FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Grinev, A
Lu, Z
Chizhikov, V
Rios, M
AF Grinev, Andriyan
Lu, Zhong
Chizhikov, Vladimir
Rios, Maria
TI Application of a full-genome microarray-based assay for the study of
genetic variability of West Nile virus
SO JOURNAL OF VIROLOGICAL METHODS
LA English
DT Article
DE West Nile virus; Flavivirus; Microarray technology; PCR; Mutations;
Genetic variability
ID OLIGONUCLEOTIDE MICROARRAY; PHYLOGENETIC ANALYSIS; BLOOD-DONORS;
DISCRIMINATION; GENOTYPE; IDENTIFICATION; HYBRIDIZATION; EVOLUTION;
MOSQUITOS; STRAINS
AB Viral adaptation through fixation of spontaneous mutations is an important factor potentially associated with reoccurrence of West Nile virus (WNV) outbreaks in the New World. The emergence of new genetic variants of WNV represents an important public health issue because it may affect the sensitivity of WNV screening and diagnostic assays, as well as the development and efficacy of WNV vaccines and anti-viral drugs. A microarray assay was developed and optimized to enable simple monitoring of WNV genetic variability and rapid detection of any nucleotide mutations within the entire viral genome. The assay was validated using 11 WNV isolates from the 2007 and 2009 U.S. epidemics. The developed microarray system can potentially serve as a high throughput, rapid, and effective approach for the detection of circulating WNV genetic variants. Published by Elsevier B.V.
C1 [Grinev, Andriyan; Lu, Zhong; Rios, Maria] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Chizhikov, Vladimir] US FDA, Lab Methods Dev, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP Rios, M (reprint author), NIH Bldg 29,Room 131,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM Maria.Rios@fda.hhs.gov
NR 24
TC 3
Z9 4
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-0934
J9 J VIROL METHODS
JI J. Virol. Methods
PD AUG
PY 2012
VL 183
IS 2
BP 219
EP 223
DI 10.1016/j.jviromet.2012.04.001
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Virology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Virology
GA 966VQ
UT WOS:000305865900018
PM 22561983
ER
PT J
AU Chen, XR
Yan, J
Chen, T
AF Chen, Xinrong
Yan, Jian
Chen, Tao
TI Expression level of miR-34a rather than P53 gene status correlates with
mutability in related human lymphoblast cell lines
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE microRNA; mutant frequency; X-ray; tumor suppressor gene and TK6 cells
ID THYMIDINE KINASE LOCUS; ETHYL-N-NITROSOUREA; TUMOR-SUPPRESSOR;
DNA-DAMAGE; IN-VIVO; APOPTOSIS; CONTRIBUTES; MICRORNA; EXPOSURE;
MUTATION
AB The P53 gene is a tumor suppressor gene and can prevent mutation and tumor induction though apoptosis and DNA repair when it is activated by genotoxic stress. miR-34a expression is regulated by the P53 gene and might be required for cell response to DNA damage. TK6 cells are human lymphoblast cells with normal P53 function while WTK1 and NH32 cells derived from the same progenitor as TK6 cells are P53-deficient. Previous mutation research showed an unexpected result that NH32 cells were much less mutable than WTK1 cells, although the P53 gene in both the cell lines is not functional. To explore the possible mechanisms involved in the different mutability of the cell lines and relationship between P53 and miR-34a, we investigated the expression levels of miR-34a in the cells. The basal and X-ray-induced expression levels of miR-34a in TK6 and NH32 cells were much higher than those in WTK1 cells. The miR-34a was also able to be up-regulated to respond to X-ray exposure without a functional P53 gene in both of the NH32 and WTK1 cells. In addition, the expression levels of miR-34a in these three cell lines are inversely correlated well with their mutability: higher levels of miR-34a correspond with less mutable cells. These results suggest that alteration of miR-34a expression is at least partially independent of P53 regulation and its expression levels are closely related to cells' mutability regardless of P53 status. 2011 Wiley Periodicals, Inc.
C1 [Chen, Xinrong; Yan, Jian; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Chen, T (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 130, Jefferson, AR 72079 USA.
NR 17
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD AUG
PY 2012
VL 51
IS 8
BP 674
EP 677
DI 10.1002/mc.20830
PG 4
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 968FJ
UT WOS:000305962400008
PM 21809390
ER
PT J
AU Miesegaes, GR
Lute, S
Strauss, DM
Read, EK
Venkiteshwaran, A
Kreuzman, A
Shah, R
Shamlou, P
Chen, D
Brorson, K
AF Miesegaes, G. R.
Lute, S.
Strauss, D. M.
Read, E. K.
Venkiteshwaran, A.
Kreuzman, A.
Shah, R.
Shamlou, P.
Chen, D.
Brorson, K.
TI Monoclonal antibody capture and viral clearance by cation exchange
chromatography
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Article
DE monoclonal antibodies; viral clearance; cation exchange chromatography
ID PROTEIN-A; PURIFICATION PROCESSES; VIRUS; SEPHAROSE; REMOVAL; AUREUS;
POINT; PR772
AB Traditionally, post-production culture harvest capture of therapeutic monoclonal antibodies (mAbs) is performed using Protein A chromatography. We investigated the efficiency and robustness of cation exchange chromatography (CEX) in an effort to evaluate alternative capture methodologies. Up to five commercially available CEX resins were systematically evaluated using an experimentally optimized buffer platform and a design-of-experiment (DoE) approach for their ability to (a) capture a model mAb with a neutral isoelectric point, (b) clear three model viruses (porcine parvovirus, CHO type-C particles, and a bacteriophage). This approach identified a narrow operating space where yield, purity, and viral clearance were optimal under a CEX capture platform, and revealed trends between viral clearance of PPV and product purity (but not yield). Our results suggest that after unit operation optimization, CEX can serve as a suitable capture step. Biotechnol. Bioeng. 2012; 109:20482058. (c) 2012 Wiley Periodicals, Inc.
C1 [Miesegaes, G. R.; Lute, S.; Read, E. K.; Brorson, K.] US FDA, Off Biotechnol Prod, CDER, Silver Spring, MD 20903 USA.
[Strauss, D. M.; Venkiteshwaran, A.; Kreuzman, A.; Shamlou, P.; Chen, D.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Shah, R.] US FDA, Off Testing & Res, CDER, Silver Spring, MD 20903 USA.
RP Brorson, K (reprint author), US FDA, Off Biotechnol Prod, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM kurt.brorson@fda.hhs.gov
FU CDER/FDA; Eli Lilly Co.
FX We thank Laurie Graham and Chikako Torigoe (CDER/FDA) for careful review
of this manuscript. This work was funded in part by a cooperative
research and development agreement (CRADA) between CDER/FDA and Eli
Lilly & Co.
NR 32
TC 11
Z9 11
U1 1
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD AUG
PY 2012
VL 109
IS 8
BP 2048
EP 2058
DI 10.1002/bit.24480
PG 11
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 961GE
UT WOS:000305451400018
PM 22488719
ER
PT J
AU Jagadeesh, G
Balakumar, P
Stockbridge, N
AF Jagadeesh, Gowraganahalli
Balakumar, Pitchai
Stockbridge, Norman
TI How well do aliskiren's purported mechanisms track its effects on
cardiovascular and renal disorders?
SO CELLULAR SIGNALLING
LA English
DT Review
DE Aliskiren; (Pro)renin receptor; Wnt/Fz signal transduction; PPAR gamma;
Cardiovascular-renal disorders; Renin-angiotensin-aldosterone system
ID DIRECT RENIN INHIBITOR; INDUCED CARDIAC-HYPERTROPHY;
ACTIVATED-RECEPTOR-GAMMA; CHRONIC KIDNEY-DISEASE; DOUBLE-BLIND TRIAL;
DEPENDENT DIABETES-MELLITUS; ANGIOTENSIN-II PRODUCTION; LOWERS
BLOOD-PRESSURE; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS
AB The overactivation of the renin-angiotensin-aldosterone system (RAAS) is associated with cardiovascular and renal abnormalities, which can be mitigated by angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II (Ang-II)-AT(1) receptor blockers (ARBs). Both prorenin and renin bind to the (pro)renin receptor (PRR) to activate Ang-II-dependent and -independent signaling cascades. Renin cleaves angiotensinogen to Ang-I, which is subsequently converted into Ang-II leading to cardiovascular and renal compensatory responses and eventually dysfunction. This initial step is blocked by renin inhibitor aliskiren, thus explaining its anti-hypertensive effect. Aliskiren is approved for the treatment of hypertension either as monotherapy or in combination with amlodipine, hydrochlorothiazide, or valsartan. Several clinical trials have suggested an organoprotective potential of aliskiren beyond its anti-hypertensive action, but the mechanism by which this might occur is less clear. Like ACEIs and ARBs, aliskiren increases plasma renin concentration: however, aliskiren reduces plasma renin activity. Intriguingly, aliskiren has additional abilities to downregulate the expression of the PRR and the AT(1) receptor, adding novel mechanistic insights to our current knowledge. Importantly, a few questions remain unresolved, such as the potential effects of aliskiren on (i) prorenin and its receptor-mediated Mg-II-independent pathways, and (ii) the signal network that comprises of PRR-associated vacuolar-H+-ATPase-linked Wnt/Frizzled signal transduction, including canonical-beta-catenin and non-canonical Wnt-JNK-Ca2+ signals. Discrepant outcomes in ALTITUDE study make more complex understanding aliskiren's therapeutic potential in treating cardio-renal disorders. This review attempts to address some of the remaining questions regarding aliskiren's action in cardiovascular and renal disorders. Published by Elsevier Inc.
C1 [Jagadeesh, Gowraganahalli; Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Balakumar, Pitchai] Rajendra Inst Technol & Sci, Cardiovasc Pharmacol Div, Dept Pharmacol, Inst Pharm, Sirsa 125055, India.
RP Jagadeesh, G (reprint author), US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 4128, Silver Spring, MD 20993 USA.
EM Gowra.Jagadeesh@fda.hhs.gov; pbala2006@gmail.com;
Norman.Stockbridge@fda.hhs.gov
NR 111
TC 5
Z9 5
U1 1
U2 9
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 AUG
PY 2012
VL 24
IS 8
BP 1583
EP 1591
DI 10.1016/j.cellsig.2012.04.003
PG 9
WC Cell Biology
SC Cell Biology
GA 964QW
UT WOS:000305712800013
PM 22522051
ER
PT J
AU Lanzarotta, A
Crowe, JB
Witkowski, M
Gamble, BM
AF Lanzarotta, Adam
Crowe, John B.
Witkowski, Mark
Gamble, Bryan M.
TI A multidisciplinary approach for the analysis of an adulterated dietary
supplement where the active pharmaceutical ingredient was embedded in
the capsule shell
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Infrared imaging; Raman spectroscopy; Optical microscopy; LC/MS; Dietary
supplement; Adulteration
ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE
LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY;
ELECTROSPRAY-IONIZATION; STRUCTURAL ELUCIDATION; SILDENAFIL; TADALAFIL;
VARDENAFIL; ANALOG; IDENTIFICATION
AB Fourier transform infrared (FT-IR) microspectroscopic imaging, Raman microspectroscopy, optical microscopy and high performance liquid chromatography with mass spectrometric (LC/MS) detection were employed to examine a dietary supplement adulterated with an undeclared active pharmaceutical ingredient (API). While a trace level of the API was detected in the capsule contents, a higher concentration of API was found in the capsule shell, which indicated the use of an unconventional manufacturing process to hide the API and thus avoid detection. This study demonstrates the need for a multidisciplinary approach to provide a complete assessment of a suspect adulterated dietary supplement. Published by Elsevier B.V.
C1 [Lanzarotta, Adam; Crowe, John B.; Witkowski, Mark; Gamble, Bryan M.] US FDA, Forens Chem Ctr, Trace Examinat Sect, Cincinnati, OH 45237 USA.
RP Lanzarotta, A (reprint author), US FDA, Forens Chem Ctr, Trace Examinat Sect, Cincinnati, OH 45237 USA.
EM adam.lanzarotta@fda.hhs.gov
NR 25
TC 15
Z9 16
U1 2
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD AUG-SEP
PY 2012
VL 67-68
BP 22
EP 27
DI 10.1016/j.jpba.2012.04.023
PG 6
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 963AG
UT WOS:000305591900004
PM 22633604
ER
PT J
AU Sommers, CD
Montpas, N
Adam, A
Keire, DA
AF Sommers, Cynthia D.
Montpas, Nicolas
Adam, Albert
Keire, David A.
TI Characterization of currently marketed heparin products: Adverse event
relevant bioassays
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Heparin; OSCS; Protamine; Kallikrein activity; Bradykinin; Compliment
activation
ID OVERSULFATED CHONDROITIN SULFATE; MOLECULAR-WEIGHT HEPARINS; MICROPLATE
BASED ASSAY; CONTAMINATED HEPARIN; ACTIVATION; PROTAMINE; PROTEINS;
BINDING; SODIUM; SYSTEM
AB The polyanion oversulfated chondroitin sulfate (OSCS) was identified as a contaminant in heparin products and was associated with severe hypotensive responses and other symptoms in patients receiving the drug. The OSCS associated adverse reactions were attributed to activation of the contact system via the plasma mediator, activated factor XII (FXIla), which triggers kallikrein (KK) activity. Unlike heparin alone, OSCS, is able to activate FXII in plasma and stably bind to FXIla enhancing plasma KM activity and the induction of vasoactive mediators such as bradykinin (BK), C3a and C5a. Similarly OSCS can interfere with heparin neutralization by the polycationic drug protamine. Here, we assess heparin (heparin sodium, dalteparin, tinzaparin or enoxaparin)-protamine complex formation and plasma based bioassays of KK, BK and C5a in a 96-well plate format. We establish the normal range of variation in the optimized bioassays across multiple lots from 9 manufacturers. In addition, because other oversulfated (OS) glycosamino-glycans (GAGs) besides OSCS could also serve as possible economically motivated adulterants (EMAs) to heparin, we characterize OS-dermatan sulfate (OSDS), OS-heparan sulfate (OSHS) and their native forms in the same assays. For the protamine test, OS-GAGs could be distinguished from heparin. For the KM assay, OSCS and OSDS were most potent followed by OSHS, and all had similar efficacies. Finally, OSDS had a greater efficacy in the C5a and BK assays followed by OSCS then OSHS. These data established the normal range of response of heparin products in these assays and the alteration in the responses in the presence of possible EMAs. Published by Elsevier B.V.
C1 [Sommers, Cynthia D.; Keire, David A.] US FDA, CDER, DPA, St Louis, MO 63101 USA.
[Montpas, Nicolas; Adam, Albert] Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada.
RP Keire, DA (reprint author), US FDA, CDER, DPA, 1114 Market St, St Louis, MO 63101 USA.
EM David.Keire@fda.hhs.gov
NR 30
TC 4
Z9 4
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD AUG-SEP
PY 2012
VL 67-68
BP 28
EP 35
DI 10.1016/j.jpba.2012.04.017
PG 8
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 963AG
UT WOS:000305591900005
PM 22591805
ER
PT J
AU Wang, B
Buhse, LF
Al-Hakim, A
Ii, MTB
Keire, DA
AF Wang, Bo
Buhse, Lucinda F.
Al-Hakim, Ali
Ii, Michael T. Boyne
Keire, David A.
TI Characterization of currently marketed heparin products: Analysis of
heparin digests by RPIP-UHPLC-QTOF-MS
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Heparin; LMWH; QTOF-MS; UHPLC; RPIP
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TRAP MASS-SPECTROMETRY;
MOLECULAR-WEIGHT HEPARINS; NUCLEAR-MAGNETIC-RESONANCE;
CAPILLARY-ELECTROPHORESIS; FLAVOBACTERIUM-HEPARINUM; DISACCHARIDE
COMPOSITION; SUBSTRATE-SPECIFICITY; FLUORESCENCE DETECTION; SULFATE
AB Previously, the FDA validated a method to assess the structure and composition of heparin products by separating and quantifying disaccharide level digests by reverse-phase-ion-pairing liquid chromatography (RPIP-HPLC) coupled to a low resolution and low sensitivity ion trap mass-spectrometer. Here, improved separation, information content and sensitivity were obtained through the use of reverse phase ion-pairing ultra-high pressure liquid chromatography (RPIP-UHPLC) coupled with a quadrupole time-of-flight (Q-TOF) mass spectrometer. Thus, with the new method, improved structural characterization of the same 20 lots of heparin sodium active pharmaceutical ingredients (APIs) as were analyzed in the previous work were obtained. In addition, for the first time, 10 low molecular weight heparin (LMWH) lots were characterized representing multiple lots manufactured by three different processes (dalteparin, tinzaparin or enoxaparin). In this study, UHPLC separation conditions and the enzymatic digesting protocol were optimized for analysis of disaccharide level digests of heparin and positive and negative electrospray ionization (ESI) modes were tested. The negative ion mode ESI analysis was found to be superior to the positive ion mode for these measurements, and a combination of heparin lyase II and III were optimal for heparin digestion. The data obtained establishes the normal variation in the composition of heparin sodium or LMWHs in this assay. These values are useful as possible product benchmarks and for surveillance of the heparin products being imported into the US market. Published by Elsevier B.V.
C1 [Wang, Bo; Buhse, Lucinda F.; Ii, Michael T. Boyne; Keire, David A.] US FDA, CDER, DPA, St Louis, MO 63101 USA.
[Al-Hakim, Ali] Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA.
RP Keire, DA (reprint author), US FDA, CDER, DPA, 1114 Market St, St Louis, MO 63101 USA.
EM David.Keire@fda.hhs.gov
NR 40
TC 20
Z9 21
U1 0
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD AUG-SEP
PY 2012
VL 67-68
BP 42
EP 50
DI 10.1016/j.jpba.2012.04.033
PG 9
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 963AG
UT WOS:000305591900007
PM 22633605
ER
PT J
AU Laksanalamai, P
Joseph, LA
Silk, BJ
Burall, LS
Tarr, CL
Gerner-Smidt, P
Datta, AR
AF Laksanalamai, Pongpan
Joseph, Lavin A.
Silk, Benjamin J.
Burall, Laurel S.
Tarr, Cheryl L.
Gerner-Smidt, Peter
Datta, Atin R.
TI Genomic Characterization of Listeria monocytogenes Strains Involved in a
Multistate Listeriosis Outbreak Associated with Cantaloupe in US
SO PLOS ONE
LA English
DT Article
ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; ESCHERICHIA-COLI; PULSENET;
MEAT; DIVERSITY; ENVIRONMENT; EVOLUTION; INFECTION; PROTOCOL
AB A multistate listeriosis outbreak associated with cantaloupe consumption was reported in the United States in September, 2011. The outbreak investigation recorded a total of 146 invasive illnesses, 30 deaths and one miscarriage. Subtyping of the outbreak associated clinical, food and environmental isolates revealed two serotypes (1/2a and 1/2b) and four pulsed-field gel electrophoresis two-enzyme pattern combinations I, II, III, and IV, including one rarely seen before this outbreak. A DNA-microarray, Listeria GeneChip (R), developed by FDA from 24 Listeria monocytogenes genome sequences, was used to further characterize a representative sample of the outbreak isolates. The microarray data ( in the form of present or absent calls of specific DNA sequences) separated the isolates into two distinct groups as per their serotypes. The gene content of the outbreak-associated isolates was distinct from that of the previously-reported outbreak strains belonging to the same serotypes. Although the 1/2b outbreak associated isolates are closely related to each other, the 1/2a isolates could be further divided into two distinct genomic groups, one represented by pattern combination I strains and the other represented by highly similar pattern combinations III and IV strains. Gene content analysis of these groups revealed unique genomic sequences associated with these two 1/2a genovars. This work underscores the utility of multiple approaches, such as serotyping, PFGE and DNA microarray analysis to characterize the composition of complex polyclonal listeriosis outbreaks.
C1 [Laksanalamai, Pongpan; Burall, Laurel S.; Datta, Atin R.] FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
[Joseph, Lavin A.; Silk, Benjamin J.; Tarr, Cheryl L.; Gerner-Smidt, Peter] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
RP Laksanalamai, P (reprint author), FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
EM Atin.datta@fda.hhs.gov
NR 48
TC 48
Z9 50
U1 1
U2 26
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 31
PY 2012
VL 7
IS 7
AR e42448
DI 10.1371/journal.pone.0042448
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 982LS
UT WOS:000307045600101
PM 22860127
ER
PT J
AU Schmued, L
Raymick, J
Tolleson, W
Sarkar, S
Zhang, YH
Bell-Cohn, A
AF Schmued, Larry
Raymick, James
Tolleson, William
Sarkar, Sumit
Zhang, Yi-Hong
Bell-Cohn, Ashlee
TI Introducing Amylo-Glo, a novel fluorescent amyloid specific
histochemical tracer especially suited for multiple labeling and large
scale quantification studies
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Amyloid plaques; A-beta; Alzheimer's disease; Amylo-Glo; Histology;
Multiple labeling; Fluorescent dye
ID ALZHEIMERS-DISEASE; PLAQUES; K114
AB One of the hallmark pathologies associated with Alzheimer's disease (AD) is the conspicuous deposition of extracellular amyloid plaques within the forebrain. These plaques are primarily composed of fibrular aggregates of the A-beta peptide. Traditional methods for the histological localization of these plaques typically rely on the use of the tracers Congo Red or Thioflavin S. This study describes the characterization of a novel fluorescent histochemical probe, Amylo-Glo, for the high resolution and contrast localization of amyloid plaques in brain tissue sections. Potential advantages over conventional amyloid plaque stains such as Congo Red or Thioflavin S can be attributed to its unique chemical and spectral properties. Specifically, it results in a very bright blue UV excitable stain under physiological conditions that will not bleed through when illuminated with other filters. Its brightness makes it ideal for low magnification quantification studies, while its unique excitation/emission profile and mild staining conditions makes it ideal for combination with multiple immunofluorescent labeling studies. Published by Elsevier B.V.
C1 [Schmued, Larry; Sarkar, Sumit; Zhang, Yi-Hong] US FDA, Div Neurotoxicol, NCTR, Jefferson, AR 72079 USA.
[Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Tolleson, William] US FDA, Div Biochem Toxicol, NCTR, Jefferson, AR 72079 USA.
[Bell-Cohn, Ashlee] Univ Arkansas, Dept Chem, Fayetteville, AR 72701 USA.
RP Schmued, L (reprint author), US FDA, Div Neurotoxicol, NCTR, Jefferson, AR 72079 USA.
EM larry.schmued@fda.hhs.gov
FU FDA protocol [E-7273]
FX The authors would like to thank Ms. Melanie Dumas and Ms. Florene Lewis
for her help with the animal care. We would also like to thank Mr.
Joseph Whatley for help in determining brightness assessments. This work
was supported by FDA protocol E-7273.
NR 10
TC 10
Z9 11
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD JUL 30
PY 2012
VL 209
IS 1
BP 120
EP 126
DI 10.1016/j.jneumeth.2012.05.019
PG 7
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 983QB
UT WOS:000307132700015
PM 22705750
ER
PT J
AU Shibeko, AM
Woodle, SA
Lee, TK
Ovanesov, MV
AF Shibeko, Alexey M.
Woodle, Samuel A.
Lee, Timothy K.
Ovanesov, Mikhail V.
TI Unifying the mechanism of recombinant FVIIa action: dose dependence is
regulated differently by tissue factor and phospholipids
SO BLOOD
LA English
DT Article
ID ACTIVATED FACTOR-VII; THROMBIN GENERATION; HEMOPHILIA PATIENTS;
BLOOD-COAGULATION; INHIBITORS; RFVIIA; HEMOSTASIS; DISORDERS; ZYMOGEN;
PROCOAGULANT
AB Recombinant factor VIIa (rFVIIa) is used for treatment of hemophilia patients with inhibitors, as well for off-label treatment of severe bleeding in trauma and surgery. Effective bleeding control requires supraphysiological doses of rFVIIa, posing both high expense and uncertain thrombotic risk. Two major competing theories offer different explanations for the supraphysiological rFVIIa dosing requirement: (1) the need to overcome competition between FVIIa and FVII zymogen for tissue factor (TF) binding, and (2) a high-dose-requiring phospholipid-related pathway of FVIIa action. In the present study, we found experimental conditions in which both mechanisms contribute simultaneously and independently to rFVIIa-driven thrombin generation in FVII-deficient human plasma. From mathematical simulations of our model of FX activation, which were confirmed by thrombin-generation experiments, we conclude that the action of rFVIIa at pharmacologic doses is dominated by the TF-dependent pathway with a minor contribution from a phospholipid-dependent mechanism. We established a dose-response curve for rFVIIa that is useful to explain dosing strategies. In the present study, we present a pathway to reconcile the 2 major mechanisms of rFVIIa action, a necessary step to understanding future dose optimization and evaluation of new rFVIIa analogs currently under development. (Blood. 2012;120(4):891-899)
C1 [Shibeko, Alexey M.; Woodle, Samuel A.; Lee, Timothy K.; Ovanesov, Mikhail V.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Ovanesov, MV (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, 29 Lincoln Dr,N29-306, Bethesda, MD 20892 USA.
EM mikhail.ovanesov@fda.hhs.gov
RI Shibeko, Alexey/A-9447-2014
OI Shibeko, Alexey/0000-0003-1494-3125
FU postgraduate and postbaccalaureate research fellowship; US Department of
Energy
FX This study was supported in part by postgraduate and postbaccalaureate
research fellowship awards to A.M.S. and S.A.W. from the Oak Ridge
Institute for Science and Education through an inter-agency agreement
between the US Department of Energy and the US Food and Drug
Administration.
NR 48
TC 21
Z9 22
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 JUL 26
PY 2012
VL 120
IS 4
BP 891
EP 899
DI 10.1182/blood-2011-11-393371
PG 9
WC Hematology
SC Hematology
GA 987VH
UT WOS:000307445400023
PM 22563088
ER
PT J
AU Al Safadi, R
Abu-Ali, GS
Sloup, RE
Rudrik, JT
Waters, CM
Eaton, KA
Manning, SD
AF Al Safadi, Rim
Abu-Ali, Galeb S.
Sloup, Rudolph E.
Rudrik, James T.
Waters, Christopher M.
Eaton, Kathryn A.
Manning, Shannon D.
TI Correlation between In Vivo Biofilm Formation and Virulence Gene
Expression in Escherichia coli O104:H4
SO PLOS ONE
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; CELLS; PATHOGENESIS; ADHERENCE; O157-H7;
STRAINS; DISEASE; GROWTH; ROLES; LOCUS
AB The emergence of novel pathogens poses a major public health threat causing widespread epidemics in susceptible populations. The Escherichia coli O104:H4 strain implicated in a 2011 outbreak in northern Germany caused the highest frequency of hemolytic uremic syndrome (HUS) and death ever recorded in a single E. coli outbreak. Therefore, it has been suggested that this strain is more virulent than other pathogenic E. coli (e.g., E. coli O157:H7). The E. coli O104:H4 outbreak strain possesses multiple virulence factors from both Shiga toxin (Stx)-producing E. coli (STEC) and enteroaggregative E. coli (EAEC), though the mechanism of pathogenesis is not known. Here, we demonstrate that E. coli O104:H4 produces a stable biofilm in vitro and that in vivo virulence gene expression is highest when E. coli O104:H4 overexpresses genes required for aggregation and exopolysaccharide production, a characteristic of bacterial cells residing within an established biofilm. Interrupting exopolysaccharide production and biofilm formation may therefore represent effective strategies for combating future E. coli O104:H4 infections.
C1 [Al Safadi, Rim; Sloup, Rudolph E.; Waters, Christopher M.; Manning, Shannon D.] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
[Abu-Ali, Galeb S.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
[Rudrik, James T.] Michigan Dept Community Hlth, Bur Labs, Lansing, MI USA.
[Eaton, Kathryn A.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
RP Al Safadi, R (reprint author), Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA.
EM mannin71@msu.edu
OI Manning, Shannon/0000-0001-9581-0660
FU National Institutes of Health Enterics Research Investigational Network
Cooperative Research Center at Michigan State University [U19AI090872];
United States Department of Agriculture, National Institute of Food and
Agriculture [2011-67005-30004]
FX This work was supported by the National Institutes of Health Enterics
Research Investigational Network Cooperative Research Center at Michigan
State University [grant number U19AI090872 (SDM)] and in part by the
United States Department of Agriculture, National Institute of Food and
Agriculture [grant number 2011-67005-30004 (SDM)]. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 34
TC 22
Z9 22
U1 2
U2 18
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 25
PY 2012
VL 7
IS 7
AR e41628
DI 10.1371/journal.pone.0041628
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 979GX
UT WOS:000306806600097
PM 22848550
ER
PT J
AU Skoog, SA
Bayati, MR
Petrochenko, PE
Stafslien, S
Daniels, J
Cilz, N
Comstock, DJ
Elam, JW
Narayan, RJ
AF Skoog, S. A.
Bayati, M. R.
Petrochenko, P. E.
Stafslien, S.
Daniels, J.
Cilz, N.
Comstock, D. J.
Elam, J. W.
Narayan, R. J.
TI Antibacterial activity of zinc oxide-coated nanoporous alumina
SO MATERIALS SCIENCE AND ENGINEERING B-ADVANCED FUNCTIONAL SOLID-STATE
MATERIALS
LA English
DT Article
DE Aluminum oxide; Zinc oxide; Atomic layer deposition; Nanoporous
material; Antibacterial material
ID ATOMIC-LAYER DEPOSITION; THIN-FILMS; ANTIBIOTIC-RESISTANCE; SKIN
INFECTIONS; POWDER SLURRY; ZNO; MEMBRANES; BACTERIA; NANOPARTICLES;
TEMPLATES
AB Nanoporous alumina membranes, also known as anodized aluminum oxide membranes, are being investigated for use in treatment of burn injuries and other skin wounds. In this study, atomic layer deposition was used for coating the surfaces of nanoporous alumina membranes with zinc oxide. Agar diffusion assays were used to show activity of zinc oxide-coated nanoporous alumina membranes against several bacteria found on the skin surface, including Bacillus subtilis, Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis. On the other hand, zinc oxide-coated nanoporous alumina membranes did not show activity against Pseudomonas aeruginosa, Enterococcus faecalis, and Candida albicans. These results suggest that zinc oxide-coated nanoporous alumina membranes have activity against some Gram-positive and Gram-negative bacteria that are associated with skin colonization and skin infection. (c) 2012 Elsevier B.V. All rights reserved.
C1 [Skoog, S. A.; Petrochenko, P. E.; Narayan, R. J.] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC 27695 USA.
[Bayati, M. R.; Narayan, R. J.] N Carolina State Univ, Dept Mat Sci & Engn, Raleigh, NC 27695 USA.
[Petrochenko, P. E.] US FDA, Ctr Devices & Radiol Hlth, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
[Stafslien, S.; Daniels, J.; Cilz, N.] N Dakota State Univ, Ctr Nanoscale Sci & Engn, Fargo, ND 58102 USA.
[Comstock, D. J.; Elam, J. W.] Argonne Natl Lab, Div Energy Syst, Argonne, IL 60439 USA.
RP Narayan, RJ (reprint author), Univ N Carolina, Joint Dept Biomed Engn, Box 7115, Raleigh, NC 27695 USA.
EM roger_narayan@msn.com
RI Narayan, Roger/J-2789-2013
OI Narayan, Roger/0000-0002-4876-9869
FU Army Research Office Contract [W911NF-10-1-0519]; Argonne; U.S.
Department of Energy Office of Science laboratory [DE-AC02-06CH11357]
FX SS, JD, and NC would like acknowledge support from Army Research Office
Contract Number W911NF-10-1-0519. The submitted manuscript has been
created in part by UChicago Argonne, LLC, Operator of Argonne National
Laboratory ("Argonne"). Argonne, a U.S. Department of Energy Office of
Science laboratory, is operated under Contract No. DE-AC02-06CH11357.
NR 45
TC 9
Z9 10
U1 0
U2 25
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0921-5107
J9 MATER SCI ENG B-ADV
JI Mater. Sci. Eng. B-Adv. Funct. Solid-State Mater.
PD JUL 25
PY 2012
VL 177
IS 12
BP 992
EP 998
DI 10.1016/j.mseb.2012.04.024
PG 7
WC Materials Science, Multidisciplinary; Physics, Condensed Matter
SC Materials Science; Physics
GA 978YG
UT WOS:000306781100012
ER
PT J
AU Chen, HC
Kodell, RL
Cheng, KF
Chen, JJ
AF Chen, Hung-Chia
Kodell, Ralph L.
Cheng, Kuang Fu
Chen, James J.
TI Assessment of performance of survival prediction models for cancer
prognosis
SO BMC MEDICAL RESEARCH METHODOLOGY
LA English
DT Article
ID CELL-LUNG-CANCER; GENE-EXPRESSION SIGNATURES; HIGH-DIMENSIONAL DATA;
CROSS-VALIDATION; BREAST-CANCER; RISK STRATIFICATION; MICROARRAY DATA;
LYMPHOMA; CLASSIFIERS; RECURRENCE
AB Background: Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient's class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments.
Methods: We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models.
Results: A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1) For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2) The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3) Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results.
Conclusions: 1) Different performance metrics for evaluation of a survival prediction model may give different conclusions in its discriminatory ability. 2) Evaluation using a high-risk versus low-risk group comparison depends on the selected risk-score threshold; a plot of p-values from all possible thresholds can show the sensitivity of the threshold selection. 3) A randomization test of the significance of Somers' rank correlation can be used for further evaluation of performance of a prediction model. 4) The cross-validated power of survival prediction models decreases as the training and test sets become less balanced.
C1 [Chen, Hung-Chia; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA.
[Cheng, Kuang Fu; Chen, James J.] China Med Univ, Sch Publ Hlth, Ctr Biostat, Taichung, Taiwan.
[Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA.
RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA.
EM jamesj.chen@fda.hhs.gov
NR 54
TC 14
Z9 14
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2288
J9 BMC MED RES METHODOL
JI BMC Med. Res. Methodol.
PD JUL 23
PY 2012
VL 12
AR 102
DI 10.1186/1471-2288-12-102
PG 11
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA 984YW
UT WOS:000307230900001
PM 22824262
ER
PT J
AU Ding, YJ
Chen, MJ
Liu, ZC
Ding, D
Ye, YB
Zhang, M
Kelly, R
Guo, L
Su, ZQ
Harris, SC
Qian, F
Ge, WG
Fang, H
Xu, XW
Tong, WD
AF Ding, Yijun
Chen, Minjun
Liu, Zhichao
Ding, Don
Ye, Yanbin
Zhang, Min
Kelly, Reagan
Guo, Li
Su, Zhenqiang
Harris, Stephen C.
Qian, Feng
Ge, Weigong
Fang, Hong
Xu, Xiaowei
Tong, Weida
TI atBioNet- an integrated network analysis tool for genomics and biomarker
discovery
SO BMC GENOMICS
LA English
DT Article
DE Protein-protein interaction; Network analysis; Functional module;
Disease biomarker; KEGG pathway analysis; Visualization tool; Genomics
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PROTEIN-INTERACTION NETWORK; BIOLOGICAL
NETWORKS; BREAST-CANCER; CHINESE PATIENTS; EXPRESSION DATA; GENE
ONTOLOGY; HUMAN-DISEASE; VISUALIZATION; MODULES
AB Background: Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity.
Results: atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis.
Conclusion: atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.
C1 [Ding, Yijun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Kelly, Reagan; Su, Zhenqiang; Qian, Feng; Fang, Hong] FDAs Natl Ctr Toxicol Res, ICF Int, Jefferson, AR 72079 USA.
[Chen, Minjun; Zhang, Min; Harris, Stephen C.; Ge, Weigong; Xu, Xiaowei; Tong, Weida] US FDA, Div Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chen, Minjun; Zhang, Min; Harris, Stephen C.; Ge, Weigong; Xu, Xiaowei; Tong, Weida] US FDA, Div Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zhang, Min] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77054 USA.
[Guo, Li] Chinese Acad Sci, Inst Proc Engn, State Key Lab Multiphase Complex Syst, Beijing 100190, Peoples R China.
[Xu, Xiaowei] Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA.
RP Fang, H (reprint author), FDAs Natl Ctr Toxicol Res, ICF Int, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM hong.fang@fda.hhs.gov; xwxu@ualr.edu; weida.tong@fda.hhs.gov
RI Su, Zhiguo/G-2422-2011; Su, Zhenqiang/H-3914-2012; Liu,
Zhichao/C-4035-2011
NR 65
TC 12
Z9 13
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 20
PY 2012
VL 13
AR 325
DI 10.1186/1471-2164-13-325
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 008DS
UT WOS:000308938200001
PM 22817640
ER
PT J
AU Lee, KH
Johmura, Y
Yu, LR
Park, JE
Gao, Y
Bang, JK
Zhou, M
Veenstra, TD
Kim, BY
Lee, KS
AF Lee, Kyung Ho
Johmura, Yoshikazu
Yu, Li-Rong
Park, Jung-Eun
Gao, Yuan
Bang, Jeong K.
Zhou, Ming
Veenstra, Timothy D.
Kim, Bo Yeon
Lee, Kyung S.
TI Identification of a novel Wnt5a-CK1 epsilon-Dvl2-Plk1-mediated primary
cilia disassembly pathway
SO EMBO JOURNAL
LA English
DT Article
DE Cilia; CK1; Dvl2; Plk1; Wnt
ID POLO-LIKE KINASE-1; BETA-CATENIN; CELL-CYCLE; BOX DOMAIN; I FAMILY;
PROTEIN-KINASE; MITOTIC ENTRY; WNT; CILIOGENESIS; PLK1
AB Non-motile primary cilium is an antenna-like structure whose defect is associated with a wide range of pathologies, including developmental disorders and cancer. Although mechanisms regulating cilia assembly have been extensively studied, how cilia disassembly is regulated remains poorly understood. Here, we report unexpected roles of Dishevelled 2 (Dvl2) and interphase polo-like kinase 1 (Plk1) in primary cilia disassembly. We demonstrated that Dvl2 is phosphorylated at S143 and T224 in a manner that requires both non-canonical Wnt5a ligand and casein kinase 1 epsilon (CK1 epsilon), and that this event is critical to interact with Plk1 in early stages of the cell cycle. The resulting Dvl2-Plk1 complex mediated Wnt5a-CK1 epsilon-Dvl2-dependent primary cilia disassembly by stabilizing the HEF1 scaffold and activating its associated Aurora-A (AurA), a kinase crucially required for primary cilia disassembly. Thus, via the formation of the Dvl2-Plk1 complex, Plk1 plays an unanticipated role in primary cilia disassembly by linking Wnt5a-induced biochemical steps to HEF1/AurA-dependent cilia disassembly. This study may provide new insights into the mechanism underlying ciliary disassembly processes and various cilia-related disorders. The EMBO Journal (2012) 31, 3104-3117. doi: 10.1038/emboj.2012.144; Published online 18 May 2012
C1 [Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yu, Li-Rong; Gao, Yuan] US FDA, Div Syst Biol, Ctr Prote, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Bang, Jeong K.] Korea Basic Sci Inst, Div Magnet Resonance, Chung Buk, South Korea.
[Zhou, Ming; Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Kim, Bo Yeon] Korea Res Inst Biosci & Biotechnol, Chem Biol Res Ctr, Chung Buk, South Korea.
[Kim, Bo Yeon] Korea Res Inst Biosci & Biotechnol, World Class Inst, Chung Buk, South Korea.
RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 3118, Bethesda, MD 20892 USA.
EM kyunglee@mail.nih.gov
FU National Cancer Institute (NCI); US Food and Drug Administration (FDA);
Korea Basic Science Institute (KBSI) [F30601]; World Class Institute
(WCI) research programme of the National Research Foundation of Korea;
Ministry of Education, Science and Technology of Korea
FX We thank Sean B Lee and Jeff R Rubin for critical reading of the
manuscript; Eric R Fearon, Chou-Zen Giam, Erica A Golemis, Prasad
Jallepalli, Sean B Lee, Randall T Moon, Elena N Pugacheva, Philip A
Sharp, Shiela A Stewart, Dave Virshup, and Michael B Yaffe for reagents.
This work was supported in part by National Cancer Institute's (NCI's)
intramural grants (KSL and TDV), US Food and Drug Administration (FDA)
grant (L-RY), Korea Basic Science Institute (KBSI)'s International Joint
Research programme Grant F30601 (JKB), and the World Class Institute
(WCI) research programme of the National Research Foundation of Korea,
funded by the Ministry of Education, Science and Technology of Korea
(BYK). Revision experiments, which yielded several main and
supplementary figures, were performed by KHL at his present address. The
views presented in this article do not necessarily reflect those of the
NCI, US FDA, KBSI, and WCI.
NR 69
TC 32
Z9 32
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0261-4189
J9 EMBO J
JI Embo J.
PD JUL 18
PY 2012
VL 31
IS 14
BP 3104
EP 3117
DI 10.1038/emboj.2012.144
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 975QC
UT WOS:000306524900007
PM 22609948
ER
PT J
AU Wood, SC
Antony, S
Brown, RP
Chen, J
Gordon, EA
Hitchins, VM
Zhang, Q
Liu, YB
Maruvada, S
Harris, GR
AF Wood, Steven C.
Antony, Sible
Brown, Ronald P.
Chen, Jin
Gordon, Edward A.
Hitchins, Victoria M.
Zhang, Qin
Liu, Yunbo
Maruvada, Subha
Harris, Gerald R.
TI Effects of ultrasound and ultrasound contrast agent on vascular tissue
SO CARDIOVASCULAR ULTRASOUND
LA English
DT Article
ID TARGETED MICROBUBBLE DESTRUCTION; ENDOTHELIAL GROWTH-FACTOR; IN-VIVO;
PULSED ULTRASOUND; LOCAL-DELIVERY; DRUG-DELIVERY; GENE-TRANSFER; CELL
DAMAGE; ECHOCARDIOGRAPHY; EXPRESSION
AB Background: Ultrasound (US) imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology.
Aim: While ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail.
Methods and results: In the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) staining of treated aortas demonstrated incipient apoptosis in the endothelium.
Conclusions: Taken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question.
C1 [Wood, Steven C.; Antony, Sible; Brown, Ronald P.; Gordon, Edward A.; Hitchins, Victoria M.; Zhang, Qin; Liu, Yunbo; Maruvada, Subha; Harris, Gerald R.] US FDA, CDRH, Silver Spring, MD 20993 USA.
[Chen, Jin] US FDA, CDER, Silver Spring, MD 20993 USA.
[Antony, Sible] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA.
RP Wood, SC (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM steven.wood@fda.hhs.gov
FU FDA Office of Women's Health; FDA CDRH Office of Science and Engineering
Laboratories
FX These studies were supported by funds provided by the FDA Office of
Women's Health, and the FDA CDRH Office of Science and Engineering
Laboratories.
NR 47
TC 4
Z9 4
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1476-7120
J9 CARDIOVASC ULTRASOUN
JI Cardiovasc. Ultrasound
PD JUL 17
PY 2012
VL 10
AR 29
DI 10.1186/1476-7120-10-29
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 040LA
UT WOS:000311322900001
PM 22805356
ER
PT J
AU Norcross, MA
Luo, S
Lu, L
Boyne, MT
Gomarteli, M
Rennels, AD
Woodcock, J
Margulies, DH
McMurtrey, C
Vernon, S
Hildebrand, WH
Buchli, R
AF Norcross, Michael A.
Luo, Shen
Lu, Li
Boyne, Michael T.
Gomarteli, Mary
Rennels, Aaron D.
Woodcock, Janet
Margulies, David H.
McMurtrey, Curtis
Vernon, Stephen
Hildebrand, William H.
Buchli, Rico
TI Abacavir induces loading of novel self-peptides into HLA-B*57:01: an
autoimmune model for HLA-associated drug hypersensitivity
SO AIDS
LA English
DT Article
DE abacavir; antiretroviral therapy; autoimmunity; drug hypersensitivity;
HIV; human leucocyte antigen; pharmocogenetics
ID STEVENS-JOHNSON-SYNDROME; FLUORESCENCE POLARIZATION; BINDING;
HLA-A-ASTERISK-0201; ACTIVATION; DATABASE; MARKER
AB Background: Abacavir drug hypersensitivity in HIV-treated patients is associated with HLA-B*57:01 expression. To understand the immunochemistry of abacavir drug reactions, we investigated the effects of abacavir on HLA-B*57:01 epitope-binding in vitro and the quality and quantity of self-peptides presented by HLA-B*57:01 from abacavir-treated cells.
Design and methods: An HLA-B*57:01-specific epitope-binding assay was developed to test for effects of abacavir, didanosine or flucloxacillin on self-peptide binding. To examine whether abacavir alters the peptide repertoire in HLA-B*57:01, a B-cell line secreting soluble human leucocyte antigen (sHLA) was cultured in the presence or absence of abacavir, peptides were eluted from purified human leucocyte antigen (HLA), and the peptide epitopes comparatively mapped by mass spectroscopy to identify drug-unique peptides.
Results: Abacavir, but not didansosine or flucloxacillin, enhanced binding of the FITC-labeled self-peptide LF9 to HLA-B*57:01 in a dose-dependent manner. Endogenous peptides isolated from abacavir-treated HLA-B*57:01 B cells showed amino acid sequence differences compared with peptides from untreated cells. Novel drug-induced peptides lacked typical carboxyl (C) terminal amino acids characteristic of the HLA-B*57:01 peptide motif and instead contained predominantly isoleucine or leucine residues. Drug-induced peptides bind to soluble HLA-B*57:01 with high affinity that was not altered by abacavir addition.
Conclusion: Our results support a model of drug-induced autoimmunity in which abacavir alters the quantity and quality of self-peptide loading into HLAB*57:01. Drug-induced loading of novel self-peptides into HLA, possibly by abacavir either altering the binding cleft or modifying the peptide-loading complex, generates an array of neo-antigen peptides that drive polyclonal T-cell autoimmune responses and multiorgan systemic toxicity. (C) 2012 Wolters Kluwer Health vertical bar| Lippincott Williams & Wilkins
C1 [Norcross, Michael A.; Luo, Shen; Lu, Li] US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Boyne, Michael T.] US FDA, Div Pharmaceut Anal, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Gomarteli, Mary; Rennels, Aaron D.; Buchli, Rico] Pure Prot LLC, Oklahoma City, OK USA.
[Woodcock, Janet] US FDA, Off Ctr Director, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, Bethesda, MD 20892 USA.
[McMurtrey, Curtis; Vernon, Stephen; Hildebrand, William H.] Univ Oklahoma, Hlth Sci Ctr, Sch Med, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA.
RP Norcross, MA (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
EM Michael.norcross@fda.hhs.gov
RI Margulies, David/H-7089-2013; Lu, Li/A-2237-2014;
OI Margulies, David/0000-0001-8530-7375
FU FDA intramural research program; NIAID, NIH
FX The work was supported by the FDA intramural research program. D.H.M. is
supported by the intramural research program of the NIAID, NIH.
NR 24
TC 81
Z9 86
U1 0
U2 19
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 17
PY 2012
VL 26
IS 11
BP F21
EP F29
DI 10.1097/QAD.0b013e328355fe8f
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 970LO
UT WOS:000306130700001
PM 22617051
ER
PT J
AU Thornton, K
Kim, G
Maher, VE
Chattopadhyay, S
Tang, SH
Moon, YJ
Song, PF
Marathe, A
Balakrishnan, S
Zhu, H
Garnett, C
Liu, Q
Booth, B
Gehrke, B
Dorsam, R
Verbois, L
Ghosh, D
Wilson, W
Duan, J
Sarker, H
Miksinski, SP
Skarupa, L
Ibrahim, A
Justice, R
Murgo, A
Pazdur, R
AF Thornton, Katherine
Kim, Geoffrey
Maher, V. Ellen
Chattopadhyay, Somesh
Tang, Shenghui
Moon, Young Jin
Song, Pengfei
Marathe, Anshu
Balakrishnan, Suchitra
Zhu, Hao
Garnett, Christine
Liu, Qi
Booth, Brian
Gehrke, Brenda
Dorsam, Robert
Verbois, Leigh
Ghosh, Debasis
Wilson, Wendy
Duan, John
Sarker, Haripada
Miksinski, Sarah Pope
Skarupa, Lisa
Ibrahim, Amna
Justice, Robert
Murgo, Anthony
Pazdur, Richard
TI Vandetanib for the Treatment of Symptomatic or Progressive Medullary
Thyroid Cancer in Patients with Unresectable Locally Advanced or
Metastatic Disease: U.S. Food and Drug Administration Drug Approval
Summary
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RET PROTOONCOGENE MUTATIONS; CARCINOMA; DOXORUBICIN; CALCITONIN;
THERAPY; TRIAL
AB On April 6, 2011, the U.S. Food and Drug Administration approved vandetanib (Caprelsa tablets; AstraZeneca Pharmaceuticals LP) for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable, locally advanced, or metastatic disease. Vandetanib is the first drug approved for this indication, and this article focuses on the basis of approval. Approval was based on the results of a double-blind trial conducted in patients with medullary thyroid carcinoma. Patients were randomized 2:1 to vandetanib, 300 mg/d orally (n = 231), or to placebo (n = 100). The primary objective was demonstration of improvement in progression-free survival (PFS) with vandetanib compared with placebo. Other end-points included evaluation of overall survival and objective response rate. The PFS analysis showed a marked improvement for patients randomized to vandetanib (hazard ratio = 0.35; 95% confidence interval, 0.24-0.53; P < 0.0001). The objective response rate for the vandetanib arm was 44% compared with 1% for the placebo arm. The most common grade 3 and 4 toxicities (>5%) were diarrhea and/or colitis, hypertension and hypertensive crisis, fatigue, hypocalcemia, rash, and corrected QT interval (QTc) prolongation. This approval was based on a statistically significant and clinically meaningful improvement in PFS. Given the toxicity profile, which includes prolongation of the QT interval and sudden death, only prescribers and pharmacies certified through the vandetanib Risk Evaluation Mitigation Strategy Program are able to prescribe and dispense vandetanib. Treatment-related risks should be taken into account when considering the use of vandetanib in patients with indolent, asymptomatic, or slowly progressing disease. Clin Cancer Res; 18(14); 3722-30. (C)2012 AACR.
C1 [Thornton, Katherine; Kim, Geoffrey; Maher, V. Ellen; Chattopadhyay, Somesh; Tang, Shenghui; Moon, Young Jin; Song, Pengfei; Marathe, Anshu; Balakrishnan, Suchitra; Zhu, Hao; Garnett, Christine; Liu, Qi; Booth, Brian; Gehrke, Brenda; Dorsam, Robert; Verbois, Leigh; Ghosh, Debasis; Wilson, Wendy; Duan, John; Sarker, Haripada; Miksinski, Sarah Pope; Skarupa, Lisa; Ibrahim, Amna; Justice, Robert; Murgo, Anthony; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, White Oak, MD 20993 USA.
RP Kim, G (reprint author), US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, White Oak, MD 20993 USA.
EM Geoffrey.kim@fda.hhs.gov
NR 27
TC 48
Z9 51
U1 0
U2 10
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2012
VL 18
IS 14
BP 3722
EP 3730
DI 10.1158/1078-0432.CCR-12-0411
PG 9
WC Oncology
SC Oncology
GA 988PN
UT WOS:000307503100002
PM 22665903
ER
PT J
AU Jain, HV
Kalman, TI
AF Jain, Harsh V.
Kalman, Thomas I.
TI Synthesis and study of cyclic pronucleotides of 5-fluoro-2
'-deoxyuridine
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Prodrug; Nucleoside; Anticancer; Pronucleotide
ID ARYLOXY PHOSPHORAMIDATE TRIESTERS; ANTICANCER; PRODRUGS; MONOPHOSPHATE;
HYDROLYSIS; CELLS
AB A one-step method for the synthesis of cyclic pronucleotide (cProTide) derivatives of 5-fluoro-2 '-deoxyuridine (FdUrd), utilizing a novel phosphoramidating reagent, is described. Stereochemistry at phosphorus was established by NMR studies and modeling. Cytotoxicity data of representative cProTide derivatives of FdUrd are presented. The observed cell-to-cell variations in activity suggests that it is feasible to screen for structural variations in the cProTide moiety favoring metabolic activation in cancer cells, which may lead to an increase in the therapeutic effectiveness of FdUrd. The method described is applicable to all anticancer and antiviral nucleoside analogs having both the 5 '-and the 3 '-OH groups available for modification, forming cProTide derivatives capable of delivering the 5 '-monophosphates to cells. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Jain, Harsh V.; Kalman, Thomas I.] SUNY Buffalo, Dept Chem, Buffalo, NY 14260 USA.
RP Jain, HV (reprint author), US FDA, Chem Lab, CDER OPS OBP DTP, 8800 Rockville Pike,Bldg 29A,Room 3B08, Bethesda, MD 20892 USA.
EM hvjain@buffalo.edu; tkalman@buffalo.edu
OI Jain, Harsh/0000-0001-8163-6219
NR 20
TC 4
Z9 4
U1 1
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD JUL 15
PY 2012
VL 22
IS 14
BP 4497
EP 4501
DI 10.1016/j.bmcl.2012.06.011
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 970AU
UT WOS:000306101300001
PM 22738636
ER
PT J
AU Deyrup, CL
Southern, KJ
Cornett, JA
Shultz, CE
Cera, DA
AF Deyrup, Cynthia L.
Southern, Kristal J.
Cornett, Julie A.
Shultz, Craig E.
Cera, Deborah A.
TI Examining the occurrence of residues of flunixin meglumine in cull dairy
cows by use of the flunixin cull cow survey
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS
AB Objective-To determine whether cull dairy cows with signs of certain clinical conditions, termed suspect, are more likely than healthy-appearing cull dairy cows to have violative concentrations of flunixin meglumine in their tissues at slaughter.
Design-Cross-sectional study.
Animals-961 cull dairy cows.
Procedures-Suspect cull dairy cows were selected from 21 beef slaughter establishments with a high production volume of dairy cows, and kidney and liver tissues were collected for screening. Kidney tissues were screened for antibiotics and sulfonamides with the fast antimicrobial screening test (FAST). Liver tissues were screened for flunixin meglumine with an ELISA, and quantitative analysis of ELISA-positive samples was performed with high-performance liquid chromatography. During the same time period, liver tissues from 251 healthy-appearing cull dairy cows were collected for the Food Safety and Inspection Service National Residue Program Scheduled Sampling Plan, but were screened only for flunixin meglumine.
Results-Of 710 suspect cull dairy cows, 50(704%) had liver tissue flunixin concentrations higher than the flunixin tolerance concentration (0.125 ppm). Thirty-one of 168 (18.45%) FAST-positive and 19 of 542 (3.51%) FAST-negative suspect cull dairy cows had violative tissue flunixin concentrations. Two of the 251 (0.80%) healthy-appearing cull dairy cows had violative tissue flunixin concentrations.
Conclusions and Clinical Relevance-Suspect cull dairy cows, especially those that were also FAST positive, had a significantly higher incidence of violative tissue flunixin concentrations than healthy-appearing cull dairy cows at slaughter. Targeted sampling plans for flunixin meglumine in suspect dairy cows can help to support more efficient use of resources and further safeguard the nation's food supply. (J Am Vet Med Assoc 2012;241:249-253)
C1 [Deyrup, Cynthia L.; Southern, Kristal J.] US Food Safety & Inspect Serv, Off Publ Hlth Sci, USDA, Washington, DC 20250 USA.
[Cornett, Julie A.; Shultz, Craig E.] US Food Safety & Inspect Serv, Off Field Operat, USDA, Washington, DC 20250 USA.
[Cera, Deborah A.] US FDA, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA.
RP Southern, KJ (reprint author), US Food Safety & Inspect Serv, Off Publ Hlth Sci, USDA, 1400 Independence Ave SW, Washington, DC 20250 USA.
EM kristal.southern@fsis.usda.gov
NR 16
TC 9
Z9 9
U1 0
U2 5
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD JUL 15
PY 2012
VL 241
IS 2
BP 249
EP 253
PG 5
WC Veterinary Sciences
SC Veterinary Sciences
GA 971ZN
UT WOS:000306246400014
PM 22765373
ER
PT J
AU Murakami, Y
Narayanan, S
Su, S
Childs, R
Krzewski, K
Borrego, F
Weck, J
Coligan, JE
AF Murakami, Yousuke
Narayanan, Sriram
Su, Su
Childs, Richard
Krzewski, Konrad
Borrego, Francisco
Weck, Jennifer
Coligan, John E.
TI Toso, a Functional IgM Receptor, Is Regulated by IL-2 in T and NK Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; INDUCED APOPTOSIS; DEATH; FAS; CYTOTOXICITY;
SURFACE; ROLES; INTERLEUKIN-2; LYMPHOCYTES; HOMEOSTASIS
AB We find that the cell surface receptor Toso is dramatically downregulated by in vitro stimulation of human Tand NK cells with IL-2 in a STAT5-dependent manner. The fact that IL-2 is known to prime NK and T cells for Fas/TNF-mediated activation-induced cell death (AICD) fits nicely with the original and recent descriptions of Toso as an inhibitor of Fas/TNF-induced apoptosis. In support of this possibility, effector memory T cells express markedly lower levels of Toso than those of naive T cells, indicating that activation in vivo correlates with the downregulation of Toso. Moreover, in vitro activation of memory T cells through TCR dramatically downregulates Toso expression compared with that of naive CD4 T cells. However, overexpression of Toso in human NK cells and Jurkat T cells does not inhibit Fas-mediated apoptosis, and, in agreement with other recent reports, Toso clearly functions as an IgM receptor. Unlike CD16, Toso expression by NK cells does not convey cytotoxic potential, but its ligation does trigger intracellular signaling in NK cells. In summary, our data indicate that Toso is a functional IgM receptor that is capable of activating signaling molecules, is regulated by IL-2, and is not inherently an antiapoptotic molecule. The Journal of Immunology, 2012, 189: 587-597.
C1 [Murakami, Yousuke; Narayanan, Sriram; Krzewski, Konrad; Weck, Jennifer; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Su, Su; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,Room 205,12441 Parklawn Dr, Rockville, MD 20852 USA.
EM jcoligan@niaid.nih.gov
OI Narayanan, Sriram/0000-0002-6484-2800; Weck,
Jennifer/0000-0002-3246-7380
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute
FX This work was supported by the intramural program of the National
Institute of Allergy and Infectious Diseases and the intramural program
of the National Heart, Lung, and Blood Institute.
NR 29
TC 14
Z9 15
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2012
VL 189
IS 2
BP 587
EP 597
DI 10.4049/jimmunol.1200840
PG 11
WC Immunology
SC Immunology
GA 970HU
UT WOS:000306119800017
PM 22675200
ER
PT J
AU da Costa, GG
Jacob, CC
Von Tungeln, LS
Hasbrouck, NR
Olson, GR
Hattan, DG
Reimschuessel, R
Beland, FA
AF da Costa, Goncalo Gamboa
Jacob, Cristina C.
Von Tungeln, Linda S.
Hasbrouck, Nicholas R.
Olson, Greg R.
Hattan, David G.
Reimschuessel, Renate
Beland, Frederick A.
TI Dose-response assessment of nephrotoxicity from a twenty-eight-day
combined-exposure to melamine and cyanuric acid in F344 rats
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Melamine; Cyanuric acid; Melamine cyanurate; Nephrotoxicity
ID CATS; TOXICITY; PIGS; DOGS
AB The adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of cats and dogs in the USA and other countries. In a previous 7-day dietary study in F344 rats, we established a no-observed-adverse-effect level (NOAEL) for a co-exposure to melamine and cyanuric acid of 8.6 mg/kg bw/day of each compound, and a benchmark dose lower confidence limit (BMDL) of 8.4-10.9 mg/kg bw/day of each compound. To ascertain the role played by the duration of exposure, we treated F344 rats for 28 days. Groups of male and female rats were fed diet containing 0 (control), 30, 60, 120, 180, 240, or 360 ppm of both melamine and cyanuric acid. The lowest dose that produced histopathological alterations in the kidney was 120 ppm, versus 229 ppm in the 7-day study. Wet-mount analysis of kidney sections demonstrated the formation of melamine cyanurate spherulites in one male and two female rats at the 60 ppm dose and in one female rat at the 30 ppm dose, establishing a NOAEL of 2.1 mg/kg bw/day for males and <2.6 mg/kg bw/day for females, and BMDL values as low as 1.6 mg/kg bw/day for both sexes. These data demonstrate that the length of exposure is an important component in the threshold of toxicity from a co-exposure to these compounds and suggest that the current risk assessments based on exposures to melamine alone may not reflect sufficiently the risk of a co-exposure to melamine and cyanuric acid. Published by Elsevier Inc.
C1 [da Costa, Goncalo Gamboa; Jacob, Cristina C.; Von Tungeln, Linda S.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Hasbrouck, Nicholas R.; Reimschuessel, Renate] Ctr Vet Med, Laurel, MD 20708 USA.
[Olson, Greg R.] Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Hattan, David G.] Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP da Costa, GG (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM goncalo.gamboa@fda.hhs.gov
RI Jacob, Cristina/A-3885-2015
OI Jacob, Cristina/0000-0003-2652-3865
FU FDA; National Toxicology Program at NIEHS [FDA IAG:224-07-0007, NIH
Y1ES1027]
FX This study was supported through an interagency agreement between the
FDA and the National Toxicology Program at NIEHS (FDA IAG:224-07-0007;
NIH Y1ES1027).
NR 24
TC 15
Z9 15
U1 0
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUL 15
PY 2012
VL 262
IS 2
BP 99
EP 106
DI 10.1016/j.taap.2012.04.031
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 966NT
UT WOS:000305845400001
ER
PT J
AU Guo, LW
Wu, QG
Green, B
Nolen, G
Shi, LM
LoSurdo, J
Deng, HL
Bauer, S
Fang, JL
Ning, BT
AF Guo, Li-Wu
Wu, Qiangen
Green, Bridgett
Nolen, Greg
Shi, Leming
LoSurdo, Jessica
Deng, Helen
Bauer, Steven
Fang, Jia-Long
Ning, Baitang
TI Cytotoxicity and inhibitory effects of low-concentration triclosan on
adipogenic differentiation of human mesenchymal stem cells
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Adipocyte differentiation; Human mesenchymal stem cell; Triclosan;
Cytotoxicity
ID FATTY-ACID SYNTHASE; PERSONAL CARE PRODUCTS; BREAST-CANCER; IN-VITRO;
EXPOSURE; BIOSYNTHESIS; TOXICITY; TARGET; MILK; TOXICOLOGY
AB Humans at all ages are continually exposed to triclosan (TCS), a widely used antimicrobial agent that can be found in many daily hygiene products, such as toothpastes and shampoos; however, the toxicological and biological effects of TCS in the human body after long-term and low-concentration exposure are far from being well understood. In the current study, we investigated the effects of TCS on the differentiation of human mesenchymal stem cells (hMSCs) by measuring the cytotoxicity, morphological changes, lipid accumulation, and the expression of adipocyte differentiation biomarkers during 21-day adipogenesis. Significant cytotoxicity was observed in un-induced hMSCs treated with high-concentration TCS (>= 5.0 mu M TCS), but not with low-concentration treatments (<= 2.5 mu M TCS). TCS inhibited adipocyte differentiation of hMSCs in a concentration-dependent manner in the 0.156 to 2.5 mu M range as indicated by morphological changes with Oil Red O staining, which is an index of lipid accumulation. The inhibitory effect was confirmed by a decrease in gene expression of specific adipocyte differentiation biomarkers including adipocyte protein 2, lipoprotein lipase, and adiponectin. Our study demonstrates that TCS inhibits adipocyte differentiation of hMSCs under concentrations that are not cytotoxic and in the range observed in human blood. Published by Elsevier Inc.
C1 [Wu, Qiangen; Fang, Jia-Long] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Guo, Li-Wu; Green, Bridgett; Nolen, Greg; Ning, Baitang] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Shi, Leming] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[LoSurdo, Jessica; Bauer, Steven] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Deng, Helen] Arkansas Dept Hlth, Little Rock, AR 72205 USA.
RP Fang, JL (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT110, Jefferson, AR 72079 USA.
EM jia-long.fang@fda.hhs.gov; baitang.ning@fda.hhs.gov
RI Wu, Qiangen/F-7581-2014;
OI Wu, Qiangen/0000-0002-7595-2837; Bauer, Steven/0000-0003-2831-846X
FU National Center for Toxicological Research, U.S. Food and Drug
Administration; National Toxicology Program, National Institute of
Environmental Health Sciences; [FDA IAG: 224-07-0007]; [NIH Y1ES1027]
FX This research was partially supported through an interagency agreement
between the National Center for Toxicological Research, U.S. Food and
Drug Administration, and the National Toxicology Program, National
Institute of Environmental Health Sciences (FDA IAG: 224-07-0007; NIH
Y1ES1027).
NR 39
TC 9
Z9 11
U1 3
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUL 15
PY 2012
VL 262
IS 2
BP 117
EP 123
DI 10.1016/j.taap.2012.04.024
PG 7
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 966NT
UT WOS:000305845400003
PM 22726953
ER
PT J
AU Feinstone, SM
Hu, DJ
Major, ME
AF Feinstone, Stephen M.
Hu, Dale J.
Major, Marian E.
TI Prospects for Prophylactic and Therapeutic Vaccines Against Hepatitis C
Virus
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID T-CELL RESPONSES; INJECTION-DRUG USERS; NEUTRALIZING ANTIBODIES;
PHASE-I; ENVELOPE GLYCOPROTEINS; HEALTHY-VOLUNTEERS; IMMUNE-RESPONSES;
UNITED-STATES; INFECTION; HCV
AB Natural cross-protective immunity is induced after spontaneous clearance of primary hepatitis C virus (HCV) infection. Although this suggests that effective prophylactic vaccines against HCV are possible, there are still several areas that require further study. Current data indicate that, at best, vaccine-induced immunity may not completely prevent HCV infection but rather prevent persistence of the virus. However, this may be an acceptable goal, because chronic persistence of the virus is the main cause of pathogenesis and the development of serious liver conditions. Therapeutic vaccine development is also highly challenging; however, strategies have been pursued in combination with current or new treatments in an effort to reduce the costs and adverse effects associated with antiviral therapy. This review summarizes the current state of HCV vaccines and the challenges faced for future development and clinical trial design.
C1 [Feinstone, Stephen M.; Major, Marian E.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Hu, Dale J.] Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA USA.
RP Major, ME (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg29A,Rm1D10,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM marian.major@fda.hhs.gov
RI Cheng, Yushao/E-6256-2011
FU Abbott Laboratories; Boehringer Ingelheim; Bristol-Myers Squibb;
Genentech (Roche); Gilead Sciences; Glaxo-SmithKline; Janssen
Therapeutics; Merck Sharp Dohme; OraSure Technologies; Vertex
Pharmaceuticals; Viral Hepatitis Action Coalition of the CDC Foundation
FX The Viral Hepatitis Action Coalition of the CDC Foundation receives
support from Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers
Squibb, Genentech (Roche), Gilead Sciences, Glaxo-SmithKline, Janssen
Therapeutics, Merck Sharp & Dohme, OraSure Technologies, and Vertex
Pharmaceuticals.; This article was published as part of a supplement
entitled "The Evolving Paradigm of Hepatitis C," sponsored by an
unrestricted grant from the Viral Hepatitis Action Coalition of the CDC
Foundation.
NR 50
TC 28
Z9 29
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 15
PY 2012
VL 55
SU 1
BP S25
EP S32
DI 10.1093/cid/cis362
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 963IJ
UT WOS:000305613400005
PM 22715210
ER
PT J
AU Kandagaddala, LD
Kang, MJ
Haque, MM
Im, HY
Seo, JE
Chung, BC
Jung, BH
Patterson, TA
Kwon, OS
AF Kandagaddala, Lakshmi Devi
Kang, Min-Jung
Haque, Md. Mamunul
Im, Hye-Yeon
Seo, Ji-Eun
Chung, Bong Chul
Jung, Byung Hwa
Patterson, Tucker A.
Kwon, Oh-Seung
TI In vitro screening of NADPH oxidase inhibitors and in vivo effects of
L-leucinethiol on experimental autoimmune encephalomyelitis-induced mice
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE MMP-9; NADPH oxidase; EAE; L-Leucinethiol; Mice; Cytokines
ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; MATRIX
METALLOPROTEINASES MMPS; REMITTING MULTIPLE-SCLEROSIS;
CENTRAL-NERVOUS-SYSTEM; GELATINASE-B; EXTRACELLULAR-MATRIX;
CEREBROSPINAL-FLUID; ANIMAL-MODELS; T-CELLS
AB Experimental autoimmune encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system, shares many pathological and clinical similarities with multiple sclerosis (MS). The objectives of this study were i) to evaluate the suppressive effects of L-leucinethiol (LeuSH), a metalloprotease inhibitor on EAE-induced mice and ii) to study the effects of LeuSH on matrix metalloproteinase-9 (MMP-9), NADPH oxidase and cytokines (IFN-gamma, IL-5 and IL-10) in tissues and plasma of EAE mice as a measure of potential markers associated with EAE disease. C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG35-55) peptide in complete Freund's adjuvant to induce EAE. A significant difference was observed in body weights and clinical signs of LeuSH (8 mg/kg) administered EAE-induced mice compared to control mice. The findings of this study include alterations in the enzymatic expression of MMP-9, NADPH oxidase and cytokine levels in the brain, spinal cord, spleen, thymus and plasma of inhibitor-treated EAE mice as well as EAE-induced mice. The enzyme activities of NADPH oxidase were inhibited by LeuSH. From these results, it can be considered that LeuSH acts as one of the antigen candidates in ameliorating the clinical symptoms of EAE disease in mice. (C) 2012 Published by Elsevier B.V.
C1 [Kandagaddala, Lakshmi Devi; Kang, Min-Jung; Haque, Md. Mamunul; Im, Hye-Yeon; Seo, Ji-Eun; Chung, Bong Chul; Jung, Byung Hwa; Kwon, Oh-Seung] Korea Inst Sci & Technol, Toxicol Lab, Seoul 136791, South Korea.
[Kandagaddala, Lakshmi Devi; Kang, Min-Jung; Haque, Md. Mamunul; Seo, Ji-Eun; Chung, Bong Chul; Jung, Byung Hwa; Kwon, Oh-Seung] Univ Sci & Technol, Taejon 305333, South Korea.
[Patterson, Tucker A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Kwon, OS (reprint author), Korea Inst Sci & Technol, Toxicol Lab, Hwarang 14 Gil, Seoul 136791, South Korea.
EM oskwon@kist.re.kr
NR 83
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-510X
J9 J NEUROL SCI
JI J. Neurol. Sci.
PD JUL 15
PY 2012
VL 318
IS 1-2
BP 36
EP 44
DI 10.1016/j.jns.2012.04.009
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 964BK
UT WOS:000305668500005
PM 22554692
ER
PT J
AU Fujisawa, T
Joshi, BH
Puri, RK
AF Fujisawa, Toshio
Joshi, Bharat H.
Puri, Raj K.
TI IL-13 regulates cancer invasion and metastasis through IL-13R alpha 2
via ERK/AP-1 pathway in mouse model of human ovarian cancer
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE IL-13Ra2; Metastasis; Ovarian cancer; matrix metalloproteinase; ERK1; 2
ID INTERLEUKIN-13 RECEPTOR ALPHA-2; SIGNAL-TRANSDUCTION; PSEUDOMONAS
EXOTOXIN; THERAPY; EXPRESSION; CELLS; CHAIN; PROTEIN; ERK;
PHOSPHORYLATION
AB Previously, we have demonstrated that a variety of human cancers including the ovarian cancer express IL-13Ra2, a high affinity receptor for IL-13. Herein, we have examined if IL-13 regulates invasion and metastasis of ovarian cancer through IL-13Ra2 in vitro and in vivo in animal models of human ovarian cancer. We tested cell invasion and protease activity in IL-13Ra2-overexpressing and IL-13Ra2-negative ovarian tumor cell lines. IL-13 treatment significantly augmented both cell invasion and enzyme activities in only IL-13Ra2-positive cells but not in IL-13Ra2-negative cells in vitro. Mechanistically, IL-13 enhanced ERK1/2, AP-1 and MMP activities only in IL-13Ra2-positive cells but not in IL-13Ra2-negative cells. In contrast, other signaling pathways such as IRS1/2, PI3K and AKT do not seem to be involved in IL-13 induced signaling in ovarian cancer cell lines. Highly specific inhibitors for MMP and AP-1 efficiently inhibited both invasion and protease activities without impacting the basal level invasion and protease activities in vitro. In orthotopic animal model of human ovarian cancer, IL-13Ra2-positive tumors metastasized to lymph nodes and peritoneum earlier than IL-13Ra2-negative tumors. Interestingly, the IL-13Ra2-positive tumor bearing mice died earlier than mice with IL-13Ra2-negative tumor. Intraperitoneal injection of IL-13 further shortened survival of IL-13Ra2-positive tumor bearing mice compared to IL-13Ra2-negative tumor mice. IL-13Ra2-positive tumors and lymph node metastasis expressed higher levels of MMPs and higher ERK1/2 activation compared to IL-13Ra2-negative tumors. Taken together, IL-13Ra2 is involved in cancer metastasis through activation of ERK/AP-1 and that targeting IL-13Ra2 might not only directly kill primary tumors but also prevent cancer metastasis.
C1 [Fujisawa, Toshio; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20 HFM 735,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov
NR 35
TC 38
Z9 43
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2012
VL 131
IS 2
BP 344
EP 356
DI 10.1002/ijc.26366
PG 13
WC Oncology
SC Oncology
GA 946KN
UT WOS:000304350600026
PM 21858811
ER
PT J
AU Kim, DH
Shin, DH
Ryu, SH
Song, CG
AF Kim, Do-Hyun
Shin, Dong-Ho
Ryu, Sang Hun
Song, Chul-Gyu
TI Patterned thin metal film for the lateral resolution measurement of
photoacoustic tomography
SO BIOMEDICAL ENGINEERING ONLINE
LA English
DT Article
DE Photoacoustic tomography; Resolution measurement; Ultrasound imaging
ID LASER-GENERATED ULTRASOUND; IN-VIVO; RECONSTRUCTION; MICROSCOPY
AB Background: Image quality assessment method of photoacoustic tomography has not been completely standardized yet. Due to the combined nature of photonic signal generation and ultrasonic signal transmission in biological tissue, neither optical nor ultrasonic traditional methods can be used without modification. An optical resolution measurement technique was investigated for its feasibility for resolution measurement of photoacoustic tomography.
Methods: A patterned thin metal film deposited on silica glass provides high contrast in optical imaging due to high reflectivity from the metal film and high transmission from the glass. It provides high contrast when it is used for photoacoustic tomography because thin metal film can absorb pulsed laser energy. An US Air Force 1951 resolution target was used to generate patterned photoacoustic signal to measure the lateral resolution. Transducer with 2.25 MHz bandwidth and a sample submerged in water and gelatinous block were tested for lateral resolution measurement.
Results: Photoacoustic signal generated from a thin metal film deposited on a glass can propagate along the surface or through the surrounding medium. First, a series of experiments with tilted sample confirmed that the measured photoacoustic signal is what is propagating through the medium. Lateral resolution of the photoacoustic tomography system was successfully measured for water and gelatinous block as media: 0.33 mm and 0.35 mm in water and gelatinous material, respectively, when 2.25 MHz transducer was used. Chicken embryo was tested for biomedical applications.
Conclusions: A patterned thin metal film sample was tested for its feasibility of measuring lateral resolution of a photoacoustic tomography system. Lateral resolutions in water and gelatinous material were successfully measured using the proposed method. Measured resolutions agreed well with theoretical values.
C1 [Kim, Do-Hyun] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Shin, Dong-Ho; Ryu, Sang Hun; Song, Chul-Gyu] Chonbuk Natl Univ, Dept Elect Engn, Jeonju 561756, Jeonbuk, South Korea.
RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM do-hyun.kim@fda.hhs.gov; song133436@gmail.com
FU National Research Foundation of Korea (NRF) grant; Korea government
(MEST) [2011-0030075, 2011-0030781]; Ministry of Knowledge Economy(MKE);
Korea Institute for Advancement of Technology(KIAT); Gangwon Leading
Industry Office through the Leading Industry Development for Economic
Region
FX (DHS, SHR, CGS) This work was supported by the National Research
Foundation of Korea (NRF) grant funded by the Korea government (MEST)
(No. 2011-0030075, 2011-0030781). This research was financially
supported by the Ministry of Knowledge Economy(MKE), Korea Institute for
Advancement of Technology(KIAT) and Gangwon Leading Industry Office
through the Leading Industry Development for Economic Region.
NR 17
TC 0
Z9 0
U1 0
U2 10
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 JUL 13
PY 2012
VL 11
AR 37
DI 10.1186/1475-925X-11-37
PG 11
WC Engineering, Biomedical
SC Engineering
GA 006CI
UT WOS:000308796600001
PM 22794510
ER
PT J
AU Zaitseva, M
Romantseva, T
Blinova, K
Beren, J
Sirota, L
Drane, D
Golding, H
AF Zaitseva, Marina
Romantseva, Tatiana
Blinova, Ksenia
Beren, Joel
Sirota, Lev
Drane, Debbie
Golding, Hana
TI Use of human MonoMac6 cells for development of in vitro assay predictive
of adjuvant safety in vivo
SO VACCINE
LA English
DT Article
DE Adjuvants; Human monocytes; Cytokines; TLR agonists; Prostaglandin E2
ID TOLL-LIKE RECEPTORS; TUMOR NECROSIS FACTOR; VACCINE ADJUVANTS;
IMMUNE-RESPONSES; DENDRITIC CELLS; FEVER; BRAIN; MONOCYTES; PYROGEN;
CANCER
AB Subunit vaccines composed of recombinant or purified antigens have a good safety record but are poorly immunogenic and require adjuvants to activate innate immunity and facilitate antigen specific immune response. Of the many adjuvant formulations that are under development, very few are licensed mainly due to concerns about adverse side effects. The goal of our study was to develop in vitro assays that could predict toxicity of adjuvants in vivo. Pro-inflammatory cytokines IL-beta, IL-6, TNF-alpha, and IL-8 were measured in human primary monocytes and the monocytoid cell line, MonoMac 6 (MM6), activated with a panel of TLR agonists or with adjuvants. A 0.5 EU/ml dose of Standard for endotoxin (previously shown to provide a margin between pyrogenic and non-pyrogenic substances in rabbits) was used as a comparator to establish a "safety threshold". FSL-1, Pam3CSK4, flagellin, and R848 TLR agonists but not Alum, MF59, Poly I:C, or MPL adjuvants induced cytokines in MM6 cells above the safety threshold. To confirm the predictive value of the in vitro assays, FSL-1 and flagellin were injected intramuscularly into New Zealand White (NZW) rabbits. Both TLR agonists induced fever within 6-8 h post-injection followed 24-48 h later by increased C reactive protein (CRP). Importantly, an early peak in plasma prostaglandin E2 (PGE(2)) levels preceded rise in body temperature. In vitro production of PGE(2) in monocytes and MM6 cells was found following treatments with various TLR agonists but not with alum, MF59. MPL, or Poly I:C adjuvants. Together, our studies demonstrated a strong correlation between production of pro-inflammatory cytokines above a "safety threshold" and production of PGE(2) in vitro and an increase in body temperature in rabbits. The developed human cell based assays could provide an important tool for early screening of new molecular moieties and adjuvant formulations and may assist in selection of safer products. Published by Elsevier Ltd.
C1 [Zaitseva, Marina; Romantseva, Tatiana; Blinova, Ksenia; Beren, Joel; Sirota, Lev; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Zaitseva, Marina; Romantseva, Tatiana; Blinova, Ksenia; Beren, Joel; Sirota, Lev; Golding, Hana] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Zaitseva, Marina; Romantseva, Tatiana; Blinova, Ksenia; Beren, Joel; Sirota, Lev; Golding, Hana] US FDA, Div Biostat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Drane, Debbie] CSL Behring, King Of Prussia, PA 19406 USA.
RP Zaitseva, M (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,Room 4NN06,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM marina.zaitseva@fda.hhs.gov
FU Critical Path Initiative at CBER, FDA
FX This project has been funded in part with Federal funds from the
Critical Path Initiative at CBER, FDA.
NR 37
TC 22
Z9 23
U1 1
U2 15
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 JUL 6
PY 2012
VL 30
IS 32
BP 4859
EP 4865
DI 10.1016/j.vaccine.2012.05.002
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 978UJ
UT WOS:000306771000022
PM 22609036
ER
PT J
AU Mecker, LC
Tyner, KM
Kauffman, JF
Arzhantsev, S
Mans, DJ
Gryniewicz-Ruzicka, CM
AF Mecker, Laura C.
Tyner, Katherine M.
Kauffman, John F.
Arzhantsev, Sergey
Mans, Daniel J.
Gryniewicz-Ruzicka, Connie M.
TI Selective melamine detection in multiple sample matrices with a portable
Raman instrument using surface enhanced Raman spectroscopy-active gold
nanoparticles
SO ANALYTICA CHIMICA ACTA
LA English
DT Article
DE Melamine; Nanoparticles; Surface enhanced Raman spectroscopy
ID MASS-SPECTROMETRIC DETECTION; VISUAL DETECTION; CYANURIC ACID; RAW-MILK;
SCATTERING; CYROMAZINE; FOODS
AB Melamine adulteration of food and pharmaceutical products is a major concern and there is a growing need to protect the public from exposure to contaminated or adulterated products. One approach to reduce this threat is to develop a portable method for on-site rapid testing. We describe a universal and selective method for the detection of melamine in a variety of solid matrices at the 100-200 mu g L-1 level by surface enhanced Raman spectroscopy (SERS) with gold nanoparticles. With minimal sample preparation and the use of a portable Raman spectrometer, this work will lead to field-based screening for melamine adulteration. Citrate coated gold nanoparticles (Au NPs) were investigated for both colorimetric and Raman-based responses. Several non-hazardous solvents were evaluated in order to develop a melamine extraction procedure safe for field applications. Au NP agglomerates formed by the addition of isopropanol (IPA) prior to sample introduction enhanced the Raman signal for melamine and eliminated matrix interference for substrate formation. The melamine Raman signal resulted in a 10(5) enhancement through the use of Au NP agglomerates. To our knowledge, we have developed the first portable SERS method using Au NPs to selectively screen for the presence of melamine adulteration in a variety of food and pharmaceutical matrices, including milk powder, infant formula, lactose, povidone, whey protein, wheat bran and wheat gluten. Published by Elsevier B.V.
C1 [Mecker, Laura C.; Kauffman, John F.; Arzhantsev, Sergey; Mans, Daniel J.; Gryniewicz-Ruzicka, Connie M.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA.
[Tyner, Katherine M.] US FDA, CDER, Div Drug Safety Res, Silver Spring, MD 20993 USA.
RP Mecker, LC (reprint author), US FDA, CDER, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA.
EM laura.mecker@fda.hhs.gov
NR 35
TC 33
Z9 37
U1 7
U2 121
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0003-2670
J9 ANAL CHIM ACTA
JI Anal. Chim. Acta
PD JUL 6
PY 2012
VL 733
BP 48
EP 55
DI 10.1016/j.aca.2012.05.001
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 966YA
UT WOS:000305872100007
PM 22704375
ER
PT J
AU Xu, J
Kelly, R
Zhou, GX
Turner, SA
Ding, D
Harris, SC
Hong, HX
Fang, H
Tong, WD
AF Xu, Joshua
Kelly, Reagan
Zhou, Guangxu
Turner, Steven A.
Ding, Don
Harris, Stephen C.
Hong, Huixiao
Fang, Hong
Tong, Weida
TI SNPTrack (TM) : an integrated bioinformatics system for genetic
association studies
SO HUMAN GENOMICS
LA English
DT Article
AB A genetic association study is a complicated process that involves collecting phenotypic data, generating genotypic data, analyzing associations between genotypic and phenotypic data, and interpreting genetic biomarkers identified. SNPTrack is an integrated bioinformatics system developed by the US Food and Drug Administration (FDA) to support the review and analysis of pharmacogenetics data resulting from FDA research or submitted by sponsors. The system integrates data management, analysis, and interpretation in a single platform for genetic association studies. Specifically, it stores genotyping data and single-nucleotide polymorphism (SNP) annotations along with study design data in an Oracle database. It also integrates popular genetic analysis tools, such as PLINK and Haploview. SNPTrack provides genetic analysis capabilities and captures analysis results in its database as SNP lists that can be cross-linked for biological interpretation to gene/protein annotations, Gene Ontology, and pathway analysis data. With SNPTrack, users can do the entire stream of bioinformatics jobs for genetic association studies. SNPTrack is freely available to the public at http://www.fda.gov/ScienceResearch/BioinformaticsTools/SNPTrack/default.htm.
C1 [Xu, Joshua; Kelly, Reagan; Zhou, Guangxu; Turner, Steven A.; Ding, Don; Fang, Hong] ICF Int NCTR, Jefferson, AR 72079 USA.
[Harris, Stephen C.; Hong, Huixiao; Tong, Weida] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Fang, H (reprint author), ICF Int NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM hong.fang@fda.hhs.gov; weida.tong@fda.hhs.gov
NR 7
TC 1
Z9 1
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1473-9542
J9 HUM GENOMICS
JI Hum. Genomics
PD JUL 5
PY 2012
VL 6
AR 5
DI 10.1186/1479-7364-6-5
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 121CT
UT WOS:000317221000005
PM 23245293
ER
PT J
AU Tolleson, WH
Jackson, LS
Triplett, OA
Aluri, B
Cappozzo, J
Banaszewski, K
Chang, CW
Nguyen, KT
AF Tolleson, William H.
Jackson, Lauren S.
Triplett, Odbert A.
Aluri, Bharat
Cappozzo, Jack
Banaszewski, Katie
Chang, Claire W.
Nguyen, Kiet T.
TI Chemical Inactivation of Protein Toxins on Food Contact Surfaces
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE ricin; abrin; bioterrorism; chemical inactivation
ID HYPOCHLOROUS ACID; AMINO-ACIDS; SODIUM-HYPOCHLORITE; HYDROGEN-PEROXIDE;
PERACETIC-ACID; PLANT TOXIN; RICIN; OXIDATION; DEGRADATION; CHLORAMINES
AB We compared the kinetics and efficacies of sodium hypochlorite, peracetic acid, phosphoric acid-based detergent, chlorinated alkaline detergent, quaternary ammonium-based sanitizer, and peracetic acid-based sanitizer for inactivating the potential bioterrorism agents ricin and abrin in simple buffers, food slurries (infant formula, peanut butter, and pancake mix), and in dried food residues on stainless steel. The intrinsic fluorescence and cytotoxicity of purified ricin and abrin in buffers decreased rapidly in a pH- and temperature-dependent manner when treated with sodium hypochlorite but more slowly when treated with peracetic acid. Cytotoxicity assays showed rapid and complete inactivation of ricin and crude abrin in food slurries and dried food residues treated 0-5 min with sodium hypochlorite. Toxin epitopes recognized by ELISA decayed more gradually under these conditions. Higher concentrations of peracetic acid were required to achieve comparable results. Chlorinated alkaline detergent was the most effective industrial agent tested for inactivating ricin in dried food residues.
C1 [Tolleson, William H.; Triplett, Odbert A.; Nguyen, Kiet T.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Jackson, Lauren S.; Chang, Claire W.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA.
[Aluri, Bharat; Cappozzo, Jack; Banaszewski, Katie] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA.
RP Tolleson, WH (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM william.tolleson@fda.hhs.gov
FU National Center for Food Protection and Defense
FX This project was funded in part by a grant from the National Center for
Food Protection and Defense.
NR 42
TC 3
Z9 3
U1 1
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JUL 4
PY 2012
VL 60
IS 26
BP 6627
EP 6640
DI 10.1021/jf301601v
PG 14
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 966UV
UT WOS:000305863800020
PM 22690810
ER
PT J
AU Battistel, MD
Shangold, M
Trinh, L
Shiloach, J
Freedberg, DI
AF Battistel, Marcos D.
Shangold, Michael
Loc Trinh
Shiloach, Joseph
Freedberg, Daron I.
TI Evidence for Helical Structure in a Tetramer of alpha 2-8 Sialic Acid:
Unveiling a Structural Antigen
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID B MENINGOCOCCAL POLYSACCHARIDE; NEISSERIA-MENINGITIDIS; HYDROGEN-BONDS;
SCALAR COUPLINGS; AQUEOUS-SOLUTION; BASE-PAIRS; NMR; PROTEINS;
SPECTROSCOPY; EXCHANGE
AB Characteristic H-bonding patterns define secondary structure in proteins and nucleic acids. We show that similar patterns apply for alpha 2-8 sialic acid (SiA) in H2O and that H-bonds define its structure. A N-15,C-13 alpha 2-8 SiA tetramer, (SiA)(4), was used as a model system for the polymer. At 263 K, we detected intra-residue through-H-bond J couplings between N-15 and C8 for residues R-I-R-III of the tetramer, indicating H-bonds between the N-15's and the O8's of these residues. Additional J couplings between the N-15's and C2's of the adjacent residues confirm the putative H-bonds. NH groups showing this long-range correlation also experience slower H-1/H-2 exchange. Additionally, detection of couplings between H7 and C2 for R-II and R-III implies that the conformations of the linkers between these residues are different than in the monomers. These structural elements are consistent with two left-handed helical models: 2 residues/turn (2(4) helix) and 4 residues/turn (1(4) helix). To discriminate between models, we resorted to H-1,H-1 NOEs. The 2(4) helical model is in better agreement with the experimental data. We provide direct evidence of H-bonding for (SiA)(4) and show how H-bonds can be a determining factor for shaping its 3D structure.
C1 [Battistel, Marcos D.; Shangold, Michael; Freedberg, Daron I.] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Loc Trinh; Shiloach, Joseph; Freedberg, Daron I.] NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA.
RP Freedberg, DI (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA.
EM daron_freedberg@nih.gov
FU Intramural NIH HHS [Z01 DK070011-01]
NR 33
TC 19
Z9 19
U1 3
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUL 4
PY 2012
VL 134
IS 26
BP 10717
EP 10720
DI 10.1021/ja300624j
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 966UW
UT WOS:000305863900001
PM 22703338
ER
PT J
AU Carson, JL
Grossman, BJ
Kleinman, S
Tinmouth, AT
Marques, MB
Fung, MK
Holcomb, JB
Illoh, O
Kaplan, LJ
Katz, LM
Rao, SV
Roback, JD
Shander, A
Tobian, AAR
Weinstein, R
McLaughlin, LGS
Djulbegovic, B
AF Carson, Jeffrey L.
Grossman, Brenda J.
Kleinman, Steven
Tinmouth, Alan T.
Marques, Marisa B.
Fung, Mark K.
Holcomb, John B.
Illoh, Orieji
Kaplan, Lewis J.
Katz, Louis M.
Rao, Sunil V.
Roback, John D.
Shander, Aryeh
Tobian, Aaron A. R.
Weinstein, Robert
McLaughlin, Lisa Grace Swinton
Djulbegovic, Benjamin
CA Clinical Transfusion Med Comm AAB
TI Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; CRITICAL-CARE; CRITICALLY-ILL;
UNITED-STATES; RESTRICTIVE TRANSFUSION; CORONARY STENOSIS; KNEE
ARTHROPLASTY; RESIDUAL RISK; HIP FRACTURE; ADULT TRAUMA
AB Description: Although approximately 85 million units of red blood cells (RBCs) are transfused annually worldwide, transfusion practices vary widely. The AABB (formerly, the American Association of Blood Banks) developed this guideline to provide clinical recommendations about hemoglobin concentration thresholds and other clinical variables that trigger RBC transfusions in hemodynamically stable adults and children.
Methods: These guidelines are based on a systematic review of randomized clinical trials evaluating transfusion thresholds. We performed a literature search from 1950 to February 2011 with no language restrictions. We examined the proportion of patients who received any RBC transfusion and the number of RBC units transfused to describe the effect of restrictive transfusion strategies on RBC use. To determine the clinical consequences of restrictive transfusion strategies, we examined overall mortality, nonfatal myocardial infarction, cardiac events, pulmonary edema, stroke, thromboembolism, renal failure, infection, hemorrhage, mental confusion, functional recovery, and length of hospital stay.
Recommendation 1: The AABB recommends adhering to a restrictive transfusion strategy (7 to 8 g/dL) in hospitalized, stable patients (Grade: strong recommendation; high-quality evidence).
Recommendation 2: The AABB suggests adhering to a restrictive strategy in hospitalized patients with preexisting cardiovascular disease and considering transfusion for patients with symptoms or a hemoglobin level of 8 g/dL or less (Grade: weak recommendation; moderate-quality evidence).
Recommendation 3: The AABB cannot recommend for or against a liberal or restrictive transfusion threshold for hospitalized, hemodynamically stable patients with the acute coronary syndrome (Grade: uncertain recommendation; very low-quality evidence).
Recommendation 4: The AABB suggests that transfusion decisions be influenced by symptoms as well as hemoglobin concentration (Grade: weak recommendation; low-quality evidence).
C1 [Carson, Jeffrey L.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, New Brunswick, NJ 08903 USA.
Washington Univ, Sch Med, St Louis, MO USA.
AABB, Bethesda, MD USA.
Johns Hopkins Univ, Sch Med, Bethesda, MD USA.
Univ British Columbia, Victoria, BC, Canada.
Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
Univ Alabama Birmingham, Birmingham, AL USA.
Fletcher Allen Hlth Care, Burlington, VT USA.
Univ Texas Houston, Med Ctr, Ctr Translat Injury Res, Houston, TX USA.
Univ Texas Houston, Med Ctr, Dept Surg, Houston, TX USA.
US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
Yale Med Grp, New Haven, CT USA.
Univ Iowa, Mississippi Valley Reg Blood Ctr, Davenport, IA USA.
Univ Iowa, Carver Coll Med, Davenport, IA USA.
Duke Univ, Sch Med, Durham, NC USA.
Emory Univ, Sch Med, Atlanta, GA USA.
Englewood Hosp & Med Ctr, Englewood, NJ USA.
Univ Massachusetts, Sch Med, Worcester, MA USA.
Amer Red Cross, Rockville, MD USA.
Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
Res Inst, Tampa, FL USA.
RP Carson, JL (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Gen Internal Med, 125 Paterson St, New Brunswick, NJ 08903 USA.
EM carson@umdnj.edu
RI Djulbegovic, Benjamin/I-3661-2012;
OI Djulbegovic, Benjamin/0000-0003-0671-1447; Grossman,
Brenda/0000-0002-1500-8211; Marques, Marisa/0000-0002-6689-7856
FU AABB, Bethesda, Maryland
FX Support for the development of this guideline was provided by the AABB,
Bethesda, Maryland.
NR 63
TC 376
Z9 396
U1 2
U2 30
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 3
PY 2012
VL 157
IS 1
BP 49
EP U95
DI 10.7326/0003-4819-157-1-201206190-00429
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA 992NS
UT WOS:000307784900005
PM 22751760
ER
PT J
AU Zhang, K
Wong, JW
Yang, P
Hayward, DG
Sakuma, T
Zou, YY
Schreiber, A
Borton, C
Nguyen, TV
Kaushik, B
Oulkar, D
AF Zhang, Kai
Wong, Jon W.
Yang, Paul
Hayward, Douglas G.
Sakuma, Takeo
Zou, Yunyun
Schreiber, Andre
Borton, Christopher
Tung-Vi Nguyen
Kaushik, Banerjee
Oulkar, Dasharath
TI Protocol for an Electrospray Ionization Tandem Mass Spectral Product Ion
Library: Development and Application for Identification of 240
Pesticides in Foods
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID MULTIRESIDUE ANALYSIS; LC-MS/MS; SPECTROMETRY; TRAP; RESIDUES; MS;
SYSTEM
AB Modern determination techniques for pesticides must yield identification quickly with high confidence for timely enforcement of tolerances. A protocol for the collection of liquid chromatography (LC) electrospray ionization (ESI)-quadruple linear ion trap (QLIT) mass spectrometry (MS) library spectra was developed. Following the protocol, an enhanced product ion (EPI) library of 240 pesticides was developed by use of spectra collected from two laboratories. A LC-Q-LIT-MS workflow using scheduled multiple reaction monitoring (sMRM) survey scan, information-dependent acquisition (IDA) triggered collection of EPI spectra, and library search was developed and tested to identify the 240 target pesticides in one single LC-Q-LIT MS analysis. By use of LC retention time, one sMRM survey scan transition, and a library search, 75-87% of the 240 pesticides were identified in a single LC/MS analysis at fortified concentrations of 10 ng/g in 18 different foods. A conventional approach with LC-MS/MS using two MRM transitions produced the same identifications and comparable quantitative results with the same incurred foods as the LC-Q-LIT using EPI library search, finding 1.2-49 ng/g of either carbaryl, carbendazim, fenbuconazole, propiconazole, or pyridaben in peaches; carbendazim, imazalil, terbutryn, and thiabendazole in oranges; terbutryn in salmon; and azoxystrobin in ginseng. Incurred broccoli, cabbage, and kale were screened with the same EPI library using three LC-Q-LIT and a LC-quadruple time-of-flight (Q-TOF) instruments. The library search identified azoxystrobin, cyprodinil, fludioxinil, imidacloprid, metalaxyl, spinosyn A, D, and J, amd spirotetramat with each instrument. The approach has a broad application in LC-MS/MS type targeted screening in food analysis.
C1 [Zhang, Kai; Wong, Jon W.; Hayward, Douglas G.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Yang, Paul; Tung-Vi Nguyen] Ontario Minist Environm, Etobicoke, ON M9P 3V6, Canada.
[Sakuma, Takeo; Zou, Yunyun; Schreiber, Andre; Borton, Christopher] AB Sciex, Concord, ON L4K 4V8, Canada.
[Kaushik, Banerjee; Oulkar, Dasharath] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India.
RP Zhang, K (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 706, College Pk, MD 20740 USA.
EM kai.zhang@fda.hhs.gov
NR 26
TC 16
Z9 17
U1 2
U2 76
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 JUL 3
PY 2012
VL 84
IS 13
BP 5677
EP 5684
DI 10.1021/ac300844d
PG 8
WC Chemistry, Analytical
SC Chemistry
GA 966XS
UT WOS:000305871300033
PM 22686274
ER
PT J
AU Parkinson, DR
Dracopoli, N
Petty, BG
Compton, C
Cristofanilli, M
Deisseroth, A
Hayes, DF
Kapke, G
Kumar, P
Lee, JSH
Liu, MC
McCormack, R
Mikulski, S
Nagahara, L
Pantel, K
Pearson-White, S
Punnoose, EA
Roadcap, LT
Schade, AE
Scher, HI
Sigman, CC
Kelloff, GJ
AF Parkinson, David R.
Dracopoli, Nicholas
Petty, Brenda Gumbs
Compton, Carolyn
Cristofanilli, Massimo
Deisseroth, Albert
Hayes, Daniel F.
Kapke, Gordon
Kumar, Prasanna
Lee, Jerry S. H.
Liu, Minetta C.
McCormack, Robert
Mikulski, Stanislaw
Nagahara, Larry
Pantel, Klaus
Pearson-White, Sonia
Punnoose, Elizabeth A.
Roadcap, Lori T.
Schade, Andrew E.
Scher, Howard I.
Sigman, Caroline C.
Kelloff, Gary J.
TI Considerations in the development of circulating tumor cell technology
for clinical use
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Review
DE Circulating tumor cells; Prognostic biomarker; Predictive biomarker;
Analytical validation; Clinical validation; Biomarker qualification;
Oncologic drug development
ID METASTATIC BREAST-CANCER; RESISTANT PROSTATE-CANCER; PERIPHERAL-BLOOD;
LUNG-CANCER; CELLSEARCH SYSTEM; COLORECTAL-CANCER; HER2 EXPRESSION;
STEM-CELL; BIOMARKER; SURVIVAL
AB This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC) technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development-analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA) and the US National Cancer Institute (NCI).
C1 [Parkinson, David R.] New Enterprise Associates, Menlo Pk, CA 94025 USA.
[Dracopoli, Nicholas] Johnson & Johnson, Radnor, PA 19087 USA.
[Petty, Brenda Gumbs; Sigman, Caroline C.] CCS Associates, Mountain View, CA 94043 USA.
[Compton, Carolyn] Crit Path Inst, Tucson, AZ 85718 USA.
[Cristofanilli, Massimo] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Deisseroth, Albert] US FDA, Ctr Drug Evaluat Res, Silver Spring, MD 20903 USA.
[Hayes, Daniel F.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kapke, Gordon] Covance Cent Labs, Covance Genom Lab, Seattle, WA 98382 USA.
[Kumar, Prasanna] Daiichi Sankyo Pharma Dev, Edison, NJ 08837 USA.
[Lee, Jerry S. H.; Nagahara, Larry; Kelloff, Gary J.] NCI, Bethesda, MD 20892 USA.
[Liu, Minetta C.] Georgetown Univ, Washington, DC 20007 USA.
[McCormack, Robert] Veridex LLC, Raritan, NJ 08869 USA.
[Mikulski, Stanislaw] EMD Serono, Rockland, MA 02370 USA.
[Pantel, Klaus] Univ Med Ctr Hamburg Eppendorf, D-20246 Hamburg, Germany.
[Pearson-White, Sonia] Fdn Natl Inst Hlth, Bethesda, MD 20814 USA.
[Punnoose, Elizabeth A.] Genentech Inc, San Francisco, CA 94080 USA.
[Roadcap, Lori T.] GlaxoSmithKline, Collegeville, PA 19426 USA.
[Schade, Andrew E.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
RP Parkinson, DR (reprint author), New Enterprise Associates, Menlo Pk, CA 94025 USA.
EM dparkinson@nea.com
RI Lee, Jerry/A-3189-2008; Lee, Jerry/K-4553-2014
OI Lee, Jerry/0000-0003-1515-0952;
FU Veridex LLC; Johnson Johnson
FX Several of the authors are past or current employees of, stockholders
in, consultants to, or have received research funding or honoraria from
Veridex LLC, the manufacturer of the CellSearch System (TM) for
detection of CTCs, or its parent company Johnson & Johnson (ND, DH, MCL,
RM, KP, HS). DH has also been a consultant to Biomarker Strategies of
Baltimore, Maryland on CTCs and is named as an inventor or co-inventor
on patents on applying CTCs in clinical settings. MC is a consultant to
Alere, Inc. on CTCs; GK is an employee and stockholder of Covance, Inc.,
which includes CTC assays (particularly the Veridex CellSearch (TM)
system) among its commercial offerings; and DP has been an employee of
Nodality, Inc. which is developing technology that has potential
application in CTC analysis. The remaining authors have no relevant
competing interests (CC, BGP, AD, GJK, PK, JL, SM, LN, SPW, EP, LR, AS,
CCS).
NR 65
TC 131
Z9 140
U1 7
U2 91
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 2
PY 2012
VL 10
AR 138
DI 10.1186/1479-5876-10-138
PG 20
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 026GX
UT WOS:000310263800001
PM 22747748
ER
PT J
AU Hoelzer, K
Pouillot, R
Gallagher, D
Silverman, MB
Kause, J
Dennis, S
AF Hoelzer, Karin
Pouillot, Regis
Gallagher, Daniel
Silverman, Meryl B.
Kause, Janell
Dennis, Sherri
TI Estimation of Listeria monocytogenes transfer coefficients and efficacy
of bacterial removal through cleaning and sanitation
SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
LA English
DT Article
DE L. monocytogenes; Transfer coefficient; Food slicing; Sanitization;
Mathematical model
ID HIGH-DENSITY POLYETHYLENE; MICROBIAL CROSS-CONTAMINATION; QUANTITATIVE
RISK-ASSESSMENT; ESCHERICHIA-COLI O157-H7; STAINLESS-STEEL; MODELING
TRANSFER; COMMERCIAL DISINFECTANTS; CAMPYLOBACTER TRANSFER;
STAPHYLOCOCCUS-AUREUS; INACTIVATION KINETICS
AB Listeria monocytogenes is readily found in the environment of retail deli establishments and can occasionally contaminate food handled in these establishments. Here we synthesize the available scientific evidence to derive probability distributions and mathematical models of bacterial transfers between environmental surfaces and foods, including those during slicing of food, and of bacterial removal during cleaning and sanitizing (models available at www.foodrisk.org).
Transfer coefficients varied considerably by surface type, and after log(10) transformation were best described by normal distributions with means ranging from -0.29 to -4.96 and standard deviations that ranged from 0.07 to 1.39. 'Transfer coefficients' during slicing were best described by a truncated logistic distribution with location 0.07 and scale 0.03. In the absence of protein residues, mean log inactivation indicated a greater than 5 logic, reduction for sanitization with hypochlorite (mean: 6.5 log(10); 95% confidence interval (CI): 5.0-8.1 log(10)) and quaternary ammonium compounds (mean: 5.5 log(10); 95% CI: 3.6-7.3 log(10)), but in the presence of protein residues efficacy reduced dramatically for hypochlorite (mean: 3.8 log(10); 95% CI: 2.1-5.4 log(10)) as well as quaternary ammonium compounds (mean: 4.4log(10); 95% Cl: 2.5-6.4 log(10)).
Overall, transfer coefficients are therefore low, even though cross-contamination can be extremely efficient under certain conditions. Dozens of food items may consequently be contaminated from a single contaminated slicer blade, albeit at low concentrations. Correctly performed sanitizing efficiently reduces L monocytogenes contamination in the environment and therefore limits cross-contamination, even though sanitization is only performed a few times per day. However, under unfavorable conditions reductions in bacterial concentration may be far below 5 log(10).
The probability distributions and mathematical models derived here can be used to evaluate L monocytogenes cross-contamination dynamics in environments where foods are handled, and to assess the potential impact of different intervention strategies. (C) 2012 Elsevier By. All rights reserved.
C1 [Hoelzer, Karin; Pouillot, Regis; Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Gallagher, Daniel] Virginia Polytech Inst & State Univ, Civil & Environm Engn Dept, Blacksburg, VA 24061 USA.
[Silverman, Meryl B.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Kause, Janell] US Food Safety & Inspect Serv, Risk Assessment Div, Off Publ Hlth Sci, USDA, Washington, DC 20228 USA.
RP Hoelzer, K (reprint author), US FDA, Risk Assessment Coordinat Team, Ctr Food Safety & Appl Nutr HFS 005, 5100 Paint Branch Pkwy,Room 2A-031, College Pk, MD 20740 USA.
EM Karin.Hoelzer@fda.hhs.gov
RI Pouillot, Regis/E-8103-2010
OI Pouillot, Regis/0000-0002-6107-5212
FU Virginia Tech; U.S. Department of Agriculture, Food Safety and
Inspection Service (FSIS) [AG-3A94-P-08-0166]; US Department of Energy;
U.S. Food and Drug Administration
FX This work was supported in part by appointments to the Research
Participation Program at the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the US Department of
Energy and the U.S. Food and Drug Administration. Support for this work
was also provided by Virginia Tech in collaboration with the U.S.
Department of Agriculture, Food Safety and Inspection Service (FSIS
contract # AG-3A94-P-08-0166).
NR 74
TC 25
Z9 25
U1 0
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1605
J9 INT J FOOD MICROBIOL
JI Int. J. Food Microbiol.
PD JUL 2
PY 2012
VL 157
IS 2
BP 267
EP 277
DI 10.1016/j.ijfoodmicro.2012.05.019
PG 11
WC Food Science & Technology; Microbiology
SC Food Science & Technology; Microbiology
GA 987QR
UT WOS:000307432700021
PM 22704063
ER
PT J
AU Kurczewski, FE
Edwards, GB
Kimsey, LS
Kurczewski, KE
AF Kurczewski, Frank E.
Edwards, G. B.
Kimsey, Lynn S.
Kurczewski, Keith E.
TI Observations on the nesting behavior of Miscophus (Nitelopterus)
laticeps (Hymenoptera: Crabronidae)
SO PAN-PACIFIC ENTOMOLOGIST
LA English
DT Article
DE Theridiidae; Asagena fulva; Euryopis formosa; Araneidae; Hypsosinga
funebris; Lycosidae; Pardosa ?californica; Salticidae; Habronattus
californicus; Habronattus ?peckhami; oligophagy; polyphagy; Machimus
occidentalis; Hedychridium paulum; Montana de Oro State Park
AB A study of the nesting behavior of Miscophus (Nitelopterus) laticeps was undertaken at Montana de Oro State Park, San Luis Obispo County, California in 2010, 2011, and 2012 to clarify variation in previous reports on this species. Specific areas of study included (1) manner of prey transport, (2) presence or absence of temporary entrance closure, (3) manner of nest entry, (4) families of prey spiders, and (5) wasp's egg affixation site. New prey records, including two new families, were discovered as part of this study. The behavioral components of M. laticeps are discussed in relation to other North American congeners.
C1 [Edwards, G. B.] FDACS, Div Plant Ind, Gainesville, FL 32614 USA.
[Kimsey, Lynn S.] Univ Calif Davis, Ctr Biosystemat, Davis, CA 95616 USA.
[Kimsey, Lynn S.] Univ Calif Davis, RM Bohart Museum Entomol, Davis, CA 95616 USA.
RP Kurczewski, FE (reprint author), POB 13215, Syracuse, NY USA.
EM fkurczewski@twcny.rr.com; GB.Edwards@freshfromflorida.com;
lskimsey@ucdavis.edu; kkurczewski@yahoo.com
NR 11
TC 0
Z9 0
U1 1
U2 2
PU PACIFIC COAST ENTOMOL SOC
PI SAN FRANCISCO
PA C/O CALIFORNIA ACADEMY SCIENCES, 875 HOWARD STREET, SAN FRANCISCO, CA
94103-3009 USA
SN 0031-0603
J9 PAN-PAC ENTOMOL
JI Pan-Pacific Entomol.
PD JUL
PY 2012
VL 88
IS 3
BP 311
EP 318
PG 8
WC Entomology
SC Entomology
GA 053NA
UT WOS:000312278500005
ER
PT J
AU Abouzied, M
Driksna, D
Walsh, C
Sarzynski, M
Walsh, A
Ankrapp, D
Klein, F
Rice, J
Mozola, M
Kijak, P
Boison, J
Agin, J
AF Abouzied, Mohamed
Driksna, Dana
Walsh, Coilin
Sarzynski, Michael
Walsh, Aaron
Ankrapp, David
Klein, Frank
Rice, Jennifer
Mozola, Mark
Kijak, Phil
Boison, Joe
Agin, James
TI Validation Study of the BetaStar (R) Plus Lateral Flow Assay for
Detection of Beta-Lactam Antibiotics in Milk
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Article
AB A validation study designed to meet the requirements of the AOAC Research Institute and the U.S. Food and Drug Administration, Center for Veterinary Medicine (FDA/CVM) was conducted for a receptor and antibody-based, immunochromatographic method (Beta Star Plus) for detection of beta-lactam antibiotic residues in raw, commingled bovine milk. The assay was found to detect amoxicillin, ampicillin, ceftiofur, cephapirin, cloxacillin, and penicillin Oat levels below the FDA tolerance/safe levels, but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments (NCIMS). Results of the Part I (internal) and Part II (independent laboratory) dose-response studies employing spiked samples were in close agreement. The test was able to detect all six drugs at the approximate 90/95% sensitivity levels when presented as incurred residues in milk collected from cows that had been treated with the specific drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing of 1031 control milk samples. Results of ruggedness experiments established the operating parameter tolerances for the BetaStar Plus assay. Results of cross-reactivity testing established that the assay detects certain other beta-lactam drugs (dicloxacillin and ticarcillin), but it does not cross-react with any of 30 drugs belonging to other classes. Abnormally high bacterial or somatic cell counts in raw milk produced no interference with the ability of the test to detect beta-lactams at tolerance/safe levels.
C1 [Abouzied, Mohamed; Driksna, Dana; Walsh, Coilin; Sarzynski, Michael; Walsh, Aaron; Ankrapp, David; Klein, Frank; Rice, Jennifer; Mozola, Mark] Neogen Corp, Lansing, MI 48912 USA.
[Kijak, Phil] US FDA, Ctr Vet Med, Laurel, MD 20708 USA.
[Boison, Joe] Canadian Food Inspect Agcy, Saskatoon, SK S7N 2R3, Canada.
[Agin, James] Q Labs, Cincinnati, OH 45214 USA.
RP Mozola, M (reprint author), Neogen Corp, 620 Lesher Pl, Lansing, MI 48912 USA.
EM mmozola@neogen.com
NR 5
TC 2
Z9 2
U1 2
U2 14
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 JUL-AUG
PY 2012
VL 95
IS 4
BP 1211
EP 1221
DI 10.5740/jaoacint.11-252
PG 11
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 994CB
UT WOS:000307907400035
PM 22970593
ER
PT J
AU An, H
Henry, M
Cain, T
Tran, B
Paek, HC
Farley, D
AF An, Haejung
Henry, Mark
Cain, Teresa
Tran, Bichsa
Paek, Han Chol
Farley, Dennis
TI Determination of Total Nitrofuran Metabolites in Shrimp Muscle Using
Liquid Chromatography/Tandem Mass Spectrometry in the Atmospheric
Pressure Chemical Ionization Mode
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Article
ID BOUND METABOLITES; POULTRY MUSCLE; FURAZOLIDONE; RESIDUES;
3-AMINO-2-OXAZOLIDINONE; TISSUE; EGGS; AOZ
AB The method of Mac Mahon and Lohne for analysis of nitrofuran metabolites in shrimp was optimized to streamline the extraction processes and the LC analysis. This revised method includes 16 h of mild acid hydrolysis/derivatization followed by ethyl acetate extraction and analysis by LC/MS/MS in the atmospheric pressure chemical ionization mode. This revised method was validated in shrimp for concentrations of 0.25 to 2.0 ng/g. The LOQ was 0.25 ng/g for all metabolites. The LOD was 0.052 ng/g for 1-aminohydantoin (AHD), 0.206 ng/g for 3-amino-2-oxazolidinone (AOZ), 0.108 ng/g for semicarbazide (SC), and 0.062 ng/g for 3-amino-5morpholinomethyl-2-oxazolidinone (AMOZ). The spike recoveries with RSD into negative matrix at 1 ng/g were 100.2% (3.2%) for AHD, 102.5% (1.0%) for AOZ, 103.7% (2.3%) for SC, and 104.0% (3.3%) for AMOZ. The spike recoveries at 1 ng/g into unknown samples (n = 108) containing varied levels of nitrofuran metabolites were 112.6% (25.7%) for AHD, 108.1% (12.1%) for AOZ, 103.0% (12.0%) for SC, and 100.3% (6.9%) for AMOZ. Interday precision with samples containing incurred AOZ concentrations of 0.92 to 17.8 ppb performed over a year was 10.4% RSD. The method is accurate and precise for determining nitrofuran concentrations in the edible tissue of shrimp.
C1 [An, Haejung; Henry, Mark; Cain, Teresa; Tran, Bichsa; Paek, Han Chol; Farley, Dennis] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA.
RP An, H (reprint author), US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA.
EM Haejung.An@fda.hhs.gov
NR 16
TC 4
Z9 10
U1 0
U2 18
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 JUL-AUG
PY 2012
VL 95
IS 4
BP 1222
EP 1233
DI 10.5740/jaoacint.11-305
PG 12
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 994CB
UT WOS:000307907400036
PM 22970594
ER
PT J
AU Patel, M
Miller, MA
AF Patel, Meghal
Miller, Margaret Ann
TI Impact of regulatory science on global public health
SO KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
LA English
DT Review
DE Globalization; Innovation; Regulatory science
AB Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted following public health tragedies, and often the research tools and techniques required to execute these laws lagged behind the public health needs. Throughout history, similar public health problems relating to food and pharmaceutical products have occurred in countries around the world, and have usually led to the development of equivalent solutions. For example, most countries require a demonstration of pharmaceutical safety and efficacy prior to marketing these products using approaches that are similar to those initiated in the United States. The globalization of food and medical products has created a shift in regulatory compliance such that gaps in food and medical product safety can generate international problems. Improvements in regulatory research can advance the regulatory paradigm toward a more preventative, proactive framework. These improvements will advance at a greater pace with international collaboration by providing additional resources and new perspectives for approaching and anticipating public health problems. The following is a review of how past public health disasters have shaped the current regulatory landscape, and where innovation can facilitate the shift from reactive policies to proactive policies. Copyright (c) 2012, Elsevier Taiwan LLC. All rights reserved.
C1 [Patel, Meghal; Miller, Margaret Ann] US FDA, Natl Ctr Toxicol Res, Silver Spring, MD 20993 USA.
RP Miller, MA (reprint author), US FDA, Natl Ctr Toxicol Res, 10903 New Hampshire Ave,Bldg 32,Room 2208, Silver Spring, MD 20993 USA.
EM Margaret.Miller@fda.hhs.gov
NR 20
TC 2
Z9 2
U1 1
U2 12
PU ELSEVIER TAIWAN
PI TAIPEI
PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2,
TAIPEI, 10449, TAIWAN
SN 1607-551X
J9 KAOHSIUNG J MED SCI
JI Kaohsiung J. Med. Sci.
PD JUL
PY 2012
VL 28
IS 7
SU S
BP S5
EP S9
DI 10.1016/j.kjms.2012.05.003
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 003NN
UT WOS:000308618700003
PM 22871603
ER
PT J
AU Rallabhandi, P
Phillips, RL
Boukhvalova, MS
Pletneva, LM
Shirey, KA
Gioannini, TL
Weiss, JP
Chow, JC
Hawkins, LD
Vogel, SN
Blanco, JCG
AF Rallabhandi, Prasad
Phillips, Rachel L.
Boukhvalova, Marina S.
Pletneva, Lioubov M.
Shirey, Kari Ann
Gioannini, Theresa L.
Weiss, Jerrold P.
Chow, Jesse C.
Hawkins, Lynn D.
Vogel, Stefanie N.
Blanco, Jorge C. G.
TI Respiratory Syncytial Virus Fusion Protein-Induced Toll-Like Receptor 4
(TLR4) Signaling Is Inhibited by the TLR4 Antagonists Rhodobacter
sphaeroides Lipopolysaccharide and Eritoran (E5564) and Requires Direct
Interaction with MD-2
SO MBIO
LA English
DT Article
ID MONOPHOSPHORYL-LIPID-A; FRANCISELLA-TULARENSIS; IN-VIVO;
MONOCLONAL-ANTIBODY; TLR4-MD-2 COMPLEX; ESCHERICHIA-COLI;
F-GLYCOPROTEIN; CUTTING EDGE; COTTON RATS; SUBGROUP-B
AB Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Toll-like receptor 4 (TLR4), a signaling receptor for structurally diverse microbe-associated molecular patterns, is activated by the RSV fusion (F) protein and by bacterial lipopolysaccharide (LPS) in a CD14-dependent manner. TLR4 signaling by LPS also requires the presence of an additional protein, MD-2. Thus, it is possible that F protein-mediated TLR4 activation relies on MD-2 as well, although this hypothesis has not been formally tested. LPS-free RSV F protein was found to activate NF-kappa B in HEK293T transfectants that express wild-type (WT) TLR4 and CD14, but only when MD-2 was coexpressed. These findings were confirmed by measuring F-protein-induced interleukin 1 beta (IL-1 beta) mRNA in WT versus MD-2(-/-) macrophages, where MD-2(-/-) macrophages failed to show IL-1 beta expression upon F-protein treatment, in contrast to the WT. Both Rhodobacter sphaeroides LPS and synthetic E5564 (eritoran), LPS antagonists that inhibit TLR4 signaling by binding a hydrophobic pocket in MD-2, significantly reduced RSV F-protein-mediated TLR4 activity in HEK293T-TLR4-CD14-MD-2 transfectants in a dose-dependent manner, while TLR4-independent NF-kappa B activation by tumor necrosis factor alpha (TNF-alpha) was unaffected. In vitro coimmunoprecipitation studies confirmed a physical interaction between native RSV F protein and MD-2. Further, we demonstrated that the N-terminal domain of the F1 segment of RSV F protein interacts with MD-2. These data provide new insights into the importance of MD-2 in RSV F-protein-mediated TLR4 activation. Thus, targeting the interaction between MD-2 and RSV F protein may potentially lead to novel therapeutic approaches to help control RSV-induced inflammation and pathology.
IMPORTANCE This study shows for the first time that the fusion (F) protein of respiratory syncytial virus (RSV), a major cause of bronchiolitis and death, particularly in infants and young children, physically interacts with the Toll-like receptor 4 (TLR4) coreceptor, MD-2, through its N-terminal domain. We show that F protein-induced TLR4 activation can be blocked by lipid A analog antagonists. This observation provides a strong experimental rationale for testing such antagonists in animal models of RSV infection for potential use in people.
C1 [Rallabhandi, Prasad; Shirey, Kari Ann; Vogel, Stefanie N.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Rallabhandi, Prasad] US FDA, Laurel, MD USA.
[Phillips, Rachel L.; Gioannini, Theresa L.; Weiss, Jerrold P.] Univ Iowa, Iowa City, IA USA.
[Boukhvalova, Marina S.; Pletneva, Lioubov M.; Blanco, Jorge C. G.] Sigmovir Biosyst Inc, Rockville, MD USA.
[Gioannini, Theresa L.] Dept Vet Affairs, Iowa City, IA USA.
[Chow, Jesse C.; Hawkins, Lynn D.] EISAI Inc, Andover, MA USA.
RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM svogel@som.maryland.edu; j.blanco@sigmovir.com
FU NIAID, NIH [AI-057575, AI-18797, AI05732]; VA Merit grant
FX This work was supported by NIAID, NIH, grants AI-057575 to J.C.G.B.,
AI-18797 to S.N.V., and AI05732 to J.P.W. and by a VA Merit grant to
T.L.G.
NR 57
TC 20
Z9 22
U1 0
U2 21
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2012
VL 3
IS 4
AR e00218-12
DI 10.1128/mBio.00218-12
PG 8
WC Microbiology
SC Microbiology
GA 003DQ
UT WOS:000308588800029
ER
PT J
AU Li, J
Shao, ZH
Xie, JT
Wang, CZ
Ramachandran, S
Yin, JJ
Aung, H
Li, CQ
Qin, G
Vanden Hoek, T
Yuan, CS
AF Li, Jing
Shao, Zuo-Hui
Xie, Jing-Tian
Wang, Chong-Zhi
Ramachandran, Srinivasan
Yin, Jun-Jie
Aung, Han
Li, Chang-Qing
Qin, Gina
Vanden Hoek, Terry
Yuan, Chun-Su
TI The effects of ginsenoside Rb1 on JNK in oxidative injury in
cardiomyocytes
SO ARCHIVES OF PHARMACAL RESEARCH
LA English
DT Article
DE Ginsenoside Rb1; Oxidative stress; Cardiomyocyte; JNK
ID N-TERMINAL KINASE; OXIDANT STRESS; C-JUN; SIGNAL-TRANSDUCTION;
REPERFUSION INJURY; HYDROGEN-PEROXIDE; CARDIAC MYOCYTES; DNA-DAMAGE;
ACTIVATION; ISCHEMIA
AB Reactive oxygen species (ROS) can induce oxidative injury via iron interactions (i.e. Fenton chemistry and hydroxyl radical formation). Our prior work suggested that American ginseng berry extract and ginsenoside Re were highly cardioprotective against oxidant stress. To extend this study, we evaluated the protective effect of protopanaxadiol-type ginsenoside Rb1 (gRb1) on H2O2-induced oxidative injury in cardiomyocytes and explored the ROS-mediated intracellular signaling mechanism. Cultured embryonic chick cardiomyocytes (4-5 day) were used. Cell death was assessed by propidium iodide and lactate dehydrogenase release. Pretreatment with gRb1 (0.01, 0.1, or 1 mu M) for 2 h and concurrent treatment with H2O2 (0.5 mM) for 2 h resulted in a dose-dependent reduction of cell death, 36.6 +/- 2.9% (n = 12, p < 0.05), 30.5 +/- 5.1% (n = 12, p < 0.05) and 28.6 +/- 3.1% (n = 12, p < 0.01) respectively, compared to H2O2-exposed cells (48.2 +/- 3.3%, n = 12). This cardioprotective effect of gRb1 was associated with attenuated intracellular ROS generation as measured by 6-carboxy-2', 7'-dichlorodihydrofluorescein diacetate, preserved the mitochondrial membrane potential as determined using JC-1. In the ESR study, gRb1 exhibited the scavenging DPPH and hydroxyl radical activities. Furthermore, our data showed the increased JNK phosphorylation (p-JNK) in H2O2-exposed cells was suppressed by the pretreatment with gRb 1 (1 mu M) (p < 0.01). Co-treatment of gRb1 with a specific inhibitor of JNK SP600125 (10 mu M) further reduced the p-JNK and enhanced the cell survival after H2O2 exposure. Collectively, our results suggest that gRb1 conferred cardioprotection that was mediated via attenuating ROS and suppressing ROS-induced JNK activation.
C1 [Xie, Jing-Tian; Wang, Chong-Zhi; Aung, Han; Yuan, Chun-Su] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
[Xie, Jing-Tian; Wang, Chong-Zhi; Aung, Han; Yuan, Chun-Su] Univ Chicago, Tang Ctr Herbal Med Res, Chicago, IL 60637 USA.
[Li, Jing; Shao, Zuo-Hui; Li, Chang-Qing; Qin, Gina; Vanden Hoek, Terry] Univ Illinois Hosp & Hlth Sci Syst, Dept Emergency Med, Chicago, IL 60612 USA.
[Ramachandran, Srinivasan] Univ Calif San Diego, Dept Mech & Aerosp Engn, La Jolla, CA 92093 USA.
[Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Yuan, CS (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, 5841 S Maryland Ave,MC 4028, Chicago, IL 60637 USA.
EM tvh@uic.edu; CYuan@uchicago.edu
RI Yin, Jun Jie /E-5619-2014
FU NIH/NCCAM [AT003441, AT004418, AT005362]
FX This work was supported in part by the NIH/NCCAM grants AT003441,
AT004418 and AT005362.
NR 45
TC 24
Z9 28
U1 1
U2 21
PU PHARMACEUTICAL SOC KOREA
PI SEOUL
PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA
SN 0253-6269
J9 ARCH PHARM RES
JI Arch. Pharm. Res.
PD JUL
PY 2012
VL 35
IS 7
BP 1259
EP 1267
DI 10.1007/s12272-012-0717-3
PG 9
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 985VQ
UT WOS:000307299000018
PM 22864749
ER
PT J
AU Ilev, IK
Boppart, SA
Andersson-Engels, S
Kim, BM
Vo-Dinh, T
AF Ilev, Ilko K.
Boppart, Stephen A.
Andersson-Engels, Stefan
Kim, Beop-Min
Vo-Dinh, Tuan
TI Introduction to the Issue on Biophotonics-Part 2
SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS
LA English
DT Editorial Material
C1 [Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Bioengn, Urbana, IL 61801 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Med, Urbana, IL 61801 USA.
[Andersson-Engels, Stefan] Lund Univ, Div Atom Phys, SE-22100 Lund, Sweden.
[Kim, Beop-Min] Korea Univ, Dept Biomed Engn, Seoul 136703, South Korea.
[Vo-Dinh, Tuan] Duke Univ, Fitzpatrick Inst Photon, Durham, NC 27708 USA.
RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM ilko.ilev@fda.hhs.gov
RI Andersson-Engels, Stefan/C-5515-2012
OI Andersson-Engels, Stefan/0000-0001-5640-3122
NR 0
TC 0
Z9 0
U1 0
U2 9
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1077-260X
J9 IEEE J SEL TOP QUANT
JI IEEE J. Sel. Top. Quantum Electron.
PD JUL-AUG
PY 2012
VL 18
IS 4
BP 1267
EP 1269
DI 10.1109/JSTQE.2012.2202206
PG 3
WC Engineering, Electrical & Electronic; Optics; Physics, Applied
SC Engineering; Optics; Physics
GA 996SD
UT WOS:000308113800001
ER
PT J
AU Decker, KB
James, TD
Stibitz, S
Hinton, DM
AF Decker, Kimberly B.
James, Tamara D.
Stibitz, Scott
Hinton, Deborah M.
TI The Bordetella pertussis model of exquisite gene control by the global
transcription factor BvgA
SO MICROBIOLOGY-SGM
LA English
DT Review
ID ESCHERICHIA-COLI SIGMA(70); P-R PROMOTER; RNA-POLYMERASE; PHASE
VARIATION; DNA-BINDING; CONFORMATIONAL-CHANGES; FRAMESHIFT MUTATION;
SIGNAL-TRANSDUCTION; 2-COMPONENT SYSTEM; CRYSTAL-STRUCTURE
AB Bordetella pertussis causes whooping cough, an infectious disease that is reemerging despite widespread vaccination. A more complete understanding of B. pertussis pathogenic mechanisms will involve unravelling the regulation of its impressive arsenal of virulence factors. Here we review the action of the B. pertussis response regulator BvgA in the context of what is known about bacterial RNA polymerase and various modes of transcription activation. At most virulence gene promoters, multiple dimers of phosphorylated BvgA (BvgA similar to P) bind upstream of the core promoter sequence, using a combination of high- and low-affinity sites that fill through cooperativity. Activation by BvgA similar to P is typically mediated by a novel form of class I/II mechanisms, but two virulence genes, fim2 and fim3, which encode serologically distinct fimbrial subunits, are regulated using a previously unrecognized RNA polymerase/activator architecture. In addition, the fim genes undergo phase variation because of an extended cytosine (C) tract within the promoter sequences that is subject to slipped-strand mispairing during replication. These sophisticated systems of regulation demonstrate one aspect whereby B. pertussis, which is highly clonal and lacks the extensive genetic diversity observed in many other bacterial pathogens, has been highly successful as an obligate human pathogen.
C1 [Decker, Kimberly B.; James, Tamara D.; Hinton, Deborah M.] NIDDKD, Gene Express & Regulat Sect, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Stibitz, Scott] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA.
RP Decker, KB (reprint author), Eunice Kennedy Shriver NICHHD, Microbial Pathogenesis Unit, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
EM deckerkb@mail.nih.gov
FU Intramural Research Program of the National institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases
FX We thank Karen Usdin, Saheli Jha, Alice Boulanger-Castaing and Leslie
Knipling (NIDDK, NIH) for helpful discussions and especially Seth Darst
(Rockerfeller University) for sharing the modelled structure of
cII/sigma region 4/alpha CTD at PRE. Research was supported
in part by the Intramural Research Program of the National institutes of
Health, National Institute of Diabetes and Digestive and Kidney
Diseases.
NR 92
TC 18
Z9 19
U1 0
U2 18
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 1350-0872
J9 MICROBIOL-SGM
JI Microbiology-(UK)
PD JUL
PY 2012
VL 158
BP 1665
EP 1676
DI 10.1099/mic.0.058941-0
PN 7
PG 12
WC Microbiology
SC Microbiology
GA 990BM
UT WOS:000307606000001
PM 22628479
ER
PT J
AU Capriotti, E
Nehrt, NL
Kann, MG
Bromberg, Y
AF Capriotti, Emidio
Nehrt, Nathan L.
Kann, Maricel G.
Bromberg, Yana
TI Bioinformatics for personal genome interpretation
SO BRIEFINGS IN BIOINFORMATICS
LA English
DT Article
DE genomic variation; genome interpretation; genomic variant databases;
gene prioritization; deleterious variants
ID PROTEIN STABILITY CHANGES; NON-SYNONYMOUS SNPS; SINGLE NUCLEOTIDE
POLYMORPHISMS; CANDIDATE GENE PRIORITIZATION; SUPPORT VECTOR MACHINES;
COMPLEX HUMAN TRAITS; SEMANTIC SIMILARITY; MISSENSE MUTATIONS; WIDE
ASSOCIATION; POINT MUTATIONS
AB An international consortium released the first draft sequence of the human genome 10 years ago. Although the analysis of this data has suggested the genetic underpinnings of many diseases, we have not yet been able to fully quantify the relationship between genotype and phenotype. Thus, a major current effort of the scientific community focuses on evaluating individual predispositions to specific phenotypic traits given their genetic backgrounds. Many resources aim to identify and annotate the specific genes responsible for the observed phenotypes. Some of these use intra-species genetic variability as a means for better understanding this relationship. In addition, several online resources are now dedicated to collecting single nucleotide variants and other types of variants, and annotating their functional effects and associations with phenotypic traits. This information has enabled researchers to develop bioinformatics tools to analyze the rapidly increasing amount of newly extracted variation data and to predict the effect of uncharacterized variants. In this work, we review the most important developments in the field-the databases and bioinformatics tools that will be of utmost importance in our concerted effort to interpret the human variome.
C1 [Capriotti, Emidio] Univ Balearic Isl, Dept Math & Comp Sci, Palma De Mallorca 07122, Spain.
[Capriotti, Emidio] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
[Nehrt, Nathan L.] US FDA, Res Participat Program, Rockville, MD 20857 USA.
[Kann, Maricel G.] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA.
[Bromberg, Yana] Rutgers State Univ, Dept Biochem & Microbiol, Sch Environm & Biol Sci, New Brunswick, NJ 08901 USA.
RP Capriotti, E (reprint author), Univ Balearic Isl, Dept Math & Comp Sci, Ctra Valldemossa,Km 7-5, Palma De Mallorca 07122, Spain.
EM emidio.capriotti@uib.es
RI Capriotti, Emidio/D-9318-2011;
OI Capriotti, Emidio/0000-0002-2323-0963; Bromberg,
Yana/0000-0002-8351-0844
FU European Community [PIOF-GA-2009-237225]; National Institutes of Health
(NIH) [1K22CA143148]; Rutgers University, New Brunswick, School of
Environmental and Biological Science (SEBS)
FX The European Community through the Marie Curie International Outgoing
Fellowship program (PIOF-GA-2009-237225 to E.C.); this work was
supported by the National Institutes of Health (NIH) (1K22CA143148 to
M.G.K.); Rutgers University, New Brunswick, School of Environmental and
Biological Science (SEBS) start-up funds (to Y.B.); the Research
Participation Program administered by Oak Ridge Institute for Science
and Education (ORISE) through an inter-agency agreement between
Department of Energy (DOE) and Food and Drug Administration (FDA) (to
N.N.).
NR 177
TC 31
Z9 31
U1 1
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1467-5463
J9 BRIEF BIOINFORM
JI Brief. Bioinform.
PD JUL
PY 2012
VL 13
IS 4
SI SI
BP 495
EP 512
DI 10.1093/bib/bbr070
PG 18
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA 980WN
UT WOS:000306925000008
PM 22247263
ER
PT J
AU Myers, MB
Wang, YY
Mckim, KL
Parsons, BL
AF Myers, Meagan B.
Wang, Yiying
Mckim, Karen L.
Parsons, Barbara L.
TI Hotspot oncomutations: implications for personalized cancer treatment
SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
LA English
DT Review
DE biomarker; BRAF; colon cancer; EGFR; KRAS; lung cancer; mutation;
mutation detection; personalized medicine; PIK3CA
ID CELL LUNG-CANCER; GROWTH-FACTOR-RECEPTOR; METASTATIC COLORECTAL-CANCER;
TYROSINE KINASE INHIBITORS; K-RAS MUTATIONS; CETUXIMAB PLUS IRINOTECAN;
RESECTED COLON-CANCER; RANDOMIZED PHASE-III; BRAF V600E MUTATION;
WILD-TYPE BRAF
AB Understanding the extent to which specific tumor mutations impact or mediate patient response to particular cancer therapies has become a rapidly increasing area of research. Recent research findings regarding four predominant mutational targets (KRAS, BRAF, EGFR and PIK3CA) show that these tumor mutations have predictive power for identifying which patients are likely to respond to particular therapies, and have prognostic significance irrespective of treatment. However, in this regard, the literature is frequently nuanced and sometimes contradictory. This lack of clarity may be due, at least in part, to the utilization of mutation detection methods with varying sensitivities across studies of different patient populations. Nevertheless, considerable evidence suggests minor tumor subpopulations may be contributing to inappropriate patient stratification, development of resistance to treatment, and the relapse that often follows treatment with molecularly targeted therapies. Consequently, mutant tumor subpopulations need to be considered in order to improve strategies for personalized cancer treatment.
C1 [Myers, Meagan B.; Wang, Yiying; Mckim, Karen L.; Parsons, Barbara L.] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA.
RP Myers, MB (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM meagan.myers@fda.hhs.gov
NR 142
TC 7
Z9 7
U1 0
U2 8
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1473-7159
J9 EXPERT REV MOL DIAGN
JI Expert Rev. Mol. Diagn.
PD JUL
PY 2012
VL 12
IS 6
BP 603
EP 620
DI 10.1586/ERM.12.51
PG 18
WC Pathology
SC Pathology
GA 994MW
UT WOS:000307935900012
PM 22845481
ER
PT J
AU Maisel, WH
AF Maisel, William H.
TI Innovation at the Food and Drug Administration's Device Center
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Editorial Material
DE aortic valve; medical device; regulatory clinical trials
C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Maisel, WH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO Bldg 66,Room 5410, Silver Spring, MD 20993 USA.
EM william.maisel@fda.hhs.gov
NR 1
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-8798
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD JUL
PY 2012
VL 5
IS 7
BP 797
EP 798
DI 10.1016/j.jcin.2012.06.002
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 979QZ
UT WOS:000306836200014
PM 22814786
ER
PT J
AU Maldonado, PD
Perez-De La Cruz, V
Torres-Ramos, M
Silva-Islas, C
Lecona-Vargas, R
Lugo-Huitron, R
Blanco-Ayala, T
Ugalde-Muniz, P
Vazquez-Cervantes, GI
Fortoul, TI
Ali, SF
Santamaria, A
AF Maldonado, Perla D.
Perez-De La Cruz, Veronica
Torres-Ramos, Monica
Silva-Islas, Carlos
Lecona-Vargas, Ramon
Lugo-Huitron, Rafael
Blanco-Ayala, Tonali
Ugalde-Muniz, Perla
Ignacio Vazquez-Cervantes, Gustavo
Fortoul, Teresa I.
Ali, Syed F.
Santamaria, Abel
TI Selenium-induced antioxidant protection recruits modulation of
thioredoxin reductase during excitotoxic/pro-oxidant events in the rat
striatum
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Article
DE Antioxidant defense; Thioredoxin reductase system; Neurotoxicity;
Oxidative stress
ID ACID-INDUCED NEUROTOXICITY; QUINOLINIC-ACID; HUNTINGTONS-DISEASE;
GLUTATHIONE-PEROXIDASE; PHYSIOLOGICAL ROLES; BRAIN SYNAPTOSOMES;
OXIDATIVE DAMAGE; ELEMENT PATHWAY; CORPUS STRIATUM; S-ALLYLCYSTEINE
AB Selenium (Se) is a crucial element exerting antioxidant and neuroprotective effects in different toxic models. It has been suggested that Se acts through selenoproteins, of which thioredoxin reductase (TrxR) is relevant for reduction of harmful hydroperoxides and maintenance of thioredoxin (Trx) redox activity. Of note, the Trx/TrxR system remains poorly studied in toxic models of degenerative disorders. Despite previous reports of our group have demonstrated a protective role of Se in the excitotoxic/pro-oxidant model induced by quinolinic acid (QUIN) in the rat striatum (Santamaria et al., 2003, 2005), the precise mechanism(s) by which Se is inducing protection remains unclear. In this work, we characterized the time course of protective events elicited by Se as pretreatment (Na2SO3, 0.625 mg/kg/day, i.p., administered for 5 consecutive days) in the toxic pattern produced by a single infusion of QUIN (240 nmol/mu l) in the rat striatum, to further explore whether TrxR is involved in the Se-induced protection and how is regulated. Se attenuated the QUIN-induced early reactive oxygen species formation, lipid peroxidation, oxidative damage to DNA, loss of mitochondrial reductive capacity and morphological alterations in the striatum. Our results also revealed a novel pattern in which QUIN transiently stimulated an early TrxR cellular localization/distribution (at 30 min and 2 h post-lesion, evidenced by immunohistochemistry), to further stimulate a delayed protein activation (at 24 h) in a manner likely representing a compensatory response to the oxidative damage in course. In turn, Se induced an early stimulation of TrxR activity and expression in a time course that "matches" with the reduction of the QUIN-induced oxidative damage, suggesting that the Trx/TrxR system contributes to the resistance of nerve tissue to QUIN toxicity. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Perez-De La Cruz, Veronica; Torres-Ramos, Monica; Lugo-Huitron, Rafael; Blanco-Ayala, Tonali; Ugalde-Muniz, Perla; Ignacio Vazquez-Cervantes, Gustavo; Santamaria, Abel] Inst Nacl Neurol & Neurocirug, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico.
[Maldonado, Perla D.; Silva-Islas, Carlos; Lecona-Vargas, Ramon] Inst Nacl Neurol & Neurocirug, Lab Patol Vasc Cerebral, Mexico City 14269, DF, Mexico.
[Fortoul, Teresa I.] Univ Nacl Autonoma Mexico, Fac Med, Dept Biol Celular & Tisular, Mexico City 04510, DF, Mexico.
[Ali, Syed F.; Santamaria, Abel] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA.
RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirug, Lab Aminoacidos Excitadores, Insurgentes 3877, Mexico City 14269, DF, Mexico.
EM absada@yahoo.com
FU Armstrong Foundation, Mexico; CONACyT [1035]
FX Authors gratefully acknowledge Elizabeth M. Serrano-Lopez and Yoselin A.
Gonzalez-Muniz for technical support. Ramon Lecona Vargas received
scholarship from Armstrong Foundation, Mexico. This work was supported
by CONACyT (Grant 1035).
NR 59
TC 8
Z9 9
U1 0
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
J9 NEUROCHEM INT
JI Neurochem. Int.
PD JUL
PY 2012
VL 61
IS 2
BP 195
EP 206
DI 10.1016/j.neuint.2012.05.004
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 991HH
UT WOS:000307691600008
PM 22579569
ER
PT J
AU Cohen, MH
Johnson, JR
Justice, R
Pazdur, R
AF Cohen, Martin H.
Johnson, John R.
Justice, Robert
Pazdur, Richard
TI Approval Summary: Imatinib Mesylate for One or Three Years in the
Adjuvant Treatment of Gastrointestinal Stromal Tumors
SO ONCOLOGIST
LA English
DT Article
DE Imatinib; Gleevec; Kit; CD117; Gastrointestinal stromal tumors
ID TRIAL
AB On January 31,2012, the U.S. Food and Drug Administration granted regular approval of imatinib mesylate tablets (Gleevec (R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumors (GISTs). The recommended dose of imatinib is 400 mg/day administered daily for 3 years.
Three hundred ninety-seven patients were enrolled in a randomized adjuvant, multicenter, open label, phase III trial comparing 12 months with 36 months of imatinib treatment. Eligible patients had one of the following: tumor diameter > 5 cm and mitotic count > 5 per 50 high power fields (HPFs); tumor diameter > 10 cm and any mitotic count; tumor of any size with mitotic count > 10/50 HPFs; or tumor ruptured into the peritoneal cavity. The primary endpoint was the recurrence-free survival (RFS) interval.
The median follow-up for patients without an RFS event was 42 months. There were 84 (42%) RFS events in the 12-month treatment arm and 50 (25%) RFS events in the 36-month treatment arm. Thirty-six months of imatinib treatment led to a significantly longer RFS interval than with 12 months of treatment.
The median follow-up for overall survival (OS) evaluation in patients still living was 48 months. Thirty-six months of imatinib treatment led to a significantly longer OS time than with 12 months of imatinib treatment.
The most common adverse reactions, as noted in previous imatinib studies, were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. The Oncologist 2012;17:992-997
C1 [Cohen, Martin H.; Johnson, John R.; Justice, Robert; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Cohen, MH (reprint author), US FDA, Off Hematol & Oncol 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 8
TC 1
Z9 1
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
PD JUL
PY 2012
VL 17
IS 7
BP 992
EP 997
DI 10.1634/theoncologist.2012-0109
PG 6
WC Oncology
SC Oncology
GA 979LL
UT WOS:000306821400017
PM 22643537
ER
PT J
AU Laskey, W
Awad, K
Lum, J
Skodacek, K
Zimmerman, B
Selzman, K
Zuckerman, B
AF Laskey, Warren
Awad, Khaled
Lum, Jeremy
Skodacek, Ken
Zimmerman, Barbara
Selzman, Kimberly
Zuckerman, Bram
TI An Analysis of Implantable Cardiac Device Reliability. The Case for
Improved Postmarketing Risk Assessment and Surveillance
SO AMERICAN JOURNAL OF THERAPEUTICS
LA English
DT Article
DE implantable cardiac devices; device reliability
ID CHRONIC HEART-FAILURE; CARDIOVERTER-DEFIBRILLATOR; RESYNCHRONIZATION
THERAPY; CARDIOVASCULAR DEVICES; UNITED-STATES; PACEMAKER; GUIDELINES;
INFECTION; APPROVAL; REGISTRY
AB Implantable cardiac devices have become the mainstay of the treatment of patients with heart disease. However, data regarding their reliability and, inferentially, safety have been called into question. We reviewed annual reports submitted to the Food and Drug Administration Office of Device Evaluation by device manufacturers from 2003 to 2007. The annual number of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillator (CRT-D) implants, explants, and returned devices were tabulated along with the cumulative (Cum) number of implants for each device. We derived an annual explantation rate (AER) defined as the ratio of the annual number of explants less the number of normal battery depletions/Cum (x1000). From 2003 to 2007, 256,392 CRT-D and 459,300 ICD devices were implanted in the United States. The overall mean (+/-SD) AERs for ICD and CRT-D devices were, respectively, 49.5 (15.6) per 1000 ICD devices and 82.6 (35.5) per 1000 CRT-D devices. The AER for each device type significantly decreased over the study period (P for trend <0.001) although the AER for CRT-D devices was 38% higher than that for ICD devices (P < 0.001). On average, 20.3% of CRT-D devices and 22.6% of ICD devices were returned to the manufacturer for analysis after explantation. The rates of explanted CRT-D and ICD devices decreased from 2003 to 2007. Notwithstanding this favorable trend, the AER for CRT-D devices was higher than that for ICD devices. Improved methods for tracking individual device histories are needed for more precise estimates of the risk of device explantation for suspected malfunction. The proportion of devices returned to the manufacturer is suboptimal and needs to be improved to better understand the mechanisms of device malfunction.
