien, Debbie Marcinak, John TI Severe eczema vaccinatum in a household contact of a smallpox vaccinee SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ANTIPOXVIRUS COMPOUND ST-246; STAPHYLOCOCCUS-AUREUS; ATOPIC-DERMATITIS; UNITED-STATES; COMPLICATIONS; INFECTIONS; VIRUS; EFFICACY; MICE; EXPERIENCE AB Background. We report the first confirmed case of eczema vaccinatum in the United States related to smallpox vaccination since routine vaccination was discontinued in 1972. A 28-month-old child with refractory atopic dermatitis developed eczema vaccinatum after exposure to his father, a member of the US military who had recently received smallpox vaccine. The father had a history of inactive eczema but reportedly reacted normally to the vaccine. The child's mother also developed contact vaccinia infection. Methods. Treatment of the child included vaccinia immune globulin administered intravenously, used for the first time in a pediatric patient; cidofovir, never previously used for human vaccinia infection; and ST-246, an investigational agent being studied for the treatment of orthopoxvirus infection. Serological response to vaccinia virus and viral DNA levels, correlated with clinical events, were utilized to monitor the course of disease and to guide therapy. Burn patient-type management was required, including skin grafts. Results. The child was discharged from the hospital after 48 days and has recovered with no apparent systemic sequelae or significant scarring. Conclusion. This case illustrates the need for careful screening prior to administration of smallpox vaccine and awareness by clinicians of the ongoing vaccination program and the potential risk for severe adverse events related to vaccinia virus. C1 [Vora, Surabhi; Weber, Stephen G.; Daum, Robert S.; Marcinak, John] Univ Chicago, Med Ctr, Dept Pediat, Infect Dis Sect, Chicago, IL 60637 USA. [Kahana, Madelyn] Univ Chicago, Med Ctr, Sect Crit Care, Dept Pediat, Chicago, IL 60637 USA. [Weber, Stephen G.; Garcia-Houchins, Sylvia] Univ Chicago, Med Ctr, Infect Control Program, Chicago, IL 60637 USA. [Stein, Sarah L.] Univ Chicago, Med Ctr, Dermatol Sect, Chicago, IL 60637 USA. [Thompson, Kenneth] Univ Chicago, Med Ctr, Dept Pathol, Chicago, IL 60637 USA. [Gerber, Susan I.] Chicago Dept Publ Hlth, Chicago, IL USA. [Damon, Inger; Lederman, Edith; Regnery, Russell; Hughes, Christine; Li, Yu; Zhao, Hui; Smith, Scott; Braden, Zach; Karem, Kevin; Olson, Victoria; Davidson, Whitni; Trindade, Giliane] Ctr Dis Control & Prevent, Poxvirus & Rabies Branch, Atlanta, GA USA. [Barson, John V.] Ctr Dis Control & Prevent, Div Bioterrorism Preparedness & Response, Atlanta, GA USA. [Fulginiti, Vincent] Univ Arizona, Tucson, AZ USA. [Fulginiti, Vincent] Univ Colorado, Denver, CO 80202 USA. [Hruby, Dennis; Bolken, Tove; Jordan, Robert; Tien, Debbie] SIGA Technol, Corvallis, OR USA. [Scott, Dorothy] US FDA, Washington, DC 20204 USA. RP Vora, S (reprint author), Univ Chicago, Med Ctr, Dept Pediat, Infect Dis Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM sbhargav@uchicago.edu NR 30 TC 98 Z9 101 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2008 VL 46 IS 10 BP 1555 EP 1561 DI 10.1086/587668 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 289KA UT WOS:000255052200011 PM 18419490 ER PT J AU Chan-Tack, KM Murray, JS AF Chan-Tack, Kirk M. Murray, Jeffrey S. TI Antiviral therapy and outcomes in hospitalized patients with influenza SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Chan-Tack, Kirk M.; Murray, Jeffrey S.] US FDA, DAVP, Ctr Drug Evaluat & Res, OND, Silver Spring, MD 20993 USA. RP Chan-Tack, KM (reprint author), US FDA, DAVP, Ctr Drug Evaluat & Res, OND, 10903 New Hampshire Ave,Bldg 22,Rm 6337, Silver Spring, MD 20993 USA. EM kirk.chan-tack@fda.hhs.gov NR 5 TC 5 Z9 6 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 15 PY 2008 VL 46 IS 10 BP 1628 EP 1629 DI 10.1086/587751 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 289KA UT WOS:000255052200025 PM 18419504 ER PT J AU Cole, LE Santiago, A Barry, E Kang, TJ Shirey, KA Roberts, ZJ Elkins, KL Cross, AS Vogel, SN AF Cole, Leah E. Santiago, Araceli Barry, Eileen Kang, Tae Jin Shirey, Kari Ann Roberts, Zachary J. Elkins, Karen L. Cross, Alan S. Vogel, Stefanie N. TI Macrophage proinflammatory response to Francisella tularensis live vaccine strain requires coordination of multiple signaling pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNE-RESPONSE; MURINE MACROPHAGES; IFN-GAMMA; INTRACELLULAR BACTERIUM; PROTECTIVE IMMUNITY; INTERFERON-BETA; INFECTION; IDENTIFICATION; ACTIVATION; TULAREMIA AB The macrophage proinflammatory response to Francisella tularensis (Ft) live vaccine strain (LVS) was shown previously to be TLR2 dependent. The observation that intracellular Ft LVS colocalizes with TLR2 and MyD88 inside macrophages suggested that Ft LVS might signal from within the phagosome. Macrophages infected with LVSAig/C, a Ft LVS mutant that fails to escape from the phagosorne, displayed greatly increased expression of a subset of TLR2-dependent, proinflammatory genes (e.g., Tnf) but decreased expression of others (e.g., Ifnb1). This latter subset was similarly mitigated in IFN-beta(-/-) macrophages indicating that while Ft LVS-induced TLR2 signaling is necessary, cytosolic sensing of Ft to induce IFN-beta is required for full induction of the macrophage proinflammatory response. Although LVS Delta iglC greatly increased IL-1 beta mRNA in wild-type macrophages, protein secretion was not observed. IL-1 beta secretion was also diminished in Ft LVS-infected IFN-beta(-/-) macrophages. rIFN-beta failed to restore IL-1 beta secretion in LVS Delta iglC-infected macrophages, suggesting that signals in addition to IFN-beta are required for assembly of the inflammasome and activation of caspase-1. IFN-beta plays a central role in controlling the macrophage bacterial burden: bacterial recovery was greater in IFN-beta(-/-) than in wild-type macrophages and treatment of Ft LVS-infected macrophages with rIFN-beta or 5,6-dimethylxanthenone-4-acetic acid, a potent IFN-beta inducer, greatly decreased the intracellular Ft LVS burden. In toto, these observations support the hypothesis that the host inflammatory response to Ft LVS is complex and requires engagement of multiple signaling pathways downstream of TLR2 including production of IFN-beta via an unknown cytosolic sensor and activation of the inflammasome. C1 [Cole, Leah E.; Shirey, Kari Ann; Roberts, Zachary J.; Vogel, Stefanie N.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. [Santiago, Araceli; Barry, Eileen; Kang, Tae Jin; Cross, Alan S.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Allergen & Parasit Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Vogel, SN (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 W Redwood St,Room 324, Baltimore, MD 21201 USA. EM svogel@som.umaryland.edu FU NIAID NIH HHS [R56 AI018797, AI 18797, R01 AI018797, R37 AI018797, T32 AI007540, U54 AI 157168, U54 AI057168, U54 AI057168-05S20015] NR 45 TC 56 Z9 57 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2008 VL 180 IS 10 BP 6885 EP 6891 PG 7 WC Immunology SC Immunology GA 324GW UT WOS:000257507100054 PM 18453609 ER PT J AU Soldin, OP Tonning, JM AF Soldin, Offie P. Tonning, Joseph M. CA Obstet Fetal Pharmacol Res Unit Ne TI Serotonin syndrome associated with triptan monotherapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Soldin, Offie P.] Georgetown Univ, Med Ctr, Washington, DC 20057 USA. [Tonning, Joseph M.] US FDA, Silver Spring, MD 20993 USA. RP Soldin, OP (reprint author), Georgetown Univ, Med Ctr, Washington, DC 20057 USA. EM os35@georgetown.edu FU NCRR NIH HHS [M01 RR023942, M01 RR020359]; NICHD NIH HHS [5U10HD047890-03] NR 4 TC 12 Z9 12 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 MAY 15 PY 2008 VL 358 IS 20 BP 2185 EP U19 DI 10.1056/NEJMc0706410 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 300TY UT WOS:000255849300034 PM 18480219 ER PT J AU Hubbard, K Catalano, J Puri, RK Gnatt, A AF Hubbard, Kyle Catalano, Jennifer Puri, Raj K. Gnatt, Averell TI Knockdown of TFIIS by RNA silencing inhibits cancer cell proliferation and induces apoptosis SO BMC CANCER LA English DT Article ID ELONGATION-FACTOR TFIIS; POLYMERASE-II; C-MYC; GENE-EXPRESSION; BREAST-CANCER; TRANSCRIPTION ELONGATION; MOLECULAR PORTRAITS; INTERFERING RNAS; T-CELLS; TERMINATION AB Background: A common element among cancer cells is the presence of improperly controlled transcription. In these cells, the degree of specific activation of some genes is abnormal, and altering the aberrant transcription may therefore directly target cancer. TFIIS is a transcription elongation factor, which directly binds the transcription motor, RNA Polymerase II and allows it to read through various transcription arrest sites. We report on RNA interference of TFIIS, a transcription elongation factor, and its affect on proliferation of cancer cells in culture. Methods: RNA interference was performed by transfecting siRNA to specifically knock down TFIIS expression in MCF7, MCF10A, PL45 and A549 cells. Levels of TFIIS expression were determined by the Quantigene method, and relative protein levels of TFIIS, c-myc and p53 were determined by C-ELISA. Induction of apoptosis was determined by an enzymatic Caspase 3/7 assay, as well as a non-enzymatic assay detecting cytoplasmic mono- and oligonucleosomes. A gene array analysis was conducted for effects of TFIIS siRNA on MCF7 and MCF10A cell lines. Results: Knockdown of TFIIS reduced cancer cell proliferation in breast, lung and pancreatic cancer cell lines. More specifically, TFIIS knockdown in the MCF7 breast cancer cell line induced cancer cell death and increased c-myc and p53 expression whereas TFIIS knockdown in the noncancerous breast cell line MCF10A was less affected. Differential effects of TFIIS knockdown in MCF7 and MCF10A cells included the estrogenic, c-myc and p53 pathways, as observed by C-ELISA and gene array, and were likely involved in MCF7 cell-death. Conclusion: Although transcription is a fundamental process, targeting select core transcription factors may provide for a new and potent avenue for cancer therapeutics. In the present study, knockdown of TFIIS inhibited cancer cell proliferation, suggesting that TFIIS could be studied as a potential cancer target within the transcription machinery. C1 [Hubbard, Kyle; Gnatt, Averell] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Catalano, Jennifer; Puri, Raj K.] US FDA, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. [Gnatt, Averell] Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Gnatt, A (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA. EM hubbard.kyle@gmail.com; jennifer.catalano@fda.hhs.gov; raj.puri@fda.hhs.gov; agnat001@umaryland.edu FU NIGMS NIH HHS [GM64474, R01 GM064474] NR 71 TC 18 Z9 18 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAY 12 PY 2008 VL 8 AR 133 DI 10.1186/1471-2407-8-133 PG 16 WC Oncology SC Oncology GA 309GC UT WOS:000256447700001 PM 18474089 ER PT J AU Faustino, PJ Yang, Y Progar, JJ Brownell, CR Sadrieh, N May, JC Leutzinger, E Place, DA Duffy, EP Houn, F Loewke, SA Mecozzi, VJ Ellison, CD Khan, MA Hussain, AS Lyon, RC AF Faustino, Patrick J. Yang, Yongsheng Progar, Joseph J. Brownell, Charles R. Sadrieh, Nakissa May, Joan C. Leutzinger, Eldon Place, David A. Duffy, Eric P. Houn, Florence Loewke, Sally A. Mecozzi, Vincent J. Ellison, Christopher D. Khan, Mansoor A. Hussain, Ajaz S. Lyon, Robbe C. TI Quantitative determination of cesium binding to ferric hexacyanoferrate: Prussian blue SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Prussian blue; cesium binding; pH-profile; GI model; particle size; moisture; atomic emission spectroscopy; product quality ID EFFECTIVE ANTIDOTE; CYANIDE RELEASE; RADIOCESIUM; CHERNOBYL; CS-137; RADIOCAESIUM; BODY; RETENTION; AFCF; SOIL AB Ferric hexacyanoferrate (Fe4(III)[Fe-II(CN)(6)](3)), also known as insoluble Prussian blue (PB) is the active pharmaceutical ingredient (API) of the drug product, Radiogardase (R). Radiogardase (R) is the first FDA approved medical countermeasure for the treatment of internal contamination with radioactive cesium (Cs) or thallium in the event of a major radiological incident such as a "dirty bomb". A number of pre-clinical and clinical studies have evaluated the use of PB as an investigational decorporation agent to enhance the excretion of metal cations. There are few sources of published in vitro data that detail the binding capacity of cesium to insoluble PB under various chemical and physical conditions. The study objective was to determine the in vitro binding capacity of PB APIs and drug products by evaluating certain chemical and physical factors such as medium pH, particle size, and storage conditions (temperature). In vitro experimental conditions ranged from pH I to 9, to cover the range of pH levels that PB may encounter in the gastrointestinal (GI) tract in humans. Measurements of cesium binding were made between I and 24 h, to cover gastric and intestinal tract residence time using a validated atomic emission spectroscopy (AES) method. The results indicated that pH, exposure time, storage temperature (affecting moisture content) and particle size play significant roles in the cesium binding to both the PB API and the drug product. The lowest cesium binding was observed at gastric pH of I and 2, whereas the highest cesium binding was observed at physiological pH of 7.5. It was observed that dry storage conditions resulted in a loss of moisture from PB, which had a significant negative effect on the PB cesium binding capacity at time intervals consistent with gastric residence. Differences were also observed in the binding capacity of PB with different particle sizes. Significant batch to batch differences were also observed in the binding capacity of some PB API and drug products. Our results suggest that certain physiochemical properties affect the initial binding capacity and the overall binding capacity of PB APIs and drug products during conditions that simulated gastric and GI residence time. These physiochemical properties can be utilized as quality attributes to monitor and predict drug product quality under certain manufacturing and storage conditions and may be utilized to enhance the clinical efficacy of PB. Published by Elsevier B.V. C1 [Faustino, Patrick J.; Yang, Yongsheng; Brownell, Charles R.; Mecozzi, Vincent J.; Ellison, Christopher D.; Khan, Mansoor A.; Lyon, Robbe C.] US FDA, Div Prod Qual Res, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Progar, Joseph J.; May, Joan C.; Houn, Florence] US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Sadrieh, Nakissa; Hussain, Ajaz S.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Leutzinger, Eldon; Place, David A.; Duffy, Eric P.] US FDA, Off New Drug Qual Assurance, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Loewke, Sally A.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Faustino, PJ (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 60 TC 52 Z9 53 U1 3 U2 37 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAY 12 PY 2008 VL 47 IS 1 BP 114 EP 125 DI 10.1016/j.jpba.2007.11.049 PG 12 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 300TW UT WOS:000255849100013 PM 18242038 ER PT J AU Xia, QS Yan, J Chou, MW Fu, PP AF Xia, Qingsu Yan, Jian Chou, Ming W. Fu, Peter P. TI Formation of DHP-derived DNA adducts from metabolic activation of the prototype heliotridine-type pyrrolizidine alkaloid, heliotrine SO TOXICOLOGY LETTERS LA English DT Article DE pyrrolizidine alkaloid; heliotrine; DNA adducts; dehydroheliotridine (DHH) ID FORMATION IN-VIVO; DIETARY-SUPPLEMENTS; RIDDELLIINE; RATS AB Pyrrolizidine alkaloid-containing plants are widespread in the world and may be the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids require metabolism to exert their genotoxicity and tumorigenicity. Our mechanistic studies have determined that metabolism of the retronecine-type (riddelliine, retrorsine, and monocrotaline), heliotridine-type (lasiocarpine), and otonecine-type (clivorine) tumorigenic pyrrolizidine alkaloids in vivo and/or in vitro all generates a common set of 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts responsible for tumor induction. All the pyrrolizidine alkaloids studied previously are diesters with an ester linkage at the C7 and C9 positions of the necine base. In this study, we report that F344 rat liver microsomal metabolism of heliotrine, a tumorigenic monoester bearing a hydroxyl group at the C7 of the necine base, resulted in the formation of the dehydroheliotridine (DHH) metabolite. When incubations of heliotrine were carried out in the presence of calf thymus DNA, the same set of DHP-derived DNA adducts was formed. These results support that DHP-derived DNA adducts are potential common biomarkers of pyrrolizidine alkaloid exposure and tumorigenicity. For comparison, the dehydroretronecine (DHR)-derived DNA adducts formed from metabolism of riddleiine, retrorsine, monocrotaline, riddelleiine N-oxide, and retrorsine N-oxide were measured in parallel; the levels of DHP-derived DNA adduct formation were in the order: riddelliine approximate to retrorsine > monocrotaline > retrorsine N-oxide >= riddelliine N-oxide > heliotrine. Published by Elsevier Ireland Ltd. C1 [Xia, Qingsu; Yan, Jian; Chou, Ming W.; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov NR 28 TC 21 Z9 25 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAY 5 PY 2008 VL 178 IS 2 BP 77 EP 82 DI 10.1016/j.toxlet.2008.02.008 PG 6 WC Toxicology SC Toxicology GA 306LP UT WOS:000256250100002 PM 18395999 ER PT J AU Chang, S Ball, R Braun, MM AF Chang, Soju Ball, Robert Braun, M. Miles TI Elective termination of pregnancy after vaccination reported to the Vaccine Adverse Event Reporting System (VAERS): 1990-2006 SO VACCINE LA English DT Article DE vaccine; elective termination of pregnancy; VAERS ID RUBELLA VACCINATION; IMMUNIZATION; WOMEN AB Generally, live-virus vaccines are contraindicated for pregnant women because of the theoretical risk of transmission of the vaccine virus to the fetus. Advisory groups recommend avoiding pregnancy in the immediate period after administration of such contraindicated vaccines (CVs) and stress benefit-to-risk evaluation for live or inactivated vaccines regarding pregnancy. Given the Limited available data and theoretical risks associated particularly with live-virus vaccines, inadvertent immunization with CVs may lead to elective termination of pregnancy (ETP), despite advisory group statements that "vaccination is not ordinarily an indication to terminate the pregnancy." The Vaccine Adverse Event Reporting System (VAERS), a national. passive surveillance system managed by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), accepts reports of adverse events after vaccination. The objectives of this review were to describe reports of ETP in VAERS and characterize the circumstances of inadvertent administration of vaccines to pregnant women among ETP reports. We reviewed VAERS reports of ETP submitted from 1990 to 2006. Reports of ETP for reasons other than vaccination during or shortly before pregnancy, such as fetal abnormalities or deaths, were excluded. Of 80 ETP reports, 62 (78%) originated from the US; 79 (99%) were reported by manufacturers. Median age of vaccinees was 26 years (range: 13-43 years; 67 reports). Seventy-three vaccinees (91%) received a single vaccine; 65 (81%) received at least one Live-virus vaccine. In 48 (60%) ETP reports, vaccinees were unaware of pregnancy at time of immunization. In 15 (19%) reports, vaccinees became pregnant within 3 months of vaccination; in 13 (16%) reports, vaccinees might have been pregnant before vaccination; in 4 (5%) reports, information was missing. All 80 reports of ETP involved vaccines for which possible effects on fetal development are unknown. However, no cases of vaccine-associated congenital rubella or varicella syndromes have been reported in the medical, Literature. Also, these syndromes have not been reported to varicella or rubella vaccine pregnancy registries. VAERS has the limitations of passive surveillance systems. Under-reporting of ETP in VAERS could be substantial. More attention may be needed to assess the likelihood of pregnancy when administering vaccines to women with child-bearing potential, and to inform women who learn they are pregnant shortly after being immunized of current information on risks. Quantifying the frequency of ETP related to CVs and the risk (if any) to the fetus of such vaccines can help to inform policy, practice, and individual decision making. Good quality information may be obtained from controlled observational studies. Published by Elsevier Ltd. C1 [Chang, Soju; Ball, Robert; Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20852 USA. RP Chang, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, 1401 Rockville Pike,HFM-222, Rockville, MD 20852 USA. EM soju.chang@fda.hhs.gov NR 34 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 2 PY 2008 VL 26 IS 19 BP 2428 EP 2432 DI 10.1016/j.vaccine.2008.02.052 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 301VD UT WOS:000255922900015 PM 18406499 ER PT J AU Jackson, K Gersh, BJ Stockbridge, N Fleming, TR Temple, R Califf, RM Connolly, SJ Wallentin, L Granger, CB AF Jackson, Kevin Gersh, Bernard J. Stockbridge, Norman Fleming, Thomas R. Temple, Robert Califf, Robert M. Connolly, Stuart J. Wallentin, Lars Granger, Christopher B. CA Participants Duke Clin Res Inst Am TI Antithrombotic drug development for atrial fibrillation: Proceedings, Washington, DC, July 25-27, 2005 SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; STROKE PREVENTION; ANTICOAGULANT-THERAPY; ORAL ANTICOAGULATION; CLINICAL-PRACTICE; CONTROLLED TRIALS; RANDOMIZED TRIAL; RISK-FACTORS; WARFARIN; ASPIRIN AB In July 2005, leaders from academia, government, and industry convened in Washington, DC, to discuss key issues in the development of antithrombotic treatments for atrial fibrillation (AF). In addition to summarizing available data on the relative benefits and risks of currently available therapies in diverse clinical practice settings, we reviewed designs of ongoing trials and registries, focusing on areas of methodological controversy and uncertainty. Participants in this meeting described the growing burden of AF, summarized the data showing effectiveness of warfarin for prevention of stroke in AF, and noted that warfarin is both underused and poorly monitored and adjusted in general practice. There was consensus that there is an important unmet clinical need for better treatment of patients with AF at risk of stroke, including alternatives to warfarin that address its limitations. Comparative noninferiority trials to develop alternatives to warfarin must include warfarin management that is at least as good as that provided in historical trials. There was agreement that noninferiority trials can be done based on historical warfarin trials, and that placebo-controlled trials focused on patients not receiving warfarin in general practice can provide important information as well. Statistical principles for noninferiority in this setting were discussed, and a standard approach was proposed. A majority of clinical trial representatives suggested that large, simple, open-label trials would provide the most meaningful information relevant to future practice, but regulators cautioned that, in such a simple trial, one needs to ensure that the control group does at least as well as the historical controls for the noninferiority design to be interpretable. With this summary document, we hope to provide a helpful resource for future drug development for AF. C1 [Jackson, Kevin; Califf, Robert M.; Granger, Christopher B.] Duke Clin Res Inst, Durham, NC USA. [Gersh, Bernard J.] Mayo Clin, Rochester, MN USA. [Stockbridge, Norman; Temple, Robert] US FDA, Silver Spring, MD USA. [Fleming, Thomas R.] Univ Washington, Seattle, WA 98195 USA. [Connolly, Stuart J.] McMaster Univ, Hamilton, ON, Canada. [Wallentin, Lars] Univ Uppsala Hosp, Uppsala, Sweden. RP Granger, CB (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Room 0311 Terrace Level,2400 Pratt St, Durham, NC 27705 USA. EM grang001@dcri.duke.edu RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 NR 44 TC 11 Z9 11 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2008 VL 155 IS 5 BP 829 EP 840 DI 10.1016/j.ahj.2008.01.023 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 302WU UT WOS:000256001500006 PM 18440329 ER PT J AU Rappaport, BA AF Rappaport, Bob A. TI FDA response to droperidol black box warning editorials SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. RP Rappaport, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. EM bob.rappaport@fda.hhs.gov NR 2 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2008 VL 106 IS 5 BP 1585 EP 1585 DI 10.1213/ane.0b013e3181693844 PG 1 WC Anesthesiology SC Anesthesiology GA 291UP UT WOS:000255222700046 PM 18420886 ER PT J AU Felson, DT Zhang, B Siegel, JN AF Felson, David T. Zhang, Bin Siegel, Jeffrey N. TI Trials in rheumatoid arthritis: choosing the right outcome measure when minimal disease is achievable SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DOUBLE-BLIND; RANDOMIZED-TRIAL; CLINICAL-TRIAL; METHOTREXATE TREATMENT; ETANERCEPT; EFFICACY; PLACEBO; SAFETY; MULTICENTER; HAD C1 [Felson, David T.; Zhang, Bin] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Siegel, Jeffrey N.] US FDA, Silver Spring, MD USA. RP Felson, DT (reprint author), Boston Univ, Sch Med, Clin Epidemiol Unit, Room X200,650 Albany St, Boston, MA 02118 USA. EM dfelson@bu.edu OI Felson, David/0000-0002-2668-2447 FU NIAMS NIH HHS [AR47785, P60 AR047785-07, P60 AR047785] NR 20 TC 4 Z9 4 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAY PY 2008 VL 67 IS 5 BP 580 EP 583 DI 10.1136/ard.2007.079632 PG 4 WC Rheumatology SC Rheumatology GA 287LM UT WOS:000254918600002 PM 18408109 ER PT J AU Sheng, L Cai, F Zhu, Y Pal, A Athanasiou, M Orrison, B Blair, DG Hughes, SH Coffin, JM Lewis, AM Peden, K AF Sheng, Li Cai, Fang Zhu, Yong Pal, Achintya Athanasiou, Meropi Orrison, Brian Blair, Donald G. Hughes, Stephen H. Coffin, John M. Lewis, Andrew M. Peden, Keith TI Oncogenicity of DNA in vivo: Tumor induction with expression plasmids for activated H-ras and c-myc SO BIOLOGICALS LA English DT Article DE DNA oncogenicity; T24-H-ras; c-myc; tumor induction; vaccine cell substrate ID VIRUS EARLY REGION; TRANSGENIC MICE; EMBRYO FIBROBLASTS; CELL-LINE; BK VIRUS; CHROMOSOMAL INSERTION; PROMOTER INSERTION; EPITHELIAL-CELLS; GENE-TRANSFER; FOREIGN DNA AB All vaccines and other biological products contain contaminating residual DNA derived from the production cell substrate. Whether this residual cell-substrate DNA can induce tumors in vaccine recipients and thus represent a risk factor has been debated for over 50 years without resolution. As a first step in resolving this issue, we have generated expression plasmids for the activated human H-ras oncogene and for the murine c-myc proto-oncogene. Their oncogenic activity was confirmed in vitro using the focus-formation transformation assay. Two strains of adult and newborn immune-competent mice were inoculated with different amounts of either plasmid alone or with a combination of the H-ras and c-myc plasmids. Tumors developed only in mice inoculated with both plasmids and only at the highest amount of DNA (12.5 mu g of each plasmid). The NIH Swiss mouse was more sensitive than the C57BL/6 mouse, and newborn animals were more sensitive than adults. Cell lines were established from the tumors. PCR and Southern hybridization analyses demonstrated that both inoculated oncogenes were present in all of the tumor-derived cell lines and that the cells in the tumors were clonal. Western analysis demonstrated that both oncoproteins were expressed in these cell lines. These results demonstrate that cellular oncogenes can induce tumors following subcutaneous inoculation. Such information provides a possible way of evaluating and estimating the theoretical oncogenic risk posed by residual cell-substrate DNA in vaccines. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Sheng, Li; Cai, Fang; Zhu, Yong; Pal, Achintya; Orrison, Brian; Lewis, Andrew M.; Peden, Keith] US FDA, Div Viral Prod, OVRR, CBER, Bethesda, MD 20892 USA. [Blair, Donald G.; Hughes, Stephen H.; Coffin, John M.] NCI, Frederick Canc Res Facil, Frederick, MD 21701 USA. [Coffin, John M.] Tufts Univ, Dept Microbiol & Mol Biol, Boston, MA 02111 USA. RP Peden, K (reprint author), US FDA, Div Viral Prod, OVRR, CBER, Bldg 29A,Room 3D08 29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hhs.gov; andrew.lewis@fda.hhs.gov FU NCI NIH HHS [R01 CA089441] NR 56 TC 12 Z9 14 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAY PY 2008 VL 36 IS 3 BP 184 EP 197 DI 10.1016/j.biologicals.2007.11.003 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 296MF UT WOS:000255548000005 PM 18218323 ER PT J AU Williams, D Irvin, EA Puckett, AM Raybourne, RB Smith, MA AF Williams, D. Irvin, E. A. Puckett, A. M. Raybourne, R. B. Smith, M. A. TI Maternal and fetal tissue infectivity following an oral challenge with listeria monocytogenes and an anti-internalin peptide in pregnant guinea pigs SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Williams, D.; Irvin, E. A.; Smith, M. A.] Univ Georgia, Environm Hlth Sci Dept, Athens, GA 30602 USA. [Puckett, A. M.] Univ Georgia, Coll Vet Med, Athens, GA 30602 USA. [Smith, M. A.] Univ Georgia, Ctr Food Safety, Athens, GA 30602 USA. [Raybourne, R. B.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 289 EP 289 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000010 ER PT J AU Kaput, J AF Kaput, J. TI Concepts and challenges in developing personalized nutrition medicine for pregnant women and infants SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Kaput, J.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 321 EP 321 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000068 ER PT J AU Paule, MG AF Paule, M. G. TI Acrylamide in food and issues of safety during development SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Paule, M. G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 321 EP 321 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000067 ER PT J AU Gruber, MF AF Gruber, M. F. TI Regulatory considerations pertaining to maternal immunization SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Gruber, M. F.] FDA, CBER, OVRR, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 330 EP 330 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000085 ER PT J AU Feibus, KB Mathis, L AF Feibus, K. B. Mathis, L. TI USFDA perspective on pregnancy registry data: What do we want in the label SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Feibus, K. B.; Mathis, L.] US FDA, CDER, Off New Drugs, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 339 EP 339 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000101 ER PT J AU Gibson, L Marchant, CA Patel, ML Surfraz, MB Benz, RD Matthews, EJ AF Gibson, L. Marchant, C. A. Patel, M. L. Surfraz, M. B. Benz, R. D. Matthews, E. J. TI Developing structural alerts for the prediction of teratogenicity SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Gibson, L.; Marchant, C. A.; Patel, M. L.; Surfraz, M. B.] Lhasa Ltd, Leeds, W Yorkshire, England. [Benz, R. D.; Matthews, E. J.] Food & Drug Adm, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2008 VL 82 IS 5 BP 354 EP 354 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 312FR UT WOS:000256655000123 ER PT J AU Zivny, JH Gelderman, MP Xu, F Piper, J Holada, K Simak, J Vostal, JG AF Zivny, Jan H. Gelderman, Monique P. Xu, Fei Piper, John Holada, Karel Simak, Jan Vostal, Jaroslav G. TI Reduced erythroid cell and erythropoietin production in response to acute anemia in prion protein-deficient (Pmp(-/-)) mice SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE prion protein; erythroid cell; Terl 19+; erythropoietin; anemia ID CONFORMATIONAL-CHANGE; COPPER-BINDING; HUMAN NEURONS; BLOOD-CELLS; ACTIVATION; EXPRESSION; PHYSIOLOGY; APOPTOSIS; DISEASES; HYPOXIA AB Cellular prion protein (PrPc) participates in the pathogenesis of priori diseases but its normal function remains unclear. PrPc is expressed on hematopoietic cells, including erythroid precursors. We investigated the role of PrPc in erythropoiesis in vivo with phenylhydrazine-induced acute anemia. Induction of equivalent anemia in wild-type (WT) and Pmp-/- mice resulted in a higher number of circulating reticulocytes, hematocrits, and spleen weights in WT mice than in Pmp-/- mice on Days 5 and 7. Examination of bone marrow erythroid precursor cells (Terl 19+) on Day 5 revealed no significant differences in the number of these cells between the two types of animals. However, a higher percentage of Terl 19+ cells were going through apoptosis in Pmp-/- mice than in WT mice. Plasma crythropoietin (Epo) levels and Epo mRNA in kidneys peaked on Day 3 in response to anemia for both types of animals but rose less in Pmp-/- (5500 pg/ml) than in WT (18,000 pg/ml) animals. Administration of recombinant human Epo to mice produced an equivalent reticulocyte response in both types of animals suggesting that the potential for erythroid generation is intact in Pmp-/- animals. These observations indicate that PrPc may modulate tissue hypoxia-sensing mechanisms or effect hypoxia target gene expression. Published by Elsevier Inc. C1 [Gelderman, Monique P.; Xu, Fei; Piper, John; Simak, Jan; Vostal, Jaroslav G.] US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20014 USA. [Zivny, Jan H.; Holada, Karel] Charles Univ Prague, Sch Med 1, Prague, Czech Republic. RP Vostal, JG (reprint author), Ctr Biol Evaluat & Res, OBRR, Div Hematol, Lab Cellular Hematol, 1401 Rockville Pike,HFM-335, Rockville, MD 20852 USA. EM jaroslav.vostal@fda.hhs.gov RI Simak, Jan/C-1153-2011 NR 36 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2008 VL 40 IS 3 BP 302 EP 307 DI 10.1016/j.bcmd.2007.09.009 PG 6 WC Hematology SC Hematology GA 293EH UT WOS:000255317500002 PM 17964827 ER PT J AU Xiang, LB Szebeni, K Szebeni, A Klimek, V Stockmeier, CA Karolewicz, B Kalbfleisch, J Ordway, GA AF Xiang, Lianbin Szebeni, Katalin Szebeni, Attila Klimek, Violetta Stockmeier, Craig A. Karolewicz, Beata Kalbfleisch, John Ordway, Gregory A. TI Dopamine receptor gene expression in human amygdaloid nuclei: Elevated D4 receptor mRNA in major depression SO BRAIN RESEARCH LA English DT Article DE dopamine receptor; gene expression; amygdala; depression; major depression; real-time PCR; human brain; dopamine ID CHRONIC MILD STRESS; PARKINSONS-DISEASE; HUMAN BRAIN; BASOLATERAL AMYGDALA; RAT-BRAIN; ANTIDEPRESSANT TREATMENT; MEMORY CONSOLIDATION; I-125 EPIDEPRIDE; NEURAL RESPONSE; HUMAN FOREBRAIN AB Previous findings from this laboratory demonstrating changes in dopamine (DA) transporter and D2 receptors in the amygdaloid complex of subjects with major depression indicate that disruption of dopamine neurotransmission to the amygdala may contribute to behavioral symptoms associated with depression. Quantitative real-time RT-PCR was used to investigate the regional distribution of gene expression of DA receptors in the human amygdala. In addition, relative levels of mRNA of DA receptors in the basal amygdaloid nucleus were measured postmortem in subjects with major depression and normal control subjects. All five subtypes of DA receptor mRNA were detected in all amygdaloid subnuclei, although D1, D2, and D4 receptor mRNAs were more abundant than D3 and D5 mRNAs by an order of magnitude. The highest level of D1 mRNA was found in the central nucleus, whereas D2 mRNA was the most abundant in the basal nucleus. Levels of D4 mRNA were highest in the basal and central nuclei. In the basal nucleus, amounts of D4, but not D1 or D2, mRNAs were significantly higher in subjects with major depression as compared to control subjects. These findings demonstrate that the D1, D2 and D4 receptors are the major subtypes of DA receptors in the human amygdala. Elevated DA receptor gene expression in depressive subjects further implicates altered dopaminergic transmission in the amygdala in depression. (C) 2008 Elsevier B.V. All rights reserved. C1 [Xiang, Lianbin; Szebeni, Katalin; Szebeni, Attila; Ordway, Gregory A.] E Tennessee State Univ, James H Quillen Coll Med, Dept Pharmacol, Johnson City, TN 37614 USA. [Klimek, Violetta] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Stockmeier, Craig A.; Karolewicz, Beata] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [Kalbfleisch, John] E Tennessee State Univ, Div Biometry & Med Comp, Johnson City, TN 37614 USA. RP Ordway, GA (reprint author), E Tennessee State Univ, James H Quillen Coll Med, Dept Pharmacol, POB 70577, Johnson City, TN 37614 USA. EM ordway@etsu.edu FU NCRR NIH HHS [RR17701, P20 RR017701-03, P20 RR017701]; NIMH NIH HHS [MH02031, K02 MH002031-05, R01 MH046692, MH63187, R01 MH067996, R01 MH046692-11, MH67996, K02 MH002031-04, R01 MH063187, R01 MH063187-04, R01 MH046692-13, MH46692, R01 MH063187-01A1, R01 MH063187-03, K02 MH002031-06, R01 MH063187-02, R01 MH046692-12, R01 MH063187-05, K02 MH002031] NR 79 TC 26 Z9 26 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 2008 VL 1207 BP 214 EP 224 DI 10.1016/j.brainres.2008.02.009 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 299AW UT WOS:000255729200022 PM 18371940 ER PT J AU Tamminga, J Koturbash, I Baker, M Kutanzi, K Kathiria, P Pogribny, IP Sutherland, RJ Kovalchuk, O AF Tamminga, Jan Koturbash, Igor Baker, Mike Kutanzi, Kristy Kathiria, Palak Pogribny, Igor P. Sutherland, Robert J. Kovalchuk, Olga TI Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring SO CELL CYCLE LA English DT Article DE germ cells; DNA damage; bystander effect; radiation exposure; transgeneration effect; epigenetics; DNA methylation; H2AX ID INDUCED GENOMIC INSTABILITY; STRAND BREAK REPAIR; IONIZING-RADIATION; IN-VIVO; X-IRRADIATION; HISTONE H2AX; METHYLATION; CELLS; MICE; METHYLTRANSFERASES AB It is now well accepted that parental whole body irradiation causes transgenerational genome and epigenome instability in the offspring. The majority of human exposures to radiation, such as therapeutic and diagnostic irradiation, are localized and focused. The potential of localized body-part exposures to affect the germline and thus induce deleterious changes in the progeny has not been studied. To investigate whether or not the paternal cranial irradiation can exert deleterious changes in the protected germline, we studied the accumulation of DNA damage in the shielded testes tissue. Here we report that the localized paternal cranial irradiation results in a significant accumulation of unrepaired DNA lesions in sperm cells and leads to a profound epigenetic dysregulation in the unexposed progeny conceived a week after paternal exposure. C1 [Tamminga, Jan; Koturbash, Igor; Baker, Mike; Kutanzi, Kristy; Kathiria, Palak; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Sutherland, Robert J.] Univ Lethbridge, Dept Neurosci, Lethbridge, AB T1K 3M4, Canada. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 47 TC 28 Z9 32 U1 2 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAY 1 PY 2008 VL 7 IS 9 BP 1238 EP 1245 DI 10.4161/cc.7.9.5806 PG 8 WC Cell Biology SC Cell Biology GA 304IH UT WOS:000256102700019 PM 18418050 ER PT J AU Pfeiffer, CM Osterloh, JD Kennedy-Stephenson, J Picciano, MF Yetley, EA Rader, JI Johnson, CL AF Pfeiffer, Christine M. Osterloh, John D. Kennedy-Stephenson, Jocelyn Picciano, Mary Frances Yetley, Elizabeth A. Rader, Jeanne I. Johnson, Clifford L. TI Trends in circulating concentrations of total homocysteine among US adolescents and adults: Findings from the 1991-1994 and 1999-2004 National Health and Nutrition Examination Surveys SO CLINICAL CHEMISTRY LA English DT Article ID PLASMA TOTAL HOMOCYSTEINE; FOLIC-ACID FORTIFICATION; GLOMERULAR-FILTRATION-RATE; EXAMINATION SURVEY NHANES; UNITED-STATES; RANDOMIZED-TRIALS; SERUM; DISEASE; FOLATE; METAANALYSIS AB BACKGROUND: The National Health and Nutrition Examination Survey (NHANES) has monitored total homocysteine (tHcy) concentrations in a nationally-representative sample of the US population since 1991. Until recently, however, data could not be compared across survey periods because of changes in analytical methods and specimen matrices. Such an analysis of these data could supplement current knowledge regarding whether the US folic acid fortification program has modified national plasma tHcy concentrations. METHODS: We examined tHcy data in the prefortification NHANES III survey (phase 11, 1991-1994) and in 3 postfortification survey periods (1999-2000, 20012002, and 2003-2004). We applied method adjustment equations to the survey data based on method comparison studies of separate samples. Persons with chronic kidney disease were excluded from the analyses. RESULTS: Mean plasma tHcy concentrations decreased by 8%, 9%, and 10% for adolescent, adult, and older men andby6%,3%, and 13% for women, respectively, from before to after fortification. Concentrations remained unchanged between the first and third postfortification survey periods. Prevalence estimates of increased plasma tHcy concentrations (> 13 mu mol/L) for older men and women decreased from prefortification (32% and 20%, respectively) to postfortification (14% and 5%, respectively) but remained unchanged thereafter (16% and 14%, respectively [males] and 5% and 9%, respectively [females]). CONCLUSIONS: After adjusting for method changes, we quantified a prefortification to postfortification decrease in circulating tHcy concentrations of about 10% in a national sample of the US population. This change is similar to effects seen in intervention trials with folic acid and in smaller observational studies. (c) 2008 American Association for Clinical Chemistry. C1 [Pfeiffer, Christine M.; Osterloh, John D.