FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Udeinya, JI Shu, EN Quakyi, I Ajayi, FO AF Udeinya, J. I. Shu, E. N. Quakyi, I. Ajayi, F. O. TI An antimalarial neem leaf extract has both schizonticidal and gametocytocidal activities SO AMERICAN JOURNAL OF THERAPEUTICS LA English DT Article DE malaria; neem leaf extract; antimalarial; schizonticidal; gametocytocidal ID MALARIA PARASITES; CULTURE; LEAVES AB A crude acetone/water (50/50) extract of neem leaves (IRAB) was evaluated for activity against the asexual (trophozoites/schizonts) and the sexual (gametocytes) forms of the malarial parasite, Plasmodium falciparum, in vitro. In separate 72 hour cultures of both asexual parasites and mature gametocytes treated with IRAB (0.5 mu g/mL), parasite numbers were less than 50% of the numbers in control cultures, which had 8.0% and 8.5% parasitemia, respectively. In cultures containing 2.5 mu g/mL, asexual parasites and mature and immature gametocytes were reduced to 0.1%, 0.2%, and 0% parasitemia, respectively. There were no parasites in the cultures containing 5.0 mu g/mL. This extract, if found safe, may provide materials for development of new antimalarial drugs that may be useful both in treatment of malaria as well as the control of its transmission through gametocytes. C1 [Shu, E. N.] Univ Nigeria, Coll Med, Dept Pharmacol & Therapeut, Enugu, Nigeria. [Udeinya, J. I.] Howard Univ, Coll Med, Washington, DC USA. [Quakyi, I.] Georgetown Univ, Washington, DC USA. [Ajayi, F. O.] US FDA, Rockville, MD 20857 USA. RP Shu, EN (reprint author), Univ Nigeria, Coll Med, Dept Pharmacol & Therapeut, Enugu Campus,PMB 01129, Enugu, Nigeria. EM enshu1@yahoo.com NR 14 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1075-2765 J9 AM J THER JI Am. J. Ther. PD MAR-APR PY 2008 VL 15 IS 2 BP 108 EP 110 DI 10.1097/MJT.0b013e31804c6d1d PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 306WD UT WOS:000256277700004 PM 18356629 ER PT J AU Rafii, F Park, M Bryant, AE Johnson, SJ Wagner, RD AF Rafii, Fatemeh Park, Miseon Bryant, Amy E. Johnson, Shemedia J. Wagner, Robert D. TI Enhanced production of phospholipase C and perfringolysin O (alpha and theta toxins) in a gatifloxacin-resistant strain of Clostridium perfringens SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIBIOTIC-ASSOCIATED DIARRHEA; GAS-GANGRENE; DIFFICILE; OUTBREAK; FLUOROQUINOLONES; PREVALENCE; EXPRESSION; INFECTION; EPIDEMIC; CULTURE AB Clostridium perfringens-induced gas gangrene is mediated by potent extracellular toxins, especially alpha toxin (a phospholipase C [PLC]) and theta toxin (perfringolysin O [PFO], a thiol-activated cytolysin); and antibiotic-induced suppression of toxin synthesis is an important clinical goal. The production of PLC and PFO by a gatifloxacin-induced, fluoroquinolone-resistant mutant strain of C. perfringens, strain 10G, carrying a stable mutation in DNA gyrase was compared with that of the wild-type (WT) parent strain. Zymography (with sheep red blood cell and egg yolk overlays) and time course analysis [with hydrolysis of egg yolk lecithin and O-(4 nitrophenyl-phosphoryl)choline] demonstrated that strain 10G produced more PLC and PFO than the WT strain. Increased toxin production in strain 10G was not related either to differences in growth characteristics between the wild-type and the mutant strain or to nonsynonymous polymorphisms in PLC, PFO, or their known regulatory proteins. Increased PLC and PFO production by strain 10G was associated with increased cytotoxic activity for HT-29 human adenocarcinoma cells and with increased platelet-neutrophil aggregate formation. Four other gatifloxacin-induced gyrase mutants did not show increased toxin production, suggesting that gatifloxacin resistance was not always associated with increased toxin production in all strains of C. perfringens. This is the first report of increased toxin production in a fluoroquinolone-resistant strain of C. perfringens. C1 [Rafii, Fatemeh; Park, Miseon; Johnson, Shemedia J.; Wagner, Robert D.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Bryant, Amy E.] Vet Affairs Med Ctr, Boise, ID USA. [Bryant, Amy E.] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 300 NCTR Dr, Jefferson, AR 72079 USA. EM Fatemeh.Rafii@fda.hhs.gov FU NCRR NIH HHS [P20 RR015587, P20RR15587] NR 38 TC 5 Z9 5 U1 0 U2 1 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 MAR PY 2008 VL 52 IS 3 BP 895 EP 900 DI 10.1128/AAC.01316-07 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 268BS UT WOS:000253553500011 PM 18160514 ER PT J AU Gordon, KV Vickery, MC DePaola, A Staley, C Harwood, VJ AF Gordon, Katrina V. Vickery, Michael C. DePaola, Angelo Staley, Christopher Harwood, Valerie J. TI Real-time PCR assays for quantification and differentiation of Vibrio vulnificus strains in oysters and water SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GULF-COAST; IDENTIFICATION; VIRULENCE; INDICATOR; SEQUENCES; SHELLFISH; CHOLERAE; PROBES; GENES AB Vibrio vulnificus is an autochthonous estuarine bacterium and a pathogen that is frequently transmitted via raw shellfish. Septicemia can occur within 24 h; however, isolation and confirmation from water and oysters require days. Real-time PCR assays were developed to detect and differentiate two 16S rRNA variants, types A and B, which were previously associated with environmental sources and clinical fatalities, respectively. Both assays could detect 102 to 103 V. vulnificus total cells in seeded estuarine water and in oyster homogenates. PCR assays on 11 reference V. vulnificus strains and 22 nontarget species gave expected results (type A or B for V. vulnificus and negative for nontarget species). The relationship between cell number and cycle threshold for the assays was linear (R-2 = >0.93). The type A/B ratio of Florida clinical isolates was compared to that of isolates from oysters harvested in Florida waters. This ratio was 19:17 in clinical isolates and 5:8 (n = 26) in oysters harvested from restricted sites with poor water quality but was 10:1 (n = 22) in oysters from permitted sites with good water quality. A substantial percentage of isolates from oysters (19.4%) were type AB (both primer sets amplified), but no isolates from overlying waters were type AB. The real-time PCR assays were sensitive, specific, and quantitative in water samples and could also differentiate the strains in oysters without requiring isolation of V. vulnificus and may therefore be useful for rapid detection of the pathogen in shellfish and water, as well as further investigation of its population dynamics. C1 [Gordon, Katrina V.; Staley, Christopher; Harwood, Valerie J.] Univ S Florida, Dept Biol, Tampa, FL 33620 USA. [DePaola, Angelo] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Vickery, Michael C.] BioGX Inc, Birmingham, AL 35203 USA. RP Harwood, VJ (reprint author), Univ S Florida, Dept Biol, 4202 E Fowler Ave,SCA 110, Tampa, FL 33620 USA. EM vharwood@cas.usf.edu NR 34 TC 37 Z9 38 U1 1 U2 6 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 MAR PY 2008 VL 74 IS 6 BP 1704 EP 1709 DI 10.1128/AEM.01100-07 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 275IR UT WOS:000254065600004 PM 18245234 ER PT J AU Chen, EA Patel-Raman, SM Berman, MR Zuckerman, BD AF Chen, Eric A. Patel-Raman, Sonna M. Berman, Michael R. Zuckerman, Bram D. TI Food and Drug Administration's perspectives on pediatric cardiac assist devices SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 4th International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion CY MAY 22-24, 2008 CL Portland, OR AB Dual missions of the Center for Devices and Radiological Health at the Food and Drug Administration (FDA) are 1) promoting public health by promptly reviewing and taking appropriate, timely action regarding the marketing of regulated medical devices while at the same time, and 2) protecting public health by ensuring a reasonable assurance of the safety and effectiveness of medical devices deemed appropriate for human use. In the past, clinicians have used cardiac assist devices intended for adults to treat pediatric heart failure patients. However, because of the larger size of the approved devices, many pediatric patients are underserved by this approach. Currently, several cardiac assist devices intended for use in pediatric patients are being developed. FDA believes that clinical data used to support such safety and probable benefit may be derived from a small focused clinical trial in this target population, and developers may want to consider this approach for approval of the humanitarian device exemption application. Pediatric device development is challenging and early communication with FDA to develop an appropriate regulatory and scientific pathway for device submission is advised and warranted. This early interaction can facilitate the development of a small but necessary trial for these life-sustaining pediatric cardiac assist devices. C1 [Chen, Eric A.; Patel-Raman, Sonna M.; Berman, Michael R.; Zuckerman, Bram D.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Chen, EA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-450 Room 220V, Rockville, MD 20850 USA. NR 9 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAR-APR PY 2008 VL 54 IS 2 BP 147 EP 149 DI 10.1097/MAT.0b013e318164a667 PG 3 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 358NA UT WOS:000259922700002 PM 18356646 ER PT J AU Tsang, RSW Tsai, CM Henderson, AM Tyler, S Law, DKS Zollinger, W Jamieson, F AF Tsang, Raymond S. W. Tsai, Chao Ming Henderson, Averil M. Tyler, Shaun Law, Dennis K. S. Zollinger, Wendell Jamieson, Frances TI Immunochemical studies and genetic background of two Neisseria meningitidis isolates expressing unusual capsule polysaccharide antigens with specificities of both serogroup Y and W135 SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE N. meningitidis; serogroup Y; W135 ID SIAD PCR-ELISA; MENINGOCOCCAL DISEASE; STRUCTURAL DETERMINATION; MONOCLONAL-ANTIBODIES; CHEMICAL PROPERTIES; IDENTIFICATION; W135; SIALYLTRANSFERASE; STRAINS; PROTEIN AB We described 2 unusual Neisseria meningitidis strains isolated from epidemiologically unrelated invasive meningococcal disease cases in Ontario, Canada. Both isolates have features typical of serogroup Y N.ameningitidis: are of serotype 2c, are of the multi-locus sequence types typical of the serogroup Y strains in Canada, and are genotyped as serogroup Y based on a previously described PCR-ELISA method that detects the serogroup-Y-specific siaD gene. However, both strains were poly-agglutinable in both anti-Y and anti-W135 antisera. Further studies on 1 of these 2 isolates showed the presence of glucose and galactose as well as sialic acids in its purified capsular polysaccharide, suggesting the presence of both serogroup Y and serogroup W135 polysaccharides. Rabbit antisera produced to this strain contained antibodies to both purified serogroup Y and serogroup W135 capsular polysaccharides. Absorption experiments with either serogroup Y or serogroup W135 bacteria confirmed the presence of antibodies to these 2 different polysaccharides. DNA sequencing of the cps operon from both isolates revealed a siaD gene with 99.7% homology to the published siaD sequence from a serogroup Y strain but with 3 point mutations that all resulted in amino acid changes. How these strains may affect results of routine surveillance, PCR diagnosis, and immuno-protection by vaccination are discussed. C1 [Tsang, Raymond S. W.; Henderson, Averil M.; Law, Dennis K. S.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Lab Vaccine Preventable Bacterial Dis, Winnipeg, MB R3E 3R2, Canada. [Tsai, Chao Ming] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. [Tyler, Shaun] Publ Hlth Agcy Canada, Natl Microbiol Lab, DNA Core Facil, Winnipeg, MB R3E 3R2, Canada. [Zollinger, Wendell] Walter Reed Army Inst Res, Dept Bacterial Dis, Silver Spring, MD 20910 USA. [Jamieson, Frances] Minist Hlth & Long Term Care, Ontario Publ Hlth Lab, Toronto, ON M9P 3T1, Canada. RP Tsang, RSW (reprint author), Publ Hlth Agcy Canada, Natl Microbiol Lab, Lab Vaccine Preventable Bacterial Dis, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM raymond_tsang@phac-aspc.gc.ca RI Zollinger, Wendell/B-2887-2011; Jamieson, Frances/B-2040-2013 FU Wellcome Trust NR 33 TC 13 Z9 13 U1 0 U2 4 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD MAR PY 2008 VL 54 IS 3 BP 229 EP 234 DI 10.1139/W07-132 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 285EL UT WOS:000254760000008 PM 18388994 ER PT J AU Bagnyukovay, TV Tryndyaky, VP Montgomery, B Churchwell, MI Karpf, AR James, SR Muskhelishvili, L Beland, FA Pogribny, IP AF Bagnyukovay, Tetyana V. Tryndyaky, Volodymyr P. Montgomery, Beverly Churchwell, Mona I. Karpf, Adam R. James, Smitha R. Muskhelishvili, Levan Beland, Frederick A. Pogribny, Igor P. TI Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene SO CARCINOGENESIS LA English DT Article ID HISTONE LYSINE METHYLATION; DNA ADDUCT FORMATION; MASS-SPECTROMETRY; DOSE-RESPONSE; HUMAN CANCER; HEPATOCARCINOGENESIS; CARCINOGENESIS; CELLS; H4; ACETYLAMINOFLUORENE AB Genotoxic carcinogens, including 2-acetylaminofluorene (2-AAF), in addition to exerting their genotoxic effects, often cause a variety of non-genotoxic alterations in cells. It is believed that these non-genotoxic effects may be indispensable events in tumorigenesis; however, there is insufficient knowledge to clarify the role of carcinogens in both the genetic and epigenetic changes in premalignant tissues and a lack of conclusive information on the link between epigenetic alterations and carcinogenic exposure. In the current study, we investigated whether or not the mechanism of 2-AAF-induced hepatocarcinogenesis consists of both genotoxic (genetic) and non-genotoxic (epigenetic) alterations. Male and female Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 6, 12, 18 or 24 weeks. The levels of DNA adducts obtained from 2-AAF in liver and kidney tissues were assessed by high-performance liquid chromatography combined with electrospray tandem mass spectrometry (HPLC-ES-MS/MS). N-(Deoxyguanosine-8-yl)-2-aminofluorene was the major adduct detected at all time points in both tissues. Global DNA methylation in the livers and kidneys, as determined by an HpaII-based cytosine extension assay and by HPLC-ES-MS/MS, did not change over the 24-week period. In the livers of male rats, there was a progressive decrease of global and long interspersed nucleotide element-1-associated histone H4 lysine 20 trimethylation, as well as hypermethylation of the p16(INK4A) gene. These epigenetic changes were not observed in the livers of female rats or the kidneys of both sexes. Importantly, morphological evidence of formation and progression of neoplastic process was observed in the liver of male rats only. In conclusion, we have demonstrated that exposure of rats to genotoxic hepatocarcinogen 2-AAF, in addition to formation of 2-AAF-specific DNA lesions, resulted in substantial alterations in cellular epigenetic status. C1 [Bagnyukovay, Tetyana V.; Tryndyaky, Volodymyr P.; Montgomery, Beverly; Churchwell, Mona I.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Karpf, Adam R.; James, Smitha R.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Assoc, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU NCI NIH HHS [R01 CA116674, R01 CA116674-03] NR 56 TC 41 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2008 VL 29 IS 3 BP 638 EP 646 DI 10.1093/carcin/bgm303 PG 9 WC Oncology SC Oncology GA 274NP UT WOS:000254008300023 PM 18204080 ER PT J AU Khoie, T Zinderman, CE Solomon, R Wise, RP Lee, KC Nether, K AF Khoie, Tina Zinderman, Craig E. Solomon, Ruth Wise, Robert P. Lee, Karen C. Nether, Klaus TI Clarification of FDA and The Joint Commission reporting requirements for US tissue recipient adverse reactions SO CELL AND TISSUE BANKING LA English DT Letter C1 [Khoie, Tina; Zinderman, Craig E.; Solomon, Ruth; Wise, Robert P.; Lee, Karen C.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Nether, Klaus] Int Joint Commiss, Div Stand & Survey Methods, Oak Brook Terrace, IL USA. RP Khoie, T (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM tina.khoie@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9333 J9 CELL TISSUE BANK JI Cell Tissue Banking PD MAR PY 2008 VL 9 IS 1 BP 67 EP 68 DI 10.1007/s10561-007-9043-2 PG 2 WC Cell Biology; Engineering, Biomedical SC Cell Biology; Engineering GA 309DE UT WOS:000256440100009 PM 17473991 ER PT J AU Giusti, RM Shastri, K Pilaro, AM Fuchs, C Cordoba-Rodriguez, R Koti, K Rothmann, M Men, AY Zhao, H Hughes, M Keegan, P Weiss, KD Pazdur, R AF Giusti, Ruthann M. Shastri, Kaushikkumar Pilaro, Anne M. Fuchs, Chana Cordoba-Rodriguez, Ruth Koti, Kallappa Rothmann, Mark Men, Angela Yuxin Zhao, Hong Hughes, Monica Keegan, Patricia Weiss, Karen D. Pazdur, Richard TI US Food and Drug Administration approval: Panitumumab for epidermal growth factor receptor-expressing metestetic colorectal carcinoma with progression following fluropyrimidine-, oxelipletin-, and irinotecen-containing chemotherapy regimens SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; SUPPORTIVE CARE; PHASE-II; CANCER; TRIAL; CETUXIMAB; PLUS AB Purpose: To describe the Food and Drug Administration review and marketing approval considerations for panitumumab (Vectibix) for the third-line treatment of patients with epidermal growth factor receptor-expressing metastatic colorectal carcinoma. Experimental Design: Food and Drug Administration reviewed a single, open-label, multicenter trial in which 463 patients with epidermal growth factor receptor-expressing metastatic colorectal cancer who had progressed on or following treatment with a regimen containing a fluoropyrimidine, oxaliplatin, and irinotecan were randomized (1:1) to receive best supportive care (BSc) with or without panitumumab (6 mg/kg every other week) administered until disease progression or intolerable toxicity. Progression and response were confirmed by an independent review committee masked to treatment assignment. At progression, patients in the BSc-alone arm were eligible to receive panitumumab. Results: Although median progression-free survival (PFS) was similar in both treatment arms (similar to 8 weeks), the mean PFS was similar to 50% longer among patients receiving panitumumab than among those receiving BSC alone (96 versus 60 days, respectively) and the objective response rate in patients receiving panitumumab was 8%. However, no difference in overall survival was shown between the two study arms. Conclusions: Panitumumab received accelerated approval based on improvement in PFS and an independently confirmed response rate of 8%, similar to that observed with other active agents at this advanced stage of disease. Confirmation of clinical benefit will be required for full approval. C1 [Giusti, Ruthann M.; Shastri, Kaushikkumar; Pilaro, Anne M.; Hughes, Monica; Keegan, Patricia; Weiss, Karen D.; Pazdur, Richard] US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Fuchs, Chana; Cordoba-Rodriguez, Ruth] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Koti, Kallappa; Rothmann, Mark] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Giusti, RM (reprint author), US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2316, Silver Spring, MD 20993 USA. EM ruthann.giusti@fda.hhs.gov NR 10 TC 51 Z9 52 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 MAR 1 PY 2008 VL 14 IS 5 BP 1296 EP 1302 DI 10.1158/1078-0432.CCR-07-1354 PG 7 WC Oncology SC Oncology GA 268FR UT WOS:000253565000005 PM 18316547 ER PT J AU Woo, J Wolfgang, S Batista, H AF Woo, J. Wolfgang, S. Batista, H. TI The effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration ( FDA) in ensuring the safety and quality of the drug supply. Explosive growth in pharmaceutical manufacturing for the US market is particularly evident in the developing regions of Asia. Manufacturing sites in China and India now comprise similar to 40% of all FDA-registered foreign sites, having increased from 30% in 2002. ( In 2001, when legislation first went into effect requiring registration of all foreign drug manufacturing sites, 140 registered sites in China listed 797 drug items for potential importation; as of 1 October 2007, that number had grown to 815 registered sites and well over 3,000 listed items.) In total in 2006, the United States received > 145,000 line entries of imported drug products from > 160 countries, up from only 1,300 line entries in 2000. FDA regulatory oversight resources ( e. g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. ( In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.) C1 [Woo, J.] US FDA, Off Compliance, Ctr Drug Evaluat & Res, Rockville, MD USA. [Wolfgang, S.] US FDA, Div Mfg & Prod Qual, Ctr Drug Evaluat & Res, Rockville, MD USA. [Batista, H.] US FDA, Div New Drug & Labeling Compliance, Ctr Drug Evaluat & Res, Rockville, MD USA. RP Woo, J (reprint author), US FDA, Off Compliance, Ctr Drug Evaluat & Res, Rockville, MD USA. EM jason.woo@fda.hhs.gov NR 11 TC 9 Z9 9 U1 0 U2 5 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 MAR PY 2008 VL 83 IS 3 BP 494 EP 497 DI 10.1038/sj.clpt.6100493 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267ZN UT WOS:000253547800028 PM 18253142 ER PT J AU Dic, K Hogeland, G Rezk, N White, N Lamba, J Lee, C Kashuba, AD Schuetz, EG Lindley, CM Chen, ML Hawke, RL AF Dic, K. Hogeland, G. Rezk, N. White, N. Lamba, J. Lee, C. Kashuba, A. D. Schuetz, E. G. Lindley, C. M. Chen, M. L. Hawke, R. L. TI The influence of sex, race/ethnicity and CYP2B6 genotype on bupropion (B) metabolism. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Dic, K.; Hogeland, G.; Rezk, N.; White, N.; Lee, C.; Kashuba, A. D.; Lindley, C. M.; Hawke, R. L.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Lamba, J.; Schuetz, E. G.] St Jude Childrens Hosp, Memphis, TN USA. [Chen, M. L.] US FDA, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S81 EP S81 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800260 ER PT J AU Gevorkian, N Sharma, P Pinnow, E Parekh, A AF Gevorkian, N. Sharma, P. Pinnow, E. Parekh, A. TI Qt prolongation potential for new molecular entity drugs approved by FDA, 2003-2006: Labeling review. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Gevorkian, N.; Sharma, P.; Pinnow, E.; Parekh, A.] US FDA, Rockville, MD USA. NR 0 TC 1 Z9 1 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 MAR PY 2008 VL 83 SU 1 BP S44 EP S44 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800141 ER PT J AU Huang, S Abraham, S Apparaju, S Atkinson, A Burckart, G Lee, C Roy, K Strong, J Xiao, S Wu, T Zhang, L Zhang, Y Lesko, L AF Huang, S. Abraham, S. Apparaju, S. Atkinson, A., Jr. Burckart, G. Lee, C. Roy, K. Strong, J. Xiao, S. Wu, T. Zhang, L. Zhang, Y. Lesko, L. TI Impact of the 1998 renal guidance on recent new drug application submissions. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Huang, S.; Abraham, S.; Apparaju, S.; Roy, K.; Wu, T.; Zhang, L.; Zhang, Y.; Lesko, L.] US FDA, CDER, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. [Atkinson, A., Jr.; Burckart, G.; Lee, C.] US FDA, Sabbatical, Silver Spring, MD USA. [Strong, J.] US FDA, CDER, Off Pharmaceut Sci, Silver Spring, MD USA. [Xiao, S.] US FDA, CDER, Off New Drug, Silver Spring, MD USA. NR 0 TC 1 Z9 1 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 MAR PY 2008 VL 83 SU 1 BP S85 EP S85 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800274 ER PT J AU Knudsen, JF Sokol, G AF Knudsen, J. F. Sokol, G. TI Glucosamine use with warfarin is associated with elevated international normalized ratio (INR) value. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Knudsen, J. F.; Sokol, G.] US FDA, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S76 EP S77 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800246 ER PT J AU Pinnow, E Parekh, A Sharma, P Gevorkian, N Uhl, K AF Pinnow, E. Parekh, A. Sharma, P. Gevorkian, N. Uhl, K. TI Inclusion of subpopulations in early phase clinical trials submitted to the FDA: A review of NMES approved in 2006. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 109th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY APR 02-05, 2008 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 [Pinnow, E.; Parekh, A.; Sharma, P.; Gevorkian, N.; Uhl, K.] US FDA, Rockville, 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 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2008 VL 83 SU 1 BP S86 EP S87 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 266ER UT WOS:000253417800279 ER PT J AU Beaucage, SL AF Beaucage, Serge L. TI Solid-phase synthesis of siRNA oligonucleotides SO CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT LA English DT Review DE 2 '-hydroxyl protection; modified RNA oligonucleotide; ribonucleoside phosphoramidite; RNA interference; solid-phase; synthesis; siRNA ID SMALL INTERFERING RNAS; CHEMICAL-SYNTHESIS; PROTECTING GROUP; NUCLEASE RESISTANCE; SILENCING ACTIVITY; OLIGORIBONUCLEOTIDES; EXPRESSION; CHEMISTRY; MONOMERS; NUCLEOTIDES AB Since the discovery of RNA interference (RNAi) as a means to silence the expression of specific genes, small interfering RNA (siRNA) oligonucleotides have been recognized as powerful tools for targeting therapeutically important mRNAs and eliciting their destruction. This discovery has created a high demand for synthetic oligoribonucleotides as potential therapeutics and has spurred a renaissance in the development of rapid, efficient methods for solid-phase RNA synthesis. The design and implementation of 2'-hydroxyl protecting groups that provide ribonucleoside phosphoramidites with coupling kinetics and coupling efficiencies comparable to those of deoxyribonucleoside phosphoramidites are key to the production of RNA oligonucleotides in sufficient quantity and purity for pharmaceutical applications. In this context, various siRNAs were chemically modified to identify the biophysical and biochemical parameters necessary for effective and stable RNAi-mediated gene-silencing activities. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM serge.beaucage@fda.hhs.gov NR 56 TC 37 Z9 38 U1 2 U2 29 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1367-6733 J9 CURR OPIN DRUG DISC JI Curr. Opin. Drug Discov. Dev. PD MAR PY 2008 VL 11 IS 2 BP 203 EP 216 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263LM UT WOS:000253218600006 PM 18283608 ER PT J AU Zaidi, MB Calva, JJ Estrada-Garcia, MT Leon, V Vazquez, G Figueroa, G Lopez, E Contreras, J Abbott, J Zhao, S McDermott, P Tollefson, L AF Zaidi, Mussaret B. Jose Calva, Juan Teresa Estrada-Garcia, Maria Leon, Veronica Vazquez, Gabriela Figueroa, Gloria Lopez, Estela Contreras, Jesus Abbott, Jason Zhao, Shaohua McDermott, Patrick Tollefson, Linda TI Integrated food chain surveillance system for Salmonella spp. in Mexico SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the International-Association-for-Food-Protection CY AUG 13-16, 2006 CL Calgary, CANADA SP Int Assoc Food Protect ID ENTERICA SEROTYPE TYPHIMURIUM; UNITED-STATES; RESISTANT; INFECTIONS; ILLNESS; DIARRHEA; BURDEN; DEATH AB Few developing countries have foodborne pathogen surveillance systems, and none of these integrates data from humans, food, and animals. We describe the implementation of a 4-state, integrated food chain surveillance system (IFCS) for Salmonella spp. in Mexico. Significant findings were 1) high rates of meat contamination (21.3%-36.4%), 2) high rates of ceftriaxone-resistant S. Typhimurium in chicken, ill humans, and swine (77.3%, 66.3%, and 40.4% of S. Typhimurium isolates, respectively), and 3) the emergence of ciprofloxacin resistance in S. Heidelberg (10.4%) and S. Typhimurium (1.7%) from swine. A strong association between Salmonella spp. contamination in beef and asymptomatic Salmonella spp. infection was only observed in the state with the lowest poverty level (Pearson r = 0.91, p<0.001). Pulsed-field gel electrophoresis analysis of 311 S. Typhimurium isolates showed 14 clusters with 102 human, retail meat, and food-animal isolates with indistinguishable patterns. An IFCS is technically and economically feasible in developing countries and can effectively identify major public health priorities. C1 [Zaidi, Mussaret B.; Leon, Veronica] Hosp Gen OHoran, Dept Invest, Merida 97000, Yucatan, Mexico. [Jose Calva, Juan] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico. [Teresa Estrada-Garcia, Maria] Inst Politecn Nacl, Ctr Invest & Estudios Avanzados, Mexico City, DF, Mexico. [Vazquez, Gabriela; Figueroa, Gloria] Secretaria Salud Estado Michoacan, Morelia, Michoacan, Mexico. [Lopez, Estela] Serv Salud Estado San Luis Potosi, Lab Estatal Salud Publ, San Luis Potosi, Mexico. [Abbott, Jason] Hosp Infantil Estado Sonora, Hermosillo, Sonora, Mexico. [Abbott, Jason; Zhao, Shaohua; McDermott, Patrick] US FDA, Laurel, MD USA. [Tollefson, Linda] US FDA, Rockville, MD 20857 USA. [Lopez, Estela] Cent Hosp, Serv Salud Estado San Luis Potosi, San Luis Potosi, Mexico. RP Zaidi, MB (reprint author), Hosp Gen OHoran, Dept Invest, Av Itzaes X Jacinto Canek, Merida 97000, Yucatan, Mexico. EM mbzaidi@prodigy.net.mx NR 25 TC 34 Z9 36 U1 0 U2 6 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2008 VL 14 IS 3 BP 429 EP 435 DI 10.3201/eid1403.071057 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 270BV UT WOS:000253695800011 PM 18325258 ER PT J AU Grinev, A Daniel, S Stramer, S Rossmann, S Caglioti, S Rios, M AF Grinev, Andriyan Daniel, Sylvester Stramer, Susan Rossmann, Susan Caglioti, Sally Rios, Maria TI Genetic variability of West Nile virus in US blood donors, 2002-2005 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID 3'-TERMINAL STEM-LOOP; UNITED-STATES; PHYLOGENETIC ANALYSIS; NEW-YORK; 3'-UNTRANSLATED REGION; NORTH-AMERICA; PROTEIN; GLYCOSYLATION; ENCEPHALITIS; EPIDEMIC AB West Nile virus (WNV) was detected in the United States in 1999, has reoccurred every summer since, and has become endemic. Transfusion transmission was documented in 2002, and screening of blood donations for WNV began in 2003. We investigated genetic variation of WNV in human isolates obtained from specimens collected from 30 infected blood donors who tested positive for WNV RNA during 2002-2005. Complete genomic sequences of 8 isolates and structural gene sequences from 22 additional isolates were analyzed. We found some genetic diversity in isolates from different geographic regions and genetic divergence from reported sequences from epidemics in 1999-2001. Nucleotide divergence of structural genes showed a small increase from 2002 (0.18%) to 2005 (0.37%), suggesting absence of strong selective pressure and limited genetic evolution of WNV during that period. Nevertheless, WNV has continued to diverge from precursor isolates as geographic distribution of the virus has expanded. C1 [Grinev, Andriyan; Daniel, Sylvester; Rios, Maria] NIH, Mol Virol Lab, Div Emerging Transfus Transmitted dis, US FDA, Bethesda, MD 20892 USA. [Stramer, Susan] Amer Red Cross, Gaithersburg, MD USA. [Rossmann, Susan] Gulf Coast Reg Blood Ctr, Houston, TX USA. [Caglioti, Sally] Blood Syst Labs, Tempe, AZ USA. RP Rios, M (reprint author), NIH, Mol Virol Lab, Div Emerging Transfus Transmitted dis, US FDA, Bldg 29,Rm 131, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM maria.rios@fda.hhs.gov FU Intramural NIH HHS NR 34 TC 26 Z9 27 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2008 VL 14 IS 3 BP 436 EP 444 DI 10.3201/eid1403.070463 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 270BV UT WOS:000253695800012 PM 18325259 ER PT J AU Perez-De La Cruz, V Konigsberg, M Pedraza-Chaverri, J Herrera-Mundo, N Diaz-Munoz, M Moran, J Fortoul-van der Goes, T Rondan-Zarate, A Maldonado, PD Ali, SF Santamaria, A AF Perez-De La Cruz, Veronica Konigsberg, Mina Pedraza-Chaverri, Jose Herrera-Mundo, Nieves Diaz-Munoz, Mauricio Moran, Julio Fortoul-van der Goes, Teresa Rondan-Zarate, Adrian Maldonado, Perla D. Ali, Syed F. Santamaria, Abel TI Cytoplasmic calcium mediates oxidative damage in an excitotoxic/energetic deficit synergic model in rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE 3-nitropropionic acid; cytoplasmic Ca(2+); lipid peroxidation; quinolinate; synergism ID ACID-INDUCED NEUROTOXICITY; INDUCED LIPID-PEROXIDATION; D-ASPARTATE RECEPTOR; QUINOLINIC ACID; 3-NITROPROPIONIC ACID; HUNTINGTONS-DISEASE; IN-VIVO; SUCCINATE-DEHYDROGENASE; ENERGY-METABOLISM; SUBTHRESHOLD CONCENTRATIONS AB Excessive calcium is responsible for triggering different potentially fatal metabolic pathways during neurodegeneration. In this study, we evaluated the role of calcium on the oxidative damage produced in an in vitro combined model of excitotoxicity/energy deficit produced by the co-administration of quinolinate and 3-nitropropionate to brain synaptosomal membranes. Synaptosomal fractions were incubated in the presence of subtoxic concentrations of these agents (21 and 166 mu M, respectively). In order further to characterize possible toxic mechanisms involved in oxidative damage in this experimental paradigm, agents with different properties - dizocilpine, acetyl L-carnitine, iron porphyrinate and S-allylcysteine - were tested at increasing concentrations (10-1000 mu m). Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. For confirmatory purposes, additional fractions were incubated in parallel in the presence of the intracellular calcium chelator 1,2-bis(2-aminophenoxy) ethane- N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). Under physiological conditions of extracellular calcium availability, synaptomes exposed to both toxins displayed an increased lipoperoxidation (76% above controls), and this effect was partially attenuated by the tested agents as follows: dizocilpine = iron porphyrinate > acetyl L-carnitine > S-allylcysteine. When the incubation medium was deprived of calcium, the lipoperoxidative effect achieved in this experimental paradigm was still high (49% above the control), and the order of attenuation was: iron porphyrinate > S-allylcysteine > acetyl L-carnitine > dizocilpine. BAPTA-AM was effective in preventing the pro-oxidant action of both toxins, promoting even lower peroxidative levels than those quantified under basal conditions. Our results suggest that the lipid peroxidation induced in synaptosomal fractions by quinolinate plus 3-nitropropionate is largely dependent on the cytoplasmic concentrations of calcium. C1 [Perez-De La Cruz, Veronica; Herrera-Mundo, Nieves; Santamaria, Abel] SSA, Inst Nacl Neurol & Neurocirug Manuel Velasco Suar, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. [Perez-De La Cruz, Veronica; Pedraza-Chaverri, Jose] Univ Autonoma Metropolitana Iztapalapa, Div Ciencias Biol & Salud, Dept Ciencias Salud, Mexico City 09340, DF, Mexico. [Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol, Fac Quim, Mexico City 04510, DF, Mexico. [Fortoul-van der Goes, Teresa] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Biol Celular, Fac Quim, Mexico City 04510, DF, Mexico. [Perez-De La Cruz, Veronica; Konigsberg, Mina] Univ Autonoma Metropolitana Iztapalapa, Dept Ciencias Salud, Mexico City 09340, DF, Mexico. [Maldonado, Perla D.] SSA, Inst Nacl Neurol & Neurocirug Manuel Velasco Suar, Lab Pathol Vac Med Cerebral, Mexico City 14269, DF, Mexico. [Herrera-Mundo, Nieves] Campus Univ Nacl Autonoma Mexico Juuriquilla, Inst Neurobiol, Dept Neurobiol Celluat & Mol, Queretaro 76230, QRO, Mexico. [Ali, Syed F.; Santamaria, Abel] Natl Ctr Toxicol Res, Food & Drug Adm, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), SSA, Inst Nacl Neurol & Neurocirug Manuel Velasco Suar, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. EM absada@yahoo.com NR 58 TC 22 Z9 23 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2008 VL 27 IS 5 BP 1075 EP 1085 DI 10.1111/j.1460-9568.2008.06088.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 278GP UT WOS:000254273400003 PM 18364032 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 uvexposures of human skin SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Arbeitsgemeinschaft-Dermatolog-Forschung CY FEB 28-MAR 01, 2008 CL Eriangen, GERMANY SP Arbeitsgemeinsch Dermatolog Forschung C1 [Brenner, M.] Univ Munich, Dept Dermatol, Munich, Germany. [Coelho, S. G.; Hearing, V. J.] NIH, Natl Canc Inst, Lab Cell Biol, 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 BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD MAR PY 2008 VL 17 IS 3 BP 273 EP 273 PG 1 WC Dermatology SC Dermatology GA 258VN UT WOS:000252897700201 ER PT J AU Nichols, WL Hultin, MB James, AH Manco-Johnson, MJ Montgomery, RR Ortel, TL Rick, ME Sadler, JE Weinstein, M Yawn, BP AF Nichols, W. L. Hultin, M. B. James, A. H. Manco-Johnson, M. J. Montgomery, R. R. Ortel, T. L. Rick, M. E. Sadler, J. E. Weinstein, M. Yawn, B. P. TI von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA) SO HAEMOPHILIA LA English DT Review DE acquired von Willebrand syndrome; bleeding disorder; clotting factor concentrate; coagulation factor VIII; desmopressin; haemorrhage; menorrhagia; platelet disorder; von Willebrand disease; von Willebrand factor ID INHERITED BLEEDING DISORDERS; IIB VONWILLEBRANDS DISEASE; 1-DESAMINO-8-D-ARGININE VASOPRESSIN DDAVP; CENTER DOCTORS ORGANIZATION; GLYCOPROTEIN-IB-ALPHA; HEMOPHILIA TREATMENT CENTERS; RISTOCETIN COFACTOR ACTIVITY; NORMAL PLATELET TRANSFUSION; INHIBITOR TRANEXAMIC ACID; CANDIDATE GENE HAPLOTYPES AB von Willebrand disease (VWD) is a commonly encountered inherited bleeding disorder affecting both males and females, causing mucous membrane and skin bleeding symptoms, and bleeding with surgical or other haemostatic challenges. VWD may be disproportionately symptomatic in women of child-bearing age. It may also occur less frequently as an acquired disorder (acquired von Willebrand syndrome). VWD is caused by deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates platelet haemostatic function and stabilizes blood coagulation factor VIII. The pathophysiology, classification, diagnosis and management of VWD are relatively complex, but understanding them is important for proper diagnosis and management of patients with VWD. These evidence-based guidelines for diagnosis and management of VWD from the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel (USA) review relevant publications, summarize current understanding of VWD pathophysiology and classification, and present consensus diagnostic and management recommendations based on analysis of the literature and expert opinion. They also suggest an approach for clinical and laboratory evaluation of individuals with bleeding symptoms, history of bleeding or conditions associated with increased bleeding risk. This document summarizes needs for further research in VWF, VWD and bleeding disorders, including clinical research to obtain more objective information about bleeding symptoms, advancements in diagnostic and therapeutic tools, and enhancement in the education and training of clinicians and scientists in bleeding and thrombotic disorders. The NHLBI Web site (http://www.nhlbi.nih.gov/guidelines/vwd) has a more detailed document, a synopsis of these recommendations, and patient education information. C1 [Nichols, W. L.] Mayo Clin, Coll Med, Dept Lab Med & Pathol, Special Coagulat Lab,Div Hematopathol, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Coagulat Clin, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Comprehens Hemophilia Ctr, Div Hematol & Internal Med, Rochester, MN 55905 USA. [Hultin, M. B.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [James, A. H.] Duke Univ, Ctr Med, Dept Obstet & Gynecol, Durham, NC USA. [Manco-Johnson, M. J.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Manco-Johnson, M. J.] Childrens Hosp Denver, Ctr Canc & Blood Disorders, Denver, CO USA. [Montgomery, R. R.] Med Coll Wisconsin, Dept Pediat, Blood Res Inst, BloodCtr Wisconsin, Milwaukee, WI 53226 USA. [Montgomery, R. R.] Med Coll Wisconsin, Dept Pediat, Sect Pediat Hematol, Milwaukee, WI 53226 USA. [Ortel, T. L.] Duke Univ, Med Ctr, Dept Pathol, Clin Coagulat Lab, Durham, NC USA. [Ortel, T. L.] Duke Univ, Med Ctr, Div Hematol, Dept Med, Durham, NC USA. [Rick, M. E.] NIH, Warren Grant Magnuson Clin Ctr, Serv Hematol, Bethesda, MD 20892 USA. [Sadler, J. E.] Washington Univ, Dept Med, St Louis, MO USA. [Yawn, B. P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, B. P.] Univ Minnesota, Dept Family & Community Med, Minneapolis, MN USA. [Weinstein, M.] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. RP Nichols, WL (reprint author), Mayo Clin, Coll Med, Dept Lab Med & Pathol, Special Coagulat Lab,Div Hematopathol, 200 SCL,Mayo Clin,200 1st St SW, Rochester, MN 55905 USA. EM nichols.william@mayo.edu RI Sadler, Evan/D-8556-2011; OI Sadler, J. Evan/0000-0001-5705-469X NR 411 TC 327 Z9 330 U1 3 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAR PY 2008 VL 14 IS 2 BP 171 EP 232 DI 10.1111/j.1365-2516.2007.01643.x PG 62 WC Hematology SC Hematology GA 269CC UT WOS:000253626100001 PM 18315614 ER PT J AU Anders, JJ Romanczyk, TB Ilev, IK Moges, H Longo, L Wu, X Waynant, RW AF Anders, J. J. Romanczyk, T. B. Ilev, I. K. Moges, H. Longo, L. Wu, X. Waynant, R. W. TI Light supports neurite outgrowth of human neural progenitor cells in vitro: The role of P2Y receptors (vol 14, pg 118, 2008) SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Correction C1 [Anders, J. J.; Romanczyk, T. B.; Moges, H.; Wu, X.] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Ilev, I. K.; Waynant, R. W.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Longo, L.] Univ Siena, Inst Laser Med, I-53100 Siena, Italy. [Longo, L.] Univ San Marino, San Marino 47890, San Marino. RP Anders, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. EM janders@usuhs.mil; tromanczyk@usuhs.mil; ilko.ilev@fda.hhs.gov; hmoges@usuhs.mil; longo@dada.it; xiwu@usuhs.mil; waynant@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD MAR-APR PY 2008 VL 14 IS 2 BP 521 EP 521 DI 10.1109/JSTQE.2008.921188 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 342CY UT WOS:000258763400035 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 comparison of statistical methods for development of a prediction model for acute hepatotoxicity SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Flynn, Thomas J.] US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Ferguson, Martine S.] US FDA, Div Biostat, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM thomas.flynn@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2008 VL 44 SU S BP S32 EP S32 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 338XL UT WOS:000258542600086 ER PT J AU Janota, J Simak, J Stranak, Z Matthews, T Clarke, T Corcoran, D AF Janota, J. Simak, J. Stranak, Z. Matthews, T. Clarke, T. Corcoran, D. TI Critically ill newborns with multiple organ dysfunction: assessment by NEOMOD score in a tertiary NICU SO IRISH JOURNAL OF MEDICAL SCIENCE LA English DT Article DE mortality; multiple organ dysfunction; preterm newborn; scoring system ID NEONATAL INTENSIVE-CARE; BIRTH-WEIGHT INFANTS; CLINICAL RISK INDEX; BABIES SCORE; SEVERITY; FAILURE; MORTALITY; SYSTEM; THERAPY; SEPSIS AB Background The neonatal multiple organ dysfunction score (NEOMOD) predicts mortality during the first 28 days of life, and provides information on organ functions influencing mortality. Aim To test the predictive and descriptive accuracy of NEOMOD in very low birth weight (VLBW) infants. Methods The system was used in 112 infants. It evaluates the central nervous system (CNS), coagulation, respiratory, gastrointestinal (GIT), cardiovascular (CVS), renal system, and acid-base balance in 24-h intervals during the first 28 days of life. Results A NEOMOD of >= 9 was associated with 100% mortality. A receiver operating characteristic (ROC) curve was used for assessing the accuracy of NEOMOD score in prediction of mortality. The area under curve (AUC) attained by NEOMOD was 0.93 for mortality. Conclusions The NEOMOD evaluates daily the severity of the multiple organ dysfunction syndrome (MODS) and is an accurate predictor of mortality. C1 [Janota, J.; Matthews, T.; Clarke, T.; Corcoran, D.] Rotunda Hosp, Dept Paediat, Dublin 1, Ireland. [Simak, J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Stranak, Z.] Inst Care Mother & Child, Prague, Czech Republic. [Matthews, T.; Clarke, T.; Corcoran, D.] Childrens Hosp, Dublin, Ireland. RP Janota, J (reprint author), Rotunda Hosp, Dept Paediat, Parnell Sq, Dublin 1, Ireland. EM janjanota@yahoo.com RI Simak, Jan/C-1153-2011 NR 31 TC 6 Z9 14 U1 0 U2 3 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0021-1265 J9 IRISH J MED SCI JI Irish J. Med. Sci. PD MAR PY 2008 VL 177 IS 1 BP 11 EP 17 DI 10.1007/s11845-008-0115-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 282PW UT WOS:000254580700003 PM 18219516 ER PT J AU Limb, SL Lee, CE Starke, PR Chowdhury, BA AF Limb, Susan L. Lee, Charles E. Starke, Peter R. Chowdhury, Badrul A. TI Delayed allergic reactions to omalizumab: Are patients reporting all cases? Reply SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 [Limb, Susan L.; Lee, Charles E.; Starke, Peter R.; Chowdhury, Badrul A.] US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Prod, Silver Spring, MD USA. RP Limb, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Prod, Silver Spring, MD USA. EM susan.limb@fda.hhs.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2008 VL 121 IS 3 BP 786 EP 786 DI 10.1016/j.jaci.2007.12.1187 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 273GR UT WOS:000253918900051 ER PT J AU Garber, EAE O'Brien, TW AF Garber, Eric A. E. O'Brien, Thomas W. TI Detection of ricin in food using electrochemiluminescence-based technology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID A-CHAIN; MASS-SPECTROMETRY; T-2 TOXIN; IDENTIFICATION; SPECTROSCOPY; AGENTS; 2.5-A AB Ricin is a toxic ribosome inactivating protein (RIP-II) present in beans of the castor plant, Ricinus communis. Its potential as a biodefense threat has made the rapid, sensitive detection of ricin in food important to the U.S. Food and Drug Administration. Samples of juice, dairy products, soda, vegetables, bakery products, chocolate, and condiments were spiked with varying concentrations of ricin and analyzed using a 96-well format, electrochemiluminescence (ECL) immunoassay. Assay configurations included the use of a monoclonal capture antibody coupled with either a polyclonal or monoclonal detector antibody. The samples and detector antibodies were either added sequentially or in combination during the capture step. Using the polyclonal antibody, 0.04 ng/mL ricin was detected in analytical samples prepared from several beverages. By simultaneously incubating the sample with detector antibody, it was possible to decrease the assay time to a single 20 min incubation step with a limit of detection <10 ng/mL. Assays run according to this single incubation step exhibited a hook effect (decrease in signal at high concentrations of ricin), but because of the large signal-to-noise ratio associated with the ECL assay, the response remained above background and detectable. Thus, the ECL assay was uniquely suited for the screening of samples for ricin. C1 [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, Div Bioanalyt Chem, Off Regulatory Sci, College Pk, MD 20740 USA. [O'Brien, Thomas W.] Teracore Inc, Rockville, MD 20850 USA. RP Garber, EAE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Bioanalyt Chem, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Eric.Garber@fda.hhs.gov NR 30 TC 28 Z9 30 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 MAR-APR PY 2008 VL 91 IS 2 BP 376 EP 382 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 289YA UT WOS:000255088600017 PM 18476351 ER PT J AU Ali, L Perfetti, G Diachenko, G AF Ali, Laila Perfetti, Gracia Diachenko, Gregory TI Rapid method for the determination of coumarin, vanillin, and ethyl vanillin in vanilla extract by reversed-phase liquid chromatography with ultraviolet detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PRODUCTS AB A method is described for determining coumarin, vanillin, and ethyl vanillin in vanilla extract products. A product is diluted one-thousand-fold and then analyzed by reversed-phase liquid chromatography using a C18 column and a mobile phase consisting of 55% acetonitrile-45% aqueous acetic acid (1%) solution at a flow rate of 1.0 mL/min. Peaks are detected with a UV detector set at 275 nm. Vanilla extracts were spiked with 250, 500, and 1000 mu g/g each of coumarin, vanillin, and ethyl vanillin. Recoveries averaged 97.4, 97.8, and 99.8% for coumarin, vanillin, and ethyl vanillin, respectively, with coefficient of variation values of 1.8,1.3, and 1.3%, respectively. No significant difference was observed among the 3 spiking levels. A survey of 23 domestic and imported vanilla extract products was conducted using the method. None of the samples contained coumarin. The surveyed samples contained between 0.4 to 13.1 and 0.4 to 2.2 mg/g vanillin and ethyl vanillin, respectively. C1 [Ali, Laila; Perfetti, Gracia; Diachenko, Gregory] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ali, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Laila.Ali@fda.hhs.gov NR 8 TC 5 Z9 6 U1 1 U2 4 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 MAR-APR PY 2008 VL 91 IS 2 BP 383 EP 386 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 289YA UT WOS:000255088600018 PM 18476352 ER PT J AU Nyman, PJ Morehouse, KM Perfetti, GA Diachenko, GW Holcomb, JR AF Nyman, Patricia J. Morehouse, Kim M. Perfetti, Gracia A. Diachenko, Gregory W. Holcomb, Jim R. TI Single-laboratory validation of a method for the determination of furan in foods by using headspace gas chromatography/mass spectrometry, Part 2 - Low-moisture snack foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In 2004, a quantitative headspace (HS) gas chromatographic/mass spectrometric method was developed and used to determine furan in approximately 300 foods. This method was modified and validated for the determination of furan in low-moisture snack foods. The modifications include a smaller test portion size and lower HS oven temperature. The limits of detection ranged from 0.4 ng/g in graham crackers to 4.4 ng/g in pretzels. Recoveries from samples fortified at 0.5, 1, 2, and 3 times the levels of incurred furan found in the samples ranged from 96 to 102%, and HorRat values showed that the recovery data met the criteria for repeatability. The modified method was shown to be reliable for the determination of furan in foods when test portions were equilibrated for 30 min in a 60 degrees C HS oven. The modified method was used to conduct a survey of furan in 22 low-moisture snack foods. All of the samples were found to contain furan ranging from 3.7 ng/g in graham crackers to 60 ng/g in corn chips. Results from the survey were consistent with results obtained for similar snack foods analyzed by a U.S. Food and Drug Administration field laboratory. C1 [Nyman, Patricia J.; Morehouse, Kim M.; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Holcomb, Jim R.] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. RP Nyman, PJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HSF 706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM patricia.nyman@fda.hhs.gov NR 18 TC 16 Z9 16 U1 0 U2 5 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 MAR-APR PY 2008 VL 91 IS 2 BP 414 EP 421 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 289YA UT WOS:000255088600023 PM 18476357 ER PT J AU Schenck, FJ Brown, AN Podhorniak, LV Parker, A Reliford, M Wong, JW AF Schenck, Frank J. Brown, Amy N. Podhorniak, Lynda V. Parker, Alesia Reliford, Michelle Wong, Jon W. TI A rapid multiresidue method for determination of pesticides in fruits and vegetables by using acetonitrile extraction/partitioning and solid-phase extraction column cleanup SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FAST GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; RESIDUE ANALYSIS; AGRICULTURAL PRODUCTS; ULTRATRACE ANALYSIS; BABY FOOD AB A modification of a rapid and inexpensive multiresidue method for determination of pesticides in fruits and vegetables (QuEChERS method) is presented. Samples were extracted by shaking with acetic acid-acetonitrile (1 + 99). Water was removed by liquid-liquid partitioning with magnesium sulfate and sodium acetate. The extract was subjected to a single solid-phase extraction (SPE) column cleanup, which produced a cleaner extract than did the dispersive SPE cleanup used in the original QuEChERS method. Recovery data were obtained for 316 pesticide residues, at levels ranging from 20 ppb to 1.0 ppm. Data were provided by 3 different laboratories. The modified QuEChERS method resulted in a 65% reduction in solvent usage, when compared with the traditional multiresidue methods previously used in our laboratories. C1 [Schenck, Frank J.; Parker, Alesia] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Brown, Amy N.; Reliford, Michelle] Florida Dept Agr & Consumer Serv, Chem Residue Lab, Tallahassee, FL 32399 USA. [Podhorniak, Lynda V.] US EPA, Ctr Environm Sci, Ft George G Meade, MD 20755 USA. [Wong, Jon W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Schenck, FJ (reprint author), US FDA, SE Reg Lab, Atlanta, GA 30309 USA. EM Frank.Schenck@fda.hhs.gov NR 16 TC 38 Z9 40 U1 0 U2 8 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 MAR-APR PY 2008 VL 91 IS 2 BP 422 EP 438 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 289YA UT WOS:000255088600024 PM 18476358 ER PT J AU Rummel, N Shaikh, B AF Rummel, Nathan Shaikh, Badar TI Determination of albendazole and its metabolites in the muscle tissue of hybrid striped and largemouth bass using liquid chromatography with fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELECTROSPRAY-MASS-SPECTROMETRY; BENZIMIDAZOLE ANTHELMINTICS; FLUOROMETRIC DETECTION; MAIN METABOLITES; ATLANTIC SALMON; RAINBOW-TROUT; PLASMA; MILK; SULFOXIDE; RESIDUE AB A liquid chromatographic method was developed for the determination of albendazole and its metabolites albendazole sulfoxide, albendazole sulfone, and albendazole-2-aminosulfone from largemouth and hybrid striped bass muscle tissue with adhering skin. The muscle tissue samples were made alkaline with potassium carbonate and extracted with ethyl acetate. The extracts were further subjected to cleanup by using a series of liquid-liquid extractions. After solvent evaporation, the residue was reconstituted in mobile phase and chromatographed. The chromatography was carried out on a reversed-phase Luna C18 column, using acetonitrile-methanol buffer as the mobile phase. The analytes were detected by fluorescence with excitation and emission wavelengths of 290 and 330 nm, respectively. The average recoveries from the fortified muscle tissue of the 2 fish species for albendazole (25-100 ppb), albendazole sulfoxide (8.75-52.5 ppb), albendazole sulfone (1-10 ppb), and albendazole-2-aminosulfone (10-100 ppb) were 89, 82, 99, and 74%, respectively. The coefficient of variation for each compound was <= 20% in all cases. The procedure was applied to the determination of albendazole and its 3 metabolites in the muscle tissue of the 2 fish species after orally dosing them with albendazole. C1 [Rummel, Nathan; Shaikh, Badar] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM badaruddin.shaikh@fda.hhs.gov NR 24 TC 4 Z9 5 U1 4 U2 8 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 MAR-APR PY 2008 VL 91 IS 2 BP 469 EP 477 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 289YA UT WOS:000255088600028 PM 18476362 ER PT J AU Mukherjee, A Mammel, MK LeClerc, JE Cebula, TA AF Mukherjee, Amit Mammel, Mark K. LeClerc, J. Eugene Cebula, Thomas A. TI Altered utilization of N-acetyl-D-galactosamine by Escherichia coli O157 : H7 from the 2006 spinach outbreak SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MANNOSE TRANSPORTER; MOLECULAR-CLONING; ACETYLGLUCOSAMINE; METABOLISM; EXPRESSION; RESOLUTION; DEAMINASE; PATHWAYS; BACTERIA; SEQUENCE AB In silico analyses of previously sequenced strains of Escherichia coli O157:117, EDL933 and Sakai, localized the gene cluster for the utilization of N-acetyl-D-galactosamine (Aga) and D-galactosamine (Gam). This gene cluster encodes the Aga phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) and other catabolic enzymes responsible for transport and catabolism of Aga. As the complete coding sequences for enzyme IIA (EIIA)(Aga/Gam), EIIB(Aga), EIIC(Aga), and EIID(Aga) of the Aga PTS are present, E. coli O157:H7 strains normally are able to utilize Aga as a sole carbon source. The Gam PTS complex, in contrast, lacks EIIC(Gam), and consequently, E. coli O157:117 strains cannot utilize Gam. Phenotypic analyses of 120 independent isolates of E. coli O157:117 from our culture collection revealed that the overwhelming majority (118/120) displayed the expected Aga(+) Gam(-) phenotype. Yet, when 194 individual isolates, derived from a 2006 spinach-associated E. coli O157:117 outbreak, were analyzed, all (194/194) displayed an Aga(-) Gam(-) phenotype. Comparison of aga/gam sequences from two spinach isolates with those of EDL933 and Sakai revealed a single nucleotide change (G:C -> A:T) in the agaF gene in the spinach-associated isolates. The base substitution in agaF, which encodes EIIA(Aga/Gam) of the PTS, changes a conserved glycine residue to serine (Gly91Ser). Pyrosequencing of this region showed that all spinach-associated E. coli O157:H7 isolates harbored this same G:C -> A:T substitution. Notably, when agaF(+) was cloned into an expression vector and transformed into six spinach isolates, all (6/6) were able to grow on Aga, thus demonstrating that the Gly91Ser substitution underlies the Aga(-) phenotype in these isolates. C1 [Mukherjee, Amit; Mammel, Mark K.; LeClerc, J. Eugene; Cebula, Thomas A.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA HFS 25, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Thomas.Cebula@fda.hhs.gov NR 26 TC 17 Z9 17 U1 0 U2 4 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 MAR PY 2008 VL 190 IS 5 BP 1710 EP 1717 DI 10.1128/JB.01737-07 PG 8 WC Microbiology SC Microbiology GA 268CA UT WOS:000253554300026 PM 18156259 ER PT J AU Ning, BT Dial, S Sun, YY Wang, J Yang, JP Guo, L AF Ning, Baitang Dial, Stacey Sun, Yanyang Wang, Jie Yang, Jingping Guo, Lei TI Systematic and simultaneous gene profiling of 84 drug-metabolizing genes in primary human hepatocytes SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE real time-PCR; gene expression; drug-metabolizing enzyme; drug-metabolizing gene ID ARYL-HYDROCARBON RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; QUANTITATIVE RT-PCR; PREGNANE-X-RECEPTOR; CYTOCHROME-P450 ENZYMES; GLUCOCORTICOID-RECEPTOR; NUCLEAR RECEPTORS; PRIMARY CULTURES; HUMAN CYP2B6; CYP1A1 GENE AB Drug-metabolizing enzymes are an important battery of proteins that are involved in drug metabolism, xenobiotic detoxification, and drug-induced toxicity. Systematic, efficient, and simultaneous evaluation of drug-metabolizing gene expression in response to chemicals has a wide variety of implications in drug development, disease prevention, and personalized medicine and nutrition. In the current study, the authors have systematically and simultaneously evaluated the hepatic expression profile of drug-metabolizing enzymes in cultured human hepatocytes exposed to the xenobiotics rifampicin, omeprazole, and 3-methylcholanthrene ( 3-MC) using the Drug Metabolism RT(2)Profiler (TM) PCR Arrays. This new high-throughput tool allowed the authors to evaluate the expression of genes coding for 84 drug-metabolizing enzymes ( including phase 1 and phase 2 drug-metabolizing enzymes and transporters) simultaneously, in a 96-well format using a small amount of experimental materials. To validate the quality of the Drug Metabolism RT(2)Profiler (TM) PCR Arrays, the PCR Array was compared with the well-documented platform TaqMan assay, and a high concordance was shown between these 2 methods, indicating the high reliability of the Drug Metabolism RT(2)Profiler (TM) PCR Arrays. In addition, increasing or decreasing the expression of drug-metabolizing enzymes by these 3 compounds was observed, and underlying mechanisms are discussed. C1 [Dial, Stacey; Guo, Lei] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Ning, Baitang] US FDA, Natl Ctr Toxicol Res, Div Perosnalized Nutr & Med, Jefferson, AR 72079 USA. [Sun, Yanyang; Wang, Jie; Yang, Jingping] SuperArray Biosci, Frederick, MD USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 33 TC 14 Z9 14 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD MAR PY 2008 VL 13 IS 3 BP 194 EP 201 DI 10.1177/1087057108315513 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 282OF UT WOS:000254576400002 PM 18270363 ER PT J AU Dasari, MS Richards, KM Alt, ML Crawford, CFP Schleiden, A Ingram, J Hamiclou, AAA Williams, A Chernovitz, PA Luo, RS Sun, GY Luchtefeld, R Smith, RE AF Dasari, Mina S. Richards, Kristy M. Alt, Mikaela L. Crawford, Clark F. P. Schleiden, Amanda Ingram, Jai Hamiclou, Abdel Axiz Amadou Williams, Angela Chernovitz, Patricia A. Luo, Rensheng Sun, Grace Y. Luchtefeld, Ron Smith, Robert E. TI Synthesis of diapocynin SO JOURNAL OF CHEMICAL EDUCATION LA English DT Article ID APOCYNIN; NEUTROPHILS; INHIBITION C1 [Dasari, Mina S.; Richards, Kristy M.; Alt, Mikaela L.; Crawford, Clark F. P.; Schleiden, Amanda; Ingram, Jai; Hamiclou, Abdel Axiz Amadou; Williams, Angela; Chernovitz, Patricia A.; Smith, Robert E.] Park Univ, Dept Chem, Parkville, MO 64152 USA. [Luo, Rensheng] Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. [Sun, Grace Y.] Univ Missouri, Dept Biochem, Columbia, MO 65212 USA. [Luchtefeld, Ron; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Dasari, MS (reprint author), Park Univ, Dept Chem, Parkville, MO 64152 USA. EM robert.smith@fda.hhs.gov NR 14 TC 6 Z9 6 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-9584 J9 J CHEM EDUC JI J. Chem. Educ. PD MAR PY 2008 VL 85 IS 3 BP 411 EP 412 PG 2 WC Chemistry, Multidisciplinary; Education, Scientific Disciplines SC Chemistry; Education & Educational Research GA 264SR UT WOS:000253311200013 ER PT J AU Liu, CW Lou, YY Lizee, G Qin, H Liu, SJ Rabinovich, B Kim, GJ Wang, YH Ye, Y Sikora, AG Overwijk, WW Liu, YJ Wang, G Hwu, P AF Liu, Chengwen Lou, Yanyan Lizee, Gregory Qin, Hong Liu, Shujuan Rabinovich, Brian Kim, Grace J. Wang, Yi-Hong Ye, Yang Sikora, Andrew G. Overwijk, Willem W. Liu, Yong-Jun Wang, Gang Hwu, Patrick TI Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NATURAL-KILLER-CELLS; INTERFERON-ALPHA PRODUCTION; MHC CLASS-I; ADAPTIVE IMMUNITY; INNATE IMMUNITY; ANTIVIRAL IMMUNITY; ANTITUMOR-ACTIVITY; CUTTING EDGE; LYMPH-NODE; IFN-ALPHA AB A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid. DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCRS via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells. C1 [Liu, Chengwen; Lou, Yanyan; Lizee, Gregory; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J.; Ye, Yang; Sikora, Andrew G.; Overwijk, Willem W.; Wang, Gang; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Ctr Canc Immunol Res, Houston, TX USA. [Qin, Hong] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Ctr Canc Immunol Res, Houston, TX USA. [Wang, Yi-Hong; Liu, Yong-Jun] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Ctr Canc Immunol Res, Houston, TX USA. RP Wang, G (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-675, Rockville, MD 20852 USA. EM gang.wang@fda.hhs.gov; phwu@mdanderson.org FU NCI NIH HHS [R01 CA123182, R01 CA123182-02] NR 51 TC 141 Z9 145 U1 0 U2 13 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2008 VL 118 IS 3 BP 1165 EP 1175 DI 10.1172/JCI33583 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 269JX UT WOS:000253646400040 PM 18259609 ER PT J AU Englberger, L Schierle, J Kraemer, K Aalbersberg, W Dolodolotawake, U Humphries, J Graham, R Reld, AP Lorens, A Alberta, K Levendusky, A Johnson, E Paul, Y Sengebau, F AF Englberger, Lois Schierle, Joseph Kraemer, Klaus Aalbersberg, William Dolodolotawake, Usaia Humphries, Julia Graham, Robin Reld, Anne P. Lorens, Adelino Alberta, Kiped Levendusky, Amy Johnson, Eliaser Paul, Yumiko Sengebau, Fernando TI Carotenoid and mineral content of Micronesian giant swamp taro (Cyrtosperma) cultivars SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE carotenoid; vitamin a; mineral; chronic disease; Micronesia; indigenous food; dietary change; giant swamp taro; cyrtosperma merkusii; taro cultivars ID PROVITAMIN-A; FOODS; BANANA; PHYTATE AB Dietary change in Micronesia has led to serious problems of vitamin A deficiency and other nutritionally-related health problems. It is essential to identify nutrient-rich indigenous foods that may be promoted for health improvements. Giant swamp taro (Cyrtosperma merkusii) is important for food and culture on atoll and mountainous islands of Micronesia. There are many Cyrtosperma cultivars, but few have been analyzed for nutrient content. Samples were collected in the Federated States of Micronesia (Pohnpei, Chuuk and Yap) and the Republic of Palau, assessed for corm flesh color and other attributes, and analyzed for carotenoids (beta- and alpha-carotene, beta-cryptoxanthin, lutein, zeaxanthin, and lycopene) and minerals (including iron, zinc, and calcium). Of 34 cultivars analyzed, beta-carotene concentrations varied from 50 to 4486 mu g/100 g. Yellow-fleshed cultivars generally contained higher carotenoid concentrations. Of the ten cultivars analyzed for mineral content (wet weight basis), substantial concentrations of zinc (5.4-46.1 mg/100 g), iron (0.3-0.8 mg/100 g) and calcium (121--305mg/100g) were found. All cultivars were acceptable for taste and production factors. These carotenoid- and mineral-rich cultivars should be considered for promotion in Micronesia and other areas for potential health benefits. (C) 2007 Elsevier Inc. All rights reserved. C1 [Schierle, Joseph; Kraemer, Klaus] DSM Nutr Prod Ltd, Kaiseraugst, Switzerland. [Aalbersberg, William; Dolodolotawake, Usaia] Univ S Pacific, Inst Appl Sci, Suva, Fiji. [Humphries, Julia] Flinders Med Ctr, Sch Pharmacol, Bedford Pk, SA, Australia. [Graham, Robin] Univ Adelaide, Fac Sci, Sch Agr & Wine, Glen Osmond, SA, Australia. [Reld, Anne P.] US FDA, Atlanta Ctr Nutr Anal, Atlanta, GA USA. [Sengebau, Fernando] Dept Agr, Koror, Palau. EM nutrition@mail.fm NR 61 TC 18 Z9 19 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD MAR PY 2008 VL 21 IS 2 BP 93 EP 106 DI 10.1016/j.jfca.2007.09.007 PG 14 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 245BK UT WOS:000251909200001 ER PT J AU Garber, EAE AF Garber, Eric A. E. TI Detection of melamine using commercial enzyme-linked immunosorbent assay technology SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CYROMAZINE AB Recent cases of adulteration with melamine have led to the need for rapid and reliable screening methods. To meet this need, commercial enzyme-linked immunosorbent assay (ELISA) test kits for the detection of triazines were evaluated. The recently released Melamine Plate kit (Abraxis, Warminster, Pa.) displayed a limit of detection of 9 ng/ml for melamine in phosphate-buffered saline (PBS) and approximately 1 mu g/ml for melamine added to dog food. An atrazine ELISA test kit produced by Abraxis required 0.2 mg/ml to generate a response more than four times the standard deviation from background. In contrast, with the EnviroGard Triazine Plate kit (Strategic Diagnostics, Inc., Newark, Del.), 1.5 mg/ml melamine in PBS generated a signal only one standard deviation from background, which was insufficient to define a limit of detection. Extraction based on dilution with 105 mM sodium phosphate/75 mM NaCl/2.5% nonfat milk/0.05% Tween 20 (UD) enabled detection of fivefold less melamine in dog food than did use of the procedure recommended by the manufacturer, which entailed extraction into 60% methanol, sonication, centrifugation, filtration, and further dilution into 10% methanol/PBS. Using the Abraxis Melamine ELISA, both extraction protocols yielded identical results with a dog food sample adulterated with melamine. The recovery of melamine spiked into gravy from dog food using UD was 74% +/- 4%. In conclusion, the recently released Abraxis ELISA for melamine proved to be a useful alternative to more cumbersome methods. C1 US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Garber, EAE (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM eric.garber@fda.hhs.gov NR 14 TC 133 Z9 145 U1 1 U2 21 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 MAR PY 2008 VL 71 IS 3 BP 590 EP 594 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 271YI UT WOS:000253824200019 PM 18389705 ER PT J AU Chaves, SS Haber, P Walton, K Wise, RP Izurieta, HS Schmid, DS Seward, JF AF Chaves, Sandra S. Haber, Penina Walton, Kimp Wise, Robert P. Izurieta, Hector S. Schmid, D. Scott Seward, Jane F. TI Safety of varicella vaccine after licensure in the United States: Experience from reports to the vaccine adverse event reporting system, 1995-2005 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ZOSTER-VIRUS REACTIVATION; HERPES-ZOSTER; ASEPTIC-MENINGITIS; HEALTHY-CHILDREN; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; IMMUNIZATION; INFECTION; STRAIN; IMMUNOCOMPETENT; SURVEILLANCE AB Widespread use of varicella vaccine in the United States could enable detection of rare adverse events not identified previously. We reviewed data from 1995 to 2005 from the Vaccine Adverse Event Reporting System, including data from laboratory analyses, to distinguish adverse events associated with wild-type varicellazoster virus (VZV) versus those associated with vaccine strain. Almost 48 million doses of varicella vaccine were distributed between 1995 and 2005. There were 25,306 adverse events reported (52.7/100,000 doses distributed); 5.0% were classified as serious (2.6/100,000 doses distributed). Adverse events associated with evidence of vaccine-strain VZV included meningitis in patients with concurrent herpes zoster. Patients with genetic predispositions may rarely have disease triggered by receipt of varicella vaccine. Overall, serious adverse events reported after varicella vaccination continue to be rare and must be considered relative to the substantial benefits of varicella vaccination. Ongoing safety surveillance and further studies may shed light on some of the hypothesized associations. C1 [Chaves, Sandra S.; Haber, Penina; Walton, Kimp; Schmid, D. Scott; Seward, Jane F.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Wise, Robert P.; Izurieta, Hector S.] US FDA, Rockville, MD 20857 USA. RP Chaves, SS (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,NE MS A-47, Atlanta, GA 30333 USA. EM schaves@cdc.gov NR 52 TC 55 Z9 66 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 MAR 1 PY 2008 VL 197 SU 2 BP S170 EP S177 DI 10.1086/522161 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 271FF UT WOS:000253773600026 PM 18419393 ER PT J AU Chiao, JC Goldman, JM David, H Kazanzides, P Peine, WJ Stiehl, JB Yen, D Dagalakis, NG AF Chiao, J. C. Goldman, Julian M. David, Heck Kazanzides, Peter Peine, William J. Stiehl, James B. Yen, Dwight Dagalakis, Nicholas G. TI Metrology and standards needs for some categories of medical devices SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE computer assisted surgical navigation; medical devices; networked medical device interoperability; neurostimulation implants; surgical robots; surgical simulation systems ID SPINAL-CORD STIMULATION; TOTAL KNEE ARTHROPLASTY; ROBOTIC SYSTEM; PAIN; SURGERY AB With rapid advances in meso, micro- and nano-scale technology devices and electronics, a new generation of advanced medical devices is emerging, which promises medical treatment that is less invasive and more accurate, automated, and effective. We examined the technological and economic status of five categories of medical devices. A set of metrology needs is identified for each of these categories and suggestions are made to address them. C1 [Chiao, J. C.] Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [David, Heck] Baylor Hlth Care Syst, Inst Hlth Care Res & Improvement, Dallas, TX 75206 USA. [Kazanzides, Peter] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Peine, William J.] Purdue Univ, Sch Mech Engn, W Lafayette, IN 47907 USA. [Peine, William J.] Purdue Univ, Regenstrief Ctr Healthcare Engn, W Lafayette, IN 47907 USA. [Stiehl, James B.] Columbia St Marys Hosp, Dept Orthopaed Surg, Milwaukee, WI 53211 USA. [Yen, Dwight] US FDA, Gen Surg Devices Branch, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Dagalakis, Nicholas G.] Natl Inst Stand & Technol, Intelligent Syst Div, Gaithersburg, MD 20899 USA. RP Chiao, JC (reprint author), Univ Texas Arlington, Dept Elect Engn, Arlington, TX 76019 USA. EM jcchiao@uta.edu; jmgoldman@partners.org; davidhec@baylorhealth.edu; pkaz@jhu.edu; peine@purdue.edu; jbstiehl@aol.com; dwight.yen@fda.hhs.gov; nicholas.dagalakis@nist.gov RI Kazanzides, Peter/A-3358-2010; OI Kazanzides, Peter/0000-0002-6117-5467 NR 31 TC 4 Z9 4 U1 0 U2 9 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD MAR-APR PY 2008 VL 113 IS 2 BP 121 EP 129 DI 10.6028/jres.113.009 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 321UD UT WOS:000257331100004 PM 27096115 ER PT J AU Hariharan, P Myers, MR Robinson, RA Maruvada, SH Sliwa, J Banerjee, RK AF Hariharan, Prasanna Myers, Matthew R. Robinson, Ronald A. Maruvada, Subha H. Sliwa, Jack Banerjee, Rupak K. TI Characterization of high intensity focused ultrasound transducers using acoustic streaming SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID PARTICLE IMAGE VELOCIMETRY; HYDROPHONE; CALIBRATION; PRESSURE; SYSTEM; FIELDS; BLOOD; BEAMS AB A new approach for characterizing high intensity focused ultrasound (HIFU) transducers is presented. The technique is based upon the acoustic streaming field generated by absorption of the HIFU beam in a liquid medium. The streaming field is quantified using digital particle image velocimetry, and a numerical algorithm is employed to compute the acoustic intensity field giving rise to the observed streaming field. The method as presented here is applicable to moderate intensity regimes, above the intensities which may be damaging to conventional hydrophones, but below the levels where nonlinear propagation effects are appreciable. Intensity fields and acoustic powers predicted using the streaming method were found to agree within 10% with measurements obtained using hydrophones and radiation force balances. Besides acoustic intensity fields, the streaming technique may be used to determine other important HIFU parameters, such as beam tilt angle or absorption of the propagation medium. 0 2008 Acoustical Society of America. C1 [Myers, Matthew R.; Robinson, Ronald A.; Maruvada, Subha H.] US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Hariharan, Prasanna] Univ Cincinnati, Dept Mech Ind & Nucl Engn, Cincinnati, OH 45221 USA. [Sliwa, Jack] AF Div, Sunnyvale, CA 94085 USA. [Banerjee, Rupak K.] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH 45221 USA. RP Myers, MR (reprint author), US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM matthew.myers@fda.hhs.gov NR 36 TC 19 Z9 19 U1 0 U2 8 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 MAR PY 2008 VL 123 IS 3 BP 1706 EP 1719 DI 10.1121/1.2835662 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 277JK UT WOS:000254208300047 PM 18345858 ER PT J AU Taylor, C Wilkening, VL AF Taylor, Christine Lewis Wilkening, Virginia L. TI How the nutrition food label was developed, Part 1: The nutrition facts panel SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID FORMATS; MEMBER C1 [Taylor, Christine Lewis; Wilkening, Virginia L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Taylor, C (reprint author), Natl Academies, Inst Med, 500 5th St,NW, Washington, DC 20001 USA. EM CLTaylor@nas.edu NR 32 TC 25 Z9 25 U1 0 U2 2 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAR PY 2008 VL 108 IS 3 BP 437 EP 442 DI 10.1016/j.jada.2007.12.010 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 270NN UT WOS:000253727600011 PM 18313424 ER PT J AU Sapsford, KE Bradburne, C Delehanty, JB Medintz, IL AF Sapsford, Kim E. Bradburne, Christopher Delehanty, James B. Medintz, Igor L. TI Sensors for detecting biological agents SO MATERIALS TODAY LA English DT Review ID RESONANCE ENERGY-TRANSFER; SINGLE-DOMAIN ANTIBODIES; MULTIDRUG-RESISTANT TUBERCULOSIS; CRYSTAL MICROBALANCE BIOSENSOR; A-CHIP DEVICES; MULTIPLEX PCR; MOLECULAR BEACONS; ANTIMICROBIAL PEPTIDES; REVERSE TRANSCRIPTION; BACTERIAL PATHOGENS AB Biological agents including viruses, bacteria, and other naturally occurring pathogenic organisms, along with the toxins they produce, are considered far harder to detect and defend against than chemical agents. Here we provide an overview of the predominant molecular sensing technologies for the detection of these agents. This includes biosensing strategies based upon use of antibodies, genomic analysis, biochemical testing, other recognition interactions, and cellular-based responses. We survey some popular sensing approaches, illustrate them with current examples showing how they have been applied, and discuss their intrinsic benefits and potential liabilities. Lastly, within the context of security applications, some approaches for integrating sensing technologies into field-portable devices are discussed. C1 [Bradburne, Christopher; Delehanty, James B.; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn Code 6900, Washington, DC 20375 USA. [Sapsford, Kim E.] US FDA, Off Sci & Engn Labs, Div Biol, Silver Spring, MD 20903 USA. RP Medintz, IL (reprint author), USN, Res Lab, Ctr Bio Mol Sci & Engn Code 6900, 4555 Overlook Ave SW, Washington, DC 20375 USA. EM Igor.Medintz@nrl.navy.mil NR 137 TC 39 Z9 40 U1 5 U2 30 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1369-7021 J9 MATER TODAY JI Mater. Today PD MAR PY 2008 VL 11 IS 3 BP 38 EP 49 DI 10.1016/S1369-7021(08)70018-X PG 12 WC Materials Science, Multidisciplinary SC Materials Science GA 268TT UT WOS:000253603200018 ER PT J AU Bingham, A Mamyrova, G Rother, KI Oral, E Cochran, E Premkumar, A Kleiner, D James-Newton, L Targoff, IN Pandey, JP Carrick, DM Sebring, N O'Hanlon, TP Ruiz-Hidalgo, M Turner, M Gordon, LB Laborda, J Bauer, SR Blackshear, PJ Imundo, L Miller, FW Rider, LG AF Bingham, April Mamyrova, Gulnara Rother, Kristina I. Oral, Efif Cochran, Elaine Premkumar, Ahalya Kleiner, David James-Newton, Laura Targoff, Ira N. Pandey, Janardan P. Carrick, Danielle Mercatante Sebring, Nancy O'Hanlon, Terrance P. Ruiz-Hidalgo, Maria Turner, Maria Gordon, Leslie B. Laborda, Jorge Bauer, Steven R. Blackshear, Perry J. Imundo, Lisa Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity S TI Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity SO MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; FAMILIAL PARTIAL LIPODYSTROPHY; IDIOPATHIC INFLAMMATORY MYOPATHIES; BODY-FAT DISTRIBUTION; NECROSIS-FACTOR-ALPHA; OF-THE-LITERATURE; METABOLIC DERANGEMENTS; LEPTIN CONCENTRATIONS; OMENTAL ADIPOCYTES; CLINICAL-FEATURES AB We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed lipodystrophy (LD) that could be categorized into I of 3 phenotypes, generalized, partial, or focal, based on the pattern of fat loss distribution. LD onset was often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis, muscle atrophy, joint contractures, and facial rash were DM disease features found to be associated with LD. Panniculitis was associated with focal lipoatrophy while the anti-p155 autoantibody, a newly described myositis-associated autoantibody, was more associated with generalized LD. Specific LD features such as acanthosis nigricans, hirsutism, fat redistribution, and steatosis/nonalcoholic steatoliepatitis were frequent in patients with LD, in a gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies frequently revealed insulin resistance and hypertriglyceridemia in patients with generalized and partial LD. Regional fat loss from the thighs, with relative sparing of fat loss from the medial thighs, was more frequent in generalized than in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not appear to play a pathogenic role in the development of LD in our patients. LD is an under-recognized sequela of JDM, and certain DM patients with a severe, prolonged clinical course and a high frequency of calcinosis appear to be at greater risk for the development of this complication. High-risk JDM patients should be screened for metabolic abnormalities, which are common in generalized and partial LD and result in much of the LD-associated morbidity. Further study is warranted to investigate the pathogenesis of acquired LD in patients with DM. C1 [Bingham, April; Mamyrova, Gulnara; James-Newton, Laura; Carrick, Danielle Mercatante; O'Hanlon, Terrance P.; Blackshear, Perry J.; Miller, Frederick W.; Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, Bethesda, MD 20892 USA. [Rother, Kristina I.; Oral, Efif; Cochran, Elaine] NIDDK, Bethesda, MD 20892 USA. [Kleiner, David; Turner, Maria] NCI, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. [Bingham, April] Penn State Milton S Hershey Med Ctr, Hershey, PA USA. [Oral, Efif] Univ Michigan, Ann Arbor, MI 48109 USA. [Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. [Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Pandey, Janardan P.] Med Univ S Carolina, Charleston, SC 29425 USA. [Ruiz-Hidalgo, Maria; Laborda, Jorge; Bauer, Steven R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Imundo, Lisa] Columbia Univ, New York, NY USA. [Ruiz-Hidalgo, Maria; Laborda, Jorge] Univ Castilla La Mancha, Fac Med, CRIB, Albacete, Spain. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Off Clin Res, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; OI Laborda, Jorge/0000-0002-9210-838X; Bauer, Steven/0000-0003-2831-846X; Oral, Elif/0000-0002-9171-1144; Kleiner, David/0000-0003-3442-4453; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101074-06, Z99 DK999999]; NIAMS NIH HHS [P30 AR053483] NR 63 TC 42 Z9 44 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAR PY 2008 VL 87 IS 2 BP 70 EP 86 DI 10.1097/MD.0b013e31816bc604 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 275WW UT WOS:000254103900003 PM 18344805 ER PT J AU Desai, VG Lee, T Delongchamp, RR Leakey, JEA Lewis, SM Lee, F Moland, CL Branham, WS Fuscoe, JC AF Desai, Varsha G. Lee, Taewon Delongchamp, Robert R. Leakey, Julian E. A. Lewis, Sherry M. Lee, Fei Moland, Carrie L. Branham, William S. Fuscoe, James C. TI Nucleoside reverse transcriptase inhibitors (NRTIs)-induced expression profile of mitochondria-related genes in the mouse liver SO MITOCHONDRION LA English DT Article DE mitochondria; Mouse MitoChip; microarray; nucleoside reverse transcriptase inhibitors; p53 haplodeficient (+/-) C3B6F(1) female mouse; p53 wild-type (+/+) C3B6F(1) female Mouse ID ANTIRETROVIRAL THERAPY; PERINATAL EXPOSURE; UNINFECTED INFANTS; INFECTED PATIENTS; ZIDOVUDINE AZT; HIV-INFECTION; TOXICITY; DNA; ANALOGS; DYSFUNCTION AB Mitochondrial dysfunction has been implicated in the adverse effects of nucleoside reverse transcriptase inhibitors (NRTIs) used to treat HIV-1 infections. To gain insight into the mechanism by which NRTIs alter mitochondrial function, the expression level of 542 genes associated with mitochondrial structure and functions was determined in the livers of p53 haplodeficient (+/-) C3136F(1) female mouse pups using mouse mitochondria-specific oligonucleotide microarray. The pups were transplacentally exposed to zidovudine (AZT) at 240 mg/kg bw/day or a combination of AZT and lamivudine (3TC) at 160 and 100 mg/kg bw/day, respectively, from gestation day 12 through 18, followed by continuous treatment by oral administration from postnatal day 1-28. In addition, AZT/3TC effect was investigated in wild-type (+/+) C3136F(1) female mice. The genotype did not significantly affect the gene expression profile induced by AZT/3TC treatment. However, the transcriptional level of several genes associated with oxidative phosphorylation, mitochondrial tRNAs, fatty acid oxidation, steroid biosynthesis, and a few transport proteins were significantly altered in pups treated with AZT and AZT/3TC compared to their vehicle counterparts. Interestingly, AZT/3TC altered the expression level of 153 genes with false discovery rate of less than 0.05, in contrast to only 20 genes by AZT alone. These results suggest that NRTI-related effect on expression level of genes associated with mitochondrial functions was much greater in response to AZT/3TC combination treatment than AZT alone. (C) 2008 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Desai, Varsha G.; Moland, Carrie L.; Branham, William S.; Fuscoe, James C.] Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. [Lee, Taewon] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Leakey, Julian E. A.; Lewis, Sherry M.; Lee, Fei] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov NR 63 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD MAR PY 2008 VL 8 IS 2 BP 181 EP 195 DI 10.1016/j.mito.2008.01.002 PG 15 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 284EO UT WOS:000254689400010 PM 18313992 ER PT J AU Brown, DG Si, J Sun, R AF Brown, David G. Si, Jennie Sun, Ron TI Special Issue on Advances in Neural Networks Research: IJCNN'07 SO NEURAL NETWORKS LA English DT Editorial Material C1 [Brown, David G.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Si, Jennie] Arizona State Univ, Tempe, AZ 85287 USA. [Sun, Ron] Rensselaer Polytech Inst, Troy, NY 12181 USA. RP Brown, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM david.brown@fda.hhs.gov; si@asu.edu; rsun@rpi.edu 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 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD MAR-APR PY 2008 VL 21 IS 2-3 BP 113 EP 113 DI 10.1016/j.neunet.2008.01.002 PG 1 WC Computer Science, Artificial Intelligence SC Computer Science GA 292AM UT WOS:000255238800001 PM 18262753 ER PT J AU Gallas, BD Brown, DG AF Gallas, Brandon D. Brown, David G. TI Reader studies for validation of CAD systems SO NEURAL NETWORKS LA English DT Article; Proceedings Paper CT International Joint Conference on Neural Networks CY AUG 12-17, 2007 CL Orlando, FL SP IEEE DE ROC; reader studies; study design; multi-reader multi-case (MRMC) variance analysis ID OPERATING CHARACTERISTIC ANALYSIS; CORRELATED ROC ANALYSIS; NONPARAMETRIC APPROACH; CHARACTERISTIC CURVES; MRMC METHOD; MULTIREADER; REGRESSION; MODEL; AREA; VARIANCE AB Evaluation of computational intelligence (Cl) systems designed to improve the performance of it human operator is complicated by the need to include the effect of human variability. In this paper we consider human (reader) variability in the context of medical imaging computer-assisted diagnosis (CAD) systems, and we outline how to compare the detection performance of readers with and without the CAD. An effective and statistically powerful comparison call be accomplished with a receiver operating characteristic (ROC) experiment, summarized by the reader-averaged area under the ROC Curve (AUC). The comparison requires sophisticated yet well-developed methods for multi-reader multi-case (MRMC) variance analysis. MRMC variance analysis accounts for random readers, random cases, and correlations in the experiment. In this paper, we extend the methods available for estimating this variability. Specifically, we present a method that can treat arbitrary study designs. Most methods treat only the fully-crossed study design, where every reader reads every case in two experimental conditions. We demonstrate our method with a computer simulation, and we assess the statistical power of a variety of study designs. Published by Elsevier Ltd. C1 [Gallas, Brandon D.; Brown, David G.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Gallas, BD (reprint author), US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. EM brandon.galias@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 48 TC 8 Z9 8 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD MAR-APR PY 2008 VL 21 IS 2-3 BP 387 EP 397 DI 10.1016/j.neunet.2007.12.013 PG 11 WC Computer Science, Artificial Intelligence SC Computer Science GA 292AM UT WOS:000255238800030 PM 18215501 ER PT J AU Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Hass, BS Thorn, BT Feuers, RJ AF Duffy, Peter H. Lewis, Sherry M. Mayhugh, Martha A. Trotter, Ronald W. Hass, Bruce S. Thorn, Brett T. Feuers, Ritchie J. TI Nonneoplastic pathology in male Sprague-Dawley rats fed the American Institute of Nutrition-93M purified diet at ad libitum and dietary-restricted intakes SO NUTRITION RESEARCH LA English DT Article DE dietary; restriction; nonneoplastic; rat; pathology ID CALORIC RESTRICTION; FISCHER-344 RATS; SURVIVAL; GROWTH; TOXICITY; RODENTS; AIN-76A AB This study evaluates the effects of age and chronic dietary restriction (DR) on nonneoplastic diseases in rats that were fed the American Institute of Nutrition (AIN)-93M purified diet. Male Sprague-Dawley (SD) rats were divided into an ad libitum (AL) group and a DR group that was fed the AIN-93M diet with intake reduced by 31%. Nonneoplastic disease profiles were developed to clarify whether the AIN-93M diet fulfills long-term nutritional requirements of rats. Subsets of rats were killed at 58 and 114 weeks of age, and histopathology was performed. At 58 weeks of age, the 2 main types of nonneoplastic diseases in AL rats were liver vacuolization and cardiomyopathy. Dietary restriction reduced the severity and incidence of both lesions. At 114 weeks of age, the most common lesions in AL rats were cardiomyopathy, nephropathy, liver vacuolization, and degeneration with renal failure and genitourinary infections causing the greatest mortality. Dietary resuriction reduced the incidence and severity of these lesions. Nonneoplastic diseases accounted for 28.9% and 0.0% of total mortalities in the AL and DR groups, respectively; however, there was a higher incidence of unknown deaths in the DR rats (52.6%) compared to AL rats (28.9%), which may have limited the success of DR to improve survival. Although the AIN-93M diet supported chronic rat growth, alterations in some dietary component concentrations may be required to lower body weight in chronic rodent and human studies. Factors such as diet composition and digestibility may alter nonneoplastic diseases and mortality in rats and humans in a similar fashion. Published by Elsevier Inc. C1 [Duffy, Peter H.; Hass, Bruce S.] US FDA, Div Genet & Reproduct Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lewis, Sherry M.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mayhugh, Martha A.] US FDA, Bionet Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Trotter, Ronald W.] US FDA, Pathol Associat Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Thorn, Brett T.] US FDA, Z Tech Incorp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Feuers, Ritchie J.] US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Duffy, PH (reprint author), US FDA, Div Genet & Reproduct Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.duffy@fda.hhs.gov RI Biguzzi, Felipe/E-4724-2015 NR 28 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAR PY 2008 VL 28 IS 3 BP 179 EP 189 DI 10.1016/j.nutres.2008.01.002 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 289JR UT WOS:000255051300008 PM 19083406 ER PT J AU Kim, DH Kang, JU Ilev, IK AF Kim, Do-Hyun Kang, Jin U. Ilev, Ilko K. TI Upconversion fiber-optic confocal microscopy under near-infrared pumping SO OPTICS LETTERS LA English DT Article AB We present a simple upconversion fiber-optic confocal microscope design using a near-infrared laser for pumping of a rare-earth-doped glass powder. The nonlinear optical frequency conversion process is highly efficient with more than 2% upconversion fluorescence efficiency at a near-infrared pumping wavelength of 1.55 mu m. The upconversion confocal design allows the use of conventional Si detectors and 1.55 mu m near-infrared pump light. The lateral and axial resolutions of the system were equal to or better than 1.10 and 13.11 mu m, respectively. (C) 2008 Optical Society of America. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Div Phys, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Div Phys, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov RI Kim, Do-Hyun/C-5311-2009; Kang, Jin/A-3228-2010 NR 7 TC 1 Z9 1 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2008 VL 33 IS 5 BP 425 EP 427 DI 10.1364/OL.33.000425 PG 3 WC Optics SC Optics GA 282KE UT WOS:000254565700005 PM 18311280 ER PT J AU Rodriguez, W Selen, A Avant, D Chaurasia, C Crescenzi, T Gieser, G Di Giacinto, J Huang, SM Lee, P Mathis, L Murphy, D Murphy, S Roberts, R Sachs, HC Suarez, S Tandon, V Uppoor, RS AF Rodriguez, William Selen, Arzu Avant, Debbie Chaurasia, Chandra Crescenzi, Terrie Gieser, Gerlie Di Giacinto, Jennifer Huang, Shiew-Mei Lee, Peter Mathis, Lisa Murphy, Dianne Murphy, Shirley Roberts, Rosemary Sachs, Hari Cheryl Suarez, Sandra Tandon, Veneeta Uppoor, Ramana S. TI Improving pediatric dosing through pediatric initiatives: What we have learned SO PEDIATRICS LA English DT Article DE pediatric dosing; safety; efficacy; labeling; exposure; bioavailability; pharmacology; pharmacokinetics; pharmacodynamics ID CHILDREN AB OBJECTIVE. The goal was to review the impact of pediatric drug studies, as measured by the improvement in pediatric dosing and other pertinent information captured in the drug labeling. METHODS. We reviewed the pediatric studies for 108 products submitted (July 1998 through October 2005) in response to a Food and Drug Administration written request for pediatric studies, and the subsequent labeling changes. We analyzed the dosing modifications and focused on drug clearance as an important parameter influencing pediatric dosing. RESULTS. The first 108 drugs with new or revised pediatric labeling changes had dosing changes or pharmacokinetic information (n = 23), new safety information (n = 34), information concerning lack of efficacy (n = 19), new pediatric formulations (n = 12), and extended age limits (n = 77). A product might have had >= 1 labeling change. We selected specific examples (n = 16) that illustrate significant differences in pediatric pharmacokinetics. CONCLUSIONS. Critical changes in drug labeling for pediatric patients illustrate that unique pediatric dosing often is necessary, reflecting growth and maturational stages of pediatric patients. These changes provide evidence that pediatric dosing should not be determined by simply applying weight-based calculations to the adult dose. Drug clearance is highly variable in the pediatric population and is not readily predictable on the basis of adult information. C1 [Rodriguez, William; Selen, Arzu; Avant, Debbie; Chaurasia, Chandra; Crescenzi, Terrie; Gieser, Gerlie; Di Giacinto, Jennifer; Huang, Shiew-Mei; Lee, Peter; Mathis, Lisa; Murphy, Dianne; Murphy, Shirley; Roberts, Rosemary; Sachs, Hari Cheryl; Suarez, Sandra; Tandon, Veneeta; Uppoor, Ramana S.] US FDA, Rockville, MD 20850 USA. RP Rodriguez, W (reprint author), US FDA, 5600 Fisher Lane,Parklawn Bldg,Room 13B-45, Rockville, MD 20850 USA. EM william.rodriguez@fda.hhs.gov NR 14 TC 73 Z9 81 U1 0 U2 8 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 MAR PY 2008 VL 121 IS 3 BP 530 EP 539 DI 10.1542/peds.2007-1529 PG 10 WC Pediatrics SC Pediatrics GA 271HS UT WOS:000253780100011 PM 18310202 ER PT J AU Braun, MM AF Braun, M. Miles TI Toward better vaccine safety data and safer vaccination SO PEDIATRICS LA English DT Editorial Material ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; UNITED-STATES; CHILDREN; MEASLES C1 US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. EM miles.braun@fda.hhs.gov NR 18 TC 6 Z9 7 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 MAR PY 2008 VL 121 IS 3 BP 625 EP 626 DI 10.1542/peds.2007-3846 PG 2 WC Pediatrics SC Pediatrics GA 271HS UT WOS:000253780100023 PM 18310214 ER PT J AU Lesko, LJ Gage, BF AF Lesko, Lawrence J. Gage, Brian F. TI Couma-Gen: implications for future randomized trials of pharmacogenetic-based warfarin therapy SO PERSONALIZED MEDICINE LA English DT Article DE adverse event; algorithm; CYP2C9; hemorrhage; pharmacogenetics; study design; treatment outcome; VKORC1; warfarin ID RECURRENT VENOUS THROMBOEMBOLISM; ORAL ANTICOAGULANT-THERAPY; HOSPITALIZED-PATIENTS; GENETIC-POLYMORPHISM; ORTHOPEDIC PATIENTS; LONG-TERM; INTENSITY; CYP2C9; PREVENTION; MORTALITY AB Evaluation of: Anderson JL, Horne BID, Stevens SM et al.: Randomized trial of genotype-guided versus standard warfarin dosing in patients initiating oral anticoagulation. Circulation 116, 2563-2570 (2007). Warfarin is an effective oral anticoagulant used to treat or prevent thromboembolic disorders in millions of patients worldwide. Even with conscientious International Normalized Ratio (INR) monitoring, warfarin initiation carries a high risk of hemorrhage. Pharmacogenetic studies have determined that variants in the CYP2C9 and VKORC1 genes help to predict the therapeutic warfarin dose. Whether using this information prospectively will prevent under- and over-dosing of warfarin is unknown. To answer this question, the Couma-Gen investigators randomized half of a 200-patient cohort beginning warfarin therapy to clinical dosing and half to pharmacogenetic dosing. Overall, pharmacogenetic dosing slightly increased time in the therapeutic INR range (p = not significant) and decreased the number of INR tests required. The trial has important implications for the new NIH-funded multicentered trial. Here, we discuss the Couma-Gen study and its implications for the design, randomization, blinding and end point definition of future studies. C1 [Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Gage, Brian F.] Washington Univ, Sch Med St Louis, Div Gen Med Sci, Dept Med, St Louis, MO 63110 USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM lawrence.lesko@fda.hhs.gov NR 21 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAR PY 2008 VL 5 IS 2 BP 163 EP 168 DI 10.2217/17410541.5.2.163 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 364QL UT WOS:000260350100014 ER PT J AU Benet, LZ Amidon, GL Barends, DM Lennernas, H Polli, JE Shah, VP Stavchansky, SA Yu, LX AF Benet, Leslie Z. Amidon, Gordon L. Barends, Dirk M. Lennernas, Hans Polli, James E. Shah, Vinod P. Stavchansky, Salomon A. Yu, Lawrence X. TI The use of BDDCS in classifying the permeability of marketed drugs SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE BCS; BDDCS; bioequivalence; elimination pathways ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; NET WATER-ABSORPTION; HUMAN JEJUNUM; INTESTINAL PERMEABILITY; BCS; BIOAVAILABILITY; ANTIPYRINE; PERFUSION; RAT AB We recommend that regulatory agencies add the extent of drug metabolism (i.e., >= 90% metabolized) as an alternate method in defining Class 1 marketed drugs suitable for a waiver of in vivo studies of bioequivalence. That is, >= 90% metabolized is an additional methodology that may be substituted for >= 90% absorbed. We propose that the following criteria be used to define >= 90% metabolized for marketed drugs: Following a single oral dose to humans, administered at the highest dose strength, mass balance of the Phase 1 oxidative and Phase 2 conjugative drug metabolites in the urine and feces, measured either as unlabeled, radioactive labeled or nonradioactive labeled substances, account for >= 90% of the drug dosed. This is the strictest definition for a waiver based on metabolism. For an orally administered drug to be >= 90% metabolized by Phase 1 oxidative and Phase 2 conjugative processes, it is obvious that the drug must be absorbed. This proposal, which strictly conforms to the present >= 90% criteria, is a suggested modification to facilitate a number of marketed drugs being appropriately assigned to Class 1. C1 [Benet, Leslie Z.] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. [Amidon, Gordon L.] Univ Michigan, Coll Pharm, Dept Pharmaceut, Ann Arbor, MI 48109 USA. [Barends, Dirk M.] RIVM Natl Inst Publ Hlth & Environ, Bilthoven, Netherlands. [Lennernas, Hans] Uppsala Univ, Dept Pharm, Dept Biopharmaceut & Pharmacokinet, S-75123 Uppsala, Sweden. [Polli, James E.] Univ Maryland, Dept Pharmaceut Sci, Sch Pharm, Baltimore, MD 21201 USA. [Stavchansky, Salomon A.] Univ Texas Austin, Coll Pharm, Div Pharmaceut, Austin, TX 78712 USA. [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Benet, LZ (reprint author), Univ Calif San Francisco, Dept Biopharmaceut Sci, 533 Parnassus Ave,Room U-68, San Francisco, CA 94143 USA. EM leslie.benet@ucsf.edu RI Benet, Leslie/K-8286-2016; Yu, Lawrence/L-6280-2016 FU NIGMS NIH HHS [R21 GM075900-02, GM 075900, R21 GM075900] NR 30 TC 85 Z9 91 U1 1 U2 21 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 MAR PY 2008 VL 25 IS 3 BP 483 EP 488 DI 10.1007/s11095-007-9523-x PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 271CG UT WOS:000253765900001 PM 18236138 ER PT J AU McAdams, M Staffa, J Dal Pan, G AF McAdams, Mara Staffa, Judy Dal Pan, Gerald TI Estimating the extent of reporting to FDA: a case study of statin-associated rhabdomyolysis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE Adverse Event Reporting System (AERS); FDA; extent of reporting; spontaneous reporting systems; stimulated reporting; rhabdomyolysis; statin; Dear Health Care Provider letter; under-reporting ID ADVERSE DRUG-REACTIONS; LABORATORY SIGNALS; GENERAL-PRACTICE; LOWERING DRUGS; SWEDEN AB Purpose To estimate the extent of reporting to FDA through statin-associated rhabdomyolysis data. Methods Data included incidence rates (IRs) of hospitalized rhabdomyolysis among statin users from a population-based study, and comparable reported AERS cases and national estimates of statin use from an AERS analysis. Using IRs, national estimates of statin use and average days supply per prescription, we estimated the number of US statin-associated cases of hospitalized rhabdomyolysis. We compared this estimate to the observed number of cases reported to FDA to evaluate the extent of reporting. We repeated this method for atorvastatin, cerivastatin, pravastatin, and simvastatin and statin combinations. We performed sensitivity analyses to check for biases such as misclassification of statin use and cohort selection bias. We evaluated potential time-dependent cerivastatin reporting by a "Dear Health Care Provider (DHCP)" letter. Results The estimated extent of reporting to FDA varied by statin (atorvastatin, 5.0%; cerivastatin, 31.2%; simvastatin, 14.2%; all four combined, 17.7%; and non-cerivastatin statins combined, 9.9%). No pravastatin-associated cohort cases occurred. Across a reasonable value range, sensitivity analyses did not significantly alter the results; overall the cohort was similar to national statin-users. There was a large increase in AERS reports after the cerivastatin DHCP letter and the estimated extent of reporting increased from 14.8 to 35.0%. Conclusions The extent of reporting of adverse events to FDA varied by statin and may be influenced by publicity. For statins-associated rhabdomyolysis, the estimated extent of reporting appears to range from 5 to 30% but in the absence of stimulated reporting appears to be 5-15%. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [McAdams, Mara; Staffa, Judy; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP McAdams, M (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Mailstop 4447, Silver Spring, MD 20993 USA. EM mara.mcadams@fda.hhs.gov OI McAdams-DeMarco, Mara/0000-0003-3013-925X NR 32 TC 32 Z9 33 U1 0 U2 9 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 MAR PY 2008 VL 17 IS 3 BP 229 EP 239 DI 10.1002/pds.1535 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 279ZP UT WOS:000254395000003 PM 18175291 ER PT J AU Andrade, SE Raebel, MA Brown, J Lane, K Livingston, J Boudreau, D Rolnick, SJ Roblin, D Smith, DH Dal Pan, GJ Scott, PE Platt, R AF Andrade, Susan E. Raebel, Marsha A. Brown, Jeffrey Lane, Kimberly Livingston, James Boudreau, Denise Rolnick, Sharon J. Roblin, Douglas Smith, David H. Dal Pan, Gerald J. Scott, Pamela E. Platt, Richard TI Outpatient use of cardiovascular drugs during pregnancy SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pregnancy; cardiovascular drugs; fetal harm ID CARDIAC-DISEASE; WORKING GROUP; EXPOSURE; HYPERTENSION; PRESCRIPTION; ANTAGONISTS; INHIBITORS AB Purpose To provide information on the prevalence of use of cardiovascular drugs, some of which may have fetotoxic or teratogenic effects, in the outpatient setting among pregnant women in the United States. Methods A retrospective study was conducted using the automated databases of seven health plans participating in the HMO Research Network Center for Education and Research on Therapeutics (CERT). Women who delivered an infant from I January 2001 to 31 December 2005 were identified. Cardiovascular drug use was evaluated assuming a gestational duration of 270 days. Results During the period 2001 through 2005, 118 935 deliveries were identified that met the criteria for study; 3.1% of women (N = 3672) were dispensed an anti hypertensive medication and 0.12% of women (N = 146) were dispensed an antihyperlipidemic medication at any time during pregnancy. The most common antihypertensive drugs dispensed during pregnancy were nifedipine (1219 deliveries; 1.0%), methyldopa (961 deliveries; 0.8%), atenolol (593 deliveries; 0.5%), and labetalol (576 deliveries; 0.5%). Overall, 134 women (0.11%) received an angiotensin converting enzyme (ACE) inhibitor and 7 women (0.006%) received an angiotensin 11 receptor blocker (ARB) during pregnancy. Statins were the most commonly dispensed antihyperlipidemic drugs (71 deliveries; 0.06%). Conclusions The prevalence of use of cardiovascular drugs that are suspected to be fetotoxic or teratogenic (ACE inhibitors, ARBs, and statins) was low in this cohort of pregnant women. Differing patterns of use across health plans suggests that further research is needed to evaluate the potential differential effects of cardiovascular drugs to assist prescribers and patients in making informed treatment decisions. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, Worcester, MA 01605 USA. [Raebel, Marsha A.] Kaiser Permanente, Denver, CO USA. [Brown, Jeffrey; Lane, Kimberly; Livingston, James; Platt, Richard] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Brown, Jeffrey; Lane, Kimberly; Livingston, James; Platt, Richard] Harvard Pilgrim Hlth Care, Boston, MA USA. [Boudreau, Denise] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Rolnick, Sharon J.] HealthPartners Res Fdn, Minneapolis, MN USA. [Roblin, Douglas] Kaiser Permanente, Atlanta, GA USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Scott, Pamela E.] US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Andrade, SE (reprint author), Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org FU PHS HHS [HHSF223200510012C] NR 22 TC 30 Z9 31 U1 0 U2 6 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 MAR PY 2008 VL 17 IS 3 BP 240 EP 247 DI 10.1002/pds.1550 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 279ZP UT WOS:000254395000004 PM 18200619 ER PT J AU Ranieri, TL Ciolino, LA AF Ranieri, Tracy L. Ciolino, Laura A. TI Rapid selective screening and determination of ephedrine alkaloids using GC-MS footnote mark SO PHYTOCHEMICAL ANALYSIS LA English DT Article DE Ephedra; ma huang; ephedrine; pseudoephedrine; gas chromatography-mass spectrometry; O-TMS; N-TFA derivatives ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DIETARY-SUPPLEMENTS; GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; CAPILLARY-ELECTROPHORESIS; PSEUDOEPHEDRINE; DERIVATIVES; ULTRAVIOLET; BOTANICALS; STANDARD AB Ephedra (ma huang) has been widely used as an herb or herbal extract in both traditional Chinese medicine and Western world dietary supplements. The effects of Ephedra have been attributed to a series of six ephedrine alkaloids including ephedrine and pseudoephedrine. A GC-MS method for the ephedrine alkaloids is described which couples ammoniacal chloroform as the extraction solvent with a two-stage derivatisation scheme. This scheme produces the O-trimethylsilyl, N-trifluoracetyl derivatives (O-TMS, N-TFA) for the primary and secondary amine alkaloids, and the O-TMS derivatives for the tertiary amine alkaloids. Relatively clean extracts are obtained from complex matrices, and the six ephedrine alkaloids are effectively separated and identified. This approach was also evaluated for quantitative analysis, and was shown to provide quantitative results for ephedrine and pseudoephedrine, and good estimates for the four minor alkaloids. Figures of merit are presented for linearity, detection limits, precision and accuracy. We have applied this approach to the rapid screening and profiling of the ephedrine alkaloids in whole Ephedra plants, liquid plant extracts, dried powder plant extracts and a variety of Ephedra-containing dietary supplements. Published in 2007 by John Wiley & Sons, Ltd. C1 [Ranieri, Tracy L.; Ciolino, Laura A.] US FDA, Forens Chem Ctr, Cincinnati, OH 45231 USA. RP Ciolino, LA (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45231 USA. EM laura.ciolino@fda.hhs.gov NR 25 TC 6 Z9 6 U1 3 U2 17 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0958-0344 J9 PHYTOCHEM ANALYSIS JI Phytochem. Anal. PD MAR-APR PY 2008 VL 19 IS 2 BP 127 EP 135 DI 10.1002/pca.1025 PG 9 WC Biochemical Research Methods; Plant Sciences; Chemistry, Analytical SC Biochemistry & Molecular Biology; Plant Sciences; Chemistry GA 279IK UT WOS:000254348700005 PM 17879230 ER PT J AU Mizumachi, T Muskhelishvili, L Naito, A Furusawa, J Fan, CY Siegel, ER Kadlubar, FF Kumar, U Higuchi, M AF Mizumachi, Takatsugu Muskhelishvili, Levan Naito, Akihiro Furusawa, Jun Fan, Chun-Yang Siegel, Eric R. Kadlubar, Fred F. Kumar, Udaya Higuchi, Masahiro TI Increased distributional variance of mitochondrial DNA content associated with prostate cancer cells as compared with normal prostate cells SO PROSTATE LA English DT Article DE mitochondrial DNA; cancer initiation; cancer progression ID MUTATIONS; NUCLEAR; PROGRESSION; DETERMINES; CARCINOMA; DELETIONS; STRESS; TUMORS; GAMMA AB BACKGROUND. Mitochondria are key organelles for apoptosis, and mitochondrial DNA (mtDNA) content can regulate cancer progression. Increases in mtDNA mutations and deletions have been reported in cancer; however, a detailed investigation of mtDNA content in cancer cells has not yet been conducted. METHODS. Quantitative real-time PCR and improved extraction method were established to investigate the mtDNA content in a single prostate cell. RESULTS. The heterogeneity of mtDNA content was demonstrated between the clones of prostate cancer cell line LNCaP and individual cells in each clone. To investigate whether large distributional variance of mtDNA content is associated with cancer initiation and/or progression, we first compared PZ-HPV-7, an HPV-transformed normal prostate epithelial cell line, with CA-HPV-10, transformed from prostate cancer cells derived from the same donor. We found an enhanced distributional variance of mtDNA content in CA-HPV-10. Then, we investigated mtDNA content in individual cells in laser microdisssected cancer and adjacent normal cells from prostate cancer tissue specimens using quantitative real-time PCR method. Results showed that the mtDNA content per cell follows a higher skewed distribution in cancer cells as compared in normal cells. We also observed that mtDNA content was increased in seven of nine (78%) of prostate cancers compared to normal prostate tissue. CONCLUSIONS. These results indicate that prostate carcinogenesis may involve dysregulation of mtDNA content. C1 [Mizumachi, Takatsugu; Naito, Akihiro; Furusawa, Jun; Higuchi, Masahiro] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Div Toxicol Pathol Associates, Food & Drug Adm, Jefferson, AR 72079 USA. [Fan, Chun-Yang] Univ Arkansas Med Sci, Dept Pathol, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. [Siegel, Eric R.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Kadlubar, Fred F.] Univ Arkansas Med Sci, Dept Epidemiol, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. [Kumar, Udaya] Univ Arkansas Med Sci, Dept Urol, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. RP Higuchi, M (reprint author), 4301 W Markham St,Slot 516 Little Rock, Little Rock, AR 72205 USA. EM mhiguchi@uams.edu RI Mizumachi, Takatsugu/G-5479-2012 FU NCI NIH HHS [CA100846, R01 CA100846, R01 CA100846-01A1, R01 CA100846-02, R01 CA100846-03, R01 CA100846-04, R01 CA100846-05, R01 CA100846-06] NR 29 TC 42 Z9 44 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAR 1 PY 2008 VL 68 IS 4 BP 408 EP 417 DI 10.1002/pros.20697 PG 10 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 272TM UT WOS:000253882900007 PM 18196528 ER PT J AU Bowyer, JF Robinson, B Ali, S Schmued, LC AF Bowyer, John F. Robinson, Bonnie Ali, Syed Schmued, Larry C. TI Neurotoxic-related changes in tyrosine hydroxylase, microglia, myelin, and the blood-brain barrier in the caudate-putamen from acute methamphetamine exposure SO SYNAPSE LA English DT Article DE blood-brain barrier; methamphetamine; DA; tyrosine hydroxylase; neurotoxicity ID NEURONAL DEGENERATION; DOPAMINERGIC NEUROTOXICITY; GENE-EXPRESSION; HIGH-RESOLUTION; MOUSE; AMPHETAMINE; INJURY; ACTIVATION; GLUTAMATE; MICE AB Changes in the histological morphology of the caudate-putamen (CPu) were determined after a high-dose methamphetamine (METH) exposure in an effort to elucidate whether BBB disruption plays a role in CPu neurotoxicity. This was accomplished by evaluating the tyrosine hydroxylase immunoreactivity (TH-IR), isolectin B4 reactivity, Black Gold II (BG-II) and Fluoro-Jade C (FJ-C) staining, and immunoreactivity to mouse immunoglobulin G (IgG-IR) in adult male mice at 90-min, 4-h, 12-h, 1-day, and 3-day post-METH exposure. The IgG-IR indicated that the BBB was only modestly altered in the CPu at time points after neurodegeneration occurred and dependent on hyperthermia and status epilepticus. The modest CPu IgG-IR changes observed in the perivascular areas indicated that immunoglobulins were present on some CPu microglia 1 day or more after METH. The first signs of CPu damage were swellings in the TH-IR axons, myelin damage, and a few degenerating neurons at 4-h post-METH. The loss of TH-IR was dependent on hyperthermia but not seizures or CPu neurodegeneration, and the TH-IR was virtually absent throughout the CPu within 12 h. Surprisingly, signs of FJ-C labeling (degenerating) axons in the CPu were seen only in the regions of pronounced somatic neurodegeneration and independent of TH-IR loss. Microglial activation did not occur until 1 day or more post-METH. In summary, a major BBB disruption within the CPu does not directly contribute to neurotoxicity in this single high-dose METH exposure. However, seizure activity produced or exacerbated by amygdalar BBB disruption can significantly increase CPu somatic neurodegeneration (but not affect dopamine (DA) terminal damage). The time course of microglial activation indicates a response to the neurodegeneration, myelin damage, and/or damaged DA terminals after loss of TH-IR. C1 [Bowyer, John F.; Robinson, Bonnie; Ali, Syed; Schmued, Larry C.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov NR 42 TC 46 Z9 47 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR PY 2008 VL 62 IS 3 BP 193 EP 204 DI 10.1002/syn.20478 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 261EX UT WOS:000253063000005 PM 18081184 ER PT J AU Wilkes, JG Hass, BS Buzatu, DA Pence, LM Archer, JC Beger, RD Schnackenberg, LK Halbert, MK Jennings, L Kodell, RL AF Wilkes, Jon G. Hass, Bruce S. Buzatu, Dan A. Pence, Lisa M. Archer, Jeffrey C. Beger, Richard D. Schnackenberg, Laura K. Halbert, Mary Kim Jennings, Lisa Kodell, Ralph L. TI Modeling and assaying dioxin-like biological effects for both dioxin-like and certain non-dioxin-like compounds SO TOXICOLOGICAL SCIENCES LA English DT Article DE regulatory/policy; dioxin; polychlorinated biphenyls; QSAR; biological modeling ID TOXIC EQUIVALENCY FACTORS; DIBENZO-P-DIOXINS; POLYCHLORINATED-BIPHENYLS PCBS; RISK-ASSESSMENT; FACTORS TEFS; HUMAN SERUM; CALUX; VALIDATION; HEALTH; METABOLITES AB 13C NMR data have been correlated to Toxic Equivalency Factors (TEFs) of the 29 PCDDs, PCDFs, or PCBs for which non-zero TEFs have been defined. Such correlations are called quantitative spectrometric data-activity relationship (QSDAR) models. An improved QSDAR model predicted TEFs of 0.037 and 0.004, respectively, for 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4,7-pentachlorodibenzo-p-dioxin (PeCDD), both among the 390 congeners for which zero value TEFs are assumed. A QSDAR model of Relative Potency (REP) values estimated the corresponding values as 0.115 and 0.020. Results from both models indicated that these two congeners may exhibit significant dioxin-like toxicity. If other such congeners have non-zero toxicity, TEF-based risk assessments of some dioxin-, furan-, or PCB-contaminated sites or foods may underestimate toxicity. Both models were extensively cross-validated and the TEF model was externally validated. We confirmed the predictions by an independent in vitro method, a luciferase gene expression assay based on mouse liver cells that found REPs of 0.027 and 0.013, respectively, for 1,3,7,8-TCDD and 1,2,3,4,7-PeCDD. The QSDAR-estimated and gene-expression assayed values agreed. The models were used to predict activity for an applicability domain including 108 non-2,3,7,8 dioxin, furan, or PCB congeners and 2,3,7,8-tetrachlorophenothiazine, a dioxin analog proposed as a drug candidate. This study showed that QSDAR prediction followed by a relatively inexpensive in vitro assay could be used to nominate a few candidates among hundreds for further investigation. It suggested that in silico and in vitro nomination protocols may facilitate practical risk assessment when chemical family members exhibit different degrees of toxicity operating via a common mechanism. C1 [Wilkes, Jon G.; Buzatu, Dan A.; Beger, Richard D.; Schnackenberg, Laura K.] Univ Arkansas Med Sci, Div Syst Toxicol, Little Rock, AR 72205 USA. [Hass, Bruce S.] Univ Arkansas Med Sci, Div Genet & Reprod Toxicol, Little Rock, AR 72205 USA. [Pence, Lisa M.; Archer, Jeffrey C.; Halbert, Mary Kim; Jennings, Lisa] Univ Arkansas Med Sci, Dioxin Grp, Arkansas Reg Lab, Little Rock, AR 72205 USA. [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. RP Wilkes, JG (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jon.wilkes@fda.hhs.gov NR 31 TC 7 Z9 7 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2008 VL 102 IS 1 BP 187 EP 195 DI 10.1093/toxsci/kfm294 PG 9 WC Toxicology SC Toxicology GA 260PY UT WOS:000253023600019 PM 18065775 ER PT J AU Oliva, JL Caino, MC Senderowicz, AM Kazanietz, MG AF Oliva, Jose L. Caino, M. Cecilia Senderowicz, Adrian M. Kazanietz, Marcelo G. TI S-Phase-specific activation of PKC alpha induces senescence in non-small cell lung cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; VASCULAR ENDOTHELIAL-CELLS; CYCLIN-DEPENDENT KINASES; H-RAS ONCOGENE; PHORBOL ESTER; P21(WAF1/CIP1) EXPRESSION; TUMOR SUPPRESSION; MELANOMA-CELLS; MESSENGER-RNA; DNA-SYNTHESIS AB Protein kinase C (PKC) has been widely implicated in positive and negative control of cell proliferation. We have recently shown that treatment of non-small cell lung cancer (NSCLC) cells with phorbol 12-myristate 13-acetate (PMA) during G(1) phase inhibits the progression into S phase, an effect mediated by PKC delta-induced up-regulation of the cell cycle inhibitor p21(Cip1). However, PMA treatment in asynchronously growing NSCLC cells leads to accumulation of cells in G(2)/M. Studies in post-G(1) phases revealed that PMA induced an irreversible G(2)/M cell cycle arrest in NSCLC cells and conferred morphological and biochemical features of senescence, including elevated SA-beta-Gal activity and reduced telomerase activity. Remarkably, this effect was phase-specific, as it occurred only when PKC was activated in S, but not in G(1) phase. Mechanistic analysis revealed a crucial role for the classical PKC alpha isozyme as mediator of the G(2)/M arrest and senescence, as well as for inducing p21(Cip1) an obligatory event for conferring the senescence phenotype. In addition to the unappreciated role of PKC isozymes, and specifically PKC alpha, in senescence, our data introduce the paradigm that discrete PKCs trigger distinctive responses when activated in different phases of the cell cycle via a common mechanism that involves p21(Cip1) up-regulation. C1 [Kazanietz, Marcelo G.] Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. [Oliva, Jose L.; Caino, M. Cecilia; Kazanietz, Marcelo G.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Dept Pharmacol, Philadelphia, PA 19104 USA. [Oliva, Jose L.; Senderowicz, Adrian M.] CDER, Food & Drug Adm, Silver Spring, MD 20993 USA. RP Oliva, JL (reprint author), Ctr Nacl Microbiol Virol & Inmunol Sanitarias Maja, Inst Salud Carlos III, Unidad Biol Celular, Carretera Majadahonda Pozuelo,Km 2 Majahonda, Madrid 28220, Spain. EM jloliva@isciii.es; marcelo@spirit.gcrc.upenn.edu FU NCI NIH HHS [CA-92537, CA-89202] NR 55 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 29 PY 2008 VL 283 IS 9 BP 5466 EP 5476 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266IC UT WOS:000253426700027 PM 18162471 ER PT J AU Volpe, DA Gupta, A Ciavarella, AB Faustino, PJ Sayeed, VA Khan, MA AF Volpe, Donna A. Gupta, Abhay Ciavarella, Anthony B. Faustino, Patrick J. Sayeed, Vilayat A. Khan, Mansoor A. TI Comparison of the stability of split and intact gabapentin tablets SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE split-tablet; stability; gabapentin ID RELEASE THEOPHYLLINE TABLETS; VALIDATED HPLC METHOD; DRUG PRODUCTS; DISSOLUTION; WHOLE; CHOLESTEROL; INVITRO AB The purpose of this study was to determine the stability differences between split and intact gabapentin tablets. Gabapentin tablets from three different manufacturers (G1, G2 and G3) were tested for a period of 9 weeks under long-term (25 degrees C/60% RH) and intermediate stability (30 degrees C/60% RH) storage conditions after storage in closed amber pharmacy dispensing containers. Samples were analyzed for dissolution and potency using validated HPLC methods. Potency test also included the quantitation of gabapentin's main degradation product. Tablets from all manufacturers and at all time points had potency >90%. At 9 weeks, a statistically significant decrease (p <0.02) in gabapentin potency was observed for the whole and split G2 and G3 tablets under the intermediate storage conditions. At the end of 9 weeks, all samples also showed slightly higher levels of degradation product which was statistically significant (p <0.01) for samples stored under intermediate stability storage conditions and exceeded the proposed USP (PF, 2006) limit for the G3 split and intact tablets. No difference was observed between the potency and dissolution of the intact and the split tablets from the same manufacturer and the three products tested remained stable throughout the study period. The results suggest that splitting of gabapentin tablets did not affect the stability of these particular drug products tested as part of this study when stored under normal storage conditions for a period of up to 9 weeks. However, the results should not be extrapolated to other gabapentin drug products and to other tablet dosage forms. (c) 2007 Elsevier B.V. All rights reserved. C1 [Volpe, Donna A.; Ciavarella, Anthony B.; Faustino, Patrick J.; Khan, Mansoor A.] US FDA, Off Pharamceut Sci, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Off Pharamceut Sci, Ogg Gener Drugs, Rockville, MD 20855 USA. RP Khan, MA (reprint author), US FDA, Off Pharamceut Sci, Div Prod Qual Res, Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 18 TC 6 Z9 6 U1 0 U2 3 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 FEB 28 PY 2008 VL 350 IS 1-2 BP 65 EP 69 DI 10.1016/j.ijpharm.2007.08.041 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 267JA UT WOS:000253504100009 PM 17935918 ER PT J AU Shen, Y Hirsch, DS Sasiela, CA Wu, WJ AF Shen, Yi Hirsch, Dianne S. Sasiela, Christy A. Wu, Wen Jin TI Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CELL-ADHESION; EPITHELIAL-MESENCHYMAL TRANSITIONS; BREAST-CANCER CELLS; ADHERENS JUNCTIONS; BETA-CATENIN; RHO-GTPASES; DOWN-REGULATION; C-CBL; RAC1; ENDOCYTOSIS AB E-cadherins play an essential role in maintaining epithelial polarity by forming Ca2+-dependent adherens junctions between epithelial cells. Here, we report that Ca2+ depletion induces E-cadherin ubiquitination and lysosomal degradation and that Cdc42 plays an important role in regulating this process. We demonstrate that Ca2+ depletion induces activation of Cdc42. This in turn up-regulates epidermal growth factor receptor (EGFR) signaling to mediate Src activation, leading to E-cadherin ubiquitination and lysosomal degradation. Silencing Cdc42 blocks activation of EGFR and Src induced by Ca2+ depletion, resulting in a reduction in E-cadherin degradation. The role of Cdc42 in regulating E-cadherin ubiquitination and degradation is underscored by the fact that constitutively active Cdc42(F28L) increases the activity of EGFR and Src and significantly enhances E-cadherin ubiquitination and lysosomal degradation. Furthermore, we found that GTP-dependent binding of Cdc42 to E-cadherin is critical for Cdc42 to induce the dissolution of adherens junctions. Our data support a model that activation of Cdc42 contributes to mesenchyme-like phenotype by targeting of E-cadherin for lysosomal degradation. C1 [Shen, Yi; Hirsch, Dianne S.; Sasiela, Christy A.; Wu, Wen Jin] US FDA, CDER, OPS, OBP,Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, CDER, OPS, OBP,Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 53 TC 69 Z9 69 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 22 PY 2008 VL 283 IS 8 BP 5127 EP 5137 DI 10.1074/jbc.M703300200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 266IA UT WOS:000253426500070 PM 18057010 ER PT J AU Tsong, Y Levenson, M Zhang, J Zhong, JL AF Tsong, Yi Levenson, Mark Zhang, Joanne Zhong, Jinglin TI Choice of lambda-margin and dependency of non-inferiority trials SO STATISTICS IN MEDICINE LA English DT Article DE non-inferiority test; cross-trial comparison approach; dependency of two trials; percentage of retention; non-inferiority margin AB For a two-arm active control clinical trial designed to test for non-inferiority of the test treatment compared with the active control standard treatment, data of historical studies are often utilized. For example, with a cross-trial comparison approach (also called synthetic approach or lambda-margin approach), the trial is conducted to test the hypothesis that the mean difference or the ratio between the current test product and the active control is no larger than a certain portion of the mean difference or the ratio of the active control and Placebo obtained in the historical data when the positive response indicates treatment effectiveness. The regulatory agency usually requires that the clinical trials of two different test treatments are independent,in most regular cases. It also requires, in general, two independent trials of the same test treatment in order to provide confirmatory evidence of the efficacy of the test product. In this article, we derived the relationship between the correlation of the test statistics of two trials with the choice of lambda (the percentage to preserve), the sample sizes and variances under the normality assumption. We showed that the smaller a lambda, the higher the correlation between the two non-inferiority tests. It is further shown that when an 80 per cent or larger;, is used, the correlation can be controlled to be less than 10 per cent if the variances of the response variables in the current trial are not much smaller than those of the historical studies. Published in 2007 by John Wiley & Sons, Ltd. C1 [Tsong, Yi; Levenson, Mark; Zhang, Joanne; Zhong, Jinglin] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 6 TC 6 Z9 6 U1 0 U2 2 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 FEB 20 PY 2008 VL 27 IS 4 BP 520 EP 528 DI 10.1002/sim.2988 PG 9 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 265ID UT WOS:000253351400006 PM 17617797 ER PT J AU Zou, X Sadovova, N Patterson, TA Divine, RL Hotchkiss, CE Ali, SF Hanig, JP Paule, MG Slikker, W Wang, C AF Zou, X. Sadovova, N. Patterson, T. A. Divine, R. L. Hotchkiss, C. E. Ali, S. F. Hanig, J. P. Paule, M. G. Slikker, W., Jr. Wang, C. TI The effects of L-carnitine on the combination of, inhalation anesthetic-induced developmental, neuronal apoptosis in the rat frontal cortex SO NEUROSCIENCE LA English DT Article DE nitrous oxide; isoflurane; apoptosis; caspase-3; neuronal protection ID ACETYL-L-CARNITINE; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; CELL-ADHESION MOLECULE; DEVELOPING BRAIN; MITOCHONDRIAL DECAY; NMDA RECEPTORS; NITROUS-OXIDE; FLUORO-JADE; NEURODEGENERATION; PHENCYCLIDINE AB The anesthetic gas nitrous oxide (N2O) and the volatile anesthetic isoflurane (ISO) are commonly used in surgical procedures for human infants and in veterinary and laboratory animal practice to produce loss of consciousness and analgesia. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA) glutamate receptors or potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. In the present study, the question arises whether a relatively low dose of ISO alone or its combination with N2O entails significant risk of inducing enhanced apoptosis. In addition, the role Of L-carnitine to attenuate these effects was also examined. Postnatal day 7 (PND-7) rat pups were exposed to N2O (75%) or a low dose of ISO (0.55%) alone, or N2O plus ISO for 2, 4, 6 or 8 h with or without L-carnitine. The neurotoxic effects were evaluated 6 h after completion of anesthetic administration. No significant neurotoxic effects were observed for the animals exposed to N2O or ISO alone. However, enhanced apoptotic cell death was apparent when N2O was combined with ISO at exposure durations of 6 h or more. Co-administration of L-carnitine (300 or 500 mg/kg, i.p.) effectively protected neurons from the anesthetic-induced damage. These data indicate that 6 h or more of inhaled anesthetic exposure consisting of a combination of N2O and ISO results in enhanced neuronal apoptosis, and L-carnitine effectively blocks the neuronal apoptosis caused by inhalation anesthetics in the developing rat brain. Published by Elsevier Ltd on behalf of IBRO. C1 [Zou, X.; Patterson, T. A.; Ali, S. F.; Paule, M. G.; Slikker, W., Jr.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Sadovova, N.; Divine, R. L.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hotchkiss, C. E.] Bionet Corp, Jefferson, AR 72079 USA. [Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Cheng.wang@fda.hhs.gov FU PHS HHS [IAG 224-07-007] NR 60 TC 52 Z9 60 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD FEB 19 PY 2008 VL 151 IS 4 BP 1053 EP 1065 DI 10.1016/j.neuroscience.2007.12.013 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 264PS UT WOS:000253301500013 PM 18201836 ER PT J AU Jacobson-Kram, D Mattison, D Shelby, M Slikker, W Tice, R Witt, K AF Jacobson-Kram, David Mattison, Donald Shelby, Michael Slikker, William Tice, Raymond Witt, Kristine TI Methylphenidate and chromosome damage SO CANCER LETTERS LA English DT Letter ID ABERRATIONS; CHILDREN; CANCER; RISK C1 [Jacobson-Kram, David] US FDA, Ctr Drug Evaluat & Res, Off New Drug, Silver Spring, MD 20993 USA. [Mattison, Donald] Natl Inst Child Hlth & Dev, NIH, Rockville, MD 20892 USA. [Shelby, Michael; Tice, Raymond; Witt, Kristine] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. [Slikker, William] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Jacobson-Kram, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drug, Silver Spring, MD 20993 USA. EM david.jacobsonkram@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 8 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 18 PY 2008 VL 260 IS 1-2 BP 216 EP 218 DI 10.1016/j.canlet.2007.10.017 PG 3 WC Oncology SC Oncology GA 264HM UT WOS:000253278400025 PM 18055105 ER PT J AU Shah, RB Prasanna, HR Rothman, B Khan, MA AF Shah, Rakih B. Prasanna, Hullahalm R. Rothman, Barry Khan, Mansoor A. TI Stability of ranitidine syrup repackaged in unit-dose containers SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT Annual Food and Drug Administration Science Forum CY APR 18, 2006 CL Washington, DC DE chromatography; liquid; contamination; gastrointestinal drugs; hydrogen ion concentration; moisture; packaging; ranitidine hydrochloride; stability; storage; syrups; temperature ID HYDROCHLORIDE AB Purpose. The stability of ranitidine syrup repackaged in unit-dose containers was studied. Methods. Oral ranitidine hydrochloride syrup containing 16.8 mg/mL of ranitidine hydrochloride (equivalent to 15 mg of ranitidine) in original bulk containers and repackaged in unit-dose amber-colored glass bottles sealed with aluminum caps were obtained from commercial sources. For extended-stability determinations, samples were stored for 52 weeks at 25 degrees C and 40% relative humidity and analyzed at 0, 4, 13, 26, 39, and 52 weeks. For accelerated stability determinations, samples were stored for 13 weeks at 40 degrees C and 25% relative humidity and analyzed at 0, 4, 9, and 13 weeks. Stability was assessed using high-performance liquid chromatography and by measuring changes in pH and sample weight. The principal impurity and total impurities were also measured. Results. No significant changes in pH were demonstrated, and all values remained well within acceptable limits. The weight change in samples was greater for repackaged samples stored in accelerated conditions compared with that of samples in the original packaging; however, the differences were not significant. Ranitidine hydrochloride samples in both types of packaging remained stable when stored at 25 degrees C and 40% relative humidity for 52 weeks and at 40 degrees C and 25% relative humidity for 13 weeks. The impurity profiles remained within acceptable limits for all samples. Conclusion. Repackaged ranitidine syrup was stable for up to 52 weeks when stored at 25 degrees C and 40% relative humidity and for up to 13 weeks when stored at 40 degrees C and 25% relative humidity. C1 [Shah, Rakih B.; Prasanna, Hullahalm R.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, CDER, Silver Spring, MD 20993 USA. [Rothman, Barry] CDER, Off Compliance, Div Mfg & Prod Qual, Springfield, MD USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, CDER, 10903 New Hampshire Ave,Life Sci Bldg 64,Room 107, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 11 TC 5 Z9 5 U1 0 U2 2 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 FEB 15 PY 2008 VL 65 IS 4 BP 325 EP 329 DI 10.2146/ajhp060625 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 263JR UT WOS:000253213900012 PM 18238770 ER PT J AU Huber, AM Dugan, EM Lachenbruch, PA Feldman, BM Perez, MD Zemel, LS Lindsley, CB Rennebohm, RM Wallace, CA Passo, MH Reed, AM Bowyer, SL Ballinger, SH Miller, FW Rider, LG AF Huber, Adam M. Dugan, Elizabeth M. Lachenbruch, Peter A. Feldman, Brian M. Perez, Maria D. Zemel, Lawrence S. Lindsley, Carol B. Rennebohm, Robert M. Wallace, Carol A. Passo, Murray H. Reed, Ann M. Bowyer, Suzanne L. Ballinger, Susan H. Miller, Frederick W. Rider, Lisa G. CA Juvenile Dermatomyositis Dis Activ TI Preliminary validation and clinical meaning of the cutaneous assessment tool in juvenile dermatomyositis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; MYOSITIS ASSESSMENT SCALE; QUALITY-OF-LIFE; DISEASE-ACTIVITY; SKIN INVOLVEMENT; MUSCLE FUNCTION; DAMAGE INDEXES; RELIABILITY; CHILDREN AB Objective. To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores. Methods. Children with juvenile DM (n = 113) were assessed at baseline and 7-9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined. Results. Item-total correlations ranged from 0.27-0.67 for activity lesions present in >= 10% of patients; item-domain and domain-total correlations ranged from 0.25-0.99. Cronbach's alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined). Conclusion. Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM. C1 [Huber, Adam M.] IWK Hlth Ctr, Div Pediat Rheumatol, Halifax, NS B3K 6R8, Canada. [Huber, Adam M.] Dalhousie Univ, Halifax, NS B3H 3J5, Canada. [Dugan, Elizabeth M.] Washington Hosp Ctr, Washington, DC 20010 USA. [Lachenbruch, Peter A.] Ctr Biol Evaluat & Res, Rockville, MD USA. [Feldman, Brian M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Feldman, Brian M.] Univ Toronto, Toronto, ON M5G 1X8, Canada. [Perez, Maria D.] Baylor Univ, Texas Childrens Hosp, Houston, TX 77030 USA. [Perez, Maria D.] Baylor Coll Med, Houston, TX 77030 USA. [Zemel, Lawrence S.] Univ Connecticut, Connecticut Childrens Med Ctr, Hartford, CT 06112 USA. [Zemel, Lawrence S.] Univ Connecticut, Hartford, CT 06112 USA. [Lindsley, Carol B.] Univ Kansas, Kansas City, KS 66045 USA. [Rennebohm, Robert M.] Ohio State Univ, Columbus Childrens Hosp, Columbus, OH 43210 USA. [Rennebohm, Robert M.] Ohio State Univ, Columbus, OH 43210 USA. [Wallace, Carol A.] Univ Washington, Childrens Hosp, Seattle, WA 98195 USA. [Wallace, Carol A.] Univ Washington, Seattle, WA 98195 USA. [Passo, Murray H.] Univ Cincinnati, Childrens Hosp, Cincinnati, OH USA. [Passo, Murray H.] Univ Cincinnati, Cincinnati, OH USA. [Reed, Ann M.] Mayo Clin, Rochester, MN USA. [Bowyer, Suzanne L.; Ballinger, Susan H.] Indiana Univ Sch Med, Riley Children Hosp, Indianapolis, IN USA. [Bowyer, Suzanne L.; Ballinger, Susan H.] Indiana Univ Sch Med, Indianapolis, IN USA. [Miller, Frederick W.; Rider, Lisa G.] Natl Inst Environm Hlth Sci, NIH, Environm Autoimmun Grp, Bethesda, MD USA. RP Huber, AM (reprint author), IWK Hlth Ctr, Div Pediat Rheumatol, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM adam.huber@iwk.nshealth.ca RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS NR 19 TC 20 Z9 23 U1 1 U2 1 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 FEB 15 PY 2008 VL 59 IS 2 BP 214 EP 221 DI 10.1002/art.23340 PG 8 WC Rheumatology SC Rheumatology GA 262UI UT WOS:000253173100011 PM 18240194 ER PT J AU Uehara, H Shacter, E AF Uehara, Hiroshi Shacter, Emily TI Auto-oxidation and oligomerization of protein S on the apoptotic cell surface is required for met tyrosine kinase-mediated phagocytosis of apoptotic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PIGMENT EPITHELIAL-CELLS; ARREST-SPECIFIC GENE-6; OXIDATIVE STRESS; MACROPHAGE CLEARANCE; BLOOD-COAGULATION; C-MER; PHOSPHATIDYLSERINE; GAS6; STIMULATION AB Prompt phagocytosis of apoptotic cells prevents inflammatory and autoimmune responses to dying cells. We have previously shown that the blood anticoagulant factor protein S stimulates phagocytosis of apoptotic human B lymphoma cells by human monocyte-derived macrophages. In this study, we show that protein S must first undergo oxidative activation to stimulate phagocytosis. Binding of human protein S to apoptotic cells or to phosphatidylserine multilamellar vesicles promotes auto-oxidation of Cys residues in protein S, resulting in covalent, disulfide-linked dimers and oligomers that preferentially bind to and activate the human Mer tyrosine kinase (MerTK) receptor on the macrophages. The prophagocytic activity of protein S is eliminated when disulfide-mediated oligomerization is prevented, or when MerTK is blocked with neutralizing Abs. Protein S oligomerization is independent of phospholipid oxidation. The data suggest that membranes containing phosphatidylserine serve as a scaffold for protein S-protein S interactions and that the resulting auto-oxidation and oligomerization is required for the prophagocytic activity of protein S. In this way, apoptotic cells facilitate their own uptake by macrophages. The requirement for oxidative modification of protein S can explain why this abundant blood protein does not constitutively activate MerTK in circulating monocytes and tissue macrophages. C1 [Uehara, Hiroshi; Shacter, Emily] Food & Drug Adm, Ctr Drug Evaluat & Res, Biochem Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Shacter, E (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Biochem Lab, Div Therapeut Prot, 29 Lincoln Dr,Bldg 29A,Room 2A-11,HFD-121, Bethesda, MD 20892 USA. EM emily.shacter@fda.hhs.gov NR 53 TC 41 Z9 41 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2008 VL 180 IS 4 BP 2522 EP 2530 PG 9 WC Immunology SC Immunology GA 260JC UT WOS:000253005600066 PM 18250462 ER PT J AU Dickerson, CR Saha, S Hotchkiss, CE AF Dickerson, Clark R. Saha, Subrata Hotchkiss, Charlotte E. TI Relationships between densitometric and morphological parameters as measured by peripheral computed tomography and the compressive behavior of lumbar vertebral bodies from Macaques (Macaca fascicularis) SO SPINE LA English DT Article DE vertebrae; non-invasive bone assessment; mechanical tolerance; tissue strength ID DUAL-PHOTON-ABSORPTIOMETRY; BONE-MINERAL DENSITY; BODY STRENGTH; PREDICTION; SPINE; OSTEOPOROSIS; INDIVIDUALS; FRACTURES; SHELL; LOAD AB Study Design. The measured maximum compressive force and stress of lumbar vertebral bodies from cynomolgus monkeys were compared with peripheral quantitative computed tomography (pQCT) derived densitometric and morphologic vertebral parameters. Objectives. To determine, which pQCT parameters were predictive of vertebral mechanical behavior, and of these, identify those that were the best predictors of vertebral load capacity. A secondary objective was to test the suitability of a multiple parameter-based approach for predicting vertebral mechanical load response. Summary of Background Data. Noninvasive methods for identifying and diagnosing changes in skeletal load tolerance are imperative for early detection of bone diseases such as osteoporosis. It is currently unclear, which densitometric and morphologic parameters are the best predictors of the mechanical performance of bone tissues. Methods. Seventy-seven monkey lumbar vertebrae from the species Macaca fascicularis were tested. Following midbody cross-sectional pQCT scans of each specimen, specimens were loaded in axial compression until failure. The pQCT parameters were evaluated independently for correlation with the mechanical response of the vertebral bodies. The parameters were also incorporated in a stepwise linear regression analysis to determine their correlation with the mechanical behavior of the vertebrae. Results. Several pQCT parameters correlated significantly with mechanical behavior. Of these, the trabecular area and the cortical/subcortical area had the strongest associations with the maximum load and stress magnitudes, respectively. The stepwise inclusion of additional predictors, while able to explain additional variance, did not significantly improve predictions of the response of the vertebral bodies to loading. Conclusion. pQCT parameters are quantitatively related to tissue mechanical behavior. The parameters often used in clinical evaluations were not found to be superior to some other pQCT parameters, and inferior to others. This suggests that the inclusion of additional morphologic parameters would improve estimates of the tissue mechanical tolerance over using densitometric parameters alone. C1 [Dickerson, Clark R.] Univ Waterloo, Dept Kinesiol, Fac Appl Hlth Sci, Waterloo, ON N2L 3G1, Canada. [Saha, Subrata] Suny Downstate Med Ctr, Dept Orthoped Surg, Brooklyn, NY 11203 USA. [Hotchkiss, Charlotte E.] US FDA, Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA. RP Dickerson, CR (reprint author), Univ Waterloo, Dept Kinesiol, Fac Appl Hlth Sci, 200 Univ Ave W, Waterloo, ON N2L 3G1, Canada. EM cdickers@uwaterloo.ca OI Dickerson, Clark/0000-0003-1550-9777 NR 31 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD FEB 15 PY 2008 VL 33 IS 4 BP 366 EP 372 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 267XO UT WOS:000253542700003 PM 18277866 ER PT J AU Fiorentino, RP Zuckerman, B Uchida, T AF Fiorentino, Robert P. Zuckerman, Bram Uchida, Takahiro TI Regulatory perspective on embolic protection device approval for saphenous vein graft stenting with a single-arm trial using risk-adjusted prediction model SO CIRCULATION LA English DT Editorial Material DE editorials; embolism; grafting; equipment and supplies; stents; United States Food and Drug Administration; coronary disease C1 [Fiorentino, Robert P.; Zuckerman, Bram; Uchida, Takahiro] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Uchida, T (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corporate Blvd,HFZ-450, Rockville, MD 20850 USA. EM takahiro.uchida.md@gmail.com NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 12 PY 2008 VL 117 IS 6 BP 714 EP 716 DI 10.1161/CIRCULATIONAHA.107.719617 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 261OU UT WOS:000253090700001 PM 18268158 ER PT J AU Wagner, RF AF Wagner, Robert F. TI Toward consistent use of reporting scales in imaging studies SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 US FDA, Off & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wagner, RF (reprint author), US FDA, Off & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3126, Silver Spring, MD 20993 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2008 VL 15 IS 2 BP 137 EP 138 DI 10.1016/j.acra.2007.11.009 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 256RZ UT WOS:000252748800001 PM 18206612 ER PT J AU Andrade, SE Raebel, MA Brown, J Lane, K Livingston, J Boudreau, D Rolnick, SJ Roblin, D Smith, DH Willy, ME Staffa, JA Platt, R AF Andrade, Susan E. Raebel, Marsha A. Brown, Jeffrey Lane, Kimberly Livingston, James Boudreau, Denise Rolnick, Sharon J. Roblin, Douglas Smith, David H. Willy, Mary E. Staffa, Judy A. Platt, Richard TI Use of antidepressant medications during pregnancy: a multisite study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE antidepressant drugs; pregnancy ID SEROTONIN-REUPTAKE INHIBITORS; PERSISTENT PULMONARY-HYPERTENSION; IN-UTERO EXPOSURE; DEPRESSION; WOMEN; MALFORMATIONS; OUTCOMES; NEWBORN; INFANTS; RISK AB OBJECTIVE: This study was undertaken to provide information on the prevalence of use of antidepressant drugs among pregnant women in the United States. STUDY DESIGN: A retrospective study was conducted using the automated databases of 7 health plans. Women who delivered an infant in a hospital were identified. Antidepressant drug use was evaluated assuming a gestational duration of 270 days. RESULTS: Among the 118,935 deliveries occurring from 2001-2005, 6.6% of women were dispensed an antidepressant during pregnancy. Antidepressant drug use increased from 2.0% in 1996 to 7.6% of deliveries in 2004 and 2005. Selective serotonin re-uptake inhibitor use increased from 1.5% in 1996 to 6.4% in 2004 and 6.2% in 2005. CONCLUSION: Our finding that nearly 8% of pregnant women were prescribed antidepressants drugs during the years 2004 and 2005 highlights the importance of understanding the effects of these medications on the developing fetus and on the pregnant woman. C1 [Andrade, Susan E.] Univ Massachusetts, Sch Med, Fallon Fdn, Meyers Primary Care Inst, Worcester, MA 01605 USA. [Andrade, Susan E.] Fallon Commun Hlth Plan, Worcester, MA USA. [Andrade, Susan E.; Raebel, Marsha A.; Brown, Jeffrey; Lane, Kimberly; Livingston, James; Boudreau, Denise; Rolnick, Sharon J.; Roblin, Douglas; Smith, David H.; Platt, Richard] Ctr Educ & Res Therapeut, HMO Res Network, Denver, CO USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. [Brown, Jeffrey; Lane, Kimberly; Livingston, James] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Brown, Jeffrey; Lane, Kimberly; Livingston, James] Harvard Pilgrim Hlth Care, Boston, MA USA. [Boudreau, Denise] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. [Rolnick, Sharon J.] Hlth Partners Res Fdn, Minneapolis, MN USA. [Roblin, Douglas] Kaiser Permanente Georgia, Atlanta, GA USA. [Smith, David H.] Kaiser Permanente NW, Portland, OR USA. [Willy, Mary E.; Staffa, Judy A.] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Andrade, SE (reprint author), Univ Massachusetts, Sch Med, Fallon Fdn, Meyers Primary Care Inst, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org NR 21 TC 54 Z9 55 U1 3 U2 10 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD FEB PY 2008 VL 198 IS 2 AR 194.e1 DI 10.1016/j.ajog.2007.07.036 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 268NU UT WOS:000253587300016 PM 17905176 ER PT J AU Lee, S Muniyappa, R Yan, X Chen, H Yue, LQ Hong, EG Kim, JK Quon, MJ AF Lee, Sihoon Muniyappa, Ranganath Yan, Xu Chen, Hui Yue, Lilly Q. Hong, Eun-Gyoung Kim, Jason K. Quon, Michael J. TI Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE calibration model; quantitative insulin-sensitivity check index ID HOMEOSTASIS MODEL ASSESSMENT; TYPE-2 DIABETIC-PATIENTS; FASTING PLASMA-GLUCOSE; BETA-CELL FUNCTION; CHECK INDEX; CARDIOVASCULAR-DISEASE; RECIPROCAL INDEX; MOUSE; TOLERANCE; QUICKI AB Insulin resistance contributes to the pathophysiology of diabetes, obesity, and their cardiovascular complications. Mouse models of these human diseases are useful for gaining insight into pathophysiological mechanisms. The reference standard for measuring insulin sensitivity in both humans and animals is the euglycemic glucose clamp. Many studies have compared surrogate indexes of insulin sensitivity and resistance with glucose clamp estimates in humans. However, regulation of metabolic physiology in humans and rodents differs and comparisons between surrogate indexes and the glucose clamp have not been directly evaluated in rodents previously. Therefore, in the present study, we compared glucose clamp-derived measures of insulin sensitivity (GIR and SIClamp) with surrogate indexes, including quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment (HOMA), 1/HOMA, log(HOMA), and 1/fasting insulin, using data from 87 mice with a wide range of insulin sensitivities. We evaluated simple linear correlations and performed calibration model analyses to evaluate the predictive accuracy of each surrogate. All surrogate indexes tested were modestly correlated with both GIR and SIClamp. However, a stronger correlation between body weight per se and both GIR and SIClamp was noted. Calibration analyses of surrogate indexes adjusted for body weight demonstrated improved predictive accuracy for GIR [e.g., R = 0.68, for QUICKI and log(HOMA)]. We conclude that linear correlations of surrogate indexes with clamp data and predictive accuracy of surrogate indexes in mice are not as substantial as in humans. This may reflect intrinsic differences between human and rodent physiology as well as increased technical difficulties in performing glucose clamps in mice. C1 [Lee, Sihoon; Muniyappa, Ranganath; Chen, Hui; Quon, Michael J.] NIH, NCCAM, Diabet Unit, Bethesda, MD 20892 USA. [Yan, Xu; Yue, Lilly Q.] US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20857 USA. [Hong, Eun-Gyoung; Kim, Jason K.] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA. RP Muniyappa, R (reprint author), NIH, NCCAM, Diabet Unit, 9 Mem Dr,Bldg 9,Room 1M-105 MSC 0920, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS; NIDDK NIH HHS [U24 DK 59635] NR 36 TC 72 Z9 73 U1 2 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD FEB PY 2008 VL 294 IS 2 BP E261 EP E270 DI 10.1152/ajpendo.00676.2007 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 261KN UT WOS:000253077600008 PM 18003716 ER PT J AU Burckart, GJ Amur, S Goodsaid, FM Lesko, LJ Frueh, FW Huang, SM Cavaille-Coll, MW AF Burckart, Gilbert J. Amur, Shashi Goodsaid, Federico M. Lesko, Lawrence J. Frueh, Felix W. Huang, Shiew-Mei Cavaille-Coll, Marc W. TI Qualification of biomarkers for drug development in organ transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE biomarker; drug development; drugs; end points; surrogate end points ID SURROGATE END-POINTS; RENAL-TRANSPLANTATION; DATA SUBMISSIONS; CRITICAL PATH; VISION; VALIDATION; FDA AB The drug development process is dependent upon having established end points for measuring drug efficacy and adverse effects. New drug development in organ transplantation suffers from having end points which are either outdated or which do not serve the purpose of addressing the current critical drug therapy problems. Numerous biomarkers have been examined in organ transplantation, but almost all would be classified as exploratory for drug development purposes. Some of the possible pathways out of this dilemma include investigator- or consortium-initiated research that would qualify the biomarkers as either probable or known valid biomarkers, help in identification of new end points in transplantation and their associated biomarkers, co-development of a new biomarker and drug for transplantation and the use of new clinical trial design methods which facilitate enriched or stratified transplant patient populations. With new biomarkers and new study design methodologies for drug development, improvement in the drug development process for transplantation is a real possibility that the transplant clinical and research community can help to bring about. C1 [Burckart, Gilbert J.] Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. [Amur, Shashi; Lesko, Lawrence J.; Frueh, Felix W.] Off Translat Sci, Off Clin Pharm, Silver Spring, MD USA. [Cavaille-Coll, Marc W.] US FDA, Div Special Pathogen & Tranplant Prod, Off New Drugs, Silver Spring, MD USA. RP Burckart, GJ (reprint author), Univ So Calif, Sch Pharm, Los Angeles, CA 90089 USA. EM burckart@usc.edu NR 15 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2008 VL 8 IS 2 BP 267 EP 270 DI 10.1111/j.1600-6143.2007.02063.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 252DD UT WOS:000252424300003 PM 18093264 ER PT J AU Yathavakilla, SKV Fricke, M Creed, PA Heitkemper, DT Shockey, NV Schwegel, C Caruso, JA Creed, JT AF Yathavakilla, Santha Ketavarapu V. Fricke, Michael Creed, Patricia A. Heitkemper, Douglas T. Shockey, Nohora V. Schwegel, Carol Caruso, Joseph A. Creed, John T. TI Arsenic speciation and identification of monomethylarsonous acid and monomethylthioarsonic acid in a complex matrix SO ANALYTICAL CHEMISTRY LA English DT Article ID PLASMA-MASS SPECTROMETRY; ACCELERATED SOLVENT-EXTRACTION; MARKET BASKET SURVEY; HPLC-ICP-MS; LIQUID-CHROMATOGRAPHY; CONTAMINATED SOIL; DIETARY EXPOSURE; TRIVALENT; MUSHROOMS; EXCHANGE AB Anion-exchange chromatography was utilized for speciation of arsenite (As (III)), arsenate (As(V)), dimethylarsinic acid (DMA(V)), monomethylarsonic acid (MMA(V)), monomethylarsonous acid (MMA(Ill)), and the new As species monomethylthioarsonic acid (MMTA), using inductively coupled plasma mass spectrometric (ICPMS) detection. MMA(III) and MMTA were identified for the first time in freeze-dried carrot samples that were collected over 25 years ago as part of a joint U.S. EPA, U.S. FDA, and USDA study on trace elements in agricultural crops. The discovery of MMA(III) and MMTA in terrestrial foods necessitated the analytical characterization of synthetic standards Of both species, which were used for standard addition in carrot extracts. The negative ion mode, high-resolution electrospray mass spectrometry (HR-ESI-MS) data produced molecular ions of m/z 122.9418 and 154.9152 for MMA(III) and MMTA, respectively. However, ESI-MS was not sensitive enough to directly identify, MMA(III) and MMTA in the carrot extracts. Therefore, to further substantiate the identification of MMA(III) and MMTA, two additional separations using an Ion-120 column were developed using the more sensitive ICPMS detection. The first separation used 20 mM tetramethylammonium hydroxide at pH 12.2 with MMA(III) eluting: in less than 7 min. In the second separation, MMTA eluted at 11.2 min by utilizing 40 mM ammonium carbonate at pH 9.0. Oxidation of MMA(III) and MMTA to MMA(V) with hydrogen peroxide was observed for standards and carrot extracts alike. Several samples of carrots collected from local markets in 2006 were also analyzed and found to contain low levels of inorganic arsenic species. C1 [Creed, Patricia A.; Schwegel, Carol; Creed, John T.] US EPA, ORD, NEL, MCEARD, Cincinnati, OH 45268 USA. [Yathavakilla, Santha Ketavarapu V.; Caruso, Joseph A.] Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. [Heitkemper, Douglas T.; Shockey, Nohora V.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Creed, JT (reprint author), US EPA, ORD, NEL, MCEARD, Cincinnati, OH 45268 USA. EM creed.jack@epa.gov RI Creed, John/A-9187-2009 FU PHS HHS [DW-75-92171501-1] NR 45 TC 35 Z9 36 U1 2 U2 23 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 FEB 1 PY 2008 VL 80 IS 3 BP 775 EP 782 DI 10.1021/ac0714462 PG 8 WC Chemistry, Analytical SC Chemistry GA 258LW UT WOS:000252870400033 PM 18181583 ER PT J AU Beaubrun, JJG Kothary, MH Curtis, SK Flores, NC Eribo, BE Tall, BD AF Beaubrun, J. Jean-Gilles Kothary, M. H. Curtis, S. K. Flores, N. C. Eribo, B. E. Tall, B. D. TI Isolation and characterization of Vibrio tubiashii outer membrane proteins and determination of a toxR homolog SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID BIVALVE MOLLUSKS; CHOLERAE; OMPU; PURIFICATION; VULNIFICUS; PORINS; GENE; VIRULENCE; BILE AB Outer membrane proteins (OMPs) expressed by Vibrio tubiashii under different environmental growth conditions were characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequencing, and PCR analyses. Results showed the presence of a 38- to 40-kDa OmpU-Iike protein and ompU gene, a maltoporin-like protein, several novel OMPs, and a regulatory toxR homolog. C1 [Beaubrun, J. Jean-Gilles; Eribo, B. E.] Howard Univ, Washington, DC 20050 USA. [Beaubrun, J. Jean-Gilles; Kothary, M. H.; Curtis, S. K.; Flores, N. C.; Tall, B. D.] US FDA, Laurel, MD 20708 USA. RP Beaubrun, JJG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off 3655,White Oak Bldg 21,HFD-003,10903 New Hamp, Silver Spring, MD 20993 USA. EM junia.beaubrun@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 31 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2008 VL 74 IS 3 BP 907 EP 911 DI 10.1128/AEM.02052-07 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 260OG UT WOS:000253019000045 PM 18083865 ER PT J AU Valentin-Bon, I Jacobson, A Monday, SR Feng, PCH AF Valentin-Bon, Iris Jacobson, Andrew Monday, Steven R. Feng, Peter C. H. TI Microbiological quality of bagged cut spinach and lettuce mixes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID EAT SALAD VEGETABLES; FRESH PRODUCE; RETAIL ESTABLISHMENTS AB Analysis of 100 bagged lettuce and spinach samples showed mean total bacterial counts of 7.0 log(10) CFU/g and a broad range of <4 to 8.3 log(10) CFU/g. Most probable numbers (MPN) of >= 11,000 /g coliforms were found in 55 samples, and generic Escherichia coli bacteria were detected in 16 samples, but no E. coli count exceeded 10 MPN/g. C1 [Valentin-Bon, Iris; Jacobson, Andrew; Monday, Steven R.; Feng, Peter C. H.] US FDA, Div Microbiol, College Pk, MD 20740 USA. RP Feng, PCH (reprint author), US FDA, HFS-711,5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov NR 12 TC 35 Z9 35 U1 3 U2 16 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 FEB PY 2008 VL 74 IS 4 BP 1240 EP 1242 DI 10.1128/AEM.02258-07 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 263MP UT WOS:000253221500035 PM 18156327 ER PT J AU Bassen, H AF Bassen, Howard TI Low frequency magnetic emissions and resulting induced voltages in a pacemaker by iPod portable music players SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article AB Background: Recently, malfunctioning of a cardiac pacemaker electromagnetic, caused by electromagnetic interference (EMI) by fields emitted by personal portable music players was highly publicized around the world. A clinical study of one patient was performed and two types of interference were observed when the clinicians placed a pacemaker programming head and an iPod were placed adjacent to the patient's implanted pacemaker. The authors concluded that " Warning labels may be needed to avoid close contact between pacemakers and iPods". We performed an in-vitro study to evaluate these claims of EMI and present our findings of no-effects" in this paper. Methods: We performed in-vitro evaluations of the low frequency magnetic field emissions from various models of the Apple Inc. iPod music player. We measured magnetic field emissions with a 3-coil sensor (diameter of 3.5 cm) placed within 1 cm of the surface of the player. Highly localized fields were observed (only existing in a one square cm area). We also measured the voltages induced inside an ' instrumented-can' pacemaker with two standard unipolar leads. Each iPod was placed in the air, 2.7 cm above the pacemaker case. The pacemaker case and leads were placed in a saline filled torso simulator per pacemaker electromagnetic compatibility standard ANSI/AAMI PC69: 2000. Voltages inside the can were measured. Results: Emissions were strongest (approximate to 0.2 mu T pp) near a few localized points on the cases of the two iPods with hard drives. Emissions consisted of 100 kHz sinusoidal signal with lower frequency (20 msec wide) pulsed amplitude modulation. Voltages induced in the iPods were below the noise level of our instruments (0.5 mV pp in the 0-1 kHz band or 2 mV pp in the 0-5 MHz bandwidth. Conclusion: Our measurements of the magnitude and the spatial distribution of low frequency magnetic flux density emissions by 4 different models of iPod portable music players. Levels of less than 0.2 mu T exist very close (1 cm) from the case. The measured voltages induced inside an ' instrumented-can' pacemaker were below the noise level of our instruments. Based on the observations of our in-vitro study we conclude that no interference effects can occur in pacemakers exposed to the iPod devices we tested. C1 US FDA, Silver Spring, MD 20993 USA. RP Bassen, H (reprint author), US FDA, Silver Spring, MD 20993 USA. EM howard.bassen@fda.hhs.gov NR 5 TC 10 Z9 10 U1 0 U2 2 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 FEB 1 PY 2008 VL 7 AR 7 DI 10.1186/1475-925X-7-7 PG 5 WC Engineering, Biomedical SC Engineering GA 274LR UT WOS:000254003300001 PM 18241327 ER PT J AU Lange, BJ Smith, FO Feusner, J Barnard, DR Dinndorf, P Feig, S Heerema, NA Arndt, C Arceci, RJ Seibel, N Weiman, M Dusenbery, K Shannon, K Luna-Fineman, S Gerbing, RB Alonzo, TA AF Lange, Beverly J. Smith, Franklin O. Feusner, James Barnard, Dorothy R. Dinndorf, Patricia Feig, Stephen Heerema, Nyla A. Arndt, Carola Arceci, Robert J. Seibel, Nita Weiman, Margie Dusenbery, Kathryn Shannon, Kevin Luna-Fineman, Sandra Gerbing, Robert B. Alonzo, Todd A. TI Outcomes in CCG-2961, a Children's Oncology Group Phase 3 Trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CYTARABINE; ACUTE MYELOBLASTIC-LEUKEMIA; COLONY-STIMULATING FACTOR; IDARUBICIN FLAG-IDA; CANCER-STUDY-GROUP; G-CSF; COMPARING IDARUBICIN; INDUCTION THERAPY AB CCG-2961 incorporated 3 new agents, idarubicin, fludarabine and interleukin-2, into a phase 3 AML trial using Intensive-timing remission induction/consolidation and related donor marrow transplantation or high-dose cytarabine intensification. Among 901 patients under age 21 years, 5-year survival was 52%, and event-free survival was 42%. Survival improved from 44% between 1996 and 1998 to 58% between 2000 and 2002 (P =.005), and treatment-related mortality declined from 19% to 12% (P =.025). Partial replacement of daunomycin with idarubicin in the 5-drug induction combination achieved a remission rate of 88%, similar to historical controls. Postremission survival was 56% in patients randomized to either 5-drug reinduction or fludarabine/ cytarabine/idarubicin. For patients with or without a related donor, respective 5-year disease-free survival was 61% and 50% (P =.021); respective survival was 68% and 62% (P =.425). Donor availability conferred no benefit on those with inv(16) or t(8;21) cytogenetics. After cytarabine intensification, patients randomized to interleukin-2 or none experienced similar outcomes. Factors predictive of inferior survival were age more than 16 years, non-white ethnicity, absence of related donor, obesity, white blood cell count more than 100 000 x 10(9)/L, -7/7q-, -5/5q-, and/or complex karyotype. No new agent improved outcomes; experience may have contributed to better results time. C1 [Lange, Beverly J.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Oncol, Philadelphia, PA 19104 USA. [Smith, Franklin O.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Cincinnati, OH 45221 USA. [Feusner, James] Childrens Hosp Oakland, Oakland, CA USA. [Barnard, Dorothy R.] Izaak W Killam Hosp Children, Halifax, NS, Canada. [Dinndorf, Patricia] Food & Drug Adm, Silver Spring, MD USA. [Feig, Stephen; Weiman, Margie] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Heerema, Nyla A.] Ohio State Univ, Columbus, OH 43210 USA. [Arndt, Carola] Mayo Clin, Rochester, MN USA. [Arceci, Robert J.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Seibel, Nita] Children Natl Med Ctr, Washington, DC USA. [Dusenbery, Kathryn] Univ Minnesota, Sch Med, Minneapolis, MN USA. [Shannon, Kevin] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [Luna-Fineman, Sandra] Calif Pacific Med Ctr, San Francisco, CA USA. [Gerbing, Robert B.; Alonzo, Todd A.] Childrens Oncol Grp, Arcadia, CA USA. [Alonzo, Todd A.] Univ So Calif, Los Angeles, CA 90089 USA. FU NCI NIH HHS [U10 CA098543, CA 13538, CA 98543, CA 13539] NR 69 TC 147 Z9 155 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 1 PY 2008 VL 111 IS 3 BP 1044 EP 1053 DI 10.1182/blood-2007-04-084293 PG 10 WC Hematology SC Hematology GA 257IR UT WOS:000252792900022 PM 18000167 ER PT J AU Lu, Q Teng, GJ Zhang, Y Niu, HZ Zhu, GY An, YL Yu, H Li, GZ Qiu, DH Wu, CG AF Lu, Qin Teng, Gao-Jun Zhang, Yue Niu, Huan-Zhang Zhu, Guang-Yu An, Yan-Li Yu, Hui Li, Guo-Zhao Qiu, Ding-Hong Wu, Chuan-Ging TI Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by transferrin receptor through trans-arterial delivery SO CANCER BIOLOGY & THERAPY LA English DT Article DE transferrin; trans-arterial; p53; transfection efficiency; hepatic tumor ID GLYCOL-POLYETHYLENIMINE/DNA COMPLEXES; HEPATOCELLULAR-CARCINOMA; DRUG-DELIVERY; RABBIT MODEL; IN-VITRO; THERAPY; CANCER; ADENOVIRUS; CELLS; STRATEGIES AB Transferrin-DNA complex mediated by transferrin receptor in combination with interventional trans-arterial injection into a target organ may be a duel-target-oriented delivery means to achieve an efficient gene therapy. In this study, transferrin receptor expression in normal human hepatocyte and two hepatocellular-carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different amounts of transferrin was transfected into the cells and the gene transfection efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established, the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery via interventional techniques to analyze the therapeutic p53 gene transfer efficiency in vivo by Western blot, immunohistochemical/immunofluorescence staining analysis and survival time. The results were transferrin receptor expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte. Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1 cells with increasing transferrin in a dose-dependent manner. As compared to intravenous administration, interventional injection of p53-gene complex into hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer efficiency in vivo as evaluated by Western blot, immunohistochemical/immunofluorenscence staining analyses and improved animal survival (H = 12.567, p = 0.0019). These findings show the transferrin-transferrin receptor system combined with interventional techniques enhanced p53-gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be an effective approach for gene therapy. C1 [Lu, Qin; Teng, Gao-Jun; Niu, Huan-Zhang; Zhu, Guang-Yu; An, Yan-Li; Yu, Hui; Li, Guo-Zhao] SE Univ, Dept Radiol, Zhong Da Hosp, Mol Image Lab, Nanjing 210009, Peoples R China. [Qiu, Ding-Hong] SE Univ, Coll Med, Dept Biochem, Nanjing 210009, Peoples R China. [Zhang, Yue] Fudan Univ, Sch Life Sci, Inst Genet, State Key Lab Genet Engn, Shanghai 200433, Peoples R China. [Wu, Chuan-Ging] US FDA, Div Gastroenterol Prod, Off New Drug Review, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Teng, GJ (reprint author), SE Univ, Dept Radiol, Zhong Da Hosp, Mol Image Lab, 87 Ding Jia Qiao Rd, Nanjing 210009, Peoples R China. EM gjteng@vip.sina.com NR 43 TC 10 Z9 11 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD FEB PY 2008 VL 7 IS 2 BP 218 EP 224 DI 10.4161/cbt.7.2.5258 PG 7 WC Oncology SC Oncology GA 312GZ UT WOS:000256658500010 PM 18347429 ER PT J AU Mattia, A Merker, R AF Mattia, Antonia Merker, Robert TI Regulation of probiotic substances as ingredients in foods: Premarket approval or "Generally Recognized as Safe" notification SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Workshop on Scientific and Regulatory Challenges of Development of Probiotics as Foods and Drugs CY OCT 16-17, 2006 CL Adelphi, MD AB This article discusses options and examples of regulations or "generally recognized as safe" determinations that are related to microorganisms in food. A balanced picture of information about the microorganism and its characteristics is needed to make conclusions about its safety. C1 [Mattia, Antonia] US FDA, Div Biotechnol & GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Merker, Robert] US FDA, Div Petit Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mattia, A (reprint author), US FDA, Div Biotechnol & GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-255, College Pk, MD 20740 USA. EM antonia.mattia@fda.hhs.gov NR 0 TC 17 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2008 VL 46 SU 2 BP S115 EP S118 DI 10.1086/523329 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 249YV UT WOS:000252268100014 PM 18181714 ER PT J AU Altar, CA Amakye, D Bounos, D Bloom, J Clack, G Dean, R Devanarayan, V Fu, D Furlong, S Hinman, L Girman, C Lathia, C Lesko, L Madani, S Mayne, J Meyer, J Raunig, D Sager, P Williams, SA Wong, P Zerba, K AF Altar, C. A. Amakye, D. Bounos, D. Bloom, J. Clack, G. Dean, R. Devanarayan, V. Fu, D. Furlong, S. Hinman, L. Girman, C. Lathia, C. Lesko, L. Madani, S. Mayne, J. Meyer, J. Raunig, D. Sager, P. Williams, S. A. Wong, P. Zerba, K. TI A prototypical process for creating evidentiary standards for biomarkers and diagnostics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB A framework for developing evidentiary standards for qualification of biomarkers is a key need identified in the Food and Drug Administration's Critical Path Initiative. 1 This article describes a systematic framework that was developed by Pharmaceutical Research and Manufacturers of America (PhRMA) committees and tested at a workshop in collaboration with the Food and Drug Administration and academia. With some necessary refinements, this could be applied to create an appropriately individualized evidentiary standard for any biomarker purpose. C1 [Bounos, D.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Bloom, J.; Dean, R.] Lilly, Indianapolis, IN USA. [Clack, G.; Furlong, S.; Sager, P.] Astra Zeneca, Wilmington, DE USA. [Fu, D.] PhRMA, Washington, DC USA. [Hinman, L.; Wong, P.] Novartis, Cambridge, MA USA. [Girman, C.] Merck & Co Inc, Rahway, NJ 07065 USA. [Lesko, L.] US FDA, Washington, DC 20204 USA. [Madani, S.; Raunig, D.] Novartis, Rockville, MD USA. [Meyer, J.] Pfizer, New London, CT USA. [Altar, C. A.] Fdn Natl Inst Hlth, Washington, DC USA. [Zerba, K.] Bristol Myers Squibb Co, Princeton, NJ USA. EM stephen.a.williams@decisionability.com NR 4 TC 38 Z9 42 U1 0 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 FEB PY 2008 VL 83 IS 2 BP 368 EP 371 DI 10.1038/sj.clpt.6100451 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254KH UT WOS:000252585000036 PM 18091762 ER PT J AU Robertson, SM Davey, RT Voell, J Formentini, E Alfaro, RM Penzak, SR AF Robertson, Sarah M. Davey, Richard T. Voell, Jocelyn Formentini, Elizabeth Alfaro, Raul M. Penzak, Scott R. TI Effect of Ginkgo biloba extract on lopinavir, midazolarn and fexofenadine pharmacokinetics in healthy subjects SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE CYP3A4; Ginkgo biloba; lopinavir; P-glycoprotein; ritonavir ID HIV-INFECTED PATIENTS; CYP3A ACTIVITY; LOPINAVIR/RITONAVIR; CYTOCHROME-P-450; PHARMACODYNAMICS; COMPLEMENTARY; NICARDIPINE; SUPPLEMENTS; VOLUNTEERS; ENZYMES AB Objective: Animal and in vitro data suggest that Ginkgo biloba extract (GBE) may modulate CYP3A4 activity. As such, GBE may alter the exposure of HIV protease inhibitors metabolized by CYP3A4. It is also possible that GBE could alter protease inhibitor pharmacokinetics (PK) secondary to modulation of P-glycoprotein (P-gp). The primary objective of the study was to evaluate the effect of GBE on the exposure of lopinavir in healthy volunteers administered lopinavir/ritonavir. Secondary objectives were to compare ritonavir exposure pre- and post-GBE, and assess the effect of GBE on single doses of probe drugs midazolam and fexofenadine. Methods: This open-label study evaluated the effect of 2 weeks of standardized GBE administration on the steady-state exposure of lopinavir and ritonavir in 14 healthy volunteers administered lopinavir/ritonavir to steady-state. In addition, single oral doses of probe drugs midazolam and fexofenadine were administered prior to and after 4 weeks of GBE (following washout of lopinavir/ritonavir) to assess the influence of GBE on CYP3A and P-gp activity, respectively. Results: Lopinavir, ritonavir and fexofenadine exposures were not significantly affected by GBE administration. However, GBE decreased midazolam AUC(0-infinity) and C-max by 34% (p = 0.03) and 31% (p = 0.03), respectively, relative to baseline. In general, lopinavir/ritonavir and GBE were well tolerated. Abnormal laboratory results included mild elevations in hepatic enzymes, cholesterol and triglycerides, and mild-to-moderate increases in total bilirubin. Conclusions: Our results suggest that GBE induces CYP3A metabolism, as assessed by a decrease in midazolam concentrations. However, there was no change in the exposure of lopinavir, likely due to ritonavir's potent inhibition of CYP3A4. Thus, GBE appears unlikely to reduce the exposure of ritonavir-boosted protease inhibitors, while concentrations of unboosted protease inhibitors may be affected. Limitations to our study include the single sequence design and the evaluation of a ritonavir-boosted protease inhibitor exclusively. C1 [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, DHHS, Silver Spring, MD 20901 USA. [Davey, Richard T.] NIH, NIAID, Bethesda, MD 20892 USA. [Voell, Jocelyn; Formentini, Elizabeth] NIH, Clin Res Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. [Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, DHHS, Bldg 21,Rm 4653,10903 New Hampshire Ave, Silver Spring, MD 20901 USA. EM sarah.robertson@fda.hhs.gov NR 33 TC 61 Z9 66 U1 0 U2 7 PU LIBRAPHARM/INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4 LQ, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD FEB PY 2008 VL 24 IS 2 BP 591 EP 599 DI 10.1185/030079908X260871 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 273AN UT WOS:000253902900030 PM 18205997 ER PT J AU Shi, LM Perkins, RG Fang, H Tong, WD AF Shi, Leming Perkins, Roger G. Fang, Hong Tong, Weida TI Reproducible and reliable microarray results through quality control: good laboratory proficiency and appropriate data analysis practices are essential SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID GENE-EXPRESSION MEASUREMENTS; EXTERNAL RNA CONTROLS; CONTROL MAQC PROJECT; PLATFORM CONSISTENCY; PERFORMANCE; SELECTION; ARRAYS; NOISE; TECHNOLOGIES; VALIDATION AB Over a few short years, microarray gene expression profiling has permeated most areas of biomedical research. Microarrays are now poised to enter the more demanding realm of clinical applications. The prospect of using microarray data to derive biomarkers of disease or toxicity, predict prognosis, or select treatments raises the validity and reliability bar substantially higher. The potential future payoffs are huge in terms of faster approval of more efficacious and safer medical interventions, and a more personalized implementation of them. Arriving at the future sooner rather than later is the motivation for the FDA-led MicroArray Quality Control (MAQC) project. The widespread collaboration aims to assess achievable technical performance of microarrays and capabilities and limitations of methods for microarray data analysis. C1 [Shi, Leming; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Perkins, Roger G.; Fang, Hong] ICF Int Inc, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCRT Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov NR 50 TC 76 Z9 81 U1 0 U2 13 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 FEB PY 2008 VL 19 IS 1 BP 10 EP 18 DI 10.1016/j.copbio.2007.11.003 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 271CX UT WOS:000253767600003 PM 18155896 ER PT J AU Sauder, C Pedras-Vasconcelos, J Puig, M Verthelyi, D AF Sauder, Christian Pedras-Vasconcelos, Joao Puig, Montserrat Verthelyi, Daniela TI The IP10 (CXCLIO) specific cDNA probe of the mCK-5c multiprobe RNase protection assay kit carries two nucleotide insertions that complicate the interpretation of results SO CYTOKINE LA English DT Article DE RNase protection assay; mCK-5c multiprobe set; chemokines; IP-10 (CXCL10); TCA-3 (CCL1) ID CHEMOKINE GENE-EXPRESSION; MICE AB RNase protection assays (RPA) employing multiprobe sets are powerful tools to simultaneously measure transcription of several different genes. We used BD Biosciences/Pharmingen's mouse chemokine probeset mCK-5c to measure chemokine gene expression in brain and spleen tissue of mice. Depending on the RPA protocol used, we observed differences in the relative amounts of transcripts for interferon-inducible, protein 10 (IP-10) and T-cell activation-3 (TCA-3). Isolation and sequencing of the IP-10 specific gene from the mCK-5c probeset revealed two nucleotide insertions in the probe that are not present in the natural IP-10 cDNA. We show that these insertions cause RNase A-dependent degradation of the protected IP-10 mRNA yielding a fragment indistinguishable in size from that specific for TCA-3, thus leading to over-interpretation of TCA-3 expression as well as underestimation of IP-10 gene expression levels. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Sauder, Christian] Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. [Pedras-Vasconcelos, Joao; Puig, Montserrat; Verthelyi, Daniela] US FDA, Div Therapeut Prot, Off Biotechnol Prod, CDER, Bethesda, MD 20892 USA. RP Sauder, C (reprint author), Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bldg 29A,Room 2C-20,HFM460,8800 Rockville Pike, Bethesda, MD 20892 USA. EM christian.sauder@fda.hhs.gov NR 8 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 FEB PY 2008 VL 41 IS 2 BP 182 EP 186 DI 10.1016/j.cyto.2007.11.009 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 269AX UT WOS:000253623000015 PM 18226543 ER PT J AU Greene, SK Daly, ER Talbot, EA Demma, LJ Holzbauer, S Patel, NJ Hill, TA Walderhaug, MO Hoekstra, RM Lynch, MF Painter, JA AF Greene, S. K. Daly, E. R. Talbot, E. A. Demma, L. J. Holzbauer, S. Patel, N. J. Hill, T. A. Walderhaug, M. O. Hoekstra, R. M. Lynch, M. F. Painter, J. A. TI Recurrent multistate outbreak of Salmonella Newport associated with tomatoes from contaminated fields, 2005 SO EPIDEMIOLOGY AND INFECTION LA English DT Article ID RESISTANT SALMONELLA; UNITED-STATES; INFECTIONS; ILLNESS; CONSUMPTION; HAMBURGER; PULSENET; SURVIVAL; PLANTS AB Salmonella Newport causes more than an estimated 100000 infections annually in the United States. In 2002, tomatoes grown and packed on the eastern shore of Virginia contaminated with a pan-susceptible S. Newport strain caused illness in 510 patients in 26 states. In July-November 2005, the same strain caused illness in at least 72 patients in 16 states. We conducted a case-control study during the 2005 outbreak, enrolling 29 cases and 140 matched neighbourhood controls. Infection was associated with eating tomatoes (matched odds ratio 9.7, 95% confidence interval 3-3-34-9). Tomatoes were traced back to the eastern shore of Virginia, where the outbreak strain was isolated from pond water used to irrigate tomato fields. Two multistate outbreaks caused by one rare strain, and identification of that strain in irrigation ponds 2 years apart, suggest persistent contamination of tomato fields. Further efforts are needed to prevent produce contamination on farms and throughout the food supply chain. C1 [Greene, S. K.; Demma, L. J.; Holzbauer, S.; Patel, N. J.; Hoekstra, R. M.; Lynch, M. F.; Painter, J. A.] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Natl Ctr Zoonot Vectorborne & Enter Dis, Enter Dis Epidemiol Branch, Atlanta, GA 30333 USA. [Greene, S. K.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Workforce & Career Dev, Atlanta, GA 30333 USA. [Daly, E. R.; Talbot, E. A.] New Hampshire Dept Hlth & Human Serv, Div Publ Hlth Serv, Concord, NH 03301 USA. [Talbot, E. A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Demma, L. J.; Holzbauer, S.] Atlanta Res & Educ Fdn, Atlanta, GA USA. [Hill, T. A.; Walderhaug, M. O.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Greene, SK (reprint author), Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Natl Ctr Zoonot Vectorborne & Enter Dis, Enter Dis Epidemiol Branch, 1600 Clifton Rd,MS D-63, Atlanta, GA 30333 USA. EM SGreene1@cdc.gov NR 34 TC 133 Z9 136 U1 3 U2 20 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD FEB PY 2008 VL 136 IS 2 BP 157 EP 165 DI 10.1017/S095026880700859X PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 350FC UT WOS:000259337000002 PM 17475091 ER PT J AU Zhang, JJ Dhakal, I Ning, BT Kesteloot, H AF Zhang, Jianjun Dhakal, Ishwori Ning, Baitang Kesteloot, Hugo TI Patterns and trends of pancreatic cancer mortality rates in Arkansas, 1969-2002: a comparison with the US population SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE Arkansas; epidemiology; mortality; pancreatic cancer; temporal trends ID CIGARETTE-SMOKING; INTERNATIONAL VARIATION; ALCOHOLIC PANCREATITIS; DIABETES-MELLITUS; LUNG-CANCER; RISK AB Little is known about trends in pancreatic cancer mortality in individual states of the US and its whole population. This study aimed to describe the patterns and trends of pancreatic cancer mortality in Arkansas, 1969-2002, using the US national rates as a reference. Joinpoint regression analyses were performed to evaluate trends in age-standardized mortality rates of pancreatic cancer by age group, sex, and race, using data obtained from the National Center for Health Statistics. Throughout the period examined, mortality decreased in young and middle-aged people (<60 years) and men but increased in old people ( >= 60 years) and women. A continuous fall in mortality occurred among whites except for a transient rise in the late 1970s. For blacks, mortality rates did not cease to increase until 1995. Unlike in Arkansas, a monotonic upward or downward trend in mortality by age group and sex was not observed in the US. A decline of mortality stopped in 1997 for US whites. Recent decreasing trends were more pronounced in Arkansas blacks than in US blacks. Changes of pancreatic cancer mortality in the last three decades in Arkansas remarkably differed by age, sex, and race and were different in patterns from those of the US population. C1 [Zhang, Jianjun; Dhakal, Ishwori] Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Ning, Baitang] Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. [Kesteloot, Hugo] Catholic Univ, Fac Med, Dept Publ Hlth, Louvain, Belgium. RP Zhang, JJ (reprint author), Univ Arkansas Med Sci, Fay W Boozman Coll Publ Hlth, Dept Epidemiol, 4301 W Markham St,Slot 820, Little Rock, AR 72205 USA. EM Zhangjianjun@uams.edu NR 38 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD FEB PY 2008 VL 17 IS 1 BP 18 EP 27 PG 10 WC Oncology SC Oncology GA 246HZ UT WOS:000251999400004 PM 18090906 ER PT J AU Babu, US Raybourne, RB AF Babu, Uma S. Raybourne, Richard B. TI Impact of dietary components on chicken immune system and Salmonella infection SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE avian immune system; dietary factors; fatty acid; mineral; oligosaccharide; probiotic; Salmonella clearance; Salmonella enteritidis; Salmonella typhimurium; vitamin ID ENTERICA SEROVAR ENTERITIDIS; POLYUNSATURATED FATTY-ACIDS; WHITE-LEGHORN HENS; HYDROXY-BETA-METHYLBUTYRATE; MESSENGER-RNA EXPRESSION; CELLS IN-VITRO; BROILER-CHICKENS; LAYING HENS; ANTIBODY-PRODUCTION; VITAMIN-E AB Salmonella enterica serovars are facultative intracellular pathogens that may cause serious illness in poultry and humans. Human infection by two common serovars, Salmonella enteritidis (SE) and Salmonella typhimurium (ST) usually occurs via food-borne transmission. Consumption of raw or undercooked contaminated eggs usually causes SE infection, while ST is transmitted by contaminated chicken meat. There are several reports on dietary interventions, including fatty acid modifications, probiotic or prebiotic treatment on the immune system and/or Salmonella clearance in chickens. The aim of this review is to compile the information on the role of major dietary components on chicken immune system and Salmonella clearance. This may help design better poultry nutrition to lower Salmonella infection in chickens and, therefore, reduce human salmonellosis. C1 [Babu, Uma S.; Raybourne, Richard B.] US FDA, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM uma.babu@fda.hhs.gov; richard.raybourne@fda.hhs.gov NR 147 TC 10 Z9 10 U1 1 U2 10 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD FEB PY 2008 VL 6 IS 1 BP 121 EP 135 DI 10.1586/17487210.6.1.121 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 290UG UT WOS:000255147300018 PM 18251669 ER PT J AU Mei, N Hu, JX Churchwell, MI Guo, L Moore, MM Doerge, DR Chen, T AF Mei, Nan Hu, Jiaxiang Churchwell, Mona I. Guo, Lei Moore, Martha M. Doerge, Daniel R. Chen, Tao TI Genotoxic effects of acrylamide and glycidamide in mouse lymphoma cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE acrylamide; glycidamide; Genotoxicity; loss of heterozygosity; DNA adducts ID THYMIDINE KINASE GENE; MUTATIONAL SPECTRA; MAILLARD REACTION; FISCHER-344 RATS; MAMMALIAN-CELLS; DRINKING-WATER; MICE; DNA; MUTAGENICITY; CARCINOGENICITY AB In addition to occupational exposures to acrylamide (AA), concerns about AA health risks for the general population have been recently raised due to the finding of AA in food. In this study, we evaluated the genotoxicity of AA and its metabolite glycidamide (GA) in L5178Y/ Tk(+/-) mouse lymphoma cells. The cells were treated with 2-18 mM of AA or 0.125-4 mM of GA for 4 It without metabolic activation. The DNA adducts, mutant frequencies and the types of mutations for the treated cells were examined. Within the dose range tested, GA induced DNA adducts of adenine and guanine [N3-(2-carbamoyl-2-hydroxyethyl)-adenine and N7-(2-carbamoyl-2-hydroxyethyl)-guanine] in a linear dose-dependent manner. The levels of guanine adducts were consistently about 60-fold higher across the dose range than those of adenine. In contrast, no GA-derived DNA adducts were found in the cells treated with any concentrations of AA, consistent with a lack of metabolic conversion of AA to GA. However, the mutant frequency was significantly increased by AA at concentrations of 12 mM and higher. GA was mutagenic starting with the 2 mM dose, suggesting that GA is much more mutagenic than AA. The mutant frequencies were increased with increasing concentrations of AA and GA, mainly due to an increase of proportion of small colony mutants. To elucidate the underlying mutagenic mechanism, we examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome I I for mutants induced by AA or GA. Compared to GA induced mutations, AA induced more mutants whose LOH extended to D11Mit22 and D11Mit74, an alteration of DNA larger than half of the chromosome. Statistical analysis of the mutational spectra revealed a significant difference between the types of mutations induced by AA and GA treatments (P = 0.018). These results suggest that although both AA and GA generate mutations through a clastogenic mode of action in mouse lymphoma cells, GA induces mutations via a DNA adduct mechanism whereas AA induces mutations by a mechanism not involving the formation of GA adducts. Published by Elsevier Ltd. C1 [Mei, Nan; Hu, Jiaxiang; Moore, Martha M.; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Churchwell, Mona I.; Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Guo, Lei] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Mei, N (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 48 TC 30 Z9 31 U1 1 U2 12 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 FEB PY 2008 VL 46 IS 2 BP 628 EP 636 DI 10.1016/j.fct.2007.09.093 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 268JZ UT WOS:000253577400026 PM 18029077 ER PT J AU Ponce, E Khan, AA Cheng, CM Summage-West, C Cerniglia, CE AF Ponce, Elizabeth Khan, Ashraf A. Cheng, Chorng-Ming Summage-West, Christine Cerniglia, Carl E. TI Prevalence and characterization of Salmonella enterica serovar Weltevreden from imported seafood SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella enterica; epiderniology; seafood; pulsed-field gel electrophoresis; plasinid ID ANTIBIOTIC-RESISTANCE; VIBRIO-CHOLERAE; THAILAND; SHRIMP; CONTAMINATION; HUMANS; FOODS AB During 2001-2005, 2 10 Sahnonella enterica strains were isolated from seafood samples imported into US. Strains of S. enterica serovar Weltevreden were the most predominantly found among the 64 different serovars isolated. A total of 37 Sahnonella Weltevreden isolates were characterized by pulsed-field gel clectrophoresis (PFGE), plasmid profiles and antibiotic susceptibility to assess genetic diversity. Our results showed a low frequency of antibiotic resistance; 35 of the 37 isolates were sensitive to ampicillin, tetracycline, chloramphenicol, gentamicin, sulfisoxazole, streptomycin and kanamycin. Only two isolates, from samples originating in the Philippines and India, showed resistance to ampicillin and tetracycline and to streptomycin, sulfisoxazole and tetracycline, respectively. Of the 37 isolates, two isolates did not carry any plasmid and 35 isolates harbored several small and mega-plasmids. These isolates were differentiated into 10 distinct types based on plasmid profiles. Four different PFGE clusters were obtained with a genetic similarity of 66-76%. Four groups of isolates (formed by two or three isolates each) showed 100% similarity in the PFGE profiles. One of these groups included strains isolated in Vietnam in 2003, 2004 and 2005 from fish and shrimp. The other groups included strains isolated in Vietnam, Indonesia and Thailand in 2000, 2004 and 2005 front snail, shrimp and fish. Our findings show genetic diversity and temporal persistence of S. enterica serovar Weltevreden in recently monitored seafood imports. Published by Elsevier Ltd. C1 Ctr Invest Cientif & Euc Super Ensenada, Dept Biotechnol Marine, Ensenada 22860, Baja California, Mexico. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Pacific Reg Lab, Irving, TX USA. RP Khan, AA (reprint author), Ctr Invest Cientif & Euc Super Ensenada, Dept Biotechnol Marine, Km 107 carretera Tijuana-Ensenada, Ensenada 22860, Baja California, Mexico. EM ashraf.khan@fda.hhs.gov RI Ponce-Rivas, Elizabeth/K-3278-2016 OI Ponce-Rivas, Elizabeth/0000-0002-2842-7300 NR 36 TC 44 Z9 46 U1 1 U2 11 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 FEB PY 2008 VL 25 IS 1 BP 29 EP 35 DI 10.1016/j.fm.2007.09.001 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 236RZ UT WOS:000251322400004 PM 17993374 ER PT J AU Nawaz, M Khan, AA Khan, S Sung, K Steele, R AF Nawaz, Mohamed Khan, Ashraf A. Khan, Saeed Sung, Kidon Steele, Roger TI Isolation and characterization of tetracycline- resistant Citrobacter spp. from catfish SO FOOD MICROBIOLOGY LA English DT Article DE catfish; antibiotic resistance genes; PFGE; PCR ID GRAM-NEGATIVE BACTERIA; MOLECULAR CHARACTERIZATION; ANTIBIOTIC-RESISTANCE; AEROMONAS-HYDROPHILA; FISH; DETERMINANTS; OXYTETRACYCLINE; MENINGITIS; SEDIMENTS; GENES AB Fifty-two tetracycline-resistant Citrobacter spp. strains were isolated from farm-raised catfish. Morphological and biochemical characteristics indicated that 38 of the 52 citrobacters were Citrobacterfreundii, 7 were C anialonaticus and 7 were C braakii. All isolates were resistant to multiple antibiotics. Polymerase chain reaction (PCR) protocols were developed to detect the presence of 3 tetracyclineresistance genes (tetA, tetB and tetG) from Citrobacter isolates. Oligonucleotide primers specifically targeting a 967-bp region of tetB successfully amplified the PCR amplicons from 32/38(85.0%) of C. freundii strains, 5/7(71.0%) of C anialonaticits and 4/7(57%) from 38 7 7 C braakii. Oligonucleoticle primers specific for the detection of telA gene amplified the 417-bp PCR amplicons from 1 (18.0%) of 38 tetracycline-resistant C. freundii only. The assay failed to amplify tetA genes from C brakii or C anialonalicus. Plasmids (2.0-16.0 kb) were isolated from 14 of the 38 strains of C freundii. Strains of C anialonaticus and C brakii did not contain any plasmids. Dendrogram analysis of the Spel pulsed field gel electrophoresis (PFGE) results identified 23 distinct macrorestriction patterns (mrps) among the 36 strains of C freundii, 3 distinct mrps among the 7 strains of C braakii and 4 unique mrps among the 7 strains of C amalonaticus. Our results indicate that citrobacters from catfish could serve as reservoirs of tetracycline-resistance determinants. Published by Elsevier Ltd. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Nawaz, M (reprint author), Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM mohamed.nawaz@fda.hhs.gov NR 23 TC 12 Z9 15 U1 0 U2 6 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 FEB PY 2008 VL 25 IS 1 BP 85 EP 91 DI 10.1016/j.fm.2007.07.008 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 236RZ UT WOS:000251322400010 PM 17993380 ER PT J AU Blodgett, RJ AF Blodgett, Robert J. TI Mathematical treatment of plates with colony counts outside the acceptable range SO FOOD MICROBIOLOGY LA English DT Article DE agar plates; confidence intervals; EM algorithm; improb; too numerous to count (TNTC) ID DETECTION LIMITS AB The exclusion of plate counts outside of an acceptable range can bias the estimation of concentration. If these plates are too numerous to count (TNTC), then their microbes may be inhibited. If inhibition of the microbes on a plate is suspected, then its count may be best treated as a lower bound. When these lower bounds replace counts for some plates, the estimate and confidence interval must be calculated accordingly. Also, a measure of unusualness for plate counts is discussed. Published by Elsevier Ltd. 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 Parkway, College Pk, MD 20740 USA. EM robert.blodgett@fda.hhs.gov NR 9 TC 8 Z9 9 U1 1 U2 3 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 FEB PY 2008 VL 25 IS 1 BP 92 EP 98 DI 10.1016/j.fm.2007.07.006 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 236RZ UT WOS:000251322400011 PM 17993381 ER PT J AU Wear, KA AF Wear, Keith A. TI The effect of phase cancellation on estimates of broadband ultrasound attenuation and backscatter coefficient in human SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID BONE-MINERAL DENSITY; FREQUENCY-DEPENDENT ATTENUATION; SCANNING CONFOCAL ULTRASOUND; QUANTITATIVE HEEL ULTRASOUND; BOVINE CANCELLOUS BONE; HUMAN TRABECULAR BONE; CORTICAL END-PLATE; HIP FRACTURE RISK; HUMAN CALCANEUS; MECHANICAL-PROPERTIES AB Broadband ultrasound attenuation (BUA) is a clinically proven indicator of osteoporotic fracture risk. BUA measurements are typically performed in through-transmission with single-element phase sensitive (PS) receivers and therefore can be compromised by phase cancellation artifact. Phase-insensitive (PI) receivers suppress phase cancellation artifact. To study the effect of phase cancellation on BUA measurements, through-transmission measurements were performed on 16 human calcaneus samples in vitro using a two-dimensional receiver array that enabled PS and PI BUA estimation. The means plus or minus standard deviations for BUA measurements were 22.1 +/- 15.8 dB/MHz (PS) and 17.6 +/- 7.2 dB/MHz (PI), suggesting that, on the average, approximately 20% of PS BUA values in vitro can be attributed to phase cancellation artifact. Therefore, although cortical plates are often regarded as the primary source of phase cancellation artifact, the heterogeneity of cancellous bone in the calcaneal interior may also be a significant source. Backscatter coefficient estimates in human calcaneus that are based on PS attenuation compensation overestimate 1) average magnitude of backscatter coefficient at 500 kHz by a factor of about 1.6 +/- 0.3 and 2) average exponent (n) of frequency dependence by about 0.34 +/- 0.12 (where backscatter coefficient is fit to a power law form proportional to frequency to the nth power). C1 [Wear, Keith A.] US FDA, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov NR 61 TC 20 Z9 20 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 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD FEB PY 2008 VL 55 IS 2 BP 384 EP 390 DI 10.1109/TUFFC.2008.656 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 265KV UT WOS:000253358700012 PM 18334344 ER PT J AU Smith, MA Takeuchi, K Anderson, G Ware, GO McClure, HM Raybourne, RB Mytle, N Doyle, MP AF Smith, Mary Alice Takeuchi, Kazue Anderson, Gary Ware, Glenn O. McClure, Harold M. Raybourne, Richard B. Mytle, Nutan Doyle, Michael P. TI Dose-response model for Listeria monocytogenes-induced stillbirths in nonhuman primates SO INFECTION AND IMMUNITY LA English DT Article ID RAINBOW-TROUT; E-CADHERIN; GASTROENTERITIS; OUTBREAK; INTERNALIN; INFECTION AB A dose-response model using rhesus monkeys as a surrogate for pregnant women indicates that oral exposure to 10(7) CFU of Listeria monocytogenes results in about 50% stillbirths. Ten of 33 pregnant rhesus monkeys exposed orally to a single dose of 10(2) to 10(10) CFU of L. monocytogenes had stillbirths. A log-logistic model predicts a dose affecting 50% of animals at 10(7) CFU, comparable to an estimated 10(6) CFU based on an outbreak among pregnant women but much less than the extrapolated estimate (10(13) CFU) from the FDA-U.S. Department of Agriculture-CDC risk assessment using an exponential curve based on mouse data. Exposure and etiology of the disease are the same in humans and primates but not in mice. This information will aid in risk assessment, assist policy makers, and provide a model for mechanistic studies of L. monocytogenes-induced stillbirths. C1 [Smith, Mary Alice; Anderson, Gary] Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, Athens, GA 30602 USA. [Smith, Mary Alice; Takeuchi, Kazue; Mytle, Nutan; Doyle, Michael P.] Univ Georgia, Coll Agr & Environm Sci, Ctr Food Safety, Griffin, GA 30223 USA. [Ware, Glenn O.] Univ Georgia, Coll Agr & Environm Sci, Athens, GA 30602 USA. [McClure, Harold M.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Raybourne, Richard B.] US FDA, Laurel, MD 20708 USA. RP Smith, MA (reprint author), Univ Georgia, Coll Publ Hlth, Dept Environm Hlth Sci, 206 Environm Hlth Sci Bldg, Athens, GA 30602 USA. EM masmith@uga.edu FU NCRR NIH HHS [RR0016] NR 22 TC 32 Z9 32 U1 0 U2 9 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 FEB PY 2008 VL 76 IS 2 BP 726 EP 731 DI 10.1128/IAI.01366-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 259ZE UT WOS:000252978600030 PM 18070908 ER PT J AU Chan-Tack, KM Murray, JS Birnkrant, DB AF Chan-Tack, Kirk M. Murray, Jeffrey S. Birnkrant, Debra B. TI Long-term efficacy and safety of tipranavir boosted with ritonavir SO INFECTIONS IN MEDICINE LA English DT Editorial Material DE tipranavir; protease inhibitors; HIV; study BI 1182.2 ID HIV-1-INFECTED PATIENTS C1 [Chan-Tack, Kirk M.; Murray, Jeffrey S.; Birnkrant, Debra B.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chan-Tack, KM (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD FEB PY 2008 VL 25 IS 2 BP 61 EP 62 PG 2 WC Infectious Diseases SC Infectious Diseases GA 262YK UT WOS:000253184600001 ER PT J AU Koturbash, I Loree, J Kutanzi, K Koganow, C Pogribny, I Kovalchuk, O AF Koturbash, Igor Loree, Jonathan Kutanzi, Kristy Koganow, Clayton Pogribny, Igor Kovalchuk, Olga TI In vivo bystander effect: Cranial X-irradiation leads to elevated DNA damage, altered cellular proliferation and apoptosis, and increased p53 levels in shielded spleen SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE bystander effect; mouse model; apoptosis; proliferation; DNA damage; gamma H2AX; p53 ID DOUBLE-STRAND BREAKS; RADIATION-INDUCED APOPTOSIS; INDUCED GENOMIC INSTABILITY; RAT LUNG IRRADIATION; IONIZING-RADIATION; ALPHA-PARTICLES; INTERCELLULAR COMMUNICATION; CHROMOSOME-ABERRATIONS; MICROBEAM IRRADIATION; EPIGENETIC EFFECTORS AB Purpose: It is well accepted that irradiated cells may "forward" genome instability to nonirradiated neighboring cells, giving rise to the "bystander effect" phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce. Methods and Materials: We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals. Results: We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c. Conclusion: Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis. (C) 2008 Elsevier Inc. C1 [Koturbash, Igor; Loree, Jonathan; Kutanzi, Kristy; Koganow, Clayton; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Pogribny, Igor] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 60 TC 46 Z9 50 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 2008 VL 70 IS 2 BP 554 EP 562 DI 10.1016/j.ijrobp.2007.09.039 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 253MG UT WOS:000252521700033 PM 18207032 ER PT J AU Devore, N Slater, JE AF deVore, N. Slater, J. E. TI An antibody-based multiplex bead assay to determine the potency and composition of allergen extracts SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [deVore, N.; Slater, J. E.] US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 219 BP S57 EP S57 DI 10.1016/j.jaci.2007.12.228 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426400220 ER PT J AU Savage, JH Limb, SL Brereton, NH Wood, RA AF Savage, J. H. Limb, S. L. Brereton, N. H. Wood, R. A. TI The natural history of peanut allergy-extending our knowledge beyond childhood SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 14-18, 2008 CL Philadelphia, PA SP Amer Acad Allergy, Asthma & Immunol C1 [Savage, J. H.; Brereton, N. H.; Wood, R. A.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Limb, S. L.] US FDA, Rockville, MD 20857 USA. RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2008 VL 121 IS 2 SU 1 MA 567 BP S147 EP S147 DI 10.1016/j.jaci.2007.12.1122 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 266HZ UT WOS:000253426401031 ER PT J AU Tesfamariam, B AF Tesfamariam, Belay TI Drug release kinetics from stent device-based delivery systems SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Review DE stents; drug delivery; release kinetics; carrier vehicle; local vascular toxicity; restenosis ID SIROLIMUS-ELUTING STENTS; TISSUE FACTOR EXPRESSION; PORCINE CORONARY MODEL; IN-VIVO; NEOINTIMAL HYPERPLASIA; ARTERY STENTS; IMPLANTATION; RESTENOSIS; PACLITAXEL; THROMBOSIS AB In an effort to overcome the limitations of balloon-expandible intravascular metal stent-induced neointimal formation, drug-coated stent devices have been developed. The stent platform allows the local delivery of drugs to an injury site, thereby reducing the amount of drug exposure to the systemic circulation and other organs. The drug carrier matrix allows the release of the drug in a diffusion-controlled manner over an extended time period after the stent implant. The drugs are chosen such that the complex cascade of events that occurs after stent implantation that leads to smooth muscle cell proliferation and migration towards the intima are inhibited. The success of an antirestenotic drug therapy from a drug-coated stent is dependent, at least partially, on the extent of drug elution from the stent. the duration and rate of release, and accumulation of drug in the arterial wall in such a way that it covers the initiation and progression of vessel wall remodeling. The local vascular drug concentrations achieved are directly correlated with the biological effects and local vascular toxicity, and there is therefore a challenge in finding an optimum dose of drug to be delivered to tissues (ie, one that has the desired therapeutic effect without local adverse effects). There is increased focus on optimization of various factors that affect drug release from the stent system, including the physicochemical properties of the drugs, carrier vehicle formulation, and profile of elution kinetics. This review highlights the various factors involved in drug release kinetics, local vascular toxicity, carrier vehicle matrix, tissue deposition, and distribution through the arterial wall from stent-based drug delivery systems. C1 US FDA, CDER, Div Cardiovasc & Renal, Silver Spring, MD 20993 USA. RP Tesfamariam, B (reprint author), US FDA, CDER, Div Cardiovasc & Renal, Bldg 22,Rm 4176,New Hampshire Ave, Silver Spring, MD 20993 USA. EM belay.tesfamariam@fda.hhs.gov NR 48 TC 21 Z9 23 U1 2 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0160-2446 EI 1533-4023 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD FEB PY 2008 VL 51 IS 2 BP 118 EP 125 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 272QH UT WOS:000253874000002 PM 18287878 ER PT J AU Wang, Y Bhottaram, AV Jadhav, PR Lesko, LJ Madabushi, R Powell, JR Qiu, W Sun, H Yim, DS Zheng, JJ Gobburu, JVS AF Wang, Yaning Bhottaram, A. Venkatesh Jadhav, Pravin R. Lesko, Lawrence J. Madabushi, Rajanikanth Powell, J. Robert Qiu, Wei Sun, He Yim, Dong S. Zheng, Jenny J. Gobburu, Jogarao V. S. TI Leveraging prior quantitative knowledge to guide drug development decisions and regulatory science recommendations: Impact of FDA pharmacometrics during 2004-2006 SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE regulatory decisions; EOP2A meeting; modeling; simulation; FDA; drug development; phormacokinetics; pharmacodynamics; pharmacometrics ID LABELING DECISIONS; PHARMACOLOGY; EXPERIENCE; APPROVAL; ZOLPIDEM AB The End-of-Phose 2A meetings are proposed to identify opportunities to make innovative medical products available sooner and to increase the quality of drug applications through early meetings between sponsors and the FDA. This article summarizes the overall experience across 11 pilot End-of-Phase 2A meetings since 2004. Four case studies are presented in more detail to demonstrate the various issues and methods encountered at these meetings. Overall, industry and FDA scientists ranked these meetings to be "very helpful" (average score of 4 on a scale of 1 to 5). In almost all the instances the sponsors changed their drug development plans subsequent to these extensive quantitative analyses-based meetings. A draft Guidance is being developed to be issued in 2008, and we hope this initiative will be resourced by then. C1 [Wang, Yaning; Bhottaram, A. Venkatesh; Jadhav, Pravin R.; Lesko, Lawrence J.; Madabushi, Rajanikanth; Powell, J. Robert; Qiu, Wei; Sun, He; Yim, Dong S.; Zheng, Jenny J.; Gobburu, Jogarao V. S.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. RP Wang, Y (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, 10903 New Hampshire Ave,Bldg 21,Room 3662, Silver Spring, MD 20993 USA. EM yaning.wang@fda.hhs.gov OI Yim, Dong-Seok/0000-0003-2754-7500 NR 20 TC 41 Z9 47 U1 0 U2 11 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 FEB PY 2008 VL 48 IS 2 BP 146 EP 156 DI 10.1177/0091270007311111 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 256OV UT WOS:000252740400003 PM 18199891 ER PT J AU Cunningham, WC AF Cunningham, William C. TI Study of cryogenic procedures for preparation of food for element analysis SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE food analysis; homogeneity; cryogenic homogenization; element analysis; neutron activation analysis ID NEUTRON-ACTIVATION ANALYSIS; SAMPLE PREPARATION; HOMOGENIZATION AB Two cryogenic homogenization procedures, Teflon disk milling and stainless-steel impact milling, were studied for preparing food and dietary supplements for element analysis. The functionality of the disk mill was demonstrated for a fruit/nut/oatmeal granola. Improvement over a rotary cutter blending procedure was shown for three fast-food type foods-hamburger, fried chicken, and egg/ ham/cheese English muffin. The capabilities of the two procedures to process mixtures comprised of very dissimilar components were compared. The mixtures included a commercial hard candy having a chili powder coating and a 50:50 (by mass) combination of choline tablets and echinacea root capsules. Nonhomogeneities were found by calculating relative standard deviations (RSDs) for replicate analyses (n = 5) and comparing them with the random uncertainties associated with the measurements. Analytical portion masses ranged between I g and 45 mg. Element mass fractions were determined using instrumental neutron activation analysis. (C) 2007 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Chem Contaminants Branch HFS 716, College Pk, MD 20740 USA. RP Cunningham, WC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Chem Contaminants Branch HFS 716, 5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM william.cunningham@fda.hhs.gov NR 20 TC 2 Z9 3 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD FEB PY 2008 VL 21 IS 1 BP 35 EP 44 DI 10.1016/j.jfca.2007.07.004 PG 10 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 238PU UT WOS:000251460500005 ER PT J AU Jackson, LS Al-Taher, FM Moorman, M DeVries, JW Tippett, R Swanson, KMJ Fu, TJ Salter, R Dunaif, G Estes, S Albillos, S Gendel, SM AF Jackson, Lauren S. Al-Taher, Fadwa M. Moorman, Mark DeVries, Jonathan W. Tippett, Roger Swanson, Katherine M. J. Fu, Tong-Jen Salter, Robert Dunaif, George Estes, Susan Albillos, Silvia Gendel, Steven M. TI Cleaning and other control and validation strategies to prevent allergen cross-contact in food-processing operations SO JOURNAL OF FOOD PROTECTION LA English DT Review ID LINKED-IMMUNOSORBENT-ASSAY; ANAPHYLAXIS; MILK; INGESTION; CHILD AB Food allergies affect an estimated 10 to 12 million people in the United States. Some of these individuals can develop life-threatening allergic reactions when exposed to allergenic proteins. At present, the only successful method to manage food allergies is to avoid foods containing allergens. Consumers with food allergies rely on food labels to disclose the presence of allergenic ingredients. However, undeclared allergens can be inadvertently introduced into a food via cross-contact during manufacturing. Although allergen removal through cleaning of shared equipment or processing lines has been identified as one of the critical points for effective allergen control, there is little published information on the effectiveness of cleaning procedures for removing allergenic materials from processing equipment. There also is no consensus on how to validate or verify the efficacy of cleaning procedures. The objectives of this review were (i) to study the incidence and cause of allergen cross-contact, (ii) to assess the science upon which the cleaning of food contact surfaces is based, (iii) to identify best practices for cleaning allergenic foods from food contact surfaces in wet and dry manufacturing environments, and (iv) to present best practices for validating and verifying the efficacy of allergen cleaning protocols. C1 [Jackson, Lauren S.; Fu, Tong-Jen] Natl Ctr Food Safety & Technol, US FDA, Summit Argo, IL 60501 USA. [Al-Taher, Fadwa M.; Albillos, Silvia] Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL 60501 USA. [Moorman, Mark] Kellogg Co, Battle Creek, MI 49014 USA. [DeVries, Jonathan W.] James Ford Bell Tech Ctr, Gen Mills Inc, Medall Labs Div, Minneapolis, MN 55427 USA. [Tippett, Roger; Swanson, Katherine M. J.] Ecolab Inc, Eagan, MN 55121 USA. [Salter, Robert] Charm Sci Inc, Lawrence, MA 01843 USA. [Dunaif, George] Campbell Soup Co, Toxicol & Analyt Serv, Camden, NJ 08103 USA. [Estes, Susan] Pepsico Inc, Barrington, IL 60010 USA. [Gendel, Steven M.] Ctr Food Safety & Appl Nutr, US FDA, College Pk, MD 20740 USA. RP Jackson, LS (reprint author), Natl Ctr Food Safety & Technol, US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM lauren.jackson@fda.hhs.gov RI Albillos, Silvia/D-1276-2016 OI Albillos, Silvia/0000-0002-3273-0126 NR 61 TC 29 Z9 31 U1 5 U2 33 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 FEB PY 2008 VL 71 IS 2 BP 445 EP 458 PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 259VH UT WOS:000252968500033 PM 18326204 ER PT J AU Naftel, DC Rogers, JG Young, JB Baldwin, T Chen, E Sapirstein, W Kormos, RL Ascheim, DV Chisholm, KA AF Naftel, D. C. Rogers, J. G. Young, J. B. Baldwin, T. Chen, E. Sapirstein, W. Kormos, R. L. Ascheim, D. V. Chisholm, K. A. TI The use of the interagency registry for mechanically assisted circulatory support (INTERMACS) to generate objective performance criteria (OPCs) for use in MCSD trials SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation CY APR 09-12, 2008 CL Boston, MA SP Int Soc Heart & Lung Transplantat C1 [Naftel, D. C.] Univ Alabama Birmingham, Birmingham, AL USA. [Rogers, J. G.] Duke Univ, Med Ctr, Durham, NC USA. [Young, J. B.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Baldwin, T.] Natl Heart Lung & Blood Inst, Bethesda, MD USA. [Chen, E.; Sapirstein, W.] US FDA, Rockville, MD USA. [Kormos, R. L.] Univ Pittsburgh, Pittsburgh, PA USA. [Ascheim, D. V.] Columbia Univ, New York, NY USA. [Chisholm, K. A.] Univ Arizona, Med Ctr, Tucson, AZ USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 EI 1557-3117 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2008 VL 27 IS 2 SU S MA 297 BP S167 EP S167 DI 10.1016/j.healun.2007.11.306 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 265EQ UT WOS:000253342300298 ER PT J AU Regnault, WF Icenogle, TB Antonucci, JM Skrtic, D AF Regnault, William F. Icenogle, Tonya B. Antonucci, Joseph M. Skrtic, Drago TI Amorphous calcium phosphate/urethane methacrylate resin composites. I. Physicochemical characterization SO JOURNAL OF MATERIALS SCIENCE-MATERIALS IN MEDICINE LA English DT Article ID BIOACTIVE POLYMERIC COMPOSITES; DENTAL COMPOSITES; WATER SORPTION; MONOMER; MATRIX; HYBRID AB Urethane dimethacrylate (UDMA), an oligomeric poly(ethylene glycol) extended UDMA (PEG-U) and a blend of UDMA/PEG-U were chosen as model systems for introducing both hydrophobic and hydrophilic segments and a range of compliances in their derived polymers. Experimental composites based on these three resins with amorphous calcium phosphate (ACP) as the filler phase were polymerized and evaluated for mechanical strength and ion release profiles in different aqueous media. Strength of all composites decreased upon immersion in saline (pH = 7.4). Both polymer matrix composition and the pH of the liquid environment strongly affected the ion release kinetics. In saline, the UDMA/PEG-U composite showed a sustained release for at least 350 h. The initially high ion release of the PEG-U composites decreased after 72 h, seemingly due to the mineral re-deposition at the composite surface. Internal conversion from ACP to poorly crystallized apatite could be observed by X-ray diffraction. In various lactic acid (LA) environments (initial pH = 5.1) ion release kinetics was much more complex. In LA medium without thymol and/or carboxymethylcellulose, as a result of unfavorable changes in the internal calcium/phosphate ion stoichiometry, the ion release rate greatly increased but without observable conversion of ACP to apatite. C1 ADAF, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. [Antonucci, Joseph M.] NIST, Div Polymers, Gaithersburg, MD 20899 USA. [Regnault, William F.; Icenogle, Tonya B.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Skrtic, D (reprint author), ADAF, Paffenbarger Res Ctr, Gaithersburg, MD 20899 USA. EM drago.skrtic@nist.gov FU NIDCR NIH HHS [R01 DE 13169-07, R01 DE013169, R01 DE013169-07] NR 23 TC 24 Z9 24 U1 2 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-4530 J9 J MATER SCI-MATER M JI J. Mater. Sci.-Mater. Med. PD FEB PY 2008 VL 19 IS 2 BP 507 EP 515 DI 10.1007/s10856-007-3178-3 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 259YF UT WOS:000252976100004 PM 17619969 ER PT J AU Weagant, SD AF Weagant, Stephen D. TI A new chromogenic agar medium for detection of potentially virulent Yersinia enterocolitica SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE chromogenic; agar; food; virulent; biotypes; Y. enterocolitic ID ENTEROBACTER-SAKAZAKII; PLATING MEDIA; INFECTIONS; IDENTIFICATION; CHILDREN; BLOOD AB Several outbreaks of foodborne yersiniosis have been documented and this disease continues to be source of infections transmitted through foods. The selective agars most commonly used to isolate Yersinia enterocolitica in clinical, food and environmental samples, cefsulodin-irgasan-novobiocin (CIN) and MacConkey (MAC) agars, lack the ability to differentiate potentially virulent Y. enterocolitica from other Yersinia that may be present as well as some other bacterial spp. This study proposes the use of an agar medium, Y. enterocolitica chromogenic medium (YeCM), for isolation of potentially virulent Y. enterocolitica. This agar contains cellobiose as the fermentable sugar, a chromogenic substrate and selective inhibitors for suppression of colony formation by many competing bacteria. All strains of potentially virulent Yersinia of biotypes 1B, and biotypes 2-5 formed convex, red bulls-eye colonies on YeCM that were very similar to those described for CIN agar. However, Y. enterocolitica biotype 1A and other related Yersinia formed colonies that were purple/blue on YeCM while they formed typical red bulls-eye colonies on CIN agar. When a mixture of potentially virulent Y. enterocolitica biotype 1B, Y. enterocolitica biotype 1A and 5 other bacterial species was used to artificially contaminate tofti and then spread-plated on three selective agars, Y. enterocolitica biotype 1B colonies were easily distinguished from other strains on YeCM. However, Y. enterocolitica biotype 1B colonies were indistinguishable from many other colonies on CIN and only distinguishable from those of C freundii on MAC. When colonies were picked and identified from these agars, typical colonies from YeCM were confirmed only as Y. enterocolitica biotype 1B. Typical colonies on CIN and MAC were found to belong to several competing species and biotypies. Published by Elsevier B.V. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Weagant, SD (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM steve.weagant@fda.hhs.gov NR 33 TC 22 Z9 23 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD FEB PY 2008 VL 72 IS 2 BP 185 EP 190 DI 10.1016/j.mimet.2007.11.019 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 263JY UT WOS:000253214600010 PM 18177960 ER PT J AU Dworkin, RH Turk, DC Wyrwich, KW Beaton, D Cleeland, CS Farrar, JT Haythornthwaite, JA Jensen, MP Kerns, RD Ader, DN Brandenburg, N Burke, LB Cella, D Chandler, J Cowan, P Dimitrova, R Dionne, R Hertz, S Jadad, AR Katz, NP Kehlet, H Kramer, LD Manning, DC McCormick, C McDermott, MP McQuay, HJ Patel, S Porter, L Quessy, S Rappaport, BA Rauschkolb, C Revickl, DA Rothman, M Schmader, KE Stacey, BR Stauffer, JW Von Stein, T White, RE Witter, J Zavislc, S AF Dworkin, Robert H. Turk, Dennis C. Wyrwich, Kathleen W. Beaton, Dorcas Cleeland, Charles S. Farrar, John T. Haythornthwaite, Jennifer A. Jensen, Mark P. Kerns, Robert D. Ader, Deborah N. Brandenburg, Nancy Burke, Laurie B. Cella, David Chandler, Julie Cowan, Penny Dimitrova, Rozalina Dionne, Raymond Hertz, Sharon Jadad, Alejandro R. Katz, Nathaniel P. Kehlet, Henrik Kramer, Lynn D. Manning, Donald C. McCormick, Cynthia McDermott, Michael P. McQuay, Henry J. Patel, Sanjay Porter, Linda Quessy, Steve Rappaport, Bob A. Rauschkolb, Christine Revickl, Dennis A. Rothman, Margaret Schmader, Kenneth E. Stacey, Brett R. Stauffer, Joseph W. Von Stein, Thorsten White, Richard E. Witter, James Zavislc, Stojan TI Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations SO JOURNAL OF PAIN LA English DT Review DE chronic pain; randomized clinical trials; outcome measures; clinical importance; assessment; quality of life; physical functioning; emotional functioning; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; VISUAL ANALOG SCALE; RANDOMIZED CONTROLLED-TRIAL; PATIENT-REPORTED OUTCOMES; MINIMALLY IMPORTANT DIFFERENCES; BECK DEPRESSION INVENTORY; HEALTH-STATUS MEASURES; SPINAL-CORD-INJURY; IMPORTANT DIFFERENCE AB A consensus meeting was convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to provide recommendations for interpreting clinical importance of treatment outcomes in clinical trials of the efficacy and effectiveness of chronic pain treatments. A group of 40 participants from universities, governmental agencies, a patient self-help organization, and the pharmaceutical industry considered methodologic issues and research results relevant to determining the clinical importance of changes in the specific outcome measures previously recommended by IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression inventory and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome measures. Provisional benchmarks for identifying clinically important changes in specific outcome measures that can be used for outcome studies of treatments for chronic pain are proposed. Perspective: Systematically collecting and reporting the recommended information needed to evaluate the clinical importance of treatment outcomes of chronic pain clinical trials will allow additional validation of proposed benchmarks and provide more meaningful comparisons of chronic pain treatments. (c) 2008 by the American Pain Society. C1 [Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Dept Neurol, Rochester, NY 14627 USA. [Turk, Dennis C.; Jensen, Mark P.] Univ Washington, Seattle, WA 98195 USA. [Wyrwich, Kathleen W.] St Louis Univ, St Louis, MO 63103 USA. [Beaton, Dorcas] Univ Toronto, Inst Work & Hlth, Toronto, ON, Canada. [Cleeland, Charles S.] MD Anderson Canc Ctr, Houston, TX USA. [Farrar, John T.] Univ Penn, Philadelphia, PA 19104 USA. [Haythornthwaite, Jennifer A.] Johns Hopkins Univ, Baltimore, MD USA. [Kerns, Robert D.] Yale Univ, VA Connecticut Hlthcare Syst, New Haven, CT 06520 USA. [Ader, Deborah N.] NIAMSD, Bethesda, MD USA. [Brandenburg, Nancy] Pfizer Inc, New York, NY USA. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.; Witter, James] US FDA, Rockville, MD USA. [Cella, David] Northwestern Univ, Evanston Nothwestern Hlthcare, Evanston, IL 60208 USA. [Chandler, Julie] Merck & Co Inc, Blue Bell, PA USA. [Cowan, Penny] Amer Chron Pain Assoc, Rocklin, CA USA. [Dimitrova, Rozalina] Allergan Pharmaceut Inc, Irvine, CA USA. [Dionne, Raymond] NINR, Bethesda, MD USA. [Jadad, Alejandro R.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Katz, Nathaniel P.] Analgesic Res, Needham, MA USA. [Kehlet, Henrik] Univ Copenhagen, Rigshosp, DK-1168 Copenhagen, Denmark. [Kramer, Lynn D.] Purdue Pharma, Stamford, CT USA. [Manning, Donald C.] Celgene Corp, Warren, NJ USA. [McCormick, Cynthia] McCormick Consultat, Bethesda, MD USA. [McDermott, Michael P.] Univ Rochester, Rochester, NY 14627 USA. [McQuay, Henry J.] Univ Oxford, Oxford OX1 2JD, England. [Patel, Sanjay] Elan Pharmaceut Inc, San Diego, CA USA. [Porter, Linda] NINDS, Bethesda, MD USA. [Quessy, Steve] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Rauschkolb, Christine; Rothman, Margaret] Johnson & Johnson, Raritan, NJ USA. [Revickl, Dennis A.] United Biosource Corp, Hlth Care Anal Grp, Bethesda, MD USA. [Schmader, Kenneth E.] Duke Univ, Med Ctr, VA Med ctr, GRECC, Durham, NC USA. [Stacey, Brett R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Stauffer, Joseph W.] Alpharma, Elizabeth, NJ USA. [Von Stein, Thorsten] Tercica, Brisbane, CA USA. [White, Richard E.] Endo Pharmaceut Inc, Chadds Ford, PA USA. [Zavislc, Stojan] AstraZeneca, Sodertalje, Sweden. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Dept Neurol, Rochester, NY 14627 USA. EM robert-dworkin@urmc.rochester.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 NR 163 TC 910 Z9 921 U1 10 U2 65 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 FEB PY 2008 VL 9 IS 2 BP 105 EP 121 DI 10.1016/j.jpain.2007.09.005 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 263MF UT WOS:000253220500002 PM 18055266 ER PT J AU Wu, HQ Heilweil, EJ Hussain, AS Khan, MA AF Wu, Huiquan Heilweil, Edwin J. Hussain, Ajaz S. Khan, Mansocir A. TI Process analytical technology (PAT): Quantification approaches in Terahertz spectroscopy for pharmaceutical application SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE process analytical technology (PAT); Terahertz spectroscopy; chemometrics; multivariate analysis; spectral superposition; univariate method; partial least squares; spectral preprocessing algorithms; excipients; interaction ID NEAR-INFRARED SPECTRA; PULSED SPECTROSCOPY; CRYSTALLINITY AB Terahertz (THz) spectroscopy and chemometric analysis of resultant absorption spectra in the 30 - 500 cm(-1) range has been applied to perform quantitative determination of both active ingredient and excipient concentrations of tablets. Tests were performed on a series of tablets composed of various concentrations and processes of theophylline formulated with lactose, magnesium stearate, starch or Avicel, and as a function of tablet hardness. Transmission spectra of polyethylene pellets derived from each of the samples were analyzed using three approaches. Spectral superposition method was used as an indirect measure to examine whether and when the interaction among various pharmaceutical components and the tableting history could be considered insignificant for quantification purpose. Spectral characteristic peak method was able to correlate peak maxima with correction for tablets having the same hardness. Multivariate analysis (PCR and PLS 1) was capable of correlating THz spectra with tablet concentrations. The predicted concentrations of independent samples using multivariate models agreed well with nominal concentrations. The best correlations were obtained using multivariate analysis. With these studies, the advantage of using multivariate approach was demonstrated for process analytical technology (PAT) application. Further, the feasibility of integrating THz spectroscopy and chemometrics for the purpose of quantifying pharmaceutical tablet concentrations was demonstrated. (c) 2007 Wiley-Liss, Inc. C1 [Wu, Huiquan; Hussain, Ajaz S.; Khan, Mansocir A.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Testing & ResDPQR,HFD 940, Silver Spring, MD 20993 USA. [Heilweil, Edwin J.] Natl Inst Stand & Technol, Phys Lab, Opt Technol Div, Gaithersburg, MD 20899 USA. RP Wu, HQ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Testing & ResDPQR,HFD 940, Life Sci Bldg 64,FDA White Oak Campus,10903 New H, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov FU PHS HHS [CDER RSR-04-16] NR 26 TC 28 Z9 28 U1 2 U2 30 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 FEB PY 2008 VL 97 IS 2 BP 970 EP 984 DI 10.1002/jps.21004 PG 15 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 257SC UT WOS:000252817800027 PM 17722101 ER PT J AU Huque, MF Alosh, M AF Huque, Mohammad F. Alosh, Mohamed TI A flexible fixed-sequence testing method for hierarchically ordered correlated multiple endpoints in clinical trials SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE multiple endpoints; multiplicity adjustment; onset and durability of treatment effect ID BONFERRONI PROCEDURE AB Statistical approaches for addressing Multiplicity in clinical trials range from the very conservative (the Bonferroni method) to the least conservative the fixed sequence approach. Recently, several authors proposed methods that combine merits of the two extreme approaches. Wiens [2003. A fixed sequence Bonferroni procedure for testing multiple endpoints. Pharmaceutical Statist. 2003, 2, 211-215], for example, considered an extension of the Bonferroni approach where the type I error rate (alpha) is allocated among the endpoints, however, testing proceeds in a pre-determined order allowing the type I error rate to be saved for later use as long as the null hypotheses are rejected. This leads to a higher power of the test in testing later null hypotheses. In this paper, we consider an extension of Wiens' approach by taking into account correlations among endpoints for achieving higher flexibility in testing. We show strong control of the family-wise type I error rate for this extension and provide critical values and significance levels for testing up to three endpoints with equal correlations and show how to calculate them for other correlation structures. We also present results of a simulation experiment for comparing the power of the proposed method with those of Wiens' and others. The results of this experiment show that the magnitude of the gain in power of the proposed method depends on the prospective ordering of testing of the endpoints, the magnitude of the treatment effects of the endpoints and the magnitude of correlation between endpoints. Finally, we consider applications of the proposed method for clinical trials with multiple time points and multiple doses, where correlations among endpoints frequently arise. Published by Elsevier B.V. C1 [Huque, Mohammad F.; Alosh, Mohamed] US FDA, CDER, OTS, Div Biomet 4,Off Biostat, Silver Spring, MD 20993 USA. RP Huque, MF (reprint author), US FDA, CDER, OTS, Div Biomet 4,Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mohammad.huque@fda.hhs.gov NR 17 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB 1 PY 2008 VL 138 IS 2 BP 321 EP 335 DI 10.1016/j.jspi.2007.06.009 PG 15 WC Statistics & Probability SC Mathematics GA 261GN UT WOS:000253067200003 ER PT J AU Gage, BF Lesko, LJ AF Gage, Brian F. Lesko, Lawrence J. TI Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article; Proceedings Paper CT 9th National Conference on Anticoagulant Therapy CY MAY 03-05, 2007 CL Chicago, IL SP Anticoagulat Forum DE pharmacogenetics; warfarin; anticoagulation; genetic polymorphism ID PATIENTS RECEIVING WARFARIN; ORAL ANTICOAGULANT-THERAPY; K EPOXIDE REDUCTASE; ATRIAL-FIBRILLATION; RISK-FACTORS; FACTOR-IX; VENOUS THROMBOEMBOLISM; BLEEDING COMPLICATIONS; ELDERLY INPATIENTS; GENE VARIANTS AB Using pharmacogenetics-based therapy, clinicians can estimate the therapeutic warfarin dose by genotyping patients for single nucleotide polymorphisms (SNPs) that affect warfarin metabolism or sensitivity. SNPs in the cytochrome P450 complex (CYP2C9) affect warfarin metabolism: patients who have the CYP2C9*2 and/or CYP2C9*3 variants metabolize warfarin slowly and are more likely to have an elevated International Normalized Ratio INR or to hemorrhage during warfarin initiation than patients without these variants. SNPs in vitamin K epoxide reductase (VKORC1) correlate with warfarin sensitivity. Patients who are homozygous for a common VKORC1 promoter polymorphism, -1639 G > A (also designated as VKOR 3673, haplotype A, or haplotype*2), are warfarin sensitive and typically require lower warfarin doses. By providing an estimate of the therapeutic warfarin dose, pharmacogenetics-based therapy may improve the safety of anticoagulant therapy. To improve drug safety, the FDA updates labels of previously approved drugs as new clinical and genetic evidence accrues. The labels of medical products serve to inform prescribers and patients about potential ways to improve the benefit/risk ratio and/or optimize doses of medical products. On August 16, 2007, the FDA updated the label of warfarin to include information on pharmacogenetic testing and to encourage, but not require, the use of this information in dosing individual patients initiating warfarin therapy. The FDA completed the label update in August 2007. C1 [Gage, Brian F.] Washington Univ, Med Ctr, St Louis, MO 63110 USA. [Lesko, Lawrence J.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Rockville, MD 20857 USA. RP Gage, BF (reprint author), Washington Univ, Med Ctr, 660 S Euclid Ave,Campus Box 8005, St Louis, MO 63110 USA. EM bgage@im.wustl.edu FU NHLBI NIH HHS [R01 HL074724] NR 58 TC 126 Z9 141 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD FEB PY 2008 VL 25 IS 1 BP 45 EP 51 DI 10.1007/s11239-007-0104-y PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 248QF UT WOS:000252168600012 PM 17906972 ER PT J AU Smith, RE Luchtefeld, R AF Smith, Robert E. Luchtefeld, Ron TI An evaluation of the determination of the lipophilicity of apocynin and diapocynin using HPLC SO LC GC EUROPE LA English DT Article ID INHIBITION; OXIDATION; DRUG AB This study evaluates the use of HPCL to estimate the log P (the octanol-water patition coefficient of two compounds, apocynin and diapocynin. The paper will discuss the effects of an unexpected reversal of retention that occured when these compounds were chromatographed with various amounts of methanol-water mobile phases. C1 [Smith, Robert E.; Luchtefeld, Ron] US FDA, Total Diet Pesticide Res Ctr, Kansas City, KS USA. [Smith, Robert E.] Park Univ, Parkville, MO USA. RP Smith, RE (reprint author), US FDA, Total Diet Pesticide Res Ctr, Kansas City, KS USA. NR 19 TC 2 Z9 2 U1 0 U2 1 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1471-6577 J9 LC GC EUR JI LC GC Eur. PD FEB PY 2008 VL 21 IS 2 BP 103 EP + PG 4 WC Chemistry, Analytical SC Chemistry GA 258BJ UT WOS:000252843100006 ER PT J AU Rasnake, CM Trumbo, PR Heinonen, TM AF Rasnake, Crystal M. Trumbo, Paula R. Heinonen, Therese M. TI Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease SO NUTRITION REVIEWS LA English DT Review DE biomarkers; cardiovascular disease; health claims; surrogate endpoint ID CORONARY-HEART-DISEASE; HIGH-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN; PRIMARY-PREVENTION TRIAL; BLOOD-PRESSURE; SERUM-CHOLESTEROL; A-I; MEN; MORTALITY; FRAMINGHAM AB This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD). Numerous potential surrogate endpoints of CVD are being evaluated as the pathophysiology of heart disease is becoming better understood. However, these emerging biomarkers need to be validated as surrogate endpoints before they are used by CFSAN in the evaluation of a CVD health claim. (c) 2008 International Life Sciences Institute. C1 [Rasnake, Crystal M.; Trumbo, Paula R.] US FDA, Nutr Programs Staff, College Pk, MD USA. [Heinonen, Therese M.] Montreal Heart Inst Coordinating Ctr, Montreal, PQ, Canada. RP Rasnake, CM (reprint author), HFS-830,5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM crystal.rasnake@fda.hhs.gov NR 67 TC 7 Z9 8 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD FEB PY 2008 VL 66 IS 2 BP 76 EP 81 DI 10.1111/j.1753-4887.2007.00010.x PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 259HV UT WOS:000252931300002 PM 18254873 ER PT J AU Devine, S Dagher, RN Weiss, KD Santana, VM AF Devine, Susan Dagher, Ramzi N. Weiss, Karen D. Santana, Victor M. TI Good clinical practice and the conduct of clinical studies in pediatric oncology SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID PHASE-I TRIALS; METASTATIC RHABDOMYOSARCOMA; CANCER; CHILDREN; WINDOW; CYCLOPHOSPHAMIDE; TOPOTECAN AB This article discusses the principles that guide good clinical practice standards, with particular emphasis on how they to relate to pediatric oncology research and recent efforts at harmonization. The authors review the clinical trials process and the roles of the participants, highlighting the pivotal role of the clinical investigator and the research team, and briefly review the historical aspects of drug development regulations in the United States and the current regulatory paths for pediatric oncology drug development. Where relevant, historical events that underlie many of the regulations and their current applications are described, and practical examples are provided. C1 [Santana, Victor M.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Devine, Susan] Hosp Sick Children, Dept Hematol Oncol, Toronto, ON M5G 1X8, Canada. [Dagher, Ramzi N.; Weiss, Karen D.] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20903 USA. RP Santana, VM (reprint author), St Jude Childrens Hosp, Dept Oncol, 332 N Lauderdale St,MS 260, Memphis, TN 38105 USA. EM victor.santana@stjude.org FU NCI NIH HHS [P30 CA021765-29, CA 23099, P30 CA021765, P01 CA023099, CA 21765] NR 24 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD FEB PY 2008 VL 55 IS 1 BP 187 EP + DI 10.1016/j.pcl.2007.10.008 PG 25 WC Pediatrics SC Pediatrics GA 271NF UT WOS:000253794400010 PM 18242321 ER PT J AU Turujman, SA AF Turujman, S. A. TI Overview of regulatory and scientific considerations of an NDI review under DSHEA SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Turujman, S. A.] US FDA, Ctr Food Safety & Nutr, Off Nutr Labeling & Dietary Supplements, Div Dietary Supplement Programs, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA O6 BP 318 EP 318 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300062 ER PT J AU Frankos, VH AF Frankos, V. H. TI Review of FDA's current good manufacturing practices for dietary supplements regulations, dealing with herbal-botanical substances, and the global scope of industry SO PLANTA MEDICA LA English DT Meeting Abstract CT 7th Annual Oxford International Conference on the Science of Botanicals/4th Interim Meeting of the American-Society-of-Pharmacognosy CY APR 12-16, 2008 CL Univ Mississippi, Oxford, MS SP Amer Soc Pharmacognosy HO Univ Mississippi C1 [Frankos, V. H.] US FDA, CFSAN, ONLDS, Div Dietary Supplement Programs, College Pk, MD 20740 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD FEB PY 2008 VL 74 IS 3 MA S45 BP 322 EP 322 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 283IQ UT WOS:000254630300073 ER PT J AU Mayer, J Cheesemar, MA Twaroski, ML AF Mayer, J. Cheesemar, M. A. Twaroski, M. L. TI Structure-activity relationship analysis tools: Validation and applicability in predicting carcinogens SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE structure-activity relationships; QSAR; SAR; OncoLogic; MCASE; Ashby-Tennant structural alerts; FDA; food contact notifications; mutagenicity; carcinogenic potency database ID RODENT CARCINOGENICITY; CHEMICAL-STRUCTURE; GENETIC TOXICITY; IDENTIFICATION; TOXICOLOGY; PROGRAM; NONCARCINOGENS; MUTAGENICITY; THRESHOLDS; EXERCISE AB OncoLogic (R) and MultiCASE (MCASE) are two structure-activity relationship (SAR) analysis software programs available to screen compounds for potential carcinogenicity. Ashby-Tennant structural alerts [Ashby, J., Tennant, R.W., 1991. Definitive relationships among chemical structure, carcinogenicity, and mutagenicity for 301 chemicals tested by the US NTP. Mutat. Res. 257, 229-306] and genetic toxicity testing may also be used to assess/predict this endpoint. Six-hundred and fifty compounds tested for carcinogenicity whose results were tabulated in the Carcinogenic Potency Database (CPDB) were used to validate and compare the predictivity of OncoLogic (R) (Version 4.1), MCASE (Version 3.1), Ashby-Tennant structural alerts, and genetic toxicity testing, individually and in combination. The sensitivity of the methods for predicting carcinogens and the specificity for predicting non-carcinogens was examined. Potent carcinogens, defined as those with TD50 Values of less than 6.25 mg/kg bw/d, were then examined separately. It is concluded that SAR analysis programs and structural alerts perform well for compounds with low human exposure levels and have the potential to supplement the results of routinely requested genetic toxicity tests in a weight-of-evidence approach in predicting carcinogenicity, although each method of analysis has limitations regarding applicability. Published by Elsevier Inc. C1 [Mayer, J.; Cheesemar, M. A.; Twaroski, M. L.] Food & Drug Adm, Div Food Contact Notificat, College Pk, MD 20740 USA. RP Mayer, J (reprint author), Food & Drug Adm, Div Food Contact Notificat, HFS-275,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM julie.mayer@fda.hhs.gov NR 23 TC 25 Z9 25 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 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 2008 VL 50 IS 1 BP 50 EP 58 DI 10.1016/j.yrtph.2007.09.005 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 255BX UT WOS:000252632800004 PM 18023949 ER PT J AU Miller, TJ Honchel, R Espandiari, P Knapton, A Zhang, J Sistare, FD Hanig, JP AF Miller, T. J. Honchel, R. Espandiari, P. Knapton, A. Zhang, J. Sistare, F. D. Hanig, J. P. TI The utility of the K6/ODC transgenic mouse as an alternative short term dermal model for carcinogenicity testing of pharmaceuticals SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE K6/ODC; transgenic models; carcinogenesis; cancer; cell substrate DNA; ornithine decarboxylase (ODC); alternative cancer bioassay; carcinogenicity testing; short term cancer assay ID EPSTEIN-BARR-VIRUS; ORNITHINE-DECARBOXYLASE; TUMOR PROMOTION; ALPHA-DIFLUOROMETHYLORNITHINE; INCREASED SUSCEPTIBILITY; HUMAN-PAPILLOMAVIRUS; SKIN CARCINOGENESIS; TRANSFORMING GENE; CELL-LINES; IFN-GAMMA AB The use of transgenic rodents may overcome many limitations of traditional cancer studies. Regulatory perspectives continue to evolve as new models are developed and validated. The transgenic mouse, K6/ODC, develops epidermal tumors when exposed to genotoxic carcinogens. In this study, K6/ODC mice were evaluated for model fitness and health robustness in a 36-week study to determine oncogenic risk of residual DNA in vaccines from neoplastic cell substrates. K6/ODC and C57BL/6 mice were treated with T24-H-ras expression plasmid, carrier vector DNA, or saline topically or by subcutaneous injection. One group of K6/ODC mice received 7,12-dimethylbenz-[a]anthracene [DMBA] dermally. Only DMBA-treated mice developed papillomas by six weeks, increasing in incidence to 25 weeks. By week 11, many K6/ODC mice showed severe dehydration and dermal eczema. By week 32, (6/8) surviving K6/ODC mice showed loss of mobility and balance. Microscopic evaluation of tissues revealed dermal/sebaceous gland hyperplasia, follicular dystrophy, splenic atrophy, and amyloid deposition/neutrophilic infiltration within liver, heart, and spleen, in all K6/ODC mice. Pathology was not detected in C57BL/6 mice. Progressive adverse health, decreased survival, and failure to develop papillomas to the H-ras plasmid suggest that K6/ODC mice may be an inappropriate alternative model for detection of oncogenic DNA and pharmaceutical carcinogenicity testing. Published by Elsevier Inc. C1 [Miller, T. J.; Honchel, R.; Espandiari, P.; Knapton, A.; Zhang, J.; Sistare, F. D.; Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Miller, TJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, White Oak Life Sci Bldg 64,Room 2066,10903 New Ha, Silver Spring, MD 20993 USA. EM terry.miller@fda.hhs.gov NR 63 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 2008 VL 50 IS 1 BP 87 EP 97 DI 10.1016/j.yrtph.2007.10.011 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 255BX UT WOS:000252632800008 PM 18069108 ER PT J AU Soldin, OP Tonning, JM AF Soldin, Offie P. Tonning, Joseph M. TI Serotonin syndrome is associated with triptan monotherapy. SO REPRODUCTIVE SCIENCES LA English DT Meeting Abstract CT 55th Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 26-29, 2008 CL San Diego, CA SP Soc Gynecol Invest C1 [Soldin, Offie P.] Georgetown Univ, Med Ctr, Obstet Pharmacol Res Unit OPRU, Washington, DC USA. [Tonning, Joseph M.] US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Silver Spring, MD 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 1933-7191 J9 REPROD SCI JI Reprod. Sci. PD FEB PY 2008 VL 15 IS 2 SU S MA 663 BP 248A EP 248A PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 268LP UT WOS:000253581600665 ER PT J AU Dayton, AI AF Dayton, Andrew I. TI Hitting HIV where it hides SO RETROVIROLOGY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE-ANTIRETROVIRAL-THERAPY; HUMAN PRIMARY MACROPHAGES; NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS; LYMPH-NODES; TAT PROTEIN; MONONUCLEAR PHAGOCYTES; IN-VITRO; INFECTION AB The recent finding that inhibitors of PI3/Akt can sensitize HIV infected macrophages to oxidative stress-induced cell death suggest a potential new therapeutic approach to targeting HIV reservoirs. C1 [Dayton, Andrew I.] OBRR CBER FDA, Div Emerging & Transfus Transmitted Dis, Lab Mol Virol, Rockville, MD 20852 USA. RP Dayton, AI (reprint author), OBRR CBER FDA, Div Emerging & Transfus Transmitted Dis, Lab Mol Virol, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. EM Andrew.dayton@fda.hhs.gov NR 31 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD FEB 1 PY 2008 VL 5 AR 15 DI 10.1186/1742-4690-5-15 PG 3 WC Virology SC Virology GA 265HR UT WOS:000253350200001 PM 18241337 ER PT J AU Soldin, OP Dahlin, J O'Mara, DM AF Soldin, Ofie P. Dahlin, Julia O'Mara, Daniel M. TI Triptans in pregnancy SO THERAPEUTIC DRUG MONITORING LA English DT Review DE serotonin uptake agonists; serotonin receptor; 5-HT adverse drug events; pharmacology; migraine disorder/drug therapy/physiopathology; gestation ID MIGRAINE HEADACHES; MONOAMINE-OXIDASE; SUMATRIPTAN; RECEPTORS; EXPOSURE; TOLERABILITY; MECHANISMS; REACTIVITY; ARTERIES; 5-HT AB The triptans are. a class of tryptamine-based drugs indicated for in the treatment of migraine headaches. The triptans act as serotonin (5-hydroxytriptamine) (5-HT) agonists by binding to various serotonin receptors, causing vasoconstriction and neuronal inhibition to alleviate migraines. There are 7 types of triptans currently available on the U.S. market: almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. The objective of this study was to examine the use and effects of triptans in pregnancy. Although three of the triptans have pregnancy registries maintained by the manufacturer, triptan use in pregnancy has not been extensively studied. Information on the use of sumatriptan during pregnancy is relatively more abundant, because it has been on the market longer than the other triptans and may also have a higher percentage of the market share. There are no data to suggest teratogenicity for any of the triptans, although preterm birth rates appear to be elevated. C1 [Soldin, Ofie P.] Georgetown Univ, Med Ctr, Dept Med Oncol & Physiol, Washington, DC USA. [Soldin, Ofie P.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [O'Mara, Daniel M.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC USA. RP Soldin, OP (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20057 USA. EM os35@georgetown.edu FU NCRR NIH HHS [M01 RR020359]; NICHD NIH HHS [U10 HD047890] NR 40 TC 20 Z9 23 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD FEB PY 2008 VL 30 IS 1 BP 5 EP 9 PG 5 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 258OT UT WOS:000252877900002 PM 18223456 ER PT J AU Zhang, J Knapton, A Lipshultz, SE Weaver, JL Herman, EH AF Zhang, Jun Knapton, Alan Lipshultz, Steven E. Weaver, James L. Herman, Eugene H. TI Isoproterenol-induced Cardiotoxicity in Sprague-Dawley Rats: Correlation of Reversible and Irreversible Myocardial Injury with Release of Cardiac Troponin T and Roles of iNOS in Myocardial Injury SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cardiac troponins; myocardial necrosis; myocardial apoptosis; iNOS ID NITRIC-OXIDE SYNTHASE; SERUM-LEVELS; DOXORUBICIN; HEART; EXPRESSION; BIOMARKERS; INFARCTION; APOPTOSIS; MEMBRANE; MYOCYTES AB The present study was undertaken to characterize myocardial lesions in the rat induced by low doses of isoproterenol (Iso) and to correlate lesion severity with release of cardiac troponin T (cTnT) and changes in myocyte iNOS expression. Two types of cardiac injury patterns were observed. A Type I response, noted 3 or 6 hours postdosing with 8, 16, 32, or 64 mu g/kg Iso, included potential reversible myocardial alterations associated with slight increases in serum cTnT (< 0.3 ng/mL) and a slight reduction in myocyte cTnT immunoreactivity. The second type of response noted 3, 6, 12, 24 or 48 hours postdosing with 125, 250, or 500 mu g/kg Iso consisted of irreversible myocyte alterations, together with significant increases in serum cTnT (3-14 ng/mL) and a marked reduction of cTnT immunoreactivity. By 48 hours the hearts of rats dosed with 125-500 mu g/kg Iso had developed interstitial fibrosis, and serum cTnT had declined to near control levels (0.06-0.18 ng/mL). Increases in iNOS immunoreactivity correlated with the lesion severity. These findings suggest that low doses of Iso exert complex effects on the myocardium and that the generation of NO through increased expression of iNOS could be an important factor in the pathogenesis of myocyte injury. C1 [Zhang, Jun; Knapton, Alan; Weaver, James L.; Herman, Eugene H.] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Lipshultz, Steven E.] Univ Miami, Miller Sch Med, Dept Pediat, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. RP Zhang, J (reprint author), Food & Drug Adm HFD 910, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Life Sci Lab Bldg,Room 2082,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov NR 30 TC 43 Z9 45 U1 0 U2 4 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 FEB PY 2008 VL 36 IS 2 BP 277 EP 288 DI 10.1177/0192623307313010 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UK UT WOS:000267457400010 PM 18349426 ER PT J AU Lucey, C Weina, PJ AF Lucey, Charles Weina, Peter J. TI Applying the STARD (Standards for Reporting of Diagnostic Accuracy) checklist to the 2007 Transfusion article 'Evaluation of a new enzyme-linked immunosorbent assay for detection of Chagas antibody in US blood donors' SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE STARD; Chagas disease; Trypanosoma; diagnosis; assay AB A group of scientists and journal editors developed the STARD (Standards for Reporting of Diagnostic Accuracy) checklist to improve the reporting of diagnostic accuracy. This checklist provides a standardised framework to ensure all relevant information is considered and no potentially important parameters are inadvertently overlooked. Whilst the quality of reporting is crucial. to the understanding of a test's potential performance characteristics, this checklist can and should be used not only to assess the reporting itself, but also to question any potential flaws in the assay inadvertently overlooked or not challenged by others. This article uses the STARD checklist to took at a recent report on a new assay for Chagas disease and examines the strength of this work against a standard review tool. Potential. issues associated with the reporting of the work as well as potential issues with the assay are identified and additional questions are posed that might help clarify the issues identified. Published by Elsevier Ltd on behalf of Royal Society of Tropical Medicine and Hygiene. C1 [Weina, Peter J.] Walter Reed Army Inst Res, Div Expt Therapeut, Silver Spring, MD 20910 USA. [Lucey, Charles] DHHS PHS FDA OBRR, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Weina, PJ (reprint author), Walter Reed Army Inst Res, Div Expt Therapeut, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM peter.weina@na.amedd.army.mil RI Weina, Peter/A-2120-2011 NR 11 TC 3 Z9 3 U1 0 U2 0 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 FEB PY 2008 VL 102 IS 2 BP 155 EP 160 DI 10.1016/j.trstmh.2007.10.016 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 269LK UT WOS:000253650300010 PM 18082863 ER PT J AU Dimitrakov, J Joffe, HV Soldin, SJ Bolus, R Buffington, CAT Nickel, JC AF Dimitrakov, Jordan Joffe, Hylton V. Soldin, Steven J. Bolus, Roger Buffington, C. A. Tony Nickel, J. Curtis TI Adrenocortical hormone abnormalities in men with chronic prostatitis/chronic pelvic pain syndrome SO UROLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; PITUITARY-ADRENAL AXIS; 21-HYDROXYLASE DEFICIENCY; LIQUID-CHROMATOGRAPHY; HEALTHY CONTROLS; HYPOCORTISOLISM; FIBROMYALGIA; CORTISOL; STRESS; TRIAL AB OBJECTIVES To identify adrenocortical hormone abnormalities as indicators of endocrine dysfunction in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS We simultaneously measured the serum concentrations of 12 steroids in patients with CP/CPPS and controls, using isotope dilution liquid chromatography, followed by atmospheric pressure photospray ionization and tandem mass spectrometry. RESULTS We evaluated 27 patients with CP/CPPS and 29 age-matched asymptomatic healthy controls. In the mineralocorticoid pathway, progesterone was significantly greater, and the corticosterone and aldosterone concentrations were significantly lower, in the patients with CP/CPPS than in the controls. In the glucocorticoid pathway, 11-deoxycortisol was significantly lower and the cortisol concentrations were not different between the patients and controls. In the sex steroid pathway, the androstenedione and testosterone concentrations were significantly greater in those with CP/CPPS than in the controls. The estradiol, dehydroepiandrosterone, and dehydroepiandrosterone sulfate concentrations were not different between the patients and controls. The National Institutes of Health-Chronic Prostatitis Symptom Index total and pain domain scores correlated positively with the 17-hydroxyprogesterone and aldosterone (P <0.001) and negatively with the cortisol (P <0.001) concentrations. CONCLUSIONS Our results suggest reduced activity of CYP21A2(P450c21), the enzyme that converts progesterone to corticosterone and 17-hydroxyprogesterone to 11-deoxycortisol. Furthermore, these results provide insights into the biologic basis of CP/CPPS. Follow-up studies should explore the possibility that patients with CP/CPPS meet the diagnostic criteria for nonclassic congenital adrenal hyperplasia and whether the hormonal findings improve or worsen in parallel with symptom severity. C1 [Dimitrakov, Jordan] Harvard Univ, Sch Med, Harvard Urol Dis Res Ctr, Childrens Hosp Boston, Boston, MA 02115 USA. US FDA, Silver Spring, MD USA. Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD USA. George Washington Univ, Sch Med, Bioanalyt Core Lab, Georgetown Clin Res Ctr,Dept Med, Washington, DC USA. George Washington Univ, Sch Med, Bioanalyt Core Lab, Georgetown Clin Res Ctr,Dept Pharmacol, Washington, DC USA. George Washington Univ, Sch Med, Bioanalyt Core Lab, Georgetown Clin Res Ctr,Dept Pathol, Washington, DC USA. George Washington Univ, Sch Med, Bioanalyt Core Lab, Georgetown Clin Res Ctr,Dept Pediat, Washington, DC USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. Ohio State Univ, Dept Vet Clin Sci, Columbus, OH 43210 USA. Queens Univ, Dept Urol, Kingston, ON, Canada. RP Dimitrakov, J (reprint author), Harvard Univ, Sch Med, Harvard Urol Dis Res Ctr, Childrens Hosp Boston, Enders Res Bldg,Room 1061,300 Longwood Ave, Boston, MA 02115 USA. EM Jordan.Dimitrakov@childrens.harvard.edu OI Dimitrakoff, Jordan/0000-0001-6827-1382 FU NIDDK NIH HHS [R01 DK065990, R21 DK070672-02, R01 DK065990-01, R01 DK065990-06, R01 DK065990-02, R21 DK070672, R21 DK070672-01A2, R01 DK065990-03, R01 DK065990-05, R01 DK065990-04] NR 23 TC 27 Z9 28 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2008 VL 71 IS 2 BP 261 EP 266 DI 10.1016/j.urology.2007.09.025 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 265CZ UT WOS:000253338000030 PM 18308097 ER PT J AU Michel, KE Churchill, J Daristotle, L Delaney, S Freeman, LM Laflamme, D Laflamme, D McChesney, D Roudebush, P Tefend, MB Todd-Jenkins, K AF Michel, Kathryn E. Churchill, Julie Daristotle, Leighann Delaney, Sean Freeman, Lisa M. Laflamme, Dottie Laflamme, Daniel McChesney, Daniel Roudebush, Phil Tefend, Mary B. Todd-Jenkins, Karen TI Expert summit on pet food - Part two SO VETERINARY TECHNICIAN LA English DT Editorial Material C1 [Michel, Kathryn E.] Univ Penn, Med Sect, Philadelphia, PA 19104 USA. [Churchill, Julie] Univ Minnesota, Minneapolis, MN 55455 USA. [Delaney, Sean] Nat Pet Prod Inc, Girard, KS 66743 USA. [Freeman, Lisa M.] Tufts Univ, Cummings Sch Vet Med, Dept Clin Sci, Medford, MA 02155 USA. [Laflamme, Dottie] Nestle Purina PetCare Global Resources, St Louis, MO USA. [McChesney, Daniel] US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. [Roudebush, Phil] Hills Pet Nutr, Topeka, KS USA. [Tefend, Mary B.] Auburn Univ, Auburn, AL 36849 USA. RP Michel, KE (reprint author), Univ Penn, Med Sect, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU VETERINARY LEARNING SYSTEMS PI YARDLEY PA 780 TOWNSHIP LINE RD, YARDLEY, PA 19067-4200 USA SN 8750-8990 J9 VET TECH JI Vet. Tech. PD FEB PY 2008 VL 29 IS 2 BP 82 EP + PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 263IK UT WOS:000253210600006 ER PT J AU Reesink, HW Engelfriet, CP Henn, G Mayr, WR Delage, G Bernier, F Krusius, T Assal, A Gallian, P Corbi, C Morel, P David, B De Micco, P Murokawa, H Yugi, H Hino, S Tadokoro, K Flesland, O Brojer, E Letowska, M Olim, G Nascimento, F Goncalves, H Castro, L Morais, M Stezinar, SL Alvarez, M Sauleda, S Gonzalez, R Niederhauser, C Stolz, M Allain, JP Owusu-Ofori, S Eglin, R Stramer, S Busch, M Strong, DM Epstein, J Biswas, R AF Reesink, H. W. Engelfriet, C. P. Henn, G. Mayr, W. R. Delage, G. Bernier, F. Krusius, T. Assal, A. Gallian, P. Corbi, C. Morel, P. David, B. De Micco, P. Murokawa, H. Yugi, H. Hino, S. Tadokoro, K. Flesland, O. Brojer, E. Letowska, M. Olim, G. Nascimento, F. Goncalves, H. Castro, L. Morais, M. Stezinar, S. L. Alvarez, M. Sauleda, S. Gonzalez, R. Niederhauser, C. Stolz, M. Allain, J. -P. Owusu-Ofori, S. Eglin, R. Stramer, S. Busch, M. Strong, D. M. Epstein, J. Biswas, R. TI Occult hepatitis B infection in blood donors SO VOX SANGUINIS LA English DT Editorial Material ID NUCLEIC-ACID; ANTI-HBC; VIRUS INFECTION; DNA; TRANSFUSION; IMPLEMENTATION; AMPLIFICATION; TRANSMISSION; DONATIONS; SAFETY C1 [Reesink, H. W.] Sanquin Consulting Serv, NL-1066 CX Amsterdam, Netherlands. [Reesink, H. W.] Acad Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands. [Engelfriet, C. P.] Sanquin Res & Sanquin Diagnost Serv, NL-1066 CX Amsterdam, Netherlands. [Mayr, W. R.] Blutspendezentral, A-1040 Vienna, Austria. [Krusius, T.] Finnish Red Cross & Blood Transfus Serv, SF-00310 Helsinki, Finland. [Assal, A.; Gallian, P.; Corbi, C.; Morel, P.; David, B.; De Micco, P.] Direct Med & Sci, Etab Francais Sang, F-93218 St Denis, France. [Murokawa, H.; Yugi, H.; Hino, S.; Tadokoro, K.] Japanese Red Cross Blood Serv, Cent Blood Inst, Dept Nucle Acid Amplificat Testing, Oota Ku, Tokyo 1440055, Japan. [Flesland, O.] Asker & Baerum Hosp, Lab Ctr, NO-1309 Rud, Norway. [Brojer, E.; Letowska, M.] Inst Haematol & Transfus Med, PL-02776 Warsaw, Poland. [Olim, G.; Nascimento, F.; Goncalves, H.; Castro, L.; Morais, M.] Inst Portugues Sangue, P-1749005 Lisbon, Portugal. [Stezinar, S. L.] Blood Transfus Ctr Slovenia, Dept Diagnost Serv, SI-1000 Ljubljana, Slovenia. [Alvarez, M.] Ctr Transfus Alicante, Alicante 03550, Spain. [Sauleda, S.] Banc Sang & Teixits, Barcelona 08035, Spain. [Gonzalez, R.] Ctr Transfus La Cruz Roja, Madrid 28040, Spain. [Niederhauser, C.; Stolz, M.] Blood Transfus Serv SRC Berne, CH-3008 Bern, Switzerland. [Allain, J. -P.] Univ Cambridge, Dept Hematol, E Anglia Blood Ctr, Div Transfus Med, Cambridge CB2 2PT, England. [Owusu-Ofori, S.] Komfo Anokye Teaching Hosp, Transfus Med Unit, Kumasi, Ghana. [Eglin, R.] Natl Blood serv, London NW9 5BG, England. [Biswas, R.] US FDA, HFM 100, Rockville, MD 20852 USA. RP Reesink, HW (reprint author), Sanquin Consulting Serv, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. EM h.reesink@sanquin.nl; p.engelfriet@sanquin.nl; gabriela.henn@roteskreuz.at; wolfgang.mayr@roteskreuz.at; gilles.delage@hema-quebec.qc.ca; france.bernier@hema-quebec.qc.ca; tom.krusius@bts.redcross.fi; azzedine.assal@efs.sante.fr; h-murokawa@bs.jrc.or.jp; yugi@bs.jrc.or.jp; s-hino@bs.jrc.or.jp; k-tadokoro@obs.jrc.or.jp; oystein.flesland@sabhf.no; ebrojer@ihit.waw.pl; letowska@ihit.waw.pl; snezna.levicnik@ztm.si; alvarez-man@gva.es; christoph.niederhauser@bsd-be.ch; martin.stolz@bsd-be.ch; jpa1000@cam.ac.uk; roger.eglin@nbs.nhs.uk; robin.biswas@fda.hhs.gov NR 27 TC 20 Z9 23 U1 0 U2 7 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 FEB PY 2008 VL 94 IS 2 BP 153 EP 166 PG 14 WC Hematology SC Hematology GA 263PA UT WOS:000253227800011 PM 18205672 ER PT J AU Bhattacharjee, A Mishra, RS Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Mishra, Ravi S. Feldman, Gerald M. Cathcart, Martha K. TI In vivo validation of signaling pathways regulating human monocyte chemotaxis SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE monocytes; transfection; adoptive transfer; chemotaxis; PKC beta ID ACTIVATED HUMAN MONOCYTES; LOW-DENSITY-LIPOPROTEIN; SUPEROXIDE ANION PRODUCTION; KINASE-C-DELTA; 15-LIPOXYGENASE GENE-EXPRESSION; CYTOSOLIC PHOSPHOLIPASE A(2); CENTRIFUGAL ELUTRIATION CCE; MONONUCLEAR CELL SUBSETS; ENRICHED FRACTIONS; LIPID OXIDATION AB Identification of novel signal transduction pathways regulating monocyte chemotaxis can indicate unique targets for preventive therapies for treatment of chronic inflammatory diseases. To aid in this endeavor we report conditions for optimal transfection of primary human monocytes coupled with a new model system for assessing their chemotactic activity in vivo. This method can be used as a tool to identify the relevant signal transduction pathways regulating human monocyte chemotaxis to MCP-1 in the complex in vivo environment that were previously identified to regulate chemotaxis in vitro. MCP-1-dependent chemotaxis of monocytes is studied in an adoptive transfer model where human monocytes transfected with mutant cDNAs are transferred to mice followed by initiation of peritonitis. Harvesting peritoneal cells at 24 h diminishes the contribution of immunologic responses to the cross-species transfer. Validation of relevant regulatory molecules in vivo is critical for understanding the most relevant therapeutic targets for drug development. (C) 2007 Elsevier B.V. All rights reserved. C1 [Bhattacharjee, Ashish; Mishra, Ravi S.; Cathcart, Martha K.] Cleveland Clin, Dept Cell Biol, Cleveland, OH 44195 USA. [Cathcart, Martha K.] Lerner Coll Med Case Western Reserve Univ, Cleveland Clin, Dept Mol Med, Cleveland, OH 44195 USA. [Feldman, Gerald M.] Ctr Biol Evaluat & Res, Off Therapeut, Div Monoclonal Antibodies, Food & Drug Adm, Bethesda, MD 20892 USA. RP Cathcart, MK (reprint author), Cleveland Clin, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NCRR NIH HHS [M01 RR 018390, M01 RR018390]; NHLBI NIH HHS [R01 HL051068-08, R01 HL051068, P01 HL087018-01A10003, R01 HL074451-04, R01 HL074451, HL 61971, P01 HL087018, R01 HL061971, HL 74451] NR 29 TC 3 Z9 4 U1 0 U2 0 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 JAN 31 PY 2008 VL 330 IS 1-2 BP 86 EP 95 DI 10.1016/j.jim.2007.11.011 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 265GZ UT WOS:000253348400009 PM 18191414 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI Bleeding associated with warfarin use: Improving outcomes - Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 Food & Drug Adm, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), Food & Drug Adm, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 28 PY 2008 VL 168 IS 2 BP 237 EP 237 DI 10.1001/archinternmed.2007.50 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 254NR UT WOS:000252593800021 ER PT J AU Luchtefeld, R Luo, R Stine, K Alt, ML Chernovitz, PA Smith, RE AF Luchtefeld, Ron Luo, Rensheng Stine, Keith Alt, Mikaela L. Chernovitz, Patricia A. Smith, Robert E. TI Dose formulation and analysis of diapocynin SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE diapocynin; triapocynin; HPLC; LC-MS ID NADPH OXIDASE INHIBITION; APOCYNIN; NEUTROPHILS; OXIDATION; INJURY AB Procedures based on high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection and liquid chromatography-mass spectrometry (LC-MS) are described for analyzing diapocynin. Diapocynin was synthesized by oxidative coupling of two apocynin monomers, through the in situ generation of sulfate radicals. It was purified by washing 3 times each with boiling water, followed by boiling methanol. HPLC was used to determine the concentration of unreacted apocynin and other impurities and the purity of the diapocynin that had been synthesized. Negative-ion, atmospheric pressure chemical ionization (APCI) LC-MS was used to determine the molecular weights of impurities. The method using HPLC with UV detection provided a calibration curve that was linear from 0.16 to 24 mu g/mL. The LC-MS method was linear from 0.005 to 2 mu g/mL. It was found that diapocynin has low solubility in deionized water and corn oil but is soluble in dimethylsulfoxide (DMSO) and alkaline aqueous solutions. Also, diapocynin is 13 times more lipophilic than apocynin, even though both compounds have the same pK(a) of 7.4. The log of the octanol/water partition coefficient (log P) was 1.01 for apocynin and 1.82 for diapocynin. A solution of 5.5 mg/mL (16.7 mM) diapocynin in DMSO was found to be stable for at least 30 days when stored at room temperature. C1 [Luchtefeld, Ron; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. [Luo, Rensheng; Stine, Keith] Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. [Alt, Mikaela L.; Chernovitz, Patricia A.; Smith, Robert E.] Park Univ, Dept Chem, Parkville, Vic 64152, Australia. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov NR 18 TC 15 Z9 15 U1 0 U2 0 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 JAN 23 PY 2008 VL 56 IS 2 BP 301 EP 306 DI 10.1021/jf072792n PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 252GK UT WOS:000252434800001 PM 18092754 ER PT J AU Nyman, PJ Diachenko, GW Perfetti, GA McNeal, TP Hiatt, MH Morehouse, KM AF Nyman, Patricia J. Diachenko, Gregory W. Perfetti, Gracia A. McNeal, Timothy P. Hiatt, Michael H. Morehouse, Kim M. TI Survey results of benzene in soft drinks and other beverages by headspace gas chromatography/mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE benzene; beverages; headspace; gas chromatography/mass spectrometry AB Benzene, a carcinogen that can cause cancer in humans, may form at nanogram per gram levels in some beverages containing both benzoate salts and ascorbic or erythorbic acids. Through a series of reactions, a hydroxyl radical forms that can decarboxylate benzoate to form benzene. Elevated temperatures and light stimulate these reactions, while sugar and ethylenediaminetetraacetic acid (EDTA) can inhibit them. A headspace gas chromatography/mass spectrometry method for the determination of benzene in beverages was developed and validated. The method was used to conduct a survey of 199 soft drinks and other beverages. The vast majority of beverages sampled contained either no detectable benzene or levels below the U.S. Environmental Protection Agency's drinking water limit of 5 ng/g. Beverages found to contain 5 ng/g benzene or more were reformulated by the manufacturers. The amount of benzene found in the reformulated beverages ranged from none detected to 1.1 ng/g. C1 [Nyman, Patricia J.; Diachenko, Gregory W.; Perfetti, Gracia A.; McNeal, Timothy P.; Morehouse, Kim M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hiatt, Michael H.] US EPA, Natl Exposure Res Lab, Div Environm Sci, Las Vegas, NV 89193 USA. RP Nyman, PJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-706,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Patricia.Nyman@fda.hhs.gov NR 20 TC 14 Z9 14 U1 0 U2 7 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 JAN 23 PY 2008 VL 56 IS 2 BP 571 EP 576 DI 10.1021/jf0724791 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 252GK UT WOS:000252434800041 PM 18072742 ER PT J AU Murata, H Peden, K Lewis, AM AF Murata, Haruhiko Peden, Keith Lewis, Andrew M., Jr. TI Identification of a mutation in the SV40 capsid protein VP1 that influences plaque morphology, vacuolization, and receptor usage SO VIROLOGY LA English DT Article DE polyomaviruses; SV40; VP1; plaque phenotype; vacuolization; ganglioside ID MAJOR HISTOCOMPATIBILITY PROTEINS; MURINE POLYOMAVIRUS; VIRUS; SIMIAN-VIRUS-40; RESOLUTION; GANGLIOSIDES; MUTANTS; REVEALS; BINDING; COMPLEX AB A plaque variant of SV40 that was first isolated in the 1960s, designated SV40-LP(KT), was molecularly cloned and subjected to sequence analysis. The genome of SV40-LP(KT) was found to be nearly identical to the previously described isolate known as 777. However, SV40-LP (KT) contained a mutation in the VP1 coding region resulting in a change of histidine 136 to tyrosine. This VP1 mutation was identified as a genetic determinant influencing a number of phenotypes associated with SV40-LP(KT) such as plaque morphology, intracellular vacuole formation, and ganglioside receptor usage. Published by Elsevier Inc. C1 [Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Products, CBER, Bethesda, MD 20892 USA. [Murata, Haruhiko] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Div Canc Prevent,NIH, Bethesda, MD 20892 USA. [Murata, Haruhiko; Peden, Keith] US FDA, Lab Retrovirus Res, Div Viral Products, CBER, Bethesda, MD 20892 USA. RP Lewis, AM (reprint author), US FDA, Lab DNA Viruses, Div Viral Products, CBER, Bldg 29A,Room 1B10,29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hiis.gov NR 24 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 2008 VL 370 IS 2 BP 343 EP 351 DI 10.1016/j.virol.2007.08.040 PG 9 WC Virology SC Virology GA 242BF UT WOS:000251698800013 PM 17936868 ER PT J AU Fan, YX Wong, LL Ding, JH Spiridonov, NA Johnson, RC Johnson, GR AF Fan, Ying-Xin Wong, Lily Ding, Jinhui Spiridonov, Nikolay A. Johnson, Richard C. Johnson, Gibbes R. TI Mutational activation of ErbB2 reveals a new protein kinase autoinhibition mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; EXTRACELLULAR REGION; CRYSTAL-STRUCTURE; SIGNAL-TRANSDUCTION; CATALYTIC-ACTIVITY; LUNG-CANCER; DOMAIN; EGF; COMPLEX AB Autoinhibition plays a key role in the control of protein kinase activity. ErbB2 is a unique receptor-tyrosine kinase that does not bind ligand but possesses an extracellular domain poised to engage other ErbBs. Little is known about the molecular mechanism for ErbB2 catalytic regulation. Here we show that ErbB2 kinase is strongly autoinhibited, and a loop connecting the alpha C helix and beta 4 sheet within the kinase domain plays a major role in the control of kinase activity. Mutations of two Gly residues at positions 776 and 778 in this loop dramatically increase ErbB2 catalytic activity. Kinetic analysis demonstrates that mutational activation is due to similar to 10- and similar to 7-fold increases in ATP binding affinity and turnover number, respectively. Expression of the activated ErbB2 mutants in cells resulted in elevated ligand- independent ErbB2 autophosphorylation, ErbB3 phosphorylation, and stimulation of mitogen-activated protein kinase. Molecular modeling suggests that the ErbB2 kinase domain is stabilized in an inactive state via a hydrophobic interaction between the alpha C-beta 4 and activation loops. Importantly, many ErbB2 human cancer mutations have been identified in the alpha C-beta 4 loop, including the activating G776S mutation studied here. Our findings reveal a new kinase regulatory mechanism in which the alpha C-beta 4 loop functions as an intramolecular switch that controls ErbB2 activity and suggests that loss of alpha C-beta 4 loop-mediated autoinhibition is involved in oncogenic activation of ErbB2. C1 [Fan, Ying-Xin; Wong, Lily; Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Ding, Jinhui] NIH, NIA, Neurogenet Lab, Bioinformat Sect, Bethesda, MD 20892 USA. [Johnson, Richard C.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Fan, YX (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bldg 29A,Rm 3B-20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM ying-xin.fan@fda.hhs.gov; gibbes.johnson@fda.hhs.gov RI Spiridonov, Nikolay/B-6287-2014 NR 49 TC 22 Z9 22 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 18 PY 2008 VL 283 IS 3 BP 1588 EP 1596 DI 10.1074/jbc.M708116200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250EL UT WOS:000252282700044 PM 18039657 ER PT J AU McMahon, AW Iskander, JK Haber, P Braun, MM Ball, R AF McMahon, A. W. Iskander, J. K. Haber, P. Braun, M. M. Ball, R. TI Inactivated influenza vaccine (IIV) in children < 2 years of age: Examination of selected adverse events reported to the Vaccine Adverse Event Reporting System (VAERS) after thimerosal-free or thimerosal-containing vaccine SO VACCINE LA English DT Article DE influenza vaccine; adverse event; thimerosal; infant AB Thimerosal as a preservative (in all but trace amounts) was removed from vaccines used in infants starting in the late 1990s, though the preservative-including inactivated influenza vaccine is stilt available for use in individuals >= 6 months of age. We compared the proportion of injection site reactions, rash, and infections reported to the Vaccine Adverse Event Reporting System (VAERS) after preservative-free (PFV), preservative-including (PIV), and preservative unknown (PUV) vaccines in reports from 7/1/2004 to 1/4/2006. There were 145, 175, and 216 reports after vaccination with PFV, PIV, and PUV, respectively. The most frequently reported coding terms (fever, rash, and urticaria) were seen in similar proportions in the PFV PIV, and PUV groups. No difference was detected in the proportion of injection site reactions (ISR), rash, or infections in the PIV, PFV, and PUV reports. Keeping in mind the inherent limitations of VAERS, including underreporting and potential reporting biases, we conclude that there were no substantial differences in the proportion of rash, ISR, and infection reports in the PIV, PFV and PUV reports in infants. (c) 2007 Elsevier Ltd. All rights reserved. C1 [McMahon, A. W.; Braun, M. M.; Ball, R.] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. [Iskander, J. K.; Haber, P.] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA 30333 USA. RP McMahon, AW (reprint author), Ctr Drug Evaluat & Res, Food & Drug Adm, 1093 New Hampshire Ave,Room 3474, Silver Spring, MD 20993 USA. EM ann.mcmahon@fda.hhs.gov NR 10 TC 9 Z9 12 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 JAN 17 PY 2008 VL 26 IS 3 BP 427 EP 429 DI 10.1016/j.vaccine.2007.10.071 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 261DU UT WOS:000253060100017 PM 18093701 ER PT J AU Siegel, J AF Siegel, Jeffrey TI Comparative effectiveness of treatments for rheumatoid arthritis SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID MODIFYING ANTIRHEUMATIC DRUGS; RANDOMIZED CONTROLLED-TRIAL; WEEK CLINICAL-TRIAL; COMBINATION THERAPY; SINGLE COMPONENTS; DOUBLE-BLIND; METHOTREXATE; SULFASALAZINE; EFFICACY C1 US FDA, Silver Spring, MD 20910 USA. RP Siegel, J (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 22,Room 3154, Silver Spring, MD 20910 USA. EM jeffrey.siegel@fda.hhs.gov NR 14 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 15 PY 2008 VL 148 IS 2 BP 162 EP 163 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 254NZ UT WOS:000252594600010 PM 18195341 ER PT J AU Brave, M Goodman, V Kaminskas, E Farrell, A Timmer, W Pope, S Harapanhalli, R Saber, H Morse, D Bullock, J Men, A Noory, C Ramchandani, R Kenna, L Booth, B Gobburu, J Jiang, XP Sridhara, R Justice, R Pazdur, R AF Brave, Michael Goodman, Vicki Kaminskas, Edvardas Farrell, Ann Timmer, William Pope, Sarah Harapanhalli, Ravi Saber, Haleh Morse, David Bullock, Julie Men, Angela Noory, Carol Ramchandani, Roshni Kenna, Leslie Booth, Brian Gobburu, Joga Jiang, Xiaoping Sridhara, Rajeshwari Justice, Robert Pazdur, Richard TI Sprycel for chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant to or intolerant of imatinib mesylate SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; KINASE DOMAIN MUTATIONS; CHRONIC-PHASE; INTERFERON-ALPHA; CYTOGENETIC RESPONSE; CONVENTIONAL CHEMOTHERAPY; CLINICAL RESISTANCE; ST1571 THERAPY; ABL MUTATIONS; BLAST CRISIS AB Purpose: On June 28, 2006, the U.S. Food and Drug Administration approved dasatinib (Sprycel; Bristol-Myers Squibb), a new small-molecule inhibitor of multiple tyrosine kinases, for the treatment of adults with chronic phase, accelerated phase, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy including imatinib. This summary reviews the database supporting this approval. Experimental Design: Four single-arm multicenter studies supported the efficacy and safety of dasatinib. The primary efficacy end point in chronic phase CIVIL was major cytogenetic response. The primary end point in accelerated phase, myeloid phase, and lymphoid blast phase CML, and Ph+ ALL was major hematologic response. Results: The four studies combined enrolled 445 patients. In patients with chronic phase CIVIL, the major cytogenetic response rate was 45% with a complete cytogenetic response rate of 33%. Major hematologic response rates in patients with accelerated phase CIVIL, myeloid CIVIL, lymphoid blast CIVIL, and Ph+ ALL were 59%, 32%, 31%, and 42%, respectively. Median response durations in chronic phase, accelerated phase, and myeloid phase CIVIL had not been reached. The median durations of major hematologic response were 3.7 months in lymphoid blast CIVIL and 4.8 months in Ph+ ALL. Common toxicities with dasatinib included myelosuppression, bleeding, and fluid retention. Conclusions: This report describes the Food and Drug Administration review supporting the approval of dasatinib for CIVIL and Ph+ ALL based on the rates and durability of cytogenetic and hematologic responses. C1 [Brave, Michael; Goodman, Vicki; Kaminskas, Edvardas; Farrell, Ann; Saber, Haleh; Morse, David; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Off New Drugs, Silver Spring, MD 20993 USA. [Pope, Sarah; Harapanhalli, Ravi] US FDA, Off New Drugs Qual Assement, Off Pharmaceut Sci, Silver Spring, MD USA. [Bullock, Julie; Men, Angela; Noory, Carol; Ramchandani, Roshni; Kenna, Leslie; Booth, Brian; Gobburu, Joga] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. [Jiang, Xiaoping; Sridhara, Rajeshwari] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Brave, M (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, 1093 New Hampshire Ave,Bldg 22,Room 2137, Silver Spring, MD 20993 USA. EM michael.brave@fda.hhs.gov NR 30 TC 131 Z9 134 U1 0 U2 5 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 JAN 15 PY 2008 VL 14 IS 2 BP 352 EP 359 DI 10.1158/1078-0432.CCR-07-4175 PG 8 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200005 PM 18223208 ER PT J AU Zhang, L Gao, LF Li, Y Lin, GM Shao, YT Ji, K Yu, H Kalvakolanu, DV Kopecko, DJ Zhao, XJ Xu, DQ Hu, J AF Zhang, Ling Gao, Lifang Li, Yang Lin, Guimiao Shao, Yueting Ji, Kun Yu, Hao Kalvakolanu, Dhananjaya V. Kopecko, Dennis J. Zhao, Xuejian Xu, De-Qi Hu, Jiadi TI Effects of plasmid-based stat3-specific short hairpin RNA and GRIM-19 on PC-3M tumor cell growth SO CLINICAL CANCER RESEARCH LA English DT Article ID SMALL INTERFERING RNAS; SIGNALING INDUCES APOPTOSIS; PROSTATE-CANCER CELLS; IN-VIVO; GENE-TRANSFER; CONSTITUTIVE ACTIVATION; MAMMALIAN-CELLS; STAT3 ACTIVITY; EXPRESSION; DEATH AB Purpose: Persistent activation of signal transducers and activators of transcription 3 (Stat3) and its overexpression contribute to the progression and metastasis of several different tumor types. For this reason, Stat3 is a reasonable target for RNA interference-mediated growth inhibition. Blockade of Stat3 using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth in mice. However, RNA interference does not fully ablate target gene expression in vivo, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Stat3-specific sh RNA, we applied a combination treatment involving gene associated with retinoid-IFN - induced mortality 19 (GRIM-19), another inhibitor of STAT3, along with shRNA. Experimental Design: The coding sequences for GRIM-19, a cellular STAT3-specific inhibitor, and Stat3-specific shRNAs were used to create a dual expression plasmid vector and used for prostate cancer therapy in vitro and in mouse xenograft models in vivo. Results: The coexpressed Stat3-specific shRNA and GRIM-19 synergistically and more effectively suppressed prostate tumor growth and metastases when compared with treatment with either single agent alone. Conclusion: The simultaneous use of two specific, but mechanistically different, inhibitors of STAT3 activity exerts enhanced antitumor effects. C1 [Zhang, Ling; Gao, Lifang; Li, Yang; Lin, Guimiao; Shao, Yueting; Ji, Kun; Yu, Hao; Zhao, Xuejian] Jilin Univ, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Changchun 130021, Peoples R China. [Zhang, Ling; Gao, Lifang; Li, Yang; Lin, Guimiao; Shao, Yueting; Ji, Kun; Yu, Hao; Zhao, Xuejian] Jilin Univ, Sch Basic Med, Dept Pathophysiol, Changchun 130021, Peoples R China. [Kalvakolanu, Dhananjaya V.; Hu, Jiadi] Univ Maryland, Greenebaum Canc Ctr, Dept Microbiol & Immunol, Program Mol Biol, Baltimore, MD 21201 USA. [Kopecko, Dennis J.; Xu, De-Qi] US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD USA. RP Zhao, XJ (reprint author), Jilin Univ, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Xinminn St, Changchun 130021, Peoples R China. EM pro-2@jlu.edu.cn FU NCI NIH HHS [CA105005, CA78282] NR 43 TC 59 Z9 66 U1 0 U2 6 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 JAN 15 PY 2008 VL 14 IS 2 BP 559 EP 568 DI 10.1158/1078-0432.CCR-07-1176 PG 10 WC Oncology SC Oncology GA 256JQ UT WOS:000252725200031 PM 18223232 ER PT J AU Yauk, C Polyzos, A Rowan-Carroll, A Somers, CM Godschalk, RW Van Schooten, FJ Berndt, ML Pogribny, IF Koturbash, I Williams, A Douglas, GR Kovalchuk, O AF Yauk, Carole Polyzos, Aris Rowan-Carroll, Andrea Somers, Christopher M. Godschalk, Roger W. Van Schooten, Frederik J. Berndt, M. Lynn Pogribny, Igor F. Koturbash, Igor Williams, Andrew Douglas, George R. Kovalchuk, Olga TI Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA adducts; DNA strand breaks; tandem repeat mutation ID EPIGENETIC TRANSGENERATIONAL ACTIONS; RADIATION-INDUCED MUTATION; TANDEM REPEAT INSTABILITY; MOUSE MINISATELLITE LOCUS; PREIMPLANTATION DEVELOPMENT; ENDOCRINE DISRUPTORS; GENOMIC INSTABILITY; FOLATE-DEFICIENCY; PATERNAL EXPOSURE; SOMATIC MUTATION AB Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation. C1 [Yauk, Carole; Polyzos, Aris; Rowan-Carroll, Andrea; Berndt, M. Lynn; Douglas, George R.] HECSB, Environm & Occupat Toxicol Div, Ottawa, ON K1A 0K9, Canada. [Somers, Christopher M.] McMaster Univ, Dept Biol, Hamilton, ON L8S 4K1, Canada. [Godschalk, Roger W.; Van Schooten, Frederik J.] Maastricht Univ, Dept Hlth Risk Anal & Toxicol, NUTRIM, Nutr & Toxicol Res Inst Maastricht, NL-6200 MD Maastricht, Netherlands. [Pogribny, Igor F.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Koturbash, Igor; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Williams, Andrew] Healthy Environm & Consumer Safety Branch, Biostat & Epidemiol Div, Ottawa, ON K1A 0K9, Canada. RP Yauk, C (reprint author), HECSB, Environm & Occupat Toxicol Div, Ottawa, ON K1A 0K9, Canada. EM carole_yauk@hc-sc.gc.ca OI Yauk, Carole/0000-0003-4919-876X NR 72 TC 136 Z9 144 U1 5 U2 36 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 JAN 15 PY 2008 VL 105 IS 2 BP 605 EP 610 DI 10.1073/pnas.0705896105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 253XO UT WOS:000252551100039 PM 18195365 ER PT J AU Divi, RL Doerge, DR Twaddle, NC Shockley, ME Claire, MCS Harbaugh, JW Harbaugh, SW Poirier, MC AF Divi, Rao L. Doerge, Daniel R. Twaddle, Nathan C. Shockley, Marie E. Claire, Marisa C. St. Harbaugh, Jefftey W. Harbaugh, Steven W. Poirier, Miriam C. TI Metabolism and pharmacokinetics of the combination Zidovudine plus Lamivudine in the adult Erythrocebus patas monkey determined by liquid chromatography-tandem mass spectrometric analysis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Combivir; AZT; AZT-glucuronide; AMT; 3TC; tandem mass spectrometry; serum ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; ANTIRETROVIRAL NUCLEOSIDE; MITOCHONDRIAL COMPROMISE; DRUG-INTERACTIONS; INFECTED PATIENTS; PREGNANT BABOON; RHESUS-MONKEYS; THERAPY; INFANTS AB Because of their similarity to humans, non-human primates constitute useful preclinical models in which to examine potential human drug toxicities. Antiretroviral nucleoside reverse transcriptase inhibitor (NRTI) toxicity is currently under investigation in Erythrocebus patas monkeys, and whereas NRTI pharmacokinetics have been studied in other monkey species, pharmacokinetics for Zidovudine plus Lamivudine (AZT/3TC) dosing have not been reported in the patas. Here we present 24 h serum pharmacokinetic parameters after a single oral exposure to the combination of AZT (40 mg) and 3TC (24 mg), doses equivalent to a human daily dose of Combivir (R). The patas (n = 3) AZT/3TC pharmacokinetic profiles were similar to those seen in other primate species. Average maximum serum concentrations (C-max) for AZT and 3TC were 2.35 and 2.65 mu g/ml, respectively, and were observed at 0.83 h (T-max). C-max was 13.34 mu g/ml for the AZT-glucuronide (AZT-G) and was 0.023 mu g/ml for the potentially toxic minor metabolite 3'-amino-3'-deoxythymidine (AMT), both occurring at about 1 h after dosing. Similar elimination half-times, 0.70 and 0.68 h(-1), were found for AZT and AZT-G, respectively, while 3TC was eliminated about half as fast (0.33 h(-1)) resulting in AUC((0-infinity)) values of 6.97 mu g/ml h for 3TC, 2.99 mu g/ml h for AZT, 20.5 mu g/ml h for AZT-G and 0.002 for AMT 6.97 mu g/ml h. This study shows similar metabolism and pharmacokinetics for oral administration of AZT/3TC in the adult patas monkey, other primate species and humans. The data validate the use of the patas monkey for studies of NRTI toxicity. Published by Elsevier Inc. C1 [Divi, Rao L.; Shockley, Marie E.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBR,CCR, NIH, Bethesda, MD 20892 USA. [Doerge, Daniel R.; Twaddle, Nathan C.] Natl Ctr Toxicol Res, Div Biochem Toxicol, FDA, Jefferson, AR 72079 USA. [Claire, Marisa C. St.; Harbaugh, Jefftey W.; Harbaugh, Steven W.] BioQual Inc, Rockville, MD 20850 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCBR,CCR, NIH, Bldg 37,Rm 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU Intramural NIH HHS NR 35 TC 5 Z9 5 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 2008 VL 226 IS 2 BP 206 EP 211 DI 10.1016/j.taap.2007.09.007 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 255IY UT WOS:000252652900011 PM 17949768 ER PT J AU Adkins, S Webb, SE Achor, D Kousik, CS Roberts, PD Baker, CA AF Adkins, Scott Webb, Susan E. Achor, Diann Kousik, Chandrasekar S. Roberts, Pamela D. Baker, Carlye A. TI Squash vein yellowing virus, a novel ipomovirus, isolated from squash and watermelon in Florida SO JOURNAL OF INSECT SCIENCE LA English DT Meeting Abstract C1 [Adkins, Scott] USDA ARS, Ft Pierce, FL USA. [Webb, Susan E.] Univ Florida, Gainesville, FL USA. [Achor, Diann] Univ Florida, Lake Alfred, FL USA. [Kousik, Chandrasekar S.] USDA ARS, Charleston, SC USA. [Roberts, Pamela D.] Univ Florida, Immokalee, FL USA. [Baker, Carlye A.] FDACS DPI, Gainesville, FL USA. EM SAdkins@ushrl.ars.usda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV ARIZONA PI TUCSON PA LIBRARY C327, TUCSON, AZ 85721 USA SN 1536-2442 J9 J INSECT SCI JI J Insect Sci. PD JAN 10 PY 2008 VL 8 BP 3 EP 3 PG 1 WC Entomology SC Entomology GA 261CO UT WOS:000253056900004 ER PT J AU Sheehan, KM Gulmann, C Eichler, GS Weinstein, JN Barrett, HL Kay, EW Conroy, RM Liotta, LA Petricoin, EF AF Sheehan, K. M. Gulmann, C. Eichler, G. S. Weinstein, J. N. Barrett, H. L. Kay, E. W. Conroy, R. M. Liotta, L. A. Petricoin, E. F., III TI Signal pathway pro. ling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition SO ONCOGENE LA English DT Article DE proteomics; protein microarray; colon cancer; stroma; microdissection ID PHASE PROTEIN MICROARRAYS; LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; TUMOR MICROENVIRONMENT; TISSUE INHIBITORS; CANCER-CELLS; PROGRESSION; METASTASIS; FIBROBLASTS; INVASION AB Molecular crosstalk, including reciprocal stimulation, is theorized to take place between epithelial cancer cells and surrounding non-neoplastic stromal cells. This is the rationale for stromal therapy, which could eliminate support of a cancer by its genetically stable stroma. Epithelial-stromal crosstalk is so far poorly documented in vivo, and cell cultures and animal experiments may not provide accurate models. The current study details stromal-epithelial signalling pathways in 35 human colon cancers, and compares them with matched normal tissues using quantitative proteomic microarrays. Lysates prepared from separately microdissected epithelium and stroma were analysed using antibodies against 61 cell signalling proteins, most of which recognize activated phospho-isoforms. Analyses using unsupervised and supervised statistical methods suggest that cell signalling pathway profiles in stroma and epithelium appear more similar to each other in tumours than in normal colon. This supports the concept that coordinated crosstalk occurs between epithelium and stroma in cancer and suggests epithelial-mesenchymal transition. Furthermore, the data herein suggest that it is driven by cell proliferation pathways and that, specifically, several key molecules within the mitogen-activated protein kinase pathway may play an important role. Given recent findings of epithelial-mesenchymal transition in therapy-resistant tumour epithelium, these findings could have therapeutic implications for colon cancer. C1 [Sheehan, K. M.; Gulmann, C.; Barrett, H. L.] Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. [Sheehan, K. M.; Gulmann, C.] NIH, Natl Canc Inst, Canc Res Ctr, Pathol Lab,NCI FDA Clin Proteom Program, Bethesda, MD USA. [Sheehan, K. M.; Gulmann, C.; Barrett, H. L.; Kay, E. W.] Royal Coll Surgeons Ireland, Dept Pathol, Dublin 9, Ireland. [Eichler, G. S.; Weinstein, J. N.] NIH, Natl Canc Inst, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD USA. [Conroy, R. M.] Royal Coll Surgeons Ireland, Dept Epidemiol, Dublin, Ireland. [Liotta, L. A.; Petricoin, E. F., III] George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA. [Petricoin, E. F., III] US FDA, NCI, Clin Proteom Program, Bethesda, MD USA. RP Gulmann, C (reprint author), Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. EM christian_gulmann@hotmail.com RI Conroy, Ronan/C-6416-2008 OI Conroy, Ronan/0000-0001-5983-8682 NR 42 TC 41 Z9 43 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 10 PY 2008 VL 27 IS 3 BP 323 EP 331 DI 10.1038/sj.onc.1210647 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 249UR UT WOS:000252256000008 PM 17621268 ER PT J AU Gupta, A Ciavarella, AB Sayeed, VA Khan, MA Faustino, PJ AF Gupta, Abhay Ciavarella, Anthony B. Sayeed, Vilayat A. Khan, Mansoor A. Faustino, Patrick J. TI Development and application of a validated HPLC method for the analysis of dissolution samples of gabapentin drug products SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE gabapentin; HPLC; impurity; lactam; drug products; dissolution ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; HUMAN PLASMA; MASS-SPECTROMETRY; CAPILLARY-ELECTROPHORESIS; PRECOLUMN DERIVATIZATION; FLUORESCENCE DETECTION; HUMAN SERUM; BIOEQUIVALENCE; PHARMACOKINETICS AB A simple isocratic reversed-phase HPLC method was developed and validated for the analysis of dissolution samples of gabapentin tablets and capsules. Separation of gabapentin from its major degradation impurity, 3,3-pentamethylene-4-butyrolactam was achieved on a Phenomenex Luna Cyano column using a methanol-acetonitrile-20 mM KH2PO4 (pH 2.2) (5:5:90, v/v/v) mobile phase. The compounds were eluted isocratically at a flow rate of 1.25 mL/min. Both compounds were analyzed with UV detection at 210 nm. The method was validated according to USP Category I requirements for gabapentin. The validation characteristics included accuracy, precision, linearity, range, specificity and limit of quantitation. Robustness testing was also conducted to evaluate the effect of minor changes to the chromatographic system and to establish appropriate system suitability parameters. Validation acceptance criteria were met in all cases. This method was used successfully for the quality assessment of five gabapentin drug products. Published by Elsevier B.V. C1 [Gupta, Abhay; Ciavarella, Anthony B.; Khan, Mansoor A.; Faustino, Patrick J.] US FDA, Off Pharmaceut Sci, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Faustino, PJ (reprint author), US FDA, Off Pharmaceut Sci, Div Prod Qual Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 21 TC 23 Z9 24 U1 0 U2 12 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 JAN 7 PY 2008 VL 46 IS 1 BP 181 EP 186 DI 10.1016/j.jpba.2007.08.023 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 254DK UT WOS:000252566400025 PM 17935923 ER PT J AU Peden, K Sheng, L Omeir, R Yacobucci, M Klutch, M Laassri, M Chumakov, K Pal, A Murata, H Lewis, AM AF Peden, Keith Sheng, Li Omeir, Romelda Yacobucci, Maureen Klutch, Michael Laassri, Majid Chumakov, Konstantin Pal, Achintya Murata, Haruhiko Lewis, Andrew M., Jr. TI Recovery of strains of the polyomavirus SV40 from rhesus monkey kidney cells dating from the 1950s to the early 1960s SO VIROLOGY LA English DT Article DE polyomavirus; strain; virus isolation; sequencing; monkey kidney cells ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; SIMIAN-VIRUS 40; HUMAN-BRAIN-TUMORS; LARGE T-ANTIGEN; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HUMAN PLEURAL MESOTHELIOMA; VIRAL REGULATORY REGION; NON-HODGKINS-LYMPHOMA; JC VIRUS; DNA-SEQUENCES AB From stocks of adenovirus and poliovirus prepared in primary rhesus macaque kidney cells and dating from 1956 to 196 1, the time when SV40 contaminated some poliovirus vaccine lots, we have recovered ten isolates of SV40. Of these ten isolates, based on the C-terminal region of T antigen, five novel strains of SV40 have been identified. Additionally, three pairs of isolates were found to be the same strain: one pair was strain 777, one pair was strain 776 archetype, and the third pair represented a novel strain. All strains had identical protein sequences for VP2 and VP3. There were two variants of agnoprotein and the small I antigen and three variants of VP 1. These results, and those of others, suggest that a limited number of SV40 strains might exist in rhesus macaques in the United States, and thus determining the origin of the SV40 sequences detected in human tumors might be difficult. Published by Elsevier Inc. C1 [Peden, Keith; Sheng, Li; Omeir, Romelda; Yacobucci, Maureen; Murata, Haruhiko] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Klutch, Michael; Pal, Achintya; Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Laassri, Majid; Chumakov, Konstantin] US FDA, Lab Methods Dev, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Peden, K (reprint author), US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM keith.peden@fda.hhs.gov NR 94 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 2008 VL 370 IS 1 BP 63 EP 76 DI 10.1016/j.virol.2007.06.045 PG 14 WC Virology SC Virology GA 239XW UT WOS:000251552600007 PM 17900651 ER PT B AU Kainz, W Fidler, F Bobgan, J Schaefers, G Luechinger, R Szeverenyi, N Wedan, S AF Kainz, Wolfgang Fidler, Florian Bobgan, Jean Schaefers, Gregor Luechinger, Roger Szeverenyi, Nikolaus Wedan, Steven GP IEEE TI Variation of whole body averaged phantom specific absorption rate (SAR) in seven different 1.5 TMR systems SO 2008 ASIA-PACIFIC SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY AND 19TH INTERNATIONAL ZURICH SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY, VOLS 1 AND 2 LA English DT Proceedings Paper CT Asia-Pacific Symposium on Electromagnetic Compatibility/19th International Zurich Symposium on Electromagnetic Compatibility CY MAY 19-23, 2008 CL Singapore, SINGAPORE AB This paper evaluates the whole body averaged specific absorption rate (WB-SAR) for a saline-filled standardized phantom in seven different commercial 1.5 T MR systems. Using calorimetry we measured the actual delivered WB-SAR to the phantom. The variability between different MR systems of the actual WB-SAR delivered to the phantom strongly depends on the landmark positions; it ranges for a system estimated WB-SAR of 2 W/kg from 0.6 W/kg at landmark L1 and L2 to 1.2 W/kg for landmark L3. The WB-SAR overestimation ranges from 1.7 to 8.0 depending on the landmark, MR system, and temperature sensor used. The system estimated WB-SAR overestimates the phantom WB-SAR for most cases which can lead to a proportional underestimation of the reported implant heating. Testing in various MR systems using calorimetry to assess the WB-SAR is necessary because of large implant and gel heating variations in different MR systems. C1 [Kainz, Wolfgang] US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Fidler, Florian] MRB, Wurzburg, Germany. [Bobgan, Jean] Boston Sci Corp, Leads Technol Dev, CRM Div, St Paul, MN USA. [Schaefers, Gregor] MR Co GmbH, Testing Serv MR Safety & Compatibil, Gelsenkirchen, Germany. [Luechinger, Roger] Univ Zurich, ETH Zurich, Inst Biomed Engn, Zurich, Switzerland. [Szeverenyi, Nikolaus] SUNY Upstate Med Univ, Dept Radiol, Syracuse, NY USA. [Wedan, Steven] Imricor Med Syst, Burnsville, MN USA. RP Kainz, W (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM wolfgang.kainz@fda.hhs.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-981-08-0628-6 PY 2008 BP 220 EP + DI 10.1109/APEMC.2008.4559851 PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BID20 UT WOS:000258515300056 ER PT S AU Ilev, IK Kim, DH Gandjbakhche, A AF Ilev, Ilko K. Kim, Do-Hyun Gandjbakhche, Amir GP IEEE TI Nanobiophotonics: Breaking the Diffraction Barrier in the Subwavelength Nanoscale SO 2008 DIGEST OF THE LEOS SUMMER TOPICAL MEETINGS SE Digest of the LEOS Summer Topical Meetings LA English DT Proceedings Paper CT IEEE/LEOS Summer Topical Meetings CY JUL 21-23, 2008 CL Acapulco, MEXICO SP IEEE DE nanobiophotonics; fiber-optic confocal microscopy; diffraction barrier; subwavelength nanoscale ID MICROSCOPY AB We present a novel approach for ultrahigh depth-resolution (<= 2 nm) confocal microscopy beyond the diffraction barrier in the subwavelength nanometric range (below 100 nm), which is based on a simple fiber-optic confocal design. C1 [Ilev, Ilko K.; Kim, Do-Hyun; Gandjbakhche, Amir] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. RP Ilev, IK (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ilko.ilev@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1099-4742 BN 978-1-4244-1925-8 J9 DIGEST LEOS SUM TOP PY 2008 BP 87 EP + DI 10.1109/LEOSST.2008.4590502 PG 2 WC Nanoscience & Nanotechnology; Optics; Telecommunications SC Science & Technology - Other Topics; Optics; Telecommunications GA BIJ48 UT WOS:000260073000044 ER PT S AU Gavrielides, MA Masmoudi, H Petrick, N Myers, KJ Hewitt, SM AF Gavrielides, Marios A. Masmoudi, Hela Petrick, Nicholas Myers, Kyle J. Hewitt, Stephen M. GP IEEE TI Automated evaluation of HER-2/neu immunohistochemical expression in breast cancer using digital microscopy SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1-4 SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 5th IEEE International Symposium on Biomedical Imaging CY MAY 14-17, 2008 CL Paris, FRANCE SP IEEE DE microscopy imaging; immunohistochemistry; biomarker imaging; HER2/neu; computer aided analysis ID AMPLIFICATION; CARCINOMA; ONCOGENE AB HER-2/neu (HER2) has been shown to be a valuable biomarker for breast cancer. However, inter-observer variability has been reported in the evaluation of HER2 with immunohistochemistry. It has been suggested that automated computer-based evaluation can provide a consistent and objective measure of HER2 expression. In this manuscript, we present an automated method for the quantitative assessment of HER2 using digital microscopy. The method employs imaging algorithms on whole slide images of tissue specimens for the extraction of two features describing HER2 membrane staining, namely membrane staining completeness and membrane staining intensity. A classifier was trained to merge the extracted features into an overall slide assessment score. Preliminary results showed good agreement with the provided truth. The developed automated method has the potential to be used as a computer aid for the immunohistochemical evaluation of HER2 expression with the objective of increasing observer reproducibility. C1 [Gavrielides, Marios A.; Masmoudi, Hela; Petrick, Nicholas; Myers, Kyle J.] NIBIB, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, USDA, Washington, DC 20052 USA. [Masmoudi, Hela] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA. [Hewitt, Stephen M.] Natl Inst Hlth, Tissue Array Res Program, Ctr Canc Res, Natl Canc Inst, Bethesda, MD 20892 USA. RP Gavrielides, MA (reprint author), NIBIB, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, USDA, Washington, DC 20052 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 8 TC 7 Z9 7 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-2002-5 J9 I S BIOMED IMAGING PY 2008 BP 808 EP + DI 10.1109/ISBI.2008.4541119 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Nanoscience & Nanotechnology; Imaging Science & Photographic Technology SC Engineering; Science & Technology - Other Topics; Imaging Science & Photographic Technology GA BIB70 UT WOS:000258259800203 ER PT B AU Qiang, R Jackson, D Wilton, D Chen, J Kainz, W AF Qiang, Rui Jackson, David Wilton, Don Chen, Ji Kainz, Wolfgang GP IEEE TI Time-Domain Modeling Techniques for Periodic Structures SO 2008 IEEE INTERNATIONAL SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY, VOLS 1-3 LA English DT Proceedings Paper CT IEEE International Symposium on Electromagnetic Compatibility CY AUG 18-22, 2008 CL Detroit, MI SP IEEE DE Arrays; finite source; artificial materials; FDTD; periodic structures; meta-materials ID DIELECTRIC-CONSTANT; 2-COMPONENT; MIXTURES AB Novel time-domain modeling techniques for periodic structures are described in this paper. These methods can be used to investigate electromagnetic propagations and scatterings from infinite artificial periodic arrays from arbitrary electromagnetic source illumination and extract the equivalent electric properties of composite structures.. Using this method, only a single periodic cell is required in the modeling using finite-difference time-domain method. Several periodic structures are analyzed by this proposed method to testify its computational efficiency in terms of computer memory and computing time. C1 [Qiang, Rui; Jackson, David; Wilton, Don; Chen, Ji] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. [Kainz, Wolfgang] FDA, Ctr Dev & Radiol Hlth, Rockville, MD 20852 USA. RP Qiang, R (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. EM ji.chen@mail.uh.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-1699-8 PY 2008 BP 850 EP + PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BIW65 UT WOS:000263416300160 ER PT S AU Wear, KA Harris, GR AF Wear, Keith A. Harris, Gerald R. GP IEEE TI Frequency dependence of backscatter from thin, oblique, finite-length cylinders measured with a focused transducer - with applications in cancellous bone SO 2008 IEEE ULTRASONICS SYMPOSIUM, VOLS 1-4 AND APPENDIX SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE Ultrasonics Symposium CY NOV 02-05, 2008 CL Beijing, PEOPLES R CHINA SP IEEE DE backscatter; cylinder; bone ID TRABECULAR BONE; ULTRASONIC BACKSCATTER; THICKNESS AB A model is presented for the echo from a thin, oblique, finite-length cylinder. The echo is calculated from the line integral of the transducer directivity pattern along the cylinder axis. The model was validated with broadband pulse-echo measurements from 1) a perpendicular (to the ultrasound beam) nylon wire as a function of lateral displacement from the beam center, 2) a tilted nylon wire as a function of the angle of inclination relative to the ultrasound beam, and 3) a quasi-parallel-nylon-wire phantom, which mimicked the scattering properties of cancellous bone. The transducer directivity pattern (as a function of position and frequency) was measured with a membrane hydrophone. The model predicts an approximately cubic frequency dependence of backscatter coefficient from the phantom, as has been observed experimentally in cancellous bone. The model also predicts the relationship between cylinder length and the exponent of a power law fit to backscatter coefficient vs. frequency, which is 4 for very short (compared to a wavelength) cylinders and asymptotically approaches 3 for very long cylinders. C1 [Wear, Keith A.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM keith.wear@fda.hhs.gov; gerald.harris@fda.hhs.gov NR 8 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 978-1-4244-2428-3 J9 ULTRASON PY 2008 BP 134 EP 136 DI 10.1109/ULTSYM.2008.0032 PG 3 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BKP07 UT WOS:000268845800032 ER PT S AU Liang, H Badano, A AF Liang, Honye Badano, Aldo GP SID TI Late-news paper: Observer strategies for assessment of temporal response - Effect of technology SO 2008 SID INTERNATIONAL SYMPOSIUM, DIGEST OF TECHNICAL PAPERS, VOL XXXIX, BOOKS I-III SE SID INTERNATIONAL SYMPOSIUM DIGEST OF TECHNICAL PAPERS LA English DT Proceedings Paper CT International Symposium of the Society-for-Information-Display (SID 2008) CY MAY 18-23, 2008 CL Los Angeles, CA SP Soc Informat Display AB We compare the detection performance of human observers in LCDs and CRTs using artificial complex backgrounds. Our results suggest that the degradation in performance at high browsing speeds observed in LCDs is not seen or much more Subtle in CRTs, even at 50 frames per second. C1 [Liang, Honye; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Liang, H (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 0 Z9 0 U1 0 U2 0 PU SOC INFORMATION DISPLAY PI PLAYA DEL REY PA 8055 W MANCHESTER AVE SUITE 615, PLAYA DEL REY, CA 90293 USA SN 0097-966X J9 SID INT SYMP DIG TEC PY 2008 VL 39 BP 1142 EP 1145 PN 1-3 PG 4 WC Optics; Imaging Science & Photographic Technology SC Optics; Imaging Science & Photographic Technology GA BID34 UT WOS:000258530100291 ER PT S AU Badano, A Liang, HY Albani, L AF Badano, Aldo Liang, Hongye Albani, Luigi GP SID TI Late-news poster: Noise and resolution in a dual-layer LCD SO 2008 SID INTERNATIONAL SYMPOSIUM, DIGEST OF TECHNICAL PAPERS, VOL XXXIX, BOOKS I-III SE SID INTERNATIONAL SYMPOSIUM DIGEST OF TECHNICAL PAPERS LA English DT Proceedings Paper CT International Symposium of the Society-for-Information-Display (SID 2008) CY MAY 18-23, 2008 CL Los Angeles, CA SP Soc Informat Display ID DISPLAYS AB The noise and resolution characteristics of a dual-layer LCD capable of high luminance range are presented with emphasis on the measurement and analysis methods considering the parallax effect. The results are compared to an identical panel with a single-layer structure. C1 [Badano, Aldo; Liang, Hongye] FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Badano, A (reprint author), FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 4 TC 0 Z9 0 U1 0 U2 0 PU SOC INFORMATION DISPLAY PI PLAYA DEL REY PA 8055 W MANCHESTER AVE SUITE 615, PLAYA DEL REY, CA 90293 USA SN 0097-966X J9 SID INT SYMP DIG TEC PY 2008 VL 39 BP 1537 EP 1540 PN 1-3 PG 4 WC Optics; Imaging Science & Photographic Technology SC Optics; Imaging Science & Photographic Technology GA BID34 UT WOS:000258530100391 ER PT J AU Nelson, RM AF Nelson, Robert M. TI Institutional review boards lack the moral legitimacy to reinterpret subpart D SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 US FDA, Off Pediat Therapeut, Off Commiss, Rockville, MD 20057 USA. RP Nelson, RM (reprint author), US FDA, Off Pediat Therapeut, Off Commiss, Room 13B-45,5600 Fishers Lane, Rockville, MD 20057 USA. EM Robert.Nelson@fda.hhs.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2008 VL 8 IS 4 BP 37 EP 39 DI 10.1080/15265160802147264 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 318SU UT WOS:000257113900015 PM 18576252 ER PT J AU Hampshire, VA Davis, JA AF Hampshire, Victoria A. Davis, Judith A. BE Fish, RE Brown, MJ Danneman, PJ Karas, AZ TI Postprocedural Care of Commonly Utilized Research Animal Subjects SO ANESTHESIA AND ANALGESIA IN LABORATORY ANIMALS, 2ND EDITION SE American College of Laboratory Animal Medicine Series LA English DT Article; Book Chapter ID ENVIRONMENTAL ENRICHMENT; LABORATORY-ANIMALS; HOUSING CONDITIONS; SKELETAL-MUSCLE; RODENT CARE; BEAGLE DOGS; MICE; BUPRENORPHINE; HYPOTHERMIA; NUTRITION C1 [Hampshire, Victoria A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20855 USA. [Davis, Judith A.] NIAAA, Off Lab Anim Sci, DIR, NIH, Bethesda, MD 20892 USA. RP Hampshire, VA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20855 USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-373898-1 J9 AM COLL LAB PY 2008 BP 219 EP 235 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA BED52 UT WOS:000316210000010 ER PT J AU Viswanathan, CT AF Viswanathan, Chidambaram T. TI OECD principles of GLP: what is working and what needs work SO ANNALI DELL ISTITUTO SUPERIORE DI SANITA LA English DT Article DE good laboratory practice; regulatory authorities; mutual acceptance of data; multisite studies AB The Organisation for Economic Co-operation and Development (OECD) principles of good laboratory practice (GLP) are intended to assure data quality and integrity. The pre-clinical safety data generated in an OECD member country in accordance with the principles of GLP are indeed accepted in other member countries for purposes of assessment. Regulatory authorities (RA) routinely further assess such studies to determine their applicability to specific regulatory decisions. In the experience of the author, the procedures laid out by the OECD GLP principles often support and complement the collection of robust data and aptly address complexities such as multisite study conduct. Perspectives on what works and what might benefit by further optimization are discussed. C1 [Viswanathan, Chidambaram T.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Viswanathan, CT (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,1, Silver Spring, MD 20993 USA. EM ct.viswanathan@fda.hhs.gov NR 3 TC 1 Z9 1 U1 2 U2 4 PU IST POLIGRAFICO ZECCA STATO PI ROMA PA PIAZZA VERDI 10, ROMA, 00198, ITALY SN 0021-2571 J9 ANN I SUPER SANITA JI Ann. Ist. Super. Sanita PY 2008 VL 44 IS 4 BP 341 EP 343 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V15SM UT WOS:000207821700006 PM 19351992 ER PT S AU Woodcock, J Woosley, R AF Woodcock, Janet Woosley, Raymond TI The FDA critical path initiative and its influence on new drug development SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE biomarkers; biomarker qualification; clinical trials ID CLINICAL-PHARMACOLOGY; INDUSTRY; MEDICINE AB Societal expectations about drug safety and efficacy are rising while productivity in the pharmaceutical industry is falling. In 2004, the US Food and Drug Administration introduced the Critical Path Initiative with the intent of modernizing drug development by incorporating recent scientific advances, such as genomics and advanced imaging technologies, into the process. An important part of the initiative is the use of public-private partnerships and consortia to accomplish the needed research. This article explicates the reasoning behind the Critical Path Initiative and discusses examples of successful consortia. C1 [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Woosley, Raymond] Crit Path Inst, Tucson, AZ 85721 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM janet.Woodcock@fda.hhs.gov; RWoosley@c-path.org OI Woosley, Raymond L./0000-0002-2588-328X NR 19 TC 178 Z9 187 U1 2 U2 24 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0559-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2008 VL 59 BP 1 EP 12 DI 10.1146/annurev.med.59.090506.155819 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 265YJ UT WOS:000253397600001 PM 18186700 ER PT J AU Lynne, AM Rhodes-Clark, BS Bliven, K Zhao, SH Foley, SL AF Lynne, Aaron M. Rhodes-Clark, Bobbie S. Bliven, Kimberly Zhao, Shaohua Foley, Steven L. TI Antimicrobial resistance genes associated with Salmonella enterica serovar Newport isolates from food animals SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; INTEGRONS; HUMANS; IDENTIFICATION; SWINE AB Salmonella enterica serotype Newport is an important cause of salmonellosis, with strains increasingly being resistant to multiple antimicrobial agents. The increase is associated with the acquisition of multiple resistance genes. This study characterizes the genetic basis of resistance of serotype Newport isolates collected from veterinary sources by PCR and DNA sequencing analysis. C1 [Lynne, Aaron M.; Bliven, Kimberly; Foley, Steven L.] Marshfield Med Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. [Rhodes-Clark, Bobbie S.; Foley, Steven L.] Univ Cent Arkansas, Dept Biol, Conway, AR 72035 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Foley, SL (reprint author), Marshfield Med Res Fdn, Natl Farm Med Ctr, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM foley.steven@mcrf.mfldclin.edu NR 19 TC 17 Z9 21 U1 3 U2 8 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 JAN PY 2008 VL 52 IS 1 BP 353 EP 356 DI 10.1128/AAC.00842-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 248ED UT WOS:000252133700044 PM 17967918 ER PT J AU Manohar, M Orrison, B Peden, K Lewis, AM AF Manohar, Manu Orrison, Brian Peden, Keith Lewis, Andrew M., Jr. TI Assessing the tumorigenic phenotype of VERO cells in adult and newborn nude mice SO BIOLOGICALS LA English DT Article DE VERO cells; tumorigenicity; nude mice ID LINE; CULTURE; TRANSFORMATION; VIRUS; MOUSE AB VERO cell lines are important substrates for viral vaccine manufacture. The mechanism by which these cells became neoplastically transformed is unknown. During tissue-culture passage, VERO cells can develop the capacity to form tumors. Although at the passage levels (around p140) currently used for vaccine manufacture, VERO cells are non-tumorigenic, questions have been raised about safety issues that might be associated with this capacity to acquire a tumorigenic phenotype. To begin to address these issues, the tumorigenicity of VERO cell lines, derived at different passage levels under different growth conditions, were evaluated in 365-day assays in adult and newborn nude mice. High passage (p>200) VERO cell lines established by random passaging in tissue culture produced tumors in adult (10 out of 27) mice and newborn (21 out of 30) mice, respectively. In contrast, a high passage (p>250) cell line established by passage at sub-confluence produced tumors only in newborn mice (16 out of 30). Progressively growing tumors began forming at 36 days in newborns and at 69 days in adults. Higher tumor incidences and shorter tumor latencies suggest that newborn nude mice may be more sensitive than adults in detecting the expression of a tumorigenic phenotype by some VERO cell lines. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 [Manohar, Manu; Orrison, Brian; Peden, Keith; Lewis, Andrew M., Jr.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Bethesda, MD 20892 USA. RP Lewis, AM (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Room 1B10,Bldg 29A,29 Lincoln Dr, Bethesda, MD 20892 USA. EM andrew.lewis@fda.hhs.gov NR 25 TC 23 Z9 25 U1 2 U2 4 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 JAN PY 2008 VL 36 IS 1 BP 65 EP 72 DI 10.1016/j.biologicals.2007.06.002 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 260CH UT WOS:000252987900009 PM 17933552 ER PT J AU Hendriksen, C Arciniega, JL Bruckner, L Chevalier, M Coppens, E Descamps, J Duchene, M Dusek, DM Halder, M Kreeftenberg, H Maes, A Redhead, K Ravetkar, SD Spieser, JM Swam, H AF Hendriksen, Coenraad Arciniega, Juan L. Bruckner, Lukas Chevalier, Michel Coppens, Emmanuelle Descamps, Johan Duchene, Michel Dusek, David Michael Halder, Marlies Kreeftenberg, Hans Maes, Alexandrine Redhead, Keith Ravetkar, Satish D. Spieser, Jean-Marc Swam, Hanny TI The consistency approach for the quality control of vaccines SO BIOLOGICALS LA English DT Article DE Vaccines; quality control; consistency; release testing; in vitro AB Current lot release testing of conventional vaccines emphasizes quality control of the final product and is characterized by its extensive use of laboratory animals. This report, which is based on the outcome of an ECVAM (European Centre for Validation of Alternative Methods, Institute for Health and Consumer Protection, European Commission Joint Research Centre, Ispra, Italy) workshop, discusses the concept of consistency testing as an alternative approach for lot release testing. The consistency approach for the routine release of vaccines is based upon the principle that the quality of vaccines is a consequence of a quality system and of consistent production of lots with similar characteristics to those lots that have been shown to be safe and effective in humans or the target species. The report indicates why and under which circumstances this approach can be applied, the role of the different stakeholders, and the need for international harmonization. It also gives recommendations for its implementation. (C) 2007 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 [Hendriksen, Coenraad; Kreeftenberg, Hans] Netherlands Vaccine Inst, NL-3720 AL Bilthoven, Netherlands. [Hendriksen, Coenraad] Univ Utrecht, Netherlands Ctr Alternat Anim Use, NL-3508 TB Utrecht, Netherlands. [Arciniega, Juan L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Bruckner, Lukas] Inst Virol & Immunoprophylaxis, CH-3147 Mittelhausern, Switzerland. [Chevalier, Michel; Coppens, Emmanuelle] Sanofi Pasteur, F-69280 Marcy Letoile, France. [Descamps, Johan; Duchene, Michel] GlaxoSmithKline Biol, B-1330 Rixensart, Belgium. [Dusek, David Michael] USDA, Ctr Vet Biol, Anim & Plant Hlth Inspect Serv, Ames, IA 50010 USA. [Halder, Marlies] European Commiss, Joint Res Ctr, European Ctr Validat Alternat Methods, Inst Hlth & Consumer Protect, I-21020 Ispra, Italy. [Maes, Alexandrine] Sci Inst Publ Hlth, B-1050 Brussels, Belgium. [Redhead, Keith] Intervet UK Ltd, Milton Keynes MK7 7AJ, Bucks, England. [Ravetkar, Satish D.] Serum Inst India Ltd, Pune 411028, Maharashtra, India. [Spieser, Jean-Marc] Council Europe, European Dept Quality Med, F-67081 Strasbourg, France. [Swam, Hanny] Intervet Int BV, NL-5830 AA Boxmeer, Netherlands. RP Halder, M (reprint author), Netherlands Vaccine Inst, A Van Leeuwenhoeklaan 11, NL-3720 AL Bilthoven, Netherlands. EM marlies.halder@jrc.it NR 13 TC 26 Z9 28 U1 1 U2 7 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 JAN PY 2008 VL 36 IS 1 BP 73 EP 77 DI 10.1016/j.biologicals.2007.05.002 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 260CH UT WOS:000252987900010 PM 17892948 ER PT J AU Sosnik, J Spiridonov, N Yoon, SY Fissore, R Johnson, G Visconti, P AF Sosnik, Julian Spiridonov, Nikolay Yoon, Sook-Young Fissore, Rafael Johnson, Gibbes Visconti, Pablo TI TSSK6, a member of the testis-specific serine kinase (TSSK) family, is present in mature sperm and required for sperm-egg fusion in the mouse SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 41st Annual Meeting of the Society-for-the-Study-of-Reproduction CY MAY 27-30, 2008 CL Kona, HI SP Soc Study Reprod C1 Univ Massachusetts, Amherst, MA 01003 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 73 BP 69 EP 70 PG 2 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300072 ER PT J AU Khan, A AF Khan, Abu TI Reproductive effects of heavy metals on two generations of rats SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT World Congress on Reproductive Biology CY MAY 24-25, 2008 CL Kailua Kona, HI C1 [Khan, Abu] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2008 SI SI MA 110 BP 310 EP 310 PG 1 WC Reproductive Biology SC Reproductive Biology GA 347DH UT WOS:000259120300857 ER PT J AU Hong, HX Su, ZQ Ge, WG Shi, LM Perkins, R Fang, H Xu, JS Chen, JJ Han, T Kaput, J Fuscoe, JC Tong, WD AF Hong, Huixiao Su, Zhenqiang Ge, Weigong Shi, Leming Perkins, Roger Fang, Hong Xu, Joshua Chen, James J. Han, Tao Kaput, Jim Fuscoe, James C. Tong, Weida TI Assessing batch effects of genotype calling algorithm BRLMM for the Affymetrix GeneChip Human Mapping 500 K array set using 270 HapMap samples SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 23-24, 2008 CL Oklahoma City, OK SP MidSouth Computat Biol & Bioinformat Soc ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY VARIANT; COLORECTAL-CANCER; BREAST-CANCER; CROHN-DISEASE; HAPLOTYPE MAP; SNP ARRAYS; RISK LOCI; SCAN; MICROARRAYS AB Background: Genome-wide association studies (GWAS) aim to identify genetic variants (usually single nucleotide polymorphisms [SNPs]) across the entire human genome that are associated with phenotypic traits such as disease status and drug response. Highly accurate and reproducible genotype calling are paramount since errors introduced by calling algorithms can lead to inflation of false associations between genotype and phenotype. Most genotype calling algorithms currently used for GWAS are based on multiple arrays. Because hundreds of gigabytes (GB) of raw data are generated from a GWAS, the samples are typically partitioned into batches containing subsets of the entire dataset for genotype calling. High call rates and accuracies have been achieved. However, the effects of batch size (i.e., number of chips analyzed together) and of batch composition (i.e., the choice of chips in a batch) on call rate and accuracy as well as the propagation of the effects into significantly associated SNPs identified have not been investigated. In this paper, we analyzed both the batch size and batch composition for effects on the genotype calling algorithm BRLMM using raw data of 270 HapMap samples analyzed with the Affymetrix Human Mapping 500 K array set. Results: Using data from 270 HapMap samples interrogated with the Affymetrix Human Mapping 500 K array set, three different batch sizes and three different batch compositions were used for genotyping using the BRLMM algorithm. Comparative analysis of the calling results and the corresponding lists of significant SNPs identified through association analysis revealed that both batch size and composition affected genotype calling results and significantly associated SNPs. Batchsize and batch composition effects were more severe on samples and SNPs with lower call rates than ones with higher call rates, and on heterozygous genotype calls compared to homozygous genotype calls. Conclusion: Batch size and composition affect the genotype calling results in GWAS using BRLMM. The larger the differences in batch sizes, the larger the effect. The more homogenous the samples in the batches, the more consistent the genotype calls. The inconsistency propagates to the lists of significantly associated SNPs identified in downstream association analysis. Thus, uniform and large batch sizes should be used to make genotype calls for GWAS. In addition, samples of high homogeneity should be placed into the same batch. C1 [Hong, Huixiao; Su, Zhenqiang; Ge, Weigong; Shi, Leming; Han, Tao; Fuscoe, James C.; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Perkins, Roger; Fang, Hong; Xu, Joshua] US FDA, Natl Ctr Toxicol Res, ICF Int Co, Z Tech Corp, Jefferson, AR 72079 USA. [Chen, James J.; Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Huixiao.Hong@fda.hhs.gov; Zhenqiang.Su@fda.hhs.gov; Weigong.Ge@fda.hhs.gov; Leming.Shi@fda.hhs.gov; Roger.Perkins@fda.hhs.gov; Hong.Fang@fda.hhs.gov; Joshua.Xu@fda.hhs.gov; JamesJ.Chen@fda.hhs.gov; Tao.Han@fda.hhs.gov; James.Kaput@fda.hhs.gov; James.Fuscoe@fda.hhs.gov; Weida.Tong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 40 TC 29 Z9 34 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S17 DI 10.1186/1471-2105-9-S9-S17 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600017 PM 18793462 ER PT J AU Lee, TW Desai, VG Velasco, C Reis, RJS Delongchamp, RR AF Lee, Taewon Desai, Varsha G. Velasco, Cruz Reis, Robert J. Shmookler Delongchamp, Robert R. TI Testing for treatment effects on gene ontology SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 23-24, 2008 CL Oklahoma City, OK SP MidSouth Computat Biol & Bioinformat Soc ID EXPRESSION DATA; MITOCHONDRIA; MICROARRAY; KNOWLEDGE AB In studies that use DNA arrays to assess changes in gene expression, it is preferable to measure the significance of treatment effects on a group of genes from a pathway or functional category such as gene ontology terms (GO terms, http://www.geneontology.org) because this facilitates the interpretation of effects and may markedly increase significance. A modified meta-analysis method to combine p-values was developed to measure the significance of an overall treatment effect on such functionally-defined groups of genes, taking into account the correlation structure among genes. For hypothesis testing that allows gene expression to change in both directions, p-values are calculated under the null distribution generated by a Monte Carlo method. As a test of this procedure, we attempted to distinguish altered pathways in microarray studies performed with Mitochips, oligonucleotide microarrays specific to mitochondrial DNA-encoded transcripts. We found that our analytic method improves the specificity of selection for altered pathways, due to incorporation of the inter-gene correlation structure in each pathway. It is thus a practical method to measure treatment effects on GO groups. In many actual applications, microarray experiments measure treatment effects under complicated design structures and with small sample sizes. For such applications to real data of limited statistical power, and also in computer simulations, we demonstrate that our method gives reasonable test results. C1 [Lee, Taewon] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Biometry Branch, Jefferson, AR 72079 USA. [Desai, Varsha G.] Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, Jefferson, AR 72079 USA. [Velasco, Cruz] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Dept Epidemiol, Coll Publ Hlth, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] Univ Arkansas Med Sci, Dept Pharmacol Toxicol, Little Rock, AR 72205 USA. [Reis, Robert J. Shmookler] VA Med Ctr, Little Rock, AR 72205 USA. RP Lee, TW (reprint author), Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Biometry Branch, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM taewon.lee@gmail.com; varsha.desai@fda.hhs.gov; cvelas@lsuhsc.edu; rjsr@uams.edu; RDelongchamp@uams.edu RI Shmookler Reis, Robert/C-4112-2009 NR 17 TC 6 Z9 6 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S20 DI 10.1186/1471-2105-9-S9-S20 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600020 PM 18793466 ER PT J AU Shi, LM Jones, WD Jensen, RV Harris, SC Perkins, RG Goodsaid, FM Guo, L Croner, LJ Boysen, C Fang, H Qian, F Amur, S Bao, WJ Barbacioru, CC Bertholet, V Cao, XM Chu, TM Collins, PJ Fan, XH Frueh, FW Fuscoe, JC Guo, X Han, J Herman, D Hong, HX Kawasaki, ES Li, QZ Luo, YL Ma, YQ Mei, N Peterson, RL Puri, RK Shippy, R Su, ZQ Sun, YA Sun, HM Thorn, B Turpaz, Y Wang, C Wang, SJ Warrington, JA Willey, JC Wu, J Xie, Q Zhang, L Zhang, L Zhong, S Wolfinger, RD Tong, WD AF Shi, Leming Jones, Wendell D. Jensen, Roderick V. Harris, Stephen C. Perkins, Roger G. Goodsaid, Federico M. Guo, Lei Croner, Lisa J. Boysen, Cecilie Fang, Hong Qian, Feng Amur, Shashi Bao, Wenjun Barbacioru, Catalin C. Bertholet, Vincent Cao, Xiaoxi Megan Chu, Tzu-Ming Collins, Patrick J. Fan, Xiaohui Frueh, Felix W. Fuscoe, James C. Guo, Xu Han, Jing Herman, Damir Hong, Huixiao Kawasaki, Ernest S. Li, Quan-Zhen Luo, Yuling Ma, Yunqing Mei, Nan Peterson, Ron L. Puri, Raj K. Shippy, Richard Su, Zhenqiang Sun, Yongming Andrew Sun, Hongmei Thorn, Brett Turpaz, Yaron Wang, Charles Wang, Sue Jane Warrington, Janet A. Willey, James C. Wu, Jie Xie, Qian Zhang, Liang Zhang, Lu Zhong, Sheng Wolfinger, Russell D. Tong, Weida TI The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 23-24, 2008 CL Oklahoma City, OK SP MidSouth Computat Biol & Bioinformat Soc ID QUALITY-CONTROL; OLIGONUCLEOTIDE MICROARRAYS; PLATFORM CONSISTENCY; ALTERED EXPRESSION; DNA MICROARRAY; CANCER; ARRAYS; DISCOVERY; NOISE; HYBRIDIZATION AB Background: Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists. Results: Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan - the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent P-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on P-value ranking is an expected mathematical consequence of the high variability of the t-values; the more stringent the P-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations. Conclusion: We recommend the use of FC-ranking plus a non-stringent P cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the P-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and P-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the P criterion balances sensitivity and specificity. C1 [Shi, Leming; Harris, Stephen C.; Guo, Lei; Fan, Xiaohui; Fuscoe, James C.; Mei, Nan; Su, Zhenqiang; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, Wendell D.] Express Anal Inc, Durham, NC 27713 USA. [Jensen, Roderick V.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA. [Perkins, Roger G.; Fang, Hong; Qian, Feng; Cao, Xiaoxi Megan; Hong, Huixiao; Sun, Hongmei; Thorn, Brett; Wu, Jie; Xie, Qian] US FDA, Z Tech Corp, NCTR, Jefferson, AR 72079 USA. [Goodsaid, Federico M.; Amur, Shashi; Frueh, Felix W.; Wang, Sue Jane] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Croner, Lisa J.] Biogen Idec Inc, San Diego, CA 92122 USA. [Boysen, Cecilie] ViaLogy Inc, Altadena, CA 91001 USA. [Bao, Wenjun; Chu, Tzu-Ming; Wolfinger, Russell D.] SAS Inst Inc, Cary, NC 27513 USA. [Barbacioru, Catalin C.; Sun, Yongming Andrew] Applied Biosyst, Foster City, CA 94404 USA. [Bertholet, Vincent] Eppendorf Array Technol, B-5000 Namur, Belgium. [Collins, Patrick J.] Agilent Technol, Santa Clara, CA 95051 USA. [Fan, Xiaohui; Turpaz, Yaron] Zhejiang Univ, Pharmaceut Informat Inst, Hangzhou 310027, Peoples R China. [Guo, Xu; Warrington, Janet A.] Affymetrix Inc, Santa Clara, CA 95051 USA. [Han, Jing; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Herman, Damir] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Kawasaki, Ernest S.] Natl Canc Inst, Adv Technol Ctr, Gaithersburg, MD 20877 USA. [Li, Quan-Zhen] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Luo, Yuling; Ma, Yunqing] Panomics Inc, Fremont, CA 94555 USA. [Peterson, Ron L.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Shippy, Richard] GE Healthcare, Tempe, AZ 85284 USA. [Wang, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Willey, James C.] Ohio Med Univ, Toledo, OH 43614 USA. [Zhang, Liang] CapitalBio Corp, Beijing 102206, Peoples R China. [Zhang, Lu] Solexa Inc, Hayward, CA 94545 USA. [Zhong, Sheng] Univ Illinois, Dept Bioengn, Urbana, IL 61801 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov; wjones@expressionanalysis.com; rvjensen@vt.edu; stephen.harris@fda.hhs.gov; roger.perkins@fda.hhs.gov; federico.goodsaid@fda.hhs.gov; lei.guo@fda.hhs.gov; lisa.croner@biogenidec.com; cecilie.boysen@vialogy.com; hong.fang@fda.hhs.gov; feng.qian@fda.hhs.gov; shashi.amur@fda.hhs.gov; wenjun.bao@sas.com; catalin.barbacioru@appliedbiosystems.com; bertholet.v@eppendorf.be; xiaoxicao@gmail.com; tzu-ming.chu@sas.com; jim_collins@affymetrix.com; xiao-hui.fan@fda.hhs.gov; felix@genpad.com; james.fuscoe@fda.hhs.gov; xu_guo@affymetrix.com; jing.han@fda.hhs.gov; damir.herman@gmail.com; huixiao.hong@fda.hhs.gov; kawasaki4244@yahoo.com; quan.li@utsouthwestern.edu; yluo@panomics.com; yma@panomics.com; nan.mei@fda.hhs.gov; ron.peterson@novartis.com; raj.puri@fda.hhs.gov; richard_shippy@affymetrix.com; zhenqiang.su@fda.hhs.gov; sunya@appliedbiosystems.com; hong_mei_sun@yahoo.com; brett.thorn@fda.hhs.gov; turpazmaqc@hotmail.com; charles.wang@cshs.org; suejane.wang@fda.hhs.gov; janet.warrington@jestech.net; jwilley@meduohio.edu; jiewu3@gmail.com; qianxie133@gmail.com; lzhang@capitalbio.com; lzhang@illumina.com; szhong@uiuc.edu; russ.wolfinger@sas.com; weida.tong@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011; Su, Zhenqiang/H-3914-2012; OI mei, nan/0000-0002-3501-9014; Croner, Lisa/0000-0002-3921-1484 NR 56 TC 125 Z9 127 U1 0 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S10 DI 10.1186/1471-2105-9-S9-S10 PG 19 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600010 PM 18793455 ER PT J AU Su, ZQ Hong, HX Fang, H Shi, LM Perkins, R Tong, WD AF Su, Zhenqiang Hong, Huixiao Fang, Hong Shi, Leming Perkins, Roger Tong, Weida TI Very Important Pool (VIP) genes - an application for microarray- based molecular signatures SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 5th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 23-24, 2008 CL Oklahoma City, OK SP MidSouth Computat Biol & Bioinformat Soc ID STATISTICAL PATTERN-RECOGNITION; SUPPORT VECTOR MACHINES; B-CELL LYMPHOMA; EXPRESSION DATA; DNA MICROARRAY; OLIGONUCLEOTIDE ARRAYS; PREDICT SURVIVAL; QUALITY-CONTROL; BREAST-CANCER; CLASSIFICATION AB Background: Advances in DNA microarray technology portend that molecular signatures from which microarray will eventually be used in clinical environments and personalized medicine. Derivation of biomarkers is a large step beyond hypothesis generation and imposes considerably more stringency for accuracy in identifying informative gene subsets to differentiate phenotypes. The inherent nature of microarray data, with fewer samples and replicates compared to the large number of genes, requires identifying informative genes prior to classifier construction. However, improving the ability to identify differentiating genes remains a challenge in bioinformatics. Results: A new hybrid gene selection approach was investigated and tested with nine publicly available microarray datasets. The new method identifies a Very Important Pool ( VIP) of genes from the broad patterns of gene expression data. The method uses a bagging sampling principle, where the re-sampled arrays are used to identify the most informative genes. Frequency of selection is used in a repetitive process to identify the VIP genes. The putative informative genes are selected using two methods, t-statistic and discriminatory analysis. In the t-statistic, the informative genes are identified based on p-values. In the discriminatory analysis, disjoint Principal Component Analyses (PCAs) are conducted for each class of samples, and genes with high discrimination power (DP) are identified. The VIP gene selection approach was compared with the p-value ranking approach. The genes identified by the VIP method but not by the p-value ranking approach are also related to the disease investigated. More importantly, these genes are part of the pathways derived from the common genes shared by both the VIP and p-ranking methods. Moreover, the binary classifiers built from these genes are statistically equivalent to those built from the top 50 p-value ranked genes in distinguishing different types of samples. Conclusion: The VIP gene selection approach could identify additional subsets of informative genes that would not always be selected by the p-value ranking method. These genes are likely to be additional true positives since they are a part of pathways identified by the p-value ranking method and expected to be related to the relevant biology. Therefore, these additional genes derived from the VIP method potentially provide valuable biological insights. C1 [Su, Zhenqiang; Hong, Huixiao; Shi, Leming; Tong, Weida] US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fang, Hong; Perkins, Roger] US FDA, Z Tech, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Ctr Toxicoinformat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM zhenqiang.su@fda.hhs.gov; huixiao.hong@fda.hhs.gov; hong.fang@fda.hhs.gov; leming.shi@fda.hhs.gov; roger.perkins@fda.hhs.gov; weida.tong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 58 TC 2 Z9 3 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S9 DI 10.1186/1471-2105-9-S9-S9 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600009 PM 18793473 ER PT J AU Wren, JD Wilkins, D Fuscoe, JC Bridges, S Winters-Hilt, S Gusev, Y AF Wren, Jonathan D. Wilkins, Dawn Fuscoe, James C. Bridges, Susan Winters-Hilt, Stephen Gusev, Yuriy TI Proceedings of the 2008 midsouth computational biology and bioinformatics society (MCBIOS) conference SO BMC BIOINFORMATICS LA English DT Editorial Material ID GENE-EXPRESSION DATA; OPEN-ACCESS DATABASE; WEB-BASED TOOL; REGULATORY NETWORKS; TRANSCRIPTION FACTORS; MICROARRAY DATA; SEARCH; IDENTIFICATION; CONSTRUCTION; PREDICTION C1 [Wren, Jonathan D.] Oklahoma Med Res Fdn, Arthritis & Immunol Res Program, Oklahoma City, OK 73104 USA. [Wilkins, Dawn] Univ Mississippi, Dept Comp & Informat Sci, University, MS 38677 USA. [Fuscoe, James C.] US FDA, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. [Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Bridges, Susan] Mississippi State Univ, Dept Comp Sci & Engn, Mississippi State, MS 39762 USA. [Winters-Hilt, Stephen] Univ New Orleans, Dept Comp Sci, New Orleans, LA 70118 USA. [Winters-Hilt, Stephen] Res Inst Children, New Orleans, LA 70118 USA. [Gusev, Yuriy] Univ Oklahoma, Hlth Sci Ctr, Dept Surg, Oklahoma City, OK 73104 USA. RP Wren, JD (reprint author), Oklahoma Med Res Fdn, Arthritis & Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Jonathan.Wren@OMRF.org; dwilkins@cs.olemiss.edu; james.fuscoe@fda.hhs.gov; bridges@cse.msstate.edu; winters@cs.uno.edu; Yuriy-Gusev@ouhsc.edu RI Wren, Jonathan/E-5611-2011 OI Wren, Jonathan/0000-0003-2776-3545 FU NIAMS NIH HHS [P30 AR053483] NR 82 TC 2 Z9 2 U1 4 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2008 VL 9 SU 9 AR S1 DI 10.1186/1471-2105-9-S9-S1 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 345VE UT WOS:000259024600001 PM 18793454 ER PT J AU Hu, L Kopecko, DJ AF Hu, Lan Kopecko, Dennis J. BE Nachamkin, I Szymanski, CM Blaser, MJ TI Cell Biology of Human Host Cell Entry by Campylobacter jejuni SO CAMPYLOBACTER, 3RD EDITION LA English DT Article; Book Chapter ID CYTOLETHAL DISTENDING TOXIN; INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; INTRACELLULAR SALMONELLA-ENTERICA; CULTURED-MAMMALIAN-CELLS; SIGNAL-TRANSDUCTION; INT-407 CELLS; ESCHERICHIA-COLI; EUKARYOTIC CELLS; CACO-2 CELLS C1 [Hu, Lan; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hu, L (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 139 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-437-3 PY 2008 BP 297 EP 313 PG 17 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA BPH83 UT WOS:000278888200018 ER PT J AU Aarestrup, FM McDermott, PF Wegener, HC AF Aarestrup, Frank M. McDermott, Patrick F. Wegener, Henrik C. BE Nachamkin, I Szymanski, CM Blaser, MJ TI Transmission of Antibiotic Resistance from Food Animals to Humans SO CAMPYLOBACTER, 3RD EDITION LA English DT Article; Book Chapter ID CMEABC EFFLUX PUMP; CAMPYLOBACTER-COLI STRAINS; BETA-LACTAM AGENTS; ANTIMICROBIAL DRUG-RESISTANCE; QUALITY-CONTROL RANGES; AGAR DILUTION METHODS; TARGET GENE MUTATION; JEJUNI SUBSP JEJUNI; FLUOROQUINOLONE RESISTANCE; QUINOLONE RESISTANCE C1 [Aarestrup, Frank M.; Wegener, Henrik C.] Natl Food Inst, DK-1790 Copenhagen V, Denmark. [McDermott, Patrick F.] US FDA, Natl Antimicrobial Resistance Monitoring Syst, Ctr Vet Med, Laurel, MD 20708 USA. RP Aarestrup, FM (reprint author), Natl Food Inst, Bulowsvej 27, DK-1790 Copenhagen V, Denmark. NR 123 TC 16 Z9 16 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-437-3 PY 2008 BP 645 EP 665 PG 21 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA BPH83 UT WOS:000278888200037 ER PT J AU Macias, E de Marva, PLM Senderowicz, A Cullen, J Rodriguez-Puebla, ML AF Macias, Everardo de Marva, Paula L. Miliani Senderowicz, Adrian Cullen, John Rodriguez-Puebla, Marcelo L. TI Expression of CDK4 or CDK2 in mouse oral cavity is retained in adult pituitary with distinct effects on tumorigenesis SO CANCER RESEARCH LA English DT Article ID INTERMEDIATE FILAMENT EXPRESSION; TRANSGENIC MICE; EPIDERMAL HYPERPLASIA; TUMOR-DEVELOPMENT; CELL; P27(KIP1); SKIN; PROLIFERATION; P18(INK4C); INHIBITORS AB The keratin 5 (K5) promoter drives transgenic expression to the basal cell layer of stratified epithelia. Surprisingly, analysis of K5CDK4 and K5CDK2 transgenic mouse embryos showed CDK4 and CDK2 expression not only in the expected tissues, but also in the adenohypophysis. This organ is derived from an upwards growth of the primitive oropharnyx, a K5-expressing tissue. We show that transgenic expression of CDKs in the embryonic oral ectoderm is specifically retained in undifferentiated cells from the pars intermedia of the adenohypophysis. Interestingly, we found that K5CDK4 mice show a decreased number of pituitary stem cells, even though CDK4 is not expressed in the stem cells but in transit-amplifying (TA)-like cells. Interestingly, CDK4-expressing cells, but not CDK2-expressing cells, strongly synergize with lack of p27(Kip1) to generate pituitary carcinomas that appear with shortened latency and are drastically more aggressive than those arising in p27(-/-) mice. Thus, we show that deregulation of CDK expression in the primitive oral epithelium plays a unique function, providing a selective advantage that gives rise to transgene-positive TA-like pituitary cells. Furthermore, retention of CDK4 in these TA-like pituitary cells synergizes with loss of p27(Kip1) to induce pituitary adenocarcinomas. This model suggests that forced expression of CDK4 sensitizes cells and synergizes with a second change resulting in tumor development. C1 [Macias, Everardo; Cullen, John; Rodriguez-Puebla, Marcelo L.] N Carolina State Univ, Ctr Comparat Med & Translat Res, Raleigh, NC 27606 USA. [de Marva, Paula L. Miliani] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Senderowicz, Adrian] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rodriguez-Puebla, ML (reprint author), N Carolina State Univ, 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, R01 CA116328, CA116328] NR 37 TC 12 Z9 12 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2008 VL 68 IS 1 BP 162 EP 171 DI 10.1158/0008-5472.CAN-07-2461 PG 10 WC Oncology SC Oncology GA 247IP UT WOS:000252072100023 PM 18172308 ER PT S AU Graham, J AF Graham, Jove BE Madhavan, G Oakley, B Kun, L TI Public Sector Research, Development, and Regulation SO CAREER DEVELOPMENT IN BIOENGINEERING AND BIOTECHNOLOGY SE Series in Biomedical Engineering LA English DT Article; Book Chapter C1 [Graham, Jove] US FDA, US Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth,Orthoped Spinal Devices, Off Device Evaluat,Div Gen Neurol & Restorat Devi, Rockville, MD 20857 USA. [Graham, Jove] Geisinger Ctr Hlth Res, Danville, PA USA. RP Graham, J (reprint author), US FDA, US Dept Hlth & Human Serv, Ctr Devices & Radiol Hlth,Orthoped Spinal Devices, Off Device Evaluat,Div Gen Neurol & Restorat Devi, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1864-5763 BN 978-0-387-76494-8 J9 SER BIOMED ENG PY 2008 BP 100 EP 113 DI 10.1007/978-0-387-76495-5_9 D2 10.1007/978-0-387-76495-5 PG 14 WC Biotechnology & Applied Microbiology; Engineering, Biomedical SC Biotechnology & Applied Microbiology; Engineering GA BKF49 UT WOS:000267955700010 ER PT J AU Sussman, R Sharma, SK Kuzirian, A AF Sussman, Raquel Sharma, Shashi K. Kuzirian, Alan TI Catalytic activities of recA protein are dependent on the lattice length of the single-strand DNA ligand SO CELL CYCLE LA English DT Article DE structure/function; protein/DNA complex; allostery; SOS repair ID PHAGE-LAMBDA-REPRESSOR; NUCLEIC ACID INTERACTIONS; ESCHERICHIA-COLI; BINDING-PROTEIN; GENETIC-RECOMBINATION; OPERATOR INTERACTION; DIRECTED CLEAVAGE; DUPLEX DNA; COMPLEXES; FILAMENTS AB recA protein (RecA) performs diverse catalytic activities that require a complex with single-stranded DNA and an NTP. A subset of these functions shows optimal activity at a high DNA/protein ratio and requires NTP hydrolysis, whereas other catalytic activities are optimal in RecA-saturated complexes that require NTP, but do not hydrolyze it. To analyze the mechanism of catalytic discrimination, we investigated the properties of RecA bound to small oligonucleotides (oligos) of defined sizes. We show that RecA bound to (dT)(16) is optimal for co-protease activity and not active as ATPase whereas the complex with (dT)(24) is competent in ATP hydrolysis but impaired as a co-protease. Thermodynamic measurements of the equilibrium-binding properties of these complexes showed that (dT)(24) promoted a more salt sensitive complex than the one formed with (dT)(16), indicating more ionic interactions between RecA and DNA in the former. X-ray pictures show that the oligo complexes form helixes. We propose that RecA may change its conformation as a function of the number of phosphates available to the monomer in the interacting DNA lattice, thus promoting an allosteric change in catalytic activities. This model offers explanations for the observed inhibition of co-protease activity by excess ssDNA. C1 [Sussman, Raquel; Kuzirian, Alan] Marine Biol Lab, Woods Hole, MA 02543 USA. [Sharma, Shashi K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Sussman, R (reprint author), Marine Biol Lab, Woods Hole, Woods Hole, MA 02543 USA. EM rsussman@mbl.edu NR 42 TC 2 Z9 2 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2008 VL 7 IS 1 BP 89 EP 95 PG 7 WC Cell Biology SC Cell Biology GA 259YP UT WOS:000252977100015 PM 18196977 ER PT J AU Lane, JW Rehak, NN Hortin, GL Zaoutis, T Krause, PR Walsh, TJ AF Lane, Jason W. Rehak, Nadja N. Hortin, Glen L. Zaoutis, Theoklis Krause, Philip R. Walsh, Thomas J. TI Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy SO CLINICA CHIMICA ACTA LA English DT Article DE pseudohyperphosphatemia; liposomal amphotericin B (L-AMB); synchron LX20 ID SEVERE HYPERPHOSPHATEMIA; NEUTROPENIC PATIENTS; AMBISOME; PHARMACOKINETICS; PATIENT; FORMULATION; PHOSPHORUS; TOLERANCE; SAFETY AB Background: Acute increases in serum inorganic phosphorus (Pi) up to 4.75 mmol/l in the absence of hypocalcemia and tissue deposition of calcium phosphate were noted in 3 patients receiving liposomal amphotericin B (L-AMB). We investigated L-AMB as a possible cause of pseudohyperphosphatemia. Methods: Serum samples from the index patient were analyzed for Pi content by our laboratory's primary analyzer (Synchron LX20) and by an alternate analyzer (Vitros). Clear and lipemic scrum pools, and normal saline, were spiked with L-AMB and analyzed by the LX20 Pi method. Ultrafiltration studies were performed on patient and spiked sera. Results: Increased Pi values were obtained only from the LX20 analyzer. There was a direct linear relationship between the concentration of L-AMB in the spiked samples and the LX20 Pi results, indicating a 0.9 mmol/l Pi increase for every 100 mg/l increase in L-AMB. Ultrafiltration normalized the Pi results. Conclusion: Serum Pi results may be falsely increased in patients receiving L-AMB when measured by the LX20 analyzer. This novel cause of pseudohyperphosphatemia is due to interference of L-AMB with the method and is corrected by ultrafiltration of the specimen. Since the LX20 analyzer is widely used by the clinical laboratories clinicians and laboratory personnel should recognize this interference in order to avoid unnecessary diagnostic procedures and interventions. Published by Elsevier B.V. C1 Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Dept Lab Med, Clin Chem Serv, Bethesda, MD USA. Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, Philadelphia, PA 19104 USA. Food & Drug Adm, Bethesda, MD USA. Natl Canc Inst, Pediat Oncol Branch, Bethesda, MD USA. RP Rehak, NN (reprint author), Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv, Bethesda, MD 20892 USA. EM nrehak@cc.nih.gov OI Krause, Philip/0000-0002-1045-7536 FU Intramural NIH HHS [Z01 CL010010-32] NR 22 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2008 VL 387 IS 1-2 BP 145 EP 149 DI 10.1016/j.cca.2007.08.008 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 238VK UT WOS:000251475900025 PM 17936740 ER PT J AU Aragon-Ching, JB Ning, YM Latham, L Guadagnini, J Arlen, PM Gulley, JL Wright, J Parnes, H Figg, WD Dahut, WL AF Aragon-Ching, J. B. Ning, Y. M. Latham, L. Guadagnini, J. Arlen, P. M. Gulley, J. L. Wright, J. Parnes, H. Figg, W. D. Dahut, W. L. TI Osteonecrosis of the jaw (ONJ) in androgen-independent prostate cancer (AIPC) patients receiving ATTP (Bevacizumab, Docetaxel, Thalidomide, and Prednisone) SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 [Aragon-Ching, J. B.; Latham, L.; Dahut, W. L.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Ning, Y. M.] US FDA, Bethesda, MD 20014 USA. [Guadagnini, J.] Natl Inst Dent Craniofacial Res, Bethesda, MD USA. [Arlen, P. M.; Gulley, J. L.] NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. [Wright, J.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. [Parnes, H.] NCI, Canc Prevent Div, Bethesda, MD 20892 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 SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2008 VL 25 SU S BP 33 EP 33 PG 1 WC Oncology SC Oncology GA 338GK UT WOS:000258494200049 ER PT J AU Uhl, K AF Uhl, K. TI Advancing women's health in the 21st century: Applying the tools of clinical pharmacology SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. RP Uhl, K (reprint author), US FDA, Off Womens Hlth, Rockville, MD 20857 USA. EM kathleen.uhl@fda.hhs.gov NR 16 TC 8 Z9 9 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 JAN PY 2008 VL 83 IS 1 BP 3 EP 7 DI 10.1038/sj.clpt.6100463 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254KD UT WOS:000252584600001 PM 18165819 ER PT J AU Oliva, A Pinnow, E Levin, R Uhl, K AF Oliva, A. Pinnow, E. Levin, R. Uhl, K. TI Improving women's health through modernization of our bioinformatics infrastructure SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Our nationwide bioinformatics infrastructure used to detect important sex differences associated with medical product use is antiquated. The Food and Drug Administration (FDA) has embarked on an ambitious bioinformatics modernization effort that will improve our ability to assess the safety and effectiveness of new medical products. This, in turn, will improve our ability to detect important sex differences. C1 [Oliva, A.; Levin, R.] Off Crit Path Programs, Food & Drug Adm, Rockville, MD USA. [Pinnow, E.; Uhl, K.] Off Womens Hlth Food & Drug Adm, Rockville, MD USA. RP Oliva, A (reprint author), Off Crit Path Programs, Food & Drug Adm, Rockville, MD USA. EM armando.oliva@fda.hhs.gov NR 5 TC 4 Z9 4 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 JAN PY 2008 VL 83 IS 1 BP 192 EP 195 DI 10.1038/sj.clpt.6100437 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 254KD UT WOS:000252584600034 PM 17987048 ER PT J AU Duley, L Antman, K Arena, J Avezum, A Blumenthal, M Bosch, J Chrolavicius, S Li, T Ounpuu, S Perez, AC Sleight, P Svard, R Temple, R Tsouderous, Y Yunis, C Yusuf, S AF Duley, Lelia Antman, Karen Arena, Joseph Avezum, Alvaro Blumenthal, Mel Bosch, Jackie Chrolavicius, Sue Li, Timoa Ounpuu, Stephanie Perez, Analia Cristina Sleight, Peter Svard, Robbyno Temple, Robert Tsouderous, Yannis Yunis, Carla Yusuf, Salim TI Specific barriers to the conduct of randomized trials SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Sensible Guidelines Workshop CY JAN 25-26, 2007 CL Washington, DC ID PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; HARMFUL IMPACT; UNITED-KINGDOM; FUTURE; EUROPE; MRC AB Large randomized trials are required to provide reliable evidence of the typically moderate benefit of most interventions. To be affordable, such trials need to be simple; to be widely applicable, they need to be close to normal clinical practice. However, current regulations and guidelines have hugely increased trial complexity, effectively becoming barriers to their design and conduct. Key barriers include inadequate funding, overly complex regulations producing needlessly complex trial procedures, excessive monitoring, over restrictive interpretation of privacy laws without evidence of subject benefit, and inadequate understanding of methodology. Complex regulations result in multiple ethics approvals for a multi-center study, unnecessary complexity in the study protocol, delays in securing regulatory approval, and cumbersome regulatory procedures, even for drugs widely used in clinical practice. The type of detailed safety monitoring currently needed in trials of new drugs is being applied indiscriminately to all studies including a simpler and basic level of monitoring that constitutes good practice in most trials could be agreed on, with that level being exceeded only in specific instances. More evidence about the pros and cons of alternative approaches to data quality monitoring would help inform this process. Complex procedures in the form of multiple-page consent forms, overzealous monitoring of side effects and adverse events, source data verification, and over-restrictive approaches to protocol amendments, can impede, rather than facilitate, trial objectives. Finally, further education on the nuances and functions of randomisation would facilitate trial conduct, and reduce the need for burdensome complexity. A radical re-evaluation of existing trial guidelines is needed, based on a clear understanding of the important principles of randomized trials, with the objective of eliminating unnecessary documentation and reporting without sacrificing validity or safety. Researchers should encourage public debate about how best to strike the balance between regulation and cost. C1 [Bosch, Jackie; Chrolavicius, Sue; Yusuf, Salim] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Duley, Lelia] Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. [Antman, Karen] Boston Univ, Sch Med, Boston, MA 02215 USA. [Blumenthal, Mel] Bristol Myers Squibb Global Clin Res Princeton, Princeton, NJ USA. [Sleight, Peter] Univ Oxford, Oxford OX1 2JD, England. [Svard, Robbyno] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Temple, Robert] US FDA, Rockville, MD 20857 USA. RP Yusuf, S (reprint author), McMaster Univ, Hamilton, ON L8S 4L8, Canada. EM yusufs@ccc.mcmaster.ca RI Duley, Lelia/E-8107-2015; Avezum, Alvaro/K-6137-2016; OI Duley, Lelia/0000-0001-6721-5178; Avezum, Alvaro/0000-0002-3073-6890; Antman, Karen/0000-0002-1093-8356 NR 22 TC 69 Z9 70 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 1 BP 40 EP 48 DI 10.1177/1740774507087704 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 283PR UT WOS:000254649200006 PM 18283079 ER PT J AU Granger, CB Stockbridge, NL Vogel, VG Cummings, SR AF Granger, Christopher B. Stockbridge, Norman L. Vogel, Victor G. Cummings, Steven R. TI Do we need to adjudicate major clinical events? Response SO CLINICAL TRIALS LA English DT Letter C1 [Granger, Christopher B.] Duke Clin Res Inst, Durham, NC USA. [Stockbridge, Norman L.] US FDA, Rockville, MD 20857 USA. [Vogel, Victor G.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Vogel, Victor G.] Univ Pittsburgh, Sch Med, Dept Med, Sect Hematol & Oncol, Pittsburgh, PA USA. [Cummings, Steven R.] Univ Calif San Francisco, Coordinating Ctr, San Francisco, CA 94143 USA. RP Granger, CB (reprint author), Duke Clin Res Inst, Durham, NC USA. RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 NR 2 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2008 VL 5 IS 5 BP 558 EP 558 DI 10.1177/1740774508096477 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 367RN UT WOS:000260570100011 ER PT J AU Blodgett, RJ AF Blodgett, Robert J. TI Fitting a curve to a confidence interval SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE serial dilutions; split exponential; split normal; triangular distribution ID DENSITY AB Three curves are fit to a confidence interval and its estimate. These curves allow a data user to incorporate the variability of the estimation method into further calculations. C1 Food & Drug Adm, College Pk, MD 20740 USA. RP Blodgett, RJ (reprint author), Food & Drug Adm, 5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM robert.blodgett@fda.hhs.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0361-0926 EI 1532-415X J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2008 VL 37 IS 17 BP 2681 EP 2686 DI 10.1080/03610920802040431 PG 6 WC Statistics & Probability SC Mathematics GA 320XS UT WOS:000257269100002 ER PT B AU Triventi, M Mattei, E Delogu, A Censi, F Calcagnini, G Bartolini, P Aguel, F Stohlman, J Krauthamer, V AF Triventi, M. Mattei, E. Delogu, A. Censi, F. Calcagnini, G. Bartolini, P. Aguel, F. Stohlman, J. Krauthamer, V. GP IEEE TI In-Vitro Investigation of Very Long Defibrillation Shocks: Design and Testing of a Capacitor-Free Defibrillator SO COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2 LA English DT Proceedings Paper CT 35th Annual Conference on Computers in Cardiology CY SEP 14-17, 2008 CL Bologna, ITALY ID WAVE-FORM; TRANSTHORACIC DEFIBRILLATION; VENTRICULAR-FIBRILLATION; EFFICACY AB The aim of this paper is to describe a defibrillator that allows the delivery of arbitrary waveform shocks, with energy up to 10J and duration up to 100ms. In addition, data from shocks delivered to isolated rabbit's hearts are presented The solutions adopted in the design and realization of the defibrillator were: rechargeable battery power; linear AB class power amplifier output in bridge configuration; optical isolation of analog and digital lines to and from the PC and earth ground; measure of the actual voltage, current and energy delivered to the load. Laboratory testing showed that the defibrillator is capable to deliver shocks with a rising time less than 150 us, no tilting also for very long waveforms (100ms), peak current up to 10 A. The system was then used on rabbit hearts to define a protocol to investigate the effect of waveform duration on defibrillation threshold. We demonstrate the feasibility of an experimental defibrillator for the generation and delivery of true arbitrary waveforms. C1 [Triventi, M.; Mattei, E.; Delogu, A.; Censi, F.; Calcagnini, G.; Bartolini, P.] Italian Inst Hlth, Rome, Italy. [Aguel, F.; Stohlman, J.; Krauthamer, V.] FDA, Ctr Device & Radiolog Hlth, Silver Spring, MD USA. [Mattei, E.] Univ Roma La Sapienza, Rome, Italy. RP Triventi, M (reprint author), Italian Inst Hlth, Rome, Italy. RI MATTEI, EUGENIO/E-4623-2015 OI MATTEI, EUGENIO/0000-0002-6494-9456 NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3706-1 PY 2008 BP 493 EP + DI 10.1109/CIC.2008.4749086 PG 2 WC Computer Science, Information Systems; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BIZ28 UT WOS:000263940800125 ER PT B AU Handzel, R Garnett, C Li, M McNitt, S Polonski, S Xia, X Couderc, JP AF Handzel, R. Garnett, C. Li, M. McNitt, S. Polonski, S. Xia, X. Couderc, J. P. GP IEEE TI Comparison of Highly-Automatic versus FDA-Submitted QT Measurements for the Detection of Moxifloxacin Induced Prolongation of the QTc Interval SO COMPUTERS IN CARDIOLOGY 2008, VOLS 1 AND 2 LA English DT Proceedings Paper CT 35th Annual Conference on Computers in Cardiology CY SEP 14-17, 2008 CL Bologna, ITALY AB In this study, we investigated the ability of a QT algorithm to detect small drug-induced QT interval prolongation by adopting a "highly-automatized" approach. In a set of 8,911 digital ECGs, we analyzed the drug-concentration profile of computerized QTc to the measurements submitted to the Food and Drug Administration (FDA) by pharmaceutical companies. The RR and QT intervals were measured using lead II based on a QT algorithm included in the COMPAS software package developed at University of Rochester Medical Center, NY. When comparing the time-dependent effect of the drug on the QTc interval the automatic technique produced results similar to the measurements reported by contract research organizations to the Agency (FDA). C1 [Handzel, R.] Univ Rochester, CPU Box 274020, Rochester, NY 14627 USA. [Handzel, R.] Univ Rochester, Dept Biomed Engn, Rochester, NY 14627 USA. [Garnett, C.; Li, M.] CDER, US FDA, US Dept HHS, Silver Spring, MD USA. [McNitt, S.; Polonski, S.; Xia, X.; Couderc, J. P.] Univ Rochester Med Ctr, Dept Cardiol, Heart Res Follow up Program, Rochester, NY USA. RP Handzel, R (reprint author), Univ Rochester, CPU Box 274020, Rochester, NY 14627 USA. EM Robert.M.Handzel@gmail.com FU NIH-RO1 [#1160743209] FX We would to thank Dr. Norman Stockbridge for his support. This work has been partially funded from NIH-RO1 grant #1160743209. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3706-1 PY 2008 BP 693 EP + DI 10.1109/CIC.2008.4749136 PG 2 WC Computer Science, Information Systems; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA BIZ28 UT WOS:000263940800175 ER PT J AU Ortiz, PG Hansen, SH Shah, VP Menne, T Benfeldt, E AF Ortiz, Patricia Garcia Hansen, Steen Honore Shah, Vinod P. Menne, Torkil Benfeldt, Eva TI The effect of irritant dermatitis on cutaneous bioavailability of a metronidazole formulation, investigated by microdialysis and dermatopharmacokinetic method SO CONTACT DERMATITIS LA English DT Article DE irritant dermatitis; metronidazole; microdialysis; tape-strip sampling; topical penetration ID SODIUM LAURYL SULFATE; NONINVASIVE QUANTIFICATION; BARRIER PERTURBATION; SALICYLIC-ACID; SKIN; PENETRATION; BIOEQUIVALENCE; ABSORPTION AB Background: Determination of drug penetration in diseased skin represents a challenge. Objective: To compare dermal microdialysis and tape-strip sampling of drug penetration in normal skin and skin with irritant dermatitis. Methods: The two methodologies were employed simultaneously in 16 healthy volunteers. Samples were collected in a study of the penetration of a metronidazole cream formulation (Flagyl (R) 1%) applied to forearm skin in both areas with irritant dermatitis and normal skin. Barrier perturbation and the depth of microdialysis probes were quantified by non-invasive bioengineering methods. Results: Microdialysis showed a significant threefold increase in metronidazole penetration in skin with irritant dermatitis compared with unmodified skin. Conversely, the concentration of metronidazole in tape-strip samples was significantly decreased in irritant dermatitis. Conclusion: The selection of sampling methodology should be based on the skin layer of interest as well as the integrity of the skin barrier. Whenever the dermal tissue is the target for topical treatment, microdialysis sampling should be the method of choice. C1 [Ortiz, Patricia Garcia; Menne, Torkil; Benfeldt, Eva] Gentofte Univ Hosp, Dept Dermatol, DK-2900 Hellerup, Denmark. [Hansen, Steen Honore] Univ Copenhagen, Pharmaceut Fac, Dept Pharmaceut & Analyt Chem, DK-2100 Copenhagen, Denmark. [Shah, Vinod P.] US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Ortiz, PG (reprint author), Univ Copenhagen, Dept Dermatol & Venereol, Gentofte Hosp, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. EM patriciagarcia@dadlnet.dk RI Honore Hansen, Steen/A-5179-2011 NR 12 TC 18 Z9 19 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-1873 J9 CONTACT DERMATITIS JI Contact Dermatitis PY 2008 VL 59 IS 1 BP 23 EP 30 PG 8 WC Allergy; Dermatology SC Allergy; Dermatology GA 315ZJ UT WOS:000256918400003 PM 18537995 ER PT J AU Weber, SU Schewe, JC Lehmann, LE Muller, S Book, M Klaschik, S Hoeft, A Stuber, F AF Weber, Stefan U. Schewe, Jens-Christian Lehmann, Lutz E. Mueller, Stefan Book, Malte Klaschik, Sven Hoeft, Andreas Stueber, Frank TI Induction of Bim and Bid gene expression during accelerated apoptosis in severe sepsis SO CRITICAL CARE LA English DT Article ID CIRCULATING MONONUCLEAR-CELLS; CD4(+) T-CELLS; LYMPHOCYTE APOPTOSIS; IMPROVES SURVIVAL; NEUTROPHIL APOPTOSIS; BH3-ONLY PROTEINS; IN-VIVO; POLYMICROBIAL SEPSIS; DEATH RECEPTOR; MURINE SEPSIS AB Introduction In transgenic animal models of sepsis, members of the Bcl-2 family of proteins regulate lymphocyte apoptosis and survival of sepsis. This study investigates the gene regulation of pro-apoptotic and anti-apoptotic members of the Bcl-2 family of proteins in patients with early stage severe sepsis. Methods In this prospective case- control study, patients were recruited from three intensive care units (ICUs) in a university hospital. Sixteen patients were enrolled when they fulfilled the criteria of severe sepsis. Ten critically ill but non-septic patients and 11 healthy volunteers served as controls. Blood samples were immediately obtained at inclusion. To confirm the presence of accelerated apoptosis in the patient groups, caspase-3 activation and phosphatidylserine externalisation in CD4+, CD8+ and CD19+ lymphocyte subsets were assessed using flow cytometry. Specific mRNAs of Bcl-2 family members were quantified from whole blood by real-time PCR. To test for statistical significance, Kruskal-Wallis testing with Dunn's multiple comparison test for post hoc analysis was performed. Results In all lymphocyte populations caspase-3 (p < 0.05) was activated, which was reflected in an increased phosphatidylserine externalisation (p < 0.05). Accordingly, lymphocyte counts were decreased in early severe sepsis. In CD4+ T-cells (p < 0.05) and B-cells (p < 0.001) the Bcl-2 protein was decreased in severe sepsis. Gene expression of the BH3-only Bim was massively upregulated as compared with critically ill patients (p < 0.001) and 51.6-fold as compared with healthy controls (p < 0.05). Bid was increased 12.9-fold compared with critically ill patients (p < 0.001). In the group of mitochondrial apoptosis inducers, Bak was upregulated 5.6fold, while the expression of Bax showed no significant variations. By contrast, the pro- survival members Bcl-2 and Bcl-xl were both downregulated in severe sepsis (p < 0.001 and p < 0.05, respectively). Conclusions In early severe sepsis a gene expression pattern with induction of the pro-apoptotic Bcl-2 family members Bim, Bid and Bak and a downregulation of the anti-apoptotic Bcl-2 and Bcl-xl proteins was observed in peripheral blood. This constellation may affect cellular susceptibility to apoptosis and complex immune dysfunction in sepsis. C1 [Weber, Stefan U.; Schewe, Jens-Christian; Lehmann, Lutz E.; Mueller, Stefan; Book, Malte; Hoeft, Andreas] Univ Bonn, Med Ctr, Dept Anesthesiol & Intens Care Med, D-53129 Bonn, Germany. [Klaschik, Sven] US FDA, CBER, Rockville, MD 20852 USA. [Stueber, Frank] Univ Hosp Bern, Dept Anaesthesiol & Pain Therapy, CH-3010 Bern, Switzerland. RP Weber, SU (reprint author), Univ Bonn, Med Ctr, Dept Anesthesiol & Intens Care Med, Sigmund Freud Str 25, D-53129 Bonn, Germany. EM Stefan.weber@ukb.uni-bonn.de FU BONFOR; Faculty of Medicine, University of Bonn FX The authors would like to thank Bettina Bayerer, Makbule Kobilay and Claudia Baumann for excellent technical assistance with RT-PCR. The study was supported by a grant from BONFOR (Program for the advancement of research by the Faculty of Medicine, University of Bonn). NR 49 TC 39 Z9 40 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2008 VL 12 IS 5 AR R128 DI 10.1186/cc7088 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 381UJ UT WOS:000261561100016 PM 18925930 ER PT J AU Nie, L Wu, G Zhang, WW AF Nie, Lei Wu, Gang Zhang, Weiwen TI Statistical Application and Challenges in Global Gel-Free Proteomic Analysis by Mass Spectrometry SO CRITICAL REVIEWS IN BIOTECHNOLOGY LA English DT Review DE proteomics; mass spectrometry; statistics; challenges ID SEARCHING SEQUENCE DATABASES; HIGH-THROUGHPUT PROTEOMICS; PROTEIN IDENTIFICATION; PEPTIDE IDENTIFICATION; DESULFOVIBRIO-VULGARIS; PATTERN-RECOGNITION; EXPERIMENTAL-DESIGN; MESSENGER-RNA; SPECTRAL DATA; QUANTITATIVE PROTEOMICS AB Global gel-free proteomic analysis by mass spectrometry has been widely used as an important tool for exploring complex biological systems at the whole genome level. Simultaneous analysis of a large number of protein species is a complicated and challenging task. The challenges exist throughout all stages of a global gel-free proteomic analysis: experimental design, peptide/protein identification, data preprocessing and normalization, and inferential analysis. In addition to various efforts to improve the analytical technologies, statistical methodologies have been applied in all stages of proteomic analyses to help extract relevant information efficiently from large proteomic datasets. In this review, we summarize current applications of statistics in several stages of global gel-free proteomic analysis by mass spectrometry. We discuss the challenges associated with the applications of various statistical tools. Whenever possible, we also propose potential solutions on how to improve the data collection and interpretation for mass-spectrometry-based global proteomic analysis using more sophisticated and/or novel statistical approaches. C1 [Zhang, Weiwen] Arizona State Univ, Biodesign Inst, Ctr Ecogenom, Tempe, AZ 85287 USA. [Nie, Lei] US FDA, Div Biometr 4, Off Biometr, CDER OTS, Spring, MD USA. [Wu, Gang] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Zhang, WW (reprint author), Arizona State Univ, Biodesign Inst, Ctr Ecogenom, Tempe, AZ 85287 USA. EM Weiwen.Zhang@asu.edu NR 98 TC 10 Z9 11 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0738-8551 J9 CRIT REV BIOTECHNOL JI Crit. Rev. Biotechnol. PY 2008 VL 28 IS 4 BP 297 EP 307 AR PII 905979708 DI 10.1080/07388550802543158 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 378PZ UT WOS:000261337700007 PM 19031310 ER PT J AU Ross, JJ Boucher, PE Bhattacharyya, SP Kopecko, DJ Sutkowski, EM Rohan, PJ Chandler, DKF Vaillancourt, J AF Ross, Jennifer J. Boucher, Philip E. Bhattacharyya, Siba P. Kopecko, Dennis J. Sutkowski, Elizabeth M. Rohan, Patricia J. Chandler, Donna K. F. Vaillancourt, Julienne TI Considerations in the development of live biotherapeutic products for clinical use SO CURRENT ISSUES IN MOLECULAR BIOLOGY LA English DT Review AB Food products in the United States (U.S.), including dietary supplements, may contain live microorganisms and can be promoted for general health, nutritional, or structure/function claims. In contrast, such preparations used with the intention of having a preventive or therapeutic effect in humans are regulated by the Food and Drug Administration (FDA) in the U. S. as biological products, specifically as live biotherapeutic products (LBPs). Discussion of considerations in the early development of LBPs may aid in preparation of an Investigational New Drug Application (IND) that is designed to collect clinical data to support marketing approval of a LBP in the U. S. for a specific clinical use. Product information is an important component of an IND to support a proposed clinical study. C1 US FDA, Div Vaccines & Related Prod Applicat, Rockville, MD 20857 USA. US FDA, Ctr Biolog Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Rockville, MD 20857 USA. Novartis Vaccines & Diagnost, I-53100 Siena, Italy. RP Ross, JJ (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Rockville, MD 20857 USA. EM jennifer.ross@da.hhs.gov NR 12 TC 4 Z9 4 U1 1 U2 4 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1467-3037 J9 CURR ISSUES MOL BIOL JI Curr. Issues Mol. Biol. PY 2008 VL 10 BP 13 EP 16 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 191AO UT WOS:000248102400002 PM 18525102 ER PT S AU Hungerford, JM AF Hungerford, J. M. BE Hudnell, HK TI Cyanobacterial toxins and the AOAC marine and freshwater toxins task force SO CYANOBACTERIAL HARMFUL ALGAL BLOOMS: STATE OF THE SCIENCE AND RESEARCH NEEDS SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Cyanobacterial Algal Blooms - State of the Science and Research Needs CY SEP 06-10, 2005 CL Research Triangle Park, NC C1 USFDA, Seafood Prod Res Ctr, Bothell, WA USA. RP Hungerford, JM (reprint author), USFDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-0-387-75864-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 619 BP 571 EP 572 PG 2 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA BHO77 UT WOS:000254893200051 ER PT J AU Wonnacott, K Lavoie, D Fiorentino, R McIntyre, M Huang, Y Hirschfeld, S AF Wonnacott, K. Lavoie, D. Fiorentino, R. McIntyre, M. Huang, Y. Hirschfeld, S. TI Investigational new drugs submitted to the Food and Drug Administration that are placed on clinical hold: the experience of the Office of Cellular, Tissue and Gene Therapy SO CYTOTHERAPY LA English DT Article DE cell therapy; clinical; chemistry; manufacturing and controls (CMC); Food and Drug Administration (FDA); gene therapy; hold; investigational new drugs (IND); Office of Cellular; Tissue and Gene Therapy (OCTGT); pre-clinical AB Background Cell and gene therapies are medical products regulated by the U.S. Food and Drug Administration (FDA) within its Center of Biologics Evaluation and Research (CBER) in the Office of Cellular, Tissue, and Gene Therapy (OCTGT). Clinical research using cell and gene therapies in the United States must be conducted under an Investigational New Drug (IND) application. After an initial, 30-day review FDA either places an IND on clinical hold or allows the IND to proceed. Discussion We discussed the deficiencies and the resources that can help individuals avoid those deficiencies. We believe that awareness of the common deficiencies along with the applicable resources can reduce the frequency of clinical holds and allow clinical studies to proceed without delay. We also believe that this information will guide the FDA as to bow to facilitate development of safe and effective cell and gene therapies. C1 [Wonnacott, K.; Huang, Y.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lavoie, D.] GE Healthcare, Regulatory Affairs Programs, Waukesha, WI USA. [Fiorentino, R.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [McIntyre, M.] Biol Consulting Grp Inc, Rockville, MD USA. [Hirschfeld, S.] NICHHD, Bethesda, MD 20892 USA. RP Wonnacott, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 720, Rockville, MD 20852 USA. EM keith.wonnacott@fda.hhs.gov RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2008 VL 10 IS 3 BP 312 EP 316 DI 10.1080/14653240801910905 PG 5 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 306FQ UT WOS:000256234100010 PM 18418776 ER PT S AU Agrawal, A Gavrielides, MA Weininger, S Chakrabarti, K Pfefer, J AF Agrawal, Anant Gavrielides, Marios A. Weininger, Sandy Chakrabarti, Kish Pfefer, Joshua BE Nordstrom, RJ TI Regulatory perspectives and research activities at the FDA on the use of phantoms with in vivo diagnostic devices - art. no. 687005 SO DESIGN AND PERFORMANCE VALIDATION OF PHANTOMS USED IN CONJUNCTION WITH OPTICAL MEASUREMENTS OF TISSUE SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurements of Tissue CY JAN 19-21, 2008 CL San Jose, CA SP SPIE DE phantom; regulatory; mammography; tomography; oximetry AB For a number of years, phantoms have been used to optimize device parameters and validate performance in the primary medical imaging modalities (CT, MRI, PET/SPECT, ultrasound). Furthermore, the FDA under the Mammography Quality Standards Act (MQSA) requires image quality evaluation of mammography systems using FDA-approved phantoms. The oldest quantitative optical diagnostic technology, pulse oximetry, also benefits from the use of active phantoms known as patient simulators to validate certain performance characteristics under different clinically-relevant conditions. As such, guidance provided by the FDA to its staff and to industry on the contents of pre-market notification and approval submissions includes suggestions on how to incorporate the appropriate phantoms in establishing device effectiveness. Research at the FDA supports regulatory statements on the use of phantoms by investigating how phantoms can be designed, characterized, and utilized to determine critical device performance characteristics. These examples provide a model for how novel techniques in the rapidly growing field of optical diagnostics can use phantoms during pre- and post-market regulatory testing. C1 [Agrawal, Anant; Gavrielides, Marios A.; Weininger, Sandy; Pfefer, Joshua] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Agrawal, A (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7045-4 J9 P SOC PHOTO-OPT INS PY 2008 VL 6870 BP 87005 EP 87005 DI 10.1117/12.768537 PG 8 WC Engineering, Biomedical; Optics; Physics, Applied; Imaging Science & Photographic Technology SC Engineering; Optics; Physics; Imaging Science & Photographic Technology GA BHT03 UT WOS:000256023200004 ER PT S AU Wang, QZ Agrawal, A Wang, NS Pfefer, J AF Wang, Quanzeng Agrawal, Anant Wang, Nam Sun Pfefer, Josh BE Raghavachari, R Liang, R TI Validation of a fiberoptic-based UVA-VIS optical property measurement system SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies CY JAN 21, 2008 CL San Jose, CA SP SPIE DE fiberoptic; optical properties; ultraviolet; neural network; Monte Carlo; reflectance; tissue ID DIFFUSE-REFLECTANCE MEASUREMENTS; HIGHLY SCATTERING TISSUES; MONTE-CARLO SIMULATIONS; HUMAN COLON TISSUE; ABSORPTION-COEFFICIENTS; LIGHT-PROPAGATION; EPITHELIAL TISSUE; TURBID MEDIA; SPECTROSCOPY; MODEL AB Tissue optical properties at ultraviolet A (UVA) and visible (VIS) wavelengths are needed to elucidate light-tissue interaction effects and optimize design parameters for spectroscopy-based neoplasia detection devices. Toward the goal of accurate and useful in vivo measurements, we have constructed and evaluated a system for optical property measurement at UVA-VIS wavelengths. Our approach involves a neural network-based inverse model calibrated with reflectance datasets simulated using a condensed Monte Carlo approach with absorption coefficients as high as 80 cm(-1) and reduced scattering coefficients as high as 70 cm(-1). Optical properties can be predicted with the inverse model based on spatially-resolved reflectance measured with a fiberoptic probe. Theoretical evaluation of the inverse model was performed using simulated reflectance distributions at random optical properties. Experimental evaluation involved the use of tissue phantoms constructed from bovine hemoglobin and polystyrene microspheres. An average accuracy of +/- 1.0 cm(-1) for absorption coefficients and +/- 2.7 cm(-1) for reduced scattering coefficients was found from realistic phantoms at five UVA-VIS wavelengths. While accounting for the very high attenuation levels near the 415 nm Soret absorption band required some modifications, our findings provide evidence that the current approach produces useful data over a wide range of optical properties, and should be particularly useful for in vivo characterization of highly attenuating biological tissues. C1 [Wang, Quanzeng; Agrawal, Anant; Pfefer, Josh] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7024-9 J9 P SOC PHOTO-OPT INS PY 2008 VL 6849 BP U84 EP U94 PG 11 WC Biophysics; Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BHQ90 UT WOS:000255550500011 ER PT S AU Jhoo, JW Ang, CYW Mei, N Chen, T Dragull, K Tang, CS AF Jhoo, Jin-Woo Ang, Catharina Y. W. Mei, Nan Chen, Tao Dragull, Klaus Tang, Chung-Shih BE Ho, CT Simon, JE Shahidi, F Shao, Y TI Kava (Piper methysticum) Safety Concerns and Studies on Pipermethystine, an Alkaloid in Kava SO DIETARY SUPPLEMENTS SE ACS Symposium Series LA English DT Article; Book Chapter ID PERFORMANCE LIQUID-CHROMATOGRAPHY; EXTRACTS; KAVALACTONES; TOXICITY; HEPATOTOXICITY; INHIBITION; LACTONES; ANXIETY AB Kava (Piper methysticum) extract products have been associated with a number of severe hepatotoxicity cases. Factors influencing the reported kava-linked liver injuries could include the methods of kava preparation, genetic differences between populations, herbal-drug interactions, enzyme inhibition and minor toxic kava constituents in the kava extracts. This article provides highlights of recent findings on kava safety issues, and also presents results of our current studies on pipermethystine, a kava alkaloid, in commercial products and its potential mutagenicity. The level of pipermethystine was found to be negligible in most of the kava dietary supplement products analyzed; however, one product sold as a mixture of kava roots and leaves did contain detectable amounts of pipermethystine. In vitro mutagenicity tests indicated that pipermethystine was negative in Salmonella umu assay at a dose range up to 1000 mu M and in the mouse. lymphoma assay at concentrations lower than 2.5 mu g/mL. However, it showed cytotoxicity in mouse lymphoma cells in a dose-response manner. C1 [Jhoo, Jin-Woo; Ang, Catharina Y. W.; Mei, Nan; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jhoo, Jin-Woo] Kangwon Natl Univ, Dept Food Sci & Technol Anim Resources, Chunchon 200701, Kangwon, South Korea. [Dragull, Klaus; Tang, Chung-Shih] Univ Hawaii, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. RP Jhoo, JW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. OI MEI, NAN/0000-0002-3501-9014 NR 37 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-3992-0 J9 ACS SYM SER JI ACS Symp. Ser. PY 2008 VL 987 BP 248 EP 263 D2 10.1021/bk-2008-0987 PG 16 WC Chemistry, Multidisciplinary; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA BA3XY UT WOS:000335120300018 ER PT S AU Bowyer, JF Thomas, M Schmued, LC Ali, SE AF Bowyer, John F. Thomas, Monzy Schmued, Larry C. Ali, Syed E. BE Kuhar, MJ Kuhar, MJ TI Brain Region-Specific Neurodegenerative Profiles Showing the Relative Importance of Amphetamine Dose, Hyperthermia, Seizures, and the Blood-Brain Barrier SO DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 1st International Drug-Abuse-Research-Society CY AUG 14-17, 2007 CL Merida, MEXICO DE amphetamine; blood-brain barrier disruption; hyperthermia; methamphetamine; neurodegeneration ID NEURONAL DEGENERATION; METHAMPHETAMINE NEUROTOXICITY; SOMATOSENSORY CORTEX; EXPOSURE; INJURY; ABUSE AB Understanding the neurotoxic effects of acute high-dose exposures of laboratory animals to methamphetamine (METH) and amphetamine (AMPH) is of relevance to understanding the neurotoxicity incurred in humans from overdose or abuse of these substances. We present recent findings on the neurodegenerative effects of both a single high dose of 40 mg/kg and a 4-dose exposure to AMPH in the rat. Comparing these results with those we have previously observed in rodents exposed to either AMPH or METH helps further address how dose, hyperthermia, seizures and blood-brain barrier (BBB) disruption interact to produce neurodegeneration. With regard to the 4-dose paradigm of AMPH exposure in the rat, our recent data, combined with previous findings, clearly show the importance of dose and hyperthermic interactions in producing neurodegeneration. The single high AMPH dose invariably resulted in extreme hyperthermia and brief episodes of clonic-tonic seizure activity in many rats. However, motor behavior indicative of status epilepticus was not observed in rats receiving the 40 mg/kg AMPH, which contrasts with what we have previously seen with 40 mg/kg METH dose in the mouse. This may explain why, unlike the mice given METH, there was minimal BBB disruption in the amygdala of rats. Nonetheless, in some of the surviving rats there was extensive neurodegeneration in the hippocampus and intralaminar and ventromedial/lateral thalamic nuclei. Early BBB disruption was seen in the hippocampus and may play an important role in the subsequent neurodegeneration. The fact that status epilepticus does not occur in rats that have major hippocampal and thalamic degeneration indicates that such damage may also occur in humans exposed to high doses of AMPH or METH in the absence of status epilepticus or prominent motor manifestations of seizure activity. C1 [Bowyer, John F.; Thomas, Monzy; Schmued, Larry C.; Ali, Syed E.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov NR 34 TC 22 Z9 23 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-718-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2008 VL 1139 BP 127 EP 139 DI 10.1196/annals.1432.005 PG 13 WC Multidisciplinary Sciences; Neurosciences; Physiology SC Science & Technology - Other Topics; Neurosciences & Neurology; Physiology GA BIN87 UT WOS:000261167100016 PM 18991857 ER PT J AU Strong, J Huang, SM AF Strong, John Huang, Shiew-Mei BE Li, AP TI US REGULATORY PERSPECTIVE: DRUG-DRUG INTERACTIONS SO DRUG-DRUG INTERACTIONS IN PHARMACEUTICAL DEVELOPMENT SE Wiley Series in Drug Discovery and Development LA English DT Article; Book Chapter ID ST-JOHNS-WORT; P-GLYCOPROTEIN; IN-VITRO; GRAPEFRUIT JUICE; HYPERICUM-PERFORATUM; CYP3A; DIGOXIN; VIVO; FEXOFENADINE; SUBSTRATE C1 [Strong, John] US FDA, Lab Clin Pharmacol, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Huang, Shiew-Mei] US FDA, Off Clin Pharm & Biopharm, Silver Spring, MD USA. RP Strong, J (reprint author), US FDA, Lab Clin Pharmacol, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 94 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-0-470-18792-0 J9 WILEY SER DRUG DISC PY 2008 BP 201 EP 226 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BFT16 UT WOS:000321206500010 ER PT J AU O'Neill, RT AF O'Neill, Robert T. TI A perspective on characterizing benefits and risks derived from clinical trials: Can we do more? SO DRUG INFORMATION JOURNAL LA English DT Article DE benefit; risk; metrics; study design; follow-up; withdrawals; clinical trial ID RANDOMIZED CONTROLLED-TRIAL; TREAT; EVENTS; ROFECOXIB; CELECOXIB; TIME AB This article considers a variety of issues associated with the role that clinical trials play in the evaluation of the benefits and risks (harms) of new therapies and with the communication of quantitatively assessed benefits and risks based upon the evidence derived from clinical trials. The article is organized into several sections that explore and discuss aspects of the challenging area of characterizing benefits and risks from clinical trials. We begin with a background on the interest in the topic, and then consider a theme that argues for the imbalance or asymmetry in the way benefits and risks in clinical trials are currently characterized, using examples from the medical literature to illustrate the points. We then comment on several topics, such as metrics for benefit:risk that are involved in other aspects of benefit risk analysis, which relate to other articles in this issue. Finally, we make some concluding remarks on how to make progress in the future to improve beneft:risk analysis in clinical trials. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP O'Neill, RT (reprint author), US FDA, Ctr Drug Evaluat & Res, Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ROBERT.ONEILL@fda.hhs.gov NR 35 TC 17 Z9 17 U1 1 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2008 VL 42 IS 3 BP 235 EP 245 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 296MD UT WOS:000255547800005 ER PT J AU Oliva, A Levin, R Behrman, R Woodcock, J AF Oliva, Armando Levin, Randy Behrman, Rachel Woodcock, Janet TI Bioinformatics modernization and the critical path to improved benefit-risk assessment of drugs SO DRUG INFORMATION JOURNAL LA English DT Article DE FDA; bioinformatics; information managemen 1; benefit-risk assessment; critical path AB At FDA, bioinformatics means the design, development, and use of modern computer systems to efficiently and effectively manage the regulatory product information supply chain, along which medical product information travels among many relevant organizations. The FDA relies on efficient management of this information to assess a drug's safety and effectiveness. The current bioinformatics infrastructure that supports product information exchange is inefficient and is comparable to the antiquated infrastructure of the financial industry in years past. Bioinformatics modernization requires improvements in three important information management domains: access, standards, and interface. We must have better access to information, more standardized information, and better interface with information (ie, better tools to convert information into knowledge). The FDA has taken measurable steps to modernize its bioinformatics infrastructure, but the effort is costly, complex, and time consuming. Nonetheless, it is a necessary step to improve the Critical Path and enhance benefit-risk assessments of drugs. C1 [Woodcock, Janet] US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Oliva, A (reprint author), 5600 Fishers Lane HF-18, Rockville, MD 20857 USA. EM armando.oliva@fda.hhs.gov NR 2 TC 1 Z9 1 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2008 VL 42 IS 3 BP 273 EP 279 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 296MD UT WOS:000255547800009 ER PT J AU Kong, SH Choi, S AF Kong, Seung-Ho Choi, Suktae TI Conditional exact tests for dichotomous data in the comparison of two treatments with one control group SO DRUG INFORMATION JOURNAL LA English DT Article DE Dunnett's test; multiple comparison; exact power; 2 x 3 contingency table; two-step closed Fisher's exact test ID MULTIPLE COMPARISONS; CONTINGENCY-TABLES; EXACT POWER AB When we compare two treatments with one control group for dichotomous data whose response rates are expected to be small, Dunnett's test based on the large sample theory is unreliable. Hence, exact tests that are reliable in the cases of either small response rate or small samples need to be developed. In this article, we investigate the exact unconditional powers of the three exact tests (the two-step closed Fisher's exact test, the exact conditional Dunnett test, and the new conditional exact test proposed here). The exact unconditional power is computed based on complete enumeration. In many phase 3 clinical trials, two possible optimal doses from phase 2 clinical trials are expected to be more promising than the control. Therefore, the response rates of two possible optimal closes are greater than that of the control group. In such cases, we show that the new exact test is more powerful than the other two exact tests. C1 [Kong, Seung-Ho] Ewha Womans Univ, Dept Stat, Seoul 120750, South Korea. [Choi, Suktae] US FDA, Silver Spring, MD USA. RP Kong, SH (reprint author), Ewha Womans Univ, Dept Stat, 11-1 DaeHyun Dong, Seoul 120750, South Korea. EM seungho@ewha.ac.kr NR 15 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2008 VL 42 IS 4 BP 337 EP 347 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 319HQ UT WOS:000257155100005 ER PT J AU Julious, SA Wang, SJ AF Julious, Steven A. Wang, Sue-Jane TI How Biased Are Indirect Comparisons, Particularly When Comparisons Are Made Over Time in Controlled Trials? SO DRUG INFORMATION JOURNAL LA English DT Article DE Clinical trials; Indirect comparisons; Noninfieriority; Placebo creep ID ACTIVE CONTROLLED-TRIALS; STATISTICAL-METHODS; CLINICAL-TRIALS; METAANALYSIS; EFFICACY; PLACEBO; DESIGN; ISSUES AB Indirect comparisons are undertaken when a comparison is made between two regimens, usually where the regimens have never been given concurrently in any controlled Mal investigating the same general patient population. We highlight the issues of making indirect comparisons when there has been a period of time between the studies, particularly when indirect comparison is being made to placebo. We discuss the impact of any bias in indirectly estimating any effect over placebo in context with noninferiority trials. C1 [Julious, Steven A.] Univ Sheffield, Med Stat Grp, Hlth Serv Res, Sheffield S1 4DA, S Yorkshire, England. [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Julious, SA (reprint author), Univ Sheffield, Med Stat Grp, Hlth Serv Res, Regent Court,30 Regent St, Sheffield S1 4DA, S Yorkshire, England. EM S.A.Julious@Sheffield.ac.uk NR 22 TC 24 Z9 24 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2008 VL 42 IS 6 BP 625 EP 633 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 368UY UT WOS:000260649400011 ER PT J AU Wei, XX Zhu, MS AF Wei, Xiaoxiong Zhu, Mingshe BE Zhang, D Zhu, M Humphreys, WG TI REGULATORY CONSIDERATIONS OF DRUG METABOLISM AND DRUG INTERACTION STUDIES SO DRUG METABOLISM IN DRUG DESIGN AND DEVELOPMENT: BASIC CONCEPTS AND PRACTICE LA English DT Article; Book Chapter ID HUMAN LIVER-MICROSOMES; POTENTIALLY HAZARDOUS INTERACTION; IN-VITRO METABOLISM; PHARMACEUTICAL-INDUSTRY; LIQUID-CHROMATOGRAPHY; PLASMA-CONCENTRATIONS; COCKTAIL APPROACH; SAFETY ASSESSMENT; GEMFIBROZIL; KETOCONAZOLE C1 [Wei, Xiaoxiong] US FDA, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Zhu, Mingshe] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. RP Wei, XX (reprint author), US FDA, Off Clin Pharmacol, WO Bldg 21,Room 4660,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Xiaoxiong.wei@fda.hhs.gov; mingshe.zhu@bms.com NR 73 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-0-470-19169-9 PY 2008 BP 203 EP 236 PG 34 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BFT36 UT WOS:000321242700008 ER PT J AU Woo, EJ Ball, R Burwen, DR Braun, MM AF Woo, Emily Jane Ball, Robert Burwen, Dale R. Braun, M. Miles TI Effects of stratification on data mining in the US vaccine adverse event reporting system (VAERS) SO DRUG SAFETY LA English DT Article ID SAFETY; PHARMACOVIGILANCE; DRUGS; TOOLS AB Background: Vaccines are administered differentially according to age and sex, and disease patterns also vary among people of different age and sex groups. Estimates of disproportionality should be calculated based on comparisons of groups that have a similar likelihood of receiving similar vaccines and experiencing similar adverse events, to prevent false disproportionality from occurring. Stratified empirical Bayesian (EB) methods have been compared with crude, but not stratified, proportional reporting ratios (PRRs) in their performance on adverse event data. Objectives: (i) to implement stratification of PRR; (ii) to quantify and compare vaccine-event pairs that are highlighted by PRR and EB05 (the lower bound of the 90% CI of the EB geometric mean), for both crude and stratified; and (iii) to evaluate the effects of stratification by age and sex, in identifying adverse events that are accepted to be caused by vaccines. Methods: We applied EB and PRR data mining methods to data from the US Vaccine Adverse Event Reporting System (VAERS). We stratified PRR and EB05 by age and sex. To study the effects of stratification, we compared the crude PRR and stratified PRR. We also assessed the crude EB05 and stratified EB05, and then compared the effects of stratification on EB05 and PRR. Results: Stratification not only changed the number of vaccine-event pairs that were highlighted, but also changed which pairs were highlighted. There were 283 vaccine-event pairs that were highlighted by the crude EB05, but not the stratified; 12 that were highlighted by the stratified EB05, but not the crude; and 162 that were highlighted by both. Similarly, there were 701 vaccine-event pairs that were highlighted by the crude PRR, but not the stratified; 139 that were highlighted by the stratified PRR, but not the crude; and 895 that were highlighted by both. There were 1466 vaccine-event pairs in which the effect of stratification was different for EB05 and PRR. Conclusion: To our knowledge, this is the first published analysis using stratified PRRS. In this analysis of passive surveillance data, stratification revealed and reduced confounding in EB and PRR, and also unmasked some vaccine-event pairs that the crude values did not highlight. Stratification should be applied if confounding is suspected. By decreasing the total number of highlighted vaccine-event pairs, stratification is likely to increase efficiency and therefore might reduce workload. C1 [Woo, Emily Jane; Ball, Robert; Burwen, Dale R.; Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 21 TC 28 Z9 28 U1 0 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2008 VL 31 IS 8 BP 667 EP 674 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 340ZX UT WOS:000258684600003 PM 18636785 ER PT J AU Ahmad, S Westin, L Aagaard, L Moses, G AF Ahmad, S. Westin, L. Aagaard, L. Moses, G. TI Do Consumer Reports of Adverse Drug Reactions Add Value or Noise to Postmarketing Safety Surveillance? SO DRUG SAFETY LA English DT Meeting Abstract CT 8th Annual Meeting of the International-Society-of Pharmacovigilance (ISoP) CY OCT 05-08, 2008 CL Buenos Aires, ARGENTINA SP Int Soc Pharmacovigilance C1 [Ahmad, S.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2008 VL 31 IS 10 MA 9 BP 890 EP 891 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 354HN UT WOS:000259629700015 ER PT J AU Chang, SJ Pool, V O'Connell, K Polder, JA Iskander, J Sweeney, C Ball, R Braun, MM AF Chang, Soju Pool, Vitali O'Connell, Kathryn Polder, Jacquelyn A. Iskander, John Sweeney, Colleen Ball, Robert Braun, M. Miles TI Preventable Mix-ups of Tuberculin and Vaccines Reports to the US Vaccine and Drug Safety Reporting Systems SO DRUG SAFETY LA English DT Article ID MEDICATION ERRORS; VAERS; TRANSMISSION; DIAGNOSIS AB Background: Errors involving the mix-up of tuberculin purified protein derivative (PPD) and vaccines leading to adverse reactions and unnecessary medical management have been reported previously. Objectives: To determine the frequency of PPD-vaccine mix-ups reported to the US Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS), characterize adverse events and clusters involving mix-ups and describe reported contributory factors. Methods: We reviewed AERS reports from 1969 to 2005 and VAERS reports from 1990 to 2005. We defined a mix-up error event as an incident in which a single patient or a cluster of patients inadvertently received vaccine instead of a PPD product or received a PPD product instead of vaccine. We defined a cluster as inadvertent administration of PPD or vaccine products to more than one patient in the same facility within I month. Results: Of 115 mix-up events identified, 101 involved inadvertent administration of vaccines instead of PPD. Product confusion involved PPD and multiple vaccines. The annual number of reported mix-ups increased from an average of one event per year in the early 1990s to an average of ten events per year in the early part of this decade. More than 240 adults and children were affected and the majority reported local injection site reactions. Four individuals were hospitalized (all recovered) after receiving the wrong products. Several patients were inappropriately started on tuberculosis prophylaxis as a result of a vaccine local reaction being interpreted as a positive tuberculin skin test. Reported potential contributory factors involved both system factors (e.g. similar packaging) and human errors (e.g. failure to read label before product administration). Conclusions: To prevent PPD-vaccine mix-ups, proper storage, handling and administration of vaccine and PPD products is necessary. C1 [Chang, Soju] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Res & Evaluat, Rockville, MD 20852 USA. [Pool, Vitali; Iskander, John] CDC, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA 30333 USA. [Sweeney, Colleen] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chang, SJ (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Res & Evaluat, 1401 Rockville Pike, Rockville, MD 20852 USA. EM sojuchang@hotmail.com NR 38 TC 4 Z9 4 U1 1 U2 4 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2008 VL 31 IS 11 BP 1027 EP 1033 DI 10.2165/00002018-200831110-00007 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 373ZO UT WOS:000261012200007 PM 18840022 ER PT J AU Hausner, E Fiszman, ML Hanig, J Harlow, P Zornberg, G Sobel, S AF Hausner, Elizabeth Fiszman, Monica L. Hanig, Joseph Harlow, Patricia Zornberg, Gwen Sobel, Solomon TI Long-Term Consequences of Drugs on the Paediatric Cardiovascular System SO DRUG SAFETY LA English DT Review ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; PERVASIVE DEVELOPMENTAL DISORDERS; DEFICIT HYPERACTIVITY DISORDER; RANDOMIZED CONTROLLED-TRIAL; PSYCHOTROPIC MEDICATIONS; HEART-FAILURE; ANTIEPILEPTIC DRUGS; RISK-ASSESSMENT; PHARMACOLOGICAL-TREATMENT; CLINICAL-IMPLICATIONS AB Many pharmacological and toxicological actions of drugs in children cannot be fully predicted from adult clinical experience or from standard non-clinical toxicology studies. Numerous drugs have direct or indirect pharmacological effects on the heart and are prescribed for children of all ages. Toxicity or secondary effects may be immediate or delayed for years after drug exposure has ceased. Originally, the aim of this review was to compile information on the effect of specific drugs on the post-natal development of the cardiovascular system and to examine long-term follow-up of the use of cardio-active drugs in children. The limited database of published information caused the original question to evolve into an examination of the medical literature for three areas of information: (i) whether vulnerable developmental windows have been identified that reflect the substantial functional development that the cardiovascular system undergoes after birth; (ii) what is known about pharmacological perturbation of development; and (iii) what the likelihood is of drug exposure during childhood. We examined different scenarios for exposure including random, isolated exposure, conditions historically associated with adults, primary or secondary cardiac disease, psychiatric and neurological conditions, asthma, cancer and HIV. Except for random, isolated drug exposures, each category of possible exposure contained numerous drugs known to have either primary or secondary effects on the cardiovascular system or to influence factors associated with atherosclerosis. It is likely that a significant number of children will be prescribed drugs having either direct or indirect effects upon the immature cardiovascular system. A confounding factor is the simultaneous use of over-the-counter medications and herbal or nutraceutical preparations that a patient, parent or guardian does not mention to a prescribing physician. Metabolism is also important in assessing drug effects in children. Differences in body water : body fat ratio, age-related gastrointestinal absorption, distribution, excretion, renal function and drug metabolizing capabilities make it possible for children to have a different metabolite profile for a drug compared with adults. There is little examination of drug effects on the interdependent processes of cardiac maturation and less examination of metabolite effects. It is difficult to identify delayed toxicities in children as these adverse events may take years to manifest with many patients lost to follow-up. Clearly this is an area of study where intermediate endpoints and surrogate markers would be of great benefit. Pharmacogenomics may be useful in providing markers of increased risk or susceptibility. A perspective must be kept in balancing the possibility of a problem with the very real benefits that many children experience from the use of these pharmaceuticals. C1 [Hausner, Elizabeth; Fiszman, Monica L.; Hanig, Joseph; Harlow, Patricia; Zornberg, Gwen; Sobel, Solomon] US FDA, Silver Spring, MD USA. RP Hausner, E (reprint author), US FDA, Off Drug Evaluat 1, CDER, Div Cardiovasc & Renal Drug Prod, 5901-B Ammendale Rd, Beltsville, MD 20705 USA. NR 126 TC 4 Z9 5 U1 1 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2008 VL 31 IS 12 BP 1083 EP 1096 DI 10.2165/0002018-200831120-00005 PG 14 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 393AT UT WOS:000262344000004 PM 19026026 ER PT J AU Pogribny, IF Rusyn, I Beland, FA AF Pogribny, Igor P. Rusyn, Ivan Beland, Frederick A. TI Epigenetic aspects of genotoxic and non-genotoxic hepatocarcinogenesis: Studies in rodents SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE epigenetics; hepatocarcinogenesis; rodents; genotoxic carcinogens; non-genotoxic carcinogens ID HUMAN HEPATOCELLULAR-CARCINOMA; ACID-DEFINED DIET; DNA METHYLATION; LIVER-CANCER; MOLECULAR PATHOGENESIS; PRENEOPLASTIC LIVER; CHOLINE-DEFICIENCY; GENE-EXPRESSION; MOUSE MODELS; E-CADHERIN AB Hepatocellular carcinoma which is one of the most prevalent life-threatening human cancers, is showing an increased incidence worldwide. Recent evidence indicates that the development of hepatocellular carcinoma is associated with not only genetic alterations, but also with profound epigenetic changes. This review summarizes the current knowledge about epigenetic alterations during rodent hepatocarcinogenesis, considers the similarities and differences in epigenetic effects of genotoxic and non-genotoxic rodent liver carcinogens, and discusses the possible role of these effects in the causality of liver tumor development. C1 [Pogribny, Igor P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. RP Pogribny, IF (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [R01 ES012686, R01 ES012686-04] NR 64 TC 28 Z9 29 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2008 VL 49 IS 1 BP 9 EP 15 DI 10.1002/em.20342 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 255JG UT WOS:000252653700003 PM 17879298 ER PT S AU Komolprasert, V Bailey, A AF Komolprasert, V. Bailey, A. BE Chiellini, E TI Recycled plastics for food applications: improving safety and quality SO ENVIRONMENTALLY COMPATIBLE FOOD PACKAGING SE Woodhead Publishing in Food Science Technology and Nutrition LA English DT Article; Book Chapter ID HIGH-DENSITY POLYETHYLENE; CONTACT APPLICATIONS; POLY(ETHYLENE-TEREPHTHALATE) PET; ALKALINE DEPOLYMERIZATION; PACKAGING MATERIALS; FUNCTIONAL BARRIER; TEREPHTHALATE PET; ACID-HYDROLYSIS; MIGRATION; KINETICS C1 [Komolprasert, V.; Bailey, A.] US FDA, Div Food Contact Notificat HFS 275, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Komolprasert, V (reprint author), US FDA, Div Food Contact Notificat HFS 275, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Vanee.Komolprasert@fda.hhs.gov NR 34 TC 0 Z9 0 U1 0 U2 1 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978 1 84569 194 3 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2008 IS 161 BP 326 EP 350 DI 10.1533/9781845694784.2.326 PG 25 WC Biotechnology & Applied Microbiology; Environmental Sciences; Food Science & Technology; Materials Science, Multidisciplinary SC Biotechnology & Applied Microbiology; Environmental Sciences & Ecology; Food Science & Technology; Materials Science GA BOK30 UT WOS:000276889900014 ER PT J AU Lathers, CM Schraeder, PL Bungo, MW AF Lathers, Claire M. Schraeder, Paul L. Bungo, Michael W. TI The mystery of sudden death: Mechanisms for risks SO EPILEPSY & BEHAVIOR LA English DT Review DE sudden death; sudden unexpected death in epilepsy; epilepsy; cardiac risk factors for sudden death; stress; interventions ID CARDIAC NEURAL DISCHARGE; LONG-QT SYNDROME; TEMPORAL-LOBE EPILEPSY; CENTRAL-NERVOUS-SYSTEM; PENTYLENETETRAZOL-INDUCED CONVULSIONS; RIGHT-VENTRICULAR CARDIOMYOPATHY; INTRAOSSEOUS SODIUM-BICARBONATE; INDUCED EPILEPTOGENIC ACTIVITY; OUABAIN-INDUCED ARRHYTHMIA; ELICITED SEIZURE ACTIVITY AB This review addresses the possible overlapping mechanisms that may apply to the risk of sudden unexpected death occurring in epilepsy and in cardiac disease. It explores the interaction between the central and peripheral autonomic nervous systems and the cardiopulmonary systems. Included is a discussion of the potential interactive role of genetically determined subtle cardiac risk factors for arrhythmias with a predisposition for seizure-related cardiac arrhythmias. We address the possible mechanisms that are operant in producing both epileptogenic and cardiogenic arrhythmias. Finally, we speculate about potential preventive measures to minimize the risk of both sudden unexpected death in epilepsy and sudden cardiac death. (C) 2007 Elsevier Inc. All rights reserved. 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), 115 S Manning Blvd, Albany, NY 12203 USA. EM Lathers@attglobal.net NR 253 TC 26 Z9 27 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 JAN PY 2008 VL 12 IS 1 BP 3 EP 24 DI 10.1016/j.yebeh.2007.09.016 PG 22 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 252RU UT WOS:000252465100002 PM 18086454 ER PT J AU Havert, MB AF Havert, Michael B. TI A regulatory perspective on the development of gene therapy for Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; ADENOASSOCIATED VIRUS; VECTOR; SEROTYPES C1 US FDA, Ctr Biol Evaluat & Review, Off Cellular Tissue & Gene Therapies, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Havert, MB (reprint author), US FDA, Ctr Biol Evaluat & Review, Off Cellular Tissue & Gene Therapies, Div Cellular & Gene Therapies, 1401 Rockville Pike,HFM 720, Rockville, MD 20852 USA. EM mike.havert@fda.hhs.gov NR 11 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2008 VL 209 IS 1 BP 48 EP 50 DI 10.1016/j.expneurol.2007.08.010 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 253EG UT WOS:000252500900010 PM 17949714 ER PT J AU Mattamal, GJ AF Mattamal, George J. TI USFDA perspective on the regulations of medical-grade polymers: cyanoacrylate polymer medical device tissue adhesives SO EXPERT REVIEW OF MEDICAL DEVICES LA English DT Review DE cardiovascular; cyanoacrylate; dental cement; investigational device exception; investigation device exemption; neurological; polymeric; premarket approval; sealant; skin; tissue adhesives AB This article provides a brief description of the uses and clinical applications of medical-grade polymers, in particular synthetic cyanoacrylate adhesive/glue devices that have been cleared and/or approved as medical devices by the US FDA since the Medical Device Amendments of 1976 were enacted. This includes Class I cyanoacrylate devices (e.g., liquid bandages), Class II cyanoacrylate devices (e.g., dental cements), and Class III (premarket approval) cyanoacrylate devices such as Dermabond (TM), Indermil (R) Tissue Adhesive, Histoacryl (R) and Histoacryl (R) Blue Topical Skin Adhesive, and Trufill (R) n-Butyl Cyanoacrylate Embolic Agent. By citing an example of FDA approved Class III devices in the cyanoacrylate technology, the article provides a brief discussion of the FDA approval process of medical devices. It includes the FDA issues regarding the published guidance document for 'Cyanoacrylate Topical Tissue Adhesives' that will provide guidance to regulatory personnel and manufacturers in the preparation of investigational device exception applications and in the development of valid scientific evidence to support premarket approval applications for cyanocrylate tissue adhesives intended for topical approximation of skin and others. The article provides a short regulatory description of the US FDA; under what laws its operates, how the FDA evaluates new devices for marketing, and how the device regulatory system works, for example, Class I, Class II, and Class III cyanoacrylate medical devices. C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Gen Restorat & Neurol Devices, Rockville, MD 20850 USA. RP Mattamal, GJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Gen Restorat & Neurol Devices, 9200 Corp Blvd, Rockville, MD 20850 USA. EM george.mattamal@fda.hhs.gov NR 2 TC 14 Z9 14 U1 1 U2 15 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1743-4440 J9 EXPERT REV MED DEVIC JI Expert Rev. Med. Devices PD JAN PY 2008 VL 5 IS 1 BP 41 EP 49 DI 10.1586/17434440.5.1.41 PG 9 WC Engineering, Biomedical SC Engineering GA 255JH UT WOS:000252653800013 PM 18095895 ER PT S AU Anderson, BJ Larkin, C Guja, K Schildbach, JF AF Anderson, Brian J. Larkin, Chris Guja, Kip Schildbach, Joe F. BE Brand, L Johnson, ML TI USING FLUOROPHORE-LABELED OLIGONUCLEOTIDES TO MEASURE AFFINITIES OF PROTEIN-DNA INTERACTIONS SO FLUORESCENCE SPECTROSCOPY SE Methods in Enzymology LA English DT Review; Book Chapter ID SINGLE-STRANDED-DNA; SEQUENCE-SPECIFIC BINDING; F-FACTOR RELAXASE; FLUORESCENCE ANISOTROPY; TRAI RELAXASE; DOMAIN; DYES; SPECTROSCOPY; SPECIFICITY; MOLECULE AB Changes in fluorescence emission intensity and anisotropy can reflect changes in the environment and molecular motion of a fluorophore. Researchers can capitalize on these characteristics to assess the affinity and specificity of DNA-binding proteins using fluorophore-labeled oligonucleotides. While there are many advantages to measuring binding using fluorescent oligonucleotides, there are also some distinct disadvantages. Here we describe some of the relevant issues for the novice, illustrating key points using data collected with a variety of labeled oligonucleotides and the relaxase domain of F plasmid Tral. Topics include selection of a fluorophore, experimental design using a fluorometer equipped with an automatic titrating unit, and analysis of direct binding and competition assays. C1 [Anderson, Brian J.; Larkin, Chris; Guja, Kip; Schildbach, Joe F.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [Anderson, Brian J.] George Washington Univ, Sch Med, Washington, DC USA. [Larkin, Chris] US FDA, Rockville, MD 20857 USA. [Guja, Kip] SUNY Stony Brook, Med Ctr, Sch Med, Stony Brook, NY 11794 USA. RP Anderson, BJ (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. FU National Institutes of Health [GM61017] FX The authors thank Prof. Lenny Brand, and Drs. Dima Toptygin and Mike Rodgers for their generosity with their time, equipment, and expertise. This manuscript is based on work supported by National Institutes of Health grant GM61017 to J.F.S. NR 26 TC 42 Z9 42 U1 0 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-374586-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2008 VL 450 BP 253 EP 272 DI 10.1016/S0076-6879(08)03412-5 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BIR49 UT WOS:000262254000012 PM 19152864 ER PT J AU Trucksess, MW Scott, PM AF Trucksess, M. W. Scott, P. M. TI Mycotoxins in botanicals and dried fruits: A review SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 12th IUPAC International Symposium on Mycotoxins and Phycotoxins CY MAY 21-25, 2007 CL Sci & Technol Council Turkey, Istanbul, TURKEY HO Sci & Technol Council Turkey DE botanicals; dried fruits; garlic; ginseng; ginger; capsicum; liquorice; raisins; figs; fumonisins; ochratoxin A; aflatoxins ID IMMUNOAFFINITY COLUMN CLEANUP; PERFORMANCE LIQUID-CHROMATOGRAPHY; MONASCUS FERMENTATION PRODUCTS; TANDEM MASS-SPECTROMETRY; RED YEAST RICE; OCHRATOXIN-A; MEDICINAL HERBS; AFLATOXIN CONTAMINATION; VINE FRUITS; TOXIGENIC FUNGI AB Botanicals are used in many countries for medicinal and general health-promoting purposes. Numerous natural occurrences of mycotoxins in botanicals and dried fruits have been reported. Aflatoxins or ochratoxin A (OTA) have been found in botanicals such as ginseng, ginger, liquorice, turmeric, and kava-kava in the USA, Spain, Argentina, India, and some other countries, while fumonisins have been found in medicinal wild plants in South Africa and in herbal tea and medicinal plants in Turkey. Zearalenone was identified in ginseng root. Dried fruits can be contaminated with aflatoxins, OTA, kojic acid, and, occasionally, with patulin or zearalenone. One main area of concern is aflatoxins in dried figs; bright greenish yellow fluorescence under ultraviolet light is associated with aflatoxin contamination. OTA in dried vine fruits (raisins, sultanas, and currants) is another concern. There are also reports of aflatoxins in raisins and OTA in dried figs, apricots, dried plums (prunes), dates, and quince. Maximum permitted levels in the European Union include 4 mu g kg(-1) for total aflatoxins in dried fruit intended for direct consumption and 10 mu g kg(-1) for OTA in dried vine fruit. This review discusses the occurrence of mycotoxins in botanicals and dried fruits and analytical issues such as sampling, sample preparation, and methods for analysis. Fungal contamination of these products, the influence of sorting, storage, and processing, and prevention are also considered. C1 [Trucksess, M. W.] Food & Drug Adm, College Pk, MD 20740 USA. [Scott, P. M.] Hlth Canada, Ottawa, ON K1A 0K9, Canada. RP Trucksess, MW (reprint author), Food & Drug Adm, 5100 Paint Branch Pkway, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov NR 118 TC 77 Z9 88 U1 3 U2 42 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PY 2008 VL 25 IS 2 BP 181 EP 192 DI 10.1080/02652030701567459 PG 12 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 269OY UT WOS:000253659900007 PM 18286408 ER PT J AU Morehouse, KM Nyman, PJ Mcneal, TP Dinovi, MJ Perfetti, GA AF Morehouse, Kim M. Nyman, Patricia J. Mcneal, Timothy P. Dinovi, Michael J. Perfetti, Gracia A. TI Survey of furan in heat processed foods by headspace gas chromatography/mass spectrometry and estimated adult exposure SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE furan; processed food; headspace; gas chromatography; mass spectroscopy ID VALIDATION AB Furan is a suspected human carcinogen that is formed in some processed foods at low ng per g levels. Recent improvements in analytical methodology and scientific instrumentation have made it possible to accurately measure the amount of furan in a wide variety of foods. Results from analysis of more than 300 processed foods are presented. Furan was found at levels ranging from non-detectable (LOD, 0.2-0.9 ng g(-1)) to over 100 ng g(-1). Exposure estimates for several adult food types were calculated, with brewed coffee being the major source of furan in the adult diet (0.15 mu g kg(-1) body weight day(-1)). Estimates of mean exposure to furan for different subpopulations were calculated. For consumers 2 years and older, the intake is estimated to be about 0.2 mu g kg(-1) body weight day(-1). C1 [Morehouse, Kim M.; Nyman, Patricia J.; Mcneal, Timothy P.; Dinovi, Michael J.; Perfetti, Gracia A.] CFSAN, Food & Drug Adm, College Pk, MD 20740 USA. RP Morehouse, KM (reprint author), CFSAN, Food & Drug Adm, 5100 Paint Branch Pkwy,HFS 706, College Pk, MD 20740 USA. EM kim.morehouse@fda.hhs.gov NR 20 TC 50 Z9 50 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PY 2008 VL 25 IS 3 BP 259 EP 264 DI 10.1080/02652030701552949 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 269OZ UT WOS:000253660000002 PM 18311619 ER PT J AU Begley, TH Hsu, W Noonan, G Diachenko, G AF Begley, T. H. Hsu, W. Noonan, G. Diachenko, G. TI Migration of fluorochemical paper additives from food-contact paper into foods and food simulants SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE fluorochemicals; food packaging; migration; food simulants ID EXPOSURE; ACIDS AB Fluorochemical-treated paper was tested to determine the amount of migration that occurs into foods and food-simulating liquids and the characteristics of the migration. Migration characteristics of fluorochemicals from paper were examined in Miglyol, butter, water, vinegar, water-ethanol solutions, emulsions and pure oil containing small amounts of emulsifiers. Additionally, microwave popcorn and chocolate spread were used to investigate migration. Results indicate that fluorochemicals paper additives do migrate to food during actual package use. For example, we found that microwave popcorn contained 3.2 fluorochemical mg kg(-1) popcorn after popping and butter contained 0.1 mg kg(-1) after 40 days at 4 degrees C. Tests also indicate that common food-simulating liquids for migration testing and package material evaluation might not provide an accurate indication of the amount of fluorochemical that actually migrates to food. Tests show that oil containing small amounts of an emulsifier can significantly enhance migration of a fluorochemical from paper. C1 [Begley, T. H.; Noonan, G.; Diachenko, G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hsu, W.] Univ Maryland, Joint food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Begley, TH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM timothy.begley@fda.hhs.gov NR 15 TC 71 Z9 79 U1 4 U2 45 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PY 2008 VL 25 IS 3 BP 384 EP 390 DI 10.1080/02652030701513784 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 269OZ UT WOS:000253660000016 PM 18311629 ER PT J AU Miliotis, M Dennis, S Buchanan, R Potter, M AF Miliotis, M. Dennis, S. Buchanan, R. Potter, M. TI Role of epidemiology in microbial risk assessment SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article; Proceedings Paper CT 10th International Symposium on Toxic Microorganisms and Pathogens - Implications for Food Safety and Public Health CY NOV 07-09, 2006 CL College Pk, MD SP US/Japan Coop Program, Dev & Utilizat Nat Resources, USFDA Ctr Food Safety & Nutr DE microbial risk assessment; epidemiology; hazard identification; hazard characterization; exposure assessment; risk characterization ID SALMONELLA; OUTBREAKS AB Microbial risk assessment (MRA) is a systematic tool to evaluate the likelihood of exposure to food-borne pathogens and the resulting impact of exposure on consumer health. In addition, MRA can be used to evaluate the public health impact of intervention or control measures designed to prevent or reduce pathogens at any or all of the steps in our complex food production system. Epidemiological studies provide useful information and data for MRA. This paper discusses the use and limitations of epidemiological data in the development and validation of MRA using examples from published microbial risk assessments. C1 [Miliotis, M.; Dennis, S.; Buchanan, R.; Potter, M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Miliotis, M (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM marianna.miliotis@fda.hhs.gov NR 20 TC 5 Z9 5 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2008 VL 25 IS 9 BP 1052 EP 1057 DI 10.1080/02652030802056618 PG 6 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 365LL UT WOS:000260408000003 PM 18608511 ER PT J AU Begley, TH Brandsch, J Limm, W Siebert, H Piringer, O AF Begley, T. H. Brandsch, J. Limm, W. Siebert, H. Piringer, O. TI Diffusion behaviour of additives in polypropylene in correlation with polymer properties SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE chromatography; high-performance liquid chromatography (HPLC); additives general; migration; diffusion; packaging; food simulants; modelling; polypropylene ID MIGRATION MODELS; FOOD SIMULANTS; ANTIOXIDANTS; TEMPERATURE; POLYOLEFINS AB The migration behaviour of polymer additives in 17 polypropylene (PP) samples is described. These samples cover the major types of PP used in food packaging. The diffusion coefficients of additives with relatively small molecular masses, Mr = 136 (limonene), as well as the migration of typical antioxidants used in PP up to Mr = 1178 (IRGANOX 1010), were measured at different temperatures. In addition, the diffusion data and percentages of xylene-soluble fractions were correlated. This enables a prediction of the migration behaviour of a PP sample by testing its 'isotactic index' with xylene. The results clearly indicate that PP can be subdivided, from the migration point of view, into the monophasic homopolymer (h-PP), the monophasic random copolymer (r-PP), and the heterophasic copolymer (heco-PP). The diffusion coefficients for r-PP are at least one order of magnitude higher than those of h-PP and comparable with the values for heco-PP. Upper limits for the diffusion values can be calculated based on the safety margin required by consumer protection laws. C1 [Brandsch, J.; Piringer, O.] FABES Forsch GmbH, Munich, Germany. [Begley, T. H.; Limm, W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Piringer, O (reprint author), FABES Forsch GmbH, Munich, Germany. EM otto.piringer@fabes-online.de NR 14 TC 6 Z9 9 U1 6 U2 48 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2008 VL 25 IS 11 BP 1409 EP 1415 DI 10.1080/02652030802162747 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 367SH UT WOS:000260572200015 PM 19680849 ER PT J AU Zhang, K Noonan, GO Begley, TH AF Zhang, K. Noonan, G. O. Begley, T. H. TI Determination of 2,6-diisopropylnaphthalene (DIPN) and n-dibutylphthalate (DBP) in food and paper packaging materials from US marketplaces SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE gas chromatography-ion-trap tandem mass spectrometry (GC-IT-MS; MS); 2; 6-diisopropylnaphthalene (DIPN); n-dibutylphthalate (DBP); paper food package; dry foods ID RECYCLED PAPER; MIGRATION; BOARD; CONTAMINANTS; PLASTICIZERS AB A gas chromatography-ion-trap tandem mass spectrometry procedure was developed for the determination of 2,6-diisopropylnaphthalene (DIPN) and n-dibutylphthalate (DBP) in domestic and imported paper packages and food sold in US marketplaces. The procedure involved ultrasonic extraction with dichloromethane, followed by analysis with the gas chromatography-ion-trap tandem mass spectrometry. Calibration curves for DIPN and DBP were achieved with concentrations ranging from 0.01 to 10 g ml-1 and the corresponding r2 values were 0.9976 and 0.9956, respectively. In most of the fortified samples the recoveries were higher than 80% with a relative standard deviation (RSD) 10%. Using this procedure, it was found that less than 20% of the tested domestic packages and more than 60% of the tested imported food packages contained both DIPN and DBP. The concentrations of DIPN and DBP ranged from 0.09 to 20 mg kg-1 and 0.14 to 55 mg kg-1, respectively, with most of the DINP and DBP levels lower than 20 mg kg-1. DIPN was not detected (0.01 mg kg-1) in 41 food samples and DBP was only detected in two domestic and four imported food samples with concentrations ranging from 0.01 to 0.81 mg kg-1. C1 [Zhang, K.; Noonan, G. O.; Begley, T. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Zhang, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM kai.zhang@fda.hhs.gov NR 18 TC 18 Z9 20 U1 8 U2 20 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2008 VL 25 IS 11 BP 1416 EP 1423 DI 10.1080/02652030802163380 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 367SH UT WOS:000260572200016 PM 19680850 ER PT J AU Whitaker, P Clarke, JJ San, RHC Betz, JM Seifried, HE de Jagar, LS Dunkel, VC AF Whittaker, Paul Clarke, Jane J. San, Richard H.C. Betz, Joseph M. Seifried, Harold E. Jager, Lowri S. Dunkel, Virgina C. TI Evaluation of commercial kava extracts and kavalactone standards 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 Piper methysticum; kava; kava pyrones; kavalactones; mutagenicity; mouse lymphoma ID HUMAN LIVER-MICROSOMES; PIPER-METHYSTICUM; ENZYME; INHIBITION; ANXIETY; SAFETY AB Kava (Piper methysticum) is a member of the pepper family and has been cultivated by South Pacific islanders for centuries and used as a social and ceremonial drink. Traditionally, kava extracts are prepared by grinding or chewing the rhizome and mixing with water and coconut milk. The active constituents of kava are a group of approximately 18 compounds collectively referred to as kavalactones or kava pyrones. Kawain, dihydrokawain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin are the six major kavalactones. Kava beverages and other preparations are known to be anxiolytic and are used for anxiety disorders. Dietary supplements containing the root of the kava shrub have been implicated in several cases of liver toxicity in humans, including several who required liver transplants after using kava supplements. In order to study the toxicity and mutagenicity, two commercial samples of kava, Kaviar and KavaPure, and the six pure kavalactones including both D-kawain and DL-kawain, were evaluated in L5178Y mouse lymphoma cells. Neither the kava samples nor the kavalactones induced a mutagenic response in the L5178Y mouse lymphoma mutation assay with the addition of human liver S9 activation. (c) 2007 Elsevier Ltd. All rights reserved. C1 Food & Drug Admin, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. BioReliance, Rockville, MD USA. NIH, Bethesda, MD USA. Natl Canc Inst, NIH, Bethesda, MD USA. RP Whitaker, P (reprint author), Food & Drug Admin, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov FU NCI NIH HHS [N01-CB-87016] NR 27 TC 8 Z9 8 U1 1 U2 1 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 JAN PY 2008 VL 46 IS 1 BP 168 EP 174 DI 10.1016/j.fct.2007.07.013 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 260UW UT WOS:000253036900020 PM 17822821 ER PT J AU Ju, YH Doerge, DR Helferich, WG AF Ju, Young H. Doerge, Daniel R. Helferich, William G. TI A dietary supplement for female sexual dysfunction, Avlimil, stimulates the growth of estrogen-dependent breast tumors (MCF-7) implanted in ovariectomized athymic nude mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Avlimil; breast cancer; MCF-7; black cohosh root; licorice root; isoflavones ID CANCER CELLS; CIMICIFUGA-RACEMOSA; IN-VITRO; LIQUID-CHROMATOGRAPHY; ANTIOXIDANT CAPACITY; SALVIA-OFFICINALIS; RECEPTOR BETA; VITAMIN-C; GENISTEIN; PHYTOESTROGENS AB Avlimil, a dietary supplement advertised to ameliorate female sexual dysfunction, is a mixture of eleven herbal components, and some herbal constituents of Avlimil (including black cohosh, licorice, red raspberry, red clover and kudzu) contain phenolic compounds, which are suggested to have estrogenic, anti-estrogenic, or androgenic potential for relieving menopausal symptoms. We hypothesize that Avlimil could modulate the growth of estrogen receptor positive human breast cancer (MCF-7) cells in vitro and in vivo. A dimethylsulfoxide (DMSO) extract of Avlimil (0.001-100 mu g Avlimil powder equivalents/mL media) was tested for its estrogenic and anti-estrogenic effects on the growth of MCF-7 cells in vitro. We observed that the DMSO extract of Avlimil at low concentrations (0.1-50 mu g/mL media) dose-dependently increased MCF-7 cell proliferation in vitro, and Avlimil DMSO extract at 100 mu g/mL inhibited the growth of MCF-7 cells in vitro. Avlimil and some constituents (black cohosh and licorice roots) of Avlimil were fractionated by using sequential solvent extraction (hexane, ethyl acetate, and methanol) and the activities of the fractions were monitored by effects on the growth of MCF-7 cells. Depending on dosage (0.1-100 mu g/mL media) both stimulatory and inhibitory effects of the extracts on the growth of MCF-7 cells were observed. The effect of dietary Avlimil at dosages approximating human intake was evaluated using ovariectomized mice implanted with MCF-7 cells. Animals were fed diets containing 500 ppm or 1000 ppm Avlimil for 16 weeks. Dietary Avlimil at 500 ppm stimulated MCF-7 tumors, but Avlimil at 1000 ppm had no apparent effect on the growth of MCF-7 tumors. The observation of stimulated tumor growth in the absence of uterine wet weight gains suggest that estrogenic/anti-estrogenic effects of Avlimil we observed may be dosage-and target tissue-specific and that Avlimil may not be safe for women with estrogen-dependent breast cancer. The different biological effects of fractionated Avlimil components and the different concentration dependencies warrant further compound identification and dose-response studies, especially at recommended intake levels that could have estrogenic effects in women. (C) 2007 Published by Elsevier Ltd. C1 [Ju, Young H.; Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Doerge, Daniel R.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, 905 S Goodwin,Room 580 Bevier Hall, Urbana, IL 61801 USA. EM helferic@uiuc.edu FU NCI NIH HHS [CA77355]; NIA NIH HHS [P01 AG024387] NR 55 TC 9 Z9 11 U1 0 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 JAN PY 2008 VL 46 IS 1 BP 310 EP 320 DI 10.1016/j.fct.2007.08.006 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 260UW UT WOS:000253036900036 PM 17919800 ER PT J AU Schwartz, MI AF Schwartz, Mark I. TI To ban or not to ban - That is the question: The constitutionality of a moratorium on consumer drug advertising SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID RISK; FDA; METAANALYSIS; SUICIDE; TRIALS; SAFETY; KETEK C1 US FDA, Rockville, MD 20857 USA. RP Schwartz, MI (reprint author), US FDA, Rockville, MD 20857 USA. NR 44 TC 3 Z9 3 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2008 VL 63 IS 1 BP 1 EP 33 PG 33 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 272WA UT WOS:000253890700001 PM 18561453 ER PT J AU von Eschenbach, AC AF von Eschenbach, Andrew C. TI The FDA Amendments Act: Reauthorization of the FDA SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP von Eschenbach, AC (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2008 VL 63 IS 2 BP 579 EP 584 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 306KN UT WOS:000256247000010 PM 18561478 ER PT J AU Masoudi, GF AF Masoudi, Gerald F. TI Legal developments in the enforcement of food and drug law SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Masoudi, GF (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 1 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2008 VL 63 IS 2 BP 585 EP 592 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 306KN UT WOS:000256247000011 PM 18561479 ER PT S AU Turnipseed, SB Andersen, WC AF Turnipseed, Sherri B. Andersen, Wendy C. BE Pico, Y TI Veterinary Drug Residues SO FOOD CONTAMINANTS AND RESIDUE ANALYSIS SE Wilson and Wilsons Comprehensive Analytical Chemistry LA English DT Article; Book Chapter ID TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PRESSURE CHEMICAL-IONIZATION; BETA-LACTAM ANTIBIOTICS; PLASMON RESONANCE BIOSENSOR; MALACHITE GREEN RESIDUES; EDIBLE ANIMAL PRODUCTS; LC-ESI-MS/MS C1 [Turnipseed, Sherri B.; Andersen, Wendy C.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA. NR 232 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-526X BN 978-0-08-093192-0 J9 COMP ANAL C PY 2008 VL 51 BP 307 EP 338 DI 10.1016/S0166-526X(08)00010-X PG 32 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA BCR30 UT WOS:000311082100012 ER PT S AU Trucksess, MW Oles, CJ Weaver, CM White, KD Rader, JI AF Trucksess, Mary W. Oles, Carolyn J. Weaver, Carol M. White, Kevin D. Rader, Jeanne I. BE Siantar, DP Trucksess, MW Scott, PM Herman, EM TI Determination of Fumonisin B-1 in Botanical Roots SO FOOD CONTAMINANTS: MYCOTOXINS AND FOOD ALLERGENS SE ACS Symposium Series LA English DT Proceedings Paper CT 232nd National Meeting of the American-Chemical-Society (ACS) CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc (ACS) ID AFRICA; PLANTS AB Fumonisins are toxins produced mainly by the molds Fusarium verticillioides, F. proliferatum, and several other Fusarium species that grow on agricultural commodities in the field or during storage. More than ten types of fumonisins have been isolated and characterized. Fumonisin B-1 (FB1), B-2 (FB2) and B-3 (FB3) are the major fumonisins produced. FBI is the most prevalent and most toxic. Recently, fumonisins have been found in botanical roots. Fumonisins have produced liver damage and changes in the levels of certain classes of lipids, especially sphingolipids, in all animals studied. C1 [Trucksess, Mary W.; Oles, Carolyn J.; Weaver, Carol M.; White, Kevin D.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-6954-5 J9 ACS SYM SER JI ACS Symp. Ser. PY 2008 VL 1001 BP 266 EP 275 PG 10 WC Allergy; Chemistry, Multidisciplinary; Food Science & Technology; Toxicology SC Allergy; Chemistry; Food Science & Technology; Toxicology GA BKP80 UT WOS:000268886600014 ER PT S AU Westphal, CD AF Westphal, Carmen D. BE Siantar, DP Trucksess, MW Scott, PM Herman, EM TI Improvement of Immunoassays for the Detection of Food Allergens SO FOOD CONTAMINANTS: MYCOTOXINS AND FOOD ALLERGENS SE ACS SYMPOSIUM SERIES LA English DT Proceedings Paper CT 232nd National Meeting of the American-Chemical-Society CY SEP 10-14, 2006 CL San Francisco, CA SP Amer Chem Soc ID PEANUT ALLERGENS; PROTEINS; STABILITY AB The development of immunoassays for the detection of food allergens is a challenging task because the target is usually a complex mixture of allergenic and non-allergenic proteins of diverse structural and chemical properties. Moreover, the detection of these proteins might be affected differently by food processing. Consequently, it is difficult to predict which proteins are actually being detected by the immunoassay. Indeed, the protein profile in the sample extract might not be fully comparable to that of the calibrators, which brings up the question of accuracy in a quantitative assay. A better characterization of extracts from allergenic foods is needed in order to standardize, optimize, and validate the detection methodology. This chapter will highlight some of the proteomic tools to optimize the detection of food allergens. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Westphal, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-6954-5 J9 ACS SYM SER PY 2008 VL 1001 BP 448 EP 461 PG 14 WC Allergy; Chemistry, Multidisciplinary; Food Science & Technology; Toxicology SC Allergy; Chemistry; Food Science & Technology; Toxicology GA BKP80 UT WOS:000268886600029 ER PT J AU Lineback, DR AF Lineback, David R. TI Outstanding coverage of IFT Annual Meeting & Food Expo SO FOOD TECHNOLOGY LA English DT Letter C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. EM lineback@umd.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD JAN PY 2008 VL 62 IS 1 BP 72 EP 72 PG 1 WC Food Science & Technology SC Food Science & Technology GA 254VK UT WOS:000252615900020 ER PT J AU Tsai, P Cao, GL Merkel, TJ Rosen, GM AF Tsai, Pei Cao, Guan-Liang Merkel, Tod J. Rosen, Gerald M. TI Spin labelling of Bacillus anthracis endospores: A model for in vivo tracking by EPR imaging SO FREE RADICAL RESEARCH LA English DT Article DE Bacillus anthracis; electron paramagnetic resonance spectroscopy; maleimide-containing aminoxyls; acetoxymethoxycarbonyl-containing aminoxyls ID ALVEOLAR MACROPHAGES; SPORES; GERMINATION; IDENTIFICATION; PATHOGENESIS; SENSITIVITY; CELLS; MRI AB Anthrax is caused by the gram-negative bacterium, Bacillus anthracis. Infection by this microbe results from delivery of the endospore form of the bacillus through direct contact, either topical or inhalation. With regard to the latter route of administration, it is proposed that endospores of B. anthracis enter the lungs and are phagocytized by host alveolar macrophages. Thereafter, it is unclear as to how endospores travel to distal loci and what tissues are the targets. Herein, this study describes the spin labelling of endospores through two different approaches with various aminoxyls. Indeed, after exposure to RAW 264.7 cells, these aminoxyl-containing endospores were phagocytized, as demonstrated by EPR spectroscopy of the infected macrophage, thus providing a potential tool for EPR imaging in animals. C1 [Tsai, Pei; Cao, Guan-Liang; Rosen, Gerald M.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. [Tsai, Pei; Cao, Guan-Liang; Rosen, Gerald M.] Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Baltimore, MD 21201 USA. [Tsai, Pei; Cao, Guan-Liang; Rosen, Gerald M.] Univ Maryland, Sch Pharm, Ctr EPR Imaging Vivo Physiol, Baltimore, MD 21201 USA. [Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rosen, GM (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 725 W Lombard St, Baltimore, MD 21201 USA. EM grosen@umaryland.edu FU NIAID NIH HHS [U54 AI-057168]; NIBIB NIH HHS [EB-2034] NR 23 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD JAN PY 2008 VL 42 IS 1 BP 49 EP 56 DI 10.1080/10715760701787701 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 257KN UT WOS:000252798100006 PM 18324523 ER PT S AU Calvo, KR Liotta, LA Petricoin, EF AF Calvo, Katherine R. Liotta, Lance A. Petricoin, Emanuel F. BE Ilyin, S TI Use of Protein Microarrays for Molecular Network Analysis and Signal-Pathway Profiling SO FUNCTIONAL INFORMATICS IN DRUG DISCOVERY SE Drug Discovery Series LA English DT Article; Book Chapter ID TYROSINE KINASE INHIBITORS; B-CELL LYMPHOMA; GENE-EXPRESSION; CLINICAL PROTEOMICS; OVARIAN-CANCER; BREAST-CANCER; C-SRC; THERAPY; GROWTH; TRASTUZUMAB C1 [Calvo, Katherine R.; Liotta, Lance A.] NIH, Bethesda, MD 20892 USA. [Petricoin, Emanuel F.] US FDA, Bethesda, MD 20014 USA. RP Calvo, KR (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 48 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-5200 J9 DRUG DISCOV SER JI Drug Discov. Ser. PY 2008 VL 9 BP 115 EP 130 PG 16 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BKV58 UT WOS:000269400900007 ER PT S AU Gelderman, MP Simak, J AF Gelderman, Monique P. Simak, Jan BE Thompson, JD SchaefferReiss, C Ueffing, M TI Flow Cytometric Analysis of Cell Membrane Microparticles SO FUNCTIONAL PROTEOMICS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Cell membrane microparticles; membrane microvesicles; ectosomes; flow cytometry; monoclonal antibodies; endothelial cells; platelets; vascular diseases ID CIRCULATING ENDOTHELIAL MICROPARTICLES; THROMBOTIC THROMBOCYTOPENIC PURPURA; ACUTE CORONARY SYNDROMES; TISSUE-FACTOR; PLATELET MICROPARTICLES; DISEASE; MARKERS; BLOOD; ACTIVATION; GENERATION AB Cell membrane microparticles (MPs) are phospholipid microvesicles shed from the plasma membrane of most eukaryotic cells undergoing activation or apoptosis. The presence of MPs is common in healthy individuals. However, an increase in their release is a controlled event and is considered a hallmark of cellular alteration. Microparticles display cell surface proteins that indicate their cellular origin. In addition, they may also express other markers, e.g., markers of cellular activation. Elevated levels of circulating MPs are associated with various vascular pathologies and their pathogenic potential has been widely documented. MPs have been analyzed in plasma and cell cultures by means of flow cytometry or solid phase assays. Here we present a three-color flow cytometric assay for immunophenotyping of MPs in plasma. This assay has been used to study elevated counts of different phenotypes of circulating endothelial MPs in several hematological and vascular diseases. A modified version of this assay can also be used for MP analysis in blood products and cell cultures. C1 [Gelderman, Monique P.; Simak, Jan] US FDA, Lab Cellular Hematol, CBER, Rockville, MD 20857 USA. RP Gelderman, MP (reprint author), US FDA, Lab Cellular Hematol, CBER, Rockville, MD 20857 USA. NR 39 TC 50 Z9 52 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-58829-971-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2008 VL 484 BP 79 EP 93 D2 10.1007/978-1-59745-398-1 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKN86 UT WOS:000268729100006 PM 18592174 ER PT J AU Zwanziger, LL AF Zwanziger, Lee L. BE Monroe, KR Miller, RB Tobis, JS TI Roots and Branches of the US National Debate on Human Embryonic Stem Cell Research SO FUNDAMENTALS OF THE STEM CELL DEBATE: THE SCIENTIFIC, RELIGIOUS, ETHICAL, AND POLITICAL ISSUES LA English DT Article; Book Chapter ID SCIENCE POLICY; PUBLIC BIOETHICS; CONSENSUS; DISEASES; SOCIETY C1 [Zwanziger, Lee L.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [Zwanziger, Lee L.] US FDA, Rockville, MD 20857 USA. RP Zwanziger, LL (reprint author), Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. NR 49 TC 1 Z9 1 U1 0 U2 1 PU UNIV CALIFORNIA PRESS PI BERKELEY PA 2120 BERKELEY WAY, BERKELEY, CA 94720 USA BN 978-0-520-94099-4 PY 2008 BP 108 EP 133 PG 26 WC Cell & Tissue Engineering; Cell Biology; Ethics; Medical Ethics; Social Sciences, Interdisciplinary SC Cell Biology; Social Sciences - Other Topics; Medical Ethics GA BXA36 UT WOS:000295525300007 ER PT J AU Wagner, RD AF Wagner, Robert Doug TI Effects of microbiota on GI health: Gnotobiotic research SO GI MICROBIOTA AND REGULATION OF THE IMMUNE SYSTEM SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article ID CONGENITALLY IMMUNODEFICIENT MICE; ENTERICA SEROVAR TYPHIMURIUM; GERM-FREE MICE; SYSTEMIC CANDIDIASIS; ESCHERICHIA-COLI; PROBIOTIC BACTERIA; ORAL TOLERANCE; T-CELL; LACTOBACILLUS-ACIDOPHILUS; BIFIDOBACTERIUM-LONGUM AB The complex interactions between the GI tract microbiota and the immune system can be simplified for study using gnotobiotic animal models. The importance of cytokines, such as IFN-gamma, TNF-alpha, TGF-beta, Interleukin-2, IL-4 and IL-10 in the host response to intestinal bacteria has been evaluated using gnotobiotic studies. Gnotobiotic experiments with immuno-deficient animals have revealed insights into the relationships between innate, cell-mediated and antibody-mediated immune system components in resistance to infectious microorganisms. The development and maturation of the immune system is dependent on the presence of some members of the intestinal microbiota. The commensal microorganisms, in turn, are dependent on the environment and nutrients provided by the GI tract of the host. Gnotobiotic studies are starting to reveal how the microbiota influences oral tolerance to dietary and commensal bacterial antigens. The immunomodulatory effects of microbiota and probiotics for inflammatory bowel diseases and the role of bacteria in their etiologies are being studied in gnotobiotic systems. Many aspects of the host interaction with the microbiota have been and will continue to be best addressed in gnotobiotic experimental models. This chapter reviews the contributions that gnotobiology has made to our understanding of the microbiota and host GI tract health. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov NR 54 TC 22 Z9 24 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2008 VL 635 BP 41 EP 56 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BIF01 UT WOS:000259035100004 PM 18841702 ER PT J AU Lin, ZN Zhang, XM Tuo, JS Guo, YL Green, B Chan, CC Tan, W Huang, Y Ling, WH Kadlubar, FF Lin, DX Ning, BT AF Lin, Zhongning Zhang, Xuemei Tuo, Jingsheng Guo, Yongli Green, Bridgett Chan, Chi-Chao Tan, Wen Huang, Ying Ling, Wenhua Kadlubar, Fred F. Lin, Dongxin Ning, Baitang TI A variant of the Cockayne syndrome B gene cancer ERCC6 confers risk of lung cancer SO HUMAN MUTATION LA English DT Article DE polymorphism; lung cancer; DNA repair; susceptibility; ERCC6 ID DNA-REPAIR GENES; TRANSCRIPTION-COUPLED REPAIR; BASE EXCISION-REPAIR; TOBACCO-SMOKE CARCINOGENS; ENVIRONMENT INTERACTION; POLYMORPHISMS; DAMAGE; MICE; XRCC1; FIBROBLASTS AB Cockayne syndrome B protein (ERCC6) plays an essential role in DNA repair. However, the Cockayne syndrome caused by the ERCC6 defect has not been linked to cancer predisposition; likely due to the fact that cells with severe disruption of the ERCC6 function are sensitive to lesion,induced apoptosis, thus reducing the chance of tumorigenesis. The biological function and cancer susceptibility of a common variant rs3793784:C > G (c.-6530C > G) in the ERCC6 was examined. We show that the c.-6530C allele has lower binding affinity of Sp1 by EMSA and displays a lower transcriptional activity in vitro and in vivo. We then examined the contribution of this polymorphism to the risk of lung cancer in a case-control study with 1,000 cases and 1,000 controls. The case-control analysis revealed a 1.76-fold (P = x 10(-9)) excess risk of developing lung cancer for the c.-6530CC carriers compared with noncarriers. The c.-6530CC interacts with smoking to intensify lung cancer risk, with the odds ratio (OR) = 9 for developing lung cancer among heavy smokers. Our data constituted strong evidence that ERCC6 rs3793784:C > G alters its transcriptional activity and may confer personalized susceptibility to lung cancer. C1 [Zhang, Xuemei; Guo, Yongli; Tan, Wen; Lin, Dongxin] Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. [Zhang, Xuemei; Guo, Yongli; Tan, Wen; Lin, Dongxin] Peking Union Med Coll, Beijing, Peoples R China. [Lin, Zhongning; Green, Bridgett; Huang, Ying; Ning, Baitang] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Tuo, Jingsheng] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lin, Zhongning; Ling, Wenhua] Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Peoples R China. [Kadlubar, Fred F.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. RP Lin, DX (reprint author), Chinese Acad Med Sci, Canc Hosp & Inst, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. EM dlin@public.bta.net.cn; baitang.ning@fda.hhs.gov RI zhang, xuemei/F-3818-2010 FU Intramural NIH HHS [Z01 EY000418-04]; PHS HHS [E0702101] NR 48 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JAN PY 2008 VL 29 IS 1 BP 113 EP 122 DI 10.1002/humu.20610 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 248HK UT WOS:000252143300017 PM 17854076 ER PT J AU Ilev, IK Wilson, BC Backman, V Andersson-Engels, S AF Ilev, I. K. Wilson, B. C. Backman, V. Andersson-Engels, S. TI Introduction to the special issue on biophotonics - Part 2 SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 [Ilev, I. K.] US FDA, Silver Spring, MD USA. [Wilson, B. C.] Univ Toronto, Canadian Inst Photon Innovat, Toronto, ON M5G 2M9, Canada. [Backman, V.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Andersson-Engels, S.] Lund Univ, Div Atom Phys, SE-22100 Lund, Sweden. RP Ilev, IK (reprint author), US FDA, Silver Spring, MD USA. EM ilko.ilev@fda.hhs.gov; wilson@uhnres.utoronto.ca; v-backman@northwestern.edu; Stefan.Andersson-Etigels@fysik.lth.se RI Backman, Vadim/B-6689-2009; Andersson-Engels, Stefan/C-5515-2012 OI Andersson-Engels, Stefan/0000-0001-5640-3122 NR 0 TC 1 Z9 1 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JAN-FEB PY 2008 VL 14 IS 1 BP 1 EP 3 DI 10.1109/JSTQE.2007.915922 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 268DH UT WOS:000253558100001 ER PT J AU Kim, DH Ilev, IK Kang, JU AF Kim, Do-Hyun Ilev, IlKo K. Kang, Jin U. TI Fiberoptic confocal microscopy using a 1.55-mu m fiber laser for multimodal biophotonics applications SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE biomedical optical imaging; microscopy; optical fiber applications ID LIGHT AB We have experimentally demonstrated a fiberoptic confocal microscope using a 1.55-mu m laser source. A compact and efficient Er-doped fiber laser source and conventional single-mode fiber components were used to construct a near-infrared fiberoptic confocal microscope system with 3-D scanning capability. A broadband 1.55-mu m light source was used to reduce fringe patterns and interferences that occur when a highly coherent source is used. Our system showed a lateral resolution as high as 1.1 mu m with a 60x objective lens, which is close to the theoretical limit. The system can be used in various multimodal biophotonics platforms including precise 3-D imaging, biosensing, and laser tissue ablation due to its high water absorption characteristics while maintaining low thermomechanical and self-focusing damage from high-power lasers. C1 [Kim, Do-Hyun; Ilev, IlKo K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov; ilko.ilev@fda.hhs.gov; jkang@jhu.edu RI Kim, Do-Hyun/C-5311-2009; Kang, Jin/A-3228-2010 NR 13 TC 5 Z9 5 U1 1 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JAN-FEB PY 2008 VL 14 IS 1 BP 82 EP 87 DI 10.1109/JSTQE.2007.914589 PG 6 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 268DH UT WOS:000253558100011 ER PT J AU Anders, JJ Romanczyk, TB Ilev, IK Moges, H Longo, L Wu, XJ Waynant, RW AF Anders, Juanita J. Romanczyk, Tara B. Ilev, Ilko K. Moges, Helina Longo, Leonardo Wu, Xingjia Waynant, Ronald W. TI Light supports neurite outgrowth of human neural progenitor cells in vitro: The role of P2Y receptors SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE adenosine triphosphate (ATP); growth factors; light-stimulated neurite outgrowth; neuritogenesis; receptor immunolabeling ID POWER LASER IRRADIATION; RAT-LIVER MITOCHONDRIA; CYTOCHROME-C-OXIDASE; HELIUM-NEON LASER; GROWTH-FACTOR; MYOCARDIAL-INFARCTION; NEURONAL CELLS; STEM-CELLS; ATP; BRAIN AB The purpose of this study was to compare the effects of growth factors and 810-nm-wavelength light on the differentiation of normal human neural progenitor cells (NHNPCs) in vitro. Although growth factors are routinely used to study neural stem and progenitor cells in vitro, to date, light has not been used as a replacement for growth factors. This study demonstrates that NHNPCs are not only capable of being sustained by light in the absence of growth factors, but that they are also able to differentiate normally as assessed by neurite formation. The NHNPCs had an up-regulation in the expression of endogenous fibroblast growth factor-2, brain derived neurotrophic factor, and nerve growth factor in response to the light. Suramin, a nonselective P2 receptor antagonist, significantly decreased neurite outgrowth, and P2Y2 and P2Y11 receptors were found to be expressed by the NHNPCs by immunolabeling. Based on these findings, the mechanism by which light supports the NHNPC differentiation is hypothesized to be due to increases in adenosine triphosphate acting via P2Y receptors. C1 [Anders, Juanita J.; Romanczyk, Tara B.; Ilev, Ilko K.; Wu, Xingjia] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. [Ilev, Ilko K.; Waynant, Ronald W.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Longo, Leonardo] Univ Siena, Inst Laser Med, I-53100 Siena, Italy. [Longo, Leonardo] Univ San Marino, San Marino 47890, San Marino. RP Anders, JJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. EM janders@usuhs.mil; tromanczyk@usuhs.mil; ilko.ilev@fda.hhs.gov; hmoges@usuhs.mil; longo@dada.it; xiwu@usuhs.mil; waynant@fda.hhs.gov NR 39 TC 20 Z9 21 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD JAN-FEB PY 2008 VL 14 IS 1 BP 118 EP 125 DI 10.1109/JSTQE.2007.916181 PG 8 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 268DH UT WOS:000253558100016 ER PT J AU Zhao, SH AF Zhao, Shaohua BE Doyle, MP Erickson, MC TI Antimicrobial-Resistant Food-Borne Pathogens in Imported Food SO IMPORTED FOODS: MICROBIOLOGICAL ISSUES AND CHALLENGES SE Emerging Issues in Food Safety LA English DT Article; Book Chapter ID SALMONELLA-ENTERICA SEROTYPES; ANTIBIOTIC-RESISTANCE; CAMPYLOBACTER-JEJUNI; HUMAN HEALTH; NONTYPHOIDAL SALMONELLA; DRUG-RESISTANCE; VIBRIO-CHOLERAE; ANIMALS; INFECTIONS; TYPHIMURIUM C1 US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Zhao, SH (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 76 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-413-7 J9 EMERG ISS FOOD SAF JI Emerg. Iss. Food Safety PY 2008 BP 159 EP 185 PG 27 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ49 UT WOS:000278999400008 ER PT J AU Wood, GE AF Wood, Garnett E. BE Doyle, MP Erickson, MC TI Mycotoxin Contamination of Foods from around the World SO IMPORTED FOODS: MICROBIOLOGICAL ISSUES AND CHALLENGES SE Emerging Issues in Food Safety LA English DT Article; Book Chapter ID OCHRATOXIN-A; DRIED FRUITS; BRAZIL NUTS; PATULIN; CORN; DEOXYNIVALENOL; ASPERGILLUS; FUMONISINS; AFLATOXINS; TOXICOLOGY C1 US FDA, Off Food Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wood, GE (reprint author), US FDA, Off Food Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-413-7 J9 EMERG ISS FOOD SAF JI Emerg. Iss. Food Safety PY 2008 BP 187 EP 208 PG 22 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BPJ49 UT WOS:000278999400009 ER PT S AU Reimschuessel, R AF Reimschuessel, R. BE Lie, O TI Assessing the human health implications of new veterinary drugs used in fish farming SO IMPROVING FARMED FISH QUALITY AND SAFETY SE Woodhead Publishing in Food Science Technology and Nutrition LA English DT Article; Book Chapter ID TROUT ONCORHYNCHUS-MYKISS; TEMPERATURE-RELATED ABSORPTION; SALMON SALMO-SALAR; TETRACYCLINE RESISTANCE GENE; PERSONAL CARE PRODUCTS; CYPRINUS-CARPIO L; RAINBOW-TROUT; OXOLINIC ACID; FRESH-WATER; WASTE-WATER C1 US FDA, VMD, Res Off, Laurel, MD 20708 USA. RP Reimschuessel, R (reprint author), US FDA, VMD, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM rreimsch@cvm.fda.gov NR 170 TC 4 Z9 4 U1 0 U2 0 PU WOODHEAD PUBL LTD PI CAMBRIDGE PA ABINGTON HALL ABINGTON, CAMBRIDGE CB1 6AH, CAMBS, ENGLAND SN 2042-8049 BN 978 1 84569 299 5 J9 WOODHEAD PUBL FOOD S JI Woodhead Publ. Food Sci. Technol. Nutr. PY 2008 IS 162 BP 128 EP 156 DI 10.1533/9781845694620.1.128 PG 29 WC Fisheries; Food Science & Technology SC Fisheries; Food Science & Technology GA BOI00 UT WOS:000276686000006 ER PT J AU Aravind, L Iyer, LM Oakley, M Kumar, S Anantharaman, V McCutchan, TF AF Aravind, L. Iyer, Lakshminarayan M. Oakley, Miranda Kumar, Sanjai Anantharaman, Vivek McCutchan, Thomas F. TI From genomes to biology: apprehending apicomplexan parasitism and resultant host responses. SO INTERNATIONAL JOURNAL FOR PARASITOLOGY LA English DT Meeting Abstract CT 3rd Molecular Approaches to Malaria Meeting (MAM 2008) CY FEB 03-07, 2008 CL Lorne, AUSTRALIA SP BioMalPar, Boehringer Ingelheim Foods, Burroughs Wellcome Fund, Fdn Natl Inst Hlth, PATH Malaria Vaccine Initiative, Walter & Eliza Hall Inst Med Res, Wellcome Trust, ARC/NHMRC Net Parasitol, Australian Soc Biochem & Molecular Biol, Lorne Protein Conf, GlaxoSmithKline C1 [Aravind, L.; Iyer, Lakshminarayan M.; Anantharaman, Vivek] NIH, Natl Library Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Oakley, Miranda; Kumar, Sanjai] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Trasmitted Dis, Rockville, MD 20857 USA. [McCutchan, Thomas F.] NIH, NIAID, Lab Malaria & Vector Res, Rockville, MD 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 0020-7519 J9 INT J PARASITOL JI Int. J. Parasit. PD JAN PY 2008 VL 38 SU 1 MA 38 BP S27 EP S27 PG 1 WC Parasitology SC Parasitology GA 262CW UT WOS:000253127600040 ER PT J AU Khan, SA Sung, K Layton, S Nawaz, MS AF Khan, Saeed A. Sung, Kidon Layton, Sherryll Nawaz, Mohamed S. TI Heteroresistance to vancomycin and novel point mutations in. Tn1546 of Enterococcus faecium ATCC 51559 SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE vancomycin-resistant enterococci; polymerase chain reaction; restriction fragment length polymorphism; pulsed-field gel electrophoresis; insertion element ID VANA GLYCOPEPTIDE RESISTANCE; DEPSIPEPTIDE PEPTIDOGLYCAN PRECURSORS; INSERTION SEQUENCES; MOLECULAR ANALYSIS; ELEMENTS; HUMANS; DIVERSITY; STRAINS; BM4147; LEVEL AB A clinical strain of Enterococcus faecium ATCC 51559 exhibits heteroresistance, i.e. a high level of resistance to vancomycin (minimum inhibitory concentration (MIC)>256 mu g/mL) by broth dilution but sensitivity to vancomycin by Etest (MIC = 1.8 mu g/mL). Three variants of this strain, EFl, EF2 and EF3, exhibit high levels of resistance to vancomycin both by broth dilution and Etest assays. The four strains were used to study heteroresistance by pulsed-field gel electrophoresis (PFGE), polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and sequence analysis of a partial region of the van operon. Minor differences between SalI and SmaI restriction profiles of the variants and the parental strain were observed by PFGE analysis. PCR analysis confirmed the presence of the vancomycin resistance marker vanA (0.73 kb) and a larger than expected amplicon (8.2 kb vs. 6.7 kb) of the van operon in all the strains. The 8.2 kb van operon was cloned for EcoRI RFLP and sequence analysis. All of the clones exhibited distinctly different RFLP profiles when grown in the presence of kanamycin or vancomycin + kanamycin. The presence of these antibiotics during overnight growth of EF1 on plates also resulted in altered SalI PFGE profiles. Sequence analysis of the van operon clones revealed a 1.5 kb IS.1251-like insertion element between the vanS and vanH genes in all the strains. Several novel point mutations in the vanR, vanS, vanH, vanA, vanX and vanY genes were also discovered. Some of these mutations were present in the parental strain only and included base substitutions T -> C, A -> G, T ->. A and T -> C at nucleotide positions 4202, 4597, 4763 and 6207 of Tn1546, resulting in amino acid replacements 176 -> T and K208 -> E of vanR, S19 -> T of vanS and L64 -> P of vanH genes, respectively. We believe that these are responsible for the observed heteroresistance. The present study clearly shows how independent novel mutations can give rise to polymorphism, heteroresistance and clonal diversity among vancomycin-resistant enterococci strains as a result of continuous exposure to antibiotics. Published by Elsevier B.V. on behalf of International Society of Chemotherapy. C1 [Khan, Saeed A.; Sung, Kidon; Layton, Sherryll; 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 35 TC 12 Z9 12 U1 0 U2 2 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 JAN PY 2008 VL 31 IS 1 BP 27 EP 36 DI 10.1016/j.ijantimicag.2007.08.007 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 253IT UT WOS:000252512600005 PM 17936593 ER PT J AU Su, YA Wu, J Zhang, L Zhang, QY Su, DM He, P Wang, BD Li, H Webster, MJ Rennert, OM Ursano, RJ AF Su, Yan A. Wu, Jun Zhang, Lei Zhang, Qiuyang Su, David M. He, Ping Wang, Bi-Dar Li, He Webster, Maree J. Rennert, Owen M. Ursano, Robert J. CA Traumatic Stress Brain Study Grp TI Dysregulated Mitochondrial Genes and Networks with Drug Targets in Postmortem Brain of Patients with Posttraumatic Stress Disorder (PTSD) Revealed by Human Mitochondria-Focused cDNA Microarrays SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE PTSD; Brain dorsolateral prefrontal cortex BA46; Gene expression pattern; Biomarker; Mitochondria; Canonical pathways; Molecular networks; Neuropsychiatric drug targets ID AMYLOID PRECURSOR PROTEIN; ONSET ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; PERIPHERAL-BLOOD; EXPRESSION; DYSFUNCTION; APOPTOSIS; MECHANISM; OXIDASE; ANXIETY AB Posttraumatic stress disorder (PTSD) is associated with decreased activity in the dorsolateral prefrontal cortex (DLPFC), the brain region that regulates working memory and preparation and selection of fear responses. We investigated gene expression profiles in DLPFC Brodmann area (BA) 46 of postmortem patients with (n=6) and without PTSD (n=6) using human mitochondria-focused cDNA microarrays. Our study revealed PTSD-specific expression fingerprints of 800 informative mitochondria-focused genes across all of these 12 BA46 samples, and 119 (+/->1.25, p<0.05) and 42 (+/->1.60, p<0.05) dysregulated genes between the PTSD and control samples. Quantitative RT-PCR validated the microarray results. These fingerprints can essentially distinguish the PTSD DLPFC BA46 brains from controls. Of the 119 dysregulated genes (+/->= 125%, p<0.05), the highest percentages were associated with mitochondrial dysfunction (4.8%, p=6.61x10(-6)), oxidative phosphorylation (3.8%, p=9.04x10(-4)), cell survival-apoptosis (25.2%, p<0.05) and neurological diseases (23.5%, p<0.05). Fifty (50) dysregulated genes were present in the molecular networks that are known to be involved in neuronal function-survival and contain 7 targets for neuropsychiatric drugs. Thirty (30) of the dysregulated genes are associated with a number of neuropsychiatric disorders. Our results indicate mitochondrial dysfunction in the PTSD DLPFC BA46 and provide the expression fingerprints that may ultimately serve as biomarkers for PTSD diagnosis and the drugs and molecular targets that may prove useful for development of remedies for prevention and treatment of PTSD. C1 [Su, Yan A.; Wu, Jun; Zhang, Qiuyang; Su, David M.; Wang, Bi-Dar] George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Su, Yan A.; Wu, Jun; Zhang, Qiuyang; Su, David M.; Wang, Bi-Dar] George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. [Zhang, Lei; Li, He; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Zhang, Lei; Li, He; Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Ctr Study Traumat Stress, Bethesda, MD 20814 USA. [He, Ping] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Webster, Maree J.] Stanley Med Res Inst, Chevy Chase, MD 20894 USA. [Rennert, Owen M.] NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. RP Su, YA (reprint author), Ross Hall,Room 555,2300 I St NW, Washington, DC 20037 USA. EM bcmyas@gwumc.edu FU Catherine McCormick Genomics Center; St. Laurant Institution; USUHS; FDA; Stanley Medical Research Institute; NICHD/NIH; [NIH-NIDDK-06-925]; [HU0001-07-M-V451] FX We thank Drs. Ron Duman and John Krystal at Yale University for critical review and helpful discussions of the manuscript. YAS, JW, QZ and BW were supported by the Catherine McCormick Genomics Center, NIH-NIDDK-06-925, the St. Laurant Institution and HU0001-07-M-V451; and LZ, HL and RJU by USUHS; PH by FDA, MJW by Stanley Medical Research Institute; and OMR by NICHD/NIH. DMS is a special volunteer from Walt Whitman High School. NR 48 TC 38 Z9 38 U1 0 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 4 BP 223 EP 235 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 367FE UT WOS:000260537100005 PM 18690294 ER PT J AU Zhang, XC Hashemi, SS Yousefi, M Ni, JS Wang, QY Gao, L Gong, PT Gao, CL Sheng, J Mason, J Man, YG AF Zhang, Xichen Hashemi, Shahreyar Shar Yousefi, Morvarid Ni, Jinsong Wang, Qiuyue Gao, Ling Gong, Pengtao Gao, Chunling Sheng, Joy Mason, Jeffrey Man, Yan-gao TI Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers: a trigger or sign for emergence of more aggressive cell clones? SO INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES LA English DT Article DE Tumor invasion; myoepithelial cells; c-erbB2; tumor stem cells; monoclonal proliferation ID MAMMARY EPITHELIAL-CELLS; CARCINOMA IN-SITU; MOLECULAR-DYNAMICS SIMULATIONS; CANCER DNA PHENOTYPE; TUMOR INVASION; BASEMENT-MEMBRANE; GENE-EXPRESSION; MESSENGER-RNA; PROLIFERATION; PROGRESSION AB Our recent studies revealed that cell clusters overlying focal myoepithelial cell layer disruption (FMCLD) had a significantly higher frequency of genetic instabilities and expression of invasion-related genes than their adjacent counterparts within the same duct. Our current study attempted to assess whether these cell clusters would also have elevated c-erbB2 expression. Human breast tumors (n=50) with a high frequency of FMCLD were analyzed with double immunohistochemistry, real-time RT-PCR, and chromogenic in situ hybridization for c-erbB2 protein and gene expression. Of 448 FMCLD detected, 404 (90.2%) were associated with cell clusters that had intense c-erbB2 immunoreactivities primarily in their cytoplasm, in contrast to their adjacent counterparts within the same duct, which had no or barely detectable c-erbB2 expression. These c-erbB2 positive cells were arranged as tongue-like projections, "puncturing" into the stroma, and about 20% of them were in direct continuity with tube-like structures that resembled blood vessels. Aberrant c-erbB2 expression was also seen in clusters of architecturally normal-appearing ducts that had distinct cytological abnormalities in both ME and epithelial cells, whereas not in their clear-cut normal counterparts. Molecular assays detected markedly higher c-erbB2 mRNA and gene amplification in cell clusters associated with FMCLD than in those associated with non-disrupted ME cell layers. Our findings suggest that cell clusters overlying FMCLD may represent the precursors of pending invasive lesions, and that aberrant cerbB2 expression may trigger or signify the emergence of biologically more aggressive cell clones. C1 [Man, Yan-gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Gynecol & Breast Res Lab, Washington, DC 20306 USA. [Mason, Jeffrey; Man, Yan-gao] Amer Registry Pathol, Washington, DC USA. [Zhang, Xichen; Wang, Qiuyue; Gao, Ling; Gong, Pengtao] Jilin Univ, Coll Anim Sci & Vet Med, Changchun, Jilin, Peoples R China. [Hashemi, Shahreyar Shar; Yousefi, Morvarid] Staten Isl Univ Hosp, Dept Surg, Staten Isl, NY USA. [Hashemi, Shahreyar Shar; Yousefi, Morvarid] Staten Isl Univ Hosp, Dept Internal Med, Staten Isl, NY USA. [Ni, Jinsong] Jilin Univ, Norman Bethune Coll Med Sci, Changchun, Jilin, Peoples R China. [Gao, Chunling] US FDA, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. [Sheng, Joy] Appl Biosyst Inc, Real Time PCR Tech Support Dept, Foster City, CA USA. RP Man, YG (reprint author), Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Gynecol & Breast Res Lab, 6825 16th St,NW, Washington, DC 20306 USA. EM man@afip.osd.mil FU Ministry of Chinese Science and Technology Department [2006CB910505]; US Congressionally Directed Medical Research Programs [DAMD17-01-1-0129, AMD17-01-1-0130, PC051308]; Susan G. Komen Breast Cancer Foundation [BCTR0706983]; AFIP/ARP [05AA] FX This study was supported in part by grant 2006CB910505 from the Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang and Yan-gao Man, and also by grants DAMD17-01-1-0129, AMD17-01-1-0130, and PC051308 from the US Congressionally Directed Medical Research Programs, grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation, and grant 05AA from the AFIP/ARP joint research initiative project to Dr. Yan-gao Man. NR 56 TC 11 Z9 11 U1 0 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1449-2288 J9 INT J BIOL SCI JI Int. J. Biol. Sci. PY 2008 VL 4 IS 5 BP 259 EP 269 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 367FF UT WOS:000260537200001 PM 18726004 ER PT J AU Gelderman, MP Simakova, O Clogston, JD Patri, AK Siddiqui, SF Vostal, AC Simak, J AF Gelderman, Monique P. Simakova, Olga Clogston, Jeffrey D. Patri, Anil K. Siddiqui, Sheena F. Vostal, Alexander C. Simak, Jan TI Adverse effects of fullerenes on endothelial cells: Fullerenol C-60(OH)(24) induced tissue factor and ICAM-1 membrane expression and apoptosis in vitro SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE endothelial cells; fullerenes; tissue factor; apoptosis; ICAM-1; flow cytometry ID WATER-SOLUBLE FULLERENE; CARBON NANOTUBES; POLYHYDROXYLATED C-60; LIPID-PEROXIDATION; SUBACUTE TOXICITY; OXIDATIVE STRESS; MECHANISMS; CARBOXYFULLERENE; MICROPARTICLES; CYTOTOXICITY AB We studied the effects of a C-60 water suspension at 4 mu g/mL (nC(60)) and the water soluble fullerenol C-60(OH)(24) at final concentrations of 1-100 mu g/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C-60(OH)(24) at 100 mu g/mL significantly increased cell surface expression of ICAM-1(CD54) (67 +/- 4%, CD54(+) cells vs. 19 +/- 2% CD54(+) cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD 142) on HUVECs (54 +/- 20% CD142(+) cells vs 4 +/- 2% CD142(+) cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 +/- 2% PS+ cells vs. 12 +/- 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC(60) and C-60(OH)(24) caused G1 arrest of HUVECs and C-60(OH)(24) induced significant apoptosis (21 +/- 2% TUNEL+ cells at 100 mu g/mL of C-60(OH)(24) vs. 4 +/- 2%, TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC(60) and C-60(OH)(24) induced a rapid concentration dependent elevation of intracellular calcium [Ca2+](i). This could be inhibited by EGTA, suggesting that the source of [Ca2+](i) in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C-60(OH)(24) had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium. C1 [Gelderman, Monique P.; Siddiqui, Sheena F.; Vostal, Alexander C.; Simak, Jan] US FDA, CBER, Rockville, MD 20852 USA. [Simakova, Olga] USUHS, Sch Med, Bethesda, MD USA. [Clogston, Jeffrey D.; Patri, Anil K.] SAIC Frederick, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD USA. RP Simak, J (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov RI Simak, Jan/C-1153-2011; Nanotechnology Characterization Lab, NCL/K-8454-2012 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 38 TC 43 Z9 44 U1 0 U2 10 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-9114 J9 INT J NANOMED JI Int. J. Nanomed. PY 2008 VL 3 IS 1 BP 59 EP 68 PG 10 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA 313DY UT WOS:000256722500006 PM 18488416 ER PT J AU Ahmad, IU Forman, JD Sarkar, F Hillman, G Banerjee, M Doerge, D Heath, E Vaishampayan, U Cher, M Kucuk, O AF Ahmad, I. U. Forman, J. D. Sarkar, F. Hillman, G. Banerjee, M. Doerge, D. Heath, E. Vaishampayan, U. Cher, M. Kucuk, O. TI Reduction of adverse events by soy isoflavones in patients undergoing external beam radiation therapy for prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and Oncology CY SEP 21-25, 2008 CL Boston, MA SP Amer Soc Therapeut Radiol & Oncol C1 [Ahmad, I. U.; Sarkar, F.; Hillman, G.; Heath, E.; Vaishampayan, U.; Cher, M.; Kucuk, O.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Forman, J. D.] Wayne State Univ, Farmington Hills, MI USA. [Banerjee, M.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Doerge, D.] US FDA, Jefferson, AR USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PY 2008 VL 72 IS 1 SU S BP S318 EP S318 DI 10.1016/j.ijrobp.2008.06.1096 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 342TB UT WOS:000258805301187 ER PT J AU Burns-Naas, LA Hastings, KL Ladics, GS Makris, SL Parker, GA Holsapple, MP AF Burns-Naas, Leigh Ann Hastings, Kenneth L. Ladics, Gregory S. Makris, Susan L. Parker, George A. Holsapple, Michael P. TI What's so special about the developing immune system? SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Review DE developmental immunotoxicology; DIT; immune development immune system; immune testing; immunopathology ID DEVELOPMENTAL IMMUNOTOXICOLOGY ASSESSMENT; SPRAGUE-DAWLEY RATS; POLYCHLORINATED-BIPHENYLS; CRITICAL WINDOWS; RISK-ASSESSMENT; EARLY-CHILDHOOD; ASTHMA PREVENTION; CHILDRENS HEALTH; NONHUMAN PRIMATE; ADULT EXPOSURES AB The evolution of the subdiscipline of developmental immunotoxicology (DIT) as it exists today has been shaped by significant regulatory pressures as well as key scientific advances. This review considers the role played by legislation to protect children's health, and on the emergence of immunotoxcity and developmental immunotoxicity guidelines, as well as providing some context to the need for special attention on DIT by considering the evidence that the developing immune system may have unique susceptibilities when compared to the adult immune system. Understanding the full extent of this potential has been complicated by a paucity of data detailing the development of the immune system during critical life stages as well as by the complexities of comparisons across species. Notably, there are differences between humans and nonhuman species used in toxicity testing that include specific differences relative to the timing of the development of the immune system as well as more general anatomic differences, and these differences must be factored into the interpretation of DIT studies. Likewise, understanding how the timing of the immune development impacts on various immune parameters is critical to the design of DIT studies, parameters most extensively characterized to date in young adult animals. Other factors important to DIT, which are considered in this review, are the recognition that effects other than suppression (e. g., allergy and autoimmunity) are important; the need to improve our understanding of how to assess the potential for DIT in humans; and the role that pathology has played in DIT studies in test animals. The latter point receives special emphasis in this review because pathology evaluations have been a major component of standard nonclinical toxicology studies, and could serve an important role in studies to evaluate DIT. This possibility is very consistent with recommendations to incorporate a DIT evaluation into standard developmental and reproductive toxicology (DART) protocols. The overall objective of this review is to provide a 'snapshot' of the current state-of-the-science of DIT. Despite significant progress, DIT is still evolving and it is our hope that this review will advance the science. C1 [Burns-Naas, Leigh Ann] Pfizer Global Res & Dev, Drug Safety Res & Dev, San Diego, CA 92064 USA. [Hastings, Kenneth L.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. [Ladics, Gregory S.] DuPont Co Inc, Expt Stn, Wilmington, DE USA. [Makris, Susan L.] US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Parker, George A.] WIL Biotech Inc, Hillsborough, NC USA. [Holsapple, Michael P.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. RP Burns-Naas, LA (reprint author), Pfizer Global Res & Dev, Drug Safety Res & Dev, 10777 Sci Ctr Dr, San Diego, CA 92064 USA. EM leighann.burns@pfizer.com NR 130 TC 43 Z9 47 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PY 2008 VL 27 IS 2 BP 223 EP 254 DI 10.1080/10915810801978110 PG 32 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 316HO UT WOS:000256940400006 PM 18404545 ER PT J AU Buckley, LA Benson, K Davis-Bruno, K Dempster, M Finch, GL Harlow, P Haggerty, HG Hart, T Kinter, L Leighton, JK McNulty, J Roskos, L Saber, H Stauber, A Tabrizi, M AF Buckley, L. A. Benson, K. Davis-Bruno, K. Dempster, M. Finch, G. L. Harlow, P. Haggerty, H. G. Hart, T. Kinter, L. Leighton, J. K. McNulty, J. Roskos, L. Saber, H. Stauber, A. Tabrizi, M. TI Nonclinical aspects of biopharmaceutical development: Discussion of case studies at a PhRMA-FDA workshop SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE biopharmaceuticals; nonclinical; regulatory; safety assessment ID MONOCLONAL-ANTIBODIES; PERSPECTIVE; SAFETY AB Robust assessments of the nonclinical safety profile of biopharmaceuticals are best developed on a scientifically justified, case-by-case basis, with consideration of the therapeutic molecule, molecular target, and differences/similarities between nonclinical species and humans (ICH S6). Significant experience has been gained in the 10 years ensuing since publication of the ICH S6 guidance. In a PhRMA-FDA-sponsored workshop, Nonclinical Aspects of Biopharmaceutical Development, industry and US regulatory representatives engaged in exploration of current scientific and regulatory issues relating to the nonclinical development of biopharmaceuticals in order to share scientific learning and experience and to work towards establishing consistency in application of general principles and approaches. The proceedings and discussions of this workshop confirm general alignment of strategy and tactics in development of biopharmaceuticals with regard to such areas as species selection, selection of high doses in toxicology studies, selection of clinical doses, the conduct of developmental and reproductive toxicity (DART) studies, and assessment of carcinogenic potential. However, several important aspects, including, for example, appropriate use of homologues, nonhuman primates, and/or in vitro models in the assessment of risk for potential developmental and carcinogenic effects, were identified as requiring further scientific exploration and discussion. C1 [Buckley, L. A.; Stauber, A.] Eli Lilly & Co, Greenfield, IN USA. [Benson, K.; Davis-Bruno, K.; Harlow, P.; Leighton, J. K.; Saber, H.] US FDA, Silver Spring, MD USA. [Dempster, M.] GlaxoSmithKline Inc, Ware, Herts, England. [Finch, G. L.] Pfizer Inc, Groton, CT 06340 USA. [Haggerty, H. G.] Bristol Myers Squibb Co, E Syracuse, NY USA. [Hart, T.] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Kinter, L.] AstraZeneca, Wilmington, DE USA. [McNulty, J.] AstraZeneca, Waltham, MA USA. [Roskos, L.; Tabrizi, M.] Medimmune Inc, Hayward, CA USA. RP Buckley, LA (reprint author), Eli Lilly & Co, Lilly Corp Ctr, DC 1940, Indianapolis, IN 46285 USA. EM BuckleyLA@lilly.com NR 19 TC 13 Z9 14 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PY 2008 VL 27 IS 4 BP 303 EP 312 DI 10.1080/10915810802367016 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 354NE UT WOS:000259645500001 PM 18821393 ER PT B AU Losikoff, M AF Losikoff, Mary BE Kramer, DE Brown, L TI Clostridium botulinum concerns SO INTERNATIONAL SMOKED SEAFOOD CONFERENCE PROCEEDINGS SE UNIVERSITY OF ALASKA SEA GRANT COLLEGE PROGRAM REPORT LA English DT Proceedings Paper CT International Smoked Seafood Conference CY MAR 05-07, 2007 CL Anchorage, AK SP Alaska Fisheries Dev Fdn, Alaska Sea Grant, Alaska Seafood Marketing Inst, Calif Sea Grant, Pollock Conservat Cooperat Res Ctr, PURAC Amer, State Alaska Fisheries Revitalizat Strategy, Washing State Univ Extens, Univ Minnesota Ctr Farm Financial Management C1 US FDA, College Pk, MD USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ALASKA SEA GRANT COLL PROGRAM PI FAIRBANKS PA UNIV ALASKA FAIRBANKS PO BOX 755040, FAIRBANKS, AK 99775-5040 USA BN 978-1-56612-127-9 J9 UASGCP REP PY 2008 VL 2008 IS 02 BP 5 EP 7 PG 3 WC Business; Food Science & Technology SC Business & Economics; Food Science & Technology GA BHU86 UT WOS:000256571100002 ER PT B AU Vik, J AF Vik, Jim BE Kramer, DE Brown, L TI HACCP plan SO INTERNATIONAL SMOKED SEAFOOD CONFERENCE PROCEEDINGS SE UNIVERSITY OF ALASKA SEA GRANT COLLEGE PROGRAM REPORT LA English DT Proceedings Paper CT International Smoked Seafood Conference CY MAR 05-07, 2007 CL Anchorage, AK SP Alaska Fisheries Dev Fdn, Alaska Sea Grant, Alaska Seafood Marketing Inst, Calif Sea Grant, Pollock Conservat Cooperat Res Ctr, PURAC Amer, State Alaska Fisheries Revitalizat Strategy, Washing State Univ Extens, Univ Minnesota Ctr Farm Financial Management C1 US FDA, Anchorage, AK USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ALASKA SEA GRANT COLL PROGRAM PI FAIRBANKS PA UNIV ALASKA FAIRBANKS PO BOX 755040, FAIRBANKS, AK 99775-5040 USA BN 978-1-56612-127-9 J9 UASGCP REP PY 2008 VL 2008 IS 02 BP 39 EP 42 PG 4 WC Business; Food Science & Technology SC Business & Economics; Food Science & Technology GA BHU86 UT WOS:000256571100008 ER PT J AU Ross, MP Ferguson, M Street, D Klontz, K Schroeder, T Luccioli, S AF Ross, Marianne Phelan Ferguson, Martine Street, Debra Klontz, Karl Schroeder, Tom Luccioli, Stefano TI Analysis of food-allergic and anaphylactic events in the national electronic injury surveillance system SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anaphylaxis; food allergy; emergency department; surveillance/epidemiology ID EMERGENCY-DEPARTMENT VISITS; NATURAL-HISTORY; CHILDREN; EPIDEMIOLOGY; FEATURES; ADULTS; MILK AB Background: The National Electronic Injury Surveillance System (NEISS) captures a nationally representative probability sample from hospital emergency departments (EDs) in the United States. Objective: Emergency department data from NEISS were analyzed to assess the magnitude and severity of adverse events attributable to food allergies. Methods: Emergency department events describing food-related allergic symptomatology were identified from 34 participating EDs from August 1 to September 30, 2003. Results: Extrapolation of NEISS event data predicts a total of 20,821 hospital ED visits, 2333 visits for anaphylaxis, and 520 hospitalizations caused by food allergy in the United States during the 2-month study period. The median age was 26 years; 24% of visits involved children <= 5 years old. Shellfish was the most frequently implicated food in persons >= 6 years old, whereas children <= 5 years old experienced more events from eggs, fruit, peanuts, and tree nuts. There were no reported deaths. Review of medical records found that only 19% of patients received epinephrine, and, using criteria established by a 2005 anaphylaxis symposium, 57% of likely anaphylactic events did not have an ED diagnosis of anaphylaxis. Conclusion: Analysis of NEISS data may be a useful tool for assessing the magnitude and severity of food-allergic events. A criteria-based review of medical records suggests underdiagnosis of anaphylactic events in EDs. C1 [Ross, Marianne Phelan; Ferguson, Martine; Street, Debra; Klontz, Karl; Luccioli, Stefano] Food Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Schroeder, Tom] US Consumer Prod Safety Commiss, Bethesda, MD USA. RP Ross, MP (reprint author), Food Drug Adm, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Marianne.Ross@fda.hhs.gov RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 25 TC 110 Z9 114 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2008 VL 121 IS 1 BP 166 EP 171 DI 10.1016/j.jaci.2007.10.012 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 251KM UT WOS:000252372000024 PM 18206508 ER PT J AU Doucet, FR Faustino, PJ Sabsabi, M Lyon, RC AF Doucet, Francois R. Faustino, Patrick J. Sabsabi, Mohamad Lyon, Robbe C. TI Quantitative molecular analysis with molecular bands emission using laser-induced breakdown spectroscopy and chemometrics SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID INDUCED PLASMA SPECTROSCOPY; RAMAN-SPECTROSCOPY; AMBIENT AIR; RESEARCH STRATEGIES; MAGNESIUM STEARATE; ELEMENTAL ANALYSIS; COATING THICKNESS; ORGANIC-COMPOUNDS; SAFETY EVALUATION; MINE DETECTION AB The present work describes the first quantitative molecular prediction using laser-induced molecular bands along with chemometrics. In addition, this spectroscopic procedure has demonstrated the first complete quantitative analysis utilizing traditionally insensitive elements for pharmaceutical formulations. Atomic LIBS requires certain sensitive elements, such as Cl, F, Br, S and P, in order to quantitate a specific organic compound in a complex matrix. Molecular LIBS has been demonstrated to be the first successful approach using atomic spectroscopy to evaluate a complex organic matrix. This procedure is also the first quantitative analysis using laser-induced molecular bands and chemometrics. We have successfully applied chemometrics to predict the formulation excipients and active pharmaceutical ingredient (API) in a complex pharmaceutical formulation. Using such an approach, we demonstrate that the accuracy for the API and a formulation lubricant, magnesium stearate, have less than 4% relative bias. The other formulation excipients such as Avicel (R) and lactose have been accurately predicted to have less than a 15% relative bias. Molecular LIBS and chemometrics have provided a novel approach for the quantitative analysis of several molecules that was not technically possible with the traditional atomic LIBS procedure, that required sensitive elements to be present in both API and formulation excipients. C1 [Doucet, Francois R.; Sabsabi, Mohamad] Natl Res Council Canada, IMI, Boucherville, PQ J4B 6Y4, Canada. [Faustino, Patrick J.; Lyon, Robbe C.] US FDA, Ctr Drug Evaluat & Res, Div Product Qual Res, Silver Spring, MD 20993 USA. RP Doucet, FR (reprint author), Natl Res Council Canada, IMI, 75 Mortagne Blvd, Boucherville, PQ J4B 6Y4, Canada. EM francois.doucet@cnrc-nrc.gc.ca NR 46 TC 31 Z9 31 U1 2 U2 23 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0267-9477 EI 1364-5544 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PY 2008 VL 23 IS 5 BP 694 EP 701 DI 10.1039/b714219f PG 8 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 292JY UT WOS:000255263500006 ER PT J AU Satchithanandam, S Grundel, E Roach, J White, KD Mazzola, E Ganzera, M Rader, JI AF Satchithanandam, Subramaniam Grundel, Erich Roach, John White, Kevin D. Mazzola, Eugene Ganzera, Markus Rader, Jeanne I. TI Alkaloids and saponins in dietary supplements of Blue cohosh (Caulophyllum thalictroides) SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIGHT-SCATTERING DETECTION; QUINOLIZIDINE ALKALOIDS; TRITERPENOID SAPONINS; NATURAL-PRODUCTS; RHIZOMES; ROOTS AB Preparations of blue cohosh (Caulophyllum thalictroides) have been used traditionally by Native Americans for medicinal purposes. Dietary supplements containing dried roots or extracts of blue cohosh rhizomes are available as dietary supplements. The safety and efficacy of these preparations have not been systematically evaluated. Recent studies indicate that ingestion of specific alkaloids in blue cohosh preparations can produce birth defects and neonatal heart failure. Blue cohosh also contains saponins, which may be responsible for uterine-stimulating effects. We determined the amounts of major alkaloids and saponins in preparations of blue cohosh by high-performance liquid chromatography (HPLC). Alkaloids and saponins were monitored with a photodiode array detector and an evaporative light-scattering detector, respectively. Profiles were compared with those of authenticated blue cohosh root extracts. Identities of the alkaloids and saponins were confirmed by HPLC/mass spectrometry and nuclear magnetic resonance spectrometry. Calculations based on the results of analyses of dietary supplements showed that maximum daily intake of alkaloids and saponins will vary with the form (e.g., root, liquid extract) and doses recommended in product labeling. Intakes may vary from < 1 to 75 mg/day for alkaloids and from about 9 to 420 mg/day for saponins. C1 [Satchithanandam, Subramaniam; Grundel, Erich; Roach, John; White, Kevin D.; Mazzola, Eugene; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Ganzera, Markus] Univ Innsbruck, Dept Pharmacognosy, Inst Pharm, A-6020 Innsbruck, Austria. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM jeanne.rader@fda.hhs.gov OI Ganzera, Markus/0000-0002-7407-9060 NR 27 TC 5 Z9 5 U1 0 U2 5 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 JAN-FEB PY 2008 VL 91 IS 1 BP 21 EP 32 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 262WV UT WOS:000253179700004 PM 18376582 ER PT J AU Hammack, TS Jacobson, AP Andrews, WH AF Hammack, Thomas S. Jacobson, Andrew P. Andrews, Wallace H. TI The effect of preenrichment and selective enrichment media on recovery of Salmonella Typhi from the tropical fruit mamey SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESUSCITATION; CANTALOUPES; JUICE; BROTH AB The Bacteriological Analytical Manual (BAM) Salmonella culture method did not detect Salmonella Typhi in mamey, the tropical fruit that was implicated in a 1999 typhoid outbreak. The relative effectiveness of BAM's nonselective preenrichment and selective media for the recovery of S. Typhi from mamey was examined to determine if the BAM's preenrichment/selective enrichment strategy was the cause of the method's failure with this food. The preenrichment media were lactose broth, buffered peptone water (BPW), and universal preenrichment (UP) broth. The selective enrichment media were selenite cystine (SC) broth, tetrathionate (TT) broth, and Rappaport-Vassiliadis (RV) medium. UP broth was significantly more effective (P < 0.05) than either lactose broth or BPW for the recovery of 2 different S. Typhi strains from mamey. Of 120 test portions tested, 105 S. Typhi-positive test portions were recovered using UP broth, whereas only 1 S. Typhi-positive test portion was recovered using BPW, and no S. Typhi-positive test portions were recovered using lactose broth. SC and TT broths were both significantly more effective (P < 0.05) than RV medium. Of 105 S. Typhi-positive test portions, SC broth recovered 80, TT broth recovered 67, and RV medium recovered 9. After the above comparison, an incomplete UP (UPI) broth formulation was found to be significantly more effective (P < 0.05) than the complete formulation (UPC). Of 80 total positive test portions, UPI recovered 71, whereas UPC recovered only 48. The following UP broth formulations were compared to determine if any of the components of the UP broth formulation were inhibitory to S. Typhi: UPC, UP broth without sodium pyruvate (UPS), UP broth without ferric ammonium citrate (UPF), UP broth without MgSO4 (UPM), and UPI. It was found that none of the ingredients were inhibitory to S. Typhi and that, out of 140 total test portions, UPI and UPF, with 108 and 103 positive test portions, respectively, were significantly more effective (P < 0.05) than the C1 [Hammack, Thomas S.; Jacobson, Andrew P.; Andrews, Wallace H.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Hammack, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM thomas.hammack@fda.hhs.gov NR 22 TC 4 Z9 4 U1 0 U2 4 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 JAN-FEB PY 2008 VL 91 IS 1 BP 83 EP 91 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 262WV UT WOS:000253179700011 PM 18376589 ER PT J AU Yue, LQ AF Yue, Lilly Q. TI Special issue on medical device clinical studies - Guest editor's note SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Yue, LQ (reprint author), US FDA, CDRH, 1350 Piccard Dr, Rockville, MD 20850 USA. EM lilly.yue@fda.hhs.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 1 EP 3 DI 10.1080/10543400701668217 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600001 ER PT J AU Campbell, G AF Campbell, Gregory TI Statistics in the world of medical devices: The contrast with pharmaceuticals SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian clinical trials; diagnostic test evaluation; pharmacogenomics; regulatory statistics ID CLINICAL-TRIALS; ISSUES; MODELS AB Medical devices play a vital role in people's lives as these products are revolutionizing medicine with breathtaking advances in both the treatment and the detection of many diseases. While a similar, primarily therapeutic, revolution is ongoing in the pharmaceutical world; the focus here is the effect this device revolution is having on the statistical world. The similarities and differences between medical devices and pharmaceutical drugs are explored in terms of their natures, industries, and how they are regulated in the U.S. and globally. Statistical issues concerning the evaluation of devices versus those of drugs are compared and contrasted. These trends are creating new challenges for the statistical world in the development and evaluation of these new medical products. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Campbell, G (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM campbell@fda.hhs.gov NR 34 TC 14 Z9 14 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 4 EP 19 DI 10.1080/10543400701668225 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600002 PM 18161538 ER PT J AU Lilly, HL Yue, LQ AF Lilly, Heng Li Yue, Lilly Q. TI Statistical and regulatory issues in nonrandomized medical device clinical studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE historical control; nonrandomized study; treatment group comparability ID PROPENSITY SCORE; TRIALS; BIAS AB While randomized, well-controlled, clinical trials have been viewed as the gold standard in the evaluation of medical products, it is not uncommon for medical device clinical studies to depart from the paradigm of randomized trials, due to ethical or practical reasons. In nonrandomized studies, the advantages of well-designed and conducted randomized clinical trials are no longer available, and consequently the statistical inference obtained from such studies may carry a lower level of scientific assurance, compared to randomized trials. This paper provides a brief overview of nonrandomized medical device clinical studies in terms of design and statistical analysis as well as regulatory issues, including some challenges that frequently arise in those endeavors. C1 [Lilly, Heng Li; Yue, Lilly Q.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Lilly, HL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM heng.li@fda.hhs.gov NR 17 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 20 EP 30 DI 10.1080/10543400701668233 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600003 ER PT J AU Lao, CS Bushar, HF AF Lao, Chang S. Bushar, Harry F. TI Longitudinal data analysis in medical device clinical studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE analysis of covariance (ANCOVA); piecewise linear spline model; repeated measurements; summary statistics ID SAMPLE-SIZE CALCULATIONS; DESIGN AB Several statistical approaches are discussed for analysis of longitudinal clinical data from a two independent groups, randomized, prospective, multicenter study of patients with benign prostate hyperplasia (BPH) who are treated with either a new transurethral microwave thermotherapy device (TUMT, n=147) or sham control (n=73) at baseline and at 1, 3, and 6 months follow up. The primary clinical endpoint, based on the American Urological Association (AUA) symptom score from 7 questions (each scored 0-5) with 35 as the worst total score, is illustrated in this paper. The primary effectiveness null hypothesis is no treatment effect at any follow-up time against the alternative hypothesis of a favorable treatment effect at one or more follow-up times. Based on the prespecified clinical input of TUMT improvement in AUA mean score as a possible early effect, the expected change of slope between baseline to month 1 (baseline slope) and from month 1 to the end of month 6 (longitudinal slope), with knot at one month, were analyzed. The primary effectiveness endpoint was analyzed by a piecewise linear spline regression model with knot at month 1. Statistically significant lower mean AUA score was found in the TUMT group compared to the sham group at month 3 (P=0.01) and at month 6 (P<0.0001) follow-up; no significant difference in mean AUA score was found at baseline or at month 1 follow-up, after an overall statistically significant difference in mean AUA score (P=0.004) was found between the TUMT and sham groups. C1 US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Off Surveillance & Biostat, Rockville, MD 20857 USA. RP Lao, CS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Off Surveillance & Biostat, Rockville, MD 20857 USA. EM chang.lao@fda.hhs.gov NR 13 TC 1 Z9 1 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 44 EP 53 DI 10.1080/10543400701668258 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600005 PM 18161541 ER PT J AU Kondratovich, MV AF Kondratovich, Marina V. TI Comparing two medical tests when results of reference standard are unavailable for those negative via both tests SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE diagnostic accuracy; missing values; multiple imputation; ratio of false positive rates; ratio of true positive rates; verification bias ID DIAGNOSTIC-TESTS; SCREENING-TESTS; BIAS AB In studies for comparing the diagnostic accuracy of two qualitative tests, very often the reference standard to confirm the disease status is not applied to all study subjects. We considered a situation when all subjects with a positive result by at least one of the tests had a verified disease status and none of the subjects with both tests negative results had a verification of disease status. In this paper, we discuss whether the information about the ratio of true positive rates and the ratio of false positive rates of two qualitative tests, TNew and TOld, is sufficient to draw a conclusion about effectiveness of the TNew. We show that if there is a statistically significant increase in true positive rates and the increase in true positive rates is statistically larger than increase in false positive rates, then a conclusion about effectiveness of test TNew can be made and this does not require application of the reference standard to the subjects with negative results by both tests. An application of ratio of true positive rates and ratio of false positive rates to post-market studies is also presented. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kondratovich, MV (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20857 USA. EM Marina.Kondratovich@fda.hhs.gov NR 13 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 145 EP 166 DI 10.1080/10543400701668308 PG 22 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600010 PM 18161546 ER PT J AU Lababidi, S AF Lababidi, Samir TI Challenges in DNA microarray studies from the regulatory perspective SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE classifiers; microarrays; normalization; prediction accuracy; reproducibility ID OLIGONUCLEOTIDE ARRAYS; DIAGNOSTIC-TESTS; EXPRESSION; NORMALIZATION; CLASSIFICATION AB Genomic classifiers using DNA microarrays are becoming powerful tools in the medical community with the potential to revolutionize the diagnosis and treatment of disease. However, despite the tremendous interest in using these classifiers in diagnosis and the management of disease, few genomic classifiers have made it into clinical practice. Some of the major challenges for the development and validation of genomic classifiers will be discussed in this article together with some of their difficulties. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Lababidi, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20857 USA. EM samir.lababidi@fda.hhs.gov NR 39 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 1 BP 183 EP 202 DI 10.1080/10543400701668324 PG 20 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 251DN UT WOS:000252351600012 PM 18161548 ER PT J AU Tsong, Y Zhang, J AF Tsong, Yi Zhang, Joanne TI Guest editors' notes on statistical issues in design and analysis of thorough QTc studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Tsong, Yi; Zhang, Joanne] US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat Sci, Div Biomet 4, Silver Spring, MD USA. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat Sci, Div Biomet 4, Silver Spring, MD USA. EM yi.tsong@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 3 BP 405 EP 407 DI 10.1080/10543400802029509 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 298MB UT WOS:000255690700001 PM 18470752 ER PT J AU Zhang, J Machado, SG AF Zhang, Joanne Machado, Stella G. TI Statistical issues including design and sample size calculation in thorough QT/QTc studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE QT/QTc interval; sample size; study design; thorough QT/QTc (TQT) study ID I ERROR RATE; QT INTERVAL; VENTRICULAR ARRHYTHMIA; CLINICAL-TRIALS; HEART-RATE; PROLONGATION; CISAPRIDE AB After several drugs were removed from the market in recent years because of death due to ventricular tachycardia resulting from drug-induced QT prolongation (Khongphatthanayothin et al., 1998; Lasser et al., 2002; Pratt et al., 1994; Wysowski et al., 2001), the ICH Regulatory agencies requested all sponsors of new drugs to conduct a clinical study, named a Thorough QT/QTc (TQT) study, to assess any possible QT prolongation due to the study drug. The final version of the ICH E14 guidance (ICH, 2005) for "The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Nonantiarrhythmic Drugs" was released in May 2005. The purpose of the ICH E14 guidance (ICH, 2005) is to provide recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. The guideline, however, is not specific on several issues. In this paper, we try to address some statistical issues, including study design, primary statistical analysis, assay sensitivity analysis, and the calculation of the sample size for a TQT study. C1 [Zhang, Joanne; Machado, Stella G.] US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat Sci, Div Biometr 4, Silver Spring, MD USA. RP Zhang, J (reprint author), WO22 Room 5231,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Joanne.Zhang@fda.hhs.gov NR 24 TC 49 Z9 51 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 3 BP 451 EP 467 DI 10.1080/10543400802020938 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 298MB UT WOS:000255690700004 PM 18470755 ER PT J AU Zhang, J AF Zhang, Joanne TI Testing for positive control activity in a thorough QTc study SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE assay sensitivity; QTc interval; statistical testing; thorough QTc study ID HEART-RATE; INTERVAL; TRIALS AB The ICH E14 guidance (ICH, 2005) recommend that a concurrent positive control should be included in a thorough QTc clinical trial to validate the study. The ICH E14 guidance (ICH, 2005) state that "The positive control should have an effect on the mean QTc interval of about 5ms (i.e., an effect that is close to the QTc effect that represents the threshold of regulatory concern, around 5ms)". This task may be carried out through some statistical tests. The current practice is to test at each time point where QT measurements are collected. This method is usually not efficient. In this article, I discuss two types of statistical procedures. The first one is a local statistical test to make a time-point-specific claim, i.e., to claim a mild QTc effect due to the positive control at some specific time points. A different approach, named as a global test, is also proposed, to make a general claim that the mean difference of the positive control and placebo after baseline adjustment will be about 5ms without specifying at which time points. An example will be used to illustrate how to apply the two procedures. How to best allocate sample size in a parallel QTc study is also discussed in this paper. C1 [Zhang, Joanne] US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat, Div Biometr 4, Silver Spring, MD USA. RP Zhang, J (reprint author), Room 5231,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Joanne.Zhang@fda.hhs.gov NR 13 TC 34 Z9 37 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 3 BP 517 EP 528 DI 10.1080/10543400801995478 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 298MB UT WOS:000255690700009 PM 18470760 ER PT J AU Tsong, Y Zhong, JL Chen, WJ AF Tsong, Yi Zhong, Jinglin Chen, Wen Jen TI Validation testing in thorough QT/QTc clinical trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE assay sensitivity; controlling type I error rate; QT prolongation; statistical testing ID ISSUES; QT AB In order to validate the results of a thorough QT/QTc (the duration of depolarization and repolarization of ventricles or the duration corrected for heart rate) clinical trial, ICH E14 recommended to include a concurrent positive control treatment in the trial. It further recommended that validation is achieved if the positive control has an effect on the mean QT/QTc interval of about 5ms. Zhang (2008) discussed the intersection-union test approach for testing the validation hypotheses and an alternative global average test approach. In this article, we further discuss the difference and relationship of the two sets of hypotheses and the difference in the efficiencies of the two approaches. We conclude that validation can be achieved if either one test rejects the null hypotheses without inflating the family-wise Type I error rate. However, using both approaches may improve the efficiency in validation assessment. C1 [Tsong, Yi; Zhong, Jinglin; Chen, Wen Jen] US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat Sci, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Translat Sci, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@cder.hhs.gov NR 11 TC 12 Z9 12 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 3 BP 529 EP 541 DI 10.1080/10543400801995486 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 298MB UT WOS:000255690700010 PM 18470761 ER PT J AU Tsong, Y Shen, M Zhong, J Zhang, J AF Tsong, Yi Shen, Meiyu Zhong, Jinglin Zhang, Joanne TI Statistical issues of QT prolongation assessment based on linear concentration modeling SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE bias; concentration-response relationship; linear model; underestimate ID INTERVAL PROLONGATION AB The ICH (2005) defined drug-induced prolongation of QT interval, i.e., the duration of depolarization and repolarization of ventricles, as evidenced by an upper bound of the 95% confidence interval around the mean effect on QTc (QT corrected for heart rate) of 10ms. Furthermore, it defined that a negative thorough QT/QTc study is one in which the upper bound of the 95% one-sided confidence interval for the largest time-matched mean effect of the drug on the QTc interval excludes 10ms. This objective leads to the application of intersection-union tests by testing the mean difference between test treatment and placebo of QTc change from baseline at each of the matched time points at which the observations are collected. The nature of the higher false positive rate due to more observational time points leads to the concern of study efficiency. Based on the concept of clinical pharmacology, a concentration-response modeling approach is often adopted to assess the prolongation size of QTc interval induced by a drug without carefully examining the validity of the assumptions involved. In most of the applications, the model is assumed either to be linear, log-linear, or logistic. The supporter of the modeling often emphasizes the advantage of power improvement and reduction in estimation error. However, it has been often pointed out by statisticians and pharmacologists that modeling under an invalid uniformity assumption across study population often leads to severe bias in testing and estimation. In this article, we examine data sets of New Drug Applications to illustrate the bias and lack of validity of the linearity assumptions. C1 [Tsong, Yi; Shen, Meiyu; Zhong, Jinglin; Zhang, Joanne] US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Tanslat Sci, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat Off Tanslat Sci, Room 5244,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@cder.hhs.gov NR 13 TC 20 Z9 21 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 3 BP 564 EP 584 DI 10.1080/10543400801995502 PG 21 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 298MB UT WOS:000255690700013 PM 18470764 ER PT J AU Tsong, Y AF Tsong, Yi TI Commentary on "accounting for interim safety monitoring of an adverse event upon termination of a clinical trial" SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article C1 US FDA, Off Biostat, CDER, Silver Spring, MD USA. RP Tsong, Y (reprint author), US FDA, Off Biostat, CDER, Silver Spring, MD USA. EM yi.tsong@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 4 BP 639 EP 640 DI 10.1080/10543400802071329 PG 2 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 323ID UT WOS:000257438900004 ER PT J AU Zhang, ZW Kotz, RM AF Zhang, Zhiwei Kotz, Richard M. TI Inference and sample size calculation in the fit assessment of filtering facepiece respirators SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE analysis of variance; delta method; random effect; respirator; sample size; variance component AB Filtering facepiece respirators have recently been cleared by the U.S. Food and Drug Administration (FDA) for use by the general public in public health medical emergencies such as pandemic influenza. In the fit assessment of these devices it is important to distinguish between the two sources of variability: population heterogeneity and random fluctuations over repeated donnings. The FDA Special Controls Guidance Document (SCGD) which describes these devices and their evaluation, recommends that the fit performance of a filtering facepiece respirator be evaluated in terms of the proportion of users who will receive a specified level of protection 95% of the time. A point estimator of this proportion is easily obtained under an analysis of variance model, and the SCGD suggests bootstrap as one possible approach to interval estimation. This paper describes a closed-form procedure to obtain confidence intervals and provides sample size formulas. Simulation results suggest that the proposed procedure performs well in realistic settings and compares favorably to two simple bootstrap procedures. C1 [Zhang, Zhiwei] US FDA, Div Biostat, OSB, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, OSB, Ctr Devices & Radiol Hlth, HFZ-550, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 9 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 4 BP 713 EP 723 DI 10.1080/10543400802071394 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 323ID UT WOS:000257438900011 PM 18607803 ER PT J AU Chen, JJ Lin, KK Tsong, Y AF Chen, James J. Lin, Karl K. Tsong, Yi TI Special issue on non-clinical statistics guest editors' notes SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Lin, Karl K.; Tsong, Yi] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat,Div Biometr 6, Silver Spring, MD USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 805 EP 807 DI 10.1080/10543400802334164 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800001 PM 18781517 ER PT J AU Chen, DT Schell, MJ Chen, JJ Fulp, WJ Eschrich, S Yeatman, T AF Chen, Dung-Tsa Schell, Michael J. Chen, James J. Fulp, William J. Eschrich, Steven Yeatman, Timothy TI A predictive risk probability approach for microarray data with survival as an endpoint SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE cancer risk classification; dimension reduction; log-rank test; survival tree model; top ranked genes ID BREAST-CANCER AB Gene expression profiling has played an important role in cancer risk classification and has shown promising results. Since gene expression profiling often involves determination of a set of top rank genes for analysis, it is important to evaluate how modeling performance varies with the number of selected top ranked genes incorporated in the model. We used a colon data set collected at Moffitt Cancer Center as an example of the study, and ranked genes based on the univariate Cox proportional hazards model. A set of top ranked genes was selected for evaluation. The selection was done by choosing the top k ranked genes for k = 1 to 12,500. An analysis indicated a considerable variation of classification outcomes when the number of top ranked genes was changed. We developed a predictive risk probability approach to accommodate this variation by identifying a range number of top ranked genes. For each number of top ranked genes, the procedure classifies each patient as having high risk (score = 1) or low risk (score = 0). The categorizations are then averaged, giving a risk score between 0 and 1, thus providing a ranking for the patient's need for further treatment. This approach was applied to the colon data set and demonstrated the strength of this approach by three criteria: First, a univariate Cox proportional hazards model showed a highly statistically significant level (log-rank chi(2) statistics = 110 with p-value <10(-16)) for the predictive risk probability classification. Second, the survival tree model used the risk probability to partition patients into five risk groups showing a good separation of survival curves (log-rank chi(2) statistics = 215). In addition, utilization of the risk group status identified a small set of risk genes that may be practical for biological validation. Third, analysis of resampling the risk probability suggested the variation pattern of the log-rank 2 in the colon cancer data set was unlikely caused by chance. C1 [Chen, Dung-Tsa; Schell, Michael J.; Fulp, William J.] Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Div Biostat, Tampa, FL 33612 USA. [Chen, James J.] Food & Drug Adm, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR USA. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Dept Publ Hlth, Taichung, Taiwan. RP Chen, DT (reprint author), Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Div Biostat, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM Dung-Tsa.Chen@moffitt.org RI Eschrich, Steven/K-6848-2013 FU National Institutes of Health [2P30CA76292-08, R01CA112215-03, R01CA098522-05] FX This work was supported by grants from the National Institutes of Health (2P30CA76292-08, R01CA112215-03, and R01CA098522-05). The authors acknowledge the use of the services provided by Research Computing, University of South Florida.; The views presented in this article are those of the authors and do not necessarily represent those of the U. S. Food and Drug Administration. NR 17 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 841 EP 852 DI 10.1080/10543400802277967 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800004 PM 18781520 ER PT J AU Baek, S Moon, H Ahn, H Kodell, RL Lin, CJ Chen, JJ AF Baek, Songjoon Moon, Hojin Ahn, Hongshik Kodell, Ralph L. Lin, Chien-Ju Chen, James J. TI Identifying high-dimensional biomarkers for personalized medicine via variable importance ranking SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE class prediction; cross-validation; ensembles; gene selection; risk profiling ID GENE-EXPRESSION DATA; MICROARRAY DATA; CANCER CLASSIFICATION; SELECTION AB We apply robust classification algorithms to high-dimensional genomic data to find biomarkers, by analyzing variable importance, that enable a better diagnosis of disease, an earlier intervention, or a more effective assignment of therapies. The goal is to use variable importance ranking to isolate a set of important genes that can be used to classify life-threatening diseases with respect to prognosis or type to maximize efficacy or minimize toxicity in personalized treatment of such diseases. A ranking method and present several other methods to select a set of important genes to use as genomic biomarkers is proposed, and the performance of the selection procedures in patient classification by cross-validation is evaluated. The various selection algorithms are applied to published high-dimensional genomic data sets using several well-known classification methods. For each data set, a set of genes selected on the basis of variable importance that performed the best in classification is reported. That classification algorithm with the proposed ranking method is shown to be competitive with other selection methods for discovering genomic biomarkers underlying both adverse and efficacious outcomes for improving individualized treatment of patients for life-threatening diseases. C1 [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Baek, Songjoon; Lin, Chien-Ju; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Biometry Branch, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. RP Moon, H (reprint author), Calif State Univ Long Beach, Dept Math & Stat, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM hmoon@csulb.edu FU CSULB; Oak Ridge Institute for Science and Education FX Hojin Moon's research was partially supported by the Scholarly and Creative Activities Committee (SCAC) Award from CSULB. Hongshik Ahn's research was partially supported by the Faculty Research Participation Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between USDOE and USFDA. NR 24 TC 4 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 853 EP 868 DI 10.1080/10543400802278023 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800005 PM 18781521 ER PT J AU Rahman, MA Lin, KK AF Rahman, Mohammad A. Lin, Karl K. TI A comparison of false positive rates of Peto and poly-3 methods for long-term carcinogenicity data analysis using multiple comparison adjustment method suggested by Lin and Rahman SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE carcinogenicity; dose response; false positive rate; Peto test; Poly-K test ID ANIMAL CARCINOGENICITY; TESTS; TUMORS; TREND AB Statistical analyses of two-year carcinogenicity data include tests for dose-response relationship (positive trend) among the increasing doses and pairwise comparisons of treated groups with control in tumor incidence by organ/tumor combination. There are two major concerns in analyzing carcinogenicity data, namely, adjustment for the difference in mortality due to drug toxicity and adjustment for the multiplicity due to multiple testing of trends and pairwise differences by organ tumor combination. A widely used method for testing dose-response relationship is the method suggested by Peto et al. (Peto test). The Peto test adjusts the mortality differences among treatment groups by partitioning the entire study period into several intervals, analyzing the data separately for each interval, and then combining them using the Mantel-Haenszel procedure. The denominator for the calculation of the proportion of tumor bearing animals is determined from the cause of death information tumor data. In later works, researchers have expressed concerns regarding the construction of suitable intervals for mortality adjustment. Also according to the opinion of many pathologists it is difficult to accurately specify retrospectively if a tumor is the real cause of death of an animal. This information may be imprecise. Hence, many times results of analysis using the Peto test are questioned due to the inaccurate cause of death information. An alternative to the Peto test was suggested by Bailer and Portier, popularly known as Poly-K test. Unlike the Peto test, this test does not need any arbitrary partitioning of the study period or the cause of death information. This test for trend in tumor incidence adjusts the differences in mortality among treatment groups by assigning a weight of less than one to an animal that died early without developing the tumor; and a weight of one to an animal that died with the tumor or survived to the end of the study. The sum of the assigned weights of animals in a treatment group is then used as the denominator for the calculation of proportion of tumor-bearing animals for the group. The less-than-one weight assigned to an animal is the fraction of the animal's surviving time in the study over the maximum time of the study with a power k. The power k of the fraction is determined by the distribution of tumor onset times of the tumor. The Poly-K test may have some advantages over the Peto test in the sense that it does not require the cause of death information, which is an essential part for the Peto test. However, the performance of the Poly-K test in controlling the false positive rate in comparison to the Peto test is unknown and of great interest in the regulatory environment. In this work the authors compared the overall false positive rates of the Peto and Poly-K tests using the Lin-Rahman multiple comparison adjustment based on some simulation results. C1 [Rahman, Mohammad A.; Lin, Karl K.] US FDA, CDER, OB, Div Biometr 6, Silver Spring, MD 20993 USA. RP Rahman, MA (reprint author), US FDA, CDER, OB, Div Biometr 6, Room 4658,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rahman@fda.hhs.gov NR 17 TC 5 Z9 5 U1 2 U2 12 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 949 EP 958 DI 10.1080/10543400802287628 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800011 PM 18781527 ER PT J AU Tsong, Y Shen, MY Lostritto, RT Poochikian, GK AF Tsong, Yi Shen, Meiyu Lostritto, Richard T. Poochikian, Guiragos K. TI Parametric two-tier sequential quality assurance test of delivery dose uniformity of multiple-dose inhaler and dry powder inhaler drug products SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE delivered dose uniformity; double one-sided test; FDA draft guidance method; tolerance interval; two-tier group sequential AB The delivery dose uniformity is one of the most critical requirements of dry powder inhaler and metered dose inhaler products. In 1998, the U.S. Food and Drug Administration recommended a two-tier acceptance sampling plan in the Draft Guidance of Metered Dose Inhaler and Dry Powder Inhaler Drug Products Chemistry, Manufacturing and Controls. The two-tier procedure is a modification of the United States Pharmacopeia (USP) sampling plan of dose content uniformity. It employed a zero tolerance criterion. In addition, it has a near-zero probability acceptance at the second tier. In this article, a two-tier sequential tolerance interval approach is proposed that is equivalent to a two-tier two one-sided testing procedure. It controls the probability of the product delivering below a prespecified effective dose and the probability of the product delivering over a prespecified safety dose. C1 [Tsong, Yi; Shen, Meiyu] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. [Lostritto, Richard T.; Poochikian, Guiragos K.