C1 [Laskey, Warren; Awad, Khaled; Lum, Jeremy] Univ New Mexico, Sch Med, Div Cardiol, Dept Internal Med, Albuquerque, NM 87131 USA.
[Skodacek, Ken; Zimmerman, Barbara; Selzman, Kimberly; Zuckerman, Bram] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Laskey, W (reprint author), MSC10-5550,1 Univ New Mexico, Albuquerque, NM 87131 USA.
EM wlaskey@salud.unm.edu
FU Robert Flinn Foundation for Cardiovascular Medicine
FX W.L. received a grant from Robert Flinn Foundation for Cardiovascular
Medicine and has no conflicts of interest to disclose. The other authors
have no funding or conflicts of interest to disclose.
NR 32
TC 5
Z9 5
U1 0
U2 3
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 JUL
PY 2012
VL 19
IS 4
BP 248
EP 254
DI 10.1097/MJT.0b013e3182512ca5
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 976EN
UT WOS:000306563700008
PM 22668602
ER
PT J
AU Jones, JL
Ludeke, CHM
Bowers, JC
Garrett, N
Fischer, M
Parsons, MB
Bopp, CA
DePaola, A
AF Jones, Jessica L.
Luedeke, Catharina H. M.
Bowers, John C.
Garrett, Nancy
Fischer, Markus
Parsons, Michele B.
Bopp, Cheryl A.
DePaola, Angelo
TI Biochemical, Serological, and Virulence Characterization of Clinical and
Oyster Vibrio parahaemolyticus Isolates
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID THERMOSTABLE DIRECT HEMOLYSIN; GULF-OF-MEXICO; III SECRETION SYSTEMS;
UNITED-STATES; PACIFIC-NORTHWEST; TRH GENE; STRAINS; IDENTIFICATION;
PATHOGENICITY; CYTOTOXICITY
AB In this study, 77 clinical and 67 oyster Vibrio parahaemolyticus isolates from North America were examined for biochemical profiles, serotype, and the presence of potential virulence factors (tdh, trh, and type III secretion system [T3SS] genes). All isolates were positive for oxidase, indole, and glucose fermentation, consistent with previous reports. The isolates represented 35 different serotypes, 9 of which were shared by clinical and oyster isolates. Serotypes associated with pandemic strains (O1:KUT, O1:K25, O3:K6, and O4:K68) were observed for clinical isolates, and 7 (9%) oyster isolates belonged to serotype O1:KUT. Of the clinical isolates, 27% were negative for tdh and trh, while 45% contained both genes. Oyster isolates were preferentially selected for the presence of tdh and/or trh; 34% contained both genes, 42% had trh but not tdh, and 3% had tdh but not trh. All but 1 isolate (143/144) had at least three of the four T3SS1 genes examined. The isolates lacking both tdh and trh contained no T3SS2 alpha or T3SS2 beta genes. All clinical isolates positive for tdh and negative for trh possessed all T3SS2 alpha genes, and all isolates negative for tdh and positive for trh possessed all T3SS2 beta genes. The two oyster isolates containing tdh but not trh possessed all but the vopB2 gene of T3SS2 alpha, as reported previously. In contrast to the findings of previous studies, all strains examined that were positive for both tdh and trh also carried T3SS2 beta genes. This report identifies the serotype as the most distinguishing feature between clinical and oyster isolates. Our findings raise concerns about the reliability of the tdh, trh, and T3SS genes as virulence markers and highlight the need for more-detailed pathogenicity investigations of V. parahaemolyticus.
C1 [Jones, Jessica L.; Luedeke, Catharina H. M.; DePaola, Angelo] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL USA.
[Luedeke, Catharina H. M.; Fischer, Markus] Univ Hamburg, Dept Food Chem, Hamburg, Germany.
[Bowers, John C.] US FDA, Ctr Food Safety & Nutr, Div Math, College Pk, MD USA.
[Garrett, Nancy; Parsons, Michele B.; Bopp, Cheryl A.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Jones, JL (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL USA.
EM Jessica.Jones@fda.hhs.gov
RI Fischer, Markus/G-9477-2012
NR 40
TC 52
Z9 54
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD JUL
PY 2012
VL 50
IS 7
BP 2343
EP 2352
DI 10.1128/JCM.00196-12
PG 10
WC Microbiology
SC Microbiology
GA 986RB
UT WOS:000307360800028
PM 22535979
ER
PT J
AU Li, D
Mattoo, P
Keller, JE
AF Li, D.
Mattoo, P.
Keller, J. E.
TI New equine antitoxins to botulinum neurotoxins serotypes A and B
SO BIOLOGICALS
LA English
DT Article
DE Botulinum; Antitoxin; Equine; Botulism; BoNT/A; BoNT/B; Mouse;
Neutralization
ID CLOSTRIDIUM-BOTULINUM; INTERNATIONAL STANDARDS; NEUTRALIZING ANTIBODIES;
DIPHTHERIA-TOXIN; IMMUNE-RESPONSE; VACCINATION; VACCINES; BACILLUS;
ASSAY
AB Hyperimmune monovalent antitoxins to botulinum neurotoxin serotypes A and B have been produced by immunizing horses with newly developed formalin toxoids. After primary immunization, horses developed acceptable prophylactic antibody titers (1-5 IU/mL). Three horses received additional toxoid booster injections to induce hyperimmune antibody titers with antitoxin-A and antitoxin-B titers reaching peaks of approximately 2000 IU/mL and 150-625 IU/mL, respectively. Titers were quantified throughout the process by antigen-capture ELISA and by in-vivo neutralization. ELISA titers and neutralization titers correlated (R-2 similar to 0.62-0.92), however, unique correlations between in-vitro and in-vivo titers were observed for each horse. Monovalent antitoxin pools were made by combining plasma that had been collected twice via plasmaphoresis several months after primary immunization. Neutralizing units were established for each pool relative to the current US and WHO reference standards. Titers were determined at the L+/10 and L+/40 toxin dose for Toxin types A and B. respectively, and U.S. and international units were assigned to each monovalent antitoxin. Avidity of the new Anti-A pool was equivalent to the WHO Anti-A reference at the L+, L+/10 and L+/30 dose. Each monovalent plasma pool failed to cross-neutralize other botulinum neurotoxin serotypes indicating a high degree of specificity of each antitoxin for the toxin serotype used during immunization. Published by Elsevier Ltd on behalf of The International Alliance for Biological Standardization.
C1 [Li, D.; Mattoo, P.; Keller, J. E.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20892 USA.
RP Keller, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20892 USA.
EM james.keller@fda.hhs.gov
FU CBER/FDA-NIAID/NIH [YI-AI-6153-01]; BARDA/HHS; CBER/FDA
FX This work was supported in part by CBER/FDA-NIAID/NIH Interagency
Agreement YI-AI-6153-01 and by an Interagency Agreement between
BARDA/HHS and CBER/FDA.
NR 37
TC 3
Z9 3
U1 2
U2 16
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 JUL
PY 2012
VL 40
IS 4
BP 240
EP 246
DI 10.1016/j.biologicals.2012.03.004
PG 7
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 979KW
UT WOS:000306819900003
PM 22560800
ER
PT J
AU Wahab, RA
Choi, M
Liu, YB
Krauthamer, V
Zderic, V
Myers, MR
AF Wahab, Radia Abdul
Choi, Mina
Liu, Yunbo
Krauthamer, Victor
Zderic, Vesna
Myers, Matthew R.
TI Mechanical bioeffects of pulsed high intensity focused ultrasound on a
simple neural model
SO MEDICAL PHYSICS
LA English
DT Article
DE nerve; traumatic brain injury; ultrasound bioeffects; HIFU
ID SQUID GIANT-AXON; PERIPHERAL-NERVES; CONDUCTION; INJURY; BRAIN
AB Purpose: To study how pressure pulses affect nerves through mechanisms that are neither thermal nor cavitational, and investigate how the effects are related to cumulative radiation-force impulse (CRFI). Applications include traumatic brain injury and acoustic neuromodulation.
Methods: A simple neural model consisting of the giant axon of a live earthworm was exposed to trains of pressure pulses produced by an 825 kHz focused ultrasound transducer. The peak negative pressure of the pulses and duty cycle of the pulse train were controlled so that neither cavitation nor significant temperature rise occurred. The amplitude and conduction velocity of action-potentials triggered in the worm were measured as the magnitude of the pulses and number of pulses in the pulse trains were varied.
Results: The functionality of the axons decreased when sufficient pulse energy was applied. The level of CRFI at which the observed effects occur is consistent with the lower levels of injury observed in this study relative to blast tubes. The relevant CRFI values are also comparable to CRFI values in other studies showing measureable changes in action-potential amplitudes and velocities. Plotting the measured action-potential amplitudes and conduction velocities from different experiments with widely varying exposure regimens against the single parameter of CRFI yielded values that agreed within 21% in terms of amplitude and 5% in velocity. A predictive model based on the assumption that the temporal rate of decay of action-potential amplitude and velocity is linearly proportional the radiation force experienced by the axon predicted the experimental amplitudes and conduction velocities to within about 20% agreement.
Conclusions: The functionality of axons decreased due to noncavitational mechanical effects. The radiation force, possibly by inducing changes in ion-channel permeability, appears to be a possible mechanism for explaining the observed degradation. The CRFI is also a promising parameter for quantifying neural bioeffects during exposure to pressure waves, and for predicting axon functionality. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4729712]
C1 [Wahab, Radia Abdul; Choi, Mina; Liu, Yunbo; Krauthamer, Victor; Myers, Matthew R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Wahab, Radia Abdul; Choi, Mina; Zderic, Vesna] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA.
RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM matthew.myers@fda.hhs.gov
NR 27
TC 13
Z9 13
U1 2
U2 28
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 JUL
PY 2012
VL 39
IS 7
BP 4274
EP 4283
DI 10.1118/1.4729712
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 980KV
UT WOS:000306893000025
PM 22830761
ER
PT J
AU Slavov, SH
Geesaman, EL
Pearce, BA
Schnackenberg, LK
Buzatu, DA
Wilkes, JG
Beger, RD
AF Slavov, Svetoslav H.
Geesaman, Elizabeth L.
Pearce, Bruce A.
Schnackenberg, Laura K.
Buzatu, Dan A.
Wilkes, Jon G.
Beger, Richard D.
TI C-13 NMR-Distance Matrix Descriptors: Optimal Abstract 3D Space
Granularity for Predicting Estrogen Binding
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID ARYL-HYDROCARBON RECEPTOR; RELATIONSHIP QSDAR MODELS; SPECTROMETRIC
DATA; POLYCHLORINATED DIBENZODIOXINS; CHEMICAL DESCRIPTORS; VARIABLE
SELECTION; BIPHENYLS BINDING; STEROID-BINDING; QSAR MODELS; SPECTRA
AB An improved three-dimensional quantitative spectral data activity relationship (3D-QSDAR) methodology was used to build and validate models relating the activity of 130 estrogen receptor binders to specific structural features. In 3D-QSDAR, each compound is represented by a unique fingerprint constructed from C-13 chemical shift pairs and associated interatomic distances. Grids of different granularity can be used to partition the abstract fingerprint space into congruent "bins" for which the optimal size was previously unexplored. For this purpose, the endocrine disruptor knowledge base data were used to generate 50 3D-QSDAR models with bins ranging in size from 2 ppm x 2 ppm x 0.5 angstrom to 20 ppm x 20 ppm X 2.5 angstrom, each of which was validated using 100 training/test set partitions. Best average predictivity in terms of R-test(2) was achieved at 10 ppm x 10 ppm x Z angstrom (Z = 0.5, ... , 2.5 angstrom). It was hypothesized that this optimum depends on the chemical shifts' estimation error (+/-4.13 ppm) and the precision of the calculated interatomic distances. The highest ranked bins from partial least-squares weights were found to be associated with structural features known to be essential for binding to the estrogen receptor.
C1 [Slavov, Svetoslav H.; Geesaman, Elizabeth L.; Pearce, Bruce A.; Schnackenberg, Laura K.; Buzatu, Dan A.; Wilkes, Jon G.; Beger, Richard D.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Wilkes, JG (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Wilkes@fda.hhs.gov; Richard.Beger@fda.hhs.gov
NR 49
TC 8
Z9 8
U1 0
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD JUL
PY 2012
VL 52
IS 7
BP 1854
EP 1864
DI 10.1021/ci3001698
PG 11
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA 976VA
UT WOS:000306613900015
PM 22681591
ER
PT J
AU Whittlesey, KJ
Witten, C
AF Whittlesey, Kevin J.
Witten, Celia
TI US FDA outreach to the regenerative medicine community: challenges and
opportunities
SO REGENERATIVE MEDICINE
LA English
DT Article
DE regulation; tissue engineering; US FDA
ID STEM-CELL; DEFINITION; PRODUCTS; FOOD
AB Advances in the field of regenerative medicine have yielded novel approaches to developing treatments for currently unmet medical needs. The regenerative medicine field is diverse, spanning many research and clinical disciplines; no single society or organization fully represents regenerative medicine. The US FDA maintains an active dialog with a variety of stakeholders to keep abreast of the latest available science, to anticipate regulatory challenges posed by the latest scientific developments and to educate stakeholders about regulatory expectations for product development. The diversity of stakeholders in this field makes this dialog challenging. This article provides an overview of some of the FDA's current outreach activities in this area. The FDA welcomes opportunities to enhance its interactions with the regenerative medicine community.
C1 [Whittlesey, Kevin J.] Calif Inst Regenerat Med, San Francisco, CA 94107 USA.
[Witten, Celia] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP Whittlesey, KJ (reprint author), Calif Inst Regenerat Med, 210 King St, San Francisco, CA 94107 USA.
EM kwhittlesey@cirm.ca.gov
NR 26
TC 0
Z9 0
U1 0
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0751
J9 REGEN MED
JI Regen. Med.
PD JUL
PY 2012
VL 7
IS 4
BP 595
EP 603
DI 10.2217/RME.12.36
PG 9
WC Cell & Tissue Engineering; Engineering, Biomedical
SC Cell Biology; Engineering
GA 977QJ
UT WOS:000306679200019
PM 22817631
ER
PT J
AU Pariser, A
Bauer, L
AF Pariser, Anne
Bauer, Larry
TI FDA's Flexibility in the Approval of Orphan Drugs
SO DRUG INFORMATION JOURNAL
LA English
DT Letter
C1 [Pariser, Anne; Bauer, Larry] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rare Dis Program, Silver Spring, MD 20993 USA.
RP Pariser, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rare Dis Program, 10903 New Hampshire Ave,WO22-6466, Silver Spring, MD 20993 USA.
EM anne.pariser@fda.hhs.gov
NR 4
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.
PD JUL
PY 2012
VL 46
IS 4
BP 404
EP 404
DI 10.1177/0092861512447188
PG 1
WC Health Care Sciences & Services; Pharmacology & Pharmacy
SC Health Care Sciences & Services; Pharmacology & Pharmacy
GA 969HD
UT WOS:000306045400004
ER
PT J
AU Mitchell, D
Paniker, L
Godar, D
AF Mitchell, David
Paniker, Lakshmi
Godar, Dianne
TI Nucleotide Excision Repair Is Reduced in Oral Epithelial Tissues
Compared with Skin
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID DNA-REPAIR; ALLERGIC RHINITIS; EXCIMER-LASER; NASAL-MUCOSA; CANCER; P53;
PHOTOTHERAPY; SUNLIGHT; PROTEIN; CELLS
AB Ultraviolet radiation (UVR) exposure to internal tissues for diagnostic, therapeutic and cosmetic procedures has increased dramatically over the past decade. The greatest increase in UVR exposure of internal tissues occurs in the cosmetic industry where it is combined with oxidizing agents for teeth whitening, often in conjunction with indoor tanning. To address potential carcinogenic risks of these procedures, we analyzed the formation and repair of the DNA photoproducts associated with the signature mutations of UVR. Radioimmunoassay was used to quantify the induction and repair of cyclobutane pyrimidine dimers and pyrimidine(6-4)pyrimidone photoproducts in DNA purified from three reconstructed tissues, EpiDermTM, EpiGingivalTM and EpiOralTM. We observed comparable levels of DNA damage in all tissues immediately after UVR exposure. In contrast, repair was significantly reduced in both oral tissues compared with EpiDermTM. Our data suggest that UVR exposure of oral tissues can result in accumulation of DNA damage and increase the risk for carcinoma and melanoma of the mouth. Because NER is a broad-spectrum defense against DNA damage caused by a variety of agents in addition to UVR, our data suggest that the relatively low NER efficiency observed in oral tissues may have wide-ranging consequences in this highly exposed environment.
C1 [Mitchell, David; Paniker, Lakshmi] Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA.
[Godar, Dianne] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Mitchell, D (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA.
EM dmitchel@mdanderson.org
OI GODAR, DIANNE/0000-0002-7690-5223
FU National Cancer Institute [CA113671]; National Institute of
Environmental Health Sciences [ES007784]; Food and Drug Administration's
Critical Path Initiative
FX This work was supported by the National Cancer Institute (grant
CA113671), the National Institute of Environmental Health Sciences
(center grant ES007784) and the Food and Drug Administration's Critical
Path Initiative. The authors would like to thank Robert James for
dosimetry of the UVB source and Joshua Pfefer for helpful scientific
discussions.
NR 38
TC 7
Z9 7
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD JUL-AUG
PY 2012
VL 88
IS 4
BP 1027
EP 1032
DI 10.1111/j.1751-1097.2012.01163.x
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 971CF
UT WOS:000306179900037
PM 22519509
ER
PT J
AU Sun, Y
Laird, DT
Shieh, YC
AF Sun, Y.
Laird, D. T.
Shieh, Y. C.
TI Temperature-Dependent Survival of Hepatitis A Virus during Storage of
Contaminated Onions
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID UNITED-STATES; MOLECULAR EPIDEMIOLOGY; MULTISTATE OUTBREAK; POLIOVIRUS
TYPE-1; RELATIVE-HUMIDITY; FRESH PRODUCE; GREEN ONIONS; MIXED HUMAN;
PERSISTENCE; PATHOGENS
AB Pre- or postharvest contamination of green onions by hepatitis A virus (HAV) has been linked to large numbers of food-borne illnesses. Understanding HAV survival in onions would assist in projecting the risk of the disease associated with their consumption. This study defined HAV inactivation rates in contaminated green onions contained in air-permeable, moisture-retaining high-density polyethylene packages that were stored at 3, 10, 14, 20, 21, 22, and 23 degrees C. A protocol was established to recover HAV from whole green onions, with 31% as the average recovery by infectivity assay. Viruses in eluates were primarily analyzed by a 6-well plaque assay on FRhK-4 cells. Eight storage trials, including two trials at 3 degrees C, were conducted, with 3 to 7 onion samples per sampling and 4 to 7 samplings per trial. Linear regression correlation (r(2) = 0.80 to 0.98) was observed between HAV survival and storage time for each of the 8 trials, held at specific temperatures. Increases in the storage temperature resulted in greater HAV inactivation rates, e.g., a reduction of 0.033 log PFU/day at 3.4 +/- 0.3 degrees C versus 0.185 log PFU/day at 23.4 +/- 0.7 degrees C. Thus, decimal reduction time (D) values of 30, 14, 11, and 5 days, respectively, were obtained for HAV in onions stored at 3, 10, 14, and 23 degrees C. Further regression analysis determined that 1 degree Celsius increase would increase inactivation of HAV by 0.007 log PFU/day in onions (r(2) = 0.97). The data suggest that natural degradation of HAV in contaminated fresh produce is minimal and that a preventive strategy is critical to produce safety. The results are useful in predicting the risks associated with HAV contamination in fresh produce.
C1 [Sun, Y.; Laird, D. T.; Shieh, Y. C.] US FDA, Div Food Proc Sci & Technol, Inst Food Safety & Hlth, Bedford Pk, IL USA.
RP Shieh, YC (reprint author), US FDA, Div Food Proc Sci & Technol, Inst Food Safety & Hlth, Bedford Pk, IL USA.
EM carol.shieh@fda.hhs.gov
FU U.S. Food and Drug Administration; Oak Ridge Institute for Science and
Education
FX This research was financially supported by the U.S. Food and Drug
Administration, with personnel contracted by the Oak Ridge Institute for
Science and Education.
NR 27
TC 12
Z9 12
U1 0
U2 11
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 JUL
PY 2012
VL 78
IS 14
BP 4976
EP 4983
DI 10.1128/AEM.00402-12
PG 8
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 969ZT
UT WOS:000306098600025
PM 22544253
ER
PT J
AU Lalmansingh, AS
Karmakar, S
Jin, YT
Nagaich, AK
AF Lalmansingh, Avin S.
Karmakar, Sudipan
Jin, Yetao
Nagaich, Akhilesh K.
TI Multiple modes of chromatin remodeling by Forkhead box proteins
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Forkhead box protein; Chromatin remodeling; FOXA1; FOXP3; FOXO1; Pioneer
factor
ID FOXO TRANSCRIPTION FACTORS; REGULATORY T-CELLS; NF-KAPPA-B; DNA-BINDING;
CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; HISTONE H5; GENE-EXPRESSION; NUCLEAR
FACTOR; FACTOR AFX
AB Forkhead box (FOX) proteins represent a large family of transcriptional regulators unified by their DNA binding domain (DBD) known as a 'forkhead' or 'winged helix' domain. Over 40 FOX genes have been identified in the mammalian genome. FOX proteins share significant sequence similarities in the DBD which allow them to bind to a consensus DNA response element. However, their modes of action are quite diverse as they regulate gene expression by acting as pioneer factors, transcription factors, or both. This review focuses on the mechanisms of chromatin remodeling with an emphasis on three sub-classes-FOXA. FOXO, and FOXP members. FOXA proteins serve as pioneer factors to open up local chromatin structure and thereby increase accessibility of chromatin to factors regulating transcription. FOXP proteins, in contrast, function as classic transcription factors to recruit a variety of chromatin modifying enzymes to regulate gene expression. FOXO proteins represent a hybrid subclass having dual roles as pioneering factors and transcription factors. A subset of FOX proteins interacts with condensed mitotic chromatin and may function as 'bookmarking' agents to maintain transcriptional competence at specific genomic sites. The overall diversity in chromatin remodeling function by FOX proteins is related to unique structural motifs present within the DBD flanking regions that govern selective interactions with core histones and/or chromatin coregulatory proteins. This article is part of a Special Issue entitled: Chromatin in time and space. Published by Elsevier B.V.
C1 [Lalmansingh, Avin S.; Karmakar, Sudipan; Jin, Yetao; Nagaich, Akhilesh K.] US FDA, Div Therapeut Prot, OBP, OPS,CDER, Bethesda, MD 20892 USA.
RP Nagaich, AK (reprint author), US FDA, Div Therapeut Prot, OBP, OPS,CDER, 29 Lincoln Dr, Bethesda, MD 20892 USA.
EM akhilesh.nagaich@fda.hhs.gov
FU CDER-Oak Ridge Institute for Science and Education (ORISE); FDA
FX We would like to thank Dr. Kamalpreet Arora for critical reading of the
manuscript. We would also like to thank Dr. Difei Wang for generating
the crystallography images. This project was supported in part by a
CDER-Oak Ridge Institute for Science and Education (ORISE) Fellowship to
A.S.L. and a FDA Commissioner's Fellowship to S.K.
NR 103
TC 40
Z9 42
U1 3
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD JUL
PY 2012
VL 1819
IS 7
SI SI
BP 707
EP 715
DI 10.1016/j.bbagrm.2012.02.018
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 972GK
UT WOS:000306265100013
PM 22406422
ER
PT J
AU Mei, N
Zhang, YB
Chen, Y
Guo, XQ
Ding, W
Ali, SF
Biris, AS
Rice, P
Moore, MM
Chen, T
AF Mei, Nan
Zhang, Yongbin
Chen, Ying
Guo, Xiaoqing
Ding, Wei
Ali, Syed F.
Biris, Alexandru S.
Rice, Penelope
Moore, Martha M.
Chen, Tao
TI Silver nanoparticle-induced mutations and oxidative stress in mouse
lymphoma cells
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE silver nanoparticles; mutant frequency; chromosomal damage; oxidative
stress; gene expression
ID THYMIDINE KINASE GENE; IN-VITRO; INTERNATIONAL WORKSHOP; GENOTOXICITY;
ASSAY; TOXICITY; MUTAGENICITY; CYTOTOXICITY; NANOSILVER;
PHOTOMUTAGENICITY
AB Silver nanoparticles (Ag-NPs) have increasingly been used for coatings on various textiles and certain implants, for the treatment of wounds and burns, as a water disinfectant, and in air-freshener sprays. The wide use of Ag-NPs may have potential human health impacts. In this study, the mutagenicity of 5-nm Ag-NPs was evaluated in the mouse lymphoma assay system, and modes of action were assessed using standard alkaline and enzyme-modified Comet assays and gene expression analysis. Treatments of L5178Y/Tk+/- mouse lymphoma cells with 5-nm uncoated Ag-NPs resulted in a significant yield of mutants at doses between 3 and 6 mu g/mL; the upper range was limited by toxicity. Loss of heterozygosity analysis of the Tk mutants revealed that treatments with uncoated Ag-NPs induced mainly chromosomal alterations spanning less than 34 megabase pairs on chromosome 11. Although no significant induction of DNA damage in Ag-NP-treated mouse lymphoma cells was observed in the standard Comet assay, the Ag-NP treatments induced a dose-responsive increase in oxidative DNA damage in the enzyme-modified Comet assay in which oxidative lesion-specific endonucleases were added. Gene expression analysis using an oxidative stress and antioxidant defense polymerase chain reaction (PCR) array showed that the expressions of 17 of the 59 genes on the arrays were altered in the cells treated with Ag-NPs. These genes are involved in production of reactive oxygen species, oxidative stress response, antioxidants, oxygen transporters, and DNA repair. These results suggest that 5 nm Ag-NPs are mutagenic in mouse lymphoma cells due to induction of oxidative stress by the Ag-NPs. Environ. Mol. Mutagen. 2012. (c) 2012Wiley Periodicals, Inc.
C1 [Mei, Nan; Chen, Ying; Guo, Xiaoqing; Ding, Wei; Moore, Martha M.; Chen, Tao] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA.
[Zhang, Yongbin] Natl Ctr Toxicol Res, Nanotechnol Core Facil, Jefferson, AR 72079 USA.
[Ali, Syed F.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA.
[Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA.
[Rice, Penelope] Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA.
EM tao.chen@fda.hhs.gov
RI Ding, Wei/L-1503-2014; mei, nan/E-8915-2011
OI mei, nan/0000-0002-3501-9014
NR 47
TC 42
Z9 43
U1 2
U2 40
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUL
PY 2012
VL 53
IS 6
BP 409
EP 419
DI 10.1002/em.21698
PG 11
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 970NK
UT WOS:000306137600001
PM 22576574
ER
PT J
AU Dobrovolsky, VN
Heflich, RH
Ferguson, SA
AF Dobrovolsky, Vasily N.
Heflich, Robert H.
Ferguson, Sherry A.
TI The frequency of Pig-a mutant red blood cells in rats exposed in utero
to N-ethyl-N-nitrosourea
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE mutagenicity; prenatal; neonatal; flow cytometry; GPI anchor; CD59
ID GENE MUTATION ASSAY; FLOW-CYTOMETRIC DETECTION; HEMATOPOIETIC
STEM-CELLS; BONE-MARROW ERYTHROIDS; PERIPHERAL-BLOOD; MICE;
MANIFESTATION; ERYTHROCYTES; MUTAGENICITY; PERSISTENCE
AB The Pig-a assay has been developed as a rapid sensitive measure of gene mutation in adult rats; however, no data exist on its ability to detect mutation following in utero exposures or in neonatal animals. Pregnant Sprague-Dawley rats were treated daily on gestational days 1218 with oral doses of 0, 6, or 12 mg/kg/day N-ethyl-N-nitrosourea (ENU); following parturition, the offspring and dams were monitored over a period of 5 months for the frequency of CD59-deficient erythrocytes as a marker of Pig-a mutation. Significant dose-related increases in Pig-a mutant red blood cells (RBCs) were observed in ENU-treated dams. However, only very weak increases in RBC Pig-a mutant frequency (MF) were noted in offspring treated in utero with the lower ENU dose. The higher ENU dose produced extremely variable responses in the offspring as a function of age, even among littermates, ranging from a steady low or moderately high Pig-a MF to a rapidly increasing or decreasing Pig-a MF. The manifestation kinetics of Pig-a mutant RBCs in the offspring suggest that the change from predominantly hepatic to predominantly bone marrow erythropoiesis that occurs during early development may have contributed to this variability. Our results indicate that using the RBC Pig-a model for mutation detection in animals treated in utero may require analysis of multiple offspring from the same litter to account for potential jack pot effects, and that detection of the earliest treatment effect (i.e., in neonates using the hepatic RBC fraction) may require optimization of blood processing. Environ. Mol. Mutagen. 2012. Published 2012 Wiley Periodicals, Inc.
C1 [Dobrovolsky, Vasily N.; Heflich, Robert H.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Ferguson, Sherry A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Dobrovolsky, VN (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA.
EM vasily.dobrovolsky@fda.hhs.gov
NR 22
TC 3
Z9 3
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUL
PY 2012
VL 53
IS 6
BP 440
EP 450
DI 10.1002/em.21704
PG 11
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 970NK
UT WOS:000306137600004
PM 22730214
ER
PT J
AU Folster, JP
Pecic, G
Singh, A
Duval, B
Rickert, R
Ayers, S
Abbott, J
McGlinchey, B
Bauer-Turpin, J
Haro, J
Hise, K
Zhao, S
Fedorka-Cray, PJ
Whichard, J
McDermott, PF
AF Folster, J. P.
Pecic, G.
Singh, A.
Duval, B.
Rickert, R.
Ayers, S.
Abbott, J.
McGlinchey, B.
Bauer-Turpin, J.
Haro, J.
Hise, K.
Zhao, S.
Fedorka-Cray, P. J.
Whichard, J.
McDermott, P. F.
TI Characterization of Extended-Spectrum Cephalosporin-Resistant Salmonella
enterica Serovar Heidelberg Isolated from Food Animals, Retail Meat, and
Humans in the United States 2009
SO FOODBORNE PATHOGENS AND DISEASE
LA English
DT Article
ID AMPC BETA-LACTAMASE; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE;
PLASMIDS; CMY-2; SUSCEPTIBILITY; POULTRY; STRAINS
AB Salmonella enterica is one of the most common causes of foodborne illness in the United States. Although salmonellosis is usually self-limiting, severe infections typically require antimicrobial treatment, and ceftriaxone, an extended-spectrum cephalosporin (ESC), is commonly used in both adults and children. Surveillance conducted by the National Antimicrobial Resistance Monitoring System (NARMS) has shown a recent increase in ESC resistance among Salmonella Heidelberg isolated from food animals at slaughter, retail meat, and humans. ESC resistance among Salmonella in the United States is usually mediated by a plasmid-encoded bla(CMY) beta-lactamase. In 2009, we identified 47 ESC-resistant bla(CMY)-positive Heidelberg isolates from humans (n = 18), food animals at slaughter (n = 16), and retail meats (n = 13) associated with a spike in the prevalence of this serovar. Almost 90% (26/29) of the animal and meat isolates were isolated from chicken carcasses or retail chicken meat. We screened NARMS isolates for the presence of bla(CMY), determined whether the gene was plasmid-encoded, examined pulsed-field gel electrophoresis patterns to assess the genetic diversities of the isolates, and categorized the bla(CMY) plasmids by plasmid incompatibility groups and plasmid multi-locus sequence typing (pMLST). All 47 bla(CMY) genes were found to be plasmid encoded. Incompatibility/replicon typing demonstrated that 41 were IncI1 plasmids, 40 of which only conferred bla(CMY)-associated resistance. Six were IncA/C plasmids that carried additional resistance genes. pMLST of the IncI1-bla(CMY) plasmids showed that 27 (65.8%) were sequence type (ST) 12, the most common ST among bla(CMY)-IncI1 plasmids from Heidelberg isolated from humans. Ten plasmids had a new ST profile, ST66, a type very similar to ST12. This work showed that the 2009 increase in ESC resistance among Salmonella Heidelberg was caused mainly by the dissemination of bla(CMY) on IncI1 and IncA/C plasmids in a variety of genetic backgrounds, and is likely not the result of clonal expansion.
C1 [Folster, J. P.] Ctr Dis Control & Prevent, Natl Antimicrobial Resistance Monitoring Syst, OID NCEZID DFWED EDLB, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30329 USA.
[Singh, A.; Ayers, S.; Abbott, J.; Zhao, S.; McDermott, P. F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
[Folster, J. P.; Pecic, G.] IHRC, Atlanta, GA USA.
[Duval, B.; Bauer-Turpin, J.; Haro, J.; Fedorka-Cray, P. J.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, USDA, Athens, GA USA.
RP Folster, JP (reprint author), Ctr Dis Control & Prevent, Natl Antimicrobial Resistance Monitoring Syst, OID NCEZID DFWED EDLB, Div Foodborne Waterborne & Environm Dis, 1600 Clifton Rd, Atlanta, GA 30329 USA.
EM gux8@cdc.gov
FU CDC; USDA; FDA Center for Veterinary Medicine
FX We thank the NARMS participating public health laboratories for
submitting the isolates, Anne Whitney for DNA sequencing, Alessandra
Carattoli for the plasmid incompatibility typing control strains, and
Maria Karlsson for her critical review. This work was partially
supported by an interagency agreement between CDC, USDA, and the FDA
Center for Veterinary Medicine. The findings and conclusions in this
report are those of the authors and do not necessarily represent the
official position of the CDC, FDA or USDA.
NR 32
TC 24
Z9 24
U1 1
U2 15
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1535-3141
J9 FOODBORNE PATHOG DIS
JI Foodborne Pathog. Dis.
PD JUL
PY 2012
VL 9
IS 7
BP 638
EP 645
DI 10.1089/fpd.2012.1130
PG 8
WC Food Science & Technology
SC Food Science & Technology
GA 970AX
UT WOS:000306101600010
PM 22755514
ER
PT J
AU Hoelzer, K
Pouillot, R
Dennis, S
AF Hoelzer, Karin
Pouillot, Regis
Dennis, Sherri
TI Listeria monocytogenes Growth Dynamics on Produce: A Review of the
Available Data for Predictive Modeling
SO FOODBORNE PATHOGENS AND DISEASE
LA English
DT Article
ID ESCHERICHIA-COLI O157-H7; EQUILIBRIUM-MODIFIED ATMOSPHERE; ORGANIC-ACID
TREATMENT; EAT ICEBERG LETTUCE; MILD HEAT-TREATMENT; FRESH-CUT PRODUCE;
UNITED-STATES; MICROBIAL RISK; LACTIC-ACID; SALMONELLA-TYPHIMURIUM
AB Several listeriosis outbreaks have been linked to the consumption of fresh or processed produce in recent years. One major determinant of the listeriosis risk is the ability of a food to support growth of Listeria monocytogenes during storage. However, data regarding the ability to support growth of L. monocytogenes are scarce or non-existing for many produce commodities. Here we synthesize the available data regarding growth behavior of L. monocytogenes on produce, compare the growth data with listeriosis outbreak data, and evaluate the adequacy of the data for predictive modeling. Growth rates and maximum L. monocytogenes population densities differed markedly among produce commodities, and post-harvest processing had a considerable effect on growth dynamics for certain commodities such as tomatoes. However, data scarcity prevented reliable estimation of growth rates for many commodities. Produce outbreaks seemed frequently associated with processed produce and often involved storage under suboptimal conditions (e. g., at room temperature for several hours or for several months in the refrigerator) or environmental cross-contamination after processing. However, no clear associations between high growth rates of L. monocytogenes on fresh produce and outbreaks were detected. In conclusion, produce commodities differ in the supported growth rate of L. monocytogenes, the maximum attainable L. monocytogenes population density, and possibly in the impact of post-harvest processing, but data are currently insufficient to predict growth behavior, and the listeriosis risk appears to be also governed by additional factors.
C1 [Hoelzer, Karin; Pouillot, Regis; Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Hoelzer, K (reprint author), US FDA, Risk Assessment Coordinat Team, Ctr Food Safety & Appl Nutr HFS 005, 5100 Paint Branch Pkwy,Room 2A-031, College Pk, MD 20740 USA.
EM Karin.Hoelzer@fda.hhs.gov
RI Pouillot, Regis/E-8103-2010
OI Pouillot, Regis/0000-0002-6107-5212
FU Center for Food Safety and Applied Nutrition
FX This work was supported in part by appointments to the Research
Participation Program at the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration.
NR 111
TC 12
Z9 16
U1 5
U2 39
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1535-3141
J9 FOODBORNE PATHOG DIS
JI Foodborne Pathog. Dis.
PD JUL
PY 2012
VL 9
IS 7
BP 661
EP 673
DI 10.1089/fpd.2011.1087
PG 13
WC Food Science & Technology
SC Food Science & Technology
GA 970AX
UT WOS:000306101600013
PM 22612229
ER
PT J
AU Reiman, EM
Brinton, RD
Katz, R
Petersen, RC
Negash, S
Mungas, D
Aisen, PS
AF Reiman, Eric M.
Brinton, Roberta Diaz
Katz, Russell
Petersen, Ronald C.
Negash, Selam
Mungas, Dan
Aisen, Paul S.
TI Considerations in the Design of Clinical Trials for Cognitive Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Cognition; Clinical trials; Aging
ID ALZHEIMERS-DISEASE; BRAIN; BIOMARKERS; METABOLISM; MEMORY
AB What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging.
C1 [Reiman, Eric M.] Univ Arizona, Banner Alzheimers Inst, Translat Genom Res Inst, Coll Med, Phoenix, AZ 85006 USA.
[Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA.
[Brinton, Roberta Diaz] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA USA.
[Brinton, Roberta Diaz] Univ So Calif, Dept Neurol, USC Keck Sch Med, Los Angeles, CA USA.
[Katz, Russell] US FDA, Div Neurol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA.
[Petersen, Ronald C.] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA.
[Petersen, Ronald C.] Mayo Clin, Alzheimers Dis Res Ctr, Rochester, MN USA.
[Negash, Selam] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Mungas, Dan] Univ Calif Davis, Dept Neurol, Sch Med, Sacramento, CA 95817 USA.
[Aisen, Paul S.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
RP Reiman, EM (reprint author), Univ Arizona, Banner Alzheimers Inst, Translat Genom Res Inst, Coll Med, 901 E Willetta St, Phoenix, AZ 85006 USA.
EM eric.reiman@bannerhealth.com
OI Negash, Selam/0000-0001-7150-7181
FU National Institute on Aging (NIA) [R01 AG031581, P30 AG19610, UO1
AGOO6786, P50 AGO16574]
FX The authors' contributions were supported by the following grants:
National Institute on Aging (NIA) grants R01 AG031581 and P30 AG19610 to
E. M. R.; NIA grants UO1 AGOO6786 and P50 AGO16574 to R.C.P.
NR 20
TC 7
Z9 7
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2012
VL 67
IS 7
BP 766
EP 772
DI 10.1093/gerona/gls124
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 970PD
UT WOS:000306143700010
PM 22573913
ER
PT J
AU Buchen, SY
Calogero, D
Hilmantel, G
Eydelman, MB
AF Buchen, Shelley Y.
Calogero, Don
Hilmantel, Gene
Eydelman, Malvina B.
TI Detecting Endotoxin Contamination of Ophthalmic Viscosurgical Devices
SO OPHTHALMOLOGY
LA English
DT Article
ID OCULAR INFLAMMATORY RESPONSE; INDUCED UVEITIS
AB Objective: To compare the sensitivities of intracameral and intravitreal assays in the rabbit model to determine the relative adequacy of these methods in detecting bacterial endotoxin contamination of ophthalmic viscosurgical devices (OVDs).
Design: Experimental, randomized animal study.
Participants: Twenty New Zealand white rabbits.
Methods: Rabbits were randomized into 4 groups to receive a cohesive or a dispersive OVD via intracameral or intravitreal injection. All 40 treated eyes (10 eyes of 5 animals in each group) received bilateral injection of OVD spiked with bacterial endotoxin at 7.0 endotoxin units/ml. All eyes were evaluated by slit-lamp biomicroscopy for inflammatory response at 3, 6, 9, 24, 48, and 72 hours after exposure. Eyes that received intravitreal injection were also dilated at 24, 48, and 72 hours and were re-examined by slit-lamp biomicroscopy and by indirect ophthalmoscopy.
Main Outcome Measures: Conjunctival inflammation, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, iridal hyperemia, corneal clouding, lens opacities, and onset times.
Results: Intracamerally injected eyes frequently showed conjunctival congestion, AC cells and flare, iridal hyperemia, and fibrin within 6 hours. Up to 80% showed AC cells and flare at 9 hours, and up to 70% showed fibrin at 24 hours. These signs diminished within 48 hours. Fibrin and cells also were seen on the lens surface of most of the eyes. Intravitreally injected eyes showed no signs of inflammation within 24 hours, other than some conjunctival inflammation. After the 24-hour time point, in addition to some conjunctival inflammation, some other signs of inflammation were observed infrequently in the intravitreally injected eyes, including minor vitreous cell reaction in 2 eyes. Although there was 1 dispersive OVD-treated eye with cells and fibrin on the lens capsule at 48 hours, no aqueous cells or flare were seen in the AC of any intravitreally injected eyes at any time during the course of the study.
Conclusions: The rabbit intravitreal assay, when limited to 72 hours, does not seem to have adequate sensitivity to detect endotoxin reliably in OVDs.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e11-e18 (C) 2012 by the American Academy of Ophthalmology.
C1 [Calogero, Don; Hilmantel, Gene; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD 20993 USA.
[Buchen, Shelley Y.] US FDA, ORISE, Silver Spring, MD 20993 USA.
RP Eydelman, MB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Dept Ophthalmol Neurol & ENT Devices, 10903 New Hampshire Ave,WO 66-2410, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU The Food and Drug Administration, Silver Spring, Maryland
FX The Food and Drug Administration, Silver Spring, Maryland, funded this
work. Food and Drug Administration personnel participated in the design
of the study, conducting the study, data collection, data management,
data analysis, interpretation of the data, preparation and review of the
manuscript. The mention of commercial products, their sources, or their
use in connection with material reported herein is not to be construed
as either an actual or implied endorsement of such products by
Department of Health and Human Services (DHHS).
NR 15
TC 6
Z9 6
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E11
EP E18
DI 10.1016/j.ophtha.2012.04.005
PG 8
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000002
PM 22578451
ER
PT J
AU Buchen, SY
Calogero, D
Tarver, ME
Hilmantel, G
Tang, X
Eydelman, MB
AF Buchen, Shelley Y.
Calogero, Don
Tarver, Michelle E.
Hilmantel, Gene
Tang, Xing
Eydelman, Malvina B.
TI Evaluation of Intraocular Reactivity to Organic Contaminants of
Ophthalmic Devices in a Rabbit Model
SO OPHTHALMOLOGY
LA English
DT Article
ID ANTERIOR SEGMENT SYNDROME; POTENTIAL CAUSE; UVEITIS; DEBRIS
AB Objective: To evaluate the intraocular reactivity to organic contaminants of ophthalmic devices in the rabbit.
Design: Experimental animal study.
Participants: Fifty New Zealand white rabbits.
Methods: The rabbits were allocated to 10 groups of 5 each to receive 2 different doses of human albumin and nonhuman nucleic acids and their respective vehicle controls, a denatured cohesive ophthalmic viscosurgical device (OVD) and a denatured dispersive OVD and their respective nondenatured controls. All 10 eyes in each treatment group received bilateral intracameral injection of the test materials. All the eyes in the study were examined by slit-lamp biomicroscopy at baseline and 6, 9, 24, 48, and 72 hours. Pachymetry was also performed on eyes exposed to albumin, protein vehicle control, and the OVDs at these time points.
Main Outcome Measures: Corneal thickness, grade of corneal clouding, anterior chamber (AC), cells, flare and fibrin, iridal hyperemia, cell and fibrin on lens surface, and onset time.
Results: There were no inflammatory signs in any eyes exposed to human albumin. Anterior chamber cells (1+ to 3+) and flare and fibrin (1+ to 2+), along with cells and fibrin on the lens surface, were seen in the eyes exposed to the nucleic acid samples, and they resolved in 24 hours. Mild (mostly 1+) conjunctival congestion, cells, flare, and fibrin were seen in a few eyes exposed to the 2 denatured OVDs and their controls, with the response durations being shorter in the denatured OVD eyes (24 hours) than in the nondenatured OVD eyes (48 hours). Anterior chamber inflammation was generally observed in fewer denatured OVD eyes than in nondenatured OVD eyes, particularly the dispersive OVD eyes.
Conclusions: Intracameral injection of human albumin protein did not cause ocular inflammation. Nucleic acid intracamerally injected into rabbit eyes caused acute inflammation that quickly resolved. Cohesive and dispersive OVD denatured by drying and steam sterilization alone did not cause ocular inflammation.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e24-e29 (C) 2012 by the American Academy of Ophthalmology.
C1 [Buchen, Shelley Y.] US FDA, Oak Ridge Inst Sci & Educ, Silver Spring, MD USA.
[Calogero, Don; Tarver, Michelle E.; Hilmantel, Gene; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD USA.
[Tang, Xing] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, Silver Spring, MD USA.
RP Eydelman, MB (reprint author), WO 66-2410,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU FDA (Silver Spring, MD)
FX The FDA (Silver Spring, MD) funded this work. The FDA personnel
participated in designing and conducting the study; collecting,
managing, analyzing, and interpreting data; and preparing and reviewing
the manuscript.
NR 15
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 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E24
EP E29
DI 10.1016/j.ophtha.2012.04.007
PG 6
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000004
PM 22578449
ER
PT J
AU Buchen, SY
Calogero, D
Hilmantel, G
Eydelman, MB
AF Buchen, Shelley Y.
Calogero, Don
Hilmantel, Gene
Eydelman, Malvina B.
TI Rabbit Ocular Reactivity to Bacterial Endotoxin Contained in Aqueous
Solution and Ophthalmic Viscosurgical Devices
SO OPHTHALMOLOGY
LA English
DT Article
ID ANTERIOR SEGMENT SYNDROME; DRUG-DELIVERY; CHAMBER; HUMOR; FLOW;
INFLAMMATION
AB Objective: To describe the ocular reactivity of the rabbit to bacterial endotoxin contained in an aqueous medium and in a cohesive and a dispersive ophthalmic viscosurgical device (OVD).
Design: Experimental, randomized animal study.
Participants: Seventy-five New Zealand white rabbits.
Methods: This study was performed using 75 rabbits to evaluate the ocular reactivity to bacterial endotoxin contained in Dulbecco's phosphate-buffered saline (DPBS), a cohesive OVD, and a dispersive OVD. For each test material, 25 rabbits were randomized into 5 groups and were exposed to the test material containing 0.75 endotoxin units (EU), 0.25 EU, 0.08 EU, and 0.02 EU of endotoxin or the vehicle control. The rabbits in each group received bilateral intracameral injection of 0.05 ml of the same test material. All eyes were examined by slit-lamp biomicroscopy at baseline, 3, 6, 9, 24, 48, and 72 hours after injection. At 24 and 72 hours, slit-lamp biomicroscopy (and additionally indirect ophthalmoscopy) was performed through dilated pupils.
Main Outcome Measures: Corneal clouding, anterior chamber (AC) flare, cells and fibrin, vitreous haze and cells, cells and fibrin on lens surface, lens opacities, and onset time.
Results: The inflammation seen after exposure to the 3 endotoxin-spiked materials followed the same general time course. Anterior chamber cells, flare, iris hyperemia, and conjunctival congestion were seen as early as 3 hours. They started to diminish after 6 hours (DPBS eyes) and 9 hours (OVDs) and were not detectable at 48 and 72 hours, respectively. The AC inflammation was more severe in the OVD eyes than in the DPBS eyes. Anterior chamber fibrin was seen in the OVD eyes only, which persisted through 72 hours in many eyes. A trend toward a dose-response relationship was seen for AC cells and flare and the presence of cells and fibrin on the lens surface in all 3 treatment groups in the first 24 hours.
Conclusions: Inflammation was seen after intracameral injection of as little as 0.02 and 0.08 EU in OVD and DPBS eyes, respectively. Observed responses to intracamerally injected endotoxin in OVDs were more severe and of longer duration than those in aqueous medium.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e4-e10 (C) 2012 by the American Academy of Ophthalmology.
C1 [Calogero, Don; Hilmantel, Gene; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD 20993 USA.
[Buchen, Shelley Y.] US FDA, Oak Ridge Inst Sci & Educ, Silver Spring, MD 20993 USA.
RP Eydelman, MB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, 10903 New Hampshire Ave,WO 66-2410, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU Food and Drug Administration, Silver Spring, Maryland
FX Supported by the Food and Drug Administration, Silver Spring, Maryland.
The Food and Drug Administration personnel participated in the design of
the study, conducting the study, data collection, data management, data
analyses, data interpretation, and manuscript preparation and review.
The mention of commercial products, their sources, or their use in
connection with material reported herein is not to be construed as
either an actual or implied endorsement of such products by the
Department of Health and Human Services (DHHS).
NR 23
TC 5
Z9 5
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E4
EP E10
DI 10.1016/j.ophtha.2012.04.006
PG 7
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000001
PM 22578450
ER
PT J
AU Leder, HA
Goodkin, M
Buchen, SY
Calogero, D
Hilmantel, G
Hitchins, VM
Eydelman, MB
AF Leder, Henry A.
Goodkin, Margot
Buchen, Shelley Y.
Calogero, Don
Hilmantel, Gene
Hitchins, Victoria M.
Eydelman, Malvina B.
TI An Investigation of Enzymatic Detergents as a Potential Cause of Toxic
Anterior Segment Syndrome
SO OPHTHALMOLOGY
LA English
DT Article
ID CATARACT-SURGERY; STERILE ENDOPHTHALMITIS; OUTBREAK; DEBRIS
AB Objective: To investigate whether enzymatic detergents used in cleaning ophthalmic surgical instruments can cause toxic anterior segment syndrome (TASS)-like responses in a rabbit model.
Design: Randomized, investigator-masked, controlled experimental animal study.
Participants: Thirty-five New Zealand white rabbits.
Methods: The rabbit eyes were randomized into 7 treatment groups to receive intracameral injection of 1 of 3 different doses of Medline Dual Detergent or Enzol Detergent, or sterile limulus amoebocyte lysate reagent water as a control. The eyes were evaluated for anterior segment inflammation at baseline and at 1, 3, 6, 24, 48, and 72 hours after treatment by slit-lamp biomicroscopy.
Main Outcome Measures: Anterior chamber (AC) inflammation, including cells, flare, fibrin, and iris injection; time course of inflammation; and residual detergent levels in luminated instruments.
Results: Moderate to marked injection of the iris vessels was seen as early as 1 hour after treatment with the enzymatic detergents in 41 of 60 eyes, with the response being more severe in the Enzol Detergent-exposed eyes. Severe iris hemorrhages were accompanied by blood in the AC in 13 eyes, which usually persisted through 72 hours, with an associated increase in AC cell and flare. Corneal haze was present in 52 of 56 eyes 1 hour after treatment, but was mild and resolved within 24 hours in all but the Enzol 4.5%-exposed eyes. Median AC cell and flare peaked at 6 hours and resolved by 48 hours.
Conclusions: Enzymatic detergents caused a severe but unusual response from the iris when injected intracamerally into rabbit eyes. This response has not been reported in humans with TASS. The time course of inflammation was faster (peak at 6 hours) and resolved more quickly (within 48 hours) than TASS. Simulated cleaning and extraction studies indicate that the level of residual detergent to which a patient could be exposed is significantly less than the lowest dose used in this study. Because that low dose caused no significant observations other than injection of the iris vessels, these results do not support residual enzymatic detergents on surgical instruments as a cause for TASS.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e30-e35 (C) 2012 by the American Academy of Ophthalmology.
C1 [Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD 20993 USA.
[Leder, Henry A.; Buchen, Shelley Y.] US FDA, ORISE, Silver Spring, MD 20993 USA.
RP Eydelman, MB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, 10903 New Hampshire Ave,WO 66-2410, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
NR 23
TC 7
Z9 7
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E30
EP E35
DI 10.1016/j.ophtha.2012.04.016
PG 6
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000005
PM 22578445
ER
PT J
AU Nussenblatt, RB
Calogero, D
Buchen, SY
Leder, HA
Goodkin, M
Eydelman, MB
AF Nussenblatt, Robert B.
Calogero, Don
Buchen, Shelley Y.
Leder, Henry A.
Goodkin, Margot
Eydelman, Malvina B.
TI Rabbit Intraocular Reactivity to Endotoxin Measured by Slit-Lamp
Biomicroscopy and Laser Flare Photometry
SO OPHTHALMOLOGY
LA English
DT Article
ID OCULAR INFLAMMATORY RESPONSE; ANTERIOR SEGMENT; INHIBITION; UVEITIS;
ALPHA
AB Objective: To evaluate the ocular reactivity of the rabbit to an intracameral injection of a dispersive ophthalmic viscosurgical device (OVD) containing various levels of bacterial endotoxin using slit-lamp biomicroscopy and laser flare photometry.
Design: Experimental, randomized, masked animal study.
Participants: Thirty Dutch-Belted rabbits.
Methods: The rabbits were randomized into 6 groups to receive 0.05 ml of a hydroxypropyl methylcellulose-based dispersive OVD to which had been added one of 5 different doses of bacterial endotoxin ranging from 0.02 to 1.4 endotoxin units (EUs) or a vehicle control to both eyes. The eyes were evaluated for anterior segment inflammation at baseline and 3, 6, 9, 24, 48, and 72 hours after injection using slit-lamp biomicroscopy and laser flare photometry.
Main Outcome Measures: Corneal clarity and anterior chamber (AC) inflammation.
Results: All the corneas remained clear throughout the study. Anterior chamber cells were seen at 6, 9, and 24 hours in 60% to 100% of the eyes intracamerally injected with endotoxin-containing OVD, and the response declined rapidly after 24 hours. A dose-response effect was seen between the concentration of endotoxin and the AC cell response. The aqueous flare response in eyes injected with the 2 highest doses of endotoxin was significantly greater (P<0.05) than that of controls. The amounts of fibrin observed in the AC were random, with no apparent dose-response effect seen. The flare values as obtained by laser flare photometry were consistent with the slit-lamp biomicroscopy flare findings up to grade 3+. However, the increase in laser flare value seemed to level off in eyes with more than 3+ flare. Neither measure of flare correlated with endotoxin level.
Conclusions: Among the parameters evaluated in this study, the AC cell response, evaluated by slit-lamp biomicroscopy and graded using a standard grading system, was found to be the most reliable indicator of the amount of endotoxin in the dispersive OVD. The use of laser flare photometry alone does not seem to be useful in detecting an ocular response to endotoxin contamination in OVDs.
Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:e19-e23 (C) 2012 by the American Academy of Ophthalmology.
C1 [Calogero, Don; Goodkin, Margot; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD 20993 USA.
[Nussenblatt, Robert B.] NEI, NIH, Bethesda, MD 20892 USA.
[Buchen, Shelley Y.; Leder, Henry A.] US FDA, ORISE, Silver Spring, MD 20993 USA.
RP Eydelman, MB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, 10903 New Hampshire Ave,WO 66-2410, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU Food and Drug Administration, Silver Spring, Maryland
FX Supported by the Food and Drug Administration, Silver Spring, Maryland.
The Food and Drug Administration personnel participated in the design of
the study, conducting the study, data collection, data management, data
analyses, data interpretation, and manuscript preparation and review.
The mention of commercial products, their sources, or their use in
connection with material reported herein is not to be construed as
either an actual or implied endorsement of such products by the
Department of Health and Human Services (DHHS).
NR 17
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
BP E19
EP E23
DI 10.1016/j.ophtha.2012.04.004
PG 5
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000003
PM 22578448
ER
PT J
AU Calogero, D
Buchen, SY
Tarver, ME
Hilmantel, G
Lucas, AD
Eydelman, MB
AF Calogero, Don
Buchen, Shelley Y.
Tarver, Michelle E.
Hilmantel, Gene
Lucas, Anne D.
Eydelman, Malvina B.
TI Evaluation of Intraocular Reactivity to Metallic and Ethylene Oxide
Contaminants of Medical Devices in a Rabbit Model
SO OPHTHALMOLOGY
LA English
DT Article
ID ANTERIOR SEGMENT SYNDROME; PLASMA GAS; SURGERY
AB Objective: To evaluate the intraocular reactivity to metallic and ethylene oxide (EO) contaminants of ophthalmic devices in rabbits.
Design: Two experimental animal studies.
Participants: Thirty-five New Zealand white rabbits.
Methods: A metallic exposure study and an EO exposure study were performed. In the first study, both eyes of 25 rabbits were equally allocated to intracameral injections of alumina 0.2 mu g, alumina 20 mu g, copper sulfate 0.4 mu g, copper sulfate 20 mu g, or an aqueous control. In the second study, 10 rabbits were allocated (5 per group) to receive intracamerally an ophthalmic viscosurgical device (OVD) exposed to EO or not exposed to EO (control). All eyes were examined by slit lamp at baseline and 3, 6, 9, 24, 48, and 72 hours after exposure, with dilated indirect ophthalmoscopy being performed at 24 and 72 hours. Tonometry was performed only in the first study.
Main Outcome Measures: Grade of corneal clouding, anterior chamber (AC) flare, AC cells, AC fibrin, iridal hyperemia, cell and fibrin on the lens surface, vitreous haze and cells, lens opacities, intraocular pressure, and onset time.
Results: For metallic compounds at the study's low doses, mean inflammatory grades were 0.2 or less above the control for all responses at all time points. For the high-dose alumina, mean inflammatory grades peaked at 6 to 9 hours at 0.5 to 0.7 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, and fibrin and declined over the remaining time points. For the high-dose copper sulfate, mean inflammatory grades peaked between 3 and 24 hours at 1.2 to 1.8 above the control responses for conjunctival congestion, iris hyperemia, AC cells, flare, fibrin, and corneal clouding, then subsequently declined. The intraocular pressure changes appeared significant for only high-dose copper sulfate, with mean declines of 4.3 to 7.5 mmHg at 6 to 72 hours. No clinically meaningful differences in ocular inflammation were observed between the OVD exposed to EO and the OVD not exposed to EO.
Conclusions: Alumina and copper sulfate did not cause clinically meaningful ocular inflammation at the low study levels (levels expected with ophthalmic devices). Ethylene oxide exposure of an OVD was not associated with inflammation.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;xx:xxx (C) 2012 by the American Academy of Ophthalmology.
C1 [Calogero, Don; Tarver, Michelle E.; Hilmantel, Gene; Eydelman, Malvina B.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD USA.
[Buchen, Shelley Y.] US FDA, ORISE, Silver Spring, MD USA.
[Lucas, Anne D.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, Silver Spring, MD USA.
RP Eydelman, MB (reprint author), WO 66-2410,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU Food and Drug Administration (Silver Spring, MD)
FX The Food and Drug Administration (Silver Spring, MD) funded this work.
The Food and Drug Administration personnel participated in the design of
the study, conducting the study, data collection, data management, data
analysis, interpretation of the data, and preparation and review of the
manuscript.
NR 18
TC 5
Z9 5
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
DI 10.1016/j.ophtha.2012.04.009
PG 7
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000006
PM 22578444
ER
PT J
AU Eydelman, MB
Tarver, ME
Calogero, D
Buchen, SY
Alexander, KY
AF Eydelman, Malvina B.
Tarver, Michelle E.
Calogero, Don
Buchen, Shelley Y.
Alexander, Kesia Y.
TI The Food and Drug Administration's Proactive Toxic Anterior Segment
Syndrome Program
SO OPHTHALMOLOGY
LA English
DT Review
ID CATARACT-SURGERY; CORNEAL ENDOTHELIUM; PLASMA GAS; INFLAMMATION;
OUTBREAK; STERILIZATION; IMPLANTATION; DESTRUCTION; DETERGENTS;
EXTRACTION
AB Toxic anterior segment syndrome (TASS) is a rare inflammatory condition usually observed within the first 48 hours after uncomplicated anterior segment surgery. Over the decades since its initial description, a number of TASS outbreaks have been reported. For a few of these outbreaks, the inciting factors were identified, but for the majority, the precipitating factors were often postulated but not confirmed. In light of the limitations identified in these outbreak investigations, the Food and Drug Administration's (FDA's) Center for Devices and Radiological Health staff has embarked on a number of activities aimed at mitigating medical device-related TASS outbreaks. Under the FDA-designed Proactive TASS Program (PTP), FDA scientists have conducted animal studies to better explore the inflammatory potential of suspected ophthalmic device contaminants implicated in prior cases of TASS. For contaminants displaying a TASS-like reaction in these animal models, the FDA scientists have developed analytic test methods to measure the level of those contaminants in or on ophthalmic devices. Moreover, FDA researchers have developed methods to better capture the clinical information necessary to assist investigations of potential future outbreaks. Last, the FDA has partnered with the Centers for Disease Control and Prevention to facilitate a potential TASS investigation, including expediting the analysis of potentially contaminated medical devices. The PTP is an example of the FDA proactively developing test methods and disease surveillance methods geared toward protecting the public's health.
Financial Disclosure(s):
The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;xx:xxx (C) 2012 by the American Academy of Ophthalmology.
C1 [Eydelman, Malvina B.; Tarver, Michelle E.; Calogero, Don; Alexander, Kesia Y.] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Ophthalm Neurol & Ear Nose & Throat Devices, Silver Spring, MD USA.
[Buchen, Shelley Y.] US FDA, ORISE, Silver Spring, MD USA.
RP Eydelman, MB (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM malvina.eydelman@fda.hhs.gov
FU FDA (Silver Spring, MD)
FX The FDA (Silver Spring, MD) funded this work. The FDA personnel
participated in designing and conducting the study; collecting,
managing, analyzing, and interpreting data; and preparing and reviewing
the manuscript.
NR 41
TC 10
Z9 11
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD JUL
PY 2012
VL 119
IS 7
DI 10.1016/j.ophtha.2012.04.008
PG 6
WC Ophthalmology
SC Ophthalmology
GA 968UQ
UT WOS:000306011000009
PM 22578447
ER
PT J
AU Tsou, HH
Hung, HMJ
Chen, YM
Huang, WS
Chang, WJ
Hsiao, CF
AF Tsou, Hsiao-Hui
Hung, H. M. James
Chen, Yue-Ming
Huang, Wong-Shian
Chang, Wan-jung
Hsiao, Chin-Fu
TI Establishing consistency across all regions in a multi-regional clinical
trial
SO PHARMACEUTICAL STATISTICS
LA English
DT Article
DE multi-regional clinical trial; bridging study; consistent trend
ID SAMPLE-SIZE; MULTIREGIONAL TRIAL
AB In recent years, global collaboration has become a conventional strategy for new drug development. To accelerate the development process and shorten approval time, the design of multi-regional clinical trials (MRCTs) incorporates subjects from many countries/regions around the world under the same protocol. After showing the overall efficacy of a drug in a global trial, one can also simultaneously evaluate the possibility of applying the overall trial results to all regions and subsequently support drug registration in each region. However, most of the recent approaches developed for the design and evaluation of MRCTs focus on establishing criteria to examine whether the overall results from the MRCT can be applied to a specific region. In this paper, we use the consistency criterion of Method 1 from the Japanese Ministry of Health, Labour and Welfare (MHLW) guidance to assess whether the overall results from the MRCT can be applied to all regions. Sample size determination for the MRCT is also provided to take all the consistency criteria from each individual region into account. Numerical examples are given to illustrate applications of the proposed approach. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Tsou, Hsiao-Hui; Chen, Yue-Ming; Huang, Wong-Shian; Chang, Wan-jung; Hsiao, Chin-Fu] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, Zhunan Town 350, Miaoli County, Taiwan.
[Hung, H. M. James] US FDA, Div Biometr 1, OB OTS CDER DB1, Silver Spring, MD USA.
[Hsiao, Chin-Fu] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Clin Trial Stat, Zhunan Town 350, Miaoli County, Taiwan.
RP Hsiao, CF (reprint author), Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Biostat & Bioinformat, 35 Keyan Rd, Zhunan Town 350, Miaoli County, Taiwan.
EM chinfu@nhri.org.tw
RI Tsou, Hsiao-Hui /E-3837-2010; Hsiao, Chin-Fu/E-3993-2010
OI Tsou, Hsiao-Hui /0000-0001-6773-4111;
FU National Health Research Institutes, Taiwan [PH-100-SP-03]
FX Thanks are due to the two referees and the editor for their detailed,
constructive, and thoughtful comments and suggestions that led to a
significant improvement to this paper. The study was supported by grant
PH-100-SP-03 from National Health Research Institutes, Taiwan.
NR 11
TC 4
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1539-1604
J9 PHARM STAT
JI Pharm. Stat.
PD JUL-AUG
PY 2012
VL 11
IS 4
BP 295
EP 299
DI 10.1002/pst.1512
PG 5
WC Pharmacology & Pharmacy; Statistics & Probability
SC Pharmacology & Pharmacy; Mathematics
GA 971CK
UT WOS:000306180800004
PM 22504851
ER
PT J
AU Temple, R
Laughren, T
Stockbridge, N
AF Temple, Robert
Laughren, Thomas
Stockbridge, Norman
TI Removal from labeling of 60-mg citalopram dose
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Letter
ID SUDDEN CARDIAC DEATH; RISK
C1 [Temple, Robert; Laughren, Thomas; Stockbridge, Norman] US FDA, CDER, Silver Spring, MD USA.
RP Temple, R (reprint author), US FDA, CDER, Silver Spring, MD USA.
EM robert.temple@fda.hhs.gov
NR 8
TC 5
Z9 5
U1 0
U2 0
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JUL
PY 2012
VL 21
IS 7
BP 784
EP 786
DI 10.1002/pds.3289
PG 3
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 968TE
UT WOS:000306006900016
ER
PT J
AU Southwell, BG
Kim, AE
Tessman, GK
MacMonegle, AJ
Choiniere, CJ
Evans, SE
Johnson, RD
AF Southwell, Brian G.
Kim, Annice E.
Tessman, Greta K.
MacMonegle, Anna J.
Choiniere, Conrad J.
Evans, Sarah E.
Johnson, Robin D.
TI The Marketing of Dissolvable Tobacco: Social Science and Public Policy
Research Needs
SO AMERICAN JOURNAL OF HEALTH PROMOTION
LA English
DT Editorial Material
ID PRODUCTS; SMOKELESS
C1 [Southwell, Brian G.; Kim, Annice E.; MacMonegle, Anna J.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Tessman, Greta K.; Choiniere, Conrad J.; Evans, Sarah E.; Johnson, Robin D.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA.
RP Southwell, BG (reprint author), RTI Int, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM bsouthwell@rti.org
OI Southwell, Brian/0000-0001-5091-8782
NR 16
TC 10
Z9 10
U1 0
U2 5
PU AMER JOURNAL HEALTH PROMOTION INC
PI TROY
PA PO BOX 1254, TROY, MI 48099-1254 USA
SN 0890-1171
J9 AM J HEALTH PROMOT
JI Am. J. Health Promot.
PD JUL-AUG
PY 2012
VL 26
IS 6
BP 331
EP 332
DI 10.4278/ajhp.111004-CIT-357
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 970UH
UT WOS:000306157300002
PM 22747313
ER
PT J
AU Zheteyeva, YA
Moro, PL
Tepper, NK
Rasmussen, SA
Barash, FE
Revzina, NV
Kissin, D
Lewis, PW
Yue, X
Haber, P
Tokars, JI
Vellozzi, C
Broder, KR
AF Zheteyeva, Yenlik A.
Moro, Pedro L.
Tepper, Naomi K.
Rasmussen, Sonja A.
Barash, Faith E.
Revzina, Natalia V.
Kissin, Dmitry
Lewis, Paige W.
Yue, Xin
Haber, Penina
Tokars, Jerome I.
Vellozzi, Claudia
Broder, Karen R.
TI Adverse event reports after tetanus toxoid, reduced diphtheria toxoid,
and acellular pertussis vaccines in pregnant women
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE acellular pertussis vaccine; adverse events; epidemiology; pregnancy;
reduced diphtheria toxoid; surveillance; tetanus toxoid; vaccine safety
ID IMMUNIZATION PRACTICES ACIP; UNITED-STATES; ADVISORY-COMMITTEE;
INFLUENZA VACCINE; FEBRILE SEIZURES; SAFETY; RECOMMENDATIONS; SYSTEM;
SIGNAL; RISK
AB OBJECTIVE: We sought to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) of pregnant women who received tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap).
STUDY DESIGN: We searched VAERS for reports of pregnant women who received Tdap from Jan. 1, 2005, through June 30, 2010. We conducted a clinical review of reports and available medical records.
RESULTS: We identified 132 reports of Tdap administered to pregnant women; 55 (42%) described no adverse event (AE). No maternal or infant deaths were reported. The most frequent pregnancy-specific AE was spontaneous abortion in 22 (16.7%) reports. Injection site reactions were the most frequent non-pregnancy-specific AE found in 6 (4.5%) reports. One report with a major congenital anomaly (gastroschisis) was identified.
CONCLUSION: During a time when Tdap was not routinely recommended in pregnancy, review of reports to VAERS in pregnant women after Tdap did not identify any concerning patterns in maternal, infant, or fetal outcomes.
C1 [Zheteyeva, Yenlik A.; Moro, Pedro L.; Lewis, Paige W.; Yue, Xin; Haber, Penina; Tokars, Jerome I.; Vellozzi, Claudia; Broder, Karen R.] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
[Zheteyeva, Yenlik A.] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Epidem Intelligence Serv, Atlanta, GA 30333 USA.
[Tepper, Naomi K.; Kissin, Dmitry] Ctr Dis Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Womens Hlth & Fertil Branch, Div Reprod Hlth, Atlanta, GA 30333 USA.
[Rasmussen, Sonja A.] Emory Univ, Sch Med, Div Birth Defects & Dev Disabil, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
[Revzina, Natalia V.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Barash, Faith E.] US FDA, Off Biostat, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
[Barash, Faith E.] US FDA, Off Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA.
RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd,MS D26, Atlanta, GA 30333 USA.
EM pmoro@cdc.gov
NR 30
TC 32
Z9 34
U1 0
U2 3
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 JUL
PY 2012
VL 207
IS 1
AR 59.e1
DI 10.1016/j.ajog.2012.05.006
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 965GJ
UT WOS:000305755000023
PM 22727350
ER
PT J
AU Tiwari, JL
Schneider, B
Barton, F
Anderson, SA
AF Tiwari, J. L.
Schneider, B.
Barton, F.
Anderson, S. A.
TI Islet Cell Transplantation in Type 1 Diabetes: An Analysis of Efficacy
Outcomes and Considerations for Trial Designs
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Clinical efficacy; clinical trials; islet transplantation; Kaplan-Meier
survival analysis; sample size; type 1 diabetes
AB To estimate treatment effect size and other parameters required for planning the designs and analyses of future phase 3 islet transplant trials, we analyzed key clinical and laboratory outcomes of 347 allogeneic islet transplant recipients, using data from the Collaborative Islet Transplant Registry (CITR). At 1 year, approximately 59% of all transplant recipients were free of severe hypoglycemic events and maintained hemoglobin A1c (HbA1c) level of =6.5%. The KaplanMeier (KM) survival analyses showed that 69%, 54% and 44% of these 1-year responders maintained this composite endpoint at 2, 3 and 4 years, respectively. Ninety-one percent of all recipients were free of severe hypoglycemic episodes at 1 year. Furthermore, the KM survival estimates showed that 91%, 85% and 80% of these subjects maintained this clinical benefit at 2, 3 and 4 years, respectively. These results can be very useful in developing framework for study designs, sample size estimates, and statistical analysis plans for future pivotal trials of islet cell transplantation in type 1 diabetes.
C1 [Tiwari, J. L.; Anderson, S. A.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Schneider, B.] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Barton, F.] EMMES Corp, CITR Coordinating Ctr, Rockville, MD USA.
RP Tiwari, JL (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM jawahar.tiwari@fda.hhs.gov
FU FDA Office of Critical Path Programs Grant; National Institute of
Diabetes, Digestive and Kidney Diseases; Juvenile Diabetes Research
Foundation
FX We express our sincere gratitude to all investigators and islet cell
transplant recipients who have voluntarily contributed data to the CITR
Registry. We also thank Dr. Bernhard Hering, MD (University of
Minnesota) and Scientific Advisors to the CITR Project for giving
permission to use these data for our research project. We thank Dr.
Mridul Chowdhury for his assistance in checking and verification of the
data for these analyses. We express our sincere thanks to the Editors
and the reviewers of this manuscript for many valuable comments that
were helpful in the clarification of various issues discussed in this
report. This research was supported by an FDA Office of Critical Path
Programs Grant.; F.B. is the Principal Investigator at the CITR
Coordinating Center maintained by the EMMES Corporation, Rockville, MD.
The CITR project is funded by the National Institute of Diabetes,
Digestive and Kidney Diseases with supplemental funding from the
Juvenile Diabetes Research Foundation. All other authors are employees
of the Food and Drug Administration and have no conflicts of interest to
disclose as described by the American Journal of Transplantation.
NR 8
TC 8
Z9 8
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2012
VL 12
IS 7
BP 1898
EP 1907
DI 10.1111/j.1600-6143.2012.04038.x
PG 10
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 965TE
UT WOS:000305789400028
PM 22486926
ER
PT J
AU Troendle, JF
Zhang, ZW
Mathews, ME
Guo, JC
AF Troendle, James F.
Zhang, Zhiwei
Mathews, Megan E.
Guo, Junchi
TI Methods of adjusted comparison of medians
SO BIOMETRICAL JOURNAL
LA English
DT Article
DE Box-Cox transformation; Mean squared error; Predicted values; Reference
population
ID REGRESSION-MODELS
AB Consider the problem of making an adjusted comparison of the medians of two populations on an interval type outcome variable. A common method of doing this is through the use of a linear model requiring the residuals to be normally distributed. We describe here two methods based on a linear model after BoxCox transformation of the outcome variable. The methods require a reference population, which could be either of the populations under study or their aggregate. We compare the new procedures with the comparison of normal means procedure and other procedures proposed for this problem by simulation. It is found that the procedure based on comparison of the predicted values obtained from the observed covariates of the reference population has higher power for testing and smaller mean square error of estimation than the other methods, while maintaining reasonable control of the type I error rate. We illustrate the methods by analyzing the duration of the second stage of labor for women in two large observation studies (Collaborative Perinatal Project and Consortium on Safe Labor) separated by 50 years. We recommend the method based on comparison of the predicted values of the transformed outcomes, with careful attention to how close the resulting residual distribution is to normal.
C1 [Troendle, James F.] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bethesda, MD 20892 USA.
[Zhang, Zhiwei] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Mathews, Megan E.] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Guo, Junchi] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Troendle, JF (reprint author), NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH,DHHS, Bld RLK2,Room 9195, Bethesda, MD 20892 USA.
EM jt3t@nih.gov
FU Intramural Research Program of the NICHD, National Institutes of Health
FX This research was supported in part by the Intramural Research Program
of the NICHD, National Institutes of Health.
NR 16
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0323-3847
J9 BIOMETRICAL J
JI Biom. J.
PD JUL
PY 2012
VL 54
IS 4
BP 481
EP 493
DI 10.1002/bimj.201100220
PG 13
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA 968MG
UT WOS:000305985000003
PM 22622655
ER
PT J
AU Fine, A
Bastings, E
AF Fine, Andrew
Bastings, Eric
TI Triptans and Serotonin Syndrome
SO HEADACHE
LA English
DT Letter
ID TOXICITY; ZOLMITRIPTAN; SUMATRIPTAN
C1 [Fine, Andrew; Bastings, Eric] FDA Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Fine, A (reprint author), FDA Ctr Drug Evaluat & Res, Silver Spring, MD USA.
NR 8
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-8748
J9 HEADACHE
JI Headache
PD JUL-AUG
PY 2012
VL 52
IS 7
BP 1184
EP 1185
DI 10.1111/j.1526-4610.2012.02184.x
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 967ZJ
UT WOS:000305946400015
PM 22755550
ER
PT J
AU Tsuchiya, M
Ji, C
Kosyk, O
Shymonyak, S
Melnyk, S
Kono, H
Tryndyak, V
Muskhelishvili, L
Pogribny, IP
Kaplowitz, N
Rusyn, I
AF Tsuchiya, Masato
Ji, Cheng
Kosyk, Oksana
Shymonyak, Svitlana
Melnyk, Stepan
Kono, Hiroshi
Tryndyak, Volodymyr
Muskhelishvili, Levan
Pogribny, Igor P.
Kaplowitz, Neil
Rusyn, Ivan
TI Interstrain differences in liver injury and one-carbon metabolism in
alcohol-fed mice
SO HEPATOLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; FATTY LIVER; METHIONINE METABOLISM;
GENETIC POLYMORPHISMS; LIPID-METABOLISM; ER STRESS; DISEASE; MECHANISMS;
ETHANOL; RISK
AB Alcoholic liver injury is a major public health issue worldwide. Even though the major mechanisms of this disease have been established over the past decades, little is known about genetic susceptibility factors that may predispose individuals who abuse alcoholic beverages to liver damage and subsequent pathological conditions. We hypothesized that a panel of genetically diverse mouse strains may be used to examine the role of endoplasmic reticulum (ER) stress and one-carbon metabolism in the mechanism of interindividual variability in alcoholic liver injury. We administered alcohol (up to 27 mg/kg/d) in a high-fat diet using an intragastric intubation model for 28 days to male mice from 14 inbred strains (129S1/SvImJ, AKR/J, BALB/cJ, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, C57BL/10J, DBA/2J, FVB/NJ, KK/HIJ, MOLF/EiJ, NZW/LacJ, PWD/PhJ, and WSB/EiJ). Profound interstrain differences (more than 3-fold) in alcohol-induced steatohepatitis were observed among the strains in spite of consistently high levels of urine alcohol that were monitored throughout the study. We found that ER stress genes were induced only in strains with the most liver injury. Liver glutathione and methyl donor levels were affected in all strains, albeit to a different degree. The most pronounced effects that were closely associated with the degree of liver injury were hyperhomocysteinemia and strain-dependent differences in expression patterns of one-carbon metabolism-related genes. Conclusion: Our data demonstrate that strain differences in alcohol-induced liver injury and steatosis are striking and independent of alcohol exposure and the most severely affected strains exhibit major differences in the expression of ER stress markers and genes of one-carbon metabolism. (HEPATOLOGY 2012;56:130139)
C1 [Tsuchiya, Masato; Kosyk, Oksana; Shymonyak, Svitlana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
[Tsuchiya, Masato; Kono, Hiroshi] Univ Yamanashi, Dept Surg 1, Chuo, Yamanashi, Japan.
[Ji, Cheng; Kaplowitz, Neil] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Melnyk, Stepan] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Tryndyak, Volodymyr; Muskhelishvili, Levan; Pogribny, Igor P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
EM iir@unc.edu
RI Rusyn, Ivan/S-2426-2016
FU National Institutes of Health [R01 AA016258, R01 ES015241, R01 AA014428,
R01 AA018846]
FX Supported, in part, by grants from the National Institutes of Health
(R01 AA016258, R01 ES015241, R01 AA014428 and R01 AA018846).
NR 48
TC 20
Z9 20
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD JUL
PY 2012
VL 56
IS 1
BP 130
EP 139
DI 10.1002/hep.25641
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 967ZQ
UT WOS:000305947200016
PM 22307928
ER
PT J
AU Wang, SJ
Petrick, N
Van Uitert, RL
Periaswamy, S
Wei, ZS
Summers, RM
AF Wang, Shijun
Petrick, Nicholas
Van Uitert, Robert L.
Periaswamy, Senthil
Wei, Zhuoshi
Summers, Ronald M.
TI Matching 3-D Prone and Supine CT Colonography Scans Using Graphs
SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE
LA English
DT Article
DE Computed tomographic colonography; colon registration; graph matching;
mean field theory
ID COMPUTER-AIDED DETECTION; COLON CENTERLINE; REGISTRATION; TRIAL;
COLONOSCOPY; REDUCTION; POLYPS
AB In this paper, we propose a new registration method for prone and supine computed tomographic colonography scans using graph matching. We formulate 3-D colon registration as a graph matching problem and propose a new graph matching algorithm based on mean field theory. In the proposed algorithm, we solve the matching problem in an iterative way. In each step, we use mean field theory to find the matched pair of nodes with highest probability. During iterative optimization, one-to-one matching constraints are added to the system in a step-by-step approach. Prominent matching pairs found in previous iterations are used to guide subsequent mean field calculations. The proposed method was found to have the best performance with smallest standard deviation compared with two other baseline algorithms called the normalized distance along the colon centerline (NDACC) (p = 0.17) with manual colon centerline correction and spectral matching (p < 1e-5). A major advantage of the proposed method is that it is fully automatic and does not require defining a colon centerline for registration. For the latter NDACC method, user interaction is almost always needed for identifying the colon centerlines.
C1 [Wang, Shijun; Wei, Zhuoshi; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Petrick, Nicholas] US FDA, Silver Spring, MD 20993 USA.
[Van Uitert, Robert L.; Periaswamy, Senthil] iCAD Inc, Nashua, NH 03062 USA.
RP Wang, SJ (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
EM wangshi@cc.nih.gov; nicholas.petrick@fda.hhs.gov;
rvanuitert@icadmed.com; speriaswamy@icadmed.com; weiz@cc.nih.gov;
rms@nih.gov
FU U.S. NIH Clinical Center; Food and Drug Administration
FX This research was supported by the Intramural Research Programs of the
U.S. NIH Clinical Center and the Food and Drug Administration.
NR 26
TC 3
Z9 3
U1 1
U2 7
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1089-7771
J9 IEEE T INF TECHNOL B
JI IEEE T. Inf. Technol. Biomed.
PD JUL
PY 2012
VL 16
IS 4
BP 676
EP 682
DI 10.1109/TITB.2012.2194297
PG 7
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA 968KK
UT WOS:000305979500017
PM 22552585
ER
PT J
AU Tavris, DR
Wang, YF
Jacobs, S
Gallauresi, B
Curtis, J
Messenger, J
Resnic, FS
Fitzgerald, S
AF Tavris, Dale R.
Wang, Yongfei
Jacobs, Samantha
Gallauresi, Beverly
Curtis, Jeptha
Messenger, John
Resnic, Frederic S.
Fitzgerald, Susan
TI Bleeding and Vascular Complications at the Femoral Access Site Following
Percutaneous Coronary Intervention (PCI): An Evaluation of Hemostasis
Strategies
SO JOURNAL OF INVASIVE CARDIOLOGY
LA English
DT Article
DE hemostasis patch; mechanical compression; vascular closure device
ID CARDIAC-CATHETERIZATION; CLOSURE DEVICES; MANUAL COMPRESSION;
ANGIO-SEAL; RISK; METAANALYSIS; TRIAL; PREDICTORS; MANAGEMENT; REGISTRY
AB Background. Previous research found at least one vascular closure device (VCD) to be associated with excess vascular complications, compared to manual compression (MC) controls, following cardiac catheterization. Since that time, several more VCDs have been approved by the Food and Drug Administration (FDA). This research evaluates the safety profiles of current frequently used VCDs and other hemostasis strategies. Methods. Of 1089 sites that submitted data to the CathPCI Registry from 2005 through the second quarter of 2009, a total of 1,819,611 percutaneous coronary intervention (PCI) procedures performed via femoral access site were analyzed. Assessed outcomes included bleeding, femoral artery occlusion, embolization, artery dissection, pseudoaneurysm, and arteriovenous fistula. Seven types of hemostasis strategy were evaluated for rate of "any bleeding or vascular complication" compared to MC controls, using hierarchical multiple logistic regression analysis, controlling for demographic factors, type of hemostasis, several indices of co-morbidity, and other potential confounding variables. Rates for different types of hemostasis strategy were plotted over time, using linear regression analysis. Results. Four of the VCDs and hemostasis patches demonstrated significantly lower bleeding or vascular complication rates than MC controls: Angio-Seal (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.65-0.70); Perclose (OR, 0.54; CI, 0.51-0.57); StarClose (OR, 0.77; CI, 0.72-0.82); Boomerang Closure Wire (OR, 0.63; CI, 0.53-0.75); and hemostasis patches (OR, 0.70; CI, 0.67-0.74). All types of hemostasis strategy, including MC, exhibited reduced complication rates over time. All trends were statistically significant except one. Conclusions. This large, nationally representative observational study demonstrated better safety profiles for most of the frequently used VCDs, compared to MC controls.
C1 [Tavris, Dale R.] US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Wang, Yongfei; Curtis, Jeptha] Yale Univ, New Haven, CT USA.
[Messenger, John] Univ Colorado, Boulder, CO 80309 USA.
[Resnic, Frederic S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Fitzgerald, Susan] Amer Coll Cardiol, Bethesda, MD USA.
RP Tavris, DR (reprint author), US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM dale.tavris@fda.hhs.gov
FU ACC Foundation; NIH/NHLBI Center for Medicare and Medicaid Services; St
Jude Medical; Office of Women's Health at the FDA
FX Disclosures: The authors have completed and returned the ICMJE Form for
Disclosure of Potential Conflicts of Interest. Dr Curtis provides expert
testimony for the Piedmont Liability Trust, holds a grant from the ACC
Foundation, NIH/NHLBI Center for Medicare and Medicaid Services, and
owns stock in Medtronic, Inc. Dr Resnic is a consultant for St Jude
Medical and Medtronic, Inc and holds a Research Registry support grant
from St Jude Medical. Dr Fitzgerald received payment in the form of a
contract to perform the analysis and is a board member of the ACC
Foundation. The other authors report no disclosures.; We would like to
acknowledge the Office of Women's Health at the FDA for providing the
funding for this research.
NR 24
TC 25
Z9 27
U1 1
U2 3
PU H M P COMMUNICATIONS
PI MALVERN
PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA
SN 1042-3931
J9 J INVASIVE CARDIOL
JI J. Invasive Cardiol.
PD JUL
PY 2012
VL 24
IS 7
BP 328
EP 334
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 967HR
UT WOS:000305898000012
PM 22781471
ER
PT J
AU Abi-Jaoudeh, N
Pritchard, WF
Amalou, H
Linguraru, M
Chiesa, OA
Adams, JD
Gacchina, C
Wesley, R
Maruvada, S
McDowell, B
Frenkel, V
Karanian, JW
Wood, BJ
AF Abi-Jaoudeh, Nadine
Pritchard, William F.
Amalou, Hayet
Linguraru, Marius
Chiesa, Oscar A.
Adams, Joshua D.
Gacchina, Carmen
Wesley, Robert
Maruvada, Subha
McDowell, Briana
Frenkel, Victor
Karanian, John W.
Wood, Bradford J.
TI Pulsed High-Intensity-focused US and Tissue Plasminogen Activator (TPA)
Versus TPA Alone for Thrombolysis of Occluded Bypass Graft in Swine
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID ULTRASOUND-ACCELERATED THROMBOLYSIS; IN-VITRO; ENHANCED THROMBOLYSIS;
MEDIATED THROMBOLYSIS; ARTERIAL OCCLUSIONS; RANDOMIZED-TRIAL; MODEL;
THERAPY; VIVO; ANGIOPLASTY
AB Purpose: Prosthetic arteriovenous or arterial-arterial bypass grafts can thrombose and be resistant to revascularization. A thrombosed bypass graft model was created to evaluate the potential therapeutic enhancement and safety profile of pulsed high intensity-focused ultrasound (pHIFU) on pharmaceutical thrombolysis.
Materials and Methods: In swine, a right carotid-carotid expanded polytetrafluoroethylene bypass graft was surgically constructed, containing a 40% stenosis at its distal end to induce graft thrombosis. The revascularization procedure was performed 7 days after surgery. After model development and dose response experiments (n = 11), two cohorts were studied: pHIFU with tissue plasminogen activator (TPA; n = 4) and sham pHIFU with TPA (n = 3). The experiments were identical in both groups except no energy was delivered in the sham pHIFU group. Serial angiograms were obtained in all cases. The area of graft opacified by contrast medium on angiograms was quantified with digital image processing software. A blinded reviewer calculated the change in the graft area pacified by contrast medium and expressed it as a percentage, representing percentage of thrombolysis.
Results: Combining pHIFU with 0.5 mg of TPA resulted in a 52% +/- 4% increase in thrombolysis on angiograms obtained at 30 minutes, compared with a 9% +/- 14% increase with sham pHIFU and 0.5 mg TPA (P = .003). Histopathologic examination demonstrated no differences between the groups.
Conclusions: Thrombolysis of occluded bypass grafts was significantly increased when combining pHIFU and TPA versus sham pHIFU and TPA. These results suggest that application of pHIFU may augment thrombolysis with a reduced time and dose.
C1 [Abi-Jaoudeh, Nadine; Amalou, Hayet; Gacchina, Carmen; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Wesley, Robert] NIH, Off Director, Ctr Clin, Bethesda, MD 20892 USA.
[Pritchard, William F.; Chiesa, Oscar A.; McDowell, Briana; Karanian, John W.] US FDA, Lab Cardiovasc & Intervent Therapeut, Ctr Devices & Radiol Hlth, Laurel, MD USA.
[Maruvada, Subha] US FDA, Off Sci, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Maruvada, Subha] US FDA, Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Adams, Joshua D.] Univ Virginia, Dept Vasc Surg, Charlottesville, VA USA.
[Adams, Joshua D.] Univ Virginia, Dept Radiol, Charlottesville, VA USA.
[Frenkel, Victor] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
[Linguraru, Marius] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
RP Abi-Jaoudeh, N (reprint author), NIH, Dept Radiol & Imaging Sci, Room 1C365,Bldg 10,MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM naj@mail.nih.gov
FU National Institutes of Health (NIH) [1Z01CL046011-01]
FX This work was supported in part by the National Institutes of Health
(NIH) Intramural Research Program Grant 1Z01CL046011-01. This project is
a collaboration between the NIH and the Food and Drug Administration as
part of an Interagency Agreement.
NR 36
TC 1
Z9 1
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUL
PY 2012
VL 23
IS 7
BP 953
EP 961
DI 10.1016/j.jvir.2012.04.001
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA 967TI
UT WOS:000305930300016
PM 22609287
ER
PT J
AU Magaldi, TG
Buch, MHC
Murata, H
Erickson, KD
Neu, U
Garcea, RL
Peden, K
Stehle, T
DiMaio, D
AF Magaldi, Thomas G.
Buch, Michael H. C.
Murata, Haruhiko
Erickson, Kimberly D.
Neu, Ursula
Garcea, Robert L.
Peden, Keith
Stehle, Thilo
DiMaio, Daniel
TI Mutations in the GM1 Binding Site of Simian Virus 40 VP1 Alter Receptor
Usage and Cell Tropism
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CERVICAL-CARCINOMA CELLS; PAPILLOMAVIRUS E2 PROTEIN; CHOLERA-TOXIN;
CAPSID PROTEIN; POLYOMAVIRUS VP1; BK VIRUS; GANGLIOSIDE; SV40;
IDENTIFICATION; ENDOCYTOSIS
AB Polyomaviruses are nonenveloped viruses with capsids composed primarily of 72 pentamers of the viral VP1 protein, which forms the outer shell of the capsid and binds to cell surface oligosaccharide receptors. Highly conserved VP1 proteins from closely related polyomaviruses recognize different oligosaccharides. To determine whether amino acid changes restricted to the oligosaccharide binding site are sufficient to determine receptor specificity and how changes in receptor usage affect tropism, we studied the primate polyomavirus simian virus 40 (SV40), which uses the ganglioside GM1 as a receptor that mediates cell binding and entry. Here, we used two sequential genetic screens to isolate and characterize viable SV40 mutants with mutations in the VP1 GM1 binding site. Two of these mutants were completely resistant to GM1 neutralization, were no longer stimulated by incorporation of GM1 into cell membranes, and were unable to bind to GM1 on the cell surface. In addition, these mutant viruses displayed an infection defect in monkey cells with high levels of cell surface GM1. Interestingly, one mutant infected cells with low cell surface GM] more efficiently than wild-type virus, apparently by utilizing a different ganglioside receptor. Our results indicate that a small number of mutations in the GM1 binding site are sufficient to alter ganglioside usage and change tropism, and they suggest that VP1 divergence is driven primarily by a requirement to accommodate specific receptors. In addition, our results suggest that GM1 binding is required for vacuole formation in permissive monkey CV-1 cells. Further study of these mutants will provide new insight into polyomavirus entry, pathogenesis, and evolution.
C1 [Magaldi, Thomas G.; DiMaio, Daniel] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Buch, Michael H. C.; Neu, Ursula; Stehle, Thilo] Univ Tubingen, Interfac Inst Biochem, Tubingen, Germany.
[Murata, Haruhiko; Peden, Keith] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Erickson, Kimberly D.; Garcea, Robert L.] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA.
[Stehle, Thilo] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA.
[DiMaio, Daniel] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA.
[DiMaio, Daniel] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA.
[DiMaio, Daniel] Yale Canc Ctr, New Haven, CT USA.
RP DiMaio, D (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
EM daniel.dimaio@yale.edu
FU National Institutes of Health [T32-HD007149]; National Cancer Institute
[P01 CA016038, R01 CA37667]; Deutsche Forschungsgemeinschaft [SFB-685]
FX T.G.M. was supported in part by a training grant from the National
Institutes of Health (T32-HD007149). This work was supported by grants
from the National Cancer Institute to D.D. (P01 CA016038) and to R.L.G.
(R01 CA37667). T.S., M.H.C.B., and U.N. acknowledge support from the
Deutsche Forschungsgemeinschaft (SFB-685).
NR 54
TC 15
Z9 15
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL
PY 2012
VL 86
IS 13
BP 7028
EP 7042
DI 10.1128/JVI.00371-12
PG 15
WC Virology
SC Virology
GA 961XA
UT WOS:000305501600002
PM 22514351
ER
PT J
AU Coakley, M
Fadiran, EO
Parrish, LJ
Griffith, RA
Weiss, E
Carter, C
AF Coakley, Meghan
Fadiran, Emmanuel Olutayo
Parrish, L. Jo
Griffith, Rachel A.
Weiss, Eleanor
Carter, Christine
TI Dialogues on Diversifying Clinical Trials: Successful Strategies for
Engaging Women and Minorities in Clinical Trials
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID ETHNIC-DIFFERENCES; PHARMACOKINETICS
AB There is mounting scientific evidence pointing to genetic or physiologic distinctions between genders and among racial and ethnic groups that influence disease risk and severity and response to treatment. The diverse enrollment of subjects engaged in clinical trials research is, thus, critical to developing safer and more effective drugs and medical devices. However, in the United States, there are striking disparities in clinical trial participation. To address this problem, the Food and Drug Administration (FDA) Office of Women's Health and the Society for Women's Health Research (SWHR) together convened the 2-day meeting, Dialogues on Diversifying Clinical Trials. The conference was held in Washington, DC, on September 22-23, 2011, and brought together a wide range of speakers from clinical research, industry, and regulatory agencies. Here, we present the major findings discussed at this meeting about female and minority patients and physicians and their willingness to participate in clinical trials and the barriers that sponsors face in recruiting a diverse trial population. We also discuss some recommendations for improving trial diversity through new technologies and greater efficiency in trial regulation and review.
C1 [Fadiran, Emmanuel Olutayo] US FDA, FDA Working Grp, Off Womens Hlth, Silver Spring, MD USA.
[Parrish, L. Jo; Griffith, Rachel A.; Weiss, Eleanor; Carter, Christine] Soc Womens Hlth Res, SWHR Working Grp, Washington, DC USA.
RP Coakley, M (reprint author), 4082 Norbeck Sq Dr, Rockville, MD 20853 USA.
EM meghancoakley@hotmail.com
RI Coakley, Meghan/F-4934-2012
OI Coakley, Meghan/0000-0002-0916-9692
NR 11
TC 15
Z9 15
U1 1
U2 4
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD JUL
PY 2012
VL 21
IS 7
BP 713
EP 716
DI 10.1089/jwh.2012.3733
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 969SP
UT WOS:000306078900002
PM 22747427
ER
PT J
AU Chai, G
Governale, L
McMahon, AW
Trinidad, JP
Staffa, J
Murphy, D
AF Chai, Grace
Governale, Laura
McMahon, Ann W.
Trinidad, James Phillip
Staffa, Judy
Murphy, Dianne
TI Trends of Outpatient Prescription Drug Utilization in US Children,
2002-2010
SO PEDIATRICS
LA English
DT Article
DE ADHD; antibiotic use; children; drug market; drug safety; frequency;
pediatric; trends; utilization
ID APPROPRIATE ANTIBIOTIC USE; PROTON-PUMP INHIBITORS; ACUTE OTITIS-MEDIA;
UNITED-STATES; MEDICATION USE; MANAGEMENT; RESISTANCE
AB OBJECTIVE: To describe trends in outpatient prescription drug utilization in US children and the changes in major areas of pediatric therapeutic use for the years 2002 through 2010.
METHODS: Large prescription databases (the IMS Vector One: National and Total Patient Tracker) were used to examine national drug utilization patterns for the US pediatric population (ages 0-17 years) from 2002 through 2010.
RESULTS: In 2010, a total of 263.6 million prescriptions were dispensed to the US pediatric population, 7% lower than in 2002, while prescriptions dispensed to the adult population increased 22% during the same time. Analysis of pediatric drug utilization trends for the top 12 therapeutic areas in 2010 compared with 2002 showed decreases in systemic antibiotics (-14%), allergies (-61%), pain (-14%), depression (-5%), and cough/cold without expectorant (-42%) prescriptions, whereas asthma (14%), attention-deficit/hyperactivity disorder (46%), and contraceptive (93%) prescriptions increased. In 2010, amoxicillin was the most frequently dispensed prescription in infants (aged 0-23 months) and children (aged 2-11 years). Methylphenidate was the top prescription dispensed to adolescents (aged 12-17 years). Off-label use was identified, particularly for lansoprazole; similar to 358 000 prescriptions were dispensed in 2010 for infants <1 year old.
CONCLUSIONS: Changes in the patterns of pediatric drug utilization were observed from 2002 to 2010. Changes include a decrease in antibiotic use and an increase in attention-deficit/hyperactivity disorder medication use during the examined time. This article provides an overview of pediatric outpatient drug utilization, which could set the stage for further in-depth analyses. Pediatrics 2012; 130: 23-31
C1 [Chai, Grace; Governale, Laura; Trinidad, James Phillip; Staffa, Judy] US PHS, Off Surveillance & Epidemiol, Div Epidemiol 2, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[McMahon, Ann W.; Murphy, Dianne] US FDA, Off Pediat Therapeut, Silver Spring, MD USA.
RP Chai, G (reprint author), US PHS, Off Surveillance & Epidemiol, Div Epidemiol 2, Ctr Drug Evaluat & Res, WO22,Mail Stop 2411,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM grace.chai@fda.hhs.gov
FU US Food and Drug Administration
FX Sponsored by the US Food and Drug Administration and included commercial
proprietary drug utilization data obtained by Food and Drug
Administration under contract.
NR 41
TC 86
Z9 87
U1 1
U2 18
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 JUL
PY 2012
VL 130
IS 1
BP 23
EP 31
DI 10.1542/peds.2011-2879
PG 9
WC Pediatrics
SC Pediatrics
GA 967KH
UT WOS:000305905900039
PM 22711728
ER
PT J
AU Siefert, AW
Jimenez, JH
Koomalsingh, KJ
West, DS
Aguel, F
Shuto, T
Gorman, RC
Gorman, JH
Yoganathan, AP
AF Siefert, Andrew W.
Jimenez, Jorge H.
Koomalsingh, Kevin J.
West, Dustin S.
Aguel, Fernando
Shuto, Takashi
Gorman, Robert C.
Gorman, Joseph H., III
Yoganathan, Ajit P.
TI Dynamic Assessment of Mitral Annular Force Profile in an Ovine Model
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID ANNULOPLASTY RING; CORONARY-SINUS; HEART-DISEASE; VALVE REPAIR;
REGURGITATION; IMPLANTATION; EXPERIENCE; VALIDATION; DEVICE
AB Background. Limited knowledge exists regarding the forces that act on devices implanted in the mitral annulus. Determining the peak magnitudes, directions, rates, variation throughout the cardiac cycle, and change with left ventricular pressure (LVP) will aid in device development and evaluation.
Methods. Novel transducers with the ability to measure forces in the septal-lateral and transverse directions were implanted in six healthy ovine subjects. Forces were measured for cardiac cycles reaching a peak LVP of 90, 125, 150, 175, and 200 mm Hg.
Results. The septal-lateral force was observed to significantly increase from 3.9 +/- 0.8 N (90) to 5.2 +/- 1.0 N (125) p < 0.001, 5.9 +/- 0.9 N (150) p < 0.001, 6.4 +/- 1.2 N (175) p < 0.001, and 6.7 +/- 1.5 N (200 mm Hg) p < 0.001. Similarly, the transverse force was seen to increase from 2.6 +/- 0.6 N (90) to 3.8 +/- 1.0 N (125) p < 0.01, 4.6 +/- 1.3 N (150) p < 0.001, 4.3 +/- 1.2 N (175) p < 0.001, and 3.5 +/- 0.7 N (200 mm Hg) p < 0.05. In comparison, the septal-lateral force was significantly greater than the transverse force at 90 (p < 0.05), 125 (p < 0.05), 175 (p < 0.001), and 200 mm Hg (p < 0.0005).
Conclusions. Annular forces and their variations with LVP through the cardiac cycle are described. The results demonstrate differences in force magnitude and rate for increasing levels of LVP between the septal-lateral and transverse directions. These directional differences have strong implications in the development of future mitral devices.
C1 Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA.
Emory Univ, Atlanta, GA 30322 USA.
Univ Penn, Gorman Cardiovasc Res Grp, Glenolden, PA USA.
US FDA, Div Cardiovasc Devices, Silver Spring, MD USA.
RP Yoganathan, AP (reprint author), 313 Ferst Dr, Atlanta, GA 30332 USA.
EM ajit.yoganathan@bme.gatech.edu
FU US Food and Drug Administration [FDA1061718]; National Heart, Lung and
Blood Institute of the National Institutes of Health, Bethesda, Maryland
[HL63954, HL73021]; American Heart Association, Dallas, Texas
FX This study was supported by a research grant awarded from the US Food
and Drug Administration (FDA1061718) and by grants from the National
Heart, Lung and Blood Institute of the National Institutes of Health,
Bethesda, Maryland (HL63954 and HL73021). Robert Gorman and Joseph
Gorman were supported by individual Established Investigator Awards from
the American Heart Association, Dallas, Texas. We acknowledge the
contributions to and development of the data acquisition platform
provided by members of the Cardiovascular Research Unit in Arhus,
Denmark.
NR 29
TC 9
Z9 9
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD JUL
PY 2012
VL 94
IS 1
BP 59
EP 65
DI 10.1016/j.athoracsur.2012.02.074
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 965XS
UT WOS:000305801600019
PM 22588012
ER
PT J
AU Lando, AM
Fein, SB
Choiniere, CJ
AF Lando, Amy M.
Fein, Sara B.
Choiniere, Conrad J.
TI Awareness of methylmercury in fish and fish consumption among pregnant
and postpartum women and women of childbearing age in the United States
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Fish consumption; Methylmercury; Awareness; Pregnancy; Survey
ID FOOD FREQUENCY QUESTIONNAIRE; MERCURY LEVELS; ADVISORY AWARENESS;
VALIDATION; CHILDREN
AB In 2004, the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) reissued joint advice recommending that pregnant women, nursing mothers, young children, and women who may become pregnant not consume fish high in mercury such as shark, swordfish, king mackerel, and tilefish, and not consume more than 12 ounces (340.2 g) of other lower mercury fish per week. These groups were encouraged to eat up to 12 ounces (340.2 g) of low mercury fish per week to get the health benefits of fish. Using a survey of 1286 pregnant women, 522 postpartum women, and a control group of 1349 non-pregnant/non-postpartum women of childbearing age, this study evaluated awareness of mercury as a problem in food and examined fish consumption levels across groups using regression analysis. We also compared awareness of mercury as a problem in food to awareness of Listeria, dioxins and PCBs. We found that the majority of all 3 groups of women were aware of mercury and that nearly all women in all 3 groups limited consumption consistent with the advice; they ate less than 340.2 g (12 oz) of fish per week and no high mercury fish. Compared with the control group, pregnant and postpartum women were more likely to be aware of mercury as a problem in food, and pregnant women ate less total fish and were less likely to eat fish, to eat more than 340.2 g (12 oz) of fish, and to eat high mercury fish. However, all groups ate much less than the recommended 340.2 g (12 oz) of low mercury fish per week for optimum health benefits. Among women who ate fish, the median intake of total fish was 51.6 g/wk (1.8 oz/wk), 71.4 g/wk (2.5 oz/wk), and 85.3 g/wk (3.0 oz/wk) for the pregnant, postpartum, and control groups, respectively. Thus, it appears that the targeted groups of women were more aware of mercury and were eating fish within the FDA/EPA guidelines, but these women may be missing the health benefits to themselves and their children of eating a sufficient amount of fish. Published by Elsevier Inc.
C1 [Lando, Amy M.; Fein, Sara B.; Choiniere, Conrad J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Choiniere, Conrad J.] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA.
RP Lando, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM amy.lando@fda.hhs.gov; sara.fein@fda.hhs.gov;
conrad.choiniere@fda.hhs.gov
FU Department of Health and Human Services; Food and Drug Administration;
Centers for Disease Control and Prevention; Office on Women's Health;
Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Office of Dietary Supplements; National Cancer Institute;
Maternal and Child Health Bureau of the Health Services and Resources
Administration
FX This data collection was funded by offices and agencies in the
Department of Health and Human Services, including the Food and Drug
Administration, Centers for Disease Control and Prevention, Office on
Women's Health, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, Office of Dietary Supplements, National
Cancer Institute, and the Maternal and Child Health Bureau of the Health
Services and Resources Administration.
NR 34
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Z9 22
U1 1
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD JUL
PY 2012
VL 116
BP 85
EP 92
DI 10.1016/j.envres.2012.04.002
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 959IR
UT WOS:000305306600011
PM 22534145
ER
PT J
AU Rump, LV
Meng, J
Strain, EA
Cao, G
Allard, MW
Gonzalez-Escalona, N
AF Rump, L. V.
Meng, J.
Strain, E. A.
Cao, G.
Allard, M. W.
Gonzalez-Escalona, N.
TI Complete DNA Sequence Analysis of Enterohemorrhagic Escherichia coli
Plasmid pO157_2 in beta-Glucuronidase-Positive E. coli O157:H7 Reveals a
Novel Evolutionary Path
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID LARGE VIRULENCE PLASMID; NUCLEOTIDE-SEQUENCE; STEPWISE EMERGENCE;
O157-H7; STRAINS; O157H7; INFECTION; HEMOLYSIN; ELEMENTS; REGION
AB Strains of enterohemorragic Escherichia coli (EHEC) O157:H7 that are non-sorbitol fermenting (NSF) and beta-glucuronidase negative (GUD(-)) carry a large virulence plasmid, pO157 (>90,000 bp), whereas closely related sorbitol-fermenting (SF) E. coli O157:H- strains carry plasmid pSFO157 (>120,000 bp). GUD(+) NSF O157:H7 strains are presumed to be precursors of GUD(-) NSF O157:H7 strains that also carry pO157. In this study, we report the complete sequence of a novel virulence plasmid, pO157-2 (89,762 bp), isolated from GUD(+) NSF O157:H7 strain G5101. PCR analysis confirmed the presence of pO157-2 in six other strains of GUD(+) NSF O157:H7. pO157-2 carries genes associated with virulence (e.g., hemolysin genes) and conjugation (tra and trb genes) but lacks katP and espP present in pO157. Comparative analysis of the three EHEC plasmids shows that pO157-2 is highly related to pO157 and pSFO157 but not ancestral to pO157. These results indicated that GUD(+) NSF O157:H7 strains might not be direct precursors to GUD(-) NSF O157:H7 as previously proposed but rather have evolved independently from a common ancestor.
C1 [Cao, G.; Allard, M. W.; Gonzalez-Escalona, N.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Strain, E. A.] US FDA, Biostat Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Rump, L. V.; Meng, J.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Meng, J.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA.
RP Gonzalez-Escalona, N (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
EM narjol.gonzalez-escalona@fda.hhs.gov
FU Research Fellowship Program for the Center for Food Safety and Applied
Nutrition; FDA
FX This project was supported by an appointment to L.V.R. through the
Research Fellowship Program for the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Associated Universities through
a contract with the FDA. This project was supported by the FDA Foods
Program Intramural Funds.
NR 31
TC 6
Z9 6
U1 1
U2 6
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 JUL
PY 2012
VL 194
IS 13
BP 3457
EP 3463
DI 10.1128/JB.00197-12
PG 7
WC Microbiology
SC Microbiology
GA 962KE
UT WOS:000305543200018
PM 22522897
ER
PT J
AU Piccardo, P
Cervenak, J
Yakovleva, O
Gregori, L
Pomeroy, K
Cook, A
Muhammad, FS
Seuberlich, T
Cervenakova, L
Asher, DM
AF Piccardo, P.
Cervenak, J.
Yakovleva, O.
Gregori, L.
Pomeroy, K.
Cook, A.
Muhammad, F. S.
Seuberlich, T.
Cervenakova, L.
Asher, D. M.
TI Squirrel Monkeys (Saimiri sciureus) Infected with the Agent of Bovine
Spongiform Encephalopathy Develop Tau Pathology
SO JOURNAL OF COMPARATIVE PATHOLOGY
LA English
DT Article
DE bovine spongiform encephalopathy; prion protein; squirrel monkey; tau
protein
ID CREUTZFELDT-JAKOB-DISEASE; GERSTMANN-STRAUSSLER-SCHEINKER; PRION
PROTEIN; NEUROFIBRILLARY TANGLES; AMYLOID PLAQUES; BSE INFECTION;
VARIANT; MUTATION; TRANSMISSION; BRAIN
AB Squirrel monkeys (Saimiri sciureus) were infected experimentally with the agent of classical bovine spongiform encephalopathy (BSE). Two to four years later, six of the monkeys developed alterations in interactive behaviour and cognition and other neurological signs typical of transmissible spongiform encephalopathy (TSE). At necropsy examination, the brains from all of the monkeys showed pathological changes similar to those described in variant Creutzfeldt Jakob disease (vCJD) of man, except that the squirrel monkey brains contained no PrP-amyloid plaques typical of that disease. Constant neuropathological features included spongiform degeneration, gliosis, deposition of abnormal prion protein (PrPTSE) and many deposits of abnormally phosphorylated tau protein (p-Tau) in several areas of the cerebrum and cerebellum. Western blots showed large amounts of proteinase K-resistant prion protein in the central nervous system. The striking absence of PrP plaques (prominent in brains of cynomolgus macaques [Macaca fascicularis] with experimentally-induced BSE and vCJD and in human patients with vCJD) reinforces the conclusion that the host plays a major role in determining the neuropathology of TSEs. Results of this study suggest that p-Tau, found in the brains of all BSE-infected monkeys, might play a role in the pathogenesis of TSEs. Whether p-Tau contributes to development of disease or appears as a secondary change late in the course of illness remains to be determined. Published by Elsevier Ltd.
C1 [Piccardo, P.; Cervenak, J.; Gregori, L.; Pomeroy, K.; Asher, D. M.] US FDA, Lab Bacterial & TSE Agents, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Piccardo, P.] Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Easter Bush, Midlothian, Scotland.
[Yakovleva, O.; Cervenakova, L.] Amer Red Cross, Transmissible Dis Dept, Jerome H Holland Lab Biomed Sci, Washington, DC 20006 USA.
[Cook, A.; Muhammad, F. S.] BIOQUAL Inc, Rockville, MD USA.
[Seuberlich, T.] Univ Bern, Vetsuisse Fac, NeuroCtr, Natl & OIE Reference Labs BSE & Scrapie, Bern, Switzerland.
RP Piccardo, P (reprint author), US FDA, Lab Bacterial & TSE Agents, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
EM pedro.piccardo@fda.hhs.gov
FU NIH-NIAID [Y1-AI-4893-02]; FDA [224-05-1307]
FX We thank D. Heim, Federal Veterinary Office, Bern, Switzerland, for
assistance in obtaining the BSE inoculum and S. Harbaugh and J. Harbaugh
(Bioqual Inc.) for dedicated care of the animals. This work was funded
by NIH-NIAID agreement No. Y1-AI-4893-02 with FDA (agreement No.
224-05-1307): Potential of Candidate Cell Substrates for Vaccine
Production to Propagate the Agents of Transmissible Spongiform
Encephalopathies; main agreement title: Assessing Safety of Cell
Substrates and Vaccine Components.
NR 66
TC 3
Z9 3
U1 0
U2 10
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0021-9975
J9 J COMP PATHOL
JI J. Comp. Pathol.
PD JUL
PY 2012
VL 147
IS 1
BP 84
EP 93
DI 10.1016/j.jcpa.2011.09.004
PG 10
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA 963CB
UT WOS:000305596600012
PM 22018806
ER
PT J
AU Anez, G
Grinev, A
Winkelman, V
Stramer, SL
Rios, M
AF Anez, G.
Grinev, A.
Winkelman, V
Stramer, S. L.
Rios, M.
TI DYNAMICS IN EVOLUTION OF WEST NILE VIRUS FROM HUMAN INFECTIONS IN THE US
AFTER 2006
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Anez, G.; Grinev, A.; Rios, M.] US FDA, Bethesda, MD 20014 USA.
[Winkelman, V] Creat Testing Solut MDL Dept, Tempe, AZ USA.
[Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 187
EP 187
PG 1
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410601153
ER
PT J
AU Anez, G
Heisey, DAR
Espina, LM
Stramer, SL
Rios, M
AF Anez, G.
Heisey, D. A. R.
Espina, L. M.
Stramer, S. L.
Rios, M.
TI PHYLOGENETIC AND TIME-SCALE ANALYSIS OF DENGUE VIRUS TYPES 1 AND 4
CIRCULATING IN BLOOD DONORS FROM PUERTO RICO AND KEY WEST, FLORIDA,
DURING 2010 EPIDEMICS
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Anez, G.; Heisey, D. A. R.; Espina, L. M.; Rios, M.] US FDA, Bethesda, MD 20014 USA.
[Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 187
EP 187
PG 1
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410601152
ER
PT J
AU Agrawal, A
Godar, DE
AF Agrawal, Anant
Godar, Dianne E.
TI Simultaneous Detection and Semiquantification of DNA Damage in Normal
and Apoptotic Cells: Triple-Immunofluorescent Labeling Using DAPI,
Antibodies, and TUNEL
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE apoptosis; cyclobutane pyrimidine dimers; DNA damage;
immunofluorescence; immunohistochemistry; 6-4 photoproducts; TUNEL;
ultraviolet
ID FRAGMENTATION; RADIATION; SECTIONS; DIMERS; REPAIR; ASSAY
AB We developed a triple-labeling immunofluorescence technique that simultaneously identifies total DNA (DAPI), DNA damage (antibodies), and dead cells [terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells] and a method that semiquantifies DNA damage in paraffin-embedded tissues. Using this technique in combination with our analysis method, scientists can now simultaneously detect and compare the relative amounts of DNA damage of almost any kind (except single-strand and double-strand breaks), using indirect fluorescent antibody labeling, in both normal and dying cells of different tissues. Simultaneous labeling of DNA damage and dead or TUNEL-positive cells can reduce processing costs and analysis time, and can lead to discoveries concerning how cells die from different DNA damages. We used increasing doses of UV (290 to 400 nm) radiation to create DNA damage in the form of cyclobutane pyrimidine dimers and 6-4 photoproducts that kill some of the cells in 3-dimensional tissue-engineered skin and vaginal samples. We describe a protocol that reliably detects and semiquantifies DNA damage in both normal and apoptotic cells. We show this triple-labeling immunofluorescence technique and analysis method yields linear UV dose response curves for damage to DNA bases that allows semiquantification of cyclobutane pyrimidine dimers and calculation of its repair rate (T = 1 and 24 h), whereas TUNEL allows quantification of the number of apoptotic cells. Scientists can now create beautiful fluorescent pictures that simultaneously detect DNA damage in both normal and apoptotic cells to assess and semiquantify the damage to understand better how different insults lead to the cell's demise.
C1 [Agrawal, Anant; Godar, Dianne E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,HFZ 120, Silver Spring, MD 20993 USA.
EM Dianne.Godar@FDA.HHS.GOV
OI GODAR, DIANNE/0000-0002-7690-5223
NR 15
TC 3
Z9 4
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1062-3345
J9 APPL IMMUNOHISTO M M
JI Appl. Immunohistochem.
PD JUL
PY 2012
VL 20
IS 4
BP 402
EP 409
PG 8
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 963DT
UT WOS:000305601000014
PM 22710818
ER
PT J
AU Nakashima, H
Miyake, K
Clark, CR
Bekisz, J
Finbloom, J
Husain, SR
Baron, S
Puri, RK
Zoon, KC
AF Nakashima, Hideyuki
Miyake, Kotaro
Clark, Christopher R.
Bekisz, Joseph
Finbloom, Joel
Husain, Syed R.
Baron, Samuel
Puri, Raj K.
Zoon, Kathryn C.
TI Potent antitumor effects of combination therapy with IFNs and monocytes
in mouse models of established human ovarian and melanoma tumors
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE IFNs; Monocytes; Combination therapy; M1 macrophages; Mouse model
ID MACROPHAGE ACTIVATION; INTERFERON-ALPHA; ADOPTIVE IMMUNOTHERAPY;
CANCER-PATIENTS; NITRIC-OXIDE; CELLS; IMMUNITY; HETEROGENEITY;
POPULATION; APOPTOSIS
AB Interferon-activated monocytes are known to exert cytocidal activity against tumor cells in vitro. Here, we have examined whether a combination of IFN-alpha 2a and IFN-gamma and human monocytes mediate significant antitumor effects against human ovarian and melanoma tumor xenografts in mouse models. OVCAR-3 tumors were treated i.t. with monocytes alone, IFN-alpha 2a and IFN-gamma alone or combination of all three on day 0, 15 or 30 post-tumor implantation. Mice receiving combination therapy beginning day 15 showed significantly reduced tumor growth and prolonged survival including complete regression in 40% mice. Tumor volumes measured on day 80 in mice receiving combination therapy (206 mm(3)) were significantly smaller than those of mice receiving the IFNs alone (1,041 mm(3)), monocytes alone (1,111 mm(3)) or untreated controls (1,728 mm(3)). Similarly, combination therapy with monocytes and IFNs of much larger tumor also inhibited OVCAR-3 tumor growth. Immunohistochemistry studies showed a large number of activated macrophages (CD31(+)/CD68(+)) infiltrating into OVCAR-3 tumors and higher densities of IL-12, IP10 and NOS2, markers of M1 (classical) macrophages in tumors treated with combination therapy compared to the controls. Interestingly, IFNs-activated macrophages induced apoptosis of OVCAR-3 tumor cells as monocytes alone or IFNs alone did not mediate significant apoptosis. Similar antitumor activity was observed in the LOX melanoma mouse model, but not as profound as seen with the OVCAR-3 tumors. Administration of either mixture of monocytes and IFN-alpha 2a or monocytes and IFN-gamma did not inhibit Lox melanoma growth; however, a significant inhibition was observed when tumors were treated with a mixture of monocytes, IFN-alpha 2a and IFN-gamma. These results indicate that monocytes and both IFN-alpha 2a and IFN-gamma may be required to mediate profound antitumor effect against human ovarian and melanoma tumors in mouse models.
C1 [Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Miyake, Kotaro; Clark, Christopher R.; Bekisz, Joseph; Finbloom, Joel; Baron, Samuel; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Food & Drug Adm,Ctr Biol Evaluat & Res, Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov; kzoon@niaid.nih.gov
FU Intramural NIH HHS [ZIA AI001038-04]
NR 52
TC 7
Z9 7
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD JUL
PY 2012
VL 61
IS 7
BP 1081
EP 1092
DI 10.1007/s00262-011-1152-x
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA 962DM
UT WOS:000305519700012
PM 22159517
ER
PT J
AU Zhao, P
Rowland, M
Huang, SM
AF Zhao, P.
Rowland, M.
Huang, S-M
TI Best Practice in the Use of Physiologically Based Pharmacokinetic
Modeling and Simulation to Address Clinical Pharmacology Regulatory
Questions
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID DRUG DEVELOPMENT
AB Physiologically based pharmacokinetic (PBPK) models are increasingly used by drug developers to evaluate the effect of patient factors on drug exposure. Between June 2008 and December 2011, the Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) received 25 submissions containing PBPK analyses. This report summarizes the essential content of a PBPK analysis needed in a regulatory submission for the purpose of addressing clinical pharmacology questions.
C1 [Zhao, P.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Rowland, M.] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England.
[Rowland, M.] Univ Calif San Francisco, Sch Pharm, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
[Rowland, M.] Univ Calif San Francisco, Sch Med, Dept Bioengn & Therapeut Sci, San Francisco, CA USA.
RP Zhao, P (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM ping.zhao@fda.hhs.gov
NR 5
TC 60
Z9 62
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUL
PY 2012
VL 92
IS 1
BP 17
EP 20
DI 10.1038/clpt.2012.68
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 962ZL
UT WOS:000305589800007
PM 22713733
ER
PT J
AU Dickey, JS
Rao, VA
AF Dickey, J. S.
Rao, V. A.
TI Current and Proposed Biomarkers of Anthracycline Cardiotoxicity in
Cancer: Emerging Opportunities in Oxidative Damage and Autophagy
SO CURRENT MOLECULAR MEDICINE
LA English
DT Review
DE Autophagy; doxorubicin; oxidative stress; protein oxidation; reactive
oxygen species; troponin
ID MITOCHONDRIAL NADH DEHYDROGENASE; ACUTE LYMPHOBLASTIC-LEUKEMIA;
TRANSCRIPTION FACTOR NRF2; METASTATIC BREAST-CANCER; L-ASPARAGINASE
THERAPY; LONG-TERM SURVIVORS; OF-THE-LITERATURE; PROTEIN OXIDATION;
CARDIAC INJURY; SYMPTOMATIC CARDIOTOXICITY
AB A biomarker is defined as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or biological responses to a therapeutic intervention". Biomarkers can be utilized to detect disease, evaluate treatment risks, or determine treatment effectiveness. In the case of cancer, anthracyclines such as doxorubicin are front-line therapy to treat a number of different malignancies including breast cancer. However, a significant fraction of patients experience drug-induced cardiotoxicity. This toxicity is dose-limiting and can cause long-term morbidity or mortality. There is an unmet medical need to identify patients who are at risk for doxorubicin-induced cardiotoxicity, to detect cardiac damage early so that patient risk can be minimized, and to monitor the success of cardioprotective strategies. Therefore, doxorubicin treatment of cancer is an excellent example of the need for biomarkers to indicate drug safety in addition to drug efficacy. In this review we will discuss the mechanism of doxorubicin-associated cardiotoxicity, as well as other cancer therapies that induce cardiac toxicity by causing oxidative damage. We will also evaluate established and proposed biomarkers for cardiotoxicity based on our evolving knowledge of oxidative damage and subsequent autophagy. Finally, we will discuss advantages of combining oxidative damage- and autophagy-based protein biomarkers with current biomarkers such as troponins to facilitate early detection and mitigation of cardiotoxicity induced by cancer therapeutic agents.
C1 [Dickey, J. S.; Rao, V. A.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Biochem Lab, Bethesda, MD 20892 USA.
RP Rao, VA (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Biochem Lab, 29 Lincoln Dr,Bldg 29A,Room 2B-24, Bethesda, MD 20892 USA.
EM ashutosh.rao@fda.hhs.gov
FU US Food and Drug Administration; NIH National Cancer Institute
Interagency Oncology Task Force fellowship
FX This work was supported by intramural funding of the US Food and Drug
Administration and by funding from the NIH National Cancer Institute
Interagency Oncology Task Force fellowship. We would like to thank Dr.
Emily Shacter (FDA) for advice and helpful discussions. We would also
like to thank Dr. Melanie Simpson (SAIC-Frederick) for critical reading
of the manuscript.
NR 106
TC 7
Z9 7
U1 1
U2 9
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1566-5240
J9 CURR MOL MED
JI Curr. Mol. Med.
PD JUL
PY 2012
VL 12
IS 6
BP 763
EP 771
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 962XP
UT WOS:000305583400010
PM 22292442
ER
PT J
AU Wang, LL
Abbasi, F
Ornatsky, O
Cole, KD
Misakian, M
Gaigalas, AK
He, HJ
Marti, GE
Tanner, S
Stebbings, R
AF Wang, Lili
Abbasi, Fatima
Ornatsky, Olga
Cole, Kenneth D.
Misakian, Martin
Gaigalas, Adolfas K.
He, Hua-Jun
Marti, Gerald E.
Tanner, Scott
Stebbings, Richard
TI Human CD4(+) lymphocytes for antigen quantification: Characterization
using conventional flow cytometry and mass cytometry
SO CYTOMETRY PART A
LA English
DT Article
DE quantitative multiparameter flow cytometry; CyTOF (TM) mass cytometry;
antibody bound per cell; cryopreserved peripheral blood mononuclear
cells; whole blood; lyophilized peripheral blood mononuclear cell;
Cyto-Trol; CD4 expression; cell membrane intactness; cell diameter;
fixation effect
ID T-LYMPHOCYTES; EXPRESSION; LEUKEMIA; IMMUNOFLUORESCENCE; SPECTROMETRY;
QUANTITATION; FIXATION; DENSITY; LYSIS
AB To transform the linear fluorescence intensity scale obtained with fluorescent microspheres to an antibody bound per cell (ABC) scale, a biological cell reference material is needed. Optimally, this material should have a reproducible and tight ABC value for the expression of a known clinical reference biomarker. In this study, we characterized commercially available cryopreserved peripheral blood mononuclear cells (PBMCs) and two lyophilized PBMC preparations, Cyto-Trol and PBMCNational Institute for Biological Standard and Control (NIBSC) relative to freshly prepared PBMC and whole blood samples. It was found that the ABC values for CD4 expression on cryopreserved PBMC were consistent with those of freshly obtained PBMC and whole blood samples. By comparison, the ABC value for CD4 expression on Cyto-Trol is lower and the value on PBMCNIBSC is much lower than those of freshly prepared cell samples using both conventional flow cytometry and CyTOF (TM) mass cytometry. By performing simultaneous surface and intracellular staining measurements on these two cell samples, we found that both cell membranes are mostly intact. Moreover, CD4+ cell diameters from both lyophilized cell preparations are smaller than those of PBMC and whole blood. This could result in steric interference in antibody binding to the lyophilized cells. Further investigation of the fixation effect on the detected CD4 expression suggests that the very low ABC value obtained for CD4+ cells from lyophilized PBMCNIBSC is largely due to paraformaldehyde fixation; this significantly decreases available antibody binding sites. This study provides confirmation that the results obtained from the newly developed mass cytometry are directly comparable to the results from conventional flow cytometry when both methods are standardized using the same ABC approach. Published 2012 Wiley Periodicals, Inc.
C1 [Wang, Lili; Cole, Kenneth D.; Misakian, Martin; Gaigalas, Adolfas K.; He, Hua-Jun] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA.
[Abbasi, Fatima] CBER FDA, Div Cell & Gene Therapies, Lab Stem Cell Biol, Cellular & Tissue Therapy Branch,Off Cellular Tis, Bethesda, MD 20892 USA.
[Ornatsky, Olga; Tanner, Scott] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada.
[Ornatsky, Olga; Tanner, Scott] DVS Sci Inc, Richmond Hill, ON L4S 1Z5, Canada.
[Marti, Gerald E.] CDRH FDA, Div Immunol & Hematol Devices, Heme Path Branch, Off In Vitro Diagnost Device Evaluat & Safety, Silver Spring, MD 20993 USA.
[Stebbings, Richard] Natl Inst Biol Stand & Controls, Biotherapeut Grp, Potters Bar EN6 3QG, Herts, England.
RP Wang, LL (reprint author), NIST, Div Biochem Sci, 100 Bur Dr,Stop 8312, Gaithersburg, MD 20899 USA.
EM lili.wang@nist.gov
RI Stebbings, Richard/E-2117-2013
OI Stebbings, Richard/0000-0001-9628-2708
NR 28
TC 24
Z9 24
U1 0
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD JUL
PY 2012
VL 81A
IS 7
BP 567
EP 575
DI 10.1002/cyto.a.22060
PG 9
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 962PZ
UT WOS:000305558700007
PM 22539147
ER
PT J
AU Haigney, MC
Gray, RA
AF Haigney, Mark C.
Gray, Richard A.
TI Assessing repolarization: Alternate hypotheses
SO HEART RHYTHM
LA English
DT Editorial Material
ID T-WAVE ALTERNANS; VENTRICULAR-ARRHYTHMIAS; ELECTRICAL ALTERNANS;
DISCORDANT ALTERNANS; FIBRILLATION; MECHANISMS; TISSUE
C1 [Haigney, Mark C.] Uniformed Serv Univ Hlth Sci, Dept Med, Div Cardiol, Bethesda, MD 20814 USA.
[Gray, Richard A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Haigney, MC (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, Div Cardiol, A3060,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM mhaigney@usuhs.edu
RI Gray, Richard/F-3916-2015
OI Gray, Richard/0000-0003-2798-6378
NR 20
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD JUL
PY 2012
VL 9
IS 7
BP 1038
EP 1040
DI 10.1016/j.hrthm.2012.03.023
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 963JP
UT WOS:000305616900004
PM 22440156
ER
PT J
AU Gendel, SM
AF Gendel, Steven M.
TI Comparison of international food allergen labeling regulations
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Food allergy; Food labeling; Allergy labeling; Allergen regulation; Food
safety
AB Food allergy is a significant public health issue worldwide. Regulatory risk management strategies for allergic consumers have focused on providing information about the presence of food allergens through label declarations. A number of countries and regulatory bodies have recognized the importance of providing this information by enacting laws, regulations or standards for food allergen labeling of "priority allergens". However, different governments and organizations have taken different approaches to identifying these "priority allergens" and to designing labeling declaration regulatory frameworks. The increasing volume of the international food trade suggests that there would be value in supporting sensitive consumers by harmonizing (to the extent possible) these regulatory frameworks. As a first step toward this goal, an inventory of allergen labeling regulations was assembled and analyzed to identify commonalities, differences, and future needs. Published by Elsevier Inc.
C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Gendel, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM steven.gendel@fda.hhs.gov
NR 22
TC 43
Z9 48
U1 2
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD JUL
PY 2012
VL 63
IS 2
BP 279
EP 285
DI 10.1016/j.yrtph.2012.04.007
PG 7
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 960IJ
UT WOS:000305380900007
PM 22565206
ER
PT J
AU Tryndyak, VP
Latendresse, JR
Montgomery, B
Ross, SA
Beland, FA
Rusyn, I
Pogribny, IP
AF Tryndyak, Volodymyr P.
Latendresse, John R.
Montgomery, Beverly
Ross, Sharon A.
Beland, Frederick A.
Rusyn, Ivan
Pogribny, Igor P.
TI Plasma microRNAs are sensitive indicators of inter-strain differences in
the severity of liver injury induced in mice by a choline- and
folate-deficient diet
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Inter-individual differences; microRNAs; Mouse; Nonalcoholic fatty liver
disease
ID NONALCOHOLIC STEATOHEPATITIS; HEPATOCELLULAR-CARCINOMA; CIRCULATING
MICRORNAS; METABOLIC SYNDROME; ANIMAL-MODELS; UNITED-STATES;
HEPATITIS-C; DISEASE; EXPRESSION; BIOMARKERS
AB MicroRNAs (miRNAs) are a class of small, conserved, tissue-specific regulatory non-coding RNAs that modulate a variety of biological processes and play a fundamental role in the pathogenesis of major human diseases, including nonalcoholic fatty liver disease (NAFLD). However, the association between inter-individual differences in susceptibility to NAFLD and altered miRNA expression is largely unknown. In view of this, the goals of the present study were (i) to determine whether or not individual differences in the extent of NAFLD-induced liver injury are associated with altered miRNA expression, and (ii) assess if circulating blood miRNAs may be used as potential biomarkers for the noninvasive evaluation of the severity of NAFLD. A panel of seven genetically diverse strains of inbred male mice (A/J, C57BL/6J, C3H/HeJ, 129S/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ) were fed a choline- and folate-deficient (CFD) diet for 12 weeks. This diet induced liver injury in all mouse strains; however, the extent of NAFLD-associated pathomorphological changes in the livers was strain-specific, with A/J, C57BL/6J, and C3H/HeJ mice being the least sensitive and WSB/EiJ mice being the most sensitive. The morphological changes in the livers were accompanied by differences in the levels of hepatic and plasma miRNAs. The levels of circulating miR-34a, miR-122, miR-181a, miR-192, and miR-200b miRNAs were significantly correlated with a severity of NAFLD-specific liver pathomorphological features, with the strongest correlation occurring with miR-34a. These observations suggest that the plasma levels of miRNAs may be used as biomarkers for noninvasive monitoring the extent of NAFLD-associated liver injury and susceptibility to NAFLD. Published by Elsevier Inc.
C1 [Tryndyak, Volodymyr P.; Montgomery, Beverly; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Latendresse, John R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
RP Pogribny, IP (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 ES015241]
NR 39
TC 38
Z9 39
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 JUL 1
PY 2012
VL 262
IS 1
BP 52
EP 59
DI 10.1016/j.taap.2012.04.018
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 960IW
UT WOS:000305382200006
PM 22561871
ER
PT J
AU Sorbello, A
Jones, SC
Carter, W
Struble, K
Boucher, R
Truffa, M
Birnkrant, D
Gada, N
Camilli, S
Chan, I
Dallas, S
Scales, T
Kosko, R
Thompson, E
Goodman, J
Francis, H
Dal Pan, G
AF Sorbello, Alfred
Jones, S. Christopher
Carter, Wendy
Struble, Kimberly
Boucher, Robert
Truffa, Melissa
Birnkrant, Debra
Gada, Neha
Camilli, Sara
Chan, Irene
Dallas, Scott
Scales, Twanda
Kosko, Robert
Thompson, Elizabeth
Goodman, Jesse
Francis, Henry
Dal Pan, Gerald
TI Emergency Use Authorization for Intravenous Peramivir: Evaluation of
Safety in the Treatment of Hospitalized Patients Infected With 2009 H1N1
Influenza A Virus
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; UNITED-STATES; A(H1N1)
AB Background. On 23 October 2009, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for intravenous peramivir, an unapproved antiviral, to treat suspected or confirmed 2009 H1N1 influenza A virus infection. Eligible hospitalized patients were unresponsive to or unable to tolerate available antivirals or lacked dependable oral or inhaled drug delivery routes. The EUA required healthcare providers to report medication errors, selected adverse events (AEs), serious AEs, and deaths to the FDA.
Methods. An FDA safety team analyzed reports submitted to the Adverse Event Reporting System (AERS) and sought follow-up in selected cases.
Results. The FDA received AERS reports for 344 patients (including 28 children and 3 pregnant women). Many patients were critically ill on mechanical ventilation (41%) and renal replacement therapies (19%); 38% had received oseltamivir. The most frequently reported serious AEs by MedDRA preferred term were death (15%), H1N1 influenza (8%), respiratory failure (8%), acute renal failure (7%), and acute respiratory distress syndrome (7%). Six medication errors were reported. Most deaths occurred among patients who were obese, immunosuppressed, aged >65 years, or received oseltamivir. Rash was the only treatment-emergent AE attributable to peramivir. Influenza severity, comorbidities, and concomitant medications confounded additional peramivir AE assessments. Missing clinical and laboratory data precluded evaluation of some reports.
Conclusions. Many peramivir recipients under the EUA were critically ill and at risk for influenza-related complications. The safety data were insufficient to assess whether peramivir affected outcome or caused adverse reactions other than rash. Clinical trials in hospitalized patients with serious influenza infections should provide additional information.
C1 [Sorbello, Alfred; Jones, S. Christopher; Truffa, Melissa; Gada, Neha; Camilli, Sara; Chan, Irene; Dallas, Scott; Scales, Twanda; Francis, Henry; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Carter, Wendy; Struble, Kimberly; Birnkrant, Debra; Kosko, Robert; Thompson, Elizabeth] US FDA, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Goodman, Jesse] US FDA, Off Chief Scientist, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Boucher, Robert] Lebanon VA Med Ctr, Lebanon, PA USA.
RP Sorbello, A (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM alfred.sorbello@fda.hhs.gov
NR 15
TC 17
Z9 18
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2012
VL 55
IS 1
BP 1
EP 7
DI 10.1093/cid/cis351
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 956KM
UT WOS:000305088500002
PM 22491501
ER
PT J
AU Loharikar, A
Newton, A
Rowley, P
Wheeler, C
Bruno, T
Barillas, H
Pruckler, J
Theobald, L
Lance, S
Brown, JM
Barzilay, EJ
Arvelo, W
Mintz, E
Fagan, R
AF Loharikar, Anagha
Newton, Anna
Rowley, Patricia
Wheeler, Charlotte
Bruno, Tami
Barillas, Haroldo
Pruckler, James
Theobald, Lisa
Lance, Susan
Brown, Jeffrey M.
Barzilay, Ezra J.
Arvelo, Wences
Mintz, Eric
Fagan, Ryan
TI Typhoid Fever Outbreak Associated With Frozen Mamey Pulp Imported From
Guatemala to the Western United States, 2010
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID FLORIDA; TRAVEL
AB Background. Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad.
Methods. We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed.
Results. We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida.
Conclusions. Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.
C1 [Loharikar, Anagha] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA.
[Newton, Anna; Pruckler, James; Theobald, Lisa; Barzilay, Ezra J.; Mintz, Eric; Fagan, Ryan] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA.
[Lance, Susan] Ctr Dis Control & Prevent, US Food & Drug Adm Liaison, Atlanta, GA 30333 USA.
[Newton, Anna] Atlanta Res & Educ Fdn, Atlanta, GA USA.
[Rowley, Patricia; Bruno, Tami] Nevada Dept Hlth, Las Vegas, NV USA.
[Wheeler, Charlotte] Calif Dept Publ Hlth, Infect Dis Branch, Richmond, CA USA.
[Brown, Jeffrey M.] US FDA, College Pk, MD USA.
[Barillas, Haroldo] Guatemalan Minist Publ Hlth & Welf, Field Epidemiol Training Program, Guatemala City, Guatemala.
[Arvelo, Wences] Reg Off Cent Amer & Panama, Int Emerging Infect Program, Ctr Dis Control & Prevent, Guatemala City, Guatemala.
RP Loharikar, A (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, 1600 Clifton Rd NE,MS A38, Atlanta, GA 30333 USA.
EM anagha.loharikar@gmail.com
FU Centers for Disease Control and Prevention (CDC)
FX This work was supported by the Centers for Disease Control and
Prevention (CDC). The CDC employs some of the authors, who were involved
in study design and analysis of data, and some of the authors are
employed by local and state health departments.
NR 15
TC 6
Z9 6
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2012
VL 55
IS 1
BP 61
EP 66
DI 10.1093/cid/cis296
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 956KM
UT WOS:000305088500010
PM 22423132
ER
PT J
AU Marcus, KA
Sorbello, A
Truffa, M
Williams, J
Raine, JM
Powderly, WG
AF Marcus, Kendall A.
Sorbello, Alfred
Truffa, Melissa
Williams, Julie
Raine, June M.
Powderly, William G.
TI Current advances in pharmacovigilance in the USA and Europe: meeting the
challenges of safety monitoring in HIV
SO CURRENT OPINION IN HIV AND AIDS
LA English
DT Review
DE antiretroviral therapy; HIV; long-term toxicity; pharmacovigilance;
treatment
ID RECONSTITUTION INFLAMMATORY SYNDROME; COMBINATION ANTIRETROVIRAL
THERAPY; MYOCARDIAL-INFARCTION; INFECTED PATIENTS; PROTEASE INHIBITORS;
ADVERSE EVENTS; SUPPRESSED HIV; RISK; ABACAVIR; LIPODYSTROPHY
AB Purpose of review
The success of antiretroviral therapy in HIV disease comes currently with the realization that patients are committed to life-long treatment, which raises the possibility of long-term toxicity. Such long-term side effects may not be identified in initial clinical trials requiring, therefore, a different approach to monitoring patients over time - a pharmacovigilance approach.
Recent findings
Several key issues in long-term management of HIV infection have been addressed by a pharmacovigilance approach - including unusual and rare side effects and elucidation of emerging toxicities such as cardiovascular, bone and renal disease. Recent changes in legislation in the USA and Europe are aimed to strengthen pharmacovigilance in developed countries.
Summary
HIV infection and its treatment provide an important example of the role of pharmacovigilance. As clinical trials can rarely address the question of long-term tolerability, effective pharmacovigilance programs are and will remain essential.
C1 [Marcus, Kendall A.] US FDA, Off New Drugs, Silver Spring, MD USA.
[Sorbello, Alfred; Truffa, Melissa] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA.
[Williams, Julie; Raine, June M.] Med & Healthcare Prod Regulatory Agcy, London, England.
[Powderly, William G.] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland.
RP Powderly, WG (reprint author), Univ Coll Dublin, Hlth Sci Ctr, UCD Sch Med & Med Sci, Dublin 4, Ireland.
EM Bill.powderly@ucd.ie
NR 53
TC 4
Z9 4
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1746-630X
J9 CURR OPIN HIV AIDS
JI Curr. Opin. HIV AIDS
PD JUL
PY 2012
VL 7
IS 4
BP 292
EP 298
DI 10.1097/COH.0b013e328354dcac
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 957EK
UT WOS:000305141300002
PM 22647589
ER
PT J
AU Zou, P
Zheng, N
Yang, YS
Yu, LX
Sun, DX
AF Zou, Peng
Zheng, Nan
Yang, Yongsheng
Yu, Lawrence X.
Sun, Duxin
TI Prediction of volume of distribution at steady state in humans:
comparison of different approaches
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE allometric scaling; in silico prediction; physiologically based
prediction; tissue composition-based prediction; tissue-plasma partition
coefficient; volume of distribution at steady state
ID PLASMA PARTITION-COEFFICIENTS; INTRAVENOUS PHARMACOKINETIC PARAMETERS;
COMPOSITION-BASED MODEL; WEAKLY BASIC DRUGS; TISSUE DISTRIBUTION;
IN-VIVO; V-SS; ENTEROHEPATIC CIRCULATION; DISTRIBUTION VALUES;
ORGANIC-CHEMICALS
AB Introduction: Reasonable prediction of volume of distribution at steady state (Vd(ss)) in humans is required for screening drug candidates, evaluating drug safety, and estimating first-in-human doses.
Areas covered: This review summarizes methods for the prediction of human Vd(ss) and tissue plasma partition coefficients (K-p). The methods reviewed includes allometric scaling, physiologically based models, correlation with animal Vd(ss) and in silico models. The assumptions, equations, input data required, advantages, and limitations of each approach are discussed. Due to the variations among test datasets, some studies have reached inconsistent conclusions. Hence, a comprehensive comparison of various approaches using a large and exhaustive dataset is warranted to address the controversies in human Vd(ss) prediction.
Expert opinion: Compared with allometric scaling, the Oie-Tozer method and correlations between human and animal Vd(ss) are more accurate. All the three methods can be used for accurate predictions of human Vd(ss) just prior to first-in-human studies. Although in vivo animal data are not required, tissue composition-based approaches and inter-tissue correlation of K-p provide reasonable predictive accuracies and are promising for physiologically based pharmaco-kinetic modeling. The in silico models are most suitable for high-throughput screening of compounds, which are at an early stage of development.
C1 [Zou, Peng; Zheng, Nan; Sun, Duxin] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA.
[Yang, Yongsheng] US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Yu, Lawrence X.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA.
RP Sun, DX (reprint author), Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, 428 Church St, Ann Arbor, MI 48109 USA.
EM duxins@umich.edu
RI Zou, Peng/J-9300-2015; Yu, Lawrence/L-6280-2016
FU National Institutes of Health [RO1 CA120023]; University of Michigan
Cancer Center (Munn); University of Michigan Cancer Center
FX This work was partially supported by the National Institutes of Health
(RO1 CA120023), as well as by the University of Michigan Cancer Center
Research Grant (Munn) and the University of Michigan Cancer Center Core
Grant. LX Yu and Y Yang are U.S. FDA employees. No official support or
endorsement by the US FDA is intended or should be inferred.