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Kennedy-Stephenson, Jocelyn; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Picciano, Mary Frances; Yetley, Elizabeth A.] NIH, Off Regulatory Supplements, Bethesda, MD 20892 USA. [Rader, Jeanne I.] Food & Drug Adm, Off Regulatory Sci, College Pk, MD USA. RP Pfeiffer, CM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy,MS F55, Atlanta, GA 30341 USA. EM cpfeiffer@cdc.gov NR 39 TC 33 Z9 36 U1 0 U2 0 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 MAY PY 2008 VL 54 IS 5 BP 801 EP 813 DI 10.1373/clinchem.2007.100214 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 293OM UT WOS:000255344600006 PM 18375482 ER PT J AU Struble, KA Reynolds, KS AF Struble, Kimberly A. Reynolds, Kellie Schoolar TI A regulatory perspective on the role of drug interactions in antiretroviral drug development SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE antiretroviral drug development; drug interaction studies; regulatory perspective AB Purpose of review To provide a regulatory perspective on the role of drug interaction information in the development of antiretroviral drugs. Additionally, this review highlights novel studies that provided important information for the safe and effective use of antiretroviral medications. The management of drug interactions in HIV therapy becomes more complex with the introduction of each new drug because many antiretroviral drugs are involved in multiple metabolic and transporter-based interactions. Therefore, a comprehensive preclinical evaluation to characterize a new drug's metabolic pathway(s) followed by in-vivo studies is critical for the safe use of combination antiretroviral therapy. Recent findings This review highlights published studies to illustrate several clinical and regulatory issues for in-vivo drug interaction studies such as general design issues, study-population selection, study-design options, use of historical controls and interpretation of results. Summary Early identification of potential drug interactions can help identify and prioritize clinically important interaction studies essential to the overall development process. Understanding the clinical implications and management of drug interactions can lead to more effective long-term therapy, reduce toxicity, and delay the development of resistance. C1 [Struble, Kimberly A.] US FDA, Off New Drugs, Div Antiviral Prod, Silver Spring, MD 20993 USA. [Reynolds, Kellie Schoolar] US FDA, Off Clin Pharmacol, Div Clin Pharmacol 4, Silver Spring, MD 20993 USA. RP Struble, KA (reprint author), US FDA, Off New Drugs, Div Antiviral Prod, 10903 New Hampshire Ave,Bldg 22,Room 6347, Silver Spring, MD 20993 USA. EM kimberly.struble@fda.hhs.gov FU US Food and Drug Administration FX The views expressed are those of the authors. No official support or endorsements by the US Food and Drug Administration are provided or should be inferred. NR 15 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD MAY PY 2008 VL 3 IS 3 BP 325 EP 329 DI 10.1097/COH.0b013e3282f5f509 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NZ UT WOS:000208418400020 PM 19372986 ER PT J AU Lloyd, R Harris, J Wadhwa, S Chambers, W AF Lloyd, Rhea Harris, Jennifer Wadhwa, Sonal Chambers, Wiley TI Food and Drug Administration approval process for ophthalmic drugs in the US SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE biologic license application (BLA); drug regulation in the US; FDA; new drug application (NDA); ophthalmic drug approval ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; ENDOTHELIAL GROWTH-FACTOR AB Purpose of review The purpose of this review is to provide the overall framework of the review and approval of ophthalmic drugs in the US. Recent findings Examples from the recent approval of the ranibizumab injection (Lucentis; Genentech, South San Francisco, California, USA) are offered to illustrate the current approval process at the Food and Drug Administration (FDA). Summary New drugs are brought to the US market after review of the New Drug Application or Biologic License Application by the FDA. This review process requires the teamwork of an interdisciplinary team of clinicians, scientists and regulatory personnel. This team is ultimately responsible for recommending to the Secretary of Health and Human Services (or designee) the approvability of a drug based on defined requirements including the drug's risk/benefit profile, quality and purity, and the drug's ability to be labeled effectively. Within the Center for Drug Evaluation and Research this review team for ophthalmic drugs resides primarily within the Division of Anti-infective and Ophthalmology Products. C1 [Lloyd, Rhea; Harris, Jennifer; Wadhwa, Sonal; Chambers, Wiley] US FDA, Ctr Drug Evaluat & Res, Div Antiinfect & Ophthalmol Prod, Silver Spring, MD 20903 USA. RP Lloyd, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Antiinfect & Ophthalmol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Rhea.Lloyd@fda.hhs.gov NR 6 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD MAY PY 2008 VL 19 IS 3 BP 190 EP 194 DI 10.1097/ICU.0b013e3282f97fa1 PG 5 WC Ophthalmology SC Ophthalmology GA 296MG UT WOS:000255548100004 PM 18408492 ER PT J AU Cederroth, CR Vinciguerra, M Gjinovci, A Kuhne, F Klein, M Cederroth, M Caille, D Suter, M Neumann, D James, RW Doerge, DR Wallimann, T Meda, P Foti, M Rohner-Jeanrenaud, F Vassalli, JD Nef, S AF Cederroth, Christopher R. Vinciguerra, Manlio Gjinovci, Asllan Kuehne, Francoise Klein, Marcella Cederroth, Manon Caille, Dorothee Suter, Mariane Neumann, Dietbert James, Richard W. Doerge, Daniel R. Wallimann, Theo Meda, Paolo Foti, Michelangelo Rohner-Jeanrenaud, Francoise Vassalli, Jean-Dominique Nef, Serge TI Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism SO DIABETES LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; ACETYL-COA CARBOXYLASE; FATTY-ACID OXIDATION; LONG-TERM CONTROL; ADIPOSE-TISSUE; INSULIN-SECRETION; SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; COACTIVATOR PGC-1; OVARIAN HORMONES AB OBJECTIVE-Emerging evidence suggests that dietary phytoestrogens can have beneficial effects on obesity and diabetes, although their mode of action is not known. Here, we investigate the mechanisms mediating the action of dietary phytoestrogens on lipid and glucose metabolism in rodents. RESEARCH DESIGN AND METHODS-Male CD-1 mice were fed from conception to adulthood with either a high soy-containing diet or a soy-free diet. Serum levels of circulating isoflavones, ghrelin, leptin, free fatty acids, triglycerides, and cholesterol were quantified. Tissue samples were analyzed by quantitative RT-PCR and Western blotting to investigate changes of gene expression and phosphorylation state of key metabolic proteins. Glucose and insulin tolerance tests and euglycemic-hyperinsulinernic clamp were used to assess changes in insulin sensitivity and glucose uptake. In addition, insulin secretion was determined by in situ pancreas perfusion. RESULTS-In peripheral tissues of soy-fed mice, especially in white adipose tissue, phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase was increased, and expression of genes implicated in peroxisomal fatty acid oxidation and mitochondrial biogenesis was upregulated. Soy-fed mice also showed reduced serum insulin levels and pancreatic insulin content and improved insulin sensitivity due to increased glucose uptake into skeletal muscle. Thus, mice fed with a soy-rich diet have improved adipose and glucose metabolism. CONCLUSIONS-Dietary soy could prove useful to prevent obesity and associated disorders. Activation of the AMPK pathway by dietary soy is likely involved and may mediate the beneficial effects of dietary soy in peripheral tissues. C1 [Cederroth, Christopher R.; Kuehne, Francoise; Cederroth, Manon; Vassalli, Jean-Dominique] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. [Vinciguerra, Manlio; Gjinovci, Asllan; Caille, Dorothee; Meda, Paolo; Foti, Michelangelo] Univ Geneva, Dept Cellular Physiol & Metab, Fac Med, Geneva, Switzerland. [Klein, Marcella; Rohner-Jeanrenaud, Francoise] Univ Geneva, Lab Metab, Geneva, Switzerland. [Suter, Mariane; Neumann, Dietbert; Wallimann, Theo] ETH, Inst Cell Biol, CH-8093 Zurich, Switzerland. [James, Richard W.] Univ Geneva, Fac Med, Div Endocrinol Diabetol & Nutr, Clin Diabet Unit, Geneva, Switzerland. [Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nef, S (reprint author), Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Dept Genet Med & Dev, CH-1211 Geneva 4, Switzerland. EM serge.nef@medecine.unige.ch RI Cederroth, Christopher/B-9539-2008; Cederroth, Christopher/B-9932-2011; Wallimann, Theo/C-6047-2008; Neumann, Dietbert/A-1832-2008; OI Neumann, Dietbert/0000-0002-4316-684X; Vinciguerra, Manlio/0000-0002-1768-3894; Cederroth, Christopher/0000-0001-7267-5136 NR 48 TC 101 Z9 112 U1 3 U2 12 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 MAY PY 2008 VL 57 IS 5 BP 1176 EP 1185 DI 10.2337/db07-0630 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 297PN UT WOS:000255628700007 PM 18420492 ER PT J AU French, JA Meador, K Cnaan, A Gilliam, F Conway, J Araojo, R Feibus, K AF French, Jacqueline A. Meador, Kimford Cnaan, Avital Gilliam, Frank Conway, Jill Araojo, Richardae Feibus, Karen TI Ethical and regulatory issues related to pregnancy registries and their outcomes SO EPILEPSY & BEHAVIOR LA English DT Review DE epilepsy; pregnancy; registries; ethics ID ANTIEPILEPTIC DRUGS; SEIZURE CONTROL; MALFORMATIONS AB Pregnancy registries should be devised so that the interests of science, society, and the individual are all considered. For example, there may be ethical issues that relate to how women are chosen to participate in the registry and how informed consent is obtained. In most cases, consent is required for both the mother and the infant. Some institutional review boards will require that consent be obtained by someone other than the woman's physician. Once data are obtained, there may be an issue as to when results should be released. Options are to release data when there is the first indication of a concerning finding, thereby potentially preventing exposure in the largest number of women, versus waiting until the finding is absolutely confirmed. In a related issue, there are questions of when and how regulatory agencies should change labeling based on findings. (C) 2007 Elsevier Inc. All rights reserved. C1 [French, Jacqueline A.] NYU, Comprehens Epilepsy Ctr, New York, NY 10016 USA. [Meador, Kimford] Univ Florida, Gainesville, FL USA. [Cnaan, Avital] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gilliam, Frank] Columbia Univ, New York, NY USA. [Conway, Jill] Univ Penn, Philadelphia, PA 19104 USA. [Araojo, Richardae; Feibus, Karen] US FDA, Washington, DC 20204 USA. RP French, JA (reprint author), NYU, Comprehens Epilepsy Ctr, 403 E 34th St,4th Floor, New York, NY 10016 USA. EM Jacqueline.French@comcast.net OI French, Jacqueline/0000-0003-2242-8027 NR 13 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD MAY PY 2008 VL 12 IS 4 BP 587 EP 591 DI 10.1016/j.yebeh.2007.11.005 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 284JX UT WOS:000254703800006 PM 18158272 ER PT J AU Plant, EP Dinman, JD AF Plant, Ewan P. Dinman, Jonathan D. TI The role of programmed-1 ribosomal frameshifting in coronavirus propagation SO FRONTIERS IN BIOSCIENCE LA English DT Article DE coronavirus; SARS; frameshifting; review ID RESPIRATORY-SYNDROME CORONAVIRUS; IMMUNODEFICIENCY-VIRUS TYPE-1; RNA PSEUDOKNOT; SARS CORONAVIRUS; INFECTIOUS CDNA; MESSENGER-RNA; E-SITE; SIGNAL; POLYMERASE; EXPRESSION AB Coronaviruses have the potential to cause significant economic, agricultural and health problems. The severe acute respiratory syndrome (SARS) associated coronavirus outbreak in late 2002, early 2003 called attention to the potential damage that coronaviruses could cause in the human population. The ensuing research has enlightened many to the molecular biology of coronaviruses. A programmed -1 ribosomal frameshift is required by coronaviruses for the production of the RNA dependent RNA polymerase which in turn is essential for viral replication. The frameshifting signal encoded in the viral genome has additional features that are not essential for frameshifting. Elucidation of the differences between coronavirus frameshift signals and signals from other viruses may help our understanding of these features. Here we summarize current knowledge and add additional insight regarding the function of the programmed -1 ribosomal frameshift signal in the coronavirus lifecycle. C1 [Plant, Ewan P.] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. [Dinman, Jonathan D.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. RP Plant, EP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, HFM-310,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Ewan.Plant@FDA.hhs.gov OI Plant, Ewan/0000-0003-0166-5939; Dinman, Jonathan/0000-0002-2402-9698 FU NIAID NIH HHS [R01 AI064307, R01 AI064307-02, R01 AI064307-01A2] NR 48 TC 14 Z9 15 U1 1 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY PY 2008 VL 13 BP 4873 EP 4881 DI 10.2741/3046 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 301GS UT WOS:000255885000126 PM 18508552 ER PT J AU Webby, RJ Sandbulte, MR AF Webby, Richard John Sandbulte, Matthew Robert TI Influenza vaccines SO FRONTIERS IN BIOSCIENCE-LANDMARK LA English DT Review DE influenza; vaccine; H5N1; epidemic; pandemic; review ID A/DUCK/SINGAPORE/97 H5N3 VACCINE; RANDOMIZED CONTROLLED-TRIAL; LIVE ATTENUATED VACCINES; KIDNEY VERO CELLS; A VIRUS; REVERSE-GENETICS; MF59-ADJUVANTED INFLUENZA; PANDEMIC INFLUENZA; ANTIBODY-RESPONSES; M2 PROTEIN AB Influenza viruses pose a major challenge to those concerned with global public health. Not only do influenza viruses cause yearly epidemics that are associated with slight changes in viral antigenicity, but occasionally new viruses cross from animal reservoirs into humans causing major pandemics. The most effective method to lower the mortality and morbidity associated with influenza is vaccination. In this review current and pending influenza vaccine technologies will be discussed in the context of both epidemic and pandemic influenza. C1 [Webby, Richard John] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Sandbulte, Matthew Robert] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Webby, RJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 332 N Lauderdale St, Memphis, TN 38105 USA. EM richard.webby@stjude.org NR 105 TC 10 Z9 10 U1 4 U2 6 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI-LANDMRK JI Front. Biosci. PD MAY PY 2008 VL 13 BP 4912 EP 4924 DI 10.2741/3050 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 301GS UT WOS:000255885000130 PM 18508556 ER PT J AU Heemskerk, B Liu, K Dudley, ME Johnson, LA Kaiser, A Downey, S Zheng, Z Shelton, TE Matsuda, K Robbins, PF Morgan, RA Rosenberg, SA AF Heemskerk, Bianca Liu, Ke Dudley, Mark. E. Johnson, Laura A. Kaiser, Andrew Downey, Stephanie Zheng, Zhili Shelton, Thomas E. Matsuda, Kant Robbins, Paul F. Morgan, Richard A. Rosenberg, Steven A. TI Adoptive cell therapy for patients with melanoma, using tumor-infiltrating lymphocytes genetically engineered to secrete interleukin-2 SO HUMAN GENE THERAPY LA English DT Article ID CD8(+) T-CELLS; IN-VIVO PERSISTENCE; METASTATIC MELANOMA; CANCER REGRESSION; SECONDARY EXPANSION; EXOGENOUS IL-2; GENE; MEMORY; PROLIFERATION; EFFECTOR AB Adoptive cell transfer of tumor-infiltrating lymphocytes (TILs) after lymphodepletion mediates regression in 50% of patients with metastatic melanoma. In vivo persistence and telomere length of the transferred cells correlate with antitumor response. In an attempt to prolong the in vivo survival of the transferred cells, TILs were genetically engineered to produce interleukin (IL)-2. In vitro, these transduced TILs secreted IL-2 while retaining tumor specificity and exhibited prolonged survival after IL-2 withdrawal. In a phase I/II clinical trial, seven evaluable patients received transduced TILs and one patient experienced a partial response associated with in vivo persistence of IL-2-transduced TILs in circulating lymphocytes. An additional five patients received transduced TILs in conjunction with IL-2 administration. Persistence of IL-2-transduced TILs was observed in three patients, including one partial responder. The transgene DNA as well as vector-derived IL-2 mRNA could be detected for 4 months in responding patients. The low response rate in this trial was possibly due to a reduction in telomere length in cells as a result of prolonged in vitro culture. In this study, insertion of the IL-2 gene into antitumor TILs increased their ability to survive after IL-2 withdrawal in vitro but did not increase their in vivo persistence or clinical effectiveness. C1 [Heemskerk, Bianca; Liu, Ke; Dudley, Mark. E.; Johnson, Laura A.; Kaiser, Andrew; Downey, Stephanie; Zheng, Zhili; Shelton, Thomas E.; Robbins, Paul F.; Morgan, Richard A.; Rosenberg, Steven A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Liu, Ke] US FDA, Rockville, MD 20852 USA. [Matsuda, Kant] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, CRC 3W-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@mail.nih.gov RI Kaiser, Andrew/C-2617-2012; Heemskerk, Bianca/C-4635-2012; Johnson, Laura/H-4861-2013; OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS [Z01 SC003811-33] NR 33 TC 65 Z9 66 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2008 VL 19 IS 5 BP 496 EP 510 DI 10.1089/hum.2007.0171 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 308ZW UT WOS:000256430500009 PM 18444786 ER PT J AU Smith, JS Xu, ZL Tian, J Stevenson, SC Byrnes, AP AF Smith, Jeffrey S. Xu, Zhili Tian, Jie Stevenson, Susan C. Byrnes, Andrew P. TI Interaction of systemically delivered adenovirus vectors with Kupffer cells in mouse liver SO HUMAN GENE THERAPY LA English DT Article ID VIVO GENE-TRANSFER; ALVEOLAR MACROPHAGES; FIBER-SHAFT; IN-VITRO; BINDING ABLATION; CAR-BINDING; INTERNALIZATION; ACTIVATION; EXPRESSION; INFECTION AB When adenovirus (Ad) vectors are injected intravenously they are rapidly taken up by Kupffer cells (KCs) in the liver. This results in massive KC necrosis within minutes, followed by a more gradual disappearance of KCs from the liver. It is not known how KCs recognize Ad, or why Ad kills KCs. We used a variety of mutated and fiber-pseudotyped Ad vectors to evaluate how capsid proteins influence Ad uptake by KCs and to define the viral proteins that are involved in the destruction of KCs. We found that depletion of KCs from the liver was partially dependent on interactions between Ad and integrins, but was independent of the coxsackievirus and Ad receptor. The Ad5 fiber shaft was proven to be a particularly important contributory factor, because vectors with the shorter Ad35 shaft were not as effective at depleting KCs. In contrast, the fiber head played no discernible role. Variations in the ability of Ad vectors to deplete KCs could not be explained by differences in the amount of Ad that reached KCs, because all mutant Ads were accumulated by KCs at similar levels. Interestingly, we found that the Ad mutant ts1 did not cause KC death; this virus is known to bind and enter cells normally, but the capsid is unable to disassemble or lyse membranes. We conclude that Ad vectors kill KCs at a postbinding step and that this cell death can be mitigated if downstream events in viral entry are blocked. C1 [Smith, Jeffrey S.; Xu, Zhili; Tian, Jie; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Stevenson, Susan C.] Novartis Inst Biomed Res, Dept Diabet & Metab, Cambridge, MA 02139 USA. RP Byrnes, AP (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 29B,Room 2E20,HFM-725, Bethesda, MD 20892 USA. EM Andrew.Byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 44 TC 31 Z9 32 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2008 VL 19 IS 5 BP 547 EP 554 DI 10.1089/hum.2008.004 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 308ZW UT WOS:000256430500013 PM 18447633 ER PT J AU Harvill, ET Osorio, M Loving, CL Lee, GM Kelly, VK Merkel, TJ AF Harvill, Eric T. Osorio, Manuel Loving, Crystal L. Lee, Gloria M. Kelly, Vanessa K. Merkel, Tod J. TI Anamnestic protective immunity to Bacillus anthracis is antibody mediated but independent of complement and Fc receptors SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL INHALATION ANTHRAX; T-LYMPHOCYTE ACTIVATION; LETHAL TOXIN; PASSIVE PROTECTION; GENE-EXPRESSION; NATIONAL-PARK; HIGH-AFFINITY; CUTTING EDGE; GUINEA-PIGS; IN-VIVO AB The threat of bioterrorist use of Bacillus anthracis has focused urgent attention on the efficacy and mechanisms of protective immunity induced by available vaccines. However, the mechanisms of infection-induced immunity have been less well studied and defined. We used a combination of complement depletion along with immunodeficient mice and adoptive transfer approaches to determine the mechanisms of infection-induced protective immunity to B. anthracis. B- or T-cell-deficient mice lacked the complete anamnestic protection observed in immunocompetent mice. In addition, T-cell-deficient mice generated poor antibody titers but were protected by the adoptive transfer of serum from B. anthracis-challenged mice. Adoptively transferred sera were protective in mice lacking complement, Fc receptors, or both, suggesting that they operate independent of these effectors. Together, these results indicate that antibody-mediated neutralization provides significant protection in B. anthracis infection-induced immunity. C1 [Osorio, Manuel; Loving, Crystal L.; Lee, Gloria M.; Kelly, Vanessa K.; Merkel, Tod J.] US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. [Harvill, Eric T.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. RP Merkel, TJ (reprint author), US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Resp & Special Pathogens, Bldg 29,Rm 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM tod.merkel@fda.hhs.gov FU NIAID NIH HHS [R01 AI053075-05, R01 AI053075]; PHS HHS [A1-6153-01] NR 54 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2008 VL 76 IS 5 BP 2177 EP 2182 DI 10.1128/IAI.00647-07 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 292LJ UT WOS:000255267200042 PM 18316379 ER PT J AU Wu, Y Woodworth, JS Shin, DS Morris, S Behar, SM AF Wu, Ying Woodworth, Joshua S. Shin, Daniel S. Morris, Sheldon Behar, Samuel M. TI Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8(+) T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection SO INFECTION AND IMMUNITY LA English DT Article ID DNA VACCINE; ENHANCED IMMUNOGENICITY; PULMONARY TUBERCULOSIS; BOOST VACCINATION; VIRUS ANKARA; ANTIGEN 85A; IMMUNITY; EFFICACY; MICE; RESPONSES AB The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are frequently recognized by T cells from infected people. The genes encoding these proteins have been deleted from the genome of the vaccine strain Mycobacterium bovis bacillus Calmette-Guerin (BCG), and it is hypothesized that these proteins are important targets of protective immunity. Indeed, vaccination with ESAT-6 elicits protective CD4(+) T cells in C57BL/6 mice. We have previously shown that M. tuberculosis infection of C3H mice elicits CFP-10-specific CD8(+) and CD4(+) T cells. Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a specific T-cell response only to the H-2K(k)-restricted epitope CFP-10(32-31). These CFP-10(32-39)- specific CD8(+) cells undergo a rapid expansion and accumulate in the lung following challenge of immunized mice with aerosolized M. tuberculosis. Protective immunity is induced by CFP-10 DNA vaccination as measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge with M. tuberculosis. These data demonstrate that CFP-10 is a protective antigen and that CFP-10(32-39)-specfic CD8(+) T cells elicited by vaccination are sufficient to mediate protection against tuberculosis. C1 [Wu, Ying; Woodworth, Joshua S.; Shin, Daniel S.; Behar, Samuel M.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Wu, Ying; Woodworth, Joshua S.; Shin, Daniel S.; Behar, Samuel M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Morris, Sheldon] US FDA, CBER, Lab Mycobacteriol Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Behar, SM (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith Bldg,Room 516C,1 Jimmy Fund Way, Boston, MA 02115 USA. EM sbehar@rics.bwh.harvard.edu OI Behar, Samuel/0000-0002-3374-6699 FU NIAID NIH HHS [R01 AI067731, R01 AI67731] NR 30 TC 34 Z9 35 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2008 VL 76 IS 5 BP 2249 EP 2255 DI 10.1128/IAI.00024-08 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 292LJ UT WOS:000255267200051 PM 18332205 ER PT J AU Malejka-Giganti, D Parkin, DR Decker, RW Niehans, GA Bliss, RL Churchwell, MI Beland, FA AF Malejka-Giganti, Danuta Parkin, Daniel R. Decker, Richard W. Niehans, Gloria A. Bliss, Robin L. Churchwell, Mona I. Beland, Frederick A. TI Tumorigenicity and genotoxicity of an environmental pollutant 2,7-dinitrofluorene after systemic administration at a low dose level to female rats SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE environmental nitroaromatic; rat; mammary cancer; genotoxicity ID POLYCYCLIC AROMATIC-HYDROCARBONS; SPRAGUE-DAWLEY RATS; GLAND IN-VITRO; MAMMARY-GLAND; GAS-CHROMATOGRAPHY; DNA-ADDUCTS; CANCER; CARCINOGENICITY; NITROREDUCTION; AIR AB Environmental pollution with nitroaromatic compounds may pose health hazards. We have examined the tumorigenicity in female Sprague-Dawley rats of 2,7-dinitrofluorene (2,7-diNF) and 9-oxo-2,7-diNF administered by intraperitoneal (i.p.) and oral routes at 10 mu mol/kg body weight, 3 times per week for 4 weeks. After i.p. treatment, the estimated median latency for the combined malignant and benign mammary tumors was decreased in 2,7-diNF- (p = 0.003) or 9-oxo-2,7-diNF-treated (p = 0.007), relative to vehicle-treated rats (42 or 64 vs. 80 weeks, respectively), whereas after oral dosing, there were no significant differences. At 90 weeks, the malignant mammary tumor incidence in 2,7-diNF-, 9-oxo-2,7-diNF- and vehicle-i.p. treated rats was 44 (p = 0.02 vs. vehicle-treated), 25 and 6%, respectively. Liver and mammary gland DNA was analyzed by HPLC combined with electrospray tandem mass spectrometry for the presence of a deoxyguanosine (dG-2,7-diNF) adduct and a deoxyadenosine (dA-2,7-diNF) adduct derived from 2,7-diNF, and a deoxyguanosine (dG-9-oxo-2,7-diNF) adduct derived from 9-oxo-2,7-diNF. Both dG-2,7-diNF and dA-2,7-diNF were detected in DNA of 2,7-diNF-treated rats, whereas only very low levels of dG-9-oxo-2,7-diNF were detected in DNA of 9-oxo2,7-diNF-treated rats. After i.p. treatment, the dA-2,7-diNF level was higher (p < 0.01) in the mammary gland than liver (13.6 vs. 7.8 adducts/10(8) nucleotides). In the mammary gland, the dG-2,7-diNF level was higher (p < 0.05) after i.p. than oral dosing and also higher (p < 0.05) than in the liver (36 vs. 8.6 and vs. 9.1 adducts/10(8) nucleotides, respectively). The preferential display of carcinogenicity and genotoxicity in the mammary gland by low doses of 2,7-diNF signifies its potential relevance for environmental breast cancer. (C) 2008 Wiley-Liss, Inc. C1 [Malejka-Giganti, Danuta; Decker, Richard W.; Niehans, Gloria A.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Malejka-Giganti, Danuta; Parkin, Daniel R.; Niehans, Gloria A.] Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. [Bliss, Robin L.] Univ Minnesota, Ctr Comprehens Canc, Minneapolis, MN USA. [Churchwell, Mona I.; Beland, Frederick A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Malejka-Giganti, D (reprint author), Vet Affairs Med Ctr, 1 Vt Dr, Minneapolis, MN 55417 USA. EM malej001@umn.edu NR 36 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2008 VL 122 IS 9 BP 1958 EP 1965 DI 10.1002/ijc.23352 PG 8 WC Oncology SC Oncology GA 277OR UT WOS:000254224100006 PM 18183586 ER PT J AU Gay, ML Musser, SM AF Gay, Martha L. Musser, Steven M. TI Single-laboratory validated method for determination of nordihydroguaiaretic acid in chaparral-containing dietary supplements SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LARREA-TRIDENTATA; LIGNANS; MOUSE AB Nordihydroguaiaretic acid (NDGA) occurs naturally in chaparral (Larrea tridentate Coville), a plant which commonly grows in the Southwest United States and has been used for medicinal purposes by Native Americans indigenous to that region. In addition to its traditional use as a tea, manufacturers of dietary supplements have marketed chaparral-containing products in a variety of formulations. Because of the hepatotoxicity of NDGA, and its occurrence in regulated products, we have developed a method for the determination of NDGA in dietary supplements and have tested this method in several dietary supplement formulations. Products were extracted with 80% methanol, filtered, and analyzed by high-performance liquid chromatography. NDGA was detected and determined with both a diode array detector and negative-ion electrospray. Fragmentation in the triple-quadru pole mass spectrometer was obtained by collisional activation of the [M-H](-) ion. Collisional activation produced sufficient fragmentation to provide unambiguous identification. Lack of a stable isotope labeled internal standard has led us to compare quantitations based on UV detection with quantitations based on tandem mass spectrometry (MS/MS). Presence of NDGA was confirmed in several dietary supplement products. Quantitative results from the 2 detection methods were comparable for most products. The limit of quantitation using MS/MS was lower and fewer interferences were observed, although UV detection provided better linearity. C1 [Gay, Martha L.; Musser, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20770 USA. RP Gay, ML (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-707,5100 Paint Branch Pkwy, College Pk, MD 20770 USA. EM Martha.Gay@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 2 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2008 VL 91 IS 3 BP 501 EP 505 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 310BU UT WOS:000256504700003 PM 18567293 ER PT J AU Trucksess, MW Weaver, CM Oles, CJ Fry, FS Noonan, GO Betz, JM Pader, JI AF Trucksess, Mary W. Weaver, Carol M. Oles, Carolyn J. Fry, Frederick S., Jr. Noonan, Gregory O. Betz, Joseph M. Pader, Jeanne I. TI Determination of aflatoxins B(1), B(2), G(1), and G(2) and ochratoxin A in ginseng and ginger by multitoxin immunoaffinity column cleanup and liquid chromatographic quantitation: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MEDICINAL-PLANTS; FUMONISINS B-1; PERFORMANCE; PRECISION; DIETARY; HERBS; TEA AB The accuracy, repeatability, and reproducibility characteristics of a method using multitoxin immunoaffinity column cleanup with liquid chromatography (LC) for determination of aflatoxins (AF; sum of aflatoxins B(1), B(2), G(1), and G(2)) and ochratoxin A (OTA) in powdered ginseng and ginger have been established in a collaborative study involving 13 laboratories from 7 countries. Blind duplicate samples of blank, spiked (AF and OTA added) at levels ranging from 0.25 to 16.0 mu g/kg for AF and 0.25 to 8.0 mu g/kg for OTA were analyzed. A naturally contaminated powdered ginger sample was also included. Test samples were extracted with methanol and 0.5% aqueous sodium hydrogen carbonate solution (700 + 300, v/v). The extract was centrifuged, diluted with phosphate buffer (PB), filtered, and applied to an immunoaffinity column containing antibodies specific for AF and OTA. After washing the column with water, the toxins were eluted from the column with methanol, and quantified by high-performance LC with fluorescence detection. Average recoveries of AF from ginseng and ginger ranged from 70 to 87% (at spiking levels ranging from 2 to 16 mu g/kg), and of OTA, from 86 to 113% (at spiking levels ranging from 1 to 8 mu g/kg). Relative standard deviations for with in-laboratory repeatability (RSD(r)) ranged from 2.6 to 8.3% for AF, and from 2.5 to 10.7% for OTA. Relative standard deviations for between-laboratory reproducibility (RSD(R)) ranged from 5.7 to 28.6% for AF, and from 5.5 to 10.7% for OTA. HorRat values were <= 2 for the multi-analytes in the 2 matrixes. C1 [Trucksess, Mary W.; Weaver, Carol M.; Oles, Carolyn J.; Fry, Frederick S., Jr.; Noonan, Gregory O.; Pader, Jeanne I.] US FDA, College Pk, MD 20740 USA. [Betz, Joseph M.] NIH, Bethesda, MD 20892 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov FU None [223-01-2464]; PHS HHS [223-01-2464] NR 15 TC 41 Z9 44 U1 2 U2 10 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2008 VL 91 IS 3 BP 511 EP 523 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 310BU UT WOS:000256504700005 PM 18567295 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI Uncertainties of method performance statistics based on a balanced completely randomized model interlaboratory study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Using exact and asymptotic distributions, formulas were developed to derive population variances and uncertainties, and their corresponding unbiased estimates, for the method performance statistics, i.e., the sample mean (y..), the repeatability variance and standard deviation and (s(r)(2) and S-r), and the reproducibility variance and standard deviation (S-R(2) and S-R) and obtained from collaborative study of an analytical method. C1 [McClure, Foster D.; Lee, Jung K.] US FDA, Ctr Food Safety & Appl Nutr,Biostat Branch, Dept Hlth & Human Serv,Div Publ Hlth & Biostat, Off Food Def Communicat & Emergency Response, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr,Biostat Branch, Dept Hlth & Human Serv,Div Publ Hlth & Biostat, Off Food Def Communicat & Emergency Response, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM fdmc5100@yahoo.com NR 9 TC 1 Z9 1 U1 0 U2 0 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2008 VL 91 IS 3 BP 660 EP 669 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 310BU UT WOS:000256504700024 PM 18567314 ER PT J AU Das, SS Schroeder, LW AF Das, Srilekha Sarkar Schroeder, LeRoy W. TI Estimation of shelf life of natural rubber latex exam-gloves based on creep behavior SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE accelerated aging; shelf life; creep; latex gloves; Arrhenius ID DEGRADATION AB Samples of full-length glove-ringers cut from chlorinated and nonchlorinated latex medical examination gloves were aged for various times at several fixed temperatures and 25% relative humidity. Creep testing was performed using an applied stress of 50 kPa on rectangular specimens (10 mm X 8 mm) of aged and unaged glove fingers as an assessment of glove loosening during usage. Variations in creep curves obtained were compared to determine the threshold aging time when the amount of creep became larger than the initial value. These times were then used in various models to estimate shelf lives at lower temperatures. Several different methods of extrapolation were used for shelf-life estimation and comparison. Neither Q-factor nor Arrhenius activation energies, as calculated from 10 degrees C interval shift factors, were constant over the temperature range; in fact, both decreased at lower temperatures. Values of Q-factor and activation energies predicted up to 5 years of shelf life. Predictions are more sensitive to values of activation energy as the storage temperature departs from the experimental aging data. Averaging techniques for prediction of average activation energy predicted the longest shelf life as the curvature is reduced. (c) 2007 Wiley Periodicals, Inc. C1 [Das, Srilekha Sarkar; Schroeder, LeRoy W.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Das, SS (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM Srilekha.Das@fda.hhs.gov NR 27 TC 2 Z9 2 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD MAY PY 2008 VL 85B IS 2 BP 398 EP 408 DI 10.1002/jbm.b.30958 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 291GB UT WOS:000255180900012 PM 17969017 ER PT J AU Fu, TJ Reineke, KF Chirtel, S Vanpelt, OM AF Fu, Tong-Jen Reineke, Karl F. Chirtel, Stuart Vanpelt, Olif M. TI Factors influencing the growth of Salmonella during sprouting of naturally contaminated alfalfa seeds SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; MULTISTATE OUTBREAK; ELIMINATE SALMONELLA; KILLING SALMONELLA; IRRIGATION WATER; CHLORINE; SURVIVAL; EFFICACY; ENTERICA; HEAT AB In this study, the factors that affect Salmonella growth during sprouting of naturally contaminated alfalfa seeds associated with two previous outbreaks of salmonellosis were examined. A minidrum sprouter equipped with automatic irrigation and rotation systems was built to allow sprouting to be conducted under conditions similar to those used commercially. The growth of Salmonella during sprouting in the minidrum was compared with that observed in sprouts grown in glass jars under conditions commonly used at home. The level of Salmonella increased by as much as 4 log units after 48 h of sprouting in jars but remained constant during the entire sprouting period in the minidrum. The effect of temperature and irrigation frequency on Salmonella growth was examined. Increasing the sprouting temperature from 20 to 30 degrees C increased the Salmonella counts by as much as 2 log units on sprouts grown both in the minidrum and in the glass jars. Decreasing the irrigation frequency from every 20 min to every 2 h during sprouting in the minidrum or from every 4 h to every 24 h during sprouting in the glass jars resulted in an approximately 2-log increase in Salmonella counts. The levels of total aerobic mesophilic bacteria, coliforms, and Salmonella in spent irrigation water closely reflected those found in sprouts, confirming that monitoring of spent irrigation water is a good way to monitor pathogen levels during sprouting. C1 [Fu, Tong-Jen; Reineke, Karl F.] US FDA, Summit Argo, IL 60501 USA. [Vanpelt, Olif M.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Chirtel, Stuart] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, TJ (reprint author), US FDA, Summit Argo, IL 60501 USA. EM tong.fu@fda.hhs.gov NR 41 TC 15 Z9 15 U1 1 U2 11 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2008 VL 71 IS 5 BP 888 EP 896 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 296RS UT WOS:000255564100003 PM 18522019 ER PT J AU Buchanan, R Dennis, S Gendel, S Acheson, D Assimon, SA Beru, N Bolger, P Carlson, D Carvajal, R Copp, C Falci, K Garber, E Harden, E Kane, R Kvenberg, J Luccioli, S Park, D Raybourne, R Troxell, T Vierk, K AF Buchanan, Robert Dennis, Sherri Gendel, Steven Acheson, David Assimon, Sue Anne Beru, Nega Bolger, Philip Carlson, David Carvajal, Ricardo Copp, Catherine Falci, Kenneth Garber, Eric Harden, Elizabeth Kane, Rhonda Kvenberg, John Luccioli, Stefano Park, Douglas Raybourne, Richard Troxell, Terry Vierk, Katherine CA Threshold Working Grp TI Approaches to establish thresholds for major food allergens and for gluten in food SO JOURNAL OF FOOD PROTECTION LA English DT Review ID CHILDHOOD CELIAC-DISEASE; HYPOALLERGENIC INFANT FORMULAS; SHRIMP-SENSITIVE INDIVIDUALS; CASEIN HYDROLYSATE FORMULA; COWS MILK ALLERGY; DOUBLE-BLIND; CROSS-REACTIVITY; PEANUT ALLERGY; SOY LECITHIN; HYPERSENSITIVITY REACTIONS C1 [Buchanan, Robert; Dennis, Sherri; Gendel, Steven; Acheson, David; Assimon, Sue Anne; Beru, Nega; Bolger, Philip; Carlson, David; Carvajal, Ricardo; Copp, Catherine; Falci, Kenneth; Garber, Eric; Harden, Elizabeth; Kane, Rhonda; Kvenberg, John; Luccioli, Stefano; Park, Douglas; Raybourne, Richard; Troxell, Terry; Vierk, Katherine; Threshold Working Grp] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gendel, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM steven.gendel@fda.hhs.gov NR 255 TC 44 Z9 44 U1 1 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2008 VL 71 IS 5 BP 1043 EP 1088 PG 46 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 296RS UT WOS:000255564100028 PM 18522044 ER PT J AU Silva-Adaya, D Perez-De La Cruz, V Herrera-Mundo, MN Mendoza-Macedo, K Villeda-Hernandez, J Binienda, Z Ali, SF Santamaria, A AF Silva-Adaya, Daniela Perez-De La Cruz, Veronica Nieves Herrera-Mundo, Maria Mendoza-Macedo, Karina Villeda-Hernandez, Juana Binienda, Zbigniew Ali, Syed F. Santamaria, Abel TI Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of L-carnitine SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 3-nitropropionic acid; energy metabolism deficit; excitotoxicity; L-carnitine; neuroprotection; quinolinic acid ID ACID-INDUCED NEUROTOXICITY; NMDA RECEPTOR BLOCKADE; 3-NITROPROPIONIC ACID; HUNTINGTONS-DISEASE; QUINOLINIC ACID; MITOCHONDRIAL DYSFUNCTION; LIPID-PEROXIDATION; S-ALLYLCYSTEINE; NEURODEGENERATIVE DISORDERS; SUCCINATE-DEHYDROGENASE AB Excitotoxicity and disrupted energy metabolism are major events leading to nerve cell death in neurodegenerative disorders. These cooperative pathways share one common aspect: triggering of oxidative stress by free radical formation. In this work, we evaluated the effects of the antioxidant and energy precursor, levocarnitine (L-CAR), on the oxidative damage and the behavioral, morphological, and neurochemical alterations produced in nerve tissue by the excitotoxin and free radical precursor, quinolinic acid (2,3-pyrindin dicarboxylic acid; QUIN), and the mitochondrial toxin, 3-nitropropionic acid (3-NP). Oxidative damage was assessed by the estimation of reactive oxygen species formation, lipid peroxidation, and mitochondrial dysfunction in synaptosomal fractions. Behavioral, morphological, and neurochemical alterations were evaluated as markers of neurotoxicity in animals systemically administered with L-CAR, chronically injected with 3-NP and/or intrastriatally infused with QUIN. At micromolar concentrations, L-CAR reduced the three markers of oxidative stress stimulated by both toxins alone or in combination. L-CAR also prevented the rotation behavior evoked by QUIN and the hypokinetic pattern induced by 3-NP in rats. Morphological alterations produced by both toxins (increased striatal glial fibrillary acidic protein-immunoreactivity for QUIN and enhanced neuronal damage in different brain regions for 3-NP) were reduced by L-CAR. In addition, L-CAR prevented the synergistic action of 3-NP and QUIN to increase motor asymmetry and depleted striatal GABA levels. Our results suggest that the protective properties of L-CAR in the neurotoxic models tested are mostly mediated by its characteristics as an antioxidant agent. C1 [Binienda, Zbigniew; Ali, Syed F.; Santamaria, Abel] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. [Silva-Adaya, Daniela; Perez-De La Cruz, Veronica; Nieves Herrera-Mundo, Maria; Mendoza-Macedo, Karina; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, Mexico City, DF, Mexico. [Villeda-Hernandez, Juana] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Enfermedades Neurodegenerativas, Mexico City, DF, Mexico. RP Santamaria, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT-132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov NR 51 TC 67 Z9 69 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2008 VL 105 IS 3 BP 677 EP 689 DI 10.1111/j.1471-4159.2007.05174.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 290RF UT WOS:000255139200010 PM 18194214 ER PT J AU Cunningham, WC Anderson, DL Lamont, WH South, PK Rury, MA Beachley, GM Ondov, JM AF Cunningham, W. C. Anderson, D. L. Lamont, W. H. South, P. K. Rury, M. A. Beachley, G. M. Ondov, J. M. TI Development of a transportable system for radionuclide analysis SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article ID FOODS AB Transportable radioanalytical systems were assembled and tested for quantitative determination of gamma-emitting radionuclides and screening of beta-emitting radionuclides. Standard operating procedures (SOPs), including instructions for assembly, disassembly, operation, sample collection and analysis, and all other procedures needed, were developed. Foods, as well as National Institute of Standards and Technology, International Atomic Energy Agency, and in-house Reference Materials were analyzed. An SOP for gamma-emitting radionuclides was successfully tested at 3 locations. C1 [Cunningham, W. C.; Anderson, D. L.; Lamont, W. H.] US FDA, Elemental Res Branch HFS 338, College Pk, MD 20740 USA. [South, P. K.] US FDA, Regulatory Policy Branch HFS 306, College Pk, MD 20740 USA. [Rury, M. A.; Beachley, G. M.; Ondov, J. M.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RP Cunningham, WC (reprint author), US FDA, Elemental Res Branch HFS 338, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD MAY PY 2008 VL 276 IS 2 BP 317 EP 322 DI 10.1007/s10967-008-0505-1 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 296ZT UT WOS:000255585300005 ER PT J AU Kirkpatrick, JS Stevens, T AF Kirkpatrick, John S. Stevens, Theodore TI The FDA process for the evaluation and approval of orthopaedic devices SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article AB The US Food and Drug Administration (FDA) is a scientific, regulatory, and public health agency whose authority includes overseeing the marketing of products relevant to medical practice. Devices are classified based on the extent of oversight needed to ensure public safety. Divisions within the FDA provide specific expertise regarding drugs, devices, biologic products, and combinations thereof. Various pathways exist to apply for marketing through the FDA, depending on the nature of the product and its intended use. Expert panels advise the agency on issues related to product safety and efficacy, and clinical studies may be required to provide data based on these parameters. Clinical data are monitored postapproval for potential adverse events not evident in earlier trials. Orthopaedic surgeons are involved in all aspects of the FDA as employees, consultants, product advocates, participants in clinical trials and advisory panels, and experts involved in the appropriate reporting of adverse events. C1 [Kirkpatrick, John S.] Univ Florida, Coll Med, Dept Orthopaed Surg, Jacksonville, FL USA. [Stevens, Theodore] US FDA, Orthopaed Spine Devices Branch, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Rockville, MD 20857 USA. RP Kirkpatrick, JS (reprint author), Univ Florida, Coll Med, Dept Orthopaed & Rehabil, 655 W 8th St, Jacksonville, FL 32209 USA. NR 15 TC 6 Z9 6 U1 0 U2 1 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD MAY PY 2008 VL 16 IS 5 BP 260 EP 267 PG 8 WC Orthopedics SC Orthopedics GA 294PX UT WOS:000255419100004 PM 18460686 ER PT J AU Retta, SM Sagripanti, JL AF Retta, S. M. Sagripanti, J. -L. TI Modeling the inactivation kinetics of bacillus spores by glutaraldehyde SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE bacillus; decontamination; disinfection; glutaraldehyde; spore ID FLEXIBLE ENDOSCOPY; APIC GUIDELINE; INFECTION PREVENTION; DISINFECTION; CHLORINE; DEMAND; WATER AB Aims: Our goal was to develop a mathematical kinetic model to predict the sporicidal activity of glutaraldehyde, which is an active ingredient frequently used in commercial products employed for liquid disinfection and decontamination. Methods and Results: We used our previously published data on spore inactivation by glutaraldehyde to develop a predictive model obtained by calculating multiple independent modifying functions. The model was then validated by comparing model predicted values to new experimental data. For model validation, quality-controlled spores of Bacillus athrophaeus (previously and generally known as Bacillus subtilis globigii) were exposed under conditions where several physicochemical variables were modified simultaneously, and the spore surviving fractions were measured by titration. Conclusions: The model predicted within one order of magnitude variations in sporicidal effectiveness due to changes in main parameters (glutaraldehyde concentration, temperature or time-duration of the treatment). Other parameters such pH, salinity and the effect of serum concentration were also addressed, albeit with less accuracy. Significance and Impact of the study: The model should be useful to quantitatively estimate the effectiveness of glutaraldehyde-based disinfectants, decontaminants, and germicides under the described conditions, particularly when limited data are available or when spore virulence (like that of Bacillus anthracis) precludes extensive experimentation. A similar approach could predict the effectiveness of a variety of decontaminant and disinfecting agents. C1 [Sagripanti, J. -L.] USA, AMSRD ECB RT, Edgewood Chem Biol Ctr, Aberdeen Proving Ground, MD 21010 USA. [Retta, S. M.] Food Drug Adm, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD USA. RP Sagripanti, JL (reprint author), USA, AMSRD ECB RT, Edgewood Chem Biol Ctr, 5183 Blackhawk Rd,Edgewood Area, Aberdeen Proving Ground, MD 21010 USA. EM joseluis.sagripanti@us.army.mil NR 32 TC 2 Z9 3 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD MAY PY 2008 VL 46 IS 5 BP 568 EP 574 DI 10.1111/j.1472-765X.2008.02358.