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off New Drug Qual Assurance, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Room 4628,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov NR 6 TC 7 Z9 7 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 976 EP 984 DI 10.1080/10543400802287222 PG 9 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800013 PM 18781529 ER PT J AU Djira, GD Hothorn, LA Tsong, Y AF Djira, Gemechis D. Hothorn, Ludwig A. Tsong, Yi TI Equivalence tests for shelf life and average drug content in stability studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE average drug content; label claim; multiple comparison; shelf life ID CONFIDENCE SETS; POOLING BATCHES AB Stability testing is a procedure frequently used in the pharmaceutical industry to estimate the shelf life of a drug. Hereby, a standard problem of interest is whether or not to pool a given number of batches to assign a single shelf life for the combined batches. In this paper, we propose two modified methods for the pooling process. One is based on the relative average drug contents of batches at a target shelf life, which basically involves specification of thresholds in relative terms, and the other is tests for the equivalence of shelf lives (using ratios of shelf lives) at a specified lower acceptance criteria of label claim. For both approaches, marginal and simultaneous confidence intervals are established. The methods will be illustrated using two different stability data. A simulation study is conducted to investigate the coverage probability of the proposed methods. C1 [Djira, Gemechis D.] S Dakota State Univ, Dept Math & Stat, Brookings, SD 57007 USA. [Hothorn, Ludwig A.] Leibniz Univ Hannover, Inst Biostat, Hannover, Germany. [Tsong, Yi] US FDA, Off Biostat, Rockville, MD 20857 USA. RP Djira, GD (reprint author), S Dakota State Univ, Dept Math & Stat, Harding Hall 123, Brookings, SD 57007 USA. EM gemechis.djira@sdstate.edu NR 16 TC 2 Z9 2 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 985 EP 995 DI 10.1080/10543400802287230 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800014 PM 18781530 ER PT J AU Zhong, JL Lee, K Tsong, Y AF Zhong, Jinglin Lee, Kathy Tsong, Yi TI Statistical assessment of analytical method transfer SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE analytical method transfer; concordance correlation coefficient; double one-sided test; tolerance interval ID CONCORDANCE CORRELATION-COEFFICIENT; ASSESSING AGREEMENT AB Analytical method transfer is an important part of analytical method development and maintenance. The current common practice of analytical method transfer is based on the equivalence of the means between the original laboratory and the receiving laboratory. However, for some assays the most scientifically sound approach would be to show the equivalency of individual sample readings between the two laboratories. In this study, statistical approaches such as limit of agreement, total deviation index, and tolerance interval approach to address individual equivalence between laboratories are discussed. Using a tolerance interval approach that is equivalent to the two one-sided hypothesis testing is proposed. These approaches are compared with each other and also with the mean equivalence approach on their statistical properties. Examples are presented to illustrate each analysis approach and the comparisons. C1 [Zhong, Jinglin; Lee, Kathy; Tsong, Yi] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tsong, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Room 4628,Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yi.tsong@fda.hhs.gov FU CDER/FDA Regulatory Science Research Fund RSR [07-08] FX This article was written with most of the materials presented at 2007 FDA Visitation Day of PhRMA CMC Statistical Expert Team, 2007 ICSA Applied Statistical Symposium, 2007 Joint Statistical Meetings and 2007 FDA/Industry Statistical Workshop. The authors thank the organizers, Drs. Timothy Schonfield, David Christopher, James R. Schwenke, and Stella Machado, for their encouragement and constructive discussions. The authors also thank Dr. Meiyu Shen of FDA for the many discussions on tolerance interval. The article is part of the project on applications of tolerance interval in pharmaceutical quality control and assurance supported by the 2007 CDER/FDA Regulatory Science Research Fund RSR # 07-08. NR 17 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2008 VL 18 IS 5 BP 1005 EP 1012 DI 10.1080/10543400802287347 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 346UC UT WOS:000259093800016 PM 18781532 ER PT J AU Gannavaram, S Vedvyas, C Debrabant, A AF Gannavaram, Sreenivas Vedvyas, Chetan Debrabant, Alain TI Conservation of the pro-apoptotic nuclease activity of endonuclease G in unicellular trypanosomatid parasites SO JOURNAL OF CELL SCIENCE LA English DT Article DE trypanosomatid parasites; programmed cell death; DNA fragmentation; apoptotic Nucleases; endonuclease G ID PROGRAMMED CELL-DEATH; LEISHMANIA-DONOVANI; DNA-DEGRADATION; SUBCELLULAR-LOCALIZATION; BRUCEI-RHODESIENSE; C-ELEGANS; EXPRESSION; PROTEIN; PROMASTIGOTES; ENDOG AB Endonuclease G is a mitochondrial protein implicated in DNA fragmentation during apoptosis in cell types ranging from fungi to mammals. Features of programmed cell death have been reported in a number of single-celled organisms, including the human trypanosomatid parasites Leishmania and Trypanosoma. However, the protozoan cell death pathways and the effector molecules involved in such processes remain to be identified. In this report, we describe the pro-apoptotic function of endonuclease G in trypanosomatid parasites. Similar to metazoans, trypanosome endoG showed intrinsic nuclease activity, is localized in mitochondria and is released from this organelle when cell death is triggered. Overexpression of endoG strongly promoted apoptotic cell death under oxidant or differentiation-related stress in Leishmania and, conversely, loss of endoG expression conferred robust resistance to oxidant-induced cell death in T. brucei. These data demonstrate the conservation of the proapoptotic endonuclease activity of endoG in these evolutionarily ancient eukaryotic organisms. Furthermore, nuclear DNA degradation by endoG upon release from mitochondria might represent a caspase-independent cell death mechanism in trypanosomatid parasites as genes encoding caspase-like proteins have not been identified in their genomes. C1 [Gannavaram, Sreenivas; Vedvyas, Chetan; Debrabant, Alain] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Debrabant, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM alain.debrabant@fda.hhs.gov NR 54 TC 54 Z9 58 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JAN 1 PY 2008 VL 121 IS 1 BP 99 EP 109 DI 10.1242/jcs.014050 PG 11 WC Cell Biology SC Cell Biology GA 249QH UT WOS:000252243400014 PM 18073240 ER PT J AU Evans, RL Siitonen, PH AF Evans, Ronald L. Siitonen, Paul H. TI Determination of caffeine and sympathomimetic alkaloids in weight loss supplements by high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID EPHEDRINE-TYPE ALKALOIDS; L. VAR. AMARA; DIETARY-SUPPLEMENTS; CITRUS-AURANTIUM; HERBAL PRODUCTS; PRIMARY HEADACHES; SUDDEN-DEATH; MA-HUANG; SYNEPHRINE; AMINES C1 [Evans, Ronald L.; Siitonen, Paul H.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Evans, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ronald.evans@fda.hhs.gov FU PHS HHS [224-93-0001] NR 38 TC 12 Z9 12 U1 1 U2 6 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD JAN PY 2008 VL 46 IS 1 BP 61 EP 67 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 248BR UT WOS:000252126800011 PM 18218190 ER PT J AU Garnett, CE Beasley, N Bhattaram, VA Jadhav, PR Madabushi, R Stockbridge, N Tornoe, CW Wang, Y Zhu, H Gobburu, JV AF Garnett, Christine E. Beasley, Nhi Bhattaram, V. Atul Jadhav, Pravin R. Madabushi, Rajanikanth Stockbridge, Norman Tornoe, Christoffer W. Wang, Yaning Zhu, Hao Gobburu, Jogarao V. TI Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE pharmacokinetics; pharmacodynamics; modeling; QT interval; ICH E14 ID VENTRICULAR TACHYARRHYTHMIA; CLINICAL-PHARMACOLOGY; INTERVAL PROLONGATION; PHARMACOKINETICS; PHARMACODYNAMICS; SOTALOL; POPULATION; ELECTROCARDIOGRAM; VARIABILITY; DOFETILIDE AB The criterion for assessing whether a drug prolongs QT as described in the International Conference on Harmonization topic E14 guideline does not explicitly account for individual drug concentrations. The authors' experience with reviewing QT studies indicates that understanding the relationship, if any, between individual drug concentration and QT change provides important additional information to support regulatory decision making. Therefore, regulatory reviews of "thorough QT" studies routinely include a characterization of the concentration-QT relationship. The authors provide examples to illustrate how the concentration-QT relationship has been used to plan and interpret the thorough QT study, to evaluate QT risk for drugs that have no thorough QT studies, to assess QT risk in subpopulations, to make dose adjustments, and to write informative drug labels. C1 [Garnett, Christine E.; Bhattaram, V. Atul; Jadhav, Pravin R.; Tornoe, Christoffer W.; Wang, Yaning; Zhu, Hao; Gobburu, Jogarao V.] US FDA, CDER, OTS, Off Clin Pharmacol, Silver Spring, MD 20903 USA. [Beasley, Nhi; Stockbridge, Norman] US FDA, Ctr Drug Evaluat & Res, Div Cardiovasc & Renal Drug Prod, Silver Spring, MD 20903 USA. RP Garnett, CE (reprint author), US FDA, CDER, OTS, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM christine.garnett@fda.hhs.gov NR 26 TC 130 Z9 134 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 JAN PY 2008 VL 48 IS 1 BP 13 EP 18 DI 10.1177/0091270007307881 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248JS UT WOS:000252150200003 PM 18094216 ER PT J AU Fu, PP Xia, QS Guo, L Yu, HT Chan, PC AF Fu, Peter P. Xia, Qingsu Guo, Lei Yu, Hongtao Chan, Po-Chuen TI Toxicity of kava kava SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Kava; anti-anxiety herbal beverage; top-selling botanical; hepatotoxicity; metabolism; mechanism ID FULMINANT HEPATIC-FAILURE; HERB-DRUG INTERACTIONS; PERFORMANCE LIQUID-CHROMATOGRAPHY; PIPER-METHYSTICUM; IN-VITRO; NATURAL THERAPY; BEVERAGE KAVA; F344 RATS; KAVALACTONES; EXTRACT AB Kava is a traditional beverage of various Pacific Basin countries. Kava has been introduced into the mainstream U.S. market principally as an anti-anxiety preparation. The effects of the long-term consumption of kava have not been documented adequately. Preliminary studies suggest possible serious organ system effects. The potential carcinogenicity of kava and its principal constituents are unknown. As such, kava extract was nominated for the chronic tumorigenicity bioassay conducted by the National Toxicology Program (NTP). At present toxicological evaluation of kava extract is being conducted by the NTP. The present review focuses on the recent findings on kava toxicity and the mechanisms by which kava induces hepatotoxicity. C1 [Fu, Peter P.; Xia, Qingsu; Guo, Lei] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov; chanp@niehs.nih.gov RI Guo, Lei/E-9232-2011 NR 91 TC 36 Z9 36 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2008 VL 26 IS 1 BP 89 EP 112 DI 10.1080/10590500801907407 PG 24 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 270QJ UT WOS:000253735000003 PM 18322868 ER PT J AU Guo, L Shi, Q Fang, JL Mei, N Ali, AA Lewis, SM Leakey, JEA Frankos, VH AF Guo, Lei Shi, Qiang Fang, Jia-Long Mei, Nan Ali, A. Afshan Lewis, Sherry M. Leakey, Julian E. A. Frankos, Vasilios H. TI Review of Usnic Acid and Usnea Barbata Toxicity SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Weight loss dietary supplement; usnic acid and Usnea barbata toxicity ID METABOLITE (+)-USNIC ACID; IN-VITRO; DIETARY-SUPPLEMENT; LICHEN METABOLITE; (-)-USNIC ACID; WEIGHT-LOSS; HEPATOTOXICITY; IDENTIFICATION; DINITROPHENOL; CONSTITUENTS AB Usnic acid is a prominent secondary lichen metabolite that has been used for various purposes worldwide. Crude extracts of usnic acid or pure usnic acid have been marketed in the United States as dietary supplements to aid in weight loss. The US Food and Drug Administration (FDA) received 21 reports of liver toxicity related to the ingestion of dietary supplements that contain usnic acid. This prompted the FDA to issue a warning about one such supplement, LipoKinetix, in 2001 (http://www.cfsan.fda.gov/similar to dms/ds-lipo.html). Subsequently, usnic acid and Usnea barbata lichen were nominated by the National Toxicology Program (NTP) for toxicity evaluations. At present, a toxicological evaluation of usnic acid is being conducted by the NTP. This review focuses on the recent findings of usnic acid-induced toxicities and their underlying mechanisms of action. C1 [Guo, Lei; Shi, Qiang; Fang, Jia-Long; Mei, Nan; Ali, A. Afshan; Lewis, Sherry M.; Leakey, Julian E. A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Frankos, Vasilios H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011; Qiang, Shi/E-6266-2012 OI mei, nan/0000-0002-3501-9014; NR 67 TC 43 Z9 43 U1 0 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2008 VL 26 IS 4 BP 317 EP 338 DI 10.1080/10590500802533392 PG 22 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 400IZ UT WOS:000262862600001 PM 19034791 ER PT J AU Grant, MA AF Grant, Michael A. TI Comparison of Escherichia coli O157 : H7 enrichment in spiked produce samples SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SEPARATION METHODS; BOVINE FECES; GROUND-BEEF; GROWTH; GENES; MEDIA; SENSITIVITY; PATHOGENS; RECOVERY; MILK AB Two strains of Escherichia coli O157:H7 were spiked into six varieties of produce at approximately 0.5 CFU g(-1). Samples were enriched by using the U.S. Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) method and by using an experimental method incorporating acid shock. Target colonies were detectable on selective agars after 30 of 48 analyses with BAM enrichment and 48 of 48 analyses with acid enrichment. Real-time PCR screening of 24-h enrichment broths revealed the presence of the diagnostic stx(1) or stx(2) genes after 27 of 48 analyses with BAM enrichment and 42 of 48 analyses with acid enrichment. The efficiency of the enrichment varied with strain and type of produce spiked but overall was better with the experimental enrichment method. Modifications of both the acid enrichment and BAM enrichment methods also were tested. The acid method with a modified incubation temperature consistently yielded high rates of recovery (> 10(8) CFU ml(-1)), with no instances in which target cells could not be detected. Modification of the BAM procedure did not reproducibly improve enrichment efficiency. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Grant, MA (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM mike.grant@fda.hhs.gov NR 37 TC 8 Z9 9 U1 2 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 JAN PY 2008 VL 71 IS 1 BP 139 EP 145 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 248OH UT WOS:000252162900019 PM 18236674 ER PT J AU Yancy, HF Zemlak, TS Mason, JA Washington, JD Tenge, BJ Nguyen, NLT Barnett, JD Savary, WE Hill, WE Moore, MM Fry, FS Randolph, SC Rogers, PL Hebert, PDN AF Yancy, Haile F. Zemlak, Tyler S. Mason, Jacquline A. Washington, Jewell D. Tenge, Bradley J. Nguyen, Ngoc-Lan T. Barnett, James D. Savary, Warren E. Hill, Walter E. Moore, Michelle M. Fry, Frederick S. Randolph, Spring C. Rogers, Patricia L. Hebert, Paul D. N. TI Potential use of DNA barcodes in regulatory science: Applications of the Regulatory Fish Encyclopedia SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IDENTIFICATION; SEQUENCES; SEBASTES; LIFE AB The use of a DNA-based identification system (DNA barcoding) founded on the mitochondrial gene cytochrome c oxidase subunit I (COI) was investigated for updating the U.S. Food and Drug Administration Regulatory Fish Encyclopedia (RFE; http://www.cfsan.fda.gov/similar to frf/rfe0.html). The RFE is a compilation of data used to identify fish species. It was compiled to help regulators identify species substitution that could result in potential adverse health consequences or could be a source of economic fraud. For each of many aquatic species commonly sold in the United States, the RFE includes high-resolution photographs of whole fish and their marketed product forms and species-specific biochemical patterns for authenticated fish species. These patterns currently include data from isoelectric focusing studies. In this article, we describe the generation of DNA barcodes for 172 individual authenticated fish representing 72 species from 27 families contained in the RFE. These barcode sequences can be used as an additional identification resource. In a blind study, 60 unknown fish muscle samples were barcoded, and the results were compared with the RFE barcode reference library. All 60 samples were correctly identified to species based on the barcoding data. Our study indicates that DNA barcoding can be a powerful tool for species identification and has broad potential applications. C1 [Yancy, Haile F.; Washington, Jewell D.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Zemlak, Tyler S.; Hebert, Paul D. N.] Univ Guelph, Biodivers Inst Ontario, Guelph, ON N1G 2W1, Canada. [Mason, Jacquline A.] Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. [Tenge, Bradley J.; Nguyen, Ngoc-Lan T.; Barnett, James D.; Savary, Warren E.; Hill, Walter E.; Moore, Michelle M.] US FDA, Off Regulatory Affairs, Seafood Prod Res Ctr, Bothell, WA 98021 USA. [Fry, Frederick S.; Randolph, Spring C.; Rogers, Patricia L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yancy, HF (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM haile.yancy@fda.hhs.gov RI Hebert, Paul/C-4161-2013 OI Hebert, Paul/0000-0002-3081-6700 NR 31 TC 73 Z9 86 U1 1 U2 20 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 JAN PY 2008 VL 71 IS 1 BP 210 EP 217 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 248OH UT WOS:000252162900032 PM 18236687 ER PT J AU Yu, H Lin, Q Ito, Y AF Yu, Henry Lin, Qi Ito, Yoichiro TI New design in centrifugal precipitation chromatography for the preparative separation of proteins SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE centrifugal precipitation chromatography; ammonium sulfate; protein fractionation; protein separation; preparative separation AB Centrifugal Precipitation Chromatography (CPC) utilizes a moving solvent gradient to separate proteins and macromolecules by repetitive steps of precipitation and dissolution in a column. Proteins fractionate at locations that depend on their solubility in differing ammonium sulfate concentrations. Prior to the current study, construction of a CPC instrument has been difficult due to the complicated design of the separation column and its connections. The current manuscript introduces an innovation that replaces the custom designed column with a commercial one. This change still results in efficient separations of human albumin and -globulin in a mixture, as well as in human serum. C1 [Yu, Henry; Ito, Yoichiro] NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. [Lin, Qi] OPS, CDER, FDA, Off New Drug Qual Assessment, Silver Spring, MD USA. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2008 VL 31 IS 4 BP 517 EP 525 DI 10.1080/10826070701812756 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251CL UT WOS:000252348200005 ER PT J AU Zidan, AS Sammour, OA Hammad, MA Megrab, NA Habib, MJ Khan, MA AF Zidan, A. S. Sammour, O. A. Hammad, M. A. Megrab, N. A. Habib, M. J. Khan, M. A. TI Process analytical technology: Non-destructive assessment of anastrozole entrapment within PLGA microparticles by near infrared spectroscopy and chemical imaging SO JOURNAL OF MICROENCAPSULATION LA English DT Article DE microencapsulation; anastrozole; PLGA; near infrared; NIR imaging ID RELEASE; MICROSPHERES; VARIABLES AB The objective of this study was to evaluate near-infrared (NIR) spectroscopy and imaging as approaches to assess anastrozole entrapment within PLGA microparticles. By varying the polymer concentration, three batches containing the same amount of the drug were prepared. The spectral features that allow NIR drug quantitation were evaluated and compared with a best fit line algorithm. Actual entrapment efficiencies (EEF) determined via a destructive method were used for construction of calibration models using partial least square regression (PLS) or the algorithm. On the other hand, a chemical imaging system based on array detector technology was used to rapidly collect high contrast NIR images of the formulated microparticles. A quantitative measure of anastrozole entrapped was determined by calculating the percentage standard deviation of the distribution of pixel intensities in the PLS score images and histograms. Concerning conventional NIR analysis, both methods were equivalent for the prediction of EEF over the range of polymer levels studied. Correlation coefficients of more than 0.992 were obtained for either the calibration or prediction of EEF by the two methods; 0.392% and 0.374% were the standard errors of calibration and prediction (SEC and SEP) obtained for the prediction of EEF using the fit line, respectively, whereas the prediction of the EEF by the partial least square regression showed a SEC of 0.195% and SEP of 0.179%. As a result, the spectral best fit algorithm method compared favourably to the multivariate PLS method, but was easier to develop. In contrast, NIR spectral imaging was capable of clearly differentiating the three batches, both qualitatively and quantitatively. The percentage standard deviation increased progressively by increasing the ratio of drug-to-polymer concentrations. In conclusion, both NIR approaches were capable of accurate assessment of drug entrapment within microparticles. In addition, the NIR spectral imaging system provides a rapid approach for acquiring spatial and spectral information on microparticles. C1 [Zidan, A. S.; Khan, M. A.] US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. [Zidan, A. S.; Sammour, O. A.; Hammad, M. A.; Megrab, N. A.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. [Zidan, A. S.; Habib, M. 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 17 TC 3 Z9 3 U1 0 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0265-2048 J9 J MICROENCAPSUL JI J. Microencapsul. PY 2008 VL 25 IS 3 BP 145 EP 153 DI 10.1080/02652040601034963 PG 9 WC Chemistry, Applied; Engineering, Chemical; Pharmacology & Pharmacy SC Chemistry; Engineering; Pharmacology & Pharmacy GA 282NQ UT WOS:000254574900001 PM 18382921 ER PT J AU Qi, L Carbone, KM Ye, ZP Liu, T Ovanesov, M Pletnikov, M Sauder, C Rubin, SA AF Qi, Li Carbone, Kathryn M. Ye, Zhiping Liu, Teresa Ovanesov, Mikhail Pletnikov, Mikhail Sauder, Christian Rubin, Steven A. TI Genetic contributions to influenza virus attenuation in the rat brain SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE attenuation; influenza virus; neurotoxicity; rat ID HONG-KONG; A-VIRUS; AVIAN INFLUENZA; AMINO-ACID; TEMPERATURE SENSITIVITY; ACUTE ENCEPHALOPATHY; H5N1; MICE; INFECTION; NEUROVIRULENT AB Influenza is generally regarded as an infection of the respiratory tract; however, neurological involvement is a well-recognized, although uncommon, complication of influenza A virus infection. The authors previously described the development of a rat model for studying influenza virus infection of the central nervous system (CNS). This model was used here to study the role of virus genes in virus replication and spread in brain. In the present work, an infectious cDNA clone of the neurotoxic WSN strain of influenza virus (rWSN) was altered by site-directed mutagenesis at five loci that corresponded to changes previously shown to confer temperature sensitivity and attenuation of the A/Ann Arbor/6/60 strain (PB1 Delta 391, PB1 Delta 581, and PB1 Delta 661; PB2 Delta 265, and NP Delta 34). Whereas rWSN and its mutated derivative (mu-rWSN) replicated equally well in MDCK cells at 37 degrees C (the body temperature of rats), rWSN grew to higher titers and infection was more widespread compared to mu-rWSN in rat brain. These results demonstrate that the five mutations that confer attenuation of the A/Ann Arbor/6/60 influenza virus strain for the respiratory system also confer attenuation for the central nervous system. Further in vivo and in vitro examination of these five mutations, both individually and in combination, will likely provide important information on the role of specific virus genes in virulence and pathogenesis. C1 [Qi, Li; Carbone, Kathryn M.; Ye, Zhiping; Liu, Teresa; Sauder, Christian; Rubin, Steven A.] US FDA, DVP OVRR CBER, Bethesda, MD 20892 USA. [Ovanesov, Mikhail; Pletnikov, Mikhail] Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. RP Rubin, SA (reprint author), US FDA, DVP OVRR CBER, Bldg 29A,Room 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 37 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2008 VL 14 IS 2 BP 136 EP 142 DI 10.1080/13550280701885563 PG 7 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 293ZC UT WOS:000255372900005 PM 18444085 ER PT J AU Kaput, JJ AF Kaput, J. Jim TI Nutrigenomics Research for Personalized Nutrition and Medicine SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Kaput, J. Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2008 VL 1 IS 4 BP 182 EP 183 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 494FE UT WOS:000269794800013 ER PT J AU Foy, JR Buch, BD AF Foy, Jonette R. Buch, Barbara D. TI Orthopaedic joint devices: The FDA's short answers to your questions SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article; Proceedings Paper CT AAOS/NIH Osteolysis and Implant Wear: Biological, Biomedical Engineering, and Surgical Principles CY SEP 09-11, 2007 CL Austin, TX SP Amer Adad Orthopaed Surg, Nat Inst Hlth AB This article briefly describes the US Food and Drug Administration regulatory process for medical devices, focusing on orthopaedic joint device examples. The mission of the Center for Devices and Radiological Health is to promote and protect the health of the public by ensuring that the medical devices that reach US consumers are safe and effective for their intended function. A question and answer section is included as a reference guide for the orthopaedic community to broadly address some common issues related to orthopaedic device constructs, such as hybridization of joint systems, labeling claims, modifications to ultra-high-molecular-weight polyethylene sought by manufacturers to minimize wear and osteolysis, combination products, and the responsibilities of an orthopaedic surgeon. The FDA relies on accurate scientific evidence and regulatory science to determine the safety and effectiveness of orthopaedic joint devices. C1 [Foy, Jonette R.] US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, Orthopaed Joint Devices Branch, Rockville, MD 20857 USA. RP Foy, JR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, Orthopaed Joint Devices Branch, Rockville, MD 20857 USA. NR 13 TC 4 Z9 4 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. PY 2008 VL 16 SU 1 BP S123 EP S128 PG 6 WC Orthopedics SC Orthopedics GA 323UT UT WOS:000257474600024 PM 18612007 ER PT J AU Liang, H Park, S Gallas, BD Myers, KJ Badano, A AF Liang, Hongye Park, Subok Gallas, Brandon D. Myers, Kyle J. Badano, Aldo TI Assessment of display temporal response using a computational observer SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article; Proceedings Paper CT International Symposium of the Society-for-Information-Display CY MAY 20-25, 2007 CL Long Beach, CA SP Soc Informat Display DE model observer; display quality; contrast sensitivity; temporal response AB Temporal response is one of the major concerns for liquid-crystal-display (LCD) performance. Fast response time is preferred for high-fidelity image rendering. Several methods have been proposed to improve the LCD temporal performance. A method to assess the impact of temporal responses based on measured or modeled device temporal characteristics with a contrast-sensitive computational observer that is intended to predict human performance is reported. A method to compare different devices and temporal blur reduction approaches has been applied. It was found that slow temporal response of the display device greatly affects signal contrast and observer performance. This methodology, after validation with human observers, could be used to compare different displays with different inter-gray-level transition time profiles. 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 Liang, H (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 3116, 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 10 TC 2 Z9 2 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI SAN JOSE PA 610 S SECOND STREET, SAN JOSE, CA 95112 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD JAN PY 2008 VL 16 IS 1 BP 21 EP 25 DI 10.1889/1.2835030 PG 5 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 251US UT WOS:000252401400004 ER PT J AU Smith, JS Xu, ZL Byrnes, AP AF Smith, Jeffrey S. Xu, Zhili Byrnes, Andrew P. TI A quantitative assay for measuring clearance of adenovirus vectors by Kupffer cells SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE adenovirus; Kupffer cells; confocal microscopy; image analysis ID LOW-DENSITY-LIPOPROTEIN; GENE-TRANSFER; SCAVENGER RECEPTORS; INTRAVENOUS-INJECTION; BINDING ABLATION; CAR-BINDING; LIVER; MICE; TOXICITY; SEQUESTRATION AB Kupffer cells are a major barrier to systemic adenovirus (Ad) gene therapy because they rapidly and efficiently clear virions from the circulation. The lack of a straightforward quantitative technique for selectively measuring uptake of Ad by Kupffer cells has made it difficult to study the mechanisms by which they recognize Ad. A new method was developed that relies on immunofluorescent detection of Ad within Kupffer cells in mouse liver sections, followed by confocal microscopy and computerized image analysis. The method is sensitive, quantitative and reproducible, with a linear range spanning two orders of magnitude. As an example of the utility of this method, it was found that pre-injecting mice with polyinosinic acid reduces accumulation of Ad in Kupffer cells by approximately 90%. Published by Elsevier B.V. C1 [Smith, Jeffrey S.; Xu, Zhili; Byrnes, Andrew P.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Byrnes, AP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,Room 2E20,HFM 725, Bethesda, MD 20892 USA. EM JeffreyS.Smith@fda.hhs.gov; Zhili.Xu@fda.hhs.gov; Andrew.Byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 NR 36 TC 25 Z9 25 U1 0 U2 1 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 JAN PY 2008 VL 147 IS 1 BP 54 EP 60 DI 10.1016/j.jviromet.2007.08.009 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 255VP UT WOS:000252686300007 PM 17850893 ER PT J AU Farhat, Y Mazhar, A Huang, E Pfefer, TJ Choi, B AF Farhat, Youssef Mazhar, Amaan Huang, Eugene Pfefer, T. Joshua Choi, Bernard TI MONTE-CARLO-based study of depth-resolved laser speckle imaging with spatially modulated light SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 28th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 02-06, 2008 CL Kissimmee, FL SP Amer Soc Laser Med Surg C1 [Farhat, Youssef; Mazhar, Amaan; Choi, Bernard] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA USA. [Mazhar, Amaan; Huang, Eugene; Choi, Bernard] Univ Calif Irvine, Beckman Laser Inst, Irvine, CA USA. [Huang, Eugene] Univ Calif Irvine, Dept Elect Engn, Irvine, CA 92717 USA. [Pfefer, T. Joshua] US FDA, Bethesda, MD USA. RI Pfefer, Josh/I-9055-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2008 SU 20 MA 139 BP 21 EP 21 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 323EA UT WOS:000257425600060 ER PT S AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. BE Hamblin, MR Waynant, RW Anders, J TI Laser light induced modulations in metabolic activities in human brain cancer - art. no. 684607 SO MECHANISMS FOR LOW-LIGHT THERAPY III SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy III CY JAN 20, 2008 CL San Jose, CA SP SPIE ID CELLS; IRRADIATION; RESPONSES; OXIDANTS AB The role of low visible or near infra-red laser intensity in suppressing metabolic activity of malignant human brain cancer (glioblastoma) cells was investigated through the application of either a continuous wave 633nm HeNe or a pulsed picosecond 1,552nm wavelength laser. Human glioblastomas were exposed in their growth culture medium with serum for several energy doses. For both types of laser exposures the glioblastomas exhibited a maximal decline in the metabolic activity relative to their respective sham control counterparts at 10 J/cm(2). The cellular metabolic activities for various treatment doses were measured through the colorimetric NITS metabolic assay after the laser exposure. Interestingly, addition of (the enzyme) catalase in the growth medium prior to the laser exposure was found to diminish the laser induced metabolic suppression for all fluence treatment conditions, thus suggesting a fanctional role of H2O2 in the metabolic suppression. Taken together, our findings reveal that visible or near infra-red low level light exposures could potentially be a viable tool in reducing the metabolic activity of cancers; evidence at hand implicates a role of light induced H2O2 in bringing about in part, suppression in the metabolic activity. Due to the cellular "biphasic" response to the laser exposure, further research needs to be undertaken to determine exposure parameters which would optimize metabolic and cellular growth suppression in-vivo. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, Silver Spring, MD USA. RP Tata, DB (reprint author), US FDA, Silver Spring, MD USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7021-8 J9 P SOC PHOTO-OPT INS PY 2008 VL 6846 BP 84607 EP 84607 DI 10.1117/12.763526 PG 12 WC Medicine, General & Internal; Optics SC General & Internal Medicine; Optics GA BHQ15 UT WOS:000255357000005 ER PT S AU Chen, WJ Metz, CE Giger, ML AF Chen, Weijie Metz, Charles E. Giger, Maryellen L. BE Giger, ML Karssemeijer, N TI Hybrid linear classifier for jointly normal data: theory - art. no. 691504 SO MEDICAL IMAGING 2008: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE linear discriminant analysis; "proper" ROC; hybrid linear classifier; CAD; classifier design ID MAXIMUM-LIKELIHOOD-ESTIMATION; COMPUTERIZED ANALYSIS; BREAST; MASSES AB Classifier design for a given classification task needs to take into consideration both the complexity of the classifier and the size of the data set that is available for training the classifier. With limited training data, as often is the situation in computer-aided diagnosis of medical images, a classifier with simple structure (e.g., a linear classifier) is more robust and therefore preferred. We consider the two-class classification problem in which the feature data arise from two multivariate normal distributions. A linear function is used to combine the multidimensional feature vector onto a scalar variable. This scalar variable, however, is generally not an ideal decision variable unless the covariance matrices of the two classes are equal. We propose using the likelihood ratio of this scalar variable as a decision variable and, thus, generalizing the traditional classification paradigm to a hybrid two-stage procedure: a linear combination of the feature vector elements to form a scalar variable followed by a nonlinear, nonmonotic transformation that maps the scalar variable onto its likelihood ratio (i.e., the ideal decision variable, given the scalar variable). We show that the traditional Fisher's linear discriminant function is generally not the optimal linear function for the first stage in this two-stage paradigm. We further show that the optimal linear function can be obtained with a numerical optimization procedure using the area under the "proper" ROC curve as the objective function. C1 [Chen, Weijie] US FDA, Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Lab,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Lab,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. OI Giger, Maryellen/0000-0001-5482-9728 NR 16 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7099-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6915 BP 91504 EP 91504 DI 10.1117/12.770326 PG 6 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Engineering; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging GA BHU04 UT WOS:000256380300003 ER PT S AU Kinnard, LT Gavrielides, MA Myers, KJ Zeng, R Peregoy, J Pritchard, W Karanian, JW Petrick, N AF Kinnard, Lisa T. Gavrielides, Marlos A. Myers, Kyle J. Zeng, Rongping Peregoy, Jennifer Pritchard, William Karanian, John W. Petrick, Nicholas BE Giger, ML Karssemeijer, N TI Volume error analysis for lung nodules attached to pulmonary vessels in an anthropomorphic thoracic phantom - art. no. 69152Q SO MEDICAL IMAGING 2008: COMPUTER-AIDED DIAGNOSIS, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE volume estimation; lung nodule; lung tumor measures; phantom studies; CT imaging; bias and variance ID COMPUTED-TOMOGRAPHY; CT; SEGMENTATION; THICKNESS; ACCURACY; TUMORS; RISKS AB High-resolution CT, three-dimensional (3D) methods for nodule volumetry have been introduced, with the hope that such methods will be more accurate and consistent than currently used planar measures of size. However, the error associated with volume estimation methods still needs to be quantified. Volume estimation error is multi-faceted in the sense that it is impacted by characteristics of the patient, the software tool and the CT system. The overall goal of this research is to quantify the various sources of measurement error and, when possible, minimize their effects. In the current study, we estimated nodule volume from ten repeat scans of an anthropomorphic phantom containing two synthetic spherical lung nodules (diameters: 5 and 10 mm; density: -630 HU), using a 16-slice Philips CT with 20, 50, 100 and 200 mAs exposures and 0.8 and 3.0 mm slice thicknesses. True volume was estimated from an average of diameter measurements, made using digital calipers. We report variance and bias results for volume measurements as a function of slice thickness, nodule diameter, and X-ray exposure. C1 NIBIB, CDRH,Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst,US FDA, Div Imaging & Math,Off Sci & Engn Labs, Rockville, MD 20857 USA. US FDA, Lab Cardiovasc & Intervent Therapeut, Div Biol, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Kinnard, LT (reprint author), NIBIB, CDRH,Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst,US FDA, Div Imaging & Math,Off Sci & Engn Labs, Rockville, MD 20857 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7099-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6915 BP Q9152 EP Q9152 DI 10.1117/12.773039 PG 9 WC Biophysics; Engineering, Biomedical; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Engineering; Mathematical & Computational Biology; Radiology, Nuclear Medicine & Medical Imaging GA BHU04 UT WOS:000256380300094 ER PT S AU Liang, HY Badano, A AF Liang, Hongye Badano, Aldo BE Sahiner, B Manning, DJ TI Assessment of temporal display using observers - art. no. 69170Q SO MEDICAL IMAGING 2008: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm AB Most assessments of display performance are limited to studying the display quality for static images. However, dynamic scenes constitute a large fraction of medical images and are becoming more widespread due to the increase in the number of images to be interpreted. The image quality of a dynamic scene is affected by the display's temporal characteristics and the human visual system's temporal response. We propose to use a computational observer to understand the effect of image browsing speed in medical displays. We use a 3D cluster lumpy background to study the effect of different browsing speeds using liquid crystal display (LCD) temporal response measurements reported in our previous work. The image set is then analyzed by the computational observer. This allows us to quantify the effect of slow temporal response of medical LCDs on the performance of the anthropomorphic observer. Slow temporal response of the display device affects the lesion contrast and the observer performance. Human visual system also adds to the complexity Of image perception of dynamic scenes. A human observer study was used to validate the computational observer results. C1 [Liang, Hongye; Badano, Aldo] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Liang, HY (reprint author), US FDA, CDRH, Silver Spring, MD 20993 USA. OI badano, aldo/0000-0003-3712-6670 NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7101-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6917 BP Q9170 EP Q9170 DI 10.1117/12.772626 PG 5 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHT13 UT WOS:000256058800023 ER PT S AU Park, S Clarkson, E AF Park, Subok Clarkson, Eric BE Sahiner, B Manning, DJ TI Markov-chain Monte Carlo for the performance of a channelized-ideal observer in detection tasks with non-Gaussian lumpy backgrounds - art. no. 69170T SO MEDICAL IMAGING 2008: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mole Imaging, DICOM Standards Comm DE Bayesian ideal observer; channelized-ideal observer; Markov-chain Monte Carlo; efficient channels; non-Gaussian lumpy backgrounds AB The Bayesian ideal observer is optimal among all observers and sets an upper bound for observer performance in binary detection tasks.(1) This observer provides a quantitative measure of diagnostic performance of an imaging system, summarized by the area under the receiver operating characteristic curve (AUC),(1) and thus should be used for image quality assessment whenever possible. However, computation of ideal-observer performance is difficult because this observer requires the full description of the statistical properties of the signal-absent and signal-present data, which are often unknown in tasks involving complex backgrounds. Furthermore, the dimension of the integrals that need to be calculated for the observer is huge. To estimate ideal-observer performance in detection tasks with non-Gaussian lumpy backgrounds, Kupinski et al.(2) developed a Markov-chain Monte Carlo (MCMC) method, but this method has a disadvantage of long computation times. In an attempt to reduce the computation load and still approximate ideal-observer performance, Park et al.(3,4) investigated a channelized-ideal observer (CIO) in similar tasks and found that the CIO with singular vectors of the imaging system approximated the performance of the ideal observer. But, in that work, an extension of the Kupinski MCMC was used for calculating the performance of the CIO and it did not reduce the computational burden. In the current work, we propose a new MCMC method, which we call a CIO-MCMC, to speed up the computation of the CIO. We use singular vectors of the imaging system as efficient channels for the ideal observer. Our results show that the CIO-MCMC has the potential to speed up the computation of ideal observer performance with a large number of channels. C1 [Park, Subok] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Park, S (reprint author), 10903 New Hampshire Ave,Bldg 62,Room 3111, Silver Spring, MD 20993 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7101-7 J9 P SOC PHOTO-OPT INS PY 2008 VL 6917 BP T9170 EP T9170 DI 10.1117/12.771704 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHT13 UT WOS:000256058800026 ER PT S AU Paquerault, S Samuelson, FW Petrick, N Myers, KJ AF Paquerault, Sophie Samuelson, Frank W. Petrick, Nicholas Myers, Kyle J. BE Sahiner, B Manning, DJ TI Comparing signal-based,and case-based methodologies for CAD assessment in a detection task SO MEDICAL IMAGING 2008: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm DE computer-aided detection; multiple reader multiple case (MRMC) analysis; free-response receiver operating characteristics; receiver operating characteristics ID COMPUTER-AIDED DETECTION; SCREENING MAMMOGRAPHY; SENSITIVITY AB We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance using a signal-based performance analysis derived from Free-response Receiver Operating Characteristics (FROC) versus a case-based performance analysis derived from Receiver Operating Characteristics (ROC) analysis. To consider this question, we utilized reader data from a CAD assessment study based on 100 mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low- and high-intensity set. The study thus allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) equivalent or lower than the average reader. Seven readers were asked to review each set using CAD in both second-reader and concurrent modes. Signal-based detection results were analyzed using the area under the FROC curve below 0.5 false positives per image. Case-based decision results were analyzed using the area under the parametric ROC curve. The results were consistent between the signal-based and case-based analyses for the low-intensity set, suggesting that CAD in both reading modes can increase reader signal-based detection and case-based decision accuracies. For the high-intensity set, the signal-based and case-based analysis suggested different conclusions regarding the utility of CAD, although neither analysis resulted in statistical significance. C1 [Paquerault, Sophie; Samuelson, Frank W.; Petrick, Nicholas; Myers, Kyle J.] US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. RP Paquerault, S (reprint author), US FDA, CDRH Lab Assessment Med Imaging Syst, NIBIB, Rockville, MD 20857 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7101-7 J9 PROC SPIE PY 2008 VL 6917 AR 691708 DI 10.1117/12.771498 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHT13 UT WOS:000256058800006 ER PT S AU Xu, A Saha, A Guarnieri, G Ramponi, G Badano, A AF Xu, An Saha, Anindita Guarnieri, Gabriele Ramponi, Giovanni Badano, Aldo BE Andriole, KP Siddiqui, KM TI Display methods for adjustable grayscale and luminance depth SO MEDICAL IMAGING 2008: PACS AND IMAGING INFORMATICS SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2008 Conference CY FEB 17-19, 2008 CL San Diego, CA SP SPIE, Amer Assoc Phys Med, Amer Physiol Soc, Comp Assisted Radiol & Surg, Soc Imaging Sci & Technol, Med Image Percept Soc, Radiol Soc N Amer, Soc Imaging Informat Med, Soc Mol Imaging, DICOM Standards Comm ID PERFORMANCE AB We explore the calibration of a high luminance range, dual-layer, liquid crystal display (LCD) prototype. The operation of the prototype is done by splitting a high luminance resolution image(graylevel > 2(8)) into two 8-bit depth components and sending these images to the two liquid crystal panels stacked over the backlight module. By interpolation of a small set of luminance data gathered using a specialized luminance probe, the look-up table of graylevel pairs of front/back layer LCD and the corresponding luminance values can be generated. To display images, we fit an extended DICOM model to the interpolated luminance table which is adjustable for graylevel and luminance depth. A dynamic look up table is generated in which for each luminance there are several graylevel pair candidates. We show results for one possible calibration strategy involving the pair selection criterion. By selecting the pair that maximizes back-layer smoothness, the images with arbitrary graylevel and luminance depth can be then displayed with equal perceptual distance between luminance levels, while minimizing parallax effects. Other possible strategies that minimize glare and noise are also described. The results can be used for high luminance range display performance characterization and for the evaluation of its clinical significance. C1 [Xu, An; Saha, Anindita; Badano, Aldo] Ctr Devices & Radiol Hlth, US FDA, Silver Spring, MD USA. RP Xu, A (reprint author), Ctr Devices & Radiol Hlth, US FDA, Silver Spring, MD USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7103-1 J9 PROC SPIE PY 2008 VL 6919 AR 69190Q DI 10.1117/12.771675 PG 7 WC Engineering, Biomedical; Optics; Imaging Science & Photographic Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Imaging Science & Photographic Technology; Physiology; Radiology, Nuclear Medicine & Medical Imaging GA BHU33 UT WOS:000256422200024 ER PT J AU Jackson, LS Al-Taher, F AF Jackson, Lauren S. Al-Taher, Fadwa BE BarkaiGolan, R Paster, N TI Factors Affecting Mycotoxin Production in Fruits SO MYCOTOXINS IN FRUITS AND VEGETABLES LA English DT Article; Book Chapter ID ALTERNARIOL METHYL-ETHER; OCHRATOXIN-A PRODUCTION; DRIED VINE FRUITS; ASPERGILLUS-CARBONARIUS GROWTH; COMMERCIAL APPLE PRODUCTS; PENICILLIUM-EXPANSUM; PATULIN PRODUCTION; DATE FRUITS; AFLATOXIN CONTAMINATION; LIQUID-CHROMATOGRAPHY AB Fungi belonging to the genera Aspergillus, Pencillium and Alternaria are major contributors to fruit spoilage and are responsible for significant financial losses for any segment of the food industry that harvests, stores, processes or uses fruits or fruit-derived ingredients. In addition to their ability to cause fruit spoilage, these fungi produce mycotoxins that are of concern to human health. The mycotoxins most commonly associated with fruit and fruit products are patulin, aflatoxin, Alternaria toxins and ochratoxin A. Factors known to affect production of these mycotoxins in fruit include the fruit type and cultivar, geographical location where the fruit is grown and harvested, climate, pre-harvest treatments, method of harvest, presence of surface defects on the fruit, post-harvest treatments and storage conditions. Mycotoxin accumulation in fruits can occur in the field, during harvest, post-harvest and during storage. Gentle and sanitary handling of the fruit during harvest and in storage and processing facilities is essential for reducing fungal decay and mycotoxin production in fruits. Although consumers will likely reject fresh fruit that is visibly moldy or rotten, processed fruit products may contribute significant amounts of these toxins if decayed or moldy fruit is not removed before processing or packaging. Thus, only sound, intact fruit should be used for processed fruit products. Fruits used for dried fruit production should be dried rapidly and completely, and stored under conditions that prevent rewetting. Research is needed to identify fruit cultivars that are resistant to fungal decay and to evaluate treatments that could be used to control fungal pathogens in the field or post-harvest. Finally, more work is needed to determine the fate of mycotoxins during processing. C1 [Jackson, Lauren S.] US FDA, NCFST, Summit Argo, IL 60501 USA. [Al-Taher, Fadwa] IIT, NCFST, Summit Argo, IL 60501 USA. RP Jackson, LS (reprint author), US FDA, NCFST, Summit Argo, IL 60501 USA. NR 189 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055785-4 PY 2008 BP 75 EP 104 DI 10.1016/B978-0-12-374126-4.00004-8 PG 30 WC Food Science & Technology; Mycology SC Food Science & Technology; Mycology GA BGM60 UT WOS:000323511300005 ER PT J AU Ramalingam, TR Pescel, JT Sheikh, F Cheever, AW Mentink-Kane, MM Wilson, MS Stevens, S Valenzuela, DM Murphy, AJ Yancopoulos, GD Urban, JF Donnelly, RP Wynn, TA AF Ramalingam, Thirumalai R. Pescel, John T. Sheikh, Faruk Cheever, Allen W. Mentink-Kane, Margaret M. Wilson, Mark S. Stevens, Sean Valenzuela, David M. Murphy, Andrew J. Yancopoulos, George D. Urban, Joseph F., Jr. Donnelly, Raymond P. Wynn, Thomas A. TI Unique functions of the type 11 interleukin 4 receptor identified in mice lacking the interleukin 13 receptor alpha 1 chain SO NATURE IMMUNOLOGY LA English DT Article ID ALTERNATIVELY ACTIVATED MACROPHAGES; IL-13 INDUCES PROLIFERATION; HUMAN B-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; GRANULOMATOUS PATHOLOGY; NEMATODE PARASITES; IMMUNE-RESPONSE; GENE-EXPRESSION; TH2 CYTOKINES; TNF-ALPHA AB The interleukin 4 receptor (IL-4R) is a central mediator of T helper type 2 (T(H)2)-mediated disease and associates with either the common gamma-chain to form the type I IL-4R or with the IL-13R alpha 1 chain (IL-13R alpha 1) to form the type II IL-4R. Here we used II13ral(-/-) mice to characterize the distinct functions of type I and type II IL-4 receptors in vivo. In contrast to II4ra(-/-) mice, which have weak T(H)2 responses, II13ra1(-/-) mice had exacerbated T(H)2 responses. II13ra1(-/-) mice showed much less mortality after infection with Schistosoma mansoni and much more susceptibility to Nippostrongylus brasiliensis. IL-13R alpha 1 was essential for allergen-induced airway hyperreactivity and mucus hypersecretion but not for fibroblast or alternative macrophage activation. Thus, type I and II IL-4 receptors exert distinct effects on immune responses. C1 [Ramalingam, Thirumalai R.; Pescel, John T.; Mentink-Kane, Margaret M.; Wilson, Mark S.; Wynn, Thomas A.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. [Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. [Cheever, Allen W.] Inst Biomed Res, Rockville, MD 20892 USA. [Stevens, Sean; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Urban, Joseph F., Jr.] USDA, BHNRC, Diet Genom & Immunol Lab, Beltsville, MD 20705 USA. RP Wynn, TA (reprint author), NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Murphy, Andrew/0000-0003-4152-4081 FU Intramural NIH HHS [Z01 AI001019-01, Z01 AI000829-10] NR 49 TC 104 Z9 106 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JAN PY 2008 VL 9 IS 1 BP 25 EP 33 DI 10.1038/ni1544 PG 9 WC Immunology SC Immunology GA 243TS UT WOS:000251820800008 PM 18066066 ER PT B AU Dair, BJ Saylor, DM Kennedy, KM Casas, RS AF Dair, Benita J. Saylor, David M. Kennedy, Kristen M. Casas, Rachel S. BE Laudon, M Romanowicz, B TI Effect of Medical Device Substrate Material on Nanoparticulate Silver Efficacy SO NSTI NANOTECH 2008, VOL 2, TECHNICAL PROCEEDINGS: LIFE SCIENCES, MEDICINE, AND BIO MATERIALS LA English DT Proceedings Paper CT Nanotechnology Conference and Trade Show (Nanotech 2008) CY JUN 01-05, 2008 CL Boston, MA SP Accelrys Software, Ace Glass, Advance Reprod Corp, Adv Mat Technolog Pte Ltd, Agilent Technol, AIXTRON AG, AJA Int, ALM, Amuneal Mfg Corp, ANSYS, Anton Paar, Appl MicroStruct, Appl Surface Technol, Arkalon Chem Technolog, LLC, Arkema Grp, Artech House Publishers, Asemblon, ASML, Asylum Res, AZoNano, Banner & Witcoff, Beckman Coulter, Bio Nano Counsulting, BioForce Nanosci, Boneer Corp, Birck Nanotechnol Ctr, Purdue Univ, Discovery Pk, Brookhaven Instruments Corp, Buchanan Ingersoll & Rooney PC, Buhler AG, Business Week, Calif NanoSyst Inst, Capovani Brothers, Los Alamos, Ctr Integrated Nanotechnologies, Sandia Natl Labs, Ctr Integrated Nanotechnologies, Oak Ridge Natl Lab, Ctr Nanophase Mat Sci, Argonne Natl Lab, Ctr Nanoscale Mat, Cheap tubes, Clean Technol & Sustainable Ind Org, COMSOL, Cooley Godward Kronish LLP, Core Technol Grp, CRESTEC Corp, CSEM, CVI Melles Griot, Dept Innovat, Ind, Sci & Res, Digital Matrix, Draiswerke, ETH Zurich, Eulitha AG, Marks & Clerk, Marubent Techno Syst Corp, Massachusetts Technol Transfer Ctr, Mat Res Soc, Merck & Co, Microfluidics, Micromerit Instrument Corp, Microtrac, MINAT 2008, Messe Stuttgart, Minus K Technol, Misonix, Lawrence Berkeley Natl Lab, Mol Foundry, Motorola, Nano Korea 2008, Nano Sci & Technol Inst, nano tech 2009 Japan, Nano Technol Res Assoc Korea, NanoAndMore USA, NanoDynamics, NanoEurope 2008, NanoInk, Nanomotion, Nanon Imaging Ltd, NANOSENSORS, Nanosyst Initiat Munich, Nanotech No Europe 2008, nano Tox, Nano World AG, NCI, Natl Inst Stand & Technol, NIH, Natl Nanomfg Network, Natl Nanotechnol Infrastruct, GATech, Microelect Res Ctr, Nat Nano, Nat Publishing Grp, NETZSCH Fine Particle Technol LLC, NIL Technol ApS, Novomer, NTT Adv Technol Corp, Olympus Ind Amer, OSEC, Business Network Switzerland, Oxford Instruments, Particle Technol Labs, Penn State Univ, Photon Spectra, Physik Instrumente LP, picoDrill SA, Piezo Inst, PVD Prod, Q Sense, Quantum Analyt, Raith USA, European Patent Off, Evans Analyt Grp, EXAKT Technologies, First Nano, Flow Sci, FDA, Goodwin Procter LLP, Greater Houston Partnership, Greenberg Traurig LLP, Halcyonics, Headwaters Technol Innovat LLC, Heidelberg Instruments, Hielscher USA, HighNano Analyti, Hiscock & Barclay LLP, Hitachi High Technologies Amer, Hochschule Offenburg Univ Appl Sci, HOCKMEYER Equipment Corp, HORIBA Jobin Yvon, IBU-tec adv mat GmbH, IDA Ireland, ImageXpert, Inspec, Inc, IEEE, Inst Nanoscale & Quantum Sci & Technol Adv Res, IntelliSense Software Corp, Invest Germany, IOP Publishing, Italian Trade Commiss, JENOPTIK, Justus Liebig Univ, KAUST, Keithley Instruments, Kelvin Nanotechnol Ltd, Kodak, Kotobuki Ind Co, Ltd, Lake Shore Cryotron, MACRO M, NanoClay, Res Germany Land Ideas, RKS Legal Solut LLC, Dandia Natl Labs, Scottish Enterprise, SEMTech Solut, Serendip, Silvix Corp, SNS Nano Fiber Technol LLC, SoftMEMS LLC, Son & Mat, SW Nano Technologies, Specialty Coating Syst, Spectrum Labs, SPEX SamplePrep LLC, Springer, Sterne, Kessler, Goldstein & Fox PLLC, Strem Chem, Sukgyung A T Co, Lts, Surrey NanoSyst, SUSS MicroTec, Swissnanotech Pavilion, Taylor & Francis Grp LLC, CRC Press, TechConnect, Technovel Corp, Tekna Plasma Syst, Thinky Corp, Thomas Swan & Co Ltd, UGL Unicco, UK Trade & Investment, UniJet, Univ Munster, Univ Appl Sci, Univ Duisburg, Ctr Nanointegrat Duisburg, Vecco Instruments, Wasatch Mol Inc, Weidmann Plast Technol, Whiteman Osterman & Hanna LLP, Willy A Bachofen AG, WITec GmbH, World Gold Council DE medical device; silver nanoparticle; coating; antimicrobial AB Silver is one of the oldest known natural antimicrobial materials, the active form being the Ag+ ion, which disrupts critical cell functions in bacteria. Reducing the size of silver particles to the nanoscale regime increases the surface area and hence the availability of silver ions, thereby enhancing their potential antimicrobial efficacy relative to their bulk counterparts. Nanoparticulate silver systems have been used as antimicrobial agents for medical device applications such as bandages, wound dressings, surgical masks, endotracheal tubes, and catheters. However the surface onto which the silver nanoparticles are deposited will impact the availability of Ag+ ions due to the chemistry of the substrate surface and its affinity for silver ions. The effect of substrate material on the efficacy of nanoparticulate silver will be discussed, along with the implications of materials selection in medical device applications. C1 [Dair, Benita J.; Saylor, David M.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Kennedy, Kristen M.] Amer Univ, Washington, DC 20016 USA. [Casas, Rachel S.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Dair, BJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM benita.dair@fda.hhs.gov OI Casas, Rachel/0000-0003-2848-3107 NR 4 TC 0 Z9 0 U1 0 U2 4 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-8504-4 PY 2008 BP 188 EP + PG 2 WC Nanoscience & Nanotechnology; Medicine, General & Internal; Medicine, Research & Experimental; Materials Science, Biomaterials SC Science & Technology - Other Topics; General & Internal Medicine; Research & Experimental Medicine; Materials Science GA BMF49 UT WOS:000272169900051 ER PT J AU Hoadley, JE Rowlands, JC AF Hoadley, James E. Rowlands, J. Craig BE Bagchi, D TI FDA Perspectives on Food Label Claims in the USA SO NUTRACEUTICAL AND FUNCTIONAL FOOD REGULATIONS IN THE UNITED STATES AND AROUND THE WORLD SE Food Science and Technology-International Series LA English DT Article; Book Chapter AB Under the US laws that FDA enforces, food label claims generally fall into three categories: nutrient content claims, health claims and structure/function claims. Nutrient content claims are statements that characterize the level of a nutrient in a food. Nutrient content claims on food labels must be used in accordance with FDA authorizing regulations. Health claims describe a relationship of a food, food component or dietary supplement in reducing the risk of a disease or health-related condition. Health claims must be evaluated and authorized prior to their use in food labeling. There are three ways by which FDA exercises its oversight in determining which health claims may be used in food labeling. One way is the issuance of authorizing regulations based on FDA's conclusion that there is significant scientific agreement that the available scientific evidence supports the relationship. A second way is through a notification to FDA of a health claim based on authoritative statements from a scientific body of the US government or the National Academy of Sciences that ensues from that scientific body's deliberative review of scientific evidence on the substance/disease relationship. The third way provides for qualified health claims where the quality and strength of the scientific evidence falls below that required for FDA to issue an authorizing regulation. Structure/function claims are food label statements that describe the role of a nutrient or dietary supplement ingredient to affect normal structure or function in humans. Structure/function claims have historically appeared on the labels of conventional foods and dietary supplements. However, the Dietary Supplement Health and Education Act of 1994 established special regulatory procedures for the use of such statements on dietary supplement labels. C1 [Hoadley, James E.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Rowlands, J. Craig] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI USA. RP Hoadley, JE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 9 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092052-8 J9 FOOD SCI TECHNOL-INT PY 2008 BP 115 EP 132 PG 18 WC Food Science & Technology SC Food Science & Technology GA BFN16 UT WOS:000320593100010 ER PT J AU Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Hass, BS Latendresse, JR Thorn, BT Tobin, G Feuers, RJ AF Duffy, Peter H. Lewis, Sherry M. Mayhugh, Martha A. Trotter, Ronald W. Hass, Bruce S. Latendresse, John R. Thorn, Brett T. Tobin, Graham Feuers, Ritchie J. TI Neoplastic pathology in male Sprague-Dawley rats fed AIN-93M diet ad libitum or at restricted intakes SO NUTRITION RESEARCH LA English DT Article DE dietary; restriction; neoplastic; pathology; AIN-93M diet; rat ID CALORIC RESTRICTION; MAMMARY-TUMORS; INCREASED CARCINOGENICITY; FISCHER-344 RATS; PURIFIED DIETS; DOSE LEVELS; SURVIVAL; GROWTH; MICE; PROTEIN AB The primary purpose of this study was to evaluate the effects of age and long-term dietary reduction on neoplastic diseases in rats fed the AIN-93M purified diet. Second, pathologic profiles are critical to comprehensive dietary evaluation. Male Sprague-Dawley rats assigned to 2 groups, ad libitum (AL) and dietary restricted (DR), were fed the AIN-93M (casein protein) diet free choice and reduced in amount by 31 %, respectively. At 58 weeks of age, the predominant types of lesions in AL and DR rats were pituitary and skin tumors. At 114 weeks of age, the most common lesions were pituitary, adrenal gland, skin, mammary, brain, and pancreatic tumors and mononuclear cell leukemia. However, DR had no significant effect on these lesions. Primary findings demonstrate that DR significantly reduced the total number of tumors per rat and incidence of benign and primary tumors (all organs) but did not reduce the incidence of malignant tumors (all organs). Dietary restriction increased the percentage of unknown deaths. These results may explain why survival rates for AL and DR rats were not significantly different at 114 weeks (43.3 vs 57.5%, respectively). These findings differ from previous studies using NIH-31 cereal diet (Aging Clin Exp Res 2001;13:263; J Nutr 2002;132:101; Aging Clin Exp Res 2003;16(6):68; Aging Clin Exp Res 2004;16:448) where neoplastic lesions rather than nonneoplastic lesions were linked to a significant increase in survival rate among cohorts of DR-fed rats (J Nutr 2002;132:101). Factors such as diet composition and digestibility, although not independent of body weight, may have contributed to differences in rat mortality and may affect humans in a similar manner. Published by Elsevier Inc. C1 [Duffy, Peter H.; Hass, Bruce S.] US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. [Lewis, Sherry M.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Mayhugh, Martha A.] US FDA, Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA. [Trotter, Ronald W.; Latendresse, John R.] US FDA, Natl Ctr Toxicol Res, Pathol Assoc Int, Jefferson, AR 72079 USA. [Thorn, Brett T.] US FDA, Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. [Feuers, Ritchie J.] US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. [Tobin, Graham] Harlan Teklad, Bicester OX25 1TP, Oxon, England. RP Duffy, PH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. EM petetduffy@fda.hhs.gov RI Latendresse, John/A-9215-2009; Biguzzi, Felipe/E-4724-2015 NR 44 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2008 VL 28 IS 1 BP 36 EP 42 DI 10.1016/j.nutres.2007.09.018 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 256VY UT WOS:000252759200007 PM 19083386 ER PT J AU Pazdur, R AF Pazdur, Richard TI Endpoints for assessing drug activity in clinical trials SO ONCOLOGIST LA English DT Article DE endpoints; survival; time to progression; response rate ID APPROVAL AB Overall survival remains the gold standard for the demonstration of clinical benefit. An improvement in overall survival is a direct clinical benefit to patients. An analysis of overall survival requires larger patient numbers and longer follow-up than other endpoints. Survival analysis may be confounded by subsequent therapies. Time to progression usually requires smaller clinical trials and may be more rapidly assessed than trials using overall survival as an endpoint. This endpoint is not confounded by subsequent therapies. Time to progression must use the same evaluation techniques and schedules for all therapies being evaluated. Blinding of trials or the use of an external blinded radiographic review committee is recommended in assessing time to progression. Unlike overall survival and time to progression, which must be evaluated in randomized trials, response rates can be accurately assessed using a single-arm trial. Stable disease is not included in a response rate determination and is optimally evaluated by assessing tumor progression in a randomized trial. Improvement in disease-related symptoms is considered clinical benefit and may be an appropriate endpoint for drug approval. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20825 USA. RP Pazdur, R (reprint author), US FDA, Ctr Drug Evaluat & Res, 1451 Rockville Pike,Woodmont Off Complex 2, Rockville, MD 20825 USA. EM pazdurr@cder.fda.gov NR 2 TC 107 Z9 109 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 SU 2 BP 19 EP 21 DI 10.1634/theoncologist.13-S2-19 PG 3 WC Oncology SC Oncology GA 293PS UT WOS:000255347800005 PM 18434634 ER PT J AU Demko, S Summers, J Keegan, P Pazdur, R AF Demko, Suzanne Summers, Jeffrey Keegan, Patricia Pazdur, Richard TI FDA drug approval summary: Alemtuzumab as single-agent treatment for B-Cell chronic lymphocytic leukemia SO ONCOLOGIST LA English DT Article DE chronic lymphocytic leukemia; progressive disease; first-line therapy; alemtuzumab; chlorambucil ID HUMAN CD52 ANTIBODY AB On September 19, 2007, the U. S. Food and Drug Administration granted regular approval and expanded labeling for alemtuzumab (Campath((R)); Genzyme Corporation, Cambridge, MA) as single-agent treatment for B-cell chronic lymphocytic leukemia (B-CLL). Alemtuzumab was initially approved in 2001 under accelerated approval regulations. Conversion to regular approval was based on a single study submitted to verify clinical benefit. Efficacy and safety were demonstrated in an open-label, international, multicenter, randomized trial of 297 patients with previously untreated, Rai stage I-IV B-CLL experiencing progression of their disease. Patients were randomized to either alemtuzumab, 30 mg i.v. over 2 hours three times per week on alternate days for a maximum of 12 weeks, or chlorambucil, 40 mg/m(2) orally every 28 days for a maximum of 12 months. The progression-free survival time, the primary study endpoint, was significantly longer in the alemtuzumab arm than in the chlorambucil arm. Both the overall and complete response rates were also significantly higher in the alemtuzumab arm. No differences in survival were observed. There were no new safety signals identified in patients receiving alemtuzumab. The most serious, and sometimes fatal, toxicities of alemtuzumab are cytopenias, infusion reactions, and infections. C1 [Demko, Suzanne; Summers, Jeffrey; Keegan, Patricia; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Div Biol Oncol Prod, Silver Spring, MD 20993 USA. RP Demko, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Div Biol Oncol Prod, 10903 New Hampshire Ave,WO 22 Room 2307,Mail Stop, Silver Spring, MD 20993 USA. EM suzanne.demko@fda.hhs.gov NR 7 TC 43 Z9 45 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 2 BP 167 EP 174 DI 10.1634/theoncologist.2007-0218 PG 8 WC Oncology SC Oncology GA 268LJ UT WOS:000253581000011 PM 18305062 ER PT J AU Kane, RC McGuinn, WD Dagher, R Justice, R Pazdur, R AF Kane, Robert C. McGuinn, W. David, Jr. Dagher, Ramzi Justice, Robert Pazdur, Richard TI Dexrazoxane (Totect (TM)): FDA review and approval for the treatment of accidental extravasation following intravenous anthracycline chemotherapy SO ONCOLOGIST LA English DT Article DE anthracycline extravasation; Totect (TM); dexrazoxane ID PHASE-II TRIAL; TOPOISOMERASE-II; ICRF-187; INHIBITION AB Management of anthracycline extravasation is problematic and most reports are anecdotal. On September 6, 2007, the U. S. Food and Drug Administration approved Totect (TM) 500 mg (dexrazoxane hydrochloride for injection) for the treatment of extravasation resulting from i.v. anthracycline chemotherapy. In two studies, a total of 57 evaluable patients experienced extravasation from peripheral vein or central venous access sites with local swelling, pain, or redness. The presence of anthracycline in skin biopsy tissue was confirmed by tissue fluorescence, and treatment with a 3-day schedule of dexrazoxane began within 6 hours of the event. The primary endpoint was a reduction in the need for surgical intervention. Only one patient required surgical repair of the injury site, and late sequelae in the remainder were absent or mild. Also, the sponsor, TopoTarget A/S, Copenhagen, Denmark, performed controlled nonclinical studies in support of dexrazoxane dose and timing for the reduction of tissue injury resulting from anthracycline extravasation. For this uncommon but serious complication of anthracycline therapy, the need for surgical intervention was 1.7% with this regimen. C1 [Kane, Robert C.; McGuinn, W. David, Jr.; Dagher, Ramzi; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 2109, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 10 TC 24 Z9 26 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 4 BP 445 EP 450 DI 10.1634/theoncologist.2007-0247 PG 6 WC Oncology SC Oncology GA 294QU UT WOS:000255421400014 PM 18448560 ER PT J AU Cohen, MH Johnson, JR Justice, R Pazdur, R AF Cohen, Martin H. Johnson, John R. Justice, Robert Pazdur, Richard TI FDA drug approval summary: Nelarabine (Arranon (R)) for the treatment of T-cell lymphoblastic leukemia/lymphoma SO ONCOLOGIST LA English DT Article DE nelarabine; Arranon (R); T-cell lymphoblastic leukemia/lymphoma; relapsed disease ID REFRACTORY HEMATOLOGIC MALIGNANCIES; PHASE-I; CHILDREN; PHARMACOKINETICS; LEUKEMIA; 506U78; ADULTS AB Purpose. To describe the clinical trials leading to U. S. Food and Drug Administration (FDA) approval of nelarabine (Arranon (R)), a new purine analogue, for the treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Experimental Design. Two phase II trials, one conducted in pediatric patients and the other in adult patients, were reviewed. Patients were in their first or subsequent relapse and/or were refractory to first-line therapy. The dose and schedule of i. v. nelarabine in the pediatric and adult studies were 650 mg/m(2) per day daily for 5 days and 1,500 mg/m(2) i. v. on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study endpoints were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*). Results. The pediatric efficacy population consisted of 39 patients who had relapsed after, or had been refractory to, two or more induction regimens. CR to nelarabine treatment was observed in five patients (13%) and CR + CR* was observed in nine patients (23%). The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in five patients (18%) and CR + CR* was observed in six patients (21%). Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included hematologic, hepatic, and metabolic laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults. Conclusions. On October 28, 2005, the FDA granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-ALL/T-LBL after at least two prior regimens. This use is based on the induction of CR. The applicant will conduct postmarketing clinical trials to demonstrate clinical benefit, for example, survival prolongation. C1 [Cohen, Martin H.; Johnson, John R.; Justice, Robert; Pazdur, Richard] US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 9 TC 33 Z9 33 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 6 BP 709 EP 714 DI 10.1634/theoncologist.2006-0017 PG 6 WC Oncology SC Oncology GA 323FA UT WOS:000257428500010 PM 18586926 ER PT J AU Dmytrijuk, A Robie-Suh, K Cohen, MH Rieves, D Weiss, K Pazdur, R AF Dmytrijuk, Andrew Robie-Suh, Kathy Cohen, Martin H. Rieves, Dwaine Weiss, Karen Pazdur, Richard TI FDA Report: Eculizumab (Soliris (R)) for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria SO ONCOLOGIST LA English DT Article DE Eculizumab; Paroxysmal nocturnal hemoglobinuria; PNH; Drug approval ID COMPLEMENT INHIBITOR ECULIZUMAB; MANAGEMENT; HEMOLYSIS AB On March 16, 2007, eculizumab (Soliris (R); Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U. S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion-dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated. The Oncologist 2008; 13: 993-1000 C1 [Dmytrijuk, Andrew; Robie-Suh, Kathy; Cohen, Martin H.; Rieves, Dwaine; Weiss, Karen; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Dmytrijuk, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM andrew.dmytrijuk@fda.hhs.gov FU U.S. Food and Drug Administration FX The views expressed are the result of independent work and do not necessarily represent the views and findings of the U.S. Food and Drug Administration. NR 13 TC 46 Z9 48 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 9 BP 993 EP 1000 DI 10.1634/theoncologist.2008-0086 PG 8 WC Oncology SC Oncology GA 358BZ UT WOS:000259892800010 PM 18784156 ER PT J AU Ryan, Q Ibrahim, A Cohen, MH Johnson, J Ko, CW Sridhara, R Justice, R Pazdur, R AF Ryan, Qin Ibrahim, Amna Cohen, Martin H. Johnson, John Ko, Chia-wen Sridhara, Rajeshwari Justice, Robert Pazdur, Richard TI FDA Drug Approval Summary: Lapatinib in Combination with Capecitabine for Previously Treated Metastatic Breast Cancer That Overexpresses HER-2 SO ONCOLOGIST LA English DT Article DE FDA summary; Metastatic breast cancer; Multidrug resistant; Lapatinib; Capecitabine ID DOCETAXEL; INHIBITOR; PLUS AB On March 13, 2007, the U.S. Food and Drug Administration approved lapatinib (Tykerb (R) tablets; GlaxoSmithKline, Philadelphia), an oral, small molecule, dual tyrosine kinase inhibitor of ErbB-2 and ErbB-1, for use in combination with capecitabine for the treatment of patients with human epidermal growth factor receptor (HER)-2-overexpressing metastatic breast cancer who had received prior therapy including an anthracycline, a taxane, and trastuzumab. One multicenter, open-label, randomized trial was submitted. Eligible patients had stage IIIb or IV breast cancer, ErbB-2 overexpression (immunohistochemistry 3+ or 2+ with fluorescence in situ hybridization confirmation), measurable disease, a 0 or 1 Eastern Cooperative Oncology Group performance status score, a cardiac ejection fraction within the institutional normal range, and adequate laboratory function. Patients received either lapatinib (1,250 mg once daily on days 1-21) plus capecitabine (1,000 mg/m(2) every 12 hours on days 1-14) every 21 days or capecitabine alone (1,250 mg/m(2) every 12 hours on days 1-14) every 21 days. The primary endpoint was time to progression (TTP) determined by a blinded independent review panel. After TTP results of a prespecified interim analysis were made available, study enrollment was discontinued (399 patients enrolled). The median TTP was 27.1 versus 18.6 weeks (hazard ratio, 0.57; p = .00013) favoring the lapatinib plus capecitabine arm. Response rates were 23.7% (lapatinib plus capecitabine) versus 13.9% (capecitabine alone). Survival data were not mature. Although the toxicities observed in the lapatinib and capecitabine combination arm were generally similar to those in the capecitabine alone arm, a higher incidence of diarrhea and rash was noted with the combination. Grade 3 or 4 adverse reactions that occurred with a frequency of >5% in patients on the combination arm were diarrhea (13%) and palmar-plantar erythrodys-esthesia (12%). There was a 2% incidence of reversible decreased left ventricular function in the combination arm. The Oncologist 2008; 13: 1114-1119 C1 [Ryan, Qin; Ibrahim, Amna; Cohen, Martin H.; Johnson, John; Ko, Chia-wen; Sridhara, Rajeshwari; Justice, Robert; Pazdur, Richard] US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ryan, Q (reprint author), US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM qin.ryan@fda.hhs.gov NR 8 TC 81 Z9 82 U1 0 U2 5 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 10 BP 1114 EP 1119 DI 10.1634/theoncologist.2008-0816 PG 6 WC Oncology SC Oncology GA 369VL UT WOS:000260721900011 PM 18849320 ER PT J AU Hazarika, M Rock, E Williams, G Dagher, R Sridhara, R Booth, B Farrell, A Justice, R Pazdur, R AF Hazarika, Maitreyee Rock, Edwin Williams, Gene Dagher, Ramzi Sridhara, Rajeshwari Booth, Brian Farrell, Ann Justice, Robert Pazdur, Richard TI Lenalidomide in Combination with Dexamethasone for the Treatment of Multiple Myeloma After One Prior Therapy SO ONCOLOGIST LA English DT Article DE Lenalidomide; Multiple myeloma; Approval AB Purpose. Lenalidomide (CC-5013, Revlimid (R); Celgene Corporation, Summit, N.J), a thalidomide analogue, was granted approval by the U. S. Food and Drug Administration (FDA) on June 29, 2006, for use in combination with dexamethasone in patients with multiple myeloma (MM) who have received at least one prior therapy. The FDA approved lenalidomide with a restricted distribution program, RevAssist (R). Experimental Design. In two randomized, doubleblind, multicenter studies, the combination of lenalidomide and dexamethasone (LD) was compared with placebo and dexamethasone (PD) in patients with MM who had received at least one prior therapy. The primary endpoint was time to progression (TTP). Results. Following a prespecified interim analysis of TTP, an independent data-monitoring committee advised the sponsor to halt the two studies. For both studies, the interim analysis for efficacy revealed a statistically significant longer TTP with LD than with PD. The most clinically relevant grade 3 and 4 adverse events that occurred more frequently in the LD arm were neutropenia, thrombocytopenia, deep vein thrombosis, pulmonary embolism, and atrial fibrillation. Thrombotic or thromboembolic events, including deep vein thrombosis, pulmonary embolism, thrombosis, and intracranial venous sinus thrombosis were reported more frequently in patients treated with LD than with PD. Conclusions. The FDA approved lenalidomide based on interim results from two multicenter, placebo-controlled, randomized trials comparing the combination of LD with PD that revealed a longer TTP with LD than with PD. The major toxicity observed during these trials was myelosuppression. The serious toxicities included thromboembolic events. Lenalidomide is only available under the RevAssist (R) Program. The Oncologist 2008; 13: 1120-1127 C1 [Hazarika, Maitreyee; Rock, Edwin; Dagher, Ramzi; Farrell, Ann; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Sridhara, Rajeshwari] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Williams, Gene; Booth, Brian] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Farrell, A (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM ann.farrell@fda.hhs.gov NR 6 TC 16 Z9 16 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 10 BP 1120 EP 1127 DI 10.1634/theoncologist.2008-0077 PG 8 WC Oncology SC Oncology GA 369VL UT WOS:000260721900012 PM 18922829 ER PT J AU Kane, RC AF Kane, Robert C. TI The Clinical Significance of Statistical Significance SO ONCOLOGIST LA English DT Editorial Material DE Statistical significance; Alpha; False positive inference ID CELL LUNG-CANCER; CHEMOTHERAPY AB Modern clinical trials provide the evidence for most therapeutic advances, and that evidence, expressed in a statistical format, is used to draw inferences about a population from the study's results. Clinician judgment translates these inferences for best individual patient care, but many clinicians struggle with the statistical interpretation of trial results. This review provides a clinical and non-Bayesian perspective on some key elements in the statistical design, analysis, and interpretation of randomized, comparative, phase III clinical trials intended to demonstrate a better outcome ( superiority) than with a control treatment. The Oncologist 2008; 13: 1129-1133 C1 US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Robert.kane@fda.hhs.gov NR 9 TC 4 Z9 5 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2008 VL 13 IS 11 BP 1129 EP 1133 DI 10.1634/theoncologist.2008-0186 PG 5 WC Oncology SC Oncology GA 380UO UT WOS:000261491100001 PM 18984874 ER PT J AU Sapsford, K Taitt, CR Ligler, FS AF Sapsford, Kim Taitt, Chris Rowe Ligler, Frances S. BE Ligler, FS Taitt, CR TI PLANAR WAVEGUIDES FOR FLUORESCENCE BIOSENSORS SO OPTICAL BIOSENSORS: TODAY AND TOMORROW, 2ND EDITION LA English DT Article; Book Chapter ID TOTAL-INTERNAL-REFLECTION; SITE-SPECIFIC IMMOBILIZATION; SELF-ASSEMBLED MONOLAYERS; STAPHYLOCOCCAL-ENTEROTOXIN-B; SURFACE-PLASMON RESONANCE; POLYMERASE-CHAIN-REACTION; COWPEA MOSAIC-VIRUS; ARRAY BIOSENSOR; PROTEIN ADSORPTION; ENHANCED FLUORESCENCE AB While confocal scanners and other microscopy techniques are routinely used for imaging genomic and proteomic microarrays, the leading methods for fluorescence-based, multianalyte detection are based on total internal reflection fluorescence (TIRF). Immobilization of multiple capture biomolecules on planar wave guides provides for multianalyte detection on a single substrate. Planar wave guide TIRF has been used to measure a variety of analytes including hormones, toxins, bacteria, and viruses, leading to applications such as environmental and food safety monitoring, clinical diagnostics, and military defense. Many of the analytes have been measured in both buffer and complex matrices, such as whole blood, nasal secretions, food, beverages, ground water, and soil suspensions. Detection limits in both buffer and complex matrices have been comparable. The continued development and miniaturization of the biosensor instrumentation has led to systems that are fully automated, portable, and highly competitive with laboratory techniques. Such biosensors are now transitioning into the commercial market. C1 [Sapsford, Kim] US FDA, CDRH OSEL DB, Silver Spring, MD 20993 USA. [Taitt, Chris Rowe; Ligler, Frances S.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Sapsford, K (reprint author), US FDA, CDRH OSEL DB, Silver Spring, MD 20993 USA. EM kim.sapsford@fda.hhs.gov; chris.taitt@nrl.navy.mil; frances.ligler@nrl.navy.mil NR 215 TC 21 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-056494-4 PY 2008 BP 139 EP 184 DI 10.1016/B978-044453125-4.50005-X PG 46 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BEQ47 UT WOS:000317686300004 ER PT J AU Shein, MJ Moynahan, M AF Shein, Mitchell J. Moynahan, Megan TI FDA viewpoint SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material C1 [Shein, Mitchell J.; Moynahan, Megan] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Shein, MJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM mitchell.shein@fda.hhs.gov NR 0 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD JAN PY 2008 VL 31 IS 1 BP 16 EP 16 PG 1 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 265PM UT WOS:000253373400006 PM 18181904 ER PT J AU Haidar, SH Davit, B Chen, ML Conner, D Lee, L Li, QH Lionberger, R Makhlouf, F Patel, D Schuirmann, DJ Yu, LX AF Haidar, Sam H. Davit, Barbara Chen, Mei-Ling Conner, Dale Lee, LaiMing Li, Qian H. Lionberger, Robert Makhlouf, Fairouz Patel, Devvrat Schuirmann, Donald J. Yu, Lawrence X. TI Bioequivalence approaches for highly variable drugs and drug products SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; highly variable drugs; highly variable drug products; scaled average bioequivalence; statistical approach; study design ID SCALED AVERAGE BIOEQUIVALENCE; LIMITS; BIOAVAILABILITY AB Over the past decade, concerns have been expressed increasingly regarding the difficulty for highly variable drugs and drug products (%CV greater than 30) to meet the standard bioequivalence (BE) criteria using a reasonable number of study subjects. The topic has been discussed on numerous occasions at national and international meetings. Despite the lack of a universally accepted solution for the issue, regulatory agencies generally agree that an adjustment of the traditional BE limits for these drugs or products may be warranted to alleviate the resource burden of studying relatively large numbers of subjects in bioequivalence trials. This report summarizes a careful examination of all the statistical methods available and extensive simulations for BE assessment of highly variable drugs/products. Herein, the authors present an approach of scaling an average BE criterion to the within-subject variability of the reference product in a crossover BE study, together with a point-estimate constraint imposed on the geometric mean ratio between the test and reference products. The use of a reference-scaling approach involves the determination of variability of the reference product, which requires replication of the reference treatment in each individual. A partial replicated-treatment design with this new data analysis methodology will thus provide a more efficient design for BE studies with highly variable drugs and drug products. C1 [Haidar, Sam H.; Davit, Barbara; Conner, Dale; Lee, LaiMing; Lionberger, Robert; Patel, Devvrat; Yu, Lawrence X.] Office Gener Drugs Food & Drug Adm, Rockville, MD 20855 USA. [Chen, Mei-Ling] Office Pharmaceut Sci, Food Drug Adm, Silver Spring, MD 20993 USA. [Li, Qian H.; Makhlouf, Fairouz; Schuirmann, Donald J.] Office Biostat Food & Drug Adm, Silver Spring, MD 20993 USA. RP Yu, LX (reprint author), Office Gener Drugs Food & Drug Adm, 7500 Standish Pl, Rockville, MD 20855 USA. EM lawrence.yu@fda.hhs.gov NR 18 TC 89 Z9 101 U1 4 U2 15 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 JAN PY 2008 VL 25 IS 1 BP 237 EP 241 DI 10.1007/s11095-007-9434-x PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 249TW UT WOS:000252253700024 PM 17891552 ER PT J AU Blake, MS AF Blake, Milan S. BE Siber, GR Klugman, KP Makela, PH TI Pneumococcal Vaccines: Manufacture and Quality Control for Product Release SO PNEUMOCOCCAL VACCINES: THE IMPACT OF CONJUGATE VACCINE LA English DT Article; Book Chapter ID CAPSULAR POLYSACCHARIDE PREPARATIONS; DIPHTHERIA-TOXIN; CORYNEBACTERIUM-DIPHTHERIAE; STREPTOCOCCUS-PNEUMONIAE; QUANTIFICATION; SUBSTANCE; PROTEINS; CRM197; ASSAY C1 US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Blake, MS (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 27 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-582-0 PY 2008 BP 175 EP 182 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BOY53 UT WOS:000278065300013 ER PT J AU Gruber, MF Pratt, D Haase, M AF Gruber, Marion F. Pratt, Douglas Haase, Manfred BE Siber, GR Klugman, KP Makela, PH TI Licensing of Pneumococcal Conjugate Vaccines for Children and Adults: Regulatory Perspective from the European Medicines Agency and the US Food and Drug Administration SO PNEUMOCOCCAL VACCINES: THE IMPACT OF CONJUGATE VACCINE LA English DT Article; Book Chapter ID COMMUNITY-ACQUIRED PNEUMONIA; EFFICACY; DISEASE; SAFETY; TRIAL; ERA C1 [Gruber, Marion F.; Pratt, Douglas] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Haase, Manfred] Paul Ehrlich Inst, Div Bacteriol, D-63207 Langen, Germany. RP Gruber, MF (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike WOC 360 N, Rockville, MD 20852 USA. NR 37 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-582-0 PY 2008 BP 183 EP 196 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA BOY53 UT WOS:000278065300014 ER PT J AU Glauert, HP Calfee-Mason, K Li, YX Nilakantan, V Twaroski, ML Tharappel, J Spear, BT AF Glauert, Howard P. Calfee-Mason, Karen Li, Yixin Nilakantan, Vani Twaroski, Michelle L. Tharappel, Job Spear, Brett T. TI The Role of NF-kappa B in PPAR alpha-Mediated Hepatocarcinogenesis SO PPAR RESEARCH LA English DT Review AB In this review, the role of NF-kappa B in the induction of hepatocarcinogenesis by peroxisome proliferators is examined. The administration of peroxisome proliferators for more than a three-day period leads to the activation of NF-kappa B in the livers of rats and mice. On the other hand, peroxisome proliferator activated receptor-alpha (PPAR alpha) activation in non-hepatic tissues can lead to the inhibition of NF-kappa B activation. Several lines of evidence support the hypothesis that the activation of NF-kappa B by peroxisome proliferators in the liver is mediated by oxidative stress. The role of NF-kappa B in peroxisome proliferator-induced hepatocarcinogenesis has been examined using NF-kappa B knockout models. Specifically, the induction of cell proliferation and the promotion of liver carcinogenesis are inhibited in mice lacking the p50 subunit of NF-kappa B. Overall, the activation of NF-kappa B appears to be important in the carcinogenic activity of peroxisome proliferators. Copyright (C) 2008 Howard P. Glauert et al. C1 [Glauert, Howard P.; Tharappel, Job] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. [Calfee-Mason, Karen] Western Kentucky Univ, Coll Hlth & Human Serv, Bowling Green, KY 42101 USA. [Li, Yixin] Appl Biosyst Inc, Foster City, CA 94404 USA. [Nilakantan, Vani] Med Coll Wisconsin, Kidney Dis Ctr, Div Transplant Surg, Milwaukee, WI 53226 USA. [Twaroski, Michelle L.] US FDA, CFSAN OFAS DFCN, College Pk, MD 20740 USA. [Spear, Brett T.] Univ Kentucky, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA. RP Glauert, HP (reprint author), Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY 40536 USA. EM hglauert@uky.edu OI Spear, Brett/0000-0002-4343-9393 NR 73 TC 4 Z9 5 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-4757 J9 PPAR RES JI PPAR Res. PY 2008 AR 286249 DI 10.1155/2008/286249 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V13TM UT WOS:000207689100001 ER PT S AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. BA Tata, DB BF Tata, DB BE Waynant, R TI Mechanisms SO PROCEEDINGS OF LIGHT-ACTIVATED TISSUE REGENERATION AND THERAPY CONFERENCE SE Lecture Notes in Electrical Engineering LA English DT Proceedings Paper CT 2nd International Engineering Conference on Light-Activated Tissue Regeneration and Therapy CY JUN 24-29, 2007 CL Tomar, PORTUGAL DE Light therapy; hydrogen peroxide; stimulation; inhibition; dose; catalase ID CELLS AB Our work shows that light exposures of cell Cultures results in the production of hydrogen peroxide in direct relation to the (lose (J/cm(2)) of light,given. However, cell growth is stimulated (with respect to unexposed controls) only at low doses, inhibition occurs as dose is increased reaching maximum inhibition near 50 J/cm(2), then at higher doses stimulation of cell growth returns as dose reaches 100 J/cm(2). We believe hydrogen peroxide production is responsible for many of the positive results attributed to laser therapy. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Tata, DB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 10 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1876-1100 BN 978-0-387-71808-8 J9 LECT NOT EL ENGR PY 2008 VL 12 BP 3 EP 9 PG 7 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BIK11 UT WOS:000260249400001 ER PT S AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. BA Tata, DB BF Tata, DB BE Waynant, R TI Near-IR Picosecond Pulsed Laser Induced Suppression of Metabolic Activity in Malignant Human Brain Cancer: An In-Vitro Study SO PROCEEDINGS OF LIGHT-ACTIVATED TISSUE REGENERATION AND THERAPY CONFERENCE SE Lecture Notes in Electrical Engineering LA English DT Proceedings Paper CT 2nd International Engineering Conference on Light-Activated Tissue Regeneration and Therapy CY JUN 24-29, 2007 CL Tomar, PORTUGAL DE Human brain cancer (glioblastoma); inhibition; cell cultures; catalase; near infrared ID CELLS; IRRADIATION; RESPONSES; OXIDANTS; LIGHT AB The role of low light intensity in suppressing metabolic activity of malignant human brain cancer (glioblastoma) cell line was investigated through the application of a 1,552 nm wavelength pulsed picosecond laser. Human glioblastomas were grown in T-75 flasks and were utilized when the cells were 5-70% confluent and thereafter transferred into 96 well plates and exposed in their growth culture medium with serum under various energy closes (i.e., fluence) ranging from 0.115-50 J/cm(2) All exposure doses were reached with all average intensity of 0.115 W/cm(2); 25 kHz repetition rate with 1.6 mu J per pulsed pulse duration = 2.93 ps. The glioblastomas exhibited a maximal decline in the metabolic activity (down 50-60%) relative to their respective sham exposed control counterparts between the fluence dose values of 5.0-10 J/cm(2). The cellular metabolic activities for various treatment doses were measured through the colorimetric MTS metabolic assay 3 days after the laser exposure. Interestingly, the metabolic activity was found to return back to the sham 2 exposed control levels as the fluence of exposure was increased Lip to 50 J/cm(2) Addition of (the enzyme) Catalase in the growth medium prior to the laser exposure was found to diminish the laser induced metabolic Suppression for all fluence treatment conditions, thus suggesting it functional role of H(2)O(2) in the metabolic suppression. In view of this evidence, a hypothesis is formulated which attributes the classical biphasic response, in pail, to the light induced production of H(2)O(2). Furthermore, it was observed that if the glioblastoma cells were allowed to reach 100% confluency within the T-75 flasks the characteristic laser induced metabolic suppression was found to be severely abrogated. Exploratory steps were also undertaken to maximize the suppression in the metabolic activity through repetitive laser dose of exposure every 24 hours for 3 consecutive days. In addition, the efficacy in the metabolic suppression of the 1,552 nm pulsed laser was also compared to a continuous wave broad band continuous wave heating lamp soul-cc channeled through a fiber-optic bundle with identical intensity of exposure. Taken together. Our findings reveal that near-IR low level light exposures could potentially be a viable tool in reducing the metabolic activity of cancers: however, due to the cellular "biphasic" response to the non-ionizing irradiation. further research needs to be undertaken to determine exposure parameters which Would optimize metabolic and Cellular growth Suppression in-vivo.. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, White Oak, MD USA. RP Tata, DB (reprint author), US FDA, White Oak, MD USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1876-1100 BN 978-0-387-71808-8 J9 LECT NOT EL ENGR PY 2008 VL 12 BP 11 EP 19 PG 9 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BIK11 UT WOS:000260249400002 ER PT S AU Basu, S AF Basu, Sankar BA Tata, DB BF Tata, DB BE Waynant, R TI Requirements for FDA Approval SO PROCEEDINGS OF LIGHT-ACTIVATED TISSUE REGENERATION AND THERAPY CONFERENCE SE Lecture Notes in Electrical Engineering LA English DT Proceedings Paper CT 2nd International Engineering Conference on Light-Activated Tissue Regeneration and Therapy CY JUN 24-29, 2007 CL Tomar, PORTUGAL DE 510(k); pre-IDE; IDE; PMA AB In the United States the Food and Drug Administration regulates the sale of medical devices. Questions concerning the approval process of light therapy devices where discussed by a distinguished FDA staff member. C1 US FDA, Off Device Evaluat, Rockville, MD 20850 USA. RP Basu, S (reprint author), US FDA, Off Device Evaluat, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1876-1100 BN 978-0-387-71808-8 J9 LECT NOT EL ENGR PY 2008 VL 12 BP 269 EP 269 PG 1 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BIK11 UT WOS:000260249400025 ER PT S AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. BA Tata, DB BF Tata, DB BE Waynant, R TI Independent Applications of Near-IR Broadband Light Source and Pulsed Electric Potential in the Suppression of Human Brain Cancer Metabolic Activity: An In-Vitro Study SO PROCEEDINGS OF LIGHT-ACTIVATED TISSUE REGENERATION AND THERAPY CONFERENCE SE Lecture Notes in Electrical Engineering LA English DT Proceedings Paper CT 2nd International Engineering Conference on Light-Activated Tissue Regeneration and Therapy CY JUN 24-29, 2007 CL Tomar, PORTUGAL DE rf irradiation; glioblastoma cells ID IRREVERSIBLE ELECTROPORATION; CELLS; ABLATION AB The roles of two different non-conventional techniques in suppressing the metabolic activity of a malignant human brain cancer (glioblastoma) cell line were explored through the application of (i) pulsed electric field, or (ii) independent application with a continuous wave broadband near infrared light channeled through a fiber-optic bundle exposing cancer cells within growth medium. Human glioblastomas were grown in T-75 flasks and were utilized when the cells were 50-70% confluent. The cells were either transferred into 96 well plates for exposures through a fiber bundle, or into 1.4 ml sterile eppendoff tubes for exposures to pulsed electric potential. The glioblastomas within wells were light exposed through a fiber bundle at an average intensity of 0.115 W/cm(2) from the underside of the well, with the light dose (fluence) values ranging from 0.115-50 J/cm(2). Glioblastomas exhibited a maximal decline in the metabolic activity (down 80%) relative to their respective sham exposed control counterparts between the fluence dose values of 5.0-10 J/cm(2). The cellular metabolic activities for various treatment doses were measured through the colorimetric NITS metabolic assay 3 days after the broadband near infrared light exposure. Interestingly, the metabolic activity was found to return back to the (sham exposed) control levels as the fluence of exposure was increased up to 50 J/cm(2). Glioblastomas in suspension within sterile eppendoff tubes were exposed to pulsed electrical potential fluctuations: rectangular pulse width = 250 mu s with pulse amplitude = 100 V, with 8 square pulses per burst, 2 bursts per second. A time course study of treatment exposure revealed a complete obliteration of glioblastomas for in-vitro treatment duration beyond 7 min. C1 [Tata, Darrell B.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Tata, DB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Darrell.Tata@fda.hhs.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1876-1100 BN 978-0-387-71808-8 J9 LECT NOTES ELECTR EN PY 2008 VL 12 BP 307 EP + PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BIK11 UT WOS:000260249400031 ER PT B AU Chen, J Qiang, R Kainz, W AF Chen, Ji Qiang, Rui Kainz, Wolfgang BE Cui, TJ Smith, DR TI Time-Domain Modeling Techniques for Periodic Structures SO PROCEEDINGS OF THE 2008 INTERNATIONAL WORKSHOP ON METAMATERIALS LA English DT Proceedings Paper CT International Workshop on Metamaterials CY NOV 09-12, 2008 CL Nanjing, PEOPLES R CHINA SP IEEE AP-MTT-EMC Nanjing Joint Chapter, Natl Nat Sci Fdn China, Minist Educ, SE Univ, State Key Lab Millimeter Waves DE Arrays; finite source; artificial materials; FDTD; periodic structures; meta-materials ID DIELECTRIC-CONSTANT; 2-COMPONENT; MIXTURES AB A novel time-domain modeling techniques for periodic structures are described in this paper. The three. methods discussed here are the spectral FDTD method, array scanning FDTD method, and equivalent electrical parameter extraction for periodic structures. C1 [Chen, Ji; Qiang, Rui] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. [Kainz, Wolfgang] FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Chen, J (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77004 USA. EM Ji.Chen@mail.uh.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2608-9 PY 2008 BP 16 EP + DI 10.1109/META.2008.4723517 PG 2 WC Materials Science, Multidisciplinary; Physics, Applied SC Materials Science; Physics GA BIT81 UT WOS:000262656300011 ER PT J AU Castagnetti, GB Delmonte, P Melia, S Gori, A Losi, G AF Castagnetti, G. B. Delmonte, P. Melia, S. Gori, A. Losi, G. TI The effect of extruded whole linseed flour intake on the variation of CLA (Conjugated Linoleic Acid) content in milk - The Reggiana cattle's case SO PROGRESS IN NUTRITION LA Italian DT Article DE CLA (Conjugated Linoleic Acid); rumenic acid (C-18:2 c9-t11); vaccenic acid (C-18:1 trans-11) ID LACTATING DAIRY-COWS; TRANS-FATTY-ACIDS; SHORT-COMMUNICATION; DIETARY SUPPLEMENTATION; BOVINE-MILK; CIS-9,TRANS-11-OCTADECADIENOIC ACID; CALCIUM SALTS; FISH-OIL; CHEESE; YIELD AB The experiment was conducted on Regglana cattle over an 8 months period in 2005. By integrating extruded whole linseed flour (300 g/d) to the basal ration (fresh or preserved forage) which changes according to the season, the possibility to modify both the milk fatty acid composition in general, and the CLA content (Conjugated Linoleic Acids) in particular, has been confirmed. The principal and statistically significant results find that Rumenic Acid (C-18:2 c9-t11) and Vaccenic Acid (C-18:1 trans-11) have risen up to 45% and 47% respectively on the milk fat content, subsequent to the extruded whole linseed flour administration. Moreover the results confirm the correlation between these two fatty acids in milk. However, saturated and monounsaturated fatty acids (SFA, MUFA) are not suitable to be modified, with the exception of the monounsaturated Oleic Acid that increases during the extruded whole linseed flour integration and decreases when it is suspended. In conclusion, it is possible to increase the CLA content in milk and dairy products and to improve their nutritional values in human nutrition through an appropriate and targeted cattle's ration integration. C1 [Castagnetti, G. B.; Melia, S.; Gori, A.; Losi, G.] Univ Bologna, Fac Agr, Dipartimento Sci Alimenti, Sede Di Reggio Emilia, Italy. [Delmonte, P.] US FDA, Ctr Food Sci & Appl Nutr, College Pk, MD 20740 USA. RP Castagnetti, GB (reprint author), Via Flli Rosselli 107, I-42100 Reggio Emilia, Italy. EM gian.castagnetti@unibo.it NR 48 TC 1 Z9 1 U1 0 U2 1 PU MATTIOLI 1885 PI FIDENZA PA VIA DELLA LODESANA 649-SX, FIDENZA, 43046 PR, ITALY SN 1129-8723 J9 PROG NUTR JI Prog. Nutr. PY 2008 VL 10 IS 3 BP 174 EP 183 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 361WR UT WOS:000260158700006 ER PT J AU Petrick, N Haider, M Summers, RM Yeshwant, SC Brown, L Iuliano, EM Louie, A Choi, JR Pickhardt, PJ AF Petrick, Nicholas Haider, Maruf Summers, Ronald M. Yeshwant, Srinath C. Brown, Linda Iuliano, Edward M. Louie, Adeline Choi, J. Richard Pickhardt, Perry J. TI CT colonography with computer-aided detection as a second reader: Observer performance study SO RADIOLOGY LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; POLYP DETECTION; COLONIC POLYPS; LUNG NODULES; POPULATION; FEASIBILITY; DIAGNOSIS; ISSUES; ROC AB Purpose: To evaluate the effect of computer-aided detection (CAD) as second reader on radiologists' diagnostic performance in interpreting computed tomographic (CT) colonographic examinations by using a primary two-dimensional (2D) approach, with segmental, unblinded optical colonoscopy as the reference standard. Materials and Methods: This HIPAA-compliant study was IRB-approved with written informed consent. Four board-certified radiologists analyzed 60 CT examinations with a commercially available review system. Two-dimensional transverse views were used for initial polyp detection, while three-dimensional (3D) endoluminal and 2D multiplanar views were available for problem solving. After initial review without CAD, the reader was shown CAD-identified polyp candidates. The readers were then allowed to add to or modify their original diagnoses. Polyp location, CT Colonography Reporting and Data System categorization, and reader confidence as to the likelihood of a candidate being a polyp were recorded before and after CAD reading. The area under the receiver operating characteristic (ROC) curve (AUC), sensitivity, and specificity were estimated for CT examinations with and without CAD readings by using multireader multicase analysis. Results: Use of CAD led to nonsignificant average reader AUC increases of 0.03, 0.03, and 0.04 for patients with adenomatous polyps 6 mm or larger, 6-9 mm, and 10 mm or larger, respectively (P >=.25); likewise, CAD increased average reader sensitivity by 0.15, 0.16, and 0.14 for those respective groups, with a corresponding decrease in specificity of 0.14. These changes achieved significance for the 6 mm or larger group (P <.01), 6-9 mm group (P <.02), and for specificity (P <.01), but not for the 10 mm or larger group (P <.16). The average reading time was 5.1 minutes +/- 3.4 (standard deviation) without CAD. CAD added an average of 3.1 minutes +/- 4.3 (62%) to each reading (supine and prone positions combined); average total reading time, 8.2 minutes +/- 5.8. Conclusion: Use of CAD led to a significant increase in sensitivity for detecting polyps in the 6 mm or larger and 6-9 mm groups at the expense of a similar significant reduction in specificity. C1 [Haider, Maruf; Summers, Ronald M.; Yeshwant, Srinath C.; Brown, Linda; Louie, Adeline] NIH, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Devices & Radiol Hlth, Joint Lab Assessment Med Imaging Syst, Rockville, MD USA. [Iuliano, Edward M.] Georgetown Univ, Sch Med, Dept Radiol, Washington, DC USA. [Choi, J. Richard] Walter Reed Army Med Ctr, Dept Radiol, Washington, DC 20307 USA. [Pickhardt, Perry J.] Univ Wisconsin, Dept Radiol, Sch Med, Madison, WI 53706 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Dept Diagnost Radiol, Bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 22 TC 66 Z9 67 U1 2 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2008 VL 246 IS 1 BP 148 EP 156 DI 10.1148/radiol.2453062161 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000252795300020 PM 18096536 ER PT J AU Badal, A Kyprianou, L Badano, A Sempau, J AF Badal, Andreu Kyprianou, Lacovos Badano, Aldo Sempau, Josep TI Monte Carlo simulation of a realistic anatomical phantom described by triangle meshes: Application to prostate brachytherapy imaging SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Monte Carlo; PENELOPE; penMesh; triangle mesh; NCAT; computer-aided design ID ESTRO/EAU/EORTC RECOMMENDATIONS; PACKAGE; PHOTON AB Purpose: Monte Carlo codes can simulate the transport of radiation within matter with high accuracy and can be used to study medical applications of ionising radiations. The aim of our work was to develop a Monte Carlo code capable of generating projection images of the human body. In order to obtain clinically realistic images a detailed anthropomorphic phantom was prepared. These two simulation tools are intended to study the multiple applications of imaging in radiotherapy, from image guided treatments to portal imaging. Methods: We adapted the general-purpose code PENELOPE 2006 to simulate a radiation source, an ideal digital detector, and a realistic model of the patient anatomy. The anthropomorphic phantom was developed using computer-aided design tools, and is based on the NCAT phantom. The surface of each organ is modelled using a closed triangle mesh, and the full phantom contains 330 organs and more than 5 million triangles. A novel object-oriented geometry package, which includes an octree structure to sort the triangles, has been developed to use this complex geometry with PENELOPE. Results: As an example of the capabilities of the new code, projection images of the human pelvis region were simulated. Radioactive seeds were included inside the phantom's prostate. Therefore, the resulting simulated images resemble what would be obtained in a clinical procedure to assess the positioning of the seeds in a prostate brachytherapy treatment. Conclusions: The new code can produce projection images of the human body that are comparable to those obtained by a real imaging system (within the limitations of the anatomical phantom and the detector model). The simulated images can be used to study and optimise an imaging task (i.e., maximise the object detectability, minimise the delivered dose, find the optimum beam energy, etc.). Since PENELOPE can simulate radiation from 50 eV to 1 GeV, the code can also be used to simulate radiotherapy treatments and portal imaging. Using the octree data structure, the new geometry model does not significantly increase the computing time when compared to the simulation of a much simpler quadric geometry. In conclusion, we have shown that it is feasible to use PENELOPE and a complex triangle mesh geometry to simulate real medical physics applications. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Badal, Andreu; Sempau, Josep] Univ Politecn Cataluna, Inst Tech Energet, E-08028 Barcelona, Spain. [Kyprianou, Lacovos; Badano, Aldo] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Washington, DC 20204 USA. RP Badal, A (reprint author), Univ Politecn Cataluna, Inst Tech Energet, Avinguda Diagonal 647, E-08028 Barcelona, Spain. EM andreu.badal@upc.edu RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 FU NCI NIH HHS [224-07-6030]; None [224-04-6055]; PHS HHS [224-04-6055, 224-07-6030] NR 17 TC 9 Z9 9 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD JAN PY 2008 VL 86 IS 1 BP 99 EP 103 DI 10.1016/j.radonc.2007.11.009 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 264QG UT WOS:000253303000016 PM 18061695 ER PT J AU Li, SL Lin, G Fu, PP Chan, CL Li, M Jiang, ZH Zhao, ZZ AF Li, Song-Lin Lin, Ge Fu, Peter P. Chan, Chi-Leung Li, Mi Jiang, Zhi-Hong Zhao, Zhong-Zhen TI Identification of five hepatotoxic pyrrolizidine alkaloids in a commonly used traditional Chinese medicinal herb, Herba Senecionis scandentis (Qianliguang) SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; METABOLIC-ACTIVATION; MICROSOMAL METABOLITES; N-OXIDE; CLIVORINE; RAT AB fSenecio scandens Buch.-Ham is a plant source for a commonly used traditional Chinese medicinal (TCM) herb Qianliguang. A TCM herbal proprietary product containing Qianliguang as the major herb for the treatment of sinusitis has been used in China for several decades, and has also been exported to other regions and countries worldwide. In the present study, the aqueous extract of S. scandens collected in the Shanxi Province of China was determined, for the first time, to contain hepatotoxic and tumorigenic pyrrolizidine alkaloids (PAs) by using high-performance liquid chromatography/mass spectrometric (HPLC/MS) analysis in various scanning modes. A total of nine toxic and two non-toxic PAs were detected in the aqueous extract of S. scandens, of which six PAs, namely neoplatyphylline, senecionine, senecionine N-oxide, seneciphylline, seneciphylline N-oxide and senkirkine, were unequivocally characterized, while other PAs were tentatively assigned as jacobine, jacozine N-oxide (or erucifoline N-oxide), 7-tigloylplatynecine, usaramine and an isomer of yamataimine. The estimated total content of toxic PAs in S. scandens was 10.82 mu g/g herb, which was significantly higher than that ( >= 1 mu g/g herb) recommended by Belgium and Germany not to be used clinically. Among the PAs definitively identified, senecionine, seneciphylline, and senkirkine are known tumorigens capable of inducing liver tumors in experimental animals, while seneciphylline N-oxide and senecionine N-oxide are probably tumorigenic due to their potential conversion into seneciphylline and senecionine via metabolic reduction in the body. Thus, the current finding of the presence of toxic/tumorigenic PAs in S. scandens challenges the safety of using this TCM herb and its proprietary products. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Li, Song-Lin; Lin, Ge; Li, Mi] Chinese Univ Hong Kong, Dept Pharmacol, Fac Med, Shatin, Hong Kong, Peoples R China. [Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Chan, Chi-Leung; Jiang, Zhi-Hong; Zhao, Zhong-Zhen] Hong Kong Baptist Univ, Sch Chinese Med, Kwloon Tung, Hong Kong, Peoples R China. RP Lin, G (reprint author), Chinese Univ Hong Kong, Dept Pharmacol, Fac Med, Shatin, Hong Kong, Peoples R China. EM linge@cuhk.edu.hk NR 36 TC 36 Z9 40 U1 1 U2 34 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. PY 2008 VL 22 IS 4 BP 591 EP 602 DI 10.1002/rcm.3398 PG 12 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 269GR UT WOS:000253638000022 PM 18220326 ER PT J AU Neill, MA AF Neill, Marguerite A. BE Mayer, KH Pizer, HF TI Food safety in the industrialized world SO SOCIAL ECOLOGY OF INFECTIOUS DISEASES LA English DT Article; Book Chapter ID ENTEROTOXIGENIC ESCHERICHIA-COLI; DRUG-RESISTANT SALMONELLA; HEMOLYTIC-UREMIC-SYNDROME; UNITED-STATES; MULTISTATE OUTBREAK; FOODBORNE DISEASE; O157-H7 INFECTION; ILLNESS; GASTROENTERITIS; SURVEILLANCE C1 [Neill, Marguerite A.] USDA, Washington, DC USA. [Neill, Marguerite A.] US FDA, Rockville, MD 20857 USA. NR 77 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-055714-4 PY 2008 BP 215 EP 240 DI 10.1016/B978-012370466-5.50013-3 PG 26 WC Infectious Diseases SC Infectious Diseases GA BFE74 UT WOS:000319510600010 ER PT J AU MacCuspie, RI Banerjee, IA Pejoux, C Gummalla, S Mostowski, HS Krause, PR Matsui, H AF MacCuspie, Robert I. Banerjee, Ipsita A. Pejoux, Christophe Gummalla, Sanjay Mostowski, Howard S. Krause, Philip R. Matsui, Hiroshi TI Virus assay using antibody-functionalized peptide nanotubes SO SOFT MATTER LA English DT Article ID NANOCRYSTAL GROWTH; CARBON NANOTUBES; FLOW-CYTOMETRY; NANOPARTICLES; RECOGNITION; TEMPLATES; PATHOGENS; PROTEINS AB Robust trace-level detection of viruses is crucial to meet urgent needs in fighting the spread of disease or detecting bioterrorism events. We report a new method for rapid and highly sensitive detection of viruses utilizing fluorescent antibody nanotubes. When viral pathogens were mixed with these antibody nanotubes, the nanotubes rapidly aggregated around the viruses to form a networking structure. Trace quantities of viruses such as herpes simplex virus type 2, adenovirus, vaccinia and influenza type B were detected on attomolar order by changes in fluorescence and light scattering intensities associated with aggregation of dye-loaded antibody nanotubes around viruses. High specificity of each antibody nanotube toward its targeted virus was demonstrated by quantifying concentrations of two different viruses in mixtures. This antibody nanotube assay detects targeted pathogens within 30 minutes after incubation with antibody nanotubes. This antibody nanotube assay could fill a pressing need to detect and quantify viruses both rapidly and sensitively. C1 [MacCuspie, Robert I.; Banerjee, Ipsita A.; Pejoux, Christophe; Matsui, Hiroshi] CUNY, Dept Chem, Huner Coll, New York, NY 10065 USA. [MacCuspie, Robert I.; Banerjee, Ipsita A.; Pejoux, Christophe; Matsui, Hiroshi] CUNY, Dept Chem, Grad Ctr, New York, NY 10065 USA. [Gummalla, Sanjay; Mostowski, Howard S.] Food & Drug Adm, Ctr Biol Evalut & Res, Off Vac Res & Review, Div Viral Prod, Rockville, MD 20852 USA. RP MacCuspie, RI (reprint author), CUNY, Dept Chem, Huner Coll, 695 Pk Ave, New York, NY 10065 USA. EM philip.krause@fda.hhs.gov; hmatsui@hunter.cuny.edu OI MacCuspie, Robert/0000-0002-6618-6499 NR 29 TC 16 Z9 16 U1 0 U2 5 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1744-683X J9 SOFT MATTER JI Soft Matter PY 2008 VL 4 IS 4 BP 833 EP 839 DI 10.1039/b714470a PG 7 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Multidisciplinary; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 279WV UT WOS:000254386800025 ER PT S AU Vogt, RF Marti, GE Zenger, V AF Vogt, Robert F., Jr. Marti, Gerald E. Zenger, Vincent BE ReschGenger, U TI Quantitative Fluorescence Calibration: a Tool for Assessing the Quality of Data Obtained by Fluorescence Measurements SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS I: TECHNIQUES SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Flow cytometry; Fluorescence; Fluorescence intensity standard; Molecules of equivalent soluble fluorochrome; Quality assurance; Quantification ID STANDARDIZING FLOW-CYTOMETRY; T-LYMPHOCYTES; INDIRECT IMMUNOFLUORESCENCE; CD4 EXPRESSION; CELL ANALYSIS; INTENSITY; SENSITIVITY; CD38; PERFORMANCE; RESOLUTION AB Over the last three decades, fluorescence has become the most widely used detection method in biomedical science. Fluorescence measurements are utilized in basic and translational research, method development, medical laboratory tests, clinical trials and epidemiologic studies. This renders the availability of objective methods to assess the quality of data obtained by these measurements very critical for research scientists, clinical laboratory personnel, and regulatory reviewers as is addressed in this chapter. C1 [Vogt, Robert F., Jr.] CDC, Ctr Dis Control & Prevent, Div Sci Lab, Newborn Screening Branch, Atlanta, GA 30341 USA. [Marti, Gerald E.; Zenger, Vincent] Food & Drug Adm, Ctr Biol Evaluat & Res, Atlanta, GA 30341 USA. RP Vogt, RF (reprint author), CDC, Ctr Dis Control & Prevent, Div Sci Lab, Newborn Screening Branch, Mailstop F19, Atlanta, GA 30341 USA. EM rvogt@cdc.gov NR 50 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-75206-6 J9 SPRINGER SER FLUORES PY 2008 VL 05 BP 3 EP 31 DI 10.1007/4243_2008_055 PG 29 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV85 UT WOS:000267284500001 ER PT S AU Zou, SG He, HJ Zong, YP Shi, LM Wang, LL AF Zou, Sige He, Hua-Jun Zong, Yaping Shi, Leming Wang, Lili BE ReschGenger, U TI DNA Microarrays: Applications, Future Trends, and the Need for Standardization SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Bead-based arrays; cDNA arrays; Expression profiling; External RNA control; Genotyping; Oligonucleotide arrays; Scanner performance validation ID GENE-EXPRESSION PATTERNS; NF-KAPPA-B; GENOME-WIDE; DROSOPHILA-MELANOGASTER; POINT MUTATIONS; OLIGONUCLEOTIDE MICROARRAY; PROTEIN EXPRESSION; OXIDATIVE STRESS; CELL MICROARRAYS; GLASS SLIDES AB Microarray technology allows high-throughput analysis of tens or even hundreds of thousands of genes in a single experiment, and has been applied broadly to address a wide variety of questions in basic and applied sciences. The applications of the microarray technology range from gene-expression profiling and genotyping to DNA-protein interactions and genome sequencing, and the list of applications keeps growing, especially when combined with other technologies such as proteomic technologies. However, many steps are involved in each microarray experiment and a number of microarray platforms exist, each with its unique features. The challenge is how to standardize the methods and materials to allow intra- and inter-comparison of microarray data collected in the same or different set of experiments. With the challenge in mind, we address the need for standardization for each step of the microarray experiments with emphasis on quality control of array fabrication and scanner calibration and verification. The proposed standards are designed for checking the quality of mRNA, fabricating slides, hybridization, and collecting, analyzing, and storing data. By implementing standards for each step of the microarray process, the full potential of the microarray technology will be realized, especially in the area of disease diagnosis and drug development. C1 [He, Hua-Jun; Wang, Lili] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. [Zou, Sige; Wang, Lili] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Zong, Yaping] Full Moon Biosyst, Sunnyvale, CA 94085 USA. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, LL (reprint author), Natl Inst Stand & Technol, Div Biochem Sci, 100 Bur Dr MS 8312, Gaithersburg, MD 20899 USA. EM lili.wang@nist.gov NR 83 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 215 EP 237 DI 10.1007/4243_2008_036 D2 10.1007/978-3-540-70571-0 PG 23 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000008 ER PT S AU Shi, LM Goodsaid, FM Frueh, FW Tong, WD AF Shi, Leming Goodsaid, Federico M. Frueh, Felix W. Tong, Weida BE ReschGenger, U TI Microarray Technology: Unresolved Issues and Future Challenges from a Regulatory Perspective SO STANDARDIZATION AND QUALITY ASSURANCE IN FLUORESCENCE MEASUREMENTS II: BIOANALYTICAL AND BIOMEDICAL APPLICATIONS SE Springer Series on Fluorescence LA English DT Article; Book Chapter DE Data analysis and interpretation; Microarray; Quality control metrics and thresholds; Regulatory decision-making; Reproducibility ID GENE-EXPRESSION MEASUREMENTS; EXTERNAL RNA CONTROLS; CONTROL MAQC PROJECT; QUALITY-CONTROL; OLIGONUCLEOTIDE MICROARRAYS; PLATFORM CONSISTENCY; PERFORMANCE; CANCER; CLASSIFICATION; NOISE AB Despite their growing popularity in the research community, DNA microarray-based gene expression assays have not yet been approved or licensed by the US. Food and Drug Administration for clinical or regulatory decision-making. While recent publications demonstrated the technical reliability of microarray technology, there are several challenges that still need to be addressed so that micro array-based gene expression data can be accepted for routine use in clinical and regulatory environments. First, appropriate quality-control metrics and thresholds are needed for objectively assessing the quality of microarray data from individual laboratories. Secondly, consensus on the analysis of microarray data is needed. Thirdly, adequate evaluation and validation of microarray results is needed so that non-reproducible chance correlations can be avoided in handling high-dimensional microarray data. C1 [Shi, Leming; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Goodsaid, Federico M.; Frueh, Felix W.