NR 66
TC 8
Z9 8
U1 0
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1742-5255
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD JUL
PY 2012
VL 8
IS 7
BP 855
EP 872
DI 10.1517/17425255.2012.682569
PG 18
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 959CB
UT WOS:000305286600006
PM 22591253
ER
PT J
AU Yan, QQ
Condell, O
Power, K
Butler, F
Tall, BD
Fanning, S
AF Yan, Q. Q.
Condell, O.
Power, K.
Butler, F.
Tall, B. D.
Fanning, S.
TI Cronobacter species (formerly known as Enterobacter sakazakii) in
powdered infant formula: a review of our current understanding of the
biology of this bacterium
SO JOURNAL OF APPLIED MICROBIOLOGY
LA English
DT Review
DE Cronobacter; detection protocols; manufacturing environment control;
powdered infant formula; taxonomy
ID MICROVASCULAR ENDOTHELIAL-CELLS; LIPOPOLYSACCHARIDE O-ANTIGEN;
INTENSIVE-CARE-UNIT; MEMBRANE PROTEIN-A; DUBLINENSIS SP-NOV; 16S
RIBOSOMAL-RNA; REAL-TIME-PCR; ESCHERICHIA-COLI; ENVIRONMENTAL-SAMPLES;
TRANS-CINNAMALDEHYDE
AB Cronobacter species (formerly known as Enterobacter sakazakii) are opportunistic pathogens that can cause necrotizing enterocolitis, bacteraemia and meningitis, predominantly in neonates. Infection in these vulnerable infants has been linked to the consumption of contaminated powdered infant formula (PIF). Considerable research has been undertaken on this organism in the past number of years which has enhanced our understanding of this neonatal pathogen leading to improvements in its control within the PIF production environment. The taxonomy of the organism resulted in the recognition of a new genus, Cronobacter, which consists of seven species. This paper presents an up-to-date review of our current knowledge of Cronobacter species. Taxonomy, genome sequencing, current detection protocols and epidemiology are all discussed. In addition, consideration is given to the control of this organism in the manufacturing environment, as a first step towards reducing the occurrence of this pathogen in PIF.
C1 [Yan, Q. Q.; Condell, O.; Power, K.; Fanning, S.] Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, UCD Ctr Food Safety, WHO Collaborating Ctr Res Reference & Training Cr, Dublin 4, Ireland.
[Butler, F.] Univ Coll Dublin, UCD Sch BioSyst Engn, Dublin 4, Ireland.
[Tall, B. D.] US FDA, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, OARSA,MOD Facil 1,Virulence Mechanisms Branch HFS, Laurel, MD 20708 USA.
RP Fanning, S (reprint author), Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, UCD Ctr Food Safety, UCD Vet Sci Ctr, Dublin 4, Ireland.
EM sfanning@ucd.ie
OI Fanning, Seamus/0000-0002-1922-8836; Tall, Ben/0000-0003-0399-3629;
Butler, Francis/0000-0003-3925-5863
NR 117
TC 46
Z9 58
U1 7
U2 68
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1364-5072
J9 J APPL MICROBIOL
JI J. Appl. Microbiol.
PD JUL
PY 2012
VL 113
IS 1
BP 1
EP 15
DI 10.1111/j.1365-2672.2012.05281.x
PG 15
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 957TE
UT WOS:000305184900001
PM 22420458
ER
PT J
AU Lin, D
Foley, SL
Qi, Y
Han, J
Ji, C
Li, R
Wu, C
Shen, J
Wang, Y
AF Lin, D.
Foley, S. L.
Qi, Y.
Han, J.
Ji, C.
Li, R.
Wu, C.
Shen, J.
Wang, Y.
TI Characterization of antimicrobial resistance of Pseudomonas aeruginosa
isolated from canine infections
SO JOURNAL OF APPLIED MICROBIOLOGY
LA English
DT Article
DE antimicrobial resistance; canine; integrons; Pseudomonas aeruginosa
ID II TOPOISOMERASE MUTATIONS; CLASS 1 INTEGRON; FLUOROQUINOLONE
RESISTANCE; ANTIBIOTIC-RESISTANCE; GENE CASSETTES; OTITIS-EXTERNA;
SUSCEPTIBILITY; DOGS; MECHANISMS; STRAINS
AB Aims: To determine the prevalence of Pseudomonas aeruginosa among dogs with suspected soft tissue infections and to characterize these isolates. Methods and Results: Swabs were taken from infected soft tissues of 402 dogs. Pseudomonas aeruginosa strains were confirmed phenotypically and tested for susceptibility to 11 antimicrobial agents and genotyped by SpeI pulsed-field gel electrophoresis (PFGE). The genetic basis of fluoroquinolone (FQ) resistance and the presence of integrons were also characterized. A total of 27 (6.7%) dogs tested positive for Ps.aeruginosa. Fourteen different SpeI patterns were observed in 25 typeable strains. Among the beta-lactams, three isolates presented resistance to ticarcillin and carbenicillin, while only one isolate exhibited resistance to ceftazidime. Among the aminoglycosides (AGs), three strains showed resistance to amikacin, and four strains exhibited resistance to gentamicin and tobramycin. Four strains with mutations that led to the substitution of Thr at position 83 with Ile in GyrA and the exchange of Ser at position 87 with Leu in ParC displayed resistance to all tested FQs. These strains also carried class 1 integrons and showed resistance to between 6 and 10 antimicrobials. These integrons included four different gene cassettes (aacA4-aadA1, blaOXA-31-aadA2, aadA1-arr-3-catB3 and cmlA5-cmlA-aadA1). Conclusions: A small proportion of infected dogs treated in two animal hospitals in Beijing, China carried Ps.aeruginosa isolates. Low levels of resistance to anti-pseudomonal agents were observed in these strains. Significance and Impact of the Study: This study is the first report on the antimicrobial resistance profiles of Ps.aeruginosa isolated from infected canine origin in China. Additionally, this is the first report of the oxacillin resistance gene blaOXA-31 in a canine Ps.aeruginosa isolate.
C1 [Ji, C.; Li, R.; Wu, C.; Shen, J.; Wang, Y.] China Agr Univ, Beijing Key Lab Detect Technol Anim Derived Food, Coll Vet Med, Beijing 100193, Peoples R China.
[Lin, D.] China Agr Univ, Dept Small Anim Clin Sci, Coll Vet Med, Beijing 100193, Peoples R China.
[Foley, S. L.; Han, J.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Qi, Y.] Henan Inst Sci & Technol, Coll Anim Sci, Xinxiang, Peoples R China.
RP Wang, Y (reprint author), China Agr Univ, Beijing Key Lab Detect Technol Anim Derived Food, Coll Vet Med, Beijing 100193, Peoples R China.
EM wangyang@cau.edu.cn
RI li, ruichao/E-5132-2015
OI li, ruichao/0000-0001-8333-9891
FU Innovative Research Team at the University of China [IRT0866]; National
Natural Science Foundation of China [U0631006]; Oak Ridge Institute for
Science and Education; programme for Chang Jiang Scholars
FX This study was supported by the programme for Chang Jiang Scholars and
the Innovative Research Team at the University of China (no. IRT0866),
and the grant from the National Natural Science Foundation of China (no.
U0631006). Dr Jing Han is supported through the Oak Ridge Institute for
Science and Education.
NR 34
TC 9
Z9 9
U1 2
U2 23
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1364-5072
J9 J APPL MICROBIOL
JI J. Appl. Microbiol.
PD JUL
PY 2012
VL 113
IS 1
BP 16
EP 23
DI 10.1111/j.1365-2672.2012.05304.x
PG 8
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 957TE
UT WOS:000305184900002
PM 22487022
ER
PT J
AU Simonetti, A
Mariotto, A
Krapcho, M
Feuer, EJ
AF Simonetti, Arianna
Mariotto, Angela
Krapcho, Martin
Feuer, Eric J.
TI Improved population-based probability of developing cancer when direct
estimates of the cancer-free population are available
SO LIFETIME DATA ANALYSIS
LA English
DT Article
DE Lifetime risk; Cancer; Prevalence; Life table
ID AGE-CONDITIONAL PROBABILITIES; DEVELOPING BREAST-CANCER; REGISTRY DATA;
PREVALENCE; VARIANCE; LIFETIME
AB Age-conditional probabilities of developing a first cancer represent the transition from being cancer-free to developing a first cancer. Natural inputs into their calculation are rates of first cancer per person-years alive and cancer-free. However these rates are not readily available because they require information on the cancer-free population. Instead rates of first cancer per person-years alive, calculated using as denominator the mid-year populations, available from census data, can be easily calculated from cancer registry data. Methods have been developed to estimate age-conditional probabilities of developing cancer based on these easily available rates per person-years alive that do not directly account for the cancer-free population. In the last few years models (Merrill et al., Int J Epidemiol 29(2):197-207, 2000; Mariotto et al., SEER Cancer Statistics Review, 2002; Clegg et al., Biometrics 58(3):684-688, 2002; Gigli et al., Stat Methods Med Res 15(3):235-253, 2006, and software (ComPrev:Complete Prevalence Software, Version 1.0, 2005) have been developed that allow estimation of cancer prevalence (DevCan: Probability of Developing or Dying of Cancer Software, Version 6.0, 2005). Estimates of population-based cancer prevalence allows for the estimation of the cancer-free population and consequently of rates per person-years alive and cancer-free. In this paper we present a method that directly estimates the age-conditional probabilities of developing a first cancer using rates per person-years alive and cancer-free obtained from prevalence estimates. We explore conditions when the previous and the new estimators give similar or different values using real data from the Surveillance, Epidemiology and End Results (SEER) program.
C1 [Simonetti, Arianna] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Simonetti, Arianna] Ist Super Sanita, Dept Canc Epidemiol, Natl Ctr Epidemiol Surveillance & Hlth Promot, I-00161 Rome, Italy.
[Simonetti, Arianna] Univ Roma La Sapienza, Dept Stat Probabil & Appl Stat, Rome, Italy.
[Mariotto, Angela; Feuer, Eric J.] NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Krapcho, Martin] Informat Management Serv IMS Inc, Silver Spring, MD USA.
RP Simonetti, A (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 210 WOC1,Suite 316N, Rockville, MD 20852 USA.
EM Arianna.Simonetti@fda.hhs.gov
FU National Cancer Institute (NCI) Office of International Affairs (OIA)
FX This work was partially funded by the National Cancer Institute (NCI)
Office of International Affairs (OIA) Scientific Exchange Program.
NR 18
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1380-7870
J9 LIFETIME DATA ANAL
JI Lifetime Data Anal.
PD JUL
PY 2012
VL 18
IS 3
BP 284
EP 301
DI 10.1007/s10985-012-9216-6
PG 18
WC Mathematics, Interdisciplinary Applications; Statistics & Probability
SC Mathematics
GA 958FG
UT WOS:000305221300002
PM 22430932
ER
PT J
AU Rahman, Z
Samy, R
Sayeed, VA
Khan, MA
AF Rahman, Ziyaur
Samy, Raghu
Sayeed, Vilayat A.
Khan, Mansoor A.
TI Physicochemical and mechanical properties of carbamazepine cocrystals
with saccharin
SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
LA English
DT Article
DE Carbamazepine; saccharin; solubility; intrinsic dissolution; dehydrate;
stability
ID CRYSTALLINE SOLIDS; HECKEL EQUATION; DIHYDRATE; SOLUBILITY; DISSOLUTION;
DRUGS; PHASE; BIOAVAILABILITY; POLYMORPHS; TRANSITION
AB The aim of present research was to investigate the physicochemical, mechanical properties, and stability characteristics of cocrystal of carbamazepine (CBZ) using saccharin (SAC) as a coformer. The cocrystals were prepared by solubility method and characterized by pH-solubility profile, intrinsic dissolution by static disk method, and surface morphology by scanning electron microscopy (SEM), crystallinity by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), and mechanical properties by Heckel analysis. Stability of the cocrystals were assessed by storing them at 60 degrees C for two weeks, 25 degrees C/60%RH, 40 degrees C/75%RH and 40 degrees C/94%RH for one month and compared with the stability of CBZ. The solubility profile of cocrystal was similar to CBZ. The cocrystal and CBZ have shown the same stability profile at all the conditions of studies except at 40 degrees C/94%RH. Unlike the CBZ, cocrystal was stable against dihydrate transformation. The compacts of cocrystal have a greater tensile strength and more compressibility. The Heckel analysis suggested that plastic deformation started at low compression pressure in the cocrystal than CBZ. In summary, the cocrystal form of carbamazepine provides another avenue for product development which is more stable than the parent drug.
C1 [Rahman, Ziyaur; Samy, Raghu; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Sayeed, Vilayat A.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA.
RP Khan, MA (reprint author), US FDA, CDER, DPQR White Oak, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Mansoor.Khan@fda.hhs.gov
OI Rahman, Ziyaur/0000-0002-0402-825X
FU Oak Ridge Institute for Science and Education (ORISE)
FX The authors would like to thank the Oak Ridge Institute for Science and
Education (ORISE) for supporting the post doctoral research program.
NR 41
TC 4
Z9 4
U1 3
U2 21
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1083-7450
J9 PHARM DEV TECHNOL
JI Pharm. Dev. Technol.
PD JUL-AUG
PY 2012
VL 17
IS 4
BP 457
EP 465
DI 10.3109/10837450.2010.546412
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 958NX
UT WOS:000305247300008
PM 21265708
ER
PT J
AU Follea, G
Foster, R
Epstein, J
Sherratt, D
MacPherson, J
de Wit, HJC
Sher, G
AF Follea, G.
Foster, R.
Epstein, J.
Sherratt, D.
MacPherson, J.
de Wit, H. J. C.
Sher, G.
TI MANAGED CONVERGENCE, A POTENTIAL COLLABORATION BETWEEN BLOOD
ESTABLISHMENTS, SUPPLIERS AND REGULATORS: IMPROVING SAFETY OF APHERESIS
CONNECTORS
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Follea, G.] European Blood Alliance, Brussels, Belgium.
[Foster, R.] Eucomed Caridian BCT, Brussels, Belgium.
[Epstein, J.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Sherratt, D.] Caridian BCT, Denver, CO USA.
[MacPherson, J.] Amer Blood Ctr, Washington, DC USA.
[de Wit, H. J. C.] European Blood Alliance Sanquin, Amsterdam, Netherlands.
[Sher, G.] Alliance Blood Operators Canadian Blood Serv, Ottawa, ON, Canada.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 50
EP 50
PG 1
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410600131
ER
PT J
AU Rios, M
Anez, G
Chancey, C
Grinev, A
AF Rios, M.
Anez, G.
Chancey, C.
Grinev, A.
TI DENGUE VIRUS AND OTHER ARBOVIRUSES: A GLOBAL VIEW OF THE RISKS
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Rios, M.; Anez, G.; Chancey, C.; Grinev, A.] US FDA, CBER, OBRR, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 1
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 62
EP 63
PG 2
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410600164
ER
PT J
AU Taylor, R
Nyan, DC
Rios, M
AF Taylor, R.
Nyan, D. C.
Rios, M.
TI DEVELOPMENT OF A REVERSE-TRANSCRIPTION ISOTHERMAL AMPLIFICATION ASSAY
FOR RAPID DETECTION AND GENOTYPING OF HEPATITIS C VIRUS INFECTION IN
BLOOD
SO VOX SANGUINIS
LA English
DT Meeting Abstract
C1 [Taylor, R.; Nyan, D. C.; Rios, M.] CBER FDA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0042-9007
J9 VOX SANG
JI Vox Sang.
PD JUL
PY 2012
VL 103
SU 1
SI SI
BP 170
EP 170
PG 1
WC Hematology
SC Hematology
GA 960SP
UT WOS:000305410601101
ER
PT J
AU Gannavaram, S
Debrabant, A
AF Gannavaram, Sreenivas
Debrabant, Alain
TI Programmed cell death in Leishmania: biochemical evidence and role in
parasite infectivity
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Review
DE apoptosis; endonuclease; Leishmania; metacaspase; programmed cell death;
protozoa; trypanosomatid
ID APOPTOTIC DNA-DEGRADATION; TRYPANOSOMA-BRUCEI; ENDONUCLEASE-G;
PLASMODIUM-FALCIPARUM; CYTOCHROME-C; MUCOCUTANEOUS LEISHMANIASIS;
SACCHAROMYCES-CEREVISIAE; DONOVANI PROMASTIGOTES; UNICELLULAR ORGANISM;
CYSTEINE PROTEASES
AB Demonstration of features of a programmed cell death (PCD) pathway in protozoan parasites initiated a great deal of interest and debate in the field of molecular parasitology. Several of the markers typical of mammalian apoptosis have been shown in Leishmania which suggested the existence of an apoptosis like death in these organisms. However, studies to elucidate the downstream events associated with phosphotidyl serine exposure, loss of mitochondrial membrane potential, cytochrome c release, and caspase-like activities in cells undergoing such cell death remain an ongoing challenge. Recent advances in genome sequencing, chemical biology should help to solve some of these challenges. Leishmania genetic mutants that lack putative regulators/effectors of PCD pathway should not only help to demonstrate the mechanisms of PCD but also provide tools to better understand the putative role for this pathway in population control and in the establishment of a successful infection of the host.
C1 [Gannavaram, Sreenivas; Debrabant, Alain] US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Lab Emerging Pathogens, Bethesda, MD 20892 USA.
RP Debrabant, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Lab Emerging Pathogens, 29 Lincoln Dr,B29,Rm425,HFM 310, Bethesda, MD 20892 USA.
EM alain.debrabant@fda.hhs.gov
NR 94
TC 10
Z9 10
U1 2
U2 9
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD JUL
PY 2012
VL 2
AR UNSP 95
DI 10.3389/fcimb.2012.00095
PG 9
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 221AO
UT WOS:000324629600006
PM 22919685
ER
PT J
AU Bartz, J
Mahovic, M
Spiceland, D
Teplitski, M
AF Bartz, J.
Mahovic, M.
Spiceland, D.
Teplitski, M.
TI Detached leaf assay adapted to tomato pericarp sections for modeling
contamination of tomato fruit by Salmonella Typhimurium
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Phytopathological-Society (APS)
CY AUG 04-08, 2012
CL Providence, RI
SP Amer Phytopathol Soc (APS)
C1 [Bartz, J.] Univ Florida, Dept Plant Pathol, Gainesville, FL 32611 USA.
[Mahovic, M.] US FDA, CFSAN, Off Food Safety, College Pk, MD USA.
[Spiceland, D.] Univ Florida, Gainesville, FL USA.
[Teplitski, M.] Univ Florida, Soil & Water Sci Dept, Gainesville, FL USA.
NR 0
TC 2
Z9 2
U1 0
U2 1
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUL
PY 2012
VL 102
IS 7
SU 4
BP 9
EP 9
PG 1
WC Plant Sciences
SC Plant Sciences
GA 196SX
UT WOS:000322797800045
ER
PT J
AU Chiyaka, C
Singer, BH
Halbert, SE
Morris, JG
Van Bruggen, AH
AF Chiyaka, C.
Singer, B. H.
Halbert, S. E.
Morris, J. G.
Van Bruggen, A. H.
TI Modeling flush-to-flush transmission of huanglongbing in a citrus tree
and effects of control strategies on disease dynamics
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Phytopathological-Society (APS)
CY AUG 04-08, 2012
CL Providence, RI
SP Amer Phytopathol Soc (APS)
C1 [Chiyaka, C.; Singer, B. H.; Morris, J. G.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Halbert, S. E.] FDACS Div Plant Ind, Gainesville, FL USA.
[Van Bruggen, A. H.] Univ Florida, Gainesville, FL USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUL
PY 2012
VL 102
IS 7
SU 4
BP 23
EP 23
PG 1
WC Plant Sciences
SC Plant Sciences
GA 196SX
UT WOS:000322797800125
ER
PT J
AU Dobhal, S
Zhang, G
Ma, LM
Arif, M
AF Dobhal, S.
Zhang, G.
Ma, L. M.
Arif, M.
TI Screening of biological control agents from fresh produce against
foodborne human pathogens
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Phytopathological-Society (APS)
CY AUG 04-08, 2012
CL Providence, RI
SP Amer Phytopathol Soc (APS)
C1 [Dobhal, S.; Ma, L. M.] Oklahoma State Univ, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA.
[Zhang, G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Arif, M.] Oklahoma State Univ, Stillwater, OK 74078 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUL
PY 2012
VL 102
IS 7
SU 4
BP 30
EP 30
PG 1
WC Plant Sciences
SC Plant Sciences
GA 196SX
UT WOS:000322797800158
ER
PT J
AU Keremane, M
Ramadugu, C
Stover, E
Halbert, SE
Duan, Y
Lee, RF
AF Keremane, M.
Ramadugu, C.
Stover, E.
Halbert, S. E.
Duan, Y.
Lee, R. F.
TI Screening citrus and its relatives in Aurantioideae for tolerance to
huanglongbing
SO PHYTOPATHOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Phytopathological-Society (APS)
CY AUG 04-08, 2012
CL Providence, RI
SP Amer Phytopathol Soc (APS)
C1 [Keremane, M.] ARS, USDA, Riverside, CA USA.
[Ramadugu, C.] Univ Calif Riverside, Riverside, CA 92521 USA.
[Stover, E.; Duan, Y.] ARS, USDA, USHRL, Ft Pierce, FL USA.
[Halbert, S. E.] FDACS Div Plant Ind, Gainesville, FL USA.
[Lee, R. F.] ARS, Natl Clonal Germplasm Repository Citrus & Dates, USDA, Riverside, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUL
PY 2012
VL 102
IS 7
SU 4
BP 63
EP 63
PG 1
WC Plant Sciences
SC Plant Sciences
GA 196SX
UT WOS:000322797800328
ER
PT J
AU Kaplan, DS
Hitchins, VM
Vegella, TJ
Malinauskas, RA
Ferlin, KM
Fisher, JP
Frondoza, CG
AF Kaplan, David S.
Hitchins, Victoria M.
Vegella, Thomas J.
Malinauskas, Richard A.
Ferlin, Kimberly M.
Fisher, John P.
Frondoza, Carmelita G.
TI Centrifugation Assay for Measuring Adhesion of Serially Passaged Bovine
Chondrocytes to Polystyrene Surfaces
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID HUMAN ARTICULAR CHONDROCYTES; COLLAGEN TYPE CONVERSION; CELL-ADHESION;
GENE-EXPRESSION; CARTILAGE; CULTURE; DEDIFFERENTIATION; PROLIFERATION;
EXPANSION; GELS
AB A major obstacle in chondrocyte-based therapy for cartilage repair is the limited availability of cells that maintain their original phenotype. Propagation of chondrocytesas monolayer cultures on polystyrene surfaces is used extensively for amplifying cell numbers. However, chondrocytes undergo a phenotypic shift when propagated in this manner and display characteristics of more adherent fibroblastic cells. Little information is available about the effect of this phenotypic shift on cellular adhesion properties. We evaluated changes in adhesion property as bovine chondrocytes were serially propagated up to five passages in monolayer culture using a centrifugation cell adhesion assay, which was based on counting of cells before and after being exposed to centrifugal dislodgement forces of 120 and 350 g. Chondrocytes proliferated well in a monolayer culture with doubling times of 2-3 days, but they appeared more fibroblastic and exhibited elongated cell morphology with continued passage. The centrifugation cell adhesion assay showed that chondrocytes became more adhesive with passage as the percentage of adherent cells after centrifugation increased and was not statistically different from the adhesion of the fibroblast cell line, L929, starting at passage 3. This increased adhesiveness correlated with a shift to a fibroblastic morphology and increased collagen I mRNA expression starting at passage 2. Our findings indicate that the centrifugation cell adhesion assay may serve as a reproducible tool to track alterations in chondrocyte phenotype during their extended propagation in culture.
C1 [Kaplan, David S.; Hitchins, Victoria M.; Vegella, Thomas J.; Malinauskas, Richard A.; Ferlin, Kimberly M.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Ferlin, Kimberly M.; Fisher, John P.] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Frondoza, Carmelita G.] Nutramax Labs Inc, Edgewood, MD USA.
[Frondoza, Carmelita G.] Johns Hopkins Univ, Dept Orthopaed Surg, Baltimore, MD USA.
RP Kaplan, DS (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 2212, Silver Spring, MD 20993 USA.
EM david.kaplan@fda.hhs.gov
RI Fisher, John/F-8078-2012
FU FDA; Office of Science and Health Coordination
FX This work was supported by the FDA, Office of Science and Health
Coordination. The authors wish to thank Dr. Andres Garcia for technical
discussions and protocols for running centrifugation cell adhesion
assays. They would also like to thank Dongha Le, Priyanka Durai, Natasha
Lodha, and Brian Nalls for their help in running the cell adhesion
assays. They also thank Megan Shoff for her assistance in isolating the
bovine chondrocytes. Additionally, they thank Dr. Maureen Dreher for
technical help with the acquisition and handling of the bovine
chondrocytes and Shiling Ruan and Dr. Dreher for their assistance with
the statistical analysis of the data.
NR 40
TC 5
Z9 5
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD JUL
PY 2012
VL 18
IS 7
BP 537
EP 544
DI 10.1089/ten.tec.2011.0043
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 966AQ
UT WOS:000305809400006
PM 22235797
ER
PT J
AU Kim, KP
Miller, DL
de Gonzalez, AB
Balter, S
Kleinerman, RA
Ostroumova, E
Simon, SL
Linet, MS
AF Kim, Kwang Pyo
Miller, Donald L.
de Gonzalez, Amy Berrington
Balter, Stephen
Kleinerman, Ruth A.
Ostroumova, Evgenia
Simon, Steven L.
Linet, Martha S.
TI OCCUPATIONAL RADIATION DOSES TO OPERATORS PERFORMING
FLUOROSCOPICALLY-GUIDED PROCEDURES
SO HEALTH PHYSICS
LA English
DT Article
DE exposure, occupational; fluoroscopy; medical radiation; radiation
protection
ID INTERVENTIONAL CARDIOLOGY PROCEDURES; ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY; CARDIAC-CATHETERIZATION PROCEDURES;
PERCUTANEOUS NEPHROLITHOTOMY; RADIOLOGY PROCEDURES; STAFF DOSIMETRY;
MEDICAL STAFF; RAD-IR; NEUROINTERVENTIONAL PROCEDURES; ORTHOPEDIC
SURGEONS
AB In the past 30 y, the numbers and types of fluoroscopically-guided (FG) procedures have increased dramatically. The objective of the present study is to provide estimated radiation doses to physician specialists, other than cardiologists, who perform FG procedures. The authors searched Medline to identify English-language journal articles reporting radiation exposures to these physicians. They then identified several primarily therapeutic FG procedures that met specific criteria: well-defined procedures for which there were at least five published reports of estimated radiation doses to the operator, procedures performed frequently in current medical practice, and inclusion of physicians from multiple medical specialties. These procedures were percutaneous nephrolithotomy (PCNL), vertebroplasty, orthopedic extremity nailing for treatment of fractures, biliary tract procedures, transjugular intrahepatic portosystemic shunt creation (TIPS), head/neck endovascular therapeutic procedures, and endoscopic retrograde cholangiopancreatography (ERCP). Radiation doses and other associated data were abstracted, and effective dose to operators was estimated. Operators received estimated doses per patient procedure equivalent to doses received by interventional cardiologists. The estimated effective dose per case ranged from 1.7-56 mu Sv for PCNL, 0.1-101 mu Sv for vertebroplasty, 2.5-88 mu Sv for orthopedic extremity nailing, 2.0-46 mu Sv for biliary tract procedures, 2.5-74 mu Sv for TIPS, 1.8-53 mu Sv for head/neck endovascular therapeutic procedures, and 0.2-49 mu Sv for ERCP. Overall, mean operator radiation dose per case measured over personal protective devices at different anatomic sites on the head and body ranged from 19-800 (median = 113) mu Sv at eye level, 6-1,180 (median = 75) mu Sv at the neck, and 2-1,600 (median = 302) mu Sv at the trunk. Operators' hands often received greater doses than the eyes, neck, or trunk. Large variations in operator doses suggest that optimizing procedure protocols and proper use of protective devices and shields might reduce occupational radiation dose substantially. Health Phys. 103(1): 0-99; 2012
C1 [Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Yongin, Gyeonggi Do, South Korea.
[Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[de Gonzalez, Amy Berrington; Kleinerman, Ruth A.; Ostroumova, Evgenia; Simon, Steven L.; Linet, Martha S.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10027 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Med, New York, NY 10027 USA.
RP Kim, KP (reprint author), Kyung Hee Univ, Dept Nucl Engn, 1 Seocheon Dong, Yongin, Gyeonggi Do, South Korea.
EM kpkim@khu.ac.kr
OI Kleinerman, Ruth/0000-0001-7415-2478
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health.
NR 121
TC 31
Z9 33
U1 1
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD JUL
PY 2012
VL 103
IS 1
BP 80
EP 99
DI 10.1097/HP.0b013e31824dae76
PG 20
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 955MY
UT WOS:000305025300016
PM 22647920
ER
PT J
AU Koturbash, I
Simpson, NE
Beland, FA
Pogribny, IP
AF Koturbash, Igor
Simpson, Natalie E.
Beland, Frederick A.
Pogribny, Igor P.
TI Alterations in Histone H4 Lysine 20 Methylation: Implications for Cancer
Detection and Prevention
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Review
ID DNA-DAMAGE; GENE-EXPRESSION; RAT-LIVER; TRANSCRIPTIONAL REPRESSION;
S-ADENOSYLMETHIONINE; CHROMATIN REGULATION; EPIGENETIC CHANGES;
METABOLIC SYNDROME; TUMOR PROGRESSION; DEFICIENT DIETS
AB Significance: Cancer development and progression are associated with numerous genetic, epigenetic, and metabolic changes. Recent Advances: A number of epigenetic aberrations have been characterized in cancer, including DNA methylation and various histone modification changes. One of the most unique and enigmatic epigenetic marks that is noticeably altered in several major human cancers is methylation of histone H4 lysine 20; however, there is insufficient knowledge of the underlying molecular mechanisms associated with this abberation. Critical Issues: This review presents current evidence of the role of histone H4 lysine 20 methylation in normal and cancer cells and during tumorigenesis induced by genotoxic and nongenotoxic carcinogens. Additionally, it describes molecular mechanisms that may cause this alteration and highlights the significance of this epigenetic mark as an early indicator of carcinogenesis. Future Directions: Accumulating evidence suggests that dietary components may be significant regulators of the cellular epigenome, including histone methylation, by providing and maintaining the adequate levels of S-adenosyl-L-methionine, flavin adenine dinucleotide, alpha-ketoglutarate, and iron. Future research should elucidate the potential for modifying cellular metabolism through dietary intervention for timely regulation of the epigenome as means for the prevention of cancer development. Antioxid. Redox Signal. 17, 365-374.
C1 [Koturbash, Igor; Simpson, Natalie E.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, 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
NR 93
TC 10
Z9 10
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1523-0864
EI 1557-7716
J9 ANTIOXID REDOX SIGN
JI Antioxid. Redox Signal.
PD JUL
PY 2012
VL 17
IS 2
BP 365
EP 374
DI 10.1089/ars.2011.4370
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 944MQ
UT WOS:000304207700013
PM 22035019
ER
PT J
AU Wang, X
Gao, YM
Tan, JY
Devadas, K
Ragupathy, V
Takeda, K
Zhao, JQ
Hewlett, I
AF Wang, Xue
Gao, Yamei
Tan, Jiying
Devadas, Krishnakumar
Ragupathy, Viswanath
Takeda, Kazuyo
Zhao, Jiangqin
Hewlett, Indira
TI HIV-1 and HIV-2 infections induce autophagy in Jurkat and CD4(+) T cells
SO CELLULAR SIGNALLING
LA English
DT Article
DE HIV; Autophagy; Beclin-1; LC3; Electron microscopy
ID APOPTOSIS; DEATH; PHOSPHORYLATION; MACROPHAGES; LYSOSOMES; PROTEINS;
VACUOLES; GLUCAGON; PATHWAY; LIVER
AB Autophagy plays important roles during innate and adaptive immune responses to pathogens, including virus infection. Viruses develop ways to subvert the pathway for their own benefit in order to escape restriction by autophagy, leading to increased viral replication and/or control over apoptosis of their host cells. The effects of HIV infection on the autophagic pathway in host cells have been little documented. Using the susceptible Jurkat cell line and CD4(+) T cells, we studied the relationship of HIV-1 and -2 infections with autophagy. We found that HIV infections significantly increase transcription of ULK1, a member of the autophagy-initiated complex. Two ubiquitin-like conjugation systems, the Atg12 conjugation system and the microtubule-associated protein L chain 3 (LC3) conjugation system that control the elongation of the autophore to form the autophagosome, were activated after HIV infection, with upregulation of Atg12-Atg5 complex and increased transcription of LC3, and formed more autophagosome in infected cells detected using an EM assay. We also found that HIV-1 induced more autophagic death in Jurkat cells relative to HIV-2, and the inhibition of autophagy with 3MA and Beclin-1 knockdown decreased HIV-1 replication significantly. The results indicate that HIV is able to induce the autophagic signaling pathway in HIV-infected host cells, which may be required for HIV infection-mediated apoptotic cell death. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Wang, Xue; Tan, Jiying; Devadas, Krishnakumar; Ragupathy, Viswanath; Zhao, Jiangqin; Hewlett, Indira] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Gao, Yamei] US FDA, EM Lab, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Takeda, Kazuyo] US FDA, Confocal Microscopy Core Facil, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Wang, X (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bldg 29B,Rm 4NN22,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM xue.wang@fda.hhs.gov
NR 29
TC 20
Z9 23
U1 0
U2 17
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 JUL
PY 2012
VL 24
IS 7
BP 1414
EP 1419
DI 10.1016/j.cellsig.2012.02.016
PG 6
WC Cell Biology
SC Cell Biology
GA 944XA
UT WOS:000304235900007
PM 22406083
ER
PT J
AU Jung, HA
Augsburger, LL
AF Jung, Huijeong Ashley
Augsburger, Larry L.
TI Application of a novel automatic disintegration apparatus for the
development and evaluation of a direct compression rapidly
disintegrating tablet
SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
LA English
DT Article
DE Calcium silicate; croscarmellose sodium; crospovidone; disintegration
mechanism; disintegration efficiency; expansion coefficient; expansion
rate constant; moisture sensitivity; sodium starch glycolate
AB An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab (R) concentration, DiPac (R)/Xylitab (R) ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability < 10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab (R) and/or Xylitab (R), magnesium stearate, and Explotab (R) suggested that the amount of Explotab (R) was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel (R) and Explotab (R), which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone (R) XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol (R) showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.
C1 [Jung, Huijeong Ashley] US FDA, CDER, Off Gener Drugs, Rockville, MD 20855 USA.
[Augsburger, Larry L.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
RP Jung, HA (reprint author), US FDA, CDER, Off Gener Drugs, 7500 Standish Pl,HFD 640, Rockville, MD 20855 USA.
EM huijeong.jung@fda.hhs.gov
NR 14
TC 1
Z9 1
U1 1
U2 13
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0363-9045
J9 DRUG DEV IND PHARM
JI Drug Dev. Ind. Pharm.
PD JUL
PY 2012
VL 38
IS 7
BP 825
EP 836
DI 10.3109/03639045.2011.630007
PG 12
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 946NF
UT WOS:000304357900007
PM 22091970
ER
PT J
AU Garcia, MC
Flynn, TJ
AF Garcia, Martha C.
Flynn, Thomas J.
TI Mechanisms of Oxidative Damage Studied with In Vitro Models of
Non-alcoholic Fatty Liver Disease
SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
LA English
DT Meeting Abstract
C1 [Garcia, Martha C.; Flynn, Thomas J.] FDA Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD USA.
EM Martha.garcia@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 JUL
PY 2012
VL 48
SU 1
BP 12
EP 12
PG 1
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 947BU
UT WOS:000304402400028
ER
PT J
AU Chen, WJ
Gallas, BD
Yousef, WA
AF Chen, Weijie
Gallas, Brandon D.
Yousef, Waleed A.
TI Classifier variability: Accounting for training and testing
SO PATTERN RECOGNITION
LA English
DT Article
DE Classifier evaluation; Training variability; Classifier stability;
U-statistics; AUC
ID ROC ANALYSIS; NONPARAMETRIC APPROACH; FOLLICULAR LYMPHOMA;
CROSS-VALIDATION; VARIANCE; BOOTSTRAP; AREA; PREDICTION; SELECTION;
MODELS
AB We categorize the statistical assessment of classifiers into three levels: assessing the classification performance and its testing variability conditional on a fixed training set, assessing the performance and its variability that accounts for both training and testing, and assessing the performance averaging over training sets and its variability that accounts for both training and testing. We derived analytical expressions for the variance of the estimated AUC and provide freely available software implemented with an efficient computation algorithm. Our approach can be applied to assess any classifier that has ordinal (continuous or discrete) outputs. Applications to simulated and real datasets are presented to illustrate our methods. Published by Elsevier Ltd.
C1 [Chen, Weijie; Gallas, Brandon D.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Yousef, Waleed A.] Helwan Univ, Fac Comp & Informat, Human Comp Interact Lab, Cairo, Egypt.
RP Chen, WJ (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM weijie.chen@fda.hhs.gov
RI Chen, Weijie/A-3712-2012;
OI Gallas, Brandon/0000-0001-7332-1620
NR 38
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U1 4
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0031-3203
J9 PATTERN RECOGN
JI Pattern Recognit.
PD JUL
PY 2012
VL 45
IS 7
BP 2661
EP 2671
DI 10.1016/j.patcog.2011.12.024
PG 11
WC Computer Science, Artificial Intelligence; Engineering, Electrical &
Electronic
SC Computer Science; Engineering
GA 921AS
UT WOS:000302451000018
ER
PT J
AU Gu, Q
Schmued, LC
Sarkar, S
Paule, MG
Raymick, B
AF Gu, Qiang
Schmued, Larry C.
Sarkar, Sumit
Paule, Merle G.
Raymick, Bryan
TI One-step labeling of degenerative neurons in unfixed brain tissue
samples using Fluoro-Jade C
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Neurodegeneration; Neuronal death; Fluoro-Jade; Fluorescence labeling
ID CELL-DEATH; LOCALIZATION; MARKER
AB Neurodegeneration is the underlying cause of a vast majority of neurological disorders and often a result of brain trauma, stroke, or neurotoxic insult. Here we describe a simple method for labeling degenerating neurons in unfixed brain tissue samples. This method could provide a new avenue for identifying and harvesting degenerative neurons from unfixed brain tissues for subsequent molecular analyses. Published by Elsevier B.V.
C1 [Gu, Qiang; Schmued, Larry C.; Sarkar, Sumit; Paule, Merle G.; Raymick, Bryan] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Gu, Q (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM qiang.gu@fda.hhs.gov
FU U.S. Food and Drug Administration, National Center for Toxicological
Research [E7312, E7477]
FX This work was supported by the U.S. Food and Drug Administration,
National Center for Toxicological Research, protocol numbers E7312 and
E7477. The views expressed here are those of the authors and not
necessarily those of the U.S. Food and Drug Administration.
NR 15
TC 7
Z9 8
U1 1
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD JUN 30
PY 2012
VL 208
IS 1
BP 40
EP 43
DI 10.1016/j.jneumeth.2012.04.012
PG 4
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 966VN
UT WOS:000305865600005
PM 22546475
ER
PT J
AU Roche, CJ
Dantsker, D
Alayash, AI
Friedman, JM
AF Roche, Camille J.
Dantsker, David
Alayash, Abdu I.
Friedman, Joel M.
TI Enhanced nitrite reductase activity associated with the haptoglobin
complexed hemoglobin dimer: Functional and antioxidative implications
SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY
LA English
DT Article
DE Nitrite reductase; Haptoglobin; Hemoglobin
ID CELL-FREE HEMOGLOBIN; QUATERNARY ENHANCEMENT; CARBON-MONOXIDE; BLOOD
SUBSTITUTES; SUSTAINED-RELEASE; REACTION-KINETICS; OXYGEN-BINDING;
CENTRAL CAVITY; BAND-III; T-STATE
AB The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the alpha beta dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb-Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound alpha beta Hb dimer. The presented results show that the Hb dimer in the Hb-Hp complex has oxygen binding. CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb-Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb-Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Roche, Camille J.; Dantsker, David; Friedman, Joel M.] Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA.
[Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA.
RP Friedman, JM (reprint author), Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA.
EM jfriedma@aecom.yu.edu
FU NHLBI [NIH R21 HL106421]; FJC, a Foundation of Philanthropic Funds
FX Francine Wood for carrying out the oxygen equilibrium studies on the
hemoglobin and the hemoglobin/haptoglobin complex solutions. Fantao Meng
for contributing the beta beta XL P2K modified Hb. This work was
supported through the NHLBI (NIH R21 HL106421)(JMF) and FJC, a
Foundation of Philanthropic Funds (JMF).
NR 67
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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 1089-8603
J9 NITRIC OXIDE-BIOL CH
JI Nitric Oxide-Biol. Chem.
PD JUN 30
PY 2012
VL 27
IS 1
BP 32
EP 39
DI 10.1016/j.niox.2012.04.002
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 961CK
UT WOS:000305441300005
PM 22521791
ER
PT J
AU Edwards, NC
Hing, ZA
Perry, A
Blaisdell, A
Kopelman, DB
Fathke, R
Plum, W
Newell, J
Allen, CE
Geetha, S
Shapiro, A
Okunji, C
Kosti, I
Shomron, N
Grigoryan, V
Przytycka, TM
Sauna, ZE
Salari, R
Mandel-Gutfreund, Y
Komar, AA
Kimchi-Sarfaty, C
AF Edwards, Nathan C.
Hing, Zachary A.
Perry, Avital
Blaisdell, Adam
Kopelman, David B.
Fathke, Robert
Plum, William
Newell, Jordan
Allen, Courtni E.
Geetha, S.
Shapiro, Aaron
Okunji, Chinyere
Kosti, Idit
Shomron, Noam
Grigoryan, Vahan
Przytycka, Teresa M.
Sauna, Zuben E.
Salari, Raheleh
Mandel-Gutfreund, Yael
Komar, Anton A.
Kimchi-Sarfaty, Chava
TI Characterization of Coding Synonymous and Non-Synonymous Variants in
ADAMTS13 Using Ex Vivo and In Silico Approaches
SO PLOS ONE
LA English
DT Article
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; RNA SECONDARY STRUCTURE;
MESSENGER-RNA; CODON USAGE; CLEAVING PROTEASE; ENDOPLASMIC-RETICULUM;
GENE-EXPRESSION; ESCHERICHIA-COLI; QUALITY-CONTROL; MUTATIONS
AB Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s). However, mounting evidence shows that these "silent" variations can have a significant impact on protein expression and function and should no longer be considered "silent". Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF) cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein.
C1 [Edwards, Nathan C.; Hing, Zachary A.; Perry, Avital; Blaisdell, Adam; Kopelman, David B.; Fathke, Robert; Plum, William; Newell, Jordan; Allen, Courtni E.; Geetha, S.; Shapiro, Aaron; Okunji, Chinyere; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Kosti, Idit; Mandel-Gutfreund, Yael] Technion Israel Inst Technol, Dept Biol, IL-32000 Haifa, Israel.
[Shomron, Noam] Tel Aviv Univ, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel.
[Grigoryan, Vahan; Przytycka, Teresa M.; Salari, Raheleh] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Komar, Anton A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
RP Edwards, NC (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM a.komar@csuohio.edu; chava.kimchi-sarfaty@fda.hhs.gov
FU Food and Drug Administration, Intramural Research Program of the
National Institutes of Health, National Library of Medicine; HFSP
[RGP0024]
FX This research was supported by the Food and Drug Administration,
Intramural Research Program of the National Institutes of Health,
National Library of Medicine and by HFSP RGP0024 to AAK. The funders had
no role in study design, data collection, and analysis, decision to
publish, or preparation of the manuscript.
NR 75
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U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 29
PY 2012
VL 7
IS 6
AR e38864
DI 10.1371/journal.pone.0038864
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 967FO
UT WOS:000305892100020
PM 22768050
ER
PT J
AU Heller, NM
Gwinn, WM
Donnelly, RP
Constant, SL
Keegan, AD
AF Heller, Nicola M.
Gwinn, William M.
Donnelly, Raymond P.
Constant, Stephanie L.
Keegan, Achsah D.
TI IL-4 Engagement of the Type I IL-4 Receptor Complex Enhances Mouse
Eosinophil Migration to Eotaxin-1 In Vitro
SO PLOS ONE
LA English
DT Article
ID PHOSPHOINOSITIDE 3-KINASE GAMMA; SIGNAL-TRANSDUCTION PATHWAYS;
PROTEIN-COUPLED RECEPTORS; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-4
RECEPTOR; ALLERGIC INFLAMMATION; AIRWAY INFLAMMATION; CYTOKINE
PRODUCTION; BLOOD EOSINOPHILS; INSULIN-RECEPTOR
AB Background: Previous work from our laboratory demonstrated that IL-4R alpha expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function.
Methods: Standard Transwell chemotaxis assay was used to assay migration of mouse eosinophils and signal transduction was assessed by Western blotting.
Results: Here we determined that (i) mouse eosinophils express both type I and type II IL-4 receptors, (ii) in contrast to human eosinophils, mouse eosinophils do not chemotax to IL-4 or IL-13 although (iii) pre-treatment with IL-4 but not IL-13 enhanced migration to eotaxin-1. This IL-4-mediated enhancement was dependent on type I IL-4 receptor expression: gamma C-deficient eosinophils did not show enhancement of migratory capacity when pre-treated with IL-4. In addition, mouse eosinophils responded to IL-4 with the robust tyrosine phosphorylation of STAT6 and IRS-2, while IL-13-induced responses were considerably weaker.
Conclusions: The presence of IL-4 in combination with eotaxin-1 in the allergic inflammatory milieu could potentiate infiltration of eosinophils into the lungs. Therapies that block IL-4 and chemokine receptors on eosinophils might be more effective clinically in reducing eosinophilic lung inflammation.
C1 [Heller, Nicola M.; Keegan, Achsah D.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Heller, Nicola M.; Keegan, Achsah D.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA.
[Gwinn, William M.; Constant, Stephanie L.] George Washington Univ, Med Ctr, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA.
[Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
RP Heller, NM (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM akeegan@som.umaryland.edu
FU United States Public Health Service from National Institute of Allergy
and Infectious Diseases, National Institutes of Health [AI038985]
FX This work was funded by the United States Public Health Service grant
AI038985 (to ADK) from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health (www.niaid.nih.gov). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 65
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U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2012
VL 7
IS 6
AR e39673
DI 10.1371/journal.pone.0039673
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GR
UT WOS:000305826400025
PM 22761864
ER
PT J
AU Senturker, S
Thomas, JT
Mateshaytis, J
Moos, M
AF Senturker, Sema
Thomas, John Terrig
Mateshaytis, Jennifer
Moos, Malcolm, Jr.
TI A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to
Anterior Neural Development in Xenopus
SO PLOS ONE
LA English
DT Article
ID IN-SITU HYBRIDIZATION; LENS INDUCTION; PROCESSING REQUIREMENTS;
MORPHOGENETIC PROTEIN; GENE-EXPRESSION; CRYSTALLIN GENE; EYE
DEVELOPMENT; BMP4; INVOLVEMENT; ACTIVATION
AB Background: Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously.
Methodology/Principal Findings: We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain-and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (beta-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7-perhaps, at least in part, due to activation of one or more BMPs-in early patterning of the anterior neural plate and its derivatives.
Conclusion/Significance: SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded.
C1 [Senturker, Sema; Thomas, John Terrig; Mateshaytis, Jennifer; Moos, Malcolm, Jr.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Senturker, S (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM malcolm.moos@fda.hhs.gov
RI Moos, Malcolm/F-3673-2011
OI Moos, Malcolm/0000-0002-9575-9938
NR 36
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U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 28
PY 2012
VL 7
IS 6
AR e39380
DI 10.1371/journal.pone.0039380
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 966GR
UT WOS:000305826400014
PM 22761776
ER
PT J
AU Prowell, TM
Pazdur, R
AF Prowell, Tatiana M.
Pazdur, Richard
TI Pathological Complete Response and Accelerated Drug Approval in Early
Breast Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CHEMOTHERAPY; TRASTUZUMAB
C1 [Prowell, Tatiana M.; Pazdur, Richard] US FDA, Off Hematol Oncol Prod, Silver Spring, MD USA.
[Prowell, Tatiana M.] Johns Hopkins Univ, Breast Canc Program, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Prowell, TM (reprint author), US FDA, Off Hematol Oncol Prod, Silver Spring, MD USA.
NR 6
TC 134
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U1 0
U2 5
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUN 28
PY 2012
VL 366
IS 26
BP 2438
EP 2441
DI 10.1056/NEJMp1205737
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 965DP
UT WOS:000305747000003
PM 22646508
ER
PT J
AU Gidudu, JF
Walco, GA
Taddio, A
Zempsky, WT
Halperin, SA
Calugar, A
Gibbs, NA
Hennig, R
Jovancevic, M
Netterlid, E
O'Connor, T
Oleske, JM
Varricchio, F
Tsai, TF
Seifert, H
Schuind, AE
AF Gidudu, Jane F.
Walco, Gary A.
Taddio, Anna
Zempsky, William T.
Halperin, Scott A.
Calugar, Angela
Gibbs, Neville A.
Hennig, Renald
Jovancevic, Milivoj
Netterlid, Eva
O'Connor, Terri
Oleske, James M.
Varricchio, Frederick
Tsai, Theodore F.
Seifert, Harry
Schuind, Anne E.
CA Brighton Immunization Site Pain
TI Immunization site pain: Case definition and guidelines for collection,
analysis, and presentation of immunization safety data
SO VACCINE
LA English
DT Article
DE Immunization site pain; Adverse event; Immunization; Guidelines; Case
definition
ID RANDOMIZED CONTROLLED-TRIALS; ACTIVE ANTIRETROVIRAL THERAPY; REDUCING
INJECTION PAIN; ADVERSE EVENTS; PEDIATRIC PAIN; SELF-REPORT; 6-YEAR-OLD
CHILDREN; BEHAVIORAL MEASURES; VACCINATION; VACCINES
C1 [Gidudu, Jane F.; Calugar, Angela] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA 30333 USA.
[Walco, Gary A.] Univ Washington, Sch Med, Seattle Childrens Hosp, Dept Anesthesiol & Pain Med, Seattle, WA USA.
[Taddio, Anna] Univ Toronto, Leslie L Dan Fac Pharm, Div Clin Social & Adm Pharm, Toronto, ON, Canada.
[Taddio, Anna] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Zempsky, William T.] Univ Connecticut, Sch Med, Connecticut Childrens Med Ctr, Div Pain & Palliat Med, Storrs, CT USA.
[Halperin, Scott A.] Dalhousie Univ, Dept Pediat & Microbiol & Immunol, Canadian Ctr Vaccinol, Halifax, NS, Canada.
[Gibbs, Neville A.] US FDA, Div Anesthesia Analgesia & Rheumatol Prod, Rockville, MD 20857 USA.
[Hennig, Renald] Scratch GbR, Pharmacovigilance Serv, Butzbach, Germany.
[Jovancevic, Milivoj] Univ Zagreb, Zagreb 41000, Croatia.
[O'Connor, Terri] Penn Dept Hlth, Bur Community Hlth Syst Northcent Dist 1, Harrisburg, PA 17108 USA.
[Oleske, James M.] Univ Med & Dent New Jersey, Dept Pediat, Div Pulm Allergy Immunol & Infect Dis, Newark, NJ USA.
[Tsai, Theodore F.] Novartis Vaccines, Cambridge, MA USA.
[Seifert, Harry; Schuind, Anne E.] GlaxoSmithKline Biol, King Of Prussia, PA USA.
RP Gidudu, JF (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA 30333 USA.
EM contact@brightoncollaboration.org
RI Oleske, James/C-1951-2016
OI Oleske, James/0000-0003-2305-5605
NR 92
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U1 1
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
EI 1873-2518
J9 VACCINE
JI Vaccine
PD JUN 22
PY 2012
VL 30
IS 30
BP 4558
EP 4577
DI 10.1016/j.vaccine.2012.03.085
PG 20
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 024NY
UT WOS:000310117100021
PM 22521267
ER
PT J
AU Wagner, RD
Johnson, SJ
AF Wagner, R. Doug
Johnson, Shemedia J.
TI Probiotic lactobacillus and estrogen effects on vaginal epithelial gene
expression responses to Candida albicans
SO JOURNAL OF BIOMEDICAL SCIENCE
LA English
DT Article
DE Probiotic; Epithelial cells; Gene expression; Signal transduction genes;
Candidiasis; Estrogen
ID UROGENITAL INFECTIONS; RHAMNOSUS GR-1; REUTERI RC-14; HOST-DEFENSE;
CELLS; PREVENTION; PROTECTION; SECRETION; INDUCE; TRACT
AB Background: Vaginal epithelial cells have receptors, signal transduction mechanisms, and cytokine secretion capabilities to recruit host defenses against Candida albicans infections. This research evaluates how probiotic lactobacilli affect the defensive epithelial response.
Methods: This study used quantitative reverse transcription-polymerase chain reaction assay (qRT-PCR), flow cytometry, and a multiplex immunoassay to observe changes in the regulation of gene expression related to cytokine responses in the VK2 (E6/E7) vaginal epithelial cell line treated with 17 beta-estradiol, exposed to probiotic Lactobacillus rhamnosus GR-1 (R) and Lactobacillus reuteri RC-14 (R) and challenged with C. albicans. Data were statistically evaluated by repeated measures analysis of variance and paired t-tests where appropriate.
Results: C. albicans induced mRNA expression of genes related to inflammatory cytokine responses associated with nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinase (MAPK) signal transduction pathways. 17 beta-estradiol suppressed expression of interleukin-1 alpha (IL-1 alpha), IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) mRNA. Probiotic lactobacilli suppressed C. albicans-induced nuclear factor-kappa B inhibitor kinase kinase alpha (I kappa kappa alpha), Toll-like receptor-2 (TLR2), TLR6, IL-8, and TNF alpha, also suggesting inhibition of NF-kappa B signaling. The lactobacilli induced expression of IL-1a, and IL-1 beta mRNA, which was not inhibited by curcumin, suggesting that they induce an alternate inflammatory signal transduction pathway to NF-kappa B, such as the mitogen activated protein kinase and activator protein-1 (MAPK/AP-1) signal transduction pathway. Curcumin inhibited IL-13 secretion, suggesting that expression of this cytokine is mainly regulated by NF-kappa B signaling in VK2 cells.
Conclusions: The results suggest that C. albicans infection induces pro-inflammatory responses in vaginal epithelial cells, and estrogen and lactobacilli suppress expression of NF-kappa B-related inflammatory genes. Probiotic lactobacilli may induce IL-1 alpha and IL-1 beta expression by an alternate signal transduction pathway, such as MAPK/AP-1. Activation of alternate signaling mechanisms by lactobacilli to modify epithelial cell cytokine production may be a mechanism for probiotic modulation of morbidity in vulvovaginal candidiasis.
C1 [Wagner, R. Doug; Johnson, Shemedia J.] 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
FU Food and Drug Administration of the Public Health Service
FX This work was supported by funds from the Food and Drug Administration
of the Public Health Service. The authors thank Dr. Mark Hart and Dr.
Marli Azevedo for critical review of the manuscript. The opinions
expressed in this manuscript are the authors' and do not necessarily
reflect the position of the Food and Drug Administration.
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U2 11
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1021-7770
J9 J BIOMED SCI
JI J. Biomed. Sci.
PD JUN 20
PY 2012
VL 19
AR 58
DI 10.1186/1423-0127-19-58
PG 8
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA 979GG
UT WOS:000306804700001
PM 22715972
ER
PT J
AU McFarland, HI
Puig, M
Grajkowska, LT
Tsuji, K
Lee, JP
Mason, KP
Verthelyi, D
Rosenberg, AS
AF McFarland, Hugh I.
Puig, Montserrat
Grajkowska, Lucja T.
Tsuji, Kazuhide
Lee, Jay P.
Mason, Karen P.
Verthelyi, Daniela
Rosenberg, Amy S.
TI Regulatory T Cells in gamma Irradiation-Induced Immune Suppression
SO PLOS ONE
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; VERSUS-HOST-DISEASE; ALLOGRAFT-REJECTION;
IONIZING-RADIATION; CD4(+)CD25(+); LYMPHOCYTES; TRANSPLANTATION;
PROLIFERATION; LYMPHOPENIA; POPULATION
AB Sublethal total body gamma irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naive mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies.
C1 [McFarland, Hugh I.; Puig, Montserrat; Grajkowska, Lucja T.; Tsuji, Kazuhide; Lee, Jay P.; Mason, Karen P.; Verthelyi, Daniela; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
RP McFarland, HI (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
EM hugh.mcfarland@fda.hhs.gov
RI McFarland, Hugh/K-1503-2016
OI McFarland, Hugh/0000-0002-3322-038X
FU U.S. Food and Drug Administration
FX This work was funded by the U.S. Food and Drug Administration. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 37
TC 13
Z9 13
U1 1
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 19
PY 2012
VL 7
IS 6
AR e39092
DI 10.1371/journal.pone.0039092
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 963VI
UT WOS:000305652700047
PM 22723935
ER
PT J
AU Ostrov, DA
Grant, BJ
Pompeu, YA
Sidney, J
Harndahl, M
Southwood, S
Oseroff, C
Lu, S
Jakoncic, J
de Oliveira, CAF
Yang, L
Mei, H
Shi, LM
Shabanowitz, J
English, AM
Wriston, A
Lucas, A
Phillips, E
Mallal, S
Grey, HM
Sette, A
Hunt, DF
Buus, S
Peters, B
AF Ostrov, David A.
Grant, Barry J.
Pompeu, Yuri A.
Sidney, John
Harndahl, Mikkel
Southwood, Scott
Oseroff, Carla
Lu, Shun
Jakoncic, Jean
de Oliveira, Cesar Augusto F.
Yang, Lun
Mei, Hu
Shi, Leming
Shabanowitz, Jeffrey
English, A. Michelle
Wriston, Amanda
Lucas, Andrew
Phillips, Elizabeth
Mallal, Simon
Grey, Howard M.
Sette, Alessandro
Hunt, Donald F.
Buus, Soren
Peters, Bjoern
TI Drug hypersensitivity caused by alteration of the MHC-presented
self-peptide repertoire
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 3D structure; small molecule; binding site
ID STEVENS-JOHNSON-SYNDROME; T-CELL-RECEPTOR; CLASS-I; CRYSTAL-STRUCTURE;
IMMUNE-RESPONSES; ABACAVIR; HLA; ACTIVATION; IDENTIFICATION;
PATHOGENESIS
AB Idiosyncratic adverse drug reactions are unpredictable, dose-independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkages between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8(+) T cells that required HLA-B*57:01 molecules for their function; however, the mechanism by which abacavir induces this pathologic T-cell response remains unclear. Here we show that abacavir can bind within the F pocket of the peptide-binding groove of HLA-B*57: 01, thereby altering its specificity. This provides an explanation for HLA-linked idiosyncratic adverse drug reactions, namely that drugs can alter the repertoire of self-peptides presented to T cells, thus causing the equivalent of an alloreactive T-cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir and that were recognized by T cells of hypersensitive patients. The assays that we have established can be applied to test additional compounds with suspected HLA-linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA-linked hypersensitivities, and guide the development of safer drugs.
C1 [Sidney, John; Southwood, Scott; Oseroff, Carla; Grey, Howard M.; Sette, Alessandro; Peters, Bjoern] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
[Ostrov, David A.; Lu, Shun] Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA.
[Grant, Barry J.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Pompeu, Yuri A.] Univ Florida, Dept Chem, Gainesville, FL 32611 USA.
[Harndahl, Mikkel; Buus, Soren] Univ Copenhagen, Fac Hlth Sci, Lab Expt Immunol, DK-2200 Copenhagen, Denmark.
[Jakoncic, Jean] Brookhaven Natl Lab, Upton, NY 11973 USA.
[de Oliveira, Cesar Augusto F.] Univ Calif San Diego, Dept Chem, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[de Oliveira, Cesar Augusto F.] Univ Calif San Diego, Dept Biochem, Howard Hughes Med Inst, La Jolla, CA 92037 USA.
[de Oliveira, Cesar Augusto F.] Univ Calif San Diego, Ctr Theoret Biol Phys, San Diego, CA 92037 USA.
[Yang, Lun; Mei, Hu; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Shabanowitz, Jeffrey; English, A. Michelle; Wriston, Amanda; Hunt, Donald F.] Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA.
[Lucas, Andrew; Phillips, Elizabeth; Mallal, Simon] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA 6150, Australia.
RP Grey, HM (reprint author), La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA.
EM hgrey@liai.org; bpeters@liai.org
RI Hunt, Donald/I-6936-2012; Buus, Soren/F-5446-2010; Yang, Lun/B-4859-2012
OI Hunt, Donald/0000-0003-2815-6368; Grant, Barry/0000-0002-2215-4196;
Buus, Soren/0000-0001-8363-1999;
FU National Institute of Health [AI 33993, HHSN 272 200900045C]
FX We thank Amiyah Steen, Sandy Ngo, Carrie Moore, and Victoria Tripple for
technical assistance; Patrick Hogan for helpful discussions; and Janet
Woodcock and Donna Mendrick for support. Funding was provided by
National Institute of Health Grants AI 33993 (to D. F. H.) and HHSN 272
200900045C (to S.B.).
NR 42
TC 123
Z9 130
U1 1
U2 40
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 JUN 19
PY 2012
VL 109
IS 25
BP 9959
EP 9964
DI 10.1073/pnas.1207934109
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 969NC
UT WOS:000306061400062
PM 22645359
ER
PT J
AU Nehrt, NL
Peterson, TA
Park, D
Kann, MG
AF Nehrt, Nathan L.
Peterson, Thomas A.
Park, DoHwan
Kann, Maricel G.
TI Domain landscapes of somatic mutations in cancer
SO BMC GENOMICS
LA English
DT Article; Proceedings Paper
CT 1st SNP Special-Interesting-Group (SNP-SIG) Meeting on Identification
and Annotation of SNPs in the Context of Structure, Function, and
Disease/ISMB/ECCB Conference
CY JUL 15, 2011
CL Vienna, AUSTRIA
SP Special Interesting Grp (SIG)
ID TUMOR-SUPPRESSOR PROTEIN; COLORECTAL CANCERS; HUMAN BREAST; GENE;
DATABASE; SEQUENCES; ACTIVATION; PHENOTYPE; CANDIDATE; PATHWAYS
AB Background: Large-scale tumor sequencing projects are now underway to identify genetic mutations that drive tumor initiation and development. Most studies take a gene-based approach to identifying driver mutations, highlighting genes mutated in a large percentage of tumor samples as those likely to contain driver mutations. However, this gene-based approach usually does not consider the position of the mutation within the gene or the functional context the position of the mutation provides. Here we introduce a novel method for mapping mutations to distinct protein domains, not just individual genes, in which they occur, thus providing the functional context for how the mutation contributes to disease. Furthermore, aggregating mutations from all genes containing a specific protein domain enables the identification of mutations that are rare at the gene level, but that occur frequently within the specified domain. These highly mutated domains potentially reveal disruptions of protein function necessary for cancer development.
Results: We mapped somatic mutations from the protein coding regions of 100 colon adenocarcinoma tumor samples to the genes and protein domains in which they occurred, and constructed topographical maps to depict the "mutational landscapes" of gene and domain mutation frequencies. We found significant mutation frequency in a number of genes previously known to be somatically mutated in colon cancer patients including APC, TP53 and KRAS. In addition, we found significant mutation frequency within specific domains located in these genes, as well as within other domains contained in genes having low mutation frequencies. These domain "peaks" were enriched with functions important to cancer development including kinase activity, DNA binding and repair, and signal transduction.
Conclusions: Using our method to create the domain landscapes of mutations in colon cancer, we were able to identify somatic mutations with high potential to drive cancer development. Interestingly, the majority of the genes involved have a low mutation frequency. Therefore, themethod shows good potential for identifying rare driver mutations in current, large-scale tumor sequencing projects. In addition, mapping mutations to specific domains provides the necessary functional context for understanding how the mutations contribute to the disease, and may reveal novel or more refined gene and domain target regions for drug development.
C1 [Nehrt, Nathan L.; Peterson, Thomas A.; Kann, Maricel G.] Univ Maryland Baltimore Cty, Dept BiologicalSci, Baltimore, MD 21250 USA.
[Nehrt, Nathan L.] US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA.
[Park, DoHwan] Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21250 USA.
RP Kann, MG (reprint author), Univ Maryland Baltimore Cty, Dept BiologicalSci, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM mkann@umbc.edu
FU NCI NIH HHS [1K22CA143148]
NR 45
TC 23
Z9 23
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 18
PY 2012
VL 13
SU 4
AR S9
DI 10.1186/1471-2164-13-S4-S9
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 970PP
UT WOS:000306145100009
PM 22759657
ER
PT J
AU Felix, C
Sonia, F
William, T
Zhang, YB
Xu, Y
de Lourdes, BM
Alexandru, B
Syed, A
AF Felix, Carvalho
Sonia, Fraga
William, Trickler
Zhang Yongbin
Xu Yang
de Lourdes, Bastos Maria
Alexandru, Biris
Syed, Ali
TI Effects of iron oxide nanoparticles on bovine microvascular endothelial
cells
SO TOXICOLOGY LETTERS
LA English
DT Meeting Abstract
CT 48th Congress of the European-Societies-of-Toxicology (EUROTOX)
CY JUN 17-20, 2012
CL Stockholm, SWEDEN
SP European Soc Toxicol (EUROTOX), Molnlycke Hlth Care, Ferring Pharmaceut, AstraZeneca, Agilent Technol
C1 [Felix, Carvalho] Univ Porto, Fac Pharm, Oporto, Portugal.
[Sonia, Fraga; de Lourdes, Bastos Maria] Univ Porto, REQUIMTE, Oporto, Portugal.
[William, Trickler; Zhang Yongbin; Syed, Ali] US FDA, NCTR, Rockville, MD 20857 USA.
[Xu Yang; Alexandru, Biris] Arkansas Nanotechnol Ctr, Little Rock, AR USA.
RI REQUIMTE, AL/H-9106-2013; Chaves, Pedro/K-1288-2013
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUN 17
PY 2012
VL 211
SU S
BP S207
EP S207
DI 10.1016/j.toxlet.2012.03.740
PG 1
WC Toxicology
SC Toxicology
GA 957PB
UT WOS:000305173900675
ER
PT J
AU Deisseroth, A
Kaminskas, E
Grillo, J
Chen, W
Saber, H
Lu, HL
Rothmann, MD
Brar, S
Wang, J
Garnett, C
Bullock, J
Burke, LB
Rahman, A
Sridhara, R
Farrell, A
Pazdur, R
AF Deisseroth, Albert
Kaminskas, Edvardas
Grillo, Joseph
Chen, Wei
Saber, Haleh
Lu, Hong L.
Rothmann, Mark D.
Brar, Satjit
Wang, Jian
Garnett, Christine
Bullock, Julie
Burke, Laurie B.
Rahman, Atiqur
Sridhara, Rajeshwari
Farrell, Ann
Pazdur, Richard
TI U.S. Food and Drug Administration Approval: Ruxolitinib for the
Treatment of Patients with Intermediate and High-Risk Myelofibrosis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID INTERNATIONAL-WORKING-GROUP; MYELOID METAPLASIA
AB On November 16, 2011, the U.S. Food and Drug Administration (FDA) granted full approval to ruxolitinib, (Jakafi; Incyte Corp.), an inhibitor of the Janus kinases 1 and 2, for the treatment of patients with intermediate-or high-risk myelofibrosis, including primary myelofibrosis, postpolycythemia vera myelofibrosis, and postessential thrombocythemia myelofibrosis. This approval was based on the results of 2 large randomized phase III trials that enrolled patients with intermediate-2 or high-risk myelofibrosis and compared ruxolitinib with placebo (study 1) or best available therapy (study 2). The primary efficacy endpoint was the proportion of patients who experienced a reduction in spleen volume of >= 35% at 24 weeks (study 1) or 48 weeks (study 2). The key secondary endpoint in study 1 was the proportion of patients who experienced a >= 50% improvement from baseline in myelofibrosis total symptom score at 24 weeks. The results of these studies showed that a greater proportion of patients treated with ruxolitinib experienced a >= 35% reduction in spleen volume as compared with those treated with placebo (42% vs. 1%, P < 0.0001) or best available therapy (29% vs. 0%, P < 0.0001). A greater proportion of patients in study 1 experienced a >= 50% reduction in the myelofibrosis total symptom score during treatment with ruxolitinib than with placebo (46% vs. 5%, P < 0.0001). Ruxolitinib treatment was associated with an increased incidence of grades III and IV anemia, thrombocytopenia, and neutropenia. This is the first drug approved for myelofibrosis. Clin Cancer Res; 18(12); 3212-7. (C) 2012 AACR.
C1 [Deisseroth, Albert] US FDA, Ctr Drug Evaluat & Res, Div Hematol Prod, Off Hematol & Oncol Drug Prod, Silver Spring, MD 20993 USA.
[Burke, Laurie B.] US FDA, Study Endpoints & Label Dev, Off New Drugs, Silver Spring, MD USA.
[Grillo, Joseph; Brar, Satjit; Wang, Jian; Garnett, Christine; Bullock, Julie; Rahman, Atiqur] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA.
[Lu, Hong L.; Rothmann, Mark D.; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD USA.
RP Deisseroth, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Hematol Prod, Off Hematol & Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 2334, Silver Spring, MD 20993 USA.
EM albert.deisseroth@fda.hhs.gov
NR 10
TC 42
Z9 44
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUN 15
PY 2012
VL 18
IS 12
BP 3212
EP 3217
DI 10.1158/1078-0432.CCR-12-0653
PG 6
WC Oncology
SC Oncology
GA 988PD
UT WOS:000307502100002
PM 22544377
ER
PT J
AU Shin, EJ
Duong, CX
Nguyen, XKT
Li, Z
Bing, GY
Bach, JH
Park, DH
Nakayama, K
Ali, SF
Kanthasamy, AG
Cadet, JL
Nabeshima, T
Kim, HC
AF Shin, Eun-Joo
Duong, Chu Xuan
Xuan-Khanh Thi Nguyen
Li, Zhengyi
Bing, Guoying
Bach, Jae-Hyung
Park, Dae Hun
Nakayama, Keiichi
Ali, Syed F.
Kanthasamy, Anumantha G.
Cadet, Jean Lud
Nabeshima, Toshitaka
Kim, Hyoung-Chun
TI Role of oxidative stress in methamphetamine-induced dopaminergic
toxicity mediated by protein kinase C delta
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Methamphetamine; PKC isozymes; PKC delta gene deletion; Rottlerin;
Dopamine; Oxidative stress
ID VESICULAR MONOAMINE TRANSPORTER-2; TYROSINE-HYDROXYLASE PHOSPHORYLATION;
DISMUTASE TRANSGENIC MICE; PANCREATIC ACINAR-CELLS; PKC-DELTA; INDUCED
NEUROTOXICITY; RAT-BRAIN; NEURONAL APOPTOSIS; TERMINAL MARKERS; STRIATAL
SYNAPTOSOMES
AB This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKC alpha, PKC beta I PKC beta II, or PKC zeta expression in the striatum, but did significantly increase PKC delta expression. Go6976 (a co-inhibitor of PKC alpha and -beta), hispidin (PKC beta inhibitor), and PKC zeta pseudosubstrate inhibitor (PKC zeta inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKC delta inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKC delta knockout (-/-) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKC delta (-/-) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore. MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKC delta (-/-) mice. Our results suggest that PKC delta gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKC delta may be a useful target for protection against MA-induced neurotoxicity. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Shin, Eun-Joo; Duong, Chu Xuan; Xuan-Khanh Thi Nguyen; Li, Zhengyi; Bach, Jae-Hyung; Park, Dae Hun; Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea.
[Bing, Guoying] Univ Kentucky, Coll Med, Dept Anat & Neurobiol, Lexington, KY 40536 USA.
[Nakayama, Keiichi] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan.
[Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA.
[Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA.
[Cadet, Jean Lud] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA.
[Nabeshima, Toshitaka] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Reg Pharmaceut Care & Sci, Nagoya, Aichi 4688503, Japan.
[Nabeshima, Toshitaka] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Chem Pharmacol, Nagoya, Aichi 4688503, Japan.
RP Kim, HC (reprint author), Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea.
EM kimhc@kangwon.ac.kr
FU Brain Research Center from 21st Century Frontier Research Program
[2011K000271]; Ministry of Science and Technology, Republic of Korea;
Ministry of Health Labour and Welfare (MHLW): Research on Risk of
Chemical Substances; Ministry of Education, Culture, Sports, Science and
Technology (MEST): Academic Frontier Project; BK 21 program
FX This study was supported by a grant (#2011K000271) from the Brain
Research Center from 21st Century Frontier Research Program funded by
the Ministry of Science and Technology, Republic of Korea. This work
was, in part, supported by grants from Ministry of Health Labour and
Welfare (MHLW): Research on Risk of Chemical Substances, and Ministry of
Education, Culture, Sports, Science and Technology (MEST): Academic
Frontier Project. Xuan-Khanh Thi Nguyen and Jae-Hyung Bach were
supported by BK 21 program. Equipment at the Institute of Pharmaceutical
Science (Kangwon National University) was used for this study.
NR 105
TC 22
Z9 22
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD JUN 15
PY 2012
VL 232
IS 1
BP 98
EP 113
DI 10.1016/j.bbr.2012.04.001
PG 16
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 963BR
UT WOS:000305595600014
PM 22512859
ER
PT J
AU Hoinka, J
Zotenko, E
Friedman, A
Sauna, ZE
Przytycka, TM
AF Hoinka, Jan
Zotenko, Elena
Friedman, Adam
Sauna, Zuben E.
Przytycka, Teresa M.
TI Identification of sequence-structure RNA binding motifs for
SELEX-derived aptamers
SO BIOINFORMATICS
LA English
DT Article; Proceedings Paper
CT 20th Annual International Conference on Intelligent Systems for
Molecular Biology
CY JUL 15-17, 2012
CL Long Beach, CA
ID SECONDARY STRUCTURE; MULTIPLE SEQUENCES; IN-VITRO; PROTEIN; SELECTION;
ALIGNMENT; PREDICTION; LIGANDS; TIME; VIVO
AB Motivation: Systematic Evolution of Ligands by EXponential Enrichment (SELEX) represents a state-of-the-art technology to isolate single-stranded (ribo) nucleic acid fragments, named aptamers, which bind to a molecule (or molecules) of interest via specific structural regions induced by their sequence-dependent fold. This powerful method has applications in designing protein inhibitors, molecular detection systems, therapeutic drugs and antibody replacement among others. However, full understanding and consequently optimal utilization of the process has lagged behind its wide application due to the lack of dedicated computational approaches. At the same time, the combination of SELEX with novel sequencing technologies is beginning to provide the data that will allow the examination of a variety of properties of the selection process.
Results: To close this gap we developed, Aptamotif, a computational method for the identification of sequence-structure motifs in SELEX-derived aptamers. To increase the chances of identifying functional motifs, Aptamotif uses an ensemble-based approach. We validated the method using two published aptamer datasets containing experimentally determined motifs of increasing complexity. We were able to recreate the author's findings to a high degree, thus proving the capability of our approach to identify binding motifs in SELEX data. Additionally, using our new experimental dataset, we illustrate the application of Aptamotif to elucidate several properties of the selection process.
C1 [Friedman, Adam; Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Hoinka, Jan; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20894 USA.
[Zotenko, Elena] St Vincents Hosp, Garvan Inst Med Res, Darlinghurst, NSW 2010, Australia.
RP Sauna, ZE (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
EM Zuben.Sauna@fda.hhs.gov; przytyck@ncbi.nlm.nih.gov
OI Zotenko, Elena/0000-0002-0256-3195
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine; Center for Biologics Evaluation and
Research, Food and Drug Administration's Modernization of Science
program
FX Funding: Intramural Research Program of the National Institutes of
Health, National Library of Medicine (partial); and Center for Biologics
Evaluation and Research, Food and Drug Administration's Modernization of
Science program (ZES) (partial). The findings and conclusions in this
article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 42
TC 25
Z9 25
U1 1
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JUN 15
PY 2012
VL 28
IS 12
BP I215
EP I223
DI 10.1093/bioinformatics/bts210
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 960VK
UT WOS:000305419800027
PM 22689764
ER
PT J
AU Hansen, DK
George, NI
White, GE
Pellicore, LS
Abdel-Rahman, A
Fabricant, D
AF Hansen, Deborah K.
George, Nysia I.
White, Gene E.
Pellicore, Linda S.
Abdel-Rahman, Ali
Fabricant, Daniel
CA Food Drug Adm
TI Physiological effects following administration of Citrus aurantium for
28 days in rats
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Bitter orange; Citrus aurantium; Cardiotoxicology; Blood pressure; Heart
rate; Weight loss
ID WEIGHT-LOSS SUPPLEMENTS; HEALTHY OVERWEIGHT ADULTS; EPHEDRA-FREE
XENADRINE; BITTER-ORANGE; DIETARY-SUPPLEMENTS; P-SYNEPHRINE;
CLINICAL-TRIAL; UNITED-STATES; CAFFEINE; ALKALOIDS
AB Background: Since ephedra-containing dietary supplements were banned from the US market, manufacturers changed their formulations by eliminating ephedra and replacing with other botanicals, including Citrus aurantium, or bitter orange. Bitter orange contains, among other compounds, synephrine, a chemical that is chemically similar to ephedrine. Since ephedrine may have cardiovascular effects, the goal of this study was to investigate the cardiovascular effects of various doses of bitter orange extract and pure synephrine in rats.
Method: Female Sprague-Dawley rats were dosed daily by gavage for 28 days with synephrine from two different extracts. One extract contained 6% synephrine, and the other extract contained 95% synephrine. Doses were 10 or 50 mg synephrine/kg body weight from each extract. Additionally, caffeine was added to these doses, since many dietary supplements also contain caffeine. Telemetry was utilized to monitor heart rate, blood pressure, body temperature and QT interval in all rats.
Results and conclusion: Synephrine, either as the bitter orange extract or as pure synephrine, increased heart rate and blood pressure. Animals treated with 95% synephrine showed minimal effects on heart rate and blood pressure; more significant effects were observed with the bitter orange extract suggesting that other components in the botanical can alter these physiological parameters. The increases in heart rate and blood pressure were more pronounced when caffeine was added. None of the treatments affected uncorrected QT interval in the absence of caffeine. Published by Elsevier Inc.
C1 [Hansen, Deborah K.; George, Nysia I.] US FDA, Div Personalized Nutr & Med, NCTR, Jefferson, AR 72079 USA.
[White, Gene E.] Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Pellicore, Linda S.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[Abdel-Rahman, Ali; Fabricant, Daniel] US FDA, Off Nutr Labeling & Dietary Supplements, Ctr Food Safety & Nutr, College Pk, MD 20740 USA.
RP Hansen, DK (reprint author), US FDA, Div Personalized Nutr & Med, NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM deborah.hansen@fda.hhs.gov
FU FDA:NCTR; NIEHS:NTP [FDA 224-07-0007, NIH Y1ES1027]
FX This work was supported by Interagency Agreement between FDA:NCTR and
the NIEHS:NTP (FDA 224-07-0007) (NIH Y1ES1027).
NR 53
TC 10
Z9 11
U1 0
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUN 15
PY 2012
VL 261
IS 3
BP 236
EP 247
DI 10.1016/j.taap.2012.04.006
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 961XK
UT WOS:000305502600002
PM 22521485
ER
PT J
AU Miller, HI
AF Miller, Henry I.
TI Waste and Abuse in Federal Research Funding
SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS
LA English
DT Editorial Material
C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA.
[Miller, Henry I.] NIH, Bethesda, MD USA.
[Miller, Henry I.] US FDA, Rockville, MD 20857 USA.
RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA.
EM henry.miller@stanford.edu
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 1935-472X
J9 GENET ENG BIOTECHN N
JI Genet. Eng. Biotechnol. News
PD JUN 15
PY 2012
VL 32
IS 12
BP 6
EP +
PG 3
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 961CI
UT WOS:000305441100003
ER
PT J
AU Kunz, AN
Begum, AA
Wu, H
D'Ambrozio, JA
Robinson, JM
Shafer, WM
Bash, MC
Jerse, AE
AF Kunz, Anjali N.
Begum, Afrin A.
Wu, Hong
D'Ambrozio, Jonathan A.
Robinson, James M.
Shafer, William M.
Bash, Margaret C.
Jerse, Ann E.
TI Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and
In Vivo Selection for Compensatory Mutations
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID SEXUALLY-TRANSMITTED-DISEASES; GENITAL-TRACT INFECTION; MTRRCDE EFFLUX
SYSTEM; NEISSERIA-GONORRHOEAE; ANTIBIOTIC-RESISTANCE; BIOLOGICAL COST;
STAPHYLOCOCCUS-AUREUS; QUINOLONE RESISTANCE; TREATMENT GUIDELINES;
SUSCEPTIBILITY
AB Background. Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA(91/95) and parC(86) mutations on gonococcal fitness.
Methods. Mutant gyrA(91/95) and parC(86) alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR(-79) mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection.
Results. In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA(91/95) mutation conferred an in vivo fitness benefit to wild-type and mtrR(-79) mutant gonococci. The gyrA(91/95), parC(86) mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA(91/95), parC(86), mtrR(-79) mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (Cip(R)) mutant was selected during infection with the gyrA(91/95), parC(86), mtrR(-79) mutant in which the mtrR(-79) mutation was repaired and the gyrA(91) mutation was altered. This in vivo-selected mutant grew as well as the wild-type strain in vitro.
Conclusions. gyrA(91/95) mutations may contribute to the spread of QRNG. Further acquisition of a parC(86) mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain Cip(R).
C1 [Kunz, Anjali N.; Begum, Afrin A.; Wu, Hong; D'Ambrozio, Jonathan A.; Robinson, James M.; Jerse, Ann E.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Silver Spring, MD USA.
[Kunz, Anjali N.] Walter Reed Army Inst Res, Mil HIV Res Program, Silver Spring, MD USA.
[Shafer, William M.] Vet Affairs Med Ctr, VA Med Res Serv, Labs Microbial Pathogenesis, Decatur, GA 30033 USA.
[Shafer, William M.] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA.
[Bash, Margaret C.] US FDA, Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Bethesda, MD USA.
RP Jerse, AE (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
EM ajerse@usuhs.mil
FU National Institute of Allergy and Infectious Diseases at the National
Institute of Health [RO1 AI42053, U19 AI31496, R37 AI21150]; Uniformed
Services University of the Health Sciences [C073-RT]; VA Medical
Research Service
FX This work was supported by the National Institute of Allergy and
Infectious Diseases at the National Institute of Health (RO1 AI42053 and
U19 AI31496 to A. E. J.; R37 AI21150 to W. M. S.), and a Uniformed
Services University of the Health Sciences training grant (C073-RT to A.
N. K.). W. M. S. was supported in part by Senior Research Career
Scientist and VA Merit awards from the VA Medical Research Service.
NR 48
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U1 2
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUN 15
PY 2012
VL 205
IS 12
BP 1821
EP 1829
DI 10.1093/infdis/jis277
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 948YI
UT WOS:000304539600010
PM 22492860
ER
PT J
AU Li, Y
Chen, DH
Yan, J
Chen, Y
Mittelstaedt, RA
Zhang, YB
Biris, AS
Heflich, RH
Chen, T
AF Li, Yan
Chen, David H.
Yan, Jian
Chen, Ying
Mittelstaedt, Roberta A.
Zhang, Yongbin
Biris, Alexandru S.
Heflich, Robert H.
Chen, Tao
TI Genotoxicity of silver nanoparticles evaluated using the Ames test and
in vitro micronucleus assay
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Silver nanoparticles; Ames test; In vitro micronucleus assay;
Genotoxicity
ID TITANIUM-DIOXIDE PARTICLES; HUMAN LYMPHOBLASTOID-CELLS; ULTRAFINE TIO2
PARTICLES; EPITHELIAL-CELLS; OXIDATIVE STRESS; FEPT NANOPARTICLES;
CARBON NANOTUBES; MUTAGENICITY; CYTOTOXICITY; TOXICITY
AB Silver nanoparticles (AgNPs) have antimicrobial properties, which have contributed to their widespread use in consumer products. A current issue regarding nanomaterials is the extent to which existing genotoxicity assays are useful for evaluating the risks associated with their use. In this study, the genotoxicity of 5 nm AgNPs was assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus assay. Using the preincubation version of the Ames assay, Salmonella strains TA102, TA100, TA1537, TA98, and TA1535 were treated with 0.15-76.8 mu g/plate of the AgNPs. Toxicity limited the doses that could be assayed to 2.4-38.4 mu g/plate; no increases in mutant frequency over the vehicle control were found for the concentrations that could be assayed. Human lymphoblastoid TK6 cells were treated with 10-30 mu g/ml AgNPs, and additional cells were treated with water and 0.73 gy X-rays as vehicle and positive controls. Micronucleus frequency was increased by the AgNP treatment in a dose-dependent manner. At a concentration of 30 mu g/ml (with 45.4% relative population doubling), AgNPs induced a significant, 3.17-fold increase with a net increase of 1.60% in micronucleus frequency over the vehicle control, a weak positive response by our criteria. These results demonstrate that the 5 nm AgNP are genotoxic in TK6 cells. Also, the data suggest that the in vitro micronucleus assay may be more appropriate than the Ames test for evaluating the genotoxicity of the AgNPs. Published by Elsevier B.V.
C1 [Li, Yan; Yan, Jian; Chen, Ying; Mittelstaedt, Roberta A.; Heflich, Robert H.; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chen, David H.] Little Rock Cent High Sch, Little Rock, AR 72202 USA.
[Zhang, Yongbin] US FDA, Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA.
RP Chen, T (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, HFT 130,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM tao.chen@fda.hhs.gov
RI Li, Yan/F-9560-2012; Li, Yan/G-5158-2012
FU CORES from the U.S. Food and Drug Administration; Oak Ridge Institute
for Science and Education
FX Y.L. is supported by an appointment to the Oak Ridge Institute for
Science and Education. This project was partially funded by the CORES
program from the U.S. Food and Drug Administration.
NR 60
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U1 1
U2 47
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 JUN 14
PY 2012
VL 745
IS 1-2
SI SI
BP 4
EP 10
DI 10.1016/j.mrgentox.2011.11.010
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 951TC
UT WOS:000304741900002
PM 22138422
ER
PT J
AU Sadiq, R
Bhalli, JA
Yan, J
Woodruff, RS
Pearce, MG
Li, Y
Mustafa, T
Watanabe, F
Pack, LM
Biris, AS
Khan, QM
Chen, T
AF Sadiq, Rakhshinda
Bhalli, Javed A.
Yan, Jian
Woodruff, Robert S.
Pearce, Mason G.
Li, Yan
Mustafa, Thikra
Watanabe, Fumiya
Pack, Lindsay M.
Biris, Alexandru S.
Khan, Qaiser M.
Chen, Tao
TI Genotoxicity of TiO2 anatase nanoparticles in B6C3F1 male mice evaluated
using Pig-a and flow cytometric micronucleus assays
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Titanium dioxide nanoparticles; Phosphatidylinositol glycan class A
gene; Flow cytometry; CD24; %MN-RET frequency; In vivo genotoxicity
assays
ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; TITANIUM-DIOXIDE NANOPARTICLES;
RED-BLOOD-CELLS; SPLEEN T-CELLS; IN-VIVO; ULTRAFINE PARTICLES;
MEMBRANE-PROTEINS; MUTATION; GENE; RAT
AB In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were conducted to evaluate the genotoxicity of 10 nm titanium dioxide anatase nanoparticles (TiO2-NPs) in mice. Groups of five 6-7-week-old male B6C3F1 mice were treated intravenously for three consecutive days with 0.5, 5.0, and 50 mg/kg TiO2-NPs for the two assays: mouse blood was sampled one day before the treatment and on Day 4, and Weeks 1,2, 4, and 6 after the beginning of the treatment: Pig-a mutant frequencies were determined at Day -1 and Weeks 1, 2, 4 and 6, while percent micronucleated-reticulocyte (%MN-RET) frequencies were measured on Day 4 only. Additional animals were treated intravenously with three daily doses of 50 mg/kg TiO2-NPs for the measurement of titanium levels in bone marrow after 4, 24, and 48 h of the last treatment. The measurement indicated that the accumulation of the nanoparticles reached the peak in the tissue 4 h after the administration and the levels were maintained for a few days. No increase in either Pig-a mutant frequency or the frequency of %MN-RETs was detected, although the %RETs was reduced in the treated animals on Day 4 in a dose-dependent manner indicating cytotoxicity of TiO2-NPs in the bone marrow. These results suggest that although TiO2-NPs can reach the mouse bone marrow and are capable of inducing cytotoxicity, the nanoparticles are not genotoxic when assessed with in vivo micronucleus and Pig-a gene mutation tests. Published by Elsevier
C1 [Sadiq, Rakhshinda; Bhalli, Javed A.; Yan, Jian; Pearce, Mason G.; Li, Yan; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Sadiq, Rakhshinda; Khan, Qaiser M.] NIBGE, Faisalabad, Pakistan.
[Woodruff, Robert S.] US FDA, Div Microbiol, Arkansas Reg Lab, Jefferson, AR 72079 USA.
[Mustafa, Thikra; Watanabe, Fumiya; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA.
[Pack, Lindsay M.] US FDA, Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Chen, T (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM tao.chen@fda.hhs.gov
RI Li, Yan/F-9560-2012; Li, Yan/G-5158-2012; Khan, Qaiser
Mahmood/I-6401-2015
FU Higher Education Commission (HEC), Pakistan; CORES from the U.S. Food
and Drug Administration
FX The authors are thankful to the Higher Education Commission (HEC),
Pakistan, for providing financial support (to R.S.) under the
International Research Support Initiative Program (IRSIP) and to the Oak
Ridge Institute for Science and Education (ORISE) for hosting the
scientific interaction that resulted in this study. The authors also
wish to thank director of the Division of Genetic and Molecular
Toxicology, National Center for Toxicological Research/U.S. Food and
Drug Administration, Martha M. Moore, for her support to complete this
research project.; This project was partially funded by the CORES
program from the U.S. Food and Drug Administration.
NR 60
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U1 2
U2 12
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 JUN 14
PY 2012
VL 745
IS 1-2
SI SI
BP 65
EP 72
DI 10.1016/j.mrgentox.2012.02.002
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 951TC
UT WOS:000304741900009
PM 22712079
ER
PT J
AU Jing, XH
Phy, K
Li, X
Ye, ZP
AF Jing, Xianghong
Phy, Kathryn
Li, Xing
Ye, Zhiping
TI Increased hemagglutinin content in a reassortant 2009 pandemic H1N1
influenza virus with chimeric neuraminidase containing donor A/Puerto
Rico/8/34 virus transmembrane and stalk domains
SO VACCINE
LA English
DT Article
DE Influenza virus; Vaccine; Reassortant; Neuraminidase
ID HPLC METHOD; A VIRUS; H5N1; GLYCOPROTEINS; REPLICATION; PH
AB The glycoproteins, heamagglutinin (HA) and neuraminidase (NA) of influenza virus confer host protective immune responses during vaccination, which is the most effective approach for preventing influenza-associated morbidity and mortality. Since the functional balance between the HA and NA proteins may affect viral receptor binding and replication, a pandemic influenza A virus (H1N1 pdm09), strain A/Texas/05/2009, was optimized to elevate its HA antigen content by modifying the NA gene. In this study, we have constructed two 2:6 reassortant viruses between pdmH1N1 (A/Texas/05/2009) and A/Puerto Rico/8/34 (PR8), in which the NA gene of A/Texas/05/2009 was modified to contain part of the NA gene from PR8. One chimeric NA virus has the PR8 transmembrane (TM) region (HNtm 2:6) and the other contains both the PR8 NA TM and stem regions (HNst 2:6). Using quantitative reverse phase-HPLC (RP-HPLC) analysis, we observed that the HNst2:6 virus contains a higher HA1 content than HN2:6 wild type. In addition, this mutant virus displays a higher HA1 to nucleoprotein (NP) ratio, based on gel electrophoresis densitometry analysis. Furthermore, the neuraminidase activity of purified HNst 2:6 virus is approximately 30% lower than that of HN2:6 virus, which is suggestive of a lower incorporation of NA into the viral envelope. Therefore, we propose that the reduction of NA packaging in the virion may lead to a compensatory increase of HA. Such an improvement in HA yield is possibly beneficial to H1N1 pdm09 vaccine production. Published by Elsevier Ltd.
C1 [Jing, Xianghong; Phy, Kathryn; Li, Xing; Ye, Zhiping] US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review, Bethesda, MD 20014 USA.
RP Ye, ZP (reprint author), US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review, Bethesda, MD 20014 USA.
EM Zhiping.ye@fda.hhs.gov
FU Biomedical Advanced Research and Development Authority, Department of
Health and Human Services
FX We thank CDC for providing the A/Texas/05/2009 HA plasmid, and CBER core
facility for RP-HPLC service, especially to Dr. Rongfong Shen and
Sang-eun Lee for the technical support. We thank Stephanie Polo and Dr.
Maryna Eichelberger for reviewing this manuscript. This work was
supported in part by the Biomedical Advanced Research and Development
Authority, Department of Health and Human Services.
NR 27
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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 JUN 13
PY 2012
VL 30
IS 28
BP 4144
EP 4152
DI 10.1016/j.vaccine.2012.04.073
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 965PT
UT WOS:000305780400004
PM 22561313
ER
PT J
AU Tadapaneni, RK
Banaszewski, K
Patazca, E
Edirisinghe, I
Cappozzo, J
Jackson, L
Burton-Freeman, B
AF Tadapaneni, Ravi Kiran
Banaszewski, Katarzyna
Patazca, Eduardo
Edirisinghe, Indika
Cappozzo, Jack
Jackson, Lauren
Burton-Freeman, Britt
TI Effect of High-Pressure Processing and Milk on the Anthocyanin
Composition and Antioxidant Capacity of Strawberry-Based Beverages
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE anthocyanin; ORAC; antioxidant capacity; high-pressure processing
LC-MS/MS
ID RECONSTITUTED ORANGE JUICE; VITAMIN-C; ASSAYS; FLAVONOIDS; PRODUCTS;
PROTEIN; STORAGE; PLASMA; WOMEN; FRUIT
AB The present study investigated processing strategies and matrix effects on the antioxidant capacity (AC) and polyphenols (PP) content of fruit-based beverages: (1) strawberry powder (Str) + dairy, D-Str; (2) Str + water, ND-Str; (3) dairy + no Str, D-NStr. Beverages were subjected to high-temperature short-time (HTST) and high-pressure processing (HPP). AC and PP were measured before and after processing and after a 5 week shelf-life study. Unprocessed D-Str had significantly lower AC compared to unprocessed ND-Str. Significant reductions in AC were apparent in HTST-compared to HPP-processed beverages (up to 600 MPa). PP content was significantly reduced in D-Str compared to ND-Str and in response to HPP and HTST in all beverages. After storage (5 weeks), AC and PP were reduced in all beverages compared to unprocessed and week 0 processed beverages. These findings indicate potentially negative effects of milk and processing on AC and PP of fruit-based beverages.
C1 [Tadapaneni, Ravi Kiran; Banaszewski, Katarzyna; Patazca, Eduardo; Edirisinghe, Indika; Cappozzo, Jack; Jackson, Lauren; Burton-Freeman, Britt] IIT, Inst Food Safety & Hlth, Ctr Nutr Res, Bedford Pk, IL 60501 USA.
[Jackson, Lauren] US FDA, Bedford Pk, IL 60501 USA.
RP Burton-Freeman, B (reprint author), IIT, Inst Food Safety & Hlth, Ctr Nutr Res, 6502 S Archer Rd, Bedford Pk, IL 60501 USA.
EM bburton@iit.edu
FU National Center for Food Safety and Technology; FDA
FX This research project was supported by the National Center for Food
Safety and Technology and an FDA cooperative agreement grant. The
scientific views and opinions expressed in this paper do not reflect
those of the U.S. Food and Drug Administration.
NR 34
TC 14
Z9 14
U1 2
U2 39
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JUN 13
PY 2012
VL 60
IS 23
BP 5795
EP 5802
DI 10.1021/jf2035059
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 956RU
UT WOS:000305107600015
PM 22224588
ER
PT J
AU Tulio, AZ
Chang, C
Edirisinghe, I
White, KD
Jablonski, JE
Banaszewski, K
Kangath, A
Tadapaneni, RK
Burton-Freeman, B
Jackson, LS
AF Tulio, Artemio Z., Jr.
Chang, Claire
Edirisinghe, Indika
White, Kevin D.
Jablonski, Joseph E.
Banaszewski, Katarzyna
Kangath, Archana
Tadapaneni, Ravi K.
Burton-Freeman, Britt
Jackson, Lauren S.
TI Berry Fruits Modulated Endothelial Cell Migration and Angiogenesis via
Phosphoinositide-3 Kinase/Protein Kinase B Pathway in Vitro in
Endothelial Cells
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE wild blueberry; cranberry; strawberry; polyphenolic compounds;
anthocyanins; p-Akt; cell migration; tube formation
ID LIQUID-CHROMATOGRAPHY; DEPENDENT RELAXATION; ANTHOCYANIN CONTENT;
STRAWBERRY; DYSFUNCTION; CRANBERRY; DISEASE; URINE; POLYPHENOLS;
METABOLITES
AB Polyphenolic-rich berry fruits are known to activate redox-sensitive cellular signaling molecules such as phosphatidylinosito1-3-kinase (PI3 kinase)/kinase B (Akt), resulting in a cascade of downstream signaling pathways. This study investigated the ability of strawberry (SB), wild blueberry (WBB), and cranberry (CB) extracts to induce the activation of PI3 kinase/Akt signaling in vitro in human umbilical endothelial cells (HUVECs) and whether this activation would enhance cell migration and angiogenesis. Anthocyanin profiles of the extracts were characterized using HPLC-ESI/MS, and Akt activation was investigated using the Alpha Screen SureFire assay. The total anthocyanin contents of SB, WBB, and CB extracts were 81.7, 82.5, and 83.0 mg/100 g fresh weight, respectively. SB, WBB, and CB extracts activated Akt in a dose-dependent manner via PI3 kinase and induced cell migration and angiogenesis in vitro in HUVECs. The results from this study suggest that polyphenolics in berry fruits may play a role in promoting vascular health.
C1 [Edirisinghe, Indika; Banaszewski, Katarzyna; Kangath, Archana; Tadapaneni, Ravi K.; Burton-Freeman, Britt] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA.
[Tulio, Artemio Z., Jr.; Chang, Claire; Jablonski, Joseph E.; Jackson, Lauren S.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA.
[White, Kevin D.] US FDA, Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA.
RP Burton-Freeman, B (reprint author), IIT, Inst Food Safety & Hlth, 6502 S Archer Road, Bedford Pk, IL 60501 USA.
EM bburton@iit.edu
FU FDA/NCFST
FX Funding for this project was provided by an FDA/NCFST cooperative
agreement grant. The scientific views and opinions expressed in this
paper are those of the individual authors and do not necessary reflect
those of the U.S. Food and Drug Administration.
NR 37
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U1 2
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PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD JUN 13
PY 2012
VL 60
IS 23
BP 5803
EP 5812
DI 10.1021/jf3001636
PG 10
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 956RU
UT WOS:000305107600016
PM 22448669
ER
PT J
AU Gunn, JP
Blair, NA
Cogswell, ME
Merritt, RK
Labarthe, DR
Curtis, CJ
Fasano, J
Neuwelt, AV
Popovic, T
AF Gunn, Janelle P.
Blair, Nicole A.
Cogswell, Mary E.
Merritt, Robert K.
Labarthe, Darwin R.
Curtis, Christine J.
Fasano, Jeremiah
Neuwelt, Amy V.
Popovic, Tanja
TI CDC Grand Rounds: Dietary Sodium Reduction-Time for Choice (Reprinted
from MMWR, vol 61, pg 89-91, 2012)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Reprint
C1 [Gunn, Janelle P.; Blair, Nicole A.; Cogswell, Mary E.; Merritt, Robert K.; Labarthe, Darwin R.] CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
[Curtis, Christine J.] New York City Dept Hlth & Mental Hyg, New York, NY USA.
[Fasano, Jeremiah] US FDA, Rockville, MD 20857 USA.
[Neuwelt, Amy V.] CDC, Off Surveillance Epidemiol & Lab Svcs, Atlanta, GA 30333 USA.
[Popovic, Tanja] CDC, Off Director, Atlanta, GA 30333 USA.
RP Gunn, JP (reprint author), CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA.
EM jperalez-gunn@cdc.gov
NR 1
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUN 13
PY 2012
VL 307
IS 22
BP 2365
EP 2367
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 956UX
UT WOS:000305115900009
ER
PT J
AU White, JR
Patel, J
Ottesen, A
Arce, G
Blackwelder, P
Lopez, JV
AF White, James R.
Patel, Jignasa
Ottesen, Andrea
Arce, Gabriela
Blackwelder, Patricia
Lopez, Jose V.
TI Pyrosequencing of Bacterial Symbionts within Axinella corrugata Sponges:
Diversity and Seasonal Variability
SO PLOS ONE
LA English
DT Article
ID SULFUR-OXIDIZING BACTERIA; MARINE SPONGES; IN-VITRO; DEEP-SEA;
TEICHAXINELLA-MORCHELLA; EMENDED DESCRIPTION; GEN. NOV.; DEMOSPONGIAE;
CELL; ECTOTHIORHODOSPIRACEAE
AB Background: Marine sponge species are of significant interest to many scientific fields including marine ecology, conservation biology, genetics, host-microbe symbiosis and pharmacology. One of the most intriguing aspects of the sponge "holobiont" system is the unique physiology, interaction with microbes from the marine environment and the development of a complex commensal microbial community. However, intraspecific variability and temporal stability of sponge-associated bacterial symbionts remain relatively unknown.
Methodology/Principal Findings: We have characterized the bacterial symbiont community biodiversity of seven different individuals of the Caribbean reef sponge Axinella corrugata, from two different Florida reef locations during variable seasons using multiplex 454 pyrosequencing of 16 S rRNA amplicons. Over 265,512 high-quality 16 S rRNA sequences were generated and analyzed. Utilizing versatile bioinformatics methods and analytical software such as the QIIME and CloVR packages, we have identified 9,444 distinct bacterial operational taxonomic units (OTUs). Approximately 65,550 rRNA sequences (24%) could not be matched to bacteria at the class level, and may therefore represent novel taxa. Differentially abundant classes between seasonal Axinella communities included Gammaproteobacteria, Flavobacteria, Alphaproteo-bacteria, Cyanobacteria, Acidobacter and Nitrospira. Comparisons with a proximal outgroup sponge species (Amphimedon compressa), and the growing sponge symbiont literature, indicate that this study has identified approximately 330 A. corrugata-specific symbiotic OTUs, many of which are related to the sulfur-oxidizing Ectothiorhodospiraceae. This family appeared exclusively within A. corrugata, comprising >34.5% of all sequenced amplicons. Other A. corrugata symbionts such as Deltaproteobacteria, Bdellovibrio, and Thiocystis among many others are described.
Conclusions/Significance: Slight shifts in several bacterial taxa were observed between communities sampled during spring and fall seasons. New 16 S rDNA sequences and concomitant identifications greatly expand the microbial community profile for this model reef sponge, and will likely be useful as a baseline for any future comparisons regarding sponge microbial community dynamics.
C1 [White, James R.; Patel, Jignasa; Blackwelder, Patricia; Lopez, Jose V.] Nova SE Univ, Oceanog Ctr, Dania, FL USA.
[Ottesen, Andrea; Arce, Gabriela] US FDA, Off Regulatory Sci, Div Microbiol, College Pk, MD USA.
[Blackwelder, Patricia] Univ Miami, Ctr Adv Microscopy & Marine Geol & Geophys, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL USA.
RP White, JR (reprint author), Nova SE Univ, Oceanog Ctr, Dania, FL USA.
EM joslo@nova.edu
FU National Science Foundation [DEB-0829271]; NSU President's Faculty
Research Development Grant
FX PI Lopez is funded through National Science Foundation grant
DEB-0829271, and an internal NSU President's Faculty Research
Development Grant. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 72
TC 33
Z9 33
U1 2
U2 49
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUN 12
PY 2012
VL 7
IS 6
AR e38204
DI 10.1371/journal.pone.0038204
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UJ
UT WOS:000305340000013
PM 22701613
ER
PT J
AU Cokic, VP
Bhattacharya, B
Beleslin-Cokic, BB
Noguchi, CT
Puri, RK
Schechter, AN
AF Cokic, Vladan P.
Bhattacharya, Bhaskar
Beleslin-Cokic, Bojana B.
Noguchi, Constance T.
Puri, Raj K.
Schechter, Alan N.
TI JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells
through ontogeny
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Erythroid progenitors; Microarray; Ontogeny; JAK-STAT pathway; AKT
pathway
ID TRANSCRIPTION FACTOR GATA-1; PHOSPHATIDYLINOSITOL 3-KINASE;
FETAL-HEMOGLOBIN; GLOBIN GENE; IN-VITRO; EXPRESSION; ERYTHROPOIETIN;
DIFFERENTIATION; ACTIVATION; PROTEIN
AB Background: It has been reported that the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway regulates erythropoietin (EPO)-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34(+) progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny.
Methods: Hematopoietic CD34(+) progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells.
Results: In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11), while others were downregulated (PTPN6, PIAS, SPRED2). In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB). Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1) and downregulated (FOXO1, PDPK1, PIK3CG) genes in the PI3K-AKT signaling pathway, we also observed intermittently regulated gene expression (NFKBIA, YWHAH).
Conclusions: This broad overview of gene expression in erythropoiesis revealed transcription factors differentially expressed in some stages of ontogenesis. Finally, our results show that EPO-mediated proliferation and survival of erythroid progenitors occurs mainly through modulation of JAK-STAT pathway associated STATs, GRB2 and PIK3 genes, as well as AKT pathway-coupled NFKBIA and YWHAH genes.
C1 [Cokic, Vladan P.] Univ Belgrade, Inst Med Res, Lab Expt Hematol, Belgrade 11129, Serbia.
[Bhattacharya, Bhaskar; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20892 USA.
[Beleslin-Cokic, Bojana B.] Univ Clin Ctr, Sch Med, Inst Endocrinol Diabet & Dis Metab, Belgrade, Serbia.
[Noguchi, Constance T.; Schechter, Alan N.] NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
RP Cokic, VP (reprint author), Univ Belgrade, Inst Med Res, Lab Expt Hematol, Belgrade 11129, Serbia.
EM vl@imi.bg.ac.rs
OI Schechter, Alan N/0000-0002-5235-9408
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Serbian Ministry of Education and Science
[175053]
FX This research was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
grant from the Serbian Ministry of Education and Science [175053].
NR 35
TC 4
Z9 5
U1 0
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUN 7
PY 2012
VL 10
AR 116
DI 10.1186/1479-5876-10-116
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 984LT
UT WOS:000307191900001
PM 22676255
ER
PT J
AU Wang, DX
Baudys, J
Rees, J
Marshall, KM
Kalb, SR
Parks, BA
Nowaczyk, L
Pirkle, JL
Barr, JR
AF Wang, Dongxia
Baudys, Jakub
Rees, Jon
Marshall, Kristin M.
Kalb, Suzanne R.
Parks, Bryan A.
Nowaczyk, Louis, II
Pirkle, James L.
Barr, John R.
TI Subtyping Botulinum Neurotoxins by Sequential Multiple Endoproteases
In-Gel Digestion Coupled with Mass Spectrometry
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; FOOD SAMPLES; CLOSTRIDIUM; IDENTIFICATION;
STRAINS; TOXIN; PROTEOMICS; PCR; A5; DIFFERENTIATION
AB Botulinum neurotoxin (BoNT) is one of the most toxic substances known. BoNT is classified into seven distinct serotypes labeled A G. Among individual serotypes, researchers have identified subtypes based on amino acid variability within a serotype and toxin variants with minor amino acid sequence differences within a subtype. BoNT subtype identification is valuable for tracing and tracking bacterial pathogens. A proteomics approach is useful for BoNT subtyping since botulism is caused by botulinum neurotoxin and does not require the presence of the bacteria or its DNA. Enzymatic digestion and peptide identification using tandem mass spectrometry determines toxin protein sequences. However, with the conventional one-step digestion method, producing sufficient numbers of detectable peptides to cover the entire protein sequence is difficult, and incomplete sequence coverage results in uncertainty in distinguishing BoNT subtypes and toxin variants because of high sequence similarity. We report here a method of multiple enzymes and sequential in-gel digestion (MESID) to characterize the BoNT protein sequence. Complementary peptide detection from toxin digestions has yielded near-complete sequence coverage for all seven BoNT serotypes. Application of the method to a BoNT-contaminated carrot juice sample resulted in the identification of 98.4% protein sequence which led to a confident determination of the toxin subtype.
C1 [Wang, Dongxia; Baudys, Jakub; Rees, Jon; Kalb, Suzanne R.; Parks, Bryan A.; Pirkle, James L.; Barr, John R.] Ctr Dis Control & Prevent CDC, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
[Marshall, Kristin M.; Nowaczyk, Louis, II] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA.
RP Barr, JR (reprint author), Ctr Dis Control & Prevent CDC, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA.
EM jbarr@cdc.gov
OI Kalb, Suzanne/0000-0002-8067-136X
FU Intramural CDC HHS [CC999999]
NR 28
TC 9
Z9 9
U1 0
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0003-2700
EI 1520-6882
J9 ANAL CHEM
JI Anal. Chem.
PD JUN 5
PY 2012
VL 84
IS 11
BP 4652
EP 4658
DI 10.1021/ac3006439
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 952HK
UT WOS:000304783100004
PM 22577857
ER
PT J
AU Mazari, PM
Argaw, T
Valdivieso, L
Zhang, X
Marcucci, KT
Salomon, DR
Wilson, CA
Roth, MJ
AF Mazari, Peter M.
Argaw, Takele
Valdivieso, Leonardo
Zhang, Xia
Marcucci, Katherine T.
Salomon, Daniel R.
Wilson, Carolyn A.
Roth, Monica J.
TI Comparison of the convergent receptor utilization of a retargeted feline
leukemia virus envelope with a naturally-occurring porcine endogenous
retrovirus A
SO VIROLOGY
LA English
DT Article
DE Feline leukemia virus; FeLV CP Env isolate; Human PAR-1 receptor; Human
PAR-2 receptor; Viral entry; Retroviral receptors; Porcine endogenous
retrovirus A (PERV A)
ID FUNCTIONAL-CHARACTERIZATION; RIBOFLAVIN TRANSPORTER; BINDING DOMAIN;
HOST-RANGE; HIGH-TITER; IDENTIFICATION; CELLS; INFECTION; TROPISM;
PROTEIN
AB In vitro screening of randomized FeLV Envelope libraries identified the CP isolate, which enters cells through HuPAR-1, one of two human receptors utilized by porcine endogenous retrovirus-A (PERV-A), a distantly related gammaretrovirus. The CP and PERV-A Envs however, share little amino acid homology. Their receptor utilization was examined to define the common receptor usage of these disparate viral Envs. We demonstrate that the receptor usage of CP extends to HuPAR-2 but not to the porcine receptor PoPAR, the cognate receptor for PERV-A. Reciprocal interference between virus expressing CP and PERV-A Envs was observed on human cells. Amino acid residues localized to within the putative second extracellular loop (ECL-2) of PAR-1 and PAR-2 are found to be critical for CP envelope function. Through a panel of receptor chimeras and point mutations, this area was also found to be responsible for the differential usage of the PoPAR receptor between CP and PERV-A. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Mazari, Peter M.; Valdivieso, Leonardo; Zhang, Xia; Roth, Monica J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, Piscataway, NJ 08854 USA.
[Argaw, Takele; Wilson, Carolyn A.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Marcucci, Katherine T.; Salomon, Daniel R.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA.
[Marcucci, Katherine T.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
RP Roth, MJ (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Biochem, 675 Hoes Lane,Rm 636, Piscataway, NJ 08854 USA.
EM mazaripm@umdnj.edu; Takele.Argaw@fda.hhs.gov; valdivle@umdnj.edu;
zhangx3@umdnj.edu; MARCUCCIK@email.chop.edu; dsalomon@scripps.edu;
Carolyn.Wilson@fda.hhs.gov; roth@umdnj.edu
RI Salomon, Daniel/E-9380-2012;
OI Valdivieso-Torres, Leonardo/0000-0002-8848-7284
FU NIH [RO1 CA49932, T32 GM008360, R01 A1052349]; NJCCR [707060]
FX This is work is supported by NIH grant RO1 CA49932 to MJR. PM was
supported by fellowship 707060 from the NJCCR and T32 GM008360 from the
NIH. The contributions by DRS were supported by NIH grant R01 A1052349.
NR 32
TC 6
Z9 6
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD JUN 5
PY 2012
VL 427
IS 2
BP 118
EP 126
DI 10.1016/j.virol.2012.02.012
PG 9
WC Virology
SC Virology
GA 917TQ
UT WOS:000302201900006
PM 22405627
ER
PT J
AU Khin, NA
Chen, YF
Yang, Y
Yang, PL
Laughren, TP
AF Khin, Ni A.
Chen, Yeh-Fong
Yang, Yang
Yang, Peiling
Laughren, Thomas P.
TI Exploratory Analyses of Efficacy Data From Schizophrenia Trials in
Support of New Drug Applications Submitted to the US Food and Drug
Administration
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Review
ID PSYCHIATRIC CLINICAL-TRIALS; NEGATIVE SYNDROME SCALE; PLACEBO RUN-IN;
DESIGN; DEPRESSION; DISORDERS; TRENDS; ISSUES; PERIOD
AB Objective:There has been concern about a high rate of placebo response and a decline in treatment effect over time in schizophrenia trials as well as the implications of increasing conduct of such trials outside North America. This report explores differences in efficacy data over an 18-year period from randomized placebo-controlled trials submitted in support of new drug applications (NDAs) for the treatment of schizophrenia and differences in results between trials conducted in North America and elsewhere.
Data Sources: Clinical trial data that were submitted to the US Food and Drug Administration (FDA) as part of NDAs for the indication of schizophrenia between 1991 and 2009.
Study Selection: Efficacy data were compiled from 32 clinical trials with 11,567 evaluable patients with schizophrenia. Data from completed, randomized, multicenter, double-blind, placebo-controlled, 4- to 8-week clinical trials in adult patients diagnosed with schizophrenia according to DSM-III or DSM-IV criteria were included.
Data Extraction: Baseline demographic and disease characteristics, including mean Positive and Negative Syndrome Scale (PANSS) total scores, were summarized and compared between North American and multiregional trials. Mean change from baseline to endpoint in PANSS total scores was utilized as the primary outcome of interest. We explored differences in treatment effect and success rate of these trials based on when and where the studies were conducted, sample size, trial duration, and baseline patient characteristics.
Results:Twenty-one of the 32 trials were conducted solely in North America, and 11 were carried out in multiple regions. Of those 11 multiregional trials, 2 were conducted exclusively in foreign countries. Although the observed responses (change from baseline) in placebo and drug-treated groups in multiregional trials tended to be larger than in North American trials, the treatment effects (drug-placebo difference) were -9 and -8 PANSS units for North American and multiregional trials, respectively. When time of trial conduct was taken into account, an increasing placebo response and a diminishing treatment effect over time were observed in North American trials from -10.8 PANSS units for the first period (1991-1998) to -6.0 PANSS units for the later period (1999-2008). The overall trial success rate over the almost 2 decades was 78%, declining slightly in trials conducted after 1999, the time period during which multiregional trials were first conducted (74% for 1999-2008 vs 85% for 1991-1998), despite increasing sample sizes in the later period. The mean baseline PANSS total score was in the range of 87-100 for most of these trials. Trials in patients with higher mean baseline PANSS total scores tended to show larger treatment effects than those in patients with lower trials. Trials mean body weight and body mass index (BMI) were higher in patients in North American trials and North America predominant multiregional trials compared to those in foreign-predominant multiregional trials (mean body weights of 85 kg and 81 kg vs 72 kg, and BMIs of 29 and 27 vs 25, respectively). Treatment effects decreased as body weights increased, especially in North American trials. In foreign-predominant multiregional trials, there were higher proportions of women than in North American trials and North America-predominant multiregional trials (40% vs 22% and 27%, respectively) and a relatively larger proportion of Asians (21% vs 1% and 8%, respectively).
Condusions: A high and increasing placebo response and a declining treatment effect are of great concern in schizophrenia trials conducted in North America. In this era of global clinical trials, close attention is needed to the design and conduct of these trials. J Clin Psychiatry 2012;73(6):856-864 (c) Copyright 2012 Physicians Postgraduate Press, Inc.
C1 [Chen, Yeh-Fong; Yang, Yang; Yang, Peiling] US FDA, CDER, Div Biometr 1, Off Biostat,Off Translat Sci, Silver Spring, MD 20993 USA.
RP Khin, NA (reprint author), US FDA, Div Psychiat Prod, HFD 130,10903 New Hampshire Ave,Bldg WO22,Rm 4110, Silver Spring, MD 20993 USA.
EM ni.khin@fda.hhs.gov
NR 31
TC 33
Z9 35
U1 0
U2 8
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUN
PY 2012
VL 73
IS 6
BP 856
EP 864
DI 10.4088/JCP.11r07539
PG 9
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA 090SK
UT WOS:000315000100012
PM 22687813
ER
PT J
AU Burns, DL
AF Burns, Drusilla L.
TI Licensure of vaccines using the Animal Rule
SO CURRENT OPINION IN VIROLOGY
LA English
DT Article
AB A number of new vaccines are being developed against microbial pathogens that might be used as bioweapons. For some of these vaccines, because of the lack of endemic disease and the lethal nature of the disease, human efficacy studies would not be ethical or feasible to conduct. In such cases, a regulation, known as the 'Animal Rule', can be used which allows the United States Food and Drug Administration to consider appropriate animal studies as evidence of effectiveness of a vaccine. Using this rule, pathways to licensure are being developed for new vaccines against bioweapons based on well-designed animal studies. The results of those animal protection studies together with the best scientific information available concerning immune mechanisms of protection allow protection in the animals to be bridged to effectiveness in humans, usually through the use of an appropriate immune marker.
C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Room 130,HFM-434,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM drusilla.bums@fda.hhs.gov
NR 12
TC 14
Z9 14
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1879-6257
J9 CURR OPIN VIROL
JI Curr. Opin. Virol.
PD JUN
PY 2012
VL 2
IS 3
BP 353
EP 356
DI 10.1016/j.coviro.2012.01.004
PG 4
WC Virology
SC Virology
GA 051FY
UT WOS:000312112800019
PM 22709520
ER
PT J
AU Peng, SC
Chatterjee, M
Lu, N
AF Peng, Shu-Chen
Chatterjee, Monita
Lu, Nelson
TI Acoustic Cue Integration in Speech Intonation Recognition With Cochlear
Implants
SO TRENDS IN AMPLIFICATION
LA English
DT Article
DE cochlear implants; perception; intonation; prosody; cue weighting
ID NORMAL-HEARING LISTENERS; TEMPORAL CUES; ELECTRIC HEARING; PHONETIC
IDENTIFICATION; VOWEL IDENTIFICATION; SPECTRAL RESOLUTION; MUSIC
PERCEPTION; ENVELOPE CUES; NOISE; USERS
AB The present article reports on the perceptual weighting of prosodic cues in question-statement identification by adult cochlear implant (CI) listeners. Acoustic analyses of normal-hearing (NH) listeners' production of sentences spoken as questions or statements confirmed that in English the last bisyllabic word in a sentence carries the dominant cues (F0, duration, and intensity patterns) for the contrast. Furthermore, these analyses showed that the F0 contour is the primary cue for the question-statement contrast, with intensity and duration changes conveying important but less reliable information. On the basis of these acoustic findings, the authors examined adult CI listeners' performance in two question-statement identification tasks. In Task 1, 13 CI listeners' question-statement identification accuracy was measured using naturally uttered sentences matched for their syntactic structures. In Task 2, the same listeners' perceptual cue weighting in question-statement identification was assessed using resynthesized single-word stimuli, within which fundamental frequency (F0), intensity, and duration properties were systematically manipulated. Both tasks were also conducted with four NH listeners with full-spectrum and noise-band-vocoded stimuli. Perceptual cue weighting was assessed by comparing the estimated coefficients in logistic models fitted to the data. Of the 13 CI listeners, 7 achieved high performance levels in Task 1. The results of Task 2 indicated that multiple sources of acoustic cues for question-statement identification were utilized to different extents depending on the listening conditions (e. g., full spectrum vs. spectrally degraded) or the listeners' hearing and amplification status (e.g., CI vs. NH).
C1 [Peng, Shu-Chen] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Off Device Evaluat, Silver Spring, MD 20993 USA.
[Chatterjee, Monita] Univ Maryland, College Pk, MD 20742 USA.
RP Peng, SC (reprint author), US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Off Device Evaluat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM shu-chen.peng@fda.hhs.gov
FU NIH/NIDCD [R01DC004786, P30DC004664]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
funded by the NIH/NIDCD (R01DC004786, PI: M. Chatterjee and P30DC004664,
PI: R.Dooling). The views presented in this article do not necessarily
reflect those of the Food and Drug Administration.
NR 62
TC 10
Z9 11
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1084-7138
J9 TRENDS AMPLIF
JI Trends Amplif.
PD JUN
PY 2012
VL 16
IS 2
BP 67
EP 82
DI 10.1177/1084713812451159
PG 16
GA 031ZZ
UT WOS:000310682800001
PM 22790392
ER
PT J
AU Giridhar, D
Robinson, RA
Liu, YB
Sliwa, J
Zderic, V
Myers, MR
AF Giridhar, Dushyanth
Robinson, Ronald A.
Liu, Yunbo
Sliwa, Jack
Zderic, Vesna
Myers, Matthew R.
TI Quantitative estimation of ultrasound beam intensities using infrared
thermography-Experimental validation
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID FOCUSED ULTRASOUND; CALIBRATION
AB Infrared (IR) thermography is a technique that has the potential to rapidly and noninvasively determine the intensity fields of ultrasound transducers. In the work described here, IR temperature measurements were made in a tissue phantom sonicated with a high-intensity focused ultrasound (HIFU) transducer, and the intensity fields were determined using a previously published mathematical formulation relating intensity to temperature rise at a tissue/air interface. Intensity fields determined from the IR technique were compared with those derived from hydrophone measurements. Focal intensities and beam widths determined via the IR approach agreed with values derived from hydrophone measurements to within a relative difference of less than 10%, for a transducer with a gain of 30, and about 13% for a transducer with a gain of 60. At axial locations roughly 1 cm in front (pre-focal) and behind (post-focal) the focus, the agreement with hydrophones for the lower-gain transducer remained comparable to that in the focal plane. For the higher-gain transducer, the agreement with hydrophones at the pre-focal and post-focal locations was around 40%. [http://dx.doi.org/10.1121/1.4711006]
C1 [Giridhar, Dushyanth; Robinson, Ronald A.; Liu, Yunbo; Myers, Matthew R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Zderic, Vesna] George Washington Univ, Dept Elect & Comp Engn, Washington, DC 20052 USA.
[Sliwa, Jack] St Jude Med, AF Div, Sunnyvale, CA 94085 USA.
RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10993 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM matthew.myers@fda.hhs.gov
NR 9
TC 6
Z9 6
U1 0
U2 1
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 JUN
PY 2012
VL 131
IS 6
BP 4283
EP 4291
DI 10.1121/1.4711006
PG 9
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 010ZQ
UT WOS:000309133500020
PM 22712903
ER
PT J
AU Soneson, JE
AF Soneson, Joshua E.
TI A parametric study of error in the parabolic approximation of focused
axisymmetric ultrasound beams
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID FIELD
AB The parabolic approximation results in a tractible model for studying ultrasound beams, but the limits of validity of the approximation are often presented only qualitatively. In this work the most common model for axisymmetric ultrasound beam propagation, the Kuznetsov-Zabolotskaya-Khokhlov equation, is directly compared with the more general Westervelt equation with regard to diffractive and absorptive effects in continuous wave beams. The parametric study compares the solutions of the two models as a function of source frequency and focusing geometry using peak focal pressure, the axial location at which that peak occurs, and the loss due to absorption as metrics.
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
NR 7
TC 11
Z9 12
U1 0
U2 0
PU ACOUSTICAL SOC AMER AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0001-4966
EI 1520-8524
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD JUN
PY 2012
VL 131
IS 6
BP EL481
EP EL486
DI 10.1121/1.4722170
PG 6
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 010ZQ
UT WOS:000309133500010
PM 22713025
ER
PT J
AU Mallick, TK
Mosquera, A
Zinderman, CE
Martin, LS
Wise, RP
AF Mallick, Tarun K.
Mosquera, Alexis
Zinderman, Craig E.
Martin, Laura St.
Wise, Robert P.
TI Reported infections after human tissue transplantation before and after
new food and drug administration (FDA) regulations, United States, 2001
through June, 2010
SO CELL AND TISSUE BANKING
LA English
DT Article
DE Allografts; Tissue; Infections; Surveillance
ID CREUTZFELDT-JAKOB-DISEASE; CORNEAL TRANSPLANTS; ALLOGRAFTS; RECIPIENTS
AB Processors distributed about 1.5 million human tissue allografts in the U. S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.
C1 [Mallick, Tarun K.; Mosquera, Alexis; Zinderman, Craig E.; Wise, Robert P.] US FDA, Off Biostat & Epidemiol, CBER, Rockville, MD 20852 USA.
[Martin, Laura St.] US FDA, Off Cellular Tissue & Gene Therapies, CBER, Rockville, MD 20852 USA.
RP Mosquera, A (reprint author), US FDA, Off Biostat & Epidemiol, CBER, 1401 Rockville Pike,Suite 400 S, Rockville, MD 20852 USA.
EM alexis.mosquera@fda.hhs.gov
NR 24
TC 8
Z9 8
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9333
J9 CELL TISSUE BANK
JI Cell Tissue Banking
PD JUN
PY 2012
VL 13
IS 2
BP 259
EP 267
DI 10.1007/s10561-011-9253-5
PG 9
WC Cell Biology; Engineering, Biomedical
SC Cell Biology; Engineering
GA 985EE
UT WOS:000307245400007
PM 21479712
ER
PT J
AU Rosenzweig, JA
Chopra, AK
AF Rosenzweig, Jason A.
Chopra, Ashok K.
TI The future of plague vaccines: hopes raised by a surrogate,
live-attenuated recombinant vaccine candidate
SO EXPERT REVIEW OF VACCINES
LA English
DT Article
DE balanced lethal plasmids; F1; LcrV antigen; Salmonella
typhimurium-attenuated Delta phoP/Q mutant; Yersinia pestis vaccine
ID SALMONELLA-TYPHIMURIUM; YERSINIA-PESTIS; MACROPHAGE; VIRULENCE; MUTANTS;
PHOP
AB Yersinia pestis (YP) is the Gram-negative etiological agent of plague against which no commercial vaccine exists to prophylactically prevent a potential outbreak due to natural or bio-warfare/terrorism-mediated causes. The US FDA only recently approved levofloxacin to combat this deadly pathogen. In the article under review, an attenuated, recombinant Salmonella typhimurium Delta phoPQ mutant strain producing YP antigens F1, LcrV and F1-V (fusion protein) from either low-copy pBR or high-copy pUC vectors (maintained by plasmid addiction rather than antibiotic selection pressure) were evaluated for their ability to induce a humoral immune response in both mice and rabbits. This study highlights the need for developing a well-tolerated YP vaccine that, through the oral route, can be readily administered and elicit both mucosal and systemic anti-plague humoral immunity.
C1 [Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
[Rosenzweig, Jason A.] Texas So Univ, Dept Biol, CBER, Houston, TX 77004 USA.
[Chopra, Ashok K.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX USA.
[Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX USA.
[Chopra, Ashok K.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX USA.
RP Chopra, AK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
EM achopra@utmb.edu
NR 9
TC 7
Z9 7
U1 3
U2 12
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD JUN
PY 2012
VL 11
IS 6
BP 659
EP 661
DI 10.1586/ERV.12.34
PG 3
WC Immunology
SC Immunology
GA 007OK
UT WOS:000308897800008
PM 22873124
ER
PT J
AU Brunner, CC
Abboud, SF
Hoeschen, C
Kyprianou, IS
AF Brunner, Claudia C.
Abboud, Samir F.
Hoeschen, Christoph
Kyprianou, Iacovos S.
TI Signal detection and location-dependent noise in cone-beam computed
tomography using the spatial definition of the Hotelling SNR
SO MEDICAL PHYSICS
LA English
DT Article
DE cone-beam CT; image quality; discrete object transfer matrix; covariance
matrix; MTF; NPS; SNR; detectability
ID CT SCANNER; SYSTEM; POWER; RECONSTRUCTION; OBSERVER
AB Purpose: Quality assurance in computed tomography (CT) is commonly performed with the Fourier-based modulation transfer function (MTF) and the noise variance, while more recently the noise power spectrum (NPS) has increased in popularity. The Fourier-based methods make assumptions such as shift-invariance and cyclostationarity. These assumptions are violated in real clinical systems and consequently are expected to result in systematic errors. A spatial approach, based on the object transfer matrix (T) and the covariance matrix (K) theory, does not require these assumptions and can provide a more general description of the imaging system. In this paper, the authors present an experimental methodology and data treatment for quality assessment of a lab cone-beam CT system by comparing the spatial with the Fourier approach in 2D reconstructed slices.
Methods: In order to have control over all experimental parameters and image reconstruction, a bench-top flat-panel-based cone-beam CT scanner and a cylindrical water-filled poly(methyl methacrylate) (PMMA) phantom were used for the noise measurements. An aluminum foil inserted in the water phantom enabled the estimation of the line response function (LRF) with a limited number of assumptions. The authors evaluated the spatial blur, the noise and the signal-to-noise ratio (SNR) using the spatial approach as well as the Fourier-based approach. In order to evaluate the degree of noise nonstationarity of their cone-beam CT system, the authors evaluated both the local and global CT noise properties and compared them using both approaches.
Results: For the laboratory cone-beam CT, the location-dependent noise evaluation showed that in addition to the noise variance, the NPS and covariance eigenvector symmetry depend on the location in the image. The estimated signal transfer was similar for both approaches. Unlike the Fourier approach which uses the same exponential wave function basis for both MTF and NPS, the eigenvectors of T and K were significantly different.
Conclusions: By using the eigenvectors of the noise and object transfer to characterize the system, the spatial approach provides additional information to the Fourier approach and is therefore an important tool for a thorough understanding of a CT system. [http://dx.doi.org/10.1118/1.4718572]
C1 [Brunner, Claudia C.; Abboud, Samir F.; Kyprianou, Iacovos S.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Brunner, Claudia C.; Hoeschen, Christoph] Helmholtz Zentrum Munchen, Res Unit Med Radiat Phys & Diagnost, D-85764 Neuherberg, Germany.
[Abboud, Samir F.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Abboud, Samir F.] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA.
RP Brunner, CC (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM claudia.brunner@fda.hhs.gov
RI Hoeschen, Christoph/N-5867-2014
FU German Academic Exchange Service (DAAD); Life Science Foundation; German
Federal Ministry of Education and Research (BMBF) [03NUK008A]; FDA
Office of Women's Health; U.S. Food and Drug Administration Office of
Women's Health
FX Claudia Brunner was partially funded by the German Academic Exchange
Service (DAAD) and the Life Science Foundation. This study was partly
funded by the German Federal Ministry of Education and Research (BMBF)
through Grant No. 03NUK008A ("Verbund Kompetenzerhalt
Strahlenforschung-Innovative Verfahren der biomed. Bildgebung zur
Optimierung von med. Strahlenanwendungen"). Samir Abboud was supported
by the FDA Office of Women's Health and in part with an appointment to
the Research Participation Program at the FDA Center for Devices and
Radiological Health administered through the Oak Ridge Institute for
Science and Education. Iacovos Kyprianou's research was partly funded by
the U.S. Food and Drug Administration Office of Women's Health.
NR 34
TC 12
Z9 12
U1 1
U2 4
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2012
VL 39
IS 6
BP 3214
EP 3228
DI 10.1118/1.4718572
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905801010
PM 22755705
ER
PT J
AU Siewerdsen, J
Fessler, J
Myers, K
AF Siewerdsen, J.
Fessler, J.
Myers, K.
TI Assessment of Image Quality in the New CT
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Siewerdsen, J.] Johns Hopkins Univ, Baltimore, MD USA.
[Fessler, J.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Myers, K.] US FDA, Off Sci & Engn Labs, CDRH, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2012
VL 39
IS 6
BP 3878
EP 3878
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805296
ER
PT J
AU Gu, S
Badal-Soler, A
Kyprianou, I
Badano, A
AF Gu, S.
Badal-Soler, A.
Kyprianou, I.
Badano, A.
TI Method to Study Image Quality in Cardiac Angiography Using a
Computational Observer and Monte Carlo Simulations
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Gu, S.; Badal-Soler, A.; Kyprianou, I.; Badano, A.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
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 JUN
PY 2012
VL 39
IS 6
BP 3894
EP 3894
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805357
ER
PT J
AU Jennings, R
AF Jennings, R.
TI Spectrally Neutral X-Ray Attenuators
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Jennings, R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
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 JUN
PY 2012
VL 39
IS 6
BP 3895
EP 3896
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805363
ER
PT J
AU Kontson, K
Jennings, R
Kyprianou, I
AF Kontson, K.
Jennings, R.
Kyprianou, I.
TI X-Ray Spectra for Breast CT
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Kontson, K.; Jennings, R.; Kyprianou, I.] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA.
[Kontson, K.; Jennings, R.; Kyprianou, I.] US FDA, Ctr Devices & Radiol, Silver Spring, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 JUN
PY 2012
VL 39
IS 6
BP 3913
EP 3914
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805434
ER
PT J
AU Dobbins, J
Chakrabarti, K
AF Dobbins, J.
Chakrabarti, K.
TI Digital Breast Tomosynthesis: Basic Principles and the QMP's Role
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Dobbins, J.] Duke Univ, Med Ctr, Durham, NC USA.
[Chakrabarti, K.] US FDA, CDRH, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
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 JUN
PY 2012
VL 39
IS 6
BP 3954
EP 3954
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805597
ER
PT J
AU Mills, T
Winter, D
Keith, S
Fletcher, D
AF Mills, T.
Winter, D.
Keith, S.
Fletcher, D.
TI Medical Physics in Federal and State Governments
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Mills, T.] US FDA, Silver Spring, MD USA.
[Winter, D.] David Grant Med Ctr, Vacaville, AA USA.
[Keith, S.] Natl Ctr Environm, Atlanta, GA USA.
[Fletcher, D.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUN
PY 2012
VL 39
IS 6
BP 3955
EP 3955
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805599
ER
PT J
AU Petrick, N
AF Petrick, N.
TI Methodologies for Evaluation of Effects of CAD On Users
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Petrick, N.] US FDA, Silver Spring, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD JUN
PY 2012
VL 39
IS 6
BP 3962
EP 3962
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805629
ER
PT J
AU Sahiner, B
AF Sahiner, B.
TI Methodologies for Evaluation of Standalone CAD System Performance
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Sahiner, B.] US FDA, Silver Spring, MD USA.
NR 0
TC 1
Z9 1
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 JUN
PY 2012
VL 39
IS 6
BP 3962
EP 3962
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805628
ER
PT J
AU Jennings, R
Bettolo, CM
Kontson, K
Beg, S
Akinnagbe, E
AF Jennings, R.
Bettolo, C. Marini
Kontson, K.
Beg, S.
Akinnagbe, E.
TI Liquids for the Simulation of the X-Ray Properties of Breast Tissue
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting and Exhibition of the
American-Association-of-Physicists-in-Medicine (AAPM)
CY JUL 29-AUG 02, 2012
CL Charlotte, NC
SP Amer Assoc Physicists Med (AAPM)
C1 [Jennings, R.; Bettolo, C. Marini] US FDA, Silver Spring, MD USA.
[Kontson, K.; Beg, S.; Akinnagbe, E.] George Washington Univ, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 JUN
PY 2012
VL 39
IS 6
BP 4015
EP 4015
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 007RM
UT WOS:000308905805835
ER
PT J
AU Anez, G
Grinev, A
Rios, M
AF Anez, G.
Grinev, A.
Rios, M.
TI Evolutionary dynamics of WNV in North America after 2006: differential
analysis of the phylogeny and selection pressure in humans, bird, and
mosquito hosts
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Anez, G.; Grinev, A.; Rios, M.] US FDA, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD JUN
PY 2012
VL 16
SU 1
BP E106
EP E106
DI 10.1016/j.ijid.2012.05.245
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 999YX
UT WOS:000308353100230
ER
PT J
AU Anez, G
Heisey, D
Espina, LM
Stramer, SL
Rios, M
AF Anez, G.
Heisey, D.
Espina, L. M.
Stramer, S. L.
Rios, M.
TI Phylogenetic and time-scale analysis of dengue virus types 1 and 4
circulating in Puerto Rico and Key West, Florida, during 2010 epidemics
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Anez, G.; Heisey, D.; Espina, L. M.; Rios, M.] FDA, Bethesda, MD USA.
[Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD JUN
PY 2012
VL 16
SU 1
BP E68
EP E68
DI 10.1016/j.ijid.2012.05.167
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 999YX
UT WOS:000308353100152
ER
PT J
AU Taylor, D
Nyan, DC
Rios, M
AF Taylor, D.
Nyan, D. -C.
Rios, M.
TI Development of a reverse-transcription isothermal amplification assay
for rapid detection and genotyping of Hepatitis C virus infection in
blood
SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
LA English
DT Meeting Abstract
C1 [Taylor, D.; Nyan, D. -C.; Rios, M.] US FDA, Bethesda, MD 20014 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 1201-9712
J9 INT J INFECT DIS
JI Int. J. Infect. Dis.
PD JUN
PY 2012
VL 16
SU 1
BP E404
EP E404
DI 10.1016/j.ijid.2012.05.547
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA 999YX
UT WOS:000308353101533
ER
PT J
AU Simpson, NE
Tryndyak, VP
Beland, FA
Pogribny, IP
AF Simpson, Natalie E.
Tryndyak, Volodymyr P.
Beland, Frederick A.
Pogribny, Igor P.
TI An in vitro investigation of metabolically sensitive biomarkers in
breast cancer progression
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Epigenetics; Glutamine metabolism; Histone acetylation;
Biomarkers
ID MAMMARY EPITHELIAL-CELLS; E-CADHERIN EXPRESSION; NF-KAPPA-B; MESENCHYMAL
TRANSITION; HISTONE MODIFICATIONS; GROWTH; TRIMETHYLATION; EPIGENETICS;
INHIBITION; CHROMATIN
AB Epigenetic biomarkers are emerging as determinants of breast cancer prognosis. Breast cancer cells display unique alterations in major cellular metabolic pathways and it is becoming widely recognized that enzymes that regulate epigenetic alterations are metabolically sensitive. In this study, we used microarray data from the GEO database to compare gene expression for regulators of metabolism and epigenetic alterations among non-invasive epithelial (MCF-7, MDA-MB-361, and T-47D) and invasive mesenchymal (MDA-MB-231, Hs-578T, and BT-549) breast cancer cell lines. The expression of genes, including GLS1, GFPT2, LDHA, HDAC9, MYST2, and SUV420H2, was assessed using RT-PCR. There was differential expression between epithelial and mesenchymal cell lines. MYST2 and SUV420H2 regulate the levels of the epigenetic biomarkers histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3), respectively. Reduced amounts of H4K16ac and H4K20me3 correlated with lower levels of MYST2 and SUV420H2 in mesenchymal cells and, along with reduced amounts of histone H3 lysine 9 acetylation (H3K9ac), were found to distinguish epithelial from mesenchymal cells. In addition, both GLS1 and GFPT2 play roles in glutamine metabolism and were observed to be more highly expressed in mesenchymal cell lines, and when glutamine and glutamate levels reported in the NCI-60 metabolomics dataset were compared, the ratio of glutamate/glutamine was found to be higher in mesenchymal cells. Blocking the conversion of glutamine to glutamate using an allosteric inhibitor, Compound 968, against GLS1, increased H4K16ac in T-47D and MDA-MB-231 cells, linking glutamine metabolism to a particular histone modification in breast cancer. These findings support the concept that metabolically sensitive histone modifications and corresponding histone modifying enzymes can be used as diagnostic and prognostic biomarkers for breast cancer. It also further emphasizes the importance of glutamine metabolism in tumor progression and that inhibitors of cellular metabolic pathways may join histone deacetylase inhibitors as a form of epigenetic therapy.
C1 [Simpson, Natalie E.; Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, 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
NR 50
TC 16
Z9 16
U1 0
U2 14
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUN
PY 2012
VL 133
IS 3
BP 959
EP 968
DI 10.1007/s10549-011-1871-x
PG 10
WC Oncology
SC Oncology
GA 967NM
UT WOS:000305914900015
PM 22101407
ER
PT J
AU Narrod, C
Zinsstag, J
Tiongco, M
AF Narrod, Clare
Zinsstag, Jakob
Tiongco, Marites
TI A One Health Framework for Estimating the Economic Costs of Zoonotic
Diseases on Society
SO ECOHEALTH
LA English
DT Article
DE one health; economic costs; zoonotic diseases
ID AVIAN INFLUENZA; ANIMAL HEALTH; LIVESTOCK; RABIES; BRUCELLOSIS; CHAD;
TRANSMISSION; VACCINATION; VALUATION; KNOWLEDGE
AB This article presents an integrated epidemiological and economic framework for assessing zoonoses using a "one health" concept. The framework allows for an understanding of the cross-sector economic impact of zoonoses using modified risk analysis and detailing a range of analytical tools. The goal of the framework is to link the analysis outputs of animal and human disease transmission models, economic impact models and evaluation of risk management options to gain improved understanding of factors affecting the adoption of risk management strategies so that investment planning includes the most promising interventions (or sets of interventions) in an integrated fashion. A more complete understanding of the costs of the disease and the costs and benefits of control measures would promote broader implementation of the most efficient and effective control measures, contributing to improved animal and human health, better livelihood outcomes for the poor and macroeconomic growth.
C1 [Zinsstag, Jakob] Univ Basel, Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Narrod, Clare] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA.
[Tiongco, Marites] Int Food Policy Res Inst, Washington, DC 20006 USA.
RP Zinsstag, J (reprint author), Univ Basel, Swiss Trop & Publ Hlth Inst, POB 4002, Basel, Switzerland.
EM jakob.zinsstag@unibas.ch
RI Zinsstag, Jakob/A-8317-2008
OI Zinsstag, Jakob/0000-0002-8899-6097
FU WB Central Asia program; National Centre for Competence in Research
North-South (NCCR North-South); European Union [221948]
FX This framework is based on a methodology submitted to the World Bank for
implementing a one health approach in the operations program in Central
Asia. We would like to acknowledge the WB Central Asia program for
partial funding of this work. We thank the National Centre for
Competence in Research North-South (NCCR North-South) for supporting
this work. The research leading to these results has received funding
from the European Union's Seventh Framework Programme (FP7/2007-2013)
under grant agreement no. 221948 (ICONZ).
NR 42
TC 40
Z9 41
U1 3
U2 37
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1612-9202
J9 ECOHEALTH
JI EcoHealth
PD JUN
PY 2012
VL 9
IS 2
BP 150
EP 162
DI 10.1007/s10393-012-0747-9
PG 13
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA 987GV
UT WOS:000307406100006
PM 22395956
ER
PT J
AU Gong, JP
Schulz, S
Hyslop, T
Waldman, SA
AF Gong, Jian P.
Schulz, Stephanie
Hyslop, Terry
Waldman, Scott A.
TI GUCY2C molecular staging personalizes colorectal cancer patient
management
SO BIOMARKERS IN MEDICINE
LA English
DT Review
DE biomarker; colorectal cancer; guanylyl cyclase C; occult tumor burden;
prediction; prognosis; quantitative reverse transcriptase-PCR; racial
disparities; staging
ID GUANYLYL CYCLASE-C; HEAT-STABLE ENTEROTOXIN; II COLON-CANCER;
GENE-EXPRESSION PROFILES; SURGICAL ADJUVANT BREAST; SURROGATE
END-POINTS; ESCHERICHIA-COLI; DRUG DEVELOPMENT; LYMPH-NODES; CYCLIC-GMP
AB While the most significant prognostic and predictive marker in the management of colorectal cancer patients is cancer cells in regional lymph nodes, approximately 30% of patients whose lymph nodes are ostensibly free of tumor cells by histopathology ultimately develop recurrent disease reflecting occult metastases. Molecular techniques utilizing highly specific markers and ultra-sensitive detection technologies have emerged as powerful staging platforms to establish prognosis and predict responsiveness to chemotherapy in colorectal cancer patients. This review describes the evolution of the tumor suppressor GUCY2C as a prognostic and predictive molecular biomarker that quantifies occult tumor burden in regional lymph nodes for staging patients with colorectal cancer.