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 288MY UT WOS:000254991700011 PM 18397220 ER PT J AU Pogribna, M Freeman, JP Paine, D Boudreau, MD AF Pogribna, M. Freeman, J. P. Paine, D. Boudreau, M. D. TI Effect of Aloe vera whole leaf extract on short chain fatty acids production by Bacteroides fragilis, Bifidobacterium infantis and Eubacterium limosum SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article DE Aloe vera; bacteria; intestine; short chain fatty acids ID CANCER CELL-LINE; BARBADENSIS MILLER; SODIUM-BUTYRATE; DIETARY FIBER; COLON; FLORA; POLYSACCHARIDES; MICROFLORA; METABOLISM; BACTERIA AB Aims: To investigate the effect of Aloe vera whole leaf extract on pure and mixed human gut bacterial cultures by assessing the bacterial growth and changes in the production of short chain fatty acids. Methods and Results: Bacteroides fragilis, Bifidobacterium infantis, and Eubacterium limosum were incubated with Aloe vera extracts [0%, 0.5%, 1%, 1.5% and 2%; (w/v)] for 24 and 48 h. Short chain fatty acids production was measured by gas chromatography/mass spectrometry analyses. A significant linear increase in growth response to Aloe vera supplementation was observed at 24 h for each of the bacterial cultures; however, only B. infantis and a mixed bacterial culture showed a significant positive linear dose response in growth at 48 h. In pure bacteria cultures, a significantly enhanced dose response to Aloe vera supplementation was observed in the production of acetic acid by B. infantis at 24 h and of butyric acid by E. limosum at 24 and 48 h. In the mixed bacterial culture, the production of propionic acid was reduced significantly at 24 and 48 h in a dose-dependent fashion, whereas butyric acid production showed a significant linear increase. Conclusions: The results indicated that Aloe vera possessed bacteriogenic activity in vitro and altered the production of acetic, butyric and propionic acids by micro-organisms selected for the study. Significance and Impact of the Study: The results of the study suggest that consumption of a dietary supplement, Aloe vera, may alter the production of short chain fatty acids by human intestinal microflora. C1 [Pogribna, M.; Freeman, J. P.; Boudreau, M. D.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Paine, D.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Boudreau, MD (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mary.boudreau@fda.hhs.gov NR 23 TC 9 Z9 9 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD MAY PY 2008 VL 46 IS 5 BP 575 EP 580 DI 10.1111/j.1472-765X.2008.02346.x PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 288MY UT WOS:000254991700012 PM 18363656 ER PT J AU Daskin, JH Calci, KR Burkhardt, W Carmichael, RH AF Daskin, Joshua H. Calci, Kevin R. Burkhardt, William, III Carmichael, Ruth H. TI Use of N stable isotope and microbial analyses to define wastewater influence in Mobile Bay, AL SO MARINE POLLUTION BULLETIN LA English DT Article DE fecal coliforms; male-specific bacteriophage; MSB; eastern oysters; virus; bacteria; growth ID MALE-SPECIFIC BACTERIOPHAGE; NUTRIENT ENRICHMENT; ESCHERICHIA-COLI; MOLLUSCAN SHELLFISH; COASTAL WATERSHEDS; BIVALVE MOLLUSKS; WAQUOIT BAY; FOOD WEBS; EUTROPHICATION; NITROGEN AB We assessed short-term ecological and potential human health effects of wastewater treatment plant (WTP) effluent by measuring delta N-15 parts per thousand and microbial concentrations in oysters and suspended particulate matter (SPM). We also tested male-specific bacteriophage (MSB) as an alternative to fecal coliforms, to assess potential influence of wastewater contamination on shellfish. WTP effluent did not affect oyster growth or survival, but SPM and oysters acquired wastewater-specific delta N-15 parts per thousand. delta N-15 values were depleted near the WTP, typical of low-level processed wastewater. Fecal coliform and MSB concentrations were higher in samples taken closest to the WTP, and MSB values were significantly correlated with delta N-15 parts per thousand in oyster tissues. Overall, oysters demonstrated relatively rapid integration and accumulation of wastewater-specific delta N-15 parts per thousand and indicator microorganisms compared to water samples. These data suggest oysters were superior sentinels compared to water, and MSB was a more reliable indicator of wastewater influence on shellfish than fecal coliforms. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Carmichael, Ruth H.] Dauphin Isl Sea Lab, Dauphin Isl, AL 36528 USA. [Daskin, Joshua H.] MB 0193 Brandeis Univ, Waltham, MA 02454 USA. [Calci, Kevin R.; Burkhardt, William, III] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Carmichael, Ruth H.] Univ S Alabama, Mobile, AL 36688 USA. RP Carmichael, RH (reprint author), Dauphin Isl Sea Lab, 101 Bienville Blvd, Dauphin Isl, AL 36528 USA. EM rcarmichael@disl.org NR 51 TC 14 Z9 14 U1 1 U2 13 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 MAY PY 2008 VL 56 IS 5 BP 860 EP 868 DI 10.1016/j.marpolbul.2008.02.002 PG 9 WC Environmental Sciences; Marine & Freshwater Biology SC Environmental Sciences & Ecology; Marine & Freshwater Biology GA 313AM UT WOS:000256713500017 PM 18348892 ER PT J AU Freed, M Kupinski, MA Furenlid, LR Wilson, DW Barrett, HH AF Freed, Melanie Kupinski, Matthew A. Furenlid, Lars R. Wilson, Donald W. Barrett, Harrison H. TI A prototype instrument for single pinhole small animal adaptive SPECT imaging SO MEDICAL PHYSICS LA English DT Article DE small-animal SPECT; adaptive imaging; instrumentation; optimization ID ATTENUATION; TABULATION; SYSTEM AB The authors have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the region of interest for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented, along with recommendations for system improvements. (c) 2008 American Association of Physicists in Medicine. C1 [Freed, Melanie] US FDA, Silver Spring, MD 20993 USA. [Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.; Barrett, Harrison H.] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. [Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.; Barrett, Harrison H.] Univ Arizona, Dept Radiol, Tucson, AZ 85721 USA. RP Freed, M (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62,Room 3133, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov FU NIBIB NIH HHS [P41 EB002035, P41 EB002035-09, R01 EB002146, R37 EB000803, R37 EB000803-18] NR 10 TC 34 Z9 34 U1 0 U2 1 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 MAY PY 2008 VL 35 IS 5 BP 1912 EP 1925 DI 10.1118/1.2896072 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 295DZ UT WOS:000255456500032 PM 18561667 ER PT J AU Pica-Branco, D Hudak, RP AF Pica-Branco, Denise Hudak, Ronald P. TI US military service members' perceptions of the Anthrax Vaccine Immunization Program SO MILITARY MEDICINE LA English DT Article AB This research identifies the perceptions of U.S. military service members regarding the Department of Defense Anthrax Vaccine Immunization Program (AVIP). The service members' perceptions were addressed in the dimensions of ethics, effectiveness, and safety, as well as the overall perceptions of the AVIP. The study, conducted in October 2004, randomly selected active duty service members from the uniformed services assigned to a Caribbean military base who participated in the AVIP during the period of 1998 to 2000. Their perceptions were measured with a survey instrument with 14 closed-ended, Likert-scale questions. The research demonstrated that a substantial number of service members disagreed with issues regarding the ethics, safety, and efficacy of the AVIP. We recommend enhanced training and education to increase understanding of the benefits of the AVIP. C1 [Pica-Branco, Denise] US FDA, Ctr Drug Evaluat & Res, Off Pediat & Maternal Hlth, Silver Spring, MD 20993 USA. [Hudak, Ronald P.] USA, Wounded Warrior Program, Alexandria, VA 22332 USA. RP Pica-Branco, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pediat & Maternal Hlth, Silver Spring, MD 20993 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 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 MAY PY 2008 VL 173 IS 5 BP 429 EP 433 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 300SY UT WOS:000255846700007 PM 18543562 ER PT J AU Sanhai, WR Sakamoto, JH Canady, R Ferrari, M AF Sanhai, Wendy R. Sakamoto, Jason H. Canady, RichaRd Ferrari, Mauro TI Seven challenges for nanomedicine SO NATURE NANOTECHNOLOGY LA English DT Editorial Material ID DELIVERY AB Nanomedicine offers new opportunities to fight diseases but a global effort is needed to safely translate laboratory innovation to the clinic. Seven priority areas have been identified for this endeavour. C1 [Sanhai, Wendy R.] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Sakamoto, Jason H.; Ferrari, Mauro] Univ Texas Houston, Hlth Sci Ctr, Brown Fdn Inst Mol Med, Houston, TX 77030 USA. [Canady, RichaRd] US FDA, Off Sci & Hlth Coordinat, Rockville, MD 20857 USA. [Ferrari, Mauro] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Ferrari, Mauro] Rice Univ, Dept Bioengn, Houston, TX 77005 USA. RP Sanhai, WR (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. EM mauro.ferrari@uth.tmc.edu NR 13 TC 230 Z9 232 U1 6 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD MAY PY 2008 VL 3 IS 5 BP 242 EP 244 DI 10.1038/nnano.2008.114 PG 3 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 299LD UT WOS:000255756200002 PM 18654511 ER PT J AU Wang, JY Duhart, HM Xu, ZJ Patterson, TA Newport, GD Ali, SF AF Wang, Jianyong Duhart, Helen M. Xu, Zengjun Patterson, Tucker A. Newport, Glenn D. Ali, Syed F. TI Comparison of the time courses of selective gene expression and dopaminergic depletion induced by MPP+ in MN9D cells SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE MPP+; MN9D cells; time course; gene expression; dopamine; neurotoxicity; Parkinson's disease ID ALPHA-KETOGLUTARATE DEHYDROGENASE; ENDOPLASMIC-RETICULUM STRESS; MITOCHONDRIAL COMPLEX-I; PARKINSONIAN TOXIN MPTP; UP-REGULATED PROTEIN-1; OXIDATIVE STRESS; REAL-TIME; THIOREDOXIN FUNCTION; SUBSTANTIA-NIGRA; PC12 CELLS AB Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of midbrain dopaminergic neurons with unknown etiology. MPP+ (1-methyl-4-phenylpyridinium ion) is the active metabolite of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkin son's-like symptoms in humans and animals. MPTP/MPP+ produces selective dopaminergic neuronal degeneration, therefore, these agents are commonly used to study the pathogenesis of PD. However, the mechanisms of their toxicity have not been fully elucidated. Recently, we reported in a microarray study using a midbrain-derived dopaminergic neuronal cell line, MN9D, that MPP+ induced significant changes in a number of genes known to be associated with the dopaminergic system. In this study, we investigated the expression time courses of six genes using real-time RT-PCR, and compared them with the progressive dopaminergic depletion caused by MPP+. Our data showed that dopamine content was significantly decreased after 0.5 h of MPP+ (200 mu M) exposure and was completely depleted after 40 It. The expression of Gpr37, which is closely related to the pathogenesis of autosomal recessive juvenile Parkinsonism, was up-regulated after 0.5 h, and stayed upregulated up to 48 h. Txnip, which is critical to the adjustment of cellular redox status, was down-regulated after I h and stayed down-regulated up to 48 h. Ldh1 and Cdo1, which are also involved in oxidative stress, were down-regulated after 16 h and stayed down-regulated up to 48 h. Two proapoptotic genes, Egln3 and Bnip3, were down-regulated after 2 and 4 h, and stayed down-regulated up to 48 h. These findings suggested that the time course of expression for multiple genes correlated with the dopaminergic depletion; and MPP+-induced neurotoxicity in MN9D cells could be used as a model to further explore the roles of these and other genes in the pathogenesis and possible treatment of PD. Published by Elsevier Ltd. C1 [Wang, Jianyong; Duhart, Helen M.; Xu, Zengjun; Patterson, Tucker A.; Newport, Glenn D.; Ali, Syed F.] Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. EM jianyong.wang@fda.hhs.gov; syed.ali@fda.hhs.gov NR 66 TC 9 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD MAY PY 2008 VL 52 IS 6 BP 1037 EP 1043 DI 10.1016/j.neuint.2007.10.017 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 294UH UT WOS:000255431200014 PM 18069091 ER PT J AU Ferguson, S Gopee, N Paule, M Howard, P AF Ferguson, Sherry Gopee, Neera Paule, Merle Howard, Paul TI Female mini-pig performance of Temporal Response Differentiation (TRD), Incremental Repeated Acquisition (IRA), and Progressive Ratio (PR) Operant Tasks SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the Neurobehavioral-Teratology-Society/48th Annual Meeting of the Teratology-Society/21st Annual Meeting of the Organization of Teratology Information Specialists CY JUN 28-JUL 02, 2008 CL Monterey, CA SP Neurobehav Teratol Soc, Teratol Soc C1 [Ferguson, Sherry; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Div Neurotox, Rockville, MD 20857 USA. [Gopee, Neera; Howard, Paul] US FDA, Natl Ctr Toxicol Res, Div Biochem Tox, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2008 VL 30 IS 3 MA NBTS24 BP 250 EP 250 DI 10.1016/j.ntt.2008.03.027 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321KH UT WOS:000257303100035 ER PT J AU Smith, M Gopee, N Howard, P Ferguson, S AF Smith, Melody Gopee, Neera Howard, Paul Ferguson, Sherry TI Object preferences as environmental enrichment measures in the female mini-pig SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the Neurobehavioral-Teratology-Society/48th Annual Meeting of the Teratology-Society/21st Annual Meeting of the Organization of Teratology Information Specialists CY JUN 28-JUL 02, 2008 CL Monterey, CA SP Neurobehav Teratol Soc, Teratol Soc C1 [Smith, Melody; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Rockville, MD 20857 USA. [Gopee, Neera; Howard, Paul] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2008 VL 30 IS 3 MA NBTS25 BP 250 EP 250 DI 10.1016/j.ntt.2008.03.028 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321KH UT WOS:000257303100036 ER PT J AU Boctor, S Sadovova, N Wang, C Ferguson, S AF Boctor, Sherin Sadovova, Natalya Wang, Cheng Ferguson, Sherry TI Neonatal NMDA receptor antagonist treatment has no effects on prepulse inhibition (PPI) in postnatal day (PND) 25 Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the Neurobehavioral-Teratology-Society/48th Annual Meeting of the Teratology-Society/21st Annual Meeting of the Organization of Teratology Information Specialists CY JUN 28-JUL 02, 2008 CL Monterey, CA SP Neurobehav Teratol Soc, Teratol Soc C1 [Boctor, Sherin; Wang, Cheng; Ferguson, Sherry] Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. [Boctor, Sherin; Wang, Cheng; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2008 VL 30 IS 3 MA NBTS34 BP 253 EP 253 DI 10.1016/j.ntt.2008.03.037 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321KH UT WOS:000257303100045 ER PT J AU Garey, J Paule, M AF Garey, Joan Paule, Merle TI The effect of lifelong acrylamide exposure on auditory discrimination task performance in Fischer 344 rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the Neurobehavioral-Teratology-Society/48th Annual Meeting of the Teratology-Society/21st Annual Meeting of the Organization of Teratology Information Specialists CY JUN 28-JUL 02, 2008 CL Monterey, CA SP Neurobehav Teratol Soc, Teratol Soc C1 [Garey, Joan; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2008 VL 30 IS 3 MA NBTS37 BP 254 EP 254 DI 10.1016/j.ntt.2008.03.040 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321KH UT WOS:000257303100048 ER PT J AU Paule, M Smith, M Garey, J Ferguson, S AF Paule, Merle Smith, Melody Garey, Joan Ferguson, Sherry TI Acoustic startle behavior is moderately altered by lifetime acrylamide (ACR) treatment in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 32nd Annual Meeting of the Neurobehavioral-Teratology-Society/48th Annual Meeting of the Teratology-Society/21st Annual Meeting of the Organization of Teratology Information Specialists CY JUN 28-JUL 02, 2008 CL Monterey, CA SP Neurobehav Teratol Soc, Teratol Soc C1 [Paule, Merle; Smith, Melody; Garey, Joan; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2008 VL 30 IS 3 MA NBTS36 BP 254 EP 254 DI 10.1016/j.ntt.2008.03.039 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 321KH UT WOS:000257303100047 ER PT J AU Ahmad, SR Swann, J AF Ahmad, Syed R. Swann, Joslyn TI Exenatide and rare adverse events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Ahmad, Syed R.; Swann, Joslyn] US FDA, Silver Spring, MD 20993 USA. RP Ahmad, SR (reprint author), US FDA, Silver Spring, MD 20993 USA. EM syed.ahmad@fda.hhs.gov NR 3 TC 85 Z9 91 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 1 PY 2008 VL 358 IS 18 BP 1970 EP 1971 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 294ER UT WOS:000255387900027 PM 18456920 ER PT J AU Rennels, MB Black, S Woo, EJ Campbell, S Edwards, KM AF Rennels, Margaret B. Black, Steven Woo, Emily Jane Campbell, Scott Edwards, Kathryn M. TI Safety of a fifth dose of diphtheria and tetanus toxoid and acellular pertussis vaccine in children experiencing extensive, local reactions to the fourth dose SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE DTaP; revaccination; safety; swelling ID IMMUNOGENICITY; TRIAL AB Extensive local reactions have been reported after booster doses of diphtheria and tetanus toxoid and acellular pertussis vaccine, but few data are available on revaccination after these reactions. Of 20 children with extensive local reactions after dose 4, only 4 experienced entire upper arm swelling and 7 had swelling >5 cm after dose 5. These reactions were well tolerated and support revaccination. C1 [Edwards, Kathryn M.] Vanderbilt Univ, Sch Med, Pediat Clin Res Off, Dept Pediat, Nashville, TN 37232 USA. [Rennels, Margaret B.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Dept Pediat, Baltimore, MD 21201 USA. [Black, Steven] Cincinnati Childrens Hosp, Ctr Global Child Hlth, Cincinnati, OH USA. [Woo, Emily Jane] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res,Vaccine Safety Brach, Rockville, MD 20857 USA. [Campbell, Scott] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Edwards, KM (reprint author), Vanderbilt Univ, Sch Med, Pediat Clin Res Off, Dept Pediat, CCC-5323 Med Ctr N, Nashville, TN 37232 USA. EM kathryn.edwards@vanderbilt.edu FU PHS HHS [200-20002-00732] NR 8 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2008 VL 27 IS 5 BP 464 EP 465 DI 10.1097/INF.0b013e31816591f7 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 296HN UT WOS:000255534200018 PM 18398385 ER PT J AU Cope, JU Morrison, AE Samuels-Reid, J AF Cope, Judith U. Morrison, Audrey E. Samuels-Reid, Joy TI Adolescent use of insulin and patient-controlled analgesia pump technology: A 10-year food and drug administration retrospective study of adverse events SO PEDIATRICS LA English DT Article DE medical devices; adolescent; infusion pump; diabetes; analgesia; adverse events; postmarket surveillance ID TYPE-1 DIABETES-MELLITUS; GLYCEMIC CONTROL; INFUSION; CHILDREN; THERAPY; TRIAL; SURGERY; SAFETY; ADULTS; YOUTH AB OBJECTIVES. From January 1, 2005, through December 31, 2005, the Food and Drug Administration received 5 adolescent death reports associated with the use of insulin pumps, raising concerns about use of this device in this age group. To understand better the types of infusion pump-related problems in adolescents, we performed a comprehensive evaluation of insulin and patient-controlled analgesic pump-related adverse events reported for adolescents that were received by the Food and Drug Administration from 1996 to 2005. METHODS. A search for medical device adverse event reports from January 1, 1996 through December 31, 2005, involving insulin pumps or patient-controlled analgesic pumps used by patients who were aged 12 to 21 years was conducted in the Food and Drug Administration's Manufacturer and User Facility Device Experience Database. Reports were reviewed for demographic characteristics, type of adverse event, and patient morbidity, and potential contributory factors were classified from narratives in the reports. RESULTS. A total of 1674 reports were identified: 1594 for insulin pumps and 53 for patient-controlled analgesic pumps. In reports of insulin pump events, there were 13 reported deaths, 2 reports that indicated possible suicide attempts, and several additional reports indicating severe hypoglycemic or hyperglycemic events that seemed to be device-related. A total of 102 (6.4%) insulin-pump reports highlighted factors that may have contributed to the adverse event, including problems associated with compliance, education, sports-related activities, and dropping or damaging the pump. Eighty-two percent of cases involving the insulin pump resulted in hospitalization. Half of the reports involving patient-controlled analgesic pumps indicated that the patient received an excess of medication; tampering and noncompliance were evident in some cases. CONCLUSIONS. Adolescents are a special population who deserve careful consideration of risk and benefit for use of device technology. Studies need to further identify safety problems in this age group. C1 [Cope, Judith U.; Morrison, Audrey E.] US FDA, Div Postmarket Surveillance, Off Surveillance & Biometr, Rockville, MD 20857 USA. [Samuels-Reid, Joy] US FDA, Div Anesthesiol, Gen Hosp, Off Device Evaluat,Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Cope, JU (reprint author), US FDA, Off Pediat Therapeut, Parklawn Room 13B45 HFG-2,5600 Fishers La, Rockville, MD 20850 USA. EM cope@fda.hhs.gov NR 38 TC 16 Z9 18 U1 3 U2 5 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 MAY PY 2008 VL 121 IS 5 BP E1133 EP E1138 DI 10.1542/peds.2007-1707 PG 6 WC Pediatrics SC Pediatrics GA 295VL UT WOS:000255501900055 PM 18450857 ER PT J AU McWilliam, A Lutter, R Nardinelli, C AF McWilliam, Andrew Lutter, Randall Nardinelli, Clark TI Healthcare impact of personalized medicine using genetic testing: an exploratory analysis for warfarin SO PERSONALIZED MEDICINE LA English DT Article ID ORAL ANTICOAGULANT-THERAPY; DOSE REQUIREMENTS; CYP2C9; METAANALYSIS; OUTCOMES; PHARMACOGENETICS; VARIANTS; COST AB Warfarin, an anticoagulant commonly used to prevent and control blood clots, is complicated to use because the optimal dose varies greatly among patients. If the dose is too high, the risk of serious bleeding increases; if the dose is too low, the risk of stroke increases. We estimate the potential health benefits and resulting changes in healthcare costs should it become feasible to base personalized warfarin dosing decisions on appropriate genetic testing. Using different assumptions regarding the costs and effectiveness of genetic testing, we estimate that formally integrating genetic testing into routine warfarin therapy could allow American warfarin users to avoid 4500-22,000 serious bleeding events annually. Genetic-based therapy could also reduce the incidence of strokes among patients taking warfarin. We estimate that the additional cost per patient from integrating genetic testing into warfarin therapy could range from US$300 in our pessimistic case, to substantial healthcare cost savings in the optimistic case. C1 [Lutter, Randall; Nardinelli, Clark] US FDA, Rockville, MD 20857 USA. [McWilliam, Andrew] US FDA, New York, NY 10036 USA. RP Nardinelli, C (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. EM Andrew.McWilliam@irs.gov; Randall.Lutter@fda.hhs.gov; Clark.Nardinelli@fda.hhs.gov NR 19 TC 15 Z9 15 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAY PY 2008 VL 5 IS 3 BP 279 EP 284 DI 10.2217/17410541.5.3.279 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 304QU UT WOS:000256124800017 ER PT J AU Gubernot, DM Boyer, BL Moses, MS AF Gubernot, Diane M. Boyer, Benita L. Moses, Marina S. TI Animal as early detectors of bioevents: Veterinary tools and a framework for animal-human integrated zoonotic disease surveillance SO PUBLIC HEALTH REPORTS LA English DT Article ID SENTINELS AB The threat of bioterrorism and emerging infectious diseases has prompted various public health agencies to recommend enhanced surveillance activities to supplement existing surveillance plans. The majority of emerging infectious diseases and bioterrorist agents are zoonotic. Animals are more sensitive to certain biological agents, and their use as clinical sentinels, as a means of early detection, is warranted. This article provides design methods for a local integrated zoonotic surveillance plan and materials developed for veterinarians to assist in the early detection of bioevents. Zoonotic surveillance in the U.S. is currently too limited and compartmentalized for broader public health objectives. To rapidly detect and respond to bioevents, collaboration and cooperation among various agencies at the federal, state, and local levels must be enhanced and maintained. Co-analysis of animal and human diseases may facilitate the response to infectious disease events and limit morbidity and mortality in both animal and human populations. C1 [Gubernot, Diane M.; Moses, Marina S.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Gubernot, Diane M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Boyer, Benita L.] Virginia Dept Hlth, Loudoun Cty Hlth Dept, Leesburg, VA USA. RP Gubernot, DM (reprint author), 2350 Cobble Hill Terrace, Silver Spring, MD 20902 USA. EM Gubernot@alumni.gwu.edu NR 17 TC 14 Z9 14 U1 0 U2 5 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2008 VL 123 IS 3 BP 300 EP 315 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 288HH UT WOS:000254976400012 PM 19006972 ER PT J AU Turnipseed, SB Andersen, WC Karbiwnyk, CM Madson, MR Miller, KE AF Turnipseed, Sherri B. Andersen, Wendy C. Karbiwnyk, Christine M. Madson, Mark R. Miller, Keith E. TI Multi-class, multi-residue liquid chromatography/tandem mass spectrometry screening and confirmation methods for drug residues in milk SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID SOLID-PHASE EXTRACTION; ELECTROSPRAY-IONIZATION; VETERINARY DRUGS; BOVINE-MILK; MUSCLE; ANTIBIOTICS; VALIDATION; PHARMACEUTICALS; TETRACYCLINE; PESTICIDES AB This paper describes the development and optimization of a multi-residue veterinary drug screening method for whole milk. The drug residues of regulatory interest in milk include beta-lactams, sulfonamides, tetracyclines, fluoroquinolones, and macrolides. Milk samples were extracted with acetonitrile and the samples were then subjected to a clean-up procedure using a bonded solid-phase extraction cartridge and a molecular weight cut-off filter. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) triple quadrupole electrospray methods were developed to monitor for the drugs in milk. Since established tolerance levels are set for most of these drugs in milk, the initial screening procedure was semi-quantitative, where samples were compared to the response of a positive control. The positive control, consisting of an extract from a portion of milk fortified with the drugs at half their allowed levels, was used to set the laboratory's minimum response criteria for unknown samples. Confirmatory analyses, with additional ion transitions for each residue, were performed on the same extracts. Published in 2008 by John Wiley & Sons, Ltd. C1 [Turnipseed, Sherri B.; Andersen, Wendy C.; Karbiwnyk, Christine M.; Madson, Mark R.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 34 TC 65 Z9 68 U1 3 U2 23 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD MAY PY 2008 VL 22 IS 10 BP 1467 EP 1480 DI 10.1002/rcm.3532 PG 14 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 305SO UT WOS:000256198300004 PM 18412094 ER PT J AU Fielden, MR Nie, A McMillian, M Elangbam, CS Trela, BA Yang, Y Dunn, RT Dragan, Y Fransson-Stehen, R Bogdanffy, M Adams, SP Foster, WR Chen, SJ Rossi, P Kasper, P Jacobson-Kram, D Tatsuoka, KS Wier, PJ Gollu, J Halbert, DN Roter, A Young, JK Sina, JF Marlowe, J Martus, HJ Aubrecht, J Olaharski, AJ Roome, N Nioi, P Pardo, I Snyder, R Perry, R Lord, P Mattes, W Car, BD AF Fielden, Mark R. Nie, Alex McMillian, Michael Elangbam, Chandi S. Trela, Bruce A. Yang, Yi Dunn, Robert T., II Dragan, Yvonne Fransson-Stehen, Ronny Bogdanffy, Matthew Adams, Stephen P. Foster, William R. Chen, Shen-Jue Rossi, Phil Kasper, Peter Jacobson-Kram, David Tatsuoka, Kay S. Wier, Patrick J. Gollu, Jeremy Halbert, Donald N. Roter, Alan Young, Jamie K. Sina, Joseph F. Marlowe, Jennifer Martus, Hans-Joerg Aubrecht, Jiri Olaharski, Andrew J. Roome, Nigel Nioi, Paul Pardo, Ingrid Snyder, Ron Perry, Richard Lord, Peter Mattes, William Car, Bruce D. CA Carcinogenicity Working Grp TI Interlaboratory evaluation of genomic signatures for predicting carcinogenicity in the rat SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE biomarkers; nongenotoxic; toxicogenomics ID GENE-EXPRESSION; INDUCED HEPATOCARCINOGENESIS; PHARMACEUTICALS; HEPATOTOXICITY; GENOTOXICITY; LIVER AB The Critical Path Institute recently established the Predictive Safety Testing Consortium, a collaboration between several companies and the U.S. Food and Drug Administration, aimed at evaluating and qualifying biomarkers for a variety of toxicological endpoints. The Carcinogenicity Working Group of the Predictive Safety Testing Consortium has concentrated on sharing data to test the predictivity of two published hepatic gene expression signatures, including the signature by Fielden et al. (2007, Toxicol. Sci. 99, 90-100) for predicting nongenotoxic hepatocarcinogens, and the signature by Nie et al. (2006, Mol. Carcinog. 45, 914-933) for predicting nongenotoxic carcinogens. Although not a rigorous prospective validation exercise, the consortium approach created an opportunity to perform a meta-analysis to evaluate microarray data from short-term rat studies on over 150 compounds. Despite significant differences in study designs and microarray platforms between laboratories, the signatures proved to be relatively robust and more accurate than expected by chance. The accuracy of the Fielden et al. signature was between 63 and 69%, whereas the accuracy of the Nie et al. signature was between 55 and 64%. As expected, the predictivity was reduced relative to internal validation estimates reported under identical test conditions. Although the signatures were not deemed suitable for use in regulatory decision making, they were deemed worthwhile in the early assessment of drugs to aid decision making in drug development. These results have prompted additional efforts to rederive and evaluate a QPCR-based signature using these samples. When combined with a standardized test procedure and prospective interlaboratory validation, the accuracy and potential utility in preclinical applications can be ascertained. C1 [Fielden, Mark R.; Olaharski, Andrew J.] Roche Palo Alto LLC, Palo Alto, CA 94304 USA. [Nie, Alex; McMillian, Michael; Lord, Peter] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Elangbam, Chandi S.; Tatsuoka, Kay S.; Wier, Patrick J.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Trela, Bruce A.; Yang, Yi] Abbott Labs, Abbott Pk, IL 60064 USA. [Dunn, Robert T., II] Amgen Inc, Thousand Oaks, CA USA. [Dragan, Yvonne] AstraZeneca, Boston, MA USA. [Fransson-Stehen, Ronny] AstraZeneca, Sodertalje, Sweden. [Bogdanffy, Matthew] Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. [Adams, Stephen P.; Foster, William R.; Chen, Shen-Jue; Car, Bruce D.] Bristol Myers Squibb Co, Princeton, NJ USA. [Adams, Stephen P.; Foster, William R.; Chen, Shen-Jue; Car, Bruce D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Rossi, Phil; Mattes, William] Critical Path Inst, Tucson, AZ USA. [Kasper, Peter] Fed Inst Drugs & Med Devices, Bonn, Germany. [Jacobson-Kram, David] US FDA, Washington, DC 20204 USA. [Gollu, Jeremy; Halbert, Donald N.; Roter, Alan] Iconix Biosci, Mountain View, CA USA. [Young, Jamie K.] Eli Lilly & Co, Lilly Res Labs, Greenfield, IN 46140 USA. [Sina, Joseph F.] Merck Res Labs, West Point, PA USA. [Marlowe, Jennifer; Martus, Hans-Joerg] Novartis Pharma AG, Basel, Switzerland. [Aubrecht, Jiri] Pfizer Inc, Groton, CT 06340 USA. [Roome, Nigel] Sanofi Aventis, Porcheville, France. [Nioi, Paul; Pardo, Ingrid; Snyder, Ron] Schering Plough Res Inst, Summit, NJ USA. [Perry, Richard] Wyeth Res, New York, NY USA. RP Fielden, MR (reprint author), Roche Palo Alto LLC, 3431 Hillview Ave, Palo Alto, CA 94304 USA. EM mark.fielden@roche.com NR 13 TC 50 Z9 53 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2008 VL 103 IS 1 BP 28 EP 34 DI 10.1093/toxsci/kfn022 PG 7 WC Toxicology SC Toxicology GA 287ZH UT WOS:000254955500004 PM 18281259 ER PT J AU Lu, H Choudhuri, S Ogura, K Csanaky, IL Lei, XH Cheng, XG Song, PZ Klaassen, CD AF Lu, Hong Choudhuri, Supratim Ogura, Kenichiro Csanaky, Ivan L. Lei, Xiaohong Cheng, Xingguo Song, Pei-Zhen Klaassen, Curtis D. TI Characterization of organic anion transporting polypeptide 1b2-null mice: Essential role in hepatic uptake/toxicity of phalloidin and microcystin-LR SO TOXICOLOGICAL SCIENCES LA English DT Article DE Oatp1b2; liver; knockout; mice; phalloidin; microcystin ID TISSUE DISTRIBUTION; MOLECULAR CHARACTERIZATION; XENOBIOTIC TRANSPORTERS; AMANITIN UPTAKE; ALPHA-AMANITIN; RAT; PHARMACOKINETICS; EXPRESSION; LIVER; GENE AB The liver-specific importer organic anion transporting polypeptide 1b2 (Oatp1b2, Slco1b2, also known as Oatp4 and Lst-1) and its human orthologs OATP1B1/1B3 transport a large variety of chemicals. Oatp1b2-null mice were engineered by homologous recombination and their phenotype was characterized. Oatp1b2 protein was absent in livers of Oatp1b2-null mice. Oatp1b2-null mice develop normally and breed well. However, adult Oatp1b2-null mice had moderate conjugated hyperbilirubinemia. Compared with wild-types, Oatp1b2-null mice had similar hepatic messenger RNA expression of most transporters examined except a higher Oatp1a4 but lower organic anion transporter 2. Intra-arterial injection of the mushroom toxin phalloidin (an Oatp1b2-specific substrate identified in vitro) caused cholestasis in wild-type mice but not in Oatp1b2-null mice. Hepatic uptake of fluorescence-labeled phalloidin was absent in Oatp1b2-null mice. Three hours after administration of microcystin-LR (a blue-green algae toxin), the binding of microcystin-LR to hepatic protein phosphatase 1/2a was much lower in Oatp1b2-null mice compared with wild-type mice. In contrast, Oatp1b2-null mice were transiently protected from decrease in bile flow induced by estradiol-17 beta-D-glucuronide, a common substrate for Oatps. Oatp1b2-null mice were completely resistant to the hepatotoxicity induced by phalloidin and microcystin-LR, but were similarly sensitive to alpha-amanitin-induced hepatotoxicity compared with wild-type mice. In conclusion, Oatp1b2-null mice display altered basic physiology and markedly decreased hepatic uptake/toxicity of phalloidin and microcystin-LR. Oatp1b2-null mice are useful in elucidating the role of Oatp1b2 and its human orthologs OATP1B1/1B3 in hepatic uptake and systemic disposition of toxic chemicals and therapeutic drugs. C1 [Lu, Hong; Csanaky, Ivan L.; Lei, Xiaohong; Cheng, Xingguo; Song, Pei-Zhen; Klaassen, Curtis D.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. [Choudhuri, Supratim] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. [Ogura, Kenichiro] Tokyo Univ Pharm & Life Sci, Dept Drug Metab & Mol Toxicol, Tokyo, Japan. RP Klaassen, CD (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66103 USA. EM cklaasse@kumc.edu RI Csanaky, Ivan/N-5312-2015 OI Csanaky, Ivan/0000-0001-7870-4129 FU NCRR NIH HHS [P20 RR021940, RR021940]; NIEHS NIH HHS [ES009649, ES013714, ES09716, R01 ES009649, R01 ES009716, R01 ES013714] NR 49 TC 81 Z9 85 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2008 VL 103 IS 1 BP 35 EP 45 DI 10.1093/toxsci/kfn038 PG 11 WC Toxicology SC Toxicology GA 287ZH UT WOS:000254955500005 PM 18296417 ER PT J AU Ketha, KMV Atreya, CD AF Ketha, Krishna Mohan V. Atreya, Chintamani D. TI Application of bioinformatics-coupled experimental analysis reveals a new transport-competent nuclear localization signal in the nucleoprotein of influenza A virus strain SO BMC CELL BIOLOGY LA English DT Article ID RIBONUCLEOPROTEIN COMPLEXES; A/WSN/33 VIRUS; PROTEIN; IMPORT; ROTAVIRUS; IDENTIFICATION; REPLICATION; SEQUENCE; REGIONS; DOMAIN AB Background: Two nuclear localization sequences (NLS) in influenza A virus nucleoprotein (NP) have been demonstrated to be critical for nuclear import of NP and viral ribonucleoprotein complexes. However, a deletion mutant lacking these two signals was still able to localize to the nucleus suggesting the presence of yet another (a third) potential NLS in the NP protein. In order to identify the nature of this potential NLS signal in the NP of a WS/33L influenza virus A strain, we utilized the tools of bioinformatics coupled with functional experimental analyses in the present study. Results: Comparison of the deduced aa sequence of NP of WS/33L strain with the published WS/ 33 NP sequences revealed that a single amino acid (aa) change (Met to Arg) at position 105 results in converting the flanking regions (between aa position 90 -121, a 32-residue stretch) into two classical overlapping bipartite NLS (obpNLS). GenBank search revealed that 9 out of 500 published NP sequences contain a similar Arg at position 105 (instead of Met) with a 100% homology to the obpNLS region. Various NP-green fluorescent protein (GFP) fusion constructs with and without the signal (obpNLS-Arg105) were utilized to understand the functional nature of this signal. We analyzed the transport competency of the expressed chimeric proteins in terms of their cellular localization by confocal immunofluorescence assay. Our analysis revealed that all NP-GFP constructs containing the wild-type (R105) sequence localized predominantly to the nucleus. Constructs lacking the obpNLS or constructs with reverse mutation (R105 to M105) on the other hand exhibited predominant cytoplasmic localization pattern. Interestingly, when the 32 aa obpNLS was fused with an unrelated viral protein (rotavirus NSP6) that has been known to be cytoplasmic protein, the chimeric protein (obpNLS-NSP6) was efficiently transported into the nucleus, indicating an efficient nuclear transport function of the 32-residue obpNLS in the NP of WS/33L strain of influenza A virus. Conclusion: This report while not only establishing a new NLS in the influenza A virus strain, it also reinforces the idea that proper application of bioinformatics-coupled experimental analysis serves as a powerful tool in identifying new functional signals in proteins of interest. C1 [Ketha, Krishna Mohan V.; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol,Off Blood Res & Review, Sect Cell Biol,Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Ketha, KMV (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol,Off Blood Res & Review, Sect Cell Biol,Lab Cellular Hematol, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov; chintamani.atreya@fd.hhs.gov NR 25 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD APR 28 PY 2008 VL 9 AR 22 DI 10.1186/1471-2121-9-22 PG 12 WC Cell Biology SC Cell Biology GA 301ZF UT WOS:000255934600001 PM 18442378 ER PT J AU Yu, L Nomaguchi, M Padmanabhan, R Markoff, L AF Yu, Li Nomaguchi, Masako Padmanabhan, R. Markoff, Lewis TI Specific requirements for elements of the 5 ' and 3 ' terminal regions in flavivirus RNA synthesis and viral replication SO VIROLOGY LA English DT Article DE flavivirus RNA replication; RNA cyclization; flavivirus polymerase activity ID WEST-NILE-VIRUS; YELLOW-FEVER VIRUS; JAPANESE ENCEPHALITIS-VIRUS; DENGUE-VIRUS; SECONDARY STRUCTURE; GENOMIC RNA; 3'-UNTRANSLATED REGION; NONCODING REGION; STEM-LOOP; IN-VITRO AB We initially studied requirements for 5 ' and 3 ' terminal regions (TRs) in flavivirus negative strand synthesis in vitro. Purified West Nile (WNV) and dengue-2 (DV2) RNA polymerases were both active with all-WNVor all-DV2 subgenomic RNAs containing the 5 '- and 3 ' TRs of the respective genomes. However, subgenomic RNAs in which the 5 '-noncoding region (5 ' NCR) or the 5 ' ORF (nts 100-230) in the 5 ' TR were substituted by analogous sequences derived from the heterologous genome were modestly to severely defective as templates for either polymerase. We also evaluated the infectivity of substitution mutant WNV genome-length RNAs. All WNV RNAs containing the DV2 3 ' SL were unable to replicate. However, WNV RNAs containing substitutions of the 5 ' NCR, the capsid gene, and/or 3 ' NCR nt sequences upstream from the WNV 3 ' SL, by the analogous DV2 nt sequences, were infectious. Combined results suggested that replication was not dependent upon species homology between the 3 ' SL and NS5. (c) 2007 Elsevier Inc. All rights reserved. C1 [Nomaguchi, Masako; Padmanabhan, R.] George Washington Univ, Sch Med, Dept Microbiol & Immunol, Washington, DC USA. [Yu, Li; Markoff, Lewis] US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Div Viral Prod,Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Yu, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Virus Dis, Div Viral Prod,Off Vaccines Res & Review, Bldg 29A,Rm 1B18,8800 Rockville Pike, Bethesda, MD 20892 USA. EM yuli@cber.fda.gov FU NIAID NIH HHS [R01 AI032078, R21 AI032078, R01 AI032078-08, AI32078] NR 53 TC 38 Z9 40 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 25 PY 2008 VL 374 IS 1 BP 170 EP 185 DI 10.1016/j.virol.2007.12.035 PG 16 WC Virology SC Virology GA 293HA UT WOS:000255325100015 PM 18234265 ER PT J AU Koren, E Smith, HW Shores, E Shankar, G Finko-Kent, D Rup, B Barrett, YC Devanarayan, V Gorovits, B Gupta, S Parish, T Quarmby, V Moxness, M Swanson, SJ Taniguchi, G Zuckerman, LA Stebbins, CC Mire-Sluis, A AF Koren, Eugen Smith, Holly W. Shores, Elizabeth Shankar, Gopi Finko-Kent, Deborah Rup, Bonita Barrett, Yu-Chen Devanarayan, Viswanath Gorovits, Boris Gupta, Shalini Parish, Thomas Quarmby, Valerie Moxness, Michael Swanson, Steven J. Taniguchi, Gary Zuckerman, Linda A. Stebbins, Christopher C. Mire-Sluis, Anthony TI Recommendations on risk-based strategies for detection and characterization of antibodies against biotechnology products SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE immunogenicity testing; therapeutic proteins; risk assessment ID RED-CELL APLASIA; PSORIATIC-ARTHRITIS; ANTIERYTHROPOIETIN ANTIBODIES; MONOCLONAL-ANTIBODIES; HUMAN THROMBOPOIETIN; IGA ANTIBODIES; IMMUNOGENICITY; IDENTIFICATION; THROMBOCYTOPENIA; OPTIMIZATION AB The appropriate evaluation of the immunogenicity of biopharmaccuticals is of major importance for their successful development and licensure. Antibodies elicited by these products in many cases cause no detectable clinical effects in humans. However, antibodies to some therapeutic proteins have been shown to cause a variety of clinical consequences ranging from relatively mild to serious adverse events. In addition, antibodies can affect drug efficacy. In non-clinical studies, anti-drug antibodies (ADA) can complicate interpretation of the toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) data. Therefore, it is important to develop testing strategies that provide valid assessments of antibody responses in both non-clinical and clinical studies. This document provides recommendations for antibody testing strategies stemming from the experience of contributing authors. The recommendations are intended to foster a more unified approach to antibody testing across the biopharmaceutical industry. The strategies proposed are also expected to contribute to better understanding of antibody responses and to further advance immunogenicity evaluation. (C) 2008 Elsevier B.V. All rights reserved. C1 [Koren, Eugen] Abbott Vasc Inc, Bioanalyt R&D, Santa Clara, CA 95054 USA. [Smith, Holly W.] Eli Lilly & Co, Investigat Toxicol, Greenfield, IN 46140 USA. [Shores, Elizabeth] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Biotechnol Prod, Bethesda, MD 20892 USA. [Shankar, Gopi] Centocor Res & Dev Inc, Clin Pharmacol & Expt Med, Radnor, PA 19087 USA. [Finko-Kent, Deborah] Pfizer, Drug Safety Res & Dev, Groton, CT 06340 USA. [Rup, Bonita] Wyeth Res, Bioanalyt R&D, Drug Safety & Metab, Andover, MA 01810 USA. [Barrett, Yu-Chen] Bristol Myers Squibb Co, Clin Discovery, Princeton, NJ 08543 USA. [Devanarayan, Viswanath] Merck & Co Inc, Upper Gwynedd, PA 19087 USA. [Gorovits, Boris] Wyeth, Drug Safety & Metab, Pearl River, NY 10965 USA. [Gupta, Shalini; Moxness, Michael; Swanson, Steven J.] Amgen Inc, Med Sci, Dept Clin Immunol, Thousand Oaks, CA 91320 USA. [Parish, Thomas] Procter & Gamble Pharmaceut, Dept Analyt Sci, Norwich, NY 13815 USA. [Quarmby, Valerie; Stebbins, Christopher C.] Genentech Inc, BioAnalyt Res & Dev, San Francisco, CA 94080 USA. [Taniguchi, Gary] PDL BioPharma Inc, Analyst Sci, Fremont, CA 94555 USA. [Zuckerman, Linda A.] ZymoGenet Inc, PreClin Dev Dept, Seattle, WA 98102 USA. [Mire-Sluis, Anthony] Amgen Inc, Global Prod Qual & External Affairs, Longmont, CO 80503 USA. RP Koren, E (reprint author), Abbott Vasc Inc, Bioanalyt R&D, Santa Clara, CA 95054 USA. EM eugen.koren@av.abbott.com NR 30 TC 156 Z9 157 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 20 PY 2008 VL 333 IS 1-2 BP 1 EP 9 DI 10.1016/j.jim.2008.01.001 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 299CX UT WOS:000255734500001 PM 18275969 ER PT J AU Ehrenfeld, E Glass, RI Agol, VI Chumakov, K Dowdle, W John, TJ Katz, SL Miller, M Breman, JG Modlin, J Wright, P AF Ehrenfeld, Ellie Glass, Roger I. Agol, Vadim I. Chumakov, Konstantin Dowdle, Walter John, T. Jacob Katz, Samuel L. Miller, Mark Breman, Joel G. Modlin, John Wright, Peter TI Immunisation against poliomyelitis: moving forward SO LANCET LA English DT Editorial Material ID VACCINE-DERIVED POLIOVIRUSES; POLIO ERADICATION; EFFICACY C1 [Glass, Roger I.; Miller, Mark; Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. [Agol, Vadim I.] Inst Poliomyelitis & Viral Encephalitides, Moscow, Russia. [Chumakov, Konstantin] US FDA, PHHS, Rockville, MD 20857 USA. [Dowdle, Walter] Task Force Child Survival & Dev, Atlanta, GA USA. [John, T. Jacob] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. [Katz, Samuel L.] Duke Univ, Sch Med, Durham, NC USA. [Modlin, John; Wright, Peter] Dartmouth Med Sch, Hanover, NH USA. [Wright, Peter] Vanderbilt Univ Sch Med, Nashville, TN USA. RP Glass, RI (reprint author), NIH, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA. EM glassr@mail.nih.gov RI Agol, Vadim/E-1941-2013 NR 20 TC 17 Z9 18 U1 0 U2 2 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 APR 19 PY 2008 VL 371 IS 9621 BP 1385 EP 1387 DI 10.1016/S0140-6736(08)60597-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 291PE UT WOS:000255208500029 PM 18424327 ER PT J AU Lo, CY Wu, ZQ Misplon, JA Price, GE Pappas, C Kong, WP Turnpey, TM Epstein, SL AF Lo, Chia-Yun Wu, Zhengqi Misplon, Julia A. Price, Graeme E. Pappas, Claudia Kong, Wing-Pui Turnpey, Terrence M. Epstein, Suzanne L. TI Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: Cold-adapted vaccine versus DNA prime-adenovirus boost strategies SO VACCINE LA English DT Article DE influenza; pandemic; heterosubtypic immunity ID HETEROTYPIC IMMUNITY; H5N1 VIRUSES; T-CELLS; RELATIVE IMMUNOGENICITY; INACTIVATED VACCINES; MATRIX PROTEIN-2; DONOR STRAINS; M2 PROTEIN; MICE; LIVE AB Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-1) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-1 has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-1, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Lo, Chia-Yun; Wu, Zhengqi; Misplon, Julia A.; Price, Graeme E.; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, Rockville, MD 20852 USA. [Pappas, Claudia; Turnpey, Terrence M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Cooodinating Ctr Infect Dis, Atlanta, GA 30333 USA. [Kong, Wing-Pui] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Epstein, SL (reprint author), US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA. EM suzanne.epstein@fda.hhs.gov NR 42 TC 53 Z9 59 U1 0 U2 3 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 APR 16 PY 2008 VL 26 IS 17 BP 2062 EP 2072 DI 10.1016/j.vaccine.2008.02.047 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 300LE UT WOS:000255824500004 PM 18378366 ER PT J AU Atrasheuskaya, AV Kulak, MV Neverov, AA Rubin, S Ignatyev, GM AF Atrasheuskaya, A. V. Kulak, M. V. Neverov, A. A. Rubin, S. Ignatyev, G. M. TI Measles cases in highly vaccinated population of Novosibirsk, Russia, 2000-2005 SO VACCINE LA English DT Article DE measles; Russia; genotyping; vaccine failure; neutralizing titers ID SECONDARY IMMUNE-RESPONSES; IMMUNOGLOBULIN-G AVIDITY; VIRUS INFECTION; CELLULAR-IMMUNITY; LATE CONVALESCENT; IGG AVIDITY; WILD-TYPE; ANTIBODY; FAILURE; RUBELLA AB White the proportion of measles cases in vaccinees is expected to increase as vaccine coverage increases, such cases must be carefully investigated. The present study was conducted to examine possible contributions to vaccine failures (VFs) and to genetically characterize measles virus (MV) strains circulating in Novosibirsk, Russia during 2000-2005. Totally, 27 adult measles patients admitted to a regional hospital were prospectively enrolled in our study. Genetic characterization of the MV strains revealed circulation of genotypes A, D4 and D6 between 2000 and 2003 years; a genotype D6 MV was associated with the 2005 measles outbreak. Based on IgG avidity testing, half of the vaccinated patients demonstrated evidence of secondary vaccine failure (SVF). Patients, representing both levels of vaccine failure in our study were characterized by the tack of protective titers of neutralizing antibodies against circulating MVs, despite high IgG levels in many cases and high IgG avidity in SVF cases. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Atrasheuskaya, A. V.; Kulak, M. V.; Neverov, A. A.; Ignatyev, G. M.] State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Koltsov 630559, Novosibirsk Reg, Russia. [Rubin, S.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Atrasheuskaya, AV (reprint author), State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Koltsov 630559, Novosibirsk Reg, Russia. EM marburgman3@infonet.by NR 45 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 16 PY 2008 VL 26 IS 17 BP 2111 EP 2118 DI 10.1016/j.vaccine.2008.02.028 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 300LE UT WOS:000255824500009 PM 18343536 ER PT J AU LaPointe, NMA Sun, JL Kaplan, S d'Almada, P Al-Khatib, SM AF LaPointe, Nancy M. Allen Sun, Jie-Lena Kaplan, Sigal d'Almada, Phil Al-Khatib, Sana M. TI Rhythm versus rate control in the contemporary management of atrial fibrillation in-hospital SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PULMONARY-VEIN ABLATION; ASSOCIATION TASK-FORCE; QUALITY-OF-LIFE; RANDOMIZED-TRIAL; HEART-FAILURE; SINUS RHYTHM; AMERICAN-COLLEGE; GUIDELINES; STROKE; STRATEGIES AB Little is presently known regarding whether a rhythm-control or a rate-control strategy is more frequently used in patients hospitalized for atrial fibrillation (AF). This study was conducted to assess patient and physician characteristics associated with each treatment strategy and with the use of anticoagulants. Hospitalizations for primary diagnoses of AF were examined using hospital claims from January 2000 to December 2004. Patients who received antiarrhythmic drugs, ablation, or cardioversion for AF were categorized as receiving rhythm control. Patients managed only with beta blockers, calcium channel blockers, or digoxin were categorized as receiving rate control: Characteristics associated with rhythm compared with rate control and anticoagulant use with CHADS(2) score were determined. The study cohort included 155,731 hospitalizations from 464 hospitals. Of these, 75,397 (48%) were categorized as involving rhythm control and 80,334 (52%) as involving rate control. Care by a noncardiologist (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI] 0.31 to 0.36) and increasing age >65 years (adjusted OR 0.87, 95% CI 0.86 to 0.88) were associated with lower odds of rhythm versus rate control; hypertrophic cardiomyopathy was associated with greater odds (adjusted OR 2.3, 95% CI 1.81 to 2.84) of rhythm control. Warfarin use was greater in the rhythm-control group compared with the rate-control group (adjusted OR 1.56, 95% CI 1.52 to 1.60), and warfarin use was greater with a CHADS(2) score >= 2 (unadjusted OR 1.21, 95% CI 1.19 to 1.24). In conclusion, rhythm- and rate-control strategies were used equally in patients hospitalized for AF. Some observations, such as greater use of the rate-control strategy with increasing age, were consistent with recommendations, but others, such as lower use of warfarin in the rate-control group, were not. (C) 2008 Elsevier Inc. All rights reserved. C1 [LaPointe, Nancy M. Allen; Sun, Jie-Lena; d'Almada, Phil; Al-Khatib, Sana M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Kaplan, Sigal] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP LaPointe, NMA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. EM allen003@mc.duke.edu NR 26 TC 8 Z9 9 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2008 VL 101 IS 8 BP 1134 EP 1141 DI 10.1016/j.amjcard.2007.11.067 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 288XT UT WOS:000255020200013 ER PT J AU Hoffmann, M Keys, CE Song, KY Brown, EW Fry, FS Whittaker, P AF Hoffmann, Maria Keys, Christine E. Song, Kwang-Young Brown, Eric W. Fry, Frederick S. Whittaker, Paul TI Evaluation of multiple strains of Enterobacter sakazakii using fatty acid profiles SO FOOD CHEMISTRY LA English DT Article DE gas chromatography; fatty acids; Enterobacter sakazakii ID POWDERED INFANT FORMULA; INFECTIONS; MILK AB Fatty acid profiles are useful for identifying Gram-negative Enterobacter sakazakii strains within the family Enterobacteriaceae. The majority of cases of E sakazakii infection have involved sepsis, meningitis, or enteritis, especially in neonates and infants. Gas chromatography with flame ionization detection (GC-FID) was utilized for the analysis of cellular fatty acid methyl esters (FAMEs). Thirty E. sakazakii strains isolated from food and environmental sources were cultured for 24 h on brain heart infusion (BHI) agar on three different days at 37 degrees C. Whole cell FAMEs were obtained by saponification, methylation and extraction into hexane:methyl tert-butyl ether. The day to day variations for the 30 E. sakazakii strains for each fatty acid were determined. Gram-negative bacteria commonly contain combinations of straight-chain, unsaturated, hydroxyl, and cyclo fatty acids. Major fatty acids of E. sakazakii strains evaluated in this study were straight chain 12:0, 14:0, 16:0 and unsaturated 16:1, 18:1, and 17:0 omega cyclo 7-8. Analysis of FAMEs from E. sakazakii strains grown on BHI agar by this rapid GC-FID method is highly reproducible and provides a sensitive procedure for identification of this organism. The fatty acid profile assay could be used to rapidly screen infant formula samples for E. sakazakii and reduce the time required for the current assay by up to 5 days. Published by Elsevier Ltd. C1 [Hoffmann, Maria; Keys, Christine E.; Song, Kwang-Young; Brown, Eric W.; Fry, Frederick S.; Whittaker, Paul] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 15 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD APR 15 PY 2008 VL 107 IS 4 BP 1623 EP 1628 DI 10.1016/j.foodchem.2007.10.032 PG 6 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 246JW UT WOS:000252004300033 ER PT J AU De Jager, LS Perfetti, GA Diachenko, GW AF De Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Comparison of headspace-SPME-GC-MS and LC-MS for the detection and quantification of coumarin, vanillin, and ethyl vanillin in vanilla extract products SO FOOD CHEMISTRY LA English DT Article DE coumarin; vanilla; HS-SPME; GC-MS; LC-MS; headspace ID SOLID-PHASE MICROEXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; HPLC; PLANIFOLIA; TOBACCO AB A headspace-solid phase micro-extraction (HS-SPME) GC-MS method has been developed for the determination of coumarin, vanillin and ethyl vanillin in vanilla products. Limits of detection ranged from 1.33 to 13.2 ng mL(-1). Accuracy and precision data for the method were measured and compared to those obtained using LC-ESI-MS. A survey of 24 commercially available vanilla products was completed using both techniques. No coumarin was detected in any of the samples. Examination of the GC-MS chromatograms revealed the presence of 18 other flavor related compounds in the samples. The method validation and sample analysis data using HS-SPME-GC-MS were comparable to those obtained using the LC-MS method. Because the two methods are conceptually different from one another, both methods would not be subject to the same interferences. This would allow them to be used as confirmatory methods for each other. Published by Elsevier Ltd. C1 [De Jager, Lowri S.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20785 USA. RP De Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20785 USA. EM lowri.dejager@fda.hhs.gov NR 18 TC 26 Z9 26 U1 5 U2 50 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD APR 15 PY 2008 VL 107 IS 4 BP 1701 EP 1709 DI 10.1016/j.foodchem.2007.09.070 PG 9 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA 246JW UT WOS:000252004300044 ER PT J AU Bhave, VS Donthamsetty, S Latendresse, JR Muskhelishvili, L Mehendale, HM AF Bhave, Vishakha S. Donthamsetty, Shashikiran Latendresse, John R. Muskhelishvili, Levan Mehendale, Harihara M. TI Secretory phospholipase A(2) mediates progression of acute liver injury in the absence of sufficient cyclooxygenase-2 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arachidonic acid; carbon tetrachloride; cycloxygenase-2; necrotic debris; secretory phospholipase A(2); prostaglandin E-2 ID ACUTE-PHASE RESPONSE; GROUP IIA; GENE-EXPRESSION; RECEPTOR-ALPHA; TISSUE-REPAIR; NITRIC-OXIDE; ANNEXIN-V; RAT; CELLS; INHIBITION AB Previous studies have shown that injury initiated by toxicants progresses even after most of the toxicant is eliminated from the body. One mechanism of progression of injury is the extracellular appearance of hydrolytic enzymes following leakage or upon cell lyses. Under normal conditions, after exposure to low to moderate doses of toxicants, secretory phospholipase A(2) (sPLA(2)) and other hydrolytic enzymes are known to appear in the extracellular spaces in order to cleanup the post-necrotic debris in tissues. We tested the hypothesis that sPLA2 contributes to progression of toxicant-initiated liver injury because of hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas in the absence of sufficient cyclooxygenase-2 (COX-2). Male Sprague-Dawley rats were administered either a moderately hepatotoxic dose (MD, 2 ml CCl4/kg, ip) or a highly hepatotoxic dose (HD, 3 ml CCl4/kg, ip) Of CCl4. After MD, liver sPLA(2) and COX-2 were co-localized in the necrotic and perinecrotic areas and their activities in plasma and liver increased before decreasing in tandem with liver injury (ALT and histopathology) leading to 100% survival. In contrast, after the HD, high extracellular and hepatic sPLA2 activities were accompanied by minimal COX-2 activity and localization in the liver throughout the time course. This led to progression of liver injury and 70% mortality. These data suggested a destructive role of sPLA2 in the absence of sufficient COX-2. Time- and dose-dependent destruction of hepatocytes by sPLA2 in isolated hepatocyte incubations confirmed the destructive ability of sPLA(2) when present extracellularly, suggesting its ability to spread injury in vivo. These findings suggest that sPLA(2), secreted for cleanup of necrotic debris upon initiation of hepatic necrosis, requires the co-presence of sufficiently induced COX-2 activity to prevent the run-away destructive action of sPLA2 in the absence of the tissue protective mechanisms afforded by COX-2 induction. (C) 2008 Elsevier Inc. All rights reserved. C1 [Bhave, Vishakha S.; Donthamsetty, Shashikiran; Mehendale, Harihara M.] Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. [Latendresse, John R.; Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306 B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009; OI Bhave, Vishakha/0000-0003-0149-579X NR 63 TC 16 Z9 16 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2008 VL 228 IS 2 BP 225 EP 238 DI 10.1016/j.taap.2007.12.023 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295SN UT WOS:000255494300010 PM 18329682 ER PT J AU Bhave, VS Donthamsetty, S Latendresse, JR Mehendale, HM AF Bhave, Vishakha S. Donthamsetty, Shashikiran Latendresse, John R. Mehendale, Harihara M. TI Inhibition of cyclooxygenase-2 aggravates secretory phospholipase A(2)-mediated progression of acute liver injury SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE carbon tetrachloride; cycloxygenase-2; NS-398; secretory phospholipase A(2); prostaglandin E-2 ID CARBON-TETRACHLORIDE HEPATOTOXICITY; EPITHELIAL-CELLS; RECEPTOR-ALPHA; RATS; EXPRESSION; REGENERATION; COX-2; POTENTIATION; HEPATOCYTES; MICE AB Our previous study [Bhave, V S., Donthamsetty, S., Latendresse, J. R., Muskhelishvili, L., and Mebendale, H. M. 2008-this issue. Secretory phospholipase A(2) mediates progression of acute liver injury in the absence of sufficient COX-2. Toxicol Appl Pharmacol] showed that in the absence of sufficient induction and co-presence of cyclooxygenase-2 (COX-2), secretory phospholipase A(2) (sPLA(2)) appearing in the intercellular spaces for cleanup of post-necrotic debris seems to contribute to the progression of toxicant-initiated liver injury, possibly by hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas. To further test our hypothesis on the protective role of COX-2, male Fisher-344 rats were administered a selective COX-2 inhibitor, NS-398, and then challenged with a moderately toxic dose Of CCl4. This led to a 5-fold increase in the susceptibility of the COX-2 inhibited rats to CCl4 hepatotoxicity and mortality. The CCl4 bioactivating enzyme CYP2E1 protein, CYP2E1 enzyme activity, and the (CCl4)-C-14-derived radiolabel covalently bound to the liver proteins were unaffected by the COX-2 inhibitor suggesting that the increased hepatotoxic sensitivity of the COX-2 inhibited rats was not due to higher bioactivation Of CCl4. Further investigation showed that this increased mortality was due to higher plasma and hepatic sPLA(2) activities, inhibited PGE(2) production, and progression of liver injury as compared to the non-intervened rats In conclusion, inhibition of COX-2 mitigates the tissue protective mechanisms associated with COX-2 induction, which promotes sPLA(2)-mediated progression of liver injury in an acute liver toxicity model. Because increased sPLA(2) activity in the intercellular space is associated with increased progression of injury, and induced COX-2 is associated with hepatoprotection, ratios of hepatic COX-2 and sPLA(2) activities may turn out to be a useful tool in predicting the extent of hepatotoxicities. (C) 2007 Elsevier Inc. All rights reserved. C1 [Bhave, Vishakha S.; Donthamsetty, Shashikiran; Mehendale, Harihara M.] Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. [Latendresse, John R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306 B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009; OI Bhave, Vishakha/0000-0003-0149-579X NR 35 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD APR 15 PY 2008 VL 228 IS 2 BP 239 EP 246 DI 10.1016/j.taap.2007.12.025 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 295SN UT WOS:000255494300011 PM 18336855 ER PT J AU Bullerman, LB Bianchini, A Hanna, MA Jackson, LS Jablonski, J Ryu, D AF Bullerman, Lloyd B. Bianchini, Andrfia Hanna, Milford A. Jackson, Lauren S. Jablonski, Joseph Ryu, Dorn TI Reduction of fumonisin B(1) in corn grits by single-screw extrusion SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fumonisin; reduction; N-(deoxy-D-fructos-1-yl)fumonisin; extrusion ID NEURAL-TUBE DEFECTS; ESOPHAGEAL CANCER; IN-VIVO; LIQUID-CHROMATOGRAPHY; FUSARIUM-MONILIFORME; TEXTURAL PROPERTIES; MASS-SPECTROMETRY; PRODUCTS; TEMPERATURE; MYCOTOXINS AB This study was designed to determine the efficacy of extrusion in reducing fumonisin 131 in corn flaking grits in the presence and absence of glucose. In addition, degradation products of fumonisin 131 during extrusion were identified and quantitated with a mass balance approach. Uncontaminated clean corn grits, grits spiked with 30 mu g/g fumonisin B(1), and grits fermented with Fusarium verticillioides M-2552 (40-50 mu g/g fumonisin B(1)) were extruded in the presence and absence of glucose (10%, w/w) using a single-screw extruder. Extrusion decreased fumonisin B(1) by 21-37%, whereas the same process with added glucose further decreased fumonisin B, by 77-87%. LC-fluorescence and LC-MS showed that most fumonisin in the extruded samples without added glucose was the fumonisin 131 form, whereas the main degradation product in grits extruded with glucose was N-(deoxy-D-fructos-1-yl)fumonisin B(1). The formation of hydrolyzed fumonisin B, was not significant during extrusion. Results suggest that extrusion in the presence of glucose may reduce fumonisin B(1) in corn grits significantly. C1 [Ryu, Dorn] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Bullerman, Lloyd B.; Bianchini, Andrfia; Hanna, Milford A.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. [Jackson, Lauren S.; Jablonski, Joseph] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Ryu, D (reprint author), Texas Womans Univ, Dept Nutr & Food Sci, POB 425888, Denton, TX 76204 USA. EM dryu@twu.edu NR 29 TC 20 Z9 20 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 9 PY 2008 VL 56 IS 7 BP 2400 EP 2405 DI 10.1021/jf0729513 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 283KZ UT WOS:000254636400016 PM 18327966 ER PT J AU Al-Taher, F Didsatha-Amnarj, Y Jackson, L Varelis, P AF Al-Taher, Fadwa Didsatha-Amnarj, Yanan Jackson, Lauren Varelis, Peter TI AGFD 50-Development of a headspace GC/MS method to measure furan in foods and beverages and its application to survey work SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Al-Taher, Fadwa; Didsatha-Amnarj, Yanan; Varelis, Peter] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Jackson, Lauren] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. EM altaher@iit.edu; varelis@iit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 50-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100211 ER PT J AU Benz, SA AF Benz, Sharon A. TI AGFD 150-FDA's Animal Feed Safety System (AFSS): Focus on feed contaminants SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Benz, Sharon A.] US FDA, Ctr Vet Med, Div Anim Feeds, Rockville, MD 21797 USA. EM sharon.benz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 150-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100239 ER PT J AU Beru, N Robin, LP Kim, H Wood, G AF Beru, Nega Robin, Lauren Posnick Kim, Henry Wood, Garnett TI AGFD 105-Overview of chemical contaminants in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Beru, Nega; Robin, Lauren Posnick; Kim, Henry; Wood, Garnett] US FDA, College Pk, MD 20901 USA. EM nega.beru@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 105-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100253 ER PT J AU Bolger, M AF Bolger, Michael TI AGFD 110-Food borne elemental contaminants and sensitive subpopulations SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Bolger, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Mike.Bolger@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 110-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100309 ER PT J AU Buchanan, RL AF Buchanan, Robert L. TI AGFD 137-FDA food defense and agro-terrorism programs: Being vigilant and prepared SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Buchanan, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, DHHS, College Pk, MD 20740 USA. EM Robert.Buchanan@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 137-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100275 ER PT J AU Garber, EAE O'Brien, TW Venkateswaran, KV AF Garber, Eric A. E. O'Brien, Thomas W. Venkateswaran, Kodumudi V. TI AGFD 122-Simultaneous multiplex detection of proteins in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [O'Brien, Thomas W.] Tetracore Inc, Rockville, MD USA. [Venkateswaran, Kodumudi V.] Radix Blosolut, Georgetown, TX 78626 USA. EM Eric.Garber@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 122-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100226 ER PT J AU Iha, MH Trucksess, MW Rader, JI AF Iha, Maria H. Trucksess, Mary W. Rader, Jeanne I. TI AGFD 119-Determination of ochratoxin A in dried beans SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Iha, Maria H.; Trucksess, Mary W.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM maria.iha@fda.hhs.gov; mary.trucksess@fda.hhs.gov; jeanne.rader@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 119-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100192 ER PT J AU Jackson, L Tolleson, WH Truong, P AF Jackson, Lauren Tolleson, William H. Truong, Phuong TI AGFD 19-Stability of ricin and abrin in yogurt SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Jackson, Lauren] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Tolleson, William H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Truong, Phuong] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. EM lauren.jackson@fda.hhs.gov; William.Tolleson@fda.hhs.gov; truong@iit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 19-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100242 ER PT J AU Kim, CS Saylor, DM Patwardhan, DV AF Kim, Chang-Soo Saylor, Dave M. Patwardhan, Dinesh V. TI POLY 388-Modeling structure development of release behavior of drug embedded in block copolymer matrices SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA C1 [Kim, Chang-Soo; Saylor, Dave M.; Patwardhan, Dinesh V.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20903 USA. EM chang-soo.kim@fda.hhs.gov; david.saylor@fda.hhs.gov RI Madruga, Santiago/D-2984-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 388-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519XJ UT WOS:000271802800192 ER PT J AU McLaughlin, MA Brewer, VA AF McLaughlin, Michael A. Brewer, Vickery A. TI AGFD 48-Chemistry proficiency testing program of the Food Emergency Response Network (FERN) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [McLaughlin, Michael A.; Brewer, Vickery A.] US FDA, Off Regulatory Sci, CFSAN, College Pk, MD 20740 USA. EM michael.mclaughlin@fda.hhs.gov; vickery.brewer@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 48-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100255 ER PT J AU Musser, SM Callahan, JH AF Musser, Steven M. Callahan, John H. TI AGFD 123-New approaches to the analysis of foods by mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Musser, Steven M.] Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Callahan, John H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Steven.Musser@fda.hhs.gov; john.callahan@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 123-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100262 ER PT J AU Patwardhan, DV Saylor, DM McDermott, MK Dair, BJ AF Patwardhan, Dinesh V. Saylor, Dave M. McDermott, Martin K. Dair, Benita J. TI POLY 385-Drug microstructure to drug release SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA C1 [Patwardhan, Dinesh V.; Saylor, Dave M.; McDermott, Martin K.; Dair, Benita J.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20903 USA. EM david.saylor@fda.hhs.gov; Martin.MCDermott@fda.hhs.gov; benita.dair@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 385-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519XJ UT WOS:000271802800778 ER PT J AU Satzger, RD Litzau, JJ Mulligan, KJ Flurer, RA Witkowski, MR Crowe, JB Ciolino, LA Mohrhaus, AS Jackson, DS Dasenbrock, CO Yi, TY Brzezinski, JL AF Satzger, R. Duane Litzau, J. J. Mulligan, K. J. Flurer, R. A. Witkowski, M. R. Crowe, J. B. Ciolino, L. A. Mohrhaus, A. S. Jackson, D. S. Dasenbrock, C. O. Yi, T. Y. Brzezinski, J. L. TI AGFD 126-Characterization of a pet food adulteration problem by utilizing a multidisciplinary analytical approach SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Satzger, R. Duane; Litzau, J. J.; Mulligan, K. J.; Flurer, R. A.; Witkowski, M. R.; Crowe, J. B.; Ciolino, L. A.; Mohrhaus, A. S.; Jackson, D. S.; Dasenbrock, C. O.; Yi, T. Y.; Brzezinski, J. L.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM rd.satzger@fds.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 126-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100315 ER PT J AU Scott, PM Trucksess, MW AF Scott, Peter M. Trucksess, Mary W. TI AGFD 112-Prevention of mycotoxins in dried fruit, other fruit products and botanicals SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Scott, Peter M.] Hlth Canada, Bur Chem Safety, Ottawa, ON K1A 0K9, Canada. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Peter_Scott@hc-sc.gc.ca NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 112-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100181 ER PT J AU South, PK Kim, H Bolger, M AF South, Paul K. Kim, Henry Bolger, Mike TI AGFD 153-US FDA regulatory policy for contaminants in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [South, Paul K.; Kim, Henry; Bolger, Mike] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Paul.South@fda.hhs.gov; Kim@fda.hhs.gov; Mike.Bolger@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 153-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100318 ER PT J AU Tolleson, WH AF Tolleson, William H. TI AGFD 109-Renal toxicity of pet foods contaminated with melamine and related compounds SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Tolleson, William H.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM william.tolleson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 109-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100260 ER PT J AU Trucksess, MW Whitaker, TB Weaver, CM Rader, JI Slate, A Giesbrecht, FG AF Trucksess, Mary W. Whitaker, Thomas B. Weaver, Carol M. Rader, Jeanne I. Slate, Andy Giesbrecht, Francis G. TI AGFD 114-Sampling uncertainty associated with sampling powdered ginger for aflatoxins and ochratoxin A SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Trucksess, Mary W.; Weaver, Carol M.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Whitaker, Thomas B.; Slate, Andy; Giesbrecht, Francis G.] N Carolina State Univ, ARS, USDA, Raleigh, NC 27695 USA. EM mary.trucksess@fda.hhs.gov; tom_whitaker@ncsu.edu; carol.weaver@fda.hhs.gov; Andy_Slate@ncsu.edu; Francis-Giesbrecht@ncsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 114-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100194 ER PT J AU Voss, KA Jackson, LS Snook, ME Ryu, D Bianchini, A Li, W Bullerman, LB Barach, J Rachman, N AF Voss, Kenneth A. Jackson, Lauren S. Snook, Maurice E. Ryu, Dojin Bianchini, Andreia Li, Wu Bullerman, Lloyd B. Barach, Jeff Rachman, Nancy TI AGFD 141-Effects of processing and cooking on mycotoxins: Lessons from studies on fumonisin B1 and deoxynivalenol SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Voss, Kenneth A.; Snook, Maurice E.] USDA, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA. [Jackson, Lauren S.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Ryu, Dojin] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Bianchini, Andreia; Bullerman, Lloyd B.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. [Li, Wu] Frito Lay Inc, Dept Food Safety & Nutr, Plano, TX 75024 USA. [Rachman, Nancy] GMA, FPA, Washington, DC 20005 USA. EM Ken.Voss@ars.usda.gov; ABIANCHINI2@unl.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 141-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100250 ER PT J AU Voss, KA Ryu, D Burns, TD Riley, RT Jackson, LS Bianchini, A Bullerman, LB AF Voss, Kenneth A. Ryu, Dojin Burns, Tantiana D. Riley, Ronald T. Jackson, Lauren S. Bianchini, Andreia Bullerman, Lloyd B. TI AGFD 142-Bioassay-based approach for determining the effect of cooking on fumonisin toxicity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Riley, Ronald T.] ARS, Toxicol & Mycotoxin Res Unit, USDA, Athens, GA 30604 USA. [Ryu, Dojin] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Burns, Tantiana D.] Univ Georgia, Interdisciplinary Toxicol Program, Athens, GA 30602 USA. [Jackson, Lauren S.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Bianchini, Andreia; Bullerman, Lloyd B.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. EM Ken.Voss@ars.usda.gov; ABIANCHINI2@unl.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 142-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100237 ER PT J AU Zhang, K Noonan, GO Begley, TH AF Zhang, Kai Noonan, Gregory O. Begley, Timothy H. TI AGFD 31-Determination of 2,6-diisopropylnaphthalene and n-dibutylphthalate in foods and food packaging materials from US marketplaces SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 235th American-Chemical-Society National Meeting CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc C1 [Zhang, Kai; Noonan, Gregory O.; Begley, Timothy H.] US FDA, Div Method Dev, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM kai.zhang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 6 PY 2008 VL 235 MA 31-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 519OA UT WOS:000271775100245 ER PT J AU Cieslak, J Grajkowski, A Kauffman, JS Duff, RJ Beaucage, SL AF Cieslak, Jacek Grajkowski, Andrzej Kauffman, Jon S. Duff, Robert J. Beaucage, Serge L. TI The 4-(N-dichloroacetyl-N-methylamino)benzyloxymethyl group for 2 '-hydroxyl protection of ribonucleosides in the solid-phase synthesis of oligoribonucleotides SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID CHEMICAL-SYNTHESIS; RNA INTERFERENCE; 2'-O-PROTECTING FUNCTIONS; NUCLEOTIDES; THERAPEUTICS; NUCLEOSIDES; DERIVATIVES; STRATEGIES; MICRORNAS; LINKAGES AB Emerging RNA-based technologies for controlling gene expression have triggered a high demand for synthetic oligoribonucleotides and have motivated the development of ribonucleoside phosphoramidites that would exhibit coupling kinetics and coupling efficiencies comparable to those of deoxyribonucleoside phosphoramidites. To fulfill these needs, the novel 4-(N-dichloroacetyl-N-methylamino)benzyloxymethyl group for 2'-hydroxyl protection of ribonucleoside phosphoramidites 9a-d has been implemented (Schemes 1 and 2). The solid-phase synthesis of AUCCGUAGCUAACGUCAUGG was then carried out employing 9a-d as 0.2 M solutions in dry MeCN and 5-benzylthio-1H-tetrazole as an activator. The coupling efficiency of 9a-d averaged 99% within a coupling time of 180 s. Following removal of all base-sensitive protecting groups, cleavage of the remaining 2'-[4-(N-methylamino)benzyl] acetals from the RNA oligonucleotide was effected in buffered 0.1 M AcOH (pH 3.8) within 30 min at 90 degrees C. RP-HPLC and PAGE analyses of the fully deprotected AUCCGUAGCUAACGUCAUGG were comparable to those of a commercial RNA oligonucleotide sharing an identical sequence. Enzymatic digestion of the RNA oligomer catalyzed by bovine spleen phosphodiesterase and bacterial alkaline phosphatase revealed no significant amounts of RNA fragments containing (2'-> 5')-internucleotidic phosphodiester linkages or noteworthy nucleobase modifications. C1 [Cieslak, Jacek; Grajkowski, Andrzej; Beaucage, Serge L.] US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Kauffman, Jon S.; Duff, Robert J.] Lancaster Labs, Lancaster, PA 17605 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pk, Bethesda, MD 20892 USA. EM serge.beaucage@fda.hhs.gov NR 49 TC 12 Z9 12 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 4 PY 2008 VL 73 IS 7 BP 2774 EP 2783 DI 10.1021/jo702717g PG 10 WC Chemistry, Organic SC Chemistry GA 282CI UT WOS:000254544800037 PM 18327953 ER PT J AU Shah, RB Yang, Y Khan, MA Faustino, PJ AF Shah, R. B. Yang, Y. Khan, M. A. Faustino, P. J. TI Molecular weight determination for colloidal iron by Taguchi optimized validated gel permeation chromatography SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE gel permeation chromatography; taguchi design; design of experiments; iron sucrose; validation; weight average molecular weight ID HEPARINS AB Method development of gel permeation chromatography (GPC) is a time-consuming task, since finding appropriate operating conditions has traditionally been a trial-and-error process. A novel approach in the field of GPC using experimental design called Taguchi is presented. This experimental design was used to compare the net effects of various conditions which were both qualitative and quantitative in nature. Quantitative factors included mobile phase pH, flow rate, temperature of column and detector, and injection volume. The qualitative factors were treated as noise which included enclosure of GPC system and position of waste container with respect to refractive index detector. The method was efficient as opposed to a one-factor-at-a-time approach. Taguchi optimized conditions included pH of 7.2, flow rate of 0.4 mL/rnin, temperature of 35 degrees C for column and detector, as well as injection volume of 10 mu L. The optimized factors yielded acceptable results in terms of weight average molecular weight (m.w.), standard deviation and signal-to-noise ratio. Standard curves were constructed using dextran m.w. standards (12,000-270,000 Da) over the analytical range. The method was validated according to ICH guidelines. Log-linear function was used for m.w. standard curve and weight average m.w. was calculated utilizing trapezoidal approach. A correlation coefficient of > 0.99 was obtained for both intra-day and inter-day standard calibration curves. Inter-day accuracy ranged from 91 to 108% and precision was < 2.0%. Published by Elsevier B.V. C1 [Shah, R. B.; Yang, Y.; Khan, M. A.; Faustino, P. J.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci,Off Testing & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. RP Faustino, PJ (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Patrick.Faustino@fda.hhs.gov NR 26 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD APR 2 PY 2008 VL 353 IS 1-2 BP 21 EP 27 DI 10.1016/j.ijpharm.2007.11.025 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 293FF UT WOS:000255320000004 PM 18226479 ER PT J AU Yang, YS Faustino, PJ Progar, JJ Brownell, CR Sadrieh, N May, JC Leutzinger, E Place, DA Duffy, EP Yu, LX Khan, MA Lyon, RC AF Yang, Yongsheng Faustino, Patrick J. Progar, Joseph J. Brownell, Charles R. Sadrieh, Nakissa May, Joan C. Leutzinger, Eldon Place, David A. Duffy, Eric P. Yu, Lawrence X. Khan, Mansoor A. Lyon, Robbe C. TI Quantitative determination of thallium binding to ferric hexacyanoferrate: Prussian blue SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Prussian blue; thallium binding; particle size; moisture loss; hydration; product quality ID ACTIVATED-CHARCOAL; CYANIDE RELEASE; INTOXICATION; ACCIDENT; EFFICACY; ADSORPTION; TOXICITY; ANTIDOTE; THERAPY; CESIUM AB Ferric hexacyanoferrate, (Fe-4(III) [Fe-II(CN)(6)](3)), also known as insoluble Prussian blue (PB), is the active pharmaceutical ingredient (API) of Radiogardase which is the first approved drug product (I)P) for treatment of thallium and radiocesium poisoning. The aim of this study is (1) to determine the in vitro thallium binding capacity and binding rates of insoluble PB; and (2) to evaluate the effect of physiological pH conditions, PB particle size and storage conditions on the binding to PB. Experimental pH levels from 1.0 to 7.5 were used to cover the range of pH levels that PB may encounter when traveling through the gastrointestinal (GI) tract in humans. Measurements of thallium binding were made between I and 24 It, to cover gastric and intestinal tract residence time. PB was found to have a binding capacity of approximately 1400 mg/g at pH 7.5. When the pH decreased, the binding decreased as well. The results indicated that the hydration state of PB influences the thallium binding process. It was also found that there exits a direct correlation between the moisture loss in PB and the thallium binding rate constant. The PB with 17 mol of water had a binding rate constant of 0.52, which was reduced to 0.32 when PB was dehydrated to 2.5 mot of water. Significant differences were observed in both binding capacity and binding rate constant among PB fractions with different particle size ranges. PB fraction with particle size of 220-1000 mu m had a binding rate constant of 0.43, which increased to 0.64 when the particle size was reduced to 32-90 mu m. Batch-to-batch variation in thallium binding was also observed among the APIs and the DPs and this was related to particle size and hydration state. These findings can be utilized to evaluate and predict drug product quality under certain manufacturing and dry storage conditions. Published by Elsevier B. V. C1 [Yang, Yongsheng; Faustino, Patrick J.; Brownell, Charles R.; Khan, Mansoor A.; Lyon, Robbe C.] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Progar, Joseph J.; May, Joan C.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Analyt Chem Lab, Rockville, MD 20850 USA. [Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Leutzinger, Eldon; Place, David A.; Duffy, Eric P.] US FDA, Off New Drug Qual Assessment, Div Med Imaging, Silver Spring, MD 20993 USA. [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drug, Rockville, MD 20855 USA. RP Faustino, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, Life Sci Bldg-64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM patrick.faustinop@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 44 TC 18 Z9 21 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD APR 2 PY 2008 VL 353 IS 1-2 BP 187 EP 194 DI 10.1016/j.ijpharm.2007.11.031 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 293FF UT WOS:000255320000023 PM 18226478 ER PT J AU Morris, SM Gregory, SA Varsha, GD Tsai, CA William, HT Melchior, WB Lin, CJ Fuscoe, JC Casciano, DA Chen, JJ AF Morris, Suzanne M. Akerman, Gregory S. Desai, Varsha G. Tsai, Chen-an Tolleson, William H. Melchior, William B., Jr. Lin, Chien-Ju Fuscoe, James C. Casciano, Daniel A. Chen, James J. TI Effect of p53 genotype on gene expression profiles in murine liver SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE transgenic mice; p53; microarray; real-time quantitative PCR; gene expression ID NICOTINAMIDE NUCLEOTIDE TRANSHYDROGENASE; TUMOR TRANSFORMING GENE; G-BETA-GAMMA; DNA-DAMAGE; TRANSCRIPTION FACTOR; HISTONE DEACETYLASE; INSULIN-SECRETION; SIGNALING PATHWAY; SUPPRESSOR GENE; EXCHANGE FACTOR AB The tumor suppressor protein p53 is a key regulatory element in the cell and is regarded as the "guardian of the genome". Much of the present knowledge of p53 function has come from studies of transgenic mice in which the p53 gene has undergone a targeted deletion. In order to provide additional insight into the impact on the cellular regulatory networks associated with the loss of this gene, microarray technology was utilized to assess gene expression in tissues from both the p53(-/-) and p53(+/-) mice. Six male mice from each genotype (p53(+/+), p53(+/-), and p53(-/-)) were humanely killed and the tissues processed for microarray analysis. The initial studies have been performed in the liver for which the Dunnett test revealed 1406 genes to be differentially expressed between p53(+/+) and p53(+/-) or between p53(+/-) and p53(-/-) at the level of p <= 0.05. Both genes with increased expression and decreased expression were identified in p53(+/-) and in p53(-/-) mice. Most notable in the gene list derived from the p53(+/-) mice was the significant reduction in p53 mRNA. In the p53(-/-) mice, not only was there reduced expression of the p53 genes on the array, but genes associated with DNA repair, apoptosis, and cell proliferation were differentially expressed, as expected. However, altered expression was noted for many genes in the Cdc42-GTPase pathways that influence cell proliferation. This may indicate that alternate pathways are brought into play in the unperturbed liver when loss or reduction in p53 levels occurs. Published by Elsevier B.V. C1 [Morris, Suzanne M.] US FDA, Natl Ctr Toxicol Res, Div Genet Reproduct Toxicol, Jefferson, AR 72079 USA. [Akerman, Gregory S.] US EPA, Div Hlth Effects, Toxicol Branch, Washington, DC 20460 USA. [Desai, Varsha G.; Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Tsai, Chen-an] China Med Univ, Dept Publ Hlth, Taichung 40402, Taiwan. [Tsai, Chen-an] China Med Univ, Ctr Biostat, Taichung 40402, Taiwan. [Tolleson, William H.; Melchior, William B., Jr.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Lin, Chien-Ju; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Casciano, Daniel A.] Dan Casciano & Associates, Little Rock, AR USA. RP Morris, SM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet Reproduct Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM suzanne.morris@fda.hhs.