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Leming.Shi@fda.hhs.gov NR 43 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1617-1306 BN 978-3-540-70570-3 J9 SPRINGER SER FLUORES PY 2008 VL 06 BP 265 EP 282 DI 10.1007/4243_2008_035 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Analytical; Optics; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Optics; Spectroscopy GA BJV84 UT WOS:000267284000010 ER PT J AU Gwise, TE Hu, JH Hu, FF AF Gwise, Thomas E. Hu, Jianhua Hu, Feifang TI Optimal biased coins for two-arm clinical trials SO STATISTICS AND ITS INTERFACE LA English DT Article DE Adaptive design; D-optimal biased coin; D-A-optimal biased coin; Response adaptive design; Continuous responses; Binary responses AB Atkinson (1982) introduced D-optimal and D-A-optimal biased coin designs to achieve balanced allocation. In this paper, we relax the restrictive assumptions on Atkinson's design so that it can be applied to more realistic situations of heteroscedastic data for two-arm clinic trials. A new class of adaptive biased coin designs is obtained. Further, we derive the asymptotic properties of the proposed allocation procedures, and show that the allocation targets maximizing power via a direct connection to Neyman's allocation scheme. Simulation studies illustrate that the theoretical results are valid and that the proposed design has testing power that is superior to that of the completely randomized allocation scheme. C1 [Gwise, Thomas E.] US FDA, Rockville, MD 20857 USA. [Hu, Jianhua] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Hu, Feifang] Univ Virginia, Dept Stat, Charlottesville, VA 22904 USA. RP Gwise, TE (reprint author), US FDA, Rockville, MD 20857 USA. EM fh6e@virginia.edu FU NSF [DMS-0349048] FX This work was supported by NSF Grant DMS-0349048. Special thanks go to an anonymous referee for the constructive comments, which led to an improved version of the paper. NR 20 TC 9 Z9 9 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2008 VL 1 IS 1 BP 125 EP 135 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA V13GG UT WOS:000207654700012 ER PT J AU Hisamatsu-Sakamoto, M Sakamoto, N Rosenberg, AS AF Hisamatsu-Sakamoto, Michiko Sakamoto, Norihisa 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 STEM CELLS LA English DT Article DE apolipoprotein B-100; low-density lipoproteins; fetal calf serum; conditioned medium; murine embryonic fibroblasts ID LOW-DENSITY-LIPOPROTEIN; HEPARAN-SULFATE PROTEOGLYCANS; FETAL CALF SERUM; CONDITIONED MEDIUM; LDL RECEPTOR; PROTEIN-FREE; SIALIC-ACID; GROWTH; GENE; PROLIFERATION AB Previous studies have demonstrated that cell populations that are cultured with heterologous animal products can acquire xenoantigens, potentially limiting their clinical utility because of immune responses. Embryonic stem cells (ESCs) are an attractive source of multiple potential cellular therapies and are typically derived and routinely cultured on murine embryonic fibroblast (MEF) feeder cell layers in commercially available serum replacement (SR) medium or fetal calf serum (FCS)-containing medium. Recently, we found that a strong antibody response was generated in human subjects after the second infusion of therapeutic cells cultured in FCS-containing medium. This response was specific for bovine apolipoprotein B-100 (apoB-100), which is the major protein component of low-density lipoproteins (LDL) and which targets its binding to abundant low-density lipoprotein receptors on the cell surface, from which it is internalized. Here, we have shown that ESCs cultured on MEFs in SR medium acquired bovine apoB-100 from MEFs and from the SR medium as well. Our findings also suggest that bovine LDL are used as critical nutrients for ESC propagation. C1 [Hisamatsu-Sakamoto, Michiko; Sakamoto, Norihisa; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Hisamatsu-Sakamoto, Michiko; Sakamoto, Norihisa] Okayama Univ, Dept Gastroenterol & Hepatol, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan. RP Sakamoto, N (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM norihisha.sakamoto@fda.hhs.gov NR 42 TC 19 Z9 20 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2008 VL 26 IS 1 BP 72 EP 78 DI 10.1634/stemcells.2007-0744 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 250LV UT WOS:000252302500009 PM 17951218 ER PT J AU Starlard-Davenport, A Lyn-Cook, B Radominska-Pandya, A AF Starlard-Davenport, Athena Lyn-Cook, Beverly Radominska-Pandya, Anna TI Novel identification of UDP-glucuronosyltransferase 1A10 as an estrogen-regulated target gene SO STEROIDS LA English DT Article DE UGTs; UGT1A10; Estradiol (E-2); breast cancer; estrogen receptor (ER) ID BREAST-CANCER; GLUCURONIDATION; POLYMORPHISMS; EXPRESSION; PROTEINS; DISEASE; UGT2B15; BINDING; LOCUS; DRUGS AB Recently, we have shown that UGT1A10 is actively involved in the inactivation of E-1, E-2, and their 2- and 4-hydroxylated derivatives. In the present study, we show for the first time that treatment of the MCF-7 ER-positive breast cancer cell line with E-2 produces a dose-dependent up-regulation of UGT1A10 mRNA levels, followed by a steady down-regulation. In contrast, E-2 did not stimulate mRNA expression in the MDA-MB-231 (ER)-negative breast cancer cell line. Expression of UGT1A10 mRNA was blocked by the antiestrogen, ICI 182,780, but not by the transcriptional inhibitor, actinomycin-D. These findings suggest that regulation of UGT1A10 mRNA might be a primary transcriptional response mediated through the ER. Expression of UGT1A10 mRNA was also stimulated by other estrogenic compounds including propylpyrazoletriol (PPT) and genistein (Gen). Exposure of MCF-7 cells to 0.1 nM E-2 up-regulated, and then down-regulated, UGT1A protein and enzymatic activity toward E-2 at 10 nM E-2 as determined by Western blot and glucuronidation activity assays. Collectively, these results suggest that induction of UGT1A10 mRNA expression by E-2 might be mediated through ER, and that this isoform is a novel, estrogen-regulated target gene in MCF-7, ER-positive human breast cancer cells. The finding of E-2-induced expression of UGT1A10 mRNA, followed by the down-regulation of UGT1A10 at pharmacological concentrations of E2, might have a significant moderating effect on E-2 availability for ER and estrogen clearance, thereby promoting the signaling of E-2 in breast cancer cells. (C) 2007 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 [R01 DK060109-03, R01 DK060109, R01 DK060109-03S1, DK60109]; NIGMS NIH HHS [R01 GM075893, GM075893] NR 38 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD JAN PY 2008 VL 73 IS 1 BP 139 EP 147 DI 10.1016/j.steroids.2007.09.007 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254QN UT WOS:000252602600017 PM 17981312 ER PT J AU Keenan, C Elmore, S Franckecarroll, S Kemp, R Kerlin, R Pletcher, J Rinke, M Schmidt, P Taylor, I Wolf, D AF Keenan, Charlotte Elmore, Susan Franckecarroll, Sabine Kemp, Ramon Kerlin, Roy Pletcher, John Rinke, Matthias Schmidt, Peter Taylor, Ian Wolf, Douglas TI STP Working Group for Historical Control Data of Proliferative Rodent Lesions SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Elmore, Susan] NIEHS, Res Triangle Pk, NC 27709 USA. [Franckecarroll, Sabine] US FDA, Silver Spring, MD USA. [Kemp, Ramon] Merck Res Labs, West Point, PA USA. [Kerlin, Roy] Pfizer Global Res & Dev, Groton, CT USA. [Pletcher, John] Charles River Labs, Frederick, MD USA. [Rinke, Matthias] BayerHealthCare AG, Wuppertal, Germany. [Schmidt, Peter] Pfizer Inc, Kalamazoo, MI USA. [Wolf, Douglas] US EPA, Res Triangle Pk, NC 27711 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 JAN PY 2008 VL 36 IS 1 MA P24 BP 157 EP 157 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463UF UT WOS:000267456900043 ER PT J AU Zhou, Y Vaidya, VS Brown, RP Zhang, J Rosenzweig, BA Thompson, KL Miller, TJ Bonventre, JV Goering, PL AF Zhou, Yuzhao Vaidya, Vishal S. Brown, Ronald P. Zhang, Jun Rosenzweig, Barry A. Thompson, Karol L. Miller, Terry J. Bonventre, Joseph V. Goering, Peter L. TI Comparison of kidney injury molecule-1 and other nephrotoxicity biomarkers in urine and kidney following acute exposure to gentamicin, mercury, and chromium SO TOXICOLOGICAL SCIENCES LA English DT Article DE acute kidney injury; nephrotoxicity biomarkers; kidney injury molecule-1; mercury; chromium; gentamicin ID RENAL-CELL CARCINOMA; HEPATITIS-A VIRUS; HOSPITALIZED-PATIENTS; PROXIMAL TUBULE; RAT-KIDNEY; TOXICITY; RECEPTOR; EXPRESSION; INDUCTION; BLOCKADE AB Sensitive biomarkers are needed to detect kidney injury at the earliest stages. The objective of this study was to determine whether the appearance of kidney injury molecule-1 (Kim-1) protein ectodomain in urine and kidney injury molecule-1/ hepatitis A viral cellular receptor-1 (Kim-1/Havcr1) gene expression in kidney tissue may be more predictive of renal injury after exposure to nephrotoxicants when compared to traditionally used biomarkers. Male Sprague-Dawley rats were injected with a range of doses of gentamicin, mercury (Hg; HgCl2), or chromium (Cr; K2Cr2O7). The results showed that increases in urinary Kim-1 and kidney Kim-1/Havcr1 gene expression paralleled the degree of severity of renal histopathology and were detected at lower doses of nephrotoxicants when compared to blood urea nitrogen (BUN), serum creatinine, and urinary N-acetyl-beta-D-glucosaminidase (NAG). In a time course study, urinary Kim-1 was elevated within 24 h after exposure to gentamicin (100 mg/kg), Hg (0.25 mg/kg), or Cr (5 mg/kg) and remained elevated through 72 h. NAG responses were nephrotoxicant dependent with elevations occurring early (gentamicin), late (Cr), or no change (Hg). At 72 h, after treatment with any of the three nephrotoxicants, there was increased Kim-1 immunoreactivity and necrosis involving similar to 50% of the proximal tubules; however, only urinary Kim-1 was significantly increased, while BUN, serum creatinine, and NAG were not different from controls. In rats treated with the hepatotoxicant galactosamine (1.1 mg/kg), serum alanine aminotransferase was increased, but no increase in urinary Kim-1 was observed. Urinary Kim-1 and kidney Kim-1/Havcr1 expression appear to be sensitive and tissue-specific biomarkers that will improve detection of early acute kidney injury following exposure to nephrotoxic chemicals and drugs. C1 [Zhou, Yuzhao; Brown, Ronald P.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, White Oak Life Sci Lab, Silver Spring, MD 20993 USA. [Vaidya, Vishal S.; Bonventre, Joseph V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Vaidya, Vishal S.; Bonventre, Joseph V.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Zhang, Jun; Rosenzweig, Barry A.; Thompson, Karol L.; Miller, Terry J.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, White Oak Life Sci Lab, WO64-4064,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.goering@fda.hhs.gov FU NIDDK NIH HHS [R37 DK039773, DK 039773, DK 072831, DK 074099, R01 DK039773, R01 DK072381, R01 DK072381-04, R21 DK074099, R33 DK074099]; NIEHS NIH HHS [R00 ES016723, R00 ES016723-02] NR 37 TC 142 Z9 166 U1 6 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2008 VL 101 IS 1 BP 159 EP 170 DI 10.1093/toxsci/kfm60 PG 12 WC Toxicology SC Toxicology GA 242HY UT WOS:000251717400015 PM 17934191 ER PT J AU Matthews, EJ Kruhlak, NL Benz, RD Contrera, JF Marchant, CA Yang, C AF Matthews, Edwin J. Kruhlak, Naomi L. Benz, R. Daniel Contrera, Joseph F. Marchant, Carol A. Yang, Chihae TI Combined use of MC4PC, MDL-QSAR, BioEpisteme, leadscope PDM, and derek for windows software to achieve high-performance, high-confidence, mode of action-based predictions of chemical carcinogenesis in rodents SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE BioEpisteme; Carcinogenicity; chemical carcinogenesis; computational; toxicology; derek for windows; in silico; leadscope; MC4PC; MDL-QSAR; quantitative; structure-activity relationships; QSAR software; SAR ID DISCRIMINATING STRUCTURAL FEATURES; TOXICITY HAZARD IDENTIFICATION; NATIONAL-TOXICOLOGY-PROGRAM; FALSE-POSITIVE RATES; E-STATE INDEXES; DEVELOPMENTAL TOXICITY; COMPREHENSIVE MODEL; GENETIC TOXICITY; BUILDING-BLOCKS; END-POINTS AB This report describes a coordinated use of four quantitative structure-activity relationship (QSAR) programs and an expert knowledge base system to predict the occurrence and the mode of action of chemical carcinogenesis in rodents. QSAR models were based upon a weight-of-evidence paradigm of carcinogenic activity that was linked to chemical structures (n = 1,572). Identical training data sets were configured for four QSAR programs (MC4PC, MDL-QSAR, BioEpisteme, and Leadscope PDM), and QSAR models were constructed for the male rat, female rat, composite rat, male mouse, female mouse, composite mouse, and rodent composite endpoints. Model predictions were adjusted to favor high specificity (80%). Performance was shown to be affected by the method used to score carcinogenicity study findings and the ratio of the number of active to inactive chemicals in the QSAR training data set. Results demonstrated that the four QSAR programs were complementary, each detecting different profiles of carcinogens. Accepting any positive prediction from two programs showed better overall performance than either of the single programs alone; specificity, sensitivity, and Chi-square values were 72.9%, 65.9%, and 223, respectively, compared to 84.5%, 45.8%, and 151. Accepting only consensus-positive predictions using any two programs had the best overall performance and higher confidence; specificity, sensitivity, and Chi-square values were 85.3%, 57.5%, and 287, respectively. Specific examples are provided to demonstrate that consensus-positive predictions of carcinogenicity by two QSAR programs identified both genotoxic and nongenotoxic carcinogens and that they detected 98.7% of the carcinogens linked in this study to Derek for Windows defined modes of action. C1 [Matthews, Edwin J.; Kruhlak, Naomi L.; Benz, R. Daniel; Contrera, Joseph F.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Informat & Computat Safety Anal Staff, Silver Spring, MD 20993 USA. [Marchant, Carol A.] Lhasa Ltd, Leeds LS2 9HD, W Yorkshire, England. [Yang, Chihae] Leadscope Inc, Columbus, OH 43215 USA. RP Matthews, EJ (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Informat & Computat Safety Anal Staff, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Edwin.Mattews@fda.hhs.gov NR 54 TC 54 Z9 54 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 2-3 BP 189 EP 206 DI 10.1080/15376510701857379 PG 18 WC Toxicology SC Toxicology GA 279ZW UT WOS:000254395700009 PM 20020914 ER PT J AU Contrera, JF Matthews, EJ Kruhlak, NL Benz, RD AF Contrera, Joseph F. Matthews, Edwin J. Kruhlak, Naomi L. Benz, R. Daniel TI In silico screening of chemicals for genetic toxicity using MDL-QSAR, nonparametric discriminant analysis, e-state, connectivity, and molecular property descriptors SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE clastogenicity; DNA damage; drug development; electrotopological; E-state indices; genetic toxicity; genotoxic; in silico screening; MC4PC; mutagenicity; predictive toxicology; QSAR ID DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; DRUG DISCOVERY; PREDICTION; GENOTOXICITY; INDEXES; IDENTIFICATION; MODELS; PHARMACEUTICALS; CLASSIFICATION AB Genetic toxicity testing is a critical parameter in the safety assessment of pharmaceuticals, food constituents, and environmental and industrial chemicals. Quantitative structure-activity relationship (QSAR) software offers a rapid, cost-effective means of prioritizing the genotoxic potential of chemicals. Our goal is to develop and validate a complete battery of complementary QSAR models for genetic toxicity. We previously reported the development of MDL-QSAR models for the prediction of mutations in Salmonella typhimurium and Escherichia coli (Contrera et al. 2005b); this report describes the development of eight additional models for mutagenicity, clastogenicity, and DNA damage. The models were created using MDL-QSAR atom-type E-state, simple connectivity and molecular property descriptor categories, and nonparametric discriminant analysis. In 10% leave-group-out internal validation studies, the specificity of the models ranged from 63% for the mouse lymphoma (L5178Y-tk) model to 88% for chromosome aberrations in vivo. Sensitivity ranged from a high of 74% for the mouse lymphoma model to a low of 39% for the unscheduled DNA synthesis model. The receiver operator characteristic (ROC) was 2.00, a value indicative of good predictive performance. The predictive performance of MDL-QSAR models was also shown to compare favorably to the results of MultiCase MC4PC (Matthews et al. 2006b) genotoxicity models prepared with the same training data sets. MDL-QSAR software models exhibit good specificity, sensitivity, and coverage and they can provide rapid and cost-effective large-scale screening of compounds for genotoxic potential by the chemical and pharmaceutical industry and for regulatory decision support applications. C1 [Contrera, Joseph F.; Matthews, Edwin J.; Kruhlak, Naomi L.; Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, Silver Spring, MD USA. RP Contrera, JF (reprint author), Computat Toxicol Serv, LLC, Box 1565, Olney, MD 20853 USA. EM jfcontrera@verizon.net NR 44 TC 20 Z9 20 U1 2 U2 9 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 2-3 BP 207 EP 216 DI 10.1080/15376510701857106 PG 10 WC Toxicology SC Toxicology GA 279ZW UT WOS:000254395700010 PM 20020915 ER PT J AU Kruhlak, NL Choi, SS Contrera, JF Weaver, JL Willard, JM Hastings, KL Sancilio, LF AF Kruhlak, Naomi L. Choi, Sydney S. Contrera, Joseph F. Weaver, James L. Willard, James M. Hastings, Kenneth L. Sancilio, Lawrence F. TI Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE computational toxicology; consensus predictions; cross; validation; database; in silico Modeling; MC4PC; MDL-QSAR; phospholipidosis; QSAR ID DRUG-INDUCED PHOSPHOLIPIDOSIS; CATIONIC AMPHIPHILIC DRUGS; AMIODARONE-TREATED RATS; E-STATE INDEXES; HAZARD IDENTIFICATION; TOXICITY; CHEMICALS; PHOSPHOLIPASE-A1; PHARMACEUTICALS; CONSTRUCTION AB Drug-induced phospholipidosis (PL) is a condition characterized by the accumulation of phospholipids and drug in lysosomes, and is found in a variety of tissue types. PL is frequently manifested in preclinical studies and may delay or prevent the development of pharmaceuticals. This report describes the construction of a database of PL findings in a variety of animal species and its use as a training data set for computational toxicology software. PL data and chemical structures were compiled from the published literature, existing pharmaceutical databases, and Food and Drug Administration (FDA) internal reports yielding a total of 583 compounds suitable for modeling. The database contained 190 (33%) positive drugs and 393 (77%) negative drugs, of which 39 were electron microscopy-confirmed negative compounds and 354 were classified as negatives due to the absence of positive reported data. Of the 190 positive findings, 76 were electron microscopy confirmed and 114 were considered positive based on other evidence. Quantitative structure-activity relationship (QSAR) models were constructed using two commercially available software programs, MC4PC and MDL-QSAR, and internal cross-validation (10 10%) experiments were performed to assess their predictive performance. Performance parameters for the MC4PC model were specificity 92%, sensitivity 50%, concordance 78%, positive predictivity 76%, and negative predictivity 78%. For MDL-QSAR, predictive performance was similar: specificity 80%, sensitivity 76%, concordance 79%, positive predictivity 65%, and negative predictivity 87%. By combining the output of the two QSAR programs, the overall predictive performance was vastly improved and sensitivity could be optimized to 81% without significant loss of specificity (79%). Many of the structural alerts and significant molecular descriptors obtained from the QSAR software were found to be associated with parts of active molecules known for their cationic amphiphilic drug (CAD) properties supporting the hypothesis that the endpoint of PL is statistically correlated with chemical structure. QSAR models can be useful tools for screening drug candidate molecules for potential PL. C1 [Kruhlak, Naomi L.; Choi, Sydney S.; Contrera, Joseph F.; Weaver, James L.; Willard, James M.; Hastings, Kenneth L.; Sancilio, Lawrence F.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Kruhlak, NL (reprint author), FDA CDER OPS ICSAS, 10903 New Hampshire Ave,Rm 1525,WO21, Silver Spring, MD 20993 USA. EM Naomi.Kruhlak@fda.hhs.gov NR 57 TC 32 Z9 34 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 2-3 BP 217 EP 227 DI 10.1080/15376510701857262 PG 11 WC Toxicology SC Toxicology GA 279ZW UT WOS:000254395700011 PM 20020916 ER PT J AU Arvidson, KB Valerio, LG Diaz, M Chanderbhan, RF AF Arvidson, Kirk B. Valerio, Luis G., Jr. Diaz, Marilyn Chanderbhan, Ronald F. TI In silico toxicological screening of natural products SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE computational toxicology; in silico; structure; activity relationship; SAR; QSAR; toxicity prediction; mechanisms; natural products; botanicals; dietary chemicals; carcinogenicity; cancer; rodents ID ALPHA-LIPOIC ACID; NATURALLY-OCCURRING ALKENYLBENZENES; HERB ARISTOLOCHIA-FANGCHI; POST-LABELING ANALYSIS; UROTHELIAL CARCINOMA; THIOCTIC ACID; EPIGALLOCATECHIN GALLATE; RODENT CARCINOGENICITY; DIETARY FLAVONOIDS; CHEMICAL-STRUCTURE AB This study closely examines six well-known naturally occurring dietary chemicals (estragole, pulegone, aristolochic acid I, lipoic acid, 1-octacosanol, and epicatechin) with known human exposure, chemical metabolism, and mechanism of action (MOA) using in silico screening methods. The goal of this study was to take into consideration the available information on these chemicals in terms of MOA and experimentally determined toxicological data, and compare them to the in silico predictive modeling results produced from a series of computational toxicology software. After these analyses, a consensus modeling prediction was formulated in light of the weight of evidence for each natural product. We believe this approach of examining the experimentally determined mechanistic data for a given chemical and comparing it to in silico generated predictions and data mining is a valid means to evaluating the utility of the computational software, either alone or in combination with each other. We find that consensus predictions appear to be more accurate than the use of only one or two software programs and our in silico results are in very good agreement with the experimental toxicity data for the natural products screened in this study. C1 [Valerio, Luis G., Jr.; Chanderbhan, Ronald F.] US FDA, Ctr Food Safety & Appl Nutr, Paint Branch 5100, Silver Spring, MD 20993 USA. [Valerio, Luis G., Jr.; Chanderbhan, Ronald F.] Div Biotechnol, Silver Spring, MD 20993 USA. [Arvidson, Kirk B.] Div Food Contact Notificat, College Pk, MD 20740 USA. [Diaz, Marilyn] Univ Puerto Rico, Dept Chem Engn, Mayaguez, PR 00680 USA. RP Valerio, LG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, HFD-003,10903 New Hempshire Ave, Silver Spring, MD 20993 USA. EM luis.valerio@fda.hhs.gov NR 114 TC 8 Z9 10 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1537-6516 EI 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 2-3 BP 229 EP 242 DI 10.1080/15376510701856991 PG 14 WC Toxicology SC Toxicology GA 279ZW UT WOS:000254395700012 PM 20020917 ER PT J AU Yang, C Hasselgren, CH Boyer, S Arvidson, K Aveston, S Dierkes, P Benigni, R Benz, RD Contrera, J Kruhlak, NL Matthews, EJ Han, X Jaworska, J Kemper, RA Rathman, JF Richard, AM AF Yang, C. Hasselgren, C. H. Boyer, S. Arvidson, K. Aveston, S. Dierkes, P. Benigni, R. Benz, R. D. Contrera, J. Kruhlak, N. L. Matthews, E. J. Han, X. Jaworska, J. Kemper, R. A. Rathman, J. F. Richard, A. M. TI Understanding genetic toxicity through data mining: The process of building knowledge by integrating multiple genetic toxicity databases SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE genetic toxicity; Databases; ToxML; SAR; QSAR; structural alerts ID IN-VITRO; POTENTIAL CARCINOGENICITY; DEVELOPMENTAL TOXICITY; MUTAGENICITY; CHEMICALS; IDENTIFICATION; TOXICOLOGY; SOFTWARE; ASSAY AB Genetic toxicity data from various sources were integrated into a rigorously designed database using the ToxML schema. The public database sources include the U.S. Food and Drug Administration (FDA) submission data from approved new drug applications, food contact notifications, generally recognized as safe food ingredients, and chemicals from the NTP and CCRIS databases. The data from public sources were then combined with data from private industry according to ToxML criteria. The resulting "integrated" database, enriched in pharmaceuticals, was used for data mining analysis. Structural features describing the database were used to differentiate the chemical spaces of drugs/candidates, food ingredients, and industrial chemicals. In general, structures for drugs/candidates and food ingredients are associated with lower frequencies of mutagenicity and clastogenicity, whereas industrial chemicals as a group contain a much higher proportion of positives. Structural features were selected to analyze endpoint outcomes of the genetic toxicity studies. Although most of the well-known genotoxic carcinogenic alerts were identified, some discrepancies from the classic Ashby-Tennant alerts were observed. Using these influential features as the independent variables, the results of four types of genotoxicity studies were correlated. High Pearson correlations were found between the results of Salmonella mutagenicity and mouse lymphoma assay testing as well as those from in vitro chromosome aberration studies. This paper demonstrates the usefulness of representing a chemical by its structural features and the use of these features to profile a battery of tests rather than relying on a single toxicity test of a given chemical. This paper presents data mining/profiling methods applied in a weight-of-evidence approach to assess potential for genetic toxicity, and to guide the development of intelligent testing strategies. C1 [Yang, C.] Leadscope Inc, Columbus, OH 43215 USA. [Hasselgren, C. H.; Boyer, S.] AstraZeneca R&D, Molndal 43183, Sweden. [Arvidson, K.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. [Aveston, S.; Dierkes, P.] Unilever Safety & Environm Assurance Ctr, Sharnbrook MK44 1LQ, Beds, England. [Benigni, R.] Ist Super Sanita, Environm & Hlth Dept, I-00161 Rome, Italy. [Benz, R. D.; Contrera, J.; Kruhlak, N. L.; Matthews, E. J.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, Silver Spring, MD 20993 USA. [Han, X.] DuPont Haskell Global Ctr Hlth & Environm Sci, Newark, DE 19714 USA. [Jaworska, J.] Procter & Gramble, Cent Prod Safety, Strombeek Bever, Bever, Belgium. [Kemper, R. A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Rathman, J. F.] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Richard, A. M.] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. RP Yang, C (reprint author), 1393 Dublin Rd, Columbus, OH 43215 USA. EM cyang@leadscope.com RI Dierkes, Peter/G-1461-2010 NR 33 TC 27 Z9 27 U1 2 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 2-3 BP 277 EP 295 DI 10.1080/15376510701857502 PG 19 WC Toxicology SC Toxicology GA 279ZW UT WOS:000254395700016 PM 20020921 ER PT J AU Schnackenberg, LK Beger, RD AF Schnackenberg, Laura K. Beger, Richard D. TI The role of metabolic biomarkers in drug toxicity studies SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE biomarkers; toxicity; metabolic profiling; metabolomics; metabonomics ID MAGNETIC-RESONANCE-SPECTROSCOPY; PERFORMANCE LIQUID-CHROMATOGRAPHY; MULTIVARIATE STATISTICAL-ANALYSIS; GENTAMICIN-INDUCED NEPHROTOXICITY; INTEGRATED METABONOMIC ANALYSIS; PATTERN-RECOGNITION ANALYSIS; TOF MASS-SPECTROMETRY; H-1-NMR SPECTROSCOPY; RAT URINE; ANALYTICAL REPRODUCIBILITY AB Metabolic profiling is a technique that can potentially provide more sensitive and specific biomarkers of toxicity than the current clinical measures benefiting preclinical and clinical drug studies. Both nuclear magnetic resonance (NMR) and mass spectrometry (MS) platforms have been used for metabolic profiling studies of drug toxicity. Not only can both techniques provide novel biomarker(s) of toxicity but the combination of both techniques gives a broader range of metabolites evaluated. Changes in metabolic patterns can provide insight into mechanism(s) of toxicity and help to eliminate a potentially toxic new chemical entity earlier in the developmental process. Metabolic profiling offers numerous advantages in toxicological research and screening as sample collection and preparation are relatively simple. Further, sample throughput, reproducibility, and accuracy are high. The area of drug toxicity of therapeutic compounds has already been impacted by metabolic profiling studies and will continue to be impacted as new, more specific biomarker(s) are found. In order for a biomarker or pattern of biomarkers to be accepted, it must be shown that they originate from the target tissue of interest. Metabolic profiling studies are amenable to any biofluid or tissue sample making it possible to link the changes noted in urine for instance as originating from renal injury. Additionally, the ease of sample collection makes it possible to follow a single animal or subject over time in order to determine whether and when the toxicity resolves itself. This review focuses on the advantages of metabolic profiling for drug toxicity studies. C1 [Schnackenberg, Laura K.; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 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 NR 102 TC 18 Z9 20 U1 1 U2 17 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PY 2008 VL 18 IS 4 BP 301 EP 311 DI 10.1080/15376510701623193 PG 11 WC Toxicology SC Toxicology GA 302RW UT WOS:000255988000001 PM 20020895 ER PT B AU Pfefer, TJ Drum, BA AF Pfefer, T. Joshua Drum, Bruce A. BE Azar, FS Intes, X TI Regulation and Regulatory Science for Optical Imaging SO TRANSLATIONAL MULTIMODALITY OPTICAL IMAGING SE Artech House Bioinformatics and Biomedical Imaging Series LA English DT Article; Book Chapter ID THERMAL-DAMAGE; PHOTODYNAMIC THERAPY; ULTRAVIOLET-RADIATION; PULSE OXIMETER; BLOOD; SKIN; TISSUES; PHOTOCOAGULATION; SPECTROSCOPY; ERYTHEMA C1 [Pfefer, T. Joshua] US FDA, Silver Spring, MD 20993 USA. [Drum, Bruce A.] US FDA, Rockville, MD 20850 USA. RP Pfefer, TJ (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62,Rm 1222, Silver Spring, MD 20993 USA. EM Joshua.pfefer@fda.hhs.gov; bad@cdrh.fda.gov NR 50 TC 0 Z9 0 U1 0 U2 0 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-307-1 J9 ARTECH HSE BIOINF BI JI Artech House Bioinform. Biomed. Imaging Ser. PY 2008 BP 299 EP 325 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BJL11 UT WOS:000266734600015 ER PT J AU Reed, JL Avendano, L Velozo, L Welliver, RC AF Reed, J. L. Avendano, L. Velozo, L. Welliver, R. C., Sr. TI Desired Immune Response Characteristics In An RSV Vaccine: What Infants Tell Us SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE Respiratory syncytial virus; Innate immunity; T-independent antibody; Bronchiolitis C1 [Reed, J. L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Avendano, L.] Univ Chile, Programa Virol, Santiago, Chile. NR 0 TC 0 Z9 0 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 PY 2008 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600105 ER PT J AU Zubkova, I Choi, Y Chang, E Pirollo, K Krawczynski, H Major, M AF Zubkova, I. Choi, Y. Chang, E. Pirollo, K. Krawczynski, H. Major, M. TI T-cell Vaccines that Elicit Effective Immune Responses against HCV in Chimpanzees Create Greater Immune Pressure for Viral Mutation SO VACCINE LA English DT Meeting Abstract CT 2nd Vaccine Congress CY DEC 07-09, 2008 CL Boston, MA DE hepatitis C virus; T-cell responses; chimpanzees; immune escape C1 [Zubkova, I.; Major, M.] US FDA, CBER, Rockville, MD 20857 USA. [Choi, Y.; Krawczynski, H.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Chang, E.; Pirollo, K.] Georgetown Univ, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 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 PY 2008 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 480QF UT WOS:000268750600154 ER PT J AU Michel, KE Churchill, J Daristotle, L Elaney, S Freeman, LM Roudebush, P Laflamme, D Tefend, MB McChesney, D Todd-Jenkins, K AF Michel, Kathryn E. Churchill, Julie Daristotle, Leighann Delaney, Sean Freeman, Lisa M. Roudebush, Phil Laflamme, Dottie Tefend, Mary B. McChesney, Daniel Todd-Jenkins, Karen TI Expert summit on pet food SO VETERINARY TECHNICIAN LA English DT Editorial Material C1 [Michel, Kathryn E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Churchill, Julie] Univ Minnesota, Minneapolis, MN 55455 USA. [Tefend, Mary B.] Auburn Univ, Auburn, AL 36849 USA. [McChesney, Daniel] US FDA, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20857 USA. RP Michel, KE (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU VETERINARY LEARNING SYSTEMS PI YARDLEY PA 780 TOWNSHIP LINE RD, YARDLEY, PA 19067-4200 USA SN 8750-8990 J9 VET TECH JI Vet. Tech. PD JAN PY 2008 VL 29 IS 1 BP 20 EP 26 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 253WD UT WOS:000252547400003 ER PT J AU Baylis, SA Heath, AB Chudy, M Pisani, G Klotz, A Kerby, S Gerlich, W AF Baylis, S. A. Heath, A. B. Chudy, M. Pisani, G. Klotz, A. Kerby, S. Gerlich, W. TI An international collaborative study to establish the 2nd World Health Organization International Standard for hepatitis B virus DNA nucleic acid amplification technology-based assays SO VOX SANGUINIS LA English DT Article DE hepatitis B virus; International Standard; NAT ID BIOLOGICAL STANDARDS; STABILITY; PLASMA AB Background and Objectives The aim of this study was to replace the 1(st) World Health Organization International Standard for hepatitis B virus DNA for nucleic acid amplification technique (NAT)-based assays (code 97/746) with a new International Standard. Two lyophilized preparations freeze dried from the same bulk were evaluated in the original collaborative study (coded 97/746 and 97/750, and termed AA and BB, respectively, in the original study). This present study re-evaluates these two preparations in terms of potency and real-time stability. Materials and Methods The 1(st) International Standard (97/746) and the second lyophilized preparation (97/750) were coded Samples 1 and 2, respectively, in the present study. The samples were distributed to six laboratories and assayed on four separate occasions. Accelerated thermal degradation samples of the two preparations were examined after long-term storage at 4 degrees C and 20 degrees C for more than 51 months. Results Data were returned from a total of nine different NAT-based assays, five in qualitative format and four in quantitative format. The results of this study confirm the results of the original collaborative study, with no significant differences being found in estimated international units (IU)/ml or polymerase chain reaction-detectable units/ml for the 1(st) International Standard (Sample 1 in this study) and the proposed replacement preparation, Sample 2 (97/750). Real-time and accelerated degradation studies indicate that both samples are very stable. Storage of both preparations at 20 degrees C for more than 51 months resulted in no detectable degradation. Conclusions On the basis of the data presented in this collaborative study, Sample 2 (code 97/750) was established as the 2(nd) International Standard for hepatitis B virus DNA for NAT-based assays with a potency of 10(6) IU/ml (500 000 IU/vial). C1 [Baylis, S. A.; Chudy, M.] Paul Ehrlich Inst, D-63225 Langen, Germany. [Gerlich, W.] Univ Giessen, Inst Med Virol, Giessen, Germany. [Kerby, S.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Klotz, A.] Baxter AG, Vienna, Austria. [Pisani, G.] Inst Super Sanita, Rome, Italy. [Baylis, S. A.; Heath, A. B.] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. RP Baylis, SA (reprint author), Paul Ehrlich Inst, Paul Ehrlich Str 51-59, D-63225 Langen, Germany. EM baysa@pei.de NR 11 TC 13 Z9 18 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2008 VL 94 IS 4 BP 358 EP 362 DI 10.1111/j.1423-0410.2007.01023.x PG 5 WC Hematology SC Hematology GA 288PN UT WOS:000254998400013 PM 18266781 ER PT B AU Junod, SW AF Junod, Suzanne White BE Callaos, N Lesso, W Zinn, CD Chu, HW Baralt, J Tzeng, JR TI Congressional Drug Hearing Analysis: Can the Past Inform the Present? SO WMSCI 2008: 12TH WORLD MULTI-CONFERENCE ON SYSTEMICS, CYBERNETICS AND INFORMATICS, VOL VII, PROCEEDINGS LA English DT Proceedings Paper CT 12th World Multi-Conference on Systemics, Cybernetics and Informatics/14th International Conference on Information Systems Analysis and Synthesis CY JUN 29-JUL 02, 2008 CL Orlando, FL SP Int Inst Informat & System, Int Federat Syst Res DE Food and Drug Administration; Congressional hearings; Thalidomide; Panalba; Viagra; AZT; Vioxx; Vitorin AB Congressional hearing records are not only an important source Of accurate, documented information, but studied and evaluated over time, they call reveal broader trends in institutional history that can be useful to administrators, scholars and others interested parties internal and external to,my agency or institution. In the case of the U.S. Food and Drug Administration, close study of Congressional hearings during the past fifty years revealed that the majority of hearings are focused oil drugs and the drug approval process. Congressional debates demonstrate all ongoing thematic tension between the need to proceed cautiously to insure the safety and efficacy of new drugs entering the marketplace and the need for a timely approval process which gets effective new drugs into the hands of doctors sooner rather than later, Five case studies are identified and discussed as illustrative of this ongoing debate, both historically and currently. C1 [Junod, Suzanne White] US FDA, Hist Off, Rockville, MD 20857 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU INT INST INFORMATICS & SYSTEMICS PI ORLANDO PA 14269 LORD BARCLAY DR, ORLANDO, FL 32837 USA BN 978-1-934272-37-4 PY 2008 BP 305 EP 310 PG 6 WC Chemistry, Analytical; Computer Science, Cybernetics; Computer Science, Information Systems; Computer Science, Theory & Methods; Education & Educational Research; Information Science & Library Science SC Chemistry; Computer Science; Education & Educational Research; Information Science & Library Science GA BIW56 UT WOS:000263414900055 ER PT J AU Zhang, L Zhang, Y Strong, JM Reynolds, KS Huang, SM AF Zhang, L. Zhang, Y. (D) Strong, J. M. Reynolds, K. S. Huang, S. -M. TI A regulatory viewpoint on transporter-based drug interactions SO XENOBIOTICA LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Pharmaceutical-Scientists CY NOV 11-15, 2007 CL San Diego, CA SP Amer Assoc Pharmaceut Scientists DE transporter; drug-drug interaction; regulatory; guidance; new drug application; drug development; exposure-response relationship; labelling; risk management; tipranavir ID INTESTINAL P-GLYCOPROTEIN; IN-VITRO; ORAL BIOAVAILABILITY; RENAL CLEARANCE; DIGOXIN; INHIBITION; PHARMACOKINETICS; QUINIDINE; ROSUVASTATIN; CYCLOSPORINE AB 1. Pharmacokinetic drug interactions can lead to serious adverse events and the evaluation of a new molecular entity's (NME) drug-drug interaction potential is an integral part of drug development and regulatory review before its market approval. Clinically relevant interactions mediated by transporters are of increasing interest in clinical development and research in this emerging area and it has been revealed that drug transporters can play an important role in modulating drug absorption, distribution, metabolism and elimination. 2. Acting alone or in concert with drug-metabolizing enzymes transporters can affect the pharmacokinetics and/or pharmacodynamics of a drug. The newly released drug interaction guidance by the US Food and Drug Administration (USFDA) includes new information addressing drug transporter interactions with a primary focus on P-glycoprotein (P-gp, ABCB1). 3. This paper provides a regulatory viewpoint on transporters and their potential role in drug-drug interactions. It first outlines information that might be needed during drug development and ultimately included in new drug application (NDA) submissions to address potential transporter-mediated drug interactions. Next, it explains criteria that may warrant conduct of in vivo P-gp-mediated drug interaction studies based on in vitro assessment. In addition, it includes a review case that describes the evaluation of data suggesting a P-gp-based induction interaction. C1 [Zhang, L.; Zhang, Y. (D); Reynolds, K. S.; Huang, S. -M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Strong, J. M.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bldg 51,Room 3188,White Oak,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 59 TC 108 Z9 109 U1 2 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PY 2008 VL 38 IS 7-8 BP 709 EP 724 DI 10.1080/00498250802017715 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 332JP UT WOS:000258079600005 PM 18668428 ER PT J AU Braun, MM Izurieta, HS Ball, R AF Braun, M. Miles Izurieta, Hector S. Ball, Robert TI Effectiveness of influenza vaccination SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Rockville, MD 20852 USA. EM miles.braun@fda.hhs.gov NR 4 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 27 PY 2007 VL 357 IS 26 BP 2730 EP 2730 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 245UO UT WOS:000251964500018 PM 18163275 ER PT J AU Rath, B Linder, T Cornblath, D Hudson, M Fernandopulle, R Hartmann, K Heininger, U Izurieta, H Killion, L Kokotis, P Oleske, J Vajdy, M Wong, V AF Rath, Barbara Linder, Thomas Cornblath, David Hudson, Michael Fernandopulle, Rohini Hartmann, Katharina Heininger, Ulrich Izurieta, Hector Killion, Leslie Kokotis, Pangiotis Oleske, James Vajdy, Michael Wong, Virginia CA Brighton Collaboration Bell's Pals TI "All that palsies is not Bell's" - The need to define Bell's palsy as an adverse event following immunization SO VACCINE LA English DT Review DE Bell's palsy; AEFI; clinical definition ID HERPES-SIMPLEX-VIRUS; PERIPHERAL FACIAL PALSY; VARICELLA-ZOSTER-VIRUS; INTRANASAL INFLUENZA VACCINE; NERVE GRADING SYSTEMS; RANDOMIZED CONTROLLED-TRIAL; ACUTE OTITIS-MEDIA; HEAT-LABILE TOXIN; LYME-DISEASE; HOUSE-BRACKMANN AB Bell's palsy has been reported as an adverse event following immunization (AEFI). Review of the published literature reveals that several characteristics have been used to describe Bell's palsy, which differ significantly from author to author. Evidently, the definition of "Bell's palsy" remains controversial, and consensus between different medical subspecialities is urgently needed. The Brighton Collaboration has formed an international working group with representatives of neurology, otorhinolaryngology, pediatrics, electrophysiology, pharmacology, pharmaceutical and biotech industry as well as regulatory agencies to create a case definition of Bell's palsy as an AEFI. (c) 2007 Elsevier Ltd. All rights reserved. C1 [Rath, Barbara; Heininger, Ulrich] Univ Childrens Hosp Basel, CH-4058 Basel, Switzerland. [Linder, Thomas] Kantonsspital Luzern, Dept Otorhinolaryngol, Luzern, Switzerland. [Cornblath, David] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21205 USA. [Hudson, Michael] Hlth Protect Agcy, Salisbury, Wilts, England. [Fernandopulle, Rohini] Int Med Univ, Dept Pharmacol, Kuala Lumpur, Malaysia. [Hartmann, Katharina] Berna Biotech Ltd, Bern, Switzerland. [Izurieta, Hector] US FDA, Rockville, MD 20857 USA. [Killion, Leslie] Wyeth Pharmaceut, Collegeville, PA USA. [Kokotis, Pangiotis] Univ Athens, Aeginitio Hosp, Electomyog Lab, Athens, Greece. [Oleske, James] Univ Hosp, New Jersey Med Sch, Dept Pediat, Newark, NJ USA. [Vajdy, Michael] Novartis Vaccines & Diagnost Inc, Emeryville, CA USA. [Wong, Virginia] Univ Hong Kong, Dept Paediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China. RP Rath, B (reprint author), Univ Childrens Hosp Basel, POB 4005, CH-4058 Basel, Switzerland. EM Barbara.Rath@gmail.com NR 229 TC 18 Z9 18 U1 1 U2 7 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 DEC 21 PY 2007 VL 26 IS 1 BP 1 EP 14 DI 10.1016/j.vaccine.2007.10.043 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253AR UT WOS:000252490700001 PM 18037542 ER PT J AU Cohen, BJ Audet, S Andrews, N Beeler, J AF Cohen, Bernard J. Audet, Susette Andrews, Nick Beeler, Judy CA WHO Working Grp Measles Plaque Red TI Plaque reduction neutralization test for measles antibodies: Description of a standardised laboratory method for use in immunogenicity studies of aerosol vaccination SO VACCINE LA English DT Article DE measles; plaque reduction neutralization test ID VIRUS AB Background: Clinical trials of measles vaccination administered as aerosol are planned with the aim of obtaining Licensure. Measles antibody Levels wilt be measured using the plaque reduction neutralization test (PRNT) to assess antibody responses as a surrogate marker of efficacy. Methods: A working group examined laboratory protocols for measles PRNT in use at three reference centres and agreed to a standardised procedure, which was subsequently validated. Results: Assay validation showed quantitative results varied approximately threefold both within and between assays. The lower limit of detection was approximately 20 milliInternational Units/mL. C1 [Cohen, Bernard J.; Andrews, Nick] Hlth Protect Agcy, Ctr Infect, London NW9 5EQ, England. [Audet, Susette; Beeler, Judy] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cohen, BJ (reprint author), Hlth Protect Agcy, Ctr Infect, London NW9 5EQ, England. EM Bernard.cohen@hpa.org.uk NR 20 TC 68 Z9 69 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 DEC 21 PY 2007 VL 26 IS 1 BP 59 EP 66 DI 10.1016/j.vaccine.2007.10.046 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253AR UT WOS:000252490700007 PM 18063236 ER PT J AU Kovalenko, VM Bagnyukova, TV Sergienko, OV Bondarenko, LB Shayakhmetova, GM Matvienko, AV Pogribny, IP AF Kovalenko, V. M. Bagnyukova, T. V. Sergienko, O. V. Bondarenko, L. B. Shayakhmetova, G. M. Matvienko, A. V. Pogribny, I. P. TI Epigenetic changes in the rat livers induced by pyrazinamide treatment SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE DNA methylation; pyrazinamide; liver injury; rat ID LATENT TUBERCULOSIS INFECTION; HEPATOCELLULAR-CARCINOMA; DNA METHYLATION; ANTITUBERCULOSIS DRUGS; GLOBAL DNA; HEPATOCARCINOGENESIS; HEPATOTOXICITY; INJURY; HYPOMETHYLATION; CARCINOGENESIS AB Drug-induced liver injury, including drug-induced hepatotoxicity during the treatment of tuberculosis infection, is a major health problem with increasingly significant challenges to modem hepatology. Therefore, the assessment and monitoring of the hepatotoxicity of antituberculosis drugs for prevention of liver injury are great concerns during disease treatment. The recently emerged data showing the ability of toxicants, including pharmaceutical agents, to alter cellular epigenetic status, open a unique opportunity for early detection of drug hepatotoxicity. Here we report that treatment of male Wistar rats with antituberculosis drug pyrazinamide at doses of 250, 500 or 1000 mg/kg/day body weight for 45 days leads to an early and sustained decrease in cytosine DNA methylation, progressive hypomethylation of long interspersed nucleotide elements (LINE-1), and aberrant promoter hypermethylation of placental form glutathione-S-transferase (GSTP) and p16(INK4A) genes in livers of pyrazinamide-treated rats, while serum levels of bilirubin and activity of aminotransferases changed modestly. The early occurrence of these epigenetic alterations and their association with progression of liver injury specific pathological changes indicate that alterations in DNA methylation may be useful predictive markers for the assessment of drug hepatotoxicity. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Ukraine Acad Med Sci, Inst Pharmacol & Toxicol, Kiev, Ukraine. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 44 TC 20 Z9 22 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 DEC 15 PY 2007 VL 225 IS 3 BP 293 EP 299 DI 10.1016/j.taap.2007.08.011 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 239RI UT WOS:000251535000007 PM 17920094 ER PT J AU Thakur, S Tadesse, DA Morrow, M Gebreyes, WA AF Thakur, Siddhartha Tadesse, Daniel A. Morrow, Morgan Gebreyes, Wondwossen A. TI Occurrence of multidrug resistant Salmonella in antimicrobial-free (ABF) swine production systems SO VETERINARY MICROBIOLOGY LA English DT Article DE swine; Salmonella species; antimicrobial-free production system; antimicrobials; multidrug resistance ID PREVALENCE; PIGS; TYPHIMURIUM; PORK AB This cross-sectional study was conducted to determine the prevalence and antimicrobial resistance of Salmonella species in swine reared in the intensive (indoor) and extensive (outdoor) ABF production systems at farm and slaughter in North Carolina, U.S.A. We sampled a total of 279 pigs at farm (extensive 107; intensive 172) and collected 274 carcass swabs (extensive 124; intensive 150) at slaughter. Salmonella species were tested for their susceptibility against 12 antimicrobial agents using the Kirby-Bauer disk diffusion method. Serogrouping was done using polyvalent and group specific antisera. A total of 400 salmonellae were isolated in this study with a significantly higher Salmonella prevalence from the intensive (30%) than the extensive farms (0.9%) (P < 0.001). At slaughter, significantly higher Salmonella was isolated at the pre- and post-evisceration stages from extensively (29% pre-evisceration and 33.3% post-evisceration) than the intensively (2% pre-evisceration and 6% post-evisceration) reared swine (P < 0.001). The isolates were clustered in six serogroups including B, C, El, E4, G and R. Highest frequency of antimicrobial resistance was observed against tetracycline (78.5%) and streptomycin (31.5%). A total of 13 antimicrobial resistance patterns were observed including the pentaresistant strains with ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline resistance pattern observed only among isolates from the intensive farms (n = 28) and all were serotype Salmonella typhimurium var. Copenhagen. In conclusion, this study shows that multidrug resistant Salmonella are prevalent in ABF production systems despite the absence of antimicrobial selection pressure. In addition, it also highlights the possible role played by slaughterhouse and other environmental factors in the contamination and dissemination of antimicrobial resistant Salmonella in ABF production systems. (c) 2007 Elsevier B.V. All rights reserved. C1 Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA. US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. N Carolina State Univ, Coll Agr & Life Sci, Dept Anim Sci, Raleigh, NC 27606 USA. RP Gebreyes, WA (reprint author), Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, 1920 Coffey Rd, Columbus, OH 43210 USA. EM gebreyes.1@osu.edu NR 12 TC 14 Z9 15 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD DEC 15 PY 2007 VL 125 IS 3-4 BP 362 EP 367 DI 10.1016/j.vetmic.2007.05.025 PG 6 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 234TO UT WOS:000251187100018 PM 17644277 ER PT J AU Galson, SK AF Galson, Steven K. TI The FDA and the IOM report SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Galson, SK (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 1 Z9 1 U1 0 U2 2 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 DEC 13 PY 2007 VL 357 IS 24 BP 2520 EP 2521 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 240CK UT WOS:000251564400028 PM 18077820 ER PT J AU Biris, AS Schmitt, TC Little, RB Li, Z Xu, Y Biris, AR Lupu, D Dervishi, E Trigwell, S Miller, DW Rahman, Z AF Biris, Alexandru S. Schmitt, Thomas C. Little, Reginald B. Li, Zhongrui Xu, Yang Biris, Alexandru R. Lupu, Dan Dervishi, Enkeleda Trigwell, Steve Miller, Dwight W. Rahman, Zia TI Influence of the RF excitation of the catalyst system on the morphology of multiwalled carbon nanotubes (Retracted article. See vol. 116, pg. 18571, 2012) SO JOURNAL OF PHYSICAL CHEMISTRY C LA English DT Article; Retracted Publication ID GROWTH; CCVD; DECOMPOSITION; ACETYLENE; HYDROGEN; SUPPORT AB Multiwalled carbon nanotubes were synthesized by catalytic chemical vapor deposition using two different methods of heating. By one method, an external resistive tube furnace was used, whereas the other method involved heating with radio frequency excitation by induction coil. A comprehensive comparison was made between these two methods with regards to feed gas utilization, nanotube growth efficiency, nanotube product characterization and morphology, and the formation of amorphous carbon and gaseous byproducts. The carbon nanotubes synthesized using radio frequency excitation exhibited smaller outer diameters, fewer carbon layers, less amorphous carbon, and superior crystalline properties than those produced by external tube furnace. The radio frequency process resulted in more rapid and sustained growth rates of the nanotubes and more efficient use of the carbon source. The reason for these enhanced effects by inductive heating may be due not only to the internally produced thermodynamic heat flow characteristics but perhaps also to induced electron currents generated within the magnetic and metallic catalytic clusters due to RF. C1 Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Elizabeth City State Univ, Dept Chem, Elizabeth City, NC 27909 USA. Natl Inst Res & Dev Isotop & Mol Technol, R-400293 Cluj Napoca, Romania. NASA, Electrostat & Surface Phys Lab, Kennedy Space Ctr, Kennedy Space Ctr, FL 32899 USA. Univ Cent Florida, Adv Mat Proc & Anal Ctr, Orlando, FL 32826 USA. RP Biris, AS (reprint author), Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. EM asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010; Lupu, Dan/C-3346-2009; Dervishi, Enkeleda/B-2239-2010; Biris, Alexandru /C-4517-2011 NR 22 TC 18 Z9 18 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1932-7447 J9 J PHYS CHEM C JI J. Phys. Chem. C PD DEC 6 PY 2007 VL 111 IS 48 BP 17970 EP 17975 DI 10.1021/jp0740346 PG 6 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 236GV UT WOS:000251291900046 ER PT J AU Palinkas, LA Reedy, KR Shepanek, M Smith, M Anghel, M Steel, GD Reeves, D Case, HS Van Do, N Reed, HL AF Palinkas, Lawrence A. Reedy, Kathleen R. Shepanek, Marc Smith, Mark Anghel, Mihai Steel, Gary D. Reeves, Dennis Case, H. Samuel Van Do, Nhan Reed, H. Lester TI Environmental influences on hypothalamic-pituitary-thyroid function and behavior in Antarctica SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Antarctica; cold; altitude; mood; cognition; human; thermoregulation; thyroid hormones ID SEASONAL AFFECTIVE-DISORDER; GENERAL COLD ADAPTATION; L-THYROXINE TREATMENT; SUBCLINICAL HYPOTHYROIDISM; COGNITIVE PERFORMANCE; STIMULATING HORMONE; HIGH-ALTITUDE; RESIDENCE; TRIIODOTHYRONINE; HUMANS AB We examined the physiological and psychological status of men and women who spent the summer (n=100) and/or winter (n=85) seasons in Antarctica at McMurdo (latitude 78.48 S, elevation 12 in) and South Pole (latitude 90 S, elevation 3880 in) stations to determine whether there were any significant differences by severity of the stations' physical environment. Physiological measures (body mass index, blood pressure, heart rate, tympanic temperature), serum measures of thyroid hormones, cortisol, and lipids and plasma catecholamines were obtained at predeployment (Sep-Oct) and the beginning of the summer (November) and winter (Mar-Apr) seasons. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric - Isolated and Confined Environments (ANAM-ICE), a computerized test battery. South Pole residents had a lower body mass index (p<0.05) and body temperature (p<0.01) and higher levels of plasma norepinephrine (p<0.05) in summer and winter than McMurdo residents. Upon deployment from the United States and during the summer, South Pole residents experienced significantly higher thyroid hormone values (free and total T-3 and T-4) (p<0.01) than McMurdo residents; in summer they also experienced lower levels of triglycerides (p<0.01) cortisol (p<0.05) and LDL (p<0.05). In winter, South Pole residents also experienced a 39% decrease in serum TSH compared with a 31.9% increase in McMurdo (p<0.05). South Pole residents also were significantly more accurate (p<0.05) and efficient (p<0.01) in performance of complex cognitive tasks in summer and winter. Higher thyroid hormone levels, combined with lower BMI and body temperature, may reflect increased metabolic and physiological responses to colder temperatures and/or higher altitude at South Pole with no apparent adverse effect on mood and cognition. (C) 2007 Elsevier Inc. All rights reserved. C1 [Palinkas, Lawrence A.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Reedy, Kathleen R.] US FDA, Silver Spring, MD 20993 USA. [Shepanek, Marc] NASA, Washington, DC 20546 USA. [Smith, Mark] George Washington Univ, Dept Psychiat, Washington, DC 20037 USA. [Anghel, Mihai] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. [Steel, Gary D.] Lincoln Univ, Christchurch, New Zealand. [Reeves, Dennis] Clinvest Inc, Springfield, MO 65807 USA. [Case, H. Samuel] McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD 21157 USA. [Van Do, Nhan] Madigan Army Med Ctr, Dept Med, Endocrine Serv, Tacoma, WA 98431 USA. [Reed, H. Lester] MultiCare Hlth Syst, Tacoma, WA 98415 USA. RP Palinkas, LA (reprint author), Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. EM palinkas@usc.edu NR 45 TC 8 Z9 9 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD DEC 5 PY 2007 VL 92 IS 5 BP 790 EP 799 DI 10.1016/j.physbeh.2007.06.008 PG 10 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 242BB UT WOS:000251698400002 PM 17628620 ER PT J AU Jin, T Fu, TJ Kothary, MH Howard, A Zhang, YZ AF Jin, Tengchuan Fu, Tong-Jen Kothary, Mahendra H. Howard, Andrew Zhang, Yu-Zhu TI Crystallization and initial crystallographic characterization of a vicilin-type seed storage protein from Pinus koraiensis SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID CHEMICAL-COMPOSITION; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURES; NUTS; PHASEOLIN; CANAVALIN AB The cupin superfamily of proteins includes the 7S and 11S seed storage proteins. Many members of this family of proteins are known allergens. In this study, the Korean pine ( Pinus koraiensis) vicilin-type 7S seed storage protein was isolated from defatted pine-nut extract and purified by sequential gel-filtration and anion-exchange chromatography. Well diffracting single crystals were obtained by the vapor-diffusion method in hanging drops. The crystals belong to the primitive cubic space group P2(1)3, with unit-cell parameters a = b = c = 148.174 angstrom. Two vicilin molecules were present in the asymmetric unit and the Matthews coefficient was determined to be 2.90 angstrom(3) Da(-1), with a corresponding solvent content of similar to 58%. A molecular-replacement structural solution has been obtained using the program Phaser. Refinement of the structure is currently under way. C1 [Jin, Tengchuan; Howard, Andrew; Zhang, Yu-Zhu] IIT, Dept Biol, Chicago, IL 60616 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Rockville, MD 20857 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Zhang, YZ (reprint author), IIT, Dept Biol, Chicago, IL 60616 USA. EM zhangy@iit.edu RI Zhang, Yuzhu/A-7109-2009; Jin, Tengchuan/B-5883-2014 OI Zhang, Yuzhu/0000-0001-7882-5692; Jin, Tengchuan/0000-0002-1395-188X NR 19 TC 4 Z9 4 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD DEC PY 2007 VL 63 BP 1041 EP 1043 DI 10.1107/S1744309107054310 PN 12 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 243LV UT WOS:000251799500012 PM 18084088 ER PT J AU Lal, R Kremzner, M AF Lal, Renu Kremzner, Mary TI Introduction to the new prescription drug labeling by the Food and Drug Administration SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 Genentech Inc, San Francisco, CA 94107 USA. US FDA, Div Drug Informat, Off Training & Commun, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Lal, R (reprint author), Genentech Inc, 250 King St,Unit 528, San Francisco, CA 94107 USA. NR 7 TC 12 Z9 12 U1 0 U2 1 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 DEC 1 PY 2007 VL 64 IS 23 BP 2488 EP 2494 DI 10.2146/ajhp070130 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 238TO UT WOS:000251470700018 PM 18029957 ER PT J AU Rao, VK Dowdell, KC Dale, JK Dugan, F Pesnicak, L Bi, LL Hoffmann, V Penzak, S Avila, NA Fleisher, TA Puck, JM Straus, SE AF Rao, V. Koneti Dowdell, Kennichi C. Dale, Janet K. Dugan, Faith Pesnicak, Lesley Bi, Lilia L. Hoffmann, Victoria Penzak, Scott Avila, Nilo A. Fleisher, Thomas A. Puck, Jennifer M. Straus, Stephen E. TI Pyrimethamine treatment does not ameliorate lymphoproliferation or autoimmune disease in MRL/Ipr-/- mice or In patients with autoimmune lymphoproliferative syndrome SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID LYMPHOCYTE APOPTOSIS; MYCOPHENOLATE-MOFETIL; SULFADOXINE; DISORDER; INFECTION; FEATURES; DEFECTS; MALARIA; DRUG AB Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder of lymphocyte apoptosis leading to childhood onset of marked lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias, and increased risk of lymphoma. Most cases are associated with heterozygous mutations in the gene encoding Fas protein. Prolonged use of immunosuppressive drugs that do ameliorate its autolimmune complications fail to consistently lessen lymphoproliferation in ALPS. A case series had described children with ALPS, whose spleens (SPL) and lymph nodes decreased in size when treated weekly with pyrimethamine and sulfadoxine; parallel in vitro studies showed only pyrimethamine to promote apoptosis. On the basis of that experience, we undertook additional in vitro lymphocyte apoptosis assays, and measured SPL Weights, lymphocyte numbers, and immunophenotypes in Fas-deficient MRL/Ipr-/- mice to gain further insights into the utility of combined pyrimethamine/sulfadoxine or pyrimethamine alone. Moreover, seven children with ALPS enrolled in a study of escalating dose of pyrimethamine alone given twice weekly for 12 weeks to determine if their lymphadenopathy and/or splenomegaly would diminish, as assessed by standardized computerized tomography. Neither pyrimethamine alone or with sulfadoxine in the MRL/Ipr-/- mice, nor pyrimethamine alone in ALPS patients proved efficacious. We conclude that these drugs do not warrant further use empirically or as part of clinical trials in ALPS Type la as a lympholytic agent. Am. J. Hematol. 82:1049-1055, 2007. (c) Published 2007 Wiley-Liss, Inc. C1 NIH, NIAID, LCID, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIH, Dept Vet Resources, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Rao, VK (reprint author), NIH, NIAID, LCID, 10 Ctr Dr,Room 11N234, Bethesda, MD 20892 USA. EM koneti@nih.gov FU Intramural NIH HHS NR 26 TC 11 Z9 11 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD DEC PY 2007 VL 82 IS 12 BP 1049 EP 1055 DI 10.1002/ajh.21007 PG 7 WC Hematology SC Hematology GA 235YU UT WOS:000251271000004 PM 17674358 ER PT J AU Fishman, JA Greenwald, MA Kuehnert, MJ AF Fishman, J. A. Greenwald, M. A. Kuehnert, M. J. TI Enhancing transplant safety: A new era in the microbiologic evaluation of organ donors ? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID WEST-NILE-VIRUS; RECIPIENTS; INFECTION; TRANSMISSION C1 Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. US FDA, CDR,Off Cellular Tissue & Gene Therapies, US Publ Hlth Serv,Div Human Tissues, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. CDC, Coordinating Ctr Infect Dis,US Publ Hlth Serv,CDR, Natl Ctr Preparedness Detect & Control Infect Dis, Div Healthcare Promot,Off Blood Organ & Other Tis, Atlanta, GA 30333 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Transplant Infect Dis Program, Boston, MA 02114 USA. EM jfishman@partners.org NR 11 TC 20 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2007 VL 7 IS 12 BP 2652 EP 2654 DI 10.1111/j.1600-6143.2007.02023.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 226JK UT WOS:000250585100003 PM 17983389 ER PT J AU Shang, AB Kozikowski, RT Winslow, AW Weininger, S AF Shang, Allan B. Kozikowski, Raymond T. Winslow, Andrew W. Weininger, Sandy TI Development of a Standardized Method for Motion Testing in Pulse Oximeters SO ANESTHESIA AND ANALGESIA LA English DT Article ID PERFORMANCE; ARTIFACT AB BACKGROUND: Pulse oximeter performance in the presence of motion varies among devices and manufacturers because of variations in hardware, software, testing, and calibration. Compounding these differences is a lack of uniform characterization of motion, and the consequential effects of motion upon the wide range of normal and abnormal human physiology. Traditional motion testing attempts to standardize motion into a reproducible form by using a mechanical jig to produce passive motion of a known amplitude and frequency. This type of motion challenge fails to account for the physiologic changes induced by active movement. METHODS: We postulate that a more appropriate method for testing the performance of pulse oximeters in the presence of motion is to create a feedback control loop between the device and the test subject, providing a reproducible, actively created, and controlled motion test suitable for standardized testing among manufacturers. It is hoped that relying on a signal as seen from the oximeter's perspective will enable the creation of a sensitive and reproducible test method capable of separating those oximeters that can reject motion artifact from those that cannot. RESULTS: Preliminary results have concentrated on building the tools and clinical protocols needed to evaluate this method. Some basic observations are reported, but insufficient numbers of experienced subjects precludes rigorous conclusions. CONCLUSION: We have set the stage for a feasibility demonstration using a novel form of testing. With sufficient subjects and proper statistical evaluation, a robust test method for assessing the performance of pulse oximeters in the presence of motion may be at hand. C1 [Shang, Allan B.] Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. [Shang, Allan B.] Duke Univ, Fitzpatrick Inst Photon, Durham, NC 27710 USA. [Kozikowski, Raymond T.; Winslow, Andrew W.] Duke Univ, Dept Elect & Comp Engn, Durham, NC 27710 USA. [Weininger, Sandy] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MO USA. RP Shang, AB (reprint author), Duke Univ, Med Ctr, Dept Anesthesiol, Box 3094, Durham, NC 27710 USA. EM shang004@mc.duke.edu OI Kozikowski, Raymond/0000-0002-6838-7681 FU Pooled funds; Duke University/ Department of Anesthesiology fund [399-0046]; US FDA FX Supported by Pooled funds donated by the Committee Members of ASTM committee F1415 on pulse oximetry, Duke University/ Department of Anesthesiology fund 399-0046, and US FDA 1 year grant. NR 10 TC 8 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD DEC PY 2007 VL 105 SU 6 BP S66 EP S77 DI 10.1213/01.ane.0000278132.12257.cd PG 12 WC Anesthesiology SC Anesthesiology GA V78YQ UT WOS:000205336800012 PM 18048902 ER PT J AU Weininger, S AF Weininger, Sandy TI Effective Standards and Regulatory Tools for Respiratory Gas Monitors and Pulse Oximeters: The Role of the Engineer and Clinician SO ANESTHESIA AND ANALGESIA LA English DT Article AB Developing safe and effective medical devices involves understanding the hazardous situations that can arise in clinical practice and implementing appropriate risk control measures. The hazardous situations may have their roots in the design or in the use of the device. Risk control measures may be engineering or clinically based. A multidisciplinary team of engineers and clinicians is needed to fully identify and assess the risks and implement and evaluate the effectiveness of the control measures. In this paper, I use three issues, calibration/ accuracy, response time, and protective measures/alarms, to highlight the contributions of these groups. This important information is captured in standards and regulatory tools to control risk for respiratory gas monitors and pulse oximeters. This paper begins with a discussion of the framework of safety, explaining how voluntary standards and regulatory tools work. The discussion is followed by an examination of how engineering and clinical knowledge are used to support the assurance of safety. C1 US FDA, Div Elect & Software Engn, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Weininger, S (reprint author), US FDA, Div Elect & Software Engn, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 NH Ave, Silver Spring, MD 20993 USA. EM sandy.weininger@fda.hhs.gov NR 10 TC 1 Z9 1 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 DEC PY 2007 VL 105 BP S95 EP S99 DI 10.1213/01.ane.0000278133.48241.0b PG 5 WC Anesthesiology SC Anesthesiology GA V78YQ UT WOS:000205336800015 PM 18048905 ER PT J AU Zimmerman, AM DePaola, A Bowers, JC Krantz, JA Nordstrom, JL Johnson, CN Grimes, DJ AF Zimmerman, A. M. DePaola, A. Bowers, J. C. Krantz, J. A. Nordstrom, J. L. Johnson, C. N. Grimes, D. J. TI Variability of total and pathogenic Vibrio parahaemolyticus densities in northern Gulf of Mexico water and oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID REAL-TIME PCR; CRASSOSTREA-VIRGINICA; UNITED-STATES; BACTERIA; COAST; COEFFICIENT; INFECTIONS; ABUNDANCE; SHELLFISH; CHOLERAE AB Vibrio parahaemolyticus is indigenous to coastal environments and a frequent cause of seafood-borne gastroenteritis in the United States, primarily due to raw-oyster consumption. Previous seasonal-cycle studies of V. parahaemolyticus have identified water temperature as the strongest environmental predictor. Salinity has also been identified, although it is evident that its effect on annual variation is not as pronounced. The effects of other environmental factors, both with respect to the seasonal cycle and intraseasonal variation, are uncertain. This study investigated intraseasonal variations of densities of total and pathogenic V. parahaemolyticus organisms in oysters and overlying waters during the summer of 2004 at two sites in the northern Gulf of Mexico. Regression analyses indicated significant associations (P < 0.001) between total V parahaemolyticus densities and salinity, as well as turbidity in water and in oysters at the Mississippi site but not at the Alabama site. Pathogenic V. parahaemolyticus organisms in Mississippi oyster and water samples were detected in 56% (9 out of 16) and 78% (43 out of 55) of samples, respectively. In contrast, 44% (7 out of 16) of oyster samples and 30% (14 out of 47) of water samples from Alabama were positive. At both sites, there was greater sample-to-sample variability in pathogenic V. parahaemolyticus densities than in total V. parahaemolyticus densities. These data suggest that, although total V. parahaemolyticus densities may be very informative, there is greater uncertainty when total V parahaemolyticus densities are used to predict the risk of infection by pathogenic V. parahaemolyticus than previously recognized. C1 Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. Gulf Coast Seafood Lab, US FDA, Dauphin Isl, AL USA. US FDA, College Pk, MD USA. RP Grimes, DJ (reprint author), Univ So Mississippi, Gulf Coast Res Lab, 703 E Beach Dr, Ocean Springs, MS 39564 USA. EM jay.grimes@usm.edu NR 34 TC 68 Z9 69 U1 2 U2 14 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 DEC PY 2007 VL 73 IS 23 BP 7589 EP 7596 DI 10.1128/AEM.01700-07 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 238UY UT WOS:000251474400014 PM 17921270 ER PT J AU Xu, HY Heinze, TM Chen, SW Cerniglia, CE Chen, HZ AF Xu, Haiyan Heinze, Thomas M. Chen, Siwei Cerniglia, Carl E. Chen, Huizhong TI Anaerobic metabolism of 1-amino-2-naphthol-based azo dyes (Sudan dyes) by human intestinal microflora SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FMN-DEPENDENT AZOREDUCTASE; LIQUID-CHROMATOGRAPHY; ENTEROCOCCUS-FAECALIS; CYTOCHROME-P450 1A1; CARCINOGEN; BENZIDINE; OXIDATION; PRODUCTS; CLEANUP; POWDER AB The rates of metabolism of Sudan I and II and Para Red by human intestinal microflora were high compared to those of Sudan III and IV under anaerobic conditions. Metabolites of the dyes were identified as aniline, 2,4-dimethylaniline, o-toluidine, and 4-nitroaniline through high-performance liquid chromatography and liquid chromatography electrospray ionization tandem mass spectrometry analyses. These data indicate that human intestinal bacteria are able to reduce Sudan dyes to form potentially carcinogenic aromatic amines. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov NR 23 TC 57 Z9 60 U1 0 U2 6 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 DEC PY 2007 VL 73 IS 23 BP 7759 EP 7762 DI 10.1128/AEM.01410-07 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 238UY UT WOS:000251474400036 PM 17933925 ER PT J AU Lories, RJU Peeters, J Bakker, A Tylzanowski, P Derese, I Schrooten, J Thomas, JT Luyten, FP AF Lories, Rik J. U. Peeters, Jenny Bakker, Astrid Tylzanowski, Przernko Derese, Inge Schrooten, Jan Thomas, J. Terrig Luyten, Frank P. TI Articular cartilage and biomechanical properties of the long bones in Frzb-knockout mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FRIZZLED-RELATED PROTEIN-3; WNT SIGNALING PATHWAY; HIP OSTEOARTHRITIS; MOUSE EMBRYOGENESIS; SPEMANN ORGANIZER; ANTAGONIST; GROWTH; OSTEOPOROSIS; EXPRESSION; MORPHOGENESIS AB Objective. Ligands and antagonists of the WNT pathway are linked to osteoporosis and osteoarthritis. In particular, polymorphisms in the FRZB gene, a secreted WNT antagonist, have been associated with osteoarthritis. The aim of this study was to examine cartilage and bone in Frzb(-/-) mice. Methods. The Frzb gene in mice was inactivated using a Cre/loxP strategy. Three models of osteoarthritis were used: collagenase, papain, and methylated bovine serum albumin induced. Bone biology was studied using density measurements and microfocal computed tomography. Bone stiffness and mechanical loading-induced bone adaptation were studied by compression of the ulnae. Results. Targeted deletion of the Frzb gene in mice increased articular cartilage loss during arthritis triggered by instability, enzymatic injury, or inflammation. Cartilage damage in Frzb(-/-) mice was associated with increased WNT signaling and matrix metalloproteinase 3 (MMP-3) expression and activity. Frzb(-/-) mice had increased cortical bone thickness and density, resulting in stiffer bones, as demonstrated by stressstrain relationship analyses. Moreover, Frzb(-/-) mice had an increased periosteal anabolic response to mechanical loading as compared with wild-type mice. Conclusion. The genetic association between osteoarthritis and FRZB polymorphisms is corroborated by increased cartilage proteoglycan loss in 3 different models of arthritis in Frzb(-/-) mice. Loss of Frzb may contribute to cartilage damage by increasing the expression and activity of MMPs, in a WNT-dependent and WNT-independent manner. FRZB deficiency also resulted in thicker cortical bone, with increased stiffness and higher cortical appositional bone formation after loading. This may contribute to the development of osteoarthritis by producing increased strain on the articular cartilage during normal locomotion but may protect against osteoporotic fractures. C1 [Lories, Rik J. U.; Peeters, Jenny; Bakker, Astrid; Tylzanowski, Przernko; Derese, Inge; Luyten, Frank P.] Katholieke Univ Leuven, Univ Hosp, Lab Skeletal Dev & Joint Disorders, Dept Rheumatol, Louvain, Belgium. [Schrooten, Jan] Katholieke Univ Leuven, Louvain, Belgium. [Thomas, J. Terrig] Ctr Biol Evaluat & Res, FDA, Rockville, MD USA. RP Luyten, FP (reprint author), Katholieke Univ Leuven, Univ Hosp, Lab Skeletal Dev & Joint Disorders, Dept Rheumatol, Herestraat 49, Louvain, Belgium. EM Frank.Luyten@uz.kuleuven.be RI Tylzanowski, Przemko/G-8881-2013 NR 41 TC 132 Z9 137 U1 2 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2007 VL 56 IS 12 BP 4095 EP 4103 DI 10.1002/art.23137 PG 9 WC Rheumatology SC Rheumatology GA 243FS UT WOS:000251781200026 PM 18050203 ER PT J AU Simjee, S McDermott, PF White, DG Hofacre, C Berghaus, RD Carter, PJ Stewart, L Liu, TR Maier, M Maurer, JJ AF Simjee, Shabbir McDermott, Patrick F. White, David G. Hofacre, Charles Berghaus, Roy D. Carter, Peggy J. Stewart, Leigh Liu, Tongrui Maier, Marie Maurer, John J. TI Antimicrobial Susceptibility and Distribution of Antimicrobial-Resistance Genes Among Enterococcus and Coagulase-Negative Staphylococcus Isolates Recovered from Poultry Litter SO AVIAN DISEASES LA English DT Article DE antimicrobial resistance; poultry; enterococci; staphylococci; vat(D); erm(B) ID GRAM-POSITIVE BACTERIA; ANTIBIOTIC-RESISTANCE; GENTAMICIN RESISTANCE; TN916-LIKE ELEMENT; GLYCOPEPTIDE RESISTANCE; MUPIROCIN RESISTANCE; FECAL ENTEROCOCCI; ESCHERICHIA-COLI; BROILER-CHICKENS; RETAIL POULTRY AB Data on the prevalence of antimicrobial resistant enterococci and staphylococci from the poultry production environment are sparse in the United States. This information is needed for science-based risk assessments of antimicrobial use in animal husbandry and potential public-health consequences. In this study, we assessed the susceptibility of staphylococci and enterococci isolated from poultry litter, recovered from 24 farms across Georgia, to several antimicrobials of veterinary and human health importance. Among the 90 Enterococcus isolates recovered, E. hirae (46%) was the most frequently encountered species, followed by E. faecium (27%), E. gallinarum (12%), and E. faecalis (10%). Antimicrobial resistance was most often observed to tetracycline (96%), followed by clindamycin (90%), quinupristin-dalfopristin (62%), penicillin (53%), erythromycin (50%), nitrofurantoin (49%), and clarithromycin (48%). Among the 110 staphylococci isolates recovered, only coagulase-negative staphylococci (CNS) were identified with the predominant Staphylococcus species being S. sciuri (38%), S. lentus (21%), S. xylosus (14%) and S. simulans (12%). Resistance was less-frequently observed among the Staphylococcus isolates for the majority of antimicrobials tested, as compared with Enterococcus isolates, and was primarily limited to clarithromycin (71%), erythromycin (71%), clindamycin (48%), and tetracycline (38%). Multidrug resistance (MDR) phenotypes were prevalent in both Enterococcus and Staphylococcus; however, Enterococcus exhibited a statistically significant difference in the median number of antimicrobials to which resistance was observed (median = 5.0) compared with Staphylococcus species (median = 3.0). Because resistance to several of these antimicrobials in gram-positive bacteria may be attributed to the shuttling of common drug-resistance genes, we also determined which common antimicrobial-resistance genes were present in both enterococci and staphylococci. The antimicrobial resistance genes vat(D) and erm(B) were present in enterococci, vgaB in staphylococci, and mobile genetic elements Tn916 and pheromone-inducible plasmids were only identified in enterococci. These data suggest that the disparity in antimicrobial-resistance phenotypes and genotypes between enterococci and staphylococci isolated from the same environment is, in part, because of barriers preventing exchange of mobile DNA elements. C1 [Hofacre, Charles; Berghaus, Roy D.; Stewart, Leigh; Liu, Tongrui; Maier, Marie; Maurer, John J.] Univ Georgia, Dept Populat Hlth, Athens, GA 30602 USA. [Simjee, Shabbir; McDermott, Patrick F.; White, David G.; Carter, Peggy J.] US FDA, Coll Vet Med, Laurel, MD 20708 USA. [Hofacre, Charles; Maurer, John J.] Univ Georgia, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. RP Maurer, JJ (reprint author), Univ Georgia, Dept Populat Hlth, 953 Coll Stn Rd, Athens, GA 30602 USA. EM jmaurer@vet.uga.edu FU U. S. Department of Agriculture, USDA [NRICGP 01-35212-10877] FX This work was funded by the U. S. Department of Agriculture, USDA NRICGP 01-35212-10877. NR 61 TC 14 Z9 14 U1 1 U2 6 PU AMER ASSOC AVIAN PATHOLOGISTS PI ATHENS PA 953 COLLEGE STATION RD, ATHENS, GA 30602-4875 USA SN 0005-2086 J9 AVIAN DIS JI Avian Dis. PD DEC PY 2007 VL 51 IS 4 BP 884 EP 892 DI 10.1637/7973-032607-REGR.1 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 372NF UT WOS:000260907600012 PM 18251398 ER PT J AU Engleman, D Miranda, D Ashar, B Kaufman, D Marion, J Rich, S AF Engleman, Donna Miranda, Dolores Ashar, Binita Kaufman, Diana Marion, Jill Rich, Suzanne TI Bariatric patient safety and medical device adverse events SO BARIATRIC NURSING AND SURGICAL PATIENT CARE LA English DT Meeting Abstract C1 [Engleman, Donna; Miranda, Dolores; Ashar, Binita; Kaufman, Diana; Marion, Jill; Rich, Suzanne] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1557-1459 J9 BARIAT NURS SURG PAT JI Bariatr. Nurs. Surg. Patient Care PD WIN PY 2007 VL 2 IS 4 MA 13 BP 263 EP 263 PG 1 WC Nursing SC Nursing GA 293UD UT WOS:000255359900020 ER PT J AU Caporaso, N Goldin, L Plass, C Calin, G Marti, G Bauer, S Raveche, E McMaster, ML Ng, D Landgren, O Slager, S AF Caporaso, Neil Goldin, Lynn Plass, Christoph Calin, George Marti, Gerald Bauer, Steven Raveche, Elizabeth McMaster, Mary Lou Ng, David Landgren, Ola Slager, Susan TI Chronic lymphocytic leukaemia genetics overview SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE genetic association; linkage; susceptibility; candidate genes; chronic lymphocytic leukaemia; family studies ID B-CELL LYMPHOCYTOSIS; CLL; PREDISPOSITION; EXPRESSION; REGRESSION; EXPANSION; LYMPHOMA; FAMILIES; SURVIVAL; FEATURES AB Although the familial aspect of chronic lymphocytic leukaemia (CLL) has been appreciated for decades, it is only with the recent confluence of improved molecular and gene technologies and world-wide collaborative networks that accelerated progress has become apparent. In this summary we highlight selected themes in the genetics of CLL emphasizing the opportunities and challenges of this malignancy. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Immunol & Med Genet & Comprehens Canc Ctr, Dept Mol Virol, Columbus, OH 43210 USA. US FDA, Ctr Biol Evaluat & Res, NIH, Div Cell & Gene Therapies,Cellular & Tissue T, Bethesda, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biostat, Rochester, MN USA. RP Caporaso, N (reprint author), Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov RI Slager, Susan/B-6756-2009; Plass, Christoph/H-7192-2014; OI Bauer, Steven/0000-0003-2831-846X NR 45 TC 20 Z9 21 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 630 EP 634 DI 10.1111/j.1365-2141.2007.06846.x PG 5 WC Hematology SC Hematology GA 231YC UT WOS:000250984100002 PM 18021078 ER PT J AU Scaglione, BJ Salerno, E Balan, M Coffman, F Landgraf, P Abbasi, F Kotenko, S Marti, GE Raveche, ES AF Scaglione, Brian J. Salerno, Erica Balan, Murugabaskar Coffman, Frederick Landgraf, Pablo Abbasi, Fatima Kotenko, Sergei Marti, Gerald E. Raveche, Elizabeth S. TI Murine models of chronic lymphocytic leukaemia: role of microRNA-16 in the New Zealand Black mouse model SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE mouse models of chronic lymphocytic leukaemia; New Zealand Black; microRNA ID B-CELL LYMPHOMA; SYSTEMIC LUPUS-ERYTHEMATOSUS; CYTIDINE DEAMINASE AID; TRANSGENIC MICE; TELOMERASE ACTIVITY; AUTOIMMUNE-DISEASE; BCL-2 EXPRESSION; CD5+B CELLS; WEB SERVER; NZB MICE AB Mouse models are valuable tools in the study of human chronic lymphocytic leukaemia (CLL). The New Zealand Black (NZB) strain is a naturally occurring model of late-onset CLL characterized by B-cell hyperproliferation and autoimmunity early in life, followed by progression to CLL. Other genetically engineered models of CLL that have been developed include (NZB x NZW) F1 mice engineered to express IL5, mice expressing human TCL1A, and mice overexpressing both BCL2 and a tumour necrosis factor receptor-associated factor. The applicability to human CLL varies with each model, suggesting that CLL is a multifactorial disease. Our work with the de novo NZB model has revealed many similarities to the human situation, particularly familial CLL. In NZB, the malignant clones express CD5, zap-70, and have chromosomal instability and germline Ig sequence. We also identified a point mutation in the 3'-flanking sequence of Mirn16-1, which resulted in decreased levels of the microRNA, miR-16 in lymphoid tissue. Exogenous restoration of miR-16 to an NZB malignant B-1 cell line resulted in cell cycle alterations, suggesting that the altered expression of Mirn15a/16-1 is an important molecular lesion in CLL. Future studies utilizing the NZB mouse could ascertain the role of environmental triggers, such as low dose radiation and organic chemicals in the augmentation of a pre-existing propensity to develop CLL. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Raveche, ES (reprint author), Univ Med & Dent New Jersey, Pathol & Lab Med, 185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu FU NCI NIH HHS [R01 CA071478, R01 CA071478-09, R01 CA129826] NR 92 TC 36 Z9 36 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 645 EP 657 DI 10.1111/j.1365-2141.2007.06851.x PG 13 WC Hematology SC Hematology GA 231YC UT WOS:000250984100004 PM 17941951 ER PT J AU Shim, YK Silver, SR Caporaso, NE Marti, GE Middleton, DC Linet, MS Vogt, RF AF Shim, Youn K. Silver, Sharon R. Caporaso, Neil E. Marti, Gerald E. Middleton, Dannie C. Linet, Martha S. Vogt, Robert F. CA Int CLL MbL Workshop TI B cells behaving badly SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE chronic lymphocytic leukaemia; monoclonal B-cell; lymphocytosis; aetiology; genetics ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CLL AB The pathogenesis of B-cell lymphoproliferative disorders in general and B-cell chronic lymphocytic leukaemia in particular appears to involve dysfunctional regulation of humoral and cellular immunity with the subsequent development of genetic aberrations in B cells. In theory, either component may arise de novo or may be influenced by environmental exposures including infectious agents, antigens, genotoxic chemicals, or radiation. As an intermediary within the exposure-disease continuum, monoclonal B-cell lymphocytosis may be a helpful biomarker for teasing out these various contributions to risk. This article introduces a series of papers that resulted from an International Workshop held in May 2007 entitled 'Monoclonal B-cell Lymphocytosis and Chronic Lymphocytic Leukemia: Environmental and Genetic Risk Factors'. Research efforts, such as those described in this issue, should lead to improved interventions, more predictive biomarkers, more effective treatments, and a greater appreciation of how the immune system functions over the entire human lifespan. C1 Agcy Toxic Substances & Dis Registry, Div Hlth Studies, Atlanta, GA 30333 USA. NIOSH, Ctr Dis Control & Prevent, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. RP Shim, YK (reprint author), Agcy Toxic Substances & Dis Registry, Div Hlth Studies, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM YShim@cdc.gov OI Silver, Sharon/0000-0002-7679-5028 NR 12 TC 1 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 658 EP 662 DI 10.1111/j.1365-2141.2007.06842.x PG 5 WC Hematology SC Hematology GA 231YC UT WOS:000250984100005 PM 18021079 ER PT J AU Vogt, RF Marti, GE AF Vogt, Robert F. Marti, Gerald E. TI Overview of monoclonal gammopathies of undetermined significance SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE chronic lymphocytic leukaemia; multiple myeloma; lymphoid malignancies; Waldenstrom macroglobulinaemia ID NATURAL-HISTORY; LONG-TERM; FOLLOW-UP; AMYLOIDOSIS; PREVALENCE AB Among the B-cell lymphoproliferative disorders, monoclonal gammopathy of undetermined significance (MGUS) is the humoral counterpart to monoclonal B-cell lymphocytosis. This review introduces the papers from the section devoted to MGUS at the International Workshop entitled 'Monoclonal B-cell lymphocytosis and chronic lymphocytic leukaemia: environmental and genetic risk factors.' C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, Bethesda, MD 20014 USA. RP Vogt, RF (reprint author), Ctr Dis Control & Prevent, Div Sci Lab, 4770 Buford Highway, Atlanta, GA 30341 USA. EM rvogt@cdc.gov NR 15 TC 10 Z9 10 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 687 EP 689 DI 10.1111/j.1365-2141.2007.06860.x PG 3 WC Hematology SC Hematology GA 231YC UT WOS:000250984100008 PM 18021082 ER PT J AU Vogt, RF Shim, YK Middleton, DC Buffler, PA Campolucci, SS Lybarger, JA Marti, GE AF Vogt, Robert F. Shim, Youn K. Middleton, Dannie C. Buffler, Patricia A. Campolucci, Sharon S. Lybarger, Jeffrey A. Marti, Gerald E. TI Monoclonal B-cell lymphocytosis as a biomarker in environmental health studies SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE hazardous waste; B-cell lymphoproliferative disorders; chronic lymphocytic leukaemia; aetiology; epidemiology ID IMMUNOPHENOTYPIC ANALYSIS; FLOW-CYTOMETRY; LEUKEMIA; LYMPHOMA; BLOOD; ABNORMALITIES; INDIVIDUALS; RISK AB The first studies of monoclonal B-cell lymphocytosis (MBL) in the general population were conducted as part of environmental health investigations that began in 1991. MBL was observed as an unexpected finding when blood samples were immunophenotyped by two-colour flow cytometric methods in common use at that time. The initial observations led to a workshop in 1995, at which case definitions were considered and medical follow-up investigations were recommended. Medical follow-ups were conducted in 1997 and 2003. A total of eight cases of confirmed MBL and three cases of presumptive MBL were identified. This review summarizes the findings from those investigations and discusses the issues related to using MBL as a biomarker in environmental health research and population-based studies. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. Agcy Toxic Substances & Dis Registry, Div Hlth Studies, Atlanta, GA USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapies, Bethesda, MD USA. RP Vogt, RF (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, 4770 Buford Highway, Atlanta, GA 30341 USA. EM rvogt@cdc.gov NR 30 TC 17 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 690 EP 700 DI 10.1111/j.1365-2141.2007.06861.x PG 11 WC Hematology SC Hematology GA 231YC UT WOS:000250984100009 PM 18021083 ER PT J AU Marti, G Abbasi, F Raveche, E Rawstron, AC Ghia, P Aurran, T Caporaso, N Shim, YK Vogt, RF AF Marti, Gerald Abbasi, Fatima Raveche, Elizabeth Rawstron, Andy C. Ghia, Paolo Aurran, Therese Caporaso, Neil Shim, Youn K. Vogt, Robert F. TI Overview of monoclonal B-cell lymphocytosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; monoclonal B-cell lymphocytosis ID LAMBDA-LIGHT CHAIN; PERIPHERAL-BLOOD; VARIABLE REGION; GENE-MUTATIONS; DELTA SWITCH; LEUKEMIA; CLL; EXPRESSION; DONORS; CLONE AB Monoclonal B-cell lymphocytosis (MBL) has been the subject of more intensive investigation for the last 10 years. The increased presence of MBL in unaffected, first-degree relatives with familial chronic lymphocytic leukaemia (CLL) suggest that it is surrogate marker for early disease. In normal population studies, MBL is found to be increased in ageing subjects. Consensus criteria for the diagnosis of MBL have been proposed. The differential diagnosis has been further clarified and the prevalence of MBL is most prominent in the elderly. The aetiology of MBL is unknown but probably involves immune mechanism of senescence or altered response. Environmental health studies suggest that exposure to certain toxins may lead to MBL but further work is needed. MBL is a precursor to CLL but may also regress, remain stable or progress to clinical CLL. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA. Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Leeds Teaching Hosp NHS Trust, Gen Infirm, Haematol Malignancy Diagnost Serv, Leeds, W Yorkshire, England. Univ Viat Salute San Raffaele, Dept Oncol, Unit Lymphoid Malignancies, Milan, Italy. Inst J Paoli I Calmettes, F-13009 Marseille, France. Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD USA. Agcy Toxic Substance & Dis Registry, Div Hlth Studies, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Marti, G (reprint author), US FDA, NIH, Ctr Biol Evaluat & Res, Div Cell & Gene Therapies Off Cellular, Bdg 29B Rm 2NN08, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov RI Ghia, Paolo/K-7138-2016; OI Ghia, Paolo/0000-0003-3750-7342; Rawstron, Andy/0000-0003-0798-9790 NR 38 TC 49 Z9 51 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 701 EP 708 DI 10.1111/j.1365-2141.2007.06865.x PG 8 WC Hematology SC Hematology GA 231YC UT WOS:000250984100010 PM 18021084 ER PT J AU Abbasi, F Longo, NS Lipsky, PE Raveche, E Schleinitz, TA Stetler-Stevenson, M Caporaso, N Marti, G AF Abbasi, Fatima Longo, Nancy S. Lipsky, Peter E. Raveche, Elizabeth Schleinitz, Therese A. Stetler-Stevenson, Maryalice Caporaso, Neil Marti, Gerald TI B-cell repertoire and clonal analysis in unaffected first degree relatives in familial chronic lymphocytic leukaemia kindred SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; monoclonal B-cell lymphocytosis; clonality ID CLL AB Monoclonal B cell lymphocytosis (MBL) was detected in four unaffected first-degree relatives (FDR) in a familial chronic lymphocytic leukaemia (CLL) kindred. The proband remains untreated and two male siblings have died. The four unaffected siblings have been followed for a five-year period. All four FDR developed a kappa(+)CD5(+) MBL detected by flow cytometry. Poymerase chain reaction (PCR) for IGHV rearrangement showed evidence of oligoclonality in three of these individuals. Single cell PCR of flow cytometric sorted kappa(+) cells combined with Ig kappa light chain gene sequencing revealed further evidence of monoclonality in two of these individuals. Three of these individuals all showed evidence of hyper-somatic mutations. The B-cell repertoire in unaffected FDR in familial CLL offers a new area to investigate the interface between the immune system and lymphoid neoplasm. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA. NIAMSD, Autoimmun Branch, Repertoire Anal Grp, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, NIH, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. RP Marti, G (reprint author), US FDA, NIH, Div Cell & Gene Therapies Off Cellular, Flow & Image Cytometry Sec Cell & Tissue Therapy, Bdb 29B Rm 2NN08, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov NR 11 TC 3 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 820 EP 823 DI 10.1111/j.1365-2141.2007.06857.x PG 4 WC Hematology SC Hematology GA 231YC UT WOS:000250984100024 PM 17941936 ER PT J AU Hardy, NM Grady, C Pentz, R Stetler-Stevenson, M Raffeld, M Fontaine, LS Babb, R Bishop, MR Caporaso, N Marti, GE AF Hardy, Nancy M. Grady, Christine Pentz, Rebecca Stetler-Stevenson, Maryalice Raffeld, Mark Fontaine, Laura S. Babb, Rebecca Bishop, Michael R. Caporaso, Neil Marti, Gerald E. TI Bioethical considerations of monoclonal B-cell lymphocytosis: donor transfer after haematopoietic stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; ethics; stem cell transplantation; B cells ID LEUKEMIA; CLL; FAMILIES; BLOOD; MALIGNANCIES; POPULATION; CANCER; ADULTS AB Monoclonal B-cell lymphocytosis (MBL) is a recently described laboratory finding in otherwise healthy individuals. In MBL, a light chain-restricted, clonal B-cell population, often with a chronic lymphocytic leukaemia (CLL) phenotype, is identified by flow cytometry. Although the prognostic significance remains unclear, there is an increased incidence in ageing populations and those with a family history of CLL. During the past decade of MBL study, three families have come to our attention in which prospective sibling haematopoietic stem cell donors were found to have an MBL. These families raise complex bioethical issues with regard to disclosure of research data, eligibility for clinical trials and potential donor transfer of MBL. These issues are explored in this report. Identification of MBL among prospective sibling transplant donors will become a common occurrence in transplant practice as transplantation is increasingly offered to older individuals and those with CLL. C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. Canc Res Ctr, NCI, Pathol Lab, Bethesda, MD USA. Westat Corp, Rockville, MD USA. Ctr Clin, NIH, Dept Nursing, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Div Cell & Gene Therapies,Flow & Image Cytometry, Bethesda, MD 20892 USA. EM gemarti@helix.nih.gov FU Intramural NIH HHS NR 29 TC 26 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 824 EP 831 DI 10.1111/j.1365-2141.2007.06862.x PG 8 WC Hematology SC Hematology GA 231YC UT WOS:000250984100025 PM 18021093 ER PT J AU Rachel, JM Zucker, ML Fox, CM Plapp, FV Menitove, JE Abbasi, F Marti, GE AF Rachel, Jane M. Zucker, Marjorie L. Fox, Christopher M. Plapp, Fred V. Menitove, Jay E. Abbasi, Fatima Marti, Gerald E. TI Monoclonal B-cell lymphocytosis in blood donors SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE monoclonal B-cell lymphocytosis; B cells; blood donors; chronic lymphocytic leukaemia; flow cytometry ID LEUKEMIA; ADULTS AB Monoclonal B-cell populations have been detected in the peripheral blood of apparently healthy individuals by flow cytometry. In 2005, the term monoclonal B-cell lymphocytosis (MBL) was proposed to describe these findings. MBL may be immunophenotypically similar to chronic lymphocytic leukaemia (CLL) and, like CLL, the prevalence is higher in males and older individuals. We studied the prevalence of MBL in blood donors from the Midwestern United States. Samples from 5141 donors were examined and seven (0.14%) were found to have immunophenotypic characteristics of MBL or CLL. Immunoglobulin heavy chain analysis yielded monoclonality or oligoclonality. Prior and subsequent to the study, an additional undetermined number of blood donors were screened and seven of these expressed immunophenotypic characteristics of MBL or CLL. We thus found a total of 14 healthy blood donors with monoclonal expansions of B-lymphocyte populations. Of these, 12 were presumptively classified as MBL and two as CLL. All but two of the donors were male; the mean age was 59 years. The clinical importance of these findings with regard to transfusion medicine has not been established. C1 St Lukes Hosp, Kansas City, MO USA. Community Blood Ctr, Kansas City, MO USA. US FDA, Ctr Biol Evaluat & Res, Div Gene & Cell Therapy, Flow & Image Cytometry Lab,Cellular Therapy & B, Bethesda, MD USA. RP Rachel, JM (reprint author), St Lukes Hosp, Dept Pathol, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM jrachel@saint-lukes.org NR 11 TC 36 Z9 39 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2007 VL 139 IS 5 BP 832 EP 836 DI 10.1111/j.1365-2141.2007.06870.x PG 5 WC Hematology SC Hematology GA 231YC UT WOS:000250984100026 PM 17961190 ER PT J AU Freeley, M Park, J Yang, KJ Wange, RL Volkov, Y Kelleher, D Long, A AF Freeley, Michael Park, Jongsun Yang, Keum-Jin Wange, Ronald L. Volkov, Yuri Kelleher, Dermot Long, Aideen TI Loss of PTEN expression does not contribute to PDK-1 activity and PKC activation-loop phosphorylation in Jurkat leukaemic T cells SO CELLULAR SIGNALLING LA English DT Article DE PTEN; PDK-1; PKB/Akt; PKC; PP2A; phosphorylation ID PROTEIN-KINASE-C; PHOSPHOINOSITIDE-DEPENDENT KINASE; TUMOR-SUPPRESSOR GENE; 3-PHOSPHOINOSITIDE-DEPENDENT KINASE-1; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; PLASMA-MEMBRANE; IN-VIVO AB Unopposed PI3-kinase activity and 3 '-phosphoinositide production in Jurkat T cells, due to a mutation in the PTEN tumour suppressor protein, results in deregulation of PH domain-containing proteins including the serine/threonine kinase PKB/Akt. In Jurkat cells, PKB/Akt is constitutively active and phosphorylated at the activation-loop residue (Thr308). 3 '-phosphoinositide-dependent protein kinase-1 (PDK-1), an enzyme that also contains a PH domain, is thought to catalyse Thr308 phosphorylation of PKB/Akt in addition to other kinase families such as PKC isoforms. It is unknown however if the loss of PTEN in Jurkat cells also results in unregulated PDK-1 activity and whether such loss impacts on activation-loop phosphorylation of other putative PDK-1 substrates such as PKC. In this study we have addressed if loss of PTEN in Jurkat T cells affects PDK-1 catalytic activity and intracellular localisation. We demonstrate that reducing the level of 3 '-phosphoinositides in Jurkat cells with pharmacological inhibitors of PI3-kinase or expression of PTEN does not affect PDK-1 activity, Ser241 phosphorylation or intracellular localisation. In support of this finding, we show that the levels of PKC activation-loop phosphorylation are unaffected by reductions in the levels of 3 '-phosphoinositides. Instead, the dephosphorylation that occurs on PKB/Akt at Thr308 following reductions in 3 '-phosphoinositides is dependent on PP2A-like phosphatase activity. Our finding that PDK-1 functions independently of 3 '-phosphoinositides in T cells is also confirmed by studies in HuT-78 T cells. a PTEN-expressing cell line with undetectable levels of 3 '-phosphoinositides. We conclude therefore that loss of PTEN expression in Jurkat T cells does not impact on the PDK-1/PKC pathway and that only a subset of kinases, such as PKB/Akt, are perturbed as a consequence PTEN loss. (C) 2007 Elsevier Inc. All tights reserved. C1 Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland. Chungnam Natl Univ, Coll Med, Canc Res Inst, Dept Pharmacol,Cell Signaling Lab, Taejon 301131, South Korea. NIH, NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. US FDA, Div Metab & Endocrinol Prod, Silver Spring, MD 20993 USA. RP Long, A (reprint author), Trinity Coll Dublin, Inst Mol Med, Dept Clin Med, Dublin, Ireland. EM freeleym@ted.ie; insulin@cnu.ac.kr; Ronald.Wange@FDA.HHS.GOV; yvolkov@tcd.ie; dermot.kelleher@tcd.ie; longai@tcd.ie RI Park, Jongsun/E-7465-2010; OI Park, Jongsun/0000-0002-4690-1854; Freeley, Michael/0000-0002-5763-6582; Volkov, Yuri/0000-0001-7406-518X NR 78 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD DEC PY 2007 VL 19 IS 12 BP 2444 EP 2457 DI 10.1016/j.cellsig.2007.07.020 PG 14 WC Cell Biology SC Cell Biology GA 230XT UT WOS:000250910400004 PM 17826953 ER PT J AU Xia, QS Yin, JJ Cherng, SH Freeman, JP Yu, HT Boudreau, MD Wamer, WG Fu, PP AF Xia, Qingsu Yin, Jun Jie Cherng, Shu-Hui Freeman, James P. Yu, Hongtao Boudreau, Mary D. Wamer, Wayne G. Fu, Peter P. TI Irradiation of retinol in ethanol with UVA light: Formation of photodecomposition products, reactive oxygen species, and lipid peroxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 234th ACS National Meeting CY AUG 19-23, 2007 CL Boston, MA SP Amer Chem Soc, Div Chem Toxicol C1 [Xia, Qingsu; Freeman, James P.; Boudreau, Mary D.; Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, FDA, Jefferson, AR 72079 USA. [Yin, Jun Jie; Wamer, Wayne G.] CFSAN, FDA, College Pk, MD 20740 USA. [Cherng, Shu-Hui] Natl Ctr Toxicol Res, FDA, Jefferson, AR 72079 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM qingsu.xia@fda.hhs.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 MA 86 BP 2006 EP 2007 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400117 ER PT J AU Tareke, E Ali, S Lyn-Cook, B Duhart, HM AF Tareke, Eden Ali, Syed Lyn-Cook, Beverly Duhart, Helen M. TI Role of dietary components on acrylamide induced neurotransmitter turnover alterations in PC 12 cells SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the Division of Chemical Toxicology of the American-Chemical-Society held at the 234th ACS National Meeting CY AUG 19-23, 2007 CL Boston, MA SP Amer Chem Soc, Div Chem Toxicol C1 [Tareke, Eden] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotoxic, Jefferson, AR 72079 USA. [Lyn-Cook, Beverly] NCTR, Div Biochem Toxicol, Jefferson, AR USA. [Duhart, Helen M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM etareke@nctr.fda.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2007 VL 20 IS 12 MA 127 BP 2015 EP 2015 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 242NW UT WOS:000251733400158 ER PT J AU Scott, S Moss, WJ Cousens, S Beeler, JA Audet, SA Mugala, N Quinn, TC Griffin, DE Cutts, FT AF Scott, Susana Moss, William J. Cousens, Simon Beeler, Judy A. Audet, Susette A. Mugala, Nanthalile Quinn, Thomas C. Griffin, Diane E. Cutts, Felicity T. TI The influence of HIV-1 exposure and infection on levels of passively acquired antibodies to measles virus in Zambian infants SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACENTAL-TRANSFER; MATERNAL ANTIBODY; IMMUNITY; PREVALENCE; VACCINE; MALARIA; STRAIN; WOMEN AB Background. The age at which passively acquired antibodies are lost is critical to determining the optimal age for measles vaccination. Little is known about the influence of human immunodeficiency virus type 1 (HIV-1) infection on levels of prevaccination antibodies to measles virus. Methods. Antibodies to measles virus were measured by plaque reduction neutralization assay in HIV-1-infected, HIV-seropositive but uninfected, and HIV-seronegative Zambian infants aged 6 weeks to 9 months. Regression models were used to estimate age-specific antibody concentrations. Results. Neutralizing antibodies to measles virus were measured in 652 plasma samples collected from 448 infants, of whom 61 (13.6%) were HIV-1 infected, 239 (53.4%) were HIV seropositive but uninfected, and 148 (33%) were HIV seronegative. The best fitting model suggests that HIV-1-infected infants have lower levels of passively acquired antibodies to measles virus at birth than do HIV-seronegative infants, but their antibody levels decrease more slowly. By 6 months of age, 91% (95% confidence interval, 83%-99%) of HIV-1-infected infants, 83% (95% confidence interval, 77%-89%) of HIV-seropositive but uninfected infants, and 58% (95% confidence interval, 51%-64%) of HIV-seronegative infants were estimated to have antibody levels that were unlikely to affect immune responses to measles vaccine (cutoff value for immune response, <50 mIU/ mL). By 9 months of age, 99% of all infants had antibody levels <50 mIU/ mL. Conclusions. Infants born to HIV-1-infected women are less likely to have passively acquired antibodies that would neutralize measles vaccine virus and, thus, have an increased risk of measles prior to the age of routine vaccination. Protection could be achieved by administration of the first dose of measles vaccine prior to 9 months of age. C1 Univ London London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, London WC1E 7HT, England. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. US FDA, Rockville, MD 20857 USA. Univ Teaching Hosp, Virol Lab, Lusaka, Zambia. RP Scott, S (reprint author), Univ London London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, Keppel St, London WC1E 7HT, England. EM Susana.scott@lshtm.ac.uk FU Intramural NIH HHS; NIAID NIH HHS [AI23047]; Wellcome Trust [GR059114MA] NR 28 TC 48 Z9 49 U1 0 U2 2 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 DEC 1 PY 2007 VL 45 IS 11 BP 1417 EP 1424 DI 10.1086/522989 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 233HG UT WOS:000251080800003 PM 17990222 ER PT J AU Misbin, RI AF Misbin, Robert I. TI Lessons from the avandia controversy SO DIABETES CARE LA English DT Editorial Material ID BLOOD-GLUCOSE CONTROL; CARDIOVASCULAR-DISEASE; LACTIC-ACIDOSIS; LONG-TERM; RISK; ROSIGLITAZONE; COMPLICATIONS; METFORMIN C1 US FDA, Div Endocrinol & Metab, Silver Spring, MD USA. RP Misbin, RI (reprint author), 711 Schindler Dr, Silver Spring, MD 20903 USA. EM robert.misbin@fda.hhs.gov NR 26 TC 8 Z9 8 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD DEC PY 2007 VL 30 IS 12 BP 3141 EP 3144 DI 10.2337/dc07-1908 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 237HQ UT WOS:000251365200036 PM 18042753 ER PT J AU Jay, MT Cooley, M Carychao, D Wiscomb, GW Sweitzer, RA Crawford-Miksza, L Farrar, JA Lau, DK O'Connell, J Millington, A Asmundson, RV Atwill, ER Mandrell, RE AF Jay, Michele T. Cooley, Michael Carychao, Diana Wiscomb, Gerald W. Sweitzer, Richard A. Crawford-Miksza, Leta Farrar, Jeff A. Lau, David K. O'Connell, Janice Millington, Anne Asmundson, Roderick V. Atwill, Edward R. Mandrell, Robert E. TI Escherichia coli O157 : H7 in feral swine near spinach fields and cattle, central California coast SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 107th General Meeting of the American-Society-for-Microbiology CY MAY 21-25, 2007 CL Toronto, CANADA SP Amer Soc Microbiol ID PIG-POPULATIONS; SALMONELLA; PREVALENCE; PULSENET; SIZES AB We investigated involvement of feral swine in contamination of agricultural fields and surface waterways with Escherichia coli O157:H7 after a nationwide outbreak traced to bagged spinach from California. Isolates from feral swine, cattle, surface water, sediment, and soil at 1 ranch were matched to the outbreak strain. C1 Univ Calif Davis, Food & Drug Lab Branch, Calif Dept Publ Hlth, Western Inst Food Safety & Secur, Davis, CA 95616 USA. Calif Dept Publ Hlth, Richmond, CA USA. USDA, Albany, CA USA. USDA, Sacramento, CA USA. Univ N Dakota, Grand Forks, ND 58201 USA. Calif Dept Publ Hlth, Sacramento, CA USA. US FDA, Alameda, CA USA. RP Jay, MT (reprint author), Univ Calif Davis, Food & Drug Lab Branch, Calif Dept Publ Hlth, Western Inst Food Safety & Secur, 1 Shields Ave, Davis, CA 95616 USA. EM michele.jayrussell@cdph.ca.gov NR 15 TC 183 Z9 185 U1 0 U2 17 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2007 VL 13 IS 12 BP 1908 EP 1911 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 238KN UT WOS:000251446600018 PM 18258044 ER PT J AU Zheng, J Keys, CE Zhao, SH Meng, JH Brown, EW AF Zheng, Jie Keys, Christine E. Zhao, Shaohua Meng, Jianghong Brown, Eric W. TI Enhanced Subtyping scheme for Salmonella enteritidis SO EMERGING INFECTIOUS DISEASES LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI O157-H7; UNITED-STATES; PULSENET; STRAINS AB To improve pulsed-field gel electrophoresis-based strain discrimination of 76 Salmonella Enteritidis strains, we evaluated 6 macro-restriction endonucleases, separately and in various combinations. One 3-enzyme subset, Sfil/Pacl/Notl, was highly discriminatory. Five different indices, including the Simpson diversity index, supported this 3-enzyme combination for improved differentiation of S. Enteritidis. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, College Pk, MD 20740 USA. Univ Maryland, College Pk, MD 20742 USA. US FDA, Laurel, MD USA. RP Brown, EW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, Mailstop HFS-712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM eric.brown@fda.hhs.gov NR 15 TC 37 Z9 38 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD DEC PY 2007 VL 13 IS 12 BP 1932 EP 1935 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 238KN UT WOS:000251446600025 PM 18258051 ER PT J AU Bendre, SV Shaddock, JG Dobrovolsky, VN Albertini, RJ Heflich, RH AF Bendre, Sachin V. Shaddock, Joseph G. Dobrovolsky, Vasily N. Albertini, Richard J. Heflich, Robert H. TI Effect of chronic azathioprine treatment on germ-line transmission of Hprt mutation in mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE germ cell mutation; Lesch-Nyhan syndrome; mutant selection; lymphocytes ID DEPENDENT DIABETES-MELLITUS; INFLAMMATORY-BOWEL-DISEASE; CHROMOSOME-ABERRATIONS; TRANSPLANT RECIPIENT; PURINE METABOLISM; PERIPHERAL-BLOOD; CELL MUTATIONS; T-CELLS; IN-VIVO; MOUSE AB Azathioprine (Aza), a prodrug of 6-mercaptopurine, is used in human medicine prevent transplant rejection and for the treatment of autoimmune diseases. Extremely high HPRT lymphocyte mutant frequencies (MFs) are found in humans and mice chronically treated with Aza, and these elevated MFs appear to be caused by selection and amplification of pre-existing HPRT mutant lymphocytes. In the present study, we investigated if in vivo selection by Aza also promotes the germline transmission of Hprt mutants. Fifty-five male C57BL/6 mice were treated with 10 mg/kg Aza three times/week for 24 weeks; 10 control mice were treated with the vehicle. Each of these males then was bred to unexposed females for a total of 8 weeks. Analysis of the Aza-treated males after the breeding period indicated that 12 had highly elevated Hprt lymphocyte MFs (1 X 10(-4)-2.5 X 10(-1) vs. normal MFs of < 1 X 10(-5)), indicating that the Aza treatment successfully selected somatic cell mutants. The female offspring from the breeding were sacrificed at 28 days of age and Hprt MFs were measured in spleen lymphocytes. Most of the 364 female offspring (332 from Aza-treated fathers) had Hprt MFs of 0-6 X 10(-6), but seven of the offspring had moderately elevated MFs of 16 X 10(-6) -55 X 10(-6). Since one of these mice was fathered by a control male, these relatively high MFs appear to be part of the normal variation in lymphocyte Hprt MF. The present results provide no evidence that long-term Aza treatment promotes high levels of germ-line Hprt mutation transmission in mice. C1 [Bendre, Sachin V.; Shaddock, Joseph G.; Dobrovolsky, Vasily N.; Heflich, Robert H.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Albertini, Richard J.] Univ Vermont, Burlington, VT USA. [Bendre, Sachin V.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Heflich, RH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov NR 58 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD DEC PY 2007 VL 48 IS 9 BP 744 EP 753 DI 10.1002/em.20352 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 242FC UT WOS:000251708900005 PM 18008354 ER PT J AU von Eschenbach, AC AF von Eschenbach, Andrew C. TI FDA's new approach to food protection SO FOOD TECHNOLOGY LA English DT Editorial Material C1 Food & Drug Adm, Rockville, MD 20857 USA. RP von Eschenbach, AC (reprint author), Food & Drug Adm, 5600 Fishers Ln, Rockville, MD 20857 USA. EM commissioner@fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD DEC PY 2007 VL 61 IS 12 BP 116 EP 116 PG 1 WC Food Science & Technology SC Food Science & Technology GA 244XF UT WOS:000251897900022 ER PT J AU Sherman, KE Fleischer, R Laessig, K Murray, J Tauber, W Birnkrant, D AF Sherman, Kenneth E. Fleischer, Russell Laessig, Katherine Murray, Jeffrey Tauber, Witham Birnkrant, Debra TI Development of novel agents for the treatment of chronic hepatitis C infection: Summary of the FDA Antiviral Products Advisory Committee recommendations SO HEPATOLOGY LA English DT Article ID ALPHA-2A PLUS RIBAVIRIN; VIRUS-INFECTION; UNITED-STATES; PEGINTERFERON ALPHA-2B; LIVER-TRANSPLANTATION; COMBINATION THERAPY; INTERFERON-ALPHA-2B; SUPERINFECTION; CIRRHOSIS; DISEASE C1 Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA. US FDA, Div Antiviral Prod, Silver Spring, MD USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM kenneth.sherman@uc.edu NR 32 TC 15 Z9 17 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2007 VL 46 IS 6 BP 2014 EP 2020 DI 10.1002/hep.21985 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 238TY UT WOS:000251471700040 PM 18027878 ER PT J AU Kobayashi, N Karisola, P Pena-Cruz, V Dorfman, DM Jinushi, M Umetsu, SE Butte, MJ Nagumo, H Chernova, I Zhu, BG Sharpe, AH Ito, S Dranoff, G Kaplan, GG Casasnovas, JM Umetsu, DT Dekruyff, RH Freeman, GJ AF Kobayashi, Norimoto Karisola, Piia Pena-Cruz, Victor Dorfman, David M. Jinushi, Masahisa Umetsu, Sarah E. Butte, Manish J. Nagumo, Haruo Chernova, Irene Zhu, Baogong Sharpe, Arlene H. Ito, Susumu Dranoff, Glenn Kaplan, Gerardo G. Casasnovas, Jose M. Umetsu, Dale T. Dekruyff, Rosemarie H. Freeman, Gordon J. TI TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells SO IMMUNITY LA English DT Article ID MACROPHAGE RECOGNITION; MOLECULE-1 KIM-1; KIDNEY INJURY; GENE FAMILY; T-CELLS; CLEARANCE; RECEPTOR; PHAGOCYTOSIS; ACTIVATION; SURFACE AB The T cell immunoglobulin mucin (TIM) proteins regulate T cell activation and tolerance. Here we showed that TIM-4 is expressed on human and mouse macrophages and dendritic cells, and both TIM-4 and TIM-1 specifically bound phosphatidylserine (PS) on the surface of apoptotic cells but not any other phospholipid tested. TIM-4(+) peritoneal macrophages, TIM-1(+) kidney cells, and TIM-4- or TIM-1-transfected cells efficiently phagocytosed apoptotic cells, and phagocytosis could be blocked by TIM-4 or TIM-1 monoclonal antibodies. Mutations in the unique cavity of TIM-4 eliminated PS binding and phagocytosis. TIM-4 mAbs that blocked PS binding and phagocytosis mapped to epitopes in this binding cavity. These results show that TIM-4 and TIM-1 are immunologically restricted members of the group of receptors whose recognition of PS is critical for the efficient clearance of apoptotic cells and prevention of autoimmunity. C1 [Kobayashi, Norimoto; Pena-Cruz, Victor; Jinushi, Masahisa; Nagumo, Haruo; Chernova, Irene; Zhu, Baogong; Dranoff, Glenn; Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kobayashi, Norimoto; Pena-Cruz, Victor; Jinushi, Masahisa; Nagumo, Haruo; Chernova, Irene; Zhu, Baogong; Dranoff, Glenn; Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Karisola, Piia; Umetsu, Dale T.; Dekruyff, Rosemarie H.] Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Dorfman, David M.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Umetsu, Sarah E.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Butte, Manish J.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Ito, Susumu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Casasnovas, Jose M.] CSIC, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM gordon_freeman@dfci.harvard.edu RI Jinushi, Masahisa/A-4311-2012; Casasnovas, Jose/L-6299-2014; OI Casasnovas, Jose/0000-0002-2873-6410; Butte, Manish/0000-0002-4490-5595 FU NIAID NIH HHS [P01 AI054456-019001, P01 AI054456, P01 AI054456-010002]; NINDS NIH HHS [R01 NS045937, R01 NS045937-01, R01 NS045937-02, R01 NS045937-03, R01 NS045937-04, R01 NS045937-05] NR 40 TC 264 Z9 280 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2007 VL 27 IS 6 BP 927 EP 940 DI 10.1016/j.immuni.2007.11.011 PG 14 WC Immunology SC Immunology GA 245AS UT WOS:000251907300012 PM 18082433 ER PT J AU Santiago, C Ballesteros, A Martinez-Munoz, L Mellado, M Kaplan, GG Freeman, GJ Casasnovas, JM AF Santiago, Cesar Ballesteros, Angela Martinez-Munoz, Laura Mellado, Mario Kaplan, Gerardo G. Freeman, Gordon J. Casasnovas, Jose M. TI Structures of T cell immunoglobulin mucin protein 4 show a metal-ion-dependent ligand binding site where phosphatidylserine binds SO IMMUNITY LA English DT Article ID HEPATITIS-A-VIRUS; TIM GENE FAMILY; PERIPHERAL TOLERANCE; IMMUNE-RESPONSES; RECEPTOR; RECOGNITION; MECHANISM; IDENTIFICATION; ACTIVATION; REVEALS AB The T cell immunoglobulin and mucin domain (TIM) proteins are important regulators of T cell responses. Crystal structures of the murine TIM-4 identified a metal-ion-dependent ligand binding site (MILIBS) in the immunoglobulin (Ig) domain of the TIM family. The characteristic CC' loop of the TIM domain and the hydrophobic FG loop shaped a narrow cavity where acidic compounds penetrate and coordinate to a metal ion bound to conserved residues in the TIM proteins. The structure of phosphatidylserine bound to the Ig domain showed that the hydrophilic head penetrates into the MILIBS and coordinates with the metal ion, whereas the aromatic residues on the tip of the FG loop interacted with the fatty acid chains and could insert into the lipid bilayer. Our results also revealed an important role of the MILIBS in the trafficking of TIM-1 to the cell surface. C1 [Santiago, Cesar; Ballesteros, Angela; Martinez-Munoz, Laura; Mellado, Mario; Casasnovas, Jose M.] CSIC, Ctr Nacl Biotecnol, Madrid 28049, Spain. [Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Casasnovas, JM (reprint author), CSIC, Ctr Nacl Biotecnol, Campus Univ Autonoma, Madrid 28049, Spain. EM jcasasnovas@cnb.uam.es RI Casasnovas, Jose/L-6299-2014; Mellado, Mario/M-9893-2014; Santiago, Cesar/K-4240-2014 OI Casasnovas, Jose/0000-0002-2873-6410; Mellado, Mario/0000-0001-6325-1630; Santiago, Cesar/0000-0002-5149-1722 FU NIAID NIH HHS [P01 AI054456-01, P01 AI054456, AI054456] NR 36 TC 106 Z9 114 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2007 VL 27 IS 6 BP 941 EP 951 DI 10.1016/j.immuni.2007.11.008 PG 11 WC Immunology SC Immunology GA 245AS UT WOS:000251907300013 PM 18083575 ER PT J AU Balakumar, P Murthy, S Jagadeesh, G AF Balakumar, Pitchai Murthy, Sreekant Jagadeesh, Gowraganahalli TI The basic concepts of scientific research and communication - (A report on preconference workshop held in conjunction with the 40th annual conference of the Indian Pharmacological Society-2007) SO INDIAN JOURNAL OF PHARMACOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Conference of Indian-Pharmacological-Society CY 2007 CL Chandigarh, INDIA SP Indian Pharmacol Soc C1 [Balakumar, Pitchai] ISF Coll Pharm, Dept Pharmacol, Moga 142001, Punjab, India. [Murthy, Sreekant] Drexel Univ, Coll Med, Philadelphia, PA 19102 USA. [Jagadeesh, Gowraganahalli] US FDA, Div Cardiovasc & Renal Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Balakumar, P (reprint author), ISF Coll Pharm, Dept Pharmacol, Moga 142001, Punjab, India. EM pbala2006@gmail.com RI Jagadeesh, Gowraganahalli/G-6408-2010 NR 0 TC 0 Z9 0 U1 0 U2 5 PU MEDKNOW PUBLICATIONS PI MUMBAI PA A-108-109 KANARA BUSINESS CENTRE, GHAKTOPAR, MUMBAI, 400075, INDIA SN 0253-7613 J9 INDIAN J PHARMACOL JI Indian J. Pharmacol. PD DEC PY 2007 VL 39 IS 6 BP 303 EP 306 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 281CF UT WOS:000254473300011 ER PT J AU Belyakov, IM Kozlowski, S Mage, M Ahlers, JD Boyd, LF Margulies, DH Berzofsky, JA AF Belyakov, Igor M. Kozlowski, Steven Mage, Michael Ahlers, Jeffrey D. Boyd, Lisa F. Margulies, David H. Berzofsky, Jay A. TI Role of alpha 3 domain of class I MHC molecules in the activation of high- and low-avidity CD8(+) CTLs SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE cytotoxic T lymphocytes; MHC class I; avidity; epitope; peptide; TCR ID CYTOTOXIC T-LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; PROTECTIVE IMMUNITY; IMMUNOLOGICAL SYNAPSE; MUCOSAL IMMUNIZATION; POXVIRUS INFECTION; VIRAL-INFECTION; NEW-GENERATION AB CD8 can serve as a co-receptor or accessory molecule on the surface of CTL. As a co-receptor, CD8 can bind to the alpha 3 domain of the same MHC class I molecules as the TCR to facilitate TCR signaling. To evaluate the role of the MHC class I molecule alpha 3 domain in the activation of CD8(+) CTL, we have produced a soluble 227 mutant of H-2D(d), with a point mutation in the alpha 3 domain (Glu227 -> Lys). 227 mutant class I-peptide complexes were not able to effectively activate H-2D(d)-restricted CD8 T cells in vitro, as measured by IFN-gamma production by an epitope-specific CD8(+) CTL line. However, the 227 mutant class I-peptide complexes in the presence of another MHC class I molecule (H-2K(b)) (that cannot present the peptide) with a normal alpha 3 domain can induce the activation of CD8(+) CTL. Therefore, in order to activate CD8(+) CTL, the alpha 3 domain of MHC class I does not have to be located on the same molecule with the alpha 1 and alpha 2 domains of MHC class I. A low-avidity CD8(+) CTL line was significantly less sensitive to stimulation by the 227 mutant class I-peptide complexes in the presence of the H-2K(b) molecule. Thus, low-avidity CTL may not be able to take advantage of the interaction between CD8 and the alpha 3 domain of non-presenting class I MHC molecules, perhaps because of a shorter dwell time for the TCR-MHC interaction. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM igorbelyakov@yahoo.com RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 FU Intramural NIH HHS NR 70 TC 6 Z9 6 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 2007 VL 19 IS 12 BP 1413 EP 1420 DI 10.1093/intimm/dxm111 PG 8 WC Immunology SC Immunology GA 232RL UT WOS:000251036900010 PM 17981793 ER PT J AU Palinkas, LA Reedy, KR Smith, M Anghel, M Steel, GD Reeves, D Shurtleff, D Case, HS Van Do, N Reed, HL AF Palinkas, Lawrence A. Reedy, Kathleen R. Smith, Mark Anghel, Mihai Steel, Gary D. Reeves, Dennis Shurtleff, David Case, H. Samuel Van Do, Nhan Reed, H. Lester TI Psychoneuroendocrine effects of combined thyroxine and triiodothyronine versus tyrosine during prolonged antarctic residence SO INTERNATIONAL JOURNAL OF CIRCUMPOLAR HEALTH LA English DT Article DE mood; cognition; cold; thyroid hormones; clinical trial; tyrosine ID SEASONAL AFFECTIVE-DISORDER; TO-SAMPLE PERFORMANCE; SUBCLINICAL HYPOTHYROIDISM; PLUS TRIIODOTHYRONINE; THYROID-HORMONE; PITUITARY; LEVOTHYROXINE; DEPRESSION; RESPONSES; SYMPTOMS AB Objectives. We previously reported that cognitive function improves with thyroxine and that there is a circannual pattern to mood and human TSH during Antarctic residence. To extend these findings, we examined the effects of tyrosine and a combined levothyroxine/liothyronine supplement in euthyroid men and women who spent the austral summer (n=43) and/or winter (n=42) in Antarctica. Study Design. Randomized, placebo-controlled, clinical trial. Methods. Subjects were randomized to receive the following each day for 91.6 +/- 3.2 days in summer and/or 138.0 +/- 3.2 days in winter: (1) 12g tyrosine mixed in 113g applesauce; (2) 50ug of levothyroxine and 12.5ug of liothyronine (T4-T3 Supplement); or (3) placebo. Cognitive performance and mood were assessed using the Automatic Neuropsychological Assessment Metric-Isolated and Confined Environments. Results. With placebo in summer, mood did not change while TSH decreased by 28%; in winter, there was a 136% degradation in mood (p < 0.01) and TSH increased by 18%. With combined T4-T3 supplement, there was a 51% degradation in mood in summer compared with placebo (p < 0.05) and TSH decreased by 57%; in winter there was a 135% degradation in mood while TSH was reduced by 26% (p < 0.05). Tyrosine use in summer was associated with no change in mood and a 30% decline in TSH, while in winter there was a 47% improvement in mood and TSH decreased by 28% along with a 6% increase in fT3 (p < 0.05). Conclusions. Administration of tyrosine leads to a significant reduction in serum TSH and improvement in mood in winter compared with placebo, while the combined T4-T3 supplement leads to a worsening of mood in summer and no improvement in winter. There appears to be a seasonal influence on the psychological response to interventions and the relationship to changes Zn in TSH reductions. C1 [Palinkas, Lawrence A.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Palinkas, Lawrence A.] Univ So Calif, Dept Anthropol, Los Angeles, CA 90089 USA. [Palinkas, Lawrence A.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Reedy, Kathleen R.] US FDA, Silver Spring, MD USA. [Smith, Mark] George Washington Univ, Dept Psychiat, Washington, DC USA. [Anghel, Mihai] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. [Steel, Gary D.] Lincoln Univ, Environm Society & Design Div, Christchurch, New Zealand. [Case, H. Samuel] McDaniel Coll, Dept Exercise Sci & Phys Educ, Westminster, MD USA. [Van Do, Nhan] Madigan Army Med Ctr, Dept Med, Endocrine Serv, Tacoma, WA 98431 USA. [Reed, H. Lester] MultiCare Hlth Syst, Tacoma, WA USA. RP Palinkas, LA (reprint author), Univ So Calif, Sch Social Work, 669 W 34th St, Los Angeles, CA 90089 USA. EM palinkos@usc.edu NR 52 TC 4 Z9 4 U1 0 U2 0 PU INT ASSOC CIRCUMPOLAR HEALTH PUBL PI OULU PA AAPISTIE1, OULU, FIN-90220, FINLAND SN 1239-9736 J9 INT J CIRCUMPOL HEAL JI Int. J. Circumpolar Health PD DEC PY 2007 VL 66 IS 5 BP 401 EP 417 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 251YB UT WOS:000252410900005 PM 18274206 ER PT J AU Gilhooly, CH Das, SK Golden, JK McCrory, MA Dallal, GE Saltzman, E Kramer, FM Roberts, SB AF Gilhooly, C. H. Das, S. K. Golden, J. K. McCrory, M. A. Dallal, G. E. Saltzman, E. Kramer, F. M. Roberts, S. B. TI Food cravings and energy regulation: the characteristics of craved foods and their relationship with eating behaviors and weight change during 6 months of dietary energy restriction SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE food craving; weight loss; energy density; energy restriction ID HUMAN-BODY COMPOSITION; LOW-CALORIE DIET; HEALTHY WOMEN; ELDERLY ADULTS; YOUNG-WOMEN; APPETITE; RESTRAINT; HUNGER; REWARD; BRAIN AB Objective: To examine characteristics of craved foods in relation to dietary energy restriction ( ER) with high (HG) and low glycemic load (LG) diets. Design: Assessments of food cravings before and during a randomized controlled trial of HG and LG diets provided for 6 months. Subjects: Thirty-two healthy, overweight women aged 20-42 years. Measurements: Self-reported food cravings and dietary intake, body weight, weight history and measures of eating behaviors. Results: Foods craved at baseline were more than twice as high in energy density as the habitual diet (3.7 +/- 1.5 vs 1.7 +/- 0.3 kcal/g; P < 0.001), and on average were lower in protein (P < 0.001) and fiber (P < 0.001) and higher in fat (P=0.002). There were no statistically significant changes in nutritional characteristics of craved foods after 6 months of ER. There was a significant relationship between reported portion size of craved food consumed at baseline and lifetime high body mass index (r=0.49, P=0.005). Additionally, there was a significant association between susceptibility to hunger and craving frequency at baseline, and there were significant relationships between hunger score, craving frequency, strength and percentage of time that cravings are given in to after 6 months of ER. In multiple regression models, subjects who lost a greater percentage of weight craved higher energy-dense foods at month 6 of ER, but also reported giving in to food cravings less frequently (adjusted R-2 = 0.31, P=0.009). Conclusion: High energy density and fat content, and low protein and fiber contents were identifying characteristics of craved foods. The relationships between craving variables and hunger score suggest that the relative influence of hunger susceptibility on cravings may be important before and especially after ER. Portion size of craved foods and frequency of giving in to food cravings appear to be important areas for focus in lifestyle modification programs for long-term weight loss. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA USA. US FDA, Silver Spring, MD USA. Bastyr Univ, Sch Nutr & Exercise Sci, Kenmore, WA USA. US Army Natick Soldier Ctr, Ctr Dev & Engn, Natick, MA USA. RP Roberts, SB (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Energy Met Lab, Rm 1312, 711 Washington St, Boston, MA 02111 USA. EM susan.roberts@tufts.edu RI Biguzzi, Felipe/E-4724-2015 FU NIA NIH HHS [U01-AG20480] NR 54 TC 40 Z9 42 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2007 VL 31 IS 12 BP 1849 EP 1858 DI 10.1038/sj.ijo.0803672 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 234OK UT WOS:000251173200010 PM 17593902 ER PT J AU Limb, SL Starke, PR Lee, CE Chowdhury, BA AF Limb, Susan L. Starke, Peter R. Lee, Charles E. Chowdhury, Badrul A. TI Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE anaphylaxis; omalizumab ID ALLERGIC REACTIONS; IMMUNOTHERAPY; EMERGENCY AB Background: Risk of anaphylaxis is included in the prescribing information for omalizumab, but the nature of these reactions merits further elaboration. Objective: To describe cases of anaphylaxis associated with omalizumab administration in patients with asthma. Methods: We reviewed spontaneous postmarketing adverse event reports submitted to the US Food and Drug Administration's Adverse Event Reporting System database and to the manufacturers of omalizumab and cases published in the literature through December 2006. Diagnostic criteria for anaphylaxis outlined by the National Institute of Allergy and Infectious Diseases and the Food Allergy and Anaphylaxis Network were used to screen cases. Results: One-hundred twenty-four cases of anaphylaxis associated with omalizumab administration in patients with asthma were identified. Many cases had a delayed onset of symptoms beyond 2 hours after dose administration. Many cases were also characterized by a protracted progression, with individual signs and symptoms of anaphylaxis staggered over hours. Review of the case reports did not reveal any predictive risk factors for the delayed onset or protracted progression of anaphylaxis. Conclusion: Omalizumab-induced anaphylaxis may be characterized by a delayed onset and a protracted progression of symptoms. Clinical implications: The unusual timing of anaphylaxis in these cases challenges our understanding of anaphylaxis. A delayed onset of symptoms and protracted progression of anaphylaxis should be taken into account when administering omalizumab. C1 [Limb, Susan L.; Starke, Peter R.; Lee, Charles E.; Chowdhury, Badrul A.] US FDA, Div Pulm & Allergy Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Limb, SL (reprint author), US FDA, Div Pulm & Allergy Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 3323, Silver Spring, MD 20993 USA. EM susan.limb@fda.hhs.gov NR 23 TC 73 Z9 75 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2007 VL 120 IS 6 BP 1378 EP 1381 DI 10.1016/j.jaci.2007.09.022 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 241JX UT WOS:000251653800020 PM 17936893 ER PT J AU Toutain, PL Bousquet-Melou, A Martinez, M AF Toutain, Pierre-Louis Bousquet-Melou, Alain Martinez, Marilyn TI AUC/MIC: a PK/PD index for antibiotics with a time dimension or simply a dimensionless scoring factor? SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE terminology; standardization; PK/PD index; time dimension AB A previous article on standardization of pharmacokinetic/pharmacodynamic terminology for anti-infective drugs recommended deletion of the units of the AUC/MIC ratio (actually h). We express here the difficulties presented by this proposal and we propose expressing AUC/MIC as a scaling factor corresponding to the current index divided now by 24 h. This is the scaling factor without units by which the targeted MIC should be multiplied to estimate the average in vivo plasma concentration to be achieved. Associated with this proposal, we address the specific issue of veterinary drug products for which steady conditions are seldom achieved. To accommodate the need for dose prediction during these novel therapeutic situations, we propose a general approach that is based on the targeted time interval over which some desired average concentration should be maintained. C1 ENVT, UMR Physiopathol & Toxicol Expt INRA 181, F-31076 Toulouse 03, France. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Toutain, PL (reprint author), ENVT, UMR Physiopathol & Toxicol Expt INRA 181, 23 Chemin Capelles, F-31076 Toulouse 03, France. EM pl.toutain@envt.fr RI Toutain, Pierre-Louis/G-4540-2011 OI Toutain, Pierre-Louis/0000-0002-8846-8892 NR 2 TC 27 Z9 27 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD DEC PY 2007 VL 60 IS 6 BP 1185 EP 1188 DI 10.1093/jac/dkm360 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 234XV UT WOS:000251198800001 PM 17932075 ER PT J AU Mahmood, I Green, MD AF Mahmood, Iftekhar Green, Martin David TI Drug interaction studies of therapeutic proteins or monoclonal antibodies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE drug interaction; therapeutic proteins; monoclonal antibodies ID CHRONIC HEPATITIS-C; METHADONE-MAINTENANCE THERAPY; P-GLYCOPROTEIN; INTERFERON-BETA; PHARMACODYNAMIC CHARACTERIZATION; IN-VIVO; CYTOCHROME-P-450; METABOLISM; MICE; PHARMACOKINETICS AB Drug interactions can alter the pharmacokinetics and/or pharmacodynamics of a drug. In pharmacokinetic drug interactions, the concentrations of 1 or more drugs are altered by another. This change in concentration in a given drug may be due to changes in absorption, distribution, metabolism, or elimination. The pharmacodynamic interaction can lead to additive, synergistic, or antagonistic effects of a drug. Drug interaction studies are regularly conducted with conventional drugs (small molecules), but very few drug interaction studies have been performed with macromolecules (therapeutic proteins or monoclonal antibodies). This is mainly because most macromolecules ore not metabolized by the cytochrome P450 system, and their mechanism of elimination is complex. However, it has been shown in several studies that interferons can have an impact on the cytochrome P450 system that may alter the pharmacokinetics and pharmacodynamics of a conventional drug when given with interferons. Therefore, it is important to evaluate the effect of other classes of macromolecules (cytokines, interleukins, monoclonal antibodies) on drug-metabolizing enzymes. It is also imperative that the effects of conventional drugs on the pharmacokinetics and pharmacodynamics of macromolecules be conducted. The present review encompasses several drug interaction studies that were conducted with macromolecules and highlights the impact of these studies on the pharmacokinetics and/or pharmacodynamics of the involved drugs. C1 FDA, Ctr Biol Evaluat, Off Blood Review & Res, Off Vacc Review & Res, Rockville, MD 20850 USA. RP Mahmood, I (reprint author), FDA, Ctr Biol Evaluat, Off Blood Review & Res, Off Vacc Review & Res, 1451 Rockville Pike, Rockville, MD 20850 USA. EM Iftekhar.mahmood@fda.hhs.gov NR 51 TC 34 Z9 35 U1 0 U2 4 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 DEC PY 2007 VL 47 IS 12 BP 1540 EP 1554 DI 10.1177/0091270007308616 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 234AG UT WOS:000251132400008 PM 17962422 ER PT J AU Fu, PP AF Fu, Peter P. TI Quality assurance and safety of herbal dietary supplements - Introduction SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Editorial Material C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 333 EP 334 PG 2 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600001 ER PT J AU Chen, T AF Chen, Tao TI Genotoxicity of aristolochic acid: A review SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE aristolochic acid; genotoxicity; DNA adduct; clastogenicity; mutation; mutagenicity; oncogene ID CHINESE HERBS NEPHROPATHY; DNA ADDUCT FORMATION; NATURALLY-OCCURRING SUBSTANCES; BALKAN ENDEMIC NEPHROPATHY; P-32 POSTLABELING ANALYSIS; PROSTAGLANDIN-H SYNTHASE; CYTOCHROMES P450 1A1; REDUCTIVE ACTIVATION; RENAL-FAILURE; IN-VITRO AB Aristolochic acid (AA), a mixture of aristolochic acid I (AAI) and aristolochic acid II (AAII), is present in Aristolochiaceae plants, many of which are used as herbal folk remedies. Plants containing AA, however, can be nephrotoxic, genotoxic and carcinogenic in humans. AA has been also associated with the development of tumors in mice and rats. Therefore, plant products containing AA have been banned in many countries. Because quantitative cancer risk assessment is based upon an understanding of the chemical's mode-of-action, it is necessary to determine whether the chemical is a mutagenic carcinogen. In this review, we present the available information concerning the genotoxicity of AA and discuss the possible mechanisms for mutation induction by AA. The evidences indicate that AA is mutagenic and this activity is mediated mainly by the formation of AA-DNA adducts. Not only does AA induce genetic damage and mutations in bacteria, mammalian cells, Drosophila, and rodents, but it is also demonstrated to induce mutations in the target tissues of the model animals and oncogenes from human. Many evidences from genotoxicity tests also indicate that AA is a clastogenic agent that breaks DNA and results in chromosome damage and chromosome mutations. These results indicate that AA is a mutagenic carcinogen. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 101 TC 9 Z9 9 U1 1 U2 3 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 387 EP 399 PG 13 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600008 ER PT J AU Fu, PP Xia, QS Chou, MW Lin, G AF Fu, Peter P. Xia, Qingsu Chou, Ming W. Lin, Ge TI Detection, hepatotoxicity, and tumorigenicity of pyrrolizidine alkaloids in Chinese herbal plants and herbal dietary supplements SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE pyrrolizidine alkaloid; herbal products; herbal dietary supplement; carcinogenicity ID DNA ADDUCT FORMATION; SOLID-PHASE EXTRACTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; FLAVIN-CONTAINING MONOOXYGENASE; TRAP MASS-SPECTROMETRY; RAT-LIVER MICROSOMES; SENECIO-JACOBAEA L; FORMATION IN-VIVO; LC-MS ANALYSIS; BIG BLUE RATS AB Since the U.S. Congress passed the Dietary Supplement Health and Education Act (DSHEA) in 1994, herbal products, including herbal dietary supplements, represent the fastest growing segment of the vitamin, mineral supplements, and herbal products industry. To ensure consumer health protection, the quality and safety of raw herbal plants used for dietary supplement preparations have to be determined. To date, safety issues concerning the hepatotoxic and tumorigenic ingredients in many raw herbs and herbal dietary products are quite limited. Pyrrolizidine alkaloids are a class of hepatotoxic and tumorigenic phytochemicals present in more than 6000 plants and have been detected in herbal plants and dietary supplements. In this review, the human exposure, metabolic activation leading to hepatototoxicity and tumorigenicity of the pyrrolizidine alkaloid-containing Chinese herbal plants, and analytical methods used to identify and quantify pyrrolizidine alkaloids in herbal plants and commercial samples are discussed. Suggestions for future research are provided. C1 [Fu, Peter P.; Xia, Qingsu; Chou, Ming W.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Lin, Ge] Chinese Univ Hong Kong, Dept Pharmacol, Shatin, Hong Kong, Peoples R China. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov; linge@cuhk.edu.hk NR 145 TC 29 Z9 29 U1 0 U2 16 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 400 EP 415 PG 16 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600009 ER PT J AU Chan, PC Fu, PP AF Chan, Po-Chuen Fu, Peter P. TI Toxicity of Panax genseng - An herbal medicine and dietary supplement SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Review DE ginseng dietary supplement; NTP; chronic tumorigenicity bioassay ID GINSENG EXTRACT G115; ST-JOHNS-WORT; IN-VITRO; DIGESTIVE-TRACT; EMBRYO CULTURE; RED-GINSENG; CELLS; GINSENOSIDES; RATS; SAPONINS AB Ginseng is one of the most popular herbal dietary supplements in the U.S. market, with five to six million persons using it even before the recent boom in the herbal supplement industry. Ginsana (G115 ginseng), a standardized extract of Panax ginseng (Asian ginseng, also called Chinese or Korean ginseng) controls half of this market. Numerous reports of adverse effects from products containing ginseng have been filed with the U.S. Food and Drug Administration (FDA). The literature also documents "ginseng abuse syndrome" among regular users. The chronic effects of ginseng are not well characterized. Because of its significant human exposure and little information on toxicity is available, Panax ginseng has been nominated by the U.S. National Institutes of Health (NIH) to the U.S. National Toxicology Program (NTP) for assessing its carcinogenic potential. In this review, we discuss the environmental occurrence, purported therapeutic effects, biological effects, and toxicity of ginseng, with focus on Panax ginseng. To demonstrate how NTP chronic tumorigenicity bioassays are conducted, the tumorigenicity bioassay of Panax ginseng is detailed described. C1 [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov; peter.fu@fda.hhs.gov NR 76 TC 7 Z9 7 U1 2 U2 18 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 416 EP 427 PG 12 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600010 ER PT J AU Mei, XB Chen, T AF Mei, Xunbai Chen, Tao TI The mutant frequencies and types of mutations induced by comfrey in the lungs of transgenic big blue rats SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE comfrey; pyrrolizidine alkaloids; mutation; tandem substitution ID PYRROLIZIDINE ALKALOID RIDDELLIINE; CARCINOGENIC ACTIVITY; SYMPHYTUM-OFFICINALE; GLUTATHIONE METABOLISM; MICE; MONOCROTALINE; MUTAGENICITY; GENE; LASIOCARPINE; SPECTRA AB Comfrey (Symphytum Officinale) has been used as a vegetable and herbal remedy for many years. It, however, is a mutagen and carcinogen in liver and a possible genotoxin in lung. In order to evaluate the mutagenicity of comfrey and the mechanisms of action in rat lung, we examined the mutant frequencies (MF) and mutational types in the lung cII gene from transgenic Big Blue rats treated with 8% comfrey for 12 weeks. The cII MF in the lungs for rats fed with comfrey was 48 f 9 X 10(-6), which was significantly greater than the MF for control rats, 34 f 10 x 10(-6) (p = 0.026). The mutational spectrum in lung from comfrey-fed rats is significantly different from that in the control. G:C -> T:A transversion (29%) was the major type of mutation in comfrey-fed rats, whereas G:C -> A:T transition (63%) was the predominant mutation in the controls. An unusual type of tandem-base substitution (4%) was observed among the mutations from comfrey-fed rats that were not seen in the control. This type of tandem-base substitution has been suggested as a mutational signature for the genetic damage of pyrrolizidine alkaloids (PAs). The results indicate that comfrey is mutagenic in rat lung and the types of mutations induced by comfrey are similar to those by other PAs; and suggest that the mutagenicity of comfrey in rat lung results from the genotoxicity of PAs in the plant. C1 [Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Mei, Xunbai] Washington Univ, St Louis, MO 63130 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 43 TC 4 Z9 4 U1 1 U2 2 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 458 EP 465 PG 8 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600015 ER PT J AU Wong, TC Lee, FSC Hu, GL Chang, L Wang, XR Fu, PP AF Wong, T. C. Lee, Frank Sen-Chun Hu, Guang Lin Chang, Li Wang, Xiaoru Fu, Peter P. TI A survey of heavy metal and organochlorine pesticide contaminations on commercial Lingzhi products SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE Lingzhi; heavy metal; pesticide residue; good agriculture practice (GAP); good manufacturing practice (GMP) ID GANODERMA-LUCIDUM; DIETARY-SUPPLEMENTS; POLYSACCHARIDES AB One of the major problems in the use Chinese herbal medicinal (CM) products is product safety. Alarm has been heightened internationally in recent years on the contamination of CM products by heavy metals or toxic contaminants such as pesticide residues. In this study, the levels of several representative toxic elements including lead (Pb), arsenic (As), mercury (Hg) and cadmium (Cd), and the contents of several common organochlorine pesticides in Lingzhi (Ganoderma lucidum) samples purchased commercially in China and Southeast Asia were determined. Of the 36 samples analyzed, the As in about one third, and Cd in more than one half of the samples were found to contain metal concentrations exceeding their respective allowable limits in China and the U.S. Pesticides are less of a problem. Among 7 of the 36 samples randomly selected, none of them was contaminated with pesticides exceeding the allowable limit. The metal results suggest that the quality and safety of CM products have to be critically assessed before the products can be put in clinical trials or placed on the market. Both GAP and GMP guidelines are strongly recommended to ensure the production of quality and contamination-free CM products. C1 [Lee, Frank Sen-Chun; Hu, Guang Lin; Wang, Xiaoru] Key Lab Analyt Technol Dev & Standardizat Chinese, Qingdao, Peoples R China. [Wong, T. C.; Chang, Li] Hong Kong Baptist Univ, Kowloon, Hong Kong, Peoples R China. [Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Lee, FSC (reprint author), Key Lab Analyt Technol Dev & Standardizat Chinese, Qingdao, Peoples R China. EM fsclee@yahoo.com NR 24 TC 9 Z9 9 U1 0 U2 5 PU BUREAU FOOD DRUG ANALYSIS PI TAIPEI PA 161-2 KUNYANG STREET, NANGANG, TAIPEI, 00000, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD DEC PY 2007 VL 15 IS 4 BP 472 EP 479 PG 8 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA 252GS UT WOS:000252435600017 ER PT J AU Himathongkham, S Dodd, ML Yee, JK Lau, DK Bryant, RG Badoiu, AS Lau, HK Guthertz, LS Crawford-Miksza, L Soliman, MA AF Himathongkham, Sunee Dodd, Mary Lee Yee, Jenny K. Lau, David K. Bryant, Raymond G. Badoiu, Alexandru S. Lau, Henry K. Guthertz, Linda S. Crawford-Miksza, Leta Soliman, Mary A. TI Recirculating Immunomagnetic separation and optimal enrichment conditions for enhanced detection and recovery of low levels of Escherichia coli O157 : H7 from fresh leafy produce and surface water SO JOURNAL OF FOOD PROTECTION LA English DT Article ID REAL-TIME PCR; PREENRICHMENT MEDIA; IRRIGATION WATER; SALMONELLA; LETTUCE; CANTALOUPES; TEMPERATURE; PREVALENCE; CALIFORNIA; O157H7 AB The objective of this study was to develop a rapid, simple method for enhanced detection and isolation of low levels of Escherichia coli O157:H7 from leafy produce and surface water using recirculating immunomagnetic separation (RIMS) coupled with real-time PCR and a standard culture method. The optimal enrichment conditions for the method also were determined. Analysis of real-time PCR. data (C(T) values) suggested that incubation of lettuce and spinach leaves rather than rinsates provides better enrichment of E. coli O157:H7. Enrichment of lettuce or spinach leaves at 42 degrees C for 5 h provided better detection than enrichment at 37 degrees C. Extended incubation of surface water for 20 h at 42 degrees C did not improve the detection. The optimized enrichment conditions were also employed with modified Moore swabs, which were used to sample flowing water sites. Positive isolation rates and real-time PCR results indicated an increased recovery of E. coli O157:H7 from all samples following the application of RIMS. Under these conditions, the method provided detection and/or isolation of E. coli O157:H7 at levels as low as 0.07 CFU/g of lettuce, 0.1 CFU/g of spinach, 6 CFU/100 ml of surface water, and 9 CFU per modified Moore swab. During a 6-month field study, modified Moore swabs yielded high isolation rates when deployed in natural watershed sites. The method used in this study was effective for monitoring E. coli O157:H7 in the farm environment, during postharvest processing, and in foodborne outbreak investigations. C1 California Dept Puble Hlth, Food & Drug Lab Branch, Richmond, CA 94804 USA. US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. RP Himathongkham, S (reprint author), California Dept Puble Hlth, Food & Drug Lab Branch, Richmond, CA 94804 USA. EM sunee.himathongkham@cdph.ca.gov NR 29 TC 18 Z9 18 U1 0 U2 7 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 DEC PY 2007 VL 70 IS 12 BP 2717 EP 2724 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 238XX UT WOS:000251482800002 PM 18095422 ER PT J AU Cowley, SC Sedgwick, JD Elkins, KL AF Cowley, Siobhan C. Sedgwick, Jonathon D. Elkins, Karen L. TI Differential requirements by CD4(+) and CD8(+) T cells for soluble and membrane TNF in control of Francisella tularensis live vaccine strain intramacrophage growth SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; MYCOBACTERIUM-TUBERCULOSIS INFECTION; BACILLUS-CALMETTE-GUERIN; FACTOR-ALPHA; IFN-GAMMA; PROTECTIVE IMMUNITY; TRANSMEMBRANE TNF; INTERFERON-GAMMA; ANTILEISHMANIAL DEFENSE; LISTERIA-MONOCYTOGENES AB During primary infection with intracellular bacteria, the membrane-associated form of TNF provides some TNF functions, but the relative contributions during memory responses are not well-characterized. In this study, we determined the role of T cell-derived secreted and membrane-bound TNF (memTNF) during adaptive immunity to Francisella tularensis live vaccine strain (LVS). Although transgenic mice expressing only the memTNF were more susceptible to primary LVS infection than wild-type (WT) mice, LVS-immune WT and memTNF mice both survived maximal lethal secondary Francisella challenge. Generation of CD44(high) memory T cells and clearance of bacteria were similar, although more IFN-gamma and IL-12(p40) were produced by memTNF mice. To examine T cell function, we used an in vitro tissue coculture system that measures control of LVS intramacrophage growth by LVS-immune WT and memTNF-T cells. LVS-immune CD4(+) and CD8(+) T cells isolated from WT and memTNF mice exhibited comparable control of LVS growth in either normal or TNF-alpha knockout macrophages. Although the magnitude of CD4(+) T cell-induced macrophage NO production clearly depended on TNF, control of LVS growth by both CD4(+) and CD8(+) T cells did not correlate with levels of nitrite. Importantly, intramacrophage LVS growth control by CD8(+) T cells, but not CD4(+) T cells, was almost entirely dependent on T cell-expressed TNF, and required stimulation through macrophage TNFRs. Collectively, these data demonstrate that T cell-expressed memTNF is necessary and sufficient for memory T cell responses to this intracellular pathogen, and is particularly important for intramacrophage control of bacterial growth by CD8(+) T cells. C1 US FDA, Ctr Biol Res & Evaluat, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Cowley, SC (reprint author), US FDA, Ctr Biol Res & Evaluat, Lab Mycobacterial Dis & Cellular Immunol, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM siobhan.cowley@fda.hhs.gov; karen.elkins@fda.hhs.gov NR 46 TC 17 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2007 VL 179 IS 11 BP 7709 EP 7719 PG 11 WC Immunology SC Immunology GA 237MK UT WOS:000251378300060 PM 18025217 ER PT J AU Shin, EC Seifert, U Urban, S Truong, KT Feinstone, SM Rice, CM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Urban, Sabrina Truong, Kim-Thuy Feinstone, Stephen M. Rice, Charles M. Kloetzel, Peter-M. Rehermann, Barbara TI Proteasome activator and antigen-processing aminopeptidases are regulated by virus-induced type I interferon in the hepatitis C virus-infected liver SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MHC CLASS-I; CELLULAR IMMUNE-RESPONSES; CD8(+) T-CELLS; VIRAL CLEARANCE; GAMMA; IMMUNOPROTEASOMES; PERSISTENCE; GENERATION; PEPTIDES; EPITOPES AB Many components of the class I antigen-processing pathway are thought to be regulated solely by interferon-gamma (IFN-gamma). Herein, we report type I IFN-mediated induction of proteasome activator (PA28) subunits alpha and beta, endoplasmic reticulum aminopeptidase 1 (ERAP1), ERAP2, and leucine aminopeptidase (LAP). This mechanism was initiated by either synthetic RNA (poly(I-C)) or by hepatitis C virus (HCV) RNA-mediated induction of type I IFN and abrogated by blocking of type I IFN. In serial liver biopsies of chimpanzees with acute HCV infection, increases in PA28 subunit and aminopeptidase mRNA levels correlated with intrahepatic type I IFN responses and preceded intrahepatic IFN-gamma responses by several weeks. Thus, viral RNA-induced type I IFN regulates the antigen-processing machinery early during viral infection and prior to IFN-gamma response. This mechanism may contribute to the high effectiveness of type I IFN-based therapies if administered early during acute HCV infection. C1 [Shin, Eui-Cheol; Truong, Kim-Thuy; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Seifert, Ulrike; Urban, Sabrina; Kloetzel, Peter-M.] Humboldt Univ, Charite, Inst Biochem, D-10117 Berlin, Germany. [Feinstone, Stephen M.] US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20892 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU Intramural NIH HHS; NCI NIH HHS [CA85883-01] NR 28 TC 18 Z9 18 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD DEC PY 2007 VL 27 IS 12 BP 985 EP 990 DI 10.1089/jir.2007.0039 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 248WD UT WOS:000252187000002 PM 18184038 ER PT J AU Malik, T Sauder, C Wolbert, C Zhang, C Carbone, KM Rubin, S AF Malik, Tahir Sauder, Christian Wolbert, Candie Zhang, Cheryl Carbone, Kathryn M. Rubin, Steven TI A single nucleotide change in the mumps virus F gene affects virus fusogenicity in vitro and virulence in vivo SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE infectious clone system; neurotoxicity; paramyxovirus; reverse genetics ID NEUROVIRULENCE SAFETY TEST; ASEPTIC-MENINGITIS; STRAIN; VACCINATION; VACCINES; SEQUENCE; MEASLES; HUMANS; CDNA AB Mumps virus is highly neurotropic, with evidence of infection of the central nervous system in more than half of clinical cases. In the prevaccine era, mumps was a major cause of viral meningitis in most developed countries. Despite efforts to attenuate the virus, some mumps vaccines have retained virulence properties and have caused aseptic meningitis in vaccinees, resulting in public resistance to vaccination in some countries. Ensuring the safety of mumps vaccines is an important public health objective, as the need for robust immunization programs has been made clear by the recent resurgence of mumps outbreaks worldwide, including the United States, which in 2006 experienced its largest mumps outbreak in 20 years. To better understand the molecular basis of mumps virus attenuation, the authors developed two infectious ftill-length cDNA clones for a highly neurovirulent strain of mumps virus. The clones differed at only one site, possessing either an A or G at nucleotide position 271 in the F gene, to represent the heterogeneity identified in the original virulent clinical isolate. In comparison to the clinical isolate, virus rescued from the A-variant cDNA clone grew to higher cumulative titers in vitro but exhibited similar cytopathic effects in vitro and virulence in vivo. In contrast, virus rescued from the G-variant cDNA clone, in comparison to the clinical isolate and the A-variant, was more fusogenic in vitro but replicated to lower cumulative titers and was less neurovirulent in vivo. These data suggest that nucleotide position 271 in the F gene plays a significant role in virus pathogenesis. This infectious clone system will serve as a key tool for further examination of the molecular basis for mumps virus neurovirulence and neuroattenuation. C1 [Malik, Tahir; Sauder, Christian; Wolbert, Candie; Zhang, Cheryl; Carbone, Kathryn M.; Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, DVP Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Malik, T (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP Off Vaccines Res & Review, Bethesda, MD 20892 USA. EM tahir.malik@fda.hhs.gov; christian.sauder@fda.hhs.gov NR 27 TC 11 Z9 11 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 2007 VL 13 IS 6 BP 513 EP 521 DI 10.1080/13550280701658382 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 248VM UT WOS:000252185100004 PM 18097883 ER PT J AU Hamad, ML Ellison, CD Khan, MA Lyon, RC AF Hamad, Mazen L. Ellison, Christopher D. Khan, Mansoor A. Lyon, Robbe C. TI Drug product characterization by macropixel analysis of chemical images SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE image analysis; near-infrared spectroscopy; algorithms; multivariate analysis; imaging methods; heterogeneous systems; NIR imaging; chemical imaging; heterogeneity; macropixels ID NEAR-INFRARED SPECTROSCOPY; PHARMACEUTICAL SOLID FORMS; FORMULATIONS; IMPROVEMENT; NIR AB Traditional monitoring of pharmaceutical manufacturing combines physical sampling and analytical methodologies (e.g. HPLC). Process analytical technology (PAT) can be implemented to collect real-time measurements, although successful monitoring requires that sampling be representative. The maximum spot size for a spectroscopic tool (e.g. near-infrared; Raman) should be equivalent to a single dosage size. A smaller spot size may provide a PAT tool that is sensitive to monitoring process changes, but if too small, produces non-reproducible data. The current study uses chemical imaging to determine appropriate spot size. A chemical image is an array of pixels which maps the chemical composition of the sample. "Macropixel Analysis" is introduced as a measure of image heterogeneity based on clusters of pixels (macropixels) within near-infrared chemical images. Analyses were conducted using non-overlapping tiles of macropixels (Discrete-Level Tiling) and all possible macropixels of the image (Continuous-Level Moving Block). Both methods minimize the variance between macropixel intensities by varying the size of the macropixels. Spot size is then chosen as the minimum macropixel size for which the range of macropixel intensities falls within an acceptable criterion. Both imaging-based algorithms provide useful quantitative information about the heterogeneity of pharmaceutical products. (c) 2007 Wiley-Liss, Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. RP Lyon, RC (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. EM Robbe.Lyon@FDA.HHS.gov NR 27 TC 18 Z9 18 U1 0 U2 5 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 DEC PY 2007 VL 96 IS 12 BP 3390 EP 3401 DI 10.1002/jps.20971 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 236XW UT WOS:000251337800019 PM 17630646 ER PT J AU Gallas, BD Pennello, GA Myers, KJ AF Gallas, Brandon D. Pennello, Gene A. Myers, Kyle J. TI Multireader multicase variance analysis for binary data SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DORFMAN-BERBAUM-METZ; OPERATING CHARACTERISTIC ANALYSIS; CHARACTERISTIC ROC DATA; MRMC METHOD; MODEL; VALIDATION AB Multireader multicase (MRMC) variance analysis has become widely utilized to analyze observer studies for which the summary measure is the area under the receiver operating characteristic (ROC) curve. We extend MRMC variance analysis to binary data and also to generic study designs in which every reader may not interpret every case. A subset of the fundamental moments central to MRMC variance analysis of the area under the ROC curve (AUC) is found to be required. Through multiple simulation configurations, we compare our unbiased variance estimates to naive estimates across a range of study designs, average percent correct, and numbers of readers and cases. C1 [Gallas, Brandon D.; Pennello, Gene A.; Myers, Kyle J.] US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Derices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Gallas, BD (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Derices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 15 TC 17 Z9 17 U1 0 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 BP B70 EP B80 DI 10.1364/JOSAA.24.000B70 PG 11 WC Optics SC Optics GA 248BP UT WOS:000252126600008 PM 18059916 ER PT J AU Park, S Barrett, HH Clarkson, E Kupinski, MA Myers, KJ AF Park, Subok Barrett, Harrison H. Clarkson, Eric Kupinski, Matthew A. Myers, Kyle J. TI Channelized-ideal observer using Laguerre-Gauss channels in detection tasks involving non-Gaussian distributed lumpy backgrounds and a Gaussian signal SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DETECTION PERFORMANCE; OBJECTIVE ASSESSMENT; IMAGE QUALITY; NOISE; MODEL AB We investigate a channelized-ideal observer (CIO) with Laguerre-Gauss (LG) channels to approximate ideal-observer performance in detection tasks involving non-Gaussian distributed lumpy backgrounds and a Gaussian signal. A Markov-chain Monte Carlo approach is employed to determine the performance of both the ideal observer and the CIO using a large number of LG channels. Our results indicate that the CIO with LG channels can approximate ideal-observer performance within error bars, depending on the imaging system, object, and channel parameters. The CIO also outperforms a channelized-Hotelling observer using the same channels. In addition, an alternative approach for estimating the CIO is investigated. This approach makes use of the characteristic functions of channelized data and employs an approximation method to the area under the receiver operating characteristic curve. The alternative approach provides good estimates of the performance of the CIO with five LG channels. However, for large channel cases, more efficient computational methods need to be developed for the CIO to become useful in practice. (C) 2007 Optical Society of America. C1 [Park, Subok; Myers, Kyle J.] US FDA, Natl Inst Biomed Imaging & Bioengn, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Silver Spring, MD 20993 USA. [Barrett, Harrison H.; Clarkson, Eric; Kupinski, Matthew A.] Univ Arizona, Ctr Opt Sci, Tucson, AZ 85724 USA. [Barrett, Harrison H.; Clarkson, Eric; Kupinski, Matthew A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Park, S (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn, CDRH, Lab Assessment Med Imaging Syst,Div Imaging & App, Silver Spring, MD 20993 USA. EM stibok.park@fda.hhs.gov FU Intramural NIH HHS; NIBIB NIH HHS [R37 EB000803, P41EB002035, R37EB000803, P41 EB002035-09, P41 EB002035, R37 EB000803-17] NR 19 TC 27 Z9 27 U1 1 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 BP B136 EP B150 DI 10.1364/JOSAA.24.00B136 PG 15 WC Optics SC Optics GA 248BP UT WOS:000252126600014 PM 18059906 ER PT J AU Kupinski, MA Watson, AB Siewerdsen, JH Myers, KJ Eckstein, M AF Kupinski, Matthew A. Watson, Andrew B. Siewerdsen, Jeffrey H. Myers, Kyle J. Eckstein, Miguel TI Image quality - Introduction SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Editorial Material C1 [Kupinski, Matthew A.] Univ Arizona, Coll Opt sci, Tucson, AZ 85721 USA. [Kupinski, Matthew A.] Univ Arizona, Dept Radiol, Tucson, AZ 85721 USA. [Watson, Andrew B.] NASA, Ames Res Ctr, Vis Grp, Moffett Field, CA 94035 USA. [Siewerdsen, Jeffrey H.] Univ Toronto, Div Biophys & Bioimaging, Toronto, ON M5G 2M9, Canada. [Myers, Kyle J.] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. [Eckstein, Miguel] Univ Calif Santa Barbara, Dept Psychol, Santa Barbara, CA 93106 USA. RP Kupinski, MA (reprint author), Univ Arizona, Coll Opt sci, Tucson, AZ 85721 USA. EM mkupinski@optics.arizona.edu; andrew.b.watson@nasa.gov; jsiewerd@uhnres.utoronto.ca; kyle.myers@fda.hhs.gov; eckstein@psych.ucsb.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD DEC PY 2007 VL 24 IS 12 PG 1 WC Optics SC Optics GA 248BP UT WOS:000252126600001 ER PT J AU Pavletic, SZ Zhou, G Sobocinski, K Marti, G Doney, K DiPersio, J Feremans, W Foroni, L Goodman, S Prentice, G LeMaistre, C Bandini, G Ferrant, A Jacobsen, N Khouri, J Gale, RP Wiestner, A Giralt, S Montserrat, E Chan, WC Bredeson, C AF Pavletic, S. Z. Zhou, G. Sobocinski, K. Marti, G. Doney, K. DiPersio, J. Feremans, W. Foroni, L. Goodman, S. Prentice, G. LeMaistre, C. Bandini, G. Ferrant, A. Jacobsen, N. Khouri, J. Gale, R. P. Wiestner, A. Giralt, S. Montserrat, E. Chan, W. C. Bredeson, C. CA CIBMTR TI Genetically identical twin transplantation for chronic lymphocytic leukemia SO LEUKEMIA LA English DT Article DE hematopoietic stem cell transplantation; identical twin; CLL ID STEM-CELL TRANSPLANTATION; MARROW TRANSPLANTATION; ALLOGENEIC TRANSPLANTATION; BLOOD; LYMPHOMA; GENE; ABNORMALITIES; MALIGNANCIES; OVERCOME; CANCER AB We identified 19 persons with B-cell chronic lymphocytic leukemia (CLL) who received genetically identical twin blood cell or bone marrow transplants after high-dose conditioning. Ten are alive (eight disease-free) with a median follow-up of 89 months (range, 31-171 months); 5-year relapse rate was 50% (95% confidence interval (CI), 26-73%). Estimated 5-year survival and disease-free survival were 61% (95% CI, 37-82%) and 45% (95% CI, 23-68%). In two of four patients tested at 12 and 21 months by polymerase chain reaction no evidence of residual CLL was detected post-transplant. In one recipient who relapsed at 6 years, molecular studies showed a different CLL clone from that detected pretransplant. This clone was subsequently identified in the donor suggesting transfer of occult leukemia at the time of transplant. Genetically identical twin transplants can result in long-term disease-free survival and molecular remissions, these data suggest the potential for CLL control in the absence of allogeneic graft-versus-leukemia effect. The case of leukemia transfer indicates the need for careful evaluation of donors prior to graft collection. C1 Ctr Canc Res, Natl Canc Inst, Bethesda, MD USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI USA. US FDA, Div Cell & Gene Therapies, CBER, Bethesda, MD USA. Univ Washington, Dept Med, Seattle, WA USA. Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO USA. Erasme Univ Hosp, Clin Hematol, Brussels, Belgium. UCL, Royal Free Hosp, Sch Med, Dept Haematol, London, England. Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol & Oncol, Nashville, TN USA. Texas Transplant Inst, Div Adult Stem Cell Transplantat, San Antonio, TX USA. Sant Orsola Univ Hosp, Inst Hematol, Dept Hematol Oncol, Bologna, Italy. Catholic Univ Louvain, Clin Univ St Luc, Dept Hematol, Brussels, Belgium. Rigshosp Univ Hosp, Dept Hematol, Copenhagen, Denmark. Univ Texas MD Anderson Canc Ctr Houston, Dept Stem Cell Transplantat, Houston, TX 77030 USA. NHLBI, Natl Inst Hlth, Bethesda, MD USA. Univ Barcelona, Hosp & Clin, Inst Hematol & Oncol, Dept Hematol,IDIBAPS, Barcelona, Spain. Med Coll Wisconsin, Div Neoplast Dis, Milwaukee, WI USA. RP Pavletic, SZ (reprint author), NCI, Graft Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike,10 Ctr Dr, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 29 TC 14 Z9 14 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 2007 VL 21 IS 12 BP 2452 EP 2455 DI 10.1038/sj.leu.2404928 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 234CY UT WOS:000251139500008 PM 17728782 ER PT J AU Wagner, RF AF Wagner, Robert F. TI From medical images to multiple-biomarker microarrays SO MEDICAL PHYSICS LA English DT Article ID COMPUTER-AIDED DIAGNOSIS; FINITE-SAMPLE SIZE; FOLLICULAR LYMPHOMA; IMAGING-SYSTEMS; DOSE REDUCTION; CLASSIFIERS; CANCER; BACKPROJECTION; PERFORMANCE; PREDICTION AB A favorite cliche, often attributed to Yogi Berra, is "Prediction is difficult, especially about the future!" In this brief review, we shall recall some historical difficulties in predicting the future of diagnostic medical imaging-in particular, the modern technologies of CT and MRI-and examine the analogous situation in the emerging technology of diagnostic microarrays for the multiple-biomarker problem. All of these technologies began their lives as ill-conditioned problems, i.e., there was insufficient data to solve the central problem at hand. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3126, Silver Spring, MD 20993 USA. NR 36 TC 6 Z9 6 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2007 VL 34 IS 12 BP 4944 EP 4951 DI 10.1118/1.2805252 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 245BT UT WOS:000251910200039 PM 18196819 ER PT J AU Bharti, S Inoue, H Bharti, K Hirsch, DS Nie, Z Yoon, HY Artym, V Yamada, KA Mueller, SC Barr, VA Randazzo, PA AF Bharti, Sanita Inoue, Hiroki Bharti, Kapil Hirsch, Dianne S. Nie, Zhongzhen Yoon, Hye-Young Artym, Vira Yamada, Kenneth A. Mueller, Susette C. Barr, Valarie A. Randazzo, Paul A. TI Src-dependent phosphorylation of ASAP1 regulates podosomes SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; FOCAL-ADHESION KINASE; BREAST-CANCER INVASION; HIV-1 NEF PROTEIN; SH3 DOMAIN; MEMBRANE CURVATURE; CRYSTAL-STRUCTURE; COMPLEX; EXPRESSION; RECEPTORS AB Invadopodia are Src-induced cellular structures that are thought to mediate tumor invasion. ASAP1, an Arf GTPase-activating protein (GAP) containing Src homology 3 (SH3) and Bin, amphiphysin, and RVS161/167 (BAR) domains, is a substrate of Src that controls invadopodia. We have examined the structural requirements for ASAP1-dependent formation of invadopodia and related structures in NIH 3T3 fibroblasts called podosomes. We found that both predominant splice variants of ASAP1 (ASAP1a and ASAP1b) associated with invadopodia and podosomes. Podosomes were highly dynamic, with rapid turnover of both ASAP1 and actin. Reduction of ASAP1 levels by small interfering RNA blocked formation of invadopodia and podosomes. Podosomes were formed in NIH 3T3 fibroblasts in which endogenous ASAP1 was replaced with either recombinant ASAP1a or ASAP1b. ASAP1 mutants that lacked the Src binding site or GAP activity functioned as well as wild-type ASAP1 in the formation of podosomes. Recombinant ASAP1 lacking the BAR domain, the SH3 domain, or the Src phosphorylation site did not support podosome formation. Based on these results, we conclude that ASAP1 is a critical target of tyrosine kinase signaling involved in the regulation of podosomes and invadopodia and speculate that ASAP1 may function as a coincidence detector of simultaneous protein association through the ASAP1 SH3 domain and phosphorylation by Src. C1 NCI, Ctr Canc Res, Lab Cellular & Mol Biol, Bethesda, MD USA. NINDS, Mammalian Dev Sect, Bethesda, MD USA. US FDA, Bethesda, MD USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Georgetown Univ, Washington, DC USA. RP Randazzo, PA (reprint author), Ctr Canc Res, Lab Cellular & Mol Biol, CCR, Bldg 37,Rm 4118, Bethesda, MD 20892 USA. EM Randazzo@helix.nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 37 TC 56 Z9 56 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 2007 VL 27 IS 23 BP 8271 EP 8283 DI 10.1128/MCB.01781-06 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 239OH UT WOS:000251527100020 PM 17893324 ER PT J AU Liu, RQ Blower, PE Pham, AN Fang, JL Dai, ZY Wise, C Green, B Teitel, CH Ning, BT Ling, WH Lyn-Cook, BD Kadlubar, FF Sadee, WG Huang, Y AF Liu, Ruqing Blower, Paul E. Pham, Anh-Nhan Fang, Jialong Dai, Zunyan Wise, Carolyn Green, Bridgette Teitel, Candee H. Ning, Baitang Ling, Wenhua Lyn-Cook, Beverly D. Kadlubar, Fred F. Sadee, Wolfgang Huang, Ying TI Cystine-glutamate transporter SLC7A11 mediates resistance to geldanamycin but not to 17-(allylamino)-17-demethoxygeldanamycin SO MOLECULAR PHARMACOLOGY LA English DT Article ID CYSTINE/GLUTAMATE EXCHANGE TRANSPORTER; SYSTEM X(C)(-); CANCER CHEMOSENSITIVITY; GENE-EXPRESSION; ASCORBIC-ACID; GLUTATHIONE; CHEMORESISTANCE; SENSITIVITY; INHIBITORS; INDUCTION AB The cystine-glutamate transporter SLC7A11 has been implicated in chemoresistance, by supplying cystine to the cell for glutathione maintenance. In the NCI-60 cell panel, SLC7A11 expression shows negative correlation with growth inhibitory potency of geldanamycin but not with its analog 17-(allylamino)17-demethoxygeldanamycin (17-AAG), which differs in the C-17 substituent in that the the methoxy moiety of geldanamycin is replaced by an amino group. Structure and potency analysis classified 18 geldanamycin analogs into two subgroups, "17-O/H" (C-17 methoxy or unsubstituted) and "17-N" (C-17 amino), showing distinct SLC7A11 correlation. We used three 17-O/H analogs and four 17-N analogs to test the role of the 17-substituents in susceptibility to SLC7A11-mediated resistance. In A549 cells, which are resistant to geldanamycin and strongly express SLC7A11, inhibition of SLC7A11 by (S)-4-carboxyphenylglycine or small interfering RNA increased sensitivity to 17-O/H, but had no effect on 17-N analogs. Ectopic expression of SLC7A11 in HepG2 cells, which are sensitive to geldanamycin and express low SLC7A11, confers resistance to geldanamycin, but not to 17-AAG. Antioxidant N-acetylcysteine, a precursor for glutathione synthesis, completely suppressed cytotoxic effects of 17-O/H but had no effect on 17-N analogs, whereas the prooxidant ascorbic acid had the opposite effect. Compared with 17-AAG, geldanamycin led to significantly more intracellular reactive oxygen species (ROS) production, which was quenched by addition of N-acetylcysteine. We conclude that SLC7A11 confers resistance selectively to 17-O/H (e. g., geldanamycin) but not to 17-N (e. g., 17-AAG) analogs partly as a result of differential dependence on ROS for cytotoxicity. Distinct mechanisms could significantly affect antitumor response and organ toxicity of these compounds in vivo. C1 US FDA, Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Guangdong, Peoples R China. Ohio State Univ, Coll Med & Publ Hlth, Dept Pharmacol, Program Pharmacogenom,Comprehens Canc Ctr, Columbus, OH 43210 USA. Univ Arkansas Med Sci, Dept Epidemiol, Little Rock, AR 72205 USA. Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA USA. RP Huang, Y (reprint author), US FDA, Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. EM yhuang@westernu.edu FU NIGMS NIH HHS [GM61390] NR 40 TC 10 Z9 10 U1 0 U2 1 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 DEC PY 2007 VL 72 IS 6 BP 1637 EP 1646 DI 10.1124/mol.107.039644 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 232OT UT WOS:000251029700027 PM 17875604 ER PT J AU Pogribny, IP Tryndyak, VP Woods, CG Witt, SE Rusyn, I AF Pogribny, Igor P. Tryndyak, Volodymyr P. Woods, Courtney G. Witt, Sarah E. Rusyn, Ivan TI Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor alpha SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE liver; peroxisome proliferators; epigenetics; DNA methylation; cancer ID ALTERED DNA METHYLATION; HUMAN CANCER; HISTONE H4; PPAR-ALPHA; GC-RICH; HYPOMETHYLATION; RAT; CARCINOGENESIS; HEPATOCARCINOGENESIS; MECHANISM AB Peroxisome proliferators are potent rodent liver carcinogens that act via a non-genotoxic mechanism. The mode of action these agents in rodent liver includes increased cell proliferation, decreased apoptosis, secondary oxidative stress and other events; however, it is not well understood how peroxisome proliferators are triggering the plethora of the molecular signals leading to cancer. Epigenetic changes have been implicated in the mechanism of liver carcinogenesis by a number of environmental agents. Short-term treatment with peroxisome proliferators and other non-genotoxic carcinogens leads to global and locus-specific DNA hypomethylation in mouse liver, events that were suggested to correlate with a burst of cell proliferation. In the current study, we investigated the effects of long-term exposure to a model peroxisome proliferator WY-14,643 on DNA and histone methylation. Male SV129 mice were fed a control or WY-14,643-containing (1000 ppm) diet for one week, five weeks or five months. Treatment with WY-14,643 led to progressive global hypomethylation of liver DNA as determined by an HpaII-based cytosine extension assay with the maximum effect reaching over 200% at five months. Likewise, trimethylation of histone H4 lysine 20 and H3 lysine 9 was significantly decreased at all time points. The majority of cytosine methylation in mammals resides in repetitive DNA sequences. In view of this, we measured the effect of WY-14,643 on the methylation status of major and minor satellites, as well as in IAP, LINE1 and LINE2 elements in liver DNA. Exposure to WY-14,643 resulted in a gradual loss of cytosine methylation in major and minor satellites, IAP, LINE I and LINE2 elements. The epigenetic changes correlated with the temporal effects of WY-14,643 on cell proliferation rates in liver, but no sustained effect on c-Myc promoter methylation was observed. Finally, WY-14,643 had no effect on DNA and histone methylation status in Ppar alpha-null mice at any of the time points considered in this study. These data indicate the importance of epigenetic alterations in the mechanism of action of peroxisome proliferators and the key role of Ppar alpha. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr, Chapel Hill, NC 27599 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Michael Hooker Res Ctr, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIEHS NIH HHS [R01 ES012686-04, ES11391, ES11660, ES12686, ES13342, F31 ES013342, F32 ES005920, F32 ES005920-02, K22 ES011660, K22 ES011660-03, R01 ES012686, U19 ES011391] NR 48 TC 24 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 1 PY 2007 VL 625 IS 1-2 BP 62 EP 71 DI 10.1016/j.mrfmmm.2007.05.004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 238SL UT WOS:000251467800006 PM 17586532 ER PT J AU Dong, W Chen, F Ali, S Sharma, H Tian, ZR AF Dong, W. Chen, F. Ali, S. Sharma, H. Tian, Z. R. TI Neuroprotectively repairing spinal cord, sensing neurochemicals and proteins, and filtrating cell-sized particles using nanowire-scaffolding membranes SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Arkansas, Fayetteville, AR 72701 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Uppsala Univ, Univ Hosp, Uppsala, Sweden. RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016; Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2007 VL 3 IS 4 BP 340 EP 341 DI 10.1016/j.nano.2007.10.027 PG 2 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 242OU UT WOS:000251735900032 ER PT J AU Chumakov, K Ehrenfeld, E Wimmer, E Agol, VI AF Chumakov, Konstantin Ehrenfeld, Ellie Wimmer, Eckard Agol, Vadim I. TI Vaccination against polio should not be stopped SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID IMMUNODEFICIENT PATIENT; UNITED-STATES; OPV CESSATION; PARALYTIC POLIOMYELITIS; ATTENUATED POLIOVIRUS; ERADICATION; EVOLUTION; VIRUS; DISEASE; STRAIN AB The striking 50-year-long decline in the incidence of poliomyelitis has stalled in the past 7 years, which has led to calls for an urgent re-assessment of eradication and post-eradication campaign strategies. The current plan of eliminating the circulation of wild poliovirus so that further immunization will be unnecessary does not take into account recent scientific data and political realities that limit the likelihood that this strategy can sustain prevention of the disease. It is crucially important that high levels of population immunity are maintained against polio in the foreseeable future. C1 NIH, Natl Inst Allergy & Infect Dis, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. RP Ehrenfeld, E (reprint author), NIH, Natl Inst Allergy & Infect Dis, Bldg 10, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Agol, Vadim/E-1941-2013 FU Intramural NIH HHS NR 61 TC 43 Z9 46 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2007 VL 5 IS 12 BP 952 EP U13 DI 10.1038/nrmicro1769 PG 7 WC Microbiology SC Microbiology GA 238AB UT WOS:000251417900015 PM 17965726 ER PT J AU Senderowicz, AM Johnson, JR Sridhara, R Zimmerman, P Justice, R Pazdur, R AF Senderowicz, Adrian M. Johnson, John R. Sridhara, Rajeshwari Zimmerman, Paul Justice, Robert Pazdur, Richard TI Erlotinib/gemcitabine for first-line treatment of locally adavanced or metastatic adenocarcinoma of the pancreas SO ONCOLOGY-NEW YORK LA English DT Article ID PHASE-III TRIAL; CELL LUNG-CANCER; GEMCITABINE; ERLOTINIB; CHEMOTHERAPY; COMBINATION; THERAPY AB Erlotinib (Tarceva) is a human epidermal growth factor receptor type 1/ epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor initially approved by the US Food and Drug Administration for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer after failure of at least one prior chemotherapy regimen. In this report, we present the pivotal study that led to the approval of erlotinib in combination with gemcitabine (Gemzar) in patients with locally advanced/metastatic chemonaive pancreatic cancer patients. The combination demonstrated a statistically significant increase in overall survival accompanied by an increase in toxicity. Physicians and patients now have a new option for the treatment of locally advanced/metastatic adenocarcinoma of the pancreas. C1 [Senderowicz, Adrian M.; Johnson, John R.; Sridhara, Rajeshwari; Zimmerman, Paul; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD USA. RP Senderowicz, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD USA. NR 13 TC 43 Z9 47 U1 1 U2 1 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD DEC PY 2007 VL 21 IS 14 BP 1696 EP 1706 PG 11 WC Oncology SC Oncology GA 270RX UT WOS:000253739000007 PM 18247017 ER PT J AU Brown, JS Kulldorff, M Chan, KA Davis, RL Graham, D Pettus, PT Andrade, SE Raebel, MA Herrinton, L Roblin, D Boudreau, D Smith, D Gurwitz, JH Gunter, MJ Platt, R AF Brown, Jeffrey S. Kulldorff, Martin Chan, K. Arnold Davis, Robert L. Graham, David Pettus, Parker T. Andrade, Susan E. Raebel, Marsha A. Herrinton, Lisa Roblin, Douglas Boudreau, Denise Smith, David Gurwitz, Jerry H. Gunter, Margaret J. Platt, Richard TI Early detection of adverse drug events within population-based health networks: application of sequential testing methods SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse drug event; methodology; sequential analysis; drug safety surveillance; SPRT ID VACCINE SAFETY; SURVEILLANCE; RISK AB Purpose Active surveillance of population-based health networks may improve the timeliness of detection of adverse drug events (ADEs). Active monitoring requires sequential analysis methods. Our objectives were to (1) evaluate the utility of automated healthcare claims data for near real-time drug adverse event surveillance and (2) identify key methodological issues related to the use of healthcare claims data for real-time drug safety surveillance. Methods We assessed the ability to detect ADEs using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Analyses were performed using a maximized sequential probability ratio test (maxSPRT). Five drug-event pairs representing known associations with an ADE and two pairs representing 'negative controls' were analyzed. Results Statistically significant (p < 0.05) signals of excess risk were found in four of the five drug-event pairs representing known associations; no signals were found for the negative controls. Signals were detected between 13 and 39 months after the start of surveillance. There was substantial variation in the number of exposed and expected events at signal detection. Conclusions Prospective, periodic evaluation of routinely collected data can provide population-based estimates of medication-related adverse event rates to support routine, timely post-marketing surveillance for selected ADEs. Copyright (c) 2007 John Wiley & Sons, Ltd. C1 [Brown, Jeffrey S.; Kulldorff, Martin; Pettus, Parker T.; Platt, Richard] Harvard Med Sch, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. [Brown, Jeffrey S.; Pettus, Parker T.; Andrade, Susan E.; Raebel, Marsha A.; Herrinton, Lisa; Roblin, Douglas; Boudreau, Denise; Smith, David; Gurwitz, Jerry H.; Gunter, Margaret J.; Platt, Richard] HMO Res Network Ctr Educ & Res Therapeut, Boston, MA USA. [Chan, K. Arnold] Harvard Sch Publ Hlth, Boston, MA USA. [Chan, K. Arnold] i3 Drug Safety, Waltham, MA USA. [Davis, Robert L.] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. [Graham, David] Off Drug Safety Food & Drug Adm, Rockville, MD USA. [Andrade, Susan E.; Gurwitz, Jerry H.] Univ Massachusetts, Fallon Fdn, Sch Med, Meyers Primary Care Inst,Fallon Commun Hlth Plan, Worcester, MA USA. [Raebel, Marsha A.] Kaiser Permanente, Denver, CO USA. [Herrinton, Lisa] Kaiser Permanente Northern Calif, Oakland, CA USA. [Roblin, Douglas] Kaiser Permanente, Atlanta, GA USA. [Boudreau, Denise] Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. [Smith, David] Kaiser Permanente NW, Portland, OR USA. [Gunter, Margaret J.] Lovelace Clin Fdn, Albuquerque, NM USA. RP Brown, JS (reprint author), Harvard Med Sch, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Flr, Boston, MA 02215 USA. EM jeff_brown@harvardpilgrim.org RI Kulldorff, Martin/H-4282-2011; OI Chan, Kinwei/0000-0001-8161-1986; Kulldorff, Martin/0000-0002-5284-2993 FU AHRQ HHS [2U19HS010391] NR 17 TC 62 Z9 62 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 DEC PY 2007 VL 16 IS 12 BP 1275 EP 1284 DI 10.1002/pds.1509 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 244SX UT WOS:000251886700004 PM 17955500 ER PT J AU Goodsaid, F Bandow, JE Mischak, H AF Goodsaid, Federico Bandow, Julia Elisabeth Mischak, Harald TI Grand rounds in proteomics at the FDA - White Oak, Silver Spring, MD, USA, April 3, 2007 SO PROTEOMICS CLINICAL APPLICATIONS LA English DT Article DE biomarkers; mass spectrometry AB The application of proteomics in drug development could be a major source of novel biomarkers to improve the efficacy and safety of new drugs. Training of US Food and Drug Administration (FDA) reviewers on current applications of proteomics is important for the future review of proteomic data. A Grand Rounds in Proteomics was held on April 3, 2007 at the FDA in White Oak, Silver Spring, MD, USA. The goal of this activity was to contribute to reviewer training as well as to generate discussions regarding the readiness of proteomic platforms in drug development, similar in scope to applications in genomics and metabolomics. Several speakers from industry and academia presented data on proteomic applications in drug development (meeting agenda available in the Supporting Information). An additional goal of this meeting was to encourage proteomic data submissions within the Voluntary eXploratory Data Submissions (VXDS) at the FDA. VXDS meetings represent key venues for exchange between the FDA and sponsors of scientific and clinical data on exploratory biomarkers. The FDA has received a limited number of VXDS submissions containing proteomic data. This meeting was an opportunity to identify possible areas in proteomics where future VXDS submissions may be received. Voluntary submissions have been transformed into regulatory submissions in genomics, and a similar path may also be followed by proteomic data in the future. Proteomic biomarkers may also be suitable for submission to the Pilot Process for Biomarker Qualification at the FDA. C1 [Mischak, Harald] Mosaiques Diagnost & Therapeut AG, D-30625 Hannover, Germany. [Goodsaid, Federico] US FDA, Genom Grp, Silver Spring, MD USA. [Bandow, Julia Elisabeth] Pfizer Inc, PGRD, Ann Arbor, MI USA. RP Mischak, H (reprint author), Mosaiques Diagnost & Therapeut AG, Mellendorfer Str 7-9, D-30625 Hannover, Germany. EM mischak@mosaiques-diagnostics.com RI Mischak, Harald/E-8685-2011; Bandow, Julia/K-8854-2012; OI Bandow, Julia/0000-0003-4100-8829 NR 0 TC 11 Z9 11 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1862-8346 J9 PROTEOM CLIN APPL JI Proteom. Clin. Appl. PD DEC PY 2007 VL 1 IS 12 BP 1526 EP 1531 DI 10.1002/prca.200700575 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244RN UT WOS:000251883100001 PM 21136652 ER PT J AU Contrera, JF Kruhlak, NL Matthews, EJ Benz, RD AF Contrera, Joseph F. Kruhlak, Naomi L. Matthews, Edwin J. Benz, R. Daniel TI Comparison of MC4PC and MDL-QSAR rodent carcinogenicity predictions and the enhancement of predictive performance by combining QSAR models SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE carcinogenicity; discriminant analysis; in silico; predictive toxicology; topological descriptors; QSAR; E-state; chemoinformatics; discriminant analysis; consensus prediction ID E-STATE INDEXES; DEVELOPMENTAL TOXICITY; GENETIC TOXICITY; IDENTIFICATION; CHEMICALS; PHARMACEUTICALS; INFORMATION; SOFTWARE; PROGRAM; HAZARD AB This report presents a comparison of the predictive performance of MC4PC and MDL-QSAR software as well as a method for combining the predictions from both programs to increase overall accuracy. The conclusions are based on 10x10% leave-many-out internal cross-validation studies using 1540 training set compounds with 2-year rodent carcinogenicity findings. The models were generated using the same weight of evidence scoring method previously developed [Matthews, E.J., Contrera, J.F., 1998. A new highly specific method for predicting the carcinogenic potential of pharmaceuticals in rodents using enhanced MCASE QSAR-ES software. Regul. Toxicol. Pharmacol. 28, 242-264.]. Although MC4PC and MDL-QSAR use different algorithms, their overall predictive performance was remarkably similar. Respectively, the sensitivity of MC4PC and MDL-QSAR was 61 and 63%, specificity was 71 and 75%, and concordance was 66 and 69%. Coverage for both programs was over 95% and receiver operator characteristic (ROC) intercept statistic values were above 2.00. The software programs had complimentary coverage with none of the 1540 compounds being uncovered by both MC4PC and MDL-QSAR. Merging MC4PC and MDL-QSAR predictions improved the overall predictive performance. Consensus sensitivity increased to 67%, specificity to 84%, concordance to 76%, and ROC to 4.31. Consensus rules can be tuned to reflect the priorities of the user, so that greater emphasis may be placed on predictions with high sensitivity/low false negative rates or high specificity/low false positive rates. Sensitivity was optimized to 75% by reclassifying all compounds predicted to be positive in MC4PC or MDL-QSAR as positive, and specificity was optimized to 89% by reclassifying all compounds predicted negative in MC4PC or MDL-QSAR as negative. (c) 2007 Elsevier Inc. All rights reserved. C1 [Contrera, Joseph F.; Kruhlak, Naomi L.; Matthews, Edwin J.; Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, Silver Spring, MD 20993 USA. RP Contrera, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, Mail Drop 1603,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Joseph.Contrera@fda.hhs.gov NR 31 TC 35 Z9 35 U1 0 U2 7 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 DEC PY 2007 VL 49 IS 3 BP 172 EP 182 DI 10.1016/j.yrtph.2007.07.001 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 241HJ UT WOS:000251647200004 PM 17703860 ER PT J AU Harper, SB Dertinger, SD Bishop, ME Lynch, AM Lorenzo, M Saylor, M MacGregor, JT AF Harper, Susan B. Dertinger, Stephen D. Bishop, Michelle E. Lynch, Anthony M. Lorenzo, Mari Saylor, Michelle MacGregor, James T. TI Flow cytometric analysis of micronuclei in peripheral blood reticulocytes III. An efficient method of monitoring chromosomal damage in the beagle dog SO TOXICOLOGICAL SCIENCES LA English DT Article ID CYTOGENETIC DAMAGE; ERYTHROCYTES; ASSAY; FREQUENCIES; RODENT; RAT AB Erythrocyte-based micronucleus tests have traditionally analyzed bone marrow because splenic filtration in most species removes micronucleated cells from peripheral blood. We have evaluated a flow cytometric method for monitoring micronucleated reticulocyte frequencies (%MN-RET) in the peripheral blood of beagle dogs treated with cyclophosphamide (CP) and have found that analysis of micronucleated reticulocytes (MN-RETs) in peripheral blood is a suitable surrogate for bone marrow analysis. The three-color flow cytometric method uses anti-CD71 labeling to identify reticulocytes and Plasmodium berghei-containing erythrocytes as a calibration standard. The spontaneous %MN-RET determined by flow cytometry was 0.31 +/- 0.09% (n = 22) for peripheral blood, compared with 0.38 +/- 0.13% (SD, n = 12) for bone marrow, and 0.27 +/- 0.08% (n = 12) for peripheral blood by microscopic scoring with acridine orange staining. The kinetics of appearance and disappearance of MN-RETs in blood were determined by collecting daily samples after iv treatment with CP. The maximum frequency occurred 48 h after dosing. Frequencies of MN-RETs in peripheral blood at steady state following daily CP treatment were 55-68% of corresponding bone marrow values assessed by microscopy and 55-112% as assessed by flow cytometry. This difference is presumably due to splenic removal, which appears slightly less stringent than that previously reported for CP-treated Sprague-Dawley rats. Responses in bone marrow and peripheral blood were highly correlated and similar to or greater than those reported in mice and rats at equitoxic doses. C1 Toxicol Consulting Serv, Arnold, MD 21012 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Dept Vet Affairs, Washington, DC 20422 USA. Litron Lab, Rochester, NY 14623 USA. GlaxoSmithKline Res & Dev Ltd, Ware SG12 0DP, Herts, England. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Harper, SB (reprint author), Toxicol Consulting Serv, Arnold, MD 21012 USA. NR 34 TC 16 Z9 18 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 DEC PY 2007 VL 100 IS 2 BP 406 EP 414 DI 10.1093/toxsci/kfm241 PG 9 WC Toxicology SC Toxicology GA 232RU UT WOS:000251037800009 PM 17872896 ER PT J AU Knight, TR Choudhuri, S Klaassen, CD AF Knight, Tamara Raphael Choudhuri, Supratim Klaassen, Curtis D. TI Constitutive mRNA expression of various glutathione S-Transferase isoforms in different tissues of mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE glutathione transferase; Gst; tissue distribution; mRNA; bDNA ID GASTROINTESTINAL GLUTATHIONE; OXIDATIVE STRESS; MOUSE; ISOENZYMES; INDUCTION; CANCER; GENES; EVOLUTION; STOMACH; TRACT AB Glutathione S-transferase (Gst) enzymes are instrumental in protecting cellular macromolecules against electrophiles and products of oxidative stress. Of interest primarily to pharmacologists and toxicologists is the ability of these enzymes to metabolize cancer chemotherapeutic drugs, insecticides, herbicides, and carcinogens. Thus, constitutive expression of Gsts might determine a tissue's ability to handle certain forms of chemical stress. In the present study, the constitutive mRNA expression of 19 different Gst enzymes was investigated in 14 different tissues in mice. The information obtained from the present study could be distilled into a few generalized principles: in all tissues examined, multiple isoforms of Gst were constitutively expressed; several isoforms, such as Gstk1, Gstm1, Gstm4, Gstm6, and Gstt1, were expressed in most of the tissues studied; at least five Gst isoforms were highly expressed in the gonads, about three in heart, and at least one in brain (Gstm5). Gender differences in the expression of various Gst isoforms were pronounced. With a few exceptions, most of the Gst isoforms expressed in kidney showed higher expression in females than males; the same trend was observed for heart and gonads. At least eight Gst isoforms showed very high expression in stomach. This was a unique finding in the current study because drug-metabolizing enzymes that are highly expressed in the gastrointestinal (GI) tract tend to have the highest expression in small intestine with low or no expression in the stomach. In summary, most Gst isoforms are most highly expressed in the GI tract and liver, which strongly suggests an important role of many Gst isoforms in detoxification of ingested xenobiotics. C1 Univ Kansas, Ctr Med, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. Ctr Toxicol & Environm Hlth, Little Rock, AR 72201 USA. Ctr Food Safety & Appl Nutr, OFAS, DBGNR, College Pk, MD 20740 USA. RP Klaassen, CD (reprint author), Univ Kansas, Ctr Med, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM cklaasse@kumc.edu FU NCRR NIH HHS [RR021940]; NIEHS NIH HHS [ES013714, ES07079, ES09716, R01 ES013714] NR 32 TC 47 Z9 47 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2007 VL 100 IS 2 BP 513 EP 524 DI 10.1093/toxsci/kfm233 PG 12 WC Toxicology SC Toxicology GA 232RU UT WOS:000251037800020 PM 17890767 ER PT J AU Vallerio, LG AF Vallerio, Luis G., Jr. TI Mammalian iron metabolism SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE iron metabolism; absorption; toxicity; oxidative stress; hemochromatosis; molecular regulation; evidence-based; hepcidin; ferroportin; DMT1; transferrin; ferritin; iron overload; iron regulatory protein; iron responsive element; dietary iron; liver ID ELEMENT-BINDING-PROTEIN; FERRITIN MESSENGER-RNA; HUMAN TRANSFERRIN RECEPTOR; 1Q-LINKED JUVENILE HEMOCHROMATOSIS; ANTIMICROBIAL PEPTIDE HEPCIDIN; 3' UNTRANSLATED REGION; DIETARY IRON; REGULATORY PROTEIN-1; RESPONSIVE ELEMENT; OXIDATIVE STRESS AB Iron is an essential transition metal for mammalian cellular and tissue viability. It is critical to supplying oxygen through heme, the mitochondrial respiratory chain, and enzymes such as ribonucleotide reductase. Mammalian organisms have evolved with the means of regulating the metabolism of iron, because if left unregulated, the resulting excess amounts of iron may induce chronic toxicities affecting multiple organ systems. Several homeostatic mechanisms exist to control the amount of intestinal dietary iron uptake, cellular iron uptake, distribution, and export. Within these processes, numerous molecular participants have been identified because of advancements in basic cell biology and efforts in diseasc-based research of iron Storage abnormalities. For example, dietary iron uptake across the intestinal duodenal mucosa is mediated by an intramembrane divalent metal transporter 1 (DMTI), and cellular iron efflux involves ferroportin, the only known iron exporter. In addition to duodenal enterocytes, ferroportin is present in other cell types, and exports iron into plasma. Ferroportin was recently discovered to be regulated by the expression of the circulating hormone hepcidin, a small peptide synthesized in hepatocytes. These recent studies on the role of hepcidin in the regulation of dietary, cellular, and extracellular iron have led to a better understanding of the pathways by which iron balance in humans is influenced, especially its involvement in human genetic diseases of iron overload. Other important molecular pathways include iron binding to transferrin in the bloodstream for cellular delivery through the plasma membrane transferrin receptor (TfR1). In the cytosol, iron regulatory proteins 1 and 2 (IRP1 and IRP2) play a prominent role in sensing the presence of iron in order to posttranscriptionally regulate the expression of TfR1 and ferritin, two important participants in iron metabolism. From a toxicological standpoint, posttranscriptional regulation of these genes aids in the sequestration, control, and hence prevention of cytotoxic effects from free-floating nontransferrin-bound iron. Given the importance of dietary iron in normal physiology, its potential to induce chronic toxicity, and recent discoveries in the regulation of human iron metabolism by hepcidin, this review will address the regulatory mechanisms of normal iron metabolism in mammals with emphasis on dietary exposure. It is the goal of this review that this information may provide in a concise format our current understanding of major pathways and mechanisms involved in mammalian iron metabolism, which is a basis for control of iron toxicity. Such a discussion is intended to facilitate the identification of deficiencies so that future metabolic or toxicological studies may be appropriately focused. A better knowledge of iron metabolism from normal to pathophysiological conditions will ultimately broaden the spectrum of the usefulness of this information in biomedical and toxicological sciences for improving and protecting human health. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol, College Pk, MD 20470 USA. GRAS Notice Review, College Pk, MD 20470 USA. RP Vallerio, LG (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Off New Drugs,Off Drug Evaluat 3, HFD-180,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Luis.Valerio@FDA.HHS.gov NR 240 TC 3 Z9 3 U1 2 U2 17 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD DEC PY 2007 VL 17 IS 9 BP 497 EP 517 DI 10.1080/15376510701556690 PG 21 WC Toxicology SC Toxicology GA 237HY UT WOS:000251366000001 ER PT J AU Holada, K Simak, J Brown, P Vostal, JG AF Holada, Karel Simak, Jan Brown, Paul Vostal, Jaroslav G. TI Divergent expression of cellular prion protein on blood cells of human and nonhuman primates SO TRANSFUSION LA English DT Article ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CREUTZFELDT-JAKOB-DISEASE; SCRAPIE INFECTIVITY; FLOW-CYTOMETRY; PRPC; TRANSFUSION; COMPONENTS; ACCUMULATION; PLATELETS; HAMSTER AB BACKGROUND: Four recent transmissions of variant Creutzfeldt-Jakob disease infection by transfusion highlight the need for detailed understanding of blood-related prion pathogenesis. Nonhuman primates are the most relevant models of human prion diseases. STUDY DESIGN AND METHODS: Quantitative flow cytometry with monoclonal antibodies FH11, 3F4, and 6H4 against different parts of the normal cellular form of the prion protein (PrPC) was used to evaluate its expression on blood cells of humans, chimpanzees, cynomolgus macaques, rhesus macaques, squirrel monkeys, and microcebe lemurs. RESLUTS: Chimpanzees, rhesus macaques, and squirrel monkeys displayed a much higher quantity of total blood cell membrane PrPC than humans, due to a markedly higher expression of PrPC on their red blood cells (RBCs). In contrast, cynomolgus macaques and lemurs demonstrated substantially lower levels of membrane PrPC due to the lack of significant PrPC expression on RBCs and platelets (PLTs). All species displayed PrPC on white blood cells (WBCs), with the highest levels found on human cells. Only humans, chimpanzees, and to a lesser degree rhesus macaques expressed PrPC on PLTs. CONCLUSIONS: If PrPC contributes to the propagation or transport of prion infectivity in blood, the differences reported here need to be considered when extrapolating results of transmission studies in primate models to blood and blood components in humans. C1 Charles Prague Univ, Fac Med 1, Inst Microbiol & Immunol, CZ-12820 Prague, Czech Republic. US FDA, CBER, Div Hematol, Bethesda, MD USA. RP Holada, K (reprint author), Charles Prague Univ, Fac Med 1, Inst Microbiol & Immunol, Studnickova 7, CZ-12820 Prague, Czech Republic. EM Karel.Holada@LF1.cuni.cz RI Simak, Jan/C-1153-2011 NR 30 TC 14 Z9 14 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2007 VL 47 IS 12 BP 2223 EP 2232 DI 10.1111/j.1537-2995.2007.01451.x PG 10 WC Hematology SC Hematology GA 235BD UT WOS:000251207600010 PM 17714417 ER PT J AU Shaikh, B Rummel, N Gieseker, C Chu, PS Reimschuessel, R AF Shaikh, Badar Rummel, Nathan Gieseker, Charles Chu, Pak-Sin Reimschuessel, Renate TI Residue depletion of tritium-labeled ivermectin in rainbow trout following oral administration SO AQUACULTURE LA English DT Article DE aquaculture; rainbow trout; ivermectin; metabolism ID SALMON SALMO-SALAR; GATED CHLORIDE CHANNELS; ANTI-PARASITIC AGENT; ATLANTIC SALMON; TISSUE DISTRIBUTION; METABOLISM; DISPOSITION; ALBENDAZOLE; POTENT; CATTLE AB The residue depletion and metabolism of tritium-labeled ivermectin were studied in the muscle tissue of rainbow trout following oral treatment. Fish were administered H-3-ivermectin at the dose level of 0.1 mg/kg of body weight (9.25 mu Ci) in a gel-capsule via stomach tube. At each of the following withdrawal times 6 fish were sedated with MS-222, euthanatized, bled, scaled and fillets with adhering skin and bile collected: 1, 3, 7, 14, 28, 3 5 and 42 days. The muscle tissues were homogenized in dry ice and analyzed for total radioactive residues (TRR) by sample oxidation. The homogenized tissue was further extracted with acetonitrile for residue characterization by high pressure liquid chromatography (LC). Maximum TRR of 71 ng/g and 3857 ng/mL (ivermectin equivalent concentration) were detected in muscle and bile, respectively, by sample oxidation on post-dose day 3. LC analysis of the muscle extract revealed that the maximum TRR of 55 ng/g (representing ivermectin and metabolites) was also detected on post-dose day 3. By post-dose day 35, about 65% of the TRR in the muscle tissue was an unknown metabolite. Preliminary mass spectrometry results indicated that the unknown metabolite may be 3 ''-O-demethyl-ivennectinBI..Thismetabolitecouldserveasa potential marker residue for ivermectin in rainbow trout, in contrast to cattle, swine and sheep where the parent ivermectin is known to be the marker residue. (c) 2007 Published by Elsevier B.V. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM badaruddin.shaikh@fda.hhs.gov NR 23 TC 6 Z9 10 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD NOV 26 PY 2007 VL 272 IS 1-4 BP 192 EP 198 DI 10.1016/j.aquaculture.2007.08.050 PG 7 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 238GM UT WOS:000251435400018 ER PT J AU Ashar, BS Ferriter, A AF Ashar, Binita S. Ferriter, Ann TI Radiofrequency identification technology in health care - Benefits and potential risks SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Ashar, BS (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, HFZ 410,9200 Corp Blvd, Rockville, MD 20850 USA. EM binita.ashar@fda.hhs.gov NR 16 TC 29 Z9 29 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 21 PY 2007 VL 298 IS 19 BP 2305 EP 2307 DI 10.1001/jama.298.19.2305 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 232XV UT WOS:000251055900031 PM 18029835 ER PT J AU Raval, A Akhavan-Toyserkani, G Brinker, A Avigan, M AF Raval, Angela Akhavan-Toyserkani, Gita Brinker, Allen Avigan, Mark TI Brief communication: Characteristics of spontaneous cases of tuberculosis associated with infliximab SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; MANAGEMENT AB Background: A warning for tuberculosis was added to the approved labeling for infliximab in October 2001. Objective: To describe adverse event reports of tuberculosis during infliximab therapy after labeling changes. Design: Case series. Setting: Spontaneous adverse event reports maintained in the Adverse Event Reporting System database in the United States. Patients: 130 patients with infliximab-associated tuberculosis. Measurements: Clinical and laboratory data. Results: The U. S. Food and Drug Administration received 130 domestic, spontaneous reports of tuberculosis in patients treated with infliximab between 1 November 2001 and 30 May 2006, including 59 (45%) with extrapulmonary disease. The most commonly reported risk factors included concomitant immunosuppressant use (n = 89), history of latent or active tuberculosis (n = 33), and being born into or having spent extensive time in an area where tuberculosis is endemic (n = 25). In the subset of 67 cases with documented initiation of infliximab therapy after the drug labeling change, 34 patients with a negative tuberculin skin test result before initiation of infliximab therapy developed tuberculosis after receiving infliximab. Limitation: Conclusions from spontaneous case reports may not be generalizable to the entire infliximab-receiving population. Conclusion: Clinicians should be vigilant in screening and monitoring for tuberculosis in patients receiving infliximab. C1 Ctr Drug Evaluat & Res Food & Drug Adm, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Akhavan-Toyserkani, G (reprint author), Ctr Drug Evaluat & Res Food & Drug Adm, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22,Rm 3469, Silver Spring, MD 20993 USA. NR 7 TC 41 Z9 44 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 20 PY 2007 VL 147 IS 10 BP 699 EP U124 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 235UJ UT WOS:000251259500004 PM 18025446 ER PT J AU Rahman, A Pazdur, R Wang, Y Huang, SM Lesko, L AF Rahman, Atiqur Pazdur, Richard Wang, Yaning Huang, Shiew-Mei Lesko, Lawrence TI The value meal: Effect of food on lapatinib Bioavailability SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 US FDA, Off Clin Pharmacol, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rahman, A (reprint author), US FDA, Off Clin Pharmacol, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 7 Z9 7 U1 1 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2007 VL 25 IS 33 BP 5333 EP 5334 DI 10.1200/JCO.2007.14.6381 PG 4 WC Oncology SC Oncology GA 233EY UT WOS:000251074400038 PM 18024885 ER PT J AU da Costa, GG Marques, MM Fu, X Churchwell, MI Wang, YP Doerge, DR Beland, FA AF da Costa, Goncalo Gamboa Marques, M. Matilde Fu, Xin Churchwell, Mona I. Wang, Yu-Ping Doerge, Daniel R. Beland, Frederick A. TI Effect of N,N-didesmethyltamoxifen upon DNA adduct formation by tamoxifen and alpha-hydroxytamoxifen SO CANCER LETTERS LA English DT Article DE N,N-Didesmethyltamoxifen; tamoxifen; DNA adducts ID TANDEM MASS-SPECTROMETRY; CANCER PREVENTION TRIAL; SPRAGUE-DAWLEY RATS; BREAST-CANCER; ENDOMETRIAL CANCER; METABOLIC-ACTIVATION; GENE-EXPRESSION; FOLLOW-UP; LIVER; IDENTIFICATION AB Tamoxifen undergoes sequential metabolism to N-desmethyltamoxifen and N,N-didesmethyltamoxifen. Whereas N-desmethyltamoxifen is a major metabolite in humans, nonhuman primates, and rats, appreciable concentrations of N,N-didesmethyltamoxifen are formed in humans and nonhuman primates but not in rats. This difference in the extent of N,N-didesmethyltamoxifen formation may be important because it has been proposed that N,N-didesmethyltamoxifen inhibits the cytochrome P450 (CYP)-catalyzed alpha-hydroxylation of tamoxifen and resultant tamoxifen-DNA adduct formation. To test this hypothesis directly, we compared the extent of tamoxifen-DNA adduct formation in rats co-administered 27 mu mol N, N-didesmethyltamoxifen per kg body weight and either 27 mu mol tamoxifen per kg body weight or 27 mu mol alpha-hydroxytamoxifen per kg body weight daily for 7 days. Female Sprague-Dawley rats treated with N,N-didesmethyltamoxifen had a 44% decrease (p > 0.05) in CYP 3A2 content (the CYP isoform responsible for tamoxifen alpha-hydroxylation), an 18% decrease (p = 0.010) in CYP 3A activity, and higher blood levels of tamoxifen and N-desmethyltamoxifen compared to rats treated with solvent. Total tamoxifen-DNA adduct levels were 4.1-fold higher (p < 0.001) in rats given alpha-hydroxytamoxifen as compared to tamoxifen. N,N-Didesmethyltamoxifen treatment caused a 1.2-fold increase in total tamoxifen-DNA adduct levels with both tamoxifen and alpha-hydroxytamoxifen, a difference that was not significant. These results indicate that, with this experimental model, N,N-didesmethyltamoxifen does not impair the metabolism of tamoxifen to a reactive electrophile. Published by Elsevier Ireland Ltd. C1 Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM frederick.beland@fda.hhs.gov RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014 OI Marques, M. Matilde/0000-0002-7526-4962; NR 46 TC 4 Z9 4 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 18 PY 2007 VL 257 IS 2 BP 191 EP 198 DI 10.1016/j.canlet.2007.07.014 PG 8 WC Oncology SC Oncology GA 230YK UT WOS:000250912100006 ER PT J AU Dreyer, ZE Dinndorf, P Joanne, HM Steuber, CP Mei, L Naomi, W William, CL Stephen, H Bruce, C AF Dreyer, Zoann Eckert Dinndorf, Patricia Joanne, Hilden M. Steuber, C. Philip Mei, La Naomi, Winick William, Carroll L. Stephen, Hunger Bruce, Camitta TI Unexpected toxicity with Intensified induction in infant Acute Lymphoid Leukemia SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dreyer, Zoann Eckert; Steuber, C. Philip] Texas Childrens Hosp, Houston, TX 77030 USA. [Dinndorf, Patricia] US FDA, Silver Spring, MD USA. [Joanne, Hilden M.] St Vincent Childrens Hosp Indiana, Indianapolis, IN USA. [Mei, La] Childrens Oncol Grp, Arcadia, CA USA. [Naomi, Winick] Univ Texas SW Med Ctr, Dallas, TX USA. [Bruce, Camitta] Univ Florida, Gainesville, FL USA. [Bruce, Camitta] Midwest Childrens Hosp, Milwaukee, WI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 852 BP 261A EP 261A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801121 ER PT J AU Dowdell, KC Pesnicak, L Bi, L Hoffmann, V Rao, VK Straus, SE AF Dowdell, Kennichi C. Pesnicak, Lesley Bi, Lilia Hoffmann, Victoria Rao, V. Koneti Straus, Stephen E. TI Hydroxychloroquine diminishes lymphoproliferation in the fas deficient MRL/lpr-/- murine model of autoimmune lymphoproliferative syndrome (ALPS) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Dowdell, Kennichi C.; Pesnicak, Lesley; Rao, V. Koneti; Straus, Stephen E.] NIH, NIAID, LCID, Bethesda, MD USA. [Bi, Lilia] CBER, FDA, Bethesda, MD USA. [Hoffmann, Victoria] NIH, DVM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 1385 BP 416A EP 416A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100801653 ER PT J AU Wiestner, A Lee, E Vire, B Gibellini, F Njuguna, N Herishanu, Y Liu, D Munson, P Raghavachari, N White, T Marti, GE Wilson, WH AF Wiestner, Adrian Lee, Elinor Vire, Berengere Gibellini, Federica Njuguna, Ndegwa Herishanu, Yair Liu, Delong Munson, Peter Raghavachari, Nalini White, Therese Marti, Gerald E. Wilson, Wyndham H. TI Molecular effects of rituximab on CLL cells in vivo: Rapid increase in serum interferon gamma, induction of a distinct tumor cell gene expression signature and loss of CD20 expression SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wiestner, Adrian; Lee, Elinor; Vire, Berengere; Gibellini, Federica; Njuguna, Ndegwa; Herishanu, Yair] NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter; Raghavachari, Nalini] NIH, NHLBI, Bioinformat Core, Bethesda, MD 20892 USA. [White, Therese; Wilson, Wyndham H.] NCI, CCR, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2048 BP 610A EP 610A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100802570 ER PT J AU Gelderman-Fulumann, MP Lewis, JL Tassis, EK Vostal, AC Vostal, JG AF Gelderman-Fulumann, Monique P. Lewis, Jessica L. Tassis, Elisabet K. Vostal, Alex C. Vostal, Jaroslav G. TI Comparison of UVA and UVB induced lesions in human platelets evaluated in an animal model SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Gelderman-Fulumann, Monique P.; Lewis, Jessica L.; Tassis, Elisabet K.; Vostal, Alex C.; Vostal, Jaroslav G.] US FDA, CBER, OBRR, Lab Cellular Hematol, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 2883 BP 848A EP 848A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100803665 ER PT J AU Landgren, O Albitar, MX Ma, WX Abbasi, FR Hayes, RB Marti, GE Caporaso, NE AF Landgren, Ola Albitar, Maher X. Ma, Wanlong X. Abbasi, Fatima R. Hayes, Richard B. Marti, Gerald E. Caporaso, Neil E. TI Evidence of pre-diagnostic monoclonality in blood obtained up to 6.4 years preceding diagnosis of chronic lymphocytic leukemia (CLL) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Landgren, Ola; Hayes, Richard B.; Caporaso, Neil E.] Natl Canc Inst, NIH, Bethesda, MD USA. [Albitar, Maher X.; Ma, Wanlong X.] Nichols Inst Quest Diagnost, San Juan Capistrano, CA USA. [Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3082 BP 906A EP 907A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804119 ER PT J AU Kane, RC Pratt, RG Lu, S Farrell, AT AF Kane, Robert C. Pratt, Robert G. Lu, Susan Farrell, Ann T. TI Reversible posterior leukoencephalopathy syndrome (RPLS) complicating biologic and small-molecule therapies for cancer SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kane, Robert C.; Pratt, Robert G.; Lu, Susan; Farrell, Ann T.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2007 VL 110 IS 11 MA 3341 BP 981A EP 981A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804378 ER PT J AU Pogribny, IP Bagnyukova, TV Tryndyak, VP Muskhelisbvili, L Rodriguez-Juarez, R Kovalchuk, O Han, T Fuscoe, JC Ross, SA Beland, FA AF Pogribny, Igor P. Bagnyukova, Tetyana V. Tryndyak, Volodymyr P. Muskhelisbvili, Levan Rodriguez-Juarez, Rocio Kovalchuk, Olga Han, Tao Fuscoe, James C. Ross, Sharon A. Beland, Frederick A. TI Gene expression profiling reveals underlying molecular mechanisms of the early stages of tamoxifen-induced rat hepatocarcinogenesis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE tamoxifen; rat; hepatocarcinogenesis; gene expression ID HUMAN HEPATOCELLULAR-CARCINOMA; HEPATIC STELLATE CELLS; DNA ADDUCT FORMATION; GROWTH-FACTOR; NONALCOHOLIC STEATOHEPATITIS; LIVER FIBROSIS; METABOLIZING-ENZYMES; TRANSGENIC MICE; ANGIOTENSIN-II; PDGF-B AB Tamoxifen is a widely used anti-estrogenic drug for chemotherapy and, more recently, for the chemoprevention of breast cancer. Despite the indisputable benefits of tamoxifen in preventing the occurrence and re-occurrence of breast cancer, the use of tamoxifen has been shown to induce nonalcoholic steatohepatitis, which is a life-threatening fatty liver disease with a risk of progression to cirrhosis and hepatocellular carcinoma. In recent years, the high-throughput microarray technology for large-scale analysis of gene expression has become a powerful tool for increasing the understanding of the molecular mechanisms of carcinogenesis and for identifying new biomarkers with diagnostic and predictive values. In the present study, we used the high-throughput microarray technology to determine the gene expression profiles in the liver during early stages of tamoxifen-induced rat hepatocarcinogenesis. Female Fisher 344 rats were fed a 420 ppm tamoxifen containing diet for 12 or 24 weeks, and gene expression profiles were determined in liver of control and tamoxifen-exposed rats. The results indicate that early stages of tamoxifen-induced liver carcinogenesis are characterized by alterations in several major cellular pathways, specifically those involved in the tamoxifen metabolism, lipid metabolism, cell cycle signaling, and apoptosis/cell proliferation control. One of the most prominent changes during early stages of tamoxifen-induced hepatocarcinogenesis is dysregulation of signaling pathways in cell cycle progression from the G, to S phase, evidenced by the progressive and sustained increase in expression of the Pdgfc, Calb3, Ets1, and Ccnd1 genes accompanied by the elevated level of the PI3K, p-PI3K, Akt 1/2, Akt3, and cyclin B, D1, and D3 proteins. The early appearance of these alterations suggests their importance in the mechanism of neoplastic cell transformation induced by tamoxifen. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. NCI, Div Canc Prevent, 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 59 TC 15 Z9 16 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2007 VL 225 IS 1 BP 61 EP 69 DI 10.1016/j.taap.2007.07.001 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 230AH UT WOS:000250847200005 PM 17706260 ER PT J AU Mitra, MS Donthamsetty, S White, B Latendresse, JR Mehendale, HM AF Mitra, Mayurranjan S. Donthamsetty, Shashikiran White, Brent Latendresse, John R. Mehendale, Harihara M. TI Mechanism of protection of moderately diet restricted rats against doxorubicin-induced acute cardiotoxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE doxorubicin; diet restriction; cardiotoxicity; cellular energy; JAK/STAT3 pathway; ATP synthesis ID ISCHEMIA-REPERFUSION INJURY; ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; LIVER-TISSUE REPAIR; INDUCED CARDIOMYOPATHY; UNCOUPLING PROTEINS; CALORIC RESTRICTION; ACUTE TOXICITY; PPAR-ALPHA; HEART AB Clinical use of doxombicin (Adriamycin (R)), an antitumor agent, is limited by its oxyradical-mediated cardiotoxicity. We tested the hypothesis that moderate diet restriction protects against doxorubicin-induced cardiotoxicity by decreasing oxidative stress and inducing cardioprotective mechanisms. Male Sprague-Dawley rats (250-275 g) were maintained on diet restriction [35% less food than ad libitum]. Cardiotoxicity was estimated by measuring biomarkers of cardiotoxicity, cardiac function, lipid peroxidation, and histopathology. A LD100 dose of doxorubicin (12 mg/kg, ip) administered on day 43 led to 100% mortality in ad libitum rats between 7 and 13 days due to higher cardiotoxicity and cardiac dysfunction, whereas all the diet restricted rats exhibited normal cardiac function and survived. Toxicokinetic analysis revealed equal accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the ad libitum and diet restricted hearts. Mechanistic studies revealed that diet restricted rats were protected due to (1) lower oxyradical stress from increased cardiac antioxidants leading to downregulation of uncoupling proteins 2 and 3, (2) induction of cardiac peroxisome proliferators, activated receptor-alpha and plasma adiponectin increased cardiac fatty acid oxidation (666.9 +/- 14.0 nmol/min/g heart in ad libitum versus 1035.6 +/- 32.3 nrnol/min/g heart in diet restriction) and mitochondrial AMP alpha 2 protein kinase. The changes led to 51% higher cardiac ATP levels (17.7 +/- 2.1 mu mol/g heart in ad libitum versus 26.7 +/- 1.9 mu mol/g heart in diet restriction), higher ATP/ADP ratio, and (3) increased cardiac erythropoietin and decreased suppressor of cytokine signaling 3, which upregulates cardioprotective JAK/STAT3 pathway. These findings collectively show that moderate diet restriction renders resiliency against doxorubicin cardiotoxicity by lowering oxidative stress, enhancing ATP synthesis, and inducing the JAK/STAT3 pathway. (c) 2007 Elsevier Inc. All rights reserved. C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Cummings Vet Hosp, Monroe, LA USA. Natl Ctr Toxicol Res, Pathol Toxicol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm, Dept Toxicol, 700 Univ Ave,Sugar Hall 306B, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 50 TC 20 Z9 20 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2007 VL 225 IS 1 BP 90 EP 101 DI 10.1016/j.taap.2007.07.018 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 230AH UT WOS:000250847200008 PM 17904602 ER PT J AU Cooley, M Carychao, D Crawford-Miksza, L Jay, MT Myers, C Rose, C Keys, C Farrar, J Mandrell, RE AF Cooley, Michael Carychao, Diana Crawford-Miksza, Leta Jay, Michele T. Myers, Carol Rose, Christopher Keys, Christine Farrar, Jeff Mandrell, Robert E. TI Incidence and Tracking of Escherichia coli O157:H7 in a Major Produce Production Region in California SO PLOS ONE LA English DT Article AB Fresh vegetables have become associated with outbreaks caused by Escherichia coli O157:H7 (EcO157). Between 1995-2006, 22 produce outbreaks were documented in the United States, with nearly half traced to lettuce or spinach grown in California. Outbreaks between 2002 and 2006 induced investigations of possible sources of pre-harvest contamination on implicated farms in the Salinas and San Juan valleys of California, and a survey of the Salinas watershed. EcO157 was isolated at least once from 15 of 22 different watershed sites over a 19 month period. The incidence of EcO157 increased significantly when heavy rain caused an increased flow rate in the rivers. Approximately 1000 EcO157 isolates obtained from cultures of >100 individual samples were typed using Multi-Locus Variable-number-tandem-repeat Analysis (MLVA) to assist in identifying potential fate and transport of EcO157 in this region. A subset of these environmental isolates were typed by Pulse Field Gel Electrophoresis (PFGE) in order to make comparisons with human clinical isolates associated with outbreak and sporadic illness. Recurrence of identical and closely related EcO157 strains from specific locations in the Salinas and San Juan valleys suggests that transport of the pathogen is usually restricted. In a preliminary study, EcO157 was detected in water at multiple locations in a low-flow creek only within 135 meters of a point source. However, possible transport up to 32 km was detected during periods of higher water flow associated with flooding. During the 2006 baby spinach outbreak investigation, transport was also detected where water was unlikely to be involved. These results indicate that contamination of the environment is a dynamic process involving multiple sources and methods of transport. Intensive studies of the sources, incidence, fate and transport of EcO157 near produce production are required to determine the mechanisms of pre-harvest contamination and potential risks for human illness. C1 [Cooley, Michael; Carychao, Diana; Mandrell, Robert E.] ARS, Produce Safety & Microbiol Res Unit, USDA, Western Reg Res Ctr, Albany, CA USA. [Crawford-Miksza, Leta; Jay, Michele T.] Calif Dept Hlth Serv, Food & Drug Lab Branch, Richmond, CA USA. [Rose, Christopher] Calif Environm Protect Agcy, Cent Coast Reg Water Qual Control Board, San Luis Obispo, CA USA. [Keys, Christine] US FDA, CFSAN, OPDF DMS, College Pk, MD USA. RP Cooley, M (reprint author), ARS, Produce Safety & Microbiol Res Unit, USDA, Western Reg Res Ctr, Albany, CA USA. EM mcooley@pw.usda.gov; mandrell@pw.usda.gov FU CRIS [5325-42000-045-00D, 5325-42000-044-00D]; FDA [5325-42000-045-01R]; CAL-EPA State Water Resources Control Board [05-221-130-0]; USDA-CSREES Section 32.1 [2006-01240] FX A portion of this work was funded by CRIS projects 5325-42000-045-00D and 5325-42000-044-00D, an interagency transfer of funds provided by FDA (5325-42000-045-01R), a contract with the CAL-EPA State Water Resources Control Board (05-221-130-0), and a grant from USDA-CSREES Section 32.1 (project no. 2006-01240). NR 80 TC 169 Z9 171 U1 4 U2 33 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2007 VL 2 IS 11 AR e1159 DI 10.1371/journal.pone.0001159 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JA UT WOS:000207459100002 PM 18174909 ER PT J AU Gudlavalleti, SK Lee, CH Norris, SE Paul-Satyaseela, M Vann, WF Frasch, CE AF Gudlavalleti, Seshu K. Lee, Che-Hung Norris, Scott E. Paul-Satyaseela, Maneesh Vann, Willie F. Frasch, Carl E. TI Comparison of Neisseria meningitidis serogroup W135 polysaccharide-tetanus toxoid conjugate vaccines made by periodate activation of O-acetylated, non-O-acetylated and chemically de-O-acetylated polysaccharide SO VACCINE LA English DT Article DE Neisseria meningitidis serogroup; W135; polysaccharide O-acetylation; conjugate vaccines ID MENINGOCOCCAL CAPSULAR POLYSACCHARIDE; GROUP-A; BURKINA-FASO; W135; OUTBREAK; ASSAYS; MICE AB Polysaccharide (PS) and tetanus toxoid (TT) protein conjugate vaccines were prepared using O-acetylated (OAc+), O-acetyl negative (OAc-) and chemically de-O-acetylated (de-OAc) meningococcal W135 PS. The PSs were activated by periodate oxidation and coupled to hydrazine derivatized TT. High performance anion exchange chromatography of acid hydrolysates of periodate activated W135 PSs, showed that galactose residues in OAc+ PS were more sensitive to the periodate oxidation step than they were in the OAc- PS or de-OAc PS. Mouse antisera against OAc--TT conjugate vaccines recognized both OAc- and OAc+ PS by ELISAs and had high bactericidal titers against both OAc+ and OAc- W135 strains. Purified high molecular weight (HMW) conjugates showed higher PS to protein ratios in OAc+-TT(HMW) and (HMW) conjugate. Antisera against the HMW fractions gave higher de-OAc-TT(HMW) indicating better conjugation efficiency than OAc+-TT(HMW) bactericidal titers than antisera against unfractionated conjugates. Inhibition ELISAs indicated that OAc- and OAc+ HMW conjugates induced antibodies that bound both OAc+ and OAc- PS. Thus, for W135, PS O-acetylation does not contribute a dominant immunogenic epitope. The OAc- PS may be a good starting material for preparing W135 PS-TT conjugate vaccines using periodate oxidation. (C) 2007 Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Gudlavalleti, SK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Room 109,Bldg 29,Lincoln Dr, Bethesda, MD 20892 USA. EM gudlavalletis@yahoo.com RI Paul-Satyaseela, Maneesh/F-3756-2014 OI Paul-Satyaseela, Maneesh/0000-0002-6702-4942 NR 25 TC 13 Z9 16 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 14 PY 2007 VL 25 IS 46 BP 7972 EP 7980 DI 10.1016/j.vaccine.2007.06.018 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 233PW UT WOS:000251103800013 PM 17936445 ER PT J AU Reipa, V Holden, MJ Vilker, VL AF Reipa, Vytas Holden, Marcia J. Vilker, Vincent L. TI Association and redox properties of the putidaredoxin reductase-nicotinamide adenine dinucleotide complex SO BIOCHEMISTRY LA English DT Article ID ELECTRON-TRANSFER COMPLEX; ANABAENA PCC 7119; FERREDOXIN-NADP(+) REDUCTASE; ADRENODOXIN REDUCTASE; CATALYTIC MECHANISM; CYTOCHROME P450CAM; PSEUDOMONAS-PUTIDA; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; NADP(+) BINDING AB Putidaredoxin reductase (PdR) is the flavin protein that carries out the first electron transfer involved in the-cytochrome P450cam catalytic cycle. In PdR, the flavin adenine dinucleotide (FAD/ FADH(2)) redox center acts as a transformer by accepting two electrons from soluble nicotinamide adenine dinucleotide (NAD(+)/NADH) and donating them in two separate, one-electron-transfer steps to the iron-sulfur protein putidaredoxin (Pdx). PdR, like the two more intensively studied monoflavin reductases, adrenodoxin reductase (AdR) and ferredoxin-NADP(+) reductase (FNR), has no other active redox moieties (e.g., sulfhydryl groups) and can exist in three different oxidation states: (i) oxidized quinone, (ii) one-electron reduced semiquinone (stable neutral species (blue) or unstable radical anion (red)), and (iii) two-electron fully reduced hydroquinone. Here, we present reduction potential measurements for PdR in support of a thermodynamic model for the modulation of equilibria among the redox components in this initial electron-transfer step of the P450 cycle. A spectroelectrochemical technique was used to measure the midpoint oxidation-reduction potential of PdR that had been carefully purified of all residual NAD(+), E-0 ' = -369 +/- 10 mV at pH 7.6, which is more negative than previously reported and more negative than the pyridine nucleotide NADH/NAD(+) (-330 mV). After addition of NAD(+), the formation of the oxidized reductase-oxidized pyridine nucleotide complex was followed by the two-electron-transfer redox reaction, PdRox:NAD(+) + 2e(-) -> PdRrd:NAD(+), when the electrode potential was lowered. The midpoint potential was a hyperbolic function of increasing NADI concentration, such that at concentrations of pyridine nucleotide typically found in an intracellular environment, the midpoint potential would be E-0 ' = -230 :L 10 mV, thereby providing the thermodynamically favorable redox equilibria that enables electron transfer from NADH. This thermodynamic control of electron transfer is a shared mechanistic feature with the adrenodoxin P450 and photosynthetic electron-transfer systems but is different from the kinetic control mechanisms in the microsomal P450 systems where multiple reaction pathways draw on reducing power held by NADPH-cytochrome P450 reductase. The redox measurements were combined with protein fluorescence quenching of NAD(+) binding to oxidized PdR to establish that the PdRox:NAD(+) complex (K-D = 230 mu M) is about 5 orders of magnitude weaker than PdRrd:NAD(+) binding. These results are integrated with known structural and kinetic information for PdR, as well as for AdR and FNR, in support of a compulsory ordered pathway to describe the electron-transfer processes catalyzed by all three reductases. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. US FDA, Silver Spring, MD USA. RP Vilker, VL (reprint author), Natl Inst Stand & Technol, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM Vincent.ViIker@fda.hhs.gov NR 53 TC 4 Z9 4 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 13 PY 2007 VL 46 IS 45 BP 13235 EP 13244 DI 10.1021/bi7012118 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 228XT UT WOS:000250766600034 PM 17941648 ER PT J AU Rock, EP Kennedy, DL Furness, MH Pierce, WF Pazdur, R Burke, LB AF Rock, Edwin P. Kennedy, Dianne L. Furness, Melissa H. Pierce, William F. Pazdur, Richard Burke, Laurie B. TI Patient-reported outcomes supporting anticancer product approvals SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Patient Reported Outcomes Assessment in Cancer Trials -Evaluating and Enhancing the Payoff to Decision Making Confernece CY SEP 20-21, 2006 CL Bethesda, MD ID DRUGS AB In 2006, the US Food and Drug Administration (FDA) published draft guidance to provide recommendations for development, validation, implementation, and interpretation of patient-reported outcome (PRO) measures that can support treatment benefit claims in product labeling. Here, we summarize and discuss FDA approvals of anticancer products in the context of the draft guidance. We identified anticancer product approvals having efficacy claim(s) based at least in part on a PRO. In addition, we collated limitations of PRO instruments commonly submitted for regulatory review over the period from October 1, 2004 to September 30, 2006. From 1995 onward, nine indications were approved for seven anticancer products based at least in part on a PRO. In eight of nine approvals, PRO data supplemented other evidence of clinical benefit. In seven approvals, the PRO measured a single symptom or functional domain that was directly attributable to the treatment benefit observed in the disease. The FDA's draft PRO guidance describes principles that have been used in anticancer product approvals for more than a decade. PRO end points typically support treatment benefit claims that refer to a patient's symptoms or ability to function. Single-item PROs may be acceptable. PRO data should be both internally consistent and aligned with other evidence of clinical benefit. The FDA encourages sponsors to consult with the FDA early in the process of PRO development. C1 US FDA, Study Endpoints & Label Dev Team, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Burke, LB (reprint author), US FDA, Study Endpoints & Label Dev Team, Ctr Drug Evaluat & Res, Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM laurie.burke@fda.hhs.gov NR 14 TC 21 Z9 21 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5094 EP 5099 DI 10.1200/JCO.2007.11.3803 PG 6 WC Oncology SC Oncology GA 233EW UT WOS:000251074200009 PM 17991927 ER PT J AU Lipscomb, J Reeve, BB Clauser, SB Abrams, JS Bruner, DW Burke, LB Denicoff, AM Ganz, PA Gondek, K Minasian, LM O'Mara, AM Revicki, DA Rock, EP Rowland, JH Sgambati, M Trimble, EL AF Lipscomb, Joseph Reeve, Bryce B. Clauser, Steven B. Abrams, Jeffrey S. Bruner, Deborah Watkins Burke, Laurie B. Denicoff, Andrea M. Ganz, Patricia A. Gondek, Kathleen Minasian, Lori M. O'Mara, Ann M. Revicki, Dennis A. Rock, Edwin P. Rowland, Julia H. Sgambati, Maria Trimble, Edward L. TI Patient-reported outcomes assessment in cancer trials: Taking stock, moving forward SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; STAR P-2 TRIAL; OVARIAN-CANCER; BREAST-CANCER; INTRAPERITONEAL; CHEMOTHERAPY; RALOXIFENE; MANAGEMENT; TAMOXIFEN; INSTITUTE AB To evaluate and improve the use of cancer trial end points that reflect the patient's own perspective, the National Cancer Institute organized an international conference, Patient-Reported Outcomes Assessment in Cancer Trials (PROACT), in 2006. The 13 preceding articles in this special issue of the Journal were commissioned in preparation for or in response to the PROACT conference, which was cosponsored by the American Cancer Society. Drawing from these articles and also commentary from the conference itself, this concluding report takes stock of what has been learned to date about the successes and challenges in patient-reported outcome (PRO) assessment in phase III, phase II, and symptom management trials in cancer and identifies ways to improve the scientific soundness, feasibility, and policy relevance of PROs in trials. Building on this synthesis of lessons learned, this article discusses specific administrative policies and management procedures to improve PRO data collection, analysis, and dissemination of findings; opportunities afforded by recent methodologic and technologic advances in PRO data collection and analysis to enhance the scientific soundness and cost efficiency of PRO use in trials; and the importance of better understanding the usefulness of PRO data to the full spectrum of cancer decision makers, including patients and families, health providers, public and private payers, regulatory agencies, and standards-setting organizations. C1 Emory Univ, Atlanta, GA 30322 USA. United BioSource Corp, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Bayer Pharmaceut, Montville, NJ USA. RP Lipscomb, J (reprint author), Emory Univ, 1518 Clifton Rd NE,Rm 642, Atlanta, GA 30322 USA. EM jlipsco@sph.emory.edu NR 39 TC 73 Z9 73 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5133 EP 5140 DI 10.1200/JCO.2007.12.4644 PG 8 WC Oncology SC Oncology GA 233EW UT WOS:000251074200015 PM 17991933 ER PT J AU Saylor, DM Kim, CS Patwardhan, DV Warren, JA AF Saylor, David M. Kim, Chang-Soo Patwardhan, Dinesh V. Warren, James A. TI Diffuse-interface theory for structure formation and release behavior in controlled drug release systems SO ACTA BIOMATERIALIA LA English DT Article DE controlled drug release; diffuse-interface; phase-field theory; microstructure; dissolution ID POLYMER-SOLVENT SYSTEMS; PHASE-FIELD MODEL; MULTICOMPONENT DIFFUSION; COEFFICIENTS; INVERSION; STENT AB A common method of controlling drug release has been to incorporate the drug into a polymer matrix, thereby creating a diffusion barrier that slows the rate of drug release. It has been demonstrated that the internal microstructure of these drug-polymer composites can significantly impact the drug release rate. However, the effect of processing conditions during manufacture on the composite structure and the subsequent effects on release behavior are not well understood. We have developed a diffuse-interface theory for microstructure evolution that is based on interactions between drug, polymer and solvent species, all of which may be present in either crystalline or amorphous states. Because the theory can be applied to almost any specific combination of material species and over a wide range of environmental conditions, it can be used to elucidate and quantify the relationships between processing, microstructure and release response in controlled drug release systems. Calculations based on the theory have now demonstrated that, for a characteristic delivery system, variations in microstructure arising due to changes in either drug loading or processing time, i.e. evaporation rate, could have a significant impact on both the bulk release kinetics and the uniformity of release across the system. In fact, we observed that changes in process time alone can induce differences in bulk release of almost a factor of two and typical non-uniformities of 30% during, the initial periods of release. Because these substantial variations may have deleterious clinical ramifications, it is critical that both the system microstructure and the control of that microstructure are considered to ensure the device will be both safe and effective in clinical use. Published by Elsevier Ltd. on behalf of Acta Materialia C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Lab, Silver Spring, MD 20903 USA. NIST, Mat Sci & Engn Lab, Div Met, Gaithersburg, MD 20899 USA. RP Saylor, DM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Lab, Silver Spring, MD 20903 USA. EM david.saylor@fda.hhs.gov RI Warren, James/B-1698-2008 OI Warren, James/0000-0001-6887-1206 NR 31 TC 28 Z9 28 U1 1 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD NOV PY 2007 VL 3 IS 6 BP 851 EP 864 DI 10.1016/j.actbio.2007.03.011 PG 14 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 223TA UT WOS:000250394000003 PM 17553761 ER PT J AU LaPointe, NMA Governale, L Watkins, J Mutgund, J Anstrom, KJ AF LaPointe, Nancy M. Allen Governale, Laura Watkins, Jerry Mutgund, Jyotsna Anstrom, Kevin J. TI Outpatient use of anticoagulants, rate-controlling drugs, and antiarrhythmic drugs for atrial fibrillation SO AMERICAN HEART JOURNAL LA English DT Article ID RHYTHM MANAGEMENT AFFIRM; SINUS RHYTHM; MAINTAINING STABILITY; PREDICTING STROKE; CLINICAL-PRACTICE; AMERICAN-COLLEGE; AMIODARONE; TRIAL; METAANALYSIS; PHYSICIANS AB Background The first clinical practice guidelines for management of atrial fibrillation (AF) were published in 2001. We explored the use of anticoagulants, rate-controlling drugs, and antiarrhythmic drugs in patients with AF during the 4 years surrounding publication of these guidelines. Methods Mentions of warforin, beta-blockers, digoxin, diltiazem, verapamil, and all class I and class III antiarrhythmic drugs made by US office-based physicians during patient visits for AF between October 1999 and September 2003 were evaluated using the IMS Health National Disease and Therapeutic Index (Plymouth Meeting, PA). Medication use by patient age, sex, and physician specialty was explored. Trends in use during the study period were estimated. Results Warfarin was mentioned in an average of 37% of all AF-related visits across the observation period, with no statistically significant change over time. Digoxin was the most commonly mentioned rate-controlling drug in 23% of patient visits, followed by beta-blockers in 11% and calcium-channel blockers in 8%. Over the study period, mentions of digoxin significantly decreased, and mentions of beta-blockers significantly increased. Mentions of antiarrhythmic drugs were reported in an average of 12% of patient visits, with no significant change over the study period. Conclusions Observed trends in use of digoxin, beta-blockers, and class la antiarrhythmic drugs were consistent with evidence-based recommendations. However, only approximately one third of patient visits for AF included mentions of warfarin, even among patients aged >= 60 years. These results indicate the need for continued education and interventions, especially regarding stroke prevention, in patients with AF. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. US FDA, Silver Spring, MD USA. RP LaPointe, NMA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM allen003@mc.duke.edu NR 24 TC 11 Z9 12 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2007 VL 154 IS 5 BP 893 EP 898 DI 10.1016/j.ahj.2007.06.035 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 234FT UT WOS:000251146800016 ER PT J AU Oakley, M Faucette, L Majam, V Zheng, H Mahajan, B Erexson, C Ward, J McCutchan, T Kumar, S AF Oakley, Miranda Faucette, Laurence Majam, Victoria Zheng, Hong Mahajan, Babita Erexson, Cindy Ward, Jerrold McCutchan, Thomas Kumar, Sanjai TI Molecular markers of the pathogenesis of cerebral malaria in the murine malaria Plasmodium berghei SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Oakley, Miranda; Faucette, Laurence; Erexson, Cindy; Ward, Jerrold; McCutchan, Thomas] NIAID, Rockville, MD USA. [Majam, Victoria; Zheng, Hong; Mahajan, Babita; Kumar, Sanjai] US FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2007 VL 77 IS 5 SU S MA 1017 BP 291 EP 291 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201475 ER PT J AU Frazar, CD Orlandi, PA AF Frazar, Christian D. Orlandi, Palmer A. TI Evaluation of two DNA template preparation methods for post-immunomagnetic separation detection of Cryptosporidium parvum in foods and beverages by PCR SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CYCLOSPORA-CAYETANENSIS; OOCYSTS; PREVALENCE; VEGETABLES; PARASITES; SAMPLES AB Cryptosporidium parvum oocysts were recovered by immunomagnetic separation from six artificially contaminated foods. Two DNA isolation methods were subsequently evaluated by PCR. The FTA Concentrator-PS filter provided rapid and reproducible detection, although variability increased at lower inoculum levels (88% and 15% detection in high- and low-inoculum-level samples, respectively). Total DNA extraction generated consistent results at all oocyst levels but resulted in longer analysis time (100% and 59% detection in high- and low-inoculum-level samples, respectively). Also reflected in this study was that the matrix played an important role in the ability to recover oocysts, as sample turbidity, pH, and PCR inhibitors all influenced detection. C1 US FDA, Div Virulence Assessment, CFSAN, OARSA,MOD Res Facil 1, Laurel, MD 20708 USA. RP Orlandi, PA (reprint author), US FDA, Div Virulence Assessment, CFSAN, OARSA,MOD Res Facil 1, Rm 3603 HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM palmer.orlandi@fda.hhs.gov NR 22 TC 5 Z9 5 U1 0 U2 1 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 NOV PY 2007 VL 73 IS 22 BP 7474 EP 7476 DI 10.1128/AEM.01652-07 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 233PR UT WOS:000251103300045 PM 17890339 ER PT J AU Gonzalez-Escalona, N Whitney, B Jaykus, LA DePaola, A AF Gonzalez-Escalona, Narjol Whitney, Brooke Jaykus, Lee-Ann DePaola, Angelo TI Comparison of direct genome Restriction Enzyme analysis and pulsed-field gel electrophoresis for typing of Vibrio vulnificus and their correspondence with multilocus sequence typing data SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMORPHIC DNA ANALYSIS; STRAINS; PCR; IDENTIFICATION; POPULATIONS; INFECTION; VIRULENCE; CHOLERAE; OYSTERS; GENE AB We compared the potential of direct genome restriction enzyme analysis (DGREA) and pulsed-field gel electrophoresis (PFGE) for discriminating Vibrio vulnificus isolates from clinical (23) and environmental (17) sources. The genotypes generated by both methodologies were compared to previous multilocus sequence typing (MLST) data. DGREA established clearer relationships among V. vulnificus strains and was more consistent with MLST than with PFGE. DGREA is a very promising tool for epidemiological and ecological studies of V. vulnificus. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM narjol@gmail.com RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 24 TC 15 Z9 15 U1 0 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 NOV PY 2007 VL 73 IS 22 BP 7494 EP 7500 DI 10.1128/AEM.00738-07 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 233PR UT WOS:000251103300049 PM 17720834 ER PT J AU Kong, H Volokhov, DV George, J Ikonomi, P Chandler, D Anderson, C Chizhikov, V AF Kong, Hyesuk Volokhov, Dmitriy V. George, Joseph Ikonomi, Pranvera Chandler, Donna Anderson, Christine Chizhikov, Vladimir TI Application of cell culture enrichment for improving the sensitivity of mycoplasma detection methods based on nucleic acid amplification technology (NAT) SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID COLORIMETRIC SILVER DETECTION; DNA MICROARRAYS; UREAPLASMA-UREALYTICUM; PCR; IDENTIFICATION; INFECTION; STRAINS; ASSAY; PRESERVATION; GENITALIUM AB Herein, we present data demonstrating that the application of initial cell culture enrichment could significantly improve mycoplasma testing methods based on the nucleic acid amplification technology (NAT) including a polymerase chain reaction (PCR)/microarray method. The results of the study using Vero cells demonstrated that this cell culture is able (1) to support efficient growth of mycoplasmas of primary interest, i.e., species found to be cell line contaminants, (2) to increase the sensitivity of NAT assay to the detection limits of the conventional broth/agar culture methods, and (3) to reduce the time required for mycoplasma testing fourfold in comparison with the conventional methods. Detection and identification of mycoplasmal agents were conducted using a modified PCR/microarray assay based on genetic differences among Mollicutes in the 16S-23S rRNA intergenic transcribed spacer (ITS). The application of nano-gold/silver enhancement technology instead of previously used fluorescent dyes significantly simplified the readout of microarray results and allowed us to avoid using expensive scanning equipment. This modification has the potential to expand the implementation of microarray techniques into laboratories involved in diagnostic testing of mycoplasma contamination in cell substrates and potentially in other biological and pharmaceutical products. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. American Type Culture Collect, Manassas, VA 20108 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov NR 48 TC 18 Z9 18 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD NOV PY 2007 VL 77 IS 1 BP 223 EP 232 DI 10.1007/s00253-007-1135-1 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 219VB UT WOS:000250115200025 PM 17717660 ER PT J AU Moon, H Ahn, H Kodell, RL Baek, S Lin, CJ Chen, JJ AF Moon, Hojin Ahn, Hongshik Kodell, Ralph L. Baek, Songjoon Lin, Chien-Ju Chen, James J. TI Ensemble methods for classification of patients for personalized medicine with high-dimensional data SO ARTIFICIAL INTELLIGENCE IN MEDICINE LA English DT Article DE class prediction; cross-validation; ensembles; majority voting; risk profiling ID GENE-EXPRESSION DATA; MICROARRAY DATA; CLASS DISCOVERY; BREAST-CANCER; PREDICTION; TREES AB Objective: Personalized medicine is defined by the use of genomic signatures of patients in a target population for assignment of more effective therapies as well as better diagnosis and earlier interventions that might prevent or delay disease. An objective is to find a novel classification algorithm that can be used for prediction of response to therapy in order to help individualize clinical assignment of treatment. Methods and materials: Classification algorithms are required to be highly accurate for optimal treatment on each patient. Typically, there are numerous genomic and clinical variables over a relatively small number of patients, which presents challenges for most traditional classification algorithms to avoid over-fitting the data. We developed a robust classification algorithm for high-dimensional data based on ensembles of classifiers built from the optimal number of random partitions of the feature space. The software is available on request from the authors. Results: The proposed algorithm is applied to genomic data sets on tymphoma patients and lung cancer patients to distinguish disease subtypes for optimal treatment and to genomic data on breast cancer patients to identify patients most likely to benefit from adjuvant chemotherapy after surgery. The performance of the proposed algorithm is consistently ranked highly compared to the other classification algorithms. Conclusion: The statistical classification method for individualized treatment of diseases developed in this study is expected to play a critical role in developing safer and more effective therapies that replace one-size-fits-all drugs with treatments that focus on specific patient needs. (c) 2007 Elsevier B.V. All rights reserved. C1 Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. SUNY Stony Brook, Dept Math & Stat, Stony Brook, NY 11794 USA. Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Moon, H (reprint author), Calif State Univ Long Beach, Dept Math & Stat, 1250 Bellflower Blvd, Long Beach, CA 90840 USA. EM hmoon623@yahoo.com NR 41 TC 35 Z9 39 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0933-3657 J9 ARTIF INTELL MED JI Artif. Intell. Med. PD NOV PY 2007 VL 41 IS 3 BP 197 EP 207 DI 10.1016/j.artmed.2007.07.003 PG 11 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 236SK UT WOS:000251323500002 PM 17719213 ER PT J AU Sellick, GS Goldin, LR Wild, RW Slager, SL Ressenti, L Strom, SS Dyer, MJS Mauro, FR Marti, GE Fuller, S Lyttelton, M Kipps, TJ Keating, MJ Call, TG Catovsky, D Caporaso, N Houlston, RS AF Sellick, Gabrielle S. Goldin, Lynn R. Wild, Ruth W. Slager, Susan L. Ressenti, Laura Strom, Sara S. Dyer, Martin J. S. Mauro, Francesca R. Marti, Gerald E. Fuller, Stephen Lyttelton, Matthew Kipps, Thomas J. Keating, Michael J. Call, Timothy G. Catovsky, Daniel Caporaso, Neil Houlston, Richard S. TI A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia SO BLOOD LA English DT Article ID B-CELLS; CYTOGENETIC ABNORMALITIES; CHEMOKINE RECEPTORS; GROWTH ARREST; DISEQUILIBRIUM; APOPTOSIS; LYMPHOMA; PREDISPOSITION; EXPRESSION; GUIDELINES AB Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P =.001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P = 7.7 x 10(-5)), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P <.002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci. C1 Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biostat, Rochester, MN USA. Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Div Hematol, Rome, Italy. US FDA, Ctr Biol Evaluat & Res, Div Cell Therapy, Flow & Image Cytometry Sect, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Gene Therapy, Flow & Image Cytometry Sect, Bethesda, MD USA. Univ Sydney, Nepean Hosp, Dept Med, Penrith, Australia. Gen Hosp Kettering, Kettering, England. Univ Calif San Diego, Moores Canc Ctr, Div Hematol Oncol, San Diego, CA 92103 USA. Univ Texas, MD Anderson Canc Ctr, Div Hematol, Houston, TX 77030 USA. Mayo Clin, Coll Med, Dept Med, Div Hematol, Rochester, MN USA. Inst Canc Res, Sect Hematooncol, Sutton, Surrey, England. RP Sellick, GS (reprint author), Inst Canc Res, Sect Canc Genet, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. RI Slager, Susan/B-6756-2009; Fuller, Stephen/C-1200-2009; Dyer, Martin/F-2691-2014 OI Dyer, Martin/0000-0002-5033-2236 FU Intramural NIH HHS; Medical Research Council [MC_U132670597]; NCI NIH HHS [CA 118444, U01 CA118444] NR 38 TC 45 Z9 45 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2007 VL 110 IS 9 BP 3326 EP 3333 DI 10.1182/blood-2007-05-091561 PG 8 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200036 PM 17687107 ER PT J AU Wang, L Abbasi, F Gaigalas, AK Hoffman, RA Flagler, D Marti, GE AF Wang, Lili Abbasi, Fatima Gaigalas, Adolfas K. Hoffman, Robert A. Flagler, Dan Marti, G. E. TI Discrepancy in measuring CD4 expression on T-lymphocytes using fluorescein conjugates in comparison with unimolar CD4-phycoerythrin conjugates SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD4; quantibrite((TM)) PE quantification kits; ABC value; MESF value; FITC-labeled microspheres; CYTO-TROL control cells; pH effect; antibody binding affinity; effective F/P ratio ID FLOW-CYTOMETRY; INDIRECT IMMUNOFLUORESCENCE; ANTIGEN-EXPRESSION; CELLS; QUANTITATION; INTENSITY; BLOOD; PHYCOERYTHRIN; FLUOROPHORE; ASSIGNMENT AB Background: Numerous methods for quantitative fluorescence calibration (QFC) have been developed to quantify receptor expression on lymphocytes. However, the results from the use of these different QFC methods vary considerably in the literature. To better identify the causes of these discrepancies, we measured CD4 expression using FITC and phycoerythrin (PE) conjugates to stain CYTO-TROL (TM) Control Cells and T-lymphocytes in whole blood and isolated cell preparations. We further examined pH of the cellular microenvironment as a cause of discordant results obtained with the FITC conjugate. Methods: Calibration with Quantibrite PE-labeled microspheres and the use of unimolar CD4-PE conjugates provided direct measurement of the antibody bound per cell value (ABC) for CD4 expression on normal T-lymphocytes. Calibration for CD4-FITC monoclonal antibody (Mab) labeled CYTO-TROL Control Cells and normal T-lymphocytes was based on molecules of equivalent soluble fluorochrome (MESF) as determined by FITC-labeled microspheres traceable to NIST RM 8640. The MESF value for CD4-FlTC Mab was determined that enabled the conversion of the MESF values obtained for CYTO-TROL cells to ABC. We investigated the likely pH change in the fluorescein microenvironments within FITC-labeled Mab and cells stained with FITC-labeled Mab using a pH sensitive indicator. Results: The mean ABC value for T-lymphocytes prepared from fresh whole blood using CD4-PE conjugate (48,321) was consistent with previous results, and it was much higher than the mean ABC using CD4-FlTC Mab (22,156). The mean ABC value for CYTO-TROL cells using CD4-PE conjugate (43,090) was also higher than that using CD4-FlTC conjugate (34,734), although the discrepancy was not as great. Further studies suggested the discrepancy in CYTO-TROL results may be accounted for by the low pH of the membrane microenvironment, but the greater discrepancy in T-lymphocytes could not be fully explained. Conclusion: CD4 expression on fresh normal whole blood samples and CYTO-TROL cells can be consistently quantified in ABC units using Quantibrite PE quantification beads and unimolar CD4-PE conjugates. Quantification with CD4-FlTC conjugate is not as consistent, but may be improved by the use of CD4 T-cells as biological. calibrators. This approximation is valid only for surface receptors with consensus ABC values measured by different QFC methods serving as biological standards. 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. Beckman Coulter Inc, Miami, FL 33116 USA. RP Marti, GE (reprint author), NIST, 100 Bur Dr,Stop 8312,Gaithersburg, Gaithersburg, MD 20899 USA. EM gemarti@helix.nih.gov NR 30 TC 17 Z9 17 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 BP 442 EP 449 DI 10.1002/cyto.b.20354 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000002 PM 17474131 ER PT J AU Khawaja, Z Abbasi, F Raveche, E Arthur, D Marti, G AF Khawaja, Zoya Abbasi, Fatima Raveche, Elizabeth Arthur, Diane Marti, Gerald TI The identification of three clonal B-cell populations in a single CLL patient SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Clinical-Cytometry-Society CY OCT 07-09, 2007 CL Washington, DC SP Clin Cytometry Soc C1 US FDA, Ctr Biol Res & Evaluat, Bethesda, MD 20014 USA. NIH, NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 BP 486 EP 487 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000021 ER PT J AU Khleif, S AF Khleif, S. TI Tumor biomarkers, the need for a new way to conduct business. Perspective from the USFDA SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Khleif, S.] US FDA, Natl Canc Inst, 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 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2007 VL 5 IS 8 BP 11 EP 11 DI 10.1016/S1359-6349(08)70021-1 PG 1 WC Oncology SC Oncology GA 242DX UT WOS:000251705800017 ER PT J AU Feng, PCH Monday, SR Lacher, DW Allison, L Siitonen, A Keys, C Eklund, M Nagano, H Karch, H Keen, J Whittam, TS AF Feng, Peter C. H. Monday, Steven R. Lacher, David W. Allison, Lesley Siitonen, Anja Keys, Christine Eklund, Marjut Nagano, Hideki Karch, Helge Keen, James Whittam, Thomas S. TI Genetic diversity among clonal lineages within Escherichia coli O157 : H7 stepwise evolutionary model SO EMERGING INFECTIOUS DISEASES LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; STRAINS; BETA; FINLAND; CATTLE; DEER AB Escherichia coli O157:H7 variants were examined for trait mutations and by molecular subtyping to better define clonal complexes postulated on the O157:H7 evolution model. Strains of beta-glucuroniclase-positive, sorbitol-negative O157:H7 isolated in United States and Japan were identical to A5 clonal strain and shared sequence type (ST)-65 by multilocus sequence typing (MLST); thus, they belong in A5. However, these strains exhibited pulsed-field gel electrophoresis (PFGE) profile differences that suggested genomic divergence between populations. Sorbitol-fermenting O157 (SFO157) strains from Finland, Scotland, and Germany were identical to A4 clonal strain and belong in A4. Some SFO157 strains, isolated years apart and from different countries, had identical PFGE profiles, suggesting a common origin. Despite similarities, some Finnish and Scottish and all of the German strains have ST-75 ("German clone"), whereas others have ST-76, a new variant ("Scottish clone"). MLST of strains in other clonal complexes also discriminated strains thought to be identical and showed that genetic differences will further distinguish clonal populations into subclones. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Michigan State Univ, E Lansing, MI 48824 USA. Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. Natl Publ Hlth Inst, Helsinki, Finland. Hokkaido Inst Publ Hlth, Sapporo, Hokkaido, Japan. Univ Munster, D-4400 Munster, Germany. RP Feng, PCH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov FU NIAID NIH HHS [N01AI30058, N01-AI-30058] NR 25 TC 48 Z9 48 U1 0 U2 10 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2007 VL 13 IS 11 BP 1701 EP 1706 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 230FB UT WOS:000250860500012 PM 18217554 ER PT J AU Balbus, JM Maynard, AD Colvin, VL Castranova, V Daston, GP Denison, RA Dreher, KL Goering, PL Goldberg, AM Kulinowski, KM Monteiro-Riviere, NA Oberdorster, G Omenn, GS Pinkerton, KE Ramos, KS Rest, KM Sass, JB Silbergeld, EK Wong, BA AF Balbus, John M. Maynard, Andrew D. Colvin, Vicki L. Castranova, Vincent Daston, George P. Denison, Richard A. Dreher, Kevin L. Goering, Peter L. Goldberg, Alan M. Kulinowski, Kristen M. Monteiro-Riviere, Nancy A. Oberdoerster, Guenter Omenn, Gilbert S. Pinkerton, Kent E. Ramos, Kenneth S. Rest, Kathleen M. Sass, Jennifer B. Silbergeld, Ellen K. Wong, Brian A. TI Meeting report: Hazard assessment for nanoparticles - Report from an interdisciplinary workshop SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE nanomaterials; nanoparticle; nanotechnology; nanotoxicology; particle toxicology ID ULTRAFINE PARTICLES; PARTICULATE MATTER AB In this report we present the findings from a nanotoxicology workshop held 6-7 April 2006 at the Woodrow Wilson International Center for Scholars in Washington, DC. Over 2 days, 26 scientists from government, academia, industry, and nonprofit organizations addressed two specific questions: what information is needed to understand the human health impact of engineered nanoparticles and how is this information best obtained? To assess hazards of nanoparticles in the near-term, most participants noted the need to use existing in vivo toxicologic tests because of their greater familiarity and interpretability. For all types of toxicology tests, the best measures of nanoparticle dose need to be determined. Most participants agreed that a standard set of nanoparticles should be validated by laboratories worldwide and made available for benchmarking tests of other newly created nanoparticles. The group concluded that a battery of tests should be developed to uncover particularly hazardous properties. Given the large number of diverse materials, most participants favored a tiered approach. Over the long term, research aimed at developing a mechanistic understanding of the numerous characteristics that influence nanoparticle toxicity was deemed essential. Predicting the potential toxicity of emerging nanoparticles will require hypothesis-driven research that elucidates how physicochemical parameters influence toxic effects on biological systems. Research needs should be determined in the context of the current availability of testing methods for nanoscale particles. Finally, the group identified general policy and strategic opportunities to accelerate the development and implementation of testing protocols and ensure that the information generated is translated effectively for all stakeholders. Key words: nanomaterials, nanoparticle, nanotechnology, nanotoxicology, particle toxicology. C1 Environm Def, Washington, DC 20009 USA. Woodrow Wilson Int Ctr Scholars, Washington, DC 20560 USA. Rice Univ, Houston, TX 77251 USA. NIOSH, Morgantown, WV USA. Procter & Gamble Co, Cincinnati, OH USA. US EPA, Res Triangle Pk, NC 27711 USA. US FDA, Rockville, MD 20857 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. N Carolina State Univ, Raleigh, NC 27695 USA. Univ Rochester, Rochester, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Louisville, Louisville, KY 40292 USA. Union Concerned Sci, Cambridge, MA USA. Nat Resources Def Council, Washington, DC USA. Hammer Inst Hlth Sci, Res Triangle Pk, NC USA. RP Balbus, JM (reprint author), Environm Def, 1875 Connecticut Ave NW 600, Washington, DC 20009 USA. EM jbalbus@environmentaldefense.org RI Maynard, Andrew/D-1076-2010; OI Omenn, Gilbert S./0000-0002-8976-6074; Maynard, Andrew/0000-0003-2117-5128 NR 13 TC 153 Z9 163 U1 5 U2 41 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2007 VL 115 IS 11 BP 1654 EP 1659 DI 10.1289/chp.10327 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 228YY UT WOS:000250769700034 PM 18007999 ER PT J AU Eppler, AR Kraeling, MEK Wickett, RR Bronaugh, RL AF Eppler, A. R. Kraeling, M. E. K. Wickett, R. R. Bronaugh, R. L. TI Assessment of skin absorption and irritation potential of arachidonic acid and glyceryl diffusion cell arachidonate using in vitro techniques SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE arachidonic acid (AA); glyceryl arachidonate (GA); percutaneous absorption; dermal penetration; skin irritation; alternative method ID INVITRO PERCUTANEOUS-ABSORPTION; METABOLISM; VIABILITY; RATS; VIVO AB Arachidonic acid (AA), a precursor of pro-inflammatory mediators, and its glycerin ester, glyceryl arachidonate (GA), are reportedly used in cosmetic products. In vitro skin penetration of AA and GA and GA's ester hydrolysis was determined in flow-through diffusion cells. AA penetration with human and rat skin was 19.5% and 52.3% of the applied dose respectively, a substantial amount of which remained in the skin at 24 h. Similar penetration results were obtained with GA in human skin. However, GA penetration through cultured skin (EpiDerm) was 51% of the applied dose, almost all of which appeared in the receptor fluid. At least 27.8% of GA penetrating skin was hydrolyzed to AA. In vitro methods were used to assess skin irritation in diffusion cells. Skin irritation of AA, sodium lauryl sulfate (SLS), and Tween 80 was determined by changes in transepidermal water loss (TEWL), skin viability (3-(4,5-dimethylthiaxol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, formation), and cytokine release (IL-1 alpha). SLS irritation was much less pronounced in an emulsion versus an aqueous vehicle. No significant irritation was observed in vitro from AA in an emulsion. This work predicts that AA would penetrate human skin in vivo and that it could be formed in skin from topically applied GA. (C) 2007 Elsevier Ltd. All rights reserved. C1 US FDA, Div Cosmet & Compliance, Off Cosmet & Colors, Laurel, MD USA. Univ Cincinnati, Coll Pharm, Cincinnati, OH USA. RP Eppler, AR (reprint author), Wyeth Consumer Healthcare, PO Box 26609, Richmond, VA 23261 USA. EM epplera@wyeth.com NR 29 TC 1 Z9 2 U1 1 U2 7 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 NOV PY 2007 VL 45 IS 11 BP 2109 EP 2117 DI 10.1016/j.fct.2007.05.004 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 232JE UT WOS:000251014400004 PM 17602815 ER PT J AU Bast, RC Thigpen, JT Arbuck, SG Basen-Engquist, K Burke, LB Freedman, R Horning, SJ Ozols, R Rustin, GJ Spriggs, D Wenzel, LB Pazdur, R AF Bast, Robert C. Thigpen, J. Tate Arbuck, Susan G. Basen-Engquist, Karen Burke, Laurie B. Freedman, Ralph Horning, Sandra J. Ozols, Robert Rustin, Gordon J. Spriggs, David Wenzel, Lari B. Pazdur, Richard TI Clinical trial endpoints in ovarian cancer: Report of an FDA/ASCO/AACR public workshop SO GYNECOLOGIC ONCOLOGY LA English DT Article DE CA125; cancer; endpoints; FDA; ovarian; research; therapy ID CA-125 AB Objective. The unique characteristics of cancer, particularly issues involving the use of surrogate endpoints in clinical trials, present special challenges in the development ofcancerdrugs. In response, the U.S. Food and Drug Administration (FDA) has partnered with the American Society of Clinical Oncology, the American Association for Cancer Research, and the American Society of Hematology to conduct public workshops evaluating potential endpoints for drug approvals for the most common tumor types. Methods. A workshop evaluating potential endpoints in ovarian cancer drug research was held in Bethesda, Maryland, in April 2006. Invited experts presented research findings and discussed endpoints in trials of drugs for treatment of Stage III and IV ovarian cancer. Results. The panel responded to specific questions from FDA, discussing use of progression-free survival as a surrogate for overall survival and use of CA-125 levels as an indicator of response. Panel members also addressed endpoints in first-line therapy, second-line and subsequent therapy, and maintenance therapy. Conclusion. Expert commentary provided by panel members will inform FDA's draft guidance on clinical endpoints for cancer drug approvals and will be discussed at meetings of the FDA's Oncologic Drugs Advisory Committee. FDA intends to develop a set of principles that can be used to define efficacy standards for drugs used to treat ovarian and other cancers. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Mississippi, Ctr Med, University, MS 38677 USA. MD Anderson Canc Ctr, Houston, TX USA. Schering Plough Res Inst, Kenilworth, NJ USA. US FDA, Rockville, MD 20857 USA. Stanford Univ, Ctr Canc, Stanford, CA 94305 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mt Vernon Canc Ctr, Northwood, Middx, England. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Irvine, Irvine, CA 92717 USA. RP Thigpen, JT (reprint author), Univ Mississippi, Ctr Med, University, MS 38677 USA. EM jtthigpen@att.net RI Bast, Robert/E-6585-2011 OI Bast, Robert/0000-0003-4621-8462 NR 5 TC 45 Z9 45 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2007 VL 107 IS 2 BP 173 EP 176 DI 10.1016/j.ygyno.2007.08.092 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 227KF UT WOS:000250654900005 PM 17950384 ER PT J AU Ilev, I Wilson, BC Backman, V Andersson-Engels, S AF Ilev, I. Wilson, B. C. Backman, V. Andersson-Engels, S. TI Introduction to the Special Issue on Biophotonics - Part 1 SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Editorial Material C1 [Ilev, I.] US FDA, Silver Spring, MD 20993 USA. [Wilson, B. C.] Univ Toronto, Ontario Canc Inst, Canadian Inst Photon Innovat, Biophoton Program, Toronto, ON M5G 2M9, Canada. [Backman, V.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Andersson-Engels, S.] Lund Univ, Med Laser Ctr, Div Atom Phys, SE-22100 Lund, Sweden. RP Ilev, I (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ilko.ilev@fda.hhs.gov RI Backman, Vadim/B-6689-2009; Andersson-Engels, Stefan/C-5515-2012 OI Andersson-Engels, Stefan/0000-0001-5640-3122 NR 0 TC 0 Z9 0 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2007 VL 13 IS 6 BP 1593 EP 1595 DI 10.1109/JSTQE.2007.912255 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 249UP UT WOS:000252255800001 ER PT J AU McNichol, BA Rasmussen, SB Carvalholt, HM Meysick, KC O'Brien, AD AF McNichol, Beth A. Rasmussen, Susan B. Carvalholt, Humberto M. Meysick, Karen C. O'Brien, Alison D. TI Two domains of cytotoxic necrotizing factor type I bind the cellular receptor, laminin receptor precursor protein SO INFECTION AND IMMUNITY LA English DT Article ID UROPATHOGENIC ESCHERICHIA-COLI; DERMONECROTIC TOXIN; RHO; CELLS; ACTIVATION; MECHANISM; CNF1; LOCALIZATION; PURIFICATION; DEAMIDATION AB Cytotoxic necrotizing factor type I (CNF1) and CNF2 are highly homologous toxins that are produced by certain pathogenic strains of Escherichia coli. These 1,014-amino-acid toxins catalyze the deamidation of a specific glutamine residue in RhoA, Rac1, and Cdc42 and consist of a putative N-terminal binding domain, a transmembrane region, and a C-terminal catalytic domain. To define the regions of CNF1 that are responsible for binding of the toxin to its cellular receptor, the laminin receptor precursor protein (LRP), a series of CNF1 truncated toxins were characterized and assessed for toxin binding. In particular, three truncated toxins, Delta N63, Delta N545, and Delta C469, retained conformational integrity and in vitro enzymatic activity and were immunologically reactive against a panel of anti-CNF1 monoclonal antibodies (MAbs). Based on a comparison of these truncated toxins with wild-type CNF1 and CNF2 in LRP and HEp-2 cell binding assays and in MAb and LRP competitive binding inhibition assays and based on the results of confocal microscopy, we concluded that CNF1 contains two major binding regions: one located within the N terminus, which contained amino acids 135 to 164, and one which resided in the C terminus and included amino acids 683 to 730. The data further indicate that CNF1 can bind to an additional receptor(s) on HEp-2 cells and that LRP can also serve as a cellular receptor for CNF2. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Joned Bridge Rd, Bethesda, MD 20814 USA. EM aobrien@usuhs.mil FU NIAID NIH HHS [AI38281, R01 AI038281] NR 36 TC 17 Z9 17 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 NOV PY 2007 VL 75 IS 11 BP 5095 EP 5104 DI 10.1128/IAI.00075-07 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 224MU UT WOS:000250451900004 PM 17709415 ER PT J AU Brahmbhatt, TN Janes, BK Stibitz, ES Darnell, SC Sanz, P Rasmussen, SB O'Brien, AD AF Brahmbhatt, Trupti N. Janes, Brian K. Stibitz, E. Scott Darnell, Stephen C. Sanz, Patrick Rasmussen, Susan B. O'Brien, Alison D. TI Bacillus anthracis exosporium protein Bc1A affects spore germination, interaction with extracellular matrix proteins, and hydrophobicity SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE HYDROPHOBICITY; IMMUNODOMINANT PROTEIN; EPITHELIAL-CELLS; CEREUS; ADHESION; IDENTIFICATION; THURINGIENSIS; HYDROCARBONS; SPORULATION; ADHERENCE AB Bacillus collagen-like protein of anthracis (BctA) is the immunodominant glycoprotein on the exosporium of Bacillus anthracis spores. Here, we sought to assess the impact of BclA on spore germination in vitro and in vivo, surface charge, and interaction with host matrix proteins. For that purpose, we constructed a markerless bclA null mutant in R anthracis Sterne strain 34F2. The growth and sporulation rates of the Delta bclA and parent strains were nearly indistinguishable, but germination of mutant spores occurred more rapidly than that of wild-type spores in vitro and was more complete by 60 min. Additionally, the mean time to death of A/J mice inoculated subcutaneously or intranasally with mutant spores was lower than that for the wild-type spores even though the 50% lethal doses of the two strains were similar. We speculated that these in vitro and in vivo differences between mutant and wild-type spores might reflect the ease of access of germinants to their receptors in the absence of BclA. We also compared the hydrophobic and adhesive properties of Delta bcLA and wild-type spores. The Delta bcLA spores were markedly less water repellent than wild-type spores, and, probably as a consequence, the extracellular matrix proteins laminin and fibronectin bound significantly better to mutant than to wild-type spores. These studies suggest that BclA acts as a shield to not only reduce the ease with which spores germinate but also change the surface properties of the spore, which, in turn, may impede the interaction of the spore with host matrix substances. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allerg Prod, Bethesda, MD 20892 USA. RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM aobrien@usuhs.mil FU AHRQ HHS [G173HS]; NIAID NIH HHS [R21 AI053397, AI53397, U54 AI057168, U54 AI57168] NR 27 TC 58 Z9 58 U1 0 U2 6 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 NOV PY 2007 VL 75 IS 11 BP 5233 EP 5239 DI 10.1128/IAI.00660-07 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 224MU UT WOS:000250451900018 PM 17709408 ER PT J AU Popa, I Zubkova, I Medvedovic, M Romantseva, T Mostowski, H Boyd, R Zaitseva, M AF Popa, Ileana Zubkova, Iryna Medvedovic, Mario Romantseva, Tatiana Mostowski, Howard Boyd, Richard Zaitseva, Marina TI Regeneration of the adult thymus is preceded by the expansion of K5(+)K8(+) epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE epithelial cell progenitors; gene arrays; thymic stroma; thymus regeneration; transcription factors ID THYMOCYTE DEVELOPMENT; GENE-EXPRESSION; FETAL THYMUS; STEM-CELLS; REAL-TIME; C-MYC; DIFFERENTIATION; RECONSTITUTION; MEDULLA; P63 AB Studies of HIV-1-infected individuals on anti-retroviral therapies and of patients receiving lymphoablating treatments indicate that the thymus retains restorative capacity even in adults. The contributions of the thymic epithelial cells (TECs) to the regeneration of the thymus and the identity of epithelial cell progenitors were evaluated in murine models of transient thymic atrophy followed by a complete regeneration. Using microarray approach, we analyzed the pattern of gene expression in TECs sorted from mice that were depleted of thymocytes by steroid treatment or by irradiation. The initial analysis identified significant increases in the mRNA for cMyc, Trp63 and Tcf3 transcription factors known to be expressed in early epithelial cell progenitors in tissues other than the thymus. Immunohistochemistry showed that in involuted thymuses, the cMyc and Trp63 proteins were expressed in a subset of cortical thymic epithelial cells (cTECs) that were keratin 5 positive (K5(+)), typifying cTEC precursors. Importantly, confocal microscopy established that epithelial cells with the phenotype of putative TEC progenitors (i.e. K5(+)K8(+)) expressed the Trp63 protein and confirmed that K5(+)K8(+) TEC progenitors expanded significantly during atrophy and prior to the thymic regeneration. Thus, our data demonstrated for the first time that critical steps in the recovery of the adult thymus include expansion of TEC progenitors and elevated expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. These results suggest that TEC progenitors could be reactivated in the adult thymus and, therefore, reactivation of TEC progenitors could provide a new approach for thymic reconstitution. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH 45267 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Monash Univ, Monash Immunol & Stem Cell Labs, Melbourne, Vic 3004, Australia. RP Zaitseva, M (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM zaitseva@cber.fda.gov NR 47 TC 22 Z9 25 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2007 VL 19 IS 11 BP 1249 EP 1260 DI 10.1093/intimm/dxm092 PG 12 WC Immunology SC Immunology GA 227TX UT WOS:000250681800001 PM 17823311 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI Exact one-tailed 100p% upper limits for future sample repeatability relative standard deviations obtained in single- and multilaboratory repeatability studies SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Formulas are derived to obtain exact one-tailed 100p% upper limits (kappa(p) and nu(p)) for future sample repeatability relative standard deviations, based on a noncentral t-distribution, for multi- and single-laboratory repeatability studies, respectively, used in the validation of analytical methods. C1 [McClure, Foster D.; Lee, Jung K.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat,Biostat Branch, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat,Biostat Branch, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM fdmc5100@yahoo.com NR 8 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 NOV-DEC PY 2007 VL 90 IS 6 BP 1701 EP 1705 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 243EC UT WOS:000251776800026 PM 18196644 ER PT J AU Parveen, S Taabodi, M Schwarz, JG Oscar, TP Harter-Dennis, J White, DG AF Parveen, Salina Taabodi, Maryam Schwarz, Jurgen G. Oscar, Thomas P. Harter-Dennis, Jeanine White, David G. TI Prevalence and antimicrobial resistance of salmonella recovered from processed poultry SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ANTIBIOTIC-RESISTANCE; CAMPYLOBACTER-JEJUNI; ANIMAL ORIGIN; UNITED-STATES; MULTIDRUG-RESISTANT; SAMPLING METHODS; CARCASSES; PROFILES; ENTERICA; FOODS AB This study was conducted to determine the prevalence and antimicrobial resistance of Salmonella isolates recovered from processed poultry. Four hundred eighty pre- and postchill whole broiler chicken carcasses were collected from a poultry processing plant between July 2004 and June 2005. Water samples also were collected at the entrance and exit of the chiller. After preenrichment, carcass and water samples were analyzed for the presence of Salmonella using the automated BAX system followed by traditional culture methods. The proportions of pre- and postchill carcasses that were positive for Salmonella were 88.4 and 84.1%, respectively. Ninety-two percent of water samples collected at the entrance of the chiller were positive for Salmonella, but all exit samples were negative. There was no significant difference in the prevalence of Salmonella between pre- and postchill carcasses (P > 0.05). Salmonella isolates recovered were serotyped and tested for susceptibility to antimicrobials. Thirteen serotypes were identified; the most common were Salmonella Kentucky (59.5%) and Salmonella Typhimurium (17.8%). Three hundred thirty-nine (79.8%).of the isolates were resistant to at least one antimicrobial, and 53.4% were resistant to three or more antimicrobials. Resistance was most often observed to tetracycline (73.4% of isolates), ampicillin (52.9%), amoxicillin-clavulanic acid (52%), ceftiofur (51.7%), streptomycin (35.2%), and sulfisoxazole (21.8%). These results indicate the high prevalence of Salmonella contamination in whole broiler carcasses, and a large number of these Salmonella isolates were resistant to commonly used antimicrobials. C1 Univ Maryland Eastern Shore, Food Sci & Technol Program, Dept Agr, Princess Anne, MD 21853 USA. USDA ARS, Princess Anne, MD 21853 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Parveen, S (reprint author), Univ Maryland Eastern Shore, Food Sci & Technol Program, Dept Agr, Princess Anne, MD 21853 USA. EM sparveen@umes.edu NR 47 TC 46 Z9 50 U1 0 U2 6 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 NOV PY 2007 VL 70 IS 11 BP 2466 EP 2472 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 228QH UT WOS:000250744100002 PM 18044422 ER PT J AU Abou-Zeid, KA Yoon, KS Oscar, TP Schwarz, JG Hashem, FM Whiting, RC AF Abou-Zeid, K. A. Yoon, K. S. Oscar, T. P. Schwarz, J. G. Hashem, F. M. Whiting, R. C. TI Survival and growth of listeria monocytogenes in broth as a function of temperature, pH, and potassium lactate and sodium diacetate concentrations SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LAG PHASE DURATION; ENHANCED INHIBITION; PREDICTIVE MODEL; SMOKED SALMON; 4-DEGREES-C; STORAGE; BEEF; PRODUCT; ACETATE; MEAT AB The objective of this study was to determine the antimicrobial effect of a combination of potassium lactate and sodium diacetate (0, 1.8, 3, and 4.5%; PURASAL P Opti.Forrn 4, 60% solution) on the survival and growth of Listeria monocytogenes Scott A in pH-adjusted broth (5.5, 6.0, 6.5, and 7.0) stored at 4, 10, 17, 24, 30, and 37 degrees C. Appropriate dilutions of broth were enumerated by spiral plating on tryptose agar and counted with an automated colony counter. Growth data were iteratively fit, using nonlinear regression analysis to a three-phase linear model, using GraphPad PRISM. At PH 5.5, the combination of lactate-diacetate fully inhibited (P < 0.001) the growth of L. monocytogenes at all four levels and six temperatures. At PH 6.0, addition of 1.8% lactate-diacetate reduced (P < 0.001) the specific growth rate of L. monocytogenes and increased lag time; however, 3 and 4.5% completely inhibited the growth at the six temperatures studied. Efficacy of the lactate-diacetate mixture was decreased as PH increased and incubation temperature increased. Thus, at PH 6.5, at least 3% was required to retard (P < 0.001) the growth of L. monocytogenes in broth. There was a limited effect of the lactate-diacetate level on the specific growth rate of the pathogen at pH 7.0. However, 1.8 and 3% significantly lengthened the lag time at 4 and 10 degrees C. These results suggest that 1.8% of lactate-diacetate mixture can be used as a substantial hurdle to the growth of L. monocytogenes when refrigerated temperatures are maintained for products with PH less than 6.5. C1 Univ Maryland Eastern Shore, Ctr Food Sci & Technol, USDA ARS, Princess Anne, MD 21853 USA. Univ Maryland Eastern Shore, Microbial Food Safety Res Unit, USDA ARS, Princess Anne, MD 21853 USA. Cornell Univ, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA. Kyung Hee Univ, Dept Food & Nutr, Seoul 130701, South Korea. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yoon, KS (reprint author), Univ Maryland Eastern Shore, Ctr Food Sci & Technol, USDA ARS, Princess Anne, MD 21853 USA. EM ksyoon@khu.ac.kr NR 33 TC 12 Z9 12 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 NOV PY 2007 VL 70 IS 11 BP 2620 EP 2625 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 228QH UT WOS:000250744100025 PM 18044445 ER PT J AU Puri, S Bhaskar, B Joshi, BH Moudgil, TL Ross, H Urba, WJ Fox, BA AF Puri, Sachin Bhaskar, Bhattacharva Joshi, Bharat H. Moudgil, Tarsem L. Ross, Helen Urba, Walter J. Fox, Bernard A. TI Gene expression profiling identifies unique molecular signature of non-small cell lung cancer cell lines derived from adenocarcinoma or squamous cell carcinoma tumor specimens SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Puri, Sachin; Moudgil, Tarsem L.; Ross, Helen; Urba, Walter J.; Fox, Bernard A.] Earle A Chiles Res Inst, Lab Mol & Tumorimmunol, Portland, OR USA. [Bhaskar, Bhattacharva; Joshi, Bharat H.] Ctr Biol Evaluat & Res, US FDA, Bethesda, MD USA. [Bhaskar, Bhattacharva] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Fox, Bernard A.] Dept Mol Microbiol & Immunol, OHSU, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 864 EP 864 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700038 ER PT J AU Darnell, MER Plant, EP Watanabe, H Byrum, R Claire, MS Ward, JM Taylor, DR AF Darnell, Miriam E. R. Plant, Ewan P. Watanabe, Hisayoshi Byrum, Russ Claire, Marisa St. Ward, Jerrold M. Taylor, Deborah R. TI Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PROTECTIVE IMMUNITY; NEUTRALIZING ANTIBODY; SPIKE GLYCOPROTEIN; SARS VACCINE; VIRUS; MICE; IMMUNIZATION; REPLICATION; DISEASES; TRACT AB Background. Development of vaccines to prevent severe acute respiratory syndrome (SARS) is limited by the lack of well-characterized animal models. Previous vaccine reports have noted robust neutralizing antibody and inflammatory responses in ferrets, resulting in enhanced hepatitis. Methods. We evaluated the humoral immune response and pathological end points in ferrets challenged with the Urbani strain of SARS-associated coronavirus (SARS-CoV) after having received formalin-inactivated whole-virus vaccine or mock vaccine. Results. Humoral responses were observed in ferrets that received an inactivated virus vaccine. Histopathological findings in lungs showed that infection of ferrets produced residual lung lesions not seen in both mock and vaccinated ferrets. SARS-CoV infection demonstrated bronchial and bronchiolar hyperplasia and perivascular cuffing in ferret lung tissue, as seen previously in infected mice. No evidence of enhanced disease was observed in any of the ferrets. All of the ferrets cleared the virus by day 14, 1 week earlier if vaccinated. Conclusions. The vaccine provided mild immune protection to the ferrets after challenge; however, there was no evidence of enhanced liver or lung disease induced by the inactivated whole-virus vaccine. The ferret may provide another useful model for evaluating SARS vaccine safety and efficacy. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Lab Hepatitis & Related Em, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20892 USA. NIAID, Comparat Med Branch, NIH, Bethesda, MD USA. Bioqual Inc, Rockville, MD USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Lab Hepatitis & Related Em, 8800 Rockville Pike,HFM-310,NIH Bldg 29A,1C-14, Bethesda, MD 20892 USA. EM Deborah.Taylor@FDA.HHS.gov OI Plant, Ewan/0000-0003-0166-5939 FU Intramural NIH HHS NR 28 TC 25 Z9 26 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2007 VL 196 IS 9 BP 1329 EP 1338 DI 10.1086/522431 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 218JC UT WOS:000250010800011 PM 17922397 ER PT J AU Swisher, JFA Khatri, U Feldman, GM AF Swisher, Jennifer F. A. Khatri, Utsha Feldman, Gerald M. TI Annexin A2 is a soluble mediator of macrophage activation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE mAP kinase signaling; NF-kappa B signaling; inflammatory cytokines; phagocytosis ID MONOCYTE-DERIVED MACROPHAGES; TISSUE-PLASMINOGEN ACTIVATOR; INTERCELLULAR-ADHESION MOLECULE-1; INCREASES OSTEOCLAST FORMATION; ENDOTHELIAL-CELL RECEPTOR; KINASE ACTIVATION; T-LYMPHOCYTES; BINDING; EXPRESSION; CYTOMEGALOVIRUS AB On the surface of the macrophage, annexin A2 tetramer (A2t) serves as a docking protein or recognition element for bacterial and viral pathogens. Plasma levels of free A2t have been reported to increase following infection, although the mechanistic significance of this observation is unclear. Although annexin A2 had generally been thought to play an anti-inflammatory role, soluble A2t stimulates MAP kinase activity in bone marrow stromal cells downstream of a recently cloned receptor. This raises the question of whether A2t activates human macrophages via MAP kinases and whether it might be capable of acting as an inflammatory mediator. To this end, human monocyte-derived macrophages were treated with soluble A2t and MAP kinase phosphorylation, p65 NF-kappa B activation, and inflammatory mRNA and protein levels were measured. It was found that A2t caused rapid phosphorylation of several MAP kinases, as well as translocation of p65 NF-kappa B to the nucleus. A2t stimulated the production of TNF-alpha, IL-1 beta, and IL-6, as well as several members of the chemokine family within 24 h, which are capable of recruitment and/or activation of a broad range of leukocyte classes. Furthermore, A2t-activated macrophages demonstrated enhanced phagocytic ability for the ingestion of GFP-expressing Escherichia coli. These data are the first to suggest the participation of an annexin in microbial clearance, as well as the establishment of inflammation and the immune response, including the recruitment and activation of immune cells to the site of infection. C1 US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies,Lab Mol & Dev Immunol, Bethesda, MD 20892 USA. RP Feldman, GM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies,Lab Mol & Dev Immunol, Bldg 29A,Rm 3C22,29 Lincoln Dr,HFD-123, Bethesda, MD 20892 USA. EM gerald.feldman@fda.hhs.gov NR 51 TC 46 Z9 49 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2007 VL 82 IS 5 BP 1174 EP 1184 DI 10.1189/jlb.0307154 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 225JT UT WOS:000250514900018 PM 17715360 ER PT J AU Woods, TO AF Woods, Terry O. TI Standards for medical devices in MRI: Present and future SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Review DE MRI safety; medical devices; implants; MR environment; standard test method AB The purpose of this review is to define the current standards addressing safety of medical devices in MRI and to describe ongoing standards development efforts. The American Society for Testing and Materials (ASTM International) began developing standard test methods for determining the MR safety of medical devices in MRI in 1997. To date, five ASTM standards addressing testing and marking medical devices and other items for use in the MR environment have been published. International Standards Organization (ISO) 14630, the general requirements standard for nonactive surgical implants, is currently being revised to include information about MR safety of passive implants and to reference the ASTM standards. To address the unique safety issues of active implants, and in particular active implants with leads, like pacemakers and neuro-stimulators, a joint working group between ISO TC150/SC6 on active implants and International Electrotechnical Commission (IEC) SC 62B MT40 on magnetic resonance equipment for medical diagnosis is working to develop a technical specification for active implantable medical devices (AIMDs) in MRI. While much progress has been made, work still needs to continue to develop a complete body of test methods to allow the evaluation of the safety of medical devices in the MR environment. C1 US FDA, Silver Spring, MD 20993 USA. RP Woods, TO (reprint author), US FDA, 10903 New Hempshire Ave,WO62-2116, Silver Spring, MD 20993 USA. EM terry.woods@fda.hhs.gov NR 9 TC 43 Z9 44 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2007 VL 26 IS 5 BP 1186 EP 1189 DI 10.1002/jmri.21140 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 225SR UT WOS:000250538300005 PM 17969160 ER PT J AU Soneson, JE Myers, MR AF Soneson, Joshua E. Myers, Matthew R. TI Gaussian representation of high-intensity focused ultrasound beams SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AMPLITUDE SOUND BEAMS; ACOUSTIC-WAVES AB A method for fast numerical simulation of high-intensity focused ultrasound beams is derived. The method is based on the frequency-domain representation of the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation, and assumes for each harmonic a Gaussian transverse pressure distribution at all distances from the transducer face. The beamwidths of the harmonies are constrained to vary inversely with the square root of the harmonic number, and as such this method may be viewed as an extension of a quasilinear approximation. The technique is capable of determining pressure or intensity fields of moderately nonlinear high-intensity focused ultrasound beams in water or biological tissue, usually requiring less than a minute of computer time on a modem workstation. Moreover, this method is particularly well suited to high-gain simulations since, unlike traditional finite-difference methods, it is not subject to resolution limitations in the transverse direction. Results are shown to be in reasonable agreement with numerical solutions of the full KZK equation in both tissue and water for moderately nonlinear beams. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Soneson, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.soneson@fda.hhs.gov; matthew.myers@fda.hhs.gov NR 13 TC 18 Z9 18 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 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2007 VL 122 IS 5 BP 2526 EP 2531 DI 10.1121/1.2783124 PN 1 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 224MT UT WOS:000250451800005 PM 18189543 ER PT J AU Hotchkiss, CE Wang, C Slikker, W AF Hotchkiss, Charlotte E. Wang, Cheng Slikker, William, Jr. TI Effect of prolonged ketamine exposure on cardiovascular physiology in pregnant and infant rhesus monkeys (Macaca mulatta) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID BLOOD-PRESSURE; CYNOMOLGUS MONKEYS; PARAMETERS; HEART; NEURODEGENERATION; FASCICULARIS; ADAPTATION; RESTRAINT; SYSTEM; BRAIN AB Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO2, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection. The subjects were pregnant monkeys at gestational day 120 to 123, infants 5 to 6 d old, and infants 35 to 37 d old. Heart rate and blood pressure were lower in ketamine-treated monkeys than physically restrained monkeys. Heart rate was higher in infants than adults, whereas blood pressure was lower in infants. Respiratory rate was higher in infants than adults and higher in physically restrained infants than ketamine-s e dated infants but was not affected by ketamine in pregnant adults. Hematocrit was decreased in older infants. In summary, both physical restraint and ketamine sedation altered several physiologic parameters in pregnant and infant rhesus macaques. Investigators should consider these effects when designing experiments and evaluating experimental outcomes in monkeys. C1 [Hotchkiss, Charlotte E.] Bionet Corp, Jefferson, AR 72079 USA. [Wang, Cheng; Slikker, William, Jr.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Hotchkiss, CE (reprint author), Bionet Corp, Jefferson, AR 72079 USA. EM chotchki@wanprc.org NR 37 TC 14 Z9 14 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 NOV PY 2007 VL 46 IS 6 BP 21 EP 28 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 258IX UT WOS:000252862700003 PM 17994669 ER PT J AU Badano, A Kyprianou, IS Jennings, RJ Sempau, J AF Badano, Aldo Kyprianou, Iacovos S. Jennings, Robert J. Sempau, Josep TI Anisotropic imaging performance in breast tomosynthesis SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo simulation; digital imaging; phosphor screen; cesium iodide; point response function; Swank factor ID MONTE-CARLO-SIMULATION; CESIUM IODIDE SCINTILLATORS; RAY FLUORESCENT SCREENS; POINT-SPREAD FUNCTION; X-RAY; DIGITAL MAMMOGRAPHY; CODE PENELOPE; COLUMNAR PHOSPHORS; ELECTRON; EFFICIENCY AB We describe the anisotropy in imaging performance caused by oblique x-ray incidence in indirect detectors for breast tomosynthesis based on columnar scintillator screens. We use MANTIS, a freely available combined x-ray, electron, and optical Monte Carlo transport package which models the indirect detection processes in columnar screens, interaction by interaction. The code has been previously validated against published optical distributions. In this article, initial validation results are provided concerning the blur for particular designs of phosphor screens for which some details with respect to the columnar geometry are available from scanning electron microscopy. The poly-energetic x-ray spectrum utilized comes from a database of experimental data for three different anode/filter/kVp combinations: Mo/Mo at 28 kVp, Rh/Rh at 28 kVp, and W/A1 at 42 kVp. The x-ray spectra were then filtered with breast tissue (3, 4, and 6 cm thickness), compression paddle, and support base, according to the oblique paths determined by the incidence angle. The composition of the breast tissue was 50% /50% adipose/glandular tissue mass ratio. Results are reported on the pulse-height statistics of the light output and on spatial blur, expressed as the response of the detector to a pencil beam with a certain incidence angle. Results suggest that the response is nonsymmetrical and that the resolution properties of a tomosynthesis system vary significantly with the angle of x-ray incidence. In contrast, it is found that the noise due to the variability in the number of light photons detected per primary x-ray interaction changes only a few percent. The anisotropy in the response is not less in screens with absorptive backings while the noise introduced by variations in the depth-dependent light output and optical transport is larger. The results suggest that anisotropic imaging performance across the detector area can be incorporated into reconstruction algorithms for improving the image quality of breast tomosynthesis. This study also demonstrates that the assessment of image quality of breast tomosynthesis systems requires a more complete description of the detector response beyond local, center measurements of resolution and noise that assume some degree of symmetry in the detector performance. (C) 2007 American Association of Physicists in Medicine. C1 US FDA, CDRH NIBIB Lab Anal Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. Univ Politecn Cataluna, Inst Tecn Energet, E-08028 Barcelona, Spain. RP Badano, A (reprint author), US FDA, CDRH NIBIB Lab Anal Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 FU Intramural NIH HHS NR 40 TC 25 Z9 25 U1 0 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 NOV PY 2007 VL 34 IS 11 BP 4076 EP 4091 DI 10.1118/1.2779943 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234FK UT WOS:000251145900002 PM 18074617 ER PT J AU Braun, LE Sutter, DE Eichelberger, MC Pletneva, L Kokai-Kun, JF Blanco, JCG Prince, GA Ottolini, MG AF Braun, LoRanee E. Sutter, Deena E. Eichelberger, Maryna C. Pletneva, Lioubov Kokai-Kun, John F. Blanco, Jorge C. G. Prince, Gregory A. Ottolini, Martin G. TI Co-infection of the cotton rat (Sigmodon hispidus) with Staphylococcus aureus and influenza A virus results in synergistic disease SO MICROBIAL PATHOGENESIS LA English DT Article DE cotton rat; Sigmodon hispidus; influenza; Staphylococcus aureus; co-infection ID PANTON-VALENTINE LEUKOCIDIN; RESPIRATORY SYNCYTIAL VIRUS; STREPTOCOCCUS-PNEUMONIAE; HOST-DEFENSE; INFECTION; MICE; CYTOKINE; SEPSIS; GENE; EPIDEMIOLOGY AB Bacterial super-infection of influenza patients is the primary cause of excess mortality during influenza pandemics, with Staphylococcus aureus (S. aureus) having the highest fatality rate. The cotton rat (Sigmodon hispidus) is an excellent model for both influenza and S. aureus pathogenesis, and therefore a potential tool to model co-infection. We compared physiologic and pathologic changes in cotton rats infected with both S. aureus and influenza A/Wuhan/359/95 (H3N2), with animals infected with each pathogen alone. Co-infected cotton rats demonstrated significantly higher mortality, lower temperatures on 2 and 3 days post-inoculation (p.i.), higher levels of bacteremia and pulmonary bacterial load 4 days p.i., and worse pathology 7 days p.i. Early indicators of exacerbated disease coincided with higher pulmonary mRNA levels for IL-1 beta, IL-6, IL-10 and IFNy, supporting the idea that these may contribute to disease severity. Our results demonstrate that the cotton rat is a good model of influenza and S. aureus co-infection, with increased mortality and hypothermia as well as prolonged bacterial duration indicative of synergistic disease that may be the result of increased induction of both pro- and anti-inflammatory cytokines. (C) 2007 Elsevier Ltd. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pediat, Bethesda, MD 20814 USA. Virion Syst Inc, Rockville, MD 20850 USA. Biosynexus Inc, Gaithersburg, MD USA. RP Eichelberger, MC (reprint author), US FDA, CBER, Div Viral Prod, 8800 Rockville Pike,29B 1N-N15, Bethesda, MD 20892 USA. EM Maryna.Eichelberger@fda.hhs.gov NR 32 TC 12 Z9 12 U1 0 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD NOV-DEC PY 2007 VL 43 IS 5-6 BP 208 EP 216 DI 10.1016/j,micpath.2007.03.005 PG 9 WC Immunology; Microbiology SC Immunology; Microbiology GA 220ZB UT WOS:000250194800005 PM 17689046 ER PT J AU Shi, L AF Shi, Leming TI MAQC: The microarray quality control project SO MOLECULAR & CELLULAR TOXICOLOGY LA English DT Meeting Abstract C1 [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KOREAN SOC TOXICOGENOMICS & TOXICOPROTEOMICS PI SEOUL PA KOREA INST SCIENCE & TECHNOLOGY, PO BOX 131 CHEONGRYANG, SEOUL, 130-650, SOUTH KOREA SN 1738-642X J9 MOL CELL TOXICOL JI Mol. Cell. Toxicol. PD NOV 1 PY 2007 VL 3 IS 4 SU S BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 229SK UT WOS:000250824400004 ER PT J AU Vogelbaum, MA Sampson, JH Kunwar, S Chang, SM Shaffrey, M Asher, AL Lang, FF Croteau, D Parker, K Grahn, AY Sherman, JW Husain, SR Puri, RK AF Vogelbaum, Michael A. Sampson, John H. Kunwar, Sandeep Chang, Susan M. Shaffrey, Mark Asher, Anthony L. Lang, Frederick F. Croteau, David Parker, Kristen Grahn, Amy Y. Sherman, Jeffrey W. Husain, S. Rafat Puri, Raj K. TI Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: Phase 1 study of final safety results SO NEUROSURGERY LA English DT Article DE cintredekin besudotox; convection-enhanced delivery; malignant glioma ID PSEUDOMONAS EXOTOXIN; 1ST RELAPSE; RECEPTOR; INFUSION; PROTEIN; BRAIN; GLIOBLASTOMA; CYTOTOXIN; TUMORS; TRIAL AB OBJECTIVE: Cintredekin besuclotox (CB), a recombinant cytotoxin consisting of interleukin-1 3 and truncated Pseudomonas exotoxin, binds selectively to interleukin-13R alpha 2 receptors overexpressed by malignant gliomas. This study assessed the safety of CB administered by convection-enhanced delivery followed by standard external beam radiation therapy (EBRT) with or without temozolomide (Temodar; Schering-Plough, Kenilworth, NJ) in patients with newly diagnosed malignant gliomas. METHODS: After gross total resection of the tumor, two to four intraparenchymal catheters were stereotactically placed and CB (0.25 or 0.5 mu g/mL) was infused for 96 hours. This was followed, 10 to 14 days later, by EBRT (5940-6100 cGy, 5 d/wk for 6-7 wk) with or without temozolomide (75 mg/m(2)/d, 7 d/wk during EBRT). Safety was assessed during an I I-week observation period after catheter placement RESULTS: Twenty-two patients (12 men, 10 women; median age, 55 yr; 21 with glioblastoma multiforme and one with an anaplastic mixed oligoastrocytoma) were enrolled. None of the patients experienced dose-limiting toxicities in the first two cohorts (0.25 mu g/mL CB + EBRT [n = 3] and 0.25 mu g/mL CB + EBRT + temozolomide [n = 3]). One patient experienced a dose-limiting toxicity (Grade 4 seizure) in the third cohort (0.5 mu g/mL CB + EBRT [n = 6]). Six patients in the final cohort (0.5 mu g/mL CB + EBRT + temozolomide [n = 10]) completed treatment, and one patient experienced a dose-limiting toxicity (Grade 3 aphasia and confusion). Four patients were not considered evaluable for a dose decision and were replaced. CB related adverse events occurring in more than one patient were fatigue, gait disturbance, nystagmus, and confusion. No Grade 3 to 4 hematological toxicities were observed. CONCLUSION: CB (0.5 mu g/mL) administered via convection-enhanced delivery before standard radiochemotherapy seems to be well tolerated in adults with newly diagnosed malignant gliomas. Further clinical study assessment is warranted. C1 [Vogelbaum, Michael A.] Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Sampson, John H.] Duke Univ, Dept Neurosurg, Durham, NC USA. [Kunwar, Sandeep; Chang, Susan M.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Shaffrey, Mark] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA. [Asher, Anthony L.] Carolina Neurosurg & Spine Assoc, Charlotte, NC USA. [Lang, Frederick F.] MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX USA. [Parker, Kristen; Grahn, Amy Y.; Sherman, Jeffrey W.] NeoPharm Inc, Waukegan, IL USA. [Husain, S. Rafat; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Vogelbaum, MA (reprint author), Cleveland Clin Fdn, Brain Tumor & Neurooncol Ctr, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM vogelbm@neus.ccf.org FU NCI NIH HHS [R01 CA097611]; NCRR NIH HHS [K23 RR16065]; NINDS NIH HHS [2P50-NS20023] NR 32 TC 78 Z9 78 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2007 VL 61 IS 5 BP 1031 EP 1037 DI 10.1227/01.NEU.0000280092.91489.08 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 240VY UT WOS:000251617500030 PM 18091279 ER PT J AU Ferguson, SA Cisneros, FJ Hanig, JP Berry, KJ AF Ferguson, Sherry A. Cisneros, F. Javier Hanig, Joseph P. Berry, Kimberly J. TI Oral treatment with ACCUTANE (R) does not increase measures of anhedonia or depression in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE ACCUTANE; retinoic acid; isotretinoin; depression; anhedonia; forced swim test ID CHRONIC MILD STRESS; FORCED SWIMMING TEST; SPRAGUE-DAWLEY RATS; ADULT HIPPOCAMPAL NEUROGENESIS; TRANS-RETINOIC ACID; STEADY-STATE PHARMACOKINETICS; 13-CIS-RETINOIC ACID; ISOTRETINOIN THERAPY; ANIMAL-MODEL; FEMALE RATS AB Reports of depression and/or suicide with ACCUTANE (R) (13-cis-retinoic acid (13-cis-RA)) use prompted studies in a rodent model to ascertain its potential effects. Previously, there were no effects on measures of anhedonia (intake of a saccharin-flavored solution) and depression (forced swim test (FST) behaviors) in rats treated with 7.5 or 22.5 mg/kg 13-cis-RA [S.A. Ferguson, F.J. Cisneros, B. Gough, J.P. Hanig, K.J. Berry, Chronic oral treatment with 13-cis-retinoic acid (isotretinoin) or all-trans-retinoic acid does not alter depression-like behaviors in rats, Toxicol. Sci. 87 (2005) 451-459.]. Here, dose and temporal thresholds were investigated by increasing the maximum 13-cis-RA dose to 30 mg/kg, extending treatment duration, and measuring behaviors repeatedly. Beginning on post-natal day 59, male and female Sprague-Dawley rats were gavaged with soybean oil, 7.5 or 30 mg/kg/day of 13-cis-RA for approximately 19 weeks. FST behaviors were measured after 24, 82, and 131 treatment days and saccharin intake (0.03% solution) was measured at baseline and after 14, 35, 56, and 112 treatment days. Body weight and food intake were not altered by treatment. FST durations of swim, climb/struggle, and immobility were unaffected by 13-cis-RA at any time during treatment. More males than females required "rescue" in the FST but there was no treatment effect on number of rats requiring early removal. 13-cis-RA treatment had no effects on saccharin intake at any time. Given that the 7.5 mg/kg dose produces serum levels which parallel those of humans [S.A. Ferguson, P.H. Siitonen, F.J. Cisneros, B. Gough, J.F. Young, Steady state pharmacokinetics; of oral treatment with 13-cis-retinoic acid or all-trans-retinoic acid in male and female adult rats, Basic Clin. Pharmacol. Toxicol 98 (2006) 582-587.], these results are quite relevant. Combined with previous results, these results provide further evidence that 13-cis-RA does not produce behavioral alterations indicative of depression in rats. (c) 2007 Elsevier Inc. All rights reserved. C1 [Ferguson, Sherry A.; Berry, Kimberly J.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Cisneros, F. Javier] Charles River Labs, Preclin Serv, Horsham, PA 19044 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Ferguson, SA (reprint author), Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 85 TC 13 Z9 13 U1 1 U2 5 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 NOV-DEC PY 2007 VL 29 IS 6 BP 642 EP 651 DI 10.1016/j.ntt.2007.09.003 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 242AP UT WOS:000251697200006 PM 17933491 ER PT J AU Ning, YM He, K Dagher, R Sridhara, R Farrell, AT Justice, R Pazdur, R AF Ning, Yang-Min He, Kun Dagher, Ramz Sridhara, Rajeshwari Farrell, Ann T. Justice, Robert Pazdur, Richard TI Liposomal doxorubicin in combination with bortezomib for relapsed or refractory multiple myeloma SO ONCOLOGY-NEW YORK LA English DT Article ID DRUG-ADMINISTRATION APPROVAL; HIGH-DOSE DEXAMETHASONE; THERAPY; MM AB Purpose: On May 17, 2007, doxorubicin HCl liposome injection (Doxil) in combination with bortezomib (Velcade) received approval from the US Food and Drug Administration (FDA) for the treatment of relapsed or refractory multiple myeloma after at least one prior therapy that has not included bortezomib. Liposomal doxorubicin's efficacy and safety were demonstrated in a phase III, randomized, multicenter, international trial comparing the combination of this agent plus bortezomib vs bortezomib alone in multiple myeloma patients who had not previously received bortezomib and had received at least one prior therapy. Here we summarize the FDA review of the data that support this approval. Experimental Design and Results: An interim analysis of time to disease progression (TTP), the primary end point, was conducted after 249 TTP events in this study that randomized 324 patients to liposomal doxorubicin plus bortezomib treatment and 322 patients to bortezomib monotherapy. Time to progression was significantly prolonged in the combination arm (median TTP = 9.3 months) compared with bortezomib monotherapy (median TTP = 6.5 months), P <.0001 (log-rank test); hazard ratio = 0.55 (95% confidence interval = 0.43-0.71). The response rates were similar between the two arms and not statistically different; however, among responding patients, the median duration of response was longer with the combination-10.2 months compared to 7.0 months in the monotherapy arm. Adverse reactions occurred more frequently with the combination therapy. As compared to the monotherapy, frequent grade 314 adverse reactions with the combination were neutropenia and thrombocytopenia. Conclusions: Liposomal doxorubicin received FDA approval for use in combination with bortezomib inpatients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy. C1 [Ning, Yang-Min; He, Kun; Dagher, Ramz; Sridhara, Rajeshwari; Farrell, Ann T.; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD USA. RP Ning, YM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD USA. EM ningy@cder.fda.gov NR 9 TC 25 Z9 26 U1 1 U2 6 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2007 VL 21 IS 12 BP 1503 EP 1508 PG 6 WC Oncology SC Oncology GA 270RU UT WOS:000253738700010 PM 18077994 ER PT J AU Matchette, LS Agrawal, A Pfefer, TJ AF Matchette, L. Stephanie Agrawal, Anant Pfefer, T. Joshua TI Fluoroquinolone antibiotics having the potential to interfere with fluorescence-based diagnosis SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID LASER-INDUCED FLUORESCENCE; EXCITATION WAVELENGTHS; TISSUE CONCENTRATIONS; SUBMUCOUS FIBROSIS; CIPROFLOXACIN; PENETRATION; AUTOFLUORESCENCE; SPECTROSCOPY; OFLOXACIN; COLLAGEN AB Fluorescence, both intrinsic and exogenously induced, is being used for diagnosis of abnormal tissue. Excitation wavelengths used by these methods range from 320 to 450 nm. The presence of absorbing or fluorescing drugs is rarely taken into account by practitioners of fluorescence diagnosis and has the potential to yield false-positive or false-negative results. Our aim is to quantify this potential by (1) comparing the quantum yield of fluoroquinolone antibiotics to those of known tissue fluorophores and (2) taking into account drug concentrations in the tissue during treatment. Quantum yields are determined relative to a working standard of Rhodamine 6G in ethanol. The working standard was calibrated against a fluorescein standard. We concentrated our initial efforts on (1) the fluoroquinolone antibiotics, ciprofloxacin, norfloxacin and ofloxacin and (2) the intrinsic tissue fluorophores, NADH, FAD and protoporphyrin IX. When ciprofloxacin, norfloxacin and ofloxacin were excited at wavelengths 310-390 nm, emission occurred from 350 to 650 urn with quantum yields ranging from 0.03 to 0.3. Quantum yields for intrinsic fluorophores excited at their peak absorption wavelengths were 0.02 (NADH, 340 nm), 0.035 (FAD, 450 nm) and 0.087 (protoporphyrin IX, 408 nm). A review of the literature shows that these fluoroquinolones have a large volume of distribution and can be found in high concentrations in almost every organ during a treatment regimen. The product of the drug tissue concentration and quantum yield, which we term the fluorescence effective concentration, is such that it is likely these fluoroquinolones will interfere during fluorescence diagnosis techniques. C1 US FDA, CDRH, Silver Spring, MD USA. RP Matchette, LS (reprint author), US FDA, CDRH, Silver Spring, MD USA. EM joshua.pfefer@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 42 TC 3 Z9 3 U1 2 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2007 VL 83 IS 6 BP 1386 EP 1393 DI 10.1111/j.1751-1097.2007.00175.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 236HQ UT WOS:000251294100014 PM 18028213 ER PT J AU Baker, CA Davison, D Jones, L AF Baker, C. A. Davison, D. Jones, L. TI Impatiens necrotic spot virus and Tomato spotted wilt virus diagnosed in Phalaenopsis orchids from two Florida nurseries SO PLANT DISEASE LA English DT News Item C1 FDACS, Div Plant Ind, Gainesville, FL 32614 USA. RP Baker, CA (reprint author), FDACS, Div Plant Ind, Gainesville, FL 32614 USA. NR 4 TC 3 Z9 3 U1 1 U2 4 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0191-2917 J9 PLANT DIS JI PLANT DIS. PD NOV PY 2007 VL 91 IS 11 BP 1515 EP 1515 DI 10.1094/PDIS-91-11-1515A PG 1 WC Plant Sciences SC Plant Sciences GA 221VE UT WOS:000250254700031 ER PT J AU Mitnick, CD Castro, KG Harrington, M Sacks, LV Burman, W AF Mitnick, Carole D. Castro, Kenneth G. Harrington, Mark Sacks, Leonard V. Burman, William TI Randomized trials to optimize treatment of multidrug-resistant tuberculosis SO PLOS MEDICINE LA English DT Editorial Material ID COST-EFFECTIVENESS; MYCOBACTERIUM-TUBERCULOSIS; DRUG DEVELOPMENT; COHORT; SURVEILLANCE; FEASIBILITY; EFFICACY; REGIMEN; PERU; TB C1 [Mitnick, Carole D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Harrington, Mark] Treatment Act Grp, New York, NY USA. [Sacks, Leonard V.] US FDA, Rockville, MD 20857 USA. [Burman, William] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Burman, William] Denver Publ Hlth Sch, Denver, CO USA. [Castro, Kenneth G.] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. RP Mitnick, CD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM carole_mitnick@hms.harvard.edu NR 37 TC 48 Z9 49 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2007 VL 4 IS 11 BP 1730 EP 1734 AR e292 DI 10.1371/journal.pmed.0040292 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 244OE UT WOS:000251874400009 PM 17988168 ER PT J AU Curtis, JR Kramer, JM Martin, C Saag, KG Patkar, N Shatin, D Burgess, M Xie, A Braun, MM AF Curtis, J. R. Kramer, J. M. Martin, C. Saag, K. G. Patkar, N. Shatin, D. Burgess, M. Xie, A. Braun, M. M. TI Heart failure among younger rheumatoid arthritis and Crohns patients exposed to TNF-alpha antagonists SO RHEUMATOLOGY LA English DT Article DE heart failure; rheumatoid arthritis; Crohn's disease; infliximab; etanercept; TNF-alpha antagonists; adverse events ID DISEASE; RISK; THERAPY AB Objectives. New onset heart failure (HF) has been associated with the use of TNF-alpha antagonists etanercept and infliximab based upon spontaneous adverse event reports. HF clinical trials of these agents were stopped early due to futility or worsening of existing HF. A potential association between etanercept and infliximab and new onset HF has been studied minimally at a population level. Methods. Using administrative claims from a large U. S. health care organization, we identified rheumatoid arthritis (RA) and Crohn's disease (CD) patients receiving infliximab or etanercept (exposed), and comparator cohorts of RA and CD patients receiving non-biologic immunosuppressives (unexposed). We studied adults < 50 years to reduce potential confounding related to common age-related comorbidities. Based on abstracted medical records of suspected HF cases, a physician panel adjudicated cases as definite, possible or no HF. Results. Among 4018 RA and CD patients with mean duration follow-up of 18 months, 9 of 33 suspected HF cases (identified using claims data) were adjudicated as definite (n = 5) or possible (n = 4) HF. The relative risk of HF among TNF-alpha antagonist-treated RA and CD patients was 4.3 and 1.2, respectively (P = NS for both). The absolute difference in cumulative incidence of HF among infliximab or etanercept-exposed compared to unexposed patients was 3.4 and 0.3 cases per 1000 persons for RA and CD (P = NS), respectively, yielding a number needed to harm of 294 for RA and 3333 for CD. Conclusion. We found only a small number of presumed HF cases (n = 9, or 0.2%) in a large population of relatively young RA and CD patients. Although there was an increased relative risk of incident, HF that was not statistically significant among those exposed to TNF-alpha antagonists compared to those unexposed, larger cohorts are needed to provide more precise risk estimates and permit adjustment for potential confounding. C1 US FDA, Div Epidemiol, Rockville, MD 20852 USA. Univ Alabama, Ctr Educ & Res Therapeut Musculoskeletal Disorder, Birmingham, AL USA. Duke Univ, Ctr Educ & Res Therapeut Cardiovasc Dis, Durham, NC USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Braun, MM (reprint author), US FDA, Div Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. EM braunm@cber.fda.gov FU AHRQ HHS [HS10389, U18 HS010389]; NIAMS NIH HHS [K23 AR053351-01A1, K23 AR053351, T32 AR047512, K24 AR052361-01, T32 AR47512-03, K24 AR052361] NR 13 TC 37 Z9 37 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2007 VL 46 IS 11 BP 1688 EP 1693 DI 10.1093/rheumatology/kem212 PG 6 WC Rheumatology SC Rheumatology GA 227RQ UT WOS:000250675900012 PM 17938138 ER PT J AU Miliotis, M AF Miliotis, Marianne TI Role of microbial risk assessment in food safety SO SAMJ SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article C1 [Miliotis, Marianne] US FDA, Rockville, MD 20857 USA. RP Miliotis, M (reprint author), US FDA, Rockville, MD 20857 USA. EM marianna.miliotis@fda.hhs.gov NR 23 TC 1 Z9 2 U1 1 U2 1 PU SA MEDICAL ASSOC PI PRETORIA PA BLOCK F CASTLE WALK CORPORATE PARK, NOSSOB STREET, ERASMUSKLOOF EXT3, PRETORIA, 0002, SOUTH AFRICA SN 0256-9574 J9 SAMJ S AFR MED J JI SAMJ S. Afr. Med. J. PD NOV PY 2007 VL 97 IS 11 BP 1211 EP 1214 PN 3 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 243WU UT WOS:000251828800021 PM 18250940 ER PT J AU Portilla, D Schnackenberg, L Beger, RD AF Portilla, Didier Schnackenberg, Laura Beger, Richard D. TI Metabolomics as an extension of proteomic analysis: Study of acute kidney injury SO SEMINARS IN NEPHROLOGY LA English DT Review DE metabolomics; acute kidney injury; cisplatin; nuclear magnetic resonance; mass spectrometry ID CISPLATIN-INDUCED NEPHROTOXICITY; H-1-NMR-BASED METABONOMICS; PATTERN-RECOGNITION; OXIDATIVE STRESS; DEFICIENT MICE; PPAR-ALPHA; METABOLISM; RATS; NMR; LIVER AB Although proteomics studies the global expression of proteins, metabolomics characterizes and quantifies their end products: the metabolites, produced by an organism under a certain set of conditions. From this perspective it is apparent that proteomics and metabolomics are complementary and when joined allow a fuller appreciation of an organism's phenotype. Our studies using H-1-nuclear magnetic resonance spectroscopic analysis showed the presence of glucose, amino acids, and trichloroacetic acid cycle metabolites in the urine after 48 hours of cisplatin administration. These metabolic alterations precede changes in serum creatinine. Biochemical studies confirmed the presence of glucosuria, but also showed the accumulation of nonesterified fatty acids, and triglycerides in serum, urine, and kidney tissue, despite increased levels of plasma insulin. These metabolic alterations were ameliorated by the use of fibrates. We propose that the injury-induced metabolic profile may be used as a biomarker of cisplatin-induced nephrotoxicity. These studies serve to illustrate that metabolomic studies add insight into pathophysiology not provided by proteomic analysis alone. C1 [Portilla, Didier] Univ Arkansas Med Sci, Dept Nephrol, Little Rock, AR 72205 USA. [Schnackenberg, Laura; Beger, Richard D.] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Portilla, D (reprint author), Univ Arkansas Med Sci, Dept Nephrol, 4301 W Markham St, Little Rock, AR 72205 USA. EM dportillal@uarns.edu FU NIDDK NIH HHS [R01 DK075976, R01 DK075976-01A1, R01 DK075976-02] NR 41 TC 24 Z9 27 U1 0 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2007 VL 27 IS 6 BP 609 EP 620 DI 10.1016/j.semnephrol.2007.09.006 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 242RE UT WOS:000251742400005 PM 18061843 ER PT J AU Yan, J Xia, Q Wamer, WG Boudreau, MD Warbritton, A Howard, PC Fu, PP AF Yan, J. Xia, Q. Wamer, W. G. Boudreau, M. D. Warbritton, A. Howard, P. C. Fu, P. P. TI Levels of retinyl palmitate and retinol in the skin of SKH-1 mice topically treated with retinyl palmitate and concomitant exposure to simulated solar light for thirteen weeks SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE light exposure; mouse skin; retinol; retinyl palmitate ID VITAMIN-A; STRATUM-CORNEUM; ALPHA-HYDROXY; EPIDERMIS; IRRADIATION; PHOTODECOMPOSITION; CAROTENOIDS; DERMIS; OXYGEN AB Retinyl esters account for more than 70% of the endogenous vitamin A found in human skin, and retinyl palmitate is one of the retinyl esters in this pool. Human skin is also exposed to retinyl palmitate exogenously through the topical application of cosmetic and skin care products that contain retinyl palmitate. To date, there is limited information on the penetration and distribution of retinyl palmitate and vitamin A within in the skin. In this study, the accumulation of retinyl palmitate and generation of retinol in the skin of male and female SKH-1 mice that received repeated topical applications of creams containing 0.0%, 0.1%, 0.5%, 1.0%, 5.0%, 10%, or 13% of retinyl palmitate 5 days a week for a period of 13 weeks were studied. Because products containing retinyl palmitate are frequently applied to sun-exposed skin, and because it is well established that exposure to sunlight and UV light can alter cutaneous levels of retinoids, mice in this study were additionally exposed 5 days a week to simulated solar light. The results showed that retinyl palmitate diffused into the skin and was partially hydrolyzed to retinol. The levels of retinyl palmitate in the skin of mice that were administered retinyl palmitate cream were higher than control values, and levels of both retinyl palmitate and retinol increased with the application of higher concentrations of retinyl palmitate in the cream. Our results indicate that topically applied retinyl palmitate may alter the normal physiological levels of retinyl palmitate and retinol in the skin of SKH-1 mice and may have a significant impact on vitamin A homeostasis in the skin. C1 [Yan, J.; Xia, Q.; Boudreau, M. D.; Howard, P. C.; Fu, P. P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Warbritton, A.] Toxicol Pathol Associates, Jefferson, AR USA. [Wamer, W. G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peterfu@fda.hhs.gov NR 29 TC 5 Z9 5 U1 0 U2 2 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 NOV PY 2007 VL 23 IS 10 BP 581 EP 589 DI 10.1177/0748233708090904 PG 9 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 322GN UT WOS:000257363300003 PM 18717516 ER PT J AU Yin, JJ Xia, Q Fu, PP AF Yin, J. J. Xia, Q. Fu, P. P. TI UVA photoirradiation of anhydroretinol - formation of singlet oxygen and superoxide SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE anhydroretinol; ESR; lipid peroxidation; photoirradiatioin; reactive oxygen species; UVA light ID RETINYL PALMITATE; LIPID-PEROXIDATION; VITAMIN-A; INDUCTION; RADICALS; PHOTODECOMPOSITION; ULTRAVIOLET; LINOLEATE; CELLS AB Anhydroretinol is a metabolite of vitamin A (retinol) and a major photodecomposition product of retinyl palmitate and retinyl acetate. Anhydroretinol is biologically active, inducing cell death in lymphoblastoid cells, prevention of N-methyl-N-nitrosourea-induced mammary cancer, and inhibition of cell growth in lymphocytes. We have previously determined that photoirradiation of anhydroretinol in the presence of a lipid, methyl linoleate, with UVA light-induced lipid peroxidation. In the present study, electron spin resonance (ESR) spin-trap techniques were employed to explore the mechanism of lipid peroxidation initiation. Irradiation of anhydroretinol by UVA in the presence of 2,2,6,6-tetramethylpiperidine (TEMP), a specific probe for singlet oxygen, resulted in the formation of TEMPO, indicating that singlet oxygen was generated. During photoirradiation in the presence of 5,5-dimethyl N-oxide pyrroline (DMPO), a specific probe for superoxide, ESR signals for DMPO-OOH were formed, and these signals were quenched by superoxide dismutase. The involvement of singlet oxygen on the induction of lipid peroxidation was also evidenced by the observation that lipid peroxidation was inhibited by sodium azide and enhanced by deuterium oxide. Our overall results provide evidence that photoirradiation of anhydroretinol with UVA light generates reactive oxygen species, e.g. singlet oxygen and superoxide, which mediate the induction of lipid peroxidation. C1 [Yin, J. J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Xia, Q.; Fu, P. P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 NR 25 TC 15 Z9 15 U1 0 U2 6 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 NOV PY 2007 VL 23 IS 10 BP 625 EP 631 DI 10.1177/0748233708090909 PG 7 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 322GN UT WOS:000257363300008 PM 18717521 ER PT J AU Xie, H Liu, T Chen, H Huang, XY Ye, ZP AF Xie, Hang Liu, Teresa Chen, Hong Huang, Xiaoyuan Ye, Zhiping TI Evaluating the vaccine potential of an influenza A viral hemagglutinin and matrix double insertion DNA plasmid SO VACCINE LA English DT Article DE DNA vaccine; influenza; T cell ID CD8(+) T-CELLS; ENHANCED PROTECTION; CYTOPLASMIC TAIL; M-GENE; VIRUS; PROTEIN; GLYCOPROTEINS; IMMUNIZATION; ASSOCIATION; EXPRESSION AB A DNA plasmid expressing both the influenza viral matrix protein (M1) and hemagglutinin (HA) (pHA/M1) as a potential vaccine candidate was investigated. Vaccination with pHA/M1 double insertion plasmids not only induced HA-specific protective antibodies, but also elicited HA and M1-specific CD8 T cell responses. Mice immunized with pHA/M1 dual expressing plasmid showed enhanced HA inhibition titer and increased CD69(+) CD8 alpha(+) T cell response compared to groups that received either the vector or a mixture of both pHA and pM1 (pHA + pM1). Furthermore, pHA/M1 immunization resulted in improved protection against both homologous and heterologous challenges. Published by Elsevier Ltd. C1 Ctr Biol Evaluat & Res, Div Viral Prod, Pediat Lab & Respiratory Virus Dis, Off Vaccines Res & Review,Food & Drug Adm, Bethesda, MD 20892 USA. RP Xie, H (reprint author), Ctr Biol Evaluat & Res, Div Viral Prod, Pediat Lab & Respiratory Virus Dis, Off Vaccines Res & Review,Food & Drug Adm, 29A Lincoln Dr, Rm 1B11, Bethesda, MD 20892 USA. EM Hang.Xie@fda.hhs.gov; Zhiping.Ye@fda.hhs.gov NR 20 TC 12 Z9 13 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 NOV 1 PY 2007 VL 25 IS 44 BP 7649 EP 7655 DI 10.1016/j.vaccine.2007.08.052 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 231EC UT WOS:000250928300007 PM 17913307 ER PT J AU Patrick, DL Burke, LB Powers, JH Scott, JA Rock, EP Dawisha, S O'Neill, R Kennedy, DL AF Patrick, Donald L. Burke, Laurie B. Powers, John H. Scott, Jane A. Rock, Edwin P. Dawisha, Sahar O'Neill, Robert Kennedy, Dianne L. TI Patient-reported outcomes to support medical product labeling claims: FDA perspective SO VALUE IN HEALTH LA English DT Article; Proceedings Paper CT Meeting on FDA Draft Guidance on Patient-Reported Outcomes CY FEB 23-25, 2006 CL Chantilly, VA DE clinical trials; FDA; patient-reported outcomes; PRO; QOL; statistical analysis AB This article concerns development and use of patient-reported outcomes (PROs) in clinical trials to evaluate medical products. A PRO is any report coming directly from patients, without interpretation by physicians or others, about how they function or feel in relation to a health condition and its therapy. PRO instruments are used to measure these patient reports. PROs provide a unique perspective on medical therapy, because some effects of a health condition and its therapy are known only to patients. Properly developed and evaluated PRO instruments also have the potential to provide more sensitive and specific measurements of the effects of medical therapies, thereby increasing the efficiency of clinical trials that attempt to measure the meaningful treatment benefits of those therapies. Poorly developed andevaluated instruments may provide misleading conclusions or data that cannot be used to support product labeling claims. We review selected major challenges from Food and Drug Administration's perspective in using PRO instruments, measures, and end points to support treatment benefit claims in product labeling. These challenges highlight the need for sponsors to formulate desired labeling claim(s) prospectively, to acquire and document information needed to support these claim(s), and to identify existing instruments or develop new and more appropriate PRO instruments for evaluating treatment benefit in the defined population in which they will seek claims. C1 Univ Washington, Seattle Qual Life Grp, Special Gov Employee Food & Drug Adm, Seattle, WA 98103 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Study Endpoionts & Label Dev Team, Silver Spring, MD USA. NIAID, Sci Applicat Int Corp, Natl Inst Hlth, Bethesda, MD 20892 USA. GSK Biol, Collegeville, PA USA. US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD USA. RP Patrick, DL (reprint author), Univ Washington, Seattle Qual Life Grp, Special Gov Employee Food & Drug Adm, Box 358852, Seattle, WA 98103 USA. EM donald@u.washington.edu NR 19 TC 194 Z9 194 U1 4 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2007 VL 10 SU 2 BP S125 EP S137 DI 10.1111/j.1524-4733.2007.00275.x PG 13 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 229YN UT WOS:000250842600009 PM 17995471 ER PT J AU Karnaukhova, E Ophir, Y Trinh, L Dalal, N Punt, PJ Golding, B Shiloach, J AF Karnaukhova, Elena Ophir, Yakir Trinh, Loc Dalal, Nimish Punt, Peter J. Golding, Basil Shiloach, Joseph TI Expression of human alpha(I)-proteinase inhibitor in Aspergillus niger SO MICROBIAL CELL FACTORIES LA English DT Article ID HETEROLOGOUS PROTEIN-PRODUCTION; FILAMENTOUS FUNGI; FUSION PROTEIN; SECRETION; ALPHA(1)-ANTITRYPSIN; DEFICIENCY; TRYPSIN; GENE AB Background: Human alpha(I)-proteinase inhibitor (alpha(I)-PI), also known as antitrypsin, is the most abundant serine protease inhibitor (serpin) in plasma. Its deficiency is associated with development of progressive, ultimately fatal emphysema. Currently in the United States, alpha(I)-PI is available for replacement therapy as an FDA licensed plasma-derived (pd) product. However, the plasma source itself is limited; moreover, even with efficient viral inactivation steps used in manufacture of plasma products, the risk of contamination from emerging viruses may still exist. Therefore, recombinant alpha(I)-PI (r-alpha(I)-PI) could provide an attractive alternative. Although r-alpha(I)-PI has been produced in several hosts, protein stability in vitro and rapid clearance from the circulation have been major issues, primarily due to absent or altered glycosylation. Results: We have explored the possibility of expressing the gene for human alpha(I)-PI in the filamentous fungus Aspergillus niger (A. niger), a system reported to be capable of providing more "mammalian-like" glycosylation patterns to secretable proteins than commonly used yeast hosts. Our expression strategy was based on fusion of alpha(I)-PI with a strongly expressed, secreted leader protein (glucoamylase G2), separated by dibasic processing site (N-V-I-S-K-R) that provides in vivo cleavage. SDS-PAGE, Western blot, ELISA, and alpha(I)-PI activity assays enabled us to select the transformant(s) secreting a biologically active glycosylated r-alpha(I)-PI with yields of up to 12 mg/L. Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis further confirmed that molecular mass of the r-alpha(I)-PI was similar to that of the pd-alpha(I)-PI. In vitro stability of the r-alpha(I)-PI from A. niger was tested in comparison with pd-alpha(I)-PI reference and non-glycosylated human r-alpha(I)-PI from E. coli. Conclusion: We examined the suitability of the filamentous fungus A. niger for the expression of the human gene for alpha(I)-PI, a medium size glycoprotein of high therapeutic value. The heterologous expression of the human gene for alpha(I)-PI in A. niger was successfully achieved to produce the secreted mature human r-alpha(I)-PI in A. niger as a biologically active glycosylated protein with improved stability and with yields of up to 12 mg/L in shake-flask growth. C1 [Karnaukhova, Elena; Ophir, Yakir; Golding, Basil] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Trinh, Loc; Dalal, Nimish; Shiloach, Joseph] NIDDK, Bethesda, MD 20892 USA. [Punt, Peter J.] TNO Qual Life, Dept Biol, NL-3704 HE Zeist, Netherlands. RP Karnaukhova, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov; ophiryakir@yahoo.com; loct@intra.niddk.nih.gov; nimish.dalal@bms.com; peter.punt@tno.nl; basil.golding@fda.hhs.gov; ljs@helix.nih.gov NR 34 TC 7 Z9 10 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2859 J9 MICROB CELL FACT JI Microb. Cell. Fact. PD OCT 29 PY 2007 VL 6 AR 34 DI 10.1186/1475-2859-6-34 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 250CO UT WOS:000252277800001 PM 17967194 ER PT J AU Chen, JJ Hsueh, HM Delongchamp, RR Lin, CJ Tsai, CA AF Chen, James J. Hsueh, Huey-Miin Delongchamp, Robert R. Lin, Chien-Ju Tsai, Chen-An TI Reproducibility of microarray data: a further analysis of microarray quality control (MAQC) data SO BMC BIOINFORMATICS LA English DT Letter ID GENE-EXPRESSION MEASUREMENTS; PLATFORMS; DISCOVERY; PROJECT; NOISE AB Background: Many researchers are concerned with the comparability and reliability of microarray gene expression data. Recent completion of the MicroArray Quality Control (MAQC) project provides a unique opportunity to assess reproducibility across multiple sites and the comparability across multiple platforms. The MAQC analysis presented for the conclusion of inter- and intra-platform comparability/reproducibility of microarray gene expression measurements is inadequate. We evaluate the reproducibility/comparability of the MAQC data for 12901 common genes in four titration samples generated from five high-density one-color microarray platforms and the TaqMan technology. We discuss some of the problems with the use of correlation coefficient as metric to evaluate the inter- and intra-platform reproducibility and the percent of overlapping genes (POG) as a measure for evaluation of a gene selection procedure by MAQC. Results: A total of 293 arrays were used in the intra- and inter-platform analysis. A hierarchical cluster analysis shows distinct differences in the measured intensities among the five platforms. A number of genes show a small fold-change in one platform and a large fold-change in another platform, even though the correlations between platforms are high. An analysis of variance shows thirty percent of gene expressions of the samples show inconsistent patterns across the five platforms. We illustrated that POG does not reflect the accuracy of a selected gene list. A non-overlapping gene can be truly differentially expressed with a stringent cut, and an overlapping gene can be non-differentially expressed with non-stringent cutoff. In addition, POG is an unusable selection criterion. POG can increase or decrease irregularly as cutoff changes; there is no criterion to determine a cutoff so that POG is optimized. Conclusion: Using various statistical methods we demonstrate that there are differences in the intensities measured by different platforms and different sites within platform. Within each platform, the patterns of expression are generally consistent, but there is site-by-site variability. Evaluation of data analysis methods for use in regulatory decision should take no treatment effect into consideration, when there is no treatment effect, "a fold-change cutoff with a non-stringent p-value cutoff" could result in 100% false positive error selection. C1 [Chen, James J.; Lin, Chien-Ju] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Hsueh, Huey-Miin] Natl Chengchi Univ, Dept Stat, Taipei 11623, Taiwan. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Dept Epidemiol, Little Rock, AR 72205 USA. [Tsai, Chen-An] China Med Univ, Dept Publ Hlth, Taichung, Taiwan. [Tsai, Chen-An] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov; hsueh@nccu.edu.tw; rdelongchamp@uams.edu; chien-ju.lin@fda.hhs.gov; catsai@mail.cmu.edu.tw OI Tsai, Chen-An/0000-0002-7490-4331; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 20 TC 75 Z9 77 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 25 PY 2007 VL 8 BP 1 EP 14 AR 412 DI 10.1186/1471-2105-8-412 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 253WY UT WOS:000252549500001 PM 17961233 ER PT J AU Lin, Q Li, DG Xu, XJ Zou, XJ Fang, L AF Lin, Qing Li, Dingge Xu, Xijin Zou, Xiaoju Fang, Li TI Roles of TRPV(I) and neuropeptidergic receptors in dorsal root reflex-mediated neurogenic inflammation induced by intradermal injection of capsaicin SO MOLECULAR PAIN LA English DT Article ID GENE-RELATED PEPTIDE; RAT KNEE-JOINT; SUBSTANCE-P; SPINAL-CORD; SYMPATHETIC MODULATION; PRESYNAPTIC INHIBITION; A-DELTA; ANTIDROMIC VASODILATATION; PLASMA EXTRAVASATION; SENSORY NEURONS AB Background: Acute cutaneous neurogenic inflammation initiated by activation of transient receptor potential vanilloid-I (TRPV(I)) receptors following intradermal injection of capsaicin is mediated mainly by dorsal root reflexes (DRRs). Inflammatory neuropeptides are suggested to be released from primary afferent nociceptors participating in inflammation. However, no direct evidence demonstrates that the release of inflammatory substances is due to the triggering of DRRs and how activation of TRPV(I) receptors initiates neurogenic inflammation via triggering DRRs. Results: Here we used pharmacological manipulations to analyze the roles of TRPV(I) and neuropeptidergic receptors in the DRR-mediated neurogenic inflammation induced by intradermal injection of capsaicin. The degree of cutaneous inflammation in the hindpaw that followed capsaicin injection was assessed by measurements of local blood flow (vasodilation) and paw-thickness (edema) of the foot skin in anesthetized rats. Local injection of capsaicin, calcitonin gene-related peptide (CGRP) or substance P (SP) resulted in cutaneous vasodilation and edema. Removal of DRRs by either spinal dorsal rhizotomy or intrathecal administration of the GABA(A) receptor antagonist, bicuculline, reduced dramatically the capsaicin-induced vasodilation and edema. In contrast, CGRP- or SP-induced inflammation was not significantly affected after DRR removal. Dose-response analysis of the antagonistic effect of the TRPV(I) receptor antagonist, capsazepine administered peripherally, shows that the capsaicin-evoked inflammation was inhibited in a dose-dependent manner, and nearly completely abolished by capsazepine at doses between 30-150 mu g. In contrast, pretreatment of the periphery with different doses of CGRP(8-37) (a CGRP receptor antagonist) or spantide I (a neurokinin 1 receptor antagonist) only reduced the inflammation. If both CGRP and NK(I) receptors were blocked by co-administration of CGRP(8-37) and spantide I, a stronger reduction in the capsaicin- initiated inflammation was produced. Conclusion: Our data suggest that 1) the generation of DRRs is critical for driving the release of neuropeptides antidromically from primary afferent nociceptors; 2) activation of TRPV(I) receptors in primary afferent nociceptors following intradermal capsaicin injection initiates this process; 3) the released CGRP and SP participate in neurogenic inflammation. C1 [Lin, Qing; Li, Dingge; Xu, Xijin; Zou, Xiaoju] Univ Texas Galveston, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA. [Fang, Li] Univ Texas Galveston, Med Branch, Dept Surg, Galveston, TX 77555 USA. [Zou, Xiaoju] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Lin, Q (reprint author), Univ Texas Galveston, Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA. EM qilin@utmb.edu; dili@utmb.edu; xijxu@utmb.edu; xiaju.zou@fda.hhs.gov; lfang@utmb.edu FU NIDCR NIH HHS [R03 DE014814]; NINDS NIH HHS [R01 NS040723, R01 NS40723] NR 68 TC 40 Z9 42 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD OCT 25 PY 2007 VL 3 AR 30 DI 10.1186/1744-8069-3-30 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 250BZ UT WOS:000252276300001 PM 17961222 ER PT J AU Joffe, HV Parks, MH Meyer, RJ Jenkins, JK Temple, R AF Joffe, Hylton V. Parks, Mary H. Meyer, Robert J. Jenkins, John K. Temple, Robert TI Rosiglitazone and the FDA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID BLOOD-GLUCOSE CONTROL; COMPLICATIONS C1 US FDA, Silver Spring, MD 20993 USA. RP Joffe, HV (reprint author), US FDA, Silver Spring, MD 20993 USA. EM mary.parks@fda.hhs.gov NR 6 TC 5 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 25 PY 2007 VL 357 IS 17 BP 1775 EP 1776 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 223FN UT WOS:000250355100028 PM 17761586 ER PT J AU Holland, SM DeLeo, FR Elloumi, HZ Hsu, AP Uzel, G Brodsky, N Freeman, AF Demidowich, A Davis, J Turner, ML Anderson, VL Darnell, DN Welch, PA Kuhns, DB Frucht, DM Malech, HL Gallin, JI Kobayashi, SD Whitney, AR Voyich, JM Musser, JM Woellner, C Schaffer, AA Puck, JM Grimbacher, B AF Holland, Steven M. Deleo, Frank R. Elloumi, Houda Z. Hsu, Amy P. Uzel, Gulbu Brodsky, Nina Freeman, Alexandra F. Demidowich, Andrew Davis, Joie Turner, Maria L. Anderson, Victoria L. Darnell, Dirk N. Welch, Pamela A. Kuhns, Douglas B. Frucht, David M. Malech, Harry L. Gallin, John I. Kobayashi, Scott D. Whitney, Adeline R. Voyich, Jovanka M. Musser, James M. Woellner, Cristina Schaeffer, Alejandro A. Puck, Jennifer M. Grimbacher, Bodo TI STAT3 mutations in the hyper-IgE syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HYPERIMMUNOGLOBULIN-E SYNDROME; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; CYTOKINE SIGNALS; INNATE IMMUNITY; T-CELLS; DISEASE; INTERFERON; DEFICIENCY; ACTIVATION AB Background The hyper-IgE syndrome (or Job's syndrome) is a rare disorder of immunity and connective tissue characterized by dermatitis, boils, cyst-forming pneumonias, elevated serum IgE levels, retained primary dentition, and bone abnormalities. Inheritance is autosomal dominant; sporadic cases are also found. Methods We collected longitudinal clinical data on patients with the hyper-IgE syndrome and their families and assayed the levels of cytokines secreted by stimulated leukocytes and the gene expression in resting and stimulated cells. These data implicated the signal transducer and activator of transcription 3 gene (STAT3) as a candidate gene, which we then sequenced. Results We found increased levels of proinflammatory gene transcripts in unstimulated peripheral-blood neutrophils and mononuclear cells from patients with the hyper-IgE syndrome, as compared with levels in control cells. In vitro cultures of mononuclear cells from patients that were stimulated with lipopolysaccharide, with or without interferon-(gamma), had higher tumor necrosis factor (alpha) levels than did identically treated cells from unaffected persons (P=0.003). In contrast, the cells from patients with the hyper-IgE syndrome generated lower levels of monocyte chemoattractant protein 1 in response to the presence of interleukin-6 (P=0.03), suggesting a defect in interleukin-6 signaling through its downstream mediators, one of which is STAT3. We identified missense mutations and single-codon in-frame deletions in STAT3 in 50 familial and sporadic cases of the hyper-IgE syndrome. Eighteen discrete mutations, five of which were hot spots, were predicted to directly affect the DNA-binding and SRC homology 2 (SH2) domains. Conclusions Mutations in STAT3 underlie sporadic and dominant forms of the hyper-IgE syndrome, an immunodeficiency syndrome involving increased innate immune response, recurrent infections, and complex somatic features. C1 NIAID, NIH, Bethesda, MD 20892 USA. NIAID, Hamilton, MT USA. NHGRI, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Sci Applicat Int Corp, NCI, Frederick, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Royal Free Hosp & UCL, London, England. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Holland, SM (reprint author), NIAID, NIH, CRC B3-4141 MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov RI Schaffer, Alejandro/F-2902-2012; OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 39 TC 496 Z9 522 U1 4 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 18 PY 2007 VL 357 IS 16 BP 1608 EP 1619 DI 10.1056/NEJMoa073687 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 221AY UT WOS:000250200500006 PM 17881745 ER PT J AU Bidol, SA Daly, E Rickert, R Hill, TA Al Khaldi, S Taylor, TH Lynch, MF Painter, JA Braden, CR Yu, PA Demma, L Behravesh, CB Greene, SK Schmitz, AM Blaney, DD Gershman, M AF Bidol, S. A. Daly, E. R. Rickert, R. E. Hill, T. A. Al Khaldi, S. Taylor, T. H., Jr. Lynch, M. F. Painter, J. A. Braden, C. R. Yu, P. A. Demma, L. Behravesh, C. Barton Greene, S. K. Schmitz, A. M. Blaney, D. D. Gershman, M. CA CDC TI Multistate outbreaks of Salmonella infections associated with raw tomatoes eaten in restaurants - United States, 2005-2006 (Reprinted from MMWR, vol 56, pg 909-911, 2007) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID MONTEVIDEO C1 Michigan Dept Community Hlth, Lansing, MI 48913 USA. New Hampshire Dept Hlth & Human Serv, Concord, NH 03301 USA. Penn Dept Hlth, Harrisburg, PA 17108 USA. US FDA, Rockville, MD 20857 USA. Natl Ctr Immunizat & Resp Dis, Div Bacterial Dis, Atlanta, GA USA. Natl Ctr Zoonot, Div Foodborne Bacterial & Mycot Dis, Vectorborne & Enter Dis, Atlanta, GA USA. CDC, Atlanta, GA 30333 USA. RP Bidol, SA (reprint author), Michigan Dept Community Hlth, Lansing, MI 48913 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 17 PY 2007 VL 298 IS 15 BP 1753 EP 1755 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 220WF UT WOS:000250187300009 ER PT J AU Varackar, P Ge, M McCright, B AF Varackar, Prajakta Ge, Ma McCright, Brenton TI Cardiac neural crest specific deletion of Notch2 causes defective development of the outflow tract SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Varackar, Prajakta; Ge, Ma; McCright, Brenton] US FDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 305 EP 305 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301405 ER PT J AU Li, JS Smith, PB Murphy, MD Califf, RM Benjamin, DK AF Li, Jennifer S. Smith, P. Brian Murphy, M. Dianne Califf, Robert M. Benjamin, Daniel K., Jr. TI Racial differences in blood pressure response to angiotensin converting enzyme inhibitors in children: An analysis of 6 pediatric hypertension trials SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Li, Jennifer S.; Smith, P. Brian; Califf, Robert M.] Duke Univ, Med Ctr, Durham, NC USA. [Murphy, M. Dianne; Benjamin, Daniel K., Jr.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2766 BP 614 EP 614 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302767 ER PT J AU Lapointe, NMA Sun, JL Kaplan, S Al-Khatib, SM AF Lapointe, Nancy M. Allen Sun, Jie-Lena Kaplan, Sigal Al-Khatib, Sana M. TI Factors associated with rhythm versus rate control strategies in hospitalized patients with atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lapointe, Nancy M. Allen; Al-Khatib, Sana M.] Duke Univ, Med Ctr, Durham, NC USA. [Sun, Jie-Lena] Duke Clin Res Inst, Durham, NC USA. [Kaplan, Sigal] Food & Drug Adm, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2866 BP 638 EP 638 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302865 ER PT J AU Baker-Smith, CM Benjamin, DK Murphy, D Eisenstein, EL Li, JS AF Baker-Smith, Carissa M. Benjamin, Daniel K., Jr. Murphy, Dianne Eisenstein, Eric L. Li, Jennifer S. TI The economic return of performing pediatric anti-hypertensive drug clinical trials SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Baker-Smith, Carissa M.; Benjamin, Daniel K., Jr.; Li, Jennifer S.] Duke Univ, Durham, NC 27706 USA. [Benjamin, Daniel K., Jr.] US FDA, Washington, DC USA. [Eisenstein, Eric L.] Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3624 BP 822 EP 822 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303716 ER PT J AU Jiang, SS Rasmussen, RA Nolan, KM Frankel, FR Lieberman, J McClure, HM Williams, KM Babu, US Raybourne, RB Strobert, E Ruprecht, RM AF Jiang, Shisong Rasmussen, Robert A. Nolan, Katrina M. Frankel, Fred R. Lieberman, Judy McClure, Harold M. Williams, Kristina M. Babu, Uma S. Raybourne, Richard B. Strobert, Elizabeth Ruprecht, Ruth M. TI Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys SO VACCINE LA English DT Article DE rhesus monkey; Listeria monocytogenes; D-alanine; cellular immunity; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSE; MONOCLONAL-ANTIBODIES; IN-VIVO; NEONATAL MACAQUES; VACCINE VECTOR; T-CELLS; INDUCTION; INFECTION; MICE AB Induction of strong cellular immunity will be important for AIDS vaccine candidates. Natural infection with wild-type Listeria itionocyto-genes (Lm), an orally transmitted organism, is known to generate strong cellular immunity, thus raising the possibility that live attenuated Lm could serve as a vaccine vector. We sought to examine the potential of live attenuated Lm to induce cellular immune responses to HIV Gag. Rhesus macaques were immunized with Lmdd-gag that expresses HIV gag and lacks two genes in the D-alanine (D-ala) synthesis pathway. Without this key component of the bacterial cell wall, vaccine vector replication critically depends on exogenous D-ala. Lmdd-gag was given to animals either solely orally or by oral priming followed by intramuscular (i.m.) boosting; D-ala was co-administered with all vaccinations. Lmdd-gag and D-ala were well tolerated. Oral priming/oral boosting induced (Gag-specific cellular immune responses, whereas oral priming/i.m. boosting induced systemic as well as mucosal anti-Gag antibodies. These. results suggest that the route of vaccination may bias anti-Gag immune responses either towards T-helper type 1 (Th 1) or Th2 responses; overall, our data show that live attenuated, recombinant Lmdd-gag is safe and immunogenic in primates. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Res Resources & Microbiol & Immunol, Atlanta, GA 30329 USA. US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NCRR NIH HHS [P51 RR000165-47, P51 RR000165, RR-00165]; NIAID NIH HHS [P01 AI054558, P01 AI054558-010003, R21 AI054183, R21 AI054183-01] NR 54 TC 26 Z9 28 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 OCT 16 PY 2007 VL 25 IS 42 BP 7470 EP 7479 DI 10.1016/j.vaccine.2007.08.013 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 227JV UT WOS:000250653900024 PM 17854955 ER PT J AU Dobrovolsky, VN Heflich, RH AF Dobrovolsky, Vasily N. Heflich, Robert H. TI On the use of the T-REx (TM) tetracycline-inducible gene expression system in vivo SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE transgenic; tetracycline repressor; green fluorescent protein reporter; tet-operator; tissue-specific ID GREEN FLUORESCENT PROTEIN; TRANSGENIC MICE; CELLS; PROMOTER AB Components of the commercially available T-REx (TM) system were used to create two types of transgenic mice. The first contained the tetracycline-repressor transgene under the control of the CMV promoter/enhancer; the second type contained a green fluorescent protein (GFP) reporter transgene under the control of the CMV promoter/enhancer with a tetracycline repressor operator sequence. Transgene expression was unpredictable in animals containing the individual transgenes. Animals with the reporter transgene expressed GFP in only some tissues (e.g., pancreas, kidney), and one line of reporter transgenic animals developed kidney disease, presumably due to expression of the transgene. The two types of transgenic animals were crossbred to produce double-transgenic animals with the object of regulating the expression of the reporter in vivo. When a similar double-transgenic system was constructed in cultured cells, the repressor protein suppressed the transcription of the reporter transgene. The presence of the repressor in double-transgenic animals had no effect on the expression of the reporter; double transgenic animals; developed the same kidney disease that was seen in singly transgenic mice with the reporter. Our results indicate that transgenes under the control of the CMV promoter in the T-REx system express somewhat unpredictably and in only a limited number of tissues, making the use of this system for the development of in vivo models problematical. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM vasily.dobrovolsky@fda.hhs.gov NR 9 TC 5 Z9 5 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD OCT 15 PY 2007 VL 98 IS 3 BP 719 EP 723 DI 10.1002/bit.21454 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 214ZB UT WOS:000249775800022 PM 17421042 ER PT J AU Sauna, ZE Kimchi-Sarfaty, C Ambudkar, SV Gottesman, MM AF Sauna, Zuben E. Kimchi-Sarfaty, Chava Ambudkar, Suresh V. Gottesman, Michael M. TI Silent Polymorphisms speak: How they affect pharmacogenomics and the treatment of cancer SO CANCER RESEARCH LA English DT Review ID ALZHEIMERS-DISEASE; RATIO TEST; MDR1 GENE; PROTEIN; ASSOCIATION; REGIONS AB Polymorphisms in the human genome contribute to wide variations in how individuals respond to medications, either by changing the pharmacokinetics of drugs or by altering the cellular response to therapeutic agents. The goal of the emerging discipline of pharmacogenomics is to personalize therapy based on an individual's genotype. Due to the relatively large frequency of single-nucleotide polymorphisms (SNP) in the human genome, synonymous SNPs are often disregarded in many pharmacogenomic studies based on the assumption that these are silent. We have shown recently that synonymous SNPs in ABCB1 (P-glycoprotein), which is implicated both in determining drug pharmacoldnetics and multidrug resistance in human cancer cells, can affect protein conformation and function. We discuss the importance of polymorphisms in drug metabolizing enzymes and transporters in anticancer therapy and suggest that synonymous polymorphisms may play a more significant role than is currently assumed. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov FU Intramural NIH HHS NR 29 TC 153 Z9 158 U1 1 U2 21 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 OCT 15 PY 2007 VL 67 IS 20 BP 9609 EP 9612 DI 10.1158/0008-5472.CAN-07-2377 PG 4 WC Oncology SC Oncology GA 222HG UT WOS:000250286300002 PM 17942888 ER PT J AU Shimamura, T Royal, RE Kioi, M Nakajima, A Husain, SR Puri, RK AF Shimamura, Takeshi Royal, Richard E. Kioi, Mitomu Nakajima, Atsushi Husain, Syed R. Puri, Raj K. TI Interleukin-4 cytotoxin therapy synergizes with gemcitabine in a mouse model of pancreatic ductal adenocarcinoma SO CANCER RESEARCH LA English DT Article ID RECEPTOR-DIRECTED CYTOTOXIN; RECOMBINANT HUMAN INTERLEUKIN-4; RECURRENT MALIGNANT GLIOMA; PHASE-I TRIAL; PSEUDOMONAS EXOTOXIN; ENDOTHELIAL-CELLS; ORTHOTOPIC MODEL; CANCER THERAPY; IL-4 RECEPTOR; CARCINOMA AB Targeting cell surface receptors with cytotoxins or immunotoxins provides a unique opportunity for tumor therapy. Here, we show the efficacy of the combination therapy of gemcitabine with an interleukin-4 (IL-4) cytotoxin composed of IL-4 and truncated Pseudomonas exotoxin in animal models of pancreatic ductal adenocarcinoma (PDA). We have observed that 42 of 70 (60%) tumor samples from patients with PDA express moderate- to high-density surface IL-4 receptor (11,411), whereas normal pancreatic samples express no or low-density IL-4R. IL-4 cytotoxin was specifically and highly cytotoxic [50% protein synthesis inhibition (IC50) ranging from >0.1 to 13 ng/mL] to six of eight pancreatic cancer cell lines, whereas no cytotoxicity (IC50 >1,000 ng/mL) was observed in normal human pancreatic duct epithelium cells, fibroblasts, and human umbilical vein endothelial cells (HUVEC). We also showed that IL-4 cytotoxin in combination with gemcitabine exhibited synergistic antitumor activity in vitro. To confirm synergistic antitumor activity in vivo and monitor precise real-time disease progression, we used a novel metastatic and orthotopic mouse model using green fluorescent protein-transfected cancer cells and whole-body imaging system. The combination of both agents caused complete eradication of tumors in 40% of nude mice with small established PDA tumors. In addition, combined treatment significantly prolonged the survival of nude mice bearing day 14 advanced distant metastatic PDA tumors. Similar results were observed in mice xenografted with PDA obtained from a patient undergoing surgical resection. These results indicate that IL-4 cytotoxin combined with gemcitabine may provide effective therapy for the treatment of patients with PDA. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Rockville, MD 20857 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), NIH Bldg 29B,Room 2NN0,HFM 735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 50 TC 24 Z9 25 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 OCT 15 PY 2007 VL 67 IS 20 BP 9903 EP 9912 DI 10.1158/0008-5472.CAN-06-4558 PG 10 WC Oncology SC Oncology GA 222HG UT WOS:000250286300036 PM 17942922 ER PT J AU Fitzsimmons, SP Bernstein, RM Max, EE Skok, JA Shapiro, MA AF Fitzsimmons, Sean P. Bernstein, Ralph M. Max, Edward E. Skok, Jane A. Shapiro, Marjorie A. TI Dynamic changes in accessibility, nuclear positioning, recombination, and transcription at the Ig kappa locus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL DEVELOPMENT; CHAIN GENE REARRANGEMENT; HISTONE ACETYLATION; PRE-B; V(D)J RECOMBINATION; IMMUNOGLOBULIN; DIFFERENTIATION; LYMPHOCYTES; SENSITIVITY; SEQUENCE AB The 3-megabase Ig kappa locus undergoes differentially controlled nuclear positioning events and chromatin structural changes during the course of B cell development. The temporal association of chromatin structural changes, transcription, and recombination at the Ig kappa locus was determined in a marine pre-B cell line that can be induced to recombine at the Ig kappa locus and in ex vivo-cultured murine pre-B cells. Additionally, the timing of nuclear positioning relative to the temporal order of chromatin structural changes and recombination and transcription was determined. We demonstrate that before induction, the Ig kappa locus was poised for recombination; both alleles were in a contracted state, and the enrichment of histone modifications and germline transcripts of specific V kappa genes were observed. Histone modifications of the V kappa genes did not vary upon induction but the levels of modifications correlated with the levels of germline V kappa gene transcripts and recombination. Upon induction, but before V kappa J kappa recombination, centromeric recruitment of single Ig kappa alleles occurred. DNase I sensitivity of the entire locus increased gradually over the course of differentiation while the enrichment of histone modifications downstream of the V kappa genes was increased in the silencer regions upstream of J kappa 1, within the Ig kappa sterile transcript, the kappa constant region, the E kappa i and E kappa 3 ' enhancers, and the recombining sequence. The ex vivo pre-B cells showed similar patterns of histone modifications across the locus except at the V kappa genes. In this study, H3 acetylation correlated with levels of germline transcripts while H3 methylation correlated with levels of recombination. C1 US FDA, Div Monoclonal Antibiodies, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. UCL, Dept Immunol & Mol Pathol, Div Infect & Immun, London, England. RP Shapiro, MA (reprint author), US FDA, Div Monoclonal Antibiodies, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. EM marjorie.shapiro@fda.hhs.gov NR 44 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2007 VL 179 IS 8 BP 5264 EP 5273 PG 10 WC Immunology SC Immunology GA 219QJ UT WOS:000250099400034 PM 17911612 ER PT J AU Silveira, IAFB Bastos, RC Neto, MS Laranjeira, AP Assis, EF Fernandes, SAR Leal, ML Silva, WC Lee, CH Frasch, CE Peralta, JM Jessouroun, E AF Silveira, I. A. F. B. Bastos, R. C. Neto, M. S. Laranjeira, A. P. Assis, E. F. Fernandes, S. A. R. Leal, M. L. Silva, W. C. Lee, C.-H. Frasch, C. E. Peralta, J. M. Jessouroun, E. TI Characterization and immunogenicity of meningococcal group C conjugate vaccine prepared using hydrazide-activated tetanus toxoid SO VACCINE LA English DT Article DE conjugate vaccine; meningococcal group C; reductive amination; high avidity IgG; serum bactericidal activity ID INFLUENZAE TYPE-B; MENINGITIDIS SEROGROUP-B; POLYSACCHARIDE VACCINE; GROUP-A; IMMUNOLOGICAL HYPORESPONSIVENESS; CAPSULAR POLYSACCHARIDES; MASS VACCINATION; IMMUNE-RESPONSE; UNITED-KINGDOM; PROTEIN AB The steps to produce, purify and control an immunogenic Brazilian conjugate vaccine against group C meningococcus (MenCPS-TT) using hydrazide-activated tetanus toxoid were developed. The conjugation methodology reduced the reaction time easily allowing scale-up. One freeze-dried pilot vaccine lot purified by tangential filtration, showed satisfactory quality control results including safety and stability. The pilot vaccine was immunogenic in mice in a dose-dependent fashion generating a 10-20-fold rise in 19G response in mice. The vaccine also induced high bactericidal titers. Vaccine concentrations of 1 and 0.1 mu g showed higher avidity indices, suggesting induction of immunologic memory. These results support initiation of Phase I clinical studies with the MenCPS-TT conjugate vaccine. (c) 2007 Elsevier Ltd. All rights reserved. C1 Fundacao Oswaldo Cruz, Lab Tecnol Bacteriana, Rio De Janeiro, Brazil. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Fed Rio de Janeiro, Inst Microbiol Prof Paulo Goes, Dept Imunol, Rio De Janeiro, Brazil. RP Silveira, IAFB (reprint author), Fundacao Oswaldo Cruz, Lab Tecnol Bacteriana, Rio De Janeiro, Brazil. EM ivna@bio.fiocruz.br NR 63 TC 12 Z9 13 U1 3 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 10 PY 2007 VL 25 IS 41 BP 7261 EP 7270 DI 10.1016/j.vaccine.2007.07.037 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 224NY UT WOS:000250454900030 PM 17719147 ER PT J AU Wu, DG Qiang, R Chen, J Seidman, S Witters, D Kainz, WG AF Wu, Dagang Qiang, Rui Chen, Ji Seidman, Seth Witters, Donald Kainz, Wolfgang TI Possible overexposure of pregnant women to emissions from a walk through metal detector SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INDUCED CURRENT DENSITIES; FREQUENCY MAGNETIC-FIELDS; DIELECTRIC-PROPERTIES; BIOLOGICAL TISSUES; POWER DEPOSITION; IMPEDANCE METHOD; ABSORPTION; RESOLUTION; DOSIMETRY; EXPOSURE AB This paper presents a systematic procedure to evaluate the induced current densities and electric fields due to walk-through metal detector (WTMD) exposure. This procedure is then used to assess the exposure of nine pregnant women models exposed to one WTMD model. First, we measured the magnetic field generated by the WTMD, then we extracted the equivalent current source to represent the WTMD emissions and finally we calculated the induced current densities and electric fields using the impedance method. The WTMD emissions and the induced fields in the pregnant women and fetus models are then compared to the ICNIRP Guidelines and the IEEE C95.6 exposure safety standard. The results prove the consistency between maximum permissible exposure (MPE) levels and basic restrictions for the ICNIRP Guidelines and IEEE C95.6. We also found that this particular WTMD complies with the ICNIRP basic restrictions for month 1-5 models, but leads to both fetus and pregnant women overexposure for month 6-9 models. The IEEE C95.6 restrictions (MPEs and basic restrictions) are not exceeded. The fetus overexposure of this particular WTMD calls for carefully conducted safety evaluations of security systems before they are deployed. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. RP Wu, DG (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2007 VL 52 IS 19 BP 5735 EP 5748 DI 10.1088/0031-9155/52/19/001 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 224JL UT WOS:000250443200001 PM 17881797 ER PT J AU Thybaud, V Aardema, M Casciano, D Dellarco, V Embry, MR Gollapudi, BB Hayashi, M Holsapple, MP Jacobson-Kram, D Kasper, P MacGregor, JT Rees, R AF Thybaud, Veronique Aardema, Marilyn Casciano, Daniel Dellarco, Vicki Embry, Michelle R. Gollapudi, B. Bhaskar Hayashi, Makoto Holsapple, Michael P. Jacobson-Kram, David Kasper, Peter MacGregor, James T. Rees, Robert TI Relevance and follow-up of positive results in in vitro genetic toxicity assays: An ILSI-HESI initiative SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE genotoxicity; in vitro assays; carcinogenesis; workshop report ID RISK-ASSESSMENT; DEVELOPMENTAL TOXICITY; BIOLOGICAL RELEVANCE; CARCINOGENICITY DATA; GENOTOXICITY; TOXICOLOGY; CHEMICALS; PHARMACEUTICALS; IDENTIFICATION; THRESHOLDS AB In vitro genotoxicity assays are often used to screen and predict whether chemicals might represent mutagenic and carcinogenic risks for humans. Recent discussions have focused on the high rate of positive results in in vitro tests, especially in those assays performed in mammalian cells that are not confirmed in vivo. Currently, there is no general consensus in the scientific community on the interpretation of the significance of positive results from the in vitro genotoxicity assays. To address this issue, the Health and Environmental Sciences Institute (HESI), held an international workshop in June 2006 to discuss the relevance and follow-up of positive results in in vitro genetic toxicity assays. The goals of the meeting were to examine ways to advance the scientific basis for the interpretation of positive findings in in vitro assays, to facilitate the development of follow-up testing strategies and to define criteria for determining the relevance to human health. The workshop identified specific needs in two general categories, i.e., improved testing and improved data interpretation and risk assessment. Recommendations to improve testing included: (1) re-examine the maximum level of cytotoxicity currently required for in vitro tests; (2) re-examine the upper limit concentration for in vitro mammalian studies; (3) develop improved testing strategies using current in vitro assays; (4) define criteria to guide selection of the appropriate follow-up in vivo studies; (5) develop new and more predictive in vitro and in vivo tests. Recommendations for improving interpretation and assessment included: (1) examine the suitability of applying the threshold of toxicological concern concepts to genotoxicity data; (2) develop a structured weight of evidence approach for assessing genotoxic/carcinogenic hazard; and (3) re-examine in vitro and in vivo correlations qualitatively and quantitatively. Conclusions from the workshop highlighted a willingness of scientists from various sectors to change and improve the current paradigm and move from a hazard identification approach to a "realistic" risk-based approach that incorporates information on mechanism of action, kinetics, and human exposure. (c) 2007 Elsevier B.V. All rights reserved. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. Sanofi Aventis, Drug Safety Evaluat, F-94400 Vitry Sur Seine, France. Procter & Gamble Co, Miami Valley Innovat Ctr, Cincinnati, OH 45239 USA. Dan Casciano & Associates, Little Rock, AR 72223 USA. US EPA, Off Pesticide Programs, Washington, DC 20460 USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48642 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Setagaya Ku, Tokyo 1588501, Japan. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. Fed Inst Drugs & Med Devices, D-53175 Bonn, Germany. Toxicol Consulting Serv, Arnold, MD 21012 USA. GlaxoSmithKline Inc, Genet Toxicol, Ware SG12 0DP, Herts, England. RP Embry, MR (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle,NW,9th Floor, Washington, DC 20005 USA. EM membry@hesiglobal.org NR 31 TC 20 Z9 21 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 OCT 4 PY 2007 VL 633 IS 2 BP 67 EP 79 DI 10.1016/j.mrgentox.2007.05.010 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 210XA UT WOS:000249487700001 PM 17616430 ER PT J AU Lee, S Wood, O Tang, S Hu, J Machuca, A Kerby, S Awazi, B Vockley, C Hewlett, I AF Lee, S. Wood, O. Tang, S. Hu, J. Machuca, A. Kerby, S. Awazi, B. Vockley, C. Hewlett, I. TI Detection of emerging HIV variants in blood donors from urban areas of Cameroon SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRUS TYPE-1 INFECTION; GENETIC DIVERSITY; TIME; RNA AB The U. S. Food and Drug Administration has licensed several assays for use in donor testing and management of persons with human immunodeficiency virus (HIV) infection. However, the performance of these assays for detection and quantitation of emerging HIV genetic variants has not been studied extensively. We tested 240 human plasma specimens collected from two urban blood centers in Cameroon where HIV genetic diversity and recombinant HIV strains are highly prevalent, using several FDA licensed assays. The testing record in Cameroon indicated that 149 specimens were HIV antibody positive and 91 specimens were negative using a rapid HIV-1/2 antibody assay in routine use in Cameroon blood centers. Both sets of samples were evaluated in the FDA laboratory using four ELISA tests for HIV-1 group M, HIV-1 group O, and HIV2 antibodies, one IFA for HIV-1 antibody, one Western blot for HIV-1, one HIV-1 p-24 antigen assay, and three nucleic acid tests (NAT). Our results indicate that the assays had high sensitivity for detection of emerging genetic variants, although a small number of samples harboring circulating recombinant forms (CRFs) found in Cameroon were not always consistently detected by a few assays. These findings may be due to the evolving genetic diversity of HIV strains in Cameroon. C1 US FDA, Mol Virol Lab, CBER, Rockville, MD 20852 USA. US FDA, Div Emerging & Transfus Transmitted Dis, CBER, Product Testing Sect, Rockville, MD 20852 USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, CBER, HFM-315,1401 Rockville Pike, Rockville, MD 20852 USA. EM Indira.Hewlett@FDA.HHS.GOV FU NHLBI NIH HHS [BY1-HB-5026-01] NR 23 TC 5 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2007 VL 23 IS 10 BP 1262 EP 1267 DI 10.1089/aid.2006.0301 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 228HO UT WOS:000250720900016 PM 17961114 ER PT J AU Taenaka, Y AF Taenaka, Yoshiyuki TI JSAO-IFAO Joint Congress 2007 - Abstracts SO ARTIFICIAL ORGANS LA English DT Article C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Juntendo Univ, Sch Med, Tokyo 113, Japan. Univ Alabama Hosp & Clin, Birmingham, AL USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Taenaka, Y (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 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 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD OCT PY 2007 VL 31 IS 10 BP A33 EP A100 PG 68 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 219IN UT WOS:000250078200001 ER PT J AU Karnaukhova, E Golding, B Ophir, Y AF Karnaukhova, Elena Golding, Basil Ophir, Yakir TI Development and evaluation of an ELISA for quantification of human alpha-1-proteinase inhibitor in complex biological mixtures SO BIOLOGICALS LA English DT Article DE alpha-1-proteinase inhibitor; antitrypsin; ELISA; evaluation ID DEFICIENCY AB Human alpha-1-proteinase inhibitor(1) (alpha(1)-PI) is the most abundant serine protease inhibitor in plasma. Its major function is inhibition of neutrophil elastase in lungs. alpha(1)-PI deficiency may result in severe, ultimately fatal emphysema. Three plasma-derived (pd-) alpha(1)-PI products are licensed in the US for replacement therapy of deficient patients. The recombinant versions (r-alpha(1)-PI), proposed as alternatives to pd-alpha(1)-PI products, have been under intensive investigation. For accurate determination of alpha(1)-PI from different sources and in various forms, there is an obvious need for reliable standardized assays for alpha(1)-PI quantification and potency measurements. As a part of our multi-step research focused on alpha(1)-PI structure-function investigation, we have established a simple and reproducible double-sandwich ELISA based on commercially available polyclonal antibodies. The developed ELISA allows the quantification of both pd-alpha(1)-PI and r-alpha(1)-PI in various complex matrices. A validation of the ELISA was performed with the working range of the assay (3.1-50 ng/ml) established on the bases of the following parameters: linearity (3-100 ng/ml, r(2) = 0.995); accuracy (87.3-114.6% recovery); intra-assay precision (%CV, 2.8%); inter-assay plate-to-plate precision (3.9% per day and 4.1 % day-to-day); detection limit (1.10 ng/ml); and quantification limit (3.34 ng/ml). The analytical performance of the alpha(1)-PI ELISA indicates that this assay can be used for monitoring concentration levels of alpha(1)-PI in multi-component biological matrices, based on the following: (a) quantification of r-alpha(1)-PI in various fermentation mixtures (E. coli and A. niger); (b) investigation of alpha(1)-PI enzymatically digested in the conditions of harsh fungal proteolysis; (c) evaluation of thermally polymerized alpha(1)-PI; (d) quantification of alpha(1)-PI in human serum; and (e) comparative quantification of alpha(1)-PI in commercially available products. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 United States Food & Drug Administration, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Karnaukhova, E (reprint author), United States Food & Drug Administration, Ctr Biol Evaluat & Res, Div Hematol, 29 Lincoln D, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov NR 16 TC 1 Z9 2 U1 1 U2 1 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 OCT PY 2007 VL 35 IS 4 BP 285 EP 295 DI 10.1016/j.biologicals.2006.11.002 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 230WM UT WOS:000250906900009 PM 17257853 ER PT J AU Kozlowski, S AF Kozlowski, Steven TI Protein therapeutics and the regulation of quality: A brief history from an OBP perspective SO BIOPHARM INTERNATIONAL LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, OBP, Silver Spring, MD USA. RP Kozlowski, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, OBP, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD OCT PY 2007 VL 20 IS 10 BP 37 EP + PG 10 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 227ML UT WOS:000250660700006 ER PT J AU Winkle, H AF Winkle, Helen TI FDA's hiring challenge SO BIOPHARM INTERNATIONAL LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, OPS, White Oak, MD USA. RP Winkle, H (reprint author), US FDA, Ctr Drug Evaluat & Res, OPS, White Oak, MD USA. EM helen.winkle@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD OCT PY 2007 VL 20 IS 10 BP 145 EP + PG 5 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 227ML UT WOS:000250660700014 ER PT J AU Woodcock, J AF Woodcock, J. TI Molecular medicine: How, what, and when? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Integrating molecular medicine into clinical practice will create many challenges. But the existing genetic testing paradigm may not be the right model for introducing these new technologies. C1 US FDA, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Rockville, MD 20857 USA. EM Janet.woodcock@fda.hhs.gov NR 5 TC 6 Z9 6 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 OCT PY 2007 VL 82 IS 4 BP 376 EP 378 DI 10.1038/sj.clpt.2007.6100349 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212ZU UT WOS:000249636500009 PM 17851578 ER PT J AU Lacana, E Amur, S Mummanneni, P Zhao, H Frueh, FW AF Lacana, E. Amur, S. Mummanneni, P. Zhao, H. Frueh, F. W. TI The emerging role of pharmacogenomics in Biologics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TUMOR-NECROSIS-FACTOR; METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; BIOTECHNOLOGY PRODUCTS; SAFETY EVALUATION; THERAPY; POLYMORPHISM; TRASTUZUMAB AB Biologics can be seen as "designer'' drugs whose mode of action in a specific disease mechanism is frequently well understood, making it often possible to predict better efficacy and safety profiles for biologics when compared with small molecule drugs. Biologics have been approved for the treatment of major disease classes, such as inflammatory disease, cardiovascular disease, and cancer. However, as it is true for small molecule drugs, often only a fraction of the treated population responds to biologics, and clinical markers for prediction of efficacy are seldom available. It is reasonable to expect that the use of genetic or genomic markers will contribute to improving the prediction of safety and efficacy of both biologics and small molecule drugs. In this paper, we will review the differences between biologics and small molecule drugs, focusing on studies highlighting the relevance of genetic and genomic information on safety and efficacy issues in therapies with biologics. The potential impact of these studies on the promotion of personalized medicine and on regulatory decisions will also be discussed. C1 Ctr Drugs Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD USA. US FDA, Ctr Drugs Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Frueh, FW (reprint author), Ctr Drugs Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD USA. EM Felix.Frueh@fda.hhs.gov NR 33 TC 28 Z9 28 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 OCT PY 2007 VL 82 IS 4 BP 466 EP 471 DI 10.1038/sj.clpt.6100334 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212ZU UT WOS:000249636500023 PM 17713469 ER PT J AU Yang, Y Brownell, C Sadrieh, N May, J Del Grosso, A Place, D Leutzinger, E Duffy, E He, R Houn, F Lyon, R Faustino, P AF Yang, Yongsheng Brownell, Charles Sadrieh, Nakissa May, Joan Del Grosso, Alfred Place, David Leutzinger, Eldon Duffy, Eric He, Ruyi Houn, Florence Lyon, Robbie Faustino, Patrick TI Quantitative measurement of cyanide released from Prussian Blue SO CLINICAL TOXICOLOGY LA English DT Article DE Prussian Blue; cyanide poisoning; quantitative; toxicity ID EFFECTIVE ANTIDOTE; RADIOCESIUM; ACCIDENT; MEAL; AFCF AB Background. Prussian Blue (PB), ferric hexacyanoferrate is indicated for (oral) treatment of internal contamination with radioisotopes of cesium or thallium. Cyanide is 35-40% of PB's molecular composition, thus cyanide may be released during transit through the digestive tract under physiological pH. The U.S. Food and Drug, Administration investigated the issue of cyanide release prior to drug approval to ensure the drug's benefits exceeded risks. Objectives. To determine cyanide released from. PB under pH conditions that bracket human physiological exposure. Methods. PB was incubated in situ at pH 1.0-12, 37 degrees C for 1-48 hours. Cyanide was measured using a validated colorimetric method by UV-VIS spectroscopy. Results. PB had the highest cyanide release at pH 1 (135 ug/g) and lowest release at pH 5.0-7.0 from the highest daily dose of PB (17.5 g) (21 ug/g). Considering the minimal lethal dose of cyanide is approximately 50 mg, the maximal cyanide released (1.6 mg) does not present a safety concern. C1 [Yang, Yongsheng; Brownell, Charles; Lyon, Robbie; Faustino, Patrick] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Prod Qual Res, Silver Spring, MD 20993 USA. [Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [May, Joan; Del Grosso, Alfred; Place, David; Leutzinger, Eldon; Duffy, Eric; Houn, Florence] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD USA. [He, Ruyi] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Faustino, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Prod Qual Res, Life Sci Bldg 64,Room 1078, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 27 TC 25 Z9 26 U1 3 U2 16 PU INFORMA HEALTHCARE-TAYLOR & FRANCIS PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON, OXFORSHIRE OX14 4RN, ENGLAND SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD OCT-NOV PY 2007 VL 45 IS 7 BP 776 EP 781 DI 10.1080/15563650601181562 PG 6 WC Toxicology SC Toxicology GA 240HP UT WOS:000251579000005 PM 17924254 ER PT J AU Drake, SL DePaola, A Jaykus, LA AF Drake, Stephenie L. DePaola, Angelo Jaykus, Lee-Ann TI An overview of Vibrio vulnificus and Vibrio parahaemolyticus SO COMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY LA English DT Review ID THERMOSTABLE DIRECT HEMOLYSIN; REAL-TIME PCR; OYSTERS CRASSOSTREA-VIRGINICA; GULF-OF-MEXICO; FIELD GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; LABELED OLIGONUCLEOTIDE PROBE; PHOSPHATE-BUFFERED SALINE; HIGH HYDROSTATIC-PRESSURE; POLYMORPHIC DNA ANALYSIS AB The Vibrionaceae are environmentally ubiquitous to estuarine waters. Two species in particular, V. vulnificus and V. parahaemolyticus, are important human pathogens that are transmitted by the consumption of contaminated molluscan shellfish. This document provides a comprehensive review of the current state of knowledge about these important foodborne disease agents. Topics include the epidemiology of human disease; biotypes and virulence factors; cultural and molecular-based detection methods; phenotyping and genotyping approaches; microbial ecology; and candidate control strategies. Recent international risk assessment efforts are also described. The reader will gain an understanding of why these organisms pose a public health risk and how improving our understanding of their behavior in the environment and the host can aid in reducing that risk in the future. C1 N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Drake, SL (reprint author), N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. EM sldrake@unity.ncsu.edu NR 298 TC 63 Z9 64 U1 4 U2 30 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1541-4337 J9 COMPR REV FOOD SCI F JI Compr. Rev. Food. Sci. Food Saf. PD OCT PY 2007 VL 6 IS 4 BP 120 EP 144 DI 10.1111/j.1541-4337.2007.00022.x PG 25 WC Food Science & Technology SC Food Science & Technology GA 210VU UT WOS:000249484500005 ER PT J AU McAdams, M Staffa, JA Dal Pan, GJ AF McAdams, Mara Staffa, Judy A. Dal Pan, Gerald J. TI The concomitant prescribing of ethinyl estradiol/drospirenone and potentially interacting drugs SO CONTRACEPTION LA English DT Article DE drospirenone; concomitant treatment; potassium sparing; hyperkalemia; progestin; Yasmin; oral contraceptive AB Background: Ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin drospirenone with antimineralocorticoid properties that may cause potassium retention leading to hyperkalemia. We estimated the percentage of EE/DRSP users prescribed concomitant potassium-sparing drugs [nonsteroidal antiinflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors (with diuretics), angiotensin II agonists (with diuretics), and potassium chloride] between January 1, 2002, and March 31, 2005. Study Design: We analyzed a population-based data set of 62,527 EE/DRSP users (Dimension Rx (TM), Caremark). We compared the fill date and end date for each prescription (Rx) for an interacting drug to the start and end date for each EE/DRSP episode (linked Rxs). If a day of an interacting Rx overlapped with an EE/DRSP episode, concomitant prescribing was recorded. Results: A total of 17.6% of the women concomitantly used EE/DRSP and an interacting drug. Twenty-nine percent of concomitant use occurred within a month of EE/DRSP initiation. Nonsteroidal antiinflammatory drugs and diuretics were most frequently used concomitantly with EE/DRSP. Forty percent of the women with concomitant use were 35 yearsof age or older at EE/DRSP initiation compared with 29% without concomitant use (p<.001). Obstetricians/gynecologists and family practitioners were the most common prescribers of EE/DRSP and potassium-sparing drugs, respectively. Conclusions: Concomitant prescribing of EE/DRSP and potassium-sparing drugs occurred frequently in our study population. As EE/DRSP becomes more widely used, physicians prescribing it should monitor patients for potassium-sparing drug use. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP McAdams, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. EM mara.mcadams@fda.hhs.gov OI McAdams-DeMarco, Mara/0000-0003-3013-925X NR 8 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD OCT PY 2007 VL 76 IS 4 BP 278 EP 281 DI 10.1016/j.contraception.2007.06.002 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 218QJ UT WOS:000250029700005 PM 17900437 ER PT J AU Thomas, JT Moos, M AF Thomas, John Terrig Moos, Malcolm, Jr. TI Vg1 has specific processing requirements that restrict its action to body axis patterning centers SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Vg1; proprotein convertases; BMP processing; mesoderm formation ID IN-SITU HYBRIDIZATION; ORGANIZER GENE-EXPRESSION; TGF-BETA FAMILY; XENOPUS DEVELOPMENT; EMBRYONIC-DEVELOPMENT; SIGNALING PATHWAYS; SPEMANN ORGANIZER; DORSAL MESODERM; PROTEIN; INDUCTION AB Unlike most transforming growth factor-beta (TGF-beta) superfamily members, Vg1 has been shown not to produce gross phenotypic alterations in Xenapus embryos when overexpressed by mRNA injection. Experiments with artificial chimeric constructs and a recently identified second allele of Vg1 suggest that this may be due to unusually stringent requirements for proteolytic processing. We provide biological and biochemical evidence that cleavage by two distinct proteolytic enzymes is required for effective activation of Vg1. We demonstrate a tightly restricted overlap in expression patterns of Vg1 with the proteases required to release the mature peptide. The data presented may account for the long-standing observation that the vast majority of Vg1 protein, in vivo, is present in its unprocessed form. Taken together, these observations provide a plausible mechanism for local action of Vg1 consistent with requirements imposed by current models of pattern formation in the developing body axis. Published by Elsevier Inc. C1 US FDA, Div Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Moos, M (reprint author), US FDA, Div Cellular & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM john.thomas@fda.hhs.gov RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 46 TC 2 Z9 2 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2007 VL 310 IS 1 BP 129 EP 139 DI 10.1016/j.ydbio.2007.07.032 PG 11 WC Developmental Biology SC Developmental Biology GA 219JF UT WOS:000250080000011 PM 17707366 ER PT J AU Bagnyukova, TV Luzhna, LI Pogribny, IP Lushchak, VI AF Bagnyukova, Tetyana V. Luzhna, Lidia I. Pogribny, Igor P. Lushchak, Volodymyr I. TI Oxidative stress and antioxidant defenses in goldfish liver in response to short-term exposure to arsenite SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE arsenic; oxidative stress; glutathione; antioxidant enzymes; DNA methylation; fish ID FREE-RADICAL PROCESSES; LIPID-PEROXIDATION; TRIVALENT ARSENICALS; DIMETHYLARSINIC ACID; COMPLEX-FORMATION; INDUCED TOXICITY; GENE-EXPRESSION; DNA-DAMAGE; GLUTATHIONE; CELLS AB Arsenic is an environmental pollutant capable of causing oxidative stress, disturbance of metabolism, and cancer development. The present study was undertaken to investigate the effects of exposure to sodium arsenite on the glutathione pool, lipid peroxidation, protein carbonyl levels, global DNA methylation, and activities of six antioxidant enzymes in goldfish liver. In a preliminary experiment, 7-day exposure to 200 mu M sodium arsenite, but not 10 or 100 mu M disturbed the glutathione status. A detailed investigation of oxidative stress development and antioxidant responses was further examined during different periods of exposure to 200 mu M sodium arsenite. This treatment increased lipid peroxide levels after 1 and 4 days of exposure but did not affect thiobarbituric acid reactive substances and protein carbonyls. Oxidized glutathione and the oxidative stress index rose after 4 days, but de novo glutathione synthesis decreased both parameters after 7 days. Activities of the main antioxidant enzymes - superoxide dismutase, catalase, and glutathione peroxidase, were elevated after longer periods of exposure, indicating an enhanced antioxidant response. Arsenite exposure led to DNA hypomethylation, which is an early marker of disturbed epigenetic regulations. The findings suggest that goldfish livers cope with arsenic-induced oxidative stress mainly through adaptive changes in the glutathione pool and antioxidant enzymes. Environ. Mol. Mutagen. 48:658-665, 2007. (C) 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72029 USA. Precarpathian Natl Univ, Dept Biochem, Ivano Frankivsk, Ukraine. RP Bagnyukova, TV (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCRT Rd, Jefferson, AR 72029 USA. EM Tetyana.Bagnyukova@fda.hhs.gov; lushchak@pu.if.ua NR 54 TC 45 Z9 47 U1 1 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2007 VL 48 IS 8 BP 658 EP 665 DI 10.1002/em.20328 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 222TZ UT WOS:000250321500005 PM 17685460 ER EF