C1 [Gong, Jian P.; Schulz, Stephanie; Hyslop, Terry; Waldman, Scott A.] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA.
[Gong, Jian P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Waldman, SA (reprint author), Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA.
EM Scott.Waldman@jefferson.edu
FU NIH [CA 75123, CA95026, CA112147, CA146033]; Targeted Diagnostic &
Therapeutics, Inc.; Pennsylvania Department of Health; institutional K30
Training Program In Human Investigation [K30 HL004522]; NIH
institutional award [T32 GM08562]; Scientific Advisory Board of Targeted
Diagnostics and Therapeutics, Inc.
FX This work was supported by funding from the NIH (CA 75123, CA95026,
CA112147, CA146033), Targeted Diagnostic & Therapeutics, Inc., and the
Pennsylvania Department of Health. The Pennsylvania Department of Health
specifically disclaims responsibility forany analyses, interpretations
or conclusions. JP Gong was enrolled in the NIH-supported institutional
K30 Training Program In Human Investigation (K30 HL004522) and was
supported by NIH institutional award T32 GM08562 for Postdoctoral
Training in Clinical Pharmacology. SA Waldman is the Samuel MV Hamilton
Endowed Professor. SA Waldman is the Chair (uncompensated) of the
Scientific Advisory Board of Targeted Diagnostics and Therapeutics,
Inc., which provided research funding that, in part, supported this
study and which has a license to commercialize inventions related to
this work, and the Chair of the Data Safety and Monitoring Committee for
the C-Cure Trial sponsored by Cardio3 (Belgium). The authors have no
other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 121
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U1 1
U2 3
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1752-0363
J9 BIOMARK MED
JI Biomark. Med.
PD JUN
PY 2012
VL 6
IS 3
BP 339
EP 348
DI 10.2217/BMM.12.24
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 974RW
UT WOS:000306455100017
PM 22731908
ER
PT J
AU Han, T
Chang, CW
Kwekel, JC
Chen, Y
Ge, Y
Martinez-Murillo, F
Roscoe, D
Tezak, Z
Philip, R
Bijwaard, K
Fuscoe, JC
AF Han, Tao
Chang, Ching-Wei
Kwekel, Joshua C.
Chen, Ying
Ge, Yun
Martinez-Murillo, Francisco
Roscoe, Donna
Tezak, Zivana
Philip, Reena
Bijwaard, Karen
Fuscoe, James C.
TI Characterization of whole genome amplified (WGA) DNA for use in
genotyping assay development
SO BMC GENOMICS
LA English
DT Article
DE Whole genome amplification; Array-based comparative genomic
hybridization; TaqMan copy number assay; DNA sequencing
ID MULTIPLE DISPLACEMENT AMPLIFICATION; SINGLE NUCLEOTIDE POLYMORPHISM;
PREIMPLANTATION GENETIC DIAGNOSIS; CIRCULAR BINARY SEGMENTATION;
HIGH-THROUGHPUT; FORENSIC CASEWORK; INHERITED DISEASE;
CLINICAL-PRACTICE; CYSTIC-FIBROSIS; ARRAY CGH
AB Background: Genotyping assays often require substantial amounts of DNA. To overcome the problem of limiting amounts of available DNA, Whole Genome Amplification (WGA) methods have been developed. The multiple displacement amplification (MDA) method using Phi 29 polymerase has become the preferred choice due to its high processivity and low error rate. However, the uniformity and fidelity of the amplification process across the genome has not been extensively characterized.
Results: To assess amplification uniformity, we used array-based comparative genomic hybridization (aCGH) to evaluate DNA copy number variations (CNVs) in DNAs amplified by two MDA kits: GenomiPhi and REPLI-g. The Agilent Human CGH array containing nearly one million probes was used in this study together with DNAs from a normal subject and 2 cystic fibrosis (CF) patients. Each DNA sample was amplified 4 independent times and compared to its native unamplified DNA. Komogorov distances and Phi correlations showed a high consistency within each sample group. Less than 2% of the probes showed more than 2-fold CNV introduced by the amplification process. The two amplification kits, REPLI-g and GenomiPhi, generate very similar amplified DNA samples despite the differences between the unamplified and amplified DNA samples. The results from aCGH analysis indicated that there were no obvious CNVs in the CFTR gene region due to WGA when compared to unamplified DNA. This was confirmed by quantitative real-time PCR copy number assays at 10 locations within the CFTR gene. DNA sequencing analysis of a 2-kb region within the CFTR gene showed no mutations introduced by WGA.
Conclusion: The relatively high uniformity and consistency of the WGA process, coupled with the low replication error rate, suggests that WGA DNA may be suitable for accurate genotyping. Regions of the genome that were consistently under-amplified were found to contain higher than average GC content. Because of the consistent differences between the WGA DNA and the native unamplified DNA, characterization of the genomic region of interest, as described here, will be necessary to ensure the reliability of genotyping results from WGA DNA.
C1 [Han, Tao; Kwekel, Joshua C.; Ge, Yun; Fuscoe, James C.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chang, Ching-Wei] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chen, Ying] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Martinez-Murillo, Francisco; Roscoe, Donna; Tezak, Zivana; Philip, Reena; Bijwaard, Karen] US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Han, T (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Tao.Han@fda.hhs.gov; James.Fuscoe@fda.hhs.gov
NR 48
TC 14
Z9 15
U1 3
U2 14
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUN 1
PY 2012
VL 13
AR 217
DI 10.1186/1471-2164-13-217
PG 15
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 977NO
UT WOS:000306670400001
PM 22655855
ER
PT J
AU Yazdani, SK
Farb, A
Nakano, M
Vorpahl, M
Ladich, E
Finn, AV
Kolodgie, FD
Virmani, R
AF Yazdani, Saami K.
Farb, Andrew
Nakano, Masataka
Vorpahl, Marc
Ladich, Elena
Finn, Aloke V.
Kolodgie, Frank D.
Virmani, Renu
TI Pathology of Drug-Eluting Versus Bare-Metal Stents in Saphenous Vein
Bypass Graft Lesions
SO JACC-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE bare-metal stent(s); drug-eluting stent(s); pathology; saphenous vein
bypass graft
ID CORONARY-ARTERY-DISEASE; BALLOON ANGIOPLASTY; FOLLOW-UP; SIROLIMUS;
IMPLANTATION; THROMBOSIS; INTERVENTION; PREDICTORS; RESTENOSIS;
PLACEMENT
AB Objectives The purpose of this study was to assess the pathological responses of atherosclerotic saphenous vein bypass grafts (SVBGs) to drug-eluting stents (DES) versus bare-metal stents (BMS).
Background Repeat bypass surgery is typically associated with a high rate of morbidity and mortality. Percutaneous coronary interventions have emerged as the preferred treatment; however, only limited data are available on SVBGs pathological responses to DES and BMS.
Methods Formalin-fixed SVBG of > 2 years duration (n = 31) were collected to histologically characterize advanced atherosclerotic lesions in native SVBG. In a separate group, SVBGs treated with DES (n = 9) and BMS (n = 9) for > 30 days duration were assessed for morphological and morphometric changes.
Results Necrotic core lesions were identified in 25% of SVBG sections, and plaque rupture with luminal thrombosis was observed in 6.3% of histological sections (32% [10 of 31] vein grafts examined). Morphometry of DES demonstrated reduction in neointimal thickening versus BMS (0.13 mm [interquartile range: 0.06 to 0.16 mm] vs. 0.30 mm [interquartile range: 0.20 to 0.48 mm], p = 0.004). DES lesions also showed greater delayed healing characterized by increased peristrut fibrin deposition, higher percentage of uncovered struts, and less endothelialization compared with BMS. Stent fractures (DES 56% vs. BMS 11%, p = 0.045) and late stent thrombosis (DES 44% vs. BMS 0%, p = 0.023) were more common in DES versus BMS.
Conclusions Advanced SVBG atherosclerotic lesions are characterized by large hemorrhagic necrotic cores. Stenting of such lesions is associated with delayed vascular healing and late thrombosis particularly following DES implantation, which may help explain the higher rates of cardiovascular events observed in SVBG stenting as compared with native coronary arteries. (J Am Coll Cardiol Intv 2012;5:666-74) (c) 2012 by the American College of Cardiology Foundation
C1 [Yazdani, Saami K.; Nakano, Masataka; Vorpahl, Marc; Ladich, Elena; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD 20878 USA.
[Farb, Andrew] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Finn, Aloke V.] Emory Univ, Sch Med, Dept Cardiol, Atlanta, GA USA.
RP Virmani, R (reprint author), CVPath Inst Inc, 19 Firstfield Rd, Gaithersburg, MD 20878 USA.
EM rvirmani@cvpath.org
FU National Institutes of Health grant [HL096970-01A1]; Carlyle Fraser
Heart Center at Emory University; Medtronic and St Jude Medical
FX From the *CVPath Institute Inc., Gaithersburg, Maryland; dagger Office
of Device Evaluation, Center for Devices and Radiological Health, U.S.
Food and Drug Administration, Silver Spring, Maryland; and the double
dagger Department of Cardiology, Emory University School of Medicine,
Atlanta, Georgia. Dr. Finn is supported by National Institutes of Health
grant HL096970-01A1, the Carlyle Fraser Heart Center at Emory
University, sponsored research agreement with Medtronic and St Jude
Medical, and is a consultant for Abbott Vascular and Cordis. Dr. Virmani
is a consultant for Medtronic AVE, Abbott Vascular, W.L. Gore, Atrium
Medical, Arsenal Medical, and Lutonix. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose.
NR 36
TC 11
Z9 12
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-8798
J9 JACC-CARDIOVASC INTE
JI JACC-Cardiovasc. Interv.
PD JUN
PY 2012
VL 5
IS 6
BP 666
EP 674
DI 10.1016/j.jcin.2011.12.017
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 970JG
UT WOS:000306123600012
PM 22721663
ER
PT J
AU Garrison, L
Hastak, M
Hogarth, JM
Kleimann, S
Levy, AS
AF Garrison, Loretta
Hastak, Manoj
Hogarth, Jeanne M.
Kleimann, Susan
Levy, Alan S.
TI Designing Evidence-based Disclosures: A Case Study of Financial Privacy
Notices
SO JOURNAL OF CONSUMER AFFAIRS
LA English
DT Article
ID NUTRITION INFORMATION; ONLINE PRIVACY; CONSUMER; BEHAVIOR; CHOICE;
COMPREHENSION; PROTECTION; USABILITY; KNOWLEDGE; ECONOMICS
AB Disclosure is a key component of consumer protection policy. By informing consumers about a product or service, disclosures can help consumers understand product features and shop among products and providers to find the combination of features and price that best meets their needs. For example, the Gramm-Leach-Bliley Act (GLBA, 15 U.S.C. 6801-6809) provides for disclosures of information-sharing practices of financial institutions and, in some cases, requires that these institutions offer consumers the opportunity to limit some of this sharing. Using these disclosures as a case study, this paper explores how research can help policymakers shift from a perspective of developing disclosures that are in technical compliance with the law to one of developing disclosures that consumers pay attention to, understand and use in their decision making.
C1 [Garrison, Loretta] Fed Trade Commiss, Washington, DC USA.
[Hastak, Manoj] American Univ, Kogod Sch Business, Washington, DC 20016 USA.
[Hogarth, Jeanne M.] Fed Reserve Board, Washington, DC USA.
[Levy, Alan S.] US FDA, Rockville, MD 20857 USA.
EM lorettagarrison@mac.com; mhastak@american.edu; jeanne.m.hogarth@frb.gov;
skleimann@kleimann.com; alan.levy@cfsan.fda.gov
NR 67
TC 8
Z9 8
U1 1
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-0078
J9 J CONSUM AFF
JI J. Consum. Aff.
PD SUM
PY 2012
VL 46
IS 2
SI SI
BP 204
EP 234
DI 10.1111/j.1745-6606.2012.01226.x
PG 31
WC Business; Economics
SC Business & Economics
GA 967HO
UT WOS:000305897700003
ER
PT J
AU Sarkar, S
Schmued, L
AF Sarkar, Sumit
Schmued, Larry
TI In vivo administration of fluorescent dextrans for the specific and
sensitive localization of brain vascular pericytes and their
characterization in normal and neurotoxin exposed brains
SO NEUROTOXICOLOGY
LA English
DT Article
DE Pericytes; Blood-brain barrier; Kainic acid; Endothelial cells
ID ENDOTHELIAL-CELLS; RAT-BRAIN; BARRIER; ANGIOGENESIS; MIGRATION; SYSTEM;
ENCEPHALOMYELITIS; ANGIOPOIETIN-1; FLUOROGOLD
AB We have aimed to develop novel histochemical markers for the labeling of brain pericytes and characterize their morphology in the normal and the excitotoxin-exposed brain, as this class of cells has received little attention until recently. Pericyte labeling was accomplished by the intracerebroventricular injection of certain fluorescent dextran conjugates, such as Fluoro-Gold-dextran, FR-dextran, FITC-dextran and Fluoro-Turquoise (FT)-dextran. 1-7 days after the tracer injection, extensive labeling of vascular pericytes was seen throughout the entire brain. These cells were found distal to the endothelial cells and exhibited large dye containing vacuoles. The morphology of the pericytes was somewhat variable, exhibiting round or amoeboid shapes within larger intracellular vesicles, while those wrapping around capillaries exhibited a more elongated appearance with finger-like projections. The use of FG-dextran resulted in bluish yellow fluorescently labeled pericytes, while FR-dextran resulted in red fluorescent labeled pericytes, FITC-dextran exhibited green fluorescent pericytes and FT-dextran showed fluorescent blue pericytes in the brain. We have used these tracers to study possible changes in morphology and pericyte number following kainic acid insult, observing that the number of pericytes in the injured or lesioned areas of the brain is dramatically reduced compared to the non-injured areas. These novel fluorochromes should be of use for studies involving the detection and localization of pericytes in both normal and pathological brain tissues. Published by Elsevier Inc.
C1 [Sarkar, Sumit; Schmued, Larry] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Schmued, L (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,Bldg 13,HFT-132, Jefferson, AR 72079 USA.
EM larry.schmued@fda.hhs.gov
FU FDA Protocol [E 7312]
FX This work was supported by FDA Protocol E 7312.
NR 38
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U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0161-813X
J9 NEUROTOXICOLOGY
JI Neurotoxicology
PD JUN
PY 2012
VL 33
IS 3
BP 436
EP 443
DI 10.1016/j.neuro.2012.04.004
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Toxicology
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology
GA 951OO
UT WOS:000304730100020
PM 22525936
ER
PT J
AU Achtman, M
Wain, J
Weill, FX
Nair, S
Zhou, ZM
Sangal, V
Krauland, MG
Hale, JL
Harbottle, H
Uesbeck, A
Dougan, G
Harrison, LH
Brisse, S
AF Achtman, Mark
Wain, John
Weill, Francois-Xavier
Nair, Satheesh
Zhou, Zhemin
Sangal, Vartul
Krauland, Mary G.
Hale, James L.
Harbottle, Heather
Uesbeck, Alexandra
Dougan, Gordon
Harrison, Lee H.
Brisse, Sylvain
CA S Enterica MLST Study Grp
TI Multilocus Sequence Typing as a Replacement for Serotyping in Salmonella
enterica
SO PLOS PATHOGENS
LA English
DT Article
ID MOLECULAR EVOLUTIONARY GENETICS; FRAGMENT-LENGTH-POLYMORPHISM; FIELD
GEL-ELECTROPHORESIS; PARATYPHI-B; SEROVAR TYPHIMURIUM;
POPULATION-STRUCTURE; HOST ADAPTATION; GENOME VARIATION; FLAGELLIN
GENES; YERSINIA-PSEUDOTUBERCULOSIS
AB Salmonella enterica subspecies enterica is traditionally subdivided into serovars by serological and nutritional characteristics. We used Multilocus Sequence Typing (MLST) to assign 4,257 isolates from 554 serovars to 1092 sequence types (STs). The majority of the isolates and many STs were grouped into 138 genetically closely related clusters called eBurstGroups (eBGs). Many eBGs correspond to a serovar, for example most Typhimurium are in eBG1 and most Enteritidis are in eBG4, but many eBGs contained more than one serovar. Furthermore, most serovars were polyphyletic and are distributed across multiple unrelated eBGs. Thus, serovar designations confounded genetically unrelated isolates and failed to recognize natural evolutionary groupings. An inability of serotyping to correctly group isolates was most apparent for Paratyphi B and its variant Java. Most Paratyphi B were included within a sub-cluster of STs belonging to eBG5, which also encompasses a separate sub-cluster of Java STs. However, diphasic Java variants were also found in two other eBGs and monophasic Java variants were in four other eBGs or STs, one of which is in subspecies salamae and a second of which includes isolates assigned to Enteritidis, Dublin and monophasic Paratyphi B. Similarly, Choleraesuis was found in eBG6 and is closely related to Paratyphi C, which is in eBG20. However, Choleraesuis var. Decatur consists of isolates from seven other, unrelated eBGs or STs. The serological assignment of these Decatur isolates to Choleraesuis likely reflects lateral gene transfer of flagellar genes between unrelated bacteria plus purifying selection. By confounding multiple evolutionary groups, serotyping can be misleading about the disease potential of S. enterica. Unlike serotyping, MLST recognizes evolutionary groupings and we recommend that Salmonella classification by serotyping should be replaced by MLST or its equivalents.
C1 [Achtman, Mark; Zhou, Zhemin; Hale, James L.] Natl Univ Ireland Univ Coll Cork, Environm Res Inst, Cork, Ireland.
[Achtman, Mark; Zhou, Zhemin; Hale, James L.] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland.
[Achtman, Mark; Sangal, Vartul] Max Planck Inst Infect Biol, Berlin, Germany.
[Wain, John; Nair, Satheesh; Dougan, Gordon] Wellcome Trust Sanger Inst, Cambridge, England.
[Wain, John; Nair, Satheesh] Hlth Protect Agcy, Ctr Infect, London, England.
[Krauland, Mary G.; Harrison, Lee H.] Univ Pittsburgh, Sch Med, Infect Dis Epidemiol Res Unit, Pittsburgh, PA USA.
[Krauland, Mary G.; Harrison, Lee H.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Weill, Francois-Xavier; Brisse, Sylvain] Inst Pasteur, Paris, France.
[Harbottle, Heather] US FDA, Ctr Vet Med, Derwood, MD USA.
[Uesbeck, Alexandra] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany.
RP Achtman, M (reprint author), Natl Univ Ireland Univ Coll Cork, Environm Res Inst, Cork, Ireland.
EM m.achtman@ucc.ie
RI Wain, John/B-3446-2013;
OI Wain, John/0000-0002-1257-1148; Sangal, Vartul/0000-0002-7405-8446;
Murphy, Ronan/0000-0001-7274-6563; Weill,
Francois-Xavier/0000-0001-9941-5799; Nair, Satheesh/0000-0002-7297-1485;
Achtman, Mark/0000-0001-6815-0070; Didelot, Xavier/0000-0003-1885-500X
FU Science Foundation of Ireland [05/FE1/B882]; Max-Planck Gesellschaft;
Wellcome Trust of Great Britain; BMBF [01 LW 06001]; MIWFT
[313-21200200]; Institut Pasteur; Institut de Veille Sanitaire
(Saint-Maurice, France)
FX MA and JLH were supported by the Science Foundation of Ireland
(05/FE1/B882), www.sfi.ie. Initially work by MA and VS was supported by
the Max-Planck Gesellschaft (www.mpg.de). JW, SN and GD were supported
by the Wellcome Trust of Great Britain (www.welcome.ac.uk). AE was
supported by the BMBF (grant 01 LW 06001), www.bmbf.de and MIWFT
(313-21200200)www.wissenschaft.nrw.de. Work by F-XW and SB was supported
by the Institut Pasteur (www.pasteur.fr) and a grant from the Institut
de Veille Sanitaire (Saint-Maurice, France). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 98
TC 125
Z9 130
U1 5
U2 33
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUN
PY 2012
VL 8
IS 6
AR e1002776
DI 10.1371/journal.ppat.1002776
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 968ND
UT WOS:000305987800043
PM 22737074
ER
PT J
AU Kim, BS
Kim, JN
Yoon, SH
Chun, J
Cerniglia, CE
AF Kim, Bong-Soo
Kim, Jong Nam
Yoon, Seok-Hwan
Chun, Jongsik
Cerniglia, Carl E.
TI Impact of enrofloxacin on the human intestinal microbiota revealed by
comparative molecular analysis
SO ANAEROBE
LA English
DT Article
DE Denaturing gradient gel electrophoresis; In vitro culture system;
Metatranscriptome; Pyrosequencing
ID HUMAN GUT MICROBIOTA; CIPROFLOXACIN; COMMUNITY; PHARMACOKINETICS;
RESISTANCE; MICROFLORA; RESIDUES; OBESITY; CLARITHROMYCIN; CAMPYLOBACTER
AB The indigenous human intestinal microbiota could be disrupted by residues of antibiotics in foods as well as therapeutically administered antibiotics to humans. These disruptions may lead to adverse health outcomes. To observe the possible impact of residues of antibiotics at concentrations below therapeutic levels on human intestinal microbiota, we performed studies using in vitro cultures of fecal suspensions from three individuals with 10 different concentrations (0, 0.1, 0.5, 1, 5, 10, 15, 25, 50 and 150 mu g/ml) of the fluoroquinolone, enrofloxacin. The bacterial communities of the control and enrofloxacin dosed fecal samples were analyzed by denaturing gradient gel electrophoresis (DGGE) and pyrosequencing. In addition, changes of functional gene expression were analyzed by a pyrosequencing-based random whole-community mRNA sequencing method. Although each individual had a unique microbial composition, the communities of all individuals were affected by enrofloxacin. The proportions of two phyla, namely, Bacteroidetes and Proteobacteria, were significantly reduced with increasing concentrations of enrofloxacin exposure, while the proportion of Firmicutes increased. Principal Coordinate Analysis (PCoA) using the Fast UniFrac indicated that the community structures of intestinal microbiota were shifted by enrofloxacin. Most of the mRNA transcripts and the anti-microbial drug resistance genes increased with increasing concentrations of enrofloxacin. 16S rRNA gene pyrosequencing of control and enrofloxacin treated fecal suspensions provided valuable information of affected bacterial taxa down to the species level, and the community transcriptomic analyses using mRNA revealed the functional gene expression responses of the changed bacterial communities by enrofloxacin. Published by Elsevier Ltd.
C1 [Kim, Bong-Soo; Kim, Jong Nam; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Yoon, Seok-Hwan; Chun, Jongsik] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea.
RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM carl.cerniglia@fda.hhs.gov
RI Kim, Bong-Soo/L-4779-2013
OI Kim, Bong-Soo/0000-0003-1243-8280
FU National Center for Toxicological Research
FX We thank Dr. Peter Silley and Dr. Susan F. Kotarski for their helpful
discussion, as well as Drs. John B. Sutherland, Robert D. Wagner, and
Sangeeta Khare for their critical reading of the manuscript. This
research was supported in part by an appointment to the Research
Participation Program (B.-S. Kim and J. N. Kim) at the National Center
for Toxicological Research administered by the Oak Ridge Institute for
Science and Education through an inter-agency agreement between the U.S.
Department of Energy and the Food and Drug Administration. The views
presented in this article are not necessarily those of the Food and Drug
Administration.
NR 49
TC 31
Z9 32
U1 3
U2 45
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1075-9964
J9 ANAEROBE
JI Anaerobe
PD JUN
PY 2012
VL 18
IS 3
BP 310
EP 320
DI 10.1016/j.anaerobe.2012.01.003
PG 11
WC Microbiology
SC Microbiology
GA 966RR
UT WOS:000305855600010
PM 22321759
ER
PT J
AU Nelson, CP
Patton, GW
Arvidson, K
Lee, H
Twaroski, ML
AF Nelson, Chad P.
Patton, Geoffrey W.
Arvidson, Kirk
Lee, Helen
Twaroski, Michelle L.
TI Assessing the toxicity of polymeric food-contact substances (vol 49, pg
1887, 2011)
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Correction
C1 [Patton, Geoffrey W.; Arvidson, Kirk; Lee, Helen; Twaroski, Michelle L.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notificat, College Pk, MD 20740 USA.
[Nelson, Chad P.] US FDA, Off Commissioner, Off Foods, Silver Spring, MD 20993 USA.
RP Patton, GW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notificat, 5100 Paint Branch Pkwy,HFS-275, College Pk, MD 20740 USA.
EM geoffrey.patton@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 1
U2 2
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 JUN
PY 2012
VL 50
IS 6
BP 2251
EP 2251
DI 10.1016/j.fct.2012.03.007
PG 1
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 964TN
UT WOS:000305719700058
ER
PT J
AU Wu, WW
Shen, RF
Park, SS
Martin, B
Maudsley, S
AF Wu, Wells W.
Shen, Rong-Fong
Park, Sung-Soo
Martin, Bronwen
Maudsley, Stuart
TI Precursor ion exclusion for enhanced identification of plasma biomarkers
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Article
DE Multi-dimensional fractionation; Plasma biomarkers; Precursor ion
exclusion
ID MASS-SPECTROMETRY; DISCOVERY; PROTEOME; FRACTIONATION; DEPLETION;
PEPTIDES; PROTEINS
AB Purpose Our study aims to establish a plasma biomarker analysis workflow, with fewer fractionation steps, for enhanced identification of plasma biomarkers by precursor ion exclusion (PIE). Experimental design Plasma samples were depleted for highly abundant proteins, then further fractionated by molecular weight (MW), before trypsinization for LTQ-Orbitrap mass analysis. Data-dependent acquisition (DDA) was used for baseline analysis. PIE involves the re-injection of samples with exclusion of the previously identified peptides. We compared analyses using multiple PIE iterations, compared to DDA, for plasma interrogation Results A higher percentage of unique plasma peptides was identified with PIE, compared to DDA. The first PIE iteration reveals an increase of 75112% more peptides than the DDA method alone. PIE can interrogate complex plasma samples with the percentage of peptides identified successively increasing with even =4 iterations. The total number of peptides identified increases rapidly across the first three PIE iterations and then continues more slowly up to nine iterations. Conclusions and clinical relevance Iterative injections with PIE resulted in many more peptide identifications in plasma samples of varying degrees of complexity, compared to re-injections using similar DDA parameters. PIE methods may therefore expand our ability to recover plasma peptides for plasma biomarker discovery.
C1 [Park, Sung-Soo; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Wu, Wells W.; Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@grc.nia.nih.gov
FU Intramural Research Programs of National Institute on Aging (NIA),
National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Programs of
National Institute on Aging (NIA), National Institutes of Health (NIH).
We thank Dr. Luigi Ferrucci (NIA) for helpful feedback during this study
and for critically reading our manuscript, and we also thank Dr.
Josephine M Egan (NIA) for support during the study.
NR 17
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1862-8346
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD JUN
PY 2012
VL 6
IS 5-6
BP 304
EP 308
DI 10.1002/prca.201100107
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 966FN
UT WOS:000305823200008
PM 22641611
ER
PT J
AU Asur, RS
Sharma, S
Chang, CW
Penagaricano, J
Kommuru, IM
Moros, EG
Corry, PM
Griffin, RJ
AF Asur, Rajalakshmi S.
Sharma, Sunil
Chang, Ching-Wei
Penagaricano, Jose
Kommuru, Indira M.
Moros, Eduardo G.
Corry, Peter M.
Griffin, Robert J.
TI Spatially Fractionated Radiation Induces Cytotoxicity and Changes in
Gene Expression in Bystander and Radiation Adjacent Murine Carcinoma
Cells
SO RADIATION RESEARCH
LA English
DT Article
ID CHARGED-PARTICLE MICROBEAM; PRIMARY HUMAN FIBROBLASTS; DOUBLE-STRAND
BREAKS; ALPHA-PARTICLE; IONIZING-RADIATION; INTERCELLULAR COMMUNICATION;
OXIDATIVE-METABOLISM; CLONOGENIC SURVIVAL; UNIRRADIATED CELLS;
GLIOMA-CELLS
AB Radiation-induced bystander effects have been extensively studied at low doses, since evidence of bystander induced cell killing and other effects on unirradiated cells were found to be predominant at doses up to 0.5 Gy. Therefore, few studies have examined bystander effects induced by exposure to higher doses of radiation, such as spatially fractionated radiation (GRID) treatment. In the present study, we evaluate the ability of GRID treatment to induce changes in GRID adjacent (bystander) regions, in two different murine carcinoma cell lines following exposure to a single irradiation dose of 10 Gy. Murine SCK mammary carcinoma cells and SCCVII squamous carcinoma cells were irradiated using a brass collimator to create a GRID pattern of nine circular fields 12 mm in diameter with a center-to-center distance of 18 mm. Similar to the typical clinical implementation of GRID, this is approximately a 50:50 ratio of direct and bystander exposure. We also performed experiments by irradiating separate cultures and transferring the medium to unirradiated bystander cultures. Clonogenic survival was evaluated in both cell lines to determine the occurrence of radiation-induced bystander effects. For the purpose of our study, we have defined bystander cells as GRID adjacent cells that received approximately 1 Gy scatter dose or unirradiated cells receiving conditioned medium from irradiated cells. We observed significant bystander killing of cells adjacent to the GRID irradiated regions compared to sham treated controls. We also observed bystander killing of SCK and SCCVII cells cultured in conditioned medium obtained from cells irradiated with 10 Gy. Therefore, our results confirm the occurrence of bystander effects following exposure to a high-dose of radiation and suggest that cell-to-cell contact is not required for these effects. In addition, the gene expression profile for DNA damage and cellular stress response signaling in SCCVII cells after GRID exposure was studied. The occurrence of GRID-induced bystander gene expression changes in significant numbers of DNA damage and cellular stress response signaling genes, providing molecular evidence for possible mechanisms of bystander cell killing. (C) 2012 by Radiation Research Society
C1 [Asur, Rajalakshmi S.; Sharma, Sunil; Penagaricano, Jose; Kommuru, Indira M.; Corry, Peter M.; Griffin, Robert J.] Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA.
[Chang, Ching-Wei] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Moros, Eduardo G.] MCC RADONC, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
RP Griffin, RJ (reprint author), Univ Arkansas Med Sci, Dept Radiat Oncol, 4301 W Markham St, Little Rock, AR 72205 USA.
EM rjgriffin@uams.edu
OI Moros, Eduardo/0000-0003-1964-2460
FU Central Arkansas Radiation Therapy Institute (CARTI); NIH [CA44114]
FX This work was supported by Central Arkansas Radiation Therapy Institute
(CARTI) and NIH grant CA44114. The authors thank N. Koonce and A.
Jamshidi-Parsian, for their input and guidance.
NR 61
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Z9 20
U1 0
U2 10
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD JUN
PY 2012
VL 177
IS 6
BP 751
EP 765
DI 10.1667/RR2780.1
PG 15
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 966NN
UT WOS:000305844800005
PM 22559204
ER
PT J
AU Garnett, CE
Zhu, H
Malik, M
Fossa, AA
Zhang, JN
Badilini, F
Li, JG
Darpo, B
Sager, P
Rodriguez, I
AF Garnett, Christine E.
Zhu, Hao
Malik, Marek
Fossa, Anthony A.
Zhang, Joanne
Badilini, Fabio
Li, Jianguo
Darpoe, Boerje
Sager, Philip
Rodriguez, Ignacio
TI Methodologies to characterize the QT/corrected QT interval in the
presence of drug-induced heart rate changes or other autonomic effects
SO AMERICAN HEART JOURNAL
LA English
DT Review
ID TORSADES-DE-POINTES; VENTRICULAR REPOLARIZATION; HEALTHY-SUBJECTS;
RATE-DEPENDENCE; NERVOUS-SYSTEM; THOROUGH QT; ELECTROCARDIOGRAPHIC
DIFFERENCES; CARDIAC REPOLARIZATION; ADRENERGIC-STIMULATION; INDUCED
PROLONGATION
AB This White Paper, written collaboratively by members of the Cardiac Safety Research Consortium from academia, industry, and regulatory agencies, discusses different methods to characterize the QT effects for drugs that have a substantial direct or indirect effect on heart rate. Descriptions and applications are provided for individualized QT-R-R correction, Holter bin, dynamic QT beat-to-beat, pharmacokinetic-pharmacodynamic modeling, and QT assessment at constant heart rate. Most of these techniques are optimally performed using continuous electrocardiogram data obtained in clinical studies designed to characterize a drug's effect on the QT interval. An important study design element is the collection of drug-free data over a range of heart rates seen on treatment. The range of heart rates is increased at baseline by using ambulatory electrocardiogram recordings in addition to those collected under semisupine, resting conditions. Discussions in this study summarize areas of emerging consensus and other areas in which consensus remains elusive and provide suggestions for additional research to further increase our knowledge and understanding of this topic. (Am Heart J 2012;163:912-30.)
C1 [Garnett, Christine E.; Zhu, Hao] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Malik, Marek] Univ London, London, England.
[Fossa, Anthony A.] ICardiac Technol, Rochester, NY USA.
[Zhang, Joanne] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Badilini, Fabio] AMPS, Montichiari, Italy.
[Li, Jianguo] AstraZeneca Global Med Dev, Wilmington, DE USA.
[Darpoe, Boerje] Soder Sjukhuset, Karolinska Inst, Cardiol Sect, Dept Clin Sci & Educ, Stockholm, Sweden.
[Sager, Philip] Sager Consulting Partners, Los Angeles, CA USA.
[Rodriguez, Ignacio] Hoffmann La Roche, Nutley, NJ USA.
RP Garnett, CE (reprint author), 10903 New Hampshire Ave,Bldg 51,Room 1260, Silver Spring, MD 20993 USA.
EM christine.garnett@fda.hhs.gov
NR 87
TC 37
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U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
J9 AM HEART J
JI Am. Heart J.
PD JUN
PY 2012
VL 163
IS 6
BP 912
EP 930
DI 10.1016/j.ahj.2012.02.023
PG 19
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 960YB
UT WOS:000305428200002
PM 22709743
ER
PT J
AU Jennings, DE
Edwards, GB
Rohr, JR
AF Jennings, David E.
Edwards, G. B.
Rohr, Jason R.
TI ASSOCIATIONS AMONG GROUND-SURFACE SPIDERS (ARANEAE) AND OTHER ARTHROPODS
IN MESIC FLATWOODS
SO FLORIDA ENTOMOLOGIST
LA English
DT Article
DE arthropods; biodiversity; Florida; species richness estimators; spiders
ID PREY AVAILABILITY; SAMPLING METHOD; WINTER-WHEAT; COMMUNITIES;
VEGETATION; DIVERSITY; FOREST; WEB; ASSEMBLAGES; DENSITIES
AB Mesic flatwoods in Florida are increasingly threatened by anthropogenic activities, and although they are known to be important for many species of macrofauna, little is known of the arthropod assemblages that inhabit them. As arthropods can be utilized as indicator taxa, we characterized the assemblages of ground-surface spiders (Araneae) and other arthropods at 2 mesic flatwood sites in Hillsborough County, Florida, and used the Chao 2, ICE (incidence-based coverage estimator), and Michaelis-Menten means species richness estimators to extrapolate the true species richness of ground-surface spiders. Sampling was conducted over a 4-month period at the sites using pitfall traps, with spiders being identified to the level of genus or species, and other arthropods to the level of order. We identified 31 spider species from 27 genera in 12 families, with Lycosidae being the dominant spider family at both sites. However, Collembola and Formicidae were the most abundant arthropod taxa. Ground-surface spiders were not strongly associated with any typical prey groups, indicating that environmental factors might also be important in structuring this community. Our results indicate that more intensive sampling of these habitats would be required to comprehensively sample and identify all of the species present, but from a management perspective, our results appear to be relatively consistent with previous surveys elsewhere.
C1 [Jennings, David E.; Rohr, Jason R.] Univ S Florida, Dept Integrat Biol, Tampa, FL 33620 USA.
[Edwards, G. B.] FDACS, Div Plant Ind, Gainesville, FL 32614 USA.
RP Jennings, DE (reprint author), Univ Maryland, Dept Entomol, 4112 Plant Sci Bldg, College Pk, MD 20742 USA.
OI Jennings, David/0000-0001-7179-3069
FU Fern Garden Club
FX This study was funded, in part, by a Fern Garden Club Scholarship to D.
E. J. We wish to thank Tyne Hopkins, Alyson Dagly, Camie Dencker,
Samantha Mulvany, and Neal Halstead for field assistance, and Thomas
Weekes from the Hillsborough County Parks, Recreation, and Conservation
Department for helping with the logistics of the study. We also are
grateful for comments from Dr. Waldemar Klassen and 3 anonymous
reviewers for improving the manuscript.
NR 35
TC 1
Z9 1
U1 0
U2 7
PU FLORIDA ENTOMOLOGICAL SOC
PI LUTZ
PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA
SN 0015-4040
J9 FLA ENTOMOL
JI Fla. Entomol.
PD JUN
PY 2012
VL 95
IS 2
BP 290
EP 296
PG 7
WC Entomology
SC Entomology
GA 960EL
UT WOS:000305370700008
ER
PT J
AU Trickler, WJ
Lantz, SM
Schrand, AM
Robinson, BL
Newport, GD
Schlager, JJ
Paule, MG
Slikker, W
Biris, AS
Hussain, SM
Ali, SF
AF Trickler, William J.
Lantz, Susan M.
Schrand, Amanda M.
Robinson, Bonnie L.
Newport, Glenn D.
Schlager, John J.
Paule, Merle G.
Slikker, William
Biris, Alexandru S.
Hussain, Saber M.
Ali, Syed F.
TI Effects of copper nanoparticles on rat cerebral microvessel endothelial
cells
SO NANOMEDICINE
LA English
DT Article
DE blood-brain barrier; copper nanoparticle; neuroinflammation;
neurotoxicity; rat brain microvessel endothelial cell
ID BLOOD-BRAIN-BARRIER; NECROSIS-FACTOR-ALPHA; IN-VITRO; DEPENDENT
TOXICITY; TNF-ALPHA; PERMEABILITY; MODEL; TRANSPORT; ENCEPHALOPATHY;
DYSFUNCTION
AB The purpose of the current study was to determine whether copper nanoparticles (Cu-NPs) can induce the release of proinflammatory mediators that influence the restrictive characteristics of the blood-brain barrier. Material & methods: Confluent rat brain microvessel endothelial cells (rBMECs) were treated with well-characterized Cu-NPs (40 or 60 nm). Cytotoxicity of the Cu-NPs was evaluated by cell proliferation assay (1.5-50 mu g/ml). The extracellular concentrations of proinflammatory mediators (IL-1 beta, IL-2, TNF-alpha and prostaglandin E-2) were evaluated by ELISA. Results: The exposure of Cu-NPs at low concentrations increases cellular proliferation of rBMECs, by contrast, high concentrations induce toxicity. Prostaglandin E-2 release was significantly increased (threefold; 8 h) for Cu-NPs (40 and 60 nm). The extracellular levels of both TNF-alpha and IL-1 beta were significantly elevated following exposure to Cu-NPs. The P-apparent ratio, as an indicator of increased permeability of rBMEC was approximately twofold for Cu-NPs (40 and 60 nm). Conclusion: These data suggest that Cu-NPs can induce rBMEC, proliferation at low concentrations and/or induce blood-brain barrier toxicity and potential neurotoxicity at high concentrations.
C1 [Trickler, William J.; Lantz, Susan M.; Robinson, Bonnie L.; Newport, Glenn D.; Paule, Merle G.; Slikker, William; Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Schrand, Amanda M.; Schlager, John J.; Hussain, Saber M.] USAF, Appl Biotechnol Branch HPW RHPB 711, Human Effectiveness Directorate, Res Lab, Wright Patterson AFB, OH 45433 USA.
[Biris, Alexandru S.] Univ Arkansas, Little Rock, AR 72079 USA.
RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM syed.ali@fda.hhs.gov
FU US Air Force Research Laboratory at the National Center for
Toxicological Research/US FDA (AR, USA); US Department of Energy, US Air
Force Research Laboratory/RHPB; FDA
FX This research was supported, in part, by an appointment to the
Postgraduate Research Participation Program with the US Air Force
Research Laboratory at the National Center for Toxicological Research/US
FDA (AR, USA) administered by the Oak Ridge Institute of Science and
Education (TN, USA) through an interagency agreement between the US
Department of Energy, US Air Force Research Laboratory/RHPB and the FDA.
Furthermore, the authors are responsible fir the content and writing of
the manuscript and do not necessarily reflect the position of the US
Government or FDA, nor does mention of trade names or commercial
products constitute endorsement or recommendation for use. The authors
have no other relevant affiliations or financial involvement with any
organization or entity with a financial interest in or financial
conflict with the subject matter or materials discussed in the
manuscript apart from those disclosed.
NR 41
TC 18
Z9 18
U1 1
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
J9 NANOMEDICINE-UK
JI Nanomedicine
PD JUN
PY 2012
VL 7
IS 6
BP 835
EP 846
DI 10.2217/NNM.11,154
PG 12
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA 964RC
UT WOS:000305713400012
PM 22339089
ER
PT J
AU Neef, N
Nikula, KJ
Francke-Carroll, S
Boone, L
AF Neef, Natasha
Nikula, Kristen J.
Francke-Carroll, Sabine
Boone, Laura
TI Regulatory Forum Opinion Piece: Blind Reading of Histopathology Slides
in General Toxicology Studies
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE histopathology; preclinical safety assessment/risk management;
regulatory affairs; risk assessment; toxicologic pathology
AB With the intention of reducing bias, a recent European Food Safety Authority draft guidance document included a recommendation for blinded evaluation of histopathology slides in general toxicology studies (EFSA 2011). Although blinding as to treatment status reduces bias in many types of scientific experiment and is sometimes also appropriate in toxicologic pathology (Holland and Holland 2011), it is most unlikely to help achieve the overall goal of improved human safety when used for routine histopathology evaluation of tissues in general toxicology studies. This is the case because (1) blinding is not applicable to the inductive reasoning process used to identify test article effects in the tissues and would dramatically reduce the chances of these being successfully identified; and (2) in any case, the bias that would be reduced by blinding is actually a bias favoring diagnosis of a toxicological hazard and a conservative safety evaluation, which is appropriate in this context. Other unintended consequences of blinding histopathology evaluation include reductions in sensitivity for a variety of additional reasons and increased subjectivity of the pathology data.
C1 [Neef, Natasha] Bristol Myers Squibb, New Brunswick, NJ 08901 USA.
[Nikula, Kristen J.] Seventh Wave Labs, Chesterfield, MO USA.
[Francke-Carroll, Sabine] DHHS FDA CFSAN OSAS, College Pk, MD USA.
[Boone, Laura] Covance Labs, Greenfield, IN USA.
RP Neef, N (reprint author), Bristol Myers Squibb, 1 Squibb Dr, New Brunswick, NJ 08901 USA.
EM natasha.neef@bms.com
NR 3
TC 6
Z9 6
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 JUN
PY 2012
VL 40
IS 4
BP 697
EP 699
DI 10.1177/0192623312438737
PG 3
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 961JY
UT WOS:000305461900015
PM 22407309
ER
PT J
AU He, Z
He, B
Behrle, BL
Fejleh, MPC
Cui, L
Paule, MG
Greenfield, LJ
AF He, Zhen
He, Bei
Behrle, Brian L.
Fejleh, M. Phillip C.
Cui, Li
Paule, Merle G.
Greenfield, L. John
TI Ischemia-Induced Increase in Microvascular Phosphodiesterase 4D
Expression in Rat Hippocampus Associated with Blood Brain Barrier
Permeability: Effect of Age
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Aging; microvascular PDE4D; parenchymal albumin; perimicrovascular
space; rat hippocampus; transient global ischemia
ID NITRIC-OXIDE SYNTHASE; GLOBAL-ISCHEMIA; NEUROPROTECTION; PATHOLOGY;
BREAKDOWN; CELLS; LEADS
AB Phosphodiesterase 4D (PDE4D) is one of 16 PDEs expressed in cerebral microvessels, and may be involved in regulating blood-brain barrier (BBB) permeability. To assess the possible role of PDE4D in stroke-related injury in young versus aged rats, we measured microvascular PDE4D expression, parenchymal albumin immunoreactivity, and changes in the inside bore of the brain microvasculature. Ischemia caused severe hippocampal CA1 damage, associated with significant increases in vascular PDE4D and parenchymal albumin immunoreactivities. This effect was greater in the younger animals, which also had a greater increase in PDE4D expression. Ischemia significantly decreased tissue density in the perimicrovascular space in both young and aged animals. In addition, internal bore circumference and cross-sectional area of the hippocampal microvessels increased dramatically following ischemia. Increased PDE4D expression following cerebral ischemia may play a role in changing BBB permeability, which could secondarily affect ischemic outcome.
C1 [He, Zhen; He, Bei; Behrle, Brian L.; Fejleh, M. Phillip C.; Cui, Li; Greenfield, L. John] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA.
[He, Zhen; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Silver Spring, MD 20993 USA.
RP Cui, L (reprint author), Univ Arkansas Med Sci, Dept Neurol, 4301 W Markham St 585, Little Rock, AR 72205 USA.
EM LCui@uams.edu
FU Mayo Clinic Foundation; NCTR [P00710]; NIH [R01-NS049389]; UAMS
FX The present study was partly supported by Mayo Clinic Foundation and
NCTR under Protocol # P00710 (Z.H.), NIH Grant R01-NS049389, and UAMS
institutional funds (J.L.G.).
NR 18
TC 8
Z9 8
U1 1
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUN
PY 2012
VL 3
IS 6
BP 428
EP 432
DI 10.1021/cn2001156
PG 5
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA 959ZZ
UT WOS:000305359100001
PM 22860212
ER
PT J
AU Yih, WK
Lee, GM
Lieu, TA
Ball, R
Kulldorff, M
Rett, M
Wahl, PM
McMahill-Walraven, CN
Platt, R
Salmon, DA
AF Yih, W. Katherine
Lee, Grace M.
Lieu, Tracy A.
Ball, Robert
Kulldorff, Martin
Rett, Melisa
Wahl, Peter M.
McMahill-Walraven, Cheryl N.
Platt, Richard
Salmon, Daniel A.
TI Surveillance for Adverse Events Following Receipt of Pandemic 2009 H1N1
Vaccine in the Post-Licensure Rapid Immunization Safety Monitoring
(PRISM) System, 2009-2010
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Guillain-Barre syndrome; influenza A virus; influenza A virus; H1N1
subtype; influenza vaccines; population surveillance; safety; vaccines
ID GUILLAIN-BARRE-SYNDROME; INFLUENZA VACCINATION; DATALINK PROJECT;
UNITED-STATES; COHORT
AB The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a cohort-based active surveillance network initiated by the US Department of Health and Human Services to supplement preexisting and other vaccine safety monitoring systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine in the United States during 2009-2010. PRISM investigators conducted retrospective analysis to determine whether 2009 H1N1 vaccination was associated with increased risk of any of 14 prespecified outcomes. Five health insurance and associated companies with 38 million members and 9 state/city immunization registries contributed records on more than 2.6 million doses of 2009 H1N1 vaccine. Data on outcomes came from insurance claims. Complementary designs (self-controlled risk interval, case-centered, and current-vs.-historical comparison) were used to optimize control for confounding and statistical power. The self-controlled risk interval analysis of chart-confirmed Guillain-Barre syndrome found an elevated but not statistically significant incidence rate ratio following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio 2.50, 95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009 H1N1 vaccine. The study did not control for infection prior to Guillain-Barre syndrome, which may have been a confounder. The risks of other health outcomes of interest were generally not significantly elevated after 2009 H1N1 vaccination.
C1 [Yih, W. Katherine; Lee, Grace M.; Lieu, Tracy A.; Kulldorff, Martin; Rett, Melisa; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA.
[Yih, W. Katherine; Lee, Grace M.; Lieu, Tracy A.; Kulldorff, Martin; Rett, Melisa; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.
[Lee, Grace M.] Childrens Hosp Boston, Div Infect Dis, Boston, MA USA.
[Lee, Grace M.] Childrens Hosp Boston, Dept Lab Med, Boston, MA USA.
[Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, US Dept HHS, Rockville, MD 20857 USA.
[Wahl, Peter M.] HealthCore Inc, Govt & Acad Res, Wilmington, DE USA.
[McMahill-Walraven, Cheryl N.] Aetna, Aetna Informat Operat & Technol, Program Evaluat & Anal, Blue Bell, PA USA.
[Salmon, Daniel A.] US Dept HHS, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Washington, DC 20201 USA.
RP Yih, WK (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA.
EM katherine_yih@harvardpilgrim.org
OI Kulldorff, Martin/0000-0002-5284-2993
FU Food and Drug Administration under Centers for Disease Control and
Prevention [200-2002-00732]
FX This work was supported by the Food and Drug Administration through
America's Health Insurance Plans under Centers for Disease Control and
Prevention contract 200-2002-00732.
NR 22
TC 34
Z9 34
U1 2
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUN 1
PY 2012
VL 175
IS 11
BP 1120
EP 1128
DI 10.1093/aje/kws197
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 956IC
UT WOS:000305082300004
PM 22582207
ER
PT J
AU Grinnon, ST
Miller, K
Marler, JR
Lu, Y
Stout, A
Odenkirchen, J
Kunitz, S
AF Grinnon, Stacie T.
Miller, Kristy
Marler, John R.
Lu, Yun
Stout, Alexandra
Odenkirchen, Joanne
Kunitz, Selma
TI National Institute of Neurological Disorders and Stroke Common Data
Element Project - approach and methods
SO CLINICAL TRIALS
LA English
DT Article
AB Background In neuroscience clinical research studies, much time and effort are devoted to deciding what data to collect and developing data collection forms and data management systems to capture the data. Many investigators receiving funding from National Institute of Neurological Disorders and Stroke (NINDS), the National Institutes of Health (NIH), are required to share their data once their studies are complete, but the multitude of data definitions and formats make it extremely difficult to aggregate data or perform meta-analyses across studies.
Purpose In an effort to assist investigators and accelerate data sharing in neuroscience clinical research, the NINDS has embarked upon the Common Data Element (CDE) Project. The data standards developed through the NINDS CDE Project enable clinical investigators to systematically collect data and should facilitate study start-up and data aggregation across the research community.
Methods The NINDS CDE Team has taken a systematic, iterative approach to develop the critical core and the disease-specific CDEs. The CDE development process provides a mechanism for community involvement and buy-in, offers a structure for decision making, and includes a technical support team.
Results Upon conclusion of the development process, the CDEs and accompanying tools are available on the Project Web site - http://www.commondataelements.ninds.nih.gov/. The Web site currently includes the critical core (aka general) CDEs that are applicable to all clinical research studies regardless of therapeutic area as well as several disease-specific CDEs. Additional disease-specific CDEs will be added to the Web site once they are developed and vetted over the next 12 months.
Limitations The CDEs will continue to evolve and will improve only if clinical researchers use and offer feedback about their experience with them. Thus, the NINDS program staff strongly encourages its clinical research grantees to use the CDEs and is expanding its efforts to educate the neuroscience research community about the CDEs and to train research teams to incorporate them into their studies.
Conclusions Version 1.0 of a set of CDEs has been published, but publication is not the end of the development process. All CDEs will be evaluated and revised at least annually to ensure that they reflect current clinical research practices in neuroscience.
C1 [Grinnon, Stacie T.; Miller, Kristy; Lu, Yun; Stout, Alexandra; Kunitz, Selma] KAI Res Inc, Rockville, MD 20852 USA.
[Marler, John R.] US FDA, White Oak, MD USA.
[Odenkirchen, Joanne] NINDS, NIH, Bethesda, MD 20892 USA.
RP Grinnon, ST (reprint author), KAI Res Inc, 11300 Rockville Pike,Suite 500, Rockville, MD 20852 USA.
EM SGrinnon@kai-research.com
FU NINDS NIH HHS [N01NS72372, N01-NS-7-2372]
NR 2
TC 31
Z9 31
U1 0
U2 2
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
PD JUN
PY 2012
VL 9
IS 3
BP 322
EP 329
DI 10.1177/1740774512438980
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 957JR
UT WOS:000305158200005
PM 22371630
ER
PT J
AU Evans, C
Cipolla, D
Chesworth, T
Agurell, E
Ahrens, R
Conner, D
Dissanayake, S
Dolovich, M
Doub, W
Fuglsang, A
Arieta, AG
Golden, M
Hermann, R
Hochhaus, G
Holmes, S
Lafferty, P
Lyapustina, S
Nair, P
O'Connor, D
Parkins, D
Peterson, I
Reisner, C
Sandell, D
Singh, GJP
Weda, M
Watson, P
AF Evans, Carole
Cipolla, David
Chesworth, Tim
Agurell, Eva
Ahrens, Richard
Conner, Dale
Dissanayake, Sanjeeva
Dolovich, Myrna
Doub, William
Fuglsang, Anders
Garcia Arieta, Afredo
Golden, Michael
Hermann, Robert
Hochhaus, Guenther
Holmes, Susan
Lafferty, Paul
Lyapustina, Svetlana
Nair, Parameswaran
O'Connor, Dennis
Parkins, David
Peterson, Ilse
Reisner, Colin
Sandell, Dennis
Singh, Gur Jai Pal
Weda, Marjolein
Watson, Patricia
TI Equivalence Considerations for Orally Inhaled Products for Local
Action-ISAM/IPAC-RS European Workshop Report
SO JOURNAL OF AEROSOL MEDICINE AND PULMONARY DRUG DELIVERY
LA English
DT Article
DE inhaler; IVIVC; equivalence; goalposts; pharmacokinetics;
pharmacodynamics; in vitro; device; patient handling
ID DRY-POWDER INHALERS; METERED-DOSE INHALERS; DISTRIBUTION APSD METRICS;
FLUTICASONE PROPIONATE; LUNG DEPOSITION; RELATIVE PRECISION;
HEALTHY-SUBJECTS; FULL RESOLUTION; YOUNG-CHILDREN; DRUG PRODUCTS
AB The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The article summarizes current regulatory approaches in Europe, the United States, and Canada, and presents points of consensus as well as ongoing debate in the four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies, and device similarity. Specific issues in need of further research and discussion are also identified.
C1 [Evans, Carole] Catalent Pharma Solut, Res Triangle Pk, NC 27709 USA.
[Cipolla, David] Aradigm, Hayward, CA USA.
[Chesworth, Tim] AstraZeneca, Macclesfield, Cheshire, England.
[Agurell, Eva] Swedish Med Prod Agcy, Uppsala, Sweden.
[Ahrens, Richard] Univ Iowa, Iowa City, IA USA.
[Conner, Dale] US FDA, Rockville, MD 20857 USA.
[Dissanayake, Sanjeeva] Mundipharma Res, Cambridge, England.
[Dolovich, Myrna; Nair, Parameswaran] McMaster Univ, Hamilton, ON, Canada.
[Doub, William] US FDA, St Louis, MO USA.
[Fuglsang, Anders] Fuglsang Pharma, Rudolstadt, Germany.
[Garcia Arieta, Afredo] Spanish Agcy Med & Hlth Care Prod, Madrid, Spain.
[Golden, Michael] Pearl Therapeut, Raleigh, NC USA.
[Hermann, Robert] Clin Res Appliance, Radolfzell am Bodensee, Germany.
[Hochhaus, Guenther] Univ Florida, Gainesville, FL USA.
[Holmes, Susan] GlaxoSmithKline R&D, Res Triangle Pk, NC USA.
[Lafferty, Paul] Med Technol Consulting, Hemel Hempstead, England.
[Lyapustina, Svetlana; Peterson, Ilse] Drinker Biddle & Reath, Washington, DC USA.
[O'Connor, Dennis] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA.
[Parkins, David; Watson, Patricia] GlaxoSmithKline R&D, Ware, Herts, England.
[Reisner, Colin] Pearl Therapeut, Morristown, NJ USA.
[Sandell, Dennis] S5 Consulting, Lund, Sweden.
[Singh, Gur Jai Pal] AXAR Pharmaceut, Corona, CA USA.
[Weda, Marjolein] Natl Inst Publ Hlth & Environm Rivm, Bilthoven, Netherlands.
RP Evans, C (reprint author), Catalent Pharma Solut, POB 13341, Res Triangle Pk, NC 27709 USA.
EM carole.evans@catalent.com
OI Cipolla, David/0000-0002-5773-4721
FU ISAM; IPAC-RS
FX This article represents a report of the workshop's discussions, and may
not fully reflect the positions of individual authors or of any
organization with which the authors are affiliated. The authors are
grateful to all speakers and attendees of the ISAM/IPAC-RS Workshop, as
well as to ISAM and IPAC-RS organizations for the support of this
project. The authors also thank Julianne Berry (Merck), a member of the
ISAM/IPAC-RS Workshop Organizing Committee, and ISAM/IPAC-RS Writing
Committee, for her valuable contributions and helpful discussions.
NR 93
TC 24
Z9 24
U1 1
U2 7
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1941-2711
J9 J AEROSOL MED PULM D
JI J. Aerosol Med. Pulm. Drug Deliv.
PD JUN
PY 2012
VL 25
IS 3
BP 117
EP 139
DI 10.1089/jamp.2011.0968
PG 23
WC Respiratory System
SC Respiratory System
GA 959BI
UT WOS:000305284300001
PM 22413806
ER
PT J
AU Trost, E
Blom, J
Soares, SD
Huang, IH
Al-Dilaimi, A
Schroder, J
Jaenicke, S
Dorella, FA
Rocha, FS
Miyoshi, A
Azevedo, V
Schneider, MP
Silva, A
Camello, TC
Sabbadini, PS
Santos, CS
Santos, LS
Hirata, R
Mattos-Guaraldi, AL
Efstratiou, A
Schmitt, MP
Hung, TT
Tauch, A
AF Trost, Eva
Blom, Jochen
Soares, Siomar de Castro
Huang, I-Hsiu
Al-Dilaimi, Arwa
Schroeder, Jasmin
Jaenicke, Sebastian
Dorella, Fernanda A.
Rocha, Flavia S.
Miyoshi, Anderson
Azevedo, Vasco
Schneider, Maria P.
Silva, Artur
Camello, Thereza C.
Sabbadini, Priscila S.
Santos, Cintia S.
Santos, Louisy S.
Hirata, Raphael, Jr.
Mattos-Guaraldi, Ana L.
Efstratiou, Androulla
Schmitt, Michael P.
Hung Ton-That
Tauch, Andreas
TI Pangenomic Study of Corynebacterium diphtheriae That Provides Insights
into the Genomic Diversity of Pathogenic Isolates from Cases of
Classical Diphtheria, Endocarditis, and Pneumonia
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID MICROBIAL PAN-GENOME; SIDEROPHORE BIOSYNTHESIS;
STREPTOCOCCUS-PNEUMONIAE; BACTERIAL VIRULENCE; EPITHELIAL-CELLS;
SEQUENCE; DTXR; GENE; IRON; STRAINS
AB Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the omega(tox+) phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox(+) corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions.
C1 [Trost, Eva; Blom, Jochen; Soares, Siomar de Castro; Al-Dilaimi, Arwa; Schroeder, Jasmin; Jaenicke, Sebastian; Tauch, Andreas] Univ Bielefeld, Ctr Biotechnol, Inst Genomforsch & Syst Biol, D-33615 Bielefeld, Germany.
[Trost, Eva] Univ Bielefeld, Ctr Biotechnol, CLIB Grad Cluster Ind Biotechnol, D-33615 Bielefeld, Germany.
[Blom, Jochen; Jaenicke, Sebastian] Univ Bielefeld, Ctr Biotechnol, Bioinformat Resource Facil, D-33615 Bielefeld, Germany.
[Soares, Siomar de Castro; Dorella, Fernanda A.; Rocha, Flavia S.; Miyoshi, Anderson; Azevedo, Vasco] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Lab Gent Celular & Mol, Belo Horizonte, MG, Brazil.
[Huang, I-Hsiu; Hung Ton-That] Univ Texas Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX USA.
[Schneider, Maria P.; Silva, Artur] Fed Univ Para, Inst Ciencias Biol, BR-66059 Belem, Para, Brazil.
[Camello, Thereza C.; Sabbadini, Priscila S.; Santos, Cintia S.; Santos, Louisy S.; Hirata, Raphael, Jr.; Mattos-Guaraldi, Ana L.] Univ Estado Rio de Janeiro, Fac Ciencias Med, BR-20550011 Rio De Janeiro, RJ, Brazil.
[Efstratiou, Androulla] Hlth Protect Agcy, Microbiol Serv Div, Resp & Syst Infect Lab, London, England.
[Schmitt, Michael P.] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Tauch, A (reprint author), Univ Bielefeld, Ctr Biotechnol, Inst Genomforsch & Syst Biol, D-33615 Bielefeld, Germany.
EM tauch@cebitec.uni-bielefeld.de
RI Hirata, Raphael/F-9256-2012; vasco, azevedo/F-4315-2011; Silva,
Artur/E-1474-2014; de Castro Soares, Siomar/I-2705-2012;
OI vasco, azevedo/0000-0002-4775-2280; de Castro Soares,
Siomar/0000-0001-7299-3724; Rocha, Flavia/0000-0002-4520-1389; Trost,
Eva/0000-0002-1924-1416; Ton-That, Hung/0000-0003-1611-0469
FU CLIB Graduate Cluster Industrial Biotechnology; CAPES-DAAD; German
Federal Ministry of Education and Research
FX E.T. acknowledges the receipt of a scholarship of the CLIB Graduate
Cluster Industrial Biotechnology. S.D.C.S. was supported by a CAPES-DAAD
scholarship. J.B. and S.J. acknowledge funding by the German Federal
Ministry of Education and Research "GenoMik-Transfer" project.
NR 86
TC 36
Z9 38
U1 1
U2 13
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 JUN
PY 2012
VL 194
IS 12
BP 3199
EP 3215
DI 10.1128/JB.00183-12
PG 17
WC Microbiology
SC Microbiology
GA 954WJ
UT WOS:000304978400018
PM 22505676
ER
PT J
AU Hoffmann, M
Zhao, SH
Luo, Y
Li, C
Folster, JP
Whichard, J
Allard, MW
Brown, EW
McDermott, PF
AF Hoffmann, Maria
Zhao, Shaohua
Luo, Yan
Li, Cong
Folster, Jason P.
Whichard, Jean
Allard, Marc W.
Brown, Eric W.
McDermott, Patrick F.
TI Genome Sequences of Five Salmonella enterica Serovar Heidelberg Isolates
Associated with a 2011 Multistate Outbreak in the United States
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
AB Salmonella enterica serovar Heidelberg has caused numerous outbreaks in humans. Here, we report draft genomes of five isolates of serovar Heidelberg associated with the recent (2011) multistate outbreak linked to ground turkey in the United States. Isolates 2011K-1110 and 2011K-1132 were recovered from humans, while isolates 2011K-1138, 2011K-1224, and 2011K-1225 were recovered from ground turkey. Whole-genome sequence analysis of these isolates provides a tool for studying the short-term evolution of these epidemic clones.
C1 [Hoffmann, Maria; Zhao, Shaohua; McDermott, Patrick F.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
[Luo, Yan] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Nutr, College Pk, MD USA.
[Folster, Jason P.; Whichard, Jean] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
[Li, Cong; Allard, Marc W.; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Nutr, College Pk, MD USA.
RP Hoffmann, M (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
EM maria.hoffman@fda.hhs.gov
FU Center for Veterinary Medicine
FX This project was supported by an appointment of M.H. to the Research
Fellowship Program for the Center for Veterinary Medicine administered
by the Oak Ridge Associated Universities.
NR 5
TC 10
Z9 10
U1 0
U2 3
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 JUN
PY 2012
VL 194
IS 12
BP 3274
EP 3275
DI 10.1128/JB.00419-12
PG 2
WC Microbiology
SC Microbiology
GA 954WJ
UT WOS:000304978400034
PM 22628505
ER
PT J
AU Feng, SX
Chattopadhaya, C
Kijak, P
Chiesa, OA
Tall, EA
AF Feng, Shixia
Chattopadhaya, Chaitali
Kijak, Philip
Chiesa, Oscar A.
Tall, Elizabeth A.
TI A determinative and confirmatory method for ceftiofur metabolite
desfuroylceftiofur cysteine disulfide in bovine kidney by LC-MS/MS
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Ceftiofur; Desfuroylceftiofur cysteine disulfide; Bovine kidney;
LC-MS/MS
ID BETA-LACTAM ANTIBIOTICS; TANDEM MASS-SPECTROMETRY;
LIQUID-CHROMATOGRAPHY; TISSUES; MILK
AB Ceftiofur is a cephalosporin beta-lactam antibiotic widely used for treating certain bacterial infections in beef and dairy cattle. The regulatory HPLC-UV method for ceftiofur residues in animal tissues is time consuming and non-specific. Additionally, because the regulatory method involves chemical reactions to convert the metabolites into a single moiety, it is virtually impossible to incorporate the procedure into a multi-residue method. Ceftiofur residue violations in beef and dairy cattle have been frequently reported and therefore an improved method is needed. Herein we report a rapid and sensitive LC-MS/MS method for the determination and confirmation of ceftiofur metabolite, desfuroylceftiofur cysteine disulfide (DCCD), in bovine kidney tissue. The new method utilizes a simple extraction with phosphate buffer followed by SPE cleanup. A deuterated internal standard was synthesized and used for quantitation. The matrix-based calibration curve was linear from 25 to 2000 ng/g. The average accuracy for control kidney samples from six different sources fortified at 50-1000 ng/g was 97.7-100.2% with CV <= 10.1%. The limit of confirmation was 50 ng/g. Published by Elsevier B.V.
C1 [Feng, Shixia; Chattopadhaya, Chaitali; Kijak, Philip; Chiesa, Oscar A.; Tall, Elizabeth A.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA.
RP Feng, SX (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
EM shixiafeng@fda.hhs.gov
NR 16
TC 6
Z9 6
U1 1
U2 38
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD JUN 1
PY 2012
VL 898
BP 62
EP 68
DI 10.1016/j.jchromb.2012.04.020
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 956NZ
UT WOS:000305097700008
PM 22580013
ER
PT J
AU Gottschalk, U
Brorson, K
Shukla, AA
AF Gottschalk, Uwe
Brorson, Kurt
Shukla, Abhinav A.
TI The need for innovation in biomanufacturing
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID CHROMATOGRAPHY
C1 [Gottschalk, Uwe] Sartorius Stedim Biotech, Gottingen, Germany.
[Brorson, Kurt] CDER FDA, Silver Spring, MD USA.
[Shukla, Abhinav A.] KBI Biopharma, Durham, NC USA.
RP Gottschalk, U (reprint author), Sartorius Stedim Biotech, Gottingen, Germany.
EM Uwe.Gottschalk@sartorius.com
NR 23
TC 26
Z9 26
U1 2
U2 39
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUN
PY 2012
VL 30
IS 6
BP 489
EP 492
DI 10.1038/nbt.2263
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 957JV
UT WOS:000305158600012
PM 22678380
ER
PT J
AU Manak, M
Sina, S
Anekella, B
Hewlett, I
Sanders-Buell, E
Ragupathy, V
Kim, J
Vermeulen, M
Stramer, SL
Sabino, E
Grabarczyk, P
Michael, N
Peel, S
Garrett, P
Tovanabutra, S
Busch, MP
Schito, M
AF Manak, Mark
Sina, Silvana
Anekella, Bharathi
Hewlett, Indira
Sanders-Buell, Eric
Ragupathy, Viswanath
Kim, Jerome
Vermeulen, Marion
Stramer, Susan L.
Sabino, Ester
Grabarczyk, Piotr
Michael, Nelson
Peel, Sheila
Garrett, Patricia
Tovanabutra, Sodsai
Busch, Michael P.
Schito, Marco
TI Pilot Studies for Development of an HIV Subtype Panel for Surveillance
of Global Diversity
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; VIRAL-LOAD
ASSAYS; DISEASE PROGRESSION; GENETIC-CHARACTERIZATION; TYPE-1 INFECTION;
TRANSMISSION; RESISTANCE; PROTEASE; DYNAMICS
AB The continued global spread and evolution of HIV diversity pose significant challenges to diagnostics and vaccine strategies. NIAID partnered with the FDA, WRAIR, academia, and industry to form a Viral Panel Working Group to design and prepare a panel of well-characterized current and diverse HIV isolates. Plasma samples that had screened positive for HIV infection and had evidence of recently acquired infection were donated by blood centers in North and South America, Europe, and Africa. A total of 80 plasma samples were tested by quantitative nucleic acid tests, p24 antigen, EIA, and Western blot to assign a Fiebig stage indicative of approximate time from initial infection. Evaluation of viral load using FDA-cleared assays showed excellent concordance when subtype B virus was tested, but lower correlations for subtype C. Plasma samples were cocultivated with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from normal donors to generate 30 viral isolates (50-80% success rate for samples with viral load >10,000 copies/ml), which were then expanded to 10(7)-10(9) virus copies per ml. Analysis of env sequences showed that sequences derived from cultured PBMCs were not distinguishable from those obtained from the original plasma. The pilot collection includes 30 isolates representing subtypes B, C, B/F, CRF04_cpx, and CRF02_AG. These studies will serve as a basis for the development of a comprehensive panel of highly characterized viral isolates that reflects the current dynamic and complex HIV epidemic, and will be made available through the External Quality Assurance Program Oversight Laboratory (EQAPOL).
C1 [Manak, Mark] Henry M Jackson Fdn Adv Mil Med, Dept Diagnost & Monitoring, US Mil HIV Res Program, Rockville, MD 20850 USA.
[Manak, Mark; Anekella, Bharathi; Garrett, Patricia] SeraCare Life Sci Inc, Gaithersburg, MD USA.
[Hewlett, Indira; Ragupathy, Viswanath] US FDA, CBER, Bethesda, MD 20014 USA.
[Kim, Jerome; Michael, Nelson; Peel, Sheila] Walter Reed Army Inst Res, US Mil HIV Res Program, Rockville, MD USA.
[Vermeulen, Marion] S African Natl Blood Serv, Gauteng, South Africa.
[Stramer, Susan L.] Amer Red Cross, Sci Support Off, Gaithersburg, MD USA.
[Sabino, Ester] Univ Sao Paulo, Dept Infect Dis, Sao Paulo, Brazil.
[Grabarczyk, Piotr] Inst Haematol & Blood Transfus Med, Warsaw, Poland.
[Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Schito, Marco] Henry M Jackson Fdn, Bethesda, MD USA.
[Schito, Marco] NIH, Div Aids, Bethesda, MD 20892 USA.
RP Manak, M (reprint author), Henry M Jackson Fdn Adv Mil Med, Dept Diagnost & Monitoring, US Mil HIV Res Program, 13 Taft Court, Rockville, MD 20850 USA.
EM mmanak@hivresearch.org
RI Imunologia, Inct/I-2124-2013; sourisseau, marion/M-7542-2014; Sabino,
Ester/F-7750-2010;
OI Sabino, Ester/0000-0003-2623-5126; Manak, Mark /0000-0002-9217-9129
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200800014C]; Henry M. Jackson Foundation for the Advancement of
Military Medicine, Inc. [W81XWH-07-2-0067]; U.S. Department of Defense
(DoD) [W81XWH-07-2-0067]
FX This project has been funded in part with Federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
Contract No. HHSN272200800014C. This work was also supported by a
cooperative agreement W81XWH-07-2-0067 between the Henry M. Jackson
Foundation for the Advancement of Military Medicine, Inc. and the U.S.
Department of Defense (DoD).
NR 40
TC 12
Z9 13
U1 1
U2 6
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 JUN
PY 2012
VL 28
IS 6
BP 594
EP 606
DI 10.1089/aid.2011.0271
PG 13
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 952GQ
UT WOS:000304780100011
PM 22149143
ER
PT J
AU Toby, TK
Sommers, CD
Keire, DA
AF Toby, Timothy K.
Sommers, Cynthia D.
Keire, David A.
TI Detection of native chondroitin sulfate impurities in heparin sodium
with a colorimetric micro-plate based assay
SO ANALYTICAL METHODS
LA English
DT Article
ID MOLECULAR-WEIGHT; CONTAMINANTS
AB We have recently described a 96-well plate format assay for visually detecting oversulfated chondroitin sulfate A (OSCS) in heparin that uses a water soluble cationic polythiophene polymer (3-(2-(N-(N'-methylimidazole)) ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion. Because dermatan sulfate (DS, a.k.a. chondroitin sulfate B (CSB)) and, to a lesser degree, chondroitin sulfate A (CSA) are the most common native impurities of heparin active pharmaceutical ingredients (APIs) we adapted the previously established micro-plate assay for the visual detection of DS and CSA in heparin sodium. We describe a naked-eye detection test of these common heparin impurities with sensitivity appropriate for the United States Pharmacopeia (USP) 1% percent galactosamine in total hexosamine specification. For example, the test detects DS >= 1.0% w/w visually and 0.5% using a plate reader, or CSA >= 1.0 to 2.0% w/w visually and at >= 1.0% with a plate reader. In contrast to the test developed for oversulfated glycosaminoglycans such as OSCS, the LPTP-chondroitinase test developed here utilizes chondroitinase ABC instead of heparinases and requires a centrifugal filtration step to remove un-digested heparin. The test takes advantage of the sensitivity of the LPTP chemosensor to low molecular weight glycosaminoglycan (GAG) fragments formed by digesting DS or CSA. Importantly, the LPTP-chondroitinase method detects DS and CSA in heparin sodium in a format potentially amenable to high throughput screening.
C1 [Toby, Timothy K.; Sommers, Cynthia D.; Keire, David A.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA.
RP Keire, DA (reprint author), US FDA, CDER, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA.
EM David.Keire@fda.hhs.gov
NR 18
TC 3
Z9 3
U1 3
U2 15
PU ROYAL SOC CHEMISTRY
PI CAMBRIDGE
PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS,
ENGLAND
SN 1759-9660
J9 ANAL METHODS-UK
JI Anal. Methods
PD JUN
PY 2012
VL 4
IS 6
BP 1488
EP 1491
DI 10.1039/c2ay25198a
PG 4
WC Chemistry, Analytical; Food Science & Technology; Spectroscopy
SC Chemistry; Food Science & Technology; Spectroscopy
GA 952CX
UT WOS:000304768600004
ER
PT J
AU Wang, QZ
Le, D
Ramella-Roman, J
Pfefer, J
AF Wang, Quanzeng
Le, Du
Ramella-Roman, Jessica
Pfefer, Joshua
TI Broadband ultraviolet-visible optical property measurement in layered
turbid media
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID DIFFUSE-REFLECTANCE SPECTRA; MODEL-BASED ANALYSIS; EPITHELIAL TISSUE;
FLUORESCENCE-SPECTRA; LIGHT REFLECTANCE; SPECTROSCOPY; DIAGNOSIS;
LESIONS; VALIDATION; CANCER
AB The ability to accurately measure layered biological tissue optical properties (OPs) may improve understanding of spectroscopic device performance and facilitate early cancer detection. Towards these goals, we have performed theoretical and experimental evaluations of an approach for broadband measurement of absorption and reduced scattering coefficients at ultraviolet-visible wavelengths. Our technique is based on neural network (NN) inverse models trained with diffuse reflectance data from condensed Monte Carlo simulations. Experimental measurements were performed from 350 to 600 nm with a fiber-optic-based reflectance spectroscopy system. Two-layer phantoms incorporating OPs relevant to normal and dysplastic mucosal tissue and superficial layer thicknesses of 0.22 and 0.44 mm were used to assess prediction accuracy. Results showed mean OP estimation errors of 19% from the theoretical analysis and 27% from experiments. Two-step NN modeling and nonlinear spectral fitting approaches helped improve prediction accuracy. While limitations and challenges remain, the results of this study indicate that our technique can provide moderately accurate estimates of OPs in layered turbid media. (C) 2012 Optical Society of America
C1 [Wang, Quanzeng; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Le, Du; Ramella-Roman, Jessica] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA.
RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM quanzeng.wang@fda.hhs.gov
RI Pfefer, Josh/I-9055-2012; Le, Vinh Nguyen Du/E-3859-2015
OI Le, Vinh Nguyen Du/0000-0002-4054-4200
NR 31
TC 12
Z9 13
U1 0
U2 7
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD JUN 1
PY 2012
VL 3
IS 6
BP 1226
EP 1240
PG 15
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 954RY
UT WOS:000304965700008
PM 22741070
ER
PT J
AU Kang, H
Clarke, ML
Lacerda, SHD
Karim, A
Pease, LF
Hwang, J
AF Kang, HyeongGon
Clarke, Matthew L.
Lacerda, Silvia H. De Paoli
Karim, Alamgir
Pease, Leonard F., III
Hwang, Jeeseong
TI Multimodal optical studies of single and clustered colloidal quantum
dots for the long-term optical property evaluation of quantum dot-based
molecular imaging phantoms
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID DYNAMIC FLUORESCENCE PROPERTIES; DIFFERENTIAL MOBILITY ANALYSIS;
SEMICONDUCTOR NANOCRYSTALS; NANOPARTICLES; PARTICLES; CELLS; CDSE; TIME
AB Understanding the optical properties of clustered quantum dots (QDs) is essential to the design of QD-based optical phantoms for molecular imaging. Single and clustered core/shell colloidal QDs of dimers, trimers, and tetramers are self-assembled, separated, and preferentially collected using electrospray differential mobility analysis (ES-DMA) with electrostatic deposition. Multimodal optical characterization and analysis of their dynamical photoluminescence (PL) properties enables the long-term evaluation of the physicochemical and optical properties of QDs in a single or a clustered state. A multimodal time-correlated spectroscopic confocal microscope capable of simultaneously measuring the time evolution of PL intensity fluctuation, PL lifetime, and emission spectra reveals the long-term dynamic optical properties of interacting QDs in individual dimeric clusters of QDs. This new method will benefit research into the quantitative interpretation of fluorescence intensity and lifetime results in QD-based molecular imaging techniques. The process of photooxidation leads to coupling of the QDs in a dimer, leading to unique optical properties when compared to an isolated QD. These results guide the design and evaluation of QD-based phantom materials for the validation of the PL measurements for quantitative molecular imaging of biological samples labeled with QD probes. (C) 2012 Optical Society of America
C1 [Kang, HyeongGon; Clarke, Matthew L.; Hwang, Jeeseong] NIST, Radiat & Biomol Phys Div, Gaithersburg, MD 20899 USA.
[Lacerda, Silvia H. De Paoli] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Karim, Alamgir] NIST, Div Polymers, Gaithersburg, MD 20899 USA.
[Pease, Leonard F., III] Univ Utah, Dept Chem Engn Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA.
[Pease, Leonard F., III] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA.
RP Kang, H (reprint author), NIST, Radiat & Biomol Phys Div, Gaithersburg, MD 20899 USA.
EM jch@nist.gov
FU NIST; Chemical Engineering Department
FX Authors thank Drs. Garnett Bryant, Jack Douglas, Rajasekhar Anumolu for
helpful discussions. J. H. was supported by the NIST Innovative
Measurement Science program on optical medical imaging and L. P. was
supported by startup funds from the Chemical Engineering Department.
Certain commercial equipment, instruments, or materials are identified
in this manuscript are to foster understanding. Such identification does
not imply recommendation or endorsement by the National Institute of
Standards and Technology, nor does it imply that the materials or
equipment identified are necessarily the best available for the purpose.
The findings and conclusions in this article have not been formally
disseminated by the Food and Drug Administration and should not be
construed to represent any Agency determination or policy.
NR 41
TC 12
Z9 12
U1 1
U2 22
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD JUN 1
PY 2012
VL 3
IS 6
BP 1312
EP 1325
PG 14
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 954RY
UT WOS:000304965700016
PM 22741078
ER
PT J
AU McDaniel, LP
Elander, ER
Guo, XQ
Chen, T
Arlt, VM
Mei, N
AF McDaniel, L. Patrice
Elander, Elizabeth R.
Guo, Xiaoqing
Chen, Tao
Arlt, Volker M.
Mei, Nan
TI Mutagenicity and DNA adduct formation by aristolochic acid in the spleen
of Big Blue (R) rats
SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
LA English
DT Article
DE aristolochic acid; DNA adduct; mutagenicity; Big Blue (R) rat; rat
spleen
ID CHINESE HERBS NEPHROPATHY; BALKAN ENDEMIC NEPHROPATHY; N-NITROSOUREA
ENU; UROTHELIAL CARCINOMA; MUTATIONAL SPECTRA; HUMAN-LYMPHOCYTES; P53
MUTATIONS; RAS GENE; LIVER; EXPOSURE
AB Aristolochic acid (AA) is a potent human nephrotoxin and carcinogen. We previously reported that AA treatment resulted in DNA damage and mutation in the kidney and liver of rats. In this study, we have determined the DNA adducts and mutations induced by AA in rat spleen. Big Blue (R) transgenic rats were gavaged with 0, 0.1, 1.0, and 10.0 mg AA/kg body weight five-times/week for 3 months. Three DNA adducts, [7-(deoxyadenosin-N6-yl)-aristolactam I, 7-(deoxyadenosin-N6-yl)-aristolactam II and 7-(deoxyguanosin-N2-yl)-aristolactam I], were identified by 32P-postlabeling. Over the dose range studied, there were strong linear dose-responses for AA-DNA adduct formation in the treated rat spleens, ranging from 4.6 to 217.6 adducts/108 nucleotides. Spleen cII mutant frequencies also increased in a dose-dependent manner, ranging from 32.7 to 286.2 x 10(-6) in the treated animals. Mutants isolated from the different treatment groups were sequenced; analysis of the resulting spectra indicated that there was a significant difference between the pattern of mutation in the 10 mg/kg AA-treated and the vehicle control rats. A:T ? T:A transversion was the major type of mutation in AA-treated rats, whereas G:C ? A:T transition was the main type of mutation inthe vehicle controls. These results indicate that AA is genotoxic in the spleen of rats exposed under conditions that result in DNA adduct formation and mutation induction in kidney and liver. Environ. Mol. Mutagen., 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [McDaniel, L. Patrice; Elander, Elizabeth R.; Guo, Xiaoqing; Chen, Tao; Mei, Nan] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR USA.
[Elander, Elizabeth R.] Harding Univ, Phys Assistant Program, Searcy, AR USA.
[Arlt, Volker M.] Kings Coll London, Sch Biomed Sci, Analyt & Environm Sci Div, London SE1 9NH, England.
RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR USA.
EM nan.mei@fda.hhs.gov
FU Association for International Cancer Research (AICR); Cancer Research UK
FX Grant sponsors: Association for International Cancer Research (AICR),
Cancer Research UK.
NR 50
TC 9
Z9 10
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0893-6692
J9 ENVIRON MOL MUTAGEN
JI Environ. Mol. Mutagen.
PD JUN
PY 2012
VL 53
IS 5
BP 358
EP 368
DI 10.1002/em.21696
PG 11
WC Environmental Sciences; Genetics & Heredity; Toxicology
SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology
GA 953WT
UT WOS:000304905000005
PM 22508110
ER
PT J
AU Manangeeswaran, M
Jacques, J
Tami, C
Konduru, K
Amharref, N
Perrella, O
Casasnovas, JM
Umetsu, DT
Dekruyff, RH
Freeman, GJ
Perrella, A
Kaplan, GG
AF Manangeeswaran, Mohanraj
Jacques, Jerome
Tami, Cecilia
Konduru, Krishnamurthy
Amharref, Nadia
Perrella, Oreste
Casasnovas, Jose M.
Umetsu, Dale T.
Dekruyff, Rosemarie H.
Freeman, Gordon J.
Perrella, Alessandro
Kaplan, Gerardo G.
TI Binding of Hepatitis A Virus to Its Cellular Receptor 1 Inhibits
T-Regulatory Cell Functions in Humans
SO GASTROENTEROLOGY
LA English
DT Article
DE Hepatitis A Virus Cellular Receptor 1; Viral Clearance; TGF-beta; Immune
Regulation
ID AUTOIMMUNE-DISEASES; IDENTIFICATION; ACTIVATION; INFECTION;
AUTOANTIBODIES; INDIVIDUALS; EXPRESSION; FAMILY; DEATH
AB BACKGROUND & AIMS: CD4+ T-regulatory (Treg) cells suppress immune responses and control self-tolerance and immunity to pathogens, cancer, and alloantigens. Most pathogens activate Treg cells to minimize immune-mediated tissue damage and prevent clearance, which promotes chronic infections. However, hepatitis A virus (HAV) temporarily inhibits Treg-cell functions. We investigated whether the interaction of HAV with its cellular receptor 1 (HAVCR1), a T-cell co-stimulatory molecule, inhibits the function of Treg cells to control HAV infection. METHODS: We studied the effects of HAV interaction with HAVCR1 on human T cells using binding, signal transduction, apoptosis, activation, suppression, cytokine production, and confocal microscopy analyses. Cytokines were analyzed in sera from 14 patients with HAV infection using bead arrays. RESULTS: Human Treg cells constitutively express HAVCR1. Binding of HAV to HAVCR1 blocked phosphorylation of Akt, prevented activation of the T-cell receptor, and inhibited function of Treg cells. At the peak viremia, patients with acute HAV infection had no Treg-cell suppression function, produced low levels of transforming growth factor-beta, which limited leukocyte recruitment and survival, and produced high levels of interleukin-22, which prevented liver damage. CONCLUSIONS: Interaction between HAV and its receptor HAVCR1 inhibits Treg-cell function, resulting in an immune imbalance that allows viral expansion with limited hepatocellular damage during early stages of infection-a characteristic of HAV pathogenesis. The mechanism by which HAV is cleared in the absence of Treg-cell function could be used as a model to develop anticancer therapies, modulate autoimmune and allergic responses, and prevent transplant rejection.
C1 [Manangeeswaran, Mohanraj; Jacques, Jerome; Tami, Cecilia; Konduru, Krishnamurthy; Amharref, Nadia; Kaplan, Gerardo G.] Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA.
[Perrella, Oreste; Perrella, Alessandro] Hosp D Cotugno, Div Infect Dis & Immunol 7, Naples, Italy.
[Casasnovas, Jose M.] CSIC, Ctr Nacl Biotecnol, Madrid, Spain.
[Umetsu, Dale T.; Dekruyff, Rosemarie H.] Harvard Univ, Childrens Hosp, Boston, MA 02115 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Kaplan, GG (reprint author), Ctr Biol Evaluat & Res Food & Drug Adm, 8800 Rockville Pike,Bldg 29 NIH,HFM 325, Bethesda, MD 20892 USA.
EM gk@helix.nih.gov
RI Casasnovas, Jose/L-6299-2014
OI Casasnovas, Jose/0000-0002-2873-6410
FU Food and Drug Administration; National Institutes of Health
[1P01AI54456-01 NIAID, 2P01AI054456-06A1 NIAID, R01 AI089955]
FX Jerome Jacques and Nadia Amharref are Research Fellows of the Oak Ridge
Institute for Science and Education. This work was supported by Food and
Drug Administration Intramural Funding, and National Institutes of
Health grants 1P01AI54456-01 NIAID and 2P01AI054456-06A1 NIAID (to
D.T.U, R.H.D., J.M.C., G.J.F., and G.G.K.) and R01 AI089955 (to G.J.F.
and R.H.D.).
NR 32
TC 12
Z9 12
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD JUN
PY 2012
VL 142
IS 7
BP 1516
EP +
DI 10.1053/j.gastro.2012.02.039
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 952GF
UT WOS:000304778700030
PM 22430395
ER
PT J
AU Ekins, J
Peters, SM
Jones, YL
Swaim, H
Ha, T
La Neve, F
Civera, T
Blackstone, G
Vickery, MCL
Marion, B
Myers, MJ
Yancy, HF
AF Ekins, Jason
Peters, Sharla M.
Jones, Yolanda L.
Swaim, Heidi
Ha, Tai
La Neve, Fabio
Civera, Tiziana
Blackstone, George
Vickery, Michael C. L.
Marion, Bill
Myers, Michael J.
Yancy, Haile F.
TI Development of a Multiplex Real-Time PCR Assay for the Detection of
Ruminant DNA
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; CREUTZFELDT-JAKOB-DISEASE; MEAT;
IDENTIFICATION; FEEDSTUFFS; VALIDATION; VARIANT
AB The U.S. Food and Drug Administration (FDA) has previously validated a real-time PCR-based assay that is currently being used by the FDA and several state laboratories as the official screening method. Due to several shortcomings to the assay, a multiplex real-time PCR assay (MRTA) to detect three ruminant species (bovine, caprine, and ovine) was developed using a lyophilized bead design. The assay contained two primer or probe sets: a "ruminant" set to detect bovine-, caprine-, and ovine-derived materials and a second set to serve as an internal PCR control, formatted using a lyophilized bead design. Performance of the assay was evaluated against stringent acceptance criteria developed by the FDA's Center for Veterinary Medicine's Office of Research. The MRTA for the detection of ruminant DNA passed the stringent acceptance criteria for specificity, sensitivity, and selectivity. The assay met sensitivity and reproducibility requirements by detecting 30 of 30 complete feed samples fortified with meals at 0.1% (wt/wt) rendered material from each of the three ruminant species. The MRTA demonstrated 100% selectivity (0.0% false positives) for negative controls throughout the assessment period. The assay showed ruggedness in both sample selection and reagent preparation. Second and third analyst trials confirmed the quality of the written standard operating procedure with consistency of results. An external laboratory participating in a peer-verification trial demonstrated 100% specificity in identifying bovine meat and bone meal, while exhibiting a 0.03% rate of false positives. The assay demonstrated equal levels of sensitivity and reproducibility compared with the FDA's current validated real-time PCR assay. The assay detected three prohibited species in less than 1.5 h of total assay time, a significant improvement over the current real-time assay. These results demonstrated this assay's suitability for routine regulatory use both as a primary screening tool and as a confirmatory test.
C1 [Ekins, Jason; Peters, Sharla M.; Jones, Yolanda L.; Swaim, Heidi; Myers, Michael J.; Yancy, Haile F.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA.
[Ha, Tai] Nebraska Dept Agr, Lincoln, NE 68508 USA.
[La Neve, Fabio; Civera, Tiziana] Univ Turin, Fac Vet Med, Dept Anim Pathol, I-10095 Turin, Italy.
[Blackstone, George; Vickery, Michael C. L.; Marion, Bill] BioGX Inc, Birmingham, AL 35203 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
NR 11
TC 2
Z9 2
U1 1
U2 16
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
J9 J FOOD PROTECT
JI J. Food Prot.
PD JUN
PY 2012
VL 75
IS 6
BP 1107
EP 1112
DI 10.4315/0362-028X.JFP-11-415
PG 6
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 955RV
UT WOS:000305039500014
PM 22691479
ER
PT J
AU Keller, SE
Grasso, EM
Halik, LA
Fleischman, GJ
Chirtel, SJ
Grove, SF
AF Keller, Susanne E.
Grasso, Elizabeth M.
Halik, Lindsay A.
Fleischman, Gregory J.
Chirtel, Stuart J.
Grove, Stephen F.
TI Effect of Growth on the Thermal Resistance and Survival of Salmonella
Tennessee and Oranienburg in Peanut Butter, Measured by a New Thin-Layer
Thermal Death Time Device
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID ESCHERICHIA-COLI; HEAT-RESISTANCE; WATER ACTIVITY; ENTERITIDIS;
INACTIVATION; TEMPERATURE; TOLERANCE; SEROVARS; ALMONDS; FOODS
AB In published data the thermal destruction of Salmonella species in peanut butter deviates from pseudo first-order kinetics. The reasons for such deviation are unknown. This study examined both the method used to measure the thermal destruction rate and the method of growth of the microorganisms to explain variations in destruction kinetics. Growth on a solid matrix results in a different physiological state that may provide greater resistance to adverse environments. In this study, Salmonella Tennessee and Oranienburg were grown for 24 h at 37 degrees C under aerobic conditions in broth and agar media to represent planktonic and sessile cell growth, respectively. Peanut butter was held at 25 degrees C and tested for Salmonella levels immediately after inoculation and at various time intervals up to 2 weeks. Thermal resistance was measured at 85 degrees C by use of a newly developed thin-layer metal sample holder. Although thermal heat transfer through the metal device resulted in longer tau values than those obtained with plastic bags (32.5 +/- 0.9 versus 12.4 +/- 1.9 s), the bags have a relative variability of about 15% compared with about 3% in the plates, allowing improved uniformity of sample treatment. The two serovars tested in the thin-layer device showed similar overall thermal resistance levels in peanut butter regardless of growth in sessile or planktonic states. However, thermal destruction curves from sessile cultures exhibited greater linearity than those obtained from planktonic cells (P = 0.0198 and 0.0047 for Salmonella Oranienburg and Salmonella Tennessee, respectively). In addition, both Salmonella serovars showed significantly higher survival in peanut butter at 25 degrees C when originally grown on solid media (P = 0.001) with a <1-log loss over 2 weeks as opposed to a 1- to 2-log loss when grown in liquid culture. Consequently, the use of cells grown on solid media may more accurately assess the survival of Salmonella at different temperatures in a low-water-activity environment such as peanut butter.
C1 [Keller, Susanne E.; Grasso, Elizabeth M.; Halik, Lindsay A.; Fleischman, Gregory J.] US FDA, Bedford Pk, IL 60501 USA.
[Chirtel, Stuart J.] US FDA, College Pk, MD 20740 USA.
[Grove, Stephen F.] Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA.
RP Keller, SE (reprint author), US FDA, 6502 S Archer Rd, Bedford Pk, IL 60501 USA.
EM susanne.keller@fda.hhs.gov
FU Almond Board of California
FX The research conducted in this study was funded, in part, by the Almond
Board of California.
NR 29
TC 13
Z9 13
U1 2
U2 34
PU INT ASSOC FOOD PROTECTION
PI DES MOINES
PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA
SN 0362-028X
J9 J FOOD PROTECT
JI J. Food Prot.
PD JUN
PY 2012
VL 75
IS 6
BP 1125
EP 1130
DI 10.4315/0362-028X.JFP-11-477
PG 6
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 955RV
UT WOS:000305039500017
PM 22691482
ER
PT J
AU Chen, Y
Noe, KE
Thompson, S
Elems, CA
Brown, EW
Lampel, KA
Hammack, TS
AF Chen, Yi
Noe, Kathy E.
Thompson, Sandra
Elems, Carol A.
Brown, Eric W.
Lampel, Keith A.
Hammack, Thomas S.
TI Evaluation of a Revised U.S. Food and Drug Administration Method for the
Detection of Cronobacter in Powdered Infant Formula: A Collaborative
Study
SO JOURNAL OF FOOD PROTECTION
LA English
DT Article
ID ENTEROBACTER-SAKAZAKII CRONOBACTER; IMPROVED PROTOCOL; PCR ASSAY
AB A revised U.S. Food and Drug Administration (FDA) method for the isolation and detection of Cronobacter from powdered infant formula was recently developed, which combines real-time PCR, chromogenic agars, and RAPID ID 32E biochemical tests. This method provides an expedient analysis within 24 to 48 h. A collaborative validation study involving four different laboratories was conducted to compare the revised FDA method with the reference FDA method using casein- and soy-based powdered infant formula inoculated with different Cronobacter strains. Valid results from 216 test portions and controls from collaborating laboratories were obtained and showed that the revised FDA method performed significantly better than the reference FDA method. Newly revised PCR protocols and VITEK 2 were also evaluated to be integrated into the complete detection procedure.
C1 [Chen, Yi; Brown, Eric W.; Lampel, Keith A.; Hammack, Thomas S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Noe, Kathy E.] US FDA, SE Reg Lab, Atlanta, GA 30309 USA.
[Thompson, Sandra] US FDA, NE Reg Lab, Jamaica, NY 11433 USA.
[Elems, Carol A.] US FDA, San Francisco Dist Lab, Alameda, CA 94802 USA.
RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM yi.chen@fda.hhs.gov
NR 8
TC 3
Z9 4
U1 0
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 JUN
PY 2012
VL 75
IS 6
BP 1144
EP 1147
DI 10.4315/0362-028X.JFP-11-388
PG 4
WC Biotechnology & Applied Microbiology; Food Science & Technology
SC Biotechnology & Applied Microbiology; Food Science & Technology
GA 955RV
UT WOS:000305039500021
PM 22691486
ER
PT J
AU Brajovic, S
Piazza-Hepp, T
Swartz, L
Dal Pan, G
AF Brajovic, Sonja
Piazza-Hepp, Toni
Swartz, Lynette
Dal Pan, Gerald
TI Quality assessment of spontaneous triggered adverse event reports
received by the Food and Drug Administration
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Review
DE triggered adverse event reporting; postmarketing surveillance;
electronic health records; data quality
ID SECONDARY USE
AB Purpose The Food and Drug Administration (FDA) conducted a quality assessment of the Adverse Drug Events Spontaneous Triggered Event Reporting (ASTER) pilot study, which represented the FDA's first experience with the receipt of electronic health record (EHR)-triggered adverse event reports. The EHR-triggered adverse event reports from ASTER were evaluated for their utility in conducting FDA's pharmacovigilance work. FDA is sharing these findings to assist others who are pursuing the use of patient EHR data for electronic adverse event identification and reporting.
Methods ASTER pilot study reports were identified from the FDA Adverse Event Reporting System database, then reviewed and assessed.
Results Demographic and other objective data that can be easily derived from EHRs were both present in the submitted reports and relevant to the reported adverse drug event (ADE), but other data, such as an informative description of the ADE, dates that support a temporal relationship between the product and the event, and relevant laboratory data, were often either conflicting or lacking. Most of the ADEs captured in the ASTER pilot and reported to FDA are known events (i.e. included in product labeling) for the suspect drugs.
Conclusion Triggered adverse event reporting from patient EHRs is a potentially valuable source of postmarketing safety information, especially for known adverse events. Attention to quality is needed to ensure that the data generated from EHR-triggered ADE reporting systems are relevant to the reported adverse events so that the FDA and others engaged in pharmacovigilance can fully utilize these reports. Published 2012. This article is a US Government work and is in the public domain in the USA.
C1 [Brajovic, Sonja; Piazza-Hepp, Toni; Swartz, Lynette; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
RP Brajovic, S (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Mailstop 4447, Silver Spring, MD 20903 USA.
EM sonja.brajovic@fda.hhs.gov
NR 7
TC 14
Z9 14
U1 1
U2 4
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JUN
PY 2012
VL 21
IS 6
BP 565
EP 570
DI 10.1002/pds.3223
PG 6
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 956CT
UT WOS:000305068100001
PM 22359404
ER
PT J
AU Eworuke, E
Hampp, C
Saidi, A
Winterstein, AG
AF Eworuke, Efe
Hampp, Christian
Saidi, Arwa
Winterstein, Almut G.
TI An algorithm to identify preterm infants in administrative claims data
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE prematurity; sensitivity; specificity; Medicaid; gestational age; birth
certificates; claims data; pharmacoepidemiology
ID BIRTH; EPIDEMIOLOGY; OUTCOMES
AB Purpose To develop and validate an algorithm to identify preterm infants in the absence of birth certificates within Medicaid data.
Methods Medicaid fee-for-service claims data from Florida (FL) and Texas (TX) were linked to vital statistics data for infants who were continuously eligible during the first 3 months following birth or died within that period. Prematurity was defined as less than 34 weeks gestational age. Using FL as exploratory dataset and vital statistics birth data as gold standard, we developed a logistic regression model from diagnostic and procedure codes commonly associated with preterm care, creating a prematurity score for each infant. A score cutoff was selected that maximized sensitivity while maintaining a positive predictive value (PPV)>= 90%. Confirmatory analyses were conducted in the TX datasets.
Results The prevalence of prematurity was 5.2% (95% CI: 5.1-5.2) and 4.5% (95% CI: 4.4-4.6) in FL and TX, respectively. Using only gestational age International Classification of Disease version 9, Clinical Modification (ICD-9-CM) codes (765.20-765.27) associated with inpatient claims achieved sensitivity of 25.7% (FL) and 12.5% (TX), specificity of 99.9% (FL) and (TX), and PPV of 91.7% (FL) and 84.8% (TX). The model had excellent discriminatory validity with a c-statistic of 0.928 (95% CI: 0.925-0.931). The selected cutoff point achieved sensitivity of 52.6%, specificity of 99.8%, and PPV of 91.7% in FL. In TX, sensitivity was 46.8%, specificity was 99.9%, and PPV was 82.2%.
Conclusion Identification of prematurity based on gestational age ICD-9-CM codes is not sensitive. The prematurity score has superior construct validity and allows more comprehensive identification of preterm infants in the absence of birth certificates. Copyright (C) 2012 John Wiley & Sons, Ltd.
C1 [Eworuke, Efe; Winterstein, Almut G.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32610 USA.
[Hampp, Christian] US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Rockville, MD 20857 USA.
[Winterstein, Almut G.] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL 32610 USA.
[Winterstein, Almut G.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol, Gainesville, FL 32610 USA.
[Saidi, Arwa] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL 32610 USA.
RP Eworuke, E (reprint author), Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, POB 100496, Gainesville, FL 32610 USA.
EM efe1odia@ufl.edu
RI winterstein, Almut/A-3017-2014;
OI winterstein, Almut/0000-0002-6518-5961; Hampp,
Christian/0000-0002-1094-6364
FU Florida Agency of Healthcare Administration, AHCA
FX This study was funded in part by a grant from the Florida Agency of
Healthcare Administration, AHCA.
NR 17
TC 6
Z9 6
U1 0
U2 1
PU WILEY PERIODICALS, INC
PI SAN FRANCISCO
PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD JUN
PY 2012
VL 21
IS 6
BP 640
EP 650
DI 10.1002/pds.3264
PG 11
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 956CT
UT WOS:000305068100012
PM 22504840
ER
PT J
AU Van Camp, D
Hooker, NH
Lin, CTJ
AF Van Camp, Debra
Hooker, Neal H.
Lin, Chung-Tung Jordan
TI Changes in fat contents of US snack foods in response to mandatory trans
fat labelling
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Nutrition labels; Fat; Product reformulation
ID PARTIAL HYDROGENATION; HEART-DISEASE; ACID CONTENT; OILS;
REFORMULATIONS; KNOWLEDGE; CONSUMERS; PROGRESS; RISK; DIET
AB Objective: Impact of mandatory trans fat labelling on US snack food introductions is examined.
Design: Using label information, lipid ingredients and fat profiles are compared pre- and post-labelling.
Setting: Key products in the US snack food industry contribute significant amounts of artificial trans fat. Industry efforts to reformulate products to lower trans fat may alter the overall fat profile, in particular saturates.
Subjects: Composition data for more than 5000 chip and cookie products introduced for sale between 2001 (pre-labelling) and 2009 (post-labelling) were analysed.
Results: One-way ANOVA was used to test for significant changes in saturated fat content per serving and the ratio of saturated to total fat. The shares of chip and cookie introductions containing partially hydrogenated vegetable oil declined by 45 and 42 percentage points, respectively. In cookies, there was an increase of 0.49 (98% CI 0.01, 0.98) g in the average saturated fat content per 30g serving and an increase of 9 (98% CI 3, 15) % in the average ratio of saturated to total fat. No statistically significant changes in fat content were observed in chips.
Conclusions: This research suggests that, holding other factors constant, the policy has resulted in a decreased use of partially hydrogenated vegetable oil in chip products without a corresponding increase in saturated fat content, but led to significantly higher levels of saturated fat and ratio of saturated fat to total fat in cookie products.
C1 [Hooker, Neal H.] St Josephs Univ, Dept Food Mkt, Philadelphia, PA 19131 USA.
[Van Camp, Debra] Nielsen, Bensalem, PA USA.
[Lin, Chung-Tung Jordan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Hooker, NH (reprint author), St Josephs Univ, Dept Food Mkt, 5600 City Ave, Philadelphia, PA 19131 USA.
EM nhooker@sju.edu
OI hooker, neal/0000-0002-9398-3493
FU Center for Food Safety and Applied Nutrition - FDA [HHSF223200811309P]
FX The authors gratefully acknowledge funding from Center for Food Safety
and Applied Nutrition - FDA under a Cooperative Agreement
(HHSF223200811309P). The authors have no conflicts. D.V.C. conducted the
empirical analysis; all authors jointly wrote and edited the manuscript.
NR 26
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U1 2
U2 20
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD JUN
PY 2012
VL 15
IS 6
BP 1130
EP 1137
DI 10.1017/S1368980012000079
PG 8
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA 951TF
UT WOS:000304742200024
PM 22314147
ER
PT J
AU Ding, W
Petibone, DM
Latendresse, JR
Pearce, MG
Muskhelishvili, L
White, GA
Chang, CW
Mittelstaedt, RA
Shaddock, JG
McDaniel, LP
Doerge, DR
Morris, SM
Bishop, ME
Manjanatha, MG
Aidoo, A
Heflich, RH
AF Ding, Wei
Petibone, Dayton M.
Latendresse, John R.
Pearce, Mason G.
Muskhelishvili, Levan
White, Gene A.
Chang, Ching-Wei
Mittelstaedt, Roberta A.
Shaddock, Joseph G.
McDaniel, Lea P.
Doerge, Daniel R.
Morris, Suzanne M.
Bishop, Michelle E.
Manjanatha, Mugimane G.
Aidoo, Anane
Heflich, Robert H.
TI In vivo genotoxicity of furan in F344 rats at cancer bioassay doses
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE In vivo Comet assay; Liver; DNA damage; Oxidative stress; Inflammation;
Cell proliferation
ID COMET ASSAY; REACTIVE METABOLITE; DNA-DAMAGE; OXIDATIVE STRESS;
GENE-EXPRESSION; CELL; LIVER; PROLIFERATION; SPECTROMETRY; APOPTOSIS
AB Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. Published by Elsevier Inc.
C1 [Ding, Wei; Petibone, Dayton M.; Pearce, Mason G.; Mittelstaedt, Roberta A.; Shaddock, Joseph G.; McDaniel, Lea P.; Morris, Suzanne M.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Aidoo, Anane; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA.
[Latendresse, John R.; Muskhelishvili, Levan; White, Gene A.] US FDA, Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Chang, Ching-Wei] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA.
[Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP Ding, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Wei.Ding@fda.hhs.gov
RI Ding, Wei/L-1503-2014
FU FDA/NCTR (FDA) [224-07-0007]; NIEHS/NTP (NIH) [Y1ES1027]; Oak Ridge
Institute for Science and Education
FX This work was supported in part by interagency agreements between
FDA/NCTR (FDA # 224-07-0007) and NIEHS/NTP (NIH # Y1ES1027). The views
presented in this paper are not necessarily those of the U.S. FDA.; Dr.
Wei Ding would like to acknowledge the postdoctoral fellowship support
received from the Oak Ridge Institute for Science and Education through
an interagency agreement between the U.S. Department of Energy and the
U.S. Food and Drug Administration. Our gratitude also goes to Lascelles
E. Lyn-Cook for lab support and to Florene Lewis and Cary Nobles for the
animal treatments.
NR 47
TC 19
Z9 19
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD JUN 1
PY 2012
VL 261
IS 2
BP 164
EP 171
DI 10.1016/j.taap.2012.03.021
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 951TY
UT WOS:000304744100005
PM 22507866
ER
PT J
AU Awotwe-Otoo, D
Zidan, AS
Rahman, Z
Habib, MJ
AF Awotwe-Otoo, David
Zidan, Ahmed S.
Rahman, Ziyaur
Habib, Muhammad J.
TI Evaluation of Anticancer Drug-Loaded Nanoparticle Characteristics by
Nondestructive Methodologies
SO AAPS PHARMSCITECH
LA English
DT Article
DE imaging; letrozole; nanoparticle; near-infrared; PCR; PLGA; PLS
ID NEAR-INFRARED SPECTROSCOPY; PLGA NANOPARTICLES; BREAST-CANCER;
CHEMOMETRICS; VARIABLES; QUALITY
AB The purpose of this study was to utilize near-infrared (NIR) spectroscopy and near-infrared chemical imaging (NIR-CI) as non-invasive techniques to evaluate the drug loading in letrozole-loaded PLGA nanoparticle formulations prepared by the emulsification-solvent evaporation method. A Plackett-Burman design was applied to evaluate the main effects of amount of drug (X (1)), amount of polymer (X (2)), stirring rate (X (3)), emulsifier concentration (X (4)), organic to aqueous phase volume ratio (X (5)), type of organic solvent (X (6)), and homogenization time (X (7)) on drug entrapment efficiency. The influence of three different spectral pretreatment methods (multiplicative scatter correction, standard normal variate, and Savitzky-Golay second derivative transformation with third-order polynomial) and two different regression methods (PLS regression and principal component regression (PCR)) on model prediction ability were compared. PLS of spectra that were pretreated with Savitzky-Golay second derivative transformation provided better model prediction than PCR as it revealed better linear correlation (correlation coefficient of 0.991) for both calibration and prediction models. Relatively low values of root mean square errors of calibration (RMSEC = 0.748) and prediction (RMSEP = 0.786) and low standard errors of calibration (SEC = 0.758) and prediction (SEP = 0.589) suggested good predictability for estimation of the loading of letrozole in PLGA nanoparticles. NIR-CI analysis also revealed mutual homogenous distribution of both polymer and drug and was capable of clearly distinguishing the 12 formulations both quantitatively and qualitatively. In conclusion, NIR and NIR-CI could be potentially used to characterize anticancer drug-loaded nanoparticulate matrix.
C1 [Awotwe-Otoo, David; Habib, Muhammad J.] Howard Univ, Dept Pharmaceut Sci, Coll Pharm, Washington, DC 20059 USA.
[Awotwe-Otoo, David; Zidan, Ahmed S.; Rahman, Ziyaur] US FDA, Div Prod Qual Res, Silver Spring, MD USA.
RP Habib, MJ (reprint author), Howard Univ, Dept Pharmaceut Sci, Coll Pharm, 2300 4th St NW, Washington, DC 20059 USA.
EM mhabib@Howard.edu
RI Zidan, Ahmed/I-1147-2012;
OI Rahman, Ziyaur/0000-0002-0402-825X
NR 24
TC 7
Z9 7
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-9932
J9 AAPS PHARMSCITECH
JI AAPS PharmSciTech
PD JUN
PY 2012
VL 13
IS 2
BP 611
EP 622
DI 10.1208/s12249-012-9782-7
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 950LX
UT WOS:000304651900029
PM 22535519
ER
PT J
AU Martinez, MN
Papich, MG
Drusano, GL
AF Martinez, Marilyn N.
Papich, Mark G.
Drusano, George L.
TI Dosing Regimen Matters: the Importance of Early Intervention and Rapid
Attainment of the Pharmacokinetic/Pharmacodynamic Target
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Review
ID COMMUNITY-ACQUIRED PNEUMONIA; MUTANT SELECTION WINDOW;
STAPHYLOCOCCUS-AUREUS; DRUG-RESISTANCE; PERSISTER CELLS; FLUOROQUINOLONE
RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; ANTIBIOTIC-RESISTANCE;
BACTERICIDAL ACTIVITY; EFFLUX PUMPS
AB To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent suboptimal systemic drug concentrations prior to the attainment of a steady state. Suboptimal (inadequate) exposure can produce amplification of resistant bacteria. This minireview provides an overview of published evidence supporting the positions that, in most situations, it is the exposure achieved during the first dose that is relevant for determining the therapeutic outcome of an infection, therapeutic intervention should be initiated as soon as possible to minimize the size of the bacterial burden at the infection site, and the duration of drug administration should be kept as brief as clinically appropriate to reduce the risk of selecting for resistant (or phenotypically nonresponsive) microbial strains. To support these recommendations, we briefly discuss data on inoculum effects, persister cells, and the concept of time within some defined mutation selection window.
C1 [Martinez, Marilyn N.] US FDA, Ctr Vet Med, Rockville, MD 20857 USA.
[Papich, Mark G.] N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA.
[Drusano, George L.] Univ Florida, Coll Med, Inst Therapeut Innovat, Albany, NY USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA.
EM marilyn.martinez@fda.hhs.gov
FU NIAID NIH HHS [R01 AI090802]
NR 61
TC 54
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U1 5
U2 16
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 JUN
PY 2012
VL 56
IS 6
BP 2795
EP 2805
DI 10.1128/AAC.05360-11
PG 11
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 947LZ
UT WOS:000304432800001
PM 22371890
ER
PT J
AU Nambiar, S
Madurawe, RD
Zuk, SM
Khan, SR
Ellison, CD
Faustino, PJ
Mans, DJ
Trehy, ML
Hadwiger, ME
Boyne, MT
Biswas, K
Cox, EM
AF Nambiar, S.
Madurawe, R. D.
Zuk, S. M.
Khan, S. R.
Ellison, C. D.
Faustino, P. J.
Mans, D. J.
Trehy, M. L.
Hadwiger, M. E.
Boyne, M. T., II
Biswas, K.
Cox, E. M.
TI Product Quality of Parenteral Vancomycin Products in the United States
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IN-VIVO; INNOVATOR
AB In response to concerns raised about the quality of parenteral vancomycin products, the U.S. Food and Drug Administration (FDA) is investigating the product quality of all FDA-approved parenteral vancomycin products available in the United States. Product quality was evaluated independently at two FDA Office of Testing and Research (FDA-OTR) sites. In the next phase of the investigation, being done in collaboration with the National Institute of Allergy and Infectious Diseases, the in vivo activity of these products will be evaluated in an appropriate animal model. This paper summarizes results of the FDA investigation completed thus far. One site used a validated ultrahigh-pressure liquid chromatography method (OTR-UPLC), and the second site used the high-performance liquid chromatography (HPLC) method for related substances provided in the British Pharmacopeia (BP) monograph for vancomycin intravenous infusion. Similar results were obtained by the two FDA-OTR laboratories using two different analytical methods. The products tested had 90 to 95% vancomycin B (active component of vancomycin) by the BP-HPLC method and 89 to 94% vancomycin by OTR-UPLC methods. Total impurities were 5 to 10% by BP-HPLC and 6 to 11% by OTR-UPLC methods. No single impurity was >2.0%, and the CDP-1 level was <= 2.0% across all products. Some variability in impurity profiles of the various products was observed. No adverse product quality issues were identified with the six U.S. vancomycin parenteral products. The quality parameters of all parenteral vancomycin products tested surpassed the United States Pharmacopeia acceptance criteria. Additional testing will characterize in vivo performance characteristics of these products.
C1 [Nambiar, S.; Cox, E. M.] US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Silver Spring, MD USA.
[Madurawe, R. D.] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, Silver Spring, MD USA.
[Zuk, S. M.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA.
[Khan, S. R.; Ellison, C. D.; Faustino, P. J.] US FDA, Off Testing & Res, Silver Spring, MD USA.
[Mans, D. J.; Trehy, M. L.; Hadwiger, M. E.; Boyne, M. T., II; Biswas, K.] US FDA, Off Testing & Res, St Louis, MO USA.
RP Nambiar, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Silver Spring, MD USA.
EM sumathi.nambiar@fda.hhs.gov; edward.cox@fda.hhs.gov
NR 10
TC 17
Z9 20
U1 0
U2 4
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 JUN
PY 2012
VL 56
IS 6
BP 2819
EP 2823
DI 10.1128/AAC.05344-11
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 947LZ
UT WOS:000304432800004
PM 22314525
ER
PT J
AU Hadwiger, ME
Sommers, CD
Mans, DJ
Patel, V
Boyne, MT
AF Hadwiger, Michael E.
Sommers, Cynthia D.
Mans, Daniel J.
Patel, Vikram
Boyne, Michael T., II
TI Quality Assessment of U.S. Marketplace Vancomycin for Injection Products
Using High-Resolution Liquid Chromatography-Mass Spectrometry and
Potency Assays
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID REVERSED-PHASE COLUMNS; NEPHROTOXICITY; ANTIBIOTICS; SELECTIVITY
AB In response to a published concern about the potency and quality of generic vancomycin products, the United States Food and Drug Administration investigated a small sampling of the vancomycin products available in North America with regard to purity, content, and potency. To facilitate identification of impurities, a new liquid chromatography method was developed using high-resolution mass spectrometry in addition to diode array detection to characterize impurities in several commercial products. Furthermore, a microbiological assay was utilized to link the analytical profiles with an in vitro potency. All products tested met the quality specifications outlined in the United States Pharmacopeia (USP) (vancomycin hydrochloride for injection monograph) for impurities and potency (USP, Vancomycin hydrochloride for injection. United States Pharmacopeia and National Formulary, vol USP 34-NF 29, 2011).
C1 [Hadwiger, Michael E.; Sommers, Cynthia D.; Mans, Daniel J.; Boyne, Michael T., II] US FDA, Div Pharmaceut Anal, CDER, St Louis, MO USA.
[Patel, Vikram] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA.
RP Boyne, MT (reprint author), US FDA, Div Pharmaceut Anal, CDER, St Louis, MO USA.
EM michael.boyne@fda.hhs.gov
NR 20
TC 20
Z9 22
U1 1
U2 6
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 JUN
PY 2012
VL 56
IS 6
BP 2824
EP 2830
DI 10.1128/AAC.00164-12
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 947LZ
UT WOS:000304432800005
PM 22371900
ER
PT J
AU Folster, JP
Pecic, G
Rickert, R
Taylor, J
Zhao, S
Fedorka-Cray, PJ
Whichard, J
McDermott, P
AF Folster, Jason P.
Pecic, G.
Rickert, R.
Taylor, J.
Zhao, S.
Fedorka-Cray, P. J.
Whichard, J.
McDermott, P.
TI Characterization of Multidrug-Resistant Salmonella enterica Serovar
Heidelberg from a Ground Turkey-Associated Outbreak in the United States
in 2011
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Letter
ID PLASMIDS
C1 [Folster, Jason P.; Pecic, G.; Rickert, R.; Taylor, J.; Whichard, J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA.
[Zhao, S.; McDermott, P.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
[Fedorka-Cray, P. J.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, USDA, Athens, GA USA.
RP Folster, JP (reprint author), Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA.
EM gux8@cdc.gov
NR 13
TC 9
Z9 9
U1 0
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 JUN
PY 2012
VL 56
IS 6
BP 3465
EP 3466
DI 10.1128/AAC.00201-12
PG 2
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 947LZ
UT WOS:000304432800101
PM 22450975
ER
PT J
AU Lerner, A
Bagic, A
Simmons, JM
Mari, Z
Bonne, O
Xu, B
Kazuba, D
Herscovitch, P
Carson, RE
Murphy, DL
Drevets, WC
Hallett, M
AF Lerner, Alicja
Bagic, Anto
Simmons, Janine M.
Mari, Zoltan
Bonne, Omer
Xu, Ben
Kazuba, Diane
Herscovitch, Peter
Carson, Richard E.
Murphy, Dennis L.
Drevets, Wayne C.
Hallett, Mark
TI Widespread abnormality of the gamma-aminobutyric acid-ergic system in
Tourette syndrome
SO BRAIN
LA English
DT Article
DE Tourette syndrome; tics; GABA(A) receptors; flumazenil; PET
ID OBSESSIVE-COMPULSIVE DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
DEEP BRAIN-STIMULATION; BASAL GANGLIA; FUNCTIONAL NEUROANATOMY;
BENZODIAZEPINE-RECEPTOR; STRIATAL INTERNEURONS; THALAMIC-STIMULATION;
TIC GENERATION; IN-VIVO
AB Dysfunction of the gamma-aminobutyric acid-ergic system in Tourette syndrome may conceivably underlie the symptoms of motor disinhibition presenting as tics and psychiatric manifestations, such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The purpose of this study was to identify a possible dysfunction of the gamma-aminobutyric acid-ergic system in Tourette patients, especially involving the basal ganglia-thalamo-cortical circuits and the cerebellum. We studied 11 patients with Tourette syndrome and 11 healthy controls. Positron emission tomography procedure: after injection of 20 mCi of [C-11]flumazenil, dynamic emission images of the brain were acquired. Structural magnetic resonance imaging scans were obtained to provide an anatomical framework for the positron emission tomography data analysis. Images of binding potential were created using the two-step version of the simplified reference tissue model. The binding potential images then were spatially normalized, smoothed and compared between groups using statistical parametric mapping. We found decreased binding of GABA(A) receptors in Tourette patients bilaterally in the ventral striatum, globus pallidus, thalamus, amygdala and right insula. In addition, the GABA(A) receptor binding was increased in the bilateral substantia nigra, left periaqueductal grey, right posterior cingulate cortex and bilateral cerebellum. These results are consistent with the longstanding hypothesis that circuits involving the basal ganglia and thalamus are disinhibited in Tourette syndrome patients. In addition, the abnormalities in GABA(A) receptor binding in the insula and cerebellum appear particularly noteworthy based upon recent evidence implicating these structures in the generation of tics.
C1 [Lerner, Alicja] US FDA, Ctr Drug Evaluat & Res, Controlled Substance Staff, Silver Spring, MD 20993 USA.
[Bagic, Anto] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA.
[Simmons, Janine M.] NIMH, Affect Social Behav & Social Cognit Program, NIH, Bethesda, MD 20892 USA.
[Mari, Zoltan] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA.
[Bonne, Omer] Hadassah Hebrew Univ, Dept Psychiat, Med Ctr, IL-91120 Jerusalem, Israel.
[Xu, Ben; Hallett, Mark] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Bethesda, MD 20892 USA.
[Kazuba, Diane; Murphy, Dennis L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Carson, Richard E.] Yale Univ, Sch Med, Dept Diagnost Radiol, Yale PET Ctr, New Haven, CT 06520 USA.
[Carson, Richard E.] Yale Univ, Sch Med, Dept Biomed Engn, Yale PET Ctr, New Haven, CT 06520 USA.
[Drevets, Wayne C.] Univ Oklahoma, Coll Med, Tulsa, OK 74136 USA.
[Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
RP Lerner, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Controlled Substance Staff, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM alicja.lerner@fda.hhs.gov
RI Carson, Richard/H-3250-2011
OI Carson, Richard/0000-0002-9338-7966
FU NINDS; NIMH, National Institutes of Health
FX The Intramural Research Programs of the NINDS and NIMH, National
Institutes of Health.
NR 85
TC 49
Z9 50
U1 4
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUN
PY 2012
VL 135
BP 1926
EP 1936
DI 10.1093/brain/aws104
PN 6
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 948YC
UT WOS:000304538900023
PM 22577221
ER
PT J
AU Jin, YY
Bies, R
Gastonguay, MR
Stockbridge, N
Gobburu, J
Madabushi, R
AF Jin, Yuyan
Bies, Robert
Gastonguay, Marc R.
Stockbridge, Norman
Gobburu, Jogarao
Madabushi, Rajanikanth
TI Misclassification and discordance of measured blood pressure from
patient's true blood pressure in current clinical practice: a clinical
trial simulation case study
SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
LA English
DT Article
DE Hypertension; Sphygmomanometer; Circadian rhythm; Modeling and
simulation; Blood pressure misclassification; Blood pressure
calibration; Public health
ID PRIMARY-CARE; HYPERTENSION; POPULATION; ERROR; PREVALENCE; RECORDINGS;
AWARENESS; RISK
AB Treatment decisions for hypertension using sphygmomanometer based measurements and the current clinical practice paradigm do not account for the timing of blood pressure (BP) measurement. This study aimed to evaluate the clinical implications of discordance between measured and true BP, to quantify BP misclassification rate at a typical clinical visit in current clinical practice, and to propose a BP calibration system to decrease the impact of timing of BP measurement. A clinical trial simulation case study was performed using an in silico Monte Carlo Simulation approach. The time-courses of BPs with and without an antihypertensive treatment effect were simulated from a baseline BP model combined with an antihypertensive PK/PD model. Virtual subject characteristics were sampled from the FDA internal database. The baseline BP model was qualified using observed 24 h ambulatory BP monitoring (ABPM) data from 225 subjects by a visual predictive check as well as a global sensitivity analysis. First of all, our results showed that the measured cuff BP in current typical clinical practice deviated from the true values. (1) Cuff BP deviated from the true values by more than 5 mmHg in 57 % (95 % CI: 54-61 %) of patients and more than 10 mmHg in 26 % (95 % CI: 22-32 %) of patients respectively. (2) These discordances were reduced to 28 % (deviation a parts per thousand yen5 mmHg, 95 % CI: 18-40 %) and 9 % (deviation a parts per thousand yen10 mmHg, 95 % CI: 4-18%) of patients assuming perfect sphygmomanometer measurement and thus represent the contribution of ignoring the daily circadian rhythm of BP. Secondly, our results showed 23-32 % of patients were misclassified to an incorrect BP category for a casual clinical visit based on JNC 7 guideline. In addition, the accuracy of the measured cuff BP varied by time of clinic visit. Specifically, 11:00 AM to 3:00 PM was identified to be the better time frame, while times before 9:00 AM were the worst time frame. Therefore, clinic visit time may need to be adjusted accordingly. Finally, we proposed an easy BP calibration method for clinic use to adjust for time of day differences due to circadian variability in case that the desirable clinic visit time cannot be tailored for practical reasons.
C1 [Stockbridge, Norman; Madabushi, Rajanikanth] US FDA, CDER, FDA, WO51,RM2172, Silver Spring, MD 20903 USA.
[Gastonguay, Marc R.] Metrum Inst, Tariffville, CT USA.
[Bies, Robert] Indiana Univ, Sch Med, Div Clin Pharmacol, Indianapolis, IN USA.
[Jin, Yuyan] Pfizer Inc, Clin Pharmacol, PharmaTherapeut Clin Res, Groton, CT 06340 USA.
[Gobburu, Jogarao] Univ Maryland, Sch Pharm, Ctr Translat Med, Baltimore, MD 21201 USA.
[Gobburu, Jogarao] Univ Maryland, Sch Med, Ctr Translat Med, Baltimore, MD 21201 USA.
RP Madabushi, R (reprint author), US FDA, CDER, FDA, WO51,RM2172, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM Rajnikanth.Madabushi@fda.hhs.gov
FU Indiana Clinical and Translational Sciences Institute; FDA
FX The authors would like to thank Dr. Karen A. Matthews (Distinguished
Professor of Psychiatry, Professor of Epidemiology and Psychology,
Director, Pittsburgh Mind-Body Center Director, Cardiovascular
Behavioral Medicine Research Program, Department of Psychiatry,
University of Pittsburgh School of Medicine) for providing ABPM data to
evaluate baseline BP model. The project was also supported by Indiana
Clinical and Translational Sciences Institute (Dr. Robert Bies). Funded
by FDA-Pharmacometrics Critical Path Fellowship.
NR 32
TC 9
Z9 9
U1 0
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1567-567X
J9 J PHARMACOKINET PHAR
JI J. Pharmacokinet. Pharmacodyn.
PD JUN
PY 2012
VL 39
IS 3
BP 283
EP 294
DI 10.1007/s10928-012-9250-8
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 949ZK
UT WOS:000304617500006
PM 22569889
ER
PT J
AU Kong, HS
Roberts, DP
Patterson, CD
Kuehne, SA
Heeb, S
Lakshman, DK
Lydon, J
AF Kong, Hye Suk
Roberts, Daniel P.
Patterson, Cheryl D.
Kuehne, Sarah A.
Heeb, Stephan
Lakshman, Dilip K.
Lydon, John
TI Effect of Overexpressing rsmA from Pseudomonas aeruginosa on Virulence
of Select Phytotoxin-Producing Strains of P. syringae
SO PHYTOPATHOLOGY
LA English
DT Article
ID CAROTOVORA SUBSP CAROTOVORA; PV. TOMATO DC3000; SIGNAL-TRANSDUCTION
SYSTEMS; BIOSYNTHETIC GENE-CLUSTER; MESSENGER-RNA RECOGNITION;
EXTRACELLULAR ENZYMES; ALGINATE PRODUCTION; 2-COMPONENT SYSTEM;
ESCHERICHIA-COLI; FLUORESCENS CHA0
AB The GacS/GacA two-component system functions mechanistically in conjunction with global post-transcriptional regulators of the RsmA family to allow pseudomonads and other bacteria to adapt to changing environmental stimuli. Analysis of this Gac/Rsm signal transduction pathway in phytotoxin-producing pathovars of Pseudmonas syringae is incomplete, particularly with regard to rsmA. Our approach in studying it was to overexpress rsmA in P. syringae strains through introduction of pSK61, a plasmid constitutively expressing this gene. Disease and colonization of plant leaf tissue were consistently diminished in all P syringae strains tested (pv. phaseolicola NPS3121, pv. syringae B728a, and BR2R) when harboring pSK61 relative to these isolates harboring the empty vector pME6031. Phaseolotoxin, syringomycin, and tabtoxin were not produced in any of these strains when transformed with pSK61. Production of protease and pyoverdin as well as swarming were also diminished in all of these strains when harboring pSK61. In contrast, alginate production, biofilm formation, and the hypersensitive response were diminished in some but not all of these isolates under the same growth conditions. These results indicate that rsmA is consistently important in the overarching phenotypes disease and endophtyic colonization but that its role varies with pathovar in certain underpinning phenotypes in the phytotoxin-producing strains of P. syringae.
C1 [Roberts, Daniel P.; Patterson, Cheryl D.; Lakshman, Dilip K.; Lydon, John] ARS, Sustainable Agr Syst Lab, USDA, Henry A Wallace Beltsville Agr Res Ctr, Beltsville, MD 20705 USA.
[Kong, Hye Suk] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Kuehne, Sarah A.; Heeb, Stephan] Univ Nottingham, Sch Mol Med Sci, Ctr Biomol Sci, Nottingham NG7 2RD, England.
RP Roberts, DP (reprint author), ARS, Sustainable Agr Syst Lab, USDA, Henry A Wallace Beltsville Agr Res Ctr, Beltsville, MD 20705 USA.
EM dan.roberts@ars.usda.gov
NR 87
TC 10
Z9 10
U1 2
U2 19
PU AMER PHYTOPATHOLOGICAL SOC
PI ST PAUL
PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA
SN 0031-949X
J9 PHYTOPATHOLOGY
JI Phytopathology
PD JUN
PY 2012
VL 102
IS 6
BP 575
EP 587
DI 10.1094/PHYTO-09-11-0267
PG 13
WC Plant Sciences
SC Plant Sciences
GA 948HF
UT WOS:000304493500003
PM 22568815
ER
PT J
AU Doerge, DR
Twaddle, NC
Vanlandingham, M
Fisher, JW
AF Doerge, Daniel R.
Twaddle, Nathan C.
Vanlandingham, Michelle
Fisher, Jeffrey W.
TI Pharmacokinetics of bisphenol A in serum and adipose tissue following
intravenous administration to adult female CD-1 mice
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Bisphenol A; Estrogen receptors; Adipose tissue; Mass spectrometry;
Pharmacokinetics
ID TANDEM MASS-SPECTROMETRY; SPRAGUE-DAWLEY RATS; LIQUID-CHROMATOGRAPHY;
CHLORINATED DERIVATIVES; PHTHALATE METABOLITES; RHESUS-MONKEYS; URINE
SAMPLES; EXPOSURE; QUANTIFICATION; TOXICOKINETICS
AB Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for use in food can liners. Worldwide biomonitoring studies consistently find high prevalence of BPA conjugates in urine consistent with pervasive exposure at levels typically below 1 mu g/kg bw/day. The current study used LC/MS/MS to measure serum pharmacokinetics of unconjugated (active) and conjugated (inactive) BPA in adult female CD-1 mice following intravenous (IV) injection, which produces higher serum levels by circumventing the processes of absorption from the GI tract and presystemic metabolism that occur after oral administration. Deuterated BPA (100 mu g/kg bw) was used to avoid interference by background contamination from trace amounts of native BPA. Additionally, the pharmacokinetics of unconjugated BPA were determined in adipose tissue, a proposed site of action and "depot" for BPA. After IV injection, unconjugated BPA rapidly distributed out of the circulation (t(1/2) =0.2 h) and terminal elimination also proceeded rapidly (t(1/2) = 0.8 h). Consistent with the degree of aqueous solubility, lipid/water solubility ratio, and partitioning from blood into adipose tissue in vivo, the levels of unconjugated BPA in mouse adipose tissue rapidly reached a maximal level (0.25 h) that did not exceed the serum maximum at the initial sampling time (0.08 h). Terminal elimination of unconjugated BPA from adipose tissue (t(1/2) = 7.0 h) was similar to that for conjugated BPA in serum (t(1/2) = 6.6 h) and <0.01% of the administered dose remained in adipose tissue after 24 h. These plasma and tissue kinetics are consistent with rapid equilibria and underscore the non-persistent nature of BPA, particularly when compared with slowly metabolized lipophilic organic pollutants like halogenated dibenzodioxins. Published by Elsevier Ireland Ltd.
C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM daniel.doerge@fda.hhs.gov
FU NCTR/FDA [FDA 224-07-0007, NIH Y1ES1027]; National Institute of
Environmental Health Sciences [FDA 224-07-0007, NIH Y1ES1027]
FX This research was supported in part by an Interagency Agreement (FDA
224-07-0007; NIH Y1ES1027) between NCTR/FDA and the National Institute
of Environmental Health Sciences/National Toxicology Program. The
authors are grateful to Drs. K. Barry Delclos and Luisa Camacho, NCTR,
for helpful discussions. The views presented in this article do not
necessarily reflect those of the U.S. Food and Drug Administration.
NR 46
TC 18
Z9 18
U1 3
U2 27
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUN 1
PY 2012
VL 211
IS 2
BP 114
EP 119
DI 10.1016/j.toxlet.2012.03.008
PG 6
WC Toxicology
SC Toxicology
GA 951UE
UT WOS:000304744700004
PM 22465602
ER
PT J
AU Camacho, L
Latendresse, JR
Muskhelishvili, L
Patton, R
Bowyer, JF
Thomas, M
Doerge, DR
AF Camacho, L.
Latendresse, J. R.
Muskhelishvili, L.
Patton, R.
Bowyer, J. F.
Thomas, M.
Doerge, D. R.
TI Effects of acrylamide exposure on serum hormones, gene expression, cell
proliferation, and histopathology in male reproductive tissues of
Fischer 344 rats
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Acrylamide; Cancer; Hypothalamus; Pituitary; Testes; Mesothelium
ID GAMMA-TUBULIN OVEREXPRESSION; KINESIN-RELATED PROTEINS; DNA ADDUCT
FORMATION; BIG-BLUE MICE; SERTOLI-CELLS; MICROTUBULE DISTRIBUTION;
CYTOPLASMIC DYNEIN; DRINKING-WATER; LEYDIG-CELLS; IN-VIVO
AB Acrylamide (M) is a reactive monomer used in many technological applications, but it is the incidental formation during cooking of common starchy foods that leads to pervasive human exposure, typically in the range of 1 mu g/kg body weight (bw)/day (d). AA is carcinogenic in multiple organs from both sexes of several rodent models and a consistent body of evidence points to a genotoxic mechanism based on metabolism to a DNA-reactive epoxide, glycidamide (GA). In F344 rats, tumorigenesis occurs in several hormonally regulated tissues (thyroid, mammary gland, and pen-testicular mesothelium), which has prompted speculation about endocrine dysregulation as a possible mechanism. The present study evaluated the effects of a 14 d exposure to AA administered through the drinking water on reproductive tissues and the hypothalamic-pituitary-testes (HPG) axis in male F344 rats. The doses selected encompass a range from approximately 2.5 mg/kg bw/d, which is carcinogenic after lifetime exposure, to 50 mg/kg bw/d, a maximally tolerable dose that causes hind limb paralysis. AA caused significant changes in serum hormones, histopathology, testicular gene expression, and cell proliferation, especially at the highest dose. Despite strong evidence for activation of the HPG axis subsequent to decreases in testosterone levels, and histopathological changes associated with significant effects on Leydig and germ cells, with concomitant mRNA expression changes, the precise mechanism(s) for AA-induced testicular toxicity remains unclear; however, the absence of evidence for increased proliferation of the pen-testicular mesothelium (Ki-67 immunoreactivity) does not support hormonal dysregulation as a contributing factor to the predisposition of this tissue to the carcinogenic effects of AA. Published by Elsevier Ireland Ltd.
C1 [Camacho, L.; Doerge, D. R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Latendresse, J. R.; Muskhelishvili, L.; Patton, R.] US FDA, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[Bowyer, J. F.; Thomas, M.] US FDA, Div Neurotoxicol, Jefferson, AR 72079 USA.
RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM daniel.doerge@fda.hhs.gov
FU NCTR/FDA [FDA 224-07-0007, NIH Y1ES1027]; National Institute of
Environmental Health Sciences [FDA 224-07-0007, NIH Y1ES1027]
FX This research was supported in part by an Interagency Agreement (FDA
224-07-0007; NIH Y1ES1027) between NCTR/FDA and the National Institute
of Environmental Health Sciences/National Toxicology Program. The
authors are grateful to Drs. K. Barry Delclos and Frederick A. Beland,
NCTR, for helpful discussions. The views presented in this article do
not necessarily reflect those of the U.S. Food and Drug Administration.
NR 58
TC 17
Z9 18
U1 0
U2 22
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-4274
J9 TOXICOL LETT
JI Toxicol. Lett.
PD JUN 1
PY 2012
VL 211
IS 2
BP 135
EP 143
DI 10.1016/j.toxlet.2012.03.007
PG 9
WC Toxicology
SC Toxicology
GA 951UE
UT WOS:000304744700007
PM 22459607
ER
PT J
AU Auerbach, M
Kane, RC
AF Auerbach, Michael
Kane, Robert C.
TI Caution in making inferences from FDA's Adverse Event Reporting System
SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
LA English
DT Letter
ID PARENTERAL IRON
C1 [Auerbach, Michael] Georgetown Univ, Sch Med, Washington, DC 20057 USA.
[Kane, Robert C.] US FDA, Div Hematol Prod, Ctr Drug Evaluat & Res, Washington, DC 20204 USA.
RP Auerbach, M (reprint author), Georgetown Univ, Sch Med, 3900 Reservoir Rd NW, Washington, DC 20057 USA.
EM mauerbachmd@abhemonc.com
NR 10
TC 11
Z9 11
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 JUN 1
PY 2012
VL 69
IS 11
BP 922
EP 923
DI 10.2146/ajhp120138
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 948IX
UT WOS:000304497900008
PM 22610021
ER
PT J
AU Tian, Y
Guo, B
Jia, H
Ji, K
Sun, Y
Li, Y
Zhao, T
Gao, L
Meng, Y
Kalvakolanu, DV
Kopecko, DJ
Zhao, X
Zhang, L
Xu, D
AF Tian, Y.
Guo, B.
Jia, H.
Ji, K.
Sun, Y.
Li, Y.
Zhao, T.
Gao, L.
Meng, Y.
Kalvakolanu, D. V.
Kopecko, D. J.
Zhao, X.
Zhang, L.
Xu, D.
TI Targeted therapy via oral administration of attenuated Salmonella
expression plasmid-vectored Stat3-shRNA cures orthotopically
transplanted mouse HCC
SO CANCER GENE THERAPY
LA English
DT Article
DE HCC; immune response; RNA interference; Stat3
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; HUMAN HEPATOCELLULAR-CARCINOMA;
SOMATIC TRANSGENE VACCINATION; ENDOTHELIAL GROWTH-FACTOR; SMALL
INTERFERING RNAS; SIGNAL TRANSDUCER; IN-VIVO; ANTIGEN DELIVERY;
TUMOR-GROWTH; TYPHIMURIUM
AB The development of RNA interference-based cancer gene therapies has been delayed due to the lack of effective tumor-targeting delivery systems. Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has a natural tropism for solid tumors. We report here the use of attenuated S. Typhimurium as a vector to deliver shRNA directly into tumor cells. Constitutively activated signal transducer and activator of transcription 3 (Stat3) is a key transcription factor involved in both hepatocellular carcinoma (HCC) growth and metastasis. In this study, attenuated S. Typhimurium was capable of delivering shRNA-expressing vectors to the targeted cancer cells and inducing RNA interference in vivo. More importantly, a single oral dose of attenuated S. Typhimurium carrying shRNA-expressing vectors targeting Stat3 induced remarkably delayed and reduced HCC (in 70% of mice). Cancer in these cured mice did not recur over 2 years following treatment. These data demonstrated that RNA interference combined with Salmonella as a delivery system may offer a novel clinical approach for cancer gene therapy.
C1 [Tian, Y.; Jia, H.; Ji, K.; Li, Y.; Zhao, T.; Gao, L.; Meng, Y.; Zhang, L.] Jilin Univ, Norman Bethune Coll Med, Prostate Dis Prevent & Treatment Res Ctr, Changchun 130021, Peoples R China.
[Tian, Y.; Jia, H.; Ji, K.; Li, Y.; Zhao, T.; Gao, L.; Meng, Y.; Zhang, L.] Jilin Univ, Norman Bethune Coll Med, Dept Pathophysiol, Changchun 130021, Peoples R China.
[Guo, B.] Jilin Univ, China Japan Union Hosp, Dept Emergency Med, Changchun 130021, Peoples R China.
[Sun, Y.; Zhao, X.] Jilin Univ, Hosp 1, Changchun 130021, Peoples R China.
[Kalvakolanu, D. V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Greenebaum Canc Ctr,Mol Biol Program, Baltimore, MD 21201 USA.
[Kopecko, D. J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Xu, D.] New Vaccine Natl Engn Res Ctr, Beijing, Peoples R China.
RP Zhang, L (reprint author), Jilin Univ, Norman Bethune Coll Med, Prostate Dis Prevent & Treatment Res Ctr, Changchun 130021, Peoples R China.
EM zhangling3@jlu.edu.cn; dqxujl@gmail.com
FU National Natural Science Foundation of China [30801354, 30970791]; Jilin
Provincial Science & Technology Department [20080154]; PhD Programs
Foundation of Ministry of Education of China [200801831077]; National
Cancer Institute [CA105005, CA78282]
FX We thank Dr EL Hohmann (Massachusetts General Hospital, Harvard Medical
School, Boston, MA) for supplying the S. Typhimurium strain LH430. This
work was funded by the National Natural Science Foundation of China (no.
30801354, no. 30970791), Jilin Provincial Science & Technology
Department (no. 20080154), PhD Programs Foundation of Ministry of
Education of China (no. 200801831077) and National Cancer Institute
Grants CA105005 and CA78282 (DV Kalvakolanu).
NR 39
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD JUN
PY 2012
VL 19
IS 6
BP 393
EP 401
DI 10.1038/cgt.2012.12
PG 9
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
Research & Experimental Medicine
GA 944IA
UT WOS:000304191400004
PM 22555509
ER
PT J
AU Zhichkin, PE
Athey, BD
Avigan, MI
Abernethy, DR
AF Zhichkin, P. E.
Athey, B. D.
Avigan, M. I.
Abernethy, D. R.
TI Needs for an Expanded Ontology-Based Classification of Adverse Drug
Reactions and Related Mechanisms
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
AB The growing significance of bioinformatics and systems biology in drug safety research requires a system of adverse-event classification that goes beyond a simple vocabulary. This opinion piece outlines the need for development of an ontology-based framework of describing adverse drug reactions (ADRs) and describes the potential applications for such a framework.
C1 [Zhichkin, P. E.; Abernethy, D. R.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Athey, B. D.] Univ Michigan, Sch Med, Dept Computat Med & Bioinformat, Ann Arbor, MI USA.
[Avigan, M. I.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Abernethy, DR (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM darrell.abernethy@fda.hhs.gov
OI Athey, Brian/0000-0002-9793-535X
NR 5
TC 9
Z9 9
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD JUN
PY 2012
VL 91
IS 6
BP 963
EP 965
DI 10.1038/clpt.2012.41
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 945AS
UT WOS:000304245800008
PM 22609907
ER
PT J
AU Malati, CY
Robertson, SM
Hunt, JD
Chairez, C
Alfaro, RM
Kovacs, JA
Penzak, SR
AF Malati, Christine Y.
Robertson, Sarah M.
Hunt, Jennifer D.
Chairez, Cheryl
Alfaro, Raul M.
Kovacs, Joseph A.
Penzak, Scott R.
TI Influence of Panax ginseng on Cytochrome P450 (CYP)3A and P-glycoprotein
(P-gp) Activity in Healthy Participants
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE HIV; Panax ginseng; cytochrome P450; drug interaction; midazolam; herb
ID ST-JOHNS-WORT; FEXOFENADINE PHARMACOKINETICS;
FUNCTIONAL-CHARACTERIZATION; ALTERNATIVE MEDICINE; PHENOTYPING PROBES;
DRUG-INTERACTIONS; HEPATIC-UPTAKE; CYP3A ACTIVITY; GINKGO-BILOBA; CACO-2
CELLS
AB A number of herbal preparations have been shown to interact with prescription medications secondary to modulation of cytochrome P450 (CYP) and/or P-glycoprotein (P-gp). The purpose of this study was to determine the influence of Panax ginseng on CYP3A and P-gp function using the probe substrates midazolam and fexofenadine, respectively. Twelve healthy participants (8 men) completed this open-label, single-sequence pharmacokinetic study. Healthy volunteers received single oral doses of midazolam 8 mg and fexofenadine 120 mg, before and after 28 days of P ginseng 500 mg twice daily. Midazolam and fexofenadine pharmacokinetic parameter values were calculated and compared before and after P ginseng administration. Geometric mean ratios (postginseng/preginseng) for midazolam area under the concentration-time curve from zero to infinity (AUC(0-infinity)), half-life (t(1/2)), and maximum concentration (C-max) were significantly reduced at 0.66 (0.55-0.78), 0.71 (0.53-0.90), and 0.74 (0.56-0.93), respectively. Conversely, fexofenadine pharmacokinetics were unaltered by P ginseng administration. Based on these results, P ginseng appeared to induce CYP3A activity in the liver and possibly the gastrointestinal tract. Patients taking P ginseng in combination with CYP3A substrates with narrow therapeutic ranges should be monitored closely for adequate therapeutic response to the substrate medication.