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 90 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 2 PY 2008 VL 640 IS 1-2 BP 54 EP 73 DI 10.1016/j.mrfmmm.2007.12.004 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 289UZ UT WOS:000255080700007 PM 18206960 ER PT J AU Neznanov, N Dragunsky, EM Chumakov, KM Neznanova, L Wek, RC Gudkov, AV Banerjee, AK AF Neznanov, Nickolay Dragunsky, Eugenia M. Chumakov, Konstantin M. Neznanova, Lubov Wek, Ronald C. Gudkov, Andrei V. Banerjee, Amiya K. TI Different Effect of Proteasome Inhibition on Vesicular Stomatitis Virus and Poliovirus Replication SO PLOS ONE LA English DT Article AB Proteasome activity is an important part of viral replication. In this study, we examined the effect of proteasome inhibitors on the replication of vesicular stomatitis virus (VSV) and poliovirus. We found that the proteasome inhibitors significantly suppressed VSV protein synthesis, virus accumulation, and protected infected cells from toxic effect of VSV replication. In contrast, poliovirus replication was delayed, but not diminished in the presence of the proteasome inhibitors MG132 and Bortezomib. We also found that inhibition of proteasomes stimulated stress-related processes, such as accumulation of chaperone hsp70, phosphorylation of eIF2 alpha, and overall inhibition of translation. VSV replication was sensitive to this stress with significant decline in replication process. Poliovirus growth was less sensitive with only delay in replication. Inhibition of proteasome activity suppressed cellular and VSV protein synthesis, but did not reduce poliovirus protein synthesis. Protein kinase GCN2 supported the ability of proteasome inhibitors to attenuate general translation and to suppress VSV replication. We propose that different mechanisms of translational initiation by VSV and poliovirus determine their sensitivity to stress induced by the inhibition of proteasomes. To our knowledge, this is the first study that connects the effect of stress induced by proteasome inhibition with the efficiency of viral infection. C1 [Neznanov, Nickolay; Neznanova, Lubov; Banerjee, Amiya K.] Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. [Dragunsky, Eugenia M.; Chumakov, Konstantin M.] FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. [Wek, Ronald C.] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. [Gudkov, Andrei V.] Roswell Park Canc Inst, Dept Cell Stress Biol, Buffalo, NY USA. [Gudkov, Andrei V.] Cleveland Biolabs Inc, Buffalo, NY USA. RP Neznanov, N (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM neznann@ccf.org FU NIH [AI26585, CA60730, CA88071]; Lerner Research Institute FX This work was supported by the grant from NIH to Amiya K. Banerjee (AI26585), by the grants from NIH to Andrei V. Gudkov (CA60730 and CA88071), and funds provided by Lerner Research Institute to Nickolay Neznanov. NR 71 TC 28 Z9 28 U1 0 U2 1 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 APR 2 PY 2008 VL 3 IS 4 AR e1887 DI 10.1371/journal.pone.0001887 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 370XC UT WOS:000260795400021 PM 18382670 ER PT J AU Moore, DF Goldin, E Gelderman, MP Robinson, C Baer, J Ries, M Elkahloun, A Brady, R Schiffmann, R AF Moore, David F. Goldin, Ehud Gelderman, Monique P. Robinson, Chevalia Baer, Jessica Ries, Markus Elkahloun, Abdel Brady, Roscoe Schiffmann, Raphael TI Apoptotic abnormalities in differential gene expression in peripheral blood mononuclear cells from children with Fabry disease SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT 7th International Symposium on Lysosomal Storage Diseases CY APR, 2007 CL Rome, ITALY DE apoptosis-inducing factor; enzyme replacement therapy; Fabry disease; neuronal apoptosis; inhibitory protein; peripheral blood mononuclear cells ID CEREBRAL HYPERPERFUSION; ENZYME REPLACEMENT; INHIBITORY PROTEIN; INFLAMMATION; REVERSAL; PATHWAY; PROFILE AB Aim: This study was designed to examine the effect of enzyme replacement therapy (ERT) on differential gene expression in peripheral blood mononuclear cells (PBMCs) of children with Fabry disease who had not previously been exposed to ERT. Methods: Thirteen children with Fabry disease (age range, 6.5-17.0 years) were studied as part of a 6-month, open-label study of ERT with agalsidase alfa. Paired blood samples were taken at the start of the study and after 6 months of ERT. Further blood samples were also taken from 16 age-matched control subjects. PBMCs were isolated and, following RNA extraction, differential gene expression analysis was performed using the Human Genome U 133 Plus 2.0 microarray. Results: Twenty-one genes were determined to be differentially expressed in PBMCs of ERT-naive children with Fabry disease compared with healthy controls; neuronal apoptosis inhibitory protein ranked as the most significantly differentially expressed gene. Comparison of gene expression in children with Fabry disease prior to and after ERT showed that two genes were significantly differentially expressed (p <= 0.05) following treatment; the expressed sequence tag (probe set ID, 243259-at) was downregulated, while expression of apoptosis-inducing factor was increased, possibly as an antioxidant counter-regulatory response. C1 [Goldin, Ehud; Robinson, Chevalia; Ries, Markus; Brady, Roscoe; Schiffmann, Raphael] Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. [Moore, David F.] Univ Manitoba, Neurol Sect, Winnipeg, MB, Canada. [Gelderman, Monique P.] Fed Drug Adm, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Rockville, MD USA. [Baer, Jessica] NCI, Gene Express Lab, NIH, Frederick, MD 21701 USA. [Elkahloun, Abdel] Natl Inst Neurol Disorders & Stroke Microarray Co, Bethesda, MD USA. RP Schiffmann, R (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,900 Rockville Pike, Bethesda, MD 20892 USA. EM rs4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS NR 23 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2008 VL 97 SU 457 BP 48 EP 52 DI 10.1111/j.1651-2227.2008.00654.x PG 5 WC Pediatrics SC Pediatrics GA 285BQ UT WOS:000254752700010 PM 18339188 ER PT J AU Vassalotti, JA Uribarri, J Chen, SC Li, SY Wang, CC Collins, AJ Calvo, MS Whaley-Connell, AT McCullough, PA Norris, KC AF Vassalotti, Joseph A. Uribarri, Jaime Chen, Shu-Cheng Li, Suying Wang, Changchun Collins, Allan J. Calvo, Mona S. Whaley-Connell, Adam T. McCullough, Peter A. Norris, Keith C. CA Kidney Early Evaluat Program Inves TI Trends in mineral metabolism: Kidney Early Evaluation Program (KEEP) and the National Health and Nutrition Examination Survey (NHANES) 1999-2004 SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE calcium; chronic kidney disease; Kidney Early Evaluation Program (KEEP); mineral metabolism; National Health and Nutrition Examination Survey (NHANES); parathyroid hormone (PTH); phosphorus ID STAGE RENAL-DISEASE; SECONDARY HYPERPARATHYROIDISM; SERUM PHOSPHORUS; MAINTENANCE HEMODIALYSIS; MORTALITY RISK; CALCIUM; PHOSPHATE; PTH; DIALYSIS; CALCIFICATION AB Background: Chronic kidney disease (CKD) is associated with mineral metabolism dysregulation, cardiovascular disease, and premature mortality. No study specifically examined mineral metabolism trends in a generalizable sample of patients at increased CKID risk. Methods: This cross-sectional analysis from November 1, 2005, to December 31, 2006, of calcium, phosphorus, and parathyroid hormone (PTH) includes 2,646 individuals with estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m(2) in the National Kidney Foundation Kidney Early Evaluation Program (KEEP), a community-based health-screening program targeting individuals 18 years and older with diabetes, hypertension, or family history of kidney disease, diabetes, or hypertension. A parallel analysis of National Health and Nutrition Examination Survey (NHANES) 1999-2004 data was performed. Results: In KEEP, as eGFR decreased from 55 to less than 60 mL/min/1.73 m(2) to less than 30 mL/min/1.73 m(2), calcium level decreased (9.55 0.47 to 9.34 +/- 0.62 mg/dL; P < 0.001), phosphorus level increased (3.70 +/- 0.59 to 4.15 +/- 0.80 mg/dL; P < 0.001), and PTH level increased (66.3 +/- 36.3 to 164 +/- 109 pg/mL; mean, 80.8 +/- 57.0 pg/mL; P < 0.001). NHANES 1999-2004 showed similar trends, with PTH values not as high. Individuals within opinion-based Kidney Disease Outcomes Quality Initiatives targets from the highest to the lowest eGFR group were as follows: calcium, 93.0% to 92.3% (KEEP) and 97.4% to 89.6% (NHANES); phosphorus, 90.4% to 90.3% (KEEP) and 91.6% to 87.1% (NHANES); and PTH, 46.1 % to 31.2% (KEEP) and 56.4% to 36.1% (NHANES). Conclusions: In a community-based CKID screening population, increased PTH level occurs early in patients with stage 3, typically with normal calcium and phosphorus levels. These findings support the importance of including PTH with calcium and phosphorus monitoring for individuals with eGFR less than 60 mL/min/1.73 m(2). C1 [Vassalotti, Joseph A.] Mt Sinai Med Ctr, Mt Sinai Sch Med, Natl Kidney Fdn, New York, NY 10029 USA. [Vassalotti, Joseph A.; Uribarri, Jaime] Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Med, Div Nephrol, New York, NY 10029 USA. [Collins, Allan J.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Calvo, Mona S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Whaley-Connell, Adam T.] Univ Missouri, Sch Med, Dept Med, Div Nephrol, Columbia, MO 65212 USA. [McCullough, Peter A.] Wayne State Univ, William Beaumont Hosp, Dept Med, Div Cardiol, Royal Oak, MI 48073 USA. [McCullough, Peter A.] Wayne State Univ, William Beaumont Hosp, Dept Med, Div Nutr, Royal Oak, MI 48073 USA. [McCullough, Peter A.] Wayne State Univ, William Beaumont Hosp, Dept Med, Div Prevent Med, Royal Oak, MI 48073 USA. [Norris, Keith C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Vassalotti, JA (reprint author), Mt Sinai Med Ctr, Mt Sinai Sch Med, Natl Kidney Fdn, 1 Gustave L Levy Pl,Nephrol Box 1243, New York, NY 10029 USA. EM joseph.vassalotti@mssm.edu OI Whaley-Connell, Adam/0000-0001-8955-5560 NR 29 TC 39 Z9 43 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2008 VL 51 IS 4 SU 2 BP S56 EP S68 DI 10.1053/j.ajkd.2007.12.018 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 283QA UT WOS:000254650400008 PM 18359409 ER PT J AU Wagner, RD Johnson, SJ Cerniglia, CE AF Wagner, R. Doug Johnson, Shemedia J. Cerniglia, Carl E. TI In vitro model of colonization resistance by the enteric microbiota: Effects of antimicrobial agents used in food-producing animals SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN INTESTINAL MICROFLORA; HUMAN COLONIC MICROFLORA; ANTAGONISTIC ACTIVITY; CHEMOSTAT MODEL; FLORA; CIPROFLOXACIN; ANTIBIOTICS; ECOSYSTEM; IMPACT; TETRACYCLINE AB A bioassay was developed to measure the minimum concentration of an antimicrobial drug that disrupts the colonization resistance mediated by model human intestinal microbiota against Salmonella invasion of Caco-2 intestinal cells. The bioassay was used to measure the minimum disruptive concentrations (MDCs) of drugs used in animal agriculture. The MDCs varied from 0.125 mu g/ml for some broad-spectrum antimicrobial drugs (e.g., streptomycin) to 16 mu g/ml for drugs with limited spectra of antimicrobial activity (e.g., lincomycin). The acceptable daily intake (ADI) residue concentration calculated on the basis of the MDCs were higher for erythromycin, lincomycin, and tylosin than the ADI residue concentrations calculated on the basis of the MICs. The MDC-based ADI values for apramycin, bacitracin, neomycin, novobiocin, penicillin G, streptomycin, tetracycline, and vancomycin were lower than the reported MIC-based ADI values. The effects of antimicrobial drugs at their MDCs on the bacterial composition of the microbiota were observed by denaturing gradient gel electrophoresis of 16S rRNA sequences amplified by PCR. Changes in the population composition of the model colonization resistance microbiota occurred simultaneously with reduced colonization resistance. The results of this study suggest that direct assessment of the effects of antimicrobial drugs on colonization resistance in an in vitro model can be useful in determining ADI values. C1 [Wagner, R. Doug; Johnson, Shemedia J.; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, HFT 250, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), US FDA, Natl Ctr Toxicol Res, HFT 250, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov NR 41 TC 5 Z9 6 U1 1 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2008 VL 52 IS 4 BP 1230 EP 1237 DI 10.1128/AAC.00852-07 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 286YE UT WOS:000254881900004 PM 18227184 ER PT J AU Roberts, R Styrt, B McCune, S AF Roberts, Rosemary Styrt, Barbara McCune, Susan TI FDA perspective on antivirals against biothreats: Communicate early and often SO ANTIVIRAL RESEARCH LA English DT Article DE Food and Drug Administration (FDA); highly pathogenic viruses; antiviral products; drug development; clinical trials; animal rule; biothreats; drugs; therapeutic biologics AB Development of antiviral products for certain highly pathogenic viruses with limited available treatments, such as viruses that may have biothreat potential, is critically important and challenging. The mission of the FDA is to protect the public health by assuring the safety, efficacy and quality of such products. Human clinical trials are critically important whenever relevant naturally occurring diseases can appropriately be studied. In selected situations when clinical studies are not ethical and field efficacy studies are not feasible, the Animal Rule (67 FR 37988, 2002) introduces the Possibility of drug biologic approval/licensure based on efficacy studies in animals, and appropriate human safety and pharmacokinetic information. This approach necessitates the development of well-delineated animal models predictive of human disease and treatment responses, and plans for adding human information if suitable circumstances arise. Efficient development of therapeutics against these agents requires collaborative efforts among industry, academia and federal agencies. Published by Elsevier B.V. C1 [Roberts, Rosemary; Styrt, Barbara; McCune, Susan] US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, Silver Spring, MD 20993 USA. RP Roberts, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Emergency Coordinat, 10903 New Hampshire Ave,White Oak Campus, Silver Spring, MD 20993 USA. EM rosemary.roberts@fda.hhs.gov NR 1 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 2008 VL 78 IS 1 BP 60 EP 63 DI 10.1016/j.antiviral.2007.10.001 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 290ZY UT WOS:000255163300007 PM 18037169 ER PT J AU Yamaguchi, Y Beer, JZ Hearing, VJ AF Yamaguchi, Yuji Beer, Janusz Z. Hearing, Vincent J. TI Melanin mediated apoptosis of epidermal cells damaged by ultraviolet radiation: factors influencing the incidence of skin cancer SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE apoptosis; UV; photocarcinogenesis; melanin; DNA repair ID MELANOCORTIN-1 RECEPTOR; DNA-REPAIR; DISTRIBUTION PATTERNS; UV-RADIATION; IN-VITRO; PIGMENTATION; EXPOSURE; PHOTOPROTECTION; KERATINOCYTES; MELANOSOMES AB Ultraviolet (UV)-induced skin cancers, including melanomas and basal/squamous cell carcinomas, occur more frequently in individuals with fair skin than in those with dark skin. Melanin plays an important role in protecting the skin against UV radiation and levels of melanin correlate inversely with amounts of DNA damage induced by UV in human skin of different racial/ethnic groups. The objectives of this study are to review recent progress in our understanding of mechanisms underlying differences in cancer incidence in skins of different colors, particularly between Black and White skin. More specifically, we review DNA damage and apoptosis in various types of skin before and after exposure to UV in our human study protocols using a single UV dose, either one minimal erythema dose (MED) or a similar low dose of 180 - 200 J/m(2). Our data and other published reports indicate that several major mechanisms underlie the increased rates of photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin. Second, rates of repair of DNA damage can differ significantly in individuals. Third, UV-induced apoptosis to remove potentially precancerous cells is significantly greater in darker skin. These results suggest that pigmented epidermis is an efficient UV filter and that UV damaged cells are removed more efficiently in darker skin. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin. C1 [Yamaguchi, Yuji] Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. [Yamaguchi, Yuji; Hearing, Vincent J.] Natl Inst Hlth, Pigment Cell Res Sect, Cell Biol Lab, Natl Canc Inst, Bethesda, MD USA. [Yamaguchi, Yuji] Nagoya City Univ, Grad Sch Med, Dept Geriatr & Environm Dermatol, Nagoya, Aichi, Japan. [Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Yamaguchi, Y (reprint author), Osaka Univ, Grad Sch Med, Dept Dermatol, Suita, Osaka, Japan. EM yujin@med.nagoya-cu.acjp RI Yamaguchi, Yuji/B-9312-2008 NR 44 TC 16 Z9 21 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD APR PY 2008 VL 300 SU 1 BP S43 EP S50 DI 10.1007/s00403-007-0807-0 PG 8 WC Dermatology SC Dermatology GA 293WH UT WOS:000255365600006 PM 17985102 ER PT J AU Laje, G Trivedi, MH Gibbons, RD Laughren, TP AF Laje, Gonzalo Trivedi, Madhukar H. Gibbons, Robert D. Laughren, Thomas P. TI Controversies surrounding antidepressants and suicide SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 63rd Annual Convention of the Society-of-Biological-Psychiatry CY 2008 CL Washington, DC SP Soc Biol Psychiat C1 [Laje, Gonzalo] NIMH, NIH, Bethesda, MD 20892 USA. [Trivedi, Madhukar H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Gibbons, Robert D.] Univ Illinois, Chicago, IL USA. [Laughren, Thomas P.] CBER Food & Drug Adm, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2008 VL 63 IS 7 SU S MA 450 BP 145S EP 145S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 276SV UT WOS:000254163700466 ER PT J AU Temple, R AF Temple, Robert TI Complexities in drug trials: enrichment, biomarkers and surrogates SO BIOMARKERS IN MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Bldg 22,Room 4212,10903 New Hampshire Ave, Silver Spring, MD USA. EM robert.temple@fda.hhs.gov NR 1 TC 3 Z9 3 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD APR PY 2008 VL 2 IS 2 BP 109 EP 112 DI 10.2217/17520363.2.2.109 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 344IY UT WOS:000258921300007 PM 20477432 ER PT J AU Araojo, R McCune, S Feibus, K AF Araojo, R. McCune, S. Feibus, K. TI Substance abuse in pregnant women: Making improved detection a good clinical outcome SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB In this issue, Gideon Koren and colleagues review the maternal and child health implications of drug-residue testing in maternal and neonatal hair and testing for drugs in meconium. (1)Since the 1990s, these methods have been used to varying degrees in clinical practice, but recent technological advances have increased their accuracy and usability in the clinical setting. Compared with self-reported maternal use, drug-residue testing in hair and testing for drugs in meconium are more reliable methods for detecting drug and alcohol exposure during pregnancy. These methods can also provide insights into patterns of use and abuse of these substances. C1 [Araojo, R.; Feibus, K.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs Immediate Off, Pediat & Maternal Hlth Staff,Maternal Hlth Team, Silver Spring, MD USA. [McCune, S.] US FDA, Ctr Drug Evaluat & Res, Off Counterterrorism & Emergency Coordinat, Rockville, MD USA. RP Feibus, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs Immediate Off, Pediat & Maternal Hlth Staff,Maternal Hlth Team, Silver Spring, MD USA. EM karen.feibus@fda.hhs.gov NR 8 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2008 VL 83 IS 4 BP 520 EP 522 DI 10.1038/clpt.2008.13 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 279BM UT WOS:000254330000005 PM 18349872 ER PT J AU Kaput, J AF Kaput, Jim TI Nutrigenomics research for personalized nutrition and medicine SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID QUANTITATIVE TRAIT LOCI; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; LOW-FAT DIET; GENETIC ASSOCIATION; ADMIXED POPULATIONS; METABOLIC SYNDROME; DIABETES-MELLITUS; COMPLEX TRAITS; MYOCARDIAL-INFARCTION AB Current nutritional and genetic epidemiological methods yield 'risk factors' on the basis of population studies. Risk factors, however, are statistical estimates of the percentage reduction in disease in the population if the risk were to be avoided or the gene variant were not present. These measures are often assumed to apply to individuals who are likely to differ in genetic make-up, lifestyle, and dietary patterns than to the individuals in the study population. Developing individual risk factors in light of the genetic diversity of human populations, the complexity of foods, culture and lifestyle, and the variety of metabolic processes that lead to health or disease is a significant challenge for personalizing dietary advice for healthy or individuals with chronic disease. C1 US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Kaput, J (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM James.Kaput@fda.hhs.gov FU NIMHD NIH HHS [MD 00222] NR 136 TC 52 Z9 56 U1 3 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD APR PY 2008 VL 19 IS 2 BP 110 EP 120 DI 10.1016/j.copbio.2008.02.005 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 302PX UT WOS:000255982100006 PM 18387295 ER PT J AU Wang, L Gaigalas, AK Marti, G Abbasi, F Hoffman, RA AF Wang, Lili Gaigalas, Adolfas K. Marti, Gerald Abbasi, Fatima Hoffman, Robert A. TI Toward quantitative fluorescence measurements with multicolor flow cytometry SO CYTOMETRY PART A LA English DT Article; Proceedings Paper CT 24th International Congress of the International-Society-for-Analytical-Cytology CY MAY 17-21, 2008 CL Budapest, HUNGARY SP Int Soc Analyt Cytol DE multicolor cytometry; calibration; quantitation; biological standard ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ZAP-70 EXPRESSION; CRYSTAL-STRUCTURE; HIV-1 INFECTION; CD4 EXPRESSION; T-LYMPHOCYTES; RESOLUTION; CELLS; ALLOPHYCOCYANIN; DENSITY AB A procedure is presented for calibrating the output of a multicolor flow cytometer in units of antibodies bound per cell (ABC). The procedure involves two steps. First, each of the fluorescence channels of the flow cytometer is calibrated using Ultra Rainbow beads with assigned values of equivalent number of reference fluorophores (ERF). The objective of this step is to establish a linear relation between the fluorescence signal in a given fluorescence channel of multicolor flow cytometers and the value of ERF. The second step involves a biological standard such as a lymphocyte with a known number of antibody binding sites (e.g., CD4 binding sites). The biological standard is incubated with antibodies labeled with one type of fluorophores for a particular fluorescence channel and serves to translate the ERF scale to an ABC scale. A significant part of the two-step calibration procedure involves the assignment of ERF values to the different Opulations of Ultra Rainbow beads. The assignment of ERF values quantifies the relative amount of embedded fluorophore mixture in each bead population. It is crucial to insure that the fluorescence signal in a given range of fluorescence emission wavelengths is related linearly to the assigned values of ERF. The biological standard has to posses a known number of binding sites for a given antibody. In addition, this antibody has to be amenable to labeling with different types of fluorophores associated with various fluorescence channels. The present work suggests that all of the requirements for a successful calibration of a multicolor flow cytometer in terms of ABC values can be fulfilled. The calibration procedure is based on firm scientific foundations so that it is easy to envision future improvements in accuracy and case of implementation. Published 2007 Wiley-Liss, Inc. C1 NIST, Gaithersburg, MD 20899 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. BD Biosci, San Jose, CA 95131 USA. RP Wang, L (reprint author), NIST, 100 Bureau Dr,Stop 8312, Gaithersburg, MD 20899 USA. EM lili.wang@nist.gov NR 19 TC 33 Z9 33 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD APR PY 2008 VL 73A IS 4 BP 279 EP 288 DI 10.1002/cyto.a.20507 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 284IB UT WOS:000254699000003 PM 18163471 ER PT J AU Varadkar, P Kraman, M Despres, D Ma, G Lozier, J McCright, B AF Varadkar, Prajakta Kraman, Matthew Despres, Daryl Ma, Ge Lozier, Julie McCright, Brent TI Notch2 is required for the proliferation of cardiac neural crest-derived smooth muscle cells SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Notch2; cardiac neural crest; smooth muscle; Notch ID CONGENITAL HEART-DEFECTS; ATRIAL GENE-EXPRESSION; ALAGILLE-SYNDROME; HUMAN JAGGED1; MUTATIONS; MICE; FATE; CHF1/HEY2; DISEASE; LIGAND AB Mutations in Notch receptors and their ligands have been identified as the cause of human congenital heart diseases, indicating the importance of the Notch signaling pathway during heart development. In our study, we use Cre-Lox technology to inactivate Notch2 in several cardiac cell lineages to determine the functional requirements for Notch2 during mammalian heart development. Inactivation of Notch2 in cardiac neural crest cells resulted in abnormally narrow aortas and pulmonary arteries due to a decrease in smooth muscle tissue. The reduction in smooth muscle tissue was not due to cell migration defects but instead was found to be caused by less proliferation in smooth muscle cells during mid to late gestation. Our findings demonstrate that Notch2 is required cell autonomously for proper formation of the heart outflow tract and provides insights into the role of Notch2 in vascular smooth muscle development and the cardiovascular defects associated with Alagille syndrome. C1 [Varadkar, Prajakta; Kraman, Matthew; Ma, Ge; McCright, Brent] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. [Despres, Daryl] NIH, NINDS, MIF, Bethesda, MD 20892 USA. [Lozier, Julie] Jackson Lab, Bar Harbor, ME 04609 USA. RP McCright, B (reprint author), US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. EM brenton.mccright@fda.hhs.gov NR 29 TC 26 Z9 28 U1 0 U2 1 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 APR PY 2008 VL 237 IS 4 BP 1144 EP 1152 DI 10.1002/dvdy.21502 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 287FY UT WOS:000254903700025 PM 18330927 ER PT J AU Neznanov, N Kondratova, A Chumakov, KM Neznanova, L Kondratov, R Banerjee, AK Gudkov, AV AF Neznanov, Nickolay Kondratova, Anna Chumakov, Konstantin M. Neznanova, Lubov Kondratov, Roman Banerjee, Amiya K. Gudkov, Andrei V. TI Quercetinase pirin makes poliovirus replication resistant to flavonoid quercetin SO DNA AND CELL BIOLOGY LA English DT Article ID IN-VIVO METABOLITES; PROTEIN-SYNTHESIS; NUCLEAR-PROTEIN; RNA-SYNTHESIS; BREFELDIN-A; KINASE-B; INHIBITION; 3-KINASE; INITIATION; 3-METHYLQUERCETIN AB Flavonoid quercetin and its derivative, methylquercetin, inhibit the replication of poliovirus in several cell lines. Here, we show that replication of poliovirus is inhibited by quercetin and that the extent of this inhibition depends on the intracellular content of pirin, a quercetinase. HeLa cells contain higher content of pirin protein than normal kidney human epithelial (NKE) or 293 cells do. Poliovirus replication in HeLa cells is significantly more resistant to quercetin than its replication in NKE and 293 cells. Overexpression of pirin reduced antiviral inhibitory effect of quercetin, while siRNA-induced suppression of pirin level made poliovirus replication more sensitive to the flavonoid. The results suggest that quercetinase activity of pirin determines the resistance of poliovirus infection to quercetin. C1 [Neznanov, Nickolay; Kondratova, Anna; Neznanova, Lubov; Banerjee, Amiya K.] Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, Cleveland, OH 44195 USA. [Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. [Kondratov, Roman] Cleveland State Univ, Dept Biol Geol & Environm Sci, Cleveland, OH 44115 USA. [Gudkov, Andrei V.] Roswell Pk Canc Inst, Dept Cell Stress Biol, Buffalo, NY 14263 USA. [Gudkov, Andrei V.] Cleveland Biolabs, Buffalo, NY USA. RP Neznanov, N (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Mol Genet, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM neznann@ccf.org FU NCI NIH HHS [CA88071, CA60730] NR 38 TC 5 Z9 5 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD APR PY 2008 VL 27 IS 4 BP 191 EP 198 DI 10.1089/dna.2007.0682 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 299VZ UT WOS:000255784500004 PM 18067462 ER PT J AU Allen, LH Shahab-Ferdows, S Anaya, MA Rosado, JL Pogribn, I AF Allen, Lindsay H. Shahab-Ferdows, Setareh Aracely Anaya, Miriam Louis Rosado, Jorge Pogribn, Igor TI Randomized controlled trial of vitamin B12 supplementation in Mexican women with a high prevalence of B12 deficiency; predictors of biochemical and hematological response SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Allen, Lindsay H.; Shahab-Ferdows, Setareh; Aracely Anaya, Miriam] Univ Calif Davis, Davis, CA 95616 USA. [Allen, Lindsay H.] ARS, WHNRC, USDA, Davis, CA USA. [Aracely Anaya, Miriam; Louis Rosado, Jorge] Univ Autonoma Queretaro, Queretaro, Mexico. [Pogribn, Igor] US FDA, HHS, Jackson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467806664 ER PT J AU Bhattacharjee, A Pal, S Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Pal, Srabani Feldman, Gerald M. Cathcart, Martha K. TI Extracellular regulatory kinase (ERK1/2) regulates 15-lipoxygenase Expression in Primary Human Monocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Bhattacharjee, Ashish; Pal, Srabani; Cathcart, Martha K.] Cleveland Clin, Cleveland, OH 44106 USA. [Feldman, Gerald M.] US FDA, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467801781 ER PT J AU Blakely, SR Blumberg, J O'Neill, KR Smith, TJ Pikosky, MA Young, AJ AF Blakely, Shirley R. Blumberg, Jeffrey O'Neill, Karen Rene Smith, Tracey J. Pikosky, Matthew A. Young, Andrew J. TI Increased dietary protein attenuates C-reactive protein and creatine kinase responses to exercise-induced energy deficit SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Blakely, Shirley R.] Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Blumberg, Jeffrey] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Smith, Tracey J.; Pikosky, Matthew A.; Young, Andrew J.] USA, Inst Environm Med, Mil Nutr Div, Natick, MA 01760 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467803127 ER PT J AU Civelek, M Grant, GR Irolla, CR Stoeckert, CJ Karanian, JW Chiesa, OA Pritchard, WF Davies, PF AF Civelek, Mete Grant, Gregory R. Irolla, Chrysta R. Stoeckert, Christian J. Karanian, John W. Chiesa, Oscar A. Pritchard, Wiiliam F. Davies, Peter F. TI ABCA1 is upregulated in athero-protected regions of arteries in response to brief hypercholesterolemia treatment in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Civelek, Mete; Irolla, Chrysta R.; Davies, Peter F.] Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. [Grant, Gregory R.; Stoeckert, Christian J.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Karanian, John W.; Chiesa, Oscar A.; Pritchard, Wiiliam F.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467802306 ER PT J AU Espandiari, P Mang, J Rosenzweig, BA Zhou, YZ Vaidya, VS Schnackenberg, L Goering, PL Brown, RP Bonventre, JV Herman, EH Beger, RD Thompson, KL Hanig, J Sadrieh, N AF Espandiari, Parvaneh Mang, Jun Rosenzweig, Barry A. Zhou, Yuzhao Vaidya, Vishal S. Schnackenberg, Laura Goering, Peter L. Brown, Ronald P. Bonventre, Joseph V. Herman, Eugene H. Beger, Richard D. Thompson, Karol L. Hanig, Joseph Sadrieh, Nakissa TI Age-Related Differences in Cisplatin-Induced Renal Toxicity in Rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Espandiari, Parvaneh; Mang, Jun; Rosenzweig, Barry A.; Herman, Eugene H.; Thompson, Karol L.; Hanig, Joseph; Sadrieh, Nakissa] US FDA, CDER, Silver Spring, MD USA. [Zhou, Yuzhao; Goering, Peter L.; Brown, Ronald P.] US FDA, CDRH, Silver Spring, MD USA. [Vaidya, Vishal S.; Bonventre, Joseph V.] Harvard Univ, Sch Med, Boston, MA USA. [Schnackenberg, Laura; Beger, Richard D.] US FDA, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467801147 ER PT J AU Guerraty, MA Grant, GR Karanian, JW Chiesa, OA Pritchard, WF Davies, PF AF Guerraty, Marie A. Grant, Gregory R. Karanian, John W. Chiesa, Oscar A. Pritchard, Wiiliam F. Davies, Peter F. TI Brief hypercholesterolemia induces athero-protective pathways on the patho-susceptible aortic side endothelium of swine aortic valves SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Guerraty, Marie A.; Davies, Peter F.] Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. [Grant, Gregory R.] Univ Penn, Ctr Bioinformat, Philadelphia, PA 19104 USA. [Karanian, John W.; Chiesa, Oscar A.; Pritchard, Wiiliam F.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467802178 ER PT J AU Herman, E Knapton, A Zhang, J Hiraragi, H Lipshultz, S AF Herman, Eugene Knapton, Alan Zhang, Jun Hiraragi, Hajime Lipshultz, Steven TI Gender is a factor that can impact the severity of doxorubicin (DXR) toxicity in spontaneously hypertensive rats (SHR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Herman, Eugene; Knapton, Alan; Zhang, Jun] FDA, DAPR, Silver Spring, MD USA. [Hiraragi, Hajime] Genentech Inc, San Francisco, CA 94080 USA. [Lipshultz, Steven] Univ Miami, Sch Med, Miami, FL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467806233 ER PT J AU Knapton, AD Espandiari, P Morales, A Moussazadeh, M Robins, T Herman, E AF Knapton, Alan D. Espandiari, Parvaneh Morales, Azorides Moussazadeh, Mitra Robins, Terry Herman, Eugene TI The utility of monitoring skeletal muscle troponin I to detect drug- induced skeletal muscle injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Knapton, Alan D.; Espandiari, Parvaneh; Herman, Eugene] US FDA, Silver Spring, MD USA. [Morales, Azorides] Univ Miami, Sch Med, Miami, FL USA. [Moussazadeh, Mitra; Robins, Terry] Pathway Diagnost, Malibu, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467803255 ER PT J AU Mainigi, KD AF Mainigi, Kumar D. TI Value of minipig as a recommended second (nonrodent/nonprimate) species for regulatory studies to assess the risk, and relative efficacy of topical and systemic antifungals SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Mainigi, Kumar D.] US FDA, Div Dermatol & Dent Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467803292 ER PT J AU Max, EE Arudchandran, A Bernstein, RM AF Max, Edward E. Arudchandran, Arulvathani Bernstein, Ralph M. TI DNA breaks in immunoglobulin Class Switch Recombination that depend on UNG but not AID SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Max, Edward E.; Arudchandran, Arulvathani; Bernstein, Ralph M.] OBP CDER FDA, HFD 122, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467805134 ER PT J AU Ramalingam, TR Pesce, JT Sheikh, FA Cheever, AW Mentink-Kane, MM Wilson, MS Stevens, S Valenzuela, DM Murphy, AJ Yancopoulos, GD Urban, JF Donnelly, RP Wynn, TA AF Ramalingam, Thirumalai Rajan Pesce, John T. Sheikh, Farukh A. Cheever, Allen W. Mentink-Kane, Margaret M. Wilson, Mark S. Stevens, Sean Valenzuela, David M. Murphy, Andrew J. Yancopoulos, George D. Urban, Joeseph F., Jr. Donnelly, Raymond P. Wynn, Thomas A. TI Unique functions of the type II interleukin 4 receptor revealed in mice lacking the interleukin 13 receptor alpha 1 chain SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Ramalingam, Thirumalai Rajan; Pesce, John T.; Mentink-Kane, Margaret M.; Wilson, Mark S.; Wynn, Thomas A.] NIAID, LPD, Bethesda, MD 20892 USA. [Sheikh, Farukh A.; Donnelly, Raymond P.] US FDA, CDER, Bethesda, MD 20014 USA. [Cheever, Allen W.] Biomed Res Inst, Rockville, MD 20852 USA. [Stevens, Sean; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.] Regenron, Tarrytown, NY USA. [Urban, Joeseph F., Jr.] USDA, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467804247 ER PT J AU Sakamoto, N Sakamoto, M Rosenberg, AS AF Sakamoto, Norihisa Sakamoto, Michiko Rosenberg, Amy S. TI Embryonic stem cells cultured in serum free medium acquire bovine apolipoprotein B-100 from feeder cell layers and serum replacement medium SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Sakamoto, Norihisa; Sakamoto, Michiko; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. [Sakamoto, Michiko] Okayama Univ, Dept Gastroenterol & Hepatol, Okayama 7008530, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467803054 ER PT J AU Shahab-Ferdows, S Anaya, MA Rosado, JL Pogribny, I Allen, LH AF Shahab-Ferdows, Setareh Aracely Anaya, Miriam Louis Rosado, Jorge Pogribny, Igor Allen, Lindsay H. TI Randomized controlled trial of vitamin B12 supplementation in Mexican women with a high prevalence of B12 deficiency; predictors of biochemical and hematological response SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Shahab-Ferdows, Setareh; Aracely Anaya, Miriam; Allen, Lindsay H.] Univ Calif Davis, Davis, CA 95616 USA. [Aracely Anaya, Miriam; Louis Rosado, Jorge] Univ Autonoma Queretaro, Queretaro, Mexico. [Pogribny, Igor] HHS, FDA, NTCR, Jackson, CA USA. [Allen, Lindsay H.] ARS, WHNRC, USDA, Davis, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467806818 ER PT J AU Wang, XY Tryndyak, V Apostolovi, EO Yin, XY Shah, SV Pogribny, IP Basnakian, AG AF Wang, Xiaoying Tryndyak, Volodymyr Apostolovi, Eugene O. Yin, Xiaoyan Shah, Sudhir V. Pogribny, Igor P. Basnakian, Alexei G. TI Apoptotic/Recombinogenic Endonuclease G is Regulated by Promoter Methylation and Histone Acetylation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wang, Xiaoying; Apostolovi, Eugene O.; Yin, Xiaoyan; Shah, Sudhir V.; Basnakian, Alexei G.] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA. [Tryndyak, Volodymyr; Pogribny, Igor P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shah, Sudhir V.; Basnakian, Alexei G.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467806363 ER PT J AU Whittaker, P Clarke, JJ San, RHC Betz, JM Mazzola, EP Dunkel, VC AF Whittaker, Paul Clarke, Jane J. San, Richard H. C. Betz, Joseph M. Mazzola, Eugene P. Dunkel, Virginia C. TI Evaluating kava extracts and kavalactones for mutagenicity and toxicity SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Whittaker, Paul; Mazzola, Eugene P.; Dunkel, Virginia C.] US FDA, College Pk, MD USA. [Clarke, Jane J.; San, Richard H. C.] BioReliance, Rockville, MD USA. [Betz, Joseph M.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467801081 ER PT J AU Wu, KM Ghantous, H Birnkrant, DB AF Wu, Kuei-Meng Ghantous, Hanan Birnkrant, Debra B. TI Botanical Drug Development: Waiver of Preclinical Pharm/Tox Studies and Importance of Initial Cinical Trial Design SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wu, Kuei-Meng; Ghantous, Hanan; Birnkrant, Debra B.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467800642 ER PT J AU Wu, KM Ghantous, H Birnkrant, DB AF Wu, Kuei-Meng Ghantous, Hanan Birnkrant, Debra B. TI Botanical Drug Product Development in the USA: Importance of Genotoxicity Testing SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Wu, Kuei-Meng; Ghantous, Hanan; Birnkrant, Debra B.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467800042 ER PT J AU Yin, ZW Amrute, S Lewis-antes, A Donnelly, RP Kotenko, S Bocarsly, PE AF Yin, Zhiwei Amrute, Sheela Lewis-antes, Anita Donnelly, Raymond P. Kotenko, Serguei Bocarsly, Patricia E. TI Plasmacytoid Dendritic Cells both produce interferon-lambda and respond to interferon-lambda stimulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 [Yin, Zhiwei; Amrute, Sheela; Lewis-antes, Anita; Kotenko, Serguei; Bocarsly, Patricia E.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. [Donnelly, Raymond P.] US FDA, CDER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2008 VL 22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA V25GZ UT WOS:000208467806873 ER PT J AU Nayak, R Stewart-King, T AF Nayak, Rajesh Stewart-King, Tabitha TI Molecular epidemiological analysis and microbial source tracking of Salmonella enterica serovars in a preharvest Turkey production environment SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; PRODUCTION FACILITY; GENETIC DIVERSITY; UNITED-STATES; RESISTANCE; POULTRY; ENTERITIDIS; INFECTION; INTEGRONS; PULSENET AB Epidemiological studies were conducted to source track and delineate horizontal transmission pathways of Salmonella serovars in a turkey production environment. Salmonella enterica serovar Heidelberg (n = 111), Salmonella Senftenberg (n = 14), Salmonella Muenster (n = 10), unidentifiable "roughs" (n = 5), Salmonella Anatum (n = 3), and Salmonella Worthington (n = 2) were isolated from the birds' cecal and crop contents, litter, environmental swabs, drinkers, and feed samples. These strains (n = 145) were analyzed for their antimicrobial susceptibility profiles and the bacterial horizontal transmission pathways were tracked by XbaI-digested pulsed-field gel electrophoresis (PFGE) macrorestriction profiles. Nearly 79% of the strains were resistant to one or more antimicrobials, while 44% of the strains were resistant to two to six antimicrobials. Nearly 21% of the strains were susceptible to all of the antimicrobials tested. Twenty-seven distinct PFGE fingerprint profiles (90-95% similarity) were observed among 110 Salmonella Heidelberg strains (one strain was untypeable), and 13 of the 27 profiles (48%) elicited 100% similarity among the fingerprint patterns. The prevalence of Salmonella Heidelberg strains at weeks 2 (n = 20), 10 (n = 20), and 18 (n = 70) among the sampled pens suggested cross-colonization among pens during the 20-week production cycle. Salmonella Heidelberg strains were first isolated from the birds at week 2, and identical fingerprint profiles of this serovar were subsequently isolated from birds within the same pen; birds in other pens; and litter, air, and swab samples at weeks 10 and 18, suggesting possible horizontal transmission of this serovar across the production facility during the grow-out period. C1 [Nayak, Rajesh; Stewart-King, Tabitha] US Dept Hlth & Human Serv, US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nayak, R (reprint author), US Dept Hlth & Human Serv, US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 33 TC 19 Z9 19 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD APR PY 2008 VL 5 IS 2 BP 115 EP 126 DI 10.1089/fpd.2007.0029 PG 12 WC Food Science & Technology SC Food Science & Technology GA 293HJ UT WOS:000255326000002 PM 18361686 ER PT J AU Smith, PB Li, JS Murphy, MD Califf, RM Benjamin, DK AF Smith, P. Brian Li, Jennifer S. Murphy, M. Dianne Califf, Robert M. Benjamin, Daniel K., Jr. TI Safety of placebo controls in pediatric hypertension trials SO HYPERTENSION LA English DT Article DE pediatric drug therapy; hypertension; placebo-controlled clinical trials; adverse events; medical ethics ID CLINICAL-TRIALS; BLOOD-PRESSURE; UNETHICAL USE; EXCLUSIVITY; MEDICATION; CHILDREN; DRUG AB Many clinical trials, including those in pediatric populations, use a placebo arm for medical conditions for which there are readily available therapeutic interventions. Several short-term efficacy trials of antihypertensive medications performed in response to Food and Drug Administration-issued written requests have used a placebo arm; whether the use of a placebo arm is safe in children with hypertension is unknown. We sought to define the rates of adverse events in 10 short-term antihypertensive trials to determine whether these trials resulted in increased risk to pediatric patients receiving placebo. We combined patient-level data from 10 antihypertensive efficacy trials performed in pediatric patients that were submitted to the Food and Drug Administration from 1998 to 2005. We determined the number and type of all of the adverse events reported during the placebo-controlled portion of the clinical trials and compared these numbers between the patients who received placebo and those who received active drug. Among the 1707 children in the 10 studies, we observed no differences in the rates of adverse events reported between the patients who received placebo and those who received active drug. Only 5 patients suffered a serious adverse event during the trials; none were thought by the investigators to be related to study drug, and only 1 occurred in a patient receiving placebo. Short-term exposure to placebo in pediatric trials of antihypertensive medications appears to be safe. C1 [Smith, P. Brian; Li, Jennifer S.; Murphy, M. Dianne; Benjamin, Daniel K., Jr.] US FDA, Rockville, MD 20857 USA. [Smith, P. Brian; Li, Jennifer S.; Califf, Robert M.; Benjamin, Daniel K., Jr.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Smith, P. Brian; Li, Jennifer S.; Califf, Robert M.; Benjamin, Daniel K., Jr.] Duke Univ, Dept Med, Durham, NC 27706 USA. [Smith, P. Brian; Li, Jennifer S.; Califf, Robert M.; Benjamin, Daniel K., Jr.] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. RP Smith, PB (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM brian.smith@duke.edu RI Smith, Phillip/I-5565-2014 FU NCRR NIH HHS [1UL1RR024128-01, UL1 RR024128, UL1 RR024128-01]; NICHD NIH HHS [1U10-HD45962-04, U10 HD045962] NR 18 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 2008 VL 51 IS 4 BP 829 EP 833 DI 10.1161/HYPERTENSIONAHA.107.104950 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 276SA UT WOS:000254161300008 PM 18285612 ER PT J AU Benjamin, DK Smith, PB Jadhav, P Gobburu, JV Murphy, MD Hasselblad, V Baker-Smith, C Califf, RM Li, JS AF Benjamin, Daniel K., Jr. Smith, P. Brian Jadhav, Pravin Gobburu, Jogarao V. Murphy, M. Dianne Hasselblad, Vic Baker-Smith, Carissa Califf, Robert M. Li, Jennifer S. TI Pediatric antihypertensive trial failures - Analysis of end points and dose range SO HYPERTENSION LA English DT Article DE pediatrics; antihypertensive agents; dose-response relationship; clinical trials; randomized; pediatric epidemiology ID HYPERTENSIVE CHILDREN; BLOOD-PRESSURE; DOUBLE-BLIND; SAFETY; PHARMACOKINETICS; REPRODUCIBILITY; EFFICACY AB Historically, drugs prescribed for children have not been studied in pediatric populations. Since 1997, however, a 6-month extension of marketing rights is granted if manufacturers conduct Food and Drug Administration-defined pediatric trials. In nearly half of the drugs studied, there were unexpected results in dosing, safety, or efficacy compared with adult studies, including failure of half of the antihypertensive dose-response trials, which are pivotal for deriving dosing recommendations. We sought to define design elements that might have contributed to these trial failures by combining patient-level data from 6 dose-ranging antihypertensive efficacy trials completed for pediatric exclusivity and submitted to the Food and Drug Administration from 1998 to 2005. We evaluated dosing, primary end point, and other components to assess underlying reasons for failure to show efficacy in children. Of 6 trials examined, 3 showed a dose response; 3 did not. Eligibility criteria were similar across studies, as were subject demographics. Successful studies showed large differences in doses, with little or no overlap between low, medium, and high doses; failed trials used narrow dose ranges with considerable overlap. Successful trials also provided pediatric formulations and used reduction in diastolic, not systolic, blood pressure as the primary end point. Careful attention to pediatric pharmacology and selection of primary end points can improve trial performance. We found poor dose selection, lack of acknowledgement of differences between adult and pediatric populations, and lack of pediatric formulations to be associated with failures. More importantly, our ability to combine data across trials allowed us to evaluate and potentially improve trial design. C1 [Benjamin, Daniel K., Jr.; Smith, P. Brian; Murphy, M. Dianne; Li, Jennifer S.] US FDA, Off Pediat Therapeut, Off Commissioner & Pharmacometr, Rockville, MD 20857 USA. [Jadhav, Pravin; Gobburu, Jogarao V.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Benjamin, Daniel K., Jr.; Smith, P. Brian; Hasselblad, Vic; Baker-Smith, Carissa; Li, Jennifer S.] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Benjamin, Daniel K., Jr.; Smith, P. Brian; Hasselblad, Vic; Baker-Smith, Carissa; Li, Jennifer S.] Duke Univ, Dept Biostat, Durham, NC 27706 USA. [Benjamin, Daniel K., Jr.; Smith, P. Brian; Hasselblad, Vic; Baker-Smith, Carissa; Li, Jennifer S.] Duke Univ, Dept Med, Durham, NC 27706 USA. [Benjamin, Daniel K., Jr.; Smith, P. Brian; Hasselblad, Vic; Baker-Smith, Carissa; Li, Jennifer S.] Duke Univ, Duke Clin Res Inst, Durham, NC 27706 USA. [Califf, Robert M.] Duke Univ, Duke Translat Med Inst, Durham, NC 27706 USA. RP Benjamin, DK (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM danny.benjamin@duke.edu RI Smith, Phillip/I-5565-2014 FU NCRR NIH HHS [1UL1RR024128-01, UL1 RR024128, UL1 RR024128-02]; NICHD NIH HHS [1U10-HD45962-04, U10 HD045962, U10 HD045962-04] NR 19 TC 59 Z9 64 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 2008 VL 51 IS 4 BP 834 EP 840 DI 10.1161/HYPERTENSIONAHA.107.108886 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 276SA UT WOS:000254161300009 PM 18332283 ER PT J AU Goebel, EM Wolfe, DN Elder, K Stibitz, S Harvill, ET AF Goebel, Elizabeth M. Wolfe, Daniel N. Elder, Kelly Stibitz, Scott Harvill, Eric T. TI O antigen protects Bordetella parapertussis from complement SO INFECTION AND IMMUNITY LA English DT Article ID RESPIRATORY-TRACT INFECTION; ACELLULAR PERTUSSIS VACCINES; PSEUDOMONAS-AERUGINOSA; FRANCISELLA-TULARENSIS; KLEBSIELLA-PNEUMONIAE; III SECRETION; LIPOPOLYSACCHARIDE BIOSYNTHESIS; CLASSICAL PATHWAY; ADENYLATE-CYCLASE; HOST ADAPTATION AB Bordetella pertussis, a causative agent of whooping cough, expresses BrkA, which confers serum resistance, but the closely related human pathogen that also causes whooping cough, Bordetella parapertussis, does not. Interestingly, B. parapertussis, but not B. pertussis, produces an O antigen, a factor shown in other models to confer serum resistance. Using a murine model of infection, we determined that O antigen contributes to the ability of B. parapertussis to colonize the respiratory tract during the first week of infection, but not thereafter. Interestingly, an O antigen-deficient strain of B. parapertussis was not defective in colonizing mice lacking the complement cascade. O antigen prevented both complement component C3 deposition on the surface and complement-mediated killing of B. parapertussis. In addition, O antigen was required for B. parapertussis to systemically spread in complement-sufficient mice, but not complement-deficient mice. These data indicate that O antigen enables B. parapertussis to efficiently colonize the lower respiratory tract by protecting against complement-mediated control and clearance. C1 [Goebel, Elizabeth M.; Wolfe, Daniel N.; Elder, Kelly; Harvill, Eric T.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. [Goebel, Elizabeth M.] US FDA, Grad Program Immunol & Infect Dis, Bethesda, MD 20892 USA. [Wolfe, Daniel N.] US FDA, Grad Program Pathobiol, Bethesda, MD 20892 USA. [Stibitz, Scott] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Harvill, ET (reprint author), Penn State Univ, Dept Vet & Biomed Sci, 115 Henning Bldg,Univ Pk, University Pk, PA 16802 USA. EM eth10@psu.edu FU NIAID NIH HHS [AI 053075, AI 065507, R01 AI053075, R01 AI053075-01A1, R01 AI053075-02, R01 AI053075-03, R01 AI053075-04, R01 AI053075-04S1, R01 AI053075-05, R56 AI065507]; NIGMS NIH HHS [R01 GM083113, R01 GM083113-01, R01 GM083113-02] 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 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2008 VL 76 IS 4 BP 1774 EP 1780 DI 10.1128/IAI.01629-07 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 284SI UT WOS:000254725700047 PM 18285500 ER PT J AU Smith, MJ Garrett, RH AF Smith, M. J. Garrett, R. H. TI Part III. keyword-based, boolean-logic driven data-mining discloses correlations between additional idiopathic conditions, occlusive vascular diseases such as tropical endomyocardial fibrosis with unexplained eosinophilia, and 'histamine dysmetabolism' SO INFLAMMATION RESEARCH LA English DT Article; Proceedings Paper CT 36th Meeting of the European-Histamine-Research-Society CY MAY 09-12, 2007 CL Florence, ITALY SP European Histamine Res Soc C1 [Smith, M. J.] Ctr Food Safety & Appl Nutr, Off Ctr Director, College Pk, MD 20740 USA. [Garrett, R. H.] Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA. RP Smith, MJ (reprint author), Ctr Food Safety & Appl Nutr, Off Ctr Director, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mitchell.smith@fda.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 2 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD APR PY 2008 VL 57 SU 1 BP S25 EP S26 DI 10.1007/s00011-007-0612-4 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 303PA UT WOS:000256051400012 PM 18345505 ER PT J AU Gonzalez-Escalona, N Martinez-Urtaza, J Romero, J Espejo, RT Jaykus, LA DePaola, A AF Gonzalez-Escalona, Narjol Martinez-Urtaza, Jaime Romero, Jaime Espejo, Romilio T. Jaykus, Lee-Ann DePaola, Angelo TI Determination of molecular phylogenetics of Vibrio parahaemolyticus strains by multilocus sequence typing SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PANDEMIC STRAINS; UNITED-STATES; GENE-TRANSFER; DIARRHEA; O3-K6; EMERGENCE; RECOMBINATION; EVOLUTIONARY; BACTERIA; SPREAD AB Vibrio parahaemolyticus is an important human pathogen whose transmission is associated with the consumption of contaminated seafood. There is a growing public health concern due to the emergence of a pandemic strain causing severe outbreaks worldwide. Many questions remain unanswered regarding the evolution and population structure of V. parahaemolyticus. In this work, we describe a multilocus sequence typing (MLST) scheme for V. parahaemolyticus based on the internal fragment sequences of seven housekeeping genes. This MLST scheme was applied to 100 V. parahaemolyticus strains isolated from geographically diverse clinical (n = 37) and environmental (n = 63) sources. The sequences obtained from this work were deposited and are available in a public database (http://pubmist.org/vparahaemolyticus). Sixty-two unique sequence types were identified, and most (50) were represented by a single isolate, suggesting a high level of genetic diversity. Three major clonal complexes were identified by eBURST analysis. Separate clonal complexes were observed for V. parahaemolyticus isolates originating from the Pacific and Gulf coasts of the United States, while a third clonal complex consisted of strains belonging to the pandemic clonal complex with worldwide distribution. The data reported in this study indicate that V. parahaemolyticus is genetically diverse with a semiclonal population structure and an epidemic structure similar to that of Vibrio cholerae. Genetic diversity in V. parahaemolyticus appears to be driven primarily by frequent recombination rather than mutation, with recombination ratios estimated at 2.5:1 and 8.8:1 by allelle and site, respectively. Application of this MLST scheme to more V. parahaemolyticus strains and by different laboratories will facilitate production of a global picture of the epidemiology and evolution of this pathogen. C1 [Gonzalez-Escalona, Narjol; Jaykus, Lee-Ann] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. [Martinez-Urtaza, Jaime] Univ Santiago de Compostela, Santiago De Compostela 15782, Spain. [Romero, Jaime; Espejo, Romilio T.] Univ Chile, Inst Nutr & Tecnol Alimentos, Lab Biotecnol, Santiago 11, Chile. [Gonzalez-Escalona, Narjol] US FDA, CFSAN, College Pk, MD 20740 USA. [DePaola, Angelo] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Gonzalez-Escalona, N (reprint author), US FDA, CFSAN, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM narjol@gmail.com RI Gonzalez-Escalona, Narjol/A-7598-2009; Romero, Jaime/I-2816-2013; Martinez-Urtaza, Jaime/A-5528-2015; Espejo, Romilio/J-3183-2015; OI Romero, Jaime/0000-0001-9614-2393; Espejo, Romilio/0000-0003-0495-4576; Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 41 TC 96 Z9 109 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2008 VL 190 IS 8 BP 2831 EP 2840 DI 10.1128/JB.01808-07 PG 10 WC Microbiology SC Microbiology GA 285JN UT WOS:000254773200020 PM 18281404 ER PT J AU Chen, Y Knabel, SJ AF Chen, Yi Knabel, Stephen J. TI Prophages in Listeria monocytogenes contain single-nucleotide polymorphisms that differentiate outbreak clones within epidemic clones SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID UNITED-STATES; VIRULENCE; SEQUENCE; GENOME; EVOLUTION; STRAINS AB A fragment end ligation-mediated PCR strategy was used to analyze the AscI pulsed-field gel electrophoresis patterns of Listeria monocytogenes epidemic clone II (ECII), which led to the identification of single-nucleotide polymorphisms (SNPs) in prophage regions that differentiated the two ECII outbreak clones. SNPs in prophages that differentiated the outbreak clones of ECIII and -IV were also identified. C1 [Chen, Yi; Knabel, Stephen J.] Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. RP Chen, Y (reprint author), FDA, Ctr Food Safety & Appl Nutr, HFS-712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM yi.chen@fda.hhs.gov RI Zhou, Tian/J-7175-2012 NR 16 TC 18 Z9 18 U1 0 U2 6 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 APR PY 2008 VL 46 IS 4 BP 1478 EP 1484 DI 10.1128/JCM.01873-07 PG 7 WC Microbiology SC Microbiology GA 286SN UT WOS:000254866400047 PM 18256228 ER PT J AU DiGiacinto, JL Chan-Tack, KM Robertson, SM Reynolds, KS Struble, KA AF DiGiacinto, Jennifer L. Chan-Tack, Kirk M. Robertson, Sarah M. Reynolds, Kellie S. Struble, Kimberly A. TI Are literature references sufficient for dose recommendations? an FDA case study of efavirenz and rifampin SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE tuberculosis; HIV; rifampin; efavirenz; drug interaction ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; PHARMACOKINETIC INTERACTIONS; 600 MG/DAY; TUBERCULOSIS; CYP2B6; POLYMORPHISM; METABOLISM; GENE AB One of the numerous regulatory functions of the Food and Drug Administration (FDA) is the evaluation of drug-drug interactions and the determination of appropriate dose adjustments, if necessury, to ensure the safe and effective use of medications. The FDA considers several data sources when determining the significance of drug-drug interactions. The majority of dose adjustment recommendations are based on specific drug-drug interactions studies, The FDA reviews individual patient pharmacokinetic and safety data from drug interaction studies, determines appropriate dose adjustments, and provides recommendations to update the respective product labeling. Sometimes literature references are submitted to the FDA to support dosing recommendations. Determining an appropriate dose adjustment recommendation based on literature reports is a challenge for the FDA due to the lack of individual patient pharmacokinetic or safety data from these studies. Recently, the FDA encountered a challenging regulatory situation when evaluating literature reports to determine the appropriate dose of efavirenz and rifampin, Although numerous studies were found in the literature about this combination, a dosing recommendation cannot be concluded from the reported data. This article reviews the process the FDA used to evaluate literature to support potential dose adjustments for efavirenz when co-administered with rifampin and the challenges encountered during the process. C1 [DiGiacinto, Jennifer L.; Robertson, Sarah M.; Reynolds, Kellie S.] US FDA, Off Clin Pharmacol, Div 4, Silver Spring, MD USA. [Chan-Tack, Kirk M.; Struble, Kimberly A.] US FDA, Off New Drugs, Div Antiviral Prod, Silver Spring, MD USA. RP Struble, KA (reprint author), WO 22,Rm 6374,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kimberly.struble@fda.hhs.gov NR 22 TC 11 Z9 11 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2008 VL 48 IS 4 BP 518 EP 523 DI 10.1177/0091270008315308 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 281KG UT WOS:000254495200013 PM 18303126 ER PT J AU Keller, SE Shazer, AG Fleischman, GJ Chirtel, S Anderson, N Larkin, J AF Keller, Susanne E. Shazer, Arlette G. Fleischman, Gregory J. Chirtel, Stuart Anderson, Nathan Larkin, John TI Modification of the submerged coil to prevent microbial carryover error in thermal death studies SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; LISTERIA-MONOCYTOGENES; HEAT-RESISTANCE; SALMONELLA SPP.; INACTIVATION; MICROORGANISMS; TEMPERATURE; APPARATUS; KINETICS; PH AB A submerged coil unit generates death rate data for foodborne pathogens through precise computer-controlled sequential sampling rather than the usual manually timed, labor-intensive single sampling associated with other approaches. Our work with Yersinia pseudotuberculosis and Listeria monocytogenes Scott A using the submerged coil unit indicated non-log-linear death rates with large degrees of tailing. Varying degrees of cell adhesion to the surface of the exit port resulted in carryover that was likely the primary cause of these non-log-linear kinetics. This carryover also resulted in erroneously high measured levels of thermal resistance for both organisms. To address the carryover problem, modifications were made to the exit port of the submerged coil unit to ensure continuous and uniform heat treatment. These modifications resulted in a 2-fold decrease in measured D-values for L monocytogenes Scott A and a 10-fold decrease in measured D-values for Y. pseudotuberculosis. D-values measured with the modified machine for L. monocytogenes Scott A were similar to those found in the literature. Slight tailing in survival curves persisted with the modified method, particularly for Y. pseltdotuberculosis. These results indicate that kinetic data for microbial death rates obtained using an unmodified submerged coil unit must be viewed with suspicion in light of the significant potential for carryover. C1 [Keller, Susanne E.; Fleischman, Gregory J.; Anderson, Nathan; Larkin, John] US FDA, Summit Argo, Chicago, IL 60501 USA. [Chirtel, Stuart] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. [Shazer, Arlette G.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, Chicago, IL 60501 USA. RP Keller, SE (reprint author), US FDA, Summit Argo, 6502 S Archer Rd,, Chicago, IL 60501 USA. EM susanne.keller@fda.hhs.gov NR 18 TC 7 Z9 7 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2008 VL 71 IS 4 BP 775 EP 780 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 283ZJ UT WOS:000254674700014 PM 18468032 ER PT J AU Brenner, M Coelho, SG Beer, JZ Miller, SA Hearing, VJ AF Brenner, M. Coelho, S. G. Beer, J. Z. Miller, S. A. Hearing, V. J. TI Persistent molecular changes after repetitive in situ UV exposure of human skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 14-17, 2008 CL Kyoto, JAPAN SP Japanese Soc Investigat Dermatol, Soc Investigat Dermatol, European Soc Dermatol Res, Federat Pharmaceut Manufactures Assoc Japan, Galderma, Janssen Pharmaceut KK, Maruho Co Ltd, Sanofi Aventis KK, Torii Pharmaceut Co Ltd, Abbott Japan Co Ltd, CERIES, Chanel, Clin Labs KK, Dainippon Sumitomo Pharma, Eisai Co Ltd, GlaxoSmithKline KK, Kyowa Hakko Kogyo Co Ltd, Mistubishi Tanabe Pharma Corp, Nippon Boehringer Ingelheim, Novartis Pharma KK, Schering Plough, Shionogi & Co Ltd, Shiseido Co Ltd, Japan Cosmet Ind Assoc, Igaku Shoin, Pierre Fabre Japan Co Ltd C1 [Brenner, M.] Univ Munich, Dept Dermatol, D-8000 Munich, Germany. [Coelho, S. G.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Beer, J. Z.; Miller, S. A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2008 VL 128 SU 1 MA 1270 BP S212 EP S212 PG 1 WC Dermatology SC Dermatology GA 279KJ UT WOS:000254353801266 ER PT J AU Hoashi, T Muller, J Tamaki, K Ohara, K Hearing, VJ AF Hoashi, T. Muller, J. Tamaki, K. Ohara, K. Hearing, V. J. TI The internal repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for fibrillogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 14-17, 2008 CL Kyoto, JAPAN SP Japanese Soc Investigat Dermatol, Soc Investigat Dermatol, European Soc Dermatol Res, Federat Pharmaceut Manufactures Assoc Japan, Galderma, Janssen Pharmaceut KK, Maruho Co Ltd, Sanofi Aventis KK, Torii Pharmaceut Co Ltd, Abbott Japan Co Ltd, CERIES, Chanel, Clin Labs KK, Dainippon Sumitomo Pharma, Eisai Co Ltd, GlaxoSmithKline KK, Kyowa Hakko Kogyo Co Ltd, Mistubishi Tanabe Pharma Corp, Nippon Boehringer Ingelheim, Novartis Pharma KK, Schering Plough, Shionogi & Co Ltd, Shiseido Co Ltd, Japan Cosmet Ind Assoc, Igaku Shoin, Pierre Fabre Japan Co Ltd C1 [Hoashi, T.; Tamaki, K.] Univ Tokyo, Fac Med, Dept Dermatol, Tokyo 113, Japan. [Hoashi, T.; Hearing, V. J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Hoashi, T.; Ohara, K.] Toranomon Gen Hosp, Dept Dermatol, Tokyo, Japan. [Muller, J.] US FDA, Div Viral Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2008 VL 128 SU 1 MA 1327 BP S222 EP S222 PG 1 WC Dermatology SC Dermatology GA 279KJ UT WOS:000254353801322 ER PT J AU King, KE Ponnamperuma, RM Allen, C Chen, Z Van Waes, C Weinberg, WC AF King, K. E. Ponnamperuma, R. M. Allen, C. Chen, Z. Van Waes, C. Weinberg, W. C. TI Delta Np63 alpha modulates keratinocyte growth regulation via activation of NF-kappa B/c-Rel SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 14-17, 2008 CL Kyoto, JAPAN SP Japanese Soc Investigat Dermatol, Soc Investigat Dermatol, European Soc Dermatol Res, Federat Pharmaceut Manufactures Assoc Japan, Galderma, Janssen Pharmaceut KK, Maruho Co Ltd, Sanofi Aventis KK, Torii Pharmaceut Co Ltd, Abbott Japan Co Ltd, CERIES, Chanel, Clin Labs KK, Dainippon Sumitomo Pharma, Eisai Co Ltd, GlaxoSmithKline KK, Kyowa Hakko Kogyo Co Ltd, Mistubishi Tanabe Pharma Corp, Nippon Boehringer Ingelheim, Novartis Pharma KK, Schering Plough, Shionogi & Co Ltd, Shiseido Co Ltd, Japan Cosmet Ind Assoc, Igaku Shoin, Pierre Fabre Japan Co Ltd C1 [King, K. E.; Ponnamperuma, R. M.; Weinberg, W. C.] US FDA, CDER, Off Biotechnol Prod, Bethesda, MD 20014 USA. [Allen, C.; Chen, Z.; Van Waes, C.] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RI Weinberg, Wendy/A-8920-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2008 VL 128 SU 1 MA 202 BP S34 EP S34 PG 1 WC Dermatology SC Dermatology GA 279KJ UT WOS:000254353800203 ER PT J AU Spencer, JA Gao, ZM Moore, T Buhse, LF Taday, PF Newnham, DA Shen, YC Portieri, A Husain, A AF Spencer, John A. Gao, Zongming Moore, Terry Buhse, Lucinda F. Taday, Philip F. Newnham, David A. Shen, Yaochun Portieri, Alessia Husain, Ajaz TI Delayed release tablet dissolution related to coating thickness by terahertz pulsed image mapping SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE asacol; mesalamine; mesalazine; delayed release; terahertz pulsed imaging; coating mapping; mean dissolution time (MDT); process analytical technology (PAT) ID GASTROINTESTINAL PH PROFILES; NEAR-INFRARED SPECTROSCOPY; INFLAMMATORY-BOWEL-DISEASE; 5-AMINOSALICYLIC ACID; FORMULATION; DELIVERY; THERAPY AB Delayed release dosage forms such as Asacol(R) employ coatings that are engineered to breakdown and release the drug topically at the nominal pH of the lower intestinal tract. Asacol tablets were found to dissolve in an erratic fashion when they are dissolved in buffers below pH 7 which can occur naturally, In this study Terahertz pulsed imaging (TPI) was used to accurately map the coating thickness of a group of Asacol tablets that were subsequently dissolved using the USP method at pH 6.8. The mean dissolution times were found to correlate with the average coating thickness measured over all surfaces. Thickness values for a single randomly selected face did not correlate well with the dissolution results. The speed and ease of TPI mapping may make it an attractive replacement for wet dissolution testing both in product development and eventually for process analysis. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1543-1550, 2008. C1 [Spencer, John A.; Gao, Zongming; Moore, Terry; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Taday, Philip F.; Newnham, David A.; Shen, Yaochun; Portieri, Alessia] TeraView Ltd, Cambridge CB4 0WS, England. [Husain, Ajaz] Sandoz, Princeton, NJ USA. RP Spencer, JA (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM John.Spencer@fda.hhs.gov RI Shen, Yaochun/J-6218-2012 OI Shen, Yaochun/0000-0002-8915-1993 NR 26 TC 43 Z9 43 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD APR PY 2008 VL 97 IS 4 BP 1543 EP 1550 DI 10.1002/jps.21051 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 280LN UT WOS:000254428400017 PM 17722005 ER PT J AU Wang, Y AF Wang, Yaning TI Derivation of various NONMEM estimation methods (vol 34, pg 575, 2007) SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Correction C1 Food & Drug Adm, CDER, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Wang, Y (reprint author), Food & Drug Adm, CDER, Off Clin Pharmacol, WO21 RM3662 HFD-880,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yaning.wang@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD APR PY 2008 VL 35 IS 2 BP 249 EP 249 DI 10.1007/s10928-008-9083-7 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 303BC UT WOS:000256013500007 ER PT J AU Anderson, DL Cunningham, WC AF Anderson, D. L. Cunningham, W. C. TI Compton suppression spectrometry for analysis of short-lived neutron activation products in foods SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 7th International Conference on Methods and Applications of Radioanalytical Chemistry CY APR 03-07, 2006 CL Kailua, HI ID IODINE AB Compton suppression spectrometry was used to analyze foods for elements with short-lived neutron activation products (half-lives of about 2 minutes to 1.5 days). Analysis conditions were optimized to provide quality assurance analyses for iodine in FDA's Total Diet Study. Iodine mass fractions (0.075 to 2.03 mg/kg) were measured in 19 of 42 foods analyzed, with limits of detection (LODs) ranging from 0.03 to 1.4 mg/kg, mostly depending on NaCl content. LODs were lowered by up to a factor of 2 for 16 elements. Suppression factors ranged from about 2 to 8 over the energy range 400 to 3200 keV. C1 [Anderson, D. L.; Cunningham, W. C.] US FDA, Elemental Res Branch, HFS 338, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Elemental Res Branch, HFS 338, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 8 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2008 VL 276 IS 1 BP 23 EP 28 DI 10.1007/s10967-008-0404-5 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 287MH UT WOS:000254920700004 ER PT J AU Taylor, CL Wilkening, VL AF Taylor, Christine L. Wilkening, Virginia L. TI How the nutrition food label was developed, Part 2: The purpose and promise of nutrition claims SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material C1 [Taylor, Christine L.] Natl Acad, Inst Med, Washington, DC 20001 USA. [Taylor, Christine L.; Wilkening, Virginia L.] US Food & Drug Adm Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Taylor, CL (reprint author), Natl Acad, Inst Med, 500 5th St NW, Washington, DC 20001 USA. EM CLTaylor@nas.edu NR 11 TC 15 Z9 15 U1 1 U2 1 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 APR PY 2008 VL 108 IS 4 BP 618 EP 623 DI 10.1016/j.jada.2008.01.009 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 283SZ UT WOS:000254658100010 PM 18375217 ER PT J AU Chilakamarri, A Rezende, AA Zuhl, I Nguyun, N Doi, SQ AF Chilakamarri, A. Rezende, A. A. Zuhl, I. Nguyun, N. Doi, S. Q. TI Age-dependent increase in TLR2 expression is associated with glomerular lipid accumulation and up-regulation of proinflammatory cytokines in the kidney of normal mice SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY APR 30-MAY 04, 2008 CL Washington, DC SP Amer Geriatr Soc C1 [Chilakamarri, A.] Michigan State Univ, Lansing, MI USA. [Chilakamarri, A.; Rezende, A. A.; Doi, S. Q.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Rezende, A. A.] Univ Fed Rio Grande do Norte, BR-59072970 Natal, RN, Brazil. [Nguyun, N.] CBER, Food & Drug Adm, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2008 VL 56 IS 4 SU S MA B2 BP S65 EP S65 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 286IT UT WOS:000254840300187 ER PT J AU Fowlkes, JB Abramowicz, JS Church, CC Holland, CK Miller, DL O'Brien, WD Sanghvi, NT Stratmeyer, ME Zachary, JE AF Fowlkes, J. Brian Abramowicz, Jacques S. Church, Charles C. Holland, Christy K. Miller, Douglas L. O'Brien, William D. Sanghvi, Narendra T. Stratmeyer, Melvin E. Zachary, James E. CA Bioeffects Committee Amer Inst TI American institute of ultrasound in medicine consensus report on potential bioeffects of diagnostic ultrasound SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE bioeffects; contrast; mechanical effects; safety; thermal effects AB The continued examination of potential biological effects of ultrasound and their relationship to clinical practice is a key element in evaluating the safety of diagnostic ultrasound. Periodically, the American Institute of ultrasound in Medicine (AIUM) sponsors conferences bringing experts together to examine the literature on ultrasound bioeffects and to develop conclusions and recommendations related to diagnostic ultrasound. The most recent effort included the examination of effects whose origins were thermal or nonthermal, with separate evaluations for potential effects related to fetal ultrasound. In addition, potential effects due to the introduction of ultrasound contrast agents were summarized. This information can be used to assess risks in comparison to the benefits of diagnostic ultrasound. The conclusions and recommendations are organized into 5 broad categories, with a comprehensive background and evaluation of each topic provided in the corresponding articles in this issue. The following summary is not meant as a substitute for the detailed examination of issues presented in each of the articles but rather as a means to facilitate further study of this consensus report and implementation of its recommendations. The conclusions and recommendations are the result of several rounds of deliberations at the consensus conference, subsequent review by the Bioeffects Committee of the AIUM, and approval by the AIUM Board of Governors. C1 [Fowlkes, J. Brian; Miller, Douglas L.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Abramowicz, Jacques S.] Rush Univ, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Church, Charles C.] Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. [Holland, Christy K.] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH USA. [Holland, Christy K.] Univ Cincinnati, Dept Radiol, Cincinnati, OH USA. [O'Brien, William D.] Univ Illinois, Dept Elect & Comp Engn, Bioacoust Res Lab, Urbana, IL 61801 USA. [Sanghvi, Narendra T.] Focus Surg Inc, Indianapolis, IN USA. [Stratmeyer, Melvin E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Zachary, James E.] Univ Illinois, Dept Vet Pathobiol, Urbana, IL 61801 USA. RP Fowlkes, JB (reprint author), Univ Michigan Hlth Syst, Dept Radiol, Basic Radiol Sci Div, Kresge 3,Room 3320,200 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM fowlkes@umich.edu NR 7 TC 41 Z9 43 U1 0 U2 5 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2008 VL 27 IS 4 BP 503 EP 515 PG 13 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 282TB UT WOS:000254589000003 PM 18359906 ER PT J AU O'Brien, WD Deng, CX Harris, GR Herman, BA Merritt, CR Sanghvi, N Zachary, JF AF O'Brien, William D. Deng, Cheri X. Harris, Gerald R. Herman, Bruce A. Merritt, Christopher R. Sanghvi, Naren Zachary, James F. TI The risk of exposure to diagnostic ultrasound in postnatal subjects - Thermal effects SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE arrhenius analysis; nonfetal tissue; output display standard; temperature increase threshold; thermal mechanism ID INTENSITY FOCUSED ULTRASOUND; TRANSIENT TEMPERATURE RISE; LOCALIZED PROSTATE-CANCER; ACOUSTIC RADIATION FORCE; WHOLE-BODY HYPERTHERMIA; REGULATORY CONSIDERATIONS; TISSUE-DAMAGE; SOFT-TISSUE; PHASE-I; PROTEIN DENATURATION AB T his review evaluates the thermal mechanism for ultrasound-induced biological effects in postnatal subjects. The focus is the evaluation of damage versus temperature increase. A view of ultrasound-induced temperature increase is presented, based on thermodynamic Arrhenius analyses. The hyperthermia and other literature revealed data that allowed for an estimate of a temperature increase threshold of tissue damage for very short exposure times. This evaluation yielded an exposure time extension of the 1997 American Institute of Ultrasound in Medicine Conclusions Regarding Heat statement (American Institute of Ultrasound in Medicine, Laurel, MD) to 0.1 second for nonfetal tissue, where, at this exposure time, the temperature increase threshold of tissue damage was estimated to be about 18 degrees C. The output display standard was also evaluated for soft tissue and bone cases, and it was concluded that the current thermal indices could be improved to reduce the deviations and scatter of computed maximum temperature rises. C1 [O'Brien, William D.] Univ Illinois, Dept Elect & Comp Engn, Bioacoust Res Lab, Urbana, IL 61801 USA. [Zachary, James F.] Univ Illinois, Dept Pathobiol, Urbana, IL 61801 USA. [Deng, Cheri X.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Harris, Gerald R.; Herman, Bruce A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Merritt, Christopher R.] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA. [Sanghvi, Naren] Focus Surg Inc, Indianapolis, IN USA. RP O'Brien, WD (reprint author), Univ Illinois, Dept Elect & Comp Engn, Bioacoust Res Lab, 405 N Mathews, Urbana, IL 61801 USA. EM wdo@uiuc.edu FU NIBIB NIH HHS [R37 EB002641-11, R37 EB002641, R37 EB002641-10, R37EB002641] NR 86 TC 31 Z9 31 U1 0 U2 7 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2008 VL 27 IS 4 BP 517 EP 535 PG 19 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 282TB UT WOS:000254589000004 PM 18359907 ER PT J AU Stratmeyer, ME Greenleaf, JF Dalecki, D Salvesen, KA AF Stratmeyer, Melvin E. Greenleaf, James F. Dalecki, Diane Salvesen, Kjell A. TI Fetal ultra sound - Mechanical effects SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetus; mechanical effects; obstetrics; ultrasound ID RANDOMIZED CONTROLLED-TRIAL; MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY; ROUTINE ULTRASONOGRAPHY INUTERO; PULSED ULTRASOUND; DIAGNOSTIC ULTRASOUND; FOCUSED ULTRASOUND; IN-UTERO; THERAPEUTIC ULTRASOUND; CHILDHOOD-CANCER; FOLLOW-UP AB In this discussion, any biological effect of ultrasound that is accompanied by temperature increments less than IT above normal physiologic levels is called a mechahical effect. However, one should keep in mind that the term mechanical effect also includes processes that are not of a mechanical nature but arise secondary to mechanical interaction between ultrasound and tissues, such as chemical reactions initiated by free oxygen species generated during cavitation and sonoluminescence. Investigations with laboratory animals have documented that pulsed ultrasound can produce damage to biological tissues in vivo through nonthermal mechanisms. The acoustic output used to induce these adverse bio-effects is considerably greater than the output of diagnostic devices when gas bodies are not Present. However, low-intensity pulsed ultrasound is used clinically to accelerate the bone fracture repair process and induce healing of nonunions in humans. Low-intensity pulsed ultrasound also has been shown to enhance repair of soft tissue damage and accelerate nerve regeneration in animal models. Although such exposures to low intensity do not appear to cause damage to exposed tissues, they do raise questions about the acoustic threshold that might induce potentially adverse developmental effects in the fetus. To date, bioeffects studies in humans do not substantiate a causal relationship between diagnostic ultrasound exposure during pregnancy and adverse biological effects to the fetus. However, the epidemiologic studies were conducted with commercially available devices predating 1992, having outputs not exceeding a derated spatial-peak temporal-average intensity (I-SPTA.3) of 94 mW/cm(2). Current limits in the United States allow an I-SPTA.3 of 20 mW/cm(2) for obstetric modes. At the time of this report, available evidence, experimental or epidemiologic, is insufficient to conclude that there is a causal relationship between obstetric diagnostic ultrasound exposure and adverse nonthermal effects to the fetus. However, low-intensity pulsed ultrasound effects reported in humans and animal models indicate a need for further investigation of potentially adverse developmental effects. C1 [Stratmeyer, Melvin E.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Greenleaf, James F.] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN USA. [Dalecki, Diane] Univ Rochester, Dept Biomed Engn, Rochester, NY USA. [Dalecki, Diane] Univ Rochester, Rochester Ctr Biomed Ultrasound, Rochester, NY USA. [Salvesen, Kjell A.] Univ Trondheim Hosp, St Olavs Hosp, Trondheim, Norway. [Salvesen, Kjell A.] Norwegian Univ Sci & Technol, N-7034 Trondheim, Norway. RP Stratmeyer, ME (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 9200 Corporate Blvd,HFZ-120, Rockville, MD 20850 USA. EM melvin.stratmeyer@fda.hhs.gov NR 98 TC 20 Z9 23 U1 0 U2 9 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2008 VL 27 IS 4 BP 597 EP 605 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 282TB UT WOS:000254589000007 PM 18359910 ER PT J AU Abramovvicz, JS Fowlkes, JB Skelly, AC Stratmeyer, ME Ziskin, MC AF Abramovvicz, Jacques S. Fowlkes, J. Brian Skelly, Andrea C. Stratmeyer, Melvin E. Ziskin, Marvin C. TI Conclusions regarding epidemiology for obstetric ultrasound SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; ROUTINE ULTRASONOGRAPHY INUTERO; FREQUENT PRENATAL ULTRASOUND; DIAGNOSTIC ULTRASOUND; IN-UTERO; BIRTH-WEIGHT; SUBSEQUENT HANDEDNESS; FOLLOW-UP; EXPOSURE; PREGNANCY C1 [Abramovvicz, Jacques S.] Rush Univ, Med Ctr, Dept Obstet & Gynecol, Chicago, IL 60612 USA. [Fowlkes, J. Brian] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI USA. [Skelly, Andrea C.] Spectrum Res Inc, Tacoma, WA USA. [Stratmeyer, Melvin E.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Ziskin, Marvin C.] Temple Univ, Sch Med, Ctr Biomed Phys, Philadelphia, PA 19122 USA. RP Abramovvicz, JS (reprint author), Rush Univ, Med Ctr, Dept Obstet & Gynecol, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM jacques_abramowicz@rush.edu NR 33 TC 9 Z9 9 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2008 VL 27 IS 4 BP 637 EP 644 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 282TB UT WOS:000254589000009 PM 18359912 ER PT J AU Shieh, YC Wong, CI Krantz, JA Hsu, FC AF Shieh, Y. C. Wong, C. I. Krantz, J. A. Hsu, F. C. TI Detection of naturally occurring enteroviruses in waters using direct RT-PCR and integrated cell culture-RT-PCR SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE enterovirus; culturable; RT-PCR; water; detection ID HEPATITIS-A VIRUS; WASTE-WATER; AMPLIFICATION; CALICIVIRUS; SHELLFISH; RECOVERY; ILLNESS; OYSTERS AB Viruses detected by rapid molecular assays are not always infectious. In this study we compared enterovirus levels in natural waters using culture and reverse transcription-polymerase chain reaction (RT-PCR) techniques to determine whether molecular units of naturally occurring enteroviruses can be utilized to predict viral infectivity. Viruses were concentrated from 12 river water and effluent samples using 1MDS filter-filtration and beef extract-elution. An integrated cell culture-RT-PCR (ICC-RT-PCR) was applied to the concentrates; and these waters contained up to 1.9 MPN of culturable (on BGM cells) viruses per litre (0.57 MPN/300 ml). Sample concentrates were also subjected to a direct 'molecular' approach using solvent-extraction, PEG-precipitation, and RNA-extraction before RT-PCR detection. The detection sensitivity of the direct RT-PCR was equivalent to 0.46 estimated (culturable) MPN/reaction, per 300 ml water. Two-thirds of the samples demonstrated consistent presence or absence of viruses by ICC-RT-PCR and direct RT-PCR. The direct RT-PCR approach resulted in over-estimation of naturally occurring infectious viruses as high as 91-fold in waters. Increased RT-PCR units may not reflect higher levels of culturable viruses in natural waters. The differences in virus levels detected by molecular and culture assays could be attributed to factors of volume of sample analyzed, different concentration schemes utilized that may affect the presence of residual inhibitors, and different stability exhibited by enterovirus strains/groups. Published by Elsevier B.V. C1 [Shieh, Y. C.; Krantz, J. A.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Wong, C. I.; Hsu, F. C.] Environm Hlth Lab, South Bend, IN 46617 USA. RP Shieh, YC (reprint author), US FDA, Moffett Ctr, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM carol.shieh@fda.hhs.gov NR 20 TC 24 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 2008 VL 149 IS 1 BP 184 EP 189 DI 10.1016/j.jviromet.2007.12.013 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 292XZ UT WOS:000255300700028 PM 18280589 ER PT J AU Alpers, C Bloom, RD Fabrizi, F Izopet, J Jadoul, M Lindley, E Martin, P Morales, JM Natov, S Pol, S Reddy, KR Rostaing, L Roth, D Wei, L Alter, M Lavanchy, D Meyers, C Seeff, L Eknoyan, G Lameire, N Balk, E Craig, J Earley, A Gordon, C Ioannidis, J Jadoul, M Roth, D AF Alpers, Charles Bloom, Roy D. Fabrizi, Fabrizio Izopet, Jacques Jadoul, Michel Lindley, Elizabeth Martin, Paul Morales, Jose M. Natov, Svetlozar Pol, Stanislas Reddy, K. Rajender Rostaing, Lionel Roth, David Wei, Lai Alter, Miriam Lavanchy, Daniel Meyers, Catherine Seeff, Leonard Eknoyan, Garabed Lameire, Norbert Balk, Ethan Craig, Jonathan Earley, Amy Gordon, Craig Ioannidis, John Jadoul, Michel Roth, David TI KDIGO clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease - Introduction SO KIDNEY INTERNATIONAL LA English DT Review ID RENAL-TRANSPLANT RECIPIENTS; POSTTRANSPLANT DIABETES-MELLITUS; INTERFERON-ALPHA TREATMENT; LONG-TERM IMPACT; CHRONIC-HEMODIALYSIS PATIENTS; POLYMERASE-CHAIN-REACTION; CHRONIC DIALYSIS PATIENTS; CHRONIC ACTIVE HEPATITIS; VIRUS-ASSOCIATED GLOMERULONEPHRITIS; FIBROSING CHOLESTATIC HEPATITIS C1 [Alpers, Charles] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Bloom, Roy D.] Univ Penn, Philadelphia, PA 19104 USA. [Fabrizi, Fabrizio] Maggiore Hosp, IRCCS, Milan, Italy. [Izopet, Jacques; Rostaing, Lionel] CHU Toulouse, Organ Transplantat Unit, Toulouse, France. [Jadoul, Michel] Clin Univ St Luc, Dept Nephrol, St Louis, France. [Jadoul, Michel] Univ Catholique Louvain, Louvain, Belgium. [Lindley, Elizabeth] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. [Martin, Paul] Mt Sinai Sch Med, New York, NY 10029 USA. [Morales, Jose M.] Hosp 12 Octubre, Dept Nephrol, Renal Transplant Unit, E-28041 Madrid, Spain. [Natov, Svetlozar] Kindred Hosp NE, Waltham, MA USA. [Pol, Stanislas] Hop Cochin, Paris, France. [Reddy, K. Rajender] UPHS, Div Gastroenterol, Philadelphia, PA USA. [Reddy, K. Rajender] Liver Transplantat Penn Transplant Inst, Philadelphia, PA USA. [Roth, David] Univ Miami, Sch Med, Div Nephrol & Hypertens, Coral Gables, FL 33124 USA. [Wei, Lai] Peking Univ, Peoples Hosp, Inst Hepatol, Beijing, Peoples R China. [Lavanchy, Daniel] WHO, Dept Communicalbe Dis Surveillance & Response, Washington, DC USA. [Meyers, Catherine] NIDDK, NIH, Bethesda, MD 20892 USA. [Meyers, Catherine] NIDDKD, Bethesda, MD USA. [Seeff, Leonard] NIH, Bethesda, MD 20892 USA. [Seeff, Leonard] US FDA, Rockville, MD 20857 USA. [Seeff, Leonard] VA Med Ctr, Bethesda, MD USA. [Seeff, Leonard] Georgetown Univ, Washington, DC 20057 USA. [Seeff, Leonard] Amer Assoc Study Liver Dis, New York, NY USA. [Eknoyan, Garabed] Baylor Coll Med, Nephrol Sect, Houston, TX 77030 USA. [Lameire, Norbert] State Univ Ghent Hosp, Ghent, Belgium. [Balk, Ethan] Tufts Univ, Medford, MA 02155 USA. [Balk, Ethan; Earley, Amy] Tufts Univ New England Med Ctr, CPG, NKF, Dev & Implementat, Boston, MA USA. [Craig, Jonathan] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Craig, Jonathan] Childrens Hosp Westmead, Westmead, NSW, Australia. [Ioannidis, John] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John] Fdn Res & Technol Hellas, Biomed Res Inst, Ioannina, Greece. [Ioannidis, John] Tufts Univ New England Med Ctr, Dept Med, Boston, MA USA. RP Alpers, C (reprint author), Univ Washington, Med Ctr, Seattle, WA 98195 USA. RI Jadoul, Michel/B-8779-2008; Ioannidis, John/G-9836-2011; IZOPET, Jacques/L-5756-2014; Craig, Jonathan/E-2813-2013 OI Craig, Jonathan/0000-0002-2548-4035 NR 416 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2008 VL 73 SU 109 BP S6 EP S99 DI 10.1038/ki.2008.83 PG 94 WC Urology & Nephrology SC Urology & Nephrology GA 282HT UT WOS:000254559200002 ER PT J AU Elbaz, B Alperovitch, A Gottesman, MM Kimchi-Sarfaty, C Rahamimoff, H AF Elbaz, Benayahu Alperovitch, Ariella Gottesman, Michael M. Kimchi-Sarfaty, Chava Rahamimoff, Hannah TI Modulation of Na+-Ca2+ exchanger expression by immunosuppressive drugs is isoform-specific SO MOLECULAR PHARMACOLOGY LA English DT Article ID SODIUM-CALCIUM EXCHANGE; BLOOD-BRAIN-BARRIER; CIS-TRANS ISOMERASE; CYCLOSPORINE-A; SURFACE EXPRESSION; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; NA+/CA2+ EXCHANGER; PROLYL ISOMERASE; DOWN-REGULATION AB The Na+-Ca2+ exchanger (NCX) is a major Ca2+-regulating protein encoded by three genes: NCX1, NCX2, and NCX3. They share a sequence homology of approximately 65%. NCX1 protein is expressed ubiquitously, and NCX2 and NCX3 are expressed almost exclusively in the brain. We have shown previously (Kimchi-Sarfaty et al., 2002) that treatment of NCX1-transfected human embryonic kidney (HEK) 293 cells with the immunosuppressive cyclosporin A (CsA) and its nonimmunosuppressive analog PSC833 (valspodar) results in down-regulation of surface expression and transport activity of the protein without a decrease in expression of cell NCX1 protein. In this study, we show that cyclosporin A and PSC833 treatment of NCX2- and NCX3-transfected HEK 293 cells also resulted in dose-dependent down-regulation of surface expression and transport activity of the two brain NCX proteins; however, whereas CsA had no effect on total cell NCX protein expression, PSC833 reduced mRNA and cell protein expression of NCX2 and NCX3. Moreover, tacrolimus (FK506), which had no effect on NCX1 protein expression, down-regulated NCX2 and NCX3 surface expression and transport activity without any significant effect on cell protein expression. Sirolimus (rapamycin) had no effect on NCX2 and NCX3 protein expression, yet it reduced NCX2 and NCX3 transport activity. Because all of the experimental conditions in our studies were identical, presumably the different drug response is related to structural differences between NCX isoforms. Clinical studies suggested that immunosuppressive regimes of patients who have received transplants resulted in complications related to Ca2+. Expression of NCX genes is tissue-specific. Hence, our results can potentially provide a tool for choosing the immunosuppressive protocol to be used. C1 [Elbaz, Benayahu; Alperovitch, Ariella; Rahamimoff, Hannah] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. [Elbaz, Benayahu; Gottesman, Michael M.; Rahamimoff, Hannah] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Rahamimoff, H (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, POB 12272, IL-91120 Jerusalem, Israel. EM hannah.rahamimoff@huji.ac.il OI Elbaz, Benayahu/0000-0001-5202-4598 FU Intramural NIH HHS NR 50 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2008 VL 73 IS 4 BP 1254 EP 1263 DI 10.1124/mol.107.041582 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 275IK UT WOS:000254064900023 PM 18182482 ER PT J AU Sanchez-Diaz, A Marchesi, V Murray, S Jones, R Pereira, G Edmondson, R Allen, T Labib, K AF Sanchez-Diaz, Alberto Marchesi, Vanessa Murray, Stephen Jones, Richard Pereira, Gislene Edmondson, Ricky Allen, Terry Labib, Karim TI Inn1 couples contraction of the actomyosin ring to membrane ingression during cytokinesis in budding yeast SO NATURE CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE GENOME; KINETOCHORE BIORIENTATION; ELECTRON MICROSCOPY; MITOTIC SPINDLE; CLEAVAGE FURROW; CELL CORTEX; COMPLEX; PROTEIN; TRAFFICKING; ANILLIN AB By rapidly depleting each of the essential budding yeast proteins of unknown function, we identified a novel factor that we call Inn1, which associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. We show that Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane, whereas the remainder of the protein recruits Inn1 to the actomyosin ring. The lethal effects of deleting the INN1 gene can be suppressed by artificial fusion of the C2 domain to other components of the actomyosin ring, restoring membrane ingression on contraction of the actomyosin ring. Our data indicate that recruitment of the C2 domain of Inn1 to the contractile actomyosin ring is crucial for ingression of the plasma membrane during cytokinesis in budding yeast. C1 [Sanchez-Diaz, Alberto; Marchesi, Vanessa; Murray, Stephen; Pereira, Gislene; Allen, Terry; Labib, Karim] Univ Manchester, Canc Res UK, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. [Jones, Richard; Edmondson, Ricky] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Labib, K (reprint author), Univ Manchester, Canc Res UK, Paterson Inst Canc Res, Wilmslow Rd, Manchester M20 4BX, Lancs, England. EM klabib@picr.man.ac.uk RI Sanchez-Diaz, Alberto/L-2320-2014 FU Cancer Research UK NR 46 TC 44 Z9 49 U1 0 U2 1 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 APR PY 2008 VL 10 IS 4 BP 395 EP U58 DI 10.1038/ncb1701 PG 23 WC Cell Biology SC Cell Biology GA 282IS UT WOS:000254561700009 PM 18344988 ER PT J AU Piper, BJ Fraiman, JB Owens, CB Ali, SF Meyer, JS AF Piper, Brian J. Fraiman, Joseph B. Owens, Cullen B. Ali, Syed F. Meyer, Jerrold S. TI Dissociation of the neurochemical and behavioral toxicology of MDMA ('Ecstasy') by citalopram SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE MDMA; citalopram; behavior; rats; serotonin transporter; neurotoxicity ID SEROTONIN TRANSPORTER PROTEIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SOCIAL-INTERACTION; INCREASED ANXIETY; OPEN-FIELD; (+/-)-3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; METHYLENEDIOXYMETHAMPHETAMINE MDMA; AMPHETAMINE DERIVATIVES; NEURONAL DEGENERATION; NUCLEUS-ACCUMBENS AB High or repeated doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') produce long-lasting deficits in several markers of serotonin (5-HT) system integrity and also alter behavioral function. However, it is not yet clear whether MDMA-induced serotonergic neurotoxicity is responsible for these behavioral changes or whether other mechanisms are involved. The present experiment tested the hypothesis that blocking serotonergic neurotoxicity by pretreatment with the selective 5-HT reuptake inhibitor citalopram will also prevent the behavioral and physiological consequences of an MDMA binge administration. Male, Sprague Dawley rats (N=67) received MDMA (4 x 10 mg/kg) with or without citalopram (10 mg/kg) pretreatment. Core temperature, ejaculatory response, and body weight were monitored during and immediately following drug treatments. A battery of tests assessing motor, cognitive, exploratory, anxiety, and social behaviors was completed during a 10-week period following MDMA administration. Brain tissue was collected at 1 and 10 weeks after drug treatments for measurement of regional 5-HT transporter binding and (for the 1-week samples) 5-HT and 5-HIAA concentrations. Citalopram pretreatment blocked MDMA-related reductions in aggressive and exploratory behavior measured in the social interaction and hole-board tests respectively. Such pretreatment also had the expected protective effect against MDMA-induced 5-HT neurotoxicity at 1 week following the binge. In contrast, citalopram did not prevent most of the acute effects of MDMA (eg hyperthermia and weight loss), nor did it block the decreased motor activity seen in the binge-treated animals 1 day after dosing. These results suggest that some of the behavioral and physiological consequences of a high-dose MDMA regimen in rats are mediated by mechanisms other than the drug's effects on the serotonergic system. Elucidation of these mechanisms requires further study of the influence of MDMA on other neurotransmitter systems. C1 [Fraiman, Joseph B.; Owens, Cullen B.; Meyer, Jerrold S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Piper, Brian J.; Meyer, Jerrold S.] Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. [Ali, Syed F.] Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Meyer, JS (reprint author), Univ Massachusetts, Dept Psychol, Tobin Hall 135 Hicks Way, Amherst, MA 01003 USA. EM jmeyen@psych.umass.edu OI Meyer, Jerrold/0000-0002-8382-7075 FU NINDS NIH HHS [T32 NS007490] NR 79 TC 14 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2008 VL 33 IS 5 BP 1192 EP 1205 DI 10.1038/sj.npp.1301491 PG 14 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 273UQ UT WOS:000253957600022 PM 17609680 ER PT J AU Norwood, DL Paskiet, D Ruberto, M Feinberg, T Schroeder, A Poochikian, G Wang, QX Deng, TJ DeGrazio, F Munos, MK Nagao, LM AF Norwood, Daniel L. Paskiet, Diane Ruberto, Michael Feinberg, Thomas Schroeder, Alan Poochikian, Guirag Wang, Qingxi Deng, Tian Jing DeGrazio, Fran Munos, Melinda K. Nagao, Lee M. TI Best practices for extractables and leachables in orally inhaled and nasal drug products: An overview of the PQRI recommendations SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE controlled extraction studies; leachables; OINDP; pharmaceutical development; PQRI AB The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.S. FDA for consideration in September 2006. The recommendations include proposed safety and analytical thresholds for leachables and extractables, as well as detailed "best practice" recommendations for various aspects of the OINDP pharmaceutical development process, including: materials selection for OINDP container closure system components, Controlled Extraction Studies, Leachables Studies, and Routine Extractables Testing. The Working Group's processes and the detailed and comprehensive recommendations that resulted from those processes, demonstrate that the Product Quality Research Institute collaborative process can result in consensus science-based and data driven recommendations that could have a positive effect on patient care. It is anticipated that the Working Group's recommendations will also contribute to the new "Quality by Design" pharmaceutical development paradigm. This commentary summarizes the best practice recommendations within the context of an overall pharmaceutical development process. C1 [Munos, Melinda K.; Nagao, Lee M.] Drinker Biddle & Reath LLP, Washington, DC 20005 USA. [Norwood, Daniel L.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Paskiet, Diane] W Monarch Analyt Labs, Maumee, OH USA. [Ruberto, Michael] Ciba Expert Serv, Tarrytown, NY USA. [Feinberg, Thomas] Catalent Pharma Solut Inc, Res Triangle Pk, NC USA. [Schroeder, Alan; Poochikian, Guirag] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Wang, Qingxi] Merck & Co Inc, West Point, PA USA. [Deng, Tian Jing] Pharmaceut Prod Dev Inc, Madison, WI USA. [DeGrazio, Fran] W Pharmaceut Serv, Lionville, PA USA. RP Nagao, LM (reprint author), Drinker Biddle & Reath LLP, 1500 K St NW,Suite 1100, Washington, DC 20005 USA. EM lee.nagao@dbr.com NR 3 TC 22 Z9 25 U1 3 U2 11 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2008 VL 25 IS 4 BP 727 EP 739 DI 10.1007/s11095-007-9521-z PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 285AE UT WOS:000254748900002 PM 18183477 ER PT J AU Yu, LX AF Yu, Lawrence X. TI Pharmaceutical quality by design: Product and process development, understanding, and control SO PHARMACEUTICAL RESEARCH LA English DT Article DE pharmaceutical quality by design; pharmaceutical quality by testing; process control; process design; process parameter; process variability; product design; quality attribute; question-based review ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; SOLID POLYMORPHISM; DRUG APPLICATIONS; COMPATIBILITY; DISSOLUTION; ABSORPTION; EXCIPIENTS; SELECTION AB Purpose. The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality. Materials and Methods. The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone. Results. The QbD is a systemic approach to pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality. Some of the QbD elements include: Defining target product quality profile Designing product and manufacturing processes Identifying critical quality attributes, process parameters, and sources of variability Controlling manufacturing processes to produce consistent quality over time Conclusions. Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment. C1 US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yu, LX (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM Lawrence.Yu@hhs.fda.gov NR 51 TC 322 Z9 337 U1 8 U2 124 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2008 VL 25 IS 4 BP 781 EP 791 DI 10.1007/s11095-007-9511-1 PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 285AE UT WOS:000254748900006 PM 18185986 ER PT J AU Hammad, TA Graham, DJ Staffa, JA Kornegay, CJ Dal Pan, GJ AF Hammad, Tarek A. Graham, David J. Staffa, Judy A. Kornegay, Cynthia J. Dal Pan, Gerald J. TI Onset of acute myocardial infarction after use of non-steroidal anti-inflammatory drugs SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE nonsteroidal anti-inflammatory drugs; acute myocardial infarction; new user design ID SELECTIVE CYCLOOXYGENASE-2 INHIBITORS; CARDIOVASCULAR EVENTS; COX-2 INHIBITORS; RISK; METAANALYSIS; ROFECOXIB; CELECOXIB; OPPORTUNITIES; INFORMATION; CHALLENGES AB Purpose To examine the association between cyclooxygenase-2 (COX-2) selective and traditional nonsteroidal anti-inflammatory drugs (NSAIDs) and incident acute myocardial infarction (AMI), and to address unanswered questions regarding the contour of risk over time. Methods A cohort of new NSAID users aged 40-84 years was followed for the occurrence of first AMI. Data were collected within the General Practice Research Database (GPRD) from I January 1997 to 31 December 2004. Results The study population included 1185 AMI events (889 probable and 296 possible) from a cohort of 283 136 patients. After adjustment for demographic and cardiovascular risk factors, the hazard ratio (HR) for AMI was significantly increased for both coxib (2.11, 95% confidence interval (CI) 1.04-4.26) and non-coxib (2.24, 95%CI 1.13-4.42) COX-2 selective NSAIDs when compared to remote exposure to NSAIDs, but was not increased for traditional NSAIDs. Stratifying exposure into the first month of use versus use beyond I month, the risk of AMI was increased during the first month of COX-2 selective NSAIDs use, but not later (3.43, 95%CI 1.66-7.07 and 1.88, 95%CI 0.82-4.31, respectively p-value for interaction = 0.6). Conclusions The results suggest that the use of coxib and non-coxib COX-2 selective NSAIDs was associated with an elevated risk of AMI within the first month of exposure. Recent past exposure to NSAID was not associated with a similar increase in risk. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Hammad, Tarek A.; Graham, David J.; Staffa, Judy A.; Kornegay, Cynthia J.; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Hammad, TA (reprint author), US FDA, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Room 4474,Mail St, Silver Spring, MD 20993 USA. EM tarek.hammad@fda.hhs.gov RI Research Datalink, Clinical Practice/H-2477-2013; CPRD, CPRD/B-9594-2017 NR 35 TC 16 Z9 16 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2008 VL 17 IS 4 BP 315 EP 321 DI 10.1002/pds.1560 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 290WP UT WOS:000255153800001 PM 18302311 ER PT J AU Knudsen, JE Sokol, GH AF Knudsen, James E. Sokol, Gerald H. TI Potential glucosamine-warfarin interaction resulting in increased international normalized ratio: Case report and review of the literature and MedWatch database SO PHARMACOTHERAPY LA English DT Article DE glucosamine; warfarin; chondroitin sulfate; international normalized ratio; INR; bleeding ID VITAMIN-K; VARIABILITY; CARBOXYLASE; METABOLISM AB We describe a 71-year-old man who had received warfarin 7.5 mg/day for 5 years for atrial fibrillation, which had maintained his international normalized ratio (INR) within a narrow range of 2.5-3.2. During this 5-year period, he had also been treating himself with the supplement glucosamine hydrochloride 500 mg-chondroitin sulfate 400 mg twice/day for arthritis. The patient then increased his dosage of glucosamine to 1500 mg and chondroitin to 1200 mg twice/day; his INR previous to this change was 2.3. Approximately 3 weeks later, his INR increased to 3.9. His supplement dosage was reduced to glucosamine 750 mg-chondroitin 600 mg/day; a repeat INR done 16 days later was 4.7. The supplement was then stopped, and his warfarin schedule was changed to 7.5 mg every other day alternating with 3.75 mg every other day Sixteen days later, his INR was 2.6. This case report suggests that a potential interaction exists between warfarin and glucosamine that is associated with an increase in the INR. We therefore performed a pharmacovigilance survey of spontaneously reported adverse events in warfarin-treated patients concomitantly exposed to glucosamine, glucosamine-chondroitin sulfate, or chondroitin sulfate and present a literature review of this apparent drug-drug interaction. Using the United States Food and Drug Administration (FDA) MedWatch database, 20 reports of glucosamine or glucosamine-chondroitin sulfate use with warfarin associated with altered coagulation (manifested by increased INR, or increased bleeding or bruising) were identified. In some cases, a decrease in the supplement dosage was followed by a return of the INR to the previous therapeutic range. Similarly, a decrease in warfarin dosage was followed by a decrease in INR in one patient who received long-term warfarin therapy One report described an intraventricular bleed and subdural hematoma, which resulted in a persistent vegetative state. The World Health Organization (WHO) adverse drug reactions database documented 21 spontaneous reports of increased INR associated with glucosamine use, 17 of which resolved when glucosamine was stopped. We located one published case report of concomitant use of glucosamine-chondroitin sulfate potentiating the effect of warfarin. In aggregate, the reports from the FDA and WHO, the published case report, and our case report suggest that the use of warfarin and glucosamine may lead to an increased INR. Patients should be advised that the use of the two products may cause an increase in INR, and they should inform their health care provider if they consume glucosamine. More information is necessary to define this interaction. C1 [Knudsen, James E.; Sokol, Gerald H.] US FDA, Div Neurol & Psychiat Drug Products, Drug Evaluat 1, Silver Spring, MD 20993 USA. RP Knudsen, JE (reprint author), US FDA, Div Neurol & Psychiat Drug Products, Drug Evaluat 1, 10903 New Hamshire Ave,Bldg 22,Room 4336, Silver Spring, MD 20993 USA. NR 21 TC 28 Z9 28 U1 0 U2 3 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD APR PY 2008 VL 28 IS 4 BP 540 EP 548 DI 10.1592/phco.28.4.540 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 282WQ UT WOS:000254598300013 PM 18363538 ER PT J AU Yamaguchi, Y Coelho, SG Zmudzka, BZ Takahashi, K Morita, A Beer, JZ Miller, SA Hearing, VJ AF Yamaguchi, Yuji Coelho, Sergio G. Zmudzka, Barbara Z. Takahashi, Kaoruko Morita, Akimichi Beer, Janusz Z. Miller, Sharon A. Hearing, Vincent J. TI Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV exposures SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Yamaguchi, Yuji; Morita, Akimichi] Nagoya City Univ, Grad Sch Med Sci, Dept Geriatr & Environm Dermatol, Nagoya, Aichi, Japan. [Coelho, Sergio G.; Takahashi, Kaoruko; Hearing, Vincent J.] NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. [Zmudzka, Barbara Z.; Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 270 EP 271 PG 2 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700115 ER PT J AU Hoashi, T Muller, J Tamaki, K Ohara, K Hearing, VJ AF Hoashi, Toshihiko Muller, Jacqueline Tamaki, Kunihiko Ohara, Kuniaki Hearing, Vincent J. TI The internal repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for fibrillogenesis but not for intracellular trafficking SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Hoashi, Toshihiko; Tamaki, Kunihiko] Univ Tokyo, Fac Med, Dept Dermatol, Tokyo 113, Japan. [Hearing, Vincent J.] NCI, Natl Inst Hlth, Cell Biol Lab, Bethesda, MD 20892 USA. [Ohara, Kuniaki] Toranomon Gen Hosp, Dept Dermatol, Tokyo 1058470, Japan. [Muller, Jacqueline] US FDA, Div Viral Prod, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 303 EP 303 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700225 ER PT J AU Coelho, SG Zhao, Y Bushar, HF Miller, SA Zmudzka, BZ Hearing, VJ Beer, JZ AF Coelho, Sergio G. Zhao, YanChun Bushar, Harry F. Miller, Sharon A. Zmudzka, Barbara Z. Hearing, Vincent J. Beer, Janusz Z. TI Insights into UV-induced long-lasting pigmentation in human skin SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Meeting Abstract C1 [Coelho, Sergio G.; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhao, YanChun; Bushar, Harry F.; Miller, Sharon A.; Zmudzka, Barbara Z.; Beer, Janusz Z.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD APR PY 2008 VL 21 IS 2 BP 322 EP 322 PG 1 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 289NR UT WOS:000255061700289 ER PT J AU Tuzi, NL Cancellotti, E Baybutt, H Blackford, L Bradford, B Plinston, C Coghill, A Hart, P Piccardo, P Barron, RM Manson, JC AF Tuzi, Nadia L. Cancellotti, Enrico Baybutt, Herbert Blackford, Lorraine Bradford, Barry Plinston, Chris Coghill, Anne Hart, Patricia Piccardo, Pedro Barron, Rona M. Manson, Jean C. TI Host PrP glycosylation: A major factor determining the outcome of prion infection SO PLOS BIOLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; PROTEASE-RESISTANT STATE; MOLECULAR ANALYSIS; BRAIN REGION; SCRAPIE; STRAINS; CONVERSION; CELLS; HETEROGENEITY AB The expression of the prion protein (PrP) is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved. To address the hypothesis that glycosylation of host PrP is a major factor influencing TSE infection, we have inoculated gene-targeted transgenic mice that have restricted N-linked glycosylation of PrP with three TSE strains. We have uniquely demonstrated that mice expressing only unglycosylated PrP can sustain a TSE infection, despite altered cellular location of the host PrP. Moreover we have shown that brain material from mice infected with TSE that have only unglycosylated PrP(Sc) is capable of transmitting infection to wild-type mice, demonstrating that glycosylation of PrP is not essential for establishing infection within a host or for transmitting TSE infectivity to a new host. We have further dissected the requirement of each glycosylation site and have shown that different TSE strains have dramatically different requirements for each of the glycosylation sites of host PrP, and moreover, we have shown that the host PrP has a major role in determining the glycosylation state of de novo generated PrP(Sc). C1 [Tuzi, Nadia L.; Cancellotti, Enrico; Baybutt, Herbert; Blackford, Lorraine; Bradford, Barry; Plinston, Chris; Coghill, Anne; Hart, Patricia; Barron, Rona M.; Manson, Jean C.] Roslin Inst, Neuropathogenesis Unit, Edinburgh, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Manson, JC (reprint author), Roslin Inst, Neuropathogenesis Unit, Edinburgh, Midlothian, Scotland. EM jean.manson@roslin.ed.ac.uk RI Bradford, Barry/B-3783-2013; Barron, Rona/C-7703-2013; OI Bradford, Barry/0000-0002-4007-1685; Barron, Rona/0000-0003-4512-9177; Hart, Patricia/0000-0002-9634-3483 FU Biotechnology and Biological Sciences Research Council [, BBS/E/A/00001655]; Medical Research Council NR 35 TC 52 Z9 52 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2008 VL 6 IS 4 BP 872 EP 882 AR e100 DI 10.1371/journal.pbio.0060100 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 293XL UT WOS:000255368600022 PM 18416605 ER PT J AU Jani, D Nagarkatti, R Beatty, W Angel, R Slebodnick, C Andersen, J Kumar, S Rathore, D AF Jani, Dewal Nagarkatti, Rana Beatty, Wandy Angel, Ross Slebodnick, Carla Andersen, John Kumar, Sanjai Rathore, Dharmendar TI HDP - A novel heme detoxification protein from the malaria parasite SO PLOS PATHOGENS LA English DT Article ID FALCIPARUM FOOD VACUOLE; PLASMODIUM-FALCIPARUM; BETA-HEMATIN; MOLECULAR-MECHANISM; HOST ERYTHROCYTE; GENOME SEQUENCE; POLYMERIZATION; IDENTIFICATION; CHLOROQUINE; SECRETION AB When malaria parasites infect host red blood cells (RBC) and proteolyze hemoglobin, a unique, albeit poorly understood parasite-specific mechanism, detoxifies released heme into hemozoin (Hz). Here, we report the identification and characterization of a novel Plasmodium Heme Detoxification Protein (HDP) that is extremely potent in converting heme into Hz. HDP is functionally conserved across Plasmodium genus and its gene locus could not be disrupted. Once expressed, the parasite utilizes a circuitous "Outbound-Inbound'' trafficking route by initially secreting HDP into the cytosol of infected RBC. A subsequent endocytosis of host cytosol ( and hemoglobin) delivers HDP to the food vacuole (FV), the site of Hz formation. As Hz formation is critical for survival, involvement of HDP in this process suggests that it could be a malaria drug target. C1 [Jani, Dewal; Nagarkatti, Rana; Rathore, Dharmendar] Virginia Tech, Virgina Bioinformat Inst, Blacksburg, VA USA. [Beatty, Wandy] Washington Univ, Sch Med, St Louis, MO USA. [Angel, Ross] Virginia Tech, Dept Geosci, Blacksburg, VA USA. [Slebodnick, Carla] Virginia Tech, Dept Chem, Blacksburg, VA USA. [Andersen, John] Natl Inst Hlth, Lab Malaria & Vector Res, Rockville, MD USA. [Kumar, Sanjai] US FDA, Bethesda, MD 20014 USA. RP Jani, D (reprint author), Virginia Tech, Virgina Bioinformat Inst, Blacksburg, VA USA. EM Rathore@vbi.vt.edu RI Angel, Ross/K-9924-2015 OI Angel, Ross/0000-0003-0861-398X NR 49 TC 73 Z9 74 U1 2 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2008 VL 4 IS 4 AR e1000053 DI 10.1371/journal.ppat.1000053 PG 15 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 294PU UT WOS:000255418800003 PM 18437218 ER PT J AU Zhang, J Brown, RP Shaw, M Vaidya, VS Zhou, YZ Espandiari, P Sadrieh, N Stratmeyer, M Keenan, J Kilty, CG Bonventre, JV Goering, PL AF Zhang, Jun Brown, Ronald P. Shaw, Martin Vaidya, Vishal S. Zhou, Yuzhao Espandiari, Parvaneh Sadrieh, Nakissa Stratmeyer, Melvin Keenan, Joe Kilty, Cormac G. Bonventre, Joseph V. Goering, Peter L. TI Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidney of Gentamicin-, Mercury-, or Chromium-Treated Rats: Relationship to Renal Distributions of iNOS and Nitrotyrosine SO TOXICOLOGIC PATHOLOGY LA English DT Article DE chromium; gentamicin; Kim-1 (kidney injury molecule-1); mercury; nitrotyrosine; RPA-1 (renal papillary antigen-1); RPA-2 (renal papillary antigen-2) ID NITRIC-OXIDE SYNTHASE; INJURY MOLECULE-1; MONOCLONAL-ANTIBODIES; DIABETIC-NEPHROPATHY; PAPILLARY TOXICITY; OXIDATIVE DAMAGE; URINARY ANTIGENS; ACE-INHIBITION; BIOMARKERS; NEPHROTOXICITY AB Immunohistochemical studies for kidney injury molecule-1 (Kim-1), renal papillary antigen-1 (RPA-1), and renal papillary antigen-2 (RPA-2) were conducted to explore their relationship to inducible nitric oxide synthase (iNOS) and nitrotyrosine expression. Male Sprague-Dawley rats were exposed to gentamicin (100 mg/kg/day Gen, sc, for 3 days), mercury (0.25 mg Hg/kg, iv, single dose), or chromium (5 mg Cr/kg, sc, single dose) and kidney tissue was examined 24 hours or 72 hours after the last dose of the nephrotoxicant. Another group of kidneys was evaluated 24 hours after rats were administered 3 daily doses (50, 100, 150, 200, or 300 mg/kg/day) of Gen. Gen- and Cr-treated rats exhibited increased immunoreactivity of Kim-1, RPA-1, and RPA-2 largely in the S1/S2 segments and to a lesser extent in the S3 segments of the proximal tubule of the kidney, whereas Hg-treated rats showed increased immunoreactivity of Kim-1, RPA-1, and RPA-2 in the S3 segments. Up-regulation of Kim-1, RPA-1, and RPA-2 expression correlated with injured tubular epithelial cells and also correlated with immunoreactivity of iNOS and nitrotyrosine. It is possible that iNOS activation with nitrotyrosine production in injured nephron segments may be involved in the induction of Kim-1, RPA-1, and RPA-2 following exposure to nephrotoxicants. C1 [Zhang, Jun] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Brown, Ronald P.; Zhou, Yuzhao; Stratmeyer, Melvin; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Shaw, Martin; Keenan, Joe; Kilty, Cormac G.] Biotrin Int Ltd, Dublin, Ireland. [Vaidya, Vishal S.; Bonventre, Joseph V.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div,Harvard Inst Med, Boston, MA USA. RP Zhang, J (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, HFD 910,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov FU U.S. Food and Drug Administration; Oak Ridge Associated Universities; NIH [DK-039773, DK-072831, DK-074099]; American Heart Association [0535492T] FX The authors thank Ms. Jacintha Tolson for assistance with animal injections and necropsies. This project was supported with funds provided by the U.S. Food and Drug Administration; an appointment to the Research Fellowship Program administered by the Oak Ridge Associated Universities through a contract with the U.S. Food and Drug Administration (YZ); by NIH Grants DK-039773, DK-072831, and DK-074099 (JVB); and a Scientist Development Grant 0535492T from the American Heart Association (VSV). NR 56 TC 25 Z9 28 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD APR PY 2008 VL 36 IS 3 BP 397 EP 409 DI 10.1177/0192623308315832 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UO UT WOS:000267457900005 PM 18441258 ER PT J AU Hotchkiss, CE Bishop, ME Dertinger, SD Slikker, W Moore, MM MacGregor, JT AF Hotchkiss, Charlotte E. Bishop, Michelle E. Dertinger, Stephen D. Slikker, William, Jr. Moore, Martha M. MacGregor, James T. TI Flow cytometric analysis of micronuclei in peripheral blood reticulocytes IV: An index of chromosomal damage in the rhesus monkey (Macaca mulatta) SO TOXICOLOGICAL SCIENCES LA English DT Article DE chromosomal damage; micronucleus; flow cytometry; reticulocytes; blood; bone marrow ID CYTOGENETIC DAMAGE; EFFICIENT METHOD; ERYTHROCYTES; ENUMERATION; MODEL; RAT AB We report evaluation in rhesus monkeys of a flow cytometric procedure (MicroFlow) that has previously been shown to allow assessment of micronucleated reticulocytes (MN-RETs) in the peripheral blood of rats and dogs. Reticulocytes (RETs) were labeled with anti-CD71-fluorescein isothiocyanate, DNA was stained with propidium iodide using RNase treatment, and anti-CD61-phycoerythrin was used to reduce interference from platelets. Flow cytometric data were compared with microscopic scores of peripheral blood and bone marrow using standard acridine orange staining. A single iv administration of cyclophosphamide (CP, 5 mg/kg) induced an approximately 10-fold increase in blood MN-RET frequency, with the peak occurring 2 days after administration. After daily CP treatment to approximate a steady-state condition, the frequency of MN-RETs in peripheral blood was approximately 25% of that in bone marrow, indicating strong selection against MN-RETs. Nonetheless, CP-treated animals exhibited markedly elevated blood MN-RET values (2.45-3.99%, n = 3; compared to a mean baseline of 0.12%, n = 6). These measurements closely reflected the increased frequencies observed in the bone marrow compartment (Spearman correlation coefficient = 0.9856, n = 6). These data suggest that MN-RET measurements in blood are suitable for assessing chemical-induced chromosomal damage and can be readily integrated into routine toxicity tests, allowing genotoxicity data to be obtained as an integral part of toxicity evaluations. Microscopy-based scoring is challenging due to the low frequency of RETs and MN-RET in monkeys, but sufficient numbers of cells are easily scored with the flow cytometric procedure. C1 [MacGregor, James T.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. [Hotchkiss, Charlotte E.] Bionet Corp, Jefferson, AR 72079 USA. [Bishop, Michelle E.; Slikker, William, Jr.; Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Dertinger, Stephen D.] Litron Labs, Rochester, NY 14623 USA. RP MacGregor, JT (reprint author), Toxicol Consulting Serv, 201 Nomini Dr, Arnold, MD 21012 USA. EM jtmacgregor@earthlink.net NR 25 TC 18 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2008 VL 102 IS 2 BP 352 EP 358 DI 10.1093/toxsci/kfn013 PG 7 WC Toxicology SC Toxicology GA 274LZ UT WOS:000254004100014 PM 18211907 ER PT J AU Yan, J Xia, Q Chou, MW Fu, PP AF Yan, J. Xia, Q. Chou, M. W. Fu, P. P. TI Metabolic activation of retronecine and retronecine N-oxide - formation of DHP-derived DNA adducts SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE DNA adduct; pyrollizidine alkaloid; retronecine; retronecine N-oxide ID FORMATION IN-VIVO; PYRROLIZIDINE ALKALOIDS; RIDDELLIINE; RATS; CARCINOGENICITY; MICE AB We have previously reported that metabolism of a series of pyrrolizidine alkaloids in vitro and in vivo generated a set of (+/-)6,7-dihydro-7-hydroxy-l-hydroxymethyl-5H-pyrrolizine (DHP)-derived DNA adducts. It has also been shown that the levels of the DHP-derived DNA adduct formation correlated closely with the tumorigenic potencies of the mice fed with different doses of riddelliine. Retronecine is the necine base and the Structurally smallest chemical of the retronecine-type pyrrolizidine alkaloids. Although it has been reported that microsomal metabolism of retronecine generated DHP Lis a metabolite, it was yet not known whether metabolism of retronecine in vivo could generate DHP-derived DNA adducts and if formed, whether or not the levels of DNA adducts were comparable with those formed from the other tumorigenic retronecine-type pyrrolizidine alkaloids, such as riddelliine, retrorsine, and monocrotaline. In this investigation, the in-vitro and in-vivo metabolic activation of retronecine was studied. Rat liver microsomal metabolism of retronecine in the presence of calf thymus DNA resulted in the formation of a set of DHP-DNA adducts. The metabolism of retronecine N-oxide under similar conditions also Formed the similar set of DHP-DNA adducts. The level of DNA adducts from retronecine was enhanced when metabolism by liver microsomes from phenobarbital (PB)-induced rats were used. The DHP DNA adducts were also found ill the liver DNA of female F344 rats treated with retronecine or retronecine N-oxide. The highest level of the total DHP DNA adducts was found in liver DNA from the rats treated with dehydroretronecine (DHR). The order of the levels of DNA adducts in the liver DNA samples from rats treated with various pyrrolizidine alkaloids was: DHR > riddelliine > riddelliine N-oxide >> retronecine > retronecine N-oxide. The results indicate that 1) retronecine call be metabolized to form DHP by rat liver microsomal enzymes and interacts with DNA to produce DHP-DNA adducts and 2) retronecine N-oxide undergoes the biotransformation to the parent compound, retronecine. The results from this and Our previous findings strongly suggest that formation of DHP-DNA adducts may be a potential biomarker for pyrrolizidine alkaloid carcinogenesis. Toxicology, and Industrial Health 2008; 24: 181-188. C1 [Yan, J.; Xia, Q.; Chou, M. W.; Fu, P. P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov NR 25 TC 17 Z9 19 U1 1 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD APR PY 2008 VL 24 IS 3 BP 181 EP 188 DI 10.1177/0748233708093727 PG 8 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 372PA UT WOS:000260912300007 PM 18842697 ER PT J AU Kornilayev, BA Alterman, MA AF Kornilayev, Boris A. Alterman, Michail A. TI Utility of polyclonal antibodies targeted toward unique tryptic peptides in the proteomic analysis of cytochrome P450 isozymes SO TOXICOLOGY IN VITRO LA English DT Article DE CYP-cytochrome(s) p450; proteomics; MALDI-TOF; anti-peptide antibodies ID MESSENGER-RNA; GENE-EXPRESSION; PROTEIN; PARADIGM; CANCER AB P450s are key enzymes responsible for biotransformation of numerous endogenous and exogenous compounds and are located in almost every tissue. This superfamily is the largest group of enzymes (>6000) that share a high degree of similarity in protein sequence. The human genome contains 57 CYP genes and 58 pseudogenes. A major gap exists in our knowledge about differences in CYP expression on a protein level. DNA and mRNA information are not sufficient because transcription and particularly translation events are not necessarily correlated with levels of expressed proteins. The data reported in this study complete the framework of an integrated protcomic method for the simultaneous qualitative and quantitative analysis of CYP isozyme composition using MALDI-TOF-MS and immunochernistry that has been developed in our laboratory over the last several years (Alterman et al., 2005a,b) and is based on the fact that each P450 isozyme possesses unique tryptic peptide(s) (UTP) that could be used for differential analysis of human CYP expression. Here we demonstrate that three different immunochemical techniques (ELISA, Western blot, and peptide affinity enrichment on magnetic beads with attached antibodies) have potential to be incorporated in an integrated proteomic method combining mass spectrometry and immunochernistry. Fundamentally, this approach is based on the measurement of the same chemical entity (isozyme-specific UTP) in the tryptic digest by two orthogonal analytical techniques, mass spectrometry and immunochemistry. The application of this approach is illustrated with two human CYP isozymes - CYPIA2 and CYP2E1. Published by Elsevier Ltd. C1 [Alterman, Michail A.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kornilayev, Boris A.] Univ Kansas, Biochem Res Serv Lab, Lawrence, KS 66047 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29A,Room 2D12,HFM-735, Bethesda, MD 20892 USA. EM Michail.Alterman@fda.hhs.gov NR 21 TC 5 Z9 6 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD APR PY 2008 VL 22 IS 3 BP 779 EP 787 DI 10.1016/j.tiv.2007.12.001 PG 9 WC Toxicology SC Toxicology GA 291AO UT WOS:000255164900026 PM 18207356 ER PT J AU de Oliveira, EJ Kanamura, H Takei, K Hirata, RDC Valli, LCP Nguyen, NY Rodrigues, IDC de Jesus, AR Hirata, MH AF de Oliveira, Edward Jose Kanamura, HerminiaYohko Kioko Takei Hirata, Rosario Dominguez Crespo Valli, Luiz Carlos Pedrosa Nguyen, Nga Yen Rodrigues, Izabel de Carvalho de Jesus, Amelia Ribeiro Hirata, Mario Hiroyuki TI Synthetic peptides as an antigenic base in an ELISA for laboratory diagnosts of schistosomiasis mansoni SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE Schistosoma mansoni; diagnosis; SeroLogy; ELISA; synthetic peptides; sensitivity and specificity ID ANTIBODIES; INFECTION; SM31; CYSTICERCOSIS; PROTEINS; CHAGAS; SERA AB A pool of five synthetic peptides was used as an antigenic base in an ELISA (ELISA-Pp) for laboratory diagnosis of Schistosoma mansoni. Serum samples were obtained from individuals with acute (n = 23) and chronic (n = 30) schistosomiasis, with other parasitoses (n = 39) or without parasitic infections (n = 100). ELISA-Pp was compared with other immunoenzymatic methods for detection of IgM (IgM-ELISA) or IgG (IgG-ELISA) as well as an immunofluorescence test for detection of IgM antibodies (IgM-IFT). The sensitivity and specificity of ELISA-Pp was 86.8% and 94.2% when tested on the schistosomiasis group and the non-schistosomiasis group, respectively. Comparison of ELISA-Pp with other serological methods resulted in K concordance indices varying from 0.59 to 0.75. Evaluation of anti-peptide IgG antibodies showed higher Levels in patients with acute compared with chronic schistosomiasis (P = 0.001). ELISA-Pp showed satisfactory sensitivity and high specificity and may constitute a potentially useful method for laboratory diagnosis of schistosomiasis mansoni. (c) 2007 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved. C1 [de Oliveira, Edward Jose; Kanamura, HerminiaYohko; Kioko Takei; Hirata, Rosario Dominguez Crespo; Hirata, Mario Hiroyuki] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin, BR-05508900 Sao Paulo, SP, Brazil. [Kanamura, HerminiaYohko] Univ Taubate, Inst Basico Biociencias, Taubate, SP, Brazil. [Valli, Luiz Carlos Pedrosa] Curso Farm, Fac Brasileira, Vitoria, ES, Brazil. [Nguyen, Nga Yen] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Rodrigues, Izabel de Carvalho] Inst Evandro Chagas, Secretaria Vigilancia Saude MS, Belem, Para, Brazil. [de Jesus, Amelia Ribeiro] Univ Fed Sergipe, Dept Med, Univ Hosp, Mol Biol Lab, Sergipe, Brazil. RP de Oliveira, EJ (reprint author), Avenida Lime,1715 Barro Preto, BR-30190002 Belo Horizonte, MG, Brazil. EM edwardjo@cpqrr.fiocruz.br RI Hirata, Mario/D-3593-2012; Hirata, Rosario/A-7284-2011; Imunologia, Inct/I-2124-2013; Hirata, Mario/C-9718-2013 NR 27 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD APR PY 2008 VL 102 IS 4 BP 360 EP 366 DI 10.1016/j.trstmh.2007.11.008 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 289GR UT WOS:000255043500013 PM 18314149 ER PT J AU Wilson, C Fishman, JA Sykes, M AF Wilson, Carolyn Fishman, Jay A. Sykes, Megan TI Tribute to Eda T. Bloom, PhD SO XENOTRANSPLANTATION LA English DT Biographical-Item C1 [Wilson, Carolyn] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20014 USA. [Fishman, Jay A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Infect Dis Div, Transplant Infect Dis & Compromised Hosp Program, Boston, MA USA. [Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02115 USA. RP Wilson, C (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Transfer & Immunogenic Branch, Bethesda, MD 20014 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD APR PY 2008 VL 15 IS 2 BP 69 EP 71 DI 10.1111/j.1399-3089.2008.00448.x PG 3 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 294QR UT WOS:000255421100001 ER PT J AU Phogat, S Svehla, K Tang, M Spadaccini, A Muller, J Mascola, J Berkower, I Wyatt, R AF Phogat, S. Svehla, K. Tang, M. Spadaccini, A. Muller, J. Mascola, J. Berkower, I. Wyatt, R. TI Analysis of the human immunodeficiency virus type 1 gp41 membrane proximal external region arrayed on hepatitis B surface antigen particles SO VIROLOGY LA English DT Article DE HIV-1; neutralizing antibodies; envelope glycoproteins; gp41; particles ID ENVELOPE GLYCOPROTEINS; HIV-1 ENTRY; NEUTRALIZING EPITOPE; FALCIPARUM-MALARIA; ANTIBODY-RESPONSES; CELL RESPONSES; VACCINE; PROTEIN; FUSION; IMMUNOGENICITY AB Vaccine immunogens derived from the envelope glycoproteins of the human immunodeficiency virus type 1 (HIV-1) that elicit broad neutralizing antibodies remain an elusive goal. The highly conserved 30 amino-acid membrane proximal external region (MPER) of HIV gp41 contains the hydrophobic epitopes for two rare HIV-1 broad cross-reactive neutralizing antibodies, 2F5 and 4E10. Both these antibodies possess relatively hydrophobic HCDR3 loops and demonstrate enhanced binding to their epitopes in the context of the native gp160 precursor envelope glycoprotein by the intimate juxtaposition of a lipid membrane. The hepatitis B surface antigen (HBsAg) S1 protein forms nanoparticles that can be utilized both as an immunogenic array of the MPER and to provide the lipid environment needed for enhanced 2175 and 4E10 binding. We show that recombinant HBsAg particles with MPER (HBsAg-MPER) appended at the C-terminus of the S1 protein are recognized by 2F5 and 4E10 with high affinity compared to positioning the MPER at the N-terminus or the extracellular loop (ECL) of S1. Addition of C-terminal hydrophobic residues derived from the HIV-1 Env transmembrane region further enhances recognition of the MPER by both 2F5 and 4E10. Delipidation of the HBsAg-MPER particles decreases 2F5 and 4E10 binding and subsequent reconstitution with synthetic lipids restores optimal binding. Inoculation of the particles into small animals raised cross-reactive antibodies that recognize both the MPER and HIV-1 gp160 envelope glycoproteins expressed on the cell surface; however, no neutralizing activity could be detected. Prime:Boost immunization of the HBsAg-MPER particles in sequence with HIV envelope glycoprotein proteoliposomes (Env-PLs) did not raise neutralizing antibodies that could be mapped to the MPER region. However, the Env-PLs did raise anti-Env antibodies that had the ability to neutralize selected HIV-1 isolates. The first generation HBsAg-MPER particles represent a unique means to present HIV-1 envelope glycoprotein neutralizing determinants to the immune system. Published by Elsevier Inc. C1 [Phogat, S.; Svehla, K.; Tang, M.; Mascola, J.; Wyatt, R.] NIAID, Struct Virol Sect, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Spadaccini, A.; Muller, J.; Berkower, I.] US FDA, Ctr Biol, Bethesda, MD USA. RP Wyatt, R (reprint author), NIAID, Struct Virol Sect, NIH, Vaccine Res Ctr, 40 Covent Dr,Bldg 40,Room 4512, Bethesda, MD 20892 USA. EM richardwyatt@nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 52 TC 48 Z9 48 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 2008 VL 373 IS 1 BP 72 EP 84 DI 10.1016/j.virol.2007.11.005 PG 13 WC Virology SC Virology GA 279JA UT WOS:000254350300008 PM 18155743 ER PT J AU Pal, G Dutta, A Mitra, K Grace, MS Romanczyk, TB Wu, X Chakrabarti, K Anders, J Gorman, E Waynant, RW Tata, DB AF Pal, Gopalendu Dutta, Ashim Mitra, Kunal Grace, Michael S. Romanczyk, Tara B. Wu, Xingjia Chakrabarti, Kristi Anders, Juanita Gorman, Erik Waynant, Ronald W. Tata, Darrell B. TI Effect of low intensity laser interaction with human skin fibroblast cells using fiber-optic nano-probes (vol 86, pg 252, 2007) SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Correction C1 [Pal, Gopalendu; Dutta, Ashim; Mitra, Kunal] Florida Inst Technol, Dept Mech & Aeronaut Engn, Melbourne, FL 32901 USA. [Grace, Michael S.] Florida Inst Technol, Dept Biol Sci, Melbourne, FL 32901 USA. [Romanczyk, Tara B.; Wu, Xingjia; Chakrabarti, Kristi; Anders, Juanita] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Chakrabarti, Kristi; Gorman, Erik; Waynant, Ronald W.; Tata, Darrell B.] US FDA, Rockville, MD 20857 USA. RP Mitra, K (reprint author), Florida Inst Technol, Dept Mech & Aeronaut Engn, 150 W Univ Blvd, Melbourne, FL 32901 USA. EM kmitra@fit.edu RI Mitra, Kunal/C-6560-2016 OI Mitra, Kunal/0000-0002-7277-4908 NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD MAR 28 PY 2008 VL 90 IS 3 BP 207 EP 207 DI 10.1016/j.jphotobiol.2008.01.004 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 289WA UT WOS:000255083400008 ER PT J AU Noonan, GO Begley, TH Diachenko, GW AF Noonan, Gregory O. Begley, Timothy H. Diachenko, Gregory W. TI Semicarbazide formation in flour and bread SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE azodicarbonamide; semicarbazide; bread additive; formation ID PRODUCTS AB Azodicarbonamide, an approved food additive, is commonly used as a flour additive and dough conditioner in the United States and Canada. A number of researchers have clearly established a link between the use of azodicarbonamide and semicarbazide contamination in commercial bread products. However, all of these studies have primarily focused on the final baked product and have not extensively investigated the processing and conditions that affect the final semicarbazide levels. In this study, a previously developed method for measuring free semicarbazide in bread was applied to dough samples during the mixing and kneading process. Additionally, flour and bread samples were spiked with biurea or azodicarbonamide to help elucidate semicarbazide formation pathways. The results showed that semicarbazide was not formed as a byproduct of azodicarbonamide decomposition to biurea, which occurs upon the addition of water. Indeed, semicarbazide was not detected after room temperature or elevated temperature dough maturation, but only after baking. It was concluded that although azodicarbonamide is the initial starting material, semicarbazide formation in bread occurs through a stable intermediate, biurea. C1 [Noonan, Gregory O.; Begley, Timothy H.