C1 [Malati, Christine Y.; Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Pharmacokinet Res Lab, Dept Pharm, Clin Res Ctr, Bethesda, MD 20892 USA.
[Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Dept Hlth & Human Serv, Silver Spring, MD USA.
[Hunt, Jennifer D.; Chairez, Cheryl] NIAID, NIH, Bethesda, MD 20892 USA.
[Kovacs, Joseph A.] NIH, Dept Crit Care Med, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Penzak, SR (reprint author), NIH, Ctr Clin, Dept Pharm, Bldg 10,1N 257, Bethesda, MD 20892 USA.
EM spenzak@mail.cc.nih.gov
FU National Institutes of Health (NIH) Clinical Center Pharmacy Department;
National Institute of Allergy and Infectious Diseases (NIAID)
FX This research was financially supported by the Intramural Research
Programs of the National Institutes of Health (NIH) Clinical Center
Pharmacy Department and the National Institute of Allergy and Infectious
Diseases (NIAID).
NR 45
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U1 2
U2 20
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0091-2700
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD JUN
PY 2012
VL 52
IS 6
BP 932
EP 939
DI 10.1177/0091270011407194
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 944UI
UT WOS:000304228900015
PM 21646440
ER
PT J
AU Swanson, CA
Zimmermann, MB
Skeaff, S
Pearce, EN
Dwyer, JT
Trumbo, PR
Zehaluk, C
Andrews, KW
Carriquiry, A
Caldwel, KL
Egan, SK
Long, SE
Bailey, RL
Sullivan, KM
Holden, JM
Betz, JM
Phinney, KW
Brooks, SPJ
Johnson, CL
Haggans, CJ
AF Swanson, Christine A.
Zimmermann, Michael B.
Skeaff, Sheila
Pearce, Elizabeth N.
Dwyer, Johanna T.
Trumbo, Paula R.
Zehaluk, Christina
Andrews, Karen W.
Carriquiry, Alicia
Caldwel, Kathleen L.
Egan, S. Kathleen
Long, Stephen E.
Bailey, Regan Lucas
Sullivan, Kevin M.
Holden, Joanne M.
Betz, Joseph M.
Phinney, Karen W.
Brooks, Stephen P. J.
Johnson, Clifford L.
Haggans, Carol J.
TI Summary of an NIH Workshop to Identify Research Needs to Improve the
Monitoring of Iodine Status in the United States and to Inform the DRI
SO JOURNAL OF NUTRITION
LA English
DT Article
ID URINARY IODINE; THYROID-FUNCTION; DIETARY-SUPPLEMENTS; PREGNANT-WOMEN;
IODIZED SALT; BREAST-MILK; NATIONAL-HEALTH; DOUBLE-BLIND; DEFICIENCY;
NUTRITION
AB The Office of Dietary Supplements (ODS) at the NIH sponsored a workshop on May 12-13, 2011, to bring together representatives from various NIH institutes and centers as a first step in developing an NIH iodine research initiative. The workshop also provided an opportunity to identify research needs that would inform the dietary reference intakes for iodine, which were last revised in 2001. Iodine is required throughout the life cycle, but pregnant women and infants are the populations most at risk of deficiency, because iodine is required for normal brain development and growth. The CDC monitors iodine status of the population on a regular basis, but the status of the most vulnerable populations remains uncertain. The NIH funds very little investigator-initiated research relevant to iodine and human nutrition, but the ODS has worked for several years with a number of other U.S. government agencies to develop many of the resources needed to conduct iodine research of high quality (e.g., validated analytical methods and reference materials for multiple types of samples). Iodine experts, scientists from several U.S. government agencies, and NIH representatives met for 2 d to identify iodine research needs appropriate to the NIH mission. J. Nutr. 142: 1175S-1185S, 2012.
C1 [Swanson, Christine A.; Dwyer, Johanna T.; Bailey, Regan Lucas; Betz, Joseph M.; Haggans, Carol J.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Zimmermann, Michael B.] ETH, Inst Food & Nutr, Zurich, Switzerland.
[Skeaff, Sheila] Univ Otago, Dept Human Nutr, Dunedin, New Zealand.
[Pearce, Elizabeth N.] Boston Univ, Sch Med, Evans Ctr Interdisciplinary Biomed Res, Boston, MA 02118 USA.
[Trumbo, Paula R.; Egan, S. Kathleen] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Zehaluk, Christina; Brooks, Stephen P. J.] Hlth Canada, Bur Nutr Sci, Ottawa, ON K1A 0L2, Canada.
[Andrews, Karen W.; Holden, Joanne M.] ARS, USDA, Beltsville, MD USA.
[Carriquiry, Alicia] Iowa State Univ, Dept Stat, Ames, IA USA.
[Caldwel, Kathleen L.; Sullivan, Kevin M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Long, Stephen E.; Phinney, Karen W.] Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA.
[Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Swanson, CA (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01, Bethesda, MD 20892 USA.
EM swansonc@od.nih.gov
RI Zimmermann, Michael/C-3062-2016;
OI Dwyer, Johanna/0000-0002-0783-1769
FU NIH Office of Dietary Supplements
FX Published in a supplement to The Journal of Nutrition. Presented at the
Office of Dietary Supplements Iodine Workshop, held in Rockville,
Maryland, May 12-13, 2011. The workshop was organized and sponsored by
the NIH Office of Dietary Supplements. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the NIH or other government agencies. The views
expressed in these papers are not necessarily those of the Supplement
Coordinator or Guest Editors. The Supplement Coordinator for this
supplement was Christine A. Swanson, Office of Dietary Supplements, NIH.
Supplement Coordinator disclosures: Christine A. Swanson had no
conflicts to disclose. This supplement is the responsibility of the
Guest Editor to whom the Editor of The Journal of Nutrition has
delegated supervision of both technical conformity to the published
regulations of The Journal of Nutrition and general oversight of the
scientific merit of each article. The Guest Editor for this supplement
was A. Catharine Ross, Guest Editor disclosure: A. Catharine Ross had no
conflicts to disclose. Publication costs for this supplement were
defrayed in part by the payment of page charges. This publication must
therefore be hereby marked "advertisement" in accordance with 18 USC
section 1734 solely to indicate this fact. The opinions expressed in
this publication are those of the authors and are not attributable to
the sponsors or the publisher, Editor, or Editorial Board of The Journal
of Nutrition.
NR 92
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U1 2
U2 19
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD JUN
PY 2012
VL 142
IS 6
BP 1175S
EP 1185S
DI 10.3945/jn.111.156448
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 946EY
UT WOS:000304335500030
PM 22551802
ER
PT J
AU Morrison, TM
Yan, X
Abel, DB
Fairman, RM
Glickman, MH
Fillinger, MF
AF Morrison, Tina M.
Yan, Xu
Abel, Dorothy B.
Fairman, Ron M.
Glickman, Marc H.
Fillinger, Mark F.
TI Population-based Study of Age and Gender Effects in Aneurysm Anatomy
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS)
CY JUN 07-09, 2012
CL Natl Harbor, MD
SP Soc Vasc Surg (SVS)
C1 [Morrison, Tina M.; Yan, Xu; Abel, Dorothy B.] US FDA, Div Cardiovasc Device, Off Device Evaluat, Silver Spring, MD USA.
[Fairman, Ron M.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA.
[Glickman, Marc H.] Sentara Norfolk Gen Hosp, Norfolk, VA USA.
[Fillinger, Mark F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA.
NR 0
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U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD JUN
PY 2012
VL 55
IS 6
SU S
BP 30
EP 30
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 947AL
UT WOS:000304398900053
ER
PT J
AU Dworkin, RH
Turk, DC
Peirce-Sandner, S
Burke, LB
Farrar, JT
Gilron, I
Jensen, MP
Katz, NP
Raja, SN
Rappaport, BA
Rowbotham, MC
Backonja, MM
Baron, R
Bellamy, N
Bhagwagar, Z
Costello, A
Cowan, P
Fang, WC
Hertz, S
Jay, GW
Junor, R
Kerns, RD
Kerwin, R
Kopecky, EA
Lissin, D
Malamut, R
Markman, JD
McDermott, MP
Munera, C
Porter, L
Rauschkolb, C
Rice, ASC
Sampaio, C
Skljarevski, V
Sommerville, K
Stacey, BR
Steigerwald, I
Tobias, J
Trentacosti, AM
Wasan, AD
Wells, GA
Williams, J
Witter, J
Ziegler, D
AF Dworkin, Robert H.
Turk, Dennis C.
Peirce-Sandner, Sarah
Burke, Laurie B.
Farrar, John T.
Gilron, Ian
Jensen, Mark P.
Katz, Nathaniel P.
Raja, Srinivasa N.
Rappaport, Bob A.
Rowbotham, Michael C.
Backonja, Misha-Miroslav
Baron, Ralf
Bellamy, Nicholas
Bhagwagar, Zubin
Costello, Ann
Cowan, Penney
Fang, Weikai Christopher
Hertz, Sharon
Jay, Gary W.
Junor, Roderick
Kerns, Robert D.
Kerwin, Rosemary
Kopecky, Ernest A.
Lissin, Dmitri
Malamut, Richard
Markman, John D.
McDermott, Michael P.
Munera, Catherine
Porter, Linda
Rauschkolb, Christine
Rice, Andrew S. C.
Sampaio, Cristina
Skljarevski, Vladimir
Sommerville, Kenneth
Stacey, Brett R.
Steigerwald, Ilona
Tobias, Jeffrey
Trentacosti, Ann Marie
Wasan, Ajay D.
Wells, George A.
Williams, Jim
Witter, James
Ziegler, Dan
TI Considerations for improving assay sensitivity in chronic pain clinical
trials: IMMPACT recommendations
SO PAIN
LA English
DT Review
ID CONCENTRATION CAPSAICIN PATCH; RANDOMIZED CONTROLLED-TRIALS;
PLACEBO-CONTROLLED TRIALS; PERIPHERAL NEUROPATHIC PAIN; LONG-TERM
TRIALS; LEAD-IN PERIOD; LOW-BACK-PAIN; DOUBLE-BLIND; POSTHERPETIC
NEURALGIA; ENRICHED ENROLLMENT
AB A number of pharmacologic treatments examined in recent randomized clinical trials (RCTs) have failed to show statistically significant superiority to placebo in conditions in which their efficacy had previously been demonstrated. Assuming the validity of previous evidence of efficacy and the comparability of the patients and outcome measures in these studies, such results may be a consequence of limitations in the ability of these RCTs to demonstrate the benefits of efficacious analgesic treatments vs placebo ("assay sensitivity"). Efforts to improve the assay sensitivity of analgesic trials could reduce the rate of falsely negative trials of efficacious medications and improve the efficiency of analgesic drug development. Therefore, an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials consensus meeting was convened in which the assay sensitivity of chronic pain trials was reviewed and discussed. On the basis of this meeting and subsequent discussions, the authors recommend consideration of a number of patient, study design, study site, and outcome measurement factors that have the potential to affect the assay sensitivity of RCTs of chronic pain treatments. Increased attention to and research on methodological aspects of clinical trials and their relationships with assay sensitivity have the potential to provide the foundation for an evidence-based approach to the design of analgesic clinical trials and expedite the identification of analgesic treatments with improved efficacy and safety. (C) 2012 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Dworkin, Robert H.] Univ Rochester, Med Ctr, Dept Anesthesiol, Rochester, NY 14642 USA.
[Dworkin, Robert H.] Univ Rochester, Dept Neurol, Rochester, NY 14642 USA.
[Dworkin, Robert H.] Univ Rochester, Ctr Human Expt Therapeut, Rochester, NY 14642 USA.
[Turk, Dennis C.; Jensen, Mark P.] Univ Washington, Seattle, WA 98195 USA.
[Burke, Laurie B.; Rappaport, Bob A.; Costello, Ann; Hertz, Sharon; Trentacosti, Ann Marie] US FDA, Silver Spring, MD USA.
[Farrar, John T.] Univ Penn, Philadelphia, PA 19104 USA.
[Gilron, Ian] Queens Univ, Kingston, ON, Canada.
[Katz, Nathaniel P.] Analges Solut, Natick, MA USA.
[Katz, Nathaniel P.] Tufts Univ, Boston, MA 02111 USA.
[Raja, Srinivasa N.] Johns Hopkins Univ, Baltimore, MD USA.
[Rowbotham, Michael C.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Backonja, Misha-Miroslav] Univ Wisconsin, Madison, WI USA.
[Baron, Ralf] Univ Kiel, Kiel, Germany.
[Bellamy, Nicholas] Univ Queensland, Brisbane, Qld, Australia.
[Bhagwagar, Zubin] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
[Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA.
[Fang, Weikai Christopher] DePuy Spine, Raynham, MA USA.
[Jay, Gary W.] Pfizer, New London, CT USA.
[Junor, Roderick] Eisai Ltd, Hatfield, Herts, England.
[Kerns, Robert D.] Dept Vet Affairs, West Haven, CT USA.
[Kerns, Robert D.] Yale Univ, New Haven, CT USA.
[Kerwin, Rosemary] Nuvo Res, W Chester, PA USA.
[Kopecky, Ernest A.] Endo Pharmaceut Inc, Chadds Ford, PA USA.
[Lissin, Dmitri] Durect Corp, Cupertino, CA USA.
[Malamut, Richard; Witter, James] AstraZeneca, Wilmington, DE USA.
[Munera, Catherine] Purdue Pharma, Stamford, CT USA.
[Porter, Linda] NIH, Bethesda, MD 20892 USA.
[Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
[Rice, Andrew S. C.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Sampaio, Cristina] Fac Med Lisbon, Lisbon, Portugal.
[Skljarevski, Vladimir] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Sommerville, Kenneth] King Pharmaceut, Cary, NC USA.
[Stacey, Brett R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Steigerwald, Ilona] Grunenthal GmbH, Aachen, Germany.
[Tobias, Jeffrey] NeurogesX Inc, San Carlos, CA USA.
[Wasan, Ajay D.] Harvard Univ, Sch Med, Boston, MA USA.
[Wells, George A.] Univ Ottawa, Ottawa, ON, Canada.
[Williams, Jim] Smith & Nephew, Durham, NC USA.
[Ziegler, Dan] Univ Dusseldorf, German Diabet Ctr, D-40225 Dusseldorf, Germany.
RP Dworkin, RH (reprint author), Univ Rochester, Med Ctr, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA.
EM robert_dworkin@urmc.rochester.edu
RI Bhagwagar, Zubin/H-1071-2012; Rice, Andrew/I-7501-2012; Bellamy,
Nicholas/G-3631-2010;
OI Bhagwagar, Zubin/0000-0002-1101-768X; Yang, Shuman/0000-0002-9638-0890
FU AstraZeneca; Bristol-Myers Squibb; DePuy Spine; Durect; Eisai; Eli
Lilly; Endo; Forest; Grunenthal; Johnson Johnson; King; NeurogesX; Nuvo;
Pfizer; Purdue; Smith Nephew; US Department of Veterans Affairs; US Food
and Drug Administration; US National Institutes of Health
FX The views expressed in this article are those of the authors, none of
whom have financial conflicts of interest related to the specific issues
discussed in this manuscript. At the time of the consensus meeting on
which this article is based, 15 of the authors were employed by one of
the companies that provided unrestricted grants to the University of
Rochester Office of Continuing Professional Education to support the
activities of IMMPACT, including the consensus meeting; these companies
were AstraZeneca, Bristol-Myers Squibb, DePuy Spine, Durect, Eisai, Eli
Lilly, Endo, Forest, Grunenthal, Johnson & Johnson, King, NeurogesX,
Nuvo, Pfizer, Purdue, and Smith & Nephew.; No official endorsement by
the US Department of Veterans Affairs, US Food and Drug Administration,
US National Institutes of Health, or the pharmaceutical companies that
provided unrestricted grants to the University of Rochester Office of
Continuing Professional Education should be inferred. The authors thank
Paul J. Lambiase and Mary Gleichauf for their invaluable assistance in
the organization of the IMMPACT meeting.
NR 108
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U1 0
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
J9 PAIN
JI Pain
PD JUN
PY 2012
VL 153
IS 6
BP 1148
EP 1158
DI 10.1016/j.pain.2012.03.003
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 945BZ
UT WOS:000304249100009
PM 22494920
ER
PT J
AU van der Laan, JW
Chapin, RE
Haenen, B
Jacobs, AC
Piersma, A
AF van der Laan, Jan Willem
Chapin, Robert E.
Haenen, Bert
Jacobs, Abigail C.
Piersma, Aldert
TI Testing strategies for embryo-fetal toxicity of human pharmaceuticals.
Animal models vs. in vitro approaches A workshop report
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Rat and rabbit reproductive toxicity; Embryonic stem cell tests;
Zebrafish testing; Developmental and reproductive toxicity; Human
pharmaceuticals; Validation and evaluation; International Harmonisation
ID STEM-CELL TEST; DEVELOPMENTAL TOXICITY; EMBRYOTOXICITY TESTS; TEST EST;
ZEBRAFISH; ASSAY; VIVO; RAT; RECOMMENDATIONS; CHEMICALS
AB Reproductive toxicity testing is characterized by high animal use. For registration of pharmaceutical compounds, developmental toxicity studies are usually conducted in both rat and rabbits. Efforts have been underway for a long time to design alternatives to animal use. Implementation has lagged, partly because of uncertainties about the applicability domain of the alternatives.
The reproductive cycle is complex and not all mechanisms of development can be mimicked in vitro. Therefore, efforts are underway to characterize the available alternative tests with regard to the mechanism of action they include.
One alternative test is the mouse embryonic stem cell test (EST), which has been studied since the late 1990s. It is a genuine 3R "alternative" assay as it is essentially animal-free.
A meeting was held to review the state-of-the-art of various in vitro models for prediction of developmental toxicity. Although the predictivity of individual assays is improving, a battery of several assays is likely to have even higher predictivity, which is necessary for regulatory acceptance. The workshop concluded that an important first step is a thorough survey of the existing rat and rabbit studies, to fully characterize the frequency of responses and the types of effects seen. At the same time, it is important to continue the optimization of in vitro assays. As more experience accumulates, the optimal conditions, assay structure, and applicability of the alternative assays are expected to emerge. (C) 2012 Elsevier Inc. All rights reserved.
C1 [van der Laan, Jan Willem] Med Evaluat Board, NL-3503 RG Utrecht, Netherlands.
[Chapin, Robert E.] Pfizer Global R&D, Dev & Reprod Toxicol Grp, Groton, CT 06340 USA.
[Haenen, Bert] 3 D PharmXchange, NL-5026 SK Tilburg, Netherlands.
[Jacobs, Abigail C.] FDA, CDER, ONDIO, Silver Spring, MD USA.
[Piersma, Aldert] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, Nijmegen, Netherlands.
[Piersma, Aldert] Univ Utrecht, Inst Risk assessment Sci, Utrecht, Netherlands.
RP van der Laan, JW (reprint author), Med Evaluat Board, POB 8275, NL-3503 RG Utrecht, Netherlands.
EM jw.vd.laan@cbg-meb.nl
OI Chapin, Robert/0000-0002-5997-1261
NR 31
TC 9
Z9 9
U1 1
U2 14
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 JUN
PY 2012
VL 63
IS 1
BP 115
EP 123
DI 10.1016/j.yrtph.2012.03.009
PG 9
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 944VB
UT WOS:000304230800014
PM 22449444
ER
PT J
AU Baek, JH
Zhou, YP
Harris, DR
Schaer, DJ
Palmer, AF
Buehler, PW
AF Baek, Jin Hyen
Zhou, Yipin
Harris, David R.
Schaer, Dominik J.
Palmer, Andre F.
Buehler, Paul W.
TI Down Selection of Polymerized Bovine Hemoglobins for Use as Oxygen
Releasing Therapeutics in a Guinea Pig Model
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE hemoglobin; polymerized hemoglobin; red blood cell substitute;
transfusion medicine; oxygen therapeutic; pharmacokinetics;
pharmacodynamics; toxicity
ID TANGENTIAL FLOW FILTRATION; CELL-FREE HEMOGLOBIN; BLOOD SUBSTITUTES;
NITRIC-OXIDE; HAPTOGLOBIN; DETERMINES; IRON
AB Editor's Highlight: The development of hemoglobin-based oxygen carriers (HBOCs) as a replacement for whole-blood transfusions has been impeded by their systemic toxicity. This paper presents data from a series of HBOCs, demonstrating one candidate that meets predetermined safety criteria. This approach may allow the development of an acceptable blood substitute for human use.Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as resuscitative fluids for use in multiple medical applications and in lieu of blood transfusion. However, cardiovascular, central nervous system, and renal adverse events have largely impeded progress. This has prompted a need to evaluate novel down selection approaches for HBOCs prior to in-depth preclinical and clinical safety testing. In the present study, polymerized bovine Hbs (PolybHbs) were prepared with increasing ratios of glutaraldehyde to bovine Hb (10:1, 20:1, 30:1, and 40:1). The optimal PolybHb candidate selection was based on a priori determined in vivo response to include a long circulating PolybHb with no measurable renal exposure, minimal cardiovascular response, limited oxidation to metHb in vitro, or in circulation and absence of acute end organ toxicity. Guinea pigs were dosed via a 50% blood for PolybHb exchange transfusion. Data suggested that the 30:1 preparation exhibited maximum circulatory exposure (AUC(0-infinity)) with the lowest level of oxidation (plasma metHb formation) and minimal (< 10%) blood pressure elevation. Additionally, the 30:1 preparation was absent renal iron deposition as well as abnormal glomerular/tubular histopathology or serum creatinine elevation. Clearance pathways predominantly followed those consistent with endogenous Hb clearance based pathways. Therefore, data confirmed the ability to select a single PolybHb from a small library of HBOCs based on a priori determined characteristics. Moreover, the approach to down selection described could be applied to enhance the early predictability of human safety for this class of biological therapeutics to optimize for specific indications.
C1 [Baek, Jin Hyen; Buehler, Paul W.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20892 USA.
[Zhou, Yipin; Harris, David R.; Palmer, Andre F.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
[Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland.
RP Buehler, PW (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Room 129,Bldg 29,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM paul.buehler@fda.hhs.gov
FU FDA; National Institutes of Health [R01HL078840, R01DK070862]
FX This work was supported by an FDA Critical Path grant to PWB and
National Institutes of Health grants R01HL078840 and R01DK070862 to AFP.
We would like to acknowledge the efforts of Dr Felice D'Agnillo in the
optimization of iron and HO-1 histochemistry employed in the present
work.
NR 30
TC 9
Z9 9
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUN
PY 2012
VL 127
IS 2
BP 567
EP 581
DI 10.1093/toxsci/kfs109
PG 15
WC Toxicology
SC Toxicology
GA 944JY
UT WOS:000304198400023
PM 22416071
ER
PT J
AU Li, Y
Couch, L
Higuchi, M
Fang, JL
Guo, L
AF Li, Yan
Couch, Letha
Higuchi, Masahiro
Fang, Jia-Long
Guo, Lei
TI Mitochondrial Dysfunction Induced by Sertraline, an Antidepressant Agent
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE sertraline; liver toxicity; mitochondrial dysfunction; rat primary
hepatocytes; isolated liver mitochondria
ID INDUCED LIVER-INJURY; CA-2&-INDUCED MEMBRANE TRANSITION;
ADENINE-NUCLEOTIDE TRANSLOCATOR; CEREBELLAR GRANULE CELLS;
OF-THE-LITERATURE; PERMEABILITY TRANSITION; OXIDATIVE-PHOSPHORYLATION;
PRIMARY HEPATOCYTES; GENE-EXPRESSION; INNER MEMBRANE
AB Sertraline, a selective serotonin reuptake inhibitor, has been used for the treatment of depression. Although it is generally considered safe, cases of sertraline-associated liver injury have been documented; however, the possible mechanism of sertraline-associated hepatotoxicity is entirely unknown. Here, we report that mitochondrial impairment may play an important role in liver injury induced by sertraline. In mitochondria isolated from rat liver, sertraline uncoupled mitochondrial oxidative phosphorylation and inhibited the activities of oxidative phosphorylation complexes I and V. Additionally, sertraline induced Ca2+-mediated mitochondrial permeability transition (MPT), and the induction was prevented by bongkrekic acid (BA), a specific MPT inhibitor targeting adenine nucleotide translocator (ANT), implying that the MPT induction is mediated by ANT. In freshly isolated rat primary hepatocytes, sertraline rapidly depleted cellular adenosine triphosphate (ATP) and subsequently induced lactate dehydrogenase leakage; both were attenuated by BA. Our results, including ATP depletion, induction of MPT, inhibition of mitochondrial respiration complexes, and uncoupling oxidative phosphorylation, indicate that sertraline-associated liver toxicity is possibly via mitochondrial dysfunction.
C1 [Couch, Letha; Fang, Jia-Long; Guo, Lei] US FDA, Div Biochem Toxicol, NCTR, Jefferson, AR 72079 USA.
[Li, Yan] US FDA, Div Genet & Mol Toxicol, NCTR, Jefferson, AR 72079 USA.
[Higuchi, Masahiro] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA.
RP Guo, L (reprint author), US FDA, Div Biochem Toxicol, NCTR, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM lei.guo@fda.hhs.gov
RI Li, Yan/F-9560-2012; Li, Yan/G-5158-2012
FU National Center for Toxicological Research
FX Y.L. was supported by the appointment to the Postgraduate Research
Program at the National Center for Toxicological Research administered
by Oak Ridge Institute for Science Education through an interagency
agreement between the U.S. Department of Energy and the U.S. FDA.
NR 55
TC 27
Z9 28
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD JUN
PY 2012
VL 127
IS 2
BP 582
EP 591
DI 10.1093/toxsci/kfs100
PG 10
WC Toxicology
SC Toxicology
GA 944JY
UT WOS:000304198400024
PM 22387747
ER
PT J
AU Moro, PL
Arana, J
Cano, M
Menschik, D
Yue, X
Lewis, P
Haber, P
Martin, D
Broder, K
AF Moro, Pedro L.
Arana, Jorge
Cano, Maria
Menschik, David
Yue, Xin
Lewis, Paige
Haber, Penina
Martin, David
Broder, Karen
TI Postlicensure Safety Surveillance for High-Dose Trivalent Inactivated
Influenza Vaccine in the Vaccine Adverse Event Reporting System, 1 July
2010-31 December 2010
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID GUILLAIN-BARRE-SYNDROME; OCULORESPIRATORY SYNDROME; IMMUNIZATION; RISK;
IMMUNOGENICITY; COLLECTION; RECURRENCE; GUIDELINES; TRIAL
AB Background. In December 2009, a new high-dose, trivalent, inactivated influenza vaccine (TIV-HD) was licensed for adults aged >= 65 years. We characterized clinical patterns of reports to the Vaccine Adverse Event Reporting System (VAERS) among older adults who received TIV-HD.
Methods. We searched VAERS for reports involving persons aged >= 65 years who received TIV-HD or TIV (standard dose) from 1 July 2010 through 31 December 2010. Medical records were requested for serious reports (ie, those associated with death, hospitalization or prolonged hospitalization, life-threatening illness, or disability). Clinicians reviewed information and assigned a diagnostic category to each report. Empirical Bayesian data mining was used to identify disproportional reporting following TIV-HD in VAERS. Reporting rates were calculated for reports of Guillain-Barre syndrome and anaphylaxis.
Results. VAERS received 606 reports after TIV-HD in persons aged >= 65 years (8.2% of reports involved serious events). The number of reports yielded by searches using the terms "ocular hyperemia" and "vomiting" exceeded the data mining threshold; > 80% of these reports were nonserious. Clinical review of serious reports found that a greater proportion involving gastrointestinal events were made after TIV-HD receipt (5 of 51 [9.8%]) than after TIV receipt (1 of 123 [0.8%]). Four persons who received TIV-HD had gastroenteritis, and 1 had multiple gastrointestinal symptoms; all recovered. A higher proportion of cardiac events were noted after receipt of TIV-HD (9 of 51 [17.6%]) than after receipt of TIV (6 of 123 [4.9%]). No concerning clinical pattern was apparent. The reporting rates of Guillain-Barre syndrome and anaphylaxis after TIV-HD receipt were 1.4 and 1.0 reports per million doses distributed, respectively.
Conclusions. During the first year after US licensure of TIV-HD, no new serious safety concerns were identified in VAERS. Our analyses suggested a clinically important imbalance between the reported and expected number of gastrointestinal events after TIV-HD receipt. Future studies should assess this potential association.
C1 [Moro, Pedro L.; Arana, Jorge; Cano, Maria; Yue, Xin; Lewis, Paige; Haber, Penina; Broder, Karen] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Healthcare Qual Promot, Immunizat Safety Off, Atlanta, GA 30333 USA.
[Menschik, David; Martin, David] Food & Drug Adm, Ctr Biol Evaluat & Res, Off Biostatist & Epidemiol, Rockville, MD USA.
RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Div Healthcare Qual Promot, Immunizat Safety Off, 1600 Clifton Rd,NE,MS-D26, Atlanta, GA 30333 USA.
EM psm9@cdc.gov
NR 24
TC 5
Z9 5
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2012
VL 54
IS 11
BP 1608
EP 1614
DI 10.1093/cid/cis256
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 942MO
UT WOS:000304048400014
PM 22441652
ER
PT J
AU Pouillot, R
Hoelzer, K
Jackson, KA
Henao, OL
Silk, BJ
AF Pouillot, Regis
Hoelzer, Karin
Jackson, Kelly A.
Henao, Olga L.
Silk, Benjamin J.
TI Relative Risk of Listeriosis in Foodborne Diseases Active Surveillance
Network (FoodNet) Sites According to Age, Pregnancy, and Ethnicity
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID ENGLAND; WALES
AB Background. Quantitative estimates of the relative risk (RR) of listeriosis among higher-risk populations and a nuanced understanding of the age-specific risks are crucial for risk assessments, targeted interventions, and policy decisions.
Method. The RR of invasive listeriosis was evaluated by age, pregnancy status, and ethnicity using 2004-2009 data from the Foodborne Diseases Active Surveillance Network (FoodNet). Nonparametric logistic regression was used to characterize changes in risk with age and ethnicity. Adjusted RRs and 95% confidence intervals (CIs) were evaluated using negative binomial generalized linear models.
Results. Among non-pregnancy-associated cases, listeriosis incidence rates increased gradually with age (45-59 years: RR, 4.7; 95% CI, 3.3-6.8; > 85 years: RR, 53.8; 95% CI, 37.3-78.9; reference: 15-44 years). The RR was significantly higher for Hispanics than for non-Hispanics (RR, 1.8; 95% CI, 1.3-2.5). Among women of reproductive age (15-44 years), pregnant women had a markedly higher listeriosis risk (RR, 114.6; 95% CI, 68.9-205.1) than nonpregnant women. The RR was higher for Hispanic than non-Hispanic women, regardless of pregnancy status, and this increased during the study period (2004-2006: RR, 1.9; 95% CI, 1.0-3.3; 2007-2009: RR, 4.8; 95% CI, 3.1-7.1).
Conclusions. This study quantifies the increases in risk of listeriosis among older persons, pregnant women, and Hispanics in the United States. Additional research is needed to better describe the independent effects of age on risk while accounting for underlying conditions. These estimates are needed both to optimize risk assessment models and to inform targeted interventions and policy decisions.
C1 [Pouillot, Regis; Hoelzer, Karin] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Jackson, Kelly A.; Henao, Olga L.; Silk, Benjamin J.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
RP Pouillot, R (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM regis.pouillot@fda.hhs.gov
RI Pouillot, Regis/E-8103-2010
OI Pouillot, Regis/0000-0002-6107-5212
FU US Department of Energy; US Food and Drug Administration; Division of
Foodborne, Waterborne; Environmental Diseases of the National Center for
Emerging and Zoonotic Infectious Diseases from the Centers for Disease
Control and Prevention; Association of Public Health Laboratories
FX This work was supported in part by appointments to the Research
Participation Program at the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the US Department of
Energy and the US Food and Drug Administration.; This article was
published as part of a supplement entitled "Studies From the Foodborne
Diseases Active Surveillance Network,'' sponsored by the Division of
Foodborne, Waterborne, and Environmental Diseases of the National Center
for Emerging and Zoonotic Infectious Diseases from the Centers for
Disease Control and Prevention, and the Association of Public Health
Laboratories.
NR 25
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U1 0
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2012
VL 54
SU 5
BP S405
EP S410
DI 10.1093/cid/cis269
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 942NJ
UT WOS:000304050900005
PM 22572661
ER
PT J
AU Shiferaw, B
Verrill, L
Booth, H
Zansky, SM
Norton, DM
Crim, S
Henao, OL
AF Shiferaw, Beletshachew
Verrill, Linda
Booth, Hillary
Zansky, Shelley M.
Norton, Dawn M.
Crim, Stacy
Henao, Olga L.
TI Sex-Based Differences in Food Consumption: Foodborne Diseases Active
Surveillance Network (FoodNet) Population Survey, 2006-2007
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID GENDER-DIFFERENCES; VEGETABLE CONSUMPTION; FRUIT; METAANALYSIS;
KNOWLEDGE; STUDENTS; BELIEFS
AB Background. This analysis used data from the most recent Foodborne Diseases Active Surveillance Network (FoodNet) Population Survey (May 2006 through April 2007) to examine differences in the consumption of various types of foods between men and women.
Methods. Participants were surveyed by telephone and asked whether or not they had consumed certain foods in the past 7 days, including the following "high-risk" foods commonly associated with foodborne illness: pink hamburger, raw oysters, unpasteurized milk, cheese made from unpasteurized milk, runny eggs, and alfalfa sprouts. Data were weighted to adjust for survey design and to reflect the age and sex distribution of the population under FoodNet surveillance.
Results. A total of 14 878 persons >= 18 years were interviewed, of whom 5688 (38%) were men. A higher proportion of men reported eating meat and certain types of poultry than women, whereas a higher proportion of women ate fruits and vegetables. A higher proportion of men than women reported consuming runny eggs (12% versus 8%), pink hamburger (7% versus 4%), and raw oysters (2% versus 0.4%). A higher proportion of women than men ate alfalfa sprouts (3% versus 2%). No differences by sex were observed for consumption of unpasteurized milk or cheese.
Conclusions. Data from the FoodNet Population Surveys can be useful in efforts to design targeted interventions regarding consumption of high-risk foods. Moreover, understanding the background rates of food consumption, stratified by sex, may help investigators identify the kinds of foods likely to be associated with outbreaks in which a preponderance of cases occur among members of one sex.
C1 [Shiferaw, Beletshachew; Booth, Hillary] Oregon Publ Hlth Div, Off Dis Prevent & Epidemiol, Portland, OR 97232 USA.
[Verrill, Linda] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Zansky, Shelley M.] New York State Dept Hlth, Albany, NY 12237 USA.
[Norton, Dawn M.] Calif Emerging Infect Program, Oakland, CA USA.
[Crim, Stacy; Henao, Olga L.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Shiferaw, B (reprint author), Oregon Publ Hlth Div, Off Dis Prevent & Epidemiol, 800 NE Oregon St,Ste 772, Portland, OR 97232 USA.
EM beletshachew.shiferaw@state.or.us
FU Centers for Disease Control and Prevention (CDC) [U60/CD303019]; Food
Safety Office; Department of Agriculture Food Safety and Inspection
Service; Food and Drug Administration; Division of Foodborne,
Waterborne; Environmental Diseases of the National Center for Emerging
and Zoonotic Infectious Diseases from the Centers for Disease Control
and Prevention; Association of Public Health Laboratories
FX This work was supported in part by the Centers for Disease Control and
Prevention (CDC; Cooperative Agreement U60/CD303019). FoodNet is funded
by the Food Safety Office and the Emerging Infections Program of the
CDC, the Department of Agriculture Food Safety and Inspection Service,
and the Food and Drug Administration.; This article was published as
part of a supplement entitled "Studies From the Foodborne Diseases
Active Surveillance Network,'' sponsored by the Division of Foodborne,
Waterborne, and Environmental Diseases of the National Center for
Emerging and Zoonotic Infectious Diseases from the Centers for Disease
Control and Prevention, and the Association of Public Health
Laboratories.
NR 16
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U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUN 1
PY 2012
VL 54
SU 5
BP S453
EP S457
DI 10.1093/cid/cis247
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 942NJ
UT WOS:000304050900013
PM 22572669
ER
PT J
AU Silk, BJ
Date, KA
Jackson, KA
Pouillot, R
Holt, KG
Graves, LM
Ong, KL
Hurd, S
Meyer, R
Marcus, R
Shiferaw, B
Norton, DM
Medus, C
Zansky, SM
Cronquist, AB
Henao, OL
Jones, TF
Vugia, DJ
Farley, MM
Mahon, BE
AF Silk, Benjamin J.
Date, Kashmira A.
Jackson, Kelly A.
Pouillot, Regis
Holt, Kristin G.
Graves, Lewis M.
Ong, Kanyin L.
Hurd, Sharon
Meyer, Rebecca
Marcus, Ruthanne
Shiferaw, Beletshachew
Norton, Dawn M.
Medus, Carlota
Zansky, Shelley M.
Cronquist, Alicia B.
Henao, Olga L.
Jones, Timothy F.
Vugia, Duc J.
Farley, Monica M.
Mahon, Barbara E.
TI Invasive Listeriosis in the Foodborne Diseases Active Surveillance
Network (FoodNet), 2004-2009: Further Targeted Prevention Needed for
Higher-Risk Groups
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID MEXICAN-STYLE CHEESE; MULTISTATE OUTBREAK; UNITED-STATES; EPIDEMIC
LISTERIOSIS; HANDLING BEHAVIORS; SAFETY; MONOCYTOGENES; MEAT;
PERCEPTIONS; CONSUMPTION
AB Background. Listeriosis can cause severe disease, especially in fetuses, neonates, older adults, and persons with certain immunocompromising and chronic conditions. We summarize US population-based surveillance data for invasive listeriosis from 2004 through 2009.
Methods. We analyzed Foodborne Diseases Active Surveillance Network (FoodNet) data for patients with Listeria monocytogenes isolated from normally sterile sites. We describe the epidemiology of listeriosis, estimate overall and specific incidence rates, and compare pregnancy-associated and nonpregnancy-associated listeriosis by age and ethnicity.
Results. A total of 762 listeriosis cases were identified during the 6-year reporting period, including 126 pregnancy-associated cases (17%), 234 nonpregnancy-associated cases(31%) in patients aged < 65 years, and 400 nonpregnancy-associated cases (53%) in patients aged >= 65 years. Eighteen percent of all cases were fatal. Meningitis was diagnosed in 44% of neonates. For 2004-2009, the overall annual incidence of listeriosis varied from 0.25 to 0.32 cases per 100 000 population. Among Hispanic women, the crude incidence of pregnancy-associated listeriosis increased from 5.09 to 12.37 cases per 100 000 for the periods of 2004-2006 and 2007-2009, respectively; among non-Hispanic women, pregnancy-associated listeriosis increased from 1.74 to 2.80 cases per 100 000 for the same periods. Incidence rates of nonpregnancy-associated listeriosis in patients aged >= 65 years were 4-5 times greater than overall rates annually.
Conclusions. Overall listeriosis incidence did not change significantly from 2004 through 2009. Further targeted prevention is needed, including food safety education and messaging (eg, avoiding Mexican-style cheese during pregnancy). Effective prevention among pregnant women, especially Hispanics, and older adults would substantially affect overall rates.
C1 [Date, Kashmira A.] Ctr Dis Control & Prevent Atlanta, Global Immunizat Div, Atlanta, GA USA.
[Holt, Kristin G.] US Dept Agr Washington, Food Safety & Inspect Serv, Washington, DC USA.
[Meyer, Rebecca] Emory Univ, Georgia Dept Publ Hlth, Atlanta, GA 30322 USA.
[Farley, Monica M.] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Farley, Monica M.] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA.
[Pouillot, Regis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Hurd, Sharon] Yale Univ, Connecticut Emerging Infect Program, New Haven, CT USA.
[Marcus, Ruthanne] Yale Univ, Sch Med, New Haven, CT USA.
[Shiferaw, Beletshachew] Oregon Dept Human Serv, Portland, OR USA.
[Norton, Dawn M.] Calif Emerging Infect Program, Oakland, CA USA.
[Vugia, Duc J.] Calif Dept Publ Hlth, Richmond, CA USA.
[Medus, Carlota] Minnesota Dept Hlth, St Paul, MN USA.
[Zansky, Shelley M.] New York State Dept Hlth, Albany, NY 12237 USA.
[Cronquist, Alicia B.] Colorado Dept Publ Hlth & Environm, Denver, CO USA.
[Jones, Timothy F.] Tennessee Dept Hlth, Nashville, TN USA.
[Silk, Benjamin J.; Jackson, Kelly A.; Graves, Lewis M.; Ong, Kanyin L.; Henao, Olga L.; Mahon, Barbara E.] Ctr Dis Control & Prevent Atlanta, Div Foodborne Waterborne & Environm Dis, Atlanta, GA USA.
RP Silk, BJ (reprint author), 1600 Clifton Rd,MS C-09, Atlanta, GA 30333 USA.
EM bsilk@cdc.gov
RI Pouillot, Regis/E-8103-2010
OI Pouillot, Regis/0000-0002-6107-5212
FU Centers for Disease Control and Prevention (CDC) [U60/CD303019]; Food
Safety Office; US Department of Agriculture Food Safety and Inspection
Service; Food and Drug Administration; Division of Foodborne,
Waterborne; Environmental Diseases of the National Center for Emerging
and Zoonotic Infectious Diseases from the Centers for Disease Control
and Prevention; Association of Public Health Laboratories
FX This publication was supported in part by the Centers for Disease
Control and Prevention (CDC; Cooperative Agreement U60/CD303019).
FoodNet is funded by the Food Safety Office and the Emerging Infections
Program of CDC, the US Department of Agriculture Food Safety and
Inspection Service, and the Food and Drug Administration.; This article
was published as part of a supplement entitled "Studies From the
Foodborne Diseases Active Surveillance Network,'' sponsored by the
Division of Foodborne, Waterborne, and Environmental Diseases of the
National Center for Emerging and Zoonotic Infectious Diseases from the
Centers for Disease Control and Prevention, and the Association of
Public Health Laboratories.
NR 38
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U1 3
U2 21
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 JUN 1
PY 2012
VL 54
SU 5
BP S396
EP S404
DI 10.1093/cid/cis268
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 942NJ
UT WOS:000304050900004
PM 22572660
ER
PT J
AU Yoshitomi, KJ
Zapata, R
Jinneman, KC
Weagant, SD
Fedio, W
AF Yoshitomi, K. J.
Zapata, R.
Jinneman, K. C.
Weagant, S. D.
Fedio, W.
TI Recovery of E. coli O157 strains after exposure to acidification at pH 2
SO LETTERS IN APPLIED MICROBIOLOGY
LA English
DT Article
DE acid environment; Escherichia coli; EHEC; Enterohaemorrhagic;
microflora; O157:H7
ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; ACID RESISTANCE;
IMMUNOMAGNETIC-SEPARATION; ALFALFA SPROUTS; GROUND-BEEF; ENRICHMENT;
TOLERANCE; SAMPLES; GROWTH; ENVIRONMENT
AB Aims: Rapid detection and selective isolation of E.similar to coli O157:H7 strains have been difficult owing to the potential interference from background microflora present in high background food matrices. To help selectively isolate E.coli O157H7 strains, a useful plating technique that involved acidifying the cultures to pH 2 was evaluated with a large number of E.coli O157:H7 strains to ensure response to treatment was consistent across strains. Methods and Results: Escherichia coli O157, 46 strains including ATCC 35150, were acidified to pH 2 following enrichment and plated onto Tryptic Soy Agar + 0.6% Yeast Extract (TSA-YE) and Sorbitol MacConkey Agar + cefixime and tellurite (CT-SMAC). Samples were enumerated and modest decreases in plate counts were observed on TSA-YE media, with a greater reduction observed on CT-SMAC. Conclusions: The acid-resistant character of E.coli O157:H7 is a consistent trait and may be used for improved isolation of the organism from mixed cultures. Significance and Impact of the Study: There was little difference observed between the commonly used laboratory strain E.coli O157:H7 35150 and 45 other strains of E.coli O157 when subjected to acidifying conditions prior to plating, demonstrating that an acid rinse procedure was equally effective across a wide variety of E.coli O157 strains and broadly applicable for isolating unknown strains from food samples.
C1 [Zapata, R.; Fedio, W.] New Mexico State Univ, Food Safety Lab, Las Cruces, NM 88003 USA.
[Yoshitomi, K. J.; Jinneman, K. C.] US FDA, Bothell, WA USA.
[Weagant, S. D.] Weagant Consulting, Poulsbo, WA USA.
RP Fedio, W (reprint author), New Mexico State Univ, Food Safety Lab, POB 30003,MSC 3BF, Las Cruces, NM 88003 USA.
EM wfedio@nmsu.edu
NR 33
TC 3
Z9 4
U1 2
U2 15
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0266-8254
J9 LETT APPL MICROBIOL
JI Lett. Appl. Microbiol.
PD JUN
PY 2012
VL 54
IS 6
BP 499
EP 503
DI 10.1111/j.1472-765X.2012.03250.x
PG 5
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 940UF
UT WOS:000303917900003
PM 22486412
ER
PT J
AU Dal Pan, GJ
AF Dal Pan, Gerald J.
TI Communicating the Risks of Medicines Time to Move Forward
SO MEDICAL CARE
LA English
DT Editorial Material
C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Dal Pan, GJ (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM gerald.dalpan@fda.hhs.gov
NR 5
TC 8
Z9 8
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0025-7079
J9 MED CARE
JI Med. Care
PD JUN
PY 2012
VL 50
IS 6
BP 463
EP 465
DI 10.1097/MLR.0b013e31825852f0
PG 3
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 941ST
UT WOS:000303985900001
PM 22581011
ER
PT J
AU Luccioli, S
AF Luccioli, Stefano
TI Food allergy guidelines and assessing allergic reaction risks: a
regulatory perspective
SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE allergen hazard management; food allergic reaction; oral challenge;
regulatory; risk assessment
ID QUALITY-OF-LIFE; PEANUT ALLERGY; DOUBLE-BLIND; NUT ALLERGY; UNDECLARED
ALLERGENS; CHILDREN; CHALLENGES; ANAPHYLAXIS; IGE; MANAGEMENT
AB Purpose of review
To review information in food allergy guidelines and the literature on assessing and understanding food allergic reaction risks.
Recent findings
Current food allergy guidelines have focused on tools for better diagnosis of food allergy and treatment of reactions. These guidelines have not addressed the growing body of literature on risk assessment and diagnostic tools being used to assess dose-response relationships in relation to food-allergen exposures. The literature includes substantial data from food-allergen challenges performed in sensitive individuals, and probabilistic modeling of these data may help to elucidate the relationship between allergen dose exposures, including thresholds, and reaction risk in allergic individuals. Understanding this relationship has potential to improve the health-related quality of life of allergic consumers.
Summary
Recent findings in the literature have highlighted improved diagnostic tools and other information that can be used to assess risks for allergic reaction to low-dose allergen exposures (thresholds) and reaction severity in food allergic consumers. Recommendations to better define and stratify allergic reaction risks for consumers could be adopted into guidelines for the diagnosis and clinical management of food allergy.
C1 US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Luccioli, S (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 200, College Pk, MD 20740 USA.
EM Stefano.Luccioli@fda.hhs.gov
NR 59
TC 8
Z9 8
U1 3
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1528-4050
J9 CURR OPIN ALLERGY CL
JI Curr. Opin. Allergy Clin. Immunol.
PD JUN
PY 2012
VL 12
IS 3
BP 323
EP 330
DI 10.1097/ACI.0b013e3283535aaf
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 933TJ
UT WOS:000303385300016
PM 22508192
ER
PT J
AU Yemelyanau, M
Amialchuk, A
Ali, MM
AF Yemelyanau, Maksim
Amialchuk, Aliaksandr
Ali, Mir M.
TI Evidence from the Chernobyl Nuclear Accident: The Effect on Health,
Education, and Labor Market Outcomes in Belarus (vol 33, pg 1, 2012)
SO JOURNAL OF LABOR RESEARCH
LA English
DT Correction
C1 [Amialchuk, Aliaksandr] Univ Toledo, Dept Econ, Toledo, OH 43606 USA.
[Yemelyanau, Maksim] CERGE EI, Prague 11121, Czech Republic.
[Ali, Mir M.] Univ Toledo, Dept Econ, College Pk, MD 20740 USA.
[Ali, Mir M.] US FDA, Off Regulat Policy & Social Sci, College Pk, MD 20740 USA.
RP Amialchuk, A (reprint author), Univ Toledo, Dept Econ, 2801 W Bancroft St, Toledo, OH 43606 USA.
EM maksim.yemelyanau@gmail.com; aamialc@utnet.utoledo.edu;
mir.ali@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 0
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0195-3613
J9 J LABOR RES
JI J. Labor Res.
PD JUN
PY 2012
VL 33
IS 2
BP 283
EP 283
DI 10.1007/s12122-012-9131-3
PG 1
WC Industrial Relations & Labor
SC Business & Economics
GA 935HZ
UT WOS:000303511100007
ER
PT J
AU Kumar, G
Waters, MS
Farooque, TM
Young, MF
Simon, CG
AF Kumar, Girish
Waters, Michael S.
Farooque, Tanya M.
Young, Marian F.
Simon, Carl G., Jr.
TI Freeform fabricated scaffolds with roughened struts that enhance both
stem cell proliferation and differentiation by controlling cell shape
SO BIOMATERIALS
LA English
DT Article
DE Cell proliferation; Cell spreading; Osteogenesis; Scaffold; Topography;
Stem cell
ID PROTEIN ADSORPTION; BONE REGENERATION; ARCHITECTURE; INTERFACE; BACTERIA
AB We demonstrate that freeform fabricated (FFF) scaffolds with a roughened surface topography can support hBMSC proliferation, while also inducing osteogenic differentiation, for maximized generation of calcified, bone-like tissue. Previously, hBMSCs rapidly proliferated, without osteogenic differentiation, during culture in FFF scaffolds. In contrast, hBMSCs underwent osteogenic differentiation, with slow proliferation, during culture in nanofiber scaffolds. Analysis of cell morphology showed that the topography presented by the nanofiber scaffolds drove hBMSC differentiation by guiding them into a morphology that induced osteogenic differentiation. Herein, we hypothesized that using the high-surface area architecture of FFF scaffolds to present a surface roughness that drives hBMSCs into a morphology that induces osteogenic differentiation would yield a maximum amount differentiated hBMSCs and bone-like tissue. Thus, a solvent etching method was developed that imparted a 5-fold increase in roughness to the surface of the struts of poly(epsilon-caprolactone) (PCL) FFF scaffolds. The etched scaffolds induced osteogenic differentiation of the hBMSCs while un-etched scaffolds did not. The etched scaffolds also supported the same high levels of hBMSC proliferation that un-etched scaffolds supported. Finally, hBMSCs on un-etched scaffolds had a large spread area, while hBMSCs on etched scaffolds has a smaller area and were more rounded, indicating that the surface roughness from the etched scaffolds dictated the morphology of the hBMSCs. The results demonstrate that FFF scaffolds with surface roughness can support hBMSC proliferation, while also inducing osteogenic differentiation, to maximize generation of calcified tissue. This work validates a rational approach to scaffold fabrication where the structure of the scaffold was designed to optimize stem cell function by controlling cell morphology. Published by Elsevier Ltd.
C1 [Kumar, Girish; Waters, Michael S.; Farooque, Tanya M.; Simon, Carl G., Jr.] NIST, Div Polymers, Gaithersburg, MD 20899 USA.
[Kumar, Girish; Young, Marian F.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA.
[Kumar, Girish] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Simon, CG (reprint author), NIST, Div Polymers, 100 Bur Dr, Gaithersburg, MD 20899 USA.
EM carl.simon@nist.gov
FU NIH-NIBIB/NIST NRC; NIST-ARRA NRC; NIST; NIH/NIDCR (National Institute
of Dental and Craniofacial Research); Tulane Center for Gene Therapy
through NCRR of the NIH [P40RR017447]
FX G.K., M.S.W. and T.M.F. were supported by postdoctoral fellowships from
NIH-NIBIB/NIST NRC, NIST-ARRA NRC and NIST-ARRA NRC, respectively. This
work was supported by NIST and the Intramural Program of the NIH/NIDCR
(National Institute of Dental and Craniofacial Research). The hBMSCs
employed in this work were provided by the Tulane Center for Gene
Therapy through a grant from NCRR of the NIH P40RR017447. The "standard
deviation" (S.D.) is the same as the "combined standard uncertainty of
the mean" for the purposes of this work. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of NIH, NIBIB, NIDCR or NIST. This article, a
contribution of NIST, is not subject to US copyright. Certain equipment
and instruments or materials are identified in the paper to adequately
specify the experimental details. Such identification does not imply
recommendation by NIST, nor does it imply the materials are necessarily
the best available for the purpose.
NR 33
TC 42
Z9 43
U1 1
U2 22
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD JUN
PY 2012
VL 33
IS 16
BP 4022
EP 4030
DI 10.1016/j.biomaterials.2012.02.048
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 929WL
UT WOS:000303096300002
PM 22417619
ER
PT J
AU Bennett, EP
Mandel, U
Clausen, H
Gerken, TA
Fritz, TA
Tabak, LA
AF Bennett, Eric P.
Mandel, Ulla
Clausen, Henrik
Gerken, Thomas A.
Fritz, Timothy A.
Tabak, Lawrence A.
TI Control of mucin-type O-glycosylation: A classification of the
polypeptide GalNAc-transferase gene family
SO GLYCOBIOLOGY
LA English
DT Review
DE GalNAc-T; GalNAc-transferase; GALNT; monoclonal antibodies;
O-glycoproteins; O-glycosylation
ID ALPHA-D-GALACTOSAMINE; N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY;
ACETYL-D-GALACTOSAMINE; FIBROBLAST GROWTH-FACTORS; WHOLE-GENOME
DUPLICATION; CORONARY-ARTERY-DISEASE; BREAST-CANCER CELLS; BOVINE
UDP-GALNAC; TUMORAL CALCINOSIS; LINKED GLYCOSYLATION
AB Glycosylation of proteins is an essential process in all eukaryotes and a great diversity in types of protein glycosylation exists in animals, plants and microorganisms. Mucin-type O-glycosylation, consisting of glycans attached via O-linked N-acetylgalactosamine (GalNAc) to serine and threonine residues, is one of the most abundant forms of protein glycosylation in animals. Although most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for the initiation of glycosylation, i.e. the step where the first glycan is attached to the relevant amino acid residue in the protein, mucin-type O-glycosylation is controlled by a large family of up to 20 homologous genes encoding UDP-GalNAc:polypeptide GalNAc-transferases (GalNAc-Ts) (EC 2.4.1.41). Therefore, mucin-type O-glycosylation has the greatest potential for differential regulation in cells and tissues. The GalNAc-T family is the largest glycosyltransferase enzyme family covering a single known glycosidic linkage and it is highly conserved throughout animal evolution, although absent in bacteria, yeast and plants. Emerging studies have shown that the large number of genes (GALNTs) in the GalNAc-T family do not provide full functional redundancy and single GalNAc-T genes have been shown to be important in both animals and human. Here, we present an overview of the GalNAc-T gene family in animals and propose a classification of the genes into subfamilies, which appear to be conserved in evolution structurally as well as functionally.
C1 [Bennett, Eric P.; Mandel, Ulla] Univ Copenhagen, Copenhagen Ctr Glyc, Dept Odontol, DK-2200 Copenhagen N, Denmark.
[Clausen, Henrik] Univ Copenhagen, Copenhagen Ctr Glyc, Dept Cellular & Mol Med, DK-2200 Copenhagen N, Denmark.
[Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Chem, Cleveland, OH 44106 USA.
[Fritz, Timothy A.] US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Vaccines & Related Prod Applicat, Rockville, MD 20852 USA.
[Tabak, Lawrence A.] Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv, Sect Biol Chem, NIH, Bethesda, MD 20892 USA.
RP Bennett, EP (reprint author), Univ Copenhagen, Copenhagen Ctr Glyc, Dept Odontol, Norre Alle 20, DK-2200 Copenhagen N, Denmark.
EM epb@sund.ku.dk
OI Bennett, Eric Paul/0000-0002-4976-0647
FU University of Copenhagen; Danish Research councils; Carlsberg Foundation
FX This work was supported by funds from the University of Copenhagen
(Excellence program), Danish Research councils and the Carlsberg
Foundation.
NR 181
TC 168
Z9 170
U1 7
U2 66
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD JUN
PY 2012
VL 22
IS 6
BP 736
EP 756
DI 10.1093/glycob/cwr182
PG 21
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 933BO
UT WOS:000303334400001
PM 22183981
ER
PT J
AU Zou, P
Yu, YK
Zheng, N
Yang, YS
Paholak, HJ
Yu, LX
Sun, DX
AF Zou, Peng
Yu, Yanke
Zheng, Nan
Yang, Yongsheng
Paholak, Hayley J.
Yu, Lawrence X.
Sun, Duxin
TI Applications of Human Pharmacokinetic Prediction in First-in-Human Dose
Estimation
SO AAPS JOURNAL
LA English
DT Review
DE allometric scaling; FIH dose; in vitro-in vivo correlations;
pharmacokinetics; prediction
ID HUMAN DRUG CLEARANCE; HEPATIC METABOLIC-CLEARANCE; IN-VITRO DATA;
CRYOPRESERVED HUMAN HEPATOCYTES; HUMAN LIVER-MICROSOMES; HUMAN ORAL
BIOAVAILABILITY; MEMBRANE PERMEATION ASSAY; INTRINSIC CLEARANCE;
PHASE-I; VERTICAL ALLOMETRY
AB Quantitative estimations of first-in-human (FIH) doses are critical for phase I clinical trials in drug development. Human pharmacokinetic (PK) prediction methods have been developed to project the human clearance (CL) and bioavailability with reasonable accuracy, which facilitates estimation of a safe yet efficacious FIH dose. However, the FIH dose estimation is still very challenging and complex. The aim of this article is to review the common approaches for FIH dose estimation with an emphasis on PK-guided estimation. We discuss 5 methods for FIH dose estimation, 17 approaches for the prediction of human CL, 6 methods for the prediction of bioavailability, and 3 tools for the prediction of PK profiles. This review may serve as a practical protocol for PK- or pharmacokinetic/pharmacodynamic-guided estimation of the FIH dose.
C1 [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA.
[Yang, Yongsheng] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Silver Spring, MD 20993 USA.
[Zou, Peng; Yu, Yanke; Zheng, Nan; Paholak, Hayley J.; Sun, Duxin] Univ Michigan, Coll Pharm, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA.
RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA.
EM Lawrence.Yu@fda.hhs.gov; duxins@umich.edu
RI Yu, Yanke/E-4919-2012; Zou, Peng/J-9300-2015; Yu, Lawrence/L-6280-2016
FU National Institutes of Health [RO1 CA120023]; University of Michigan
Cancer Center
FX This work was partially supported by the National Institutes of Health
(RO1 CA120023); University of Michigan Cancer Center Research Grant
(Munn); and University of Michigan Cancer Center Core Grant to DS.
NR 99
TC 14
Z9 15
U1 1
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD JUN
PY 2012
VL 14
IS 2
BP 262
EP 281
DI 10.1208/s12248-012-9332-y
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 926EU
UT WOS:000302814900013
PM 22407287
ER
PT J
AU Chiesa, OA
Li, H
Kijak, PJ
Li, JX
Lancaster, V
Smith, ML
Heller, DN
Thomas, MH
von Bredow, J
AF Chiesa, O. A.
Li, H.
Kijak, P. J.
Li, J. X.
Lancaster, V.
Smith, M. L.
Heller, D. N.
Thomas, M. H.
von Bredow, J.
TI Tissue/fluid correlation study for the depletion of sulfadimethoxine in
bovine kidney, liver, plasma, urine, and oral fluid
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID STANDING ANIMALS; BIOPSY SAMPLES; PHARMACOKINETIC MODEL; LC/MS/MS
MEASUREMENT; RESIDUES; CATTLE; PENICILLIN; STEERS; PREDICTION;
GENTAMICIN
AB Sulfonamides are among the oldest, but still effective, antimicrobial veterinary medicines. In steers and dairy cows, the sulfonamides are effective in the treatment of respiratory disease and general infections. Sulfadimethoxine (SDM) has been approved by US Food and Drug Administration (FDA) for use in steers and dairy cows with a tolerance of 100 ng/g (ppb) in edible tissues and 10 ppb in milk. The detection of SDM residue above tolerance in the animal slaughtered for food process will result in the whole carcass being discarded. This report describes a comprehensive depletion study of SDM (and its main metabolite) in plasma, urine, oral fluid, kidney, and liver. In this study, nine steers were injected intravenously with the approved dose of SDM; the loading dose was 55 mg/kg, followed by 27.5 mg/kg dose at 24 h and again at 48 h. Fluids (blood, urine, and saliva) and tissue (liver and kidney) samples were collected at intervals after the last dose of SMD. The combination of laparoscopic serial sampling technique with the liquid chromatography/mass spectrometry method provided the data to establish the tissue/fluid correlation in the depletion of SMD. A strong correlation and linearity of the log-scale concentration over time in the depletion stage has been confirmed for kidney, liver, and plasma.
C1 [Chiesa, O. A.] US FDA, Ctr Vet Med, Res Off, Div Appl Vet Res, Laurel, MD 20708 USA.
[Li, H.; Kijak, P. J.; Smith, M. L.; Heller, D. N.; Thomas, M. H.; von Bredow, J.] US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA.
[Li, J. X.; Lancaster, V.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Sci Support, Rockville, MD 20857 USA.
RP Chiesa, OA (reprint author), US FDA, Ctr Vet Med, Res Off, Div Appl Vet Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
EM oscar.chiesa@fda.hhs.gov
NR 31
TC 2
Z9 2
U1 0
U2 14
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD JUN
PY 2012
VL 35
IS 3
BP 249
EP 258
DI 10.1111/j.1365-2885.2011.01327.x
PG 10
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 928RE
UT WOS:000302999900006
PM 21831115
ER
PT J
AU Hungerford, J
Wu, WH
AF Hungerford, James
Wu, Wen-Hsin
TI Comparison study of three rapid test kits for histamine in fish:
BiooScientific MaxSignal enzymatic assay, Neogen Veratox ELISA, and the
Neogen Reveal Histamine Screening test
SO FOOD CONTROL
LA English
DT Article
DE Scombroid; Histamine; ELISA; Enzymatic; Decomposition; Lateral flow
ID BIOGENIC-AMINES; RHIZOBIUM SP; DEHYDROGENASE; MUSCLE; WHITE
AB Two new test kits for quantifying histamine in fish are investigated and compared to the Neogen Veratox ELISA. One of the kits is based on selective enzymatic conversion of histamine by histamine dehydrogenase (MaxSignal, B100 Scientific, Austin, Texas) and the other is dipstick based on lateral flow immuno-chromatography (LFIC). These new kits are compared to Veratox using spiked and naturally contaminated fresh and frozen yellowfin tuna and mahi mahi, as well as canned mackerel in broth and canned tuna in oil and in broth. Histamine levels determined using the MaxSignal enzymatic kit in spiked and naturally contaminated fish were strongly correlated with levels detected with the Veratox ELISA. Comparing both new kits and also using the AOAC performance tested Veratox, spiking at 0 and 50 mg/kg, no false negatives or false positives were found over a wide range of concentrations of histamine. In contrast to competitive ELISA kits, which give a sigmoidal (logistics curve) color response that decreases with increasing analyte, the enzymatic kit gives a linear response, increasing with histamine concentration. Linearity is excellent and samples can be analyzed without further dilution using the included standards to quantify up to 70 mg/kg histamine free base. The 450 nm endpoint color develops rapidly, and using a reaction time of 30 min, recoveries in canned tuna and mackerel were greater than 90% and apparent histamine levels reach a plateau versus time. In contrast, recoveries using the manufacturer's recommended reaction time of 10 min were low, and further study supported the presence of naturally occurring inhibitors of histamine dehydrogenase in fish. Using an extended (30 min) reaction time, the enzymatic kit performed well and was still rapid. The simplicity of the procedure results in a kit more easily mastered and potentially more rugged than competitive ELISA assays, which require multiple incubations, a wash step, additional dilution steps, and twice as many pipetting steps. The LFIC kit Reveal was also found to be simpler and easier to use than ELISA kits, having only one critical pipetting step, requiring no acylation, and only minimal sample manipulation. If accelerated sample removal and grinding could be implemented and validated, the LFIC kit Reveal appears to have excellent potential for onsite testing. Published by Elsevier Ltd.
C1 [Hungerford, James; Wu, Wen-Hsin] FDA, Appl Technol Ctr, Pacific Reg Lab, Bothell, WA 98021 USA.
RP Hungerford, J (reprint author), FDA, Appl Technol Ctr, Pacific Reg Lab, 22201 23rd Dr SE, Bothell, WA 98021 USA.
EM James.Hungerford@fda.hhs.gov
NR 28
TC 8
Z9 9
U1 4
U2 24
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-7135
J9 FOOD CONTROL
JI Food Control
PD JUN
PY 2012
VL 25
IS 2
BP 448
EP 457
DI 10.1016/j.foodcont.2011.11.007
PG 10
WC Food Science & Technology
SC Food Science & Technology
GA 898JZ
UT WOS:000300740000004
ER
PT J
AU Sahu, SN
Lewis, J
Patel, I
Bozdag, S
Lee, JH
LeClerc, JE
Cinar, HN
AF Sahu, Surasri N.
Lewis, Jada
Patel, Isha
Bozdag, Serdar
Lee, Jeong H.
LeClerc, Joseph E.
Cinar, Hediye Nese
TI Genomic Analysis of Immune Response against Vibrio cholerae Hemolysin in
Caenorhabditis elegans
SO PLOS ONE
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; EL-TOR HEMOLYSIN; INNATE IMMUNITY; BACTERIAL
PATHOGENESIS; VIRULENCE FACTORS; CELL VACUOLATION; C-ELEGANS; GENES;
RECEPTOR; EXPRESSION
AB Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore-forming toxins (PFTs). V. cholerae infects and kills Caenorhabditis elegans via cholerae toxin independent manner. VCC is required for the lethality, growth retardation and intestinal cell vacuolation during the infection. However, little is known about the host gene expression responses against VCC. To address this question we performed a microarray study in C. elegans exposed to V. cholerae strains with intact and deleted hlyA genes. Many of the VCC regulated genes identified, including C-type lectins, Prion-like (glutamine [Q]/asparagine [N]-rich)-domain containing genes, genes regulated by insulin/IGF-1-mediated signaling (IIS) pathway, were previously reported as mediators of innate immune response against other bacteria in C. elegans. Protective function of the subset of the genes up-regulated by VCC was confirmed using RNAi. By means of a machine learning algorithm called FastMEDUSA, we identified several putative VCC induced immune regulatory transcriptional factors and transcription factor binding motifs. Our results suggest that VCC is a major virulence factor, which induces a wide variety of immune response-related genes during V. cholerae infection in C. elegans.
C1 [Sahu, Surasri N.; Lee, Jeong H.; Cinar, Hediye Nese] US FDA, Div Virulence Assessment, Laurel, MD USA.
[Lewis, Jada; Patel, Isha; LeClerc, Joseph E.] US FDA, Div Mol Biol, Laurel, MD USA.
[Bozdag, Serdar] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA.
[Sahu, Surasri N.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA.
[Lee, Jeong H.] Kyungpook Natl Univ, Taegu, South Korea.
RP Sahu, SN (reprint author), US FDA, Div Virulence Assessment, Laurel, MD USA.
EM hediye.cinar@fda.hhs.gov
NR 66
TC 16
Z9 16
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 31
PY 2012
VL 7
IS 5
AR e38200
DI 10.1371/journal.pone.0038200
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TY
UT WOS:000305338500108
PM 22675448
ER
PT J
AU Whitaker, M
Guo, J
Kehoe, T
Benson, G
AF Whitaker, Marcea
Guo, Jia
Kehoe, Theresa
Benson, George
TI Bisphosphonates for Osteoporosis - Where Do We Go from Here?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID FRACTURE; TRIAL; ALENDRONATE; EXTENSION; WOMEN; FLEX
C1 [Whitaker, Marcea; Kehoe, Theresa; Benson, George] US FDA, Div Reprod & Urol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Guo, Jia] US FDA, Div Biometr 3, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Whitaker, M (reprint author), US FDA, Div Reprod & Urol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
NR 5
TC 141
Z9 141
U1 3
U2 10
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD MAY 31
PY 2012
VL 366
IS 22
BP 2048
EP 2051
DI 10.1056/NEJMp1202619
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA 949YE
UT WOS:000304613400003
PM 22571168
ER
PT J
AU Choi, YS
Cho, S
Lee, C
Luu, HMD
Guo, J
AF Choi, Yong Soo
Cho, Seungil
Lee, Christina
Luu, Hoan My-Do
Guo, Ji
TI Contamination of ultrapure water with bisphenol A leached from
polysulfone ultrafilter
SO TALANTA
LA English
DT Article
DE Bisphenol A; Polysulfone; Ultrafilter; Ultrapure water; LC-MS
ID EXPOSURE
AB Ultrapure water produced by a water purification system is one of the most essential and widely used reagents in laboratories. However, its quality is usually the least well-characterized and often overlooked. Here we investigate the contamination of ultrapure water by bisphenol A (BPA) leached from a polysulfone (PS) ultrafilter in a water purification system. To evaluate the level of BPA in ultrapure water, we used an offline solid-phase extraction (SPE) coupled with liquid chromatography mass spectrometry (LC-MS). Initial BPA level leached from a new PS ultrafilter was 0.70 +/- 0.06 ng/mL. The concentration of BPA decreased gradually with continuous dispensation of purified water and was 0.20 +/- 0.02 ng/mL at 33.5-L dispensation. The total amount of extractable BPA was 64.4 +/- 1.4 mu g per PS ultrafilter. The cumulative amount of BPA leached during dispensation of 33.5-L water was 1.2 +/- 0.1 mu g, which only accounts for 2% of the total amount of extractable BPA. Published by Elsevier B.V.
C1 [Choi, Yong Soo; Cho, Seungil; Lee, Christina; Luu, Hoan My-Do; Guo, Ji] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
RP Cho, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
EM seungil.cho@fda.hhs.gov
NR 21
TC 4
Z9 4
U1 2
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0039-9140
J9 TALANTA
JI Talanta
PD MAY 30
PY 2012
VL 94
BP 353
EP 355
DI 10.1016/j.talanta.2012.03.028
PG 3
WC Chemistry, Analytical
SC Chemistry
GA 957MO
UT WOS:000305167300054
PM 22608460
ER
PT J
AU Hassan, F
Ren, DB
Zhang, WH
Merkel, TJ
Gu, XX
AF Hassan, Ferdaus
Ren, Dabin
Zhang, Wenhong
Merkel, Tod J.
Gu, Xin-Xing
TI Moraxella catarrhalis Activates Murine Macrophages through Multiple Toll
Like Receptors and Has Reduced Clearance in Lungs from TLR4 Mutant Mice
SO PLOS ONE
LA English
DT Article
ID NONTYPABLE HAEMOPHILUS-INFLUENZAE; ACUTE OTITIS-MEDIA; IMMUNE-RESPONSE;
EPITHELIAL-CELLS; PNEUMOCOCCAL INFECTION; MOUSE MODEL; SEROTYPE-A;
RECOGNITION; EXPRESSION; LIPOPOLYSACCHARIDE
AB Moraxella catarrhalis is a Gram negative bacterium and a leading causative agent of otitis media (OM) in children. Several recent reports have provided strong evidence for an association between toll like receptors and OM. It has been found that both Streptococcus pneumoniae and nontypeable Haemophilus influenzae activate host protective immune responses through toll like receptors (TLRs), however, the precise mechanism by which Moraxella catarrhalis initiates the host immune response is currently unknown. In this report, using murine macrophages generated from a series of knock-out mice, we have demonstrated that M. catarrhalis lipooligosaccharide (LOS) and either heat killed or live bacteria are recognized by one or more TLRs. LOS activates the host immune response through a membrane bound CD14-TLR4 complex, while both heat killed and live M. cat require recognition by multiple toll like receptors such as TLR2, TLR4 and TLR9 without the requirement of CD14. We have also shown that M. cat stimuli are capable of triggering the host innate immune response by both MyD88- and TRIF- dependent signaling pathways. We further showed that M. cat induced activation of mitogen activated protein kinase (MAPK) is essential in order to achieve optimal secretion of pro-inflammatory cytokine TNF-alpha. We finally showed that TLR4 mutant C3H/HeJ mice produce significantly lower levels of pro-inflammatory cytokines TNF-alpha and IL-6 in vivo, An increased bacterial loads at 12 and 24 hours (P<0.001) in their lungs upon challenge with live M. cat in an aerosol chamber compared to wild-type (WT) control mice. These data suggest that TLRs are crucial for an effective innate immune response induced by M. cat. The results of these studies contribute to an increased understanding of molecular mechanism and possible novel treatment strategies for diseases caused by M. cat by specifically targeting TLRs and their signaling pathways.
C1 [Hassan, Ferdaus; Ren, Dabin; Zhang, Wenhong; Gu, Xin-Xing] Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD USA.
[Merkel, Tod J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Hassan, F (reprint author), Univ Missouri, Sch Med, Shock Trauma Res Ctr, Kansas City, MO 64108 USA.
EM hassanmf@umkc.edu; guxx@mail.nih.gov
RI Ren, Dabin/H-6263-2013
FU Intramural Research Program of the National Institute on Deafness and
Other Communication Disorders (NIDCD), National Institutes of Health
(NIH), United States of America [NIH0010103632]
FX This research was supported by the Intramural Research Program of the
National Institute on Deafness and Other Communication Disorders
(NIDCD), National Institutes of Health (NIH), United States of America
(#NIH0010103632). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 37
TC 10
Z9 10
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 25
PY 2012
VL 7
IS 5
AR e37610
DI 10.1371/journal.pone.0037610
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UY
UT WOS:000305342300069
PM 22662179
ER
PT J
AU Amarasinghe, K
Chu, PS
Evans, E
Reimschuessel, R
Hasbrouck, N
Jayasuriya, H
AF Amarasinghe, Kande
Chu, Pak-Sin
Evans, Eric
Reimschuessel, Renate
Hasbrouck, Nicholas
Jayasuriya, Hiranthi
TI Development of a Fast Screening and Confirmatory Method by Liquid
Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry for
Glucuronide-Conjugated Methyltestosterone Metabolite in Tilapia
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE methyltestosterone-17-O-glucuronide; tilapia bile; LC-QTOF
ID OREOCHROMIS-NILOTICUS; 17-ALPHA-METHYLTESTOSTERONE; FISH; ELECTROSPRAY;
MUSCLE; TROUT
AB This paper describes the development of a fast method to screen and confirm methyltestosterone 17-O-glucuronide (MT-glu) in tilapia bile. The method consists of solid-phase extraction (SPE) followed by high-performance liquid chromatography mass spectrometry. The system used was an Agilent 6530 Q-TOF with an Agilent Jet stream electrospray ionization interface. The glucuronide detected in the bile was characterized as MT-glu by comparison with a chemically synthesized standard. MT-glu was detected in bile for up to 7 days after dosing. Semiquantification was done with matrix-matched calibration curves, because MT-glu showed signal suppression due to matrix effects. This method provides a suitable tool to monitor the illegal use of methyltestosterone in tilapia culture.
C1 [Amarasinghe, Kande; Chu, Pak-Sin; Evans, Eric; Reimschuessel, Renate; Hasbrouck, Nicholas; Jayasuriya, Hiranthi] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA.
RP Jayasuriya, H (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA.
EM hiranthi.jayasuriya@fda.gov
NR 16
TC 5
Z9 5
U1 2
U2 14
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 MAY 23
PY 2012
VL 60
IS 20
BP 5084
EP 5088
DI 10.1021/jf300427j
PG 5
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 945OJ
UT WOS:000304285600009
PM 22548460
ER
PT J
AU Liu, JB
Hu, XN
Hou, S
Wen, T
Liu, WQ
Zhu, X
Yin, JJ
Wu, XC
AF Liu, Jianbo
Hu, Xiaona
Hou, Shuai
Wen, Tao
Liu, Wenqi
Zhu, Xing
Yin, Jun-Jie
Wu, Xiaochun
TI Au@Pt core/shell nanorods with peroxidase- and ascorbate oxidase-like
activities for improved detection of glucose
SO SENSORS AND ACTUATORS B-CHEMICAL
LA English
DT Article
DE Gold nanorods; Platinum; Core/shell nanostructures; Peroxidase mimic;
Ascorbate oxidase mimic; Glucose detection
ID PLATINUM NANOPARTICLES; O-PHENYLENEDIAMINE; GOLD NANORODS; KINETICS;
POLYELECTROLYTE; NANOSTRUCTURES; SYSTEM
AB Au nanorods @ Pt nanodots core/shell nanostructures, prepared by the Au nanorods (NRs)-mediated growth, exhibit dual functional enzyme-like (peroxidase and oxidase-like) activities. From the viewpoint of enzyme mimics, the relationship between apparent enzyme kinetic parameters and nanomaterials structure is investigated in order to rationally design the catalytic activity. Using peroxidase-like properties of the Au@Pt NRs, the determination of hydrogen peroxide (H2O2) was demonstrated with a limit of detection (LOD) 01 4.5 x 10(-5) M and a linear range of 4.5 x 10(-5)-1 X 10(-3) M using o-phenylenediamine (OPD) as chromogenic substrate. Furthermore, in combination with highly specific reactions provided by natural enzymes, selective detections of glucose and lipophilic cholesterol were demonstrated with similar LODs and linear ranges. Additionally, owing to the specific oxidase-like activity of the Au@Pt NRs (ascorbate oxidase), interference of ascorbic acid in the detection of glucose could be eliminated. In conclusion, considering the flexibility in the design of nanomatererials, there is a lot of space to improve their activity and explore their potential applications, especially in relatively harsh conditions. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Liu, Jianbo; Hu, Xiaona; Hou, Shuai; Wen, Tao; Liu, Wenqi; Wu, Xiaochun] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China.
[Liu, Jianbo; Zhu, Xing] Peking Univ, Sch Phys, State Key Lab Mesoscop Phys, Beijing 100871, Peoples R China.
RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM JunJie.Yin@fda.hhs.gov; wuxc@nanoctr.cn
RI Yin, Jun Jie /E-5619-2014
FU National Natural Science Foundation of China [21173056]; National Key
Basic Research Program of China [2012CB34001, 2011CB932802]; FY11 FDA
Nanotechnology CORES Program
FX The work was supported by National Natural Science Foundation of China
(Grant No. 21173056) and National Key Basic Research Program of China
(2012CB34001 and 2011CB932802). This article is not an official US Food
and Drug Administration (FDA) guidance or policy statement. No official
support or endorsement by the US FDA is intended or should be inferred.
This work was supported by a regulatory science grant under the FY11 FDA
Nanotechnology CORES Program (JJ Yin).
NR 26
TC 50
Z9 54
U1 16
U2 108
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 0925-4005
J9 SENSOR ACTUAT B-CHEM
JI Sens. Actuator B-Chem.
PD MAY 20
PY 2012
VL 166
BP 708
EP 714
DI 10.1016/j.snb.2012.03.045
PG 7
WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation
SC Chemistry; Electrochemistry; Instruments & Instrumentation
GA 959ZN
UT WOS:000305356900096
ER
PT J
AU Adesunloye, B
Huang, X
Ning, YM
Madan, RA
Gulley, JL
Beatson, M
Kluetz, PG
Adelberg, DE
Arlen, PM
Parnes, HL
Mulquin, M
Steinberg, SM
Wright, JJ
Trepel, JB
Dawson, NA
Chen, C
Bassim, C
Apolo, AB
Figg, WD
Dahut, WL
AF Adesunloye, Bamidele
Huang, Xuan
Ning, Yangmin M.
Madan, Ravi A.
Gulley, James L.
Beatson, Melony
Kluetz, Paul Gustav
Adelberg, David E.
Arlen, Philip M.
Parnes, Howard L.
Mulquin, Marcia
Steinberg, Seth M.
Wright, John Joseph
Trepel, Jane B.
Dawson, Nancy Ann
Chen, Clara
Bassim, Carol
Apolo, Andrea Borghese
Figg, William Douglas
Dahut, William L.
TI Dual antiangiogenic therapy using lenalidomide and bevacizumab with
docetaxel and prednisone in patients with metastatic
castration-resistant prostate cancer (mCRPC).
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY JUN 01-06, 2012
CL Chicago, IL
SP Amer Soc Clin Oncol (ASCO)
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
NCI, US FDA, Silver Spring, MD USA.
NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA.
NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
NCI, Bethesda, MD 20892 USA.
NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
NCI, Metab Branch, NIH, Bethesda, MD 20892 USA.
NCI, Biostat & Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA.
NCI, Rockville, MD USA.
Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA.
NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA.
Natl Inst Dent & Craniolfacial Res, NIH, Bethesda, MD USA.
NCI, Mol Pharmacol Sect, NIH, 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 1
Z9 1
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2012
VL 30
IS 15
SU S
MA 4569
PG 1
WC Oncology
SC Oncology
GA 131QQ
UT WOS:000318009802887
ER
PT J
AU Malik, SM
Johnson, JR
Bijwaard, K
Becker, R
Keegan, P
Pazdur, R
AF Malik, Shakun M.
Johnson, John R.
Bijwaard, Karen
Becker, Robert
Keegan, Patricia
Pazdur, Richard
TI Targeted therapies for the treatment of non-small cell lung cancer:
Bull's eye or missed target?
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY JUN 01-06, 2012
CL Chicago, IL
SP Amer Soc Clin Oncol (ASCO)
C1 US FDA, Silver Spring, MD USA.
US FDA, CDRH, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2012
VL 30
IS 15
SU S
MA 3074
PG 1
WC Oncology
SC Oncology
GA 131QQ
UT WOS:000318009802358
ER
PT J
AU Zhu, PX
Degheidy, HA
Marti, GE
Li, SH
Abbasi, F
Wiestner, A
Amstutz, PT
Tang, CM
AF Zhu, Peixuan
Degheidy, Heba A.
Marti, Gerald E.
Li, Shuhong
Abbasi, Fatima
Wiestner, Adrian
Amstutz, Platte T.
Tang, Cha-Mei
TI Quantitative detection of ZAP-70 expression in chronic lymphocytic
leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY JUN 01-06, 2012
CL Chicago, IL
SP Amer Soc Clin Oncol (ASCO)
C1 Creatv MicroTech Inc, Potomac, MD USA.
FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 20
PY 2012
VL 30
IS 15
SU S
MA 6581
PG 1
WC Oncology
SC Oncology
GA 131QQ
UT WOS:000318009803016
ER
PT J
AU Lin, M
Chandramani-Shivalingappa, P
Jin, H
Ghosh, A
Anantharam, V
Ali, S
Kanthasamy, AG
Kanthasamy, A
AF Lin, M.
Chandramani-Shivalingappa, P.
Jin, H.
Ghosh, A.
Anantharam, V.
Ali, S.
Kanthasamy, A. G.
Kanthasamy, A.
TI METHAMPHETAMINE-INDUCED NEUROTOXICITY LINKED TO UBIQUITIN-PROTEASOME
SYSTEM DYSFUNCTION AND AUTOPHAGY-RELATED CHANGES THAT CAN BE MODULATED
BY PROTEIN KINASE C DELTA IN DOPAMINERGIC NEURONAL CELLS
SO NEUROSCIENCE
LA English
DT Article
DE PKC delta; autophagy; methamphetamine; apoptosis; LC3; dopaminergic
neuronal cells
ID OXIDATIVE STRESS; PROTEOLYTIC ACTIVATION; PARKINSONS-DISEASE; MEDIATED
CLEAVAGE; UP-REGULATION; PC12 CELLS; BECLIN 1; DEATH; APOPTOSIS;
DEGENERATION
AB A compromised protein degradation machinery has been implicated in methamphetamine (MA)-induced neurodegeneration. However, the signaling mechanisms that induce autophagy and ubiquitin-proteasome system (UPS) dysfunction are not well understood. The present study investigates the contributions of protein kinase C delta (PKC delta)-mediated signaling events in MA-induced autophagy, UPS dysfunction, and cell death. Using an in vitro mesencephalic dopaminergic cell culture model, we demonstrate that MA-induced early induction of autophagy is associated with reduction in proteasomal function and concomitant dissipation of mitochondrial membrane potential (MMP), followed by significantly increased PKC delta activation, caspase-3 activation, accumulation of ubiquitin-positive aggregates and microtubule-associated light chain-3 (LC3-II) levels. Interestingly, siRNA-mediated knockdown of PKC delta or overexpression of cleavage-resistant mutant of PKC delta dramatically reduced MA-induced autophagy, proteasomal function, and associated accumulation of ubiquitinated protein aggregates, which closely paralleled cell survival. Importantly, when autophagy was inhibited either pharmacologically (3-MA) or genetically (siRNA-mediated silencing of LC3), the dopaminergic cells became sensitized to MA-induced apoptosis through caspase-3 activation. Conversely, overexpression of LC3 partially protected against MA-induced apoptotic cell death, suggesting a neuroprotective role for autophagy in MA-induced neurotoxicity. Notably, rat striatal tissue isolated from MA-treated rats also exhibited elevated LC3-II, ubiquitinated protein levels, and PKC delta cleavage. Taken together, our data demonstrate that MA-induced autophagy serves as an adaptive strategy for inhibiting mitochondria-mediated apoptotic cell death and degradation of aggregated proteins. Our results also suggest that the sustained activation of PKC delta leads to UPS dysfunction, resulting in the activation of caspase-3-mediated apoptotic cell death in the nigrostriatal dopaminergic system. Published by Elsevier Ltd on behalf of IBRO.
C1 [Lin, M.; Chandramani-Shivalingappa, P.; Jin, H.; Ghosh, A.; Anantharam, V.; Kanthasamy, A. G.; Kanthasamy, A.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA.
[Ali, S.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA.
RP Kanthasamy, A (reprint author), Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA.
EM arthik@iastate.edu
RI Ghosh, Anamitra/C-5118-2015
FU National Institutes of Health [NS74443, NS65167, ES19276]
FX This work was supported by National Institutes of Health Grants NS74443
(A.G.K.), NS65167 (AK.), and ES19276 (A.G.K.). The W. Eugene and Linda
Lloyd Endowed Chair to A.G.K. is also acknowledged.
NR 75
TC 22
Z9 23
U1 0
U2 7
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 MAY 17
PY 2012
VL 210
BP 308
EP 332
DI 10.1016/j.neuroscience.2012.03.004
PG 25
WC Neurosciences
SC Neurosciences & Neurology
GA 951ON
UT WOS:000304730000030
PM 22445524
ER
PT J
AU Mani, N
Murray, J
Gulick, RM
Josephson, F
Miller, V
Miele, P
Strobos, J
Struble, K
AF Mani, Nina
Murray, Jeffrey
Gulick, Roy M.
Josephson, Filip
Miller, Veronica
Miele, Peter
Strobos, Jur
Struble, Kimberly
TI Novel clinical trial designs for the development of new antiretroviral
agents
SO AIDS
LA English
DT Review
DE antiretroviral; clinical trial design; HIV-1; noninferiority; optimized
background regimen; superiority; treatment-experienced; treatment-naive
ID EXPERIENCED HIV-1-INFECTED PATIENTS; RESISTANT HIV-1 INFECTION; PATIENTS
96-WEEK EFFICACY; PLACEBO-CONTROLLED TRIAL; TREATMENT-NAIVE;
DOUBLE-BLIND; DARUNAVIR-RITONAVIR; TMC125 ETRAVIRINE; INITIAL TREATMENT;
TENOFOVIR DF
AB The resounding success of combination antiretroviral efficacy for both treatment-naive and treatment-experienced patients - with 70-90% viral suppression rates in recent studies has made registration trials for new agents challenging. With the inevitable specter of drug resistance, new agents must have a pathway to approval. The Forum for Collaborative HIV Research obtained input from concerned stakeholders including industry, clinical sciences, community advocacy, and regulatory sciences (Food and Drug Administration and European Medicines Agency) to discuss how safety and efficacy of new agents could be demonstrated. Recognizing the shortfalls of superiority or noninferiority trials in this environment, a new trial design for treatment-experienced patients, minimizing the risk for drug resistance but allowing full assessment of safety, was proposed. The antiviral efficacy of an active investigational drug would be assessed by comparison to placebo as an add-on to a failing regimen in a short, 10-14-day study followed by institution of an optimized background regimen (OBR) in both arms with investigational drug given to all patients. The follow-on stage would assess dose response, safety, durability of initial response, and development of resistance. Additionally, a second safety trial could be conducted comparing patients randomized to the investigational agent with a new OBR to those on a new OBR and placebo. Finally, approval decisions could consider other long-term safety endpoints. Exposing treatment-naive patients to investigational agents remains a controversial issue; stakeholders have different interpretations of risk-benefit for trials in this population that necessitate careful consideration before initiating trials in them. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
C1 [Mani, Nina; Miller, Veronica; Strobos, Jur] Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA.
[Murray, Jeffrey; Miele, Peter; Struble, Kimberly] US FDA, Silver Spring, MD USA.
[Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
[Josephson, Filip] Swedish Med Prod Agcy, Uppsala, Sweden.
RP Mani, N (reprint author), Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC USA.
EM nmani@hivforum.org
FU NIH [AI-51966]
FX Funding for the Forum for Collaborative HIV Research includes
unrestricted funds from the pharmaceutical and diagnostic industries. V.
M. is the Director of the Forum for Collaborative HIV Research. R. M. G.
receives NIH K24 funding (AI-51966). The other authors have nothing to
disclose.
NR 37
TC 8
Z9 8
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD MAY 15
PY 2012
VL 26
IS 8
BP 899
EP 907
DI 10.1097/QAD.0b013e3283519371
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 937JY
UT WOS:000303656000001
PM 22301412
ER
PT J
AU Cuevas, LE
Browning, R
Bossuyt, P
Casenghi, M
Cotton, MF
Cruz, AT
Dodd, LE
Drobniewski, F
Gale, M
Graham, SM
Grzemska, M
Heinrich, N
Hesseling, AC
Huebner, R
Jean-Philippe, P
Kabra, SK
Kampmann, B
Lewinsohn, D
Li, MJ
Lienhardt, C
Mandalakas, AM
Marais, BJ
Menzies, HJ
Montepiedra, G
Mwansambo, C
Oberhelman, R
Palumbo, P
Russek-Cohen, E
Shapiro, DE
Smith, B
Soto-Castellares, G
Starke, JR
Swaminathan, S
Wingfield, C
Worrell, C
AF Cuevas, Luis E.
Browning, Renee
Bossuyt, Patrick
Casenghi, Martina
Cotton, Mark F.
Cruz, Andrea T.
Dodd, Lori E.
Drobniewski, Francis
Gale, Marianne
Graham, Stephen M.
Grzemska, Malgosia
Heinrich, Norbert
Hesseling, Anneke C.
Huebner, Robin
Jean-Philippe, Patrick
Kabra, Sushil Kumar
Kampmann, Beate
Lewinsohn, Deborah
Li, Meijuan
Lienhardt, Christian
Mandalakas, Anna M.
Marais, Ben J.
Menzies, Heather J.
Montepiedra, Grace
Mwansambo, Charles
Oberhelman, Richard
Palumbo, Paul
Russek-Cohen, Estelle
Shapiro, David E.
Smith, Betsy
Soto-Castellares, Giselle
Starke, Jeffrey R.
Swaminathan, Soumya
Wingfield, Claire
Worrell, Carol
TI Evaluation of Tuberculosis Diagnostics in Children: 2. Methodological
Issues for Conducting and Reporting Research Evaluations of Tuberculosis
Diagnostics for Intrathoracic Tuberculosis in Children. Consensus From
an Expert Panel(a)
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID DRUG-SUSCEPTIBILITY ASSAY; POLYMERASE-CHAIN-REACTION;
MYCOBACTERIUM-TUBERCULOSIS; MICROSCOPIC-OBSERVATION; PULMONARY
TUBERCULOSIS; ACCURACY; SPUTUM; TESTS
AB Confirming the diagnosis of childhood tuberculosis is a major challenge. However, research on childhood tuberculosis as it relates to better diagnostics is often neglected because of technical difficulties, such as the slow growth in culture, the difficulty of obtaining specimens, and the diverse and relatively nonspecific clinical presentation of tuberculosis in this age group. Researchers often use individually designed criteria for enrollment, diagnostic classifications, and reference standards, thereby hindering the interpretation and comparability of their findings. The development of standardized research approaches and definitions is therefore needed to strengthen the evaluation of new diagnostics for detection and confirmation of tuberculosis in children.
In this article we present consensus statements on methodological issues for conducting research of Tuberculosis diagnostics among children, with a focus on intrathoracic tuberculosis. The statements are complementary to a clinical research case definition presented in an accompanying publication and suggest a phased approach to diagnostics evaluation; entry criteria for enrollment; methods for classification of disease certainty, including the rational use of culture within the case definition; age categories and comorbidities for reporting results; and the need to use standard operating procedures. Special consideration is given to the performance of microbiological culture in children and we also recommend for alternative methodological approaches to report findings in a standardized manner to overcome these limitations are made. This consensus statement is an important step toward ensuring greater rigor and comparability of pediatric tuberculosis diagnostic research, with the aim of realizing the full potential of better tests for children.
C1 [Cuevas, Luis E.] Univ Liverpool, Liverpool Sch Trop Med, Child & Reprod Hlth Grp, Liverpool L3 5QA, Merseyside, England.
[Browning, Renee; Jean-Philippe, Patrick] NIAID, Henry Jackson Fdn, HIV AIDS Sci & Operat Support HJF DAIDS, Bethesda, MD 20892 USA.
[Bossuyt, Patrick] Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands.
[Casenghi, Martina] Med Sans Frontieres, Geneva, Switzerland.
[Cotton, Mark F.] Univ Stellenbosch, Tygerberg Childrens Hosp, Childrens Infect Dis Clin Res Unit, Cape Town, South Africa.
[Cruz, Andrea T.; Starke, Jeffrey R.] Baylor Sch Med, Houston, TX USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Drobniewski, Francis] Barts & London Queen Marys Sch Med & Dent, Hlth Protect Agcy, Natl Mycobacterium Reference Lab, London, England.
[Drobniewski, Francis] Barts & London Queen Marys Sch Med & Dent, Clin TB & HIV Grp, London, England.
[Gale, Marianne] Med Sans Frontieres, Sydney, NSW, Australia.
[Graham, Stephen M.] Univ Melbourne, Dept Paediat, Ctr Int Child Hlth, Melbourne, Vic 3010, Australia.
[Graham, Stephen M.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Murdoch, WA, Australia.
[Grzemska, Malgosia; Lienhardt, Christian] WHO, STOP TB Dept, CH-1211 Geneva, Switzerland.
[Heinrich, Norbert] Univ Munich, Med Ctr, Div Infect Dis & Trop Med, D-80539 Munich, Germany.
[Hesseling, Anneke C.] Univ Stellenbosch, Desmond Tutu TB Ctr, Cape Town, South Africa.
[Huebner, Robin] NIAID, Epidemiol Branch, Div Aids, NIH, Bethesda, MD 20892 USA.
[Kabra, Sushil Kumar] All India Inst Med Sci, New Delhi, India.
[Kampmann, Beate] Univ London Imperial Coll Sci Technol & Med, Dept Paediat, London SW7 2AZ, England.
[Kampmann, Beate] MRC, Banjul, Gambia.
[Lewinsohn, Deborah] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97201 USA.
[Li, Meijuan] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Mandalakas, Anna M.] Texas Childrens Hosp, Baylor Coll Med, Ctr Global Hlth, Sect Retrovirol & Global Hlth, Houston, TX 77030 USA.
[Marais, Ben J.] Univ Sydney, Childrens Hosp Westmead, Sydney, NSW 2006, Australia.
[Menzies, Heather J.] Ctr Dis Control & Prevent, Int Res & Programs Branch, Div TB Eliminat, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA.
[Montepiedra, Grace; Shapiro, David E.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Mwansambo, Charles] Minist Hlth, Lilongwe, Malawi.
[Oberhelman, Richard] Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA USA.
[Oberhelman, Richard] Tulane Sch Publ Hlth & Trop Med, Dept Pediat, New Orleans, LA USA.
[Palumbo, Paul] Dartmouth Med Sch, Lebanon, NH USA.
[Russek-Cohen, Estelle] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Smith, Betsy] NIAID, Maternal Adolescent Pediat Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA.
[Soto-Castellares, Giselle] USN, Dept Emerging Infect Dis, Med Res Unit 6, Bellavista, Callao, Peru.
[Swaminathan, Soumya] Natl Inst Res TB, Madras, Tamil Nadu, India.
[Wingfield, Claire] Treatment Act Grp, New York, NY USA.
[Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
RP Cuevas, LE (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Child & Reprod Hlth Grp, Pembroke Pl, Liverpool L3 5QA, Merseyside, England.
EM lcuevas@liv.ac.uk
RI Bossuyt, Patrick/B-4557-2016; Heinrich, Norbert/B-3750-2014;
OI Bossuyt, Patrick/0000-0003-4427-0128; Cuevas, Luis
E./0000-0002-6581-0587
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; National Institute of Child Health and Human
Development; Centers for Disease Control and Prevention; Office of
Global AIDS Coordinator; US Department of Department of Health and Human
Services [HHSN272200800014C]; International Maternal Pediatric
Adolescent AIDS Clinical Trials Group Statistical and Data Management
Center [UM01 AI068616]; Thrasher Research Fund [02824-6]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases, National Institutes of Health, National Institute
of Child Health and Human Development, Centers for Disease Control and
Prevention, and Office of Global AIDS Coordinator. Funding from these
institutions was not associated with a research grant but supported
directly the scientific workshop from which this work was generated. The
project was also supported in part with US federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and US Department of Department of Health and
Human Services (contract HHSN272200800014C). D. S. and G. M. were
supported by the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group Statistical and Data Management Center grant
(grant No UM01 AI068616). L. E. C. was supported by a Thrasher Research
Fund grant (contract 02824-6).
NR 26
TC 37
Z9 37
U1 1
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 15
PY 2012
VL 205
SU 2
BP S209
EP S215
DI 10.1093/infdis/jir879
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 932ZT
UT WOS:000303329700008
PM 22476719
ER
PT J
AU Palamountain, KM
Baker, J
Cowan, EP
Essajee, S
Mazzola, LT
Metzler, M
Schito, M
Stevens, WS
Young, GJ
Domingo, GJ
AF Palamountain, Kara M.
Baker, Jeff
Cowan, Elliot P.
Essajee, Shaffiq
Mazzola, Laura T.
Metzler, Mutsumi
Schito, Marco
Stevens, Wendy S.
Young, Gloria J.
Domingo, Gonzalo J.
TI Perspectives on Introduction and Implementation of New Point-of-Care
Diagnostic Tests
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID RESOURCE-LIMITED SETTINGS; RANDOMIZED CONTROLLED-TRIAL; ANTIRETROVIRAL
THERAPY; CONSTRAINED SETTINGS; RIFAMPIN RESISTANCE; LABORATORY SYSTEMS;
INFORMATION-SYSTEM; QUALITY-ASSURANCE; POOR SETTINGS; HIV-1 STRAINS
AB In recent years, there has been significant investment from both the private and public sectors in the development of diagnostic technologies to meet the need for human immunodeficiency virus (HIV) and tuberculosis testing in low-resource settings. Future investments should ensure that the most appropriate technologies are adopted in settings where they will have a sustainable impact. Achieving these aims requires the involvement of many stakeholders, as their needs, operational constraints, and priorities are often distinct. Here, we discuss these considerations from different perspectives representing those of various stakeholders involved in the development, introduction, and implementation of diagnostic tests. We also discuss some opportunities to address these considerations.
C1 [Metzler, Mutsumi; Domingo, Gonzalo J.] PATH, Seattle, WA 98109 USA.
[Palamountain, Kara M.] Northwestern Univ, Kellogg Sch Management, Evanston, IL USA.
[Baker, Jeff] Alere, Infect Dis Strateg Business Unit, Waltham, MA USA.
[Cowan, Elliot P.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
[Essajee, Shaffiq] WHO, HIV Dept, CH-1211 Geneva, Switzerland.
[Mazzola, Laura T.] Wave 80 Biosci, San Francisco, CA USA.
[Schito, Marco] NIH, Henry M Jackson Fdn, Div Aids, Bethesda, MD 20892 USA.
[Stevens, Wendy S.] Univ Witwatersrand, Dept Mol Med & Haematol, Johannesburg, South Africa.
[Stevens, Wendy S.] Natl Hlth Lab Serv, Johannesburg, South Africa.
[Young, Gloria J.] Becton Dickinson Biosci, San Jose, CA USA.
RP Domingo, GJ (reprint author), PATH, POB 900922, Seattle, WA 98109 USA.
EM schitom@niaid.nih.gov; gdomingo@path.org
FU National Institute of Allergy and Infectious Diseases; US National
Institutes of Health (NIH); US Department of Health and Human Services
[HHSN272200800014C]; National Institute of Biomedical Imaging and
Bioengineering, NIH [1U54EB007949-01]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases, US National Institutes of Health (NIH), and the US
Department of Health and Human Services (contract HHSN272200800014C).
Preparation of the manuscript was funded in part by the National
Institute of Biomedical Imaging and Bioengineering, NIH (grant
1U54EB007949-01).
NR 60
TC 24
Z9 25
U1 0
U2 13
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAY 15
PY 2012
VL 205
SU 2
BP S181
EP S190
DI 10.1093/infdis/jis203
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 932ZT
UT WOS:000303329700005
PM 22402038
ER
PT J
AU Dal Pan, GJ
AF Dal Pan, Gerald J.
TI Potential Safety Signals and Their Significance In reply
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Dal Pan, GJ (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4304, Silver Spring, MD 20993 USA.
EM gerald.dalpan@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAY 14
PY 2012
VL 172
IS 9
BP 747
EP 747
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 941ZF
UT WOS:000304007800020
ER
PT J
AU Woo, EJ
AF Woo, Emily Jane
TI Potential Safety Signals and Their Significance
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Letter
C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 222, Rockville, MD 20852 USA.
EM jane.woo@fda.hhs.gov
NR 4
TC 0
Z9 0
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD MAY 14
PY 2012
VL 172
IS 9
BP 747
EP 747
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 941ZF
UT WOS:000304007800019
PM 22782211
ER
PT J
AU Schmeisser, F
Adamo, JE
Blumberg, B
Friedman, R
Muller, J
Soto, J
Weir, JP
AF Schmeisser, Falko
Adamo, Joan E.
Blumberg, Benjamin
Friedman, Rachel
Muller, Jacqueline
Soto, Jackeline
Weir, Jerry P.
TI Production and characterization of mammalian virus-like particles from
modified vaccinia virus Ankara vectors expressing influenza H5N1
hemagglutinin and neuraminidase
SO VACCINE
LA English
DT Article
DE Virus-like particle (VLP); Influenza immunity; Influenza vaccine; H5N1
ID PROTECTIVE IMMUNE-RESPONSES; HETEROLOGOUS STRAINS; MATRIX PROTEIN; M1
PROTEINS; MICE; NA; HA; CHALLENGE; FERRETS; INDUCE
AB Several studies have described the production of influenza virus-like particles (VLP) using a variety of platform systems. These VLPs are non-replicating particles that spontaneously self-assemble from expressed influenza virus proteins and have been proposed as vaccine candidates for both seasonal and pandemic influenza. Although still in the early stages of development and evaluation as influenza vaccines, influenza VLPs have a variety of other valuable uses such as examining and understanding correlates of protection against influenza and investigating virus-cell interactions. The most common production system for influenza VLPs is the baculovirus-insect cell expression which has several attractive features including the ease in which new gene combinations can be constructed, the immunogenicity elicited and protection afforded by the produced VLPs, and the scalability offered by the system. However, there are differences between the influenza VLPs produced by baculovirus expression systems in insect cells and the influenza viruses produced for use as current vaccines or the virus produced during a productive clinical infection. We describe here the development of a modified vaccinia virus Ankara (MVA) system to generate mammalian influenza VLPs containing influenza H5N1 proteins. The MVA vector system is flexible for manipulating and generating various VLP constructs, expresses high level of influenza hemagglutinin (HA), neuraminidase (NA), and matrix (M) proteins, and can be scaled up to produce VLPs in quantities sufficient for in vivo studies. We show that mammalian VLPs are generated from recombinant MVA vectors expressing H5N1 HA alone, but that increased VLP production can be achieved if NA is co-expressed. These mammalian H5N1 influenza VLPs have properties in common with live virus, as shown by electron microscopy analysis, their ability to hemagglutinate red blood cells, express neuraminidase activity, and to bind influenza specific antibodies. Importantly, these VLPs are able to elicit a protective immune response in a mouse challenge model, suggesting their utility in dissecting the correlates of immunity in such models. Mammalian derived VLPs may also provide a useful tool for studying virus-cell interactions and may have potential for development as pandemic vaccines. Published by Elsevier Ltd.
C1 [Schmeisser, Falko; Adamo, Joan E.; Blumberg, Benjamin; Friedman, Rachel; Muller, Jacqueline; Soto, Jackeline; Weir, Jerry P.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA.
RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA.
EM jerry.weir@fda.hhs.gov
NR 28
TC 11
Z9 11
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD MAY 14
PY 2012
VL 30
IS 23
BP 3413
EP 3422
DI 10.1016/j.vaccine.2012.03.033
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 937WW
UT WOS:000303695500010
PM 22465746
ER
PT J
AU Weisz, A
Witten, JJ
Zeng, Y
Mazzola, EP
Ito, Y
AF Weisz, Adrian
Witten, Jacob J.
Zeng, Yun
Mazzola, Eugene P.
Ito, Yoichiro
TI Preparation of two novel monobrominated 2-(2 ',4
'-dihydroxybenzoyl)-3,4,5,6-tetrachlorobenzoic acids and their
separation from crude synthetic mixtures using vortex counter-current
chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Vortex counter-current chromatography; VCCC; pH-zone-refining CCC;
Chemoselective ortho-bromination; 2-(2 '.4 '-Dihydroxy-3
'-bromobenzoyl)-3,4,5,6-tetrachlorobenzoic acid; 2-(2 '.4 '-Dihydroxy-5
'-bromobenzoyl)-3.4,5,6-tetrachlorobenzoic acid
ID COLOR ADDITIVES D; PERFORMANCE LIQUID-CHROMATOGRAPHY; RED NOS. 27;
SOLID-PHASE MICROEXTRACTION; PHLOXINE-B; PARTITION CHROMATOGRAPHY; MASS
SPECTROMETRY; ORTHO-BROMINATION; QUANTIFICATION; COMPONENTS
AB The present work describes the preparation of two compounds considered to be likely precursors of an impurity present in samples of the color additives D&C Red No. 27 (Color Index 45410:1) and D&C Red No. 28 (Color Index 45410, phloxine B) submitted to the U.S. Food and Drug Administration for batch certification. The two compounds, 2-(2',4'-dihydroxy-3'-bromobenzoyl)-3,4,5,6-tetrachlorobenzoic acid (3BrHBBA) and its 5'-brominated positional isomer (5BrHBBA), both not reported previously, were separated from synthetic mixtures by vortex counter-current chromatography (VCCC). 3BrHBBA was prepared by chemoselective ortho-bromination of the dihydroxybenzoyl moiety. Two portions of the obtained synthetic mixture, 200 mg and 210 mg, respectively, were separated by VCCC using two two-phase solvent systems that consisted of hexane-ethyl acetate-methanol-aqueous 0.2% trifluoroacetic acid (TFA) in the volume ratios of 8:2:5:5 and 7:3:5:5, respectively. These separations produced 35 mg and 78 mg of 3BrHBBA, respectively, each product of over 98% purity by HPLC at 254 urn. 5BrHBBA was prepared by monobromination of the dihydroxybenzoyl moiety in the presence of glacial acetic acid. To separate the obtained synthetic mixture. VCCC was performed in the pH-zone-refining mode with a solvent system consisting of hexane-ethyl acetate-methanol-water (6:4:5:5, v/v) and with TFA used as the retainer acid and aqueous ammonia as the eluent base. Separation of a 1-g mixture under these conditions resulted in 142 mg of 5BrHBBA of similar to 99% purity by HPLC at 254 nm. The isolated compounds were characterized by high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy. Published by Elsevier B.V.
C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Witten, Jacob J.; Zeng, Yun; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Witten, Jacob J.] Amherst Coll, Amherst, MA 01002 USA.
[Zeng, Yun] N Sichuan Med Coll, Inst Mat Med, Nanchong 637007, Sichuan Provinc, Peoples R China.
[Zeng, Yun] N Sichuan Med Coll, Dept Pharmacol, Nanchong 637007, Sichuan Provinc, Peoples R China.
[Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, HFS 106,5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM adrian.weisz@fda.hhs.gov
OI Witten, Jacob/0000-0003-0037-5999
FU Intramural NIH HHS [ZIA HL001060-03]
NR 41
TC 6
Z9 6
U1 0
U2 21
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD MAY 11
PY 2012
VL 1237
BP 106
EP 114
DI 10.1016/j.chroma.2012.03.040
PG 9
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 932CW
UT WOS:000303269000012
PM 22475185
ER
PT J
AU Cortazar, P
Justice, R
Johnson, J
Sridhara, R
Keegan, P
Pazdur, R
AF Cortazar, Patricia
Justice, Robert
Johnson, John
Sridhara, Rajeshwari
Keegan, Patricia
Pazdur, Richard
TI US Food and Drug Administration Approval Overview in Metastatic Breast
Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO)
CY MAY 30-JUN 03, 2008
CL Chicago, IL
SP Amer Soc Clin Oncol (ASCO)
ID RANDOMIZED CLINICAL-TRIALS; PHASE-III TRIAL; MONOCLONAL-ANTIBODY; PLUS
CAPECITABINE; PACLITAXEL; CHEMOTHERAPY; SURVIVAL; ANTHRACYCLINE;
DOCETAXEL; WOMEN
AB We reviewed trials that supported US Food and Drug Administration (FDA) approvals of drugs and biologics for the treatment of metastatic breast cancer (MBC) in the last two decades. This summary provides an overview of the basis for approval, including end points, trial design, major trial findings, and regulatory considerations. Approval of hormonal agents is excluded from this analysis. In the last two decades, 10 products with 14 MBC indications (four for first-line and 10 for second-to third-line treatment) were approved by the FDA. Approval decisions for these 14 indications were supported by a variety of end points that showed a favorable benefit-to-risk profile. Among these 14 indications, four were granted accelerated approval (AA), and 10 were given regular approval (RA). Of the four approved under AA, two have subsequently demonstrated clinical benefit resulting in conversion to RA. We conclude with current FDA thinking on the drug development challenges for the treatment of MBC and recommendations for future trial design.
C1 [Cortazar, Patricia; Justice, Robert; Johnson, John; Sridhara, Rajeshwari; Keegan, Patricia; Pazdur, Richard] US FDA, Silver Spring, MD USA.
RP Cortazar, P (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 2333, Silver Spring, MD 20993 USA.
EM patricia.cortazar@fda.hhs.gov
NR 28
TC 16
Z9 17
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD MAY 10
PY 2012
VL 30
IS 14
BP 1705
EP 1711
DI 10.1200/JCO.2011.39.2613
PG 7
WC Oncology
SC Oncology
GA 940TA
UT WOS:000303914800025
PM 22430273
ER
PT J
AU Turnipseed, SB
Clark, SB
Storey, JM
Carr, JR
AF Turnipseed, Sherri B.
Clark, Susan B.
Storey, Joseph M.
Carr, Justin R.
TI Analysis of Veterinary Drug Residues in Frog Legs and Other Aquacultured
Species Using Liquid Chromatography Quadrupole Time-of-Flight Mass
Spectrometry
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE LC quadrupole time-of-flight MS; veterinary drug residues; frog legs;
aquaculture
ID CHLORAMPHENICOL; CONFIRMATION; PRODUCTS; SHRIMP; MILK; IDENTIFICATION;
TRIMETHOPRIM; ANTIBIOTICS; VALIDATION; HONEY
AB A liquid chromatography quadrupole time-of-flight (Q-TOP) mass spectrometry method was developed to analyze veterinary drug residues in frog legs and other aquacultured species. Samples were extracted using a procedure based on a method developed for the analysis of fluoroquinolones (FQs) in fish. Briefly, the tissue was extracted with dilute acetic acid and acetonitrile with added sodium chloride. After centrifugation, the extracts were evaporated and reconstituted in mobile phase. A molecular weight cutoff filter was used to clean up the final extract. A set of target compounds, including trimethoprim, sulfamethoxazole, chloramphenicol, quinolones, and FQs, was used to validate the method. Screening of residues was accomplished by collecting TOP (MS1) data and comparing the accurate mass and retention times of compounds to a database containing information for veterinary drugs. An evaluation of the MS data in fortified frog legs indicated that the target compounds could be consistently detected at the level of concern. The linearity and recoveries from matrix were evaluated for these analytes to estimate the amount of residue present. MS/MS data were also generated from precursor ions, and the mass accuracy of the product ions for each compound was compared to theoretical values. When the method was used to analyze imported frog legs, many of these residues were found in the samples, often in combination and at relatively high concentrations (>10 ng/g). The data from these samples were also evaluated for nontarget analytes such as residue metabolites and other chemotherapeutics.
C1 [Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA.
[Clark, Susan B.; Storey, Joseph M.; Carr, Justin R.] US FDA, Denver Sci Branch, Denver, CO 80225 USA.
RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Bldg 20,POB 25087, Denver, CO 80225 USA.
EM sherriturnipseed@fda.hhs.gov
NR 36
TC 17
Z9 18
U1 3
U2 32
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 MAY 9
PY 2012
VL 60
IS 18
BP 4430
EP 4439
DI 10.1021/jf2049905
PG 10
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 937XB
UT WOS:000303696000003
PM 22390215
ER
PT J
AU Shaikh, B
Rummel, N
Yu, DL
Gieseker, C
Evans, E
Hasbrouck, N
Reimschuessel, R
AF Shaikh, Badar
Rummel, Nathan
Yu, Donglei
Gieseker, Charles
Evans, Eric
Hasbrouck, Nicholas
Reimschuessel, Renate
TI Marker Residue Determination of Tritium-Labeled Ivermectin in the Muscle
of Aquacultured Largemouth Bass, Hybrid Striped Bass, and Yellow Perch
following Oral Treatment
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE ivermectin; metabolism; depletion; finfish; aquaculture; marker residue
ID SALMON SALMO-SALAR; GATED CHLORIDE CHANNELS; ANTI-PARASITIC AGENT;
ATLANTIC SALMON; DEPLETION; TISSUES; POTENT
AB The residue depletion profiles of tritium-labeled ivermectin and its metabolites in the muscle of aquacultured largemouth bass (LMB), hybrid striped bass (HSB), and yellow perch (YP) following oral treatment are reported. Fish were administered H-3-ivermectin at the dose level of 0.1 mg/kg body weight (7-9 mu Ci) in a gel capsule via stomach tube. At each postdose withdrawal time, six fish of each species were sedated with buffered MS-222 and blood samples taken. Fish were then euthanized, and fillets with adhering skin (scales removed) and bile samples were collected. The muscle fillets were homogenized in dry ice to a fine powder. Aliquots of tissue, plasma, and bile were assayed for total radioactive residue (TRR). The homogenized muscle was extracted in acetonitrile or methanol followed by high-performance liquid chromatographic (HPLC) analysis to determine the presence of parent ivermectin and its potential metabolites. The highest TRR concentrations (ivermectin equivalents) of 53, 45, and 44 ng/g (ppb) were obtained on postdose day 1 for HSB, LMB, and YP, respectively. The TRR depleted most slowly in HSB to 25 ppb at day 91, followed by YP to 19 ppb at day 42 and then by LMB to 22 ppb at day 35. The total residue of ivermectin and its metabolites by HPLC analysis followed the same depletion pattern in the three species. Additionally, the depletion rate of TRR of H-3-ivermectin in the three species followed the pattern bile > plasma > muscle. The results further indicate that one of the polar metabolites of ivermectin could serve as a potential marker residue as an indication of use, rather than the parent ivermectin.
C1 [Shaikh, Badar; Rummel, Nathan; Yu, Donglei; Gieseker, Charles; Evans, Eric; Hasbrouck, Nicholas; Reimschuessel, Renate] 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 hadaruddin.shaikh@fda.hhs.gov
NR 19
TC 1
Z9 1
U1 0
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD MAY 9
PY 2012
VL 60
IS 18
BP 4465
EP 4470
DI 10.1021/jf205146s
PG 6
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 937XB
UT WOS:000303696000007
PM 22452736
ER
PT J
AU Tyburczy, C
Delmonte, P
Fardin-Kia, AR
Mossoba, MM
Kramer, JKG
Rader, JI
AF Tyburczy, Cynthia
Delmonte, Pierluigi
Fardin-Kia, Ali Reza
Mossoba, Magdi M.
Kramer, John K. G.
Rader, Jeanne I.
TI Profile of trans Fatty Acids (FAs) Including Trans Polyunsaturated FAs
in Representative Fast Food Samples
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE trans fat; fast food; AOCS Official Method Ce 1j-07; gas chromatography;
SP-2560 column; SLB-IL111 ionic liquid column
ID MILK-FAT; CHROMATOGRAPHIC-SEPARATION; LIQUID-CHROMATOGRAPHY;
LINOLEIC-ACID; DAIRY-COWS; FISH-OIL; ISOMERS; HEALTH; ASSOCIATION;
ADULTS
AB The content of trans fat in foods is most commonly determined by summing the levels of individual trans fatty acids (FM), analyzed as FA methyl esters (FAME) by gas chromatography. Current Official Methods of the American Oil Chemists Society (AOCS) enable quantitation of total trans fat in foods but were not designed for the determination of trans FA isomeric compositions. In the present study, the content of trans fat in 32 representative fast food samples ranged from 0.1 to 3.1 g per serving, as determined according to AOCS Official Method Ce 1j-07. Further analysis of FAME using the 200 m SLB-IL111 ionic liquid column yielded quantitative results of total, trans, saturated, and cis unsaturated fat that were comparable to those of Method Ce 1j-07 and also allowed for the complementary determination of individual trans 18:1, trans 18:2, and trans 18:3 FA isomeric compositions under conditions suitable for routine sample analysis.
C1 [Tyburczy, Cynthia; Delmonte, Pierluigi; Fardin-Kia, Ali Reza; Mossoba, Magdi M.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA.
[Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON N1G 5C9, Canada.
RP Tyburczy, C (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM cynthia.tyburczy@fda.hhs.gov
FU Center for Food Safety and Applied Nutrition
FX This project was supported in part by appointments to the Research
Participation Program at the Center for Food Safety and Applied
Nutrition administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration.
NR 36
TC 17
Z9 17
U1 3
U2 43
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 MAY 9
PY 2012
VL 60
IS 18
BP 4567
EP 4577
DI 10.1021/jf300585s
PG 11
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 937XB
UT WOS:000303696000019
PM 22509790
ER
PT J
AU Sachs, AN
Avant, D
Lee, CS
Rodriguez, W
Murphy, MD
AF Sachs, Aaron N.
Avant, Debbie
Lee, Catherine S.
Rodriguez, William
Murphy, M. Dianne
TI Pediatric Information in Drug Product Labeling
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Sachs, Aaron N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Avant, Debbie; Lee, Catherine S.; Rodriguez, William; Murphy, M. Dianne] US FDA, Off Pediat Therapeut, Silver Spring, MD USA.
RP Sachs, AN (reprint author), Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
EM debbie.avant@fda.hhs.gov
NR 6
TC 20
Z9 21
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 9
PY 2012
VL 307
IS 18
BP 1914
EP 1915
DI 10.1001/jama.2012.3435
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 938OD
UT WOS:000303741900019
PM 22570457
ER
PT J
AU Pacanowski, M
Amur, S
Zineh, I
AF Pacanowski, Michael
Amur, Shashi
Zineh, Issam
TI New Genetic Discoveries and Treatment for Hepatitis C
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID INFECTION
C1 [Pacanowski, Michael; Amur, Shashi; Zineh, Issam] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Pacanowski, M (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 51,Room 31, Silver Spring, MD 20993 USA.
EM michael.pacanowski@fda.hhs.gov
NR 6
TC 7
Z9 8
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 9
PY 2012
VL 307
IS 18
BP 1921
EP 1922
DI 10.1001/jama.2012.3516
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 938OD
UT WOS:000303741900024
PM 22570460
ER
PT J
AU Bannach, O
Birkmann, E
Reinartz, E
Jaeger, KE
Langeveld, JPM
Rohwer, RG
Gregori, L
Terry, LA
Willbold, D
Riesner, D
AF Bannach, Oliver
Birkmann, Eva
Reinartz, Elke
Jaeger, Karl-Erich
Langeveld, Jan P. M.
Rohwer, Robert G.
Gregori, Luisa
Terry, Linda A.
Willbold, Dieter
Riesner, Detlev
TI Detection of Prion Protein Particles in Blood Plasma of Scrapie Infected
Sheep
SO PLOS ONE
LA English
DT Article
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CREUTZFELDT-JAKOB-DISEASE;
INFECTIVITY; REMOVAL; AMPLIFICATION; COMPONENTS; CONVERSION; ANTIBODY;
MODELS; CATTLE
AB Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed.
C1 [Bannach, Oliver; Birkmann, Eva; Reinartz, Elke; Willbold, Dieter; Riesner, Detlev] Univ Dusseldorf, Inst Phys Biol, Dusseldorf, Germany.
[Birkmann, Eva; Willbold, Dieter] Res Ctr Julich, Inst Complex Syst ICS 6, Julich, Germany.
[Jaeger, Karl-Erich] Univ Dusseldorf, Res Ctr Julich, Inst Mol Enzyme Technol, Julich, Germany.
[Langeveld, Jan P. M.] Cent Vet Inst Wageningen UR CVI, Lelystad, Netherlands.
[Rohwer, Robert G.; Gregori, Luisa] VA Med Ctr, Med Res Serv 151, Mol Neurovirol Lab, VA Maryland Hlth Care Syst, Baltimore, MD USA.
[Terry, Linda A.] Anim Hlth & Vet Labs Agcy, Addlestone, Surrey, England.
[Gregori, Luisa] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
RP Bannach, O (reprint author), Ctr Biol Evaluat & Res, Food & Drug Adm, Rockville, MD USA.
EM bannacho@hhu.de
RI Willbold, Dieter/A-6280-2013; Birkmann, Eva/H-6019-2013; Bannach,
Oliver/A-4794-2015; APHA, Staff publications/E-6082-2010
OI Willbold, Dieter/0000-0002-0065-7366; Birkmann, Eva/0000-0002-2069-0630;
Bannach, Oliver/0000-0002-7438-3791;
FU UK Food Standards Agency [M03063]; VA Merit Review funding; NIH
[N01-NS-0-2327]
FX This work was supported by funding from the UK Food Standards Agency
(project M03063). RGR and LG were supported by VA Merit Review funding
and NIH Contract: N01-NS-0-2327. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 49
TC 20
Z9 20
U1 1
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAY 2
PY 2012
VL 7
IS 5
AR e36620
DI 10.1371/journal.pone.0036620
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959US
UT WOS:000305341500089
PM 22567169
ER
PT J
AU Khuda, S
Slate, A
Pereira, M
Al-Taher, F
Jackson, L
Diaz-Amigo, C
Bigley, EC
Whitaker, T
Williams, KM
AF Khuda, Sefat
Slate, Andrew
Pereira, Marion
Al-Taher, Fadwa
Jackson, Lauren
Diaz-Amigo, Carmen
Bigley, Elmer C., III
Whitaker, Thomas
Williams, Kristina M.
TI Effect of Processing on Recovery and Variability Associated with
Immunochemical Analytical Methods for Multiple Allergens in a Single
Matrix: Sugar Cookies
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE allergen detection; ELISA methods; food allergen; incurred reference
material; thermal processing
ID EGG-WHITE PROTEINS; ELISA TEST KITS; PEANUT PROTEINS; FOOD ALLERGENS;
MASS-SPECTROMETRY; HEAT-TREATMENT; IGE-BINDING; MILK; VALIDATION;
PREVALENCE
AB Among the major food allergies, peanut, egg, and milk are the most common. The immunochemical detection of food allergens depends on various factors, such as the food matrix and processing method, which can affect allergen conformation and extractability. This study aimed to (1) develop matrix specific incurred reference materials for allergen testing, (2) determine whether multiple allergens in the same model food can be simultaneously detected, and (3) establish the effect of processing on reference material stability and allergen detection. Defatted peanut flour, whole egg powder, and spray dried milk were added to cookie dough at seven incurred levels before baking. Allergens were measured using five commercial enzyme linked immunosorbent assay (ELISA) kits. All kits showed decreased recovery of all allergens after baking. Analytical coefficients of variation for most kits increased with baking time, but decreased with incurred allergen level. Thus, food processing negatively affects the recovery and variability of peanut, egg, and milk detection in a sugar cookie matrix when using immunochemical methods.
C1 [Khuda, Sefat; Pereira, Marion; Bigley, Elmer C., III; Williams, Kristina M.] US FDA, Laurel, MD 20708 USA.
[Slate, Andrew; Whitaker, Thomas] N Carolina State Univ, Raleigh, NC 27695 USA.
[Al-Taher, Fadwa] IIT, Bedford Pk, IL 60501 USA.
[Jackson, Lauren] US FDA, Bedford Pk, IL 60501 USA.
[Diaz-Amigo, Carmen] Eurofins CTC, Hamburg, Germany.
RP Williams, KM (reprint author), US FDA, Laurel, MD 20708 USA.
EM kristina.williams@fda.hhs.gov
NR 50
TC 20
Z9 20
U1 0
U2 12
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 MAY 2
PY 2012
VL 60
IS 17
BP 4195
EP 4203
DI 10.1021/jf3001839
PG 9
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 933LK
UT WOS:000303362800004
PM 22486175
ER
PT J
AU Khuda, S
Slate, A
Pereira, M
Al-Taher, F
Jackson, L
Diaz-Amigo, C
Bigley, EC
Whitaker, T
Williams, K
AF Khuda, Sefat
Slate, Andrew
Pereira, Marion
Al-Taher, Fadwa
Jackson, Lauren
Diaz-Amigo, Carmen
Bigley, Elmer C., III
Whitaker, Thomas
Williams, Kristina
TI Effect of Processing on Recovery and Variability Associated with
Immunochemical Analytical Methods for Multiple Allergens in a Single
Matrix: Dark Chocolate
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE allergen detection; chocolate matrix; ELISA methods; food allergen;
incurred reference material; thermal processing
ID EGG-WHITE PROTEINS; ELISA TEST KITS; PEANUT PROTEINS; MASS-SPECTROMETRY;
FOOD ALLERGENS; HEAT-TREATMENT; MILK; VALIDATION; RESIDUES; COOKIES
AB Immunodetection of allergens in dark chocolate is complicated by interference from the chocolate components. The objectives of this study were to establish reference Materials for detecting multiple allergens in dark chocolate and to determine the accuracy and precision of allergen detection by enzyme linked immunosorbent assay (ELISA) before and after chocolate processing. Defatted peanut flour, whole egg powder, and spray-dried milk were added to melted chocolate at seven incurred levels and tempered for 4 h. Allergen concentrations were measured using commercial ELISA kits. Tempering decreased the detection of casein and beta-lactoglobulin (BLG), but had no significant effect on the detection of peanut and egg. Total coefficients of variation were higher in tempered than untempered chocolate for casein and BLG, but total and analytical CVs were comparable for peanut and egg. These findings indicate that processing has a greater effect on recovery and variability of casein and BLG than peanut and egg detection in a dark chocolate Matrix.
C1 [Khuda, Sefat; Pereira, Marion; Bigley, Elmer C., III; Williams, Kristina] US FDA, Laurel, MD 20708 USA.
[Slate, Andrew; Whitaker, Thomas] N Carolina State Univ, Raleigh, NC 27695 USA.
[Al-Taher, Fadwa] IIT, Bedford Pk, IL 60501 USA.
[Jackson, Lauren] US FDA, Bedford Pk, IL 60501 USA.
[Diaz-Amigo, Carmen] Eurofins CTC, Hamburg, Germany.
RP Williams, K (reprint author), US FDA, Laurel, MD 20708 USA.
EM kristina.williams@fda.hhs.gov
NR 34
TC 12
Z9 12
U1 1
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD MAY 2
PY 2012
VL 60
IS 17
BP 4204
EP 4211
DI 10.1021/jf3001845
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 933LK
UT WOS:000303362800005
PM 22486152
ER
PT J
AU Hamilton, WR
Trickler, WJ
Robinson, BL
Paule, MG
Ali, SF
AF Hamilton, W. Ryan
Trickler, William J.
Robinson, Bonnie L.
Paule, Merle G.
Ali, Syed F.
TI Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on
retinal dopaminergic system in mice
SO NEUROSCIENCE LETTERS
LA English
DT Article
DE Retina; Methamphetamine; MPTP; Dopamine; Neurotoxicity
ID MONOAMINE-OXIDASE; PARKINSONS-DISEASE; INDUCED NEUROTOXICITY; MOUSE
RETINA; METHAMPHETAMINE; METABOLISM; NOREPINEPHRINE; STRIATUM;
ELECTRORETINOGRAM; CATECHOLAMINES
AB The neurotoxins methamphetamine (METH) and MPTP are well-known for their effects on the nigrostriatal dopaminergic system and use in modeling neurodegenerative disorders such as Parkinson's disease. It is not well-known though, how METH or MPTP affects the visual system and specifically the retinal dopaminergic system. This study was designed to examine acute effects of multiple doses of METH and MPTP on the retinal dopaminergic system. Mice were exposed to either low-(LD) 10 mg/kg total dose or high-dose (HD) 30 mg/kg total dose, of METH or MPTP and the retinal catecholaminergic system was analyzed by HPLC. METH produced no significant changes in dopamine (DA), its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) or DA usage in the retina. LD-MFTP produced no change in DA level, but significantly decreased DOPAC and HVA. LD-MPTP also significantly decreased DA usage as measured by the DOPAC/DA and HVA/DA ratios. HD-MFTP significantly decreased DA, DOPAC and HVA, but did not affect DA usage. Taken together these results suggest that inhibition of the DA metabolizing enzymes monoamine oxidase A (MAO) or catechol-O-methyl transferase (COMT) may take place at lower doses of MPTP treatment; conversely, higher doses of MPTP may cause decreases in DA, DOPAC and HVA through another mechanism. (C) 2012 Published by Elsevier Ireland Ltd.
C1 [Hamilton, W. Ryan; Trickler, William J.; Robinson, Bonnie L.; Paule, Merle G.; Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, NCTR, Jefferson, AR 72079 USA.
RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, NCTR, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Syed.Ali@fda.hhs.gov
FU National Center for Toxicological Research/FDA; U.S. Food and Drug
Administration
FX This research was supported in part by an appointment (WRH) to the
Postgraduate Research Participation Program at the National Center for
Toxicological Research/FDA (Jefferson, AR) administered by the Oak Ridge
Institute of Science and Education (Oak Ridge, TN) and the U.S. Food and
Drug Administration.
NR 39
TC 1
Z9 1
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3940
J9 NEUROSCI LETT
JI Neurosci. Lett.
PD MAY 2
PY 2012
VL 515
IS 2
BP 107
EP 110
DI 10.1016/j.neulet.2012.02.085
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA 936YD
UT WOS:000303625000002
PM 22414866
ER
PT J
AU Califf, RM
Zarin, DA
Kramer, JM
Sherman, RE
Aberle, LH
Tasneem, A
AF Califf, Robert M.
Zarin, Deborah A.
Kramer, Judith M.
Sherman, Rachel E.
Aberle, Laura H.
Tasneem, Asba
TI Characteristics of Clinical Trials Registered in ClinicalTrials.gov,
2007-2010
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIALS; MEDICAL-JOURNAL-EDITORS;
INTERNATIONAL-COMMITTEE; RESEARCH ENTERPRISE; PRACTICE GUIDELINES;
REGISTRATION; STATEMENT; RECOMMENDATIONS; GLOBALIZATION; QUALITY
AB Context Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio.
Objective To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database.
Methods A data set comprising 96 346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States.
Main Outcome Measures Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs).
Results The number of registered interventional clinical trials increased from 28 881(October 2004-September 2007) to 40 970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24 788/37 520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17 592/37 520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials.
Conclusion Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs. JAMA. 2012;307(17):1838-1847 www.jama.com
C1 [Califf, Robert M.; Kramer, Judith M.] Duke Translat Med Inst, Durham, NC 27710 USA.
[Zarin, Deborah A.] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Sherman, Rachel E.] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Kramer, Judith M.; Aberle, Laura H.; Tasneem, Asba] Duke Clin Res Inst, Durham, NC USA.
RP Califf, RM (reprint author), Duke Translat Med Inst, 200 Trent Dr,1117 Davison Bldg, Durham, NC 27710 USA.
EM robert.califf@duke.edu
FU Amylin; Johnson & Johnson (Scios); Merck; Novartis Pharma; Schering
Plough; Bristol-Myers Squibb Foundation; Aterovax; Bayer; Roche; Lilly;
Kowa Research Institute; Nile; Parkview; Orexigen Therapeutics; Pozen;
Servier International; WebMD; AstraZeneca; Bayer-OrthoMcNeil; BMS;
Boerhinger Ingelheim; Daiichi Sankyo; GlaxoSmithKline; Li Ka Shing
Knowledge Institute; Medtronic; Novartis; sanofi-aventis; XOMA;
University of Florida; Duke Clinical Research Institute; CTTI; Pfizer;
US Food and Drug Administration [U19FD003800]
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Califf reports receiving research
grants that partially support his salary from Amylin, Johnson & Johnson
(Scios), Merck, Novartis Pharma, Schering Plough, Bristol-Myers Squibb
Foundation, Aterovax, Bayer, Roche, and Lilly; all grants are paid to
Duke University. Dr Califf also consults for TheHeart.org, Johnson &
Johnson (Scios), Kowa Research Institute, Nile, Parkview, Orexigen
Therapeutics, Pozen, Servier International, WebMD, Bristol-Myers Squibb
Foundation, AstraZeneca, Bayer-OrthoMcNeil, BMS, Boerhinger Ingelheim,
Daiichi Sankyo, GlaxoSmithKline, Li Ka Shing Knowledge Institute,
Medtronic, Merck, Novartis, sanofi-aventis, XOMA, and University of
Florida; all income from these consultancies is donated to nonprofit
organizations, with the majority going to the clinical research
fellowship fund of the Duke Clinical Research Institute. Dr Califf holds
equity in Nitrox LLC. Dr Kramer is the executive director of the
Clinical Trials Transformation Institute (CTTI), a public-private
partnership. A portion of Dr Kramer's salary is supported by pooled
funds from CTTI members
(https://www.ctticlinicaltrials.org/about/membership). Dr Kramer reports
receiving a research grant from Pfizer that supports a small percentage
of her salary; this grant is paid to Duke University. Dr Kramer also
served on an advisory board for the "Pharmacovigilance Center of
Excellence" at GlaxoSmithKline, for which she received an honorarium.
Financial disclosure information for Drs Califf and Kramer is also
publicly available at
https://www.dcri.org/about-us/conflict-of-interest. No other disclosures
were reported.; Financial support for this project was provided by grant
U19FD003800 from the US Food and Drug Administration awarded to Duke
University for the Clinical Trials Transformation Initiative.
NR 33
TC 141
Z9 142
U1 1
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD MAY 2
PY 2012
VL 307
IS 17
BP 1838
EP 1847
DI 10.1001/jama.2012.3424
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 933TV
UT WOS:000303386800023
PM 22550198
ER
PT J
AU Colman, E
AF Colman, Eric
TI Food and Drug Administration's Obesity Drug Guidance Document A Short
History
SO CIRCULATION
LA English
DT Article
DE cholesterol; diabetes mellitus, type 2; hypertension; lipids; obesity
ID PLACEBO-CONTROLLED TRIAL; VALVULAR HEART-DISEASE; DIETARY-FAT
ABSORPTION; WEIGHT-LOSS; APPETITE-SUPPRESSANTS; CARDIOVASCULAR RISK;
HEALTHY-VOLUNTEERS; DOUBLE-BLIND; BODY-WEIGHT; SIBUTRAMINE
C1 US FDA, Div Metab & Endocrinol Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Colman, E (reprint author), US FDA, Div Metab & Endocrinol Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Bldg 22,Room 3360,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM eric.colman@fda.hhs.gov
NR 66
TC 30
Z9 30
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD MAY 1
PY 2012
VL 125
IS 17
BP 2156
EP 2164
DI 10.1161/CIRCULATIONAHA.111.028381
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 981IC
UT WOS:000306959200025
PM 22547756
ER
PT J
AU Ngundi, MM
Meade, BD
Little, SF
Quinn, CP
Corbett, CR
Brady, RA
Burns, DL
AF Ngundi, Miriam M.
Meade, Bruce D.
Little, Stephen F.
Quinn, Conrad P.
Corbett, Cindi R.
Brady, Rebecca A.
Burns, Drusilla L.
TI Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax
Toxin Neutralization Assays and Their Synergistic Action
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; LETHAL TOXIN; IN-VITRO;
INHALATIONAL ANTHRAX; RHESUS MACAQUES; FC-RECEPTORS; GUINEA-PIGS;
VACCINE; IMMUNITY
AB Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax.
C1 [Ngundi, Miriam M.; Brady, Rebecca A.; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Little, Stephen F.] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA.
[Meade, Bruce D.] Meade Biol, Hillsborough, NC USA.
[Quinn, Conrad P.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Corbett, Cindi R.] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada.
RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
EM drusilla.burns@fda.hhs.gov
FU National Institute of Allergy and Infectious Diseases, NIH; Food and
Drug Administration
FX This work was supported in part by an interagency agreement between the
National Institute of Allergy and Infectious Diseases, NIH, and the Food
and Drug Administration.
NR 42
TC 9
Z9 9
U1 0
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD MAY
PY 2012
VL 19
IS 5
BP 731
EP 739
DI 10.1128/CVI.05714-11
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 983GU
UT WOS:000307108600014
PM 22441391
ER
PT J
AU Ilev, IK
Boppart, SA
Andersson-Engels, S
Kim, BM
Vo-Dinh, T
AF Ilev, Ilko K.
Boppart, Stephen A.
Andersson-Engels, Stefan
Kim, Beop-Min
Vo-Dinh, Tuan
TI Introduction to the Issue on Biophotonics-Part 1
SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS
LA English
DT Editorial Material
C1 [Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Bioengn, Urbana, IL 61801 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Elect & Comp Engn, Urbana, IL 61801 USA.
[Boppart, Stephen A.] Univ Illinois, Beckman Inst Adv Sci & Technol, Dept Med, Urbana, IL 61801 USA.
[Andersson-Engels, Stefan] Lund Univ, Div Atom Phys, SE-22100 Lund, Sweden.
[Kim, Beop-Min] Korea Univ, Dept Biomed Engn, Seoul 136703, South Korea.
[Vo-Dinh, Tuan] Duke Univ, Fitzpatrick Inst Photon, Durham, NC 27708 USA.
RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM ilko.ilev@fda.hhs.gov
RI Andersson-Engels, Stefan/C-5515-2012
OI Andersson-Engels, Stefan/0000-0001-5640-3122
NR 0
TC 0
Z9 0
U1 0
U2 8
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1077-260X
J9 IEEE J SEL TOP QUANT
JI IEEE J. Sel. Top. Quantum Electron.
PD MAY-JUN
PY 2012
VL 18
IS 3
BP 1039
EP 1041
DI 10.1109/JSTQE.2012.2187845
PG 3
WC Engineering, Electrical & Electronic; Optics; Physics, Applied
SC Engineering; Optics; Physics
GA 975PW
UT WOS:000306524300001
ER
PT J
AU Samuels-Reid, J
Lawrence, B
Millin, C
Cope, J
AF Samuels-Reid, Joy
Lawrence, Brenda
Millin, Courtney
Cope, Judith
TI Pediatric devices and adverse events from A to Z: understanding the
benefits and risks from a US FDA perspective
SO EXPERT REVIEW OF MEDICAL DEVICES
LA English
DT Review
DE adverse events; children; device safety; harmful effects; pediatric
devices; pediatric subpopulation; medical devices
ID COCHLEAR IMPLANTS; MENINGITIS; CHILDREN; SAFETY
AB Medical devices are often overlooked as a contributor to adverse events. In clinical practice, physicians are aware of the potential for adverse effects from drug products, which are routinely included in differential diagnoses of patients' presenting complaints. However, physicians may not always consider that the use, misuse or malfunction of a medical device, and/or its components, may result in a patient's presenting signs and symptoms or lack of improvement. Consideration of medical devices is particularly important in the pediatric population, who may be especially susceptible to device-related adverse events due to their smaller body size, weight and ongoing rapid growth and development.
C1 [Samuels-Reid, Joy] US FDA, Div Anesthesiol, Gen Hosp, Off Device Evaluat,Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Millin, Courtney] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Cope, Judith] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA.
RP Samuels-Reid, J (reprint author), US FDA, Div Anesthesiol, Gen Hosp, Off Device Evaluat,Ctr Devices & Radiol Hlth, White Oak Bldg 66,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM joy.samuels-reid@fda.hhs.gov
NR 20
TC 0
Z9 0
U1 0
U2 1
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 MAY
PY 2012
VL 9
IS 3
BP 275
EP 282
DI 10.1586/ERD.12.7
PG 8
WC Engineering, Biomedical
SC Engineering
GA 975WP
UT WOS:000306542500015
PM 22702258
ER
PT J
AU He, Z
Paule, MG
Ferguson, SA
AF He, Zhen
Paule, Merle G.
Ferguson, Sherry A.
TI Low oral doses of bisphenol A increase volume of the sexually dimorphic
nucleus of the preoptic area in male, but not female, rats at postnatal
day 21
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Article
DE Bisphenol A; Calbindin D28K; Ethinyl estradiol; Perinatal oral exposure;
Sexually dimorphic nucleus
ID GONADOTROPIN-RELEASING-HORMONE; MESSENGER-RNA EXPRESSION;
SEX-DIFFERENCES; PITUITARY-RESPONSIVENESS; PHYTOESTROGEN GENISTEIN;
ANOGENITAL DISTANCE; ENDOCRINE DISRUPTOR; RECEPTOR EXPRESSION; ESTROGEN
ANTAGONIST; NEONATAL EXPOSURE
AB Perinatal treatment with relatively high doses of bisphenol A (BPA) appears to have little effect on volume of the rodent sexually dimorphic nucleus of the preoptic area (SDN-POA). However, doses more relevant to human exposures have not been examined. Here, effects of pre- and post-natal treatment with low BPA doses on SDN-POA volume of postnatal day (PND) 21 Sprague-Dawley rats were evaluated. Pregnant rats were orally gavaged with vehicle, 2.5 or 25.0 mu g/kg BPA, or 5.0 or 10.0 mu g/kg ethinyl estradiol (EE2) on gestational days 6-21. Beginning on the day after birth, offspring were orally treated with the same dose their dam had received. On PND 21, offspring (n=10-15/sex/group; 1/sex/litter) were perfused and volume evaluation was conducted blind to treatment. SDN-POA outline was delineated using calbindin D28K immunoreactivity. Pairwise comparisons of the significant treatment by sex interaction indicated that neither BPA dose affected female volume. However, females treated with 5.0 or 10.0 mu g/kg EE2 exhibited volumes that were larger than same-sex controls, respectively (p<0.001). Males treated with either BPA dose or 10.0 mu g/kg/day EE2 had larger volumes than same-sex controls (p<0.006). These data indicate that BPA can have sex-specific effects on SDN-POA volume and that these effects manifest as larger volumes in males. Sensitivity of the methodology as well as the treatment paradigm was confirmed by the expected EE2-induced increase in female volume. These treatment effects might lead to organizational changes within sexually dimorphic neuroendocrine pathways which, if persistent, could theoretically alter adult reproductive physiology and socio-sexual behavior in rats. Published by Elsevier Inc.
C1 [He, Zhen; Paule, Merle G.; Ferguson, Sherry A.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Zhen.He@fda.hhs.gov; Merle.Paule@fda.hhs.gov;
Sherry.Ferguson@fda.hhs.gov
FU National Center for Toxicological Research/FDA [P00706, P00710]
FX This study was supported by the National Center for Toxicological
Research/FDA (Protocol P00706 to S.A.F. and Protocol P00710 to Z.H.).
NR 55
TC 21
Z9 21
U1 1
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 329
EP 335
DI 10.1016/j.ntt.2012.03.004
PG 7
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600005
PM 22507915
ER
PT J
AU Chelonis, J
Osborn, S
Glenn, M
Paule, M
AF Chelonis, John
Osborn, Seth
Glenn, Matthew
Paule, Merle
TI Comparison of delayed matching-to-sample performance in children and
adult rhesus monkeys
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Chelonis, John; Paule, Merle] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chelonis, John; Osborn, Seth; Glenn, Matthew; Paule, Merle] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 369
EP 369
DI 10.1016/j.ntt.2012.05.005
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600013
ER
PT J
AU Ferguson, S
AF Ferguson, Sherry
TI Use of rodent tests of depression in neurobehavioral toxicology
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Ferguson, Sherry] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 371
EP 372
DI 10.1016/j.ntt.2012.05.013
PG 2
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600021
ER
PT J
AU Paule, M
Zhang, X
Newport, G
Liu, SL
Liu, F
Callicott, R
Berridge, M
Apana, S
Hanig, J
Slikker, W
Wang, C
AF Paule, Merle
Zhang, Xuan
Newport, Glenn
Liu, Shuliang
Liu, Fang
Callicott, Ralph
Berridge, Marc
Apana, Scott
Hanig, Joseph
Slikker, William
Wang, Cheng
TI L-carnitine attenuates anesthetic-induced increases in a marker of glial
activation in the developing monkey brain
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Paule, Merle; Zhang, Xuan; Newport, Glenn; Liu, Shuliang; Liu, Fang; Callicott, Ralph; Slikker, William; Wang, Cheng] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Berridge, Marc; Apana, Scott] 3D Imaging, Little Rock, AR USA.
[Hanig, Joseph] US FDA, Ctr Drug Evaluat & Res, White Oak, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 375
EP 375
DI 10.1016/j.ntt.2012.05.023
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600031
ER
PT J
AU Chelonis, J
Aaron, H
Belk, G
Castro, J
Baldwin, S
Sutton, A
Paule, M
AF Chelonis, John
Aaron, Haley
Belk, Georgia
Castro, Juan
Baldwin, Shelly
Sutton, Andrea
Paule, Merle
TI Effects of anxiety on motivation in children as measured by progressive
ratio task performance
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Chelonis, John; Sutton, Andrea; Paule, Merle] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Aaron, Haley; Belk, Georgia] Hendrix Coll, Conway, AR USA.
[Chelonis, John; Aaron, Haley; Belk, Georgia; Castro, Juan; Baldwin, Shelly; Sutton, Andrea; Paule, Merle] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 381
EP 381
DI 10.1016/j.ntt.2012.05.041
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600049
ER
PT J
AU Fisher, L
Ferguson, S
AF Fisher, Leah
Ferguson, Sherry
TI Decreased anxiety in adult rats developmentally exposed to
methylphenidate
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Fisher, Leah] Univ Arkansas, Little Rock, AR 72204 USA.
[Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 381
EP 382
DI 10.1016/j.ntt.2012.05.043
PG 2
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600051
ER
PT J
AU Maier, K
Ferguson, S
AF Maier, Kaitlyn
Ferguson, Sherry
TI Developmental methylphenidate exposure does not alter rodent righting
reflex or slant board behaviors
SO NEUROTOXICOLOGY AND TERATOLOGY
LA English
DT Meeting Abstract
CT 36th Annual Meeting of the Neurobehavioral-Teratology-Society
(NBTS)/52nd Annual Meeting of the Teratology-Society/25th Annual Meeting
of the Organization-of-Teratology-Information-Specialists
CY JUN 23-27, 2012
CL Baltimore, MD
SP Neurobehav Teratol Soc (NBTS), Teratol Soc, Org Teratol Informat Specialists
C1 [Maier, Kaitlyn; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0892-0362
J9 NEUROTOXICOL TERATOL
JI Neurotoxicol. Teratol.
PD MAY-JUN
PY 2012
VL 34
IS 3
BP 382
EP 382
DI 10.1016/j.ntt.2012.05.045
PG 1
WC Neurosciences; Toxicology
SC Neurosciences & Neurology; Toxicology
GA 970QE
UT WOS:000306146600053
ER
PT J
AU McCleary, BV
DeVries, JW
Rader, JI
Cohen, G
Prosky, L
Mugford, DC
Champ, M
Okuma, K
AF McCleary, Barry V.
DeVries, Jonathan W.
Rader, Jeanne I.
Cohen, Gerald
Prosky, Leon
Mugford, David C.
Champ, Martine
Okuma, Kazuhiro
TI Determination of Insoluble, Soluble, and Total Dietary Fiber (CODEX
Definition) by Enzymatic-Gravimetric Method and Liquid Chromatography:
Collaborative Study
SO JOURNAL OF AOAC INTERNATIONAL
LA English
DT Article
AB A method for the determination of insoluble (IDF), soluble (SDF), and total dietary fiber (TDF), as defined by the CODEX Alimentarius, was validated in foods. Based upon the principles of AOAC Official Methods(SM) 985.29, 991.43, 2001.03, and 2002.02, the method quantitates water-insoluble and water-soluble dietary fiber. This method extends the capabilities of the previously adopted AOAC Official Method 2009.01, Total Dietary Fiber in Foods, Enzymatic-Gravimetric-Liquid Chromatographic Method, applicable to plant material, foods, and food ingredients consistent with CODEX Definition 2009, including naturally occurring, isolated, modified, and synthetic polymers meeting that definition. The method was evaluated through an AOAC/AACC collaborative study. Twenty-two laboratories participated, with 19 laboratories returning valid assay data for 16 test portions (eight blind duplicates) consisting of samples with a range of traditional dietary fiber, resistant starch, and nondigestible oligosaccharides. The dietary fiber content of the eight test pairs ranged from 10.45 to 29.90%. Digestion of samples under the conditions of AOAC 2002.02 followed by the isolation, fractionation, and gravimetric procedures of AOAC 985.29 (and its extensions 991.42 and 993.19) and 991.43 results in quantitation of IDF and soluble dietary fiber that precipitates (SDFP). The filtrate from the quantitation of water-alcohol-insoluble dietary fiber is concentrated, deionized, concentrated again, and analyzed by LC to determine the SDF that remains soluble (SDFS), i.e., all dietary fiber polymers of degree of polymerization = 3 and higher, consisting primarily, but not exclusively, of oligosaccharides. SDF is calculated as the sum of SDFP and SDFS. TDF is calculated as the sum of IDF and SDF. The within-laboratory variability, repeatability SD (s(r)), for IDF ranged from 0.13 to 0.71, and the between-laboratory variability, reproducibility SD (s(R)), for IDF ranged from 0.42 to 2.24. The within-laboratory variability s(r) for SDF ranged from 0.28 to 1.03, and the between-laboratory variability s(R) for SDF ranged from 0.85 to 1.66. The within-laboratory variability s(r) for TDF ranged from 0.47 to 1.41, and the between-laboratory variability s(R) for TDF ranged from 0.95 to 3.14. This is comparable to other official and approved dietary fiber methods, and the method is recommended for adoption as Official First Action.
C1 [McCleary, Barry V.] Megazyme Int, Bray, Co Wicklow, Ireland.
[DeVries, Jonathan W.] Medall Labs Gen Mills, Golden Valley, MN 55427 USA.
[Rader, Jeanne I.] US FDA, College Pk, MD 20740 USA.
[Cohen, Gerald] Kraft Foods, New City, NY USA.
[Prosky, Leon] US FDA, Rockville, MD 20850 USA.
[Mugford, David C.] BRI Australia Pty Ltd, N Ryde, NSW 1670, Australia.
[Champ, Martine] Hop Hotel Dieu, UMR PhAN, INRA, CRNH, F-44093 Nantes 1, France.
[Okuma, Kazuhiro] Matsutani Chem, Res Lab, Itami, Hyogo 6648508, Japan.
RP McCleary, BV (reprint author), Megazyme Int, Bray Business Pk, Bray, Co Wicklow, Ireland.
EM barry@megazyme.com
NR 10
TC 35
Z9 38
U1 1
U2 85
PU AOAC INT
PI GAITHERSBURG
PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA
SN 1060-3271
J9 J AOAC INT
JI J. AOAC Int.
PD MAY-JUN
PY 2012
VL 95
IS 3
BP 824
EP 844
DI 10.5740/jaoacint.CS2011_25
PG 21
WC Chemistry, Analytical; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 960CW
UT WOS:000305366600030
PM 22816275
ER
PT J
AU Miller, DL
Schueler, BA
Balter, S
AF Miller, Donald L.
Schueler, Beth A.
Balter, Stephen
TI New Recommendations for Occupational Radiation Protection
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Schueler, Beth A.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Balter, Stephen] Columbia Univ, Dept Radiol, New York, NY USA.
[Balter, Stephen] Columbia Univ, Dept Med, New York, NY USA.
RP Miller, DL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM donald.miller@fda.hhs.gov
NR 10
TC 8
Z9 8
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD MAY
PY 2012
VL 9
IS 5
BP 366
EP 368
DI 10.1016/j.jacr.2012.02.006
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 961FN
UT WOS:000305449700016
PM 22554637
ER
PT J
AU Slikker, W
Zhang, X
Newport, GD
Paule, MG
Liu, F
Berridge, MS
Kabalka, G
Wang, C
AF Slikker, W.
Zhang, X.
Newport, G. D.
Paule, M. G.
Liu, F.
Berridge, M. S.
Kabalka, G.
Wang, C.
TI Assessment of Developmental Exposure to Pediatric Anesthetics Using
MicroPET Imaging
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Slikker, W.; Zhang, X.; Newport, G. D.; Paule, M. G.; Liu, F.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Berridge, M. S.] 3D Imaging, Little Rock, AR USA.
[Kabalka, G.] Univ Tennessee, Knoxville, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2012
VL 94
IS 5
SI SI
BP 330
EP 330
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 956FF
UT WOS:000305074800073
ER
PT J
AU Inselman, AL
Nakamura, N
White, G
Harrouk, W
Mcintyre, B
Foster, P
Hansen, DK
AF Inselman, A. L.
Nakamura, N.
White, G.
Harrouk, W.
Mcintyre, B.
Foster, P.
Hansen, D. K.
TI Potential Reproductive and Developmental Toxicity of Oxybenzone: A
Dose-Finding Study
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Inselman, A. L.; Nakamura, N.; White, G.; Hansen, D. K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Harrouk, W.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Mcintyre, B.; Foster, P.] Natl Inst Environm Hlth, Natl Toxicol Program, NIH, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2012
VL 94
IS 5
SI SI
BP 349
EP 349
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 956FF
UT WOS:000305074800110
ER
PT J
AU Tassinari, MS
AF Tassinari, M. S.
TI Pregnancy Registries: Lessons Learned and Opportunities Ahead
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Tassinari, M. S.] US FDA, Off New Drugs Pediat & Maternal Hlth Staff, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2012
VL 94
IS 5
SI SI
BP 364
EP 364
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 956FF
UT WOS:000305074800135
ER
PT J
AU Howard, TB
AF Howard, T. B.
TI Pregnancy Data Labeling Challenges: A Discussion with FDA Perspective
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Meeting Abstract
C1 [Howard, T. B.] US FDA, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD MAY
PY 2012
VL 94
IS 5
SI SI
BP 374
EP 374
PG 1
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 956FF
UT WOS:000305074800155
ER
PT J
AU Tomas, CR
van Wagoner, R
Tatters, AO
White, KD
Hall, S
Wright, JLC
AF Tomas, Carmelo R.
van Wagoner, Ryan
Tatters, Avery O.
White, Kevin D.
Hall, Sherwood
Wright, Jeffrey L. C.
TI Alexandrium peruvianum (Balech and Mendiola) Balech and Tangen a new
toxic species for coastal North Carolina
SO HARMFUL ALGAE
LA English
DT Article
DE Alexandrium peruvianum; A. ostenfeldii; 13-Desmethyl spirolide C, D;
STX; GTX2; 3; B1; STX; C1,2; Hemolytic activity; New River; North
Carolina
ID SPIROLIDE MARINE TOXINS; MASS-SPECTROMETRY; OSTENFELDII DINOPHYCEAE;
HEMOLYTIC COMPOUNDS; SHELLFISH TOXINS; PLANKTON; IDENTIFICATION;
RAPHIDOPHYCEAE; IMPACTS; TAYLORI
AB Routine sampling of the water quality stations in the New River Estuary (Jacksonville, North Carolina, USA) during November 2004 revealed the presence of a previously unidentified dinoflagellate. Preliminary observations of its morphology suggested it to be consistent with that of Alexandrium peruvianum (Balech et Mendiola) Balech et Tangen. Observations using brightfield, epifluorescence and scanning electron microscopy confirmed the diagnostic thecal plates to be those of A. peruvanium. Clonal cultures established from cells isolated from the New River Estuary samples were also used for further studies of morphology and for the presence of toxins. Thecal morphology was consistent with that described by Balech clearly separating it from the sister species Alexandrium ostenfeldii. Three classes of toxins were detected from these cultures. An erythrocyte lysis assay (ELA) was used to confirm the presence of hemolytic toxins in A. peruvianum cultures. A cellular EC(5)0 for lysis was 1.418 x 10(4) cells, well within the range the maximal cells densities found in the New River and more potent when compared on a cellular basis with Prymnesium parvum. Another toxin class detected in A. peruvianum cultures was the fast acting 13-desmethy C and D spirolides also produced by the sister species A. ostenfeldii. The last toxin type detected in the A. peruvianum cultures was the paralytic shellfish toxins, GTX 2, 3, B1, SIX and C1,2. These findings expand the geographic range of occurrence for A. peruvianum in the U.S. to be much greater than previously considered. The morphological characters agreed with previously reported molecular data in separating A. peruvianum from A. ostenfeldii. It is also the first confirmed report that this species produces PSP toxins, spirolides and naturally occurring hemolytic substances. In light of these findings additional attention is needed for the detection of Alexandrium species in all coastal waters of the U.S. This added effort will enhance the evaluation of the relative impacts of the species to shellfish safety and bloom surveillance. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Tomas, Carmelo R.; van Wagoner, Ryan; Tatters, Avery O.; Wright, Jeffrey L. C.] Univ N Carolina Wilmington, Ctr Marine Sci, Wilmington, NC 28409 USA.
[White, Kevin D.; Hall, Sherwood] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Tomas, CR (reprint author), Univ N Carolina Wilmington, Ctr Marine Sci, 5600 Marvin K Moss Lane, Wilmington, NC 28409 USA.
EM tomasc@uncw.edu
FU NC Water Resources Research Institute [50337]; Centers for Disease
Control through NC DHHS [01505-07]; State of North Carolina Marine
Biotechnology Program (MARBIONC)
FX We thank Ms. Stephanie Garrett of the North Carolina Department of
Environment and Natural Resources, Division of Water Quality, for
critical assistance in collecting samples from the New River. Mr. Robert
York assisted with the SEM preparations, Ms. Brooke Stuercke gave
invaluable assistance with maintaining cultures and Ms. Melissa D. Smith
assisted with the preparation of the figures. Dr. Anita Freudenthal
kindly provided clarification of sample locations in Long Island, NY.
This work was supported by the NC Water Resources Research Institute
award # 50337, and Centers for Disease Control through NC DHHS Grant #
01505-07 awarded to C. Tomas and funds from State of North Carolina
Marine Biotechnology Program (MARBIONC) (C. Tomas, R. Van Wagoner and
J.L.C. Wright). [TS]
NR 47
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Z9 24
U1 1
U2 20
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-9883
J9 HARMFUL ALGAE
JI Harmful Algae
PD MAY
PY 2012
VL 17
BP 54
EP 63
DI 10.1016/j.hal.2012.02.011
PG 10
WC Marine & Freshwater Biology
SC Marine & Freshwater Biology
GA 952MR
UT WOS:000304797100007
ER
PT J
AU Wilson, R
Hart, P
Piccardo, P
Hunter, N
Casalone, C
Baron, T
Barron, RM
AF Wilson, Rona
Hart, Patricia
Piccardo, Pedro
Hunter, Nora
Casalone, Cristina
Baron, Thierry
Barron, Rona M.
TI Bovine PrP expression levels in transgenic mice influence transmission
characteristics of atypical bovine spongiform encephalopathy
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; MOLECULAR ANALYSIS; INCUBATION
PERIOD; STRAIN VARIATION; VARIANT CJD; BSE; CATTLE; IDENTIFICATION;
ACCUMULATION
AB Until recently, transmissible spongiform encephalopathy (TSE) disease in cattle was thought to be caused by a single agent strain, bovine spongiform encephalopathy (BSE) (classical BSE or BSE-C). However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. These atypical BSE isolates have been previously transmitted to a range of transgenic mouse models overexpressing PrP from different species at different levels, on a variety of genetic backgrounds. To control for genetic background and expression level in the analysis of these isolates, we performed here a comprehensive comparison of the neuropathological and molecular properties of all three BSE agents (BASE, BSE-C and BSE-H) upon transmission into the same gene-targeted transgenic mouse line expressing the bovine prion protein (Bov6) and a wild-type control of the same genetic background. Significantly, upon challenge with these BSE agents, we found that BASE did not produce shorter survival times in these mice compared with BSE-C, contrary to previous studies using overexpressing bovine transgenic mice. Amyloid plaques were only present in mice challenged with atypical BSE and neuropathological features, including intensity of PrP deposition in the brain and severity of vacuolar degeneration were less pronounced in BASE compared with BSE-C-challenged mice.
C1 [Wilson, Rona; Hart, Patricia; Piccardo, Pedro; Hunter, Nora; Barron, Rona M.] Univ Edinburgh, Roslin Inst, Div Neurobiol, Roslin, Midlothian, Scotland.
[Wilson, Rona; Hart, Patricia; Piccardo, Pedro; Hunter, Nora; Barron, Rona M.] Univ Edinburgh, RDSVS, Roslin, Midlothian, Scotland.
[Piccardo, Pedro] US FDA, Lab Bacterial & TSE Agents, Rockville, MD 20852 USA.
[Casalone, Cristina] Ist Zooprofilatt Sperimentale Piemonte Liguria &, Turin, Italy.
[Baron, Thierry] Agence Natl Secur Sanit, Lyon, France.
RP Barron, RM (reprint author), Univ Edinburgh, Roslin Inst, Div Neurobiol, Roslin, Midlothian, Scotland.
EM rona.barron@roslin.ed.ac.uk
RI Barron, Rona/C-7703-2013;
OI Hart, Patricia/0000-0002-9634-3483; Barron, Rona/0000-0003-4512-9177
FU Food Standards Agency (FSA) UK [M03054]; NIH-NIAID [Y1-AI-4893-02]; Food
and Drug Administration (FDA) [224-05-1307]
FX The authors would like to acknowledge Professor J. Manson for the
gene-targeted bovine Tg line; I. McConnell, V. Thomson, S. Gumming, S.
Carpenter, R. Greenan and K. Hogan for experimental setup, care and
scoring of the animals; A. Coghill, A. Boyle, S. Mack and G. McGregor
for histology processing and scoring; and the Veterinary Laboratories
Agency, Weybridge, UK, for providing the cattle BSE brain pool. These
studies were partly funded by the Food Standards Agency (FSA) UK
(contract M03054) and NIH-NIAID agreement no.Y1-AI-4893-02 and Food and
Drug Administration (FDA) agreement no. 224-05-1307. The findings and
conclusions in this article have not been formally disseminated by the
FDA and should not be construed to represent any Agency determination or
policy.
NR 41
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Z9 7
U1 0
U2 6
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAY
PY 2012
VL 93
BP 1132
EP 1140
DI 10.1099/vir.0.040030-0
PN 5
PG 9
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 951QX
UT WOS:000304736200023
PM 22302882
ER
PT J
AU Miller, VA
Nelson, RM
AF Miller, Victoria A.
Nelson, Robert M.
TI Factors Related to Voluntary Parental Decision-Making in Pediatric
Oncology
SO PEDIATRICS
LA English
DT Article
DE informed consent; parental permission; decision-making; pediatrics;
oncology; ethics
ID BONE-MARROW-TRANSPLANTATION; INFORMED-CONSENT; LEUKEMIA TRIALS;
CLINICAL-TRIALS; HEALTH-CARE; CHILDREN; CANCER; PREFERENCES;
COMMUNICATION; COMPREHENSION
AB OBJECTIVE: The aim of the current study was to examine demographic and contextual correlates of voluntariness in parents making research or treatment decisions for their children with cancer.
METHODS: Participants included 184 parents of children with cancer who made a decision about enrolling the child in a research or treatment protocol within the previous 10 days. Parents completed questionnaires that assessed voluntariness, external influence by others, concern that the child's care would be negatively affected if the parent did not agree, time pressure, information adequacy, and demographics.
RESULTS: Lower perceived voluntariness was associated with lower education, male gender, minority status, and not having previous experience with a similar decision. Parents who reported lower voluntariness also perceived more external influence and time pressure, had more concern about the child's care being negatively affected if they declined, and perceived that they had either too much or not enough information about the decision. In a multivariate regression, education, minority status, gender, external influence, and too little information remained significantly associated with voluntariness.
CONCLUSIONS: Several groups of parents appear to be at risk for decreased voluntariness when making research or treatment decisions for their seriously ill children, including fathers, nonwhite parents, and those with less education. Parental voluntariness may be enhanced by helping parents to mitigate the effects of unhelpful or unwanted influences by others and ensuring that their information needs are met. Pediatrics 2012;129:903-909
C1 [Miller, Victoria A.] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA.
[Miller, Victoria A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA.
RP Miller, VA (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 34th St & Civ Ctr Blvd,CHOP N Room 1425, Philadelphia, PA 19104 USA.
EM millerv@email.chop.edu
FU National Science Foundation [SES-0527618]; National Institutes of
Health/National Cancer Institute [R21CA118377-01A1]; National Institutes
of Health (NIH)
FX Financial support was provided by grants from the National Science
Foundation (SES-0527618; Drs Nelson, Luce, and Beauchamp) and the
National Institutes of Health/National Cancer Institute (grant
R21CA118377-01A1, Dr Nelson) and an Institutional Development Grant to
the Center for Research Integrity, Department of Anesthesiology and
Critical Care, The Children's Hospital of Philadelphia. The funding
agreements ensured the authors' independence in designing the study,
interpreting the data, writing, and publishing the report. Funded by the
National Institutes of Health (NIH).
NR 30
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Z9 13
U1 1
U2 9
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD MAY
PY 2012
VL 129
IS 5
BP 903
EP 909
DI 10.1542/peds.2011-3056
PG 7
WC Pediatrics
SC Pediatrics
GA 951GT
UT WOS:000304709600039
PM 22508918
ER
PT J
AU Sauna, ZE
Pandey, GS
Jain, N
Mahmood, I
Kimchi-Sarfaty, C
Golding, B
AF Sauna, Zuben E.
Pandey, Gouri Shankar
Jain, Nisha
Mahmood, Ifthekar
Kimchi-Sarfaty, Chava
Golding, Basil
TI Plasma derivatives: New products and new approaches
SO BIOLOGICALS
LA English
DT Article; Proceedings Paper
CT 7th International-Association-of-Biological-Standardization Symposium on
Advances in Transfusion Safety (IABS)
CY JUL 15-17, 2011
CL Singapore, SINGAPORE
SP Int Assoc Biol Standardizat (IABS), Singapore Hlth Sci Author (HAS)
DE Hemophilia; Factor VIII; Factor IX; Immunogenicity; Protein
therapeutics; Pharmacogenetics
ID PREVIOUSLY UNTREATED PATIENTS; FACTOR PATHWAY INHIBITOR; RECOMBINANT
FACTOR-VIII; HEMOPHILIA-A THERAPY; FACTOR-IX; PRACTICE PATTERNS;
HALF-LIFE; GENE-THERAPY; FUSION; SAFETY
AB The infusion of plasma-derived or recombinant factors to treat bleeding disorders such as hemophila A and B is a success story in the management of a chronic disease. The effectiveness of this approach is however limited by challenges with adverse effects of treatment. The most notable of these are the development of inhibitory antibodies that target the protein therapeutic. The current standard of care for management of hemophiliacs is prophylactic treatment that includes frequent infusions of a Factor VIII product. Failure to comply with the prophylactic regimen is a major hurdle in the management of these patients. We discuss here more recent findings that argue for a pharmacogenetic approach to understanding (and eventually circumventing) immunogenicity. We also review strategies used to bioengineer coagulation factors to extend the half-lives of coagulation proteins. The rapid progress in the last few years to bioengineer coagulation factors in different ways to attain this goal is described. Finally, novel technologies and potential products are emerging that utilize synthetic molecules in lieu of replacement proteins obviating the limitations associated with replacement therapies. Published by Elsevier Ltd on behalf of International Alliance for Biological Standardization.
C1 [Golding, Basil] US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Sauna, Zuben E.; Pandey, Gouri Shankar; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Jain, Nisha] US FDA, Clin Review Branch, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Mahmood, Ifthekar] US FDA, Clin Pharmacol & Toxicol Branch, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Golding, B (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA.
EM basil.golding@fda.hhs.gov
NR 47
TC 5
Z9 5
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1045-1056
J9 BIOLOGICALS
JI Biologicals
PD MAY
PY 2012
VL 40
IS 3
SI SI
BP 191
EP 195
DI 10.1016/j.biologicals.2011.11.003
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 950HN
UT WOS:000304640300007
PM 22239993
ER
PT J
AU Epstein, JS
AF Epstein, Jay S.
TI Best practices in regulation of blood and blood products
SO BIOLOGICALS
LA English
DT Article; Proceedings Paper
CT 7th International-Association-of-Biological-Standardization Symposium on
Advances in Transfusion Safety (IABS)
CY JUL 15-17, 2011
CL Singapore, SINGAPORE
SP Int Assoc Biol Standardizat (IABS), Singapore Hlth Sci Author (HAS)
DE Blood regulation; Blood regulators network; Assessment criteria;
Precautionary principle
AB The need for blood regulation arises from the inherent risks of blood transfusion, which are minimized through implementation of standards. Regulatory oversight is advocated by the World Health Organization (WHO) as an essential element of any blood system to ensure such standards are met. The WHO Blood Regulators Network has developed "Assessment Criteria for National Blood Regulatory Systems" that describe the legal authority and functions of a fully competent blood regulator. The core functions include licensing and/or registration of blood establishments, marketing approval of blood products, oversight of all associated substances and devices, control of clinical trials, access to an independent laboratory for product assessments, lot release, and hemovigilance systems.
Regulatory policy-making for blood safety is needed to address emerging threats, to consider the risks and benefits of new products and technologies, and to respond to adverse events. Structured policy-making processes are essential to ensure that decisions are science-based, with appropriate consideration of relevant economic and social factors. Decision making is especially challenging in situations of scientific uncertainty, where prudent precautionary measures may be appropriate based on assessments of risk and feasibility of meaningful interventions. There is international interest in finding a common framework for addressing blood safety decisions. Published by Elsevier Ltd on behalf of International Alliance for Biological Standardization.
C1 US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA.
EM Jay.Epstein@fda.hhs.gov
NR 4
TC 5
Z9 5
U1 0
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 MAY
PY 2012
VL 40
IS 3
SI SI
BP 200
EP 204
DI 10.1016/j.biologicals.2011.11.002
PG 5
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Pharmacology & Pharmacy
GA 950HN
UT WOS:000304640300009
PM 22122986
ER
PT J
AU Salminen, WF
Yang, X
Shi, Q
Greenhaw, J
Davis, K
Ali, AA
AF Salminen, William F.
Yang, Xi
Shi, Qiang
Greenhaw, James
Davis, Kelly
Ali, Akhtar A.
TI Green tea extract can potentiate acetaminophen-induced hepatotoxicity in
mice
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Acetaminophen; Dietary supplement; Green tea; Hepatotoxicity; Liver
ID COVALENT BINDING; N-ACETYLCYSTEINE; IN-VIVO; POLYPHENOLS; TOXICITY;
HEPATITIS; OXIDATION; CATECHINS; EFFICACY; LIVER
AB Green tea extract (GTE) has been advocated as a hepatoprotective compound and a possible therapeutic agent for acetaminophen (APAP) overdose. This study was conducted to determine if GTE can provide protection against APAP-induced hepatotoxicity. Three different exposure scenarios were tested. The first involved administering APAP (150 mg/kg, orally) to mice followed 6 h later by GTE (500 or 1000 mg/kg). The other two involved administering GTE prior to the APAP dose. GTE (500 or 1000 mg/kg, orally) was administered 3 h prior to APAP (200 mg/kg, orally) or for three consecutive days (once-daily) followed by APAP (300 mg/kg) on the fourth day. Indices of hepatotoxicity were assessed 24 h after the APAP dose. GTE potentiated APAP-induced hepatotoxicity when administered after the APAP dose. GTE caused significant glutathione depletion and this effect likely contributed to the observed potentiation. In contrast, GTE provided protection against APAP-induced hepatotoxicity when administered prior to the APAP dose. GTE dramatically decreased APAP covalent binding to protein indicating that less reactive metabolite was available to cause hepatocellular injury. These results highlight the potential for drug-dietary supplement interactions and the importance of testing multiple exposure scenarios to adequately model different types of potential interactions. Published by Elsevier Ltd.
C1 [Salminen, William F.; Yang, Xi; Shi, Qiang; Greenhaw, James; Ali, Akhtar A.] US FDA Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA.
[Davis, Kelly] US FDA Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
RP Salminen, WF (reprint author), US FDA Natl Ctr Toxicol Res, Div Syst Biol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM william.salminen@fda.hhs.gov; xi.yang@fda.hhs.gov;
qiang.shi@fda.hhs.gov; james.greenhaw@fda.hhs.gov;
kellyj.davis@fda.hhs.gov; akhtar.ali@fda.hhs.gov
RI Qiang, Shi/E-6266-2012
FU National Center for Toxicological Research
FX X.Y. was supported by the Research Participation Program at the National
Center for Toxicological Research administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the US Department of Energy and the US Food and Drug
Administration.
NR 29
TC 15
Z9 15
U1 0
U2 6
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 MAY
PY 2012
VL 50
IS 5
BP 1439
EP 1446
DI 10.1016/j.fct.2012.01.027
PG 8
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 949JH
UT WOS:000304572000034
PM 22306919
ER
PT J
AU Bandele, OJ
Santillo, MF
Ferguson, M
Wiesenfeld, PL
AF Bandele, Omari J.
Santillo, Michael F.
Ferguson, Martine
Wiesenfeld, Paddy L.
TI In vitro toxicity screening of chemical mixtures using HepG2/C3A cells
SO FOOD AND CHEMICAL TOXICOLOGY
LA English
DT Article
DE Hepatotoxicity; HepG2/C3A cells; Oil dispersants; In vitro toxicity
screening; Chemical mixtures
ID OIL-SPILL DISPERSANTS; CRUDE-OIL; HEPATOMA-CELLS; HEPATOTOXICITY;
MODELS; ASSAY; HEPATOCYTES; STRATEGIES; PREDICTION; TOXICOLOGY
AB Traditional toxicological methods that utilize only single pure compounds may not accurately predict risks from substances with multiple chemical constituents. A complementary approach to conventional methodologies includes in vitro systems that assess toxicity of chemical mixtures and identify components that may adversely impact biological processes. Compared to animal models, in vitro assays are inexpensive, rapid, and reduce and refine related animal testing. We utilized HepG2/C3A cells as a hepatotoxicity screening model to evaluate the cytotoxic and metabolic effects of three commercially available oil dispersants, Corexit EC9500A and EC9527A and ZI-400. The surfactant DOSS, a primary active constituent of the Corexit dispersants, was also evaluated. Biologically relevant endpoints were measured including cell viability, oxidative stress, and mitochondria! activity. Significant increases in cytotoxicity were observed with Corexit dispersants (LC50 similar to 250 ppm), whereas ZI-400 was moderately cytotoxic (LC50 >> 400 ppm). Each dispersant caused an accumulation of reactive oxygen species and altered mitochondria, activity and other cellular processes. Generally, DOSS made notable contributions to the effects of EC9500A and EC9527A, however, they were observed at concentrations higher than those used in most consumer products. Overall, this system may represent a valuable complementary tool for predicting the toxicity of complex mixtures. Published by Elsevier Ltd.
C1 [Bandele, Omari J.; Santillo, Michael F.; Wiesenfeld, Paddy L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
[Ferguson, Martine] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Bandele, OJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd,MOD-1 Labs,Room 1406,HFS-025, Laurel, MD 20807 USA.
EM omari.bandele@fda.hhs.gov
RI Santillo, Michael/B-5081-2009
OI Santillo, Michael/0000-0001-8087-5859
FU U.S. Food and Drug Administration
FX We thank Dr. Thomas Flynn and his research group (Dr. Martha Garcia, Dr.
Yitong Liu and Erica Hoagland) for providing the HepG2/C3A cell line and
for their helpful insight during this study. This work was supported in
part by an appointment to the Research Participation Program at the U.S.
Food and Drug Administration administered by the Oak Ridge institute for
Science and Education through an agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration.
NR 41
TC 19
Z9 19
U1 2
U2 24
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 MAY
PY 2012
VL 50
IS 5
BP 1653
EP 1659
DI 10.1016/j.fct.2012.02.016
PG 7
WC Food Science & Technology; Toxicology
SC Food Science & Technology; Toxicology
GA 949JH
UT WOS:000304572000061
PM 22381260
ER
PT J
AU Alam, M
Kuo, J
Pereira, M
Gaines, D
Bigley, E
Ernst, P
Williams, K
AF Alam, Mohammad
Kuo, Jennifer
Pereira, Marion
Gaines, Dennis
Bigley, Elmer
Ernst, Peter
Williams, Kristina
TI Ecto-5 '-nucleotidase (CD73) regulates host inflammatory responses and
bacterial persistence during murine Salmonellosis
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Alam, Mohammad; Kuo, Jennifer; Pereira, Marion; Gaines, Dennis; Bigley, Elmer; Williams, Kristina] FDA, Ctr Food Safety & Nutr, Immunobiol DVA, Laurel, MD USA.
[Ernst, Peter] Univ Calif San Diego, Div Comparat Pathol & Med, San Diego, CA 92103 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659702002
ER
PT J
AU Berkower, I
Ni, YS
Virnik, K
AF Berkower, Ira
Ni, Yisheng
Virnik, Konstantin
TI Characterization of live, attenuated rubella viral vectors expressing
SIV Gag or HIV MPER determinants
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Berkower, Ira; Ni, Yisheng; Virnik, Konstantin] FDA, Ctr Biol, Off Vaccines, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659701108
ER
PT J
AU Borrego, F
Andersen, J
Calvo, E
Choi, SC
Coligan, J
Simhadri, V
AF Borrego, Francisco
Andersen, John
Calvo, Eric
Choi, Seung-Chul
Coligan, John
Simhadri, Venkateswara
TI CD300a binds to phosphatidylethanolamine and phosphatidylserine and
modulates the uptake of dead cells.
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Borrego, Francisco; Simhadri, Venkateswara] US FDA, Div Monoclonal Antibodies, Bethesda, MD 20014 USA.
[Andersen, John; Calvo, Eric] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Choi, Seung-Chul; Coligan, John] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659701650
ER
PT J
AU Choi, SC
Wang, HS
Tian, LJ
Murakami, Y
Shin, DM
Borrego, F
Morse, H
Coligan, J
AF Choi, Seung-Chul
Wang, Hongsheng
Tian, Linjie
Murakami, Yousuke
Shin, Dong-Mi
Borrego, Francisco
Morse, Herbert
Coligan, John
TI The IgM Fc receptor, FCMR, promotes B cell development and modulates
antigen-driven immune responses
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Choi, Seung-Chul; Wang, Hongsheng; Tian, Linjie; Murakami, Yousuke; Shin, Dong-Mi; Morse, Herbert; Coligan, John] NIAID, LIG, NIH, Rockville, MD USA.
[Borrego, Francisco] US FDA, DMA CDER, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659702230
ER
PT J
AU Endo, Y
Zaitseva, M
Romantseva, T
Golding, H
AF Endo, Yukinori
Zaitseva, Marina
Romantseva, Tatiana
Golding, Hana
TI Role of granulysin in MDP-induced PGE2 production in human monocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Endo, Yukinori; Zaitseva, Marina; Romantseva, Tatiana; Golding, Hana] US FDA, CBER, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659700518
ER
PT J
AU Oakley, M
Solanki, N
Cole, LL
Majam, V
Sahu, B
Derrick, S
Morris, S
Kumar, S
AF Oakley, Miranda
Solanki, Nehal
Cole, Leda Lotspeich
Majam, Victoria
Sahu, Bikash
Derrick, Steven
Morris, Sheldon
Kumar, Sanjai
TI The transcription factor T-bet regulates parasitemia and promotes
pathogenesis during Plasmodium berghei ANKA murine malaria
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Oakley, Miranda; Solanki, Nehal; Cole, Leda Lotspeich; Majam, Victoria; Sahu, Bikash; Derrick, Steven; Morris, Sheldon; Kumar, Sanjai] US FDA, CBER, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659700083
ER
PT J
AU Peruzzi, G
Femnou, L
Borrego, F
Krzewski, K
Coligan, J
AF Peruzzi, Giovanna
Femnou, Laurette
Borrego, Francisco
Krzewski, Konrad
Coligan, John
TI Identification of matrix metalloproteinases involved in the activation
induced CD16 down-modulation by primary NK cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT 99th Annual Meeting of the American-Association-of-Immunologists
CY MAY 04-08, 2012
CL Boston, MA
SP Amer Assoc Immunol
C1 [Peruzzi, Giovanna; Femnou, Laurette; Krzewski, Konrad; Coligan, John] NIAID, RCBS, NIH, Rockville, MD USA.
[Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD MAY 1
PY 2012
VL 188
PG 1
WC Immunology
SC Immunology
GA 950OX
UT WOS:000304659702124
ER
PT J
AU Chen, ZW
Yin, JJ
Zhou, YT
Zhang, Y
Song, L
Song, MJ
Hu, SL
Gu, N
AF Chen, Zhongwen
Yin, Jun-Jie
Zhou, Yu-Ting
Zhang, Yu
Song, Lina
Song, Mengjie
Hu, Sunling
Gu, Ning
TI Dual Enzyme-like Activities of Iron Oxide Nanoparticles and Their
Implication for Diminishing Cytotoxicity
SO ACS NANO
LA English
DT Article
DE iron oxide nanoparticles; cytotoxicity; ESR; hydroxyl radical;
peroxidase; catalase
ID OXIDATIVE STRESS; MAGNETIC NANOPARTICLES; GOLD NANOPARTICLES;
ORGANIC-COMPOUNDS; IN-VITRO; TOXICITY; CELLS; RADICALS; CANCER;
MECHANISM
AB Iron oxide nanoparticles (IONPs) are frequently used In biomedical applications, yet their toxic potential is still a major concern. While most studies of biosafety focus on cellular responses after exposure to nanomaterials, little is reported to analyze reactions on the surface of nanoparticles as a source of cytotoxicity. Here we report that different Intracellular microenvironment in which IONPs are located leads to contradictive outcomes in their abilities to produce free radicals. We first verified pH-dependent peroxidase-like and catalase-like activities of IONPs and investigated how they Interact with hydrogen peroxide (H2O2) within cells. Results showed that IONPs had a concentration-dependent cytotoxicity on human glioma U251 cells, and they could enhance H2O2-Induced cell damage dramatically. By conducting electron spin resonance spectroscopy experiments, we showed that both Fe3O4 and gamma-Fe2O3 nanoparticles could catalyze H2O2 to produce hydroxyl radicals in acidic lysosome mimic conditions, with relative potency Fe3O4 > gamma-Fe2O3, which was consistent with their peroxidase-like activities. However, no hydroxyl radicals were observed in neutral cytosol mimic conditions with both nanoparticles. Instead, they decomposed H2O2 into H2O and O-2 directly in this condition through catalase-like activities. Transmission electron micrographs revealed that IONPs located in lysosomes in cells, the acidic environment of which may contribute to hydroxyl radical production. This is the first study regarding cytotoxicity based on their enzyme-like activities. Since H2O2 is continuously produced in cells, our data indicate that lysosome-escaped strategy for IONP delivery would be an efficient way to diminish long-term toxic potential.
C1 [Chen, Zhongwen; Zhang, Yu; Song, Lina; Song, Mengjie; Hu, Sunling; Gu, Ning] Southeast Univ, State Key Lab Bioelect, Sch Biol Sci & Med Engn, Nanjing 210096, Peoples R China.
[Yin, Jun-Jie; Zhou, Yu-Ting] Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Chen, Zhongwen; Zhang, Yu; Song, Lina; Song, Mengjie; Hu, Sunling; Gu, Ning] Southeast Univ, Jiangsu Key Lab Biomat & Devices, Sch Biol Sci & Med Engn, Nanjing 210096, Peoples R China.
RP Zhang, Y (reprint author), Southeast Univ, State Key Lab Bioelect, Sch Biol Sci & Med Engn, Nanjing 210096, Peoples R China.
EM zhangyu@seu.edu.cn; guning@seu.edu.cn
RI Zhou, Yuting/I-9125-2012; Yin, Jun Jie /E-5619-2014
FU National Important Basic Research Program of China [2011CB933503];
National Science Fund for Distinguished Young Scholars of China
[60725101]; Basic Research Program of Jiangsu Province [BK2009013];
National Natural Science Foundation of China [61127002]; China-U.S.
International Science and Technology Cooperation [2009DFA31990]; FY11
FDA Nanotechnology CORES Program
FX This work was supported by the National Important Basic Research Program
of China (No. 2011CB933503), the National Science Fund for Distinguished
Young Scholars of China (60725101), the Basic Research Program of
Jiangsu Province (No. BK2009013), the Special Funds of the National
Natural Science Foundation of China for Basic Research Projects of
Scientific Instruments (No. 61127002), and the China-U.S. International
Science and Technology Cooperation Program (Grant No. 2009DFA31990).
This article is not an official U.S. Food and Drug Administration (FDA)
guidance or policy statement. No official support or endorsement by the
U.S. FDA is intended or should be inferred. This work was supported by a
regulatory science grant under the FY11 FDA Nanotechnology CORES Program
(J.J.Y.)
NR 51
TC 115
Z9 122
U1 27
U2 184
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD MAY
PY 2012
VL 6
IS 5
BP 4001
EP 4012
DI 10.1021/nn300291r
PG 12
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 944VK
UT WOS:000304231700039
PM 22533614
ER
PT J
AU Abrams, A
Enose-Akahata, Y
McCormick, M
Johnson, K
Maloney, E
Jacobson, S
AF Abrams, Anna
Enose-Akahata, Yoshimi
McCormick, Matthew
Johnson, Kory
Maloney, Elizabeth
Jacobson, Steven
TI HTLV-I/II seroindeterminate western blot patterns and correlated
serological antibody responses
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
C1 [Abrams, Anna; Enose-Akahata, Yoshimi; McCormick, Matthew; Jacobson, Steven] Natl Inst Neurol Disorders & Stroke, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20824 USA.
[Johnson, Kory] Natl Inst Neurol Disorders & Stroke, Informat Technol & Bioinformat Program, Div Intramural Res, Bethesda, MD USA.
[Maloney, Elizabeth] US FDA, Div Epidemiol 2, Off Surveillance & Epidemiol, Rockville, MD 20857 USA.
EM ahabrams@gmail.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD MAY
PY 2012
VL 18
SU 1
MA P1
BP 1
EP 1
PG 1
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 948FA
UT WOS:000304487800002
ER
PT J
AU Akahata, Y
Abrams, A
Massoud, R
Bialuk, I
Maloney, E
Jacobson, S
AF Akahata, Yoshimi
Abrams, Anna
Massoud, Raya
Bialuk, Izabela
Maloney, Elizabeth
Jacobson, Steven
TI Humoral immune response against HTLV-I HBZ in HTLV-I-infected
individuals
SO JOURNAL OF NEUROVIROLOGY
LA English
DT Meeting Abstract
C1 [Akahata, Yoshimi; Abrams, Anna; Massoud, Raya; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD USA.
[Bialuk, Izabela] Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland.
[Maloney, Elizabeth] US FDA, Div Epidemiol 2, Off Surveillance & Epidemiol, Rockville, MD 20857 USA.
EM akahatay@ninds.nih.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 1355-0284
J9 J NEUROVIROL
JI J. Neurovirol.
PD MAY
PY 2012
VL 18
SU 1
MA P8
BP 5
EP 5
PG 1
WC Neurosciences; Virology
SC Neurosciences & Neurology; Virology
GA 948FA
UT WOS:000304487800009
ER
PT J
AU Feng, H
Liu, KW
Guo, P
Zhang, P
Cheng, T
McNiven, MA
Johnson, GR
Hu, B
Cheng, SY
AF Feng, H.
Liu, K. W.
Guo, P.
Zhang, P.
Cheng, T.
McNiven, M. A.
Johnson, G. R.
Hu, B.
Cheng, S. Y.
TI Dynamin 2 mediates PDGFR alpha-SHP-2-promoted glioblastoma growth and
invasion
SO ONCOGENE
LA English
DT Article
DE Dyn2; PDGFR alpha; SHP-2; Src; glioma tumor growth; invasion
ID TYROSINE-PHOSPHATASE SHP-2; COATED VESICLE FORMATION; CELL-MIGRATION;
MALIGNANT GLIOMAS; MAMMALIAN-CELLS; CORE PATHWAYS; CANCER-CELLS;
ACTIVATION; SRC; PHOSPHORYLATION
AB Dynamin 2 (Dyn2), a large GTPase, is involved in receptor tyrosine kinase (RTK)-promoted cell migration. However, the molecular mechanisms by which Dyn2 regulates RTK-induced cell migration have not been established. Recently, we reported that tyrosine-protein phosphatase non-receptor type 11 (SHP-2) and phosphatidylinositol 3-kinase (PI3K) mediate platelet-derived growth factor receptor-alpha (PDGFR alpha)-promoted glioma tumor growth and invasion. Here, we show that Dyn2 is an effector downstream of the PDGFR alpha-PI3K/SHP-2 signaling in glioma cells. Depletion of endogenous Dyn2 by short hairpin RNAs (shRNAs) inhibited PDGFR alpha-stimulated phosphorylation of Akt, Erk1/2, Rac1 and Cdc42 activities, glioma cell migration and survival in vitro and tumor growth and invasion in the brains of mice. Dyn2 binds to SHP-2 and PI3K and colocalizes with PDGFR alpha at the invasive fronts in PDGF-A-stimulated glioma cells. Inhibition of SHP-2 by siRNA knockdown abrogated Dyn2 association with activated PDGFR alpha and PDGFR alpha activation of Rac1 and Cdc42, and glioma cell migration, thereby establishing a link between SHP-2 interaction with Dyn2 and the PDGFR alpha signaling. Furthermore, a dominant-negative SHP-2 C459S mutant inhibited PDGF-A-stimulated glioma cell migration, phosphorylation of Dyn2 and concomitantly blocked PDGFR alpha-induced Src activation. Inhibition of Src by Src inhibitors attenuated PDGF-A-stimulated phosphorylation of Akt and Dyn2 and glioma cell migration. Additionally, mutations of binding sites to PI3K, SHP-2 or Src of PDGFR alpha impaired PDGFR alpha-stimulated phosphorylation of Akt and Dyn2, and Dyn2 association with activated PDGFR alpha. Taken together, this study identifies Dyn2 as an effector that mediates PDGFR alpha-SHP-2-induced glioma tumor growth and invasion, suggesting that targeting the PDGFR alpha-SHP-2-Dyn2 pathway may be beneficial to patients with malignant glioblastomas. Oncogene (2012) 31, 2691-2702; doi:10.1038/onc.2011.436; published online 26 September 2011
C1 [Hu, B.] Univ Pittsburgh, Dept Med, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA.
[Feng, H.; Liu, K. W.; Guo, P.; Cheng, S. Y.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
[Guo, P.] Childrens Hosp, Div Pediat Gen & Thorac Surg, Pittsburgh, PA 15213 USA.
[Zhang, P.; Cheng, T.] Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA 15213 USA.
[Cheng, T.] Chinese Acad Med Sci, State Key Lab Expt Hematol, Inst Hematol, Tianjin, Peoples R China.
[Cheng, T.] Chinese Acad Med Sci, Blood Dis Hosp, Ctr Stem Cell Med, Tianjin, Peoples R China.
[Cheng, T.] Peking Union Med Coll, Tianjin, Peoples R China.
[McNiven, M. A.] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN USA.
[McNiven, M. A.] Mayo Clin, Ctr Basic Res Digest Dis, Rochester, MN USA.
[Johnson, G. R.] US FDA, Chem Lab, Div Therapeut Prot, Bethesda, MD 20014 USA.
[Johnson, G. R.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
RP Hu, B (reprint author), Univ Pittsburgh, Dept Med, Inst Canc, Hillman Canc Ctr, Suite 2-26,5117 Ctr Ave, Pittsburgh, PA 15213 USA.
EM hub@upmc.edu; chengs@upmc.edu
RI Liu, Kun-Wei/A-9370-2013; Zhang, Peng/B-6898-2014
OI Zhang, Peng/0000-0001-5574-0899
FU ACS (RSG) [CSM-107144]; NIH [CA130966]; Pennsylvania Department of
Health; Hillman Foundation; James S McDonnell Foundation
FX We thank Drs Y Zhou and E Van Meir for providing glioma cell lines and
Dr H Damke and L Vance for proofreading of this manuscript. This work
was supported in part by a grant from ACS (RSG CSM-107144), grants from
NIH (CA130966), a grant with the Pennsylvania Department of Health, and
Innovative Research Scholar Awards of the Hillman Foundation to SY Cheng
and B Hu, and a James S McDonnell Foundation Researching Award in Brain
Cancer to B Hu.
NR 42
TC 31
Z9 31
U1 1
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD MAY
PY 2012
VL 31
IS 21
BP 2691
EP 2702
DI 10.1038/onc.2011.436
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 948SS
UT WOS:000304523500008
PM 21996738
ER
PT J
AU Linguraru, M
Sandberg, J
Petrick, N
Summers, R
AF Linguraru, M.
Sandberg, J.
Petrick, N.
Summers, R.
TI Hepatic Volumetric Nomograms From Automated Analysis of Abdominal CT
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Roentgen-Ray-Society
CY APR 29-MAY 04, 2012
CL Vancouver, CANADA
SP Amer Roentgen Ray Soc
C1 [Linguraru, M.; Sandberg, J.; Summers, R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Petrick, N.] Food & Drug Adm Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM rms@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD MAY
PY 2012
VL 198
IS 5
SU S
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 937OI
UT WOS:000303667400126
ER
PT J
AU Li, RW
Magadia, J
Fein, SB
Grummer-Strawn, LM
AF Li, Ruowei
Magadia, Joselito
Fein, Sara B.
Grummer-Strawn, Laurence M.
TI Risk of Bottle-feeding for Rapid Weight Gain During the First Year of
Life
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID BODY-MASS INDEX; US CHILDREN; OVERWEIGHT; OBESITY; ADOLESCENTS;
PREVALENCE; MILK; CONSEQUENCES; METAANALYSIS; DURATION
AB Objective: To better understand the mechanisms behind breastfeeding and childhood obesity, we assessed the association of weight gain with the mode of milk delivery aside from the type of milk given to infants.
Design: A longitudinal study of infants followed up from birth to age 1 year. Multilevel analyses were conducted to estimate infant weight gain by type of milk and feeding mode.
Setting: Pregnant women were recruited from a consumer mail panel throughout the United States between May 2005 and June 2007.
Participants: One thousand eight hundred ninety nine infants with at least 3 weight measurements reported during the first year.
Main Exposures: Six mutually exclusive feeding categories and proportions of milk feedings given as breastmilk or by bottle.
Main Outcome Measures: Weight measurements reported on 3-, 5-, 7-, and 12-month surveys.
Results: Compared with infants fed at the breast, infants fed only by bottle gained 71 or 89 g more per month when fed nonhuman milk only (P < .001) or human milk only (P =. 02), respectively. Weight gain was negatively associated with proportion of breastmilk feedings, but it was positively associated with proportion of bottle-feedings among those who received mostly breastmilk. Among infants fed only breastmilk, monthly weight gain increased from 729 g when few feedings were by bottle to 780 g when most feedings were by bottle.
Conclusions: Infant weight gain might be associated not only with type of milk consumed but also with mode of milk delivery. Regardless of milk type in the bottle, bottle-feeding might be distinct from feeding at the breast in its effect on infants' weight gain. Arch Pediatr Adolesc Med. 2012; 166(5): 431-436
C1 [Li, Ruowei; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA.
[Magadia, Joselito] Univ Philippines Diliman, Sch Stat, Quezon City, Philippines.
[Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Li, RW (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, 4770 Buford Highway,MS K25, Atlanta, GA 30341 USA.
EM ril6@cdc.gov
FU Food and Drug Administration, Centers for Disease Control and
Prevention, Office of Women's Health, National Institutes of Health;
Maternal and Child Health Bureau in the US Department of Health and
Human Services
FX The Infant Feeding Practices Study II was funded by the Food and Drug
Administration, Centers for Disease Control and Prevention, Office of
Women's Health, National Institutes of Health, and Maternal and Child
Health Bureau in the US Department of Health and Human Services.
NR 34
TC 53
Z9 55
U1 2
U2 21
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 1072-4710
J9 ARCH PEDIAT ADOL MED
JI Arch. Pediatr. Adolesc. Med.
PD MAY
PY 2012
VL 166
IS 5
SI SI
BP 431
EP 436
PG 6
WC Pediatrics
SC Pediatrics
GA 937PB
UT WOS:000303669300006
PM 22566543
ER
PT J
AU Agrawal, A
Connors, M
Beylin, A
Liang, CP
Barton, D
Chen, Y
Drezek, RA
Pfefer, TJ
AF Agrawal, Anant
Connors, Megan
Beylin, Alexander
Liang, Chia-Pin
Barton, David
Chen, Yu
Drezek, Rebekah A.
Pfefer, T. Joshua
TI Characterizing the point spread function of retinal OCT devices with a
model eye-based phantom
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; SYNTHETIC-APERTURE MICROSCOPY; ARTIFACTS;
MEDIA
AB We have designed, fabricated, and tested a nanoparticle-embedded phantom (NEP) incorporated into a model eye in order to characterize the point spread function (PSF) of retinal optical coherence tomography (OCT) devices in three dimensions under realistic imaging conditions. The NEP comprises a sparse distribution of highly backscattering silica-gold nanoshells embedded in a transparent UV-curing epoxy. The commercially-available model eye replicates the key optical structures and focusing power of the human eye. We imaged the model eye-NEP combination with a research-grade spectral domain OCT system designed for in vivo retinal imaging and quantified the lateral and axial PSF dimensions across the field of view in the OCT images. We also imaged the model eye-NEP in a clinical OCT system. Subtle features in the PSF and its dimensions were consistent with independent measurements of lateral and axial resolution. This model eye-based phantom can provide retinal OCT device developers and users a means to rapidly, objectively, and consistently assess the PSF, a fundamental imaging performance metric. (c) 2012 Optical Society of America
C1 [Agrawal, Anant; Connors, Megan; Beylin, Alexander; Liang, Chia-Pin; Barton, David; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Connors, Megan] Univ Maryland, Dept Elect & Comp Engn, College Pk, MD 20742 USA.
[Liang, Chia-Pin; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Drezek, Rebekah A.] Rice Univ, Dept Bioengn, Houston, TX USA.
RP Agrawal, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM anant.agrawal@fda.hhs.gov
RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012
NR 23
TC 17
Z9 17
U1 2
U2 9
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD MAY 1
PY 2012
VL 3
IS 5
BP 1116
EP 1126
PG 11
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA 935RH
UT WOS:000303537400025
PM 22567601
ER
PT J
AU Tadesse, DA
Zhao, SH
Tong, E
Ayers, S
Singh, A
Bartholomew, MJ
McDermott, PF
AF Tadesse, Daniel A.
Zhao, Shaohua
Tong, Emily
Ayers, Sherry
Singh, Aparna
Bartholomew, Mary J.
McDermott, Patrick F.
TI Antimicrobial Drug Resistance in Escherichia coli from Humans and Food
Animals, United States, 1950-2002
SO EMERGING INFECTIOUS DISEASES
LA English
DT Article
ID SULFONAMIDE RESISTANCE; ANTIBIOTIC-RESISTANCE; CHLORAMPHENICOL; SWINE;
PLASMIDS; BACTERIA; GENES; FLORFENICOL; PERSISTENCE; APRAMYCIN
AB We conducted a retrospective study of Escherichia coli isolates recovered from human and food animal samples during 1950-2002 to assess historical changes in antimicrobial drug resistance. A total of 1,729 E. coli isolates (983 from humans, 323 from cattle, 138 from chickens, and 285 from pigs) were tested for susceptibility to 15 antimicrobial drugs. A significant upward trend in resistance was observed for ampicillin (p<0.001), sulfonamide (p<0.001), and tetracycline (p<0.001). Animal strains showed increased resistance to 11/15 antimicrobial agents, including ampicillin (p<0.001), sulfonamide (p<0.01), and gentamicin (p<0.001). Multidrug resistance (approximate to 3 antimicrobial drug classes) in E. coli increased from 7.2% during the 1950s to 63.6% during the 2000s. The most frequent co-resistant phenotype observed was to tetracycline and streptomycin (29.7%), followed by tetracycline and sulfonamide (29.0%). These data describe the evolution of resistance after introduction of new antimicrobial agents into clinical medicine and help explain the range of resistance in modern E. coli isolates.
C1 [Tadesse, Daniel A.; Zhao, Shaohua; Tong, Emily; Ayers, Sherry; Singh, Aparna; McDermott, Patrick F.] US FDA, Laurel, MD 20708 USA.
[Bartholomew, Mary J.] US FDA, Rockville, MD 20857 USA.
RP McDermott, PF (reprint author), US FDA, 8401 Muirkirk Rd, Laurel, MD 20708 USA.
EM patrick.mcdermott@fda.hhs.gov
NR 40
TC 90
Z9 94
U1 9
U2 36
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1080-6040
EI 1080-6059
J9 EMERG INFECT DIS
JI Emerg. Infect. Dis
PD MAY
PY 2012
VL 18
IS 5
BP 741
EP 749
DI 10.3201/eid1805.111153
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 935XZ
UT WOS:000303556800004
PM 22515968
ER
PT J
AU Du, DY
Goldsmith, J
Aikin, KJ
Encinosa, WE
Nardinelli, C
AF Du, Dongyi 'Tony'
Goldsmith, John
Aikin, Kathryn J.
Encinosa, William E.
Nardinelli, Clark
TI Despite 2007 Law Requiring FDA Hotline To Be Included In Print Drug Ads,
Reporting Of Adverse Events By Consumers Still Low
SO HEALTH AFFAIRS
LA English
DT Article
ID PRESCRIPTION
AB In 2007 the federal government began requiring drug makers to include in their print direct-to-consumer advertisements information for consumers on how to contact the Food and Drug Administration directly, either by phone or through the agency's website, to report any adverse events that they experienced after taking a prescription drug. Adverse events can range from minor skin problems like itching to serious injuries or illness that result in hospitalization, permanent disability, or even death. Even so, current rates of adverse event reporting are low. We studied adverse event reports about 123 drugs that came from patients before and after the enactment of the print advertising requirement and estimated that requirement's impact with model simulations. We found that if monthly spending on print direct-to-consumer advertising increased from zero to $7.7 million per drug, the presence of the Food and Drug Administration contact information tripled the increase in patient-reported adverse events, compared to what would have happened in the absence of the law. However, the absolute monthly increase was fewer than 0.24 reports per drug, suggesting that the public health impact of the increase was small and that the adverse event reporting rate would still be low. The study results suggest that additional measures, such as more publicity about the Adverse Event Reporting System or more consumer education, should be considered to promote patient reporting of adverse events.
C1 [Du, Dongyi 'Tony'] Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA.
[Goldsmith, John] Food & Drug Adm, Off Planning, Rockville, MD USA.
[Aikin, Kathryn J.] Food & Drug Adm, Off Prescript Drug Promot, Rockville, MD USA.
[Encinosa, William E.] Agcy Healthcare Res & Qual, Ctr Delivery Org & Markets, Rockville, MD USA.
[Nardinelli, Clark] Food & Drug Adm, Off Policy Planning & Budget, Rockville, MD USA.
RP Du, DY (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA.
EM dongyi.du@fda.hhs.gov
FU Food and Drug Administration's Center for Drug Evaluation and Research
FX The authors thank John Quinn, Lynette Swartz, and Elaine Hu Cunningham
of the Food and Drug Administration's Center for Drug Evaluation and
Research for their support. The authors have no financial interests in
this article and received no funding to conduct this study. The opinions
expressed in the article are those of the authors and are not intended
to represent the opinions of the Food and Drug Administration.
NR 26
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U1 1
U2 5
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAY
PY 2012
VL 31
IS 5
BP 1022
EP 1029
DI 10.1377/hlthaff.2010.1004
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 940EP
UT WOS:000303873100017
PM 22566442
ER
PT J
AU Kane, RC
AF Kane, Robert C.
TI Re: Potential Pitfalls of Crossover and Thoughts on Iniparib in
Triple-Negative Breast Cancer
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 US FDA, Div Hematol Prod, Off Hematol Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Kane, RC (reprint author), US FDA, Div Hematol Prod, Off Hematol Oncol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Rm 2109, Silver Spring, MD 20993 USA.
EM robert.kane@fda.hhs.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD MAY
PY 2012
VL 104
IS 9
DI 10.1093/jnci/djs164
PG 2
WC Oncology
SC Oncology
GA 936PM
UT WOS:000303602500014
ER
PT J
AU Verma, N
Dimitrova, M
Carter, DM
Crevar, CJ
Ross, TM
Golding, H
Khurana, S
AF Verma, Nitin
Dimitrova, Milena
Carter, Donald M.
Crevar, Corey J.
Ross, Ted M.
Golding, Hana
Khurana, Surender
TI Influenza Virus H1N1pdm09 Infections in the Young and Old: Evidence of
Greater Antibody Diversity and Affinity for the Hemagglutinin Globular
Head Domain (HA1 Domain) in the Elderly than in Young Adults and
Children
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INDUCED CYTIDINE DEAMINASE; A H1N1 VIRUS; SEASONAL INFLUENZA; B-CELLS;
CLASS SWITCH; RESPONSES; VACCINE; IMMUNITY; HUMANS; AVIDITY
AB The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of antibody responses generated following H1N1pdm09 infection of naive ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus <22% 7 M urea resistance, respectively) and lower antibody dissociation rates using surface plasmon resonance. This is the first study in humans that provides evidence for a qualitatively superior antibody response in the elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.
C1 [Verma, Nitin; Dimitrova, Milena; Golding, Hana; Khurana, Surender] US FDA, Div Viral Prod, CBER, Bethesda, MD 20014 USA.
[Carter, Donald M.; Crevar, Corey J.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA.
RP Khurana, S (reprint author), US FDA, Div Viral Prod, CBER, Bethesda, MD 20014 USA.
EM hana.golding@fda.hhs.gov; surender.khurana@fda.hhs.gov
FU FDA; NIH/NIAID [R01 GM083602-01]
FX This work was supported by FDA Pandemic Flu internal funds (H.G.) and in
part by an American Recovery and Reinvestment Act supplement to
NIH/NIAID grant R01 GM083602-01 (T.M.R.). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 41
TC 25
Z9 26
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAY
PY 2012
VL 86
IS 10
BP 5515
EP 5522
DI 10.1128/JVI.07085-11
PG 8
WC Virology
SC Virology
GA 939DJ
UT WOS:000303787100009
PM 22379097
ER
PT J
AU Vertes, A
Hitchins, V
Phillips, KS
AF Vertes, Akos
Hitchins, Victoria
Phillips, K. Scott
TI Analytical Challenges of Microbial Biofilms on Medical Devices
SO ANALYTICAL CHEMISTRY
LA English
DT Article
ID IONIZATION-MASS-SPECTROMETRY; LASER-DESORPTION POSTIONIZATION; BACTERIAL
BIOFILMS; REAL-TIME; STAPHYLOCOCCUS-EPIDERMIDIS; COMMUNITY PROTEOMICS;
IMPLANT INFECTIONS; IN-SITU; CELL; METABOLITES
C1 [Hitchins, Victoria; Phillips, K. Scott] US FDA, CDRH, Off Sci & Engn Labs, Rockville, MD 20857 USA.
[Vertes, Akos] George Washington Univ, Dept Chem, Washington, DC 20052 USA.
RP Phillips, KS (reprint author), US FDA, CDRH, Off Sci & Engn Labs, Rockville, MD 20857 USA.
EM kenneth.phillips@fda.hhs.gov
RI Vertes, Akos/B-7159-2008; Phillips, Kenneth/A-2156-2013; phillips,
kenneth/F-7560-2014
OI Vertes, Akos/0000-0001-5186-5352; Phillips, Kenneth/0000-0002-6552-0694;
phillips, kenneth/0000-0002-6552-0694
FU Chemical Sciences, Geosciences and Biosciences Division, Office of Basic
Energy Sciences, Office of Science, U.S. Department of Energy
[DE-FG02-01ER15129]; George Washington University
FX Artistic renderings in figures were created by Robert Gates. The authors
acknowledge Dinesh Patwardhan, Director of DCMS for his supervisory
oversight on this work and thank Samantha Spindel, Peter Nemes, and
Thelma Valdes for their review of the manuscript. A.V. appreciates the
financial support from the Chemical Sciences, Geosciences and
Biosciences Division, Office of Basic Energy Sciences, Office of
Science, U.S. Department of Energy (Grant DE-FG02-01ER15129) and the
George Washington University Selective Excellence Fund. Support from the
Department of Energy does not constitute an endorsement of the views
expressed in the article.
NR 54
TC 44
Z9 45
U1 1
U2 42
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 MAY 1
PY 2012
VL 84
IS 9
BP 3858
EP 3866
DI 10.1021/ac2029997
PG 9
WC Chemistry, Analytical
SC Chemistry
GA 933GS
UT WOS:000303349200002
PM 22424152
ER
PT J
AU Kim, SJ
Song, J
Kweon, O
Holland, RD
Kim, DW
Kim, J
Yu, LR
Cerniglia, CE
AF Kim, Seong-Jae
Song, Jaekyeong
Kweon, Ohgew
Holland, Ricky D.
Kim, Dae-Wi
Kim, Jongnam
Yu, Li-Rong
Cerniglia, Carl E.
TI Functional Robustness of a Polycyclic Aromatic Hydrocarbon Metabolic
Network Examined in a nidA Aromatic Ring-Hydroxylating Oxygenase Mutant
of Mycobacterium vanbaalenii PYR-1
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID SP STRAIN PYR-1; PYRENE DEGRADATION; MOLECULAR CHARACTERIZATION;
DEGRADING MYCOBACTERIUM; DIOXYGENASE; GENES; IDENTIFICATION; EXPRESSION;
SEDIMENT; PATHWAY
AB In this study, we obtained over 4,000 transposon mutants of Mycobacterium vanbaalenii PYR-1 and analyzed one of the mutants, 8F7, which appeared to lose its ability to degrade pyrene while still being able to degrade fluoranthene. This mutant was identified to be defective in nidA, encoding an aromatic ring-hydroxylating oxygenase (RHO), known to be involved in the initial oxidation step of pyrene degradation. When cultured with pyrene as a sole source of polycyclic aromatic hydrocarbon (PAH), high-pressure liquid chromatography analysis revealed that the nidA mutant showed a significant decrease in the rate of pyrene degradation compared to the wild-type PYR-1, although pyrene was still being degraded. However, when incubated with PAH mixtures including pyrene, phenanthrene, and fluoranthene, the pyrene degradation rate of the mutant was higher than that of the mutant previously incubated with pyrene as a sole source of PAH. There was no significant difference between wild-type PYR-1 and the mutant in the rates of phenanthrene and fluoranthene degradation. From the whole-cell proteome analysis of mutant 8F7 induced by pyrene, we identified expression of a number of RHO enzymes which are suspected to be responsible for pyrene degradation in the nidA mutant, which had no expression of NidA. Taken together, results in this study provide direct evidence for the in vivo functional role of nidA in pyrene degradation at the level of the ring-cleavage-process (RCP) functional module but also for the robustness of the PAH metabolic network (MN) to such a genetic perturbation.
C1 [Kim, Seong-Jae; Kweon, Ohgew; Kim, Dae-Wi; Kim, Jongnam; Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Song, Jaekyeong; Holland, Ricky D.; Yu, Li-Rong] Rural Dev Adm, Res Policy Bur, Suwon, South Korea.
[Kweon, Ohgew] Univ Arkansas Little Flock, Dept Appl Sci, Little Rock, AR USA.
RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
EM carl.cerniglia@fda.hhs.gov
FU National Center for Toxicological Research
FX This work was supported in part by an appointment to the Postgraduate
Research Fellowship Program at the National Center for Toxicological
Research, administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the U.S. Department
of Energy and the U.S. Food and Drug Administration (U.S. FDA).
NR 36
TC 10
Z9 11
U1 2
U2 22
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 MAY
PY 2012
VL 78
IS 10
BP 3715
EP 3723
DI 10.1128/AEM.07798-11
PG 9
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 935WW
UT WOS:000303553900023
PM 22407691
ER
PT J
AU Keller, B
Chen, WJ
Gavrielides, MA
AF Keller, Brad
Chen, Weijie
Gavrielides, Marios A.
TI Quantitative Assessment and Classification of Tissue-Based Biomarker
Expression With Color Content Analysis
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID HER2-POSITIVE BREAST-CANCER; CELLULAR IMAGING-SYSTEM; IN-SITU
HYBRIDIZATION; PROGESTERONE-RECEPTOR; VIRTUAL MICROSCOPY;
IMMUNOHISTOCHEMICAL EXPRESSION; INTEROBSERVER REPRODUCIBILITY; ADJUVANT
CHEMOTHERAPY; CLUSTERING-ALGORITHM; PROTEIN EXPRESSION
AB Context.-The use of computer aids has been suggested as a way to reduce interobserver variability that is known to exist in the interpretation of immunohistochemical staining in pathology. Such computer aids should be automated in their usage but also they should be trained in an automated and reproducible fashion.
Objective.-To present a computer aid for the quantitative analysis of tissue-based biomarkers, based on color content analysis.
Design.-The developed system incorporates an automated algorithm to allow retraining based on the color properties of different training sets. The algorithm first generates a color palette containing the colors present in a training subset. Based on the palette, color histograms are derived and are used as feature vectors to a pattern recognition system, which returns an output proportional to biomarker continuous expression or a categorical classification. The method was evaluated on a database of HER2/neu digital breast cancer slides, for which expression scores from a pathologist panel were available. The system was retrained and evaluated on different transformations of the database, including compression, blurring, and changes in illumination, to examine its robustness to different imaging conditions frequently met in digital pathology.
Results.-Results showed high agreement between the results of the algorithm and the truth from the pathologist panel as well as robustness to image transformations.
Conclusions.-The results of the study are encouraging for the potential of this method as a computer aid to assess biomarker expression in a consistent and reproducible manner. (Arch Pathol Lab Med. 2012;136:539-550; doi: 10.5858/arpa.2011-0195-OA)
C1 [Chen, Weijie; Gavrielides, Marios A.] US FDA, Div Imaging & Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Keller, Brad] Cornell Univ, Dept Biomed Engn, Ithaca, NY USA.
RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4114, Silver Spring, MD 20993 USA.
EM marios.gavrielides@fda.hhs.gov
NR 76
TC 8
Z9 8
U1 0
U2 8
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD MAY
PY 2012
VL 136
IS 5
BP 539
EP 550
DI 10.5858/arpa.2011-0195-OA
PG 12
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA 936OU
UT WOS:000303600700015
PM 22540303
ER
PT J
AU Sarkar, S
Raymick, J
Schmued, L
AF Sarkar, Sumit
Raymick, James
Schmued, Larry
TI Temporal Progression of Kainic Acid Induced Changes in Vascular Laminin
Expression in Rat Brain with Neuronal and Glial Correlates
SO CURRENT NEUROVASCULAR RESEARCH
LA English
DT Article
DE Kainic acid; laminin; astrocytes; GFAP; vascular elements; FJC;
neurodegeneration
ID BASEMENT-MEMBRANE GLYCOPROTEIN; CEREBRAL-CORTEX; INDUCED LESIONS;
NERVOUS-SYSTEM; ASTROCYTES; IMMUNOHISTOCHEMISTRY; DEGENERATION;
ANGIOGENESIS; FIBRONECTIN; BARRIER
AB We recently demonstrated a dramatic up regulation of laminin expression within the blood vessels of brain regions vulnerable to excitotoxin mediated neuronal degeneration. Although this effect was clearly demonstrable at 2 days post kainic acid exposure, its expression at shorter and longer post-dosing intervals has not been reported. Therefore, a primary goal of the present study was to characterize the laminin labeling at intervals ranging from 4 hours to 2 months following i.p. injection of kainic acid. To better characterize the nature and possible underlying mechanism of action of the changes in laminin expression, both Fluoro-Jade C and GFAP immunohistochemistry were employed respectively at all survival intervals. At the shortest intervals examined (4hr, 8hr), Fluoro-Jade C positive cells could be detected in the hippocampus, thalamus, and piriform cortex. In these same regions, both vascular laminin and astrocytic GFAP expression were up regulated. At intermediate survival intervals (2, 5, 14, and 21 days), the respective labeling of degenerating neurons, astrocytes and capillaries were all maximal. Morphologically, Fluoro-Jade C labeled degenerating neurons were labeled in their entirety, GFAP positive astrocytes appeared hypertrophic and blood vessels took on a fragmented appearance. Hypertrophied GFAP positive astrocytes were conspicuous around periphery of the lesion but absent within the core of the lesion at these times. At longer survival intervals (1-2 months), the number of FJ-C labeled degenerating neurons was greatly reduced, while GFAP staining essentially returned to base line and laminin expression remained noticeably elevated, although the vessels appeared to be intact morphologically. These data allow for speculation on possible mechanisms underlying these events.
C1 [Sarkar, Sumit; Schmued, Larry] Natl Ctr Toxicol Research FDA, Div Neurotoxicol, Jefferson, AR 72079 USA.
[Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA.
RP Sarkar, S (reprint author), Natl Ctr Toxicol Research FDA, Div Neurotoxicol, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA.
EM Sumit.Sarkar@FDA.HHS.GOV
FU FDA [E7312]
FX This study was supported by FDA protocol E7312. We thank Dr. James O'
Callaghan (Center for Disease Control, NIOSH) for reviewing our
manuscript.
NR 53
TC 4
Z9 4
U1 0
U2 3
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 1567-2026
J9 CURR NEUROVASC RES
JI Curr. Neurovasc. Res.
PD MAY
PY 2012
VL 9
IS 2
BP 110
EP 119
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 934UR
UT WOS:000303472700005
PM 22475395
ER
PT J
AU Hoffman, HJ
Dobie, RA
Ko, CW
Themann, CL
Murphy, WJ
AF Hoffman, Howard J.
Dobie, Robert A.
Ko, Chia-Wen
Themann, Christa L.
Murphy, William J.
TI Hearing Threshold Levels at Age 70 Years (65-74 Years) in the Unscreened
Older Adult Population of the United States, 1959-1962 and 1999-2006
SO EAR AND HEARING
LA English
DT Article
AB Objectives: To provide hearing threshold percentiles from unscreened older adults for creating new Annex B reference standards.
Design: Percentiles are calculated, and 95% confidence intervals for medians from two U. S. surveys are compared graphically.
Results: Median thresholds are lower (better) in the 1999-2006 National Health and Nutrition Examination Survey for men across all frequencies except 1 kHz. Results for women are similar; however, there is more overlap in confidence intervals across frequencies.
Conclusions: The prevalence of hearing impairment in older adults, age 70 years (65-74 years), is lower in 1999-2006 compared with 19591962, consistent with our earlier findings for younger adults.
C1 [Hoffman, Howard J.] Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Bethesda, MD 20892 USA.
[Dobie, Robert A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Otolaryngol Head & Neck Surg, San Antonio, TX 78229 USA.
[Ko, Chia-Wen] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Themann, Christa L.; Murphy, William J.] NIOSH, Hearing Loss Prevent Team, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
RP Hoffman, HJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Epidemiol & Stat Program, NIH, Suite 400A,Execut Plaza S Bldg,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM hoffmanh@nidcd.nih.gov
FU National Institute on Deafness and Other Communication Disorders;
National Institute for Occupational Safety and Health
FX The National Health and Nutrition Examination Survey 1999-2006
audiometric data collection was funded with National Institute on
Deafness and Other Communication Disorders research contract funds via
an Interagency Agreement between the National Institute on Deafness and
Other Communication Disorders and the National Center for Health
Statistics. The National Institute for Occupational Safety and Health
provided funding for the audiometric testing equipment, training and
monitoring of technicians, and editing of preliminary data files. The
National Institute for Occupational Safety and Healt collaboration was
funded and managed via Interagency Agreements with the National
Institute on Deafness and Other Communication Disorders and the National
Center for Health Statistics. Audiometric testing was conducted in the
field by health technicians employed by Westat, Inc., under contract
with the National Center for Health Statistics.
NR 15
TC 15
Z9 15
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0196-0202
J9 EAR HEARING
JI Ear Hear.
PD MAY-JUN
PY 2012
VL 33
IS 3
BP 437
EP 440
DI 10.1097/AUD.0b013e3182362790
PG 4
WC Audiology & Speech-Language Pathology; Otorhinolaryngology
SC Audiology & Speech-Language Pathology; Otorhinolaryngology
GA 934OT
UT WOS:000303454400013
PM 22080933
ER
PT J
AU Wang, SJ
McKenna, MT
Nguyen, TB
Burns, JE
Petrick, N
Sahiner, B
Summers, RM
AF Wang, Shijun
McKenna, Matthew T.
Nguyen, Tan B.
Burns, Joseph E.
Petrick, Nicholas
Sahiner, Berkman
Summers, Ronald M.
TI Seeing Is Believing: Video Classification for Computed Tomographic
Colonography Using Multiple-Instance Learning
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Computed tomographic colonography (CTC); multiple-instance learning;
semidefinite programming; video analysis
ID CT COLONOGRAPHY; AIDED DETECTION; POLYP DETECTION; VIRTUAL COLONOSCOPY;
OBJECT RECOGNITION; COLONIC POLYPS; SYSTEM; FEATURES; ENDOSCOPY;
EVOLUTION
AB In this paper, we present development and testing results for a novel colonic polyp classification method for use as part of a computed tomographic colonography (CTC) computer-aided detection (CAD) system. Inspired by the interpretative methodology of radiologists using 3-D fly-through mode in CTC reading, we have developed an algorithm which utilizes sequences of images (referred to here as videos) for classification of CAD marks. For each CAD mark, we created a video composed of a series of intraluminal, volume-rendered images visualizing the detection from multiple viewpoints. We then framed the video classification question as a multiple-instance learning (MIL) problem. Since a positive (negative) bag may contain negative (positive) instances, which in our case depends on the viewing angles and camera distance to the target, we developed a novel MIL paradigm to accommodate this class of problems. We solved the new MIL problem by maximizing a L2-norm soft margin using semidefinite programming, which can optimize relevant parameters automatically. We tested our method by analyzing a CTC data set obtained from 50 patients from three medical centers. Our proposed method showed significantly better performance compared with several traditional MIL methods.
C1 [Wang, Shijun; McKenna, Matthew T.; Nguyen, Tan B.; Summers, Ronald M.] NIH, Bethesda, MD 20892 USA.
[Burns, Joseph E.] Univ Calif Irvine, Dept Radiol Sci, Orange, CA 92868 USA.
[Petrick, Nicholas; Sahiner, Berkman] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Summers, RM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU NIH Clinical Center; Food and Drug Administration
FX This work was supported by the Intramural Research Programs of the NIH
Clinical Center and the Food and Drug Administration. No official
endorsement by the National Institutes of Health or the Food and Drug
Administration of any equipment or product of any company mentioned in
the publication should be inferred. Asterisk indicates corresponding
author.
NR 53
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U1 0
U2 5
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD MAY
PY 2012
VL 31
IS 5
BP 1141
EP 1153
DI 10.1109/TMI.2012.2187304
PG 13
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 935ES
UT WOS:000303502400013
PM 22552333
ER
PT J
AU Takefman, D
Bryan, W
AF Takefman, Daniel
Bryan, Wilson
TI The State of Gene Therapies: The FDA Perspective
SO MOLECULAR THERAPY
LA English
DT Editorial Material
ID ORPHAN; DRUGS
C1 [Takefman, Daniel; Bryan, Wilson] US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
RP Takefman, D (reprint author), US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
NR 5
TC 5
Z9 5
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
IS 5
BP 877
EP 878
DI 10.1038/mt.2012.51
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YS
UT WOS:000303484300001
PM 22549801
ER
PT J
AU Joshi, BH
Leland, P
Puri, RK
AF Joshi, Bharat H.
Leland, Pamela
Puri, Raj K.
TI Analysis of Growth and Invasion of Human Glioma Cell Lines after Gene
Silencing of IL-13Ra2 In Vitro
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Joshi, Bharat H.; Leland, Pamela; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Off Cellular & Gene Therapy,Ctr Biol Evaluat & Re, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 271
BP S107
EP S107
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600272
ER
PT J
AU Kuate, S
Marino, MP
Reiser, J
AF Kuate, Seraphin
Marino, Michael P.
Reiser, Jakob
TI A Cell-Based Assay To Detect Rare Psi-Gag Recombinants in Lentiviral
Vector Preparations
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Kuate, Seraphin; Marino, Michael P.; Reiser, Jakob] FDA CBER, Div Cellular & Gene Therapies, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 349
BP S137
EP S137
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600350
ER
PT J
AU Lynch, PJ
McGinnis, K
Stultz, B
LoSurdo, J
Bauer, S
Hursh, D
AF Lynch, Patrick J.
McGinnis, Kathleen
Stultz, Brian
LoSurdo, Jessica
Bauer, Steven
Hursh, Deborah
TI Epigenetic Status of Cell-Fate Associated Promoters during Expansion of
Bone-Marrow Derived Multipotent Mesenchymal Stromal Cells
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Lynch, Patrick J.; McGinnis, Kathleen; Stultz, Brian; LoSurdo, Jessica; Bauer, Steven; Hursh, Deborah] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 506
BP S196
EP S196
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600506
ER
PT J
AU Marino, MP
Ou, W
Reiser, J
AF Marino, Michael P.
Ou, Wu
Reiser, Jakob
TI A Simple and Scalable Method To Concentrate Measles Virus
Glycoprotein-Pseudotyped Lentiviral Vectors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Marino, Michael P.; Ou, Wu; Reiser, Jakob] FDA CBER, Div Cellular & Gene Therapies, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 754
BP S290
EP S291
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600749
ER
PT J
AU Stultz, BG
McGinnis, K
LoSurda, J
Bauer, S
Hursh, DA
AF Stultz, Brian G.
McGinnis, Kathleen
LoSurda, Jessica
Bauer, Steven
Hursh, Deborah A.
TI Spectral Karyotyping of Multipotent Stromal Cells during In Vitro
Expansion
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Stultz, Brian G.; McGinnis, Kathleen; LoSurda, Jessica; Bauer, Steven; Hursh, Deborah A.] US FDA, Div Cellular & Gene Thrapies, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 750
BP S289
EP S290
PG 2
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600745
ER
PT J
AU Xu, ZL
Qiu, Q
Tian, J
Morita, T
Byrnes, AP
AF Xu, Zhili
Qiu, Qi
Tian, Jie
Morita, Takashi
Byrnes, Andrew P.
TI Interactions of Adenovirus Vectors with Coagulation Factor X and Natural
Antibodies: Lack of an Absolute Requirement for Factor X in Liver
Transduction by Adenovirus Vectors
SO MOLECULAR THERAPY
LA English
DT Meeting Abstract
CT 15th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy
(ASGCT)
CY MAY 16-19, 2012
CL Philadelphia, PA
SP Amer Soc Gene & Cell Therapy (ASGCT)
C1 [Xu, Zhili; Qiu, Qi; Tian, Jie; Byrnes, Andrew P.] US FDA, CBER, Bethesda, MD 20014 USA.
[Morita, Takashi] Meiji Pharmaceut Univ, Kiyose, Japan.
RI Byrnes, Andrew/D-2808-2013
OI Byrnes, Andrew/0000-0003-1135-2629
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAY
PY 2012
VL 20
SU 1
MA 562
BP S218
EP S218
PG 1
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 934YU
UT WOS:000303484600562
ER
PT J
AU Thompson, A
AF Thompson, Aliza
TI Proteinuria as a surrogate end point-more data are needed
SO NATURE REVIEWS NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; CLINICAL-TRIALS; OUTCOMES; ANEMIA; HEMODIALYSIS;
NEPHROPATHY; HEMATOCRIT; MORBIDITY; MORTALITY; EPOETIN
AB Surrogate end points have the potential to facilitate drug development because effects on surrogate end points can sometimes be demonstrated more rapidly and in smaller studies than can effects on clinical outcomes of interest. Proteinuria has been repeatedly proposed as a surrogate end point for renal outcomes in drug development; however, the FDA has generally not accepted effects on proteinuria as evidence of a drug's effectiveness. Proteinuria is an early marker of some kidney diseases and increases in proteinuria can predict risk of disease progression. Whether or not treatment effects on proteinuria can reliably predict treatment effects on renal outcomes is not known. Nevertheless, it may be reasonable to use effects on proteinuria as a basis for accelerated approval of a drug if certain conditions are met. Approval under this pathway carries with it a requirement to complete a study after drug approval that verifies the anticipated treatment benefit.
C1 US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Thompson, A (reprint author), US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, White Oak Campus,Bldg 22,Room 4232,10903 New Hamp, Silver Spring, MD 20993 USA.
EM aliza.thompson@fda.hhs.gov
NR 17
TC 18
Z9 19
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5061
J9 NAT REV NEPHROL
JI Nat. Rev. Nephrol.
PD MAY
PY 2012
VL 8
IS 5
BP 306
EP 309
DI 10.1038/nrneph.2012.43
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 933OP
UT WOS:000303371900011
PM 22391455
ER
PT J
AU Paxton, EW
Ake, CF
Inacio, MC
Khatod, M
Marinac-Dabic, D
Sedrakyan, A
AF Paxton, Elizabeth W.
Ake, Christopher F.
Inacio, Maria C. S.
Khatod, Monti
Marinac-Dabic, Danica
Sedrakyan, Art
TI Evaluation of total hip arthroplasty devices using a total joint
replacement registry
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE total joint replacement; arthroplasty; registry; selection model;
bearing surfaces
ID UNITED-STATES; VALUES
AB Purpose The purpose of this paper is to describe the infrastructure of the total joint replacement registry of a large integrated healthcare system's and emphasize challenges associated with orthopedic device classification and evaluation. Methods Using a large integrated healthcare system innovative infrastructure including electronic health record data, administrative data sources, and registry data collection, we evaluated device choice and outcomes of total hip arthroplasty (THA). Devices were classified into type of bearing surface (alternative versus traditional). Multiple imputation was used to accommodate missing data, and a logistic regression model was applied to assess the impact of patient and surgeon factors on choice of bearing surface. A Cox regression model was used to evaluate risk of aseptic revision while controlling for surgeon, site, and patient characteristics. Adjusted cumulative probability-of-event curves were created, comparing survival of alternative against traditional bearings of devices, with aseptic revision as the outcome of interest. Results The study sample consisted of 25 377 primary THAs with an average follow-up of 2.7?years. Choice of bearing surface varied by surgeon and patient characteristics. After adjusting for patient, surgeon, and hospital covariates, results showed that the risk of aseptic revision associated with alternative bearings did not differ significantly from traditional bearing surfaces (hazard ratio?=?1.33; 95% confidence interval: 0.90, 1.98). Conclusions Clinically rich data from a registry with linkages to electronic health records and other administrative databases improve identification of exposures, outcomes, and patient subgroups in medical device evaluation. These various data sources facilitate refined adjustment for potential confounders such as hospital, surgeon, and patient factors and ensure comprehensive device performance evaluation within registries. Copyright (C) 2012 John Wiley & Sons, Ltd.
C1 [Paxton, Elizabeth W.; Ake, Christopher F.; Inacio, Maria C. S.] Kaiser Permanente, Dept Surg Outcomes & Anal, San Diego, CA 92109 USA.
[Khatod, Monti] Kaiser Permanente, Dept Orthoped Surg, Baldwin Pk, CA USA.
[Marinac-Dabic, Danica; Sedrakyan, Art] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Sedrakyan, Art] Cornell Univ, Weill Med Coll, New York, NY 10021 USA.
RP Paxton, EW (reprint author), Kaiser Permanente, Dept Surg Outcomes & Anal, 3033 Bunker Hill St, San Diego, CA 92109 USA.
EM liz.w.paxton@kp.org
OI Inacio, Maria/0000-0001-8261-2665
NR 19
TC 5
Z9 6
U1 3
U2 9
PU WILEY PERIODICALS, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD MAY
PY 2012
VL 21
SU 2
BP 53
EP 59
DI 10.1002/pds.3228
PG 7
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 935ET
UT WOS:000303502500008
PM 22552980
ER
PT J
AU Emmons, TL
Wrightstone, AD
Baima, ET
Brown, S
Sommers, CD
Hirsch, JL
Pegg, LE
Weinberg, RA
Fischer, HD
Wittwer, AJ
Tomasselli, AG
AF Emmons, Thomas L.
Wrightstone, Ann D.
Baima, Eric T.
Brown, Stacy
Sommers, Cynthia D.
Hirsch, Jeffrey L.
Pegg, Lyle E.
Weinberg, Robin A.
Fischer, H. David
Wittwer, Arthur J.
Tomasselli, Alfredo G.
TI Differential Kinetics and Inhibition of Purified Recombinant Tyrosine
Kinase 2 (TYK-2) and Its Catalytic Domain JH-1
SO PROTEIN AND PEPTIDE LETTERS
LA English
DT Article
DE Activation; autophosphorylation; IC50; inhibition; CP-690550; PF-956980
ID TYROSINE-KINASE-2 DEFICIENCY; JAK3; ENCEPHALOMYELITIS; SUSCEPTIBILITY;
MUTATION; ROLES; PLAYS; CELLS; MICE
AB The Janus kinase (JAK) family consists of four members: JAK-1, -2, -3 and tyrosine kinase 2 (TYK-2). Recent work suggests that cytokine signaling through TYK-2 may play a critical role in a number of inflammatory processes. We recently described the purification and characterization of phosphorylated isoforms of the TYK-2 kinase domain (TYK-2 KD) and its high resolution 3D structure in the presence of inhibitors. We now report the expression and a two-step purification procedure for the doubly tagged full-length construct, H-6-FL-TYK-2-FLAG, and examine its properties compared to those of TYK-2 KD. In the presence of ATP and a peptide substrate, H-6-FL-TYK-2-FLAG showed a marked lag in phosphopeptide product formation, while TYK-2 KD showed no such lag. This lag could be eliminated by ATP pretreatment, suggesting that the H-6-FL-TYK-2-FLAG enzyme was activated by phosphorylation. The potencies of several nanomolar inhibitors were similar for TYK-2 KD and H-6-FL-TYK-2-FLAG. However, these same inhibitors were about 1000 times less potent inhibiting the autophosphorylation of H-6-FL-TYK-2-FLAG than they were inhibiting the phosphorylation of a peptide substrate modeled after the activation loop sequence of TYK-2. This intriguing result suggests that autophosphorylation and, thus, activation of H-6-FL-TYK-2-FLAG is relatively insensitive to inhibition and that present inhibitors act to inhibit TYK-2 subsequent to activation. Inhibition of TYK-2 autophosphorylation may represent a new area of investigation for the JAK family.
C1 [Emmons, Thomas L.] Pfizer Global Res & Dev, St Louis Labs, St Louis, MO 63017 USA.
[Wrightstone, Ann D.; Pegg, Lyle E.] Sigma Aldrich Corp, St Louis, MO 63103 USA.
[Baima, Eric T.] Pfizer Inc, Anim Hlth, Kalamazoo, MI 49007 USA.
[Sommers, Cynthia D.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA.
[Hirsch, Jeffrey L.; Wittwer, Arthur J.] Confluence Life Sci Inc, St Louis, MO 63108 USA.
[Weinberg, Robin A.] St Louis Community Coll, St Louis, MO 63110 USA.
[Fischer, H. David] Jasmin Pk Court, Ballwin, MO 63021 USA.
RP Tomasselli, AG (reprint author), 1540 Garden Valley Dr, Wildwood, MO 63038 USA.
EM Thomas.l.emmons@pfizer.com; atomasse@gmail.com
FU Pfizer, Inc.
FX We would like to thank Brian Korniski and Jill Chrencik for discussions
around the catalytic domain of TYK-2. Additionally, we would like to
thank David C. Wood for consultation on technical matters, and Pfizer,
Inc. for sponsoring this research.
NR 17
TC 0
Z9 0
U1 0
U2 1
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8665
J9 PROTEIN PEPTIDE LETT
JI Protein Pept. Lett.
PD MAY
PY 2012
VL 19
IS 5
BP 485
EP 491
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 932SP
UT WOS:000303311100002
PM 22486643
ER
PT J
AU Roberts, RA
Wallis, R
Ren, J
van der Laan, JW
Sausen, PJ
Slikker, W
AF Roberts, Ruth A.
Wallis, Robert
Ren, Jin
van der Laan, Jan Willem
Sausen, Peter J.
Slikker, William, Jr.
TI What It Means to Be Global
SO TOXICOLOGICAL SCIENCES
LA English
DT Letter
DE Global; international; consensus building
C1 [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Roberts, Ruth A.] AstraZeneca, Macclesfield SK10 4DG, Cheshire, England.
[Wallis, Robert] Pfizer Inc, Global Drug Safety Res & Dev, Groton, CT 06340 USA.
[Ren, Jin] Shanghai Inst Mat Med, Shanghai 201203, Peoples R China.
[van der Laan, Jan Willem] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Sausen, Peter J.] Covance Labs Inc, Madison, WI 53704 USA.
RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HET-1, Jefferson, AR 72079 USA.
EM william.slikker@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD MAY
PY 2012
VL 127
IS 1
BP 313
EP 314
DI 10.1093/toxsci/kfs079
PG 2
WC Toxicology
SC Toxicology
GA 935AT
UT WOS:000303490100030
PM 22334561
ER
PT J
AU Valerio, LG
Cross, KP
AF Valerio, Luis G., Jr.
Cross, Kevin P.
TI Characterization and validation of an in silico toxicology model to
predict the mutagenic potential of drug impurities
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Safety; Mutagenicity; QSAR; Modeling
ID CHEMICAL-STRUCTURE; GENETIC TOXICITY; SALMONELLA MUTAGENICITY;
DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; RISK-ASSESSMENT; MDL-QSAR;
E-STATE; IDENTIFICATION; GENOTOXICITY
AB Control and minimization of human exposure to potential genotoxic impurities found in drug substances and products is an important part of preclinical safety assessments of new drug products. The FDA's 2008 draft guidance on genotoxic and carcinogenic impurities in drug substances and products allows use of computational quantitative structure-activity relationships (QSAR) to identify structural alerts for known and expected impurities present at levels below qualified thresholds. This study provides the information necessary to establish the practical use of a new in silico toxicology model for predicting Salmonella t. mutagenicity (Ames assay outcome) of drug impurities and other chemicals. We describe the model's chemical content and toxicity fingerprint in terms of compound space, molecular and structural toxicophores, and have rigorously tested its predictive power using both cross-validation and external validation experiments, as well as case studies. Consistent with desired regulatory use, the model performs with high sensitivity (81%) and high negative predictivity (81%) based on external validation with 2368 compounds foreign to the model and having known mutagenicity. A database of drug impurities was created from proprietary FDA submissions and the public literature which found significant overlap between the structural features of drug impurities and training set chemicals in the QSAR model. Overall, the model's predictive performance was found to be acceptable for screening drug impurities for Salmonella mutagenicity. Published by Elsevier Inc.
C1 [Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Cross, Kevin P.] Leadscope Inc, Columbus, OH 43215 USA.
RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51,Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM luis.valerio@fda.hhs.gov
NR 47
TC 16
Z9 16
U1 4
U2 18
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 MAY 1
PY 2012
VL 260
IS 3
BP 209
EP 221
DI 10.1016/j.taap.2012.03.001
PG 13
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 937DJ
UT WOS:000303638900001
PM 22426359
ER
PT J
AU Burckart, GJ
Figg, WD
Brooks, MM
Green, D
Girnita, DM
Troutman, S
Chinnock, R
Canter, C
Addonizio, L
Bernstein, D
Kirklin, JK
Naftel, D
Price, DK
Zeevi, A
Webber, SA
AF Burckart, G. J.
Figg, W. D., II
Brooks, M. M.
Green, D.
Girnita, D. M.
Troutman, S.
Chinnock, R.
Canter, C.
Addonizio, L.
Bernstein, D.
Kirklin, J. K.
Naftel, D.
Price, D. K.
Zeevi, A.
Webber, S. A.
TI A Multi-Institutional Study of Outcomes after Pediatric Heart
Transplantation: Effect of ABCC2 Polymorphisms
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Meeting Abstract
CT American Transplant Congress
CY MAY, 2012
CL Boston, MA
C1 [Burckart, G. J.; Green, D.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
[Figg, W. D., II; Troutman, S.; Price, D. K.] NCI, NIH, Bethesda, MD 20892 USA.
[Brooks, M. M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Girnita, D. M.; Zeevi, A.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA.
[Chinnock, R.] Washington Univ, Sch Med, Dept Pediat Cardiol, St Louis, MO USA.
[Canter, C.] Columbia Univ, Dept Pediat, New York, NY 10027 USA.
[Addonizio, L.] Stanford Univ, Div Pediat Cardiol, Palo Alto, CA 94304 USA.
[Bernstein, D.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Kirklin, J. K.; Naftel, D.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD MAY
PY 2012
VL 12
SU 3
SI SI
MA 820
BP 270
EP 270
PG 1
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 931QX
UT WOS:000303235502041
ER
PT J
AU Greenland, S
AF Greenland, Sander
TI Underestimating effects: Why causation probabilities need to be replaced
in regulation, policy, and the law
SO BULLETIN OF THE ATOMIC SCIENTISTS
LA English
DT Article
DE attributable fraction; causation; compensation; epidemiology; exposure;
probability of causation; radiation; risk
ID RELATIVE RISK; ESTIMABILITY; FRACTIONS; CANCER; MODEL
AB Causation probabilities are often a component of decisions on awarding compensation for radiation exposure and descriptions of the number of cancers caused by radiation releases. In many instances, the use of epidemiologic data to calculate such probabilities may seriously underestimate the number of people harmed and the percentage of cancers induced or accelerated by the radiation exposure. Epidemiologic studies can more reliably underpin systems that award compensation using years of healthy life lost due to the exposure. Such a system has its own imprecisions but is more scientifically supportable than using causation probabilities to award compensation.
C1 [Greenland, Sander] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Greenland, Sander] US FDA, Rockville, MD 20857 USA.
[Greenland, Sander] Ctr Dis Control, Atlanta, GA 30333 USA.
RP Greenland, S (reprint author), Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
NR 11
TC 3
Z9 3
U1 0
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0096-3402
J9 B ATOM SCI
JI Bull. Atom. Scient.
PD MAY-JUN
PY 2012
VL 68
IS 3
BP 76
EP 83
DI 10.1177/0096340212444873
PG 8
WC International Relations; Social Issues
SC International Relations; Social Issues
GA 933WL
UT WOS:000303395900010
ER
PT J
AU Epstein, RS
Huang, SM
AF Epstein, R. S.
Huang, S-M
TI The Many Sides of Off-Label Prescribing
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
ID PHYSICIANS
C1 [Epstein, R. S.] Medco Hlth Solut, UBC Div, Franklin Lakes, NJ 07417 USA.
[Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Epstein, RS (reprint author), Medco Hlth Solut, UBC Div, Franklin Lakes, NJ 07417 USA.
EM Robert_epstein@medco.com; ShiewMei.Huang@fda.hhs.gov
NR 13
TC 4
Z9 5
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAY
PY 2012
VL 91
IS 5
BP 755
EP 758
DI 10.1038/clpt.2012.37
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 929FT
UT WOS:000303047400001
PM 22513307
ER
PT J
AU Dal Pan, GJ
AF Dal Pan, G. J.
TI Monitoring the Safety of Medicines Used Off-Label
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID MUSCLE CRAMPS; REGULATORY ACTION; DRUG-TREATMENT; UNITED-STATES;
CHILDREN; SURVEILLANCE; ASSOCIATION; THERAPY; QUININE; TRIALS
AB Off-label use of medicines is common. Because many off-label uses have not been carefully studied, it is important that postmarketing drug safety systems be able to identify, assess, and monitor adverse events that occur in the off-label setting. The full range of postmarketing surveillance and analysis tools can be utilized to study the adverse effects of medicines used off-label.
C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA.
RP Dal Pan, GJ (reprint author), US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA.
EM gerald.dalpan@fda.hhs.gov
NR 32
TC 10
Z9 11
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAY
PY 2012
VL 91
IS 5
BP 787
EP 795
DI 10.1038/clpt.2012.24
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 929FT
UT WOS:000303047400011
PM 22472983
ER
PT J
AU Leong, R
Vieira, MLT
Zhao, P
Mulugeta, Y
Lee, CS
Huang, SM
Burckart, GJ
AF Leong, R.
Vieira, M. L. T.
Zhao, P.
Mulugeta, Y.
Lee, C. S.
Huang, S-M
Burckart, G. J.
TI Regulatory Experience With Physiologically Based Pharmacokinetic
Modeling for Pediatric Drug Trials
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID CHILDREN; THEOPHYLLINE; OMEPRAZOLE; PREDICTION; CLEARANCE; DISPOSITION;
MIDAZOLAM; INFANTS
AB Physiologically based pharmacokinetic (PBPK) approaches that incorporate the developmental physiology and ontogeny of cytochrome P450 (CYP) enzymes may have value in the design of pediatric trials. Four recent submissions to the US Food and Drug Administration (FDA) incorporated different PBPK applications to pediatric drug development. Further testing of PBPK models for three drugs showed that these models generally underpredicted drug clearance. PBPK modeling may have potential for improving pediatric trials through the learn-and-confirm approaches utilized in current regulatory submissions.
C1 [Leong, R.; Vieira, M. L. T.; Zhao, P.; Mulugeta, Y.; Huang, S-M; Burckart, G. J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Lee, C. S.] US FDA, Off Pediat Therapeut, Commissioners Off, Silver Spring, MD USA.
RP Burckart, GJ (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM gilbert.burckart@fda.hhs.gov
NR 25
TC 51
Z9 55
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAY
PY 2012
VL 91
IS 5
BP 926
EP 931
DI 10.1038/clpt.2012.19
PG 6
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 929FT
UT WOS:000303047400028
PM 22472993
ER
PT J
AU Bashaw, ED
Fang, L
AF Bashaw, E. D.
Fang, L.
TI Clinical Pharmacology and Orphan Drugs: An Informational Inventory
2006-2010
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
AB Clinical pharmacology can have an important impact on the development of orphan drugs, i.e., therapeutic agents for rare diseases. This topic was explored at a US Food and Drug Administration (FDA) Advisory Committee meeting in March 2011.(1) At that meeting, preliminary data were presented regarding the breakdown of the clinical pharmacology content in the approvals for orphan drugs in 2006-2010. These data, along with follow-up observations, are presented here, focusing on the in vivo study content and the relevant populations.
C1 [Bashaw, E. D.; Fang, L.] US FDA, Biol Team, Div Clin Pharmacol 3, Off Clin Pharmacol,Off Translat Sci,Ctr Drug Eval, Silver Spring, MD USA.
RP Bashaw, ED (reprint author), US FDA, Biol Team, Div Clin Pharmacol 3, Off Clin Pharmacol,Off Translat Sci,Ctr Drug Eval, Silver Spring, MD USA.
EM edward.bashaw@fda.hhs.gov
NR 3
TC 7
Z9 7
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAY
PY 2012
VL 91
IS 5
BP 932
EP 936
DI 10.1038/clpt.2012.23
PG 5
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 929FT
UT WOS:000303047400029
PM 22453190
ER
PT J
AU Koturbash, I
Beland, FA
Pogribny, IP
AF Koturbash, Igor
Beland, Frederick A.
Pogribny, Igor P.
TI Role of microRNAs in the regulation of drug metabolizing and
transporting genes and the response to environmental toxicants
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Review
DE drug metabolism; environmental toxicants; microRNA; regulation of gene
expression
ID BREAST-CANCER CELLS; ESTROGEN-RECEPTOR-ALPHA; INDUCED LIVER-INJURY;
MESSENGER-RNA; RESISTANCE PROTEIN; DOWN-REGULATION; POSTTRANSCRIPTIONAL
REGULATION; MOLECULAR EPIDEMIOLOGY; MULTIDRUG-RESISTANCE;
MDR1/P-GLYCOPROTEIN EXPRESSION
AB Introduction: MicroRNAs (miRNAs) comprise a family of short non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. Rapidly growing evidence indicates that miRNAs play a key role in drug (xenobiotic) metabolism.
Areas covered: This review summarizes the current knowledge of the role of miRNAs in the regulation of drug (xenobiotic) metabolizing genes and the cellular responses to exposure to exogenous toxicants. The literature search was performed using the PubMed database (up to March 2012).
Expert opinion: miRNAs play a major role in control of the proper functioning of the cellular drug metabolizing system. Emerging evidence indicates that exposure to environmental and occupational toxicants and therapeutic drugs may alter the expression of miRNAs, including those that regulate the expression of drug metabolizing genes. This suggests that drug-induced (xenobiotic-induced) miRNA abnormalities may be one of the underlying mechanisms in the pathogenesis of exposure-related pathologies, and that miRNAs may be potential non-invasive biomarkers of exposure and indicators of the severity of tissue injury induced by toxicants. Also, the evaluation of the expression of miRNAs may be applied for the chemical and drug safety assessment. Additionally, differences in the expression of miRNAs that target drug metabolizing genes may be important determinants for inter-individual differences in sensitivity to toxicants and can serve as critical biomarkers for identifying subpopulations sensitive to exposure.
C1 [Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, 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
NR 110
TC 15
Z9 15
U1 0
U2 17
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1742-5255
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD MAY
PY 2012
VL 8
IS 5
BP 597
EP 606
DI 10.1517/17425255.2012.673587
PG 10
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 931QM
UT WOS:000303234400007
PM 22435483
ER
PT J
AU Hungerford, L
Van Schoick, A
Baird-Heinz, H
Ranivand, DL
Pelsor, F
Bataller, N
Luddy, E
Steinschneider, J
AF Hungerford, Laura
Van Schoick, A'ndrea
Baird-Heinz, Hope
Ranivand, D. Lauren
Pelsor, Francis
Bataller, Neal
Luddy, Elizabeth
Steinschneider, Janice
TI Potassium bromide products marketed for use in dogs response
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Hungerford, Laura; Van Schoick, A'ndrea; Baird-Heinz, Hope; Ranivand, D. Lauren; Pelsor, Francis; Bataller, Neal; Luddy, Elizabeth; Steinschneider, Janice] US FDA, Ctr Vet Med, Rockville, MD 20857 USA.
RP Hungerford, L (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD MAY 1
PY 2012
VL 240
IS 9
BP 1056
EP 1057
PG 2
WC Veterinary Sciences
SC Veterinary Sciences
GA 931KX
UT WOS:000303219900016
ER
PT J
AU Amur, S
Parekh, A
Mummaneni, P
AF Amur, Shashi
Parekh, Ameeta
Mummaneni, Padmaja
TI Sex differences and genomics in autoimmune diseases
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE Genomics; Genetics; Sex; Gender; Autoimmunity; Autoimmune
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS;
SINGLE-NUCLEOTIDE POLYMORPHISM; LYMPHOID TYROSINE PHOSPHATASE;
X-CHROMOSOME INACTIVATION; GENE-EXPRESSION PROFILES; MULTIPLE-SCLEROSIS;
RHEUMATOID-ARTHRITIS; GRAVES-DISEASE; SUSCEPTIBILITY GENES
AB Autoimmune diseases (AIDs) are believed to be multifactorial diseases that commonly involve multiple organ systems. About three fourth of the patients afflicted with AIDs are women suggesting that sex differences impact the incidence of AID. However, the proportion of females to males suffering from AID varies depending on the disease. The response to some AID therapeutics also differs in females versus males, suggesting that enrollment of adequate numbers of women and men is important in clinical trials for development of AID drugs. It is known for a long time that genetic factors are important contributors to AID susceptibility. Currently available information suggests that multiple genes with modest association to AID contribute to susceptibility to AID. Also, the associations may differ for the various ethnicities. The major histocompatibility (MHC) locus appears to be a major genetic factor that confers susceptibility to multiple AIDs, even though the locus is complex and has the highest density of genes in the human genome. Thus, the association of different AIDs could be with different genes in the MHC locus. Among the non-MHC genes, some of the risk alleles are shared between different AIDs, but may not be common to all AIDs. For example, genetic polymorphisms in the Protein Tyrosine Phosphatase-22 (PTPN22) gene have reproducibly shown to have association with systemic lupus erythematosus (SLE), Graves' disease (GD), rheumatoid arthritis (RA) and multiple sclerosis (MS), but not with psoriasis. Identification of factors responsible for risk for developing AID and the of the pathways underlying these diseases are likely to help understand subsets of disease, identify responders to a specific treatment and develop better therapeutics for AID. Published by Elsevier Ltd.
C1 [Amur, Shashi; Mummaneni, Padmaja] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[Parekh, Ameeta] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
RP Amur, S (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Bldg 51,Room 2150,10903 New Hampshire Ave, Silver Spring, MD 20903 USA.
EM Shashi.amur@fda.hhs.gov
NR 135
TC 46
Z9 47
U1 0
U2 12
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
J9 J AUTOIMMUN
JI J. Autoimmun.
PD MAY
PY 2012
VL 38
IS 2-3
SI SI
BP J254
EP J265
DI 10.1016/j.jaut.2011.12.001
PG 12
WC Immunology
SC Immunology
GA 928HO
UT WOS:000302974000023
PM 22204900
ER
PT J
AU Choi, MN
Sharma, D
Zafar, F
Cheng, WC
Albani, L
Badano, A
AF Choi, Mina
Sharma, Diksha
Zafar, Fahad
Cheng, Wei-Chung
Albani, Luigi
Badano, Aldo
TI Does Veiling Glare in the Human Eye Hinder Detection in
High-Dynamic-Range Displays?
SO JOURNAL OF DISPLAY TECHNOLOGY
LA English
DT Article
DE Biomedical imaging; biological system modeling; computed tomography;
diagnostic imaging; displays; medical object detection
ID BRIGHTNESS; SCATTERING; LUMINANCE
AB Ever since Stiles and Holladay (1929), veiling glare (VG) in the human visual system has been known to hinder the visibility of subtle targets. In this work, we quantitatively study how veiling glare affects contrast detection tasks using a dual-layer high-dynamic-range (HDR) display and empirically model the VG effect on thresholds. We used a binary decision for the presence of a Gaussian target in the center of the display on white noise backgrounds. The VG source was realized using a ring pattern with varying parameters. Detection thresholds were estimated using a double-random staircase technique including signal absent trials. In addition, divergence of the subject's fixation from the target in the center was tracked in real-time and used to provide auditory feedback to minimize adaptation effects. Our results are interpreted in terms of illuminance and angular distance between source and target. Sensitivity was lower for smaller angular distances and for larger source intensities. Results from three subjects were used to formulate a bivariate model of VG effect for contrast thresholds similar to Stiles and Holladay. The model can be used to suggest optimal, content-dependent, HDR presentation modes for medical images.
C1 [Choi, Mina; Sharma, Diksha; Zafar, Fahad; Cheng, Wei-Chung; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Albani, Luigi] BARCO FIMI, I-21047 Saronno, Italy.
RP Choi, MN (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM mina.choi@fda.hhs.gov; diksha.sharma@fda.hhs.gov;
fahad.zafar@fda.hhs.gov; wei-chung.cheng@fda.hhs.gov;
aldo.badano@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
FU U.S. Food and Drug Administration; FDA; FIMI/BARCO; Critical Path, FDA
FX This work was supported in part by the U.S. Food and Drug Administration
Critical Path Grant, and in part with a Cooperative Research and
Development Agreement between FDA and FIMI/BARCO. The work of M. Choi
was supported in part by a Critical Path, FDA grant.
NR 18
TC 0
Z9 0
U1 2
U2 14
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1551-319X
J9 J DISP TECHNOL
JI J. Disp. Technol.
PD MAY
PY 2012
VL 8
IS 5
BP 273
EP 282
DI 10.1109/JDT.2011.2179636
PG 10
WC Engineering, Electrical & Electronic; Optics; Physics, Applied
SC Engineering; Optics; Physics
GA 931GV
UT WOS:000303205300001
ER
PT J
AU Magnuson, ML
Satzger, RD
Alcaraz, A
Brewer, J
Fetterolf, D
Harper, M
Hrynchuk, R
McNally, MF
Montgomery, M
Nottingham, E
Peterson, J
Rickenbach, M
Seidel, JL
Wolnik, K
AF Magnuson, Matthew L.
Satzger, R. Duane
Alcaraz, Armando
Brewer, Jason
Fetterolf, Dean
Harper, Martin
Hrynchuk, Ronald
McNally, Mary F.
Montgomery, Madeline
Nottingham, Eric
Peterson, James
Rickenbach, Michael
Seidel, Jimmy L.
Wolnik, Karen
TI Guidelines for the Identification of Unknown Samples for Laboratories
Performing Forensic Analyses for Chemical Terrorism
SO JOURNAL OF FORENSIC SCIENCES
LA English
DT Article
DE forensic science; chemical terrorism; unknown; unknown samples;
identification; sample acceptance; analysis; reporting
ID CHROMATOGRAPHY-MASS SPECTROMETRY; CRITERIA
AB Since the early 1990s, the FBI Laboratory has sponsored Scientific Working Groups to improve discipline practices and build consensus among the forensic community. The Scientific Working Group on the Forensic Analysis of Chemical, Biological, Radiological and Nuclear Terrorism developed guidance, contained in this document, on issues forensic laboratories encounter when accepting and analyzing unknown samples associated with chemical terrorism, including laboratory capabilities and analytical testing plans. In the context of forensic analysis of chemical terrorism, this guidance defines an unknown sample and addresses what constitutes definitive and tentative identification. Laboratory safety, reporting issues, and postreporting considerations are also discussed. Utilization of these guidelines, as part of planning for forensic analysis related to a chemical terrorism incident, may help avoid unfortunate consequences not only to the public but also to the laboratory personnel.
C1 [Magnuson, Matthew L.] US EPA, Natl Homeland Secur Res Ctr, Off Res & Dev, Cincinnati, OH 45268 USA.
[Satzger, R. Duane; Wolnik, Karen] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA.
[Alcaraz, Armando] Lawrence Livermore Natl Lab, Forens Sci Ctr, Livermore, CA 94551 USA.
[Brewer, Jason; Fetterolf, Dean; Montgomery, Madeline; Rickenbach, Michael] Fed Bur Invest Lab, Quantico, VA 22135 USA.
[Harper, Martin] NIOSH, Dept Hlth & Human Serv, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA.
[Hrynchuk, Ronald] Royal Canadian Mounted Police, Natl Forens Serv, Winnipeg, MB R3N OE7, Canada.
[McNally, Mary F.] USA, Dept Def, RDECOM, Aberdeen Proving Ground, MD 21010 USA.
[Nottingham, Eric] US EPA, Natl Enforcement Invest Ctr, Denver Fed Ctr, Lakewood, CO 80225 USA.
[Peterson, James] Fed Bur Invest, Aberdeen Proving Ground, MD 21010 USA.
[Seidel, Jimmy L.] US EPA, Off Criminal Enforcement Forens & Training, Forens Operat Program, Denver, CO 80225 USA.
RP Magnuson, ML (reprint author), US EPA, Natl Homeland Secur Res Ctr, Off Res & Dev, 26 W Martin Luther King Dr, Cincinnati, OH 45268 USA.
EM magnuson.matthew@epa.gov
NR 21
TC 5
Z9 5
U1 0
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-1198
J9 J FORENSIC SCI
JI J. Forensic Sci.
PD MAY
PY 2012
VL 57
IS 3
BP 636
EP 642
DI 10.1111/j.1556-4029.2011.02014.x
PG 7
WC Medicine, Legal
SC Legal Medicine
GA 928QX
UT WOS:000302999000009
PM 22211294
ER
PT J
AU Pfeiffer, CM
Hughes, JP
Lacher, DA
Bailey, RL
Berry, RJ
Zhang, M
Yetley, EA
Rader, JI
Sempos, CT
Johnson, CL
AF Pfeiffer, Christine M.
Hughes, Jeffery P.
Lacher, David A.
Bailey, Regan L.
Berry, R. J.
Zhang, Mindy
Yetley, Elizabeth A.
Rader, Jeanne I.
Sempos, Christopher T.
Johnson, Clifford L.
TI Estimation of Trends in Serum and RBC Folate in the U.S. Population from
Pre- to Postfortification Using Assay-Adjusted Data from the NHANES
1988-2010
SO JOURNAL OF NUTRITION
LA English
DT Article
ID TOTAL HOMOCYSTEINE CONCENTRATIONS; FOLIC-ACID FORTIFICATION; BIO-RAD
RADIOASSAY; UNITED-STATES; ROUND-TABLE; MICROBIOLOGIC ASSAY;
VITAMIN-B-12 STATUS; NATIONAL-HEALTH; BLOOD FOLATE; LC-MS/MS
AB The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was <= 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups, The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and post-fortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact. J. Nutr. 142: 886-893, 2012.
C1 [Pfeiffer, Christine M.; Zhang, Mindy] CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
[Hughes, Jeffery P.; Lacher, David A.; Johnson, Clifford L.] CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Bailey, Regan L.; Yetley, Elizabeth A.; Sempos, Christopher T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Berry, R. J.] CDC, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30333 USA.
[Rader, Jeanne I.] US FDA, College Pk, MD USA.
RP Pfeiffer, CM (reprint author), CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA.
EM cpfeiffer@cdc.gov
OI Berry, Robert/0000-0002-7162-5046
FU Office of Dietary Supplements, NIH
FX Supported by funding from the Office of Dietary Supplements, NIH. The
findings and conclusions in this report are those of the authors and do
not necessarily represent the official views or positions of the CDC and
Prevention/Agency for Toxic Substances and Disease Registry, the NIH, or
the Department of Health and Human Services.
NR 29
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U1 1
U2 12
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD MAY
PY 2012
VL 142
IS 5
BP 886
EP 893
DI 10.3945/jn.111.156919
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 929TX
UT WOS:000303089700012
PM 22437563
ER
PT J
AU Linguraru, MG
Sandberg, JK
Jones, EC
Petrick, N
Summers, RM
AF Linguraru, Marius George
Sandberg, Jesse K.
Jones, Elizabeth C.
Petrick, Nicholas
Summers, Ronald M.
TI Assessing Hepatomegaly: Automated Volumetric Analysis of the Liver
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Hepatomegaly; volumetric analysis; liver; segmentation; nomogram
ID SURGICAL DECISION-MAKING; MULTIDETECTOR ROW CT; COMPUTED-TOMOGRAPHY;
RIEDELS LOBE; ULTRASONIC DETERMINATION; OBSERVER VARIATION; SPLEEN
VOLUME; LIVING DONOR; SPIRAL CT; SIZE
AB Rationale and Objectives: The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly.
Materials and Methods: Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated.
Results: The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences (P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 +/- 0.25 and 2.32 +/- 0.75 L, respectively. One-way analysis of variance found that body surface area (P = .004) and gender (P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables (P > .18). H-score cutoffs of 0.92 and 1.08 L/m(2) were used to define mild and massive hepatomegaly (95% confidence interval, +/- 0.02 L/m(2)). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98.
Conclusions: Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.
C1 [Linguraru, Marius George; Sandberg, Jesse K.; Jones, Elizabeth C.; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Linguraru, MG (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM mlingura@cnmc.org
FU National Institutes of Health, Clinical Center; US Food and Drug
Administration
FX From the Imaging Biomarkers and Computer-Aided Diagnosis Laboratory,
Radiology and Imaging Sciences, Clinical Center, National Institutes of
Health, Bethesda, Maryland (M.G.L., J.K.S., E.C.J., R.M.S.); The Sheikh
Zayed Institute for Pediatric Surgical Innovation, Children's National
Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010 (M.G.L.);
and the Center for Devices and Radiological Health, US Food and Drug
Administration, Silver Spring, Maryland (N.P.). Received September 26,
2011; accepted January 28, 2012. This work was supported in part by the
Intramural Research Programs of the National Institutes of Health,
Clinical Center, and the US Food and Drug Administration. The mention of
commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either actual or
implied endorsements of such products by the US Department of Health and
Human Services. Address correspondence to: M.G.L. e-mail:
mlingura@cnmc.org
NR 58
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Z9 9
U1 0
U2 4
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 MAY
PY 2012
VL 19
IS 5
BP 588
EP 598
DI 10.1016/j.acra.2012.01.015
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 929OR
UT WOS:000303075700012
PM 22361033
ER
PT J
AU Tembhare, P
Yuan, CM
Xi, LQ
Marti, G
Raffeld, M
Stetler-Stevenson, M
AF Tembhare, Prashant
Yuan, Constance M.
Xi, Liqiang
Marti, Gerald
Raffeld, Mark
Stetler-Stevenson, Maryalice
TI Case study interpretation-Portland: Case 1
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
ID B-CELL LYMPHOCYTOSIS; LEUKEMIA; BIOLOGY; CLONES; MBL
C1 [Tembhare, Prashant] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Marti, Gerald] US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD USA.
RP Tembhare, P (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA.
EM tembharep@mail.nih.gov
FU NIH, NCI
FX Grant sponsor: Intramural Research Program of the NIH, NCI.
NR 8
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD MAY
PY 2012
VL 82B
IS 3
BP 177
EP 179
DI 10.1002/cyto.b.21012
PG 3
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 927VA
UT WOS:000302937200010
PM 22431420
ER
PT J
AU Simon, SL
Coleman, CN
Noska, MA
Bowman, T
AF Simon, Steven L.
Coleman, C. Norman
Noska, Michael A.
Bowman, Thomas
TI RESPONSE OF THE US DEPARTMENT OF HEALTH AND HUMAN SERVICES IN PROTECTING
CIVILIAN AMERICANS IN JAPAN DURING THE FUKUSHIMA NUCLEAR CRISIS
SO HEALTH PHYSICS
LA English
DT Article
DE operational topics; emergency planning; exposure, radiation; radiation
safety; emergency response
AB Following the earthquake and tsunami in northern Japan on 11 March 2011 and the ensuing damage to the Fukushima Daiichi Nuclear Power Plant complex, a request by the U. S. Ambassador to Japan to the U. S. Department of Health and Human Services (DHHS) Assistant Secretary for Preparedness and Response (ASPR) resulted in deployment of a five-person team of subject matter experts to the U. S. Embassy. The primary purpose of the deployment was to provide the U. S. Embassy in Tokyo with guidance on health and medical issues related to potential radiation exposure of U. S. citizens in Japan, including employees of the U. S. Department of State at consulates in Japan and American citizens living in or visiting Japan. At the request of the Government of Japan (GOJ), the deployed health team also assisted Japanese experts in their public health response to the radiation incident. Over a 3-wk period in Japan and continuing for weeks after their return to the U. S., the team provided expertise in the areas of medical and radiation oncology; health physics; assessment of radiation dose and cancer risk, particularly to U. S. citizens living in Tokyo and the surrounding areas; food and water contamination and the acceptable limits; countermeasures to exposure such as potassium iodide (KI); the use of KI and an offered donation from the United States;, evacuation and re-entry issues; and health/emergency-related communication strategies. This paper describes the various strategies used and observations made by the DHHS team during the first 2 mo after the Fukushima crisis began. Health Phys. 102(5):570-579; 2012
C1 [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Coleman, C. Norman] Dept Hlth & Human Serv, Off Preparedness & Emergency Operat, Washington, DC USA.
[Noska, Michael A.] US FDA, Silver Spring, MD USA.
[Bowman, Thomas] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU DHHS; NIH; NCI; NCI Division of Cancer Epidemiology
FX The authors are appreciative of support from the DHHS and individual
agencies they represent and especially Dr. Nicole Lurie, the DHHS
Assistant Secretary for Preparedness and Response. In addition, the
authors are appreciative of the support from the Directors of the NIH,
NCI, and the NCI Division of Cancer Epidemiology, the FDA Office of
International Programs, and the FDA Office of Crisis Management for
their logistic support. The authors gratefully acknowledge the
dedication and expertise of a team member, Jana Telfer of the CDC, in
the area of risk communications.
NR 24
TC 3
Z9 3
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD MAY
PY 2012
VL 102
IS 5
BP 570
EP 579
DI 10.1097/HP.0b013e31824c79e5
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 925VG
UT WOS:000302789300014
ER
PT J
AU Zou, W
Lin, WJ
Hise, KB
Chen, HC
Keys, C
Chen, JJ
AF Zou, Wen
Lin, Wei-Jiun
Hise, Kelley B.
Chen, Hung-Chia
Keys, Christine
Chen, James J.
TI Prediction System for Rapid Identification of Salmonella Serotypes Based
on Pulsed-Field Gel Electrophoresis Fingerprints
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID HIGH-DIMENSIONAL DATA; FOODBORNE PATHOGENS; MULTIPLEX; SWINE; PCR
AB A classification model is presented for rapid identification of Salmonella serotypes based on pulsed-field gel electrophoresis (PFGE) fingerprints. The classification model was developed using random forest and support vector machine algorithms and was then applied to a database of 45,923 PFGE patterns, randomly selected from all submissions to CDC PulseNet from 2005 to 2010. The patterns selected included the top 20 most frequent serotypes and 12 less frequent serotypes from various sources. The prediction accuracies for the 32 serotypes ranged from 68.8% to 99.9%, with an overall accuracy of 96.0% for the random forest classification, and ranged from 67.8% to 100.0%, with an overall accuracy of 96.1% for the support vector machine classification. The prediction system improves reliability and accuracy and provides a new tool for early and fast screening and source tracking of outbreak isolates. It is especially useful to get serotype information before the conventional methods are done. Additionally, this system also works well for isolates that are serotyped as "unknown" by conventional methods, and it is useful for a laboratory where standard serotyping is not available.
C1 [Zou, Wen; Chen, Hung-Chia; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Lin, Wei-Jiun] Feng Chia Univ, Dept Appl Math, Taichung 40724, Taiwan.
[Hise, Kelley B.] Ctr Dis Control & Prevent, PulseNet Database Unit, Enter Dis Lab Branch, Div Foodborne Waterborne & Environm Dis,Natl Ctr, Atlanta, GA USA.
[Keys, Christine] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
RP Zou, W (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA.
EM wen.zou@fda.hhs.gov
FU Oak Ridge Institute for Science and Education
FX Wei-Jiun Lin and Hung-Chia Chen acknowledge support of a fellowship from
the Oak Ridge Institute for Science and Education, administered through
an interagency agreement between the U.S. Department of Energy and the
U.S. Food and Drug Administration.
NR 27
TC 18
Z9 19
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAY
PY 2012
VL 50
IS 5
BP 1524
EP 1532
DI 10.1128/JCM.00111-12
PG 9
WC Microbiology
SC Microbiology
GA 927II
UT WOS:000302900500005
PM 22378901
ER
PT J
AU Vaidyanathan, J
Choe, S
Sahajwalla, CG
AF Vaidyanathan, Jayabharathi
Choe, Sally
Sahajwalla, Chandrahas G.
TI Type 2 Diabetes in Pediatrics and Adults: Thoughts from a Clinical
Pharmacology Perspective
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Review
DE pediatric type 2 diabetes; metformin; rosiglitazone; glimepiride;
pharmacokinetics; pharmacodynamics; Pediatric; Regulatory Science;
Clinical Pharmacokinetics
ID BLOOD-GLUCOSE CONTROL; INSULIN-RESISTANCE; DOUBLE-BLIND; FOLLOW-UP;
GLYCEMIC CONTROL; CONTROLLED-TRIAL; BODY-WEIGHT; GLIMEPIRIDE; METFORMIN;
MELLITUS
AB Type 2 diabetes results when insulin secretion is unable to keep the plasma glucose levels as per acceptable range. This leads to chronic hyperglycemia and its associated microvascular complications such as renal impairment (diabetic nephropathy), retinal abnormalities (diabetic retinopathy), and autonomic, sensory, and motor neuropathies (diabetic neuropathy) and macrovascular disease. Historically, type 2 diabetes is well known as an adult-onset disease; however, lately, the incidence of the disease is reported to be increasing in children. Despite the wealth of information concerning type 2 diabetes in adults, data unique to the pediatric age group regarding the pathophysiology and therapy for type 2 diabetes are limited. For treatment in pediatric type 2 diabetes, metformin and insulin are the only antidiabetic agents approved currently. There are data of use of other oral antidiabetic drugs including glimepiride, rosiglitazone, and glyburide (in combination with metformin) in pediatric patients; however, formal clinical trials to establish the safety and efficacy have not been conducted. This review will compare the clinical pharmacology aspects of the oral type 2 diabetic drugs in pediatric and adult populations in order to determine any differences between the two patient groups. (C) 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101: 1659-1671, 2012
C1 [Vaidyanathan, Jayabharathi; Choe, Sally; Sahajwalla, Chandrahas G.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Sahajwalla, CG (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM chandrahas.sahajwalla@fda.hhs.gov
NR 72
TC 10
Z9 10
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3549
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD MAY
PY 2012
VL 101
IS 5
BP 1659
EP 1671
DI 10.1002/jps.23085
PG 13
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 925ZC
UT WOS:000302800100003
PM 22383396
ER
PT J
AU Ibrahim, L
DiazGranados, N
Franco-Chaves, J
Brutsche, N
Henter, ID
Kronstein, P
Moaddel, R
Wainer, I
Luckenbaugh, DA
Manji, HK
Zarate, CA
AF Ibrahim, Lobna
DiazGranados, Nancy
Franco-Chaves, Jose
Brutsche, Nancy
Henter, Ioline D.
Kronstein, Phillip
Moaddel, Ruin
Wainer, Irving
Luckenbaugh, David A.
Manji, Husseini K.
Zarate, Carlos A., Jr.
TI Course of Improvement in Depressive Symptoms to a Single Intravenous
Infusion of Ketamine vs Add-on Riluzole: Results from a 4-Week,
Double-Blind, Placebo-Controlled Study
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE antidepressant; depression; glutamate; ketamine; NMDA; riluzole
ID D-ASPARTATE ANTAGONIST; RESISTANT MAJOR DEPRESSION; MOOD DISORDERS;
RATING-SCALE; TRIAL; IDEATION; STATES
AB The N-methyl-D-aspartate antagonist ketamine has rapid antidepressant effects in patients with treatment-resistant major depression (TRD); these effects have been reported to last for 1 week in some patients. However, the extent and duration of this antidepressant effect over longer periods has not been well characterized under controlled conditions. Riluzole, a glutamatergic modulator with antidepressant and synaptic plasticity-enhancing effects, could conceivably be used to promote the antidepressant effects of ketamine. This study sought to determine the extent and time course of antidepressant improvement to a single-ketamine infusion over 4 weeks, comparing the addition of riluzole vs placebo after the infusion. Forty-two subjects (18-65) with TRD and a Montgomery-Asberg Depression Rating Scale (MADRS) score of >= 22 received a single intravenous infusion of ketamine (0.5 mg/kg). Four to six hours post-infusion, subjects were randomized to double-blind treatment with either riluzole (100-200 mg/day; n = 21) or placebo (n = 21) for 4 weeks. Depressive symptoms were rated daily. A significant improvement (P<0.001) in MADRS scores from baseline was found. The effect size of improvement with ketamine was initially large and remained moderate throughout the 28-day trial. Overall, 27% of ketamine responders had not relapsed by 4 weeks following a single ketamine infusion. The average time to relapse was 13.2 days (SE = 2.2). However, the difference between the riluzole and placebo treatment groups was not significant, suggesting that the combination of riluzole with ketamine treatment did not significantly alter the course of antidepressant response to ketamine alone. Neuropsychopharmacology (2012) 37, 1526-1533; doi: 10.1038/npp.2011.338; published online 1 February 2012
C1 [Ibrahim, Lobna; DiazGranados, Nancy; Franco-Chaves, Jose; Brutsche, Nancy; Kronstein, Phillip; Luckenbaugh, David A.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[DiazGranados, Nancy] Univ Texas Hlth Sci Ctr, San Antonio, TX USA.
[Henter, Ioline D.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Kronstein, Phillip] US FDA, Silver Spring, MD USA.
[Moaddel, Ruin; Wainer, Irving] NIA, NIH, Bethesda, MD 20892 USA.
[Manji, Husseini K.] Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, NIH, 10 Ctr Dr,CRC,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
FU National Institute of Mental Health, National Institutes of Health
(NIMH-NIH)
FX This study was supported in part by the Intramural Research Program of
the National Institute of Mental Health, National Institutes of Health
(NIMH-NIH). The author(s) declare that, except for income received from
our primary employer, no financial support or compensation has been
received from any individual or corporate entity over the past 3 years
for research or professional service and there are no personal financial
holdings that could be perceived as constituting a potential conflict of
interest. A patent application for the use of ketamine in depression has
been submitted listing Drs Zarate and Manji among the inventors; they
have assigned their rights on the patent to the U. S. government, but
will share a percentage of any royalties that may be received by the
government.
NR 33
TC 115
Z9 117
U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD MAY
PY 2012
VL 37
IS 6
BP 1526
EP 1533
DI 10.1038/npp.2011.338
PG 8
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 927GY
UT WOS:000302896600019
PM 22298121
ER
PT J
AU Scholl, PF
Cole, RN
Ruczinski, I
Gucek, M
Diez, R
Rennie, A
Nathasingh, C
Schulze, K
Christian, P
Yager, JD
Groopman, JD
West, KP
AF Scholl, P. F.
Cole, R. N.
Ruczinski, I.
Gucek, M.
Diez, R.
Rennie, A.
Nathasingh, C.
Schulze, K.
Christian, P.
Yager, J. D.
Groopman, J. D.
West, K. P., Jr.
TI Maternal serum proteome changes between the first and third trimester of
pregnancy in rural Southern Nepal
SO PLACENTA
LA English
DT Article
DE Pregnancy proteins; Maternal serum proteomics; DIGE; iTRAQ; Gelsolin;
Pregnancy-specific beta-glycoprotein 4
ID CLUSTER-RANDOMIZED-TRIAL; D-BINDING PROTEIN; PLASMA-GELSOLIN;
SPHINGOSINE 1-PHOSPHATE; ZONE PROTEIN; HUMAN ALPHA-2-MACROGLOBULIN;
REGULATORY PROTEIN; SCAVENGER SYSTEM; ACTIN COMPLEXES; DOWN-SYNDROME
AB Characterization of normal changes in the serum proteome during pregnancy may enhance understanding of maternal physiology and lead to the development of new gestational biomarkers. In 23 Nepalese pregnant women who delivered at term, two-dimensional difference in-gel electrophoresis (DICE) was used to assess changes in relative protein abundance between paired serum samples collected in the first and third trimesters. One-hundred and forty-five of over 700 protein spots in DIGE gels (pI 4.2-6.8) exhibited nominally significant (p < 0.05) differences in abundance across trimesters. Additional filtering using a Bonferroni correction reduced the number of significant (p < 0.00019) spots to 61. Mass spectrometric analysis detected 38 proteins associated with gestational age, cytoskeletal remodeling, blood pressure regulation, lipid and nutrient transport, and inflammation. One new protein, pregnancy-specific beta-glycoprotein 4 was detected. A follow-up isotope tagging for relative and absolute quantitation (iTRAQ) experiment of six mothers from the DICE study revealed 111 proteins, of which 11 exhibited significant (p < 0.05) differences between trimesters. Four of these proteins: gelsolin, complement C1r subcomponent, alpha-1-acid glycoprotein, and alpha-1B-glycoprotein also changed in the DICE analysis. Although not previously associated with normal pregnancy, gelsolin decreased in abundance by the third trimester (p < 0.01) in DIGE, iTRAQ and Western analyses. Changes in abundance of proteins in serum that are associated with syncytiotrophoblasts (gelsolin, pregnancy-specific beta-1 glycoprotein 1 and beta-2-glycoprotein 1) probably reflect dynamics of a placental proteome shed into maternal circulation during pregnancy. Measurement of changes in the maternal serum proteome, when linked with birth outcomes, may yield biomarkers for tracking reproductive health in resource poor settings in future studies. Published by Elsevier Ltd.
C1 [Scholl, P. F.; Rennie, A.; Nathasingh, C.; Yager, J. D.; Groopman, J. D.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Cole, R. N.; Gucek, M.; Diez, R.] Bloomberg Sch Publ Hlth, Mass Spectrometry Core Facil, Sch Med, Baltimore, MD 21205 USA.
[Ruczinski, I.] Ctr Human Nutr, Dept Biostat, Baltimore, MD 21205 USA.
[Schulze, K.; Christian, P.; West, K. P., Jr.] Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
RP Scholl, PF (reprint author), US FDA, Ctr Food Safety & Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM peter.scholl@fda.hhs.gov
OI Scholl, Peter/0000-0002-8870-3266
FU Micronutrients for Health Cooperative Agreement [HRN-A-00-97-00015-00];
Office of Health, Nutrition and Infectious Diseases, US Agency for
International Development, Washington DC; Global Control of
Micronutrient Deficiency Grant [GH614]; Plasma Proteomic Biomarker
Indicators of Micronutrient Status and Deficiency [OPPGH5341]; Bill and
Melinda Gates Foundation, Seattle, WA, USA; JHSPH
FX The field trial and biospecimen collections for this study were
conducted by the Center for Human Nutrition within the Department of
International Health, Johns Hopkins Bloomberg School of Public Health
(JHSPH), Baltimore, MD, USA and the Nepal Nutrition Intervention Project
- Sarlahi (NNIPS) of the National Society for Comprehensive Eye Care
(Nepal Netra Jyoti Sangh), Kathmandu, Nepal, financially supported by a
Micronutrients for Health Cooperative Agreement No. HRN-A-00-97-00015-00
with the Office of Health, Nutrition and Infectious Diseases, US Agency
for International Development, Washington DC, a Global Control of
Micronutrient Deficiency Grant (No. GH614) and Plasma Proteomic
Biomarker Indicators of Micronutrient Status and Deficiency Grant (No.
OPPGH5341) with the Bill and Melinda Gates Foundation, Seattle, WA, USA.
The proteomics analysis was supported, in part, by a Faculty Innovation
Award (to KPW) from the JHSPH.
NR 61
TC 7
Z9 7
U1 0
U2 1
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
J9 PLACENTA
JI Placenta
PD MAY
PY 2012
VL 33
IS 5
BP 424
EP 432
DI 10.1016/j.placenta.2012.02.009
PG 9
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 929BV
UT WOS:000303037100015
PM 22385826
ER
PT J
AU Vodeiko, GM
Weir, JP
AF Vodeiko, Galina M.
Weir, Jerry P.
TI Determination of H5N1 vaccine potency using reference antisera from
heterologous strains of influenza
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article
DE Pandemic influenza; single radial immunodiffusion assay; vaccine potency
ID SINGLE-RADIAL-IMMUNODIFFUSION; HEMAGGLUTININ MOLECULE; PANDEMIC
INFLUENZA; VIRUS VACCINES; DIFFUSION TEST; ASSAY; QUANTIFICATION;
ANTIBODY; REACTOGENICITY; A/USSR/77
AB Background Standardization of inactivated influenza vaccines by hemagglutinin (HA) content is performed by the single radial immunodiffusion (SRID) method. Regulatory agencies prepare, calibrate, and distribute SRID reagent standards necessary for testing of seasonal influenza vaccines, and a similar process is used to produce potency reagents for candidate pandemic influenza vaccines that are manufactured for emergency stockpiles.
Objectives Because of the concerns in generating a timely strain-specific potency antiserum for an emerging pandemic virus, we evaluated the feasibility of using heterologous potency reference antiserum as a replacement for a strain-specific (homologous) antiserum in the SRID potency assay for stockpiled H5N1 vaccines.
Results The results indicate that a heterologous H5N1 antiserum can be used to determine the accurate potency of inactivated H5N1 influenza vaccines. Additionally, when H5N1 vaccine was subjected to an accelerated stability protocol, both homologous and heterologous antisera provided similar measurements of vaccine potency decline. Limitations to the heterologous antiserum approach to potency determination were shown by the inability of antiserum to recent seasonal H1N1 viruses to work in an SRID assay with the 2009 pandemic H1N1 A/California/07/2009 antigen.
Conclusions The data demonstrate the feasibility of using heterologous antiserum for potency determination of at least some candidate vaccines in case of a shortage or delay of homologous antiserum. Further, the results suggest the prudence of stockpiling a broad library of potency reagents including many strains of influenza viruses with pandemic potential to provide an added measure of assurance that reagent production would not be a bottleneck to vaccine production during a pandemic.
C1 [Vodeiko, Galina M.; Weir, Jerry P.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Weir, JP (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA.
EM jerry.weir@fda.hhs.gov
FU Biomedical Advanced Research and Development Authority (BARDA),
Department of Health and Human Services
FX We thank Zhiping Ye and Maryna Eichelberger (CBER/FDA) for critical
reading of the manuscript. This work was supported in part by the
Biomedical Advanced Research and Development Authority (BARDA),
Department of Health and Human Services.
NR 33
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1750-2640
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD MAY
PY 2012
VL 6
IS 3
BP 176
EP 187
DI 10.1111/j.1750-2659.2011.00285.x
PG 12
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 924TW
UT WOS:000302715200017
PM 21902817
ER
PT J
AU Bristol, ML
Di, X
Beckman, MJ
Wilson, EN
Henderson, SC
Maiti, A
Fan, Z
Gewirtz, DA
AF Bristol, Molly L.
Di, Xu
Beckman, Matthew J.
Wilson, Eden N.
Henderson, Scott C.
Maiti, Aparna
Fan, Zhen
Gewirtz, David A.
TI Dual functions of autophagy in the response of breast tumor cells to
radiation Cytoprotective autophagy with radiation alone and cytotoxic
autophagy in radiosensitization by vitamin D-3
SO AUTOPHAGY
LA English
DT Article
DE vitamin D-3; ionizing radiation; autophagy; apoptosis; breast cancer
ID UBIQUITIN-PROTEASOME SYSTEM; MYELOID-LEUKEMIA CELLS; CANCER-CELLS;
1,25-DIHYDROXYVITAMIN D-3; D ANALOG; PROLIFERATIVE RECOVERY;
IONIZING-RADIATION; INDUCED APOPTOSIS; CARCINOMA-CELLS; IN-VITRO
AB In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with autophagy induced by radiation resulted in growth suppression and/or cell killing (primarily by apoptosis). The hormonally active form of vitamin D, 1,25D(3), also promoted autophagy in irradiated MCF-7 cells, sensitized the cells to radiation and suppressed the proliferative recovery that occurs after radiation alone. 1,25D(3) enhanced radiosensitivity and promoted autophagy in MCF-7 cells that overexpress Her-2/neu as well as in p53 mutant Hs578t breast tumor cells. In contrast, 1,25D(3) failed to alter radiosensitivity or promote autophagy in the BT474 breast tumor cell line with low-level expression of the vitamin D receptor. Enhancement of MCF-7 cell sensitivity to radiation by 1,25D(3) was not attenuated by a genetic block to autophagy due largely to the promotion of apoptosis via the collateral suppression of protective autophagy. However, MCF-7 cells were protected from the combination of 1,25D(3) with radiation using a concentration of chloroquine that produced minimal sensitization to radiation alone. The current studies are consistent with the premise that while autophagy mediates a cytoprotective function in irradiated breast tumor cells, promotion of autophagy can also confer radiosensitivity by vitamin D (1,25D(3)). As both cytoprotective and cytotoxic autophagy can apparently be expressed in the same experimental system in response to radiation, this type of model could be utilized to distinguish biochemical, molecular and/or functional differences in these dual functions of autophagy.
C1 [Bristol, Molly L.; Beckman, Matthew J.; Wilson, Eden N.; Gewirtz, David A.] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA.
[Di, Xu] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Henderson, Scott C.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA.
[Maiti, Aparna] Virginia Commonwealth Univ, Dept Orthoped Surg, Richmond, VA USA.
[Fan, Zhen] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Gewirtz, David A.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
RP Gewirtz, DA (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23284 USA.
EM gewirtz@vcu.edu
OI Henderson, Scott/0000-0002-1076-3867
FU American Institute for Cancer Research [06A058-REV]; Department of
Defense [W81XWH-09-1-0020]; NIH-NINDS Center [P30NS047463]
FX This work was supported, in part, by American Institute for Cancer
Research Grant #06A058-REV. Molly Bristol was supported, in part, by a
predoctoral training grant (W81XWH-09-1-0020) from the Department of
Defense. Electron microscopy was performed at the VCU-Department of
Neurobiology and Anatomy Microscopy Facility, supported, in part, with
funding from NIH-NINDS Center core grant P30NS047463. The RFP-LC3 vector
was generously provided by Dr. Keith Miskimins at the University of
South Dakota and was originally developed by the laboratory of Dr. A. M.
Tolkovsky. The MCF7/ATG7-/- cells were a generous gift from
the lab of Dr. Ameeta Kelekar at University of Minnesota, Minneapolis,
MN.
NR 57
TC 44
Z9 47
U1 5
U2 10
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD MAY
PY 2012
VL 8
IS 5
BP 739
EP 753
DI 10.4161/auto.19313
PG 15
WC Cell Biology
SC Cell Biology
GA 960QU
UT WOS:000305403800004
PM 22498493
ER
PT J
AU Bowen, LE
Rivers, K
Trombley, JE
Bohannon, JK
Li, SXX
Boydston, JA
Eichelberger, MC
AF Bowen, Larry E.
Rivers, Katie
Trombley, John E.
Bohannon, J. Kyle
Li, Shixiong X.
Boydston, Jeremy A.
Eichelberger, Maryna C.
TI Development of a murine nose-only inhalation model of influenza:
comparison of disease caused by instilled and inhaled A/PR/8/34
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Article
DE influenza; inhalation; instillation; aerosol; mouse
ID RESPIRATORY-TRACT; AEROSOL CHALLENGE; VIRUS-INFECTION; A VIRUS; MICE;
TRANSMISSION; FERRETS; EXPOSURE; H5N1; PATHOGENESIS
AB Influenza continues to cause widespread disease and death during winter months. In preclinical studies to evaluate the potential efficacy of drugs and vaccines, influenza challenge virus is usually instilled into the noses of animals in the form of large liquid drops. Since inhalation of aerosolized influenza is commonly associated with human transmission, instillation of challenge virus raises uncertainty about the applicability of results. In order to compare the challenge methods, we established conditions to generate influenza aerosols with a mass median aerodynamic diameter (MMAD) of 1 urn that were delivered to mice in a nose only inhalation system. In this report, we describe the system and compare the 50% lethal dose (LD50) of instilled and inhaled A/PR/8/34 (PR8) in BALB/c mice. The estimated LD50 for inhaled virus was 8.7 plaque forming units (PFU) and the mean time to death was 7.7 days, whereas the estimated LD50 for instilled virus was 51.6 PFU and the mean time to death was 8.2 days. Our results show that mice are more sensitive to inhaled virus than virus delivered by intranasal instillation. The murine nose-only inhalation model of influenza infection can be used to infect large numbers of animals simultaneously with well-characterized, homogenous PR8 bioaerosol in a controlled and reproducible manner. This model provides the means to evaluate the efficacy of drug and vaccine candidates against the relevant route of challenge, thereby providing data that may better predict clinical outcome.
C1 [Bowen, Larry E.; Trombley, John E.; Bohannon, J. Kyle; Li, Shixiong X.; Boydston, Jeremy A.] So Res Inst, Birmingham, AL 35205 USA.
[Rivers, Katie; Eichelberger, Maryna C.] US FDA, CBER, Bethesda, MD 20014 USA.
RP Bowen, LE (reprint author), So Res Inst, 2000 9th Ave South, Birmingham, AL 35205 USA.
EM l.bowen@southernresearch.org
FU CBER PanFlu funds
FX This study was supported by CBER PanFlu funds. We thank the CBER and
Southern Research Institute animal facility technical support staff for
excellent care of the animals, Arash Hassantoufighi for technical
support, and Alpha StatConsult, Damascus, MD for statistical analysis of
data.
NR 39
TC 5
Z9 5
U1 0
U2 2
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD MAY
PY 2012
VL 2
AR UNSP 74
DI 10.3389/fcimb.2012.00074
PG 8
WC Immunology; Microbiology
SC Immunology; Microbiology
GA 220ZU
UT WOS:000324627400018
PM 22919665
ER
PT J
AU Hepp, NM
AF Hepp, Nancy M.
TI Determination of total lead in 400 lipsticks on the US market using a
validated microwave-assisted digestion, inductively coupled plasma-mass
spectrometric method
SO JOURNAL OF COSMETIC SCIENCE
LA English
DT Article
AB In 2009, the U.S. Food and Drug Administration (FDA) published lead (Pb) content results from a small survey of 20 tube lipsticks with red shades using a validated inductively coupled plasma-mass spectrometric (ICP-MS) method developed by FDA chemists. The study was prompted by a media report suggesting that potential exposure to lead from lipsticks under conditions of ordinary use might be harmful. The FDA has since investigated the lead content of tube lipsticks by conducting an expanded survey that included a variety of shades and manufacturers, at varying prices. The purposes of the expanded survey were to ascertain the levels of lead in lipsticks sold on the U.S. market, to identify any categories of lipstick with elevated levels of lead, and to compare the results to those from the initial small survey. Four hundred lipsticks available on the U.S. market in the spring of 2010 were tested for total lead content using the FDA's validated method. The analyses were performed by a private laboratory contracted by the FDA. The maximum lead level found was 7.19 mg Pb/kg. Thirteen of the 400 lipsticks were found to contain levels greater than 3.06 mg Pb/kg, the highest amount found in the initial survey. The average lead concentration found in the expanded survey was 1.11 mg Pb/kg, which was very close to the average of 1.07 mg Pb/kg found in the initial survey. Some statistically significant associations between lead level and parent company were found. The contract requirements, testing procedures, and findings from the expanded survey are described here.
C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA.
RP Hepp, NM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA.
NR 10
TC 10
Z9 10
U1 3
U2 5
PU SOC COSMETIC CHEMISTS
PI NEW YORK
PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA
SN 1525-7886
J9 J COSMET SCI
JI J. Cosmet. Sci.
PD MAY-JUN
PY 2012
VL 63
IS 3
BP 159
EP 176
PG 18
WC Chemistry, Applied; Dermatology
SC Chemistry; Dermatology
GA V38XT
UT WOS:000209376800001
PM 23193690
ER
PT J
AU Ziolkowska, NE
Bujacz, A
Randad, RS
Erickson, JW
Skalova, T
Hasek, J
Bujacz, G
AF Ziolkowska, Natasza E.
Bujacz, Anna
Randad, Ramnarayan S.
Erickson, John W.
Skalova, Tereza
Hasek, Jindrich
Bujacz, Grzegorz
TI New Active HIV-1 Protease Inhibitors Derived from 3-Hexanol:
Conformation Study of the Free Inhibitors in Crystalline State and in
Complex with the Enzyme
SO CHEMICAL BIOLOGY & DRUG DESIGN
LA English
DT Letter
DE acquired immunodeficiency syndrome; crystal structure; drug design;
human immunodeficiency virus; molecular structure; protease inhibitor
ID VIRUS TYPE-1 PROTEASE; ORALLY BIOAVAILABLE INHIBITOR; DEFICIENCY
SYNDROME AIDS; STRUCTURE-BASED DESIGN; X-RAY-ANALYSIS; DRUG-RESISTANCE;
HYDROXYETHYLAMINE ISOSTERE; ANTIVIRAL ACTIVITY; POTENT INHIBITOR;
WILD-TYPE
AB Four novel linear non-peptidic HIV-1 protease inhibitors derived from 2,5-diamino-1,6-diphenyl-3-hexanol were synthesized and characterized. All of them exhibit tight binding to HIV-1 protease, with inhibition constants Ki in the range 20 pm5 nm. The investigated inhibitors were crystallized, and their crystal structures were determined by X-ray diffraction. In all cases, the conformations found in the crystalline state differ significantly from the conformations obtained by computational docking of the inhibitor in the binding cleft of native HIV-1 protease. Owing to the prevalence of hydrophobic substituents in all these inhibitors, the conformational mobility in water solution is restricted to their compact forms. The spectrum of low-energy conformations in solution dramatically changes during the formation of inhibitor crystals (phenyl ring stacking as a leading motif) or during the formation of a complex with HIV-1 protease (elongated conformation suitable to fit the enzyme pockets as a factor responsible for tight binding). High conformational flexibility and low conformational stress in the molecules of these inhibitors most likely increase their biological activity in comparison with more rigid compounds.
C1 [Ziolkowska, Natasza E.; Bujacz, Anna; Bujacz, Grzegorz] Tech Univ Lodz, Inst Tech Biochem, PL-90924 Lodz, Poland.
[Randad, Ramnarayan S.] US FDA, Div Chem 1, Off Gener Drugs, Rockville, MD 20855 USA.
[Erickson, John W.] Sequoia Pharmaceut Inc, Gaithersburg, MD 20879 USA.
[Skalova, Tereza; Hasek, Jindrich] Acad Sci Czech Republic, Inst Macromol Chem, Prague 16206 6, Czech Republic.
RP Bujacz, G (reprint author), Tech Univ Lodz, Inst Tech Biochem, Stefanowskiego 4-10, PL-90924 Lodz, Poland.
EM gdbujacz@p.lodz.pl
RI Skalova, Tereza/G-6422-2014; Hasek, Jindrich/G-3267-2014
OI Hasek, Jindrich/0000-0001-7973-1815
NR 66
TC 1
Z9 1
U1 0
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1747-0277
J9 CHEM BIOL DRUG DES
JI Chem. Biol. Drug Des.
PD MAY
PY 2012
VL 79
IS 5
BP 798
EP 809
DI 10.1111/j.1747-0285.2012.01328.x
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Medicinal
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 919BX
UT WOS:000302296700018
PM 22296826
ER
PT J
AU Umbreit, TH
Francke-Carroll, S
Weaver, JL
Miller, TJ
Goering, PL
Sadrieh, N
Stratmeyer, ME
AF Umbreit, T. H.
Francke-Carroll, S.
Weaver, J. L.
Miller, T. J.
Goering, P. L.
Sadrieh, N.
Stratmeyer, M. E.
TI Tissue distribution and histopathological effects of titanium dioxide
nanoparticles after intravenous or subcutaneous injection in mice
SO JOURNAL OF APPLIED TOXICOLOGY
LA English
DT Article
DE titanium dioxide; nanoparticles; TiO2; mouse; distribution; in vivo
ID ULTRAFINE PARTICLES; BIODISTRIBUTION; TOXICITY; RATS
AB Nanoparticles can be formed following degradation of medical devices such as orthopedic implants. To evaluate the safety of titanium alloy orthopedic materials, data are needed on the long-term distribution and tissue effects of injected titanium nanoparticles in experimental animals. In this study, we evaluated the tissue distribution and histopathological effects of titanium dioxide (TiO2) nanoparticles (approximately 120?nm diameter) in mice after intravenous (i.v.; 56 or 560?mg kg-1 per mouse) or subcutaneous (s.c.; 560 or 5600?mg kg-1 per mouse) injection on two consecutive days. Animals were examined 1 and 3?days, and 2, 4, 12 and 26?weeks after the final injection. When examined by light microscopy, particle agglomerates identified as TiO2 were observed mainly in the major filtration organs liver, lung and spleen following i.v. injection. Particles were still observed 26?weeks after injection, indicating that tissue clearance is limited. In addition, redistribution within the histological micro-compartments of organs, especially in the spleen, was noted. Following s.c. injection, the largest particle agglomerates were found mainly in the draining inguinal lymph node, and to a lesser extent, the liver, spleen and lung. With the exception of a foreign body response at the site of s.c. injection and the appearance of an increased number of macrophages in the lung and liver, there was no histopathological evidence of tissue damage observed in any tissue at any time point. Published 2011. This article is a US Government work and is in the public domain in the USA.
C1 [Umbreit, T. H.; Goering, P. L.; Stratmeyer, M. E.] US FDA, Ctr Devices & Radiol Hlth, Off Sci, Silver Spring, MD 20903 USA.
[Umbreit, T. H.; Goering, P. L.; Stratmeyer, M. E.] US FDA, Engn Labs, Silver Spring, MD 20903 USA.
[Francke-Carroll, S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
[Weaver, J. L.; Miller, T. J.; Sadrieh, N.] US FDA, Ctr Drug Evaluat & Res, DAPR, Silver Spring, MD 20903 USA.
[Weaver, J. L.; Miller, T. J.; Sadrieh, N.] OPS, St Louis, MO USA.
RP Umbreit, TH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci, Silver Spring, MD 20903 USA.
EM thomas.umbreit@fda.hhs.gov
NR 14
TC 31
Z9 31
U1 0
U2 21
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0260-437X
J9 J APPL TOXICOL
JI J. Appl. Toxicol.
PD MAY
PY 2012
VL 32
IS 5
BP 350
EP 357
DI 10.1002/jat.1700
PG 8
WC Toxicology
SC Toxicology
GA 914AR
UT WOS:000301921000006
PM 22447616
ER
PT J
AU Karmakar, A
Iancu, C
Bartos, DM
Mahmood, MW
Ghosh, A
Xu, Y
Dervishi, E
Collom, SL
Khodakovskaya, M
Mustafa, T
Watanabe, F
Biris, AR
Zhang, YB
Ali, SF
Casciano, D
Hassen, S
Nima, Z
Biris, AS
AF Karmakar, Alokita
Iancu, Cornel
Bartos, Dana Monica
Mahmood, Meena W.
Ghosh, Anindya
Xu, Yang
Dervishi, Enkeleda
Collom, Samuel L.
Khodakovskaya, Mariya
Mustafa, Thikra
Watanabe, Fumiya
Biris, Alexandru R.
Zhang, Yongbin
Ali, Syed F.
Casciano, Dan
Hassen, Samar
Nima, Zeid
Biris, Alexandru S.
TI Raman spectroscopy as a detection and analysis tool for in vitro
specific targeting of pancreatic cancer cells by EGF-conjugated,
single-walled carbon nanotubes
SO JOURNAL OF APPLIED TOXICOLOGY
LA English
DT Article
DE cancer cells; targeting; EGF; SWCNTs; photothermolysis
ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; PHORBOL ESTERS; DELIVERY;
TRANSLOCATION; NANOMEDICINES; CYTOTOXICITY; TEMPERATURE; KINETICS;
ABLATION
AB Single-walled carbon nanotubes (SWCNTs) were covalently linked to epidermal growth factor (EGF) proteins through an esterification process that was found to be responsible for the docking of SWCNTs on the human pancreatic cancer cells (PANC-1) surface, thus providing a mechanism for the enhanced delivery and internalization of the nanotubes. Micro Raman spectroscopy and enzyme-linked immunosorbent assay were used to evaluate the delivery process and kinetics of the SWCNTs. In vitro studies indicated that the delivery kinetics of SWCNTEGF conjugates, at a concentration of 85 mu g ml-1, to the PANC-1 cell surfaces was significant in the first 30min of incubation, but reached a plateau with time in accordance with the establishment of equilibrium between the association and the dissociation of EGF with the cell receptors. SWCNTEGF conjugates could act as strong thermal ablation agents and could induce higher percentages of cellular death compared with the nontargeted SWCNTs alone. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Karmakar, Alokita; Mahmood, Meena W.; Xu, Yang; Dervishi, Enkeleda; Khodakovskaya, Mariya; Mustafa, Thikra; Watanabe, Fumiya; Casciano, Dan; Hassen, Samar; Nima, Zeid; Biris, Alexandru S.] Univ Arkansas, Dept Appl Sci, Nanotechnol Ctr, Little Rock, AR 72204 USA.
[Iancu, Cornel; Bartos, Dana Monica] Univ Med & Pharm Iuliu Hatieganu, Surg Clin 3, Cluj Napoca 3400, Romania.
[Ghosh, Anindya; Collom, Samuel L.] Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA.
[Biris, Alexandru R.] Natl Inst Res & Dev Isotop & Mol Technol, R-400293 Cluj Napoca, Romania.
[Zhang, Yongbin; Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Casciano, D (reprint author), Univ Arkansas, Dept Appl Sci, Nanotechnol Ctr, Little Rock, AR 72204 USA.
EM asbiris@ualr.edu; dacasciano@ualr.edu
RI Collom, Samuel/L-9287-2013
FU Romanian Ministry of Research [CNMP-PNCDI II: NANOHEP 42-115]; Arkansas
Science and Technology Authority [08-CAT-03]; US Army Telemedicine and
Advanced Research Center
FX The Romanian authors would like to acknowledge grant support from the
Romanian Ministry of Research (CNMP-PNCDI II: NANOHEP 42-115). The US
authors would like to acknowledge the financial support of the Arkansas
Science and Technology Authority grant no. 08-CAT-03 and the US Army
Telemedicine and Advanced Research Center, which is highly appreciated.
The editorial assistance of Dr Marinelle Ringer is also acknowledged. We
thank Ashley Fejleh for the laboratory assistance.
NR 52
TC 16
Z9 16
U1 2
U2 33
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0260-437X
J9 J APPL TOXICOL
JI J. Appl. Toxicol.
PD MAY
PY 2012
VL 32
IS 5
BP 365
EP 375
DI 10.1002/jat.1742
PG 11
WC Toxicology
SC Toxicology
GA 914AR
UT WOS:000301921000008
PM 22147491
ER
PT J
AU Chen, WJ
Yousef, WA
Gallas, BD
Hsu, ER
Lababidi, S
Tang, R
Pennello, GA
Symmans, WF
Pusztai, L
AF Chen, Weijie
Yousef, Waleed A.
Gallas, Brandon D.
Hsu, Elizabeth R.
Lababidi, Samir
Tang, Rong
Pennello, Gene A.
Symmans, W. Fraser
Pusztai, Lajos
TI Uncertainty estimation with a finite dataset in the assessment of
classification models
SO COMPUTATIONAL STATISTICS & DATA ANALYSIS
LA English
DT Article
DE Uncertainty; Training variability; Microarray classification; Area under
the ROC curve (AUC)
ID DNA MICROARRAY DATA; CROSS-VALIDATION; BREAST-CANCER; ROC ANALYSIS;
NONPARAMETRIC APPROACH; FOLLICULAR LYMPHOMA; EXPRESSION; PREDICTION;
AREA; BOOTSTRAP
AB To successfully translate genomic classifiers to the clinical practice, it is essential to obtain reliable and reproducible measurement of the classifier performance. A point estimate of the classifier performance has to be accompanied with a measure of its uncertainty. In general, this uncertainty arises from both the finite size of the training set and the finite size of the testing set. The training variability is a measure of classifier stability and is particularly important when the training sample size is small. Methods have been developed for estimating such variability for the performance metric AUC (area under the ROC curve) under two paradigms: a smoothed cross-validation paradigm and an independent validation paradigm. The methodology is demonstrated on three clinical microarray datasets in the microarray quality control consortium phase two project (MAQC-II): breast cancer, multiple myeloma, and neuroblastoma. The results show that the classifier performance is associated with large variability and the estimated performance may change dramatically on different datasets. Moreover, the training variability is found to be of the same order as the testing variability for the datasets and models considered. In conclusion, the feasibility of quantifying both training and testing variability of classifier performance is demonstrated on finite real-world datasets. The large variability of the performance estimates shows that patient sample size is still the bottleneck of the microarray problem and the training variability is not negligible. Published by Elsevier B.V.
C1 [Chen, Weijie; Gallas, Brandon D.; Hsu, Elizabeth R.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Yousef, Waleed A.] Helwan Univ, Fac Comp & Informat, Dept Comp Sci, Helwan, Egypt.
[Lababidi, Samir; Tang, Rong; Pennello, Gene A.] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Symmans, W. Fraser; Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA.
[Symmans, W. Fraser; Pusztai, Lajos] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
RP Chen, WJ (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM weijie.chen@fda.hhs.gov; wyousef@gwmail.gwu.edu;
brandon.gallas@fda.hhs.gov; hsuel@mail.nih.gov;
samir.lababidi@fda.hhs.gov; rong.tang@fda.hhs.gov;
gene.pennello@fda.hhs.gov; fsymmans@mdanderson.org;
lpusztai@mdanderson.org
RI Chen, Weijie/A-3712-2012;
OI Gallas, Brandon/0000-0001-7332-1620
NR 32
TC 3
Z9 3
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-9473
J9 COMPUT STAT DATA AN
JI Comput. Stat. Data Anal.
PD MAY 1
PY 2012
VL 56
IS 5
SI SI
BP 1016
EP 1027
DI 10.1016/j.csda.2011.05.024
PG 12
WC Computer Science, Interdisciplinary Applications; Statistics &
Probability
SC Computer Science; Mathematics
GA 910ZW
UT WOS:000301688100003
ER
PT J
AU Self, RL
Wu, WH
AF Self, Randy L.
Wu, Wen-Hsin
TI Rapid qualitative analysis of phthalates added to food and nutraceutical
products by direct analysis in real time/orbitrap mass spectrometry
SO FOOD CONTROL
LA English
DT Article
DE Phthalates; Direct analysis in real time (DART); Orbitrap; Food safety
ID SOLID-PHASE MICROEXTRACTION; GAS-CHROMATOGRAPHY; CONTACT MATERIALS;
ESTERS; IDENTIFICATION; IONIZATION; ADDITIVES; SAMPLES; WATER; MILK
AB A recent food safety issue involves the contamination of a broad range of food and nutraceutical products from Taiwan with industrial plasticizers. Among the suspected contaminants are selected phthalic acid esters, such as benzyl butyl phthalate, dibutyl phthalate, diisobutyl phthalate, di-2-ethylhexyl phthalate, di-n-octyl phthalate, diisononyl phthalate, and diisodecyl phthalate. Described in this study is an analytical method to rapidly qualitatively analyze these compounds in a wide variety of food and nutraceutical matrices suspected in this crisis. The method utilizes direct analysis in real time (DART) ionization coupled to a Thermo Exactive orbitrap mass spectrometer. The method is shown to be capable of detecting these compounds at levels greater than 1.0 mu g/mL in all food products examined and 0.5 mu g/mL in most of the samples tested. In the nutraceutical samples tested, the compounds were detected at levels of 50 mu g/g for all samples with some detected as low as 1.0 mu g/g. Published by Elsevier Ltd.
C1 [Self, Randy L.; Wu, Wen-Hsin] US FDA, Off Regulatory Affairs, Appl Technol Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA.
RP Wu, WH (reprint author), US FDA, Off Regulatory Affairs, Appl Technol Ctr, Pacific Reg Lab NW, 22201 23rd DR SE, Bothell, WA 98021 USA.
EM cindy.wu@fda.hhs.gov
NR 22
TC 28
Z9 31
U1 5
U2 59
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-7135
EI 1873-7129
J9 FOOD CONTROL
JI Food Control
PD MAY
PY 2012
VL 25
IS 1
BP 13
EP 16
DI 10.1016/j.foodcont.2011.10.013
PG 4
WC Food Science & Technology
SC Food Science & Technology
GA 900UT
UT WOS:000300917500003
ER
PT J
AU Fedio, WM
Jinneman, KC
Yoshitomi, KJ
Zapata, R
Weagant, SD
AF Fedio, Willis M.
Jinneman, Karen C.
Yoshitomi, Ken J.
Zapata, Ruben
Weagant, Stephen D.
TI Efficacy of a post enrichment acid treatment for isolation of
Escherichia coli O157:H7 from alfalfa sprouts
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Real-time PCR; Immunomagnetic separation; Escherichia coli O157:H7; Acid
treatment
ID UNITED-STATES; O157-H7; OUTBREAK; CONSUMPTION; PATHOGENS; TOLERANCE;
PRODUCE; SAMPLES; GROWTH; SEEDS
AB The enrichment, detection and isolation procedure in the current US FDA BAM have been shown effective for Escherichia coli O157:H7 in a wide variety of foods. Recently reported modifications to the enrichment protocol, including post-enrichment immunomagnetic separation (IMS) procedures have improved sensitivity of the method for alfalfa sprouts. However, cultural isolation on selective agar plates still presents a challenge in this food matrix.
The focus of this study was to reduce levels of competing microflora and enhance isolation of E. coli O157:H7 on selective agars. We optimized the use of a short acid treatment after enrichment and with post-enrichment IMS beads. The optimized acid treatments were then evaluated in alfalfa sprouts artificially contaminated with E. coli O157:H7. After 5 h enrichment of alfalfa sprouts contaminated at 0.2 cfu/g, there was significant improvement in isolation on the selective plates following acid treatment of two types of IMS beads. Following 24 h enrichment of alfalfa sprouts contaminated at low levels, E. coli O157:H7 was only recovered from 8/25 samples when no IMS or acid treatments were used. The use of only the acid treatment improved recovery to 19/25 samples. Following IMS of the enrichment broths, acid treatment increased isolation to 23/25 for Pathatrix(TM) and 24/25 for BeadRetriever(TM) IMS.
Acid treatment (pH 2) of the enrichment broth for 30 min or IMS beads for 7 min is a simple and rapid way to greatly improve isolation of E. coli O157 from alfalfa sprout enrichments by reducing the interfering microflora on the selective media. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Fedio, Willis M.; Zapata, Ruben] New Mexico State Univ, Ctr Anim Hlth Food Safety & Biosecur, Food Safety Lab, Las Cruces, NM 88003 USA.
[Jinneman, Karen C.; Yoshitomi, Ken J.] US FDA, Pacific Reg Lab NW, Bothell, WA USA.
[Weagant, Stephen D.] Weagant Consulting, Poulsbo, WA USA.
RP Fedio, WM (reprint author), New Mexico State Univ, Ctr Anim Hlth Food Safety & Biosecur, Food Safety Lab, 2990 Knox St, Las Cruces, NM 88003 USA.
EM wfedio@nmsu.edu
FU US FDA [WL5QKN-05-D-0022]
FX We would like to thank Paul Browning for technical support. This study
was supported in part by US FDA Contract No. WL5QKN-05-D-0022.
NR 24
TC 9
Z9 9
U1 4
U2 19
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0740-0020
EI 1095-9998
J9 FOOD MICROBIOL
JI Food Microbiol.
PD MAY
PY 2012
VL 30
IS 1
BP 83
EP 90
DI 10.1016/j.fm.2011.12.003
PG 8
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA 898JY
UT WOS:000300739900012
PM 22265287
ER
PT J
AU Jones, JL
Hara-Kudo, Y
Krantz, JA
Benner, RA
Smith, AB
Dambaugh, TR
Bowers, JC
DePaola, A
AF Jones, Jessica L.
Hara-Kudo, Yukiko
Krantz, Jeffrey A.
Benner, Ronald A., Jr.
Smith, Amy B.
Dambaugh, Timothy R.
Bowers, John C.
DePaola, Angelo
TI Comparison of molecular detection methods for Vibrio parahaemolyticus
and Vibrio vulnificus
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Vibrio vulnificus; Vibrio parahaemolyticus; Real-time PCR; Loop-mediated
isothermal amplification (LAMP)
ID MEDIATED ISOTHERMAL AMPLIFICATION; THERMOSTABLE DIRECT HEMOLYSIN;
REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; CLINICAL ISOLATE; RAPID
DETECTION; ASSAY; OYSTERS; TRH; TDH
AB Pathogenic vibrios are a global concern for seafood safety and many molecular methods have been developed for their detection. This study compares several molecular methods for detection of total and pathogenic Vibrio parahaemolyticus and Vibrio vulnificus, in MPN enrichments from oysters and fish intestine samples. This study employed the DuPont Qualicon BAX(R) System Real-Time PCR assay for detection of V parahaemolyticus and V. vulnificus. Multiplex real-time PCR detection of total (tlh+), tdh+, and trh+ V parahaemolyticus was conducted on the Cepheid SmartCycler II. Total (rpoD) and tdh+ V. parahaemolyticus were also detected using LAMP. V. vulnificus detection was performed using real-time PCR methods developed for the SmartCycler and the AB 7500 Fast. Recommended template preparations were compared to BAX lysis samples for suitability. There was no significant difference in detection of V parahaemolyticus and V. vulnificus using the BAX or SmartCycler assays. The AB assay showed no difference from other methods in detection of V. vulnificus unless boiled templates were utilized. There was a significant difference in detection of tdh+ V. parahaemolyticus between SmartCycler and LAMP assays unless the total (tlh+) V. parahaemolyticus gene target was omitted from the SmartCycler assay: a similar trend was observed for trh+ V. parahaemolyticus. Published by Elsevier Ltd.
C1 [Jones, Jessica L.; Krantz, Jeffrey A.; Benner, Ronald A., Jr.; DePaola, Angelo] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA.
[Hara-Kudo, Yukiko] Natl Inst Hlth Sci, Div Microbiol, Setagaya Ku, Tokyo 1588501, Japan.
[Smith, Amy B.; Dambaugh, Timothy R.] DuPont Qualicon, Wilmington, DE 19880 USA.
[Bowers, John C.] US FDA, CFSAN, College Pk, MD 20740 USA.
RP Jones, JL (reprint author), US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA.
EM Jessica.Jones@fda.hhs.gov
NR 30
TC 16
Z9 16
U1 2
U2 21
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 MAY
PY 2012
VL 30
IS 1
BP 105
EP 111
DI 10.1016/j.fm.2011.12.011
PG 7
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA 898JY
UT WOS:000300739900015
PM 22265290
ER
PT J
AU Mullis, L
Saif, LJ
Zhang, YB
Zhang, XM
Azevedo, MSP
AF Mullis, Lisa
Saif, Linda J.
Zhang, Yongbin
Zhang, Xuming
Azevedo, Marli S. P.
TI Stability of bovine coronavirus on lettuce surfaces under household
refrigeration conditions
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Coronavirus; Enveloped virus; Environmental survival
ID SURVIVAL; SARS; TRANSMISSION; INFECTIONS; VIRULENT; VIRUSES; DISEASE;
OC43
AB Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 x 10(4) to 1.7 x 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans. Published by Elsevier Ltd.
C1 [Azevedo, Marli S. P.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Saif, Linda J.] Ohio State Univ, OARDC, Food Anim Hlth Res Program, Wooster, OH 44691 USA.
[Zhang, Xuming] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA.
RP Azevedo, MSP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd,HFT-250, Jefferson, AR 72079 USA.
EM marli.azevedo@fda.hhs.gov
FU Division of Microbiology, National Center for Toxicological Research, US
Food and Drug Administration
FX This work was supported by the Division of Microbiology, National Center
for Toxicological Research, US Food and Drug Administration.
NR 30
TC 2
Z9 2
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 MAY
PY 2012
VL 30
IS 1
BP 180
EP 186
DI 10.1016/j.fm.2011.12.009
PG 7
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA 898JY
UT WOS:000300739900024
PM 22265299
ER
PT J
AU Wilkes, JG
Tucker, RK
Montgomery, JA
Cooper, WM
Sutherland, JB
Buzatu, DA
AF Wilkes, Jon G.
Tucker, Randal K.
Montgomery, James A.
Cooper, Willie M.
Sutherland, John B.
Buzatu, Dan A.
TI Reduction of food matrix interference by a combination of sample
preparation and multi-dimensional gating techniques to facilitate rapid,
high sensitivity analysis for Escherichia coli serotype O157 by flow
cytometry
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Flow cytometry; RAPID-B (TM); Food matrix interference; Near real-time
analysis; Single-cell detection; Escherichia coli O157
ID IN-GROUND BEEF; APPLE JUICE; OUTBREAK; CENTRIFUGATION
AB Escherichia coli serotype 0157 strains, which may be found in foods, often produce enterohemorrhagic toxins. The research goal was to facilitate rapid, sensitive detection in foods of E. coli serotype 0157 by flow cytometry. Sample preparation methods were developed for potential use in 15 foods. Combined with multi-dimensional gating, these methods decreased time-to-results (TTR) for determination of low-level contamination. They mitigated the effects of interfering food components, concentrated cells for analysis without growth or, when necessary, used short-term incubation. The results showed qualitative analysis that was equivalent to culture plating in accuracy and superior in sensitivity and speed. Preparation time was 10-30 min per sample and detection took 3-4 min. Culture growth, if required, took an additional 4-6 h. A protocol for raw spinach analysis, using 4 h culture incubation, was 94% correct with one false negative for a low level inoculation. Its projected limit-of-detection (LOD) was 1 viable cell per 25 g of spinach, based on an average of 28 counts detected after growth and an estimated counts-to-threshold (C/T) ratio of 1.3. The results suggested potential uses for regulatory screening and food industry process control. Published by Elsevier Ltd.
C1 [Wilkes, Jon G.; Tucker, Randal K.; Cooper, Willie M.; Sutherland, John B.; Buzatu, Dan A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Montgomery, James A.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Jon.wilkes@fda.hhs.gov; randal.tucker@fda.hhs.gov;
jamontgomery@uams.edu; willie.cooper@fda.hhs.gov;
john.sutherland@fda.hhs.gov; dan.buzatu@fda.hhs.gov
NR 22
TC 19
Z9 19
U1 3
U2 21
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0740-0020
EI 1095-9998
J9 FOOD MICROBIOL
JI Food Microbiol.
PD MAY
PY 2012
VL 30
IS 1
BP 281
EP 288
DI 10.1016/j.fm.2011.11.002
PG 8
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA 898JY
UT WOS:000300739900038
PM 22265313
ER
PT J
AU Jinneman, KC
Waite-Cusic, JG
Yoshitomi, KJ
AF Jinneman, Karen C.
Waite-Cusic, Joy G.
Yoshitomi, Ken J.
TI Evaluation of shiga toxin-producing Escherichia coli (STEC) method for
the detection and identification of STEC O104 strains from sprouts
SO FOOD MICROBIOLOGY
LA English
DT Article
DE Shiga toxin-producing E. coli (STEC); E. coli O104:H4; Real-time PCR;
Extended spectrum beta-lactamase (ESBL); Sprouts
ID REAL-TIME PCR; MULTISTATE OUTBREAK; HEMORRHAGIC COLITIS; O157-H7
INFECTIONS; PACIFIC-NORTHWEST; RAW-MILK; CONSUMPTION; O157H7; DIAGNOSIS;
SEROTYPE
AB Protocols for Shiga toxin-producing Escherichia coli (STEC) typically focus on the detection and recovery of E. coli O157:H7: however, the prevalence of outbreaks associated with non-O157 STEC are increasing and the efficacy of current testing strategies have not been fully evaluated. Non-O157 STEC are a very diverse group whose pathogenic characteristics and clinical significance have not been well established. During an outbreak situation, the rapid dissemination of specific strain characteristics can provide information needed to verify standard laboratory methodology and identify potentially effective tests to detect and recover the outbreak strain from foods. This study validated the use of a standard method to detect and recover two strains of E. coli 0104 STEC at a level of approximately 1 CFU/g from sprouts. The use of additional serotype-specific real-time PCR assays and supplemental chromogenic media to assist the detection and recovery of these organisms were also evaluated. Published by Elsevier Ltd.
C1 [Jinneman, Karen C.; Waite-Cusic, Joy G.; Yoshitomi, Ken J.] US FDA, Appl Technol Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA.
RP Jinneman, KC (reprint author), US FDA, Appl Technol Ctr, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA.
EM karen.jinneman@fda.hhs.gov; joy.waite@fda.hhs.gov;
ken.yoshitomi@fda.hhs.gov
NR 44
TC 10
Z9 10
U1 1
U2 18
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0740-0020
EI 1095-9998
J9 FOOD MICROBIOL
JI Food Microbiol.
PD MAY
PY 2012
VL 30
IS 1
BP 321
EP 328
DI 10.1016/j.fm.2011.12.007
PG 8
WC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
SC Biotechnology & Applied Microbiology; Food Science & Technology;
Microbiology
GA 898JY
UT WOS:000300739900044
PM 22265319
ER
PT J
AU Obolensky, OI
Wu, WW
Shen, RF
Yu, YK
AF Obolensky, O. I.
Wu, Wells W.
Shen, Rong-Fong
Yu, Yi-Kuo
TI Using dissociation energies to predict observability of b- and y-peaks
in mass spectra of short peptides
SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY
LA English
DT Article
ID COLLISION-INDUCED DISSOCIATION; DENSITY-FUNCTIONAL THEORY;
SURFACE-INDUCED DISSOCIATION; MAIN FRAGMENTATION PATHWAYS; AMIDE
BOND-CLEAVAGE; FT-ICR MS; PROTONATED TRIPEPTIDES; GLY-XXX; KINETIC
METHOD; GAS-PHASE
AB RATIONALE: Peptide identification reliability can be improved by excluding from analysis those m/z peaks of candidate peptides which cannot be observed in practice due to various physical, chemical or thermodynamic considerations. We propose using dissociation energies (as opposed to proton affinities) as a predictor of observability of different m/z peaks in spectra of short peptides.
METHODS: Mass spectra of the tetrapeptides AAAA, AAFA, AAVA, AFAA, AVAA, AFFA, and AVVA were measured in the collision-induced dissociation (CID) activation mode on a grid of activation times 0.05 to 100 ms and normalized collision energy 10 to 35%. The lowest energy geometries and vibrational spectra were calculated for the precursor ions and their charged and neutral fragments using density functional theory (DFT) at the TPSS/6-31G(d, p) level. Dissociation energies were calculated for all fragmentation channels leading to b- or y-fragments.
RESULTS: It is demonstrated that m/z peaks observed in the mass spectra correspond to the fragmentation channels with the lowest dissociation energies. Using 50 kcal/mol as the cut-off value of dissociation energy, it was predicted that 28 out of 42 possible peaks in the b- and y-series of the seven tetrapeptides can be observed in mass spectra. In the experiments, 26 b- or y-peaks were observed, all of which are among the 28 predicted ones.
CONCLUSIONS: The use of dissociation energies generalizes the use of proton affinities for semi-quantitative predictions of relative intensities of different m/z peaks of short peptides. Further advances in this direction will pave the way for reliable quantitative predictions and, hence, for a significant improvement in robustness and accuracy of peptide and protein identification tools. Published in 2012 by John Wiley & Sons, Ltd.
C1 [Obolensky, O. I.; Yu, Yi-Kuo] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Wu, Wells W.] NIA, NIH, Baltimore, MD 21224 USA.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Obolensky, OI (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM obolensk@ncbi.nlm.nih.gov; yyu@ncbi.nlm.nih.gov
RI Obolensky, Oleg/A-5839-2008
OI Obolensky, Oleg/0000-0003-3315-1828
FU NIH, NLM
FX We thank Dr. Julia Laskin and Dr. Aleksey Ogurtsov for useful
discussions. This research was supported by the Intramural Research
Program of the NIH, NLM. The computations were carried out on the
Biowulf computer cluster at the National Institutes of Health, Bethesda,
MD, USA (http://biowulf.nih.gov).
NR 58
TC 3
Z9 3
U1 1
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-4198
EI 1097-0231
J9 RAPID COMMUN MASS SP
JI Rapid Commun. Mass Spectrom.
PD APR 30
PY 2012
VL 26
IS 8
BP 915
EP 920
DI 10.1002/rcm.6180
PG 6
WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy
SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy
GA 904FP
UT WOS:000301179800005
PM 22396027
ER
PT J
AU DeBell, KE
Simhadri, VR
Mariano, JL
Borrego, F
AF DeBell, Karen E.
Simhadri, Venkateswara R.
Mariano, John L.
Borrego, Francisco
TI Functional requirements for inhibitory signal transmission by the
immunomodulatory receptor CD300a
SO BMC IMMUNOLOGY
LA English
DT Article
ID TYROSINE PHOSPHATASES SHP-1; FC-GAMMA-RIIB; NK CELLS; IMMUNOGLOBULIN
SUPERFAMILY; NEGATIVE REGULATION; GENETIC-EVIDENCE; IRP60 CD300A;
EXPRESSION; PATHWAYS; PHOSPHORYLATION
AB Background: Activation signals can be negatively regulated by cell surface receptors bearing immunoreceptor tyrosine-based inhibitory motifs (ITIMs). CD300a, an ITIM bearing type I transmembrane protein, is expressed on many hematopoietic cells, including subsets of lymphocytes.
Results: We have taken two approaches to further define the mechanism by which CD300a acts as an inhibitor of immune cell receptor signaling. First, we have expressed in Jurkat T cells a chimeric receptor consisting of the extracellular domains of killer-cell immunoglobulin-like receptor (KIR) 2DL2 fused to the transmembrane and cytoplasmic segments of CD300a (KIR-CD300a) to explore surrogate ligand-stimulated inhibition of superantigen stimulated T cell receptor (TCR) mediated cell signaling. We found that intact CD300a ITIMs were essential for inhibition and that the tyrosine phosphorylation of these ITIMs required the src tyrosine kinase Lck. Tyrosine phosphorylation of the CD300a ITIMs created docking sites for both src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2. Suppression of SHP-1 and SHP-2 expression in KIR-CD300a Jurkat T cells with siRNA and the use of DT40 chicken B cell lines expressing CD300a and deficient in several phosphatases revealed that SHP-1, but not SHP-2 or the src homology 2 domain containing inositol 5' phosphatase SHIP, was utilized by CD300a for its inhibitory activity.
Conclusion: These studies provide new insights into the function of CD300a in tuning T and B cell responses.
C1 [DeBell, Karen E.; Simhadri, Venkateswara R.; Mariano, John L.; Borrego, Francisco] OBP CDER FDA, HFD 123, Div Monoclonal Antibodies HFD 123, Lab Mol & Dev Immunol, Bethesda, MD 20892 USA.
RP Borrego, F (reprint author), OBP CDER FDA, HFD 123, Div Monoclonal Antibodies HFD 123, Lab Mol & Dev Immunol, 29 Lincoln Dr,Bldg 29B,Room 3NN18, Bethesda, MD 20892 USA.
EM Francisco.Borrego@fda.hhs.gov
FU Food and Drug Administration
FX We thank Dr. Lynde Meyaard for the phosphatase deficient DT40 chicken B
cells, Dr. John E. Coligan for the 721.221 cells and Dr. Eric O. Long
for plasmids encoding the phosphatases and KIR2DL2. This work was funded
by the intramural program of the Food and Drug Administration.
NR 54
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 1471-2172
J9 BMC IMMUNOL
JI BMC Immunol.
PD APR 26
PY 2012
VL 13
AR 23
DI 10.1186/1471-2172-13-23
PG 12
WC Immunology
SC Immunology
GA 994TV
UT WOS:000307956400001
PM 22537350
ER
PT J
AU Sharma, D
Badal, A
Badano, A
AF Sharma, Diksha
Badal, Andreu
Badano, Aldo
TI hybridMANTIS: a CPU-GPU Monte Carlo method for modeling indirect x-ray
detectors with columnar scintillators
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID PET IMAGE-RECONSTRUCTION; DOSE CALCULATION; SIMULATIONS; MANTIS; SYSTEM
AB The computational modeling of medical imaging systems often requires obtaining a large number of simulated images with low statistical uncertainty which translates into prohibitive computing times. We describe a novel hybrid approach for Monte Carlo simulations that maximizes utilization of CPUs and GPUs in modern workstations. We apply the method to the modeling of indirect x-ray detectors using a new and improved version of the code MANTIS, an open source software tool used for the Monte Carlo simulations of indirect x-ray imagers. We first describe a GPU implementation of the physics and geometry models in fastDETECT2 (the optical transport model) and a serial CPU version of the same code. We discuss its new features like on-the-fly column geometry and columnar crosstalk in relation to the MANTIS code, and point out areas where our model provides more flexibility for the modeling of realistic columnar structures in large area detectors. Second, we modify PENELOPE (the open source software package that handles the x-ray and electron transport in MANTIS) to allow direct output of location and energy deposited during x-ray and electron interactions occurring within the scintillator. This information is then handled by optical transport routines in fastDETECT2. A load balancer dynamically allocates optical transport showers to the GPU and CPU computing cores. Our hybridMANTIS approach achieves a significant speed-up factor of 627 when compared to MANTIS and of 35 when compared to the same code running only in a CPU instead of a GPU. Using hybridMANTIS, we successfully hide hours of optical transport time by running it in parallel with the x-ray and electron transport, thus shifting the computational bottleneck from optical to x-ray transport. The new code requires much less memory than MANTIS and, as a result, allows us to efficiently simulate large area detectors.
C1 [Sharma, Diksha; Badal, Andreu; Badano, Aldo] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Sharma, D (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM diksha.sharma@fda.hhs.gov
OI badano, aldo/0000-0003-3712-6670
NR 14
TC 8
Z9 8
U1 0
U2 9
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD APR 21
PY 2012
VL 57
IS 8
BP 2357
EP 2372
DI 10.1088/0031-9155/57/8/2357
PG 16
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 922SA
UT WOS:000302567100017
PM 22469917
ER
PT J
AU Fujisawa, T
Rubin, B
Suzuki, A
Patel, PS
Gahl, WA
Joshi, BH
Puri, RK
AF Fujisawa, Toshio
Rubin, Benjamin
Suzuki, Akiko
Patel, Prabhudas S.
Gahl, William A.
Joshi, Bharat H.
Puri, Raj K.
TI Cysteamine Suppresses Invasion, Metastasis and Prolongs Survival by
Inhibiting Matrix Metalloproteinases in a Mouse Model of Human
Pancreatic Cancer
SO PLOS ONE
LA English
DT Article
ID INTERLEUKIN-13 RECEPTOR ALPHA-2; NEPHROPATHIC CYSTINOSIS; CELL-LINES;
IN-VITRO; CHILDREN; CARCINOMA; GROWTH; RATS; ANGIOGENESIS; PROGRESSION
AB Background: Cysteamine, an anti-oxidant aminothiol, is the treatment of choice for nephropathic cystinosis, a rare lysosomal storage disease. Cysteamine is a chemo-sensitization and radioprotection agent and its antitumor effects have been investigated in various tumor cell lines and chemical induced carcinogenesis. Here, we investigated whether cysteamine has anti-tumor and anti-metastatic effects in transplantable human pancreatic cancer, an aggressive metastatic disease.
Methodology/Principal Findings: Cysteamine's anti-invasion effects were studied by matrigel invasion and cell migration assays in 10 pancreatic cancer cell lines. To study mechanism of action, we examined cell viability and matrix metalloproteinases (MMPs) activity in the cysteamine-treated cells. We also examined cysteamine's anti-metastasis effect in two orthotopic murine models of human pancreatic cancer by measuring peritoneal metastasis and survival of animals. Cysteamine inhibited both migration and invasion of all ten pancreatic cancer cell lines at concentrations (<25 mM) that caused no toxicity to cells. It significantly decreased MMPs activity (IC50 38-460 mu M) and zymographic gelatinase activity in a dose dependent manner in vitro and in vivo; while mRNA and protein levels of MMP-9, MMP-12 and MMP-14 were slightly increased using the highest cysteamine concentration. In vivo, cysteamine significantly decreased metastasis in two established pancreatic tumor models, although it did not affect the size of primary tumors. Additionally, cysteamine prolonged survival of mice in a dose-dependent manner without causing any toxicity. Similar to the in vitro results, MMP activity was significantly decreased in animal tumors treated with cysteamine. Cysteamine had no clinical or preclinical adverse effects in the host even at the highest dose.
Conclusions/Significance: Our results suggest that cysteamine, an agent with a proven safety profile, may be useful for inhibition of metastasis and prolonging the survival of a host with pancreatic cancer.
C1 [Fujisawa, Toshio; Suzuki, Akiko; Patel, Prabhudas S.; Joshi, Bharat H.; Puri, Raj K.] Ctr Biol Evaluat & Res Food & Drug Adm, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD USA.
[Rubin, Benjamin] Johns Hopkins Sch Med, Suburban Hosp, Dept Ophthalmol, Bethesda, MD USA.
[Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), Ctr Biol Evaluat & Res Food & Drug Adm, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Bethesda, MD USA.
EM raj.puri@fda.hhs.gov
NR 39
TC 12
Z9 13
U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 20
PY 2012
VL 7
IS 4
AR e34437
DI 10.1371/journal.pone.0034437
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UD
UT WOS:000305339200014
PM 22532830
ER
PT J
AU Hamburg, MA
AF Hamburg, Margaret A.
TI FDA's Approach to Regulation of Products of Nanotechnology
SO SCIENCE
LA English
DT Editorial Material
C1 US FDA, Silver Spring, MD 20993 USA.
RP Hamburg, MA (reprint author), US FDA, Silver Spring, MD 20993 USA.
EM margaret.hamburg@fda.hhs.gov
NR 13
TC 50
Z9 51
U1 1
U2 18
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD APR 20
PY 2012
VL 336
IS 6079
BP 299
EP 300
DI 10.1126/science.1205441
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928PO
UT WOS:000302995400028
PM 22517845
ER
PT J
AU Wu, WW
Wang, GH
Insel, PA
Hsiao, CT
Zou, SG
Martin, B
Maudsley, S
Shen, RF
AF Wu, Wells W.
Wang, Guanghui
Insel, Paul A.
Hsiao, Cheng-Te
Zou, Sige
Martin, Bronwen
Maudsley, Stuart
Shen, Rong-Fong
TI Discovery- and target-based protein quantification using iTRAQ and
pulsed Q collision induced dissociation (PQD)
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE Pulsed Q collision-induced dissociation (PQD); Linear ion trap; Triple
quadrupole (QqQ); Higher energy collisional dissociation (HCD); iTRAQ
(Isobaric Tag for Relative and Absolute Quantification)
ID TANDEM MASS-SPECTROMETRY; QUADRUPOLE ION-TRAP; IDENTIFICATION;
QUANTITATION; ACQUISITION; PROTEOMICS; SCAN
AB Pulsed Q collision-induced dissociation (PQD) was developed in part to facilitate detection of low-mass reporter ions using labeling reagents (e.g. iTRAQ) on LTQ platforms. It has generally been recognized that the scan speed and sensitivity of an LTQ are superior than those of an Orbitrap using the higher-energy collisional dissociation (HCD). However, the use of PQD in quantitative proteomics is limited, primarily due to the meager reproducibility of reporter ion ratios. Optimizations of PQD for iTRAQ quantification using LTQ have been reported, but a universally applicable strategy for quantifying the less abundant proteins has not been fully established. Adjustments of the AGC target, mu scan, or scan speed offer only incremental improvements in reproducibility. From our experience, however, satisfactory coefficients of variation (CVs) of reporter ion ratios were difficult to achieve using the discovery-based approach. As an alternative, we implemented a target-based approach that obviates data dependency to allow repetitive data acquisitions across chromatographic peaks. Such a strategy generates enough data points for more reliable quantification. Using cAMP treatment in S49 cell lysates and this target-based approach, we were able to validate differentially expressed proteins, which were initially identified as potential candidates using the discovery-based PQD. The target-based strategy also yielded results comparable to those obtained from HCD in an Orbitrap. Our findings should aid LTQ users who desire to explore iTRAQ quantitative proteomics but have limited access to the more costly Orbitrap or other instruments. Published by Elsevier B.V.
C1 [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA.
[Wu, Wells W.; Martin, Bronwen] NIA, Metab Unit, NIH, Baltimore, MD 21224 USA.
[Wang, Guanghui] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol & Med, La Jolla, CA 92093 USA.
[Hsiao, Cheng-Te; Zou, Sige] NIA, Funct Genom Unit, NIH, Baltimore, MD 21224 USA.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM maudsleyst@grc.nia.nih.gov; Rongfong.Shen@fda.hhs.gov
FU National Institute on Aging; National Heart, Lung, and Blood Institute,
National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Programs of
National Institute on Aging and National Heart, Lung, and Blood
Institute, National Institutes of Health (NIH). The authors would like
to acknowledge the following for technical advice: Dr. Howard Jaffe,
NINDS, NIH; Drs. Jae C. Schwartz, Mike W. Senko, and John E.P. Syka of
ThermoFisher Scientific Inc.
NR 23
TC 11
Z9 11
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD APR 18
PY 2012
VL 75
IS 8
BP 2480
EP 2487
DI 10.1016/j.jprot.2012.02.027
PG 8
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 941PJ
UT WOS:000303974800018
PM 22397766
ER
PT J
AU Nawaz, M
Khan, SA
Tran, Q
Sung, K
Khan, AA
Adamu, I
Steele, RS
AF Nawaz, Mohamed
Khan, S. A.
Tran, Q.
Sung, K.
Khan, A. A.
Adamu, I.
Steele, R. S.
TI Isolation and characterization of multidrug-resistant Klebsiella spp.
isolated from shrimp imported from Thailand
SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY
LA English
DT Article
DE Klebsiella spp.; Fluoroquinolone; Tetracycline resistance; Imported
shrimp
ID FLUOROQUINOLONE RESISTANCE; TETRACYCLINE-RESISTANT; UNITED-STATES; DNA
GYRASE; PNEUMONIAE; MECHANISMS; QUINOLONES; CATFISH; GENES;
SUSCEPTIBILITY
AB A study was undertaken to isolate and characterize tetracycline and nalidixic acid-resistant Klebsiella spp. in farm-raised, imported shrimp sold in the United States. Sixty-seven multiple antibiotic-resistant Klebsiella spp. strains were isolated from imported shrimp samples. Using morphological and biochemical methods, fifty-three strains were tentatively identified as Klebsiella pneumoniae and fourteen as K. oxytoca. Although all isolates were resistant to tetracycline, only 8 were resistant to nalidixic acid. These 8 isolates were further screened by PCR for quinolone resistance genes (qnrA, B, S, gyrA, B and parC). PCR protocols failed to amplify any qnr genes. The purified PCR amplicons of gyrA, gyrB and parC were sequenced and analyzed for point mutations that confer resistance to fluoroquinolone antibiotics. Analysis of the sequences of the gyrA amplicons from nalidixic acid-resistant Klebsiella spp. indicated two point mutations in gyrA at positions 83 (Ser -> Phe) and 87 (Asp -> Ala). Sequence analysis of the parC amplicons indicated an amino acid change at position 80 (Ser -> Ile). No mutations were detected in gyrB. Template DNA from all isolates was screened for tetracycline resistance genes (tetA-E). Oligonucleotide primers specifically targeting a 305-bp region of tetB and a 477-bp region of tetD successfully amplified sequences from 91.0 and 44.0% of the isolates, respectively. None of the isolates contained tetA, tetC or tetE genes. Plasmids (2.0-16.0 kb) were found in 23 of the 67 isolates. XbaI-PFGE identified 32 distinct macro restriction patterns (mrps) among the 61 multiple drug-resistant Klebsiella spp. that were typable. Our results indicate that imported shrimp is a reservoir for multidrug resistant Klebsiella spp. and potential health risks posed by such strains should not be underestimated. Published by Elsevier B.V.
C1 [Nawaz, Mohamed; Khan, S. A.; Tran, Q.; Sung, K.; Khan, A. A.; Steele, R. S.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Adamu, I.] Univ Cent Arkansas, Conway, AR 72035 USA.
RP Nawaz, M (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Mohamed.nawaz@fda.hhs.gov
RI Khan, Ashraf/E-8133-2013
FU National Center for Toxicological Research, US Food and Drug
Administration
FX We thank Dr Carl E. Cerniglia, J.B. Sutherland and Steve Foley for
critical review of the manuscript. This work was supported by the
National Center for Toxicological Research, US Food and Drug
Administration. Views presented here do not necessarily reflect those of
the FDA.
NR 40
TC 14
Z9 15
U1 3
U2 12
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1605
J9 INT J FOOD MICROBIOL
JI Int. J. Food Microbiol.
PD APR 16
PY 2012
VL 155
IS 3
BP 179
EP 184
DI 10.1016/j.ijfoodmicro.2012.02.002
PG 6
WC Food Science & Technology; Microbiology
SC Food Science & Technology; Microbiology
GA 932KJ
UT WOS:000303289700012
PM 22405354
ER
PT J
AU Lieu, TA
Nguyen, MD
Ball, R
Martin, DB
AF Lieu, Tracy A.
Nguyen, Michael D.
Ball, Robert
Martin, David B.
TI Health outcomes of interest for evaluation in the Post-Licensure Rapid
Immunization Safety Monitoring Program
SO VACCINE
LA English
DT Article
DE Vaccines; Safety surveillance; Active surveillance; Health outcomes;
Expert elicitation
ID VACCINE SAFETY; UNITED-STATES; SMALLPOX VACCINATION; INTUSSUSCEPTION;
DATALINK; DECADE; FOOD
AB Active vaccine safety surveillance systems commonly use computerized diagnostic codes to identify potential health outcomes of interest. Evidence concerning the accuracy of these codes is variable, and few systematic reviews are available. This project's aim was to select a list of health outcomes of interest most suitable for evaluation in the Food and Drug Administration's Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program. We conducted an expert elicitation process to develop the list. A comprehensive list of potential health outcomes of interest was formed based on input from a wide variety of vaccine safety experts. We then selected five panelists with senior leadership roles in vaccine safety from both within and outside the FDA. We elicited the experts' recommendations via a structured, iterative process that included an Internet-assisted telephone conference call and formal voting procedures. The expert panelists identified several criteria as important in their choices, including clinical severity, public health importance, rare or uncommon incidence, relevance to two or more vaccines, and historical association with vaccines. The list of 24 outcomes chosen by the experts and refined by the FDA included ten neurologic outcomes, two circulatory system outcomes, and two musculoskeletal outcomes. The PRISM program plans to conduct a set of evidence reviews on the positive predictive value and other characteristics of existing computerized codes and algorithms to identify these health outcomes of interest. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Lieu, Tracy A.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, Boston, MA 02215 USA.
[Lieu, Tracy A.] Harvard Univ, Sch Med, Boston, MA USA.
[Lieu, Tracy A.] Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA.
[Nguyen, Michael D.; Ball, Robert; Martin, David B.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
RP Lieu, TA (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Ctr Child Hlth Care Studies, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA.
EM tracy_lieu@harvardpilgrim.org
NR 21
TC 15
Z9 15
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD APR 16
PY 2012
VL 30
IS 18
BP 2824
EP 2830
DI 10.1016/j.vaccine.2012.02.057
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 928YR
UT WOS:000303028900003
PM 22394993
ER
PT J
AU Feng, JH
Kweon, O
Xu, HY
Cerniglia, CE
Chen, HZ
AF Feng, Jinhui
Kweon, Ohgew
Xu, Haiyan
Cerniglia, Carl E.
Chen, Huizhong
TI Probing the NADH- and Methyl Red-binding site of a FMN-dependent
azoreductase (AzoA) from Enterococcus faecalis
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Enterococcus faecalis; Azoreductase; Azo dye; NADH; Site-directed
mutagenesis
ID MOLECULAR-CLONING; INTESTINAL MICROFLORA; SUBSTRATE-BINDING;
ELECTRON-TRANSFER; REDUCTASE; DYES; FLAVOPROTEIN; MECHANISM;
DEGRADATION; SPECIFICITY
AB AzoA from Enterococcus faecalis is a member of the polymeric Flavin-dependent NADH-preferred azoreductase group. Little is known about the binding and interaction of NADH and azo dye in the azoreductase group. A synergetic strategy based on computational prediction, reverse genetics validation coupled with site-directed mutagenesis, and reconstruction of mutation network was used to investigate the binding and interaction of NADH and a model azo dye, Methyl Red, with AzoA. Methyl Red and NADH interacted in a unique binding mode in which the benzoic acid moiety of Methyl Red and the nicotinamide ring of NADH were not parallel to the Flavin isoalloxazine ring, but lay against it at angles of similar to 45 degrees and similar to 35 degrees, respectively. The adenine ribose moiety of NADH was surrounded by loop l2 on chain B and alpha 3 on chain A in a typical Rossmann fold. There were 12 and 19 amino acid residues that could participate in the binding of Methyl Red and NADH, respectively, especially the residues Tyr-129 and Asp-184. The functional perturbation effects of 13 residues, including Tyr-129 and Asp-184, were mapped to reconstruct the mutation network, which confirmed the proposed binding modes and also provided insights into the interaction among NADH, FMN and Methyl Red. Published by Elsevier Inc.
C1 [Feng, Jinhui; Kweon, Ohgew; Xu, Haiyan; Cerniglia, Carl E.; Chen, Huizhong] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Kweon, Ohgew] Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 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
FU National Center for Toxicological Research, United States Food and Drug
Administration; Oak Ridge Institute for Science and Education
FX We wish to thank Siwei Chen for technical assistance and Dr. Robin L.
Stingley for critical review of the manuscript. This study was funded by
The National Center for Toxicological Research, United States Food and
Drug Administration, and supported in part by appointment (J. F. and H.
X.) to the Postgraduate Research Fellowship Program by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and the U.S. Food and Drug
Administration. The views presented in this article do not necessarily
reflect those of the Food and Drug Administration.
NR 38
TC 3
Z9 4
U1 2
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-9861
J9 ARCH BIOCHEM BIOPHYS
JI Arch. Biochem. Biophys.
PD APR 15
PY 2012
VL 520
IS 2
BP 99
EP 107
DI 10.1016/j.abb.2012.02.010
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 927SO
UT WOS:000302930600005
PM 22387379
ER
PT J
AU Sun, JC
Shannon, M
Ando, Y
Schnackenberg, LK
Khan, NA
Portilla, D
Beger, RD
AF Sun, Jinchun
Shannon, Melissa
Ando, Yosuke
Schnackenberg, Laura K.
Khan, Nasim A.
Portilla, Didier
Beger, Richard D.
TI Serum metabolomic profiles from patients with acute kidney injury: A
pilot study
SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL
AND LIFE SCIENCES
LA English
DT Article
DE Acute kidney injury; Metabolic profiling; LC/MS; Serum biomarkers;
Acylcarnitines
ID ACUTE-RENAL-FAILURE; HIGH-DENSITY-LIPOPROTEIN; HOMOCYSTEINE METABOLISM;
DISEASE; ACID; METHIONINE; CARNITINE; CRITERIA; RISK; DIMETHYLARGININE
AB Low sensitivity of current clinical markers (serum creatinine and blood urea nitrogen (BUN)) in early stages of the development of acute kidney injury (AKI) limits their utility. Rapid LC/MS-based metabolic profiling of serum demonstrated in a pilot study that metabolomics could provide novel indicators of AM. Metabolic profiles of serum samples from seventeen hospitalized patients with newly diagnosed AKI were compared with the profiles of serum from age-matched subjects with normal kidney function. Increases in acylcarnitines and amino acids (methionine, homocysteine, pyroglutamate, asymmetric dimethylarginine (ADMA), and phenylalanine) and a reduction in serum levels of arginine and several lysophosphatidyl cholines were observed in patients with AKI compared to healthy subjects. Increases in homocysteine, ADMA and pyroglutamate have been recognized as biomarkers of cardiovascular and renal disease, and acylcarnitines represent biomarkers of defective fatty acid oxidation. The results of this pilot study demonstrate the utility of metabolomics in the discovery of novel serum biomarkers that can facilitate the diagnosis and determine prognosis of AKI in hospitalized patients. Published by Elsevier B.V.
C1 [Beger, Richard D.] US FDA, Ctr Metab, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Shannon, Melissa; Portilla, Didier] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA.
[Khan, Nasim A.] Univ Arkansas Med Sci, Dept Internal Med, Div Rheumatol, Little Rock, AR 72205 USA.
[Shannon, Melissa; Khan, Nasim A.; Portilla, Didier] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA.
[Ando, Yosuke] Daiichi Sankyo Co Ltd, Med Safety Res Labs, Tokyo, Japan.
RP Beger, RD (reprint author), US FDA, Ctr Metab, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM Richard.Beger@fda.hhs.gov
FU National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases [RO1 DK075976]; VA; VA REAP; NIH
FX The views presented in this article do not necessarily reflect those of
the U.S. Food and Drug Administration. This work was supported by
National Institutes of Health/National Institute of Diabetes and
Digestive and Kidney Diseases grant RO1 DK075976, VA Merit Award and VA
REAP Award to Dr Didier Portilla. Dr Melissa Shannon was supported by an
NIH funded T32 Training Grant to the Division of Nephrology at UAMS, and
she contributed significantly to this work by recruiting and obtaining
IRB approved consent from patients.
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-0232
J9 J CHROMATOGR B
JI J. Chromatogr. B
PD APR 15
PY 2012
VL 893
BP 107
EP 113
DI 10.1016/j.jchromb.2012.02.042
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 929TM
UT WOS:000303088600015
PM 22429878
ER
PT J
AU Xu, XM
Khan, MA
Burgess, DJ
AF Xu, Xiaoming
Khan, Mansoor A.
Burgess, Diane J.
TI A two-stage reverse dialysis in vitro dissolution testing method for
passive targeted liposomes
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Liposome; In vitro release; Tenofovir; Dialysis; Reverse dialysis;
Membrane diffusion
ID SUSTAINED-RELEASE; DISPERSED SYSTEMS; DRUG-RELEASE; ENCAPSULATION;
FORMULATION; DELIVERY; DESIGN
AB A novel two-stage reverse dialysis method has been developed for in vitro release testing of liposomal drug product with passive targeting characteristics. The first stage of the test is to mimic the circulation of liposomes in the body, whereas the second stage is to imitate the drug release process at the target. Buffer and surfactant solution were used during the first and second stages, respectively. For formulations containing high phase transition temperature lipids and high cholesterol content, no drug leakage was observed during the first stage of test. In the second stage, however, formulations with different compositions showed significant differences in terms of drug release rate, and discriminatory ability of the method was demonstrated. On comparing two different membrane diffusion techniques, dialysis and reverse dialysis methods, the reverse dialysis method showed significantly lower variation, and therefore is the preferred method. The developed in vitro release testing method should help to distinguish formulations with varied compositions for quality control testing purposes. This two-stage reverse dialysis method may pave the way to the development of more bio-relevant release testing methods for liposomal drug products. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Xu, Xiaoming; Burgess, Diane J.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA.
[Khan, Mansoor A.] FDA CDER DPQR, Silver Spring, MD 20993 USA.
RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut Sci, 69 N Eagleville Rd,U3092, Storrs, CT 06269 USA.
EM xiaoming.xu@me.com; mansoor.khan@fda.hhs.gov; d.burgess@uconn.edu
OI Xu, Xiaoming/0000-0003-1672-0830
FU FDA [REQ1044477]
FX The views expressed are those of authors and do not necessarily
represent the official position of the Agency. This research was
supported by FDA critical path funding (Solicitation No.: REQ1044477).
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD APR 15
PY 2012
VL 426
IS 1-2
BP 211
EP 218
DI 10.1016/j.ijpharm.2012.01.030
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 919XA
UT WOS:000302364300024
PM 22301423
ER
PT J
AU Johnson, LJ
Cohen, E
Ilg, D
Klein, R
Skeath, P
Scribner, DA
AF Johnson, Lee J.
Cohen, Ethan
Ilg, Doug
Klein, Richard
Skeath, Perry
Scribner, Dean A.
TI A novel high electrode count spike recording array using an 81,920 pixel
transimpedance amplifier-based imaging chip
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Recording electrode array; High resolution; Electroretinogram; Neuronal
spikes; Electrical imaging
ID RETINAL GANGLION-CELLS; RABBIT RETINA; NEURONAL-ACTIVITY; FIELD
POTENTIALS; BRAIN-SLICES; LARGE-SCALE; SYSTEM; LIGHT; HIPPOCAMPUS;
ACQUISITION
AB Microelectrode recording arrays of 60-100 electrodes are commonly used to record neuronal biopotentials, and these have aided our understanding of brain function, development and pathology. However, higher density microelectrode recording arrays of larger area are needed to study neuronal function over broader brain regions such as in cerebral cortex or hippocampal slices. Here, we present a novel design of a high electrode count picocurrent imaging array (PIA), based on an 81,920 pixel Indigo ISC9809 read-out integrated circuit camera chip. While originally developed for interfacing to infrared photodetector arrays, we have adapted the chip for neuron recording by bonding it to microwire glass resulting in an array with an inter-electrode pixel spacing of 30 mu m. In a high density electrode array, the ability to selectively record neural regions at high speed and with good signal to noise ratio are both functionally important. A critical feature of our PIA is that each pixel contains a dedicated low noise transimpedance amplifier (similar to 0.32 pA rms) which allows recording high signal to noise ratio biocurrents comparable to single electrode voltage amplifier recordings. Using selective sampling of 256 pixel subarray regions, we recorded the extracellular biocurrents of rabbit retinal ganglion cell spikes at sampling rates up to 7.2 kHz. Full array local electroretinogram currents could also be recorded at frame rates up to 100 Hz. A PIA with a full complement of 4 readout circuits would span 1 cm and could acquire simultaneous data from selected regions of 1024 electrodes at sampling rates up to 9.3 kHz. Published by Elsevier B.V.
C1 [Johnson, Lee J.] USN, Code 5611, Div Opt Sci, Res Lab, Washington, DC 20375 USA.
[Cohen, Ethan] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Ilg, Doug; Klein, Richard; Skeath, Perry] Global Strategies Grp NA Inc, Crofton, MD 21114 USA.
[Scribner, Dean A.] Northrop Grumman Informat Syst, Falls Church, VA 22041 USA.
RP Johnson, LJ (reprint author), USN, Code 5611, Div Opt Sci, Res Lab, 4555 Overlook Ave SW, Washington, DC 20375 USA.
EM ljohnson@rirl.navy.mil; Ethan.Cohen@fda.hhs.gov; Dean.Scribner@ngc.com
OI COHEN, ETHAN/0000-0001-6365-2266
FU DARPA Neovision II; FDA
FX This research was funded in part by DARPA Neovision II and the FDA. The
Authors would like to thank Nathalia Peixoto and Saugandhika Minnikanti
for help with device development and testing. We thank Leonardo Angelone
and Thomas Radman for editorial assistance; and Bruce Fleharty for
materials fabrication. The opinions and assertions contained herein are
the private ones of the authors and are not to be construed as official
or reflecting the view of the Department of the Navy. The mention of
commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either an actual or
implied endorsement of such products by the Department of Health and
Human Services (DHHS).
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PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0270
J9 J NEUROSCI METH
JI J. Neurosci. Methods
PD APR 15
PY 2012
VL 205
IS 2
BP 223
EP 232
DI 10.1016/j.jneumeth.2012.01.003
PG 10
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 920VC
UT WOS:000302435400001
PM 22266817
ER
PT J
AU Cai, Y
Geutjes, EJ
Roepman, P
Yu, LR
Blijswijk, JV
Wang, W
Mohammad, H
de Rink, I
Baylin, S
Bernards, R
AF Cai, Yi
Geutjes, Ernst-Jan
Roepman, Paul
Yu, Li-Rong
Blijswijk, Janneke V.
Wang, Wei
Mohammad, Helai
de Rink, Iris
Baylin, Stephen
Bernards, Rene
TI The NuRD complex cooperates with DNMTs to maintain silencing of
colorectal tumor suppressor genes.
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Cai, Yi; Wang, Wei; Mohammad, Helai; Baylin, Stephen] Johns Hopkins Univ, Baltimore, MD USA.
[Geutjes, Ernst-Jan; Blijswijk, Janneke V.; de Rink, Iris; Bernards, Rene] Netherlands Canc Inst, Amsterdam, Netherlands.
[Roepman, Paul] Agendia BV, Amsterdam, Netherlands.
[Yu, Li-Rong] US FDA, Jefferson, AR USA.
NR 0
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PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA LB-386
DI 10.1158/1538-7445.AM2012-LB-386
PG 1
WC Oncology
SC Oncology
GA V43SQ
UT WOS:000209701501244
ER
PT J
AU Feng, HZ
Guo, P
Liu, KW
Cheng, SY
Zhang, P
Hu, B
Cheng, T
McNiven, MA
Johnson, GR
AF Feng, Haizhong
Guo, Ping
Liu, Kun-wei
Cheng, Shi-Yuan
Zhang, Peng
Hu, Bo
Cheng, Tao
McNiven, Mark A.
Johnson, Gibbes R.
TI Dynamin 2 mediates PDGFR alpha-SHP-2-promoted glioblastoma growth and
invasion
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Feng, Haizhong; Guo, Ping; Liu, Kun-wei; Cheng, Shi-Yuan; Hu, Bo] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Feng, Haizhong; Liu, Kun-wei; Cheng, Shi-Yuan] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
[Guo, Ping] Childrens Hosp, Div Pediat Gen & Thorac Surg, Pittsburgh, PA 15213 USA.
[Zhang, Peng; Cheng, Tao] Univ Pittsburgh, Dept Radiat Oncol, Pittsburgh, PA USA.
[Hu, Bo] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Cheng, Tao] Inst Hematol & Blood, State Key Lab Expt Hematol, Pittsburgh, PA USA.
[McNiven, Mark A.] Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[McNiven, Mark A.] Ctr Basic Res Digest Dis, Rochester, MN USA.
[Johnson, Gibbes R.] Div Therapeut Proteins, Chem Lab, Bethesda, MD USA.
[Johnson, Gibbes R.] Ctr Drug Evaluat & Res, Bethesda, MD USA.
NR 0
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 4314
DI 10.1158/1538-7445.AM2012-4314
PG 1
WC Oncology
SC Oncology
GA V43SQ
UT WOS:000209701501423
ER
PT J
AU Jain, M
Zhang, LS
Joshi, B
Puri, R
He, M
Kebebew, E
AF Jain, Meenu
Zhang, Lisa
Joshi, Bharat
Puri, Raj
He, Mei
Kebebew, Electron
TI IL13R alpha 2 regulates cell invasion, and is a therapeutic target for
adrenocortical carcinoma
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Jain, Meenu; Zhang, Lisa; He, Mei; Kebebew, Electron] NCI, Bethesda, MD 20892 USA.
[Joshi, Bharat; Puri, Raj] US FDA, Bethesda, MD 20014 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 3932
DI 10.1158/1538-7445.AM2012-3932
PG 1
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701602167
ER
PT J
AU Liu, MM
Wen, ZN
Wang, ZJ
Zuo, Z
Chow, MSS
Shi, LM
Huang, Y
AF Liu, Mandy M.
Wen, Zhining
Wang, Zhijun
Zuo, Zhong
Chow, Moses S. S.
Shi, Leming
Huang, Ying
TI DNA microarray and connectivity map analysis reveals estrogen-like
activity of Chinese medicinal formula Si-Wu-Tang
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Liu, Mandy M.; Wang, Zhijun; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Pomona, CA USA.
[Wen, Zhining; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zuo, Zhong] Chinese Univ Hong Kong, Sch Pharm, Hong Kong, Hong Kong, Peoples R China.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 2575
DI 10.1158/1538-7445.AM2012-2575
PG 2
WC Oncology
SC Oncology
GA V43SQ
UT WOS:000209701503389
ER
PT J
AU Lyn-Cook, LE
Word, B
Mwamba, B
Lyn-Cook, BD
Hammons, G
AF Lyn-Cook, Lascelles E.
Word, Beverly
Mwamba, Bibi
Lyn-Cook, Beverly D.
Hammons, George
TI Cigarette smoke condensate (CSC) induces differential expression and
promoter methylation profiles of critical genes involved in lung cancer
in NL-20 lung cells in vitro: Short-term and chronic exposure
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Lyn-Cook, Lascelles E.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Word, Beverly; Mwamba, Bibi; Lyn-Cook, Beverly D.; Hammons, George] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 3127
DI 10.1158/1538-7445.AM2012-3127
PG 2
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701605278
ER
PT J
AU Myers, MB
Wang, YY
McKim, KL
McKinzie, PB
Parsons, BL
AF Myers, Meagan B.
Wang, Yiying
McKim, Karen L.
McKinzie, Page B.
Parsons, Barbara L.
TI The prevalence of KRAS, PIK3CA, and BRAF mutant subpopulations in tumors
may be impacting the success of personalized cancer treatment
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Myers, Meagan B.; Wang, Yiying; McKim, Karen L.; McKinzie, Page B.; Parsons, Barbara L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 1739
DI 10.1158/1538-7445.AM2012-1739
PG 1
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701601062
ER
PT J
AU Nwosu, CJ
Anyangwe, N
AF Nwosu, Chinelo Jacinta
Anyangwe, Njwen
TI Prevalence of three types of cancers in southern part of Nigeria
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Nwosu, Chinelo Jacinta] Univ Port Harcourt, Port Harcourt, Nigeria.
[Anyangwe, Njwen] US FDA, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 5519
DI 10.1158/1538-7445.AM2012-5519
PG 1
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701602182
ER
PT J
AU Simpson, NE
Pogribny, IR
Beland, FA
AF Simpson, Natalie E.
Pogribny, Igor R.
Beland, Frederick A.
TI Correction of metabolically sensitive histone epigenetic marks mediates
the drug sensitivity of MDA-MB-231 human breast cancer cells
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Simpson, Natalie E.; Pogribny, Igor R.; Beland, Frederick A.] US FDA, NCTR, Jefferson, AR USA.
NR 0
TC 0
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U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 4096
DI 10.1158/1538-7445.AM2012-4096
PG 2
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701605485
ER
PT J
AU Starlard-Davenport, A
Word, BR
Lyn-Cook, BD
AF Starlard-Davenport, Athena
Word, Beverly R.
Lyn-Cook, Beverly D.
TI UDP-Glucuronosyltransferase 1 (UGT1A1) down-regulation correlates to
menopausal status and stage of disease in human breast cancer tissues
SO CANCER RESEARCH
LA English
DT Meeting Abstract
C1 [Starlard-Davenport, Athena; Word, Beverly R.; Lyn-Cook, Beverly D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD APR 15
PY 2012
VL 72
SU 8
MA 4120
DI 10.1158/1538-7445.AM2012-4120
PG 1
WC Oncology
SC Oncology
GA V43SR
UT WOS:000209701606012
ER
PT J
AU Faix, DJ
Hawksworth, AW
Myers, CA
Hansen, CJ
Ortiguerra, RG
Halpin, R
Wentworth, D
Pacha, LA
Schwartz, EG
Garcia, SMS
Eick-Cost, AA
Clagett, CD
Khurana, S
Golding, H
Blair, PJ
AF Faix, Dennis J.
Hawksworth, Anthony W.
Myers, Christopher A.
Hansen, Christian J.
Ortiguerra, Ryan G.
Halpin, Rebecca
Wentworth, David
Pacha, Laura A.
Schwartz, Erica G.
Garcia, Shawn M. S.
Eick-Cost, Angelia A.
Clagett, Christopher D.
Khurana, Surender
Golding, Hana
Blair, Patrick J.
TI Decreased Serologic Response in Vaccinated Military Recruits during 2011
Correspond to Genetic Drift in Concurrent Circulating Pandemic A/H1N1
Viruses
SO PLOS ONE
LA English
DT Article
ID INACTIVATED INFLUENZA VACCINES; US NAVY SHIP; H1N1 VIRUS; RELATIVE
EFFICACY; BASIC TRAINEES; YOUNG-CHILDREN; H5N1 VIRUS; LIVE; ADULTS;
TRIVALENT
AB Background: Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1), including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV).
Methodology/Principal Findings: To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV), Parris Island (LAIV and trivalent inactivated vaccine [TIV]) at Cape May, New Jersey (TIV) and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN) and hemagglutination inhibition (HI) assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%). Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011) versus the vaccine strain (2009) of pH1N1 viruses (ANOVA p value = 0.0006). HI analyses revealed similar trends. Surface plasmon resonance (SPR) analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain.
Conclusions/Significance: Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV) and pH1N1 virus year (2009 vs. 2011). We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding vaccine protection from circulating pH1N1 viruses in 2011-2012.
C1 [Faix, Dennis J.; Hawksworth, Anthony W.; Myers, Christopher A.; Hansen, Christian J.; Ortiguerra, Ryan G.; Blair, Patrick J.] USN, Hlth Res Ctr, Dept Operat Infect Dis, San Diego, CA 92152 USA.
[Halpin, Rebecca; Wentworth, David] J Craig Venter Inst, Viral Programs, Rockville, MD USA.
[Pacha, Laura A.] Army Publ Hlth Command, Dis Epidemiol Program, Aberdeen Proving Ground, MD USA.
[Schwartz, Erica G.] US Coast Guard, Washington, DC USA.
[Garcia, Shawn M. S.] USN, Hosp Beaufort, Beaufort, SC USA.
[Eick-Cost, Angelia A.] Armed Forces Hlth Surveillance Ctr, Div Epidemiol & Anal, Silver Spring, MD USA.
[Clagett, Christopher D.] Navy & Marine Corps Publ Hlth Ctr, Portsmouth, VA USA.
[Khurana, Surender; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
RP Faix, DJ (reprint author), USN, Hlth Res Ctr, Dept Operat Infect Dis, San Diego, CA 92152 USA.
EM patrick.blair@med.navy.mil
RI Valle, Ruben/A-7512-2013;
OI Wentworth, David/0000-0002-5190-980X
FU U.S. Department of Defense Armed Forces Health Surveillance Center
division of the Global Emerging Infections Surveillance and Response
System; National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200900007C]
FX This work was sponsored in part by a grant from the U.S. Department of
Defense Armed Forces Health Surveillance Center division of the Global
Emerging Infections Surveillance and Response System, and in part with
federal funds from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Department of Health and Human
Services, under contract number HHSN272200900007C. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 59
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 13
PY 2012
VL 7
IS 4
AR e34581
DI 10.1371/journal.pone.0034581
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UT
UT WOS:000305341600045
PM 22514639
ER
PT J
AU Zhou, ZH
Chen, TN
Arora, K
Hyams, K
Kozlowski, S
AF Zhou, Zhao-Hua
Chen, Trina
Arora, Kamalpreet
Hyams, Kenneth
Kozlowski, Steven
TI Complement C1 Esterase Inhibitor Levels Linked to Infections and
Contaminated Heparin-Associated Adverse Events
SO PLOS ONE
LA English
DT Article
ID OVERSULFATED CHONDROITIN SULFATE; KALLIKREIN-KININ SYSTEM; HUMAN-PLASMA
KALLIKREIN; C1-INHIBITOR DEFICIENCY; ACQUIRED ANGIOEDEMA;
LUPUS-ERYTHEMATOSUS; CLINICAL EVENTS; ACTIVATION; HEREDITARY; INSIGHTS
AB Activation of kinin-kallikrein and complement pathways by oversulfated-chondroitin-sulfate (OSCS) has been linked with recent heparin-associated adverse clinical events. Given the fact that the majority of patients who received contaminated heparin did not experience an adverse event, it is of particular importance to determine the circumstances that increase the risk of a clinical reaction. In this study, we demonstrated by both the addition and affinity depletion of C1inh from normal human plasma, that the level of C1inh in the plasma has a great impact on the OSCS-induced kallikrein activity and its kinetics. OSCS-induced kallikrein activity was dramatically increased after C1inh was depleted, while the addition of C1inh completely attenuated kallikrein activity. In addition, actual clinical infection can lead to increased C1inh levels. Plasma from patients with sepsis had higher average levels of functional C1inh and decreased OSCS-induced kallikrein activity. Lastly, descriptive data on adverse event reports suggest cases likely to be associated with contaminated heparin are inversely correlated with infection. Our data suggest that low C1inh levels can be a risk factor and high levels can be protective. The identification of risk factors for contact system-mediated adverse events may allow for patient screening and clinical development of prophylaxis and treatments.
C1 [Zhou, Zhao-Hua; Chen, Trina; Arora, Kamalpreet; Kozlowski, Steven] US FDA, Div Monoclonal Antibodies, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Hyams, Kenneth; Kozlowski, Steven] US FDA, Off Biol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Zhou, ZH (reprint author), US FDA, Div Monoclonal Antibodies, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM Steven.Kozlowski@fda.hhs.gov
FU United States Food and Drug Administration (FDA); FDA/Center for Drug
Evaluation and Research
FX This research was supported by the Intramural Research Program of the
United States Food and Drug Administration (FDA) and FDA/Center for Drug
Evaluation and Research Critical Path Funds. The views expressed in this
manuscript represent the opinions of the authors, and do not necessarily
represent the official views of the FDA. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 45
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Z9 3
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 13
PY 2012
VL 7
IS 4
AR e34978
DI 10.1371/journal.pone.0034978
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959UT
UT WOS:000305341600101
PM 22514695
ER
PT J
AU Delmonte, P
Fardin-Kia, AR
Kramer, JKG
Mossoba, MM
Sidisky, L
Tyburczy, C
Rader, JI
AF Delmonte, Pierluigi
Fardin-Kia, Ali Reza
Kramer, John K. G.
Mossoba, Magdi M.
Sidisky, Len
Tyburczy, Cynthia
Rader, Jeanne I.
TI Evaluation of highly polar ionic liquid gas chromatographic column for
the determination of the fatty acids in milk fat
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Ionic liquid; SLB-IL 111; GC; Gas chromatography; trans fatty acid;
Conjugated linoleic acid; CLA; SP-2560; Milk fat
ID CP-SIL 88; CONJUGATED LINOLEIC ACIDS; STATIONARY PHASES; CIS-FATTY;
OCTADECENOIC ACIDS; ISOMERS; TRANS; IDENTIFICATION; TEMPERATURE;
SEPARATION
AB The SLB-IL111, a new ionic liquid capillary column for gas chromatography available from Supelco Inc., was recently shown to provide enhanced separation of unsaturated geometric and positional isomers of fatty acid (FAs) when it was compared to cyanopropylsiloxane (CPS) columns currently recommended for the analysis of fatty acid methyl esters (FAMEs). A 200 m SLB-IL111 capillary column, operated under a combined temperature and eluent flow gradient, was successfully used to resolve most of the FAs contained in milk farina single 80 min chromatographic separation. The selected chromatographic conditions provided a balanced, simultaneous separation of short-chain (from 4:0), long-chain polyunsaturated fatty acids (PUFAs), and most of the unsaturated FA positional/geometric isomers contained in milk fat. Among the monounsaturated fatty acids (MUFAs), these conditions separated t11-18:1 and t10-18:1 FAs, the two most abundant trans fatty acids (t-FA) contained in most dairy products. These t-FAs reportedly have different biological activities. The conjugated linoleic acid (CLA) isomers commonly found in dairy products were separated from each other, including t7,c9-18:2 from c9,t11-18:2. which eliminated the need for their complementary silver ion HPLC analysis. The application of the SLB-IL111 column provided a complementary elution profile of FAMEs to those obtained by CPS columns, allowing for a more comprehensive FA analysis of total milk fat. The FAMEs were identified by the use of available reference materials, previously synthesized and characterized reference mixtures, and prior separations of the milk fat FAMEs by silver ion chromatography based on the number/geometry of double bonds. Published by Elsevier B.V.
C1 [Delmonte, Pierluigi; Fardin-Kia, Ali Reza; Mossoba, Magdi M.; Tyburczy, Cynthia; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada.
[Sidisky, Len] Supelco Sigma Aldrich, Bellefonte, PA USA.
RP Delmonte, P (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS-717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM Pierluigi.delmonte@fda.hhs.gov
NR 49
TC 55
Z9 59
U1 6
U2 82
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD APR 13
PY 2012
VL 1233
BP 137
EP 146
DI 10.1016/j.chroma.2012.02.012
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 924AO
UT WOS:000302663000018
PM 22386057
ER
PT J
AU Rouse, R
Siwy, J
Mullen, W
Mischak, H
Metzger, J
Hanig, J
AF Rouse, Rodney
Siwy, Justyna
Mullen, William
Mischak, Harald
Metzger, Jochen
Hanig, Joseph
TI Proteomic Candidate Biomarkers of Drug-Induced Nephrotoxicity in the Rat
SO PLOS ONE
LA English
DT Article
ID ACUTE KIDNEY INJURY; SUPPORT VECTOR MACHINES; CAPILLARY-ELECTROPHORESIS;
MASS-SPECTROMETRY; URINARY PROTEOMICS; DISCOVERY; DISEASE;
QUALIFICATION; GENTAMICIN; PEPTIDES
AB Improved biomarkers of acute nephrotoxicity are coveted by the drug development industry, regulatory agencies, and clinicians. In an effort to identify such biomarkers, urinary peptide profiles of rats treated with two different nephrotoxins were investigated. 493 marker candidates were defined that showed a significant response to cis-platin comparing a cisplatin treated cohort to controls. Next, urine samples from rats that received three consecutive daily doses of 150 or 300 mg/kg gentamicin were examined. 557 potential biomarkers were initially identified; 108 of these gentamicin-response markers showed a clear temporal response to treatment. 39 of the cisplatin-response markers also displayed a clear response to gentamicin. Of the combined 147 peptides, 101 were similarly regulated by gentamicin or cis-platin and 54 could be identified by tandem mass spectrometry. Most were collagen type I and type III fragments up-regulated in response to gentamicin treatment. Based on these peptides, classification models were generated and validated in a longitudinal study. In agreement with histopathology, the observed changes in classification scores were transient, initiated after the first dose, and generally persistent over a period of 10-20 days before returning to control levels. The data support the hypothesis that gentamicin-induced renal toxicity up-regulates protease activity, resulting in an increase in several specific urinary collagen fragments. Urinary proteomic biomarkers identified here, especially those common to both nephrotoxins, may serve as a valuable tool to investigate potential new drug candidates for the risk of nephrotoxicity.
C1 [Rouse, Rodney] US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Hanig, Joseph] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Siwy, Justyna; Mischak, Harald; Metzger, Jochen] Mosa Diagnost GmbH, Hannover, Germany.
[Mullen, William; Mischak, Harald] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland.
RP Rouse, R (reprint author), US FDA, Div Drug Safety Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM rodney.rouse@fda.hhs.gov
OI Metzger, Jochen/0000-0003-4475-4499; Mischak, Harald/0000-0003-0323-0306
FU SysKID [HEALTH-F2-2009-241544]; Food and Drug Administration (FDA)
[149-09]
FX This work was supported in part by SysKID (HEALTH-F2-2009-241544), and
by the Food and Drug Administration (FDA) Cooperative Research and
Development Agreement (CRADA) #149-09. No additional external funding
was received for this study. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 51
TC 9
Z9 9
U1 0
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD APR 11
PY 2012
VL 7
IS 4
AR e34606
DI 10.1371/journal.pone.0034606
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 959TP
UT WOS:000305336600038
PM 22509332
ER
PT J
AU Corvi, R
Aardema, MJ
Gribaldo, L
Hayashi, M
Hoffmann, S
Schechtman, L
Vanparys, P
AF Corvi, Raffaella
Aardema, Marilyn J.
Gribaldo, Laura
Hayashi, Makoto
Hoffmann, Sebastian
Schechtman, Leonard
Vanparys, Philippe
TI ECVAM prevalidation study on in vitro cell transformation assays:
General outline and conclusions of the study
SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
LA English
DT Article
DE Validation; Cell transformation assay; Carcinogenicity; Regulatory
toxicology; Alternative methods
ID HAMSTER-EMBRYO CELLS; PH 6.7; PHOTO CATALOG; MORPHOLOGICAL
TRANSFORMATION; RECOMMENDED PROTOCOL; CHEMICAL CARCINOGENS;
CLASSIFICATION; IMPROVEMENT; COLONIES
AB The potential for a compound to induce carcinogenicity is a key consideration when ascertaining hazard and risk assessment of chemicals. Among the in vitro alternatives that have been developed for predicting carcinogenicity, in vitro cell transformation assays (CTAs) have been shown to involve a multistage process that closely models important stages of in vivo carcinogenesis and have the potential to detect both genotoxic and non-genotoxic carcinogens. These assays have been in use for decades and a substantial amount of data demonstrating their performance is available in the literature. However, for the standardised use of these assays for regulatory purposes, a formal evaluation of the assays, in particular focusing on development of standardised transferable protocols and further information on assay reproducibility, was considered important to serve as a basis for the drafting of generally accepted OECD test guidelines. To address this issue, a prevalidation study of the CTAs using the BALB/c 3T3 cell line, SHE cells at pH 6.7, and SHE cells at pH 7.0 was coordinated by the European Centre for the Validation of Alternative Methods (ECVAM) and focused on issues of standardisation of protocols, test method transferability and within-and between-laboratory reproducibility. The study resulted in the availability of standardised protocols that had undergone prevalidation[1,2]. The results of the ECVAM study demonstrated that for the BALB/c 3T3 method, some modifications to the protocol were needed to obtain reproducible results between laboratories, while the SHE pH 6.7 and the SHE pH 7.0 protocols are transferable between laboratories, and results are reproducible within- and between-laboratories. It is recommended that the BALB/c 3T3 and SHE protocols as instituted in this prevalidation study should be used in future applications of these respective transformation assays. To support their harmonised use and regulatory application, the development of an OECD test guideline for the SHE CTAs, based on the protocol published in this issue, is recommended. The development of an OECD test guideline for the BALB/c 3T3 CIA should likewise be further pursued upon the availability of additional supportive data and improvement of the statistical analysis. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Corvi, Raffaella] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21027 Ispra, Italy.
[Aardema, Marilyn J.] Marilyn Aardema Consulting LLC, Fairfield, OH 45014 USA.
[Gribaldo, Laura] Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, Mol Biol & Genom Unit, I-21027 Ispra, Italy.
[Hayashi, Makoto] Biosafety Res Ctr, Iwata, Shizuoka, Japan.
[Hoffmann, Sebastian] Seh Consulting Serv, D-50859 Cologne, Germany.
[Schechtman, Leonard] Innovat Toxicol Consulting LLC, Lake Worth, FL 33467 USA.
[Vanparys, Philippe] ALTOXICON BVBA, B-2350 Vosselaar, Belgium.
[Aardema, Marilyn J.] Procter & Gamble Co, Cincinnati, OH 45253 USA.
[Hayashi, Makoto] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo, Japan.
[Schechtman, Leonard] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA.
[Vanparys, Philippe] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium.
RP Corvi, R (reprint author), Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, Via Enrico Fermi 2749, I-21027 Ispra, Italy.
EM raffaella.corvi@jrc.ec.europa.eu
FU Joint Research Centre of the European Commission through ECVAM
[22578-2004-12 FIED ISP DE, CCR.IHCP.C431180.X0, CCR.IHCP.C434214.X0];
Japanese Ministry of Health; Procter & Gamble Corporation
FX This study was mainly funded by the Joint Research Centre of the
European Commission through ECVAM, via Contract Numbers 22578-2004-12
FIED ISP DE, CCR.IHCP.C431180.X0 and CCR.IHCP.C434214.X0. The HRI
laboratory was sponsored by the Japanese Ministry of Health. We
acknowledge D. Maurici, B.C. Thomas and P. Phrakonkham for their
assistance during the course of the study. Marilyn Aardema Consulting
was supported by The Procter & Gamble Corporation.
NR 53
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U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5718
EI 1879-3592
J9 MUTAT RES-GEN TOX EN
JI Mutat. Res. Genet. Toxicol. Environ. Mutagen.
PD APR 11
PY 2012
VL 744
IS 1
SI SI
BP 12
EP 19
DI 10.1016/j.mrgentox.2011.11.009
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA 934YP
UT WOS:000303484000004
PM 22138617
ER
PT J
AU Auer, R
Bauer, DC
Marques-Vidal, P
Butler, J
Min, LJ
Cornuz, J
Satterfield, S
Newman, AB
Vittinghoff, E
Rodondi, N
AF Auer, Reto
Bauer, Douglas C.
Marques-Vidal, Pedro
Butler, Javed
Min, Lauren J.
Cornuz, Jacques
Satterfield, Suzanne
Newman, Anne B.
Vittinghoff, Eric
Rodondi, Nicolas
CA Hlth ABC Study
TI Association of Major and Minor ECG Abnormalities With Coronary Heart
Disease Events
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ST-T ABNORMALITIES; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION;
PREDICTIVE ABILITY; LEIDEN 85-PLUS; ROC CURVE; FOLLOW-UP; RISK;
MORTALITY; ADULTS
AB Context In populations of older adults, prediction of coronary heart disease (CHD) events through traditional risk factors is less accurate than in middle-aged adults. Electrocardiographic (ECG) abnormalities are common in older adults and might be of value for CHD prediction.
Objective To determine whether baseline ECG abnormalities or development of new and persistent ECG abnormalities are associated with increased CHD events.
Design, Setting, and Participants A population-based study of 2192 white and black older adults aged 70 to 79 years from the Health, Aging, and Body Composition Study (Health ABC Study) without known cardiovascular disease. Adjudicated CHD events were collected over 8 years between 1997-1998 and 2006-2007. Baseline and 4-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict CHD events.
Main Outcome Measure Adjudicated CHD events (acute myocardial infarction [MI], CHD death, and hospitalization for angina or coronary revascularization).
Results At baseline, 276 participants (13%) had minor and 506 (23%) had major ECG abnormalities. During follow-up, 351 participants had CHD events (96 CHD deaths, 101 acute MIs, and 154 hospitalizations for angina or coronary revascularizations). Both baseline minor and major ECG abnormalities were associated with an increased risk of CHD after adjustment for traditional risk factors (17.2 per 1000 person-years among those with no abnormalities; 29.3 per 1000 person-years; hazard ratio [HR], 1.35; 95% CI, 1.02-1.81; for minor abnormalities; and 31.6 per 1000 person-years; HR, 1.51; 95% CI, 1.20-1.90; for major abnormalities). When ECG abnormalities were added to a model containing traditional risk factors alone, 13.6% of intermediate-risk participants with both major and minor ECG abnormalities were correctly reclassified (overall net reclassification improvement [NRI], 7.4%; 95% CI, 3.1%-19.0%; integrated discrimination improvement, 0.99%; 95% CI, 0.32%-2.15%). After 4 years, 208 participants had new and 416 had persistent abnormalities. Both new and persistent ECG abnormalities were associated with an increased risk of subsequent CHD events (HR, 2.01; 95% CI, 1.33-3.02; and HR, 1.66; 95% CI, 1.18-2.34; respectively). When added to the Framingham Risk Score, the NRI was not significant (5.7%; 95% CI, -0.4% to 11.8%).
Conclusions Major and minor ECG abnormalities among older adults were associated with an increased risk of CHD events. Depending on the model, adding ECG abnormalities was associated with improved risk prediction beyond traditional risk factors. JAMA. 2012;307(14):1497-1505
C1 [Auer, Reto; Bauer, Douglas C.; Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94107 USA.
[Auer, Reto; Cornuz, Jacques] Univ Lausanne, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
[Marques-Vidal, Pedro] Univ Lausanne, Inst Social & Prevent Med, Lausanne, Switzerland.
[Marques-Vidal, Pedro] Univ Lausanne, Clin Res Ctr, Lausanne, Switzerland.
[Butler, Javed] Emory Univ, Dept Med, Atlanta, GA 30322 USA.
[Min, Lauren J.] US FDA, Silver Spring, MD USA.
[Satterfield, Suzanne] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Rodondi, Nicolas] Univ Bern, Dept Gen Internal Med, Bern, Switzerland.
RP Auer, R (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 185 Berry St,Ste 5700, San Francisco, CA 94107 USA.
EM reto.auer@ucsf.edu
RI Newman, Anne/C-6408-2013; Marques-Vidal, Pedro/C-9449-2009;
OI Newman, Anne/0000-0002-0106-1150; Marques-Vidal,
Pedro/0000-0002-4548-8500; Kritchevsky, Stephen/0000-0003-3336-6781
FU Novartis; Amgen; National Institutes of Health; Medtronic; GE
Healthcare; Boston Scientific; National Institute on Aging
[R01-AG028050]; National Institute on Aging (NIA), National Institutes
of Health (NIH) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National
Institute of Nursing Research [R01-R012459]; Swiss National Science
Foundation [SPUM33CM30-124112, PBLAP3-136774]; Swiss Heart Foundation
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Bauer reported receiving grants
from Novartis and Amgen. Dr Butler reported receiving research support
from National Institutes of Health, Amgen, Medtronic, GE Healthcare, and
Boston Scientific; and being a consultant to Bayer, Cardiomems, Trevena,
Takeda, Ono Pharmaceutical, and Events Committee Corthera and World
Heart. Dr Satterfield reported receiving a grant contract for Health ABC
Study from the National Institute on Aging. Dr Vittinghoff reported
receiving a grant for support as consulting statistician for training
program from the National Institutes of Health. No other authors
reported any disclosures.; This work was supported by grants
N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106 from the National
Institute on Aging (NIA), National Institutes of Health (NIH); grant
R01-AG028050 from the NIA, grant R01-R012459 from the National Institute
of Nursing Research, and in part by the Intramural Research Program of
the NIH, NIA. The NIA funded the Health ABC Study, reviewed the
manuscript, and approved its publication. Dr Auer's research on
cardiovascular prevention is supported by grants SPUM33CM30-124112 and
PBLAP3-136774 from the Swiss National Science Foundation and the Swiss
Heart Foundation.
NR 38
TC 57
Z9 60
U1 0
U2 8
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD APR 11
PY 2012
VL 307
IS 14
BP 1497
EP 1505
DI 10.1001/jama.2012.434
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 922HN
UT WOS:000302538100023
PM 22496264
ER
PT J
AU Fan, TP
Deal, G
Koo, HL
Rees, D
Sun, H
Chen, S
Dou, JH
Makarov, VG
Pozharitskaya, ON
Shikov, AN
Kim, YS
Huang, YT
Chang, YS
Jia, W
Dias, A
Wong, VCW
Chan, K
AF Fan, Tai-Ping
Deal, Greer
Koo, Hoi-Lun
Rees, Daryl
Sun, He
Chen, Shaw
Dou, Jin-Hui
Makarov, Valery G.
Pozharitskaya, Olga N.
Shikov, Alexander N.
Kim, Yeong Shik
Huang, Yi-Tsau
Chang, Yuan Shiun
Jia, William
Dias, Alberto
Wong, Vivian Chi-woon
Chan, Kelvin
TI Future development of global regulations of Chinese herbal products
SO JOURNAL OF ETHNOPHARMACOLOGY
LA English
DT Review
DE Country regulatory guidelines; Categories of herbal products; Comparison
of regulatory requirements for registration
ID MEDICINES
AB Ethnopharmacological relevance: GP-TCM is the first EU-funded Coordination Action consortium dedicated to traditional Chinese medicine (TCM) research. One of the key deliverables of the Work Package 7 in GP-TCM was to investigate information of the existing requirements for registration of TCM products listed by global regulatory bodies. The paper aims to collate data and draw comparison of these regulations. Case studies are also presented to illustrate the problems involved in registering TCM products in different regions worldwide.
Materials and methods: A collaborative network task force was established during the early stage of the GP-TCM project and operated through exchanges, teleconferences and focused discussions at annual meetings. The task force involved coordinators, academics who are actively involved with R&D of Chinese herbal medicines, experts on monographic standards of Chinese materia medica, representatives from regulatory agencies, experts from industries in marketing Chinese medicines/herbal medicines and natural products. The co-ordinators took turns to chair teleconferences, led discussions on specific issues at AGM discussion sessions, at joint workshops with other work-packages such as WP1 (quality issues), WP3 (toxicology issues) and WP6 (clinical trial issues). Collectively the authors were responsible for collating discussion outcomes and updating written information.
Results: A global overview of regulations on herbal registration has been compiled during the three years of the consortium. The regulatory requirements for registration of herbal products in the EU and China were compared, and this is extended to other regions/countries: Africa, Australia, Brazil, Canada, Japan, Russia, South Korea, Taiwan, and the United States. A wide variation of the regulations for the categories of herbal products exists: food (functional food, novel foods, dietary food for special medical purpose, foods for particular nutritional use, food supplement): cosmetic, traditional herbal medicine products: herbal medicines for human use and veterinary use.
Conclusion: The regulatory issues for registration of herbal products are complicated among the countries and regions worldwide. The information summarised in the text is for reference only. Some regulations which are presented in this review are still in legislation process and may change in due course. Before taking any regulatory action, readers are advised to consult current official legislation and guidance and/or to seek appropriate professional advice. The lessons learnt from global regulation of TCM will provide valuable insights for regulation of other traditional medicine such as Ayurveda and Unani medicine, as well as other forms of indigenous medicine. The WHO is well placed to co-ordinate a consultation process with the aim of putting forward suggestions for harmonisation to key regulatory agencies. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Fan, Tai-Ping] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1PD, England.
[Koo, Hoi-Lun] Hong Kong Special Adm Reg, River Cam Int, Hong Kong, Hong Kong, Peoples R China.
[Sun, He] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin, Peoples R China.
[Chen, Shaw; Dou, Jin-Hui] US FDA, Rockville, MD 20857 USA.
[Makarov, Valery G.; Pozharitskaya, Olga N.; Shikov, Alexander N.] St Petersburg Inst Pharm, St Petersburg, Russia.
[Chang, Yuan Shiun] China Med Univ, Inst Chinese Pharmaceut Sci, Taichung, Taiwan.
[Jia, William] Univ British Columbia, Fac Med, Vancouver, BC V5Z 1M9, Canada.
[Dias, Alberto] Univ Minho, CITAB UM, Dep Biol, P-4719 Braga, Portugal.
[Wong, Vivian Chi-woon] Hong Kong Special Adm Reg, Hong Kong Hosp Author, Hong Kong, Hong Kong, Peoples R China.
[Chan, Kelvin] Univ Western Sydney, Ctr Complementary Med Res, Campbelltown, NSW 2560, Australia.
[Chan, Kelvin] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia.
RP Fan, TP (reprint author), Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England.
EM tpf1000@cam.ac.uk; Kelvin.chan@sydney.edu.ac
RI Alberto, Dias/K-5834-2013; Shikov, Alexander/B-1804-2008; Makarov,
Valery/F-8746-2016
OI Alberto, Dias/0000-0003-3641-3248; Shikov,
Alexander/0000-0003-4351-0695; Makarov, Valery/0000-0002-2447-7888
NR 28
TC 33
Z9 34
U1 6
U2 74
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-8741
J9 J ETHNOPHARMACOL
JI J. Ethnopharmacol.
PD APR 10
PY 2012
VL 140
IS 3
SI SI
BP 568
EP 586
DI 10.1016/j.jep.2012.02.029
PG 19
WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary
Medicine; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary
Medicine
GA 926PU
UT WOS:000302844100014
PM 22373513
ER
PT J
AU Silverstein, JS
Casey, BJ
Natoli, ME
Dair, BJ
Kofinas, P
AF Silverstein, Joshua S.
Casey, Brendan J.
Natoli, Mary E.
Dair, Benita J.
Kofinas, Peter
TI Rapid Modular Synthesis and Processing of Thiol-Ene Functionalized
Styrene-Butadiene Block Copolymers
SO MACROMOLECULES
LA English
DT Article
ID RADICAL-ADDITION; DIBLOCK COPOLYMERS; DERIVATIVES; MERCAPTANS;
MORPHOLOGY; ATTACHMENT; EFFICIENT; CHEMISTRY; POLYMERS; SILICON
AB Diblock and triblock copolymers of poly-(styrene)-block-poly(1,2-butadiene) (PS/PB) and PS/PB/PS were modified by photochemical thiol-ene chemistry to process selected functional nanopatterned polymers, with reaction completion in 1 h. PB molecular weight (MW) and thiol-ene ratios were systematically varied based on a model monomer, boc-cysteamine, to determine the efficiency of the reaction., The results demonstrate the polydispersity index (PDI) of modified block copolymers significantly increased when low thiol-ene ratios were employed and sometimes induced gelation of the reacted polymers. Using a 10-fold excess of thiol, functionalizations between 60% and 90% were obtained for amines, carboxylic acids, amides, and a pharmaceutical with a pendant thiol. Differential scanning calorimetry showed a 30-60 degrees C increase in the glass transition temperature of the daughter polymers. Subsequently, these polymers were spin-coated from solvents found suitable to form self-assembled block copolymer films. The microstructure domain spacing for each polymer was consistent with those originating from the parent polymer. This technique described allows for the formation of nanopatterned block copolymer films with controlled chemistries from a single source material.
C1 [Silverstein, Joshua S.; Natoli, Mary E.; Kofinas, Peter] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Silverstein, Joshua S.; Casey, Brendan J.; Dair, Benita J.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20993 USA.
RP Kofinas, P (reprint author), Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
EM kofinas@umd.edu
RI Kofinas, Peter/A-8204-2012
OI Kofinas, Peter/0000-0001-6657-3037
FU U.S. Department of Energy; U.S. Food and Drug Administration
FX This project was supported by an appointment to the University
Participation Program at the Center for Devices and Radiological Health
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the U.S. Department of Energy
and the U.S. Food and Drug Administration. NMR Spectroscopy was
performed at the University of Maryland Analytical NMR Service &
Research Center. The authors acknowledge technical advice from Dr. H.
Schlaad.
NR 27
TC 8
Z9 8
U1 2
U2 46
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0024-9297
J9 MACROMOLECULES
JI Macromolecules
PD APR 10
PY 2012
VL 45
IS 7
BP 3161
EP 3167
DI 10.1021/ma300304h
PG 7
WC Polymer Science
SC Polymer Science
GA 921XN
UT WOS:000302511500027
ER
PT J
AU Etminan, M
Forooghian, F
Brophy, JM
Bird, ST
Maberley, D
AF Etminan, Mahyar
Forooghian, Farzin
Brophy, James M.
Bird, Steven T.
Maberley, David
TI Oral Fluoroquinolones and the Risk of Retinal Detachment
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID TENDON-RUPTURE; OLDER-ADULTS; CIPROFLOXACIN; TENDINOPATHY; GATIFLOXACIN;
COLLAGEN; THERAPY
AB Context Fluoroquinolones are commonly prescribed classes of antibiotics. Despite numerous case reports of ocular toxicity, a pharmacoepidemiological study of their ocular safety, particularly retinal detachment, has not been performed.
Objective To examine the association between use of oral fluoroquinolones and the risk of developing a retinal detachment.
Design, Setting, and Patients Nested case-control study of a cohort of patients in British Columbia, Canada, who had visited an ophthalmologist between January 2000 and December 2007. Retinal detachment cases were defined as a procedure code for retinal repair surgery within 14 days of a physician service code. Ten controls were selected for each case using risk-set sampling, matching on age and the month and year of cohort entry.
Main Outcome Measure The association between retinal detachment and current, recent, or past use of an oral fluoroquinolone.
Results From a cohort of 989 591 patients, 4384 cases of retinal detachment and 43 840 controls were identified. Current use of fluoroquinolones was associated with a higher risk of developing a retinal detachment (3.3% of cases vs 0.6% of controls; adjusted rate ratio [ARR], 4.50 [95% CI, 3.56-5.70]). Neither recent use (0.3% of cases vs 0.2% of controls; ARR, 0.92 [95% CI, 0.45-1.87]) nor past use (6.6% of cases vs 6.1% of controls; ARR, 1.03 [95% CI, 0.89-1.19]) was associated with a retinal detachment. The absolute increase in the risk of a retinal detachment was 4 per 10 000 person-years (number needed to harm=2500 computed for any use of fluoroquinolones). There was no evidence of an association between development of a retinal detachment and beta-lactam antibiotics (ARR, 0.74 [95% CI, 0.35-1.57]) or short-acting beta-agonists (ARR, 0.95 [95% CI, 0.68-1.33]).
Conclusion Patients taking oral fluoroquinolones were at a higher risk of developing a retinal detachment compared with nonusers, although the absolute risk for this condition was small. JAMA. 2012;307(13):1414-1419
C1 [Etminan, Mahyar] Child & Family Res Inst British Columbia, Therapeut Evaluat Unit, Vancouver, BC, Canada.
[Etminan, Mahyar] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Forooghian, Farzin; Maberley, David] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada.
[Brophy, James M.] McGill Univ, Dept Epidemiol, Montreal, PQ, Canada.
[Brophy, James M.] McGill Univ, Dept Biostat, Montreal, PQ, Canada.
[Brophy, James M.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Bird, Steven T.] US FDA, Ctr Drug Evaluat & Res Off Management, Silver Spring, MD USA.
[Bird, Steven T.] Acad Collaborat Program, Silver Spring, MD USA.
RP Etminan, M (reprint author), 950 W 28th Ave,Room A4-195, Vancouver, BC V5Z 1L8, Canada.
EM metminan@popi.ubc.ca
FU Canadian National Institute for the Blind
FX The study was funded by the Canadian National Institute for the Blind.
NR 30
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U1 1
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD APR 4
PY 2012
VL 307
IS 13
BP 1414
EP 1419
DI 10.1001/jama.2012.383
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 919AY
UT WOS:000302294200028
PM 22474205
ER
PT J
AU Bekesova, S
Kosti, O
Chandler, KB
Wu, J
Madej, HL
Brown, KC
Simonyan, V
Goldman, R
AF Bekesova, S.
Kosti, O.
Chandler, K. B.
Wu, J.
Madej, H. L.
Brown, K. C.
Simonyan, V.
Goldman, R.
TI N-glycans in liver-secreted and immunoglogulin-derived protein fractions
SO JOURNAL OF PROTEOMICS
LA English
DT Article
DE N-glycosylation; Mass spectrometry; Serum; Liver disease
ID MASS-SPECTROMETRY DATA; ASSISTED-LASER-DESORPTION/IONIZATION;
SOLID-PHASE PERMETHYLATION; MANNAN-BINDING LECTIN;
HEPATOCELLULAR-CARCINOMA; CIRRHOTIC-PATIENTS; IMMUNOGLOBULIN-G;
VIRAL-HEPATITIS; PEAK DETECTION; SERUM
AB N-glycosylation of proteins provides a rich source of information on liver disease progression because majority of serum glycoproteins, with the exception of immunoglobulins, are secreted by the liver. In this report, we present results of an optimized workflow for MALDI-TOF analysis of permethylated N-glycans detached from serum proteins and separated into liver secreted and immunoglobulin fractions. We have compared relative intensities of N-glycans in 23 healthy controls and 23 cirrhosis patients. We were able to detect 82 N-glycans associated primarily with liver secreted glycoproteins, 54 N-glycans in the protein G bound fraction and 52 N-glycans in the fraction bound to protein A. The N-glycan composition of the fractions differed substantially, independent of liver disease. The relative abundance of approximately 53% N-glycans in all fractions was significantly altered in the cirrhotic liver. The removal of immunoglobulins allowed detection of an increase in a series of high mannose and hybrid N-glycans associated with the liver secreted protein fraction. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Bekesova, S.; Kosti, O.; Chandler, K. B.; Wu, J.; Madej, H. L.; Brown, K. C.; Goldman, R.] Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Simonyan, V.] US FDA, Ctr Biol Res & Evaluat, Rockville, MD 20857 USA.
RP Goldman, R (reprint author), Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM rg26@georgetown.edu
OI Chandler, Kevin/0000-0001-5514-9652
FU National Institutes of Health National Center for Research Resources
[M01RR-023942]; NCI [RO1 CA115625, CA135069]; Department of Defense PCRP
[PC081609]; CCSG [NIH P30 CA51008]
FX We wish to thank Allison Pollock, Anthony Roy Orden and Eric Pauley for
the recruitment of the healthy volunteers and cirrhotic patients. We
thank Drs Kirti Shetty, Jacqueline Laurin and Rohit Satoskar, Department
of Hepatology and Liver Transplantation, Georgetown University Hospital,
Washington DC for patient referral. This project was conducted through
the General Clinical Research Center at Georgetown University and
supported by the National Institutes of Health National Center for
Research Resources, Grant M01RR-023942. We are indebted to Dr Milos
Novotny, Department of Chemistry at Indiana University Bloomington for
introduction to the analysis of permethylated glycans and extensive
characterization of N-glycans associated with serum proteins. We also
thank Drs Ionut Bebu and Kepher Makambi for statistical support. This
work was supported by NCI's RO1 CA115625 and CA135069 and Department of
Defense PCRP grant PC081609 awarded to RG. The CCSG grant NIH P30
CA51008 to the Lombardi Comprehensive Cancer Center supported the
Proteomics and Metabolomics Shared Resource which allowed measurements
of N-glycans and the Clinical Molecular Epidemiology Shared Resources
which provided services for biological sample storage and tracking.
NR 53
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U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-3919
J9 J PROTEOMICS
JI J. Proteomics
PD APR 3
PY 2012
VL 75
IS 7
BP 2216
EP 2224
DI 10.1016/j.jprot.2012.01.024
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 930JV
UT WOS:000303136600019
PM 22326963
ER
PT J
AU Ou, W
Marino, MP
Suzuki, A
Joshi, B
Husain, SR
Maisner, A
Galanis, E
Puri, RK
Reiser, J
AF Ou, Wu
Marino, Michael P.
Suzuki, Akiko
Joshi, Bharat
Husain, Syed R.
Maisner, Andrea
Galanis, Evanthia
Puri, Raj K.
Reiser, Jakob
TI Specific Targeting of Human Interleukin (IL)-13 Receptor alpha
2-Positive Cells with Lentiviral Vectors Displaying IL-13
SO HUMAN GENE THERAPY METHODS
LA English
DT Article
ID VESICULAR STOMATITIS-VIRUS; CHIMERIC FUSION PROTEINS; MESENCHYMAL
STEM-CELLS; MEASLES-VIRUS; PSEUDOMONAS EXOTOXIN; GENE-TRANSFER; IN-VIVO;
TRANSGENE EXPRESSION; ADENOVIRAL VECTOR; CANCER-THERAPY
AB The ability to selectively and efficiently target transgene delivery to specific cell types in vitro and in vivo remains one of the formidable challenges in gene therapy. Lentiviral vectors have several advantages that make them attractive as gene delivery vehicles and their tropism can be altered through pseudotyping, allowing transgene delivery to specific populations of cells. The human interleukin-13 receptor alpha 2 (IL-13R alpha 2) is uniquely over-expressed in many different human tumors, making it an attractive target for cancer therapy. In this study, we examined whether IL-13R alpha 2-positive tumor cells can be specifically targeted with lentiviral vector pseudotypes containing a truncated fusion (F) protein derived from measles virus (MV) and a tail-truncated and receptor-blind MV hemagglutinin (H) protein bearing IL-13 at the C terminus. The retargeted lentiviral vector efficiently transduced cells that express high levels of IL-13R alpha 2, but not cells expressing low levels of IL-13R alpha 2 in vitro. In vivo, it specifically targeted IL-13R alpha 2-positive glioma cell xenografts in immunodeficient mice in the context of subcutaneous and intracranial glioma models. Similar lentiviral vectors may be developed for targeting other tumors expressing specific cell surface receptors.
C1 [Ou, Wu; Marino, Michael P.; Suzuki, Akiko; Joshi, Bharat; Husain, Syed R.; Puri, Raj K.; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Maisner, Andrea] Univ Marburg, Inst Virol, D-35043 Marburg, Germany.
[Galanis, Evanthia] Mayo Clin, Rochester, MN 55905 USA.
RP Reiser, J (reprint author), FDA CBER, Div Cellular & Gene Therapies, 1401 Rockville Pike,HFM 725, Rockville, MD 20852 USA.
EM Jakob.Reiser@fda.hhs.gov
FU NCI NIH HHS [P50 CA108961, R01 CA154348]
NR 51
TC 16
Z9 16
U1 0
U2 6
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1946-6536
J9 HUM GENE THER METHOD
JI Hum. Gene Ther. Methods
PD APR
PY 2012
VL 23
IS 2
BP 137
EP 147
DI 10.1089/hgtb.2012.054
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 022WM
UT WOS:000309994900007
PM 22612657
ER
PT J
AU Barraj, LM
Murphy, M
Scrafford, C
Bi, XY
DiNovi, M
AF Barraj, Leila M.
Murphy, Mary
Scrafford, Carolyn
Bi, Xiaoyu
DiNovi, Michael
TI Development of a method for estimating long-term intake of foods and
nutrients
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Barraj, Leila M.; Murphy, Mary; Scrafford, Carolyn; Bi, Xiaoyu] Exponent Inc, Chem Regulat & Food Safety, Washington, DC USA.
[DiNovi, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711306390
ER
PT J
AU Barraj, LM
Srinivasan, J
Brookmire, L
Bi, XY
DiNovi, M
AF Barraj, Leila M.
Srinivasan, Jannavi
Brookmire, Lauren
Bi, Xiaoyu
DiNovi, Michael
TI Comparison food and nutrient intake estimates modeled using 14-day
diaries to estimates derived from two 24-hour recalls
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Barraj, Leila M.; Bi, Xiaoyu] Exponent Inc, Chem Regulat & Food Safety, Washington, DC USA.
[Srinivasan, Jannavi; Brookmire, Lauren; DiNovi, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711306266
ER
PT J
AU Chung, C
Juan, WY
Yamini, E
Trumbo, P
AF Chung, Carolyn
Juan, WenYen
Yamini, Essie
Trumbo, Paula
TI Prevalence of nutrient inadequacy in pregnant women in the United States
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Chung, Carolyn; Juan, WenYen; Yamini, Essie; Trumbo, Paula] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711300918
ER
PT J
AU Dwyer, JT
Bailey, R
Saldanha, L
Holden, J
Andrews, K
Betz, J
Gahche, J
Hardy, C
Milner, J
Roseland, J
AF Dwyer, Johanna T.
Bailey, Regan
Saldanha, Leila
Holden, Joanne
Andrews, Karen
Betz, Joseph
Gahche, Jaime
Hardy, Constance
Milner, John
Roseland, Janet
TI Progress in development of dietary supplement (DS) composition and label
databases for research
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Dwyer, Johanna T.; Bailey, Regan; Saldanha, Leila; Betz, Joseph] Off Dietary Supplements, Bethesda, MD USA.
[Milner, John] NCI, NIH, Bethesda, MD 20892 USA.
[Holden, Joanne; Andrews, Karen; Roseland, Janet] USDA, Nutrient Data Lab, Beltsville, MD 20705 USA.
[Gahche, Jaime] CDC, NCHS, Hysattsville, MD USA.
[Hardy, Constance] US FDA, CFSAN, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711301264
ER
PT J
AU Kangath, A
Chang, C
Krishnankutty, S
Tadapaneni, RK
Edirisinghe, I
Freeman, BB
AF Kangath, Archana
Chang, Claire
Krishnankutty, Sandhya
Tadapaneni, Ravi Kiran
Edirisinghe, Indika
Freeman, Britt Burton
TI Strawberry extract attenuates glucose and free fatty acid-mediated
impaired insulin signaling in vitro in skeletal muscle cells
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Kangath, Archana; Krishnankutty, Sandhya; Tadapaneni, Ravi Kiran; Edirisinghe, Indika; Freeman, Britt Burton] IIT, Inst Food Safety & Hlth, Bedford Pk, IL USA.
[Chang, Claire] US FDA, Bedford Pk, IL USA.
[Freeman, Britt Burton] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711306094
ER
PT J
AU Khositseth, S
Somparn, P
Thippamon, N
Uawithya, P
Shen, RF
Chen, SH
AF Khositseth, Sookkasem
Somparn, Poorichaya
Thippamon, Nattakarn
Uawithya, Panapat
Shen, Rong-Fong
Chen, Shu-Hui
TI Quantitative phosphoproteomics of hypercalcemia induced nephrogenic
diabetes insipidus
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Khositseth, Sookkasem; Somparn, Poorichaya; Thippamon, Nattakarn] Thammasat Univ, Fac Med, Dept Pediat, Patumthanee, Thailand.
[Uawithya, Panapat] Siriraj Hosp, Fac Med, Dept Physiol, Bangkok, Thailand.
[Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Chen, Shu-Hui] Natl Cheng Kung Univ, Dept Chem, Tainan 70101, Taiwan.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711301276
ER
PT J
AU McCarthy, P
Saksena, R
Peterson, D
Lee, CH
An, YM
Vionnet, J
Cipollo, J
Vann, W
AF McCarthy, Pumtiwitt
Saksena, Rina
Peterson, Dwight
Lee, Che-Hung
An, Yanming
Vionnet, Justine
Cipollo, John
Vann, Willie
TI Towards a Well Defined Meningitis Vaccine: Chemoenzymatic Synthesis of
Meningococcal Glycoconjugate Vaccine Candidates
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [McCarthy, Pumtiwitt] NIH NIGMS, Bethesda, MD USA.
[McCarthy, Pumtiwitt; Saksena, Rina; Peterson, Dwight; Lee, Che-Hung; An, Yanming; Vionnet, Justine; Cipollo, John; Vann, Willie] CBER FDA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711305767
ER
PT J
AU Saldanha, LG
Dwyer, JT
Holden, JM
Andrews, KW
Bailey, RL
Betz, JM
Gahche, JJ
Hardy, CJ
Milner, J
Roseland, JM
AF Saldanha, Leila G.
Dwyer, Johanna T.
Holden, Joanne M.
Andrews, Karen W.
Bailey, Regan L.
Betz, Joseph M.
Gahche, Jaime J.
Hardy, Constance J.
Milner, John
Roseland, Janet M.
TI Identifying non-vitamin & mineral bioactive (non-VM) ingredients for
inclusion in Dietary Supplement (DS) Composition Databases
SO FASEB JOURNAL
LA English
DT Meeting Abstract
CT Experimental Biology Meeting
CY APR 21-25, 2012
CL San Diego, CA
C1 [Milner, John] NCI, NIH, Bethesda, MD 20892 USA.
[Saldanha, Leila G.; Dwyer, Johanna T.; Bailey, Regan L.; Betz, Joseph M.] Off Dietary Supplements, Bethesda, MD USA.
[Holden, Joanne M.; Andrews, Karen W.; Roseland, Janet M.] ARS, USDA, Beltsville, MD USA.
[Gahche, Jaime J.] CDC, NHANES, NCHS, Hyattsville, MD USA.
[Hardy, Constance J.] US FDA, CFSAN, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD APR
PY 2012
VL 26
PG 1
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 032IZ
UT WOS:000310711302966
ER
PT J
AU Klionsky, DJ
Abdalla, FC
Abeliovich, H
Abraham, RT
Acevedo-Arozena, A
Adeli, K
Agholme, L
Agnello, M
Agostinis, P
Aguirre-Ghiso, JA
Ahn, HJ
Ait-Mohamed, O
Ait-Si-Ali, S
Akematsu, T
Akira, S
Al-Younes, HM
Al-Zeer, MA
Albert, ML
Albin, RL
Alegre-Abarrategui, J
Aleo, MF
Alirezaei, M
Almasan, A
Almonte-Becerril, M
Amano, A
Amaravadi, R
Amarnath, S
Amer, AO
Andrieu-Abadie, N
Anantharam, V
Ann, DK
Anoopkumar-Dukie, S
Aoki, H
Apostolova, N
Arancia, G
Aris, JP
Asanuma, K
Asare, NYO
Ashida, H
Askanas, V
Askew, DS
Auberger, P
Baba, M
Backues, SK
Baehrecke, EH
Bahr, BA
Bai, XY
Bailly, Y
Baiocchi, R
Baldini, G
Balduini, W
Ballabio, A
Bamber, BA
Bampton, ETW
Banhegyi, G
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Zhu, CL
Zhu, WG
Zhu, XF
Zhu, XW
Zhu, YG
Zoladek, T
Zong, WX
Zorzano, A
Zschocke, J
Zuckerbraun, B
AF Klionsky, Daniel J.
Abdalla, Fabio C.
Abeliovich, Hagai
Abraham, Robert T.
Acevedo-Arozena, Abraham
Adeli, Khosrow
Agholme, Lotta
Agnello, Maria
Agostinis, Patrizia
Aguirre-Ghiso, Julio A.
Ahn, Hyung Jun
Ait-Mohamed, Ouardia
Ait-Si-Ali, Slimane
Akematsu, Takahiko
Akira, Shizuo
Al-Younes, Hesham M.
Al-Zeer, Munir A.
Albert, Matthew L.
Albin, Roger L.
Alegre-Abarrategui, Javier
Aleo, Maria Francesca
Alirezaei, Mehrdad
Almasan, Alexandru
Almonte-Becerril, Maylin
Amano, Atsuo
Amaravadi, Ravi
Amarnath, Shoba
Amer, Amal O.
Andrieu-Abadie, Nathalie
Anantharam, Vellareddy
Ann, David K.
Anoopkumar-Dukie, Shailendra
Aoki, Hiroshi
Apostolova, Nadezda
Arancia, Giuseppe
Aris, John P.
Asanuma, Katsuhiko
Asare, Nana Y. O.
Ashida, Hisashi
Askanas, Valerie
Askew, David S.
Auberger, Patrick
Baba, Misuzu
Backues, Steven K.
Baehrecke, Eric H.
Bahr, Ben A.
Bai, Xue-Yuan
Bailly, Yannick
Baiocchi, Robert
Baldini, Giulia
Balduini, Walter
Ballabio, Andrea
Bamber, Bruce A.
Bampton, Edward T. W.
Banhegyi, Gabor
Bartholomew, Clinton R.
Bassham, Diane C.
Bast, Robert C., Jr.
Batoko, Henri
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Beau, Isabelle
Bechet, Daniel M.
Begley, Thomas J.
Behl, Christian
Behrends, Christian
Bekri, Soumeya
Bellaire, Bryan
Bendall, Linda J.
Benetti, Luca
Berliocchi, Laura
Bernardi, Henri
Bernassola, Francesca
Besteiro, Sebastien
Bhatia-Kissova, Ingrid
Bi, Xiaoning
Biard-Piechaczyk, Martine
Blum, Janice S.
Boise, Lawrence H.
Bonaldo, Paolo
Boone, David L.
Bornhauser, Beat C.
Bortoluci, Karina R.
Bossis, Ioannis
Bost, Frederic
Bourquin, Jean-Pierre
Boya, Patricia
Boyer-Guittaut, Michael
Bozhkov, Peter V.
Brady, Nathan R.
Brancolini, Claudio
Brech, Andreas
Brenman, Jay E.
Brennand, Ana
Bresnick, Emery H.
Brest, Patrick
Bridges, Dave
Bristol, Molly L.
Brookes, Paul S.
Brown, Eric J.
Brumell, John H.
Brunetti-Pierri, Nicola
Brunk, Ulf T.
Bulman, Dennis E.
Bultman, Scott J.
Bultynck, Greet
Burbulla, Lena F.
Bursch, Wilfried
Butchar, Jonathan P.
Buzgariu, Wanda
Bydlowski, Sergio P.
Cadwell, Ken
Cahova, Monika
Cai, Dongsheng
Cai, Jiyang
Cai, Qian
Calabretta, Bruno
Calvo-Garrido, Javier
Camougrand, Nadine
Campanella, Michelangelo
Campos-Salinas, Jenny
Candi, Eleonora
Cao, Lizhi
Caplan, Allan B.
Carding, Simon R.
Cardoso, Sandra M.
Carew, Jennifer S.
Carlin, Cathleen R.
Carmignac, Virgine
Carneiro, Leticia A. M.
Carra, Serena
Caruso, Rosario A.
Casari, Giorgio
Casas, Caty
Castino, Roberta
Cebollero, Eduardo
Cecconi, Francesco
Celli, Jean
Chaachouay, Hassan
Chae, Han-Jung
Chai, Chee-Yin
Chan, David C.
Chan, Edmond Y.
Chang, Raymond Chuen-Chung
Che, Chi-Ming
Chen, Ching-Chow
Chen, Guang-Chao
Chen, Guo-Qiang
Chen, Min
Chen, Quan
Chen, Steve S. -L.
Chen, WenLi
Chen, Xi
Chen, Xiangmei
Chen, Xiequn
Chen, Ye-Guang
Chen, Yingyu
Chen, Yongqiang
Chen, Yu-Jen
Chen, Zhixiang
Cheng, Alan
Cheng, Christopher H. K.
Cheng, Yan
Cheong, Heesun
Cheong, Jae-Ho
Cherry, Sara
Chess-Williams, Russ
Cheung, Zelda H.
Chevet, Eric
Chiang, Hui-Ling
Chiarelli, Roberto
Chiba, Tomoki
Chin, Lih-Shen
Chiou, Shih-Hwa
Chisari, Francis V.
Cho, Chi Hin
Cho, Dong-Hyung
Choi, Augustine M. K.
Choi, DooSeok
Choi, Kyeong Sook
Choi, Mary E.
Chouaib, Salem
Choubey, Divaker
Choubey, Vinay
Chu, Charleen T.
Chuang, Tsung-Hsien
Chueh, Sheau-Huei
Chun, Taehoon
Chwae, Yong-Joon
Chye, Mee-Len
Ciarcia, Roberto
Ciriolo, Maria R.
Clague, Michael J.
Clark, Robert S. B.
Clarke, Peter G. H.
Clarke, Robert
Codogno, Patrice
Coller, Hilary A.
Colombo, Maria I.
Comincini, Sergio
Condello, Maria
Condorelli, Fabrizio
Cookson, Mark R.
Coppens, Graham H. Coombs Isabelle
Corbalan, Ramon
Cossart, Pascale
Costelli, Paola
Costes, Safia
Coto-Montes, Ana
Couve, Eduardo
Coxon, Fraser P.
Cregg, James M.
Crespo, Jose L.
Cronje, Marianne J.
Cuervo, Ana Maria
Cullen, Joseph J.
Czaja, Mark J.
D'Amelio, Marcello
Darfeuille-Michaud, Arlette
Davids, Lester M.
Davies, Faith E.
De Felici, Massimo
de Groot, John F.
de Haan, Cornelis A. M.
De Martino, Luisa
De Milito, Angelo
De Tata, Vincenzo
Debnath, Jayanta
Degterev, Alexei
Dehay, Benjamin
Delbridge, Lea M. D.
Demarchi, Francesca
Deng, Yi Zhen
Dengjel, Joen
Dent, Paul
Denton, Donna
Deretic, Vojo
Desai, Shyamal D.
Devenish, Rodney J.
Di Gioacchino, Mario
Di Paolo, Gilbert
Di Pietro, Chiara
Diaz-Araya, Guillermo
Diaz-Laviada, Ines
Diaz-Meco, Maria T.
Diaz-Nido, Javier
Dikic, Ivan
Dinesh-Kumar, Savithramma P.
Ding, Wen-Xing
Distelhorst, Clark W.
Diwan, Abhinav
Djavaheri-Mergny, Mojgan
Dokudovskaya, Svetlana
Dong, Zheng
Dorsey, Frank C.
Dosenko, Victor
Dowling, James J.
Doxsey, Stephen
Dreux, Marlene
Drew, Mark E.
Duan, Qiuhong
Duchosal, Michel A.
Duff, Karen
Dugail, Isabelle
Durbeej, Madeleine
Duszenko, Michael
Edelstein, Charles L.
Edinger, Aimee L.
Egea, Gustavo
Eichinger, Ludwig
Eissa, N. Tony
Ekmekcioglu, Suhendan
El-Deiry, Wafik S.
Elazar, Zvulun
Elgendy, Mohamed
Ellerby, Lisa M.
Eng, Kai Er
Engelbrecht, Anna-Mart
Engelender, Simone
Erenpreisa, Jekaterina
Escalante, Ricardo
Esclatine, Audrey
Eskelinen, Eeva-Liisa
Espert, Lucile
Espina, Virginia
Fan, Huizhou
Fan, Jia
Fan, Qi-Wen
Fan, Zhen
Fang, Shengyun
Fang, Yongqi
Fanto, Manolis
Fanzani, Alessandro
Farkas, Thomas
Farre, Jean-Claude
Faure, Mathias
Fechheimer, Marcus
Feng, Carl G.
Feng, Jian
Feng, Qili
Feng, Youji
Fesues, Laszlo
Feuer, Ralph
Figueiredo-Pereira, Maria E.
Fimia, Gian Maria
Fingar, Diane C.
Finkbeiner, Steven
Finkel, Toren
Finley, Kim D.
Fiorito, Filomena
Fisher, Edward A.
Fisher, Paul B.
Flajolet, Marc
Florez-McClure, Maria L.
Florio, Salvatore
Fon, Edward A.
Fornai, Francesco
Fortunato, Franco
Fotedar, Rati
Fowler, Daniel H.
Fox, Howard S.
Franco, Rodrigo
Frankel, Lisa B.
Fransen, Marc
Fuentes, Jose M.
Fueyo, Juan
Fujii, Jun
Fujisaki, Kozo
Fujita, Eriko
Fukuda, Mitsunori
Furukawa, Ruth H.
Gaestel, Matthias
Gailly, Philippe
Gajewska, Malgorzata
Galliot, Brigitte
Galy, Vincent
Ganesh, Subramaniam
Ganetzky, Barry
Ganley, Ian G.
Gao, Fen-Biao
Gao, George F.
Gao, Jinming
Garcia, Lorena
Garcia-Manero, Guillermo
Garcia-Marcos, Mikel
Garmyn, Marjan
Gartel, Andrei L.
Gatti, Evelina
Gautel, Mathias
Gawriluk, Thomas R.
Gegg, Matthew E.
Geng, Jiefei
Germain, Marc
Gestwicki, Jason E.
Gewirtz, David A.
Ghavami, Saeid
Ghosh, Pradipta
Giammarioli, Anna M.
Giatromanolaki, Alexandra N.
Gibson, Spencer B.
Gilkerson, Robert W.
Ginger, Michael L.
Ginsberg, Henry N.
Golab, Jakub
Goligorsky, Michael S.
Golstein, Pierre
Gomez-Manzano, Candelaria
Goncu, Ebru
Gongora, Celine
Gonzalez, Claudio D.
Gonzalez, Ramon
Gonzalez-Estevez, Cristina
Gonzalez-Polo, Rosa Ana
Gonzalez-Rey, Elena
Gorbunov, Nikolai V.
Gorski, Sharon
Goruppi, Sandro
Gottlieb, Roberta A.
Gozuacik, Devrim
Granato, Giovanna Elvira
Grant, Gary D.
Green, Kim N.
Gregorc, Ales
Gros, Frederic
Grose, Charles
Grunt, Thomas W.
Gual, Philippe
Guan, Jun-Lin
Guan, Kun-Liang
Guichard, Sylvie M.
Gukovskaya, Anna S.
Gukovsky, Ilya
Gunst, Jan
Gustafsson, Asa B.
Halayko, Andrew J.
Hale, Amber N.
Halonen, Sandra K.
Hamasaki, Maho
Han, Feng
Han, Ting
Hancock, Michael K.
Hansen, Malene
Harada, Hisashi
Harada, Masaru
Hardt, Stefan E.
Harper, J. Wade
Harris, Adrian L.
Harris, James
Harris, Steven D.
Hashimoto, Makoto
Haspel, Jeffrey A.
Hayashi, Shin-ichiro
Hazelhurst, Lori A.
He, Congcong
He, You-Wen
Hebert, Marie-Josee
Heidenreich, Kim A.
Helfrich, Miep H.
Helgason, Gudmundur V.
Henske, Elizabeth P.
Herman, Brian
Herman, Paul K.
Hetz, Claudio
Hilfiker, Sabine
Hill, Joseph A.
Hocking, Lynne J.
Hofman, Paul
Hofmann, Thomas G.
Hoehfeld, Joerg
Holyoake, Tessa L.
Hong, Ming-Huang
Hood, David A.
Hotamisligil, Goekhan S.
Houwerzijl, Ewout J.
Hoyer-Hansen, Maria
Hu, Bingren
Hu, Chien-An A.
Hu, Hong-Ming
Hua, Ya
Huang, Canhua
Huang, Ju
Huang, Shengbing
Huang, Wei-Pang
Huber, Tobias B.
Huh, Won-Ki
Hung, Tai-Ho
Hupp, Ted R.
Hur, Gang Min
Hurley, James B.
Hussain, Sabah N. A.
Hussey, Patrick J.
Hwang, Jung Jin
Hwang, Seungmin
Ichihara, Atsuhiro
Ilkhanizadeh, Shirin
Inoki, Ken
Into, Takeshi
Iovane, Valentine
Iovanna, Juan L.
Ip, Nancy Y.
Isaka, Yoshitaka
Ishida, Hiroyuki
Isidoro, Ciro
Isobe, Ken-ichi
Iwasaki, Akiko
Izquierdo, Marta
Izumi, Yotaro
Jaakkola, Panu M.
Jaattela, Marja
Jackson, George R.
Jackson, William T.
Janji, Bassam
Jendrach, Marina
Jeon, Ju-Hong
Jeung, Eui-Bae
Jiang, Hong
Jiang, Hongchi
Jiang, Jean X.
Jiang, Ming
Jiang, Qing
Jiang, Xuejun
Jiang, Xuejun
Jimenez, Alberto
Jin, Meiyan
Jin, Shengkan
Joe, Cheol O.
Johansen, Terje
Johnson, Daniel E.
Johnson, Gail V. W.
Jones, Nicola L.
Joseph, Bertrand
Joseph, Suresh K.
Joubert, Annie M.
Juhasz, Gabor
Juillerat-Jeanneret, Lucienne
Jung, Chang Hwa
Jung, Yong-Keun
Kaarniranta, Kai
Kaasik, Allen
Kabuta, Tomohiro
Kadowaki, Motoni
Kagedal, Katarina
Kamada, Yoshiaki
Kaminskyy, Vitaliy O.
Kampinga, Harm H.
Kanamori, Hiromitsu
Kang, Chanhee
Kang, Khong Bee
Kang, Kwang Il
Kang, Rui
Kang, Yoon-A
Kanki, Tomotake
Kanneganti, Thirumala-Devi
Kanno, Haruo
Kanthasamy, Anumantha G.
Kanthasamy, Arthi
Karantza, Vassiliki
Kaushal, Gur P.
Kaushik, Susmita
Kawazoe, Yoshinori
Ke, Po-Yuan
Kehrl, John H.
Kelekar, Ameeta
Kerkhoff, Claus
Kessel, David H.
Khalil, Hany
Kiel, Jan A. K. W.
Kiger, Amy A.
Kihara, Akio
Kim, Deok Ryong
Kim, Do-Hyung
Kim, Dong-Hou
Kim, Eun-Kyoung
Kim, Hyung-Ryong
Kim, Jae-Sung
Kim, Jeong Hun
Kim, Jin Cheon
Kim, John K.
Kim, Peter K.
Kim, Seong Who
Kim, Yong-Sun
Kim, Yonghyun
Kimchi, Adi
Kimmelman, Alec C.
King, Jason S.
Kinsella, Timothy J.
Kirkin, Vladimir
Kirshenbaum, Lorrie A.
Kitamoto, Katsuhiko
Kitazato, Kaio
Klein, Ludger
Klimecki, Walter T.
Klucken, Jochen
Knecht, Erwin
Ko, Ben C. B.
Koch, Jan C.
Koga, Hiroshi
Koh, Jae-Young
Koh, Young Ho
Koike, Masato
Komatsu, Masaaki
Kominami, Eiki
Kong, Hee Jeong
Kong, Wei-Jia
Korolchuk, Viktor I.
Kotake, Yaichiro
Koukourakis, Michael I.
Flores, Juan B. Kouri
Kovacs, Attila L.
Kraft, Claudine
Krainc, Dimitri
Kraemer, Helmut
Kretz-Remy, Carole
Krichevsky, Anna M.
Kroemer, Guido
Krueger, Rejko
Krut, Oleg
Ktistakis, Nicholas T.
Kuan, Chia-Yi
Kucharczyk, Roza
Kumar, Ashok
Kumar, Raj
Kumar, Sharad
Kundu, Mondira
Kung, Hsing-Jien
Kurz, Tino
Kwon, Ho Jeong
La Spada, Albert R.
Lafont, Frank
Lamark, Trond
Landry, Jacques
Lane, Jon D.
Lapaquette, Pierre
Laporte, Jocelyn F.
Laszlo, Lajos
Lavandero, Sergio
Lavoie, Josee N.
Layfield, Robert
Lazo, Pedro A.
Le, Weidong
Le Cam, Laurent
Ledbetter, Daniel J.
Lee, Alvin J. X.
Lee, Byung-Wan
Lee, Gyun Min
Lee, Jongdae
Lee, Ju-Hyun
Lee, Michael
Lee, Myung-Shik
Lee, Sug Hyung
Leeuwenburgh, Christiaan
Legembre, Patrick
Legouis, Renaud
Lehmann, Michael
Lei, Huan-Yao
Lei, Qun-Ying
Leib, David A.
Leiro, Jose
Lemasters, John J.
Lemoine, Antoinette
Lesniak, Maciej S.
Lev, Dina
Levenson, Victor V.
Levine, Beth
Levy, Efrat
Li, Faqiang
Li, Jun-Lin
Li, Lian
Li, Sheng
Li, Weijie
Li, Xue-Jun
Li, Yan-bo
Li, Yi-Ping
Liang, Chengyu
Liang, Qiangrong
Liao, Yung-Feng
Liberski, Pawel P.
Lieberman, Andrew
Lim, Hyunjung J.
Lim, Kah-Leong
Lim, Kyu
Lin, Chiou-Feng
Lin, Fu-Cheng
Lin, Jian
Lin, Jiandie D.
Lin, Kui
Lin, Wan-Wan
Lin, Weei-Chin
Lin, Yi-Ling
Linden, Rafael
Lingor, Paul
Lippincott-Schwartz, Jennifer
Lisanti, Michael P.
Liton, Paloma B.
Liu, Bo
Liu, Chun-Feng
Liu, Kaiyu
Liu, Leyuan
Liu, Qiong A.
Liu, Wei
Liu, Young-Chau
Liu, Yule
Lockshin, Richard A.
Lok, Chun-Nam
Lonial, Sagar
Loos, Benjamin
Lopez-Berestein, Gabriel
Lopez-Otin, Carlos
Lossi, Laura
Lotze, Michael T.
Low, Peter
Lu, Binfeng
Lu, Bingwei
Lu, Bo
Lu, Zhen
Luciano, Frederic
Lukacs, Nicholas W.
Lund, Anders H.
Lynch-Day, Melinda A.
Ma, Yong
Macian, Fernando
MacKeigan, Jeff P.
Macleod, Kay F.
Madeo, Frank
Maiuri, Luigi
Maiuri, Maria Chiara
Malagoli, Davide
Malicdan, May Christine V.
Malorni, Walter
Man, Na
Mandelkow, Eva-Maria
Manon, Stephen
Manov, Irena
Mao, Kai
Mao, Xiang
Mao, Zixu
Marambaud, Philippe
Marazziti, Daniela
Marcel, Yves L.
Marchbank, Katie
Marchetti, Piero
Marciniak, Stefan J.
Marcondes, Mateus
Mardi, Mohsen
Marfe, Gabriella
Marino, Guillermo
Markaki, Maria
Marten, Mark R.
Martin, Seamus J.
Martinand-Mari, Camille
Martinet, Wim
Martinez-Vicente, Marta
Masini, Matilde
Matarrese, Paola
Matsuo, Saburo
Matteoni, Raffaele
Mayer, Andreas
Mazure, Nathalie M.
McConkey, David J.
McConnell, Melanie J.
McDermott, Catherine
McDonald, Christine
McInerney, Gerald M.
McKenna, Sharon L.
McLaughlin, BethAnn
McLean, Pamela J.
McMaster, Christopher R.
McQuibban, G. Angus
Meijer, Alfred J.
Meisler, Miriam H.
Melendez, Alicia
Melia, Thomas J.
Melino, Gerry
Mena, Maria A.
Menendez, Javier A.
Menna-Barreto, Rubem F. S.
Menon, Manoj B.
Menzies, Fiona M.
Mercer, Carol A.
Merighi, Adalberto
Merry, Diane E.
Meschini, Stefania
Meyer, Christian G.
Meyer, Thomas F.
Miao, Chao-Yu
Miao, Jun-Ying
Michels, Paul A. M.
Michiels, Carine
Mijaljica, Dalibor
Milojkovic, Ana
Minucci, Saverio
Miracco, Clelia
Miranti, Cindy K.
Mitroulis, Ioannis
Miyazawa, Keisuke
Mizushima, Noboru
Mograbi, Baharia
Mohseni, Simin
Molero, Xavier
Mollereau, Bertrand
Mollinedo, Faustino
Momoi, Takashi
Monastyrska, Iryna
Monick, Martha M.
Monteiro, Mervyn J.
Moore, Michael N.
Mora, Rodrigo
Moreau, Kevin
Moreira, Paula I.
Moriyasu, Yuji
Moscat, Jorge
Mostowy, Serge
Mottram, Jeremy C.
Motyl, Tomasz
Moussa, Charbel E. -H.
Mueller, Sylke
Muenger, Karl
Muenz, Christian
Murphy, Leon O.
Murphy, Maureen E.
Musaro, Antonio
Mysorekar, Indira
Nagata, Eiichiro
Nagata, Kazuhiro
Nahimana, Aimable
Nair, Usha
Nakagawa, Toshiyuki
Nakahira, Kiichi
Nakano, Hiroyasu
Nakataogawa, Hitoshi
Nanjundan, Meera
Naqvi, Naweed I.
Narendra, Derek P.
Narita, Masashi
Navarro, Miguel
Nawrocki, Steffan T.
Nazarko, Taras Y.
Nemchenko, Andriy
Netea, Mihai G.
Neufeld, Thomas P.
Ney, Paul A.
Nezis, Ioannis P.
Huu Phuc Nguyen
Nie, Daotai
Nishino, Ichizo
Nislow, Corey
Nixon, Ralph A.
Noda, Takeshi
Noegel, Angelika A.
Nogalska, Anna
Noguchi, Satoru
Notterpek, Lucia
Novak, Ivana
Nozaki, Tomoyoshi
Nukina, Nobuyuki
Nuernberger, Thorsten
Nyfeler, Beat
Obara, Keisuke
Oberley, Terry D.
Oddo, Salvatore
Ogawa, Michinaga
Ohashi, Toya
Okamoto, Koji
Oleinick, Nancy L.
Oliver, F. Javier
Olsen, Laura J.
Olsson, Stefan
Opota, Onya
Osborne, Timothy F.
Ostrander, Gary K.
Otsu, Kinya
Ou, Jing-hsiung James
Ouimet, Mireille
Overholtzer, Michael
Ozpolat, Bulent
Paganetti, Paolo
Pagnini, Ugo
Pallet, Nicolas
Palmer, Glen E.
Palumbo, Camilla
Pan, Tianhong
Panaretakis, Theocharis
Pandey, Udai Bhan
Papackova, Zuzana
Papassideri, Issidora
Paris, Irmgard
Park, Junsoo
Park, Ohkmae K.
Parys, Jan B.
Parzych, Katherine R.
Patschan, Susann
Patterson, Cam
Pattingre, Sophie
Pawelek, John M.
Peng, Jianxin
Perlmutter, David H.
Perrotta, Ida
Perry, George
Pervaiz, Shazib
Peter, Matthias
Peters, Godefridus J.
Petersen, Morten
Petrovski, Goran
Phang, James M.
Piacentini, Mauro
Pierre, Philippe
Pierrefite-Carle, Valerie
Pierron, Gerard
Pinkas-Kramarski, Ronit
Piras, Antonio
Piri, Natik
Platanias, Leonidas C.
Poeggeler, Stefanie
Poirot, Marc
Poletti, Angelo
Poues, Christian
Pozuelo-Rubio, Mercedes
Praetorius-Ibba, Mette
Prasad, Anil
Prescott, Mark
Priault, Muriel
Produit-Zengaffinen, Nathalie
Progulske-Fox, Ann
Proikas-Cezanne, Tassula
Przedborski, Serge
Przyklenk, Karin
Puertollano, Rosa
Puyal, Julien
Qian, Shu-Bing
Qin, Liang
Qin, Zheng-Hong
Quaggin, Susan E.
Raben, Nina
Rabinowich, Hannah
Rabkin, Simon W.
Rahman, Irfan
Rami, Abdelhaq
Ramm, Georg
Randall, Glenn
Randow, Felix
Rao, V. Ashutosh
Rathmell, Jeffrey C.
Ravikumar, Brinda
Ray, Swapan K.
Reed, Bruce H.
Reed, John C.
Reggiori, Fulvio
Regnier-Vigouroux, Anne
Reichert, Andreas S.
Reiners, John J., Jr.
Reiter, Russel J.
Ren, Jun
Revuelta, Jose L.
Rhodes, Christopher J.
Ritis, Konstantinos
Rizzo, Elizete
Robbins, Jeffrey
Roberge, Michel
Roca, Hernan
Roccheri, Maria C.
Rocchi, Stephane
Rodemann, H. Peter
de Cordoba, Santiago Rodriguez
Rohrer, Baerbel
Roninson, Igor B.
Rosen, Kirill
Rost-Roszkowska, Magdalena M.
Rouis, Mustapha
Rouschop, Kasper M. A.
Rovetta, Francesca
Rubin, Brian P.
Rubinsztein, David C.
Ruckdeschel, Klaus
Rucker, Edmund B., III
Rudich, Assaf
Rudolf, Emil
Ruiz-Opazo, Nelson
Russo, Rossella
Rusten, Tor Erik
Ryan, Kevin M.
Ryter, Stefan W.
Sabatini, David M.
Sadoshima, Junichi
Saha, Tapas
Saitoh, Tatsuya
Sakagami, Hiroshi
Sakai, Yasuyoshi
Salekdeh, Ghasem Hoseini
Salomoni, Paolo
Salvaterra, Paul M.
Salvesen, Guy
Salvioli, Rosa
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TI Guidelines for the use and interpretation of assays for monitoring
autophagy
SO AUTOPHAGY
LA English
DT Review
DE autolysosome; autophagosome; flux; LC3; lysosome; phagophore; stress;
vacuole
ID ACTIVATED PROTEIN-KINASE; CHAPERONE-MEDIATED AUTOPHAGY; PROGRAMMED
CELL-DEATH; ISOLATED RAT HEPATOCYTES; STARVATION-INDUCED AUTOPHAGY;
VACUOLE TARGETING PATHWAY; GLUCAGON-INDUCED AUTOPHAGY; BREAST-CANCER
CELLS; BETAINE HOMOCYSTEINE METHYLTRANSFERASE; ENDOPLASMIC-RETICULUM
STRESS
AB In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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[Camougrand, Nadine; Manon, Stephen; Priault, Muriel] Univ Bordeaux Segalen, Bordeaux, France.
[Campanella, Michelangelo] Univ London, Univ London Royal Vet Coll, Consortium Mitochondrial Res, Univ Coll London, London, England.
[Campanella, Michelangelo] EBRI Rita Levi Montalcini Fdn, Rome, Italy.
[Campos-Salinas, Jenny; Gonzalez-Rey, Elena; Oliver, F. Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Dept Cell Biol & Immunol, Granada, Spain.
[Candi, Eleonora] Univ Roma Tor Vergata, Dept Biochem, Rome, Italy.
[Cao, Lizhi] Cent S Univ, Xiangya Hosp, Dept Pediat, Changsha, Hunan, Peoples R China.
[Caplan, Allan B.] Univ Idaho, Dept Plant Soil & Entomol Sci, Moscow, ID 83843 USA.
[Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, GI Tract Programme,Inst Food Res, Norwich NR4 7TJ, Norfolk, England.
[Carding, Simon R.] Univ E Anglia, Fac Hlth, Norwich Sch Med, Dept Mucosal Immunol, Norwich NR4 7TJ, Norfolk, England.
[Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Fac Med, Coimbra, Portugal.
[Cardoso, Sandra M.; Moreira, Paula I.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Carew, Jennifer S.; Nawrocki, Steffan T.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, San Antonio, TX 78229 USA.
[Carlin, Cathleen R.] Case Western Reserve Univ, Dept Mol Biol & Microbiol, Cleveland, OH 44106 USA.
[Carmignac, Virgine; Durbeej, Madeleine] Lund Univ, Dept Expt Med Sci, Muscle Biol Unit, Lund, Sweden.
[Carneiro, Leticia A. M.] Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, Brazil.
[Carra, Serena] Univ Modena & Reggio Emilia, Dept Med Biosci, Modena, Italy.
[Carra, Serena; Kampinga, Harm H.] Univ Groningen, Univ Med Ctr Groningen, Dept Cell Biol, Groningen, Netherlands.
[Caruso, Rosario A.] Univ Messina, Dept Human Pathol, Messina, Italy.
[Casari, Giorgio] Univ Vita Salute San Raffaele, Milan, Italy.
[Casari, Giorgio] Ist Sci San Raffaele, I-20132 Milan, Italy.
[Casas, Caty] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, Inst Neurosci, E-08193 Barcelona, Spain.
[Castino, Roberta; Isidoro, Ciro] Univ Piemonte Orientale, Dept Hlth Sci, Novara, Italy.
[Cebollero, Eduardo; Reggiori, Fulvio] Univ Med Ctr Utrecht, Dept Cell Biol, Utrecht, Netherlands.
[Cebollero, Eduardo; Reggiori, Fulvio] Univ Med Ctr Utrecht, Inst Biomembranes, Utrecht, Netherlands.
[Cebollero, Eduardo] Univ Med Ctr Utrecht, Dept Biochem & Cell Biol, Utrecht, Netherlands.
[Cecconi, Francesco] IRCCS Santa Lucia Fdn, Rome, Italy.
[Cecconi, Francesco; Ciriolo, Maria R.; Piacentini, Mauro] Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, I-00173 Rome, Italy.
[Celli, Jean] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Chaachouay, Hassan; Rodemann, H. Peter] Univ Tubingen, Dept Radiat Oncol, Div Radiat Biol & Mol Environm Res, Tubingen, Germany.
[Chae, Han-Jung] Chonbuk Univ, Sch Med, Cardiovasc Res Inst, Chonbuk, South Korea.
[Chae, Han-Jung] Chonbuk Univ, Dept Pharmacol, Chonbuk, South Korea.
[Chai, Chee-Yin] Kaohsiung Med Univ Hosp, Dept Pathol, Kaohsiung, Taiwan.
[Chan, David C.] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Chan, Edmond Y.; Coppens, Graham H. Coombs Isabelle] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow, Lanark, Scotland.
[Chang, Raymond Chuen-Chung] Univ Hong Kong, Li Ka Shing Fac Med, Dept Anat, Lab Neurodegenerat Dis, Hong Kong, Hong Kong, Peoples R China.
[Che, Chi-Ming; Lok, Chun-Nam; Sy, Lai-King] Univ Hong Kong, Dept Chem, Hong Kong, Hong Kong, Peoples R China.
[Chen, Ching-Chow; Lin, Wan-Wan] Natl Taiwan Univ, Coll Med, Dept Pharmacol, Taipei 10764, Taiwan.
[Chen, Guang-Chao; Yang, Wei Yuan] Acad Sinica, Inst Biol Chem, Taipei, Taiwan.
[Chen, Guo-Qiang] Shanghai Jiao Tong Univ, Sch Med, Key Lab Cell Differentiat & Apoptosis, Chinese Minist Educ, Shanghai 200030, Peoples R China.
[Chen, Min; Wang, Jin] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.
[Chen, Quan] Chinese Acad Sci, Inst Zool, State Key Lab Membrane Biol, Beijing, Peoples R China.
[Chen, Quan] Nankai Univ, Coll Life Sci, Tianjin 300071, Peoples R China.
[Chen, Steve S. -L.; Ke, Po-Yuan; Lin, Yi-Ling] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Chen, WenLi] S China Normal Univ, MOE Key Lab Laser Life Sci, Guangzhou, Guangdong, Peoples R China.
[Chen, WenLi] S China Normal Univ, Inst Laser Life Sci, Guangzhou, Guangdong, Peoples R China.
[Chen, Xi] Zhejiang Univ, Sch Med, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China.
[Chen, Xiequn] Fourth Mil Med Univ, Xijing Hosp, Dept Hematol, Xian 710032, Peoples R China.
[Chen, Ye-Guang; Liu, Yule; Yu, Li] Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China.
[Chen, Yingyu] Peking Univ, Dept Immunol, Ctr Human Dis Genom, Beijing 100871, Peoples R China.
[Chen, Yongqiang; Guan, Jun-Lin; Towns, Roberto; Wiley, John W.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Chen, Yu-Jen] Mackay Mem Hosp, Dept Radiat Oncol, Taipei, Taiwan.
[Chen, Zhixiang] Purdue Univ, Dept Bot & Plant Pathol, W Lafayette, IN 47907 USA.
[Cheng, Alan] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA.
[Cheng, Christopher H. K.] Chinese Univ Hong Kong, Sch Biomed Sci, Shatin, Hong Kong, Peoples R China.
[Cheng, Yan; Wang, Hong-Gang; Yang, Jin-Ming] Penn State Univ, Coll Med, Penn State Hershey Canc Inst, Dept Pharmacol, Hershey, PA USA.
[Cheong, Heesun; Thompson, Craig B.] Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA.
[Cheong, Jae-Ho] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Chess-Williams, Russ] Bond Univ, Fac Hlth Sci & Med, Southport, Qld 4229, Australia.
[Cheung, Zelda H.] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Chevet, Eric] Univ Bordeaux Segalen, Bordeaux, France.
[Chevet, Eric] INSERM, U1053, Bordeaux, France.
[Chiang, Hui-Ling] Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA USA.
[Chiba, Tomoki] Univ Tsukuba, Grad Sch Life & Environm Sci, Ibaraki, Japan.
[Chin, Lih-Shen; Li, Lian; Mao, Zixu] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Chiou, Shih-Hwa] Natl Yang Ming Univ, Sch Med, Inst Pharmacol, Taipei 112, Taiwan.
[Cho, Chi Hin] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Cho, Dong-Hyung] Kyung Hee Univ, Grad Sch EW Med Sci, Yongin, South Korea.
[Choi, Augustine M. K.; Haspel, Jeffrey A.; Henske, Elizabeth P.; Nakahira, Kiichi; Ryter, Stefan W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA.
[Choi, DooSeok] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Obstet & Gynecol, Seoul, South Korea.
[Choi, Kyeong Sook] Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea.
[Choi, Mary E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA.
[Chouaib, Salem] Inst Gustave Roussy, INSERM, U753 PR1, F-94805 Villejuif, France.
[Choubey, Divaker] Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA.
[Choubey, Vinay; Kaasik, Allen] Univ Tartu, Dept Pharmacol, EE-50090 Tartu, Estonia.
[Chu, Charleen T.; Rabinowich, Hannah] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Chu, Charleen T.] Univ Pittsburgh, Sch Med, Ctr Neurosci, Pittsburgh, PA USA.
[Chuang, Tsung-Hsien] Natl Hlth Res Inst, Immunol Res Ctr, Miaoli Cty, Taiwan.
[Chueh, Sheau-Huei] Natl Def Med Ctr, Dept Biochem, Taipei, Taiwan.
[Chun, Taehoon; Park, Ohkmae K.] Korea Univ, Sch Life Sci & Biotechnol, Seoul, South Korea.
[Chwae, Yong-Joon] Ajou Univ, Sch Med, Dept Microbiol, Suwon 441749, South Korea.
[Chye, Mee-Len] Univ Hong Kong, Sch Biol Sci, Pokfulam, Hong Kong, Peoples R China.
[Ciarcia, Roberto; Florio, Salvatore; Granato, Giovanna Elvira] Univ Naples Federico II, Dept Struct Funct & Biol Technol, Naples, Italy.
[Ciriolo, Maria R.] IRCCS San Raffaele, Rome, Italy.
[Clague, Michael J.] Univ Liverpool, Physiol Lab, Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
[Clark, Robert S. B.] Safar Ctr Resuscitat Res, Pittsburgh, PA USA.
[Clarke, Peter G. H.; Puyal, Julien] Univ Lausanne, Dept Biol Cellulaire & Morphol, Lausanne, Switzerland.
[Clarke, Robert; Saha, Tapas] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC USA.
[Codogno, Patrice] Univ Paris S, INSERM, U984, Paris, France.
[Coller, Hilary A.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Colombo, Maria I.] Univ Nacl Cuyo, CONICET, Inst Histol & Embriol, Lab Biol Celular & Mol, RA-5500 Mendoza, Argentina.
[Comincini, Sergio] Univ Pavia, Dept Genet & Microbiol, I-27100 Pavia, Italy.
[Condorelli, Fabrizio] Univ Piemonte Orientale, Fac Pharm, Novara, Italy.
[Cookson, Mark R.] NIA, Cell Biol & Gene Express Sect, NIH, Bethesda, MD 20892 USA.
[Corbalan, Ramon] Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Cossart, Pascale] Pontificia Univ Catolica Chile, Fac Med, Dept Enfermedades Cardiovasc, Santiago, Chile.
[Costelli, Paola] Inst Pasteur, Unite Interact Bacteries Cellules, Paris, France.
[Costelli, Paola] INSERM, INRA, U604, USC2020, Paris, France.
[Costes, Safia] Univ Turin, Dept Expt Med & Oncol, Turin, Italy.
[Coto-Montes, Ana] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA.
[Couve, Eduardo] Univ Oviedo, Dept Morfol & Biol Celular, Oviedo, Spain.
[Coxon, Fraser P.] Univ Valparaiso, Fac Ciencias, Dept Biol & Cs Ambientales, Valparaiso, Chile.
[Cregg, James M.; Helfrich, Miep H.; Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland.
[Crespo, Jose L.] Keck Grad Inst Appl Sci, Claremont, CA USA.
[Cronje, Marianne J.] Univ Seville, CSIC, Inst Bioquim Vegetal Fotosintesis, Seville, Spain.
Univ Johannesburg, Dept Biochem, Johannesburg, South Africa.
[Kaushik, Susmita] Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA.
[Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10467 USA.
[D'Amelio, Marcello; Kaushik, Susmita; Koga, Hiroshi] Albert Einstein Coll Med, Marion Bessin Liver Res Ctr, Bronx, NY 10467 USA.
Univ Iowa, Dept Surg, Iowa City, IA 52242 USA.
[D'Amelio, Marcello] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
Santa Lucia Fdn, European Ctr Brain Res, Expt Neurol Unit, Rome, Italy.
Univ Campus Biomed, Rome, Italy.
[Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] INRA, USC 2018, Clermont Ferrand, France.
[Cuervo, Ana Maria; Darfeuille-Michaud, Arlette] Univ Auvergne, INSERM, UMR 1071, Clermont Ferrand, France.
[Cullen, Joseph J.; Davids, Lester M.] Univ Cape Town, Dept Human Biol, ZA-7925 Cape Town, South Africa.
[Czaja, Mark J.; Davies, Faith E.] Inst Canc Res, Div Mol Pathol, Sutton, Surrey, England.
[Czaja, Mark J.; Davies, Faith E.] Royal Marsden Hosp, Sutton, Surrey, England.
[De Felici, Massimo] Univ Roma Tor Vergata, Dept Publ Hlth & Cell Biol, Rome, Italy.
[de Groot, John F.; Fueyo, Juan; Gomez-Manzano, Candelaria; Jiang, Hong] Univ Texas Houston, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[de Haan, Cornelis A. M.; Monastyrska, Iryna] Univ Utrecht, Dept Infect Dis & Immunol, Div Virol, Utrecht, Netherlands.
[De Martino, Luisa; Fiorito, Filomena; Iovane, Valentine; Pagnini, Ugo] Univ Naples Federico II, Dept Pathol & Anim Hlth, Naples, Italy.
[De Milito, Angelo; Joseph, Bertrand; Panaretakis, Theocharis] Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.
[De Tata, Vincenzo] Univ Pisa, Sch Med, Dept Expt Pathol, I-56100 Pisa, Italy.
[Debnath, Jayanta] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA.
[Degterev, Alexei] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA.
[Dehay, Benjamin] Univ Bordeaux Segalen, Inst Malad Neurodegenerat, CNRS, UMR 5293, Bordeaux, France.
[Delbridge, Lea M. D.] Univ Melbourne, Dept Physiol, Parkville, Vic 3052, Australia.
[Demarchi, Francesca; Schneider, Claudio] Lab Nazl Consorzio Interuniv, Trieste, Italy.
[Deng, Yi Zhen; Naqvi, Naweed I.] Natl Univ Singapore, Temasek Life Sci Lab, Fungal Pathobiol Grp, Singapore 117548, Singapore.
[Dengjel, Joen] Freiburg Inst Adv Studies FRIAS, Sch Life Sci LifeNet, Freiburg, Germany.
[Dent, Paul] Virginia Commonwealth Univ, Sch Med, VCU Massey Canc Ctr, Dept Neurosurg,VCU Inst Moleular Med, Richmond, VA USA.
[Denton, Donna] SA Pathol, Ctr Canc Biol, Adelaide, SA, Australia.
[Denton, Donna] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia.
[Deretic, Vojo] Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA.
[Desai, Shyamal D.] Louisiana State Univ, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Biol, New Orleans, LA USA.
[Devenish, Rodney J.; Mijaljica, Dalibor; Prescott, Mark; Ramm, Georg] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia.
[Devenish, Rodney J.] Monash Univ, ARC Ctr Excellence Struct & Funct Microbial Genom, Melbourne, Vic 3004, Australia.
[Di Gioacchino, Mario] Univ dAnnunzio Fdn, Ageing Res Ctr CeSI, Unit Allergy & Immunotoxicol, Chieti, Italy.
[Di Paolo, Gilbert; Duff, Karen; Yu, Wai Haung] Columbia Univ, Med Ctr, Taub Inst Alzheimers Dis Res, New York, NY USA.
[Di Paolo, Gilbert; Duff, Karen; Przedborski, Serge; Yamamoto, Ai; Yu, Wai Haung] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY USA.
[Di Pietro, Chiara; Marazziti, Daniela; Matteoni, Raffaele; Tocchini-Valentini, Glauco] EMMA CNR, Inst Cell Biol & Neurobiol, Rome, Italy.
[Diaz-Araya, Guillermo] Univ Chile, Dept Pharmacol & Toxicol Chem, Santiago, Chile.
[Diaz-Laviada, Ines] Univ Alcala De Henares, Sch Med, Dept Biochem & Mol Biol, Madrid, Spain.
[Diaz-Meco, Maria T.; Fotedar, Rati; Hansen, Malene; Moscat, Jorge; Reed, John C.; Salvesen, Guy; Yang, Zhifen] Sanford Burnham Med Res Inst, La Jolla, CA USA.
[Diaz-Nido, Javier; Izquierdo, Marta] Univ Autonoma Madrid, UAM CSIC, Dept Biol Mol, Ctr Biol Mol Severo Ochoa, Madrid, Spain.
[Dikic, Ivan] Frankfurt Inst Mol Life Sci, Frankfurt, Germany.
[Dinesh-Kumar, Savithramma P.] Univ Calif Davis, Coll Biol Sci, Genome Ctr, Davis, CA 95616 USA.
[Dinesh-Kumar, Savithramma P.] Univ Calif Davis, Dept Plant Biol, Davis, CA 95616 USA.
[Ding, Wen-Xing] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA.
[Distelhorst, Clark W.; Subauste, Carlos S.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA.
[Distelhorst, Clark W.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Pharmacol, Cleveland, OH 44106 USA.
[Distelhorst, Clark W.; Wang, Xinglong; Zhu, Xiongwei] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Pathol, Cleveland, OH 44106 USA.
[Distelhorst, Clark W.; Oleinick, Nancy L.] Case Western Reserve Univ, Univ Hosp Cleveland, Ctr Comprehens Canc, Cleveland, OH 44106 USA.
[Diwan, Abhinav] Washington Univ, Sch Med, Cardiovasc Res Ctr, St Louis, MO USA.
[Diwan, Abhinav] Washington Univ, Sch Med, Dept Internal Med, St Louis, MO 63110 USA.
[Djavaheri-Mergny, Mojgan] Univ Bordeaux, INSERM, VINCO, U916, Bordeaux, France.
[Dokudovskaya, Svetlana] Univ Paris 11, CNRS, Inst Gustave Roussy, UMR 8126, Villejuif, France.
[Dong, Zheng] Georgia Hlth Sci Univ, Charlie Norwood VA Med Ctr, Department Cellular Biol & Anat, Augusta, GA USA.
[Dorsey, Frank C.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Dosenko, Victor] Bogomoletz Inst Physiol, Gen & Mol Pathophysiol Dept, Kiev, Ukraine.
[Dowling, James J.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
[Doxsey, Stephen] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA.
[Dreux, Marlene] Ecole Normale Super Lyon, INSERM, Dept Human Virol, U758, F-69364 Lyon, France.
[Duan, Qiuhong] Huazhong Univ Techol & Sci, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan, Hubei, Peoples R China.
[Duchosal, Michel A.] Univ Lausanne Hosp, Div Hematol, Lausanne, Switzerland.
[Duchosal, Michel A.] Univ Lausanne Hosp, Cent Lab Hematol, Lausanne, Switzerland.
[Dugail, Isabelle; Maiuri, Maria Chiara] INSERM, Ctr Rech Cordeliers, Paris, France.
[Dugail, Isabelle] Univ Paris 06, Paris, France.
[Duszenko, Michael] Univ Tubingen, Dept Biochem, Tubingen, Germany.
[Edelstein, Charles L.] Univ Colorado Denver, Div Renal Dis & Hypertens, Aurora, CO USA.
[Edinger, Aimee L.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA.
[Egea, Gustavo] Univ Barcelona, Fac Med, IDIBAPS, Dept Biol Celular Inmunol & Neurociencias, Barcelona 7, Spain.
[Eichinger, Ludwig; Noegel, Angelika A.] Univ Cologne, Fac Med, Inst Biochem 1, D-50931 Cologne, Germany.
[Eissa, N. Tony; Lin, Weei-Chin] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Ekmekcioglu, Suhendan] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[El-Deiry, Wafik S.] Penn State Coll Med, Penn State Hershey Med Ctr, Dept Med Hematol Oncol, Lab Translat Oncol & Expt Canc Therapeut, Hershey, PA USA.
[Elazar, Zvulun] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Elgendy, Mohamed; Minucci, Saverio] Univ Milan, European Inst Oncol, Milan, Italy.
[Elgendy, Mohamed; Minucci, Saverio] Univ Milan, Dept Biomol Sci & Biotechnol, Milan, Italy.
[Ellerby, Lisa M.] Buck Inst Res Aging, Novato, CA USA.
[Eng, Kai Er; McInerney, Gerald M.] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Engelbrecht, Anna-Mart; Loos, Benjamin] Univ Stellenbosch, Dept Physiol Sci, ZA-7600 Stellenbosch, South Africa.
[Engelender, Simone] Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Pharmacol, IL-31096 Haifa, Israel.
[Erenpreisa, Jekaterina] Latvian Biomed Res & Study Ctr, Riga, Latvia.
[Eskelinen, Eeva-Liisa] Univ Helsinki, Dept Biosci, Helsinki, Finland.
[Espina, Virginia] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA.
[Fan, Huizhou] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA.
[Fan, Jia] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200433, Peoples R China.
[Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Neurol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Pediat, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Dept Neurol Surg, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Fan, Qi-Wen; Ilkhanizadeh, Shirin; Weiss, William A.] Univ Calif San Francisco, Brain Tumor Res Ctr, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Fang, Shengyun; Monteiro, Mervyn J.] Univ Maryland, Ctr Biomed Engn & Technol BioMET, Baltimore, MD 21201 USA.
[Fang, Shengyun] Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA.
[Fang, Yongqi] Guangzhou Univ Chinese Med, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China.
[Fanto, Manolis] Kings Coll London, MRC, Ctr Dev Neurobiol, London, England.
[Farkas, Thomas; Jaattela, Marja] Danish Canc Soc, Res Ctr, Copenhagen, Denmark.
[Farre, Jean-Claude; Nazarko, Taras Y.] Univ Calif San Diego, Div Biol Sci, Mol Biol Sect, La Jolla, CA 92093 USA.
[Faure, Mathias] Univ Lyon 1, F-69365 Lyon, France.
[Faure, Mathias] Univ Lyon, INSERM, U851, Lyon, France.
[Fechheimer, Marcus; Furukawa, Ruth H.] Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA.
[Feng, Carl G.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Feng, Jian] SUNY Buffalo, Dept Physiol & Biophys, Buffalo, NY 14260 USA.
[Feng, Qili] S China Normal Univ, Sch Life Sci, Guangdong Prov Key Lab Biotechnol Plant Dev, Guangzhou, Guangdong, Peoples R China.
[Feng, Youji] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Dept Obstet & Gynecol, Shanghai 200030, Peoples R China.
[Fesues, Laszlo] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Res Grp,Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary.
[Fesues, Laszlo] Univ Debrecen, Res Ctr Mol Med, Hungarian Acad Sci, Res Grp,Dept Apoptosis & Genom, H-4012 Debrecen, Hungary.
[Feuer, Ralph] San Diego State Univ, Dept Biol, Cell & Mol Biol Joint Doctoral Program, San Diego, CA 92182 USA.
[Figueiredo-Pereira, Maria E.] CUNY, Hunter Coll, Dept Biol Sci, New York, NY 10021 USA.
[Fimia, Gian Maria] IRCCS L Spallanzani, Natl Inst Infect Dis, Rome, Italy.
[Fingar, Diane C.; Guan, Jun-Lin; Han, Ting; Lin, Jiandie D.] Univ Michigan, Sch Med, Dept Cell & Dev Biol, Ann Arbor, MI USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Gladstone Inst, Taube Koret Ctr Huntingtons Dis, San Francisco, CA 94143 USA.
[Finkbeiner, Steven] Univ Calif San Francisco, Hellman Alzheimers Dis Program, San Francisco, CA 94143 USA.
[Finkel, Toren] NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Finley, Kim D.; Gottlieb, Roberta A.] San Diego State Univ, Biosci Ctr, San Diego, CA 92182 USA.
[Fisher, Edward A.] NYU, Sch Med, Dept Med, New York, NY USA.
[Fisher, Edward A.] NYU, Sch Med, Dept Cell Biol, Marc & Ruti Bell Program Vasc Biol, New York, NY 10016 USA.
[Fisher, Paul B.] Virginia Commonwealth Univ, Sch Med, VCU Inst Moleular Med, Dept Human & Mol Genet,VCU Massey Canc Ctr, Richmond, VA USA.
[Flajolet, Marc; Tian, Yuan] Rockefeller Univ, Lab Mol & Cellular Neurosci, New York, NY 10021 USA.
[Florez-McClure, Maria L.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA.
[Fon, Edward A.] McGill Univ, Dept Neurol & Neurosurg, McGill Parkinson Program, Montreal Neurol Inst, Montreal, PQ, Canada.
[Fornai, Francesco] Univ Pisa, Dept Human Morphol & Appl Biol, Pisa, Italy.
[Fornai, Francesco] IRCCS Neuromed, Pozzilli, Italy.
[Fortunato, Franco] Univ Heidelberg Hosp, Dept Surg, Res Lab, Heidelberg, Germany.
[Fox, Howard S.] Univ Nebraska, Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE USA.
[Franco, Rodrigo] Univ Nebraska, Sch Vet Med & Biomed Sci, Lincoln, NE USA.
[Franco, Rodrigo] Univ Nebraska, Redox Biol Ctr, Lincoln, NE USA.
[Frankel, Lisa B.; Lund, Anders H.] Univ Copenhagen, Biotech Res & Innovat Ctre, Copenhagen, Denmark.
[Fransen, Marc] Katholieke Univ Leuven, Dept Mol & Cellular Med, Louvain, Belgium.
[Fuentes, Jose M.; Gonzalez-Polo, Rosa Ana] Univ Extremadura, Dept Bioquim & Biol Mol Genet, EU Enfermeria, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Caceres, Spain.
[Fujii, Jun] Kyushu Univ, Grad Sch Med Sci, Dept Bacteriol, Kagoshima, Japan.
[Fujisaki, Kozo; Umemiya-Shirafuji, Rika] Kyushu Univ, Dept Frontier Vet Med, Lab Emerging Infect Dis, Kagoshima, Japan.
[Fujita, Eriko] Jichi Med Univ, Dept Pediat, Shimotsuke, Tochigi, Japan.
[Fukuda, Mitsunori] Tohoku Univ, Grad Sch Life Sci, Dept Dev Biol & Neurosci, Sendai, Miyagi 980, Japan.
[Gaestel, Matthias; Menon, Manoj B.] Hannover Med Sch, Inst Physiol Chem, D-3000 Hannover, Germany.
[Gailly, Philippe] Univ Louvain, Lab Cell Physiol, Brussels, Belgium.
[Gajewska, Malgorzata; Motyl, Tomasz] Warsaw Univ Life Sci, Fac Vet Med, Dept Physiol Sci, Warsaw, Poland.
[Galy, Vincent] Univ Paris 06, CNRS, UMR 7622, Paris, France.
[Ganesh, Subramaniam] Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India.
[Ganetzky, Barry] Univ Wisconsin, Genet Lab, Madison, WI 53706 USA.
[Ganley, Ian G.] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee, Scotland.
[Gao, Fen-Biao] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Gao, George F.] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China.
[Gao, Jinming] UT SW Med Ctr, Dallas, TX USA.
[Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Med, Santiago 7, Chile.
[Garcia, Lorena; Lavandero, Sergio] Univ Chile, Fac Ciencias Quim & Farmaceut, Ctr Estudios Mol Celula, Santiago 7, Chile.
[Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA.
[Garcia-Marcos, Mikel] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
[Garmyn, Marjan] Katholieke Univ Leuven, Dept Oncol, Dermatol Lab, Louvain, Belgium.
[Gartel, Andrei L.] Univ Illinois, Dept Med, Chicago, IL USA.
[Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] Univ Aix Marseille 2, Ctr Immunol Marseille Luminy, INSERM, UM2,U1104, F-13284 Marseille 07, France.
[Gatti, Evelina; Golstein, Pierre; Pierre, Philippe] CNRS, UMR7280, Marseille, France.
[Gautel, Mathias] Kings Coll London, Randall Div Cell & Mol Biophys, London WC2R 2LS, England.
[Gautel, Mathias] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England.
[Gawriluk, Thomas R.; Hale, Amber N.; Ledbetter, Daniel J.; Rucker, Edmund B., III] Univ Kentucky, Dept Biol, Lexington, KY USA.
[Gegg, Matthew E.; Schapira, Anthony H. V.] UCL, Inst Neurol, Dept Clin Neurosci, London, England.
[Geng, Jiefei; Harper, J. Wade] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Germain, Marc; Slack, Ruth S.] Univ Ottawa, Dept Cellular Mol Med, Ottawa, ON, Canada.
[Gestwicki, Jason E.; Lieberman, Andrew; Lukacs, Nicholas W.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Ghavami, Saeid; Halayko, Andrew J.; Kirshenbaum, Lorrie A.; Yeganeh, Behzad] Univ Manitoba, Dept Physiol, Manitoba Inst Child Hlth, Winnipeg, MB R3T 2N2, Canada.
[Ghosh, Pradipta; Lee, Jongdae] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Giammarioli, Anna M.; Malorni, Walter] Ist Super Sanita, Dept Therapeut Res & Med Evaluat, I-00161 Rome, Italy.
[Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Democritus Univ Thrace, Dept Pathol, Alexandroupolis, Greece.
[Giatromanolaki, Alexandra N.; Sivridis, Efthimios] Univ Gen Hosp Alexandroupolis, Alexandroupolis, Greece.
[Gibson, Spencer B.] Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB, Canada.
[Gilkerson, Robert W.; Przedborski, Serge; Sulzer, David; Yamamoto, Ai] Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA.
[Ginger, Michael L.] Univ Lancaster, Sch Hlth & Med, Lancaster, England.
[Ginsberg, Henry N.; Tabas, Ira] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
[Golab, Jakub] Med Univ Warsaw, Dept Immunol, Warsaw, Poland.
[Goligorsky, Michael S.] New York Med Coll, Renal Res Inst, Valhalla, NY 10595 USA.
[Gomez-Manzano, Candelaria] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Goncu, Ebru] Ege Univ, Fac Sci, Dept Biol, Izmir, Turkey.
[Gongora, Celine; Le Cam, Laurent; Legouis, Renaud; Pattingre, Sophie] Univ Montpellier I, INSERM, Inst Rech Cancerol Montpellier, U896, Montpellier, France.
[Gonzalez, Claudio D.; Vaccaro, Maira I.] Univ Buenos Aires, Dept Pathophysiol, Sch Pharm & Biochem, Buenos Aires, DF, Argentina.
[Gonzalez, Ramon] CSIC UR CAR, Inst Ciencias Vino, Logrono, Spain.
[Gonzalez-Estevez, Cristina] Univ Nottingham, Queens Med Ctr, Ctr Genet & Genom, Dept Dev Genet & Gene Control, Nottingham NG7 2RD, England.
[Gorbunov, Nikolai V.] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20814 USA.
[Gorski, Sharon] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Goruppi, Sandro] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA.
[Goruppi, Sandro] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA.
[Gozuacik, Devrim] Sabanci Univ, Biol Sci & Bioengn Program, Istanbul, Turkey.
[Green, Kim N.] Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA USA.
[Gregorc, Ales] Agr Inst Slovenia, Ljubljana, Slovenia.
[Gros, Frederic] Univ Strasbourg, CNRS, Strasbourg, France.
[Grose, Charles] Univ Iowa, Dept Pediat, Childrens Hosp, Iowa City, IA 52242 USA.
[Grunt, Thomas W.] Med Univ Vienna, Ctr Comprehens Canc, Dept Med 1, Signaling Networks Program,Div Oncol, Vienna, Austria.
[Guan, Kun-Liang] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA.
[Guan, Kun-Liang] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Gukovskaya, Anna S.; Gukovsky, Ilya] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Gunst, Jan; Van den Berghe, Greet; Vanhorebeek, Ilse] Katholieke Univ Leuven, Dept & Lab Intens Care Med, Louvain, Belgium.
[Gustafsson, Asa B.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, San Diego, CA 92103 USA.
[Halayko, Andrew J.] Univ Manitoba, Manitoba Inst Child Hlth, Dept Internal Med, Winnipeg, MB, Canada.
[Halonen, Sandra K.] Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA.
[Hamasaki, Maho; Noda, Takeshi; Yoshimori, Tamotsu] Osaka Univ, Dept Genet, Grad Sch Med, Osaka, Japan.
[Han, Feng] Zhejiang Univ, Inst Pharmacol,Toxicol & Biochem Pharmaceut, Hangzhou 310003, Zhejiang, Peoples R China.
[Hancock, Michael K.] Life Technol, Discovery & ADMET TOX Syst, Madison, WI USA.
[Harada, Hisashi] Virginia Commonwealth Univ, Massey Canc Ctr, Dept Oral & Craniofacial Mol Biol, Richmond, VA USA.
[Harada, Masaru] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 3, Kitakyushu, Fukuoka 807, Japan.
[Hardt, Stefan E.] Heidelberg Univ, Dept Cardiol Angiol & Pulmol, Heidelberg, Germany.
[Harris, Adrian L.] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Labs,Dept Oncol, Oxford OX3 9DU, England.
[Harris, James] Trinity Coll Dublin, Sch Biochem & Immunol, Immunol Res Ctr, Dublin, Ireland.
[Harris, Steven D.] Univ Nebraska, Ctr Plant Sci Innovat, Lincoln, NE USA.
[Hashimoto, Makoto] Tokyo Metropolitan Inst Med Sci, Div Sensory & Motor Syst, Tokyo 113, Japan.
[Haspel, Jeffrey A.] VA Boston Healthcare Syst, Boston, MA USA.
[Hayashi, Shin-ichiro] Natl Cerebral & Cardiovasc Ctr, Div Hypertens & Nephrol, Osaka, Japan.
[Hayashi, Shin-ichiro] Gifu Univ, Grad Sch Med, Dept Cell Signalling, Gifu, Japan.
[Hazelhurst, Lori A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA.
[He, Congcong; Levine, Beth; Terada, Lance S.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[He, You-Wen; Rathmell, Jeffrey C.; Taylor, Gregory A.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA.
[Hebert, Marie-Josee] CRCHUM, Dept Nephrol, Montreal, PQ, Canada.
[Heidenreich, Kim A.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO USA.
[Helgason, Gudmundur V.; Holyoake, Tessa L.] Univ Glasgow, Inst Canc Sci, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
[Herman, Brian; Reiter, Russel J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Herman, Paul K.] Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA.
[Hetz, Claudio] Univ Chile, Fac Med, ICBM, Biomed Neurosci Inst, Santiago 7, Chile.
[Hilfiker, Sabine; Navarro, Miguel] CSIC, IPBLN, Inst Parasitol & Biomed Lopez Neyra, Dept Mol Biol, Granada, Spain.
[Hill, Joseph A.; Lavandero, Sergio; Nemchenko, Andriy] Univ Texas SW Med Ctr Dallas, Div Cardiol, Dallas, TX 75390 USA.
[Hofmann, Thomas G.] DKFZ ZMBH Alliance, German Canc Res Ctr, Cellular Senescence Grp A210, Heidelberg, Germany.
[Hoehfeld, Joerg] Univ Bonn, Inst Cell Biol, Bonn, Germany.
[Hong, Ming-Huang] Sun Yat Sen Univ, GCP Ctr, Guangzhou 510275, Guangdong, Peoples R China.
[Hood, David A.] York Univ, Sch Kinesiol & Hlth Sci, Toronto, ON M3J 2R7, Canada.
[Hotamisligil, Goekhan S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Houwerzijl, Ewout J.] Univ Med Ctr Groningen, Dept Internal Med, NL-9713 AV Groningen, Netherlands.
[Hoyer-Hansen, Maria] LEO Pharma AS, Dept Mol Biomed, Ballerup, Denmark.
[Hu, Bingren] Univ Maryland, Sch Med, Shock Trauma & Anesthesiol Res Ctr, Baltimore, MD 21201 USA.
[Hu, Chien-An A.] Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA.
[Hu, Hong-Ming] Providence Portland Med Ctr, Earle A Chiles Res Inst, Lab Canc Immunobiol, Portland, OR USA.
[Hua, Ya] Univ Michigan, Dept Neurosurg, Ann Arbor, MI 48109 USA.
[Huang, Canhua; Liu, Bo] Sichuan Univ, State Key Lab Biotherapy, Chengdu 610064, Peoples R China.
[Huang, Shengbing; Sinicrope, Frank A.] Mayo Clin, Dept Med, Rochester, MN USA.
[Huang, Shengbing; Sinicrope, Frank A.] Mayo Canc Ctr, Rochester, MN USA.
[Huang, Wei-Pang] Natl Taiwan Univ, Dept Life Sci, Taipei 10764, Taiwan.
[Huang, Wei-Pang] Natl Taiwan Univ, Inst Zool, Taipei 10764, Taiwan.
[Huber, Tobias B.] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, D-79106 Freiburg, Germany.
[Huber, Tobias B.] Univ Hosp Freiburg, Div Renal, Freiburg, Germany.
[Huh, Won-Ki] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea.
[Huh, Won-Ki] Seoul Natl Univ, Res Ctr Funct Cellul, Seoul, South Korea.
[Hung, Tai-Ho] Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 10591, Taiwan.
[Hupp, Ted R.] Univ Edinburgh, Dept Expt Canc Res, Inst Genet & Mol Med, Cell Signalling Unit, Edinburgh, Midlothian, Scotland.
[Hur, Gang Min] Chungnam Natl Univ, Coll Med, Dept Pharmacol, Infect Signaling Network,Res Ctr, Taejon, South Korea.
[Hurley, James B.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Hussain, Sabah N. A.] McGill Univ, Crit Care Dept, Montreal, PQ, Canada.
[Hussey, Patrick J.] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
[Hwang, Jung Jin] Univ Ulsan, Coll Med, Inst Innovat Canc Res, Seoul, South Korea.
[Hwang, Jung Jin] Asan Med Ctr, Seoul, South Korea.
[Hwang, Seungmin] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Ichihara, Atsuhiro] Tokyo Womens Med Univ, Dept Med 2, Tokyo, Japan.
[Inoki, Ken] Univ Michigan, Sch Med, Dept Internal Med, Div Nephrol, Ann Arbor, MI USA.
[Inoki, Ken] Univ Michigan, Sch Med, Dept Mol & Integrat Physiol, Ann Arbor, MI USA.
[Into, Takeshi] Asahi Univ, Sch Dent, Dept Oral Microbiol, Div Oral Infect & Hlth Sci, Mizuho, Japan.
[Iovanna, Juan L.] Univ Aix Marseille 2, Marseille, France.
[Iovanna, Juan L.] INSERM, U624, F-13258 Marseille, France.
[Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China.
[Ip, Nancy Y.] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China.
[Isaka, Yoshitaka] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka, Japan.
[Ishida, Hiroyuki] Tohoku Univ, Grad Sch Agr Sci, Dept Appl Plant Sci, Sendai, Miyagi 980, Japan.
[Isobe, Ken-ichi] Nagoya Univ, Grad Sch Med, Dept Immunol, Nagoya, Aichi 4648601, Japan.
[Iwasaki, Akiko] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA.
[Izumi, Yotaro] Keio Univ, Sch Med, Divs Gen Thorac Surg, Tokyo, Japan.
[Jaakkola, Panu M.] Univ Turku, Ctr Biotechnol, Turku, Finland.
[Jackson, George R.] Univ Texas Med Branch, Dept Neurol, Galveston, TX USA.
[Jackson, William T.] Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA.
[Janji, Bassam] Publ Res Ctr Hlth CRP Sante, Dept Oncol, Lab Extpt Hematooncol, Luxembourg, Luxembourg.
[Jendrach, Marina] Goethe Univ Frankfurt, Dept Neurol, Univ Med Sch, Frankfurt, Germany.
[Jeon, Ju-Hong] Seoul Natl Univ, Coll Med, Dept Physiol, Seoul, South Korea.
[Jeung, Eui-Bae] Chungbuk Natl Univ, Coll Vet Med, Lab Vet Biochem & Mol Biol, Chonju, South Korea.
[Jiang, Hongchi; Ma, Yong; Wang, Dawei] Harbin Med Univ, Affiliated Hosp 1, Dept Gen Surg, Key Lab Hepatosplen Surg, Harbin, Peoples R China.
[Jiang, Jean X.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA.
[Jiang, Ming] Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA.
[Jiang, Qing] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA.
[Jiang, Xuejun; Overholtzer, Michael] Mem Sloan Kettering Canc Ctr, Dept Cell Biol, New York, NY 10021 USA.
[Jiang, Xuejun] Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing, Peoples R China.
[Jimenez, Alberto; Revuelta, Jose L.] Univ Salamanca, Dept Microbiol & Genet, E-37008 Salamanca, Spain.
[Jin, Shengkan] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA.
[Joe, Cheol O.; Lee, Gyun Min] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea.
[Johansen, Terje; Lamark, Trond] Univ Tromso, Dept Biochem, Inst Med Biol, Tromso, Norway.
[Johnson, Daniel E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Jones, Nicola L.] Univ Toronto, Dept Pediat, Cell Biol Program, Toronto, ON, Canada.
[Jones, Nicola L.] Univ Toronto, Dept Physiol, Toronto, ON, Canada.
[Joseph, Suresh K.] Thomas Jefferson Univ, Dept Pathol & Cell Biol, Philadelphia, PA 19107 USA.
[Joubert, Annie M.] Univ Pretoria, Dept Physiol, ZA-0002 Pretoria, South Africa.
[Juhasz, Gabor; Kovacs, Attila L.; Laszlo, Lajos; Low, Peter; Sass, Miklos] Eotvos Lorand Univ, Dept Anat Cell & Dev Biol, Budapest, Hungary.
[Juillerat-Jeanneret, Lucienne] CHUV Univ Lausanne, Univ Inst Pathol, Lausanne, Switzerland.
[Jung, Yong-Keun] Seoul Natl Univ, Dept Biol Sci, Seoul, South Korea.
[Kaarniranta, Kai] Univ Eastern Finland, Dept Ophthalmol, Kuopio, Finland.
[Kaarniranta, Kai] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Kabuta, Tomohiro; Wada, Keiji] Natl Ctr Neurol & Psychiat NCNP, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Tokyo, Japan.
[Kadowaki, Motoni] Niigata Univ, Dept Appl Biol Chem, Niigata, Japan.
[Kagedal, Katarina] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Linkoping, Sweden.
[Kamada, Yoshiaki] Natl Inst Basic Biol, Lab Biol Divers, Okazaki, Aichi 444, Japan.
[Kaminskyy, Vitaliy O.; Zhivotovsky, Boris] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Kanamori, Hiromitsu; Takemura, Genzou] Gifu Univ, Grad Sch Med, Div Cardiol, Gifu, Japan.
[Kang, Chanhee] Harvard Univ, Brigham & Womens Hosp, Howard Hughes Med Inst, Div Genet,Med Sch, Boston, MA 02115 USA.
[Kang, Khong Bee] Natl Canc Ctr Singapore, Humphrey Oei Inst Canc Res, Div Med Sci, Singapore, Singapore.
[Kang, Kwang Il] Korea Adv Inst Sci & Technol, Korea Sci Acad, Dept Chem & Biol, Pusan, South Korea.
[Kang, Rui; Lotze, Michael T.; Tang, Daolin] Univ Pittsburgh, Inst Canc, Dept Surg, DAMP Lab,Hillman Canc Ctr, Pittsburgh, PA USA.
[Kanki, Tomotake] Kyushu Univ, Grad Sch Med Sci, Dept Clin Chem & Lab Med, Fukuoka 812, Japan.
[Kanneganti, Thirumala-Devi] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA.
[Kanno, Haruo] Tohoku Univ, Sch Med, Dept Orthopaed Surg, Sendai, Miyagi 980, Japan.
[Karantza, Vassiliki] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Internal Med, Div Med Oncol, Piscataway, NJ 08854 USA.
[Kaushal, Gur P.] Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA.
[Kaushal, Gur P.] Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72205 USA.
[Kawazoe, Yoshinori] Kyoto Univ, Inst Chem Res, Div Biochem, Kyoto 606, Japan.
[Ke, Po-Yuan] Chang Gung Univ, Coll Med, Dept Biochem & Mol Biol, Tao Yuan, Taiwan.
[Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Kelekar, Ameeta] Univ Minnesota, Dept Lab Med & Pathol, Ctr Canc, Minneapolis, MN 55455 USA.
[Kerkhoff, Claus] Fraunhofer Grp Extracorporeal Immune Modulat EXIM, Div Nephrol, Dept Internal Med, Rostock, Germany.
[Kessel, David H.] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA.
[Khalil, Hany] Menoufiya Univ, Genet Engn & Biotechnol Res Inst, Dept Mol Biol, El Sadat City, Egypt.
[Kiel, Jan A. K. W.; van der Klei, Ida J.] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst GBB, Haren, Netherlands.
[Kiel, Jan A. K. W.; van der Klei, Ida J.] Univ Groningen, Kluyver Ctr Genom Ind Fermentat, Haren, Netherlands.
[Kiger, Amy A.] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
[Kihara, Akio; Obara, Keisuke] Hokkaido Univ, Fac Pharmaceut Sci, Sapporo, Hokkaido 060, Japan.
[Kim, Deok Ryong] Gyeongsang Natl Univ, Sch Med, Inst Hlth Sci, Jinju, South Korea.
[Kim, Deok Ryong] Gyeongsang Natl Univ, Dept Biochem, Jinju, South Korea.
[Kim, Do-Hyung] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA.
[Kim, Dong-Hou; Yoon, Seung-Yong] Univ Ulsan, Coll Med, Dept Anat & Cell Biol, CDRC, Seoul, South Korea.
[Kim, Eun-Kyoung; Yu, Seong-Woon] Daegu Gyeongbuk Inst Sci & Technol, Dept Brain Sci, Taegu, South Korea.
[Kim, Hyung-Ryong] Wonkwang Univ, Coll Dent, Dept Dent Pharmacol, Chonbuk, South Korea.
[Kim, Jae-Sung] Univ Florida, Dept Surg, Gainesville, FL USA.
[Kim, Jeong Hun] Seoul Natl Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea.
[Kim, Jeong Hun] Seoul Natl Univ, Clin Res Inst, Seoul, South Korea.
[Kim, Jin Cheon] Univ Ulsan, Coll Med, Dept Surg, Seoul, South Korea.
[Kim, John K.; Meisler, Miriam H.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Kim, Peter K.; McQuibban, G. Angus] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
[Kim, Seong Who] Univ Ulsan, Coll Med, Dept Biochem & Mol Biol, Seoul, South Korea.
[Kim, Yong-Sun; Koh, Young Ho] Hallym Univ, Coll Med, Ilsong Inst Life Sci, Chunchon, South Korea.
[Kim, Yong-Sun] Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea.
[Kim, Yonghyun; Marten, Mark R.] Univ Maryland Baltimore Cty, Dept Chem Biochem & Environm Engn, Baltimore, MD 21228 USA.
[Kimchi, Adi] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel.
[Kimmelman, Alec C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA.
[King, Jason S.; Ryan, Kevin M.] Beatson Inst Canc Res, Tumor Cell Death Biol, Glasgow G61 1BD, Lanark, Scotland.
[Kinsella, Timothy J.] Brown Univ, Dept Radiat Oncol, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Kinsella, Timothy J.] Rhode Isl Hosp, Providence, RI USA.
[Kirkin, Vladimir] Merck KGaA, Merck Serono, Darmstadt, Germany.
[Kirshenbaum, Lorrie A.] Univ Manitoba, Dept Pharmacol & Therapeut, Inst Cardiovasc Sci, St Boniface Gen Hosp,Res Ctr, Winnipeg, MB, Canada.
[Kitamoto, Katsuhiko] Univ Tokyo, Dept Biotechnol, Tokyo, Japan.
[Kitazato, Kaio] Nagasaki Univ, Grad Sch Biomed Sci, Dept Mol Microbiol & Immunol, Nagasaka, Yamanashi, Japan.
[Klein, Ludger] Univ Munich, Inst Immunol, D-8000 Munich, Germany.
[Klimecki, Walter T.] Univ Arizona, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
[Klucken, Jochen] Univ Hosp, Div Mol Neurol, Erlangen, Germany.
[Knecht, Erwin] Ctr Invest Principe, Dept Cell Biol, Valencia, Spain.
[Ko, Ben C. B.] Chinese Univ Hong Kong, State Key Lab Oncol So China, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China.
[Koch, Jan C.; Lingor, Paul; Toenges, Lars] Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany.
[Koh, Jae-Young] Univ Ulsan, Coll Med, Dept Neurol, Seoul, South Korea.
[Koike, Masato; Uchiyama, Yasuo] Juntendo Univ, Sch Med, Dept Cell Biol & Neurosci, Tokyo 113, Japan.
[Komatsu, Masaaki; Tanaka, Keiji] Tokyo Metropolitan Inst Med Sci, Prot Metab Project, Tokyo 113, Japan.
[Kominami, Eiki; Ueno, Takashi] Juntendo Univ, Sch Med, Dept Biochem, Tokyo 113, Japan.
[Kong, Hee Jeong] Natl Fisheries Res & Dev Inst NFRDI, Biotechnol Res Div, Pusan, South Korea.
[Kong, Wei-Jia] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Otorhinolaryngol, Wuhan 430074, Peoples R China.
[Korolchuk, Viktor I.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Kotake, Yaichiro] Hiroshima Univ, Grad Sch Biomed Sci, Hiroshima, Japan.
[Koukourakis, Michael I.] Democritus Univ Thrace, Dept Radiotherapy Oncol, Alexandroupolis, Greece.
Univ Vienna, Max Perutz Labs, Vienna, Austria.
[McLean, Pamela J.; Tannous, Bakhos A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA.
Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
Univ Lyon 1, CNRS, Ctr Genet & Physiol Mol & Cellulaire, UMR5534, F-69365 Lyon, France.
Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
Univ Paris 05, Fac Med, Paris, France.
Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany.
Babraham Inst, Signaling Program, Cambridge, England.
Cincinnati Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH USA.
[Zoladek, Teresa] Polish Acad Sci, Inst Biochem & Biophys, Warsaw, Poland.
Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY 40292 USA.
Commonwealth Med Coll, Dept Basic Sci, Scranton, PA USA.
St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
Univ Calif Davis, Ctr Canc, Dept Biochem & Mol Med, Sacramento, CA 95817 USA.
Yonsei Univ, Coll Life Sci & Biotechnol, Dept Biotechnol, Seoul, South Korea.
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA.
Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Spector, Stephen A.] Rady Childrens Hosp, San Diego, CA USA.
[Lafont, Frank] Univ Lille Nord France, INSERM, Inst Pasteur Lille, Ctr Infect & Immun Lille,CNRS,UMR8204,U1019, Lille, France.
[Landry, Jacques; Lavoie, Josee N.] Univ Laval, Canc Res Ctr, Quebec City, PQ G1K 7P4, Canada.
[Lane, Jon D.] Univ Bristol, Sch Biochem, Bristol, Avon, England.
[Lapaquette, Pierre] Inst Pasteur, INSERM, Nucl Org & Oncogenesis Unit, U993, F-75724 Paris, France.
[Laporte, Jocelyn F.] Univ Strasbourg, CNRS, INSERM, Dept Translat Med,IGBMC,U964,UMR7104, Illkirch Graffenstaden, France.
[Layfield, Robert] Univ Nottingham, Queens Med Ctr, Sch Biomed Sci, Nottingham NG7 2RD, England.
[Lazo, Pedro A.; Mollinedo, Faustino] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, E-37008 Salamanca, Spain.
[Le, Weidong; Legembre, Patrick] Shanghai Jiao Tong Univ, Chinese Acad Sci, Sch Med, Inst Hlth Sci, Shanghai 200030, Peoples R China.
[Le, Weidong; Legembre, Patrick; Li, Sheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China.
[Lee, Alvin J. X.; Swanton, Charles] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London, England.
[Lee, Byung-Wan] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea.
[Lee, Ju-Hyun; Levy, Efrat; Nixon, Ralph A.; Yang, Dun-Sheng] NYU, Sch Med, Nathan S Kline Inst Psychiat Res, Dept Psychiat, Orangeburg, NY USA.
[Lee, Michael] Univ Incheon, Div Life Sci, Inchon, South Korea.
[Lee, Myung-Shik] Samsung Med Ctr, Dept Med, Seoul, South Korea.
[Lee, Sug Hyung] Catholic Univ Korea, Coll Med, Dept Pathobiol, Seoul, South Korea.
[Leeuwenburgh, Christiaan] Univ Florida, Dept Aging & Geriatr, Div Biol Aging, Gainesville, FL USA.
Univ Rennes 1, IRSET, INSERM, TeamDRaTE,U1085, Rennes, France.
Univ Paris 11, CNRS, Ctr Genet Mol, UPR3404, Gif Sur Yvette, France.
[Lehmann, Michael] Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
[Lei, Huan-Yao] Natl Cheng Kung Univ, Coll Med, Dept Microbiol & Immunol, Tainan 70101, Taiwan.
[Lei, Qun-Ying] Fudan Univ, Shanghai Med Coll, Dept Biochem, Shanghai 200433, Peoples R China.
[Lei, Qun-Ying] Fudan Univ, Shanghai Med Coll, Dept Mol Biol, Shanghai 200433, Peoples R China.
[Lei, Qun-Ying] Fudan Univ, Shanghai Med Coll, Biomed Sci Inst, Shanghai 200433, Peoples R China.
[Leib, David A.] Dartmouth Med Sch, Dept Microbiol & Immunol, Lebanon, NH USA.
[Leiro, Jose] Univ Santiago Compostela, Inst Invest & Anal Alimentarios, Parasitol Lab, La Coruna, Spain.
[Lemasters, John J.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
[Lemasters, John J.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
[Lemoine, Antoinette] Univ Paris 11, INSERM, APHP, Dept Biochem & Mol Biol,U1004, Villejuif, France.
[Lesniak, Maciej S.] Univ Chicago, Dept Surg & Canc Biol, Chicago, IL 60637 USA.
[Lev, Dina; McConkey, David J.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Levenson, Victor V.] Rush Univ, Med Ctr, Dept Radiat Oncol, Chicago, IL 60612 USA.
[Levy, Efrat] NYU, Sch Med, Nathan S Kline Inst Psychiat Res, Dept Pharmacol, Orangeburg, NY USA.
[Li, Faqiang; Vierstra, Richard D.] Univ Wisconsin, Dept Genet, Madison, WI 53706 USA.
[Li, Jun-Lin] Cent Hosp Yongzhou City, Dept Gen Surg, Yongzhou City, Hunan, Peoples R China.
[Li, Sheng] Inst Plant Physiol & Ecol, Key Lab Insect Dev & Evolutionary Biol, Shanghai, Peoples R China.
[Li, Weijie] Hanshan Normal Univ, Dept Chem, Chaozhou, Peoples R China.
[Li, Xue-Jun] Peking Univ, Dept Pharmacol, Sch Basic Med Sci, Beijing 100871, Peoples R China.
[Li, Yan-bo; Yin, Jia-jing] Harbin Med Univ, Affiliated Hosp 1, Dept Endocrinol, Harbin, Peoples R China.
[Li, Yi-Ping] Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX USA.
[Liang, Chengyu; Ou, Jing-hsiung James] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90033 USA.
[Liang, Qiangrong] Univ S Dakota, Sanford Sch Med, Sioux Falls, SD USA.
[Liang, Qiangrong] Univ S Dakota, Sanford Res, Cardiovasc Hlth Res Ctr, Sioux Falls, SD USA.
[Liao, Yung-Feng] Acad Sinica, Inst Cellular & Organism Biol, Taipei 115, Taiwan.
[Liberski, Pawel P.; Sikorska, Beata] Med Univ Lodz, Dept Mol Pathol & Neuropathol, Lodz, Poland.
[Lim, Hyunjung J.] Konkuk Univ, Dept Biomed Sci & Technol, Seoul, South Korea.
[Lim, Kah-Leong; Pervaiz, Shazib; Soong, Tuck Wah] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117595, Singapore.
[Lim, Kyu] Chungnam Natl Univ, Coll Med, Dept Biochem, Canc Res Inst, Taejon, South Korea.
[Lim, Kyu] Chungnam Natl Univ, Coll Med, Infect Signaling Network Res Ctr, Taejon, South Korea.
[Lin, Chiou-Feng] Natl Cheng Kung Univ, Coll Med, Inst Clin Med, Tainan 70101, Taiwan.
[Lin, Fu-Cheng] Zhejiang Univ, Inst Biotechnol, Hangzhou 310003, Zhejiang, Peoples R China.
[Lin, Jian] Peking Univ, Coll Chem & Mol Engn, Beijing NMR Ctr, Beijing 100871, Peoples R China.
[Lin, Kui] Genentech Inc, Dept Canc Signaling, San Francisco, CA 94080 USA.
[Lin, Weei-Chin] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Linden, Rafael] Univ Fed Rio de Janeiro, Inst Biophys, Rio De Janeiro, Brazil.
[Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NIH, Bethesda, MD USA.
[Lisanti, Michael P.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Stem Cell Biol, Philadelphia, PA 19107 USA.
[Lisanti, Michael P.] Univ Manchester, Breakthrough Breast Canc Res Unit, Manchester, Lancs, England.
[Liton, Paloma B.] Duke Univ, Dept Ophthalmol, Durham, NC USA.
[Liu, Chun-Feng] Soochow Univ, Dept Neurol, Affiliated Hosp 2, Suzhou, Peoples R China.
[Liu, Chun-Feng] Soochow Univ, Inst Neurosci, Suzhou, Peoples R China.
[Liu, Kaiyu] Cent China Normal Univ, Coll Life Sci, Wuhan, Peoples R China.
[Liu, Leyuan; Wang, Fen] Texas A&M Hlth Sci Ctr, Inst Biosci & Technol, Ctr Canc & StemCell Biol, Houston, TX USA.
[Liu, Qiong A.] SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA.
[Liu, Wei; Phang, James M.; Zabirnyk, Olga] NCI Frederick, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD USA.
[Lockshin, Richard A.; Melendez, Alicia; Zakeri, Zahra] CUNY, Grad Ctr, Flushing, NY USA.
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[Lopez-Otin, Carlos] Univ Oviedo, Dept Bioquim & Biol Mol, Inst Univ Oncol, Oviedo, Spain.
[Lossi, Laura; Merighi, Adalberto] Univ Turin, Turin, Italy.
[Lu, Binfeng] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA.
[Lu, Bingwei] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Lu, Bo] Thomas Jefferson Univ & Hosp, Dept Radiat Oncol, Philadelphia, PA USA.
[Macian, Fernando; Santambrogio, Laura] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA.
[MacKeigan, Jeff P.] Van Andel Res Inst, Lab Syst Biol, Grand Rapids, MI USA.
[Macleod, Kay F.] Univ Chicago, Ben May Dept Canc Res, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
[Madeo, Frank] Graz Univ, Inst Mol Biosci, Graz, Austria.
[Maiuri, Luigi] Ist Sci San Raffaele, European Inst Res Cyst Fibrosis, I-20132 Milan, Italy.
[Malagoli, Davide] Univ Modena & Reggio Emilia, Dept Biol, Modena, Italy.
[Malicdan, May Christine V.] NHGRI, Med Genet Branch & UDP Translat Med, NIH, Bethesda, MD 20892 USA.
[Malorni, Walter] San Raffaele Sulmona Inst, Laquila, Italy.
[Man, Na; Zhou, Cong-Zhao] Univ Sci & Technol China, Sch Life Sci, Hefei 230026, Anhui, Peoples R China.
[Man, Na; Zhou, Cong-Zhao] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230026, Anhui, Peoples R China.
[Mandelkow, Eva-Maria; Wang, Yipeng] CAESAR Res Ctr, Bonn, Germany.
[Mandelkow, Eva-Maria; Wang, Yipeng] DZNE German Ctr Neurodegenerat Dis, Bonn, Germany.
[Manov, Irena] Technion Israel Inst Technol, Ruth & Bruce Rappaport Fac Med, Pediat Res & Electron Microscopy Unit, Haifa, Israel.
[Mao, Xiang] Nanjing Agr Univ, Coll Vet Med, Nanjing, Jiangsu, Peoples R China.
[Mao, Zixu] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
[Marambaud, Philippe] Feinstein Inst Med Res, Manhasset, NY USA.
[Marcel, Yves L.; Ouimet, Mireille] Univ Ottawa, Inst Heart, Ottawa, ON, Canada.
[Marchbank, Katie; Waters, Sarah L.; Whitehouse, Caroline A.] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England.
[Marchetti, Piero] Univ Pisa, Dept Endocrinol & Metab, Pisa, Italy.
[Marciniak, Stefan J.] Univ Cambridge, Sch Clin Med, CIMR, Cambridge, England.
[Mardi, Mohsen] Agr Biotechnol Res Inst Iran, Dept Genom, Karaj, Iran.
[Marino, Guillermo] Inst Gustave Roussy, INSERM, U848, Paris, France.
[Markaki, Maria; Tavernarakis, Nektarios] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Crete, Greece.
[Tavernarakis, Nektarios] Univ Crete, Sch Med, Iraklion, Crete, Greece.
[Martin, Seamus J.] Trinity Coll Dublin, Smurfit Inst, Dept Genet, Dublin, Ireland.
[Martinand-Mari, Camille] Univ Montpellier 2, Inst Sci Evolut, Montpellier, France.
[Martinet, Wim] Univ Antwerp, Dept Pharmacol, B-2020 Antwerp, Belgium.
[Martinez-Vicente, Marta; Vila, Miquel] Vall dHebron Res Inst CIBERNED, Neurodegenrat Dis Res Grp, Barcelona, Spain.
[Masini, Matilde] Univ Pisa, Dept Gen Pathol, Pisa, Italy.
[Matarrese, Paola] NIH, Dept Therapeut Res & Med Evaluat, Sect Cell Aging & Degenrat, Rome, Italy.
[Matsuo, Saburo] Osaka Prefecture Univ, Grad Sch Life & Environm Biosci, Toxicol Lab, Izumisano, Japan.
[Mayer, Andreas] Univ Lausanne, Dept Biochim, Lausanne, Switzerland.
[Mazure, Nathalie M.] Univ Nice, CNRS, Ctr Antoine Lacassagne, Inst Dev Biol & Canc Res,UMR 6543, F-06034 Nice, France.
[McConkey, David J.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
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[McConnell, Melanie J.] Malaghan Inst Med Res, Wellington, New Zealand.
[McDermott, Catherine] Bond Univ, Dept Biomed Sci, Robina, Qld, Australia.
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[McKenna, Sharon L.] Natl Univ Ireland Univ Coll Cork, Cork Canc Res Ctr, Cork, Ireland.
[McLaughlin, BethAnn] Vanderbilt Univ, Dept Neurol, Nashville, TN USA.
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[Meijer, Alfred J.] Univ Amsterdam, Acad Med Ctr, Dept Med Biochem, NL-1105 AZ Amsterdam, Netherlands.
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[Melia, Thomas J.] Yale Univ, Dept Cell Biol, New Haven, CT USA.
[Melino, Gerry] Univ Roma Tor Vergata, IDI IRCCS Lab, Rome, Italy.
[Mena, Maria A.] Hosp Ramon & Cajal, Dept Neurobiol, E-28034 Madrid, Spain.
[Menendez, Javier A.] Girona Biomed Res Inst IDIBGi, Catalan Inst Oncol ICO, Catalonia, Spain.
[Menna-Barreto, Rubem F. S.] Fiocruz MS, Inst Oswaldo Cruz, Lab Biol Celular, Rio De Janeiro, RJ, Brazil.
[Menzies, Fiona M.; Moreau, Kevin; Rubinsztein, David C.] Univ Cambridge, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England.
[Mercer, Carol A.] Univ Cincinnati, Dept Hematol Oncol, Cincinnati, OH USA.
[Merry, Diane E.] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA.
[Meyer, Christian G.] Tropenmed Grundlagenforsch, Bernhard Nocht Inst Tropenmed, Hamburg, Germany.
[Miao, Chao-Yu] Second Mil Med Univ, Dept Pharmacol, Shanghai, Peoples R China.
[Miao, Jun-Ying] Shandong Univ, Sch Life Sci, Inst Dev Biol, Jinan 250100, Peoples R China.
[Michiels, Carine] Univ Namur FUNDP, URBC NARILIS, Namur, Belgium.
[Milojkovic, Ana] Max Delbruck Ctr Mol Med, Dept Mol Immunol & Gene Therapy, Berlin, Germany.
[Miracco, Clelia] Univ Siena, Dept Human Pathol & Oncol, Sect Pathol Anat, I-53100 Siena, Italy.
[Miranti, Cindy K.] Van Andel Res Inst, Lab Integrin Signaling, Grand Rapids, MI USA.
[Mitroulis, Ioannis; Ritis, Konstantinos] Democritus Univ Thrace, Dept Internal Med 1, Alexandroupolis, Greece.
[Miyazawa, Keisuke] Tokyo Med & Dent Univ, Dept Biochem, Tokyo, Japan.
[Mizushima, Noboru] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan.
[Mohseni, Simin; Stralfors, Peter] Linkoping Univ, Dept Clin & Expt Med, Div Cell Biol, Linkoping, Sweden.
[Molero, Xavier] Hosp Univ Vall dHebron, Inst Recerca, Grp Recerca Patol Pancreat, Barcelona, Spain.
[Mollereau, Bertrand] Ecole Normale Super Lyon, Lab Mol Biol Cell, CNRS, UMR 5239, F-69364 Lyon, France.
[Momoi, Takashi] Int Univ Hlth & Welf, Ctr Med Sci, Otawara, Tochigi, Japan.
[Levenson, Victor V.] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA.
[Monteiro, Mervyn J.] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Moore, Michael N.] Plymouth Marine Lab, Plymouth, Devon, England.
[Mora, Rodrigo] Univ Costa Rica, Fac Microbiol, Dept Virol, San Pedro, Costa Rica.
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[Moriyasu, Yuji] Saitama Univ, Grad Sch Sci & Engn, Dept Regulatory Biol, Saitama 3388570, Japan.
[Mostowy, Serge] Univ London Imperial Coll Sci Technol & Med, Ctr Mol Microbiol & Infect, Microbiol Sect, London, England.
[Mottram, Jeremy C.; Mueller, Sylke] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Wellcome Trust Ctr Mol Parasitol, Glasgow, Lanark, Scotland.
[Moussa, Charbel E. -H.] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20007 USA.
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[Muenger, Karl] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.
[Muenz, Christian] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland.
[Murphy, Leon O.; Nyfeler, Beat] Novartis Inst Biomed Res, Cambridge, MA USA.
[Murphy, Maureen E.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Musaro, Antonio] Univ Roma La Sapienza, DAHFMO Unit Histol & Med Embryol, Rome, Italy.
[Mysorekar, Indira] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
[Nagata, Eiichiro] Tokai Univ, Sch Med, Dept Neurol, Hiratsuka, Kanagawa 25912, Japan.
[Nagata, Kazuhiro] Kyoto Sangyo Univ, Fac Life Sci, Mol & Cellular Biol Lab, Kyoto 603, Japan.
[Nahimana, Aimable] Univ Lausanne Hosp, Cent Lab Hematol, Lausanne, Switzerland.
[Nakagawa, Toshiyuki] Gifu Univ, Grad Sch Med, Dept Neurobiol, Gifu, Japan.
[Nakano, Hiroyasu] Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan.
[Nakataogawa, Hitoshi] Tokyo Inst Technol, Frontier Res Ctr, Yokohama, Kanagawa 227, Japan.
[Nanjundan, Meera] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA.
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[Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Med, NL-6525 ED Nijmegen, Netherlands.
[Neufeld, Thomas P.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA.
[Ney, Paul A.] New York Blood Ctr, Dept Cell & Mol Biol, Lindsley F Kimball Res Inst, New York, NY 10021 USA.
[Huu Phuc Nguyen] Univ Tubingen, Dept Med Genet, Tubingen, Germany.
[Nie, Daotai] So Illinois Univ, Sch Med, Simmons Canc Inst, Dept Med Microbiol Immunol & Cell Biol, Springfield, IL USA.
[Nishino, Ichizo; Noguchi, Satoru] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo 187, Japan.
[Nislow, Corey] Univ Toronto, Donnelly Ctr, Toronto, ON, Canada.
[Nislow, Corey] Univ Toronto, Best Dept Med Res, Toronto, ON, Canada.
[Nislow, Corey] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Notterpek, Lucia] Univ Florida, Coll Med, Dept Neurosci, McKnight Brain Inst, Gainesville, FL 32610 USA.
[Novak, Ivana] Univ Split, Sch Med, Split, Croatia.
[Nozaki, Tomoyoshi] Natl Inst Infect Dis, Dept Parasitol, Tokyo, Japan.
[Nozaki, Tomoyoshi] Univ Tsukuba, Ibaraki, Japan.
[Nukina, Nobuyuki] RIKEN, Brain Sci Inst, Lab Struct Neuropathol, Wako, Saitama, Japan.
[Nuernberger, Thorsten] Univ Tubingen, Ctr Plant Mol Biol, Tubingen, Germany.
[Oberley, Terry D.] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA.
[Oberley, Terry D.] Univ Wisconsin, Dept Lab Med, Madison, WI USA.
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[Ogawa, Michinaga; Sasakawa, Chihiro] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Tokyo, Japan.
[Ohashi, Toya; Shimada, Yohta] Jikei Univ, Sch Med, Inst DNA Med, Dept Gene Therapy, Tokyo, Japan.
[Ohashi, Toya] Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan.
[Okamoto, Koji] Osaka Univ, Grad Sch Frontier Biosci, Lab Mitochondrial Dynam, Osaka, Japan.
[Oleinick, Nancy L.; Welford, Scott M.] Case Western Reserve Univ, Dept Radiat Oncol, Cleveland, OH 44106 USA.
[Oleinick, Nancy L.] Case Western Reserve Univ, Dept Biochem & Environm Hlth Sci, Cleveland, OH 44106 USA.
[Olsson, Stefan] Univ Copenhagen, Dept Agr & Ecol, Frederiksberg C, Denmark.
[Opota, Onya] Ecole Polytech Fed Lausanne, Sch Life Sci, Global Hlth Inst, Lausanne, Switzerland.
[Osborne, Timothy F.] Sanford Burnham Med Res Inst, Orlando, FL USA.
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[Otsu, Kinya; Waters, Sarah L.] Kings Coll London, Div Cardiovasc, London WC2R 2LS, England.
[Paganetti, Paolo] Ecole Polytech Fed Lausanne, AC Immune SA, Lausanne, Switzerland.
[Pallet, Nicolas] Univ Paris 05, INSERM, U775, Paris, France.
[Palmer, Glen E.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA.
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[Pandey, Udai Bhan] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA.
[Papassideri, Issidora] Univ Athens, Dept Cell Biol & Biophys, Athens, Greece.
[Paris, Irmgard] Univ Chile, Fac Med, Santiago 7, Chile.
[Paris, Irmgard] Santo Tomas Univ, Vina Del Mar, Chile.
[Park, Junsoo] Yonsei Univ, Div Biol Sci & Technol, Wonju, South Korea.
[Patschan, Susann] Univ Gottingen, Dept Internal Med, Niedersachsen, Germany.
[Patterson, Cam] Univ N Carolina, UNC Mcallister Heart Inst, Chapel Hill, NC USA.
[Pawelek, John M.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA.
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[Peng, Jianxin] Cent China Normal Univ, Inst Entomol, Wuhan, Peoples R China.
[Perlmutter, David H.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
[Perlmutter, David H.] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Perrotta, Ida] Univ Calabria, Dept Ecol, I-87036 Arcavacata Di Rende, CS, Italy.
[Perry, George] Univ Texas San Antonio, Coll Sci, Dept Biol, San Antonio, TX USA.
[Pervaiz, Shazib; Wang, Mei] Duke NUS Grad Med Sch, Canc & Stem Cell Biol Program, Singapore, Singapore.
[Peter, Matthias] ETH, Inst Biochem, Zurich, Switzerland.
[Peters, Godefridus J.] Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands.
[Petersen, Morten] Univ Copenhagen, Dept Biol, Copenhagen, Denmark.
[Petrovski, Goran] Univ Debrecen, Med & Hlth Sci Ctr, Dept Ophthalmol, H-4012 Debrecen, Hungary.
[Petrovski, Goran] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary.
[Pierrefite-Carle, Valerie] Univ Nice Sophia Antipolis, Fac Med, CNRS, GePITOs,UMR 6235, Nice, France.
[Pierron, Gerard] Inst Gustave Roussy, CNRS, UMR 8122, Villejuif, France.
[Pinkas-Kramarski, Ronit] Tel Aviv Univ, Dept Neurobiol, IL-69978 Tel Aviv, Israel.
[Piras, Antonio] Univ Turin, NICO, Orbassano, TO, Italy.
[Piri, Natik] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA.
[Platanias, Leonidas C.; Shanmugam, Mala] Northwestern Univ, Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA.
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[Poeggeler, Stefanie] Univ Gottingen, Inst Microbiol & Genet, Dept Genet Eukaryot Microogranisms, Gottingen, Germany.
[Poirot, Marc] Inst Claudius Regaud, Toulouse, France.
[Poletti, Angelo] Univ Milan, Dipartimento Endocrinol Fisiopatol & Biol Applica, Ctr Eccellenza Malattie Neurodegenerat, Milan, Italy.
[Poues, Christian] Univ Paris 11, EA4530, Chatenay Malabry, France.
[Pozuelo-Rubio, Mercedes] CSIC, Ctr Andaluz Biol Mol & Med Regenerat, E-41080 Seville, Spain.
[Praetorius-Ibba, Mette] Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA.
[Prasad, Anil] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Med Ctr,Div Expt Med, Boston, MA 02215 USA.
[Produit-Zengaffinen, Nathalie; Schorderet, Daniel F.] IRO, Sion, Switzerland.
[Progulske-Fox, Ann] Univ Florida, Dept Oral Biol, Gainesville, FL 32610 USA.
[Progulske-Fox, Ann] Univ Florida, Ctr Mol Microbiol, Gainesville, FL 32610 USA.
[Proikas-Cezanne, Tassula] Univ Tubingen, Dept Mol Biol, Tubingen, Germany.
[Przedborski, Serge] Columbia Univ, Ctr Motor Neuron Biol & Dis, New York, NY USA.
[Przyklenk, Karin] Wayne State Univ, Sch Med, Cardiovasc Res Inst, Detroit, MI USA.
[Przyklenk, Karin] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA.
[Przyklenk, Karin] Wayne State Univ, Sch Med, Dept Emergency Med, Detroit, MI USA.
[Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Qian, Shu-Bing] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Qin, Liang] Chinese Acad Med Sci, Inst Basic Med Sci, Beijing 100730, Peoples R China.
[Qin, Liang] Chinese Acad Med Sci, Sch Basic Med, Beijing 100730, Peoples R China.
[Qin, Liang] Peking Union Med Coll, Dept Physiol, Beijing 100021, Peoples R China.
[Qin, Liang] Peking Union Med Coll, Dept Pathol, Beijing 100021, Peoples R China.
[Qin, Zheng-Hong; Wang, Guanghui; Zhang, Hui-Ling] Soochow Univ, Sch Pharmaceut Sci, Dept Pharmacol, Suzhou, Peoples R China.
[Quaggin, Susan E.] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada.
[Raben, Nina] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA.
[Rabkin, Simon W.] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Rahman, Irfan] Univ Rochester, Med Ctr, Dept Environm Med, Lung Biol & Dis Program, Rochester, NY 14642 USA.
[Rami, Abdelhaq] JWG Univ, Inst Cellular & Mol Anat, Frankfurt, Germany.
[Ramm, Georg] Monash Univ, Monash Micro Imaging, Melbourne, Vic 3004, Australia.
[Randall, Glenn] Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA.
[Randow, Felix; Williams, Roger L.] MRC, Mol Biol Lab, Cambridge CB2 2QH, England.
[Rao, V. Ashutosh] US FDA, Biochem Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Rathmell, Jeffrey C.; Yao, Tso-Pang] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA.
[Ravikumar, Brinda] EMD Serono Res Inst Inc, Billerica, MA USA.
[Ray, Swapan K.] Univ S Carolina, Sch Med, Dept Microbiol Pathol & Immunol, Columbia, SC USA.
[Reed, Bruce H.] Univ Waterloo, Dept Biol, Waterloo, ON N2L 3G1, Canada.
[Regnier-Vigouroux, Anne] Johannes Gutenberg Univ Mainz, Dept Biol, Mainz, Germany.
[Regnier-Vigouroux, Anne] Johannes Gutenberg Univ Mainz, German Canc Res Ctr, Div Tumor Virol, Mainz, Germany.
[Reichert, Andreas S.] Goethe Univ Frankfurt, Zentrum Mol Med, Buchmann Inst Mol Life Sci, Frankfurt, Germany.
[Reiners, John J., Jr.] Wayne State Univ, Inst Environm Hlth Sci, Detroit, MI USA.
[Ren, Jun] Univ Wyoming, Coll Hlth Sci, Laramie, WY 82071 USA.
[Rhodes, Christopher J.] Univ Chicago, Kovler Diabet Ctr, Chicago, IL 60637 USA.
[Rizzo, Elizete] Univ Fed Minas Gerais, Dept Morfol, Belo Horizonte, MG, Brazil.
[Robbins, Jeffrey] Cincinnati Childrens Hosp, Dept Pediat, Cincinnati, OH USA.
[Roberge, Michel] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada.
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[Rocchi, Stephane] CHU Nice, Hop Archet 2, Serv Dermatol, Nice, France.
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[Younes, Anas] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA.
[Yu, Long] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Yuan, Zhi-Min] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, San Antonio, TX 78229 USA.
[Yue, Zhenyu] Mt Sinai Sch Med, Friedman Brain Inst, Dept Neurol & Neurosci, New York, NY USA.
[Yun, Cheol-Heui] Seoul Natl Univ, Grad Sch Agr Biotechnol, Seoul, South Korea.
[Yuzaki, Michisuke] Keio Univ, Sch Med, Dept Neurophysiol, Tokyo, Japan.
NCI Frederick, Metab & Canc Susceptibil Sect, Lab Comparat Carcinogenesis, Ctr Canc Res,NIH, Frederick, MD USA.
[Zacks, David] Univ Michigan, Sch Med, Dept Ophthalmol & Visual Sci, Ann Arbor, MI USA.
[Zacksenhaus, Eldad] Univ Hlth Network, Toronto Gen Res Inst, Div Cell & Mol Biol, Toronto, ON, Canada.
[Zaffaroni, Nadia] Ist Nazl Tumori, Fdn IRCCS, Dept Expt Oncol & Mol Med, I-20133 Milan, Italy.
[Zeh, Herbert J., III] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Zeitlin, Scott O.] Univ Virginia, Dept Neurosci, Charlottesville, VA USA.
[Zhang, Hong] Natl Inst Biol Sci, Beijing, Peoples R China.
[Zhang, Hui-Ling] Soochow Univ, Coll Pharmaceut Sci, Lab Cerebrovasc Pharmacol, Suzhou, Peoples R China.
[Zhang, Lin] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA.
[Zhang, Long] Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands.
[Zhang, Ming-Yong] Chinese Acad Sci, S China Bot Garden, Key Lab Plant Resources Conservat & Sustainable U, Guangzhou, Guangdong, Peoples R China.
[Zhang, Xu Dong] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW 2308, Australia.
[Zhao, Ying] Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China.
[Zhao, Ying; Zhu, Wei-Guo] Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China.
[Zhao, Zhizhuang J.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[Zheng, Xiaoxiang] Zhejiang Univ, Qiushi Acad Adv Studies, Hangzhou 310003, Zhejiang, Peoples R China.
[Zhong, Qing] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Zhu, Changlian] Univ Gothenburg, Inst Neurosci & Physiol, Ctr Brain Repair & Rehabil, Gothenburg, Sweden.
[Zhu, Xiao-Feng] Sun Yat Sen Univ, Dept Med Oncol, State Key Lab Oncol S China, Guangzhou 510275, Guangdong, Peoples R China.
[Zong, Wei-Xing] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
[Zorzano, Antonio] Univ Barcelona, Barcelona, Spain.
[Zorzano, Antonio] CIBERDEM, Inst Res Biomed, Barcelona, Spain.
[Zschocke, Juergen] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Zuckerbraun, Brian] Univ Pittsburgh, Med Ctr, Dept Gen Surg, Pittsburgh, PA USA.
[Zuckerbraun, Brian] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Klionsky, DJ (reprint author), Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
EM klionsky@umich.edu
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Lingor, Paul/0000-0001-9362-7096; Jung, Yong-Keun/0000-0002-9686-3120;
Hwang, Seungmin/0000-0003-0846-5462; Clague,
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Zacks, David/0000-0001-8592-5165; Chen, Quan/0000-0001-7539-8728; Kim,
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Engelbrecht, Anna-Mart/0000-0003-1469-0148; Berliocchi,
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Helmut/0000-0002-1167-2676; Schiaffino, Stefano/0000-0002-5607-6421;
MATTEONI, RAFAELE/0000-0002-0314-5948
FU National Institutes of Health Public Health Service [GM53396]
FX In a rapidly expanding and highly dynamic field such as autophagy, it is
possible that some authors who should have been included on this
manuscript have been missed. D.J.K. extends his apologies to researchers
in the field of autophagy who, due to oversight or any other reason,
could not be included. This work was supported by National Institutes of
Health Public Health Service grant GM53396 to D.J.K. Due to space and
other limitations, it is not possible to include all other sources of
financial support.
NR 884
TC 1731
Z9 1809
U1 285
U2 2268
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD APR
PY 2012
VL 8
IS 4
BP 445
EP 544
DI 10.4161/auto.19496
PG 100
WC Cell Biology
SC Cell Biology
GA 960QQ
UT WOS:000305403400002
PM 22966490
ER
PT J
AU Gregori, L
Yang, H
Anderson, S
AF Gregori, Luisa
Yang, Hong
Anderson, Steven
TI Estimation of variant Creutzfeldt-Jakob disease infectivity titers in
human blood
SO PRION
LA English
DT Meeting Abstract
C1 [Gregori, Luisa; Yang, Hong; Anderson, Steven] US FDA, Rockville, MD 20857 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6896
J9 PRION
JI Prion
PD APR-JUN
PY 2012
VL 6
SU S
BP 139
EP 139
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 944WK
UT WOS:000304234300287
ER
PT J
AU Yang, H
Gregori, L
Asher, D
Piccardo, P
Anderson, S
AF Yang, Hong
Gregori, Luisa
Asher, David
Piccardo, Pedro
Anderson, Steven
TI Validation of a risk assessment model of variant Creutzfeldt-Jakob
disease (VCJD) transmission via red cell transfusion
SO PRION
LA English
DT Meeting Abstract
C1 [Yang, Hong; Gregori, Luisa; Asher, David; Piccardo, Pedro; Anderson, Steven] US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6896
J9 PRION
JI Prion
PD APR-JUN
PY 2012
VL 6
SU S
BP 139
EP 140
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 944WK
UT WOS:000304234300289
ER
PT J
AU McCabe, J
Moratz, C
Liu, YB
Burton, E
Morgan, A
Budinich, C
Lowe, D
Rosenberger, J
Chen, HZ
Liu, J
Myers, M
AF McCabe, Joseph
Moratz, Chantal
Liu, Yunbo
Burton, Ellen
Morgan, Amy
Budinich, Craig
Lowe, Dennell
Rosenberger, John
Chen, HuaZhen
Liu, Jiong
Myers, Matthew
TI High-intensity focused ultrasound (HIFU) exposure as a model for
mechanically-induced mild blast brain injury in rodents
SO BRAIN INJURY
LA English
DT Meeting Abstract
C1 [McCabe, Joseph; Moratz, Chantal; Burton, Ellen; Morgan, Amy; Budinich, Craig; Lowe, Dennell; Rosenberger, John; Chen, HuaZhen; Liu, Jiong] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Liu, Yunbo; Myers, Matthew] US FDA, White Oak, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0269-9052
J9 BRAIN INJURY
JI Brain Inj.
PD APR-MAY
PY 2012
VL 26
IS 4-5
MA 0473
BP 547
EP 548
PG 2
WC Neurosciences; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 943EZ
UT WOS:000304104600429
ER
PT J
AU Nakashima, H
Husain, SR
Puri, RK
AF Nakashima, Hideyuki
Husain, Syed R.
Puri, Raj K.
TI IL-13 receptor-directed cancer vaccines and immunotherapy
SO IMMUNOTHERAPY
LA English
DT Review
DE combination therapy; DNA vaccine; IL-13 receptor alpha 2; immunotoxin;
myeloid-derived suppressor cells
ID MYELOID SUPPRESSOR-CELLS; REGULATORY T-CELLS; GLIOMA-ASSOCIATED
ANTIGENS; MURINE TUMOR-MODELS; INTERLEUKIN-13 RECEPTOR; ALPHA-2 CHAIN;
PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; IMMUNE-RESPONSE; ANTICANCER
THERAPY
AB Many immunotherapy approaches including therapeutic cancer vaccines targeting specific tumor-associated antigens are at various stages of development. Although the significance of overexpression of (IL-13R alpha 2) in cancer is being actively investigated, we have reported that IL-13R alpha 2 is a novel tumor-associated antigen. The IL-13R alpha 2-directed cancer vaccine is one of the most promising approaches to tumor immunotherapy, because of the selective expression of IL-13R alpha 2 in various solid tumor types but not in normal tissues. In this article, we will summarize its present status and potential strategies to improve IL-13R alpha 2-directed cancer vaccines for an optimal therapy of cancer.
C1 [Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM raj.puri@fda.hhs.gov
NR 79
TC 10
Z9 10
U1 0
U2 2
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-743X
J9 IMMUNOTHERAPY-UK
JI Immunotherapy
PD APR
PY 2012
VL 4
IS 4
BP 443
EP 451
DI 10.2217/IMT.12.28
PG 9
WC Immunology
SC Immunology
GA 937VP
UT WOS:000303691400017
PM 22512637
ER
PT J
AU Ahn, Y
Sung, K
Rafii, F
Cerniglia, CE
AF Ahn, Youngbeom
Sung, Kidon
Rafii, Fatemeh
Cerniglia, Carl E.
TI Effect of sterilized human fecal extract on the sensitivity of
Escherichia coli ATCC 25922 to enrofloxacin
SO JOURNAL OF ANTIBIOTICS
LA English
DT Article
DE enrofloxacin; E. coli; fluoroquinolone; sterilized human fecal extract
ID ENTERICA SEROVAR TYPHIMURIUM; HUMAN INTESTINAL MICROFLORA;
FLUOROQUINOLONE-RESISTANCE; SALMONELLA-ENTERICA; ANTIMICROBIAL
RESISTANCE; LIQUID-CHROMATOGRAPHY; MEMBRANE-LIPIDS; DIGESTIVE-TRACT;
GYRA MUTATIONS; ACTIVE EFFLUX
AB The ingestion of antimicrobial residues in foods of animal origin has the potential risk of exposing colonic bacteria to small concentrations of antibiotics and inducing resistance in the colonic bacteria. To investigate whether human intestinal contents would influence resistance development in bacteria, Escherichia coli ATCC 25922 (MIC of enrofloxacin <0.03 mu g ml(-1)) was exposed to 0.01 to 1 mu g ml(-1) of enrofloxacin in media supplemented with glucose, sucrose, sodium acetate or sterilized human fecal extract. In the first passage, only the medium containing sterilized fecal extract supported the growth of E. coli at an enrofloxacin concentration equal to the MIC. In the second and third passages following exposure to sub-inhibitory concentrations of the drug, the bacteria in media containing sterilized fecal extract grew at 0.1 mu g ml(-1) of enrofloxacin. The efflux pump inhibitors, reserpine and carbonyl cyanide-m-chlorophenylhydrazone (CCCP), increased the sensitivity of bacteria to 0.1 mu g ml(-1) of enrofloxacin in the medium containing sucrose, but their effect was not observed in the medium supplemented with 2.5% sterilized fecal extract. The proportions of unsaturated and saturated fatty acids in E. coli grown in the medium with 2.5% sterilized fecal extract differed from those grown in the medium alone. Fecal extract may contain unknown factors that augment the ability of E. coli to grow in concentrations of enrofloxacin higher than MIC, both in the presence and absence of efflux pump inhibitors. This is the first study showing that fecal extract affects the level of sensitivity of E. coli to antimicrobial agents. The Journal of Antibiotics (2012) 65, 179-184; doi: 10.1038/ja.2012.1; published online 25 January 2012
C1 [Ahn, Youngbeom; Sung, Kidon; Rafii, Fatemeh; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Ahn, Y (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM young.ahn@fda.hhs.gov
NR 42
TC 3
Z9 3
U1 0
U2 10
PU JAPAN ANTIBIOTICS RESEARCH ASSOC
PI TOKYO
PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO, 141, JAPAN
SN 0021-8820
J9 J ANTIBIOT
JI J. Antibiot.
PD APR
PY 2012
VL 65
IS 4
BP 179
EP 184
DI 10.1038/ja.2012.1
PG 6
WC Biotechnology & Applied Microbiology; Immunology; Microbiology;
Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Immunology; Microbiology;
Pharmacology & Pharmacy
GA 935TD
UT WOS:000303542700002
PM 22274703
ER
PT J
AU Navarro, VJ
Barnhart, HX
Bonkovsky, HL
Reddy, KR
Seeff, L
Serrano, J
Talwalkar, JA
Vega, M
Vuppalanchi, R
AF Navarro, V. J.
Barnhart, H. X.
Bonkovsky, H. L.
Reddy, K. R.
Seeff, L.
Serrano, J.
Talwalkar, J. A.
Vega, M.
Vuppalanchi, R.
CA DILIN Investigators
TI DIAGNOSING HEPATOTOXICITY ATTRIBUTABLE TO HERBAL & DIETARY SUPPLEMENTS
(HDS): TEST-RETEST RELIABILITY OF A NOVEL CAUSALITY ASSESSMENT TOOL
SO JOURNAL OF HEPATOLOGY
LA English
DT Meeting Abstract
CT 47th Annual Meeting of the
European-Association-for-the-Study-of-the-Liver (EASL)
CY APR 18-22, 2012
CL Barcelona, SPAIN
SP European Assoc Study Liver (EASL)
C1 [Navarro, V. J.; Vega, M.] Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA.
[Barnhart, H. X.] Duke Clin Res Inst, Dept Biostat & Bioinformat, Durham, NC USA.
[Bonkovsky, H. L.] Carolinas Med Ctr & HealthCare Syst, Charlotte, NC USA.
[Reddy, K. R.] Univ Penn, Div Gastroenterol & Hepatol, Philadelphia, PA 19104 USA.
[Seeff, L.] US FDA, Silver Spring, MD USA.
[Serrano, J.] NIDDK, Div Digest Dis & Nutr, Bethesda, MD USA.
[Talwalkar, J. A.] Mayo Clin, Rochester, MN USA.
[Vuppalanchi, R.] Indiana Univ, Div Gastroenterol & Hepatol, Indianapolis, IN 46204 USA.
EM victor.navarro@jefferson.edu
NR 0
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD APR
PY 2012
VL 56
SU 2
MA 1364
BP S536
EP S536
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 931TD
UT WOS:000303241303039
ER
PT J
AU Micallef, SA
Goldstein, RER
George, A
Kleinfelter, L
Boyer, MS
McLaughlin, CR
Estrin, A
Ewing, L
Beaubrun, JJG
Hanes, DE
Kothary, MH
Tall, BD
Razeq, JH
Joseph, SW
Sapkota, AR
AF Micallef, Shirley A.
Goldstein, Rachel E. Rosenberg
George, Ashish
Kleinfelter, Lara
Boyer, Marc S.
McLaughlin, Cristina R.
Estrin, Andrew
Ewing, Laura
Beaubrun, Junia Jean-Gilles
Hanes, Darcy E.
Kothary, Mahendra H.
Tall, Ben D.
Razeq, Jafar H.
Joseph, Sam W.
Sapkota, Amy R.
TI Occurrence and antibiotic resistance of multiple Salmonella serotypes
recovered from water, sediment and soil on mid-Atlantic tomato farms
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Salmonella; Tomatoes; Antibiotic resistance; Immunocapture method; Food
safety
ID UNITED-STATES; RELATIVE-HUMIDITY; RAW TOMATOES; SURVIVAL; ENTERICA;
PLANTS; TEMPERATURE; PERSISTENCE; DIVERSITY; OUTBREAKS
AB Salmonella outbreaks associated with the consumption of raw tomatoes have been prevalent in recent years. However, sources of Salmonella contamination of tomatoes remain poorly understood. The objectives of this study were to identify ecological reservoirs of Salmonella on tomato farms, and to test antimicrobial susceptibilities of recovered Salmonella isolates. Fourteen Mid-Atlantic tomato farms in the U.S. were sampled in 2009 and 2010. Groundwater, irrigation pond water, pond sediment, irrigation ditch water, rhizosphere and irrigation ditch soil, leaves, tomatoes, and swabs of harvest bins and worker sanitary facilities were analyzed for Salmonella using standard culture methods and/or a flow-through immunocapture method. All presumptive Salmonella isolates (n=63) were confirmed using PCR and the Vitek (R) 2 Compact System, and serotyped using the Premi (R) Test Salmonella and a conventional serotyping method. Antimicrobial susceptibility testing was carried out using the Sensititre (TM) microbroth dilution system. Four of the 14 farms (29%) and 12 out of 1,091 samples (1.1%) were found to harbor Salmonella enterica subsp. enterica. Salmonella was isolated by the immunocapture method from soil, while the culture method recovered isolates from irrigation pond water and sediment, and irrigation ditch water. No Salmonella was detected on leaves or tomatoes. Multiple serotypes were identified from soil and water, four of which-S. Braenderup, S. Javiana, S. Newport and S. Typhimurium have been previously implicated in Salmonella outbreaks associated with tomato consumption. Resistance to sulfisoxazole was prevalent and some resistance to ampicillin, cefoxitin, amoxicillin/clavulanic acid, and tetracycline was also observed. This study implicates irrigation water and soil as possible reservoirs of Salmonella on tomato farms and irrigation ditches as ephemeral habitats for Salmonella. The findings point to the potential for pre-harvest contamination of tomatoes from contaminated irrigation water or from soil or water splash from irrigation ditches onto low-lying portions of tomato plants. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Micallef, Shirley A.; Goldstein, Rachel E. Rosenberg; George, Ashish; Kleinfelter, Lara; Joseph, Sam W.; Sapkota, Amy R.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA.
[Micallef, Shirley A.] Univ Maryland, Coll Agr & Nat Resources, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA.
[Micallef, Shirley A.] Univ Maryland, Coll Agr & Nat Resources, Ctr Food Safety & Secur Syst, College Pk, MD 20742 USA.
[Boyer, Marc S.] US FDA, Off Food Def Commun & Emergency Response, CFSAN, College Pk, MD 20740 USA.
[McLaughlin, Cristina R.; Estrin, Andrew] US FDA, Off Regulat Policy & Social Sci, CFSAN, College Pk, MD 20740 USA.
[Ewing, Laura; Beaubrun, Junia Jean-Gilles; Hanes, Darcy E.; Kothary, Mahendra H.; Tall, Ben D.] US FDA, Virulence Mech Branch, Div Virulence Assessment, OARSA,CFSAN, Laurel, MD 20708 USA.
[Razeq, Jafar H.] Maryland Dept Hlth & Mental Hyg, Labs Adm, Baltimore, MD 21201 USA.
RP Sapkota, AR (reprint author), Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, 2234P SPH Bldg, College Pk, MD 20742 USA.
EM ars@umd.edu
RI Sapkota, Amy/A-6046-2011;
OI Tall, Ben/0000-0003-0399-3629
FU University of Maryland; Joint Institute for Food Safety and Applied
Nutrition; Centers for Disease Control and Prevention (CDC)
[5U01CI000310]
FX This research was supported by the University of Maryland, Joint
Institute for Food Safety and Applied Nutrition and Grant/Cooperative
Agreement Number 5U01CI000310 from the Centers for Disease Control and
Prevention (CDC). Its contents are solely the responsibility of the
authors and do not necessarily represent the official views of CDC. The
funding sources played no role in the study design; data collection,
analysis and interpretation; manuscript writing; and decision to submit
the manuscript for publication.
NR 35
TC 34
Z9 34
U1 2
U2 40
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
J9 ENVIRON RES
JI Environ. Res.
PD APR
PY 2012
VL 114
BP 31
EP 39
DI 10.1016/j.envres.2012.02.005
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA 925ML
UT WOS:000302765200004
PM 22406288
ER
PT J
AU Dave, D
Brown, J
Gallauresi, B
AF Dave, Dipali
Brown, Jill
Gallauresi, Beverly
TI An FDA ten year review of clinical trials for approved medical devices
for women
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Dave, Dipali; Gallauresi, Beverly] US FDA, Off Womens Hlth, Silver Spring, MD USA.
[Brown, Jill] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD APR
PY 2012
VL 21
IS 4
MA P48
BP 19
EP 20
PG 2
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 926UE
UT WOS:000302856600049
ER
PT J
AU Otugo, O
Ogundare, O
Vaughan, C
Fadiran, E
Sahin, L
AF Otugo, Onyekachi
Ogundare, Olabode
Vaughan, Christopher
Fadiran, Emmanuel
Sahin, Leyla
TI Consistency of Pregnancy Labeling Across Different Therapeutic Classes
SO JOURNAL OF WOMENS HEALTH
LA English
DT Meeting Abstract
C1 [Otugo, Onyekachi; Ogundare, Olabode; Vaughan, Christopher; Fadiran, Emmanuel] US FDA, Off Womens Hlth, Silver Spring, MD USA.
[Sahin, Leyla] US FDA, Pediat & Maternal Hlth Staff, Maternal Hlth Team, CDER, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD APR
PY 2012
VL 21
IS 4
MA P102
BP 39
EP 39
PG 1
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 926UE
UT WOS:000302856600103
ER
PT J
AU Cho, YS
Dobos, KM
Prenni, J
Yang, HL
Hess, A
Rosenkrands, I
Andersen, P
Ryoo, SW
Bai, GH
Brennan, MJ
Izzo, A
Bielefeldt-Ohmann, H
Belisle, JT
AF Cho, Yun Sang
Dobos, Karen M.
Prenni, Jessica
Yang, Hongliang
Hess, Ann
Rosenkrands, Ida
Andersen, Peter
Ryoo, Sung Weon
Bai, Gill-Han
Brennan, Michael J.
Izzo, Angelo
Bielefeldt-Ohmann, Helle
Belisle, John T.
TI Deciphering the proteome of the in vivo diagnostic reagent "purified
protein derivative" from Mycobacterium tuberculosis
SO PROTEOMICS
LA English
DT Article
DE DTH; Microbiology; Mycobacterium tuberculosis; PPD
ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; DELAYED-TYPE HYPERSENSITIVITY;
HEAT-SHOCK PROTEINS; MASS-SPECTROMETRY; ACTIVE PROTEIN; CLINICAL
ISOLATE; GUINEA-PIGS; PPD RT23; BCG; IDENTIFICATION
AB Purified protein derivative (PPD) has served as a safe and effective diagnostic reagent for 60 years and is the only broadly available material to diagnose latent tuberculosis infections. This reagent is also used as a standard control for a number of in vitro immunological assays. Nevertheless, the molecular composition and specific products that contribute to the extraordinary immunological reactivity of PPD are poorly defined. Here, a proteomic approach was applied to elucidate the gene products in the U.S. Food and Drug Administration (FDA) standard PPD-S2. Many known Mycobacterium tuberculosis T-cell antigens were detected. Of significance, four heat shock proteins (HSPs) (GroES, GroEL2, HspX, and DnaK) dominated the composition of PPD. The chaperone activities and capacity of these proteins to influence immunological responses may explain the exquisite solubility and immunological potency of PPD. Spectral counting analysis of three separate PPD reagents revealed significant quantitative variances. Gross delayed-type hypersensitivity (DTH) responses in M. tuberculosis infected guinea pigs were comparable among these PPD preparations; however, detailed histopathology of the DTH lesions exposed unique differences, which may be explained by the variability observed in the presence and abundance of early secretory system (Esx) proteins. Variability in PPD reagents may explain differences in DTH responses reported among populations.
C1 [Cho, Yun Sang; Dobos, Karen M.; Yang, Hongliang; Izzo, Angelo; Bielefeldt-Ohmann, Helle; Belisle, John T.] Colorado State Univ, Mycobacteria Res Labs, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Prenni, Jessica] Colorado State Univ, Prote & Metabol Facil, Ft Collins, CO 80523 USA.
[Hess, Ann] Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA.
[Rosenkrands, Ida; Andersen, Peter] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen, Denmark.
[Ryoo, Sung Weon; Bai, Gill-Han] Korea Inst TB, Seoul, South Korea.
[Brennan, Michael J.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Belisle, JT (reprint author), Colorado State Univ, Mycobacteria Res Labs, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
EM jbelisle@colostate.edu
RI Belisle, John/B-8944-2017; Dobos, Karen/D-1170-2017; Izzo,
Angelo/F-1229-2017;
OI Belisle, John/0000-0002-2539-2798; Dobos, Karen/0000-0001-7115-8524;
Izzo, Angelo/0000-0003-3208-2330; Cho, Yun Sang/0000-0003-1346-7067;
Prenni, Jessica/0000-0002-0337-8450
FU NIH; NIAID [N01-AI-75320, N01-AI40091c]; Monfort Professorship; Korea
Research Foundation Grant (MOEHRD) [KRF-2004-214-E00034]
FX The authors wish to thank Preston Hill for assistance with mass
spectrometry. This work was supported by the NIH, NIAID Contract
N01-AI-75320 (JTB), NIH, NIAID contract N01-AI40091c (KMD), and a
Monfort Professorship (JTB). YSC was supported by the Postdoctoral
Fellowship Program of Korea Research Foundation Grant (MOEHRD, Basic
Research Promotion Fund) KRF-2004-214-E00034. PRoteomics IDEntifications
database (PRIDE) data conversions and storage made available at
http://www.ebi.ac.uk/pride/; PMID accession # 19587657.
NR 73
TC 16
Z9 18
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD APR
PY 2012
VL 12
IS 7
BP 979
EP 991
DI 10.1002/pmic.201100544
PG 13
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 929IA
UT WOS:000303053300008
PM 22522804
ER
PT J
AU Nemes, P
Vertes, A
AF Nemes, Peter
Vertes, Akos
TI Ambient mass spectrometry for in vivo local analysis and in situ
molecular tissue imaging
SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY
LA English
DT Article
DE Chemical imaging; Direct analysis; In situ analysis; In vivo analysis;
Mass spectrometry; Metabolomics; Molecular imaging; Peptidomics;
Single-cell analysis; Tissue analysis
ID DESORPTION ELECTROSPRAY-IONIZATION; SURFACE SAMPLING/IONIZATION
TECHNIQUES; TEMPERATURE PLASMA PROBE; ATMOSPHERIC-PRESSURE;
LASER-ABLATION; BIOLOGICAL TISSUES; CHEMICAL-IONIZATION; SINGLE CELLS;
HUMAN SKIN; METABOLITES
AB Recent technical innovations in mass spectrometry (MS) have extended the application of this powerful technique to direct chemical analysis at atmospheric pressure. These innovations have created an opportunity to appreciate the chemistry of biological systems in their native state, so tissues and single cells of plant, animal, or human origin can be interrogated in situ and in vivo.
Ambient MS also allows label-free detection of compounds and gives unique insights into temporal changes and tissue architecture in two and three dimensions. Compounds studied range from natural products (e.g., neurotransmitters, metabolites, organic acids, polyamines, sugars, lipids, and peptides) to xenobiotics (e.g., pharmaceuticals), dyes, polymers, explosives, and toxins.
This critical review covers analytical trends in ambient MS. Our discussions primarily touch on the mechanisms of sampling and the bioanalytical implications for in situ and in vivo experiments. We pay special attention to lateral imaging, depth profiling, and three-dimensional-MS imaging, all while working under atmospheric conditions. Our closing remarks highlight some of the present analytical challenges and developmental opportunities in this field. Published by Elsevier Ltd.
C1 [Nemes, Peter] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Silver Spring, MD 20993 USA.
[Vertes, Akos] George Washington Univ, Dept Chem, WM Keck Inst Prote Technol & Applicat, Washington, DC 20052 USA.
RP Nemes, P (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, 10903 New Hampshire Ave,Bldg 64,Room 3068, Silver Spring, MD 20993 USA.
EM Peter.Nemes@fda.hhs.gov
RI Vertes, Akos/B-7159-2008; Nemes, Peter/C-3145-2008
OI Vertes, Akos/0000-0001-5186-5352;
FU NSF [0719232]; DOE [DEFG02-01ER15129]; GWU
FX The views and conclusions expressed herein are solely those of the
authors and should not be construed to represent the Food and Drug
Administration, US National Science Foundation (NSF), US Department of
Energy (DOE), or The George Washington University (GWU). The mention of
commercial products, their sources, or their use in connection with
material reported herein is not to be construed as either actual or
implied endorsement of such products by the Department of Health and
Human Services. AV acknowledges financial support from the NSF (Grant
0719232), the DOE (Grant DEFG02-01ER15129), and the GWU Signature
Program. PN thanks Dinesh V. Patwardhan (FDA), Benita J. Dair (FDA),
Kenneth S. Phillips (FDA), and Martin K. McDermott (FDA) for their
assistance during the preparation of this publication.
NR 82
TC 77
Z9 79
U1 12
U2 160
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0165-9936
J9 TRAC-TREND ANAL CHEM
JI Trac-Trends Anal. Chem.
PD APR
PY 2012
VL 34
BP 22
EP 34
DI 10.1016/j.trac.2011.11.006
PG 13
WC Chemistry, Analytical
SC Chemistry
GA 928IP
UT WOS:000302976700012
ER
PT J
AU Azziz-Baumgartner, E
Luber, G
Conklin, L
Tosteson, TR
Granade, HR
Dickey, RW
Backer, LC
AF Azziz-Baumgartner, Eduardo
Luber, George
Conklin, Laura
Tosteson, Thomas R.
Granade, Hudson R.
Dickey, Robert W.
Backer, Lorraine C.
TI Assessing the Incidence of Ciguatera Fish Poisoning with Two Surveys
Conducted in Culebra, Puerto Rico, during 2005 and 2006
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE ciguatera; ciguatera fish poisoning; ciguatoxins; incidence; poisoning;
Puerto Rico; seafood
ID VIRGIN-ISLANDS; UNITED-STATES; HEALTH
AB BACKGROUND: Although ciguatera fish poisoning (CFP) is the most common seafood intoxication worldwide, its burden has been difficult to establish because there are no biomarkers to diagnose human exposure.
OBJECTIVE: We explored the incidence of CFP, percentage of CFP case-patients with laboratory-confirmed ciguatoxic meal remnants, cost of CFP illness, and potential risk factors for CFP.
METHODS: During 2005 and again during 2006, we conducted a census of all occupied households on the island of Culebra, Puerto Rico, where locally caught fish are a staple food. We defined CFP case-patients as persons with gastrointestinal symptoms (abdominal pain, vomiting, diarrhea, or nausea) and neurological symptoms (extremity paresthesia, arthralgia, myalgia, malaise, pruritus, headache, dizziness, metallic taste, visual disturbance, circumoral paresthesia, temperature reversal, or toothache) or systemic symptoms (e. g., bradycardia) within 72 hr of eating fish during the previous year. Participants were asked to save fish remnants eaten by case-patients for ciguatoxin analysis at the Food and Drug Administration laboratory in Dauphin Island, Alabama (USA).
RESULTS: We surveyed 340 households during 2005 and 335 households during 2006. The estimated annual incidence of possible CFP was 4.0 per 1,000 person-years, and that of probable CFP was 7.5 per 1,000 person-years. One of three fish samples submitted by probable case-patients was positive for ciguatoxins. None of the case-patients required respiratory support. Households that typically consumed barracuda were more likely to report CFP (p = 0.02).
CONCLUSIONS: Our estimates, which are consistent with previous studies using similar case findings, contribute to the overall information available to support public health decision making about CFP prevention.
C1 [Azziz-Baumgartner, Eduardo; Luber, George; Conklin, Laura; Backer, Lorraine C.] US Ctr Dis Control & Prevent, Atlanta, GA USA.
[Tosteson, Thomas R.] Univ Puerto Rico, Mayaguez, PR USA.
[Granade, Hudson R.; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA.
RP Azziz-Baumgartner, E (reprint author), 1600 Clifton Rd NE,MS A32, Atlanta, GA 30333 USA.
EM Eha9@cdc.gov
NR 25
TC 7
Z9 8
U1 0
U2 14
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 APR
PY 2012
VL 120
IS 4
BP 526
EP 529
DI 10.1289/ehp.1104003
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 921KJ
UT WOS:000302476200021
PM 22275728
ER
PT J
AU Harrington, PR
Zeng, W
Naeger, LK
AF Harrington, Patrick R.
Zeng, Wen
Naeger, Lisa K.
TI Clinical relevance of detectable but not quantifiable hepatitis C virus
RNA during boceprevir or telaprevir treatment
SO HEPATOLOGY
LA English
DT Article
ID GENOTYPE 1 INFECTION; PEGINTERFERON ALPHA-2A; HCV INFECTION; RIBAVIRIN
AB Boceprevir- and telaprevir-based treatments for chronic hepatitis C virus (HCV) infection use specific response-guided therapy (RGT) guidelines. Eligibility for shortened treatment duration is based on achieving undetectable HCV RNA early during treatment. It is unclear whether a detected HCV RNA level that is below the assay lower limit of quantitation (detectable/BLOQ) is comparable to an undetectable HCV RNA level for RGT decision making. We analyzed data from boceprevir and telaprevir clinical trials to obtain a comprehensive understanding of the frequency and clinical relevance of detectable/BLOQ HCV RNA measurements. In Phase 3 trials P05216 (boceprevir), C216 (telaprevir), and 108 (telaprevir), detectable/BLOQ levels were reported for approximately 10%-20% of all on-treatment HCV RNA measurements. In P05216 and C216, subjects with detectable/BLOQ HCV RNA, on average, had a reduced sustained virologic response (SVR) rate compared with subjects with undetectable HCV RNA at the same on-treatment timepoint. At key RGT timepoints (week 8 for boceprevir, week 4 for telaprevir), subjects with detectable/BLOQ HCV RNA had an approximately 20% lower SVR rate compared with subjects with undetectable HCV RNA, and this difference widened for later on-treatment timepoints. A similar trend was observed for Study 108, but the differences in SVR rates were modest, potentially explained by a higher frequency of reported detectable/BLOQ results. Analyses of Phase 2 boceprevir and telaprevir trials indicated subjects with detectable/BLOQ HCV RNA at RGT timepoints benefited from extended treatment duration. Conclusion: During boceprevir- and telaprevir-based treatment, subjects with detectable/BLOQ HCV RNA had a reduced virologic response compared with subjects with undetectable HCV RNA. Eligibility for shortened treatment duration should be based on achieving undetectable HCV RNA (i.e., HCV RNA not detected) at RGT decision timepoints. (Hepatology 2012)
C1 [Harrington, Patrick R.; Naeger, Lisa K.] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Zeng, Wen] US FDA, Div Biometr 4, Off Biometr, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Harrington, PR (reprint author), FDA CDER OAP DAVP, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Patrick.Harrington@fda.hhs.gov; Lisa.Naeger@fda.hhs.gov
NR 19
TC 48
Z9 49
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD APR
PY 2012
VL 55
IS 4
BP 1048
EP 1057
DI 10.1002/hep.24791
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 916AW
UT WOS:000302069900008
PM 22095516
ER
PT J
AU Woo, EJ
AF Woo, Emily Jane
TI Adverse Events Reported After the Use of Recombinant Human Bone
Morphogenetic Protein 2
SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Article
AB Purpose: The US Food and Drug Administration has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) (Infuse Bone Graft; Medtronic Sofamor Danek, Minneapolis, MN) as an alternative to autogenous bone graft for sinus augmentations and for localized alveolar ridge augmentations for defects associated with extraction sockets. The objective of this analysis was to characterize adverse events reported after the use of rhBMP-2 in oral and maxillofacial procedures.
Materials and Methods: The US Food and Drug Administration's Manufacturer and User Facility Device Experience database contains reports of adverse events involving medical devices. The publicly available version of the database was searched for reports for the brand name Infuse Bone Graft. Descriptive statistics were used to summarize the procedures and adverse events.
Results: As of April 30, 2011, the Manufacturer and User Facility Device Experience database contained 83 reports of adverse events after oral and maxillofacial operations involving rhBMP-2. Of these reports, 55 (66.3%) described off-label uses, such as reconstruction of the mandible after fracture or cancer or alveolar cleft repair. The most commonly reported adverse events included local reactions, graft failure, infections, and other wound complications. Of the reports, 25 (30.1%) stated that the patient required additional surgery to address the reported adverse event.
Conclusions: Serious adverse events, some of which may require a second operation, can occur after the use of rhBMP-2 in oral and maxillofacial procedures. In this analysis graft, failure and pseudarthrosis were more commonly reported after off-label uses of rhBMP-2 than approved uses. This is a US government work. There are no restrictions on its use. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 70:765-767, 2012
C1 US FDA, Rockville, MD 20852 USA.
RP Woo, EJ (reprint author), US FDA, HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA.
EM jane.woo@fda.hhs.gov
NR 0
TC 30
Z9 31
U1 0
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0278-2391
J9 J ORAL MAXIL SURG
JI J. Oral Maxillofac. Surg.
PD APR
PY 2012
VL 70
IS 4
BP 765
EP 767
DI 10.1016/j.joms.2011.09.008
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 921MP
UT WOS:000302482000014
PM 22177811
ER
PT J
AU Slikker, W
Miller, MA
Valdez, ML
Hamburg, MA
AF Slikker, William, Jr.
Miller, Margaret Ann
Valdez, Mary Lou
Hamburg, Margaret A.
TI Advancing global health through regulatory science research: Summary of
the Global Summit on Regulatory Science Research and Innovation
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Article
DE Regulatory science; Toxicological research; Globalization; Public health
AB As a first step in the implementation of the Food and Drug Administration's (FDA) Pathway to Global Product Safety and Quality (Anonymous, 2011), FDA's Office of International Programs (OIP) and the National Center for Toxicological Research (NCTR) sponsored a Global Summit on Regulatory Science Research and Innovation. Through a series of presentations and panel discussions, the Global Summit participants explored how research could be used more effectively as a tool for advancing regulatory science, food safety, medical technologies, and public health. Speakers provided an overview of each of the components in the global regulatory-science research initiative, including scientific innovation and modernizing toxicology; and discussed how the integration of these components is needed to achieve the promise of regulatory science at the global level. All participants agreed with the formation of a Global Coalition of Regulatory Research Scientists who will work collaboratively to build knowledge, promote the development of regulatory science, discover novel ways to clearly define research needs, and improve public health. Published by Elsevier Inc.
C1 [Slikker, William, Jr.; Miller, Margaret Ann; Valdez, Mary Lou; Hamburg, Margaret A.] US FDA, Silver Spring, MD 20993 USA.
RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM william.slikker@fda.hhs.gov
NR 1
TC 4
Z9 4
U1 1
U2 10
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 APR
PY 2012
VL 62
IS 3
BP 471
EP 473
DI 10.1016/j.yrtph.2012.02.001
PG 3
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA 917UM
UT WOS:000302204100010
PM 22342950
ER
PT J
AU Gallas, BD
Chan, HP
D'Orsi, CJ
Dodd, LE
Giger, ML
Gur, D
Krupinski, EA
Metz, CE
Myers, KJ
Obuchowski, NA
Sahiner, B
Toledano, AY
Zuley, ML
AF Gallas, Brandon D.
Chan, Heang-Ping
D'Orsi, Carl J.
Dodd, Lori E.
Giger, Maryellen L.
Gur, David
Krupinski, Elizabeth A.
Metz, Charles E.
Myers, Kyle J.
Obuchowski, Nancy A.
Sahiner, Berkman
Toledano, Alicia Y.
Zuley, Margarita L.
TI Evaluating Imaging and Computer-aided Detection and Diagnosis Devices at
the FDA
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Reader studies; designs; methods; ROC; premarket; postmarket; consensus
ID DIGITAL BREAST TOMOSYNTHESIS; FINITE-SAMPLE SIZE; OBSERVER PERFORMANCE;
FREE-RESPONSE; SCREENING MAMMOGRAPHY; ROC CURVES; RADIOLOGISTS
PERFORMANCE; LABORATORY ENVIRONMENT; SERIAL MAMMOGRAMS; VERIFICATION
BIAS
AB This report summarizes the Joint FDA-MIPS Workshop on Methods for the Evaluation of Imaging and Computer-Assist Devices. The purpose of the workshop was to gather information on the current state of the science and facilitate consensus development on statistical methods and study designs for the evaluation of imaging devices to support US Food and Drug Administration submissions. Additionally, participants expected to identify gaps in knowledge and unmet needs that should be addressed in future research. This summary is intended to document the topics that were discussed at the meeting and disseminate the lessons that have been learned through past studies of imaging and computer-aided detection and diagnosis device performance.
C1 [Gallas, Brandon D.; Myers, Kyle J.; Sahiner, Berkman] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Chan, Heang-Ping] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[D'Orsi, Carl J.] Emory Univ, Atlanta, GA 30322 USA.
[Dodd, Lori E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Giger, Maryellen L.; Metz, Charles E.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Gur, David] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA 15260 USA.
[Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA.
[Obuchowski, Nancy A.] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Toledano, Alicia Y.] Stat Collaborat Inc, Washington, DC USA.
RP Gallas, BD (reprint author), US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 3124, Silver Spring, MD 20993 USA.
EM brandon.gallas@fda.hhs.gov
OI Gallas, Brandon/0000-0001-7332-1620; Giger,
Maryellen/0000-0001-5482-9728
NR 110
TC 16
Z9 16
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD APR
PY 2012
VL 19
IS 4
BP 463
EP 477
DI 10.1016/j.acra.2011.12.016
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 916NH
UT WOS:000302110000014
PM 22306064
ER
PT J
AU Wang, F
Jiang, L
Yang, QR
Prinyawiwatkul, W
Ge, BL
AF Wang, Fei
Jiang, Lin
Yang, Qianru
Prinyawiwatkul, Witoon
Ge, Beilei
TI Rapid and Specific Detection of Escherichia coli Serogroups O26, O45,
O103, O111, O121, O145, and O157 in Ground Beef, Beef Trim, and Produce
by Loop-Mediated Isothermal Amplification
SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID ANTIGEN GENE-CLUSTER; NON-O157 SHIGA TOXIN; PCR AMPLIFICATION;
UNITED-STATES; WZY GENES; IDENTIFICATION; FOOD; SEQUENCE; ASSAYS; LAMP
AB Escherichia coli O157 and six additional serogroups of Shiga toxin-producing E. coli (STEC) (O26, O45, O103, O111, O121, and O145) account for the majority of STEC infections in the United States. In this study, O serogroup-specific genes (wzx or wzy) were used to design loop-mediated isothermal amplification (LAMP) assays for the rapid and specific detection of these leading STEC serogroups. The assays were evaluated in pure culture and spiked food samples (ground beef, beef trim, lettuce, and spinach) and compared with real-time quantitative PCR (qPCR). No false-positive or false-negative results were observed among 120 bacterial strains used to evaluate assay specificity. The limits of detection of various STEC strains belonging to these target serogroups were approximately 1 to 20 CFU/reaction mixture in pure culture and 10(3) to 10(4) CFU/g in spiked food samples, which were comparable to those of qPCR. Standard curves generated suggested good linear relationships between STEC cell numbers and LAMP turbidity signals. In various beef and produce samples spiked with two low levels (1 to 2 and 10 to 20 CFU/25 g) of respective STEC strains, the LAMP assays consistently achieved accurate detection after 6 to 8 h of enrichment. In conclusion, these newly developed LAMP assays may facilitate rapid and reliable detection of the seven major STEC serogroups in ground beef, beef trim, and produce during routine sample testing.
C1 [Wang, Fei; Jiang, Lin; Yang, Qianru; Prinyawiwatkul, Witoon; Ge, Beilei] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
RP Ge, BL (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA.
EM beilei.ge@fda.hhs.gov
RI Wang, Fei/J-4353-2014
NR 53
TC 31
Z9 34
U1 1
U2 22
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 APR
PY 2012
VL 78
IS 8
BP 2727
EP 2736
DI 10.1128/AEM.07975-11
PG 10
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 917BP
UT WOS:000302147300026
PM 22327594
ER
PT J
AU Du, MY
Yang, XJ
Hartman, JA
Cooke, PS
Doerge, DR
Ju, YH
Helferich, WG
AF Du, Mengyuan
Yang, Xujuan
Hartman, James A.
Cooke, Paul S.
Doerge, Daniel R.
Ju, Young H.
Helferich, William G.
TI Low-dose dietary genistein negates the therapeutic effect of tamoxifen
in athymic nude mice
SO CARCINOGENESIS
LA English
DT Article
ID BREAST-CANCER CELLS; ADJUVANT ENDOCRINE THERAPY; ESTROGEN-RECEPTOR;
MCF-7 CELLS; IN-VITRO; PREMENOPAUSAL WOMEN; PHYTO-ESTROGENS;
POSTMENOPAUSAL WOMEN; GROWTH; TUMORS
AB The present study examined the effect of dietary genistein, a soy isoflavone, on breast cancer patients who take tamoxifen, an antiestrogen treatment, using a preclinical model. The interaction of various doses of genistein with tamoxifen on the growth of estrogen receptor-positive breast cancer MCF-7 cells was investigated by subcutaneously injecting MCF-7 cells into the flank of ovariectomized athymic mice. Animals were randomized into eight experimental groups with 10-13 mice per group: control (C), estrogen (E) (0.08 mg E implant), tamoxifen (T) (3 mg T implant), estrogen + tamoxifen (E + T), tamoxifen + 500 p.p.m. genistein (T + G500), estrogen + tamoxifen + 250 p.p.m. genistein (E + T + G250), estrogen + tamoxifen + 500 p.p.m. genistein (E + T + G500) and estrogen + tamoxifen + 1000 p.p.m. genistein (E + T + G1000). Treatment of tamoxifen significantly reduced the estrogen-induced MCF-7 tumor prevalence and tumor size. This inhibitory effect of tamoxifen was significantly negated by the low doses of dietary genistein (250 and 500 p.p.m.), whereas the 1000 p.p.m. genistein did not have the same effect. Cells harvested from tamoxifen-treated tumors retained estrogen responsiveness of their progenitor MCF-7 cells, indicating that the abrogating effect of genistein on tamoxifen-treated tumor growth was not caused by a diminished tamoxifen response but directly by genistein. The low doses of dietary genistein abrogated the inhibitory effect of tamoxifen potentially by acting on the tumor cell proliferation/apoptosis ratio and the messenger RNA (mRNA) expression of cyclin D1 in addition to regulating the mRNA expression of progesterone receptor. Therefore, data from the current study suggest that caution is warranted regarding the consumption of dietary genistein by breast cancer patients while on tamoxifen therapy.
C1 [Cooke, Paul S.] Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA.
[Du, Mengyuan; Helferich, William G.] Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA.
[Du, Mengyuan; Yang, Xujuan; Hartman, James A.; Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA.
[Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Ju, Young H.] Virginia Polytech Inst & State Univ, Dept Human Nutr Foods & Exercise, Blacksburg, VA 24061 USA.
RP Helferich, WG (reprint author), Univ Illinois, Dept Vet Biosci, 905 S Goodwin Ave,Room 580, Urbana, IL 61801 USA.
EM helferic@uiuc.edu
FU National Cancer Institute (NCI) [CA77355, P50AT006268]; National
Institute on Aging; National Institute for Complementary and Alternative
Medicine (NCCAM); Office of Dietary Supplements (ODS); Women's Health
Initiative [P01 AG024387]
FX National Cancer Institute (NCI) (CA77355 to W. G. H.); National
Institute on Aging; National Institute for Complementary and Alternative
Medicine (NCCAM); Office of Dietary Supplements (ODS) and Women's Health
Initiative (P01 AG024387 to W. G. H. and Y.H.J.); and NCCAM, ODS and NCI
(P50AT006268 to W. G. H.). Its contents are sorely the responsibility of
the authors and do not necessarily represent the official views of the
NCCAM, ODS, NCI or the National Institutes of Health.
NR 55
TC 21
Z9 22
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD APR
PY 2012
VL 33
IS 4
BP 895
EP 901
DI 10.1093/carcin/bgs017
PG 7
WC Oncology
SC Oncology
GA 921RC
UT WOS:000302493800021
PM 22266527
ER
PT J
AU Mirzaie, S
Rafii, F
Yasunaga, K
Yoshunaga, K
Sepehrizadeh, Z
Kanno, S
Tonegawa, Y
Shahverdi, AR
AF Mirzaie, Sako
Rafii, Fatemeh
Yasunaga, Katsuaki
Yoshunaga, Kunie
Sepehrizadeh, Zargham
Kanno, Shinji
Tonegawa, Yu
Shahverdi, Ahmad Reza
TI Prediction of the mode of interaction between monoterpenes and the
nitroreductase from Enterobacter cloacae by docking simulation
SO COMPUTERS IN BIOLOGY AND MEDICINE
LA English
DT Article
DE Enterobacter cloacae; Docking simulation; Nitroreductase; Monoterpenes;
Molecular modeling
ID ESCHERICHIA-COLI NITROREDUCTASE; PROTEIN-LIGAND INTERACTIONS; MAJOR
FLAVIN REDUCTASE; ANTIMICROBIAL ACTIVITY; VIBRIO-FISCHERI;
BIOCHEMICAL-PROPERTIES; MOLECULAR RECOGNITION; NUCLEOTIDE-SEQUENCE;
WATER-MOLECULES; ESSENTIAL OILS
AB Monoterpenes from the essential oils of several plants have been shown to enhance the bactericidal activities of nitrofurantoin and furazolidone against the bacteria of Enterobacteriaceae family. In this study, computer-aided molecular modeling and docking techniques have been employed to simulate the theoretical mode of interaction between monoterpenes and Enterobacter cloacae nitroreductase. Enhancement of nitro drug potency in the presence of monoterpenes may be the result of modulation of nitroreductase activity. Binding nitroreductase with monoterpenes may decrease the efficient conversion of toxic reactive intermediates to final products lacking bactericidal activity. (c) 2012 Elsevier Ltd. All rights reserved.
C1 [Sepehrizadeh, Zargham; Shahverdi, Ahmad Reza] Univ Tehran Med Sci, Dept Pharmaceut Biotechnol, Tehran 1417614411, Iran.
[Sepehrizadeh, Zargham; Shahverdi, Ahmad Reza] Univ Tehran Med Sci, Biotechnol Res Ctr, Fac Pharm, Tehran 1417614411, Iran.
[Mirzaie, Sako] Islamic Azad Univ, Sanandaj Branch, Dept Biochem, Sanandaj, Iran.
[Rafii, Fatemeh] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Yasunaga, Katsuaki] Mitsubishi Chem Safety Inst Ltd, Genet Toxicol Grp, Toxicol Div 3, Kashima Lab, Ibaraki, Japan.
[Yoshunaga, Kunie; Kanno, Shinji; Tonegawa, Yu] Tokyo Univ Agr, Dept Nutr Sci, Fac Appl Biosci, Tokyo, Japan.
RP Shahverdi, AR (reprint author), Univ Tehran Med Sci, Dept Pharmaceut Biotechnol, Tehran 1417614411, Iran.
EM shahverd@sina.tums.ac.ir
OI mirzaie, sako/0000-0003-4080-9210
FU Deputy of Research, Tehran University of Medical Sciences, Tehran, Iran
FX The views presented in this article do not necessarily reflect those of
the U.S. Food and Drug Administration. This work was support by Deputy
of Research, Tehran University of Medical Sciences, Tehran, Iran.
Furthermore, we thank Mohhamad Reza Hemmati for his comments on the
manuscript. Also we appreciate the support of Faculty of Applied
Bio-Science, Tokyo University of Agriculture, Tokyo, Japan for umu
mutagenic tests.
NR 50
TC 3
Z9 3
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0010-4825
J9 COMPUT BIOL MED
JI Comput. Biol. Med.
PD APR
PY 2012
VL 42
IS 4
BP 414
EP 421
DI 10.1016/j.compbiomed.2011.12.009
PG 8
WC Biology; Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Mathematical & Computational Biology
SC Life Sciences & Biomedicine - Other Topics; Computer Science;
Engineering; Mathematical & Computational Biology
GA 922CL
UT WOS:000302524300008
PM 22240115
ER
PT J
AU Roessler, S
Long, EL
Budhu, A
Chen, YD
Zhao, XL
Ji, JF
Walker, R
Jia, HL
Ye, QH
Qin, LX
Tang, ZY
He, P
Hunter, KW
Thorgeirsson, SS
Meltzer, PS
Wang, XW
AF Roessler, Stephanie
Long, Ezhou Lori
Budhu, Anuradha
Chen, Yidong
Zhao, Xuelian
Ji, Junfang
Walker, Robert
Jia, Hu-Liang
Ye, Qing-Hai
Qin, Lun-Xiu
Tang, Zhao-You
He, Ping
Hunter, Kent W.
Thorgeirsson, Snorri S.
Meltzer, Paul S.
Wang, Xin Wei
TI Integrative Genomic Identification of Genes on 8p Associated With
Hepatocellular Carcinoma Progression and Patient Survival
SO GASTROENTEROLOGY
LA English
DT Article
DE Liver Cancer; Tumor Profiling; Cancer Driver Genes
ID GTPASE-ACTIVATING PROTEIN; NEGATIVE BREAST-CANCER; ARRAY CGH DATA;
TUMOR-SUPPRESSOR; LIVER-CANCER; EXPRESSION; DLC-1; METASTASIS; CELLS;
PREDICTION
AB BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is an aggressive malignancy; its mechanisms of development and progression are poorly understood. We used an integrative approach to identify HCC driver genes, defined as genes whose copy numbers associate with gene expression and cancer progression. METHODS: We combined data from high-resolution, array-based comparative genomic hybridization and transcriptome analysis of HCC samples from 76 patients with hepatitis B virus infection with data on patient survival times. Candidate genes were functionally validated using in vitro and in vivo models. RESULTS: Unsupervised analyses of array comparative genomic hybridization data associated loss of chromosome 8p with poor outcome (reduced survival time); somatic copy number alterations correlated with expression of 27.3% of genes analyzed. We associated expression levels of 10 of these genes with patient survival times in 2 independent cohorts (comprising 319 cases of HCC with mixed etiology) and 3 breast cancer cohorts (637 cases). Among the 10-gene signature, a cluster of 6 genes on 8p, (DLC1, CCDC25, ELP3, PROSC, SH2D4A, and SORBS3) were deleted in HCCs from patients with poor outcomes. In vitro and in vivo analyses indicated that the products of PROSC, SH2D4A, and SORBS3 have tumor-suppressive activities, along with the known tumor suppressor gene DLC1. CONCLUSIONS: We used an unbiased approach to identify 10 genes associated with HCC progression. These might be used in assisting diagnosis and to stage tumors based on gene expression patterns.
C1 [Roessler, Stephanie; Budhu, Anuradha; Zhao, Xuelian; Ji, Junfang; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
[Long, Ezhou Lori; Chen, Yidong; Walker, Robert] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Jia, Hu-Liang; Ye, Qing-Hai; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
[He, Ping] FDA CBER OBRR, Div Hematol, Bethesda, MD USA.
[Hunter, Kent W.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Wang, Xin/B-6162-2009
FU Center for Cancer Research, the US National Cancer Institute [Z01 BC
010313, Z01 BC 010876]
FX Supported in part by the Intramural Research Program of the Center for
Cancer Research, the US National Cancer Institute (Z01 BC 010313 and Z01
BC 010876).
NR 48
TC 71
Z9 73
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2012
VL 142
IS 4
BP 957
EP U451
DI 10.1053/j.gastro.2011.12.039
PG 22
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 919BU
UT WOS:000302296400045
PM 22202459
ER
PT J
AU Slater, JE
Menzies, SL
Bridgewater, J
Mosquera, A
Zinderman, CE
Ou, AC
Maloney, D
Cook, CM
Rabin, RL
AF Slater, Jay E.
Menzies, Sandra L.
Bridgewater, Jennifer
Mosquera, Alexis
Zinderman, Craig E.
Ou, Alan C.
Maloney, Diane
Cook, Catherine M.
Rabin, Ronald L.
TI The US Food and Drug Administration review of the safety and
effectiveness of nonstandardized allergen extracts
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Allergen extracts; immunotherapy; skin testing; safety; effectiveness
AB Background: Nonstandardized allergen extracts have been used for a century. Until 1972, these products were regulated by the National Institutes of Health, and products were not required to have an individualized showing of effectiveness. Jurisdiction was then transferred to the US Food and Drug Administration (FDA), which established external review panels to make recommendations regarding safety and effectiveness. Two external panels deliberated, the first from 1974-1979 and the second from 1982-1983.
Objective: We sought to review external panels' recommendations and assess the safety and effectiveness of nonstandardized allergen extracts, FDA-reviewed available literature, and databases since 1972.
Methods: Currently licensed nonstandardized allergen extracts were reviewed according to extract type. Available data were collected from medical and nonscientific search engines. Nomenclature was ascertained by consulting www.itis.gov or www.atcc.org. The FDA's Adverse Event Reporting System was probed for events associated with extract use. Provisional threshold levels of safety and effectiveness were established, and extracts were sorted according to whether they met the thresholds.
Results: In the Adverse Event Reporting System, there were 178 adverse event reports, including 13 deaths, associatedwith allergen extract use over 23 years. Nosingle group of extracts predominated. Among 1269 allergen extracts reviewed, there were 480 for which use in the diagnosis and treatment of allergic disease were addressed in the literature, 207 for which only diagnostic use was addressed, 565 for which minimal or no supportive literature was identified, and 17 for which potential safety concerns were found.
Conclusions: When used according to professional guidelines, almost all nonstandardized allergen extracts for diagnosis and therapy appear to be safe. Provisional thresholds of effectiveness were met by 54% of extracts reviewed. (J Allergy Clin Immunol 2012;129:1014-9.)
C1 [Slater, Jay E.; Maloney, Diane; Cook, Catherine M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
[Slater, Jay E.; Menzies, Sandra L.; Bridgewater, Jennifer; Rabin, Ronald L.] US FDA, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review, Rockville, MD 20852 USA.
[Mosquera, Alexis; Zinderman, Craig E.; Ou, Alan C.] US FDA, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20852 USA.
RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA.
EM jay.slater@fda.hhs.gov
FU US Food and Drug Administration; National Institute of Allergy and
Infectious Diseases/National Institutes of Health
FX Supported by the US Food and Drug Administration.; R. L. Rabin has
received research support from the National Institute of Allergy and
Infectious Diseases/National Institutes of Health. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 18
TC 12
Z9 12
U1 0
U2 6
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 APR
PY 2012
VL 129
IS 4
BP 1014
EP 1019
DI 10.1016/j.jaci.2012.01.066
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA 917AP
UT WOS:000302144600017
PM 22341039
ER
PT J
AU Baek, JH
D'Agnillo, F
Vallelian, F
Pereira, CP
Williams, MC
Jia, YP
Schaer, DJ
Buehler, PW
AF Baek, Jin Hyen
D'Agnillo, Felice
Vallelian, Florence
Pereira, Claudia P.
Williams, Matthew C.
Jia, Yiping
Schaer, Dominik J.
Buehler, Paul W.
TI Hemoglobin-driven pathophysiology is an in vivo consequence of the red
blood cell storage lesion that can be attenuated in guinea pigs by
haptoglobin therapy
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NITRIC-OXIDE; INTRAVASCULAR HEMOLYSIS; EXTRAVASCULAR HEMOLYSIS;
TRANSFUSION; MODEL; ERYTHROCYTES; OXYGENATION; DYSFUNCTION; CLEARANCE;
SURVIVAL
AB Massive transfusion of blood can lead to clinical complications, including multiorgan dysfunction and even death. Such severe clinical outcomes have been associated with longer red blood cell (rbc) storage times. Collectively referred to as the rbc storage lesion, rbc storage results in multiple biochemical changes that impact intracellular processes as well as membrane and cytoskeletal properties, resulting in cellular injury in vitro. However, how the rbc storage lesion triggers pathophysiology in vivo remains poorly defined. In this study, we developed a guinea pig transfusion model with blood stored under standard blood banking conditions for 2 (new), 21 (intermediate), or 28 days (old blood). Transfusion with old but not new blood led to intravascular hemolysis, acute hypertension, vascular injury, and kidney dysfunction associated with pathophysiology driven by hemoglobin (Hb). These adverse effects were dramatically attenuated when the high-affinity Hb scavenger haptoglobin (Hp) was administered at the time of transfusion with old blood. Pathologies observed after transfusion with old blood, together with the favorable response to Hp supplementation, allowed us to define the in vivo consequences of the rbc storage lesion as storage-related posttransfusion hemolysis producing Hb-driven pathophysiology. Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients.
C1 [Baek, Jin Hyen; D'Agnillo, Felice; Pereira, Claudia P.; Williams, Matthew C.; Jia, Yiping; Buehler, Paul W.] US FDA, CBER, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA.
[Vallelian, Florence; Schaer, Dominik J.] Univ Zurich Hosp, Div Clin Immunol, CH-8091 Zurich, Switzerland.
[Vallelian, Florence; Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland.
[Schaer, Dominik J.] Univ Zurich, Ctr Integrat Human Physiol, Zurich, Switzerland.
[Schaer, Dominik J.] Univ Zurich, Ctr Evolutionary Med, Zurich, Switzerland.
RP Buehler, PW (reprint author), US FDA, CBER, Div Hematol, Lab Biochem & Vasc Biol, 8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA.
EM dominik.schaer@usz.ch; paul.buehler@fda.hhs.gov
FU FDA; Swiss National Science Foundation [31003A_138500]; University of
Zurich
FX This work was supported by FDA Critical Path Funding (to P.W. Buehler
and F. D'Agnillo), Swiss National Science Foundation (grant
31003A_138500) (to D.J. Schaer), and by the University of Zurich
Research Priority Program "Integrative Human Physiology" (to DJ. Schaer
and P.W. Buehler). The authors would like to thank Francine Wood for
oxygen equilibrium measurements. The findings and conclusions in this
article have not been formally disseminated by the FDA and should not be
construed to represent any agency determination or policy.
NR 40
TC 114
Z9 115
U1 1
U2 11
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD APR
PY 2012
VL 122
IS 4
BP 1444
EP 1458
DI 10.1172/JCI59770
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 918WJ
UT WOS:000302281800036
PM 22446185
ER
PT J
AU Feingold, B
Brooks, MM
Zeevi, A
Ohmann, EL
Burckart, GJ
Ferrell, RE
Chinnock, R
Canter, C