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Noonan, GO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM gregory.noonan@fda.hhs.gov NR 9 TC 12 Z9 17 U1 2 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 26 PY 2008 VL 56 IS 6 BP 2064 EP 2067 DI 10.1021/jf073198g PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 276XM UT WOS:000254177000036 PM 18303820 ER PT J AU Goodsaid, FM Frueh, FW Mattes, W AF Goodsaid, Federico M. Frueh, Felix W. Mattes, William TI Strategic paths for biomarker qualification SO TOXICOLOGY LA English DT Article DE biomarkers; consortia ID SURROGATE END-POINTS; VALIDATION AB Biomarkers may be qualified using different qualification processes. A passive approach for qualification has been to accept the end of discussions in the scientific literature as an indication that a biomarker has been accepted. An active approach to qualification requires development of a comprehensive process by which a consensus may be reached about the qualification of a biomarker. Active strategies for qualification include those associated with context-independent as well as context-dependent qualifications. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Goodsaid, Federico M.; Frueh, Felix W.] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, Silver Spring, MD 20903 USA. RP Goodsaid, FM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Federico.Goodsaid@fda.hhs.gov NR 11 TC 64 Z9 66 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 20 PY 2008 VL 245 IS 3 BP 219 EP 223 DI 10.1016/j.tox.2007.12.023 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 282WV UT WOS:000254598900007 PM 18280028 ER PT J AU Straight, TM Ottolini, MG Prince, GA Eichelberger, MC AF Straight, Timothy M. Ottolini, Martin G. Prince, Gregory A. Eichelberger, Maryna C. TI Antibody contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats SO VIROLOGY JOURNAL LA English DT Article ID VIRUS-INFECTION; CROSS-PROTECTION; VACCINE; MICE; IMMUNITY; NEURAMINIDASE; LYMPHOCYTES; REQUIRES; ANTIGEN; CELLS AB Background: Influenza virus infection or vaccination evokes an antibody response to viral hemagglutinin ( HA) and neuraminidase (NA) surface glycoproteins, which results in immunity against influenza A viruses of the same HA and NA subtype. A heterosubtypic immune response that offers some protection against different influenza A subtypes has been suggested from epidemiologic studies in human influenza outbreaks, and has been induced in experimental animal models. Original studies of such cross-protection showed that cytotoxic T lymphocytes (CTL) protect H3N2-immune mice from a lethal H1N1 infection. More recent studies in mice demonstrate that antibodies also contribute to heterosubtypic immunity (HSI). We previously demonstrated that HSI in cotton rats ( Sigmodon hispidus) is characterized by protection of H3N2-immune animals from influenza H1N1-induced increase in respiratory rate (tachypnea). Alternatively, H1N1-immune animals are protected from H3N2-induced tachypnea. The experiments described in this report were designed to elucidate the immune mechanism that prevents this very early sign of disease. Results: Our results show that cotton rats provided with H1N1-immune serum prior to challenge with an H3N2virus were protected from influenza-associated tachypnea, with the degree of protection correlating with the antibody titer transferred. Immunization with an inactivated preparation of virus delivered intramuscularly also provided some protection suggesting that CTL and/or mucosal antibody responses are not required for protection. Antibodies specific for conserved epitopes present on the virus exterior are likely to facilitate this protection since prophylactic treatment of cotton rats with anti-M2e ( the extracellular domain of M2) but not anti-nucleoprotein (NP) reduced virus-induced tachypnea. Conclusion: In the cotton rat model of heterosubtypic immunity, humoral immunity plays a role in protecting animals from influenza-induced tachypea. Partial protection against respiratory disease caused by different influenza A subtypes can be attained with either live virus administered intranasally or inactivated virus delivered intramuscularly suggesting that either vaccine regimen may provide some protection against potential pandemic outbreaks in humans. C1 [Eichelberger, Maryna C.] US FDA, CBER, Bethesda, MD 20014 USA. [Straight, Timothy M.] Brooke Army Med Ctr, Dept Clin Invest, Ft Sam Houston, TX 78234 USA. [Straight, Timothy M.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Ottolini, Martin G.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. [Prince, Gregory A.] Virion Syst Inc, Rockville, MD USA. RP Eichelberger, MC (reprint author), US FDA, CBER, Bethesda, MD 20014 USA. EM Timothy.Straight@amedd.army.mil; mottolini@usuhs.mil; gprince@erols.com; Maryna.Eichelberger@fda.hhs.gov NR 22 TC 17 Z9 19 U1 0 U2 1 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 MAR 20 PY 2008 VL 5 AR 44 DI 10.1186/1743-422X-5-44 PG 9 WC Virology SC Virology GA 286RP UT WOS:000254864000001 PM 18355405 ER PT J AU Southworth, MR Kortepeter, C Hughes, A AF Southworth, Mary Ross Kortepeter, Cindy Hughes, Alice TI Nonbenzodiazepine hypnotic use and cases of "sleep driving" SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID SOMNAMBULISM C1 [Southworth, Mary Ross; Kortepeter, Cindy; Hughes, Alice] US FDA, Silver Spring, MD 20993 USA. RP Southworth, MR (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 2 TC 5 Z9 5 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 18 PY 2008 VL 148 IS 6 BP 486 EP 487 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 279KT UT WOS:000254354800023 PM 18347361 ER PT J AU Chen, ML AF Chen, Mei-Ling TI Lipid excipients and delivery systems for pharmaceutical development: A regulatory perspective SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY OCT 29-NOV 02, 2006 CL San Antonio, TX SP Amer Assoc Pharmaceut Sci DE lipid-based dosage form; lipid-based formulation; modified release; liposome; in vitro release; therapeutic equivalence; bioequivalence; pharmaceutical equivalence; food and drug administration ID WATER-SOLUBLE DRUGS; IN-VITRO DIGESTION; PROTEIN-SURFACTANT INTERACTIONS; BIORELEVANT DISSOLUTION MEDIA; CACO-2 CELL MONOLAYERS; P-GLYCOPROTEIN; LIPOPHILIC DRUGS; ORAL ABSORPTION; SOLUBILIZATION BEHAVIOR; CLASSIFICATION-SYSTEM AB The use of lipid-based dosage forms for enhancement of drug absorption or delivery has drawn considerable interest from pharmaceutical scientists. The unique characteristics of these dosage forms, however, present significant challenges to pharmaceutical industry and regulatory agencies in many, ways. For example, safety assessment is necessary when the use of a new lipid excipient is considered. An important question for lipid formulation is whether the drug remains in solubilised form along the gastrointestinal (GI) tract after it is administered. Certain lipid excipients and surfactants have been reported to change intestinal permeability or interfere with enzyme/transporter activity, thereby affecting drug bioavailability. The potential influence of biopharmaceutical and/or pathophysiological factors on the drug or lipid excipient(s) needs to be explored. For a complex lipid-based dosage form, the conventional in vitro dissolution methods may not be appropriate for predicting in vivo performance in view of the convoluted GI processing of the lipid vehicle and formulation. Of paramount importance is to identify any gaps in the scientific understanding of lipid-based dosage forms so that regulatory issues can be addressed. More mechanistic studies should be encouraged to facilitate a better understanding of the pharmaceutical characteristics of lipid formulations and complex interactions between lipid excipient, drug and physiological environment. This review discusses some regulatory considerations in the use of lipid excipients and delivery systems for pharmaceutical development. Implications in the regulatory determination of pharmaceutical equivalence, bioequivalence and therapeutic equivalence are also illustrated. Published by Elsevier B.V. C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 3508, Silver Spring, MD 20993 USA. EM meiling.chen@lda.hhs.gov RI Sanguansri, Luz/B-6630-2011 OI Sanguansri, Luz/0000-0003-1908-7604 NR 111 TC 76 Z9 78 U1 1 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAR 17 PY 2008 VL 60 IS 6 BP 768 EP 777 DI 10.1016/j.addr.2007.09.010 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 277MQ UT WOS:000254217300013 PM 18077051 ER PT J AU Hube, AM Lachenbruch, PA Dugan, EM Miller, FW Rider, LG AF Hube, Adam M. Lachenbruch, Peter A. Dugan, Elizabeth M. Miller, Frederick W. Rider, Lisa G. CA Juvenile Dermatomyositis Dis Activ TI Alternative scoring of the cutaneous assessment tool in juvenile dermatomyositis: Results using abbreviated formats SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; VALIDATED DISEASE-ACTIVITY; MYOSITIS ASSESSMENT SCALE; MUSCLE FUNCTION; DAMAGE INDEXES; RELIABILITY AB Objective. The Cutaneous Assessment Tool (CAT) is a comprehensive, semiquantitative tool for the assessment of skin disease in juvenile dermatomyositis (DM). The goal of this study was to determine whether alternative scoring methods would shorten the CAT without compromising its measurement characteristics. Methods. A total of 113 children with juvenile DM were assessed at baseline; 94 were assessed again 7-9 months later. Interrater reliability, internal consistency, construct validity, and responsiveness were obtained using the original scoring method and 2 alternative methods: the maximum and binary scoring methods. Results. Spearman's correlations of the maximum and binary methods with the original were both 0.98 (P < 0.0001) for the CAT activity score, and 0.96 and 0.98, respectively (P < 0.0001), for the CAT damage score. Values obtained for interrater reliability, internal consistency, construct validity, and responsiveness were similar for all 3 scoring methods. Although there was a trend toward the maximum method having higher interrater reliability and the binary method having higher responsiveness, the confidence intervals were overlapping and no statistically significant differences were observed. Correlation coefficients for the 3 scoring methods with other measures of myositis disease activity and damage were very similar. Conclusion. The maximum and binary methods of scoring the CAT have measurement characteristics similar to the original method. Adoption of one of these abbreviated scoring methods should increase its acceptability to clinicians and researchers. C1 [Hube, Adam M.] IWK Hlth Ctr, Div Pediat Rheumatol, Halifax, NS B3K 6R8, Canada. [Hube, Adam M.] Dalhousie Univ, Halifax, NS B3K 6R8, Canada. [Lachenbruch, Peter A.] US FDA, Dept Hlth & Human Serv, Rockville, MD USA. [Dugan, Elizabeth M.] Washington Hosp Ctr, Washington, DC 20010 USA. [Miller, Frederick W.; Rider, Lisa G.] NIH, Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Bethesda, MD USA. RP Hube, AM (reprint author), IWK Hlth Ctr, Div Pediat Rheumatol, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM adam.huber@iwk.nshealth.ca OI Miller, Frederick/0000-0003-2831-9593; Rider, Lisa/0000-0002-6912-2458 FU Intramural NIH HHS [Z01 ES101081-06, Z99 ES999999] NR 12 TC 13 Z9 15 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD MAR 15 PY 2008 VL 59 IS 3 BP 352 EP 356 DI 10.1002/art.23313 PG 5 WC Rheumatology SC Rheumatology GA 272IA UT WOS:000253851900009 PM 18311761 ER PT J AU Miller, HI AF Miller, Henry I. TI Designing improved humans SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 [Miller, Henry I.] US FDA, Rockville, MD 20857 USA. EM miller@hoover.stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1935-472X J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD MAR 15 PY 2008 VL 28 IS 6 BP 6 EP + PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 277FK UT WOS:000254197900003 ER PT J AU Xu, LX Fang, H Frucht, DM AF Xu, Lixin Fang, Hui Frucht, David M. TI Anthrax lethal toxin increases superoxide production in murine neutrophils via differential effects on MAPK signaling pathways SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE ACTIVATION; PROTEIN-KINASE KINASE; ACTIN-BASED MOTILITY; BACILLUS-ANTHRACIS; TNF-ALPHA; CELLS; PATHOGENESIS; RELEASE; DISEASE; SUSCEPTIBILITY AB The combination of lethal factor and its receptor-binding partner, protective Ag, is termed lethal toxin (LT) and has critical pathogenic activity during infection with Bacillus anthracis. We herein report that anthrax LT binds and enters murine neutrophils, leading to the cleavage of mitogen-activated protein kinase kinase/MEK/MAPKK 1-4 and 6, but not mitogen-activated protein kinase kinase 5 and 7. Anthrax LT treatment of neutrophils disrupts signaling to downstream MAPK targets in response to TLR stimulation. Following anthrax LT treatment, ERK family and p38 phosphorylation are nearly completely blocked, but signaling to JNK family members persists in vitro and ex vivo. In contrast to previous reports involving human neutrophils, anthrax LT treatment of murine neutrophils increases their production of superoxide in response to PMA or TLR stimulation in vitro or ex vivo. Although this enhanced superoxide production correlates with effects due to the LT-induced blockade of ERK signaling, it requires JNK signaling that remains largely intact despite the activity of anthrax LT. These findings reveal a previously unrecognized mechanism through which anthrax LT supports a critical proinflammatory response of murine neutrophils. C1 [Xu, Lixin; Fang, Hui; Frucht, David M.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bldg 29B,Room 3NN22, Bethesda, MD 20892 USA. EM david.frucht@fda.hhs.gov NR 50 TC 14 Z9 14 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2008 VL 180 IS 6 BP 4139 EP 4147 PG 9 WC Immunology SC Immunology GA 324GS UT WOS:000257506600063 PM 18322225 ER PT J AU Hviid, A Rubin, S Muhlemann, K AF Hviid, Anders Rubin, Steven Muehlemann, Kathrin TI Mumps SO LANCET LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; IDIOPATHIC THROMBOCYTOPENIC PURPURA; ENCEPHALOMYELITIS FOLLOWING MUMPS; MATERNAL VIRUS DISEASES; CONTINUOUS CELL-LINES; JERYL-LYNN-MORATEN; REAL-TIME PCR; ASEPTIC-MENINGITIS; ENDOCARDIAL FIBROELASTOSIS; RUBELLA VACCINATION AB Mumps is a common childhood infection caused by the mumps virus. The hallmark of infection is swelling of the parotid gland. Aseptic meningitis and encephalitis are common complications of mumps together with orchitis and oophoritis, which can arise in adult men and women, respectively; other complications include deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid swelling; however, this feature is not present in all cases of mumps and can also occur in various other disorders. Laboratory diagnosis is based on isolation of virus, detection of viral nucleic acid, or serological confirmation (generally presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of mumps vaccine is about 80% effective against the disease. Routine vaccination has proven highly effective in reducing the incidence of mumps, and is presently used by most developed countries; however, there have been outbreaks of disease in vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006 the American midwest had several outbreaks. In both countries, the largest proportion of cases was in young adults. In the UK, susceptible cohorts too old to have been vaccinated and too young to have been exposed to natural infections were the primary cause of the mumps epidemic. In the USA, effectiveness and uptake in combination appear not to have been sufficient to obtain herd immunity for mumps in populations such as college students. C1 [Hviid, Anders] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20982 USA. [Muehlemann, Kathrin] Univ Bern, Bern, Switzerland. RP Hviid, A (reprint author), Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. EM aii@ssi.dk NR 186 TC 140 Z9 146 U1 0 U2 32 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 MAR 15 PY 2008 VL 371 IS 9616 BP 932 EP 944 DI 10.1016/S0140-6736(08)60419-5 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 275FH UT WOS:000254056800030 PM 18342688 ER PT J AU Taylor, AD Ladd, J Etheridge, S Deeds, J Hall, S Jiang, SY AF Taylor, Allen D. Ladd, Jon Etheridge, Stacey Deeds, Jonathan Hall, Sherwood Jiang, Shaoyi TI Quantitative detection of tetrodotoxin (TTX) by a surface plasmon resonance (SPR) sensor SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE surface plasmon resonance (SPR); tetrodotoxin (TTX); pufferfish; neurotoxin; seafood toxin; antibody inhibition assay ID SELF-ASSEMBLED MONOLAYERS; POISONED PATIENTS; SODIUM-CHANNEL; IMMUNOASSAY; BIOSENSORS; CHROMATOGRAPHY; SENSITIVITY; DERIVATIVES; SAMPLES; URINE AB We report the quantitative antibody-based detection of a low-molecular weight molecule tetrodotoxin (TTX) (similar to 319 Da) by inhibition assay with a surface plasmon resonance (SPR) sensor. A novel anti-TTX antibody sensing surface was developed by chemically immobilizing TTX on a gold film with a mixed self assembled monolayer (SAM) consisting of amine terminated oligo-ethylene glycol (OEG) alkanethiol and a hydroxyl terminated OEG alkanethiol. The ratio of amine to hydroxyl terminated OEG alkanethiols and TTX immobilization chemistry were optimized to maximize specific anti-TTX binding, while minimizing non-specific binding. The calibration curves are reported for two antibody concentrations incubated with samples of varying TTX concentrations ranging from 0.01 to 10,000 ng/mL. The detection limit for TTX is defined as IC20 (20% inhibitory concentration), which is similar to 0.3 ng/mL in this work. The corresponding calibration curve has a characteristic IC50 (50% inhibitory concentration) of similar to 6 ng/mL. The ability to reproducibly regenerate the TTX-immobilized surface was also demonstrated. (C) 2007 Elsevier B.V. All rights reserved. C1 [Etheridge, Stacey; Deeds, Jonathan; Hall, Sherwood] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Taylor, Allen D.; Ladd, Jon; Jiang, Shaoyi] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. RP Etheridge, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM stacey.etheridge@fda.hhs.gov; sjiang@u.washington.edu OI DeGrasse, Stacey/0000-0001-7808-4193 NR 31 TC 35 Z9 36 U1 2 U2 19 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD MAR 14 PY 2008 VL 130 IS 1 BP 120 EP 128 DI 10.1016/j.snb.2007.07.136 PG 9 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 284CD UT WOS:000254681900020 ER PT J AU Proestel, S AF Proestel, Scott TI Subgroup analyses in clinical trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Proestel, Scott] US FDA, Silver Spring, MD 20993 USA. RP Proestel, S (reprint author), US FDA, Silver Spring, MD 20993 USA. EM scott.proestel@fda.hhs.gov NR 1 TC 2 Z9 2 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 MAR 13 PY 2008 VL 358 IS 11 BP 1199 EP 1199 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 272RK UT WOS:000253877200027 PM 18337613 ER PT J AU Lopez, MI Pettis, JS Smith, IB Chu, PS AF Lopez, Mayda I. Pettis, Jeffery S. Smith, I. Barton Chu, Pak-Sin TI Multiclass determination and confirmation of antibiotic residues in honey using LC-MS/MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE antibiotics; honey; multiclass; multiresidue; LC-MS/MS ID TANDEM MASS-SPECTROMETRY; SULFONAMIDES; FUMAGILLIN; MS AB A multiclass method has been developed for the determination and confirmation in honey of tetracyclines (chlortetracycline, doxycycline, oxytetracycline, and tetracycline), fluoroquinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, and sarafloxacin), macrolides (tylosin), lincosamides (lincomycin), aminoglycosides (streptomycin), sulfonamides (sulfathiazole), phenicols (chloramphenicol), and fumagillin residues using liquid chromatography tandem mass spectrometry (LC-MS/ MS). Erythromycin (a macrolide) and monensin (an ionophore) can be detected and confirmed but not quantitated. Honey samples (similar to 2 g) are dissolved in 10 mL of water and centrifuged. An aliquot of the supernatant is used to determine streptomycin. The remaining supernatant is filtered through a fine-mesh nylon fabric and cleaned up by solid phase extraction. After solvent evaporation and sample reconstitution, 15 antibiotics are assayed by LC-MS/MS using electrospray ionization (ESI) in positive ion mode. Afterward, chloramphenicol is assayed using ESI in negative ion mode. The method has been validated at the low part per billion levels for most of the drugs with accuracies between 65 and 104% and coefficients of variation less than 17%. The evaluation of matrix effects caused by honey of different floral origin is presented. C1 [Lopez, Mayda I.; Chu, Pak-Sin] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Pettis, Jeffery S.; Smith, I. Barton] USDA, Agr Res Serv, Bee Res Lab, Beltsville, MD 20705 USA. RP Lopez, MI (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM mayda.lopez@fda.hhs.gov NR 16 TC 83 Z9 88 U1 4 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 12 PY 2008 VL 56 IS 5 BP 1553 EP 1559 DI 10.1021/jf073236w PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 270NT UT WOS:000253728200005 PM 18257525 ER PT J AU Daugherty, CK Ratain, MJ Emanuel, EJ Farrell, AT Schilsky, RL AF Daugherty, Christopher K. Ratain, Mark J. Emanuel, Ezekiel J. Farrell, Ann T. Schilsky, Richard L. TI Ethical, scientific, and regulatory perspectives regarding the use of placebos in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID CELL LUNG-CANCER; PHASE-III TRIAL; ADVANCED PANCREATIC-CANCER; RANDOMIZED DISCONTINUATION TRIAL; REFRACTORY PROSTATE-CANCER; COOPERATIVE-ONCOLOGY-GROUP; CISPLATIN-INDUCED NAUSEA; ACTIVE-CONTROL TRIALS; DOUBLE-BLIND; 1ST-LINE CHEMOTHERAPY AB Purpose To examine the ethical, scientific, and regulatory issues in the design and conduct of placebo-controlled cancer clinical trials. Methods Several content experts contributed to this article. Results Specific criteria can be applied to determine the appropriate use of placebos in oncology drug development. Placebo controls may be justified to prove efficacy of a new treatment in diseases with high placebo response rates; in conditions that wax and wane in severity, have spontaneous remissions, or have an uncertain and unpredictable course; when existing therapies are minimally effective or have serious adverse effects; or in the absence of effective therapy. Use of placebos may also be justified to assure blinding of physicians and patients regarding treatment assignment so as to minimize bias in assessment of study end points. If a trial meets these methodologic criteria, it must then fulfill additional criteria to be considered ethical. These criteria include full disclosure to patients and an assurance that participants randomly assigned to placebo are not substantially more likely than those in active treatment group(s) to die; suffer irreversible morbidity, disability, or other substantial harms; suffer reversible but serious harm; or suffer severe discomfort. Conclusion We conclude that placebo-controlled oncology trials are scientifically feasible, ethically justifiable, and may be necessary or desirable to meet regulatory standards for drug approval. Using cross-over or randomized withdrawal trial designs, requiring inclusion of state-of-the-art palliative care, and developing valid and acceptable surrogates for survival are critical strategies to address some of the ethical dilemmas associated with placebo-controlled trials. C1 Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. US FDA, Rockville, MD 20857 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Schilsky, RL (reprint author), Univ Chicago, Pritzker Sch Med, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM rschilsk@medicine.bsd.uchicago.edu NR 57 TC 25 Z9 25 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2008 VL 26 IS 8 BP 1371 EP 1378 DI 10.1200/JCO.2007.13.5335 PG 8 WC Oncology SC Oncology GA 276XZ UT WOS:000254178300029 PM 18227527 ER PT J AU Mattei, E Triventi, M Calcagnini, G Censi, F Kainz, W Mendoza, G Bassen, HI Bartolini, P AF Mattei, Eugenio Triventi, Michele Calcagnini, Giovanni Censi, Federica Kainz, Wolfgang Mendoza, Gonzalo Bassen, Howard I. Bartolini, Pietro TI Complexity of MRI induced heating on metallic leads: Experimental measurements of 374 configurations SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article ID RESONANCE-IMAGING SAFE; IN-VITRO; CARDIAC-PACEMAKERS; GUIDE WIRES; IMPLANTS; SYSTEMS; VIVO AB Background: MRI induced heating on PM leads is a very complex issue. The widely varying results described in literature suggest that there are many factors that influence the degree of heating and that not always are adequately addressed by existing testing methods. Methods: We present a wide database of experimental measurements of the heating of metallic wires and PM leads in a 1.5 T RF coil. The aim of these measurements is to systematically quantify the contribution of some potential factors involved in the MRI induced heating: the length and the geometric structure of the lead; the implant location within the body and the lead path; the shape of the phantom used to simulate the human trunk and its relative position inside the RF coil. Results: We found that the several factors are the primary influence on heating at the tip. Closer locations of the leads to the edge of the phantom and to the edge of the coil produce maximum heating. The lead length is the other crucial factor, whereas the implant area does not seem to have a major role in the induced temperature increase. Also the lead structure and the geometry of the phantom revealed to be elements that can significantly modify the amount of heating. Conclusion: Our findings highlight the factors that have significant effects on MRI induced heating of implanted wires and leads. These factors must be taken into account by those who plan to study or model MRI heating of implants. Also our data should help those who wish to develop guidelines for defining safe medical implants for MRI patients. In addition, our database of the entire set of measurements can help those who wish to validate their numerical models of implants that may be exposed to MRI systems. C1 [Mattei, Eugenio; Triventi, Michele; Calcagnini, Giovanni; Censi, Federica; Bartolini, Pietro] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. [Kainz, Wolfgang; Mendoza, Gonzalo; Bassen, Howard I.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Mattei, E (reprint author), Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. EM eugenio.mattei@iss.it; michele.triventi@iss.it; giovanni.calcagnini@iss.it; federica.censi@iss.it; wolfgang.kainz@fda.hhs.gov; gonzalo.mendoza@fda.hhs.gov; howard.bassen@fda.hhs.gov; pietro.bartolini@iss.it RI CENSI, FEDERICA/E-3712-2015; CALCAGNINI, GIOVANNI/E-3711-2015; TRIVENTI, MICHELE/E-4624-2015; MATTEI, EUGENIO/E-4623-2015 OI TRIVENTI, MICHELE/0000-0003-2120-6959; MATTEI, EUGENIO/0000-0002-6494-9456 NR 20 TC 47 Z9 47 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-925X J9 BIOMED ENG ONLINE JI Biomed. Eng. Online PD MAR 3 PY 2008 VL 7 AR 11 DI 10.1186/1475-925X-7-11 PG 16 WC Engineering, Biomedical SC Engineering GA 286VM UT WOS:000254874100001 PM 18315869 ER PT J AU Weaver, J Willy, M Avigan, M AF Weaver, Joyce Willy, Mary Avigan, Mark TI Informatic tools and approaches in postmarketing pharmacovigilance used by FDA SO AAPS JOURNAL LA English DT Review DE postmarketing product surveillance ID EVENTS; DRUGS AB The safety profile of newly approved drugs and therapeutic biologics is less well developed by pre-marketing clinical testing than is the efficacy profile. The full safety profile of an approved product is established during years of clinical use. For nearly 40 years, the FDA has relied on the voluntary reporting of adverse events by healthcare practitioners and patients to help establish the safety of marketed products. Epidemiologic studies, including case series, secular trends, case-control and cohort studies, are used to supplement the investigation of a safety signal. Ideally, active surveillance systems would supplement the identification and exploration of safety signals. The FDA has implemented a number of initiatives to help identify safety problems with drugs and continues to evaluate their efforts. C1 [Weaver, Joyce; Willy, Mary; Avigan, Mark] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20903 USA. RP Weaver, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM joyce.weaver@fda.hhs.gov NR 21 TC 19 Z9 19 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD MAR PY 2008 VL 10 IS 1 BP 35 EP 41 DI 10.1208/s12248-007-9004-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291LG UT WOS:000255198200004 PM 18446503 ER PT J AU Lionberger, RA AF Lionberger, Robert A. TI FDA critical path initiatives: Opportunities for generic drug development SO AAPS JOURNAL LA English DT Review DE bioequivalence; critical path initiative; generic drugs ID EXHALED NITRIC-OXIDE; IN-VIVO; DOSE-RESPONSE; SKIN PENETRATION; BIOEQUIVALENCE; MICRODIALYSIS; BIOAVAILABILITY; DISSOLUTION; ASTHMA; CORTICOSTEROIDS AB FDA's critical path initiative documents have focused on the challenges involved in the development of new drugs. Some of the focus areas identified apply equally to the production of generic drugs. However, there are scientific challenges unique to the development of generic drugs as well. In May 2007, FDA released a document "Critical Path Opportunities for Generic Drugs" that identified some of the specific challenges in the development of generic drugs. The key steps in generic product development are usually characterization of the reference product, design of a pharmaceutically equivalent and bioequivalent product, design of a consistent manufacturing process and conduct of the pivotal bioequivalence study. There are several areas of opportunity where scientific progress could accelerate the development and approval of generic products and expand the range of products for which generic versions are available, while maintaining high standards for quality, safety, and efficacy. These areas include the use of quality by design to develop bioequivalent products, more efficient bioequivalence methods for systemically acting drugs (expansion of BCS waivers, highly variable drugs), and development of new bioequivalence methods for locally acting drugs. C1 US FDA, Off Gener Drugs, Rockville, MD 20850 USA. RP Lionberger, RA (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20850 USA. EM robert.lionberger@fda.hhs.gov NR 55 TC 35 Z9 40 U1 1 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD MAR PY 2008 VL 10 IS 1 BP 103 EP 109 DI 10.1208/s12248-008-9010-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291LG UT WOS:000255198200011 PM 18446510 ER PT J AU Fleischer, S Sharkey, M Mealey, K Ostrander, EA Martinez, M AF Fleischer, Steven Sharkey, Michele Mealey, Katrina Ostrander, Elaine A. Martinez, Marilyn TI Pharmacogenetic and metabolic differences between dog breeds: Their impact on canine medicine and the use of the dog as a preclinical animal model SO AAPS JOURNAL LA English DT Review DE bioavailability; breed-related differences; canine pharmacodynamics; canine pharmacogenetics; canine pharmacokinetics; drug response; population diversity ID COSTA COUNTIES CALIFORNIA; GROWTH-FACTOR-I; BODY-SIZE; IDIOSYNCRATIC TOXICITY; COPPER TOXICOSIS; HEALTHY DOGS; DOMESTIC DOG; TRANSIT-TIME; AGE; GENOME AB There is limited information describing species related pharmacogenetic differences in animals. Despite the lack of genetic information in veterinary medicine, breed specific responses to endogenous and exogenous substances have been reported across many species. This finding underscores the importance of obtaining insight into the genotypic and phenotypic variation present across breeds. This article provides a summary of the literature pertaining to canine breed differences in physiology, drug response, drug pharmacokinetics, and metabolic idiosyncrasies. The existing knowledge of pedigrees and the known phenotypes and genotypes of dogs provides important information for determining mode of inheritance, penetration, and other major characteristics of heritable traits. Understanding these breed differences will improve canine population predictions (for canine drug products) and may be of value when extrapolating toxicology data from dogs to humans. C1 [Fleischer, Steven; Sharkey, Michele; Mealey, Katrina; Ostrander, Elaine A.; Martinez, Marilyn] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS [Z99 HG999999] NR 75 TC 31 Z9 31 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD MAR PY 2008 VL 10 IS 1 BP 110 EP 119 DI 10.1208/s12248-008-9011-1 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291LG UT WOS:000255198200012 PM 18446511 ER PT J AU Davit, BM Conner, DP Fabian-Fritsch, B Haidar, SH Jiang, XJ Patel, DT Seo, PRH Suh, K Thompson, CL Yu, LX AF Davit, Barbara M. Conner, Dale P. Fabian-Fritsch, Beth Haidar, Sam H. Jiang, Xiaojian Patel, Devvrat T. Seo, Paul R. H. Suh, Keri Thompson, Christina L. Yu, Lawrence X. TI Highly variable drugs: Observations from bioequivalence data submitted to the FDA for new generic drug applications SO AAPS JOURNAL LA English DT Article DE bioequivalence; generic drugs; highly variable drugs; presystemic drug metabolism; variable drug product dissolution ID PRODUCTS AB Introduction. It is widely believed that acceptable bioequivalence studies of drugs with high within-subject pharmacokinetic variability must enroll higher numbers of subjects than studies of drugs with lower variability. We studied the scope of this issue within US generic drug regulatory submissions. Materials and Methods. We collected data from all in vivo bioequivalence studies reviewed at FDA's Office of Generic Drugs (OGD) from 2003-2005. We used the ANOVA root mean square error (RMSE) from bioequivalence statistical analyses to estimate within-subject variability. A drug was considered highly variable if its RMSE for C (max) and/or AUC was >= 0.3. To identify factors contributing to high variability, we evaluated drug substance pharmacokinetic characteristics and drug product dissolution performance. Results and Discussion. In 2003-2005, the OGD reviewed 1,010 acceptable bioequivalence studies of 180 different drugs, of which 31% (57/180) were highly variable. Of these highly variable drugs, 51%, 10%, and 39% were either consistently, borderline, or inconsistently highly variable, respectively. We observed that most of the consistent and borderline highly variable drugs underwent extensive first pass metabolism. Drug product dissolution variability was high for about half of the inconsistently highly variable drugs. We could not identify factors causing variability for the other half. Studies of highly variable drugs generally used more subjects than studies of lower variability drugs. Conclusion. About 60% of the highly variable drugs we surveyed were highly variable due to drug substance pharmacokinetic characteristics. For about 20% of the highly variable drugs, it appeared that formulation performance contributed to the high variability. C1 [Davit, Barbara M.; Conner, Dale P.; Fabian-Fritsch, Beth; Haidar, Sam H.; Jiang, Xiaojian; Patel, Devvrat T.; Seo, Paul R. H.; Suh, Keri; Thompson, Christina L.; Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Davit, BM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, 7520 Standish Pl, Rockville, MD 20855 USA. EM barbara.davit@fda.hhs.gov NR 12 TC 43 Z9 50 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD MAR PY 2008 VL 10 IS 1 BP 148 EP 156 DI 10.1208/s12248-008-9015-x PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 291LG UT WOS:000255198200016 PM 18446515 ER PT J AU Kryscio, DR Sathe, PM Lionberger, R Yu, L Bell, MA Jay, M Hilt, JZ AF Kryscio, David R. Sathe, Pradeep M. Lionberger, Robert Yu, Lawrence Bell, Michael A. Jay, Michael Hilt, J. Zach TI Spreadability measurements to assess structural equivalence (Q(3)) of topical formulations - A technical note SO AAPS PHARMSCITECH LA English DT Article DE Q(3) equivalence rheology; spreadability; topical formulations; vane method ID YIELD STRESS MEASUREMENT; FOOD SPREADABILITY; VANE METHOD C1 [Kryscio, David R.; Hilt, J. Zach] Univ Kentucky, Dept Chem & Mat Engn, Lexington, KY 40506 USA. [Bell, Michael A.; Jay, Michael] Univ Kentucky, Ctr Pharmaceut Sci & Technol, Lexington, KY USA. [Sathe, Pradeep M.; Lionberger, Robert; Yu, Lawrence] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Hilt, JZ (reprint author), Univ Kentucky, Dept Chem & Mat Engn, 177 F Paul Anderson Tower, Lexington, KY 40506 USA. EM hilt@engr.uky.edu RI Yu, Lawrence/L-6280-2016 NR 9 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2008 VL 9 IS 1 BP 84 EP 86 DI 10.1208/s12249-007-9009-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276WU UT WOS:000254175200011 PM 18446465 ER PT J AU Shah, RB Tawakkul, MA Khan, MA AF Shah, Rakhi B. Tawakkul, Mobin A. Khan, Mansoor A. TI Comparative evaluation of flow for pharmaceutical powders and granules SO AAPS PHARMSCITECH LA English DT Article DE caking strength; cohesivity; flow stability; powder flow; powder rheometer AB The objective of the present work was to carry out a systematic evaluation of flow of pharmaceutical powders and granules using compendial and non-compendial methods. Angle of repose, bulk density, tapped density, Carr's compressibility index, and Hausner ratios were evaluated. Additionally, flow was characterized using a powder rheometer in which a sensitive force transducer monitors the forces generated as a result of the sample displacement. The critical attributes such as cohesivity index, caking strength, and flow stability were determined for samples. The samples consisted of different grades of magnesium stearate powder including bovine, vegetable, and food grade, physical mixture powder blend consisting of a model formulation, granules prepared by various methods including slugging, high shear granulator, and fluid bed dryer. Lubricant efficiency was also determined for granules lubricated with various concentrations of magnesium stearate. It was observed that the compendial methods were often non-discriminating for minor variations in powder flow. The additional characterization such as cohesivity, and caking strength were helpful in understanding the flow characteristics of pharmaceutical systems. The flow stability test determined that the powders were not affected by the test conditions on the rheometer. The non-compendial tests were discriminating to even minor variations in powder flow. C1 [Shah, Rakhi B.; Tawakkul, Mobin A.; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Off Pharmaceut Sci,Div Prod Qual Res, Rockville, MD 20857 USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Off Pharmaceut Sci,Div Prod Qual Res, Rockville, MD 20857 USA. EM Mansoor.khan@fda.hhs.gov NR 14 TC 53 Z9 55 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2008 VL 9 IS 1 BP 250 EP 258 DI 10.1208/s12249-008-9046-8 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 276WU UT WOS:000254175200035 PM 18446489 ER PT J AU Liang, HY Park, S Gallas, BD Myers, KJ Badano, A AF Liang, Hongye Park, Subok Gallas, Brandon D. Myers, Kyle J. Badano, Aldo TI Image browsing in slow medical liquid crystal displays SO ACADEMIC RADIOLOGY LA English DT Article DE model observer; display quality; contrast sensitivity; temporal response ID HUMAN-OBSERVER; LUMPY BACKGROUNDS; CT SCANS; NOISE; PACS; MODEL AB Rationale and Objectives. Statistics show that radiologists are reading more studies than ever before, creating the challenge of interpreting an increasing number of images without compromising diagnostic performance. Stack-mode image display has the potential to allow radiologists to browse large three-dimensional (3D) datasets at refresh rates as high as 30 images/second. In this framework, the slow temporal response of liquid crystal displays (LCDs) can compromise the image quality when the images are browsed in a fast sequence. Materials and Methods. In this article, we report on the effect of the LCD response time at different image browsing speeds based on the performance of a contrast-sensitive channelized-hoteling observer. A stack of simulated 3D clustered lumpy background images with a designer nodule to be detected is used. The effect of different browsing speeds is calculated with LCD temporal response measurements from our previous work. The image set is then analyzed by the model observer, which has been shown to predict human detection performance in Gaussian and non-Gaussian lumpy backgrounds. This methodology allows us to quantify the effect of slow temporal response of medical liquid crystal displays on the performance of the anthropomorphic observers. Results. We find that the slow temporal response of the display device greatly affects lesion contrast and observer performance. A detectability decrease of more than 40% could be caused by the slow response of the display. Conclusions. After validation with human observers, this methodology can be applied to more realistic background data with the goal of providing recommendations for the browsing speed of large volumetric image datasets (from computed tomography, magnetic resonance, or tomosynthesis) when read in stack-mode. C1 [Liang, Hongye; Park, Subok; Gallas, Brandon D.; Myers, Kyle J.; 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. RP Badano, A (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,Bldg 62,Room 3113, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 21 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2008 VL 15 IS 3 BP 370 EP 382 DI 10.1016/j.acra.2007.10.017 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 271LD UT WOS:000253789000012 PM 18280935 ER PT J AU Jolicoeur, EM Ohman, EM Temple, R Stockbridge, N Smith, S Mark, D Califf, RM Henry, TD Chairman, BR Granger, CB AF Jolicoeur, E. Marc Ohman, E. Magnus Temple, Robert Stockbridge, Norman Smith, Sidney Mark, Daniel Califf, Robert M. Henry, Timothy D. Chairman, Bernard R. Granger, Christopher B. CA Working Grp Members TI Clinical and research issues regarding chronic advanced coronary artery disease Part II: Trial design, outcomes, and regulatory issues SO AMERICAN HEART JOURNAL LA English DT Article ID TRANSMYOCARDIAL LASER REVASCULARIZATION; CHRONIC STABLE ANGINA; PRACTICE GUIDELINES COMMITTEE; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; ASSOCIATION TASK-FORCE; COMPOSITE END-POINTS; HEALTH SURVEY SF-36; REFRACTORY ANGINA; EXERCISE PERFORMANCE AB The population of patients with advanced coronary artery disease (CAD) is growing as a result of the aging of the general population, the extensive use of revascularization, and the efficacy of therapies that have prolonged the survival of patients with severe atherosclerosis. Patients with symptomatic CAD survive to a point where little else can be done to relieve their angina. Despite an anticipated growth in the number of patients with this condition within the next few decades, advanced CAD receives relatively little attention by the medical and research communities. As a result, the scope of the disease is not well defined, its coverage in guidelines from professional associations is limited, and few new medical options are available. In response to this, a group of experts from different fields were brought together at a meeting held December 4 to 5, 2006. This document has been developed as a 2-part article. In the first part, the contemporary and emerging therapies for advanced CAD were reviewed. The present part reviews the current status of understanding of advanced CAD, the limits of contemporary therapies, and the difficulties in and barriers to the development of new treatments. C1 [Jolicoeur, E. Marc; Ohman, E. Magnus; Mark, Daniel; Califf, Robert M.; Granger, Christopher B.] Duke Univ, Durham, NC USA. [Smith, Sidney] Univ N Carolina, Chapel Hill, NC USA. [Temple, Robert; Stockbridge, Norman] US FDA, Silver Spring, MD USA. [Henry, Timothy D.] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. [Chairman, Bernard R.] St Louis Univ, Sch Med, St Louis, MO 63103 USA. RP Jolicoeur, EM (reprint author), Box 3850,2400 Pratt St,Room 0311, Durham, NC 27705 USA. EM marc.jolicoeur@duke.edu RI Granger, Christopher/D-3458-2014; OI Granger, Christopher/0000-0002-0045-3291; Mark, Daniel/0000-0001-6340-8087 NR 48 TC 25 Z9 26 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2008 VL 155 IS 3 BP 435 EP 444 DI 10.1016/j.ahj.2007.12.005 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 271OO UT WOS:000253798100005 PM 18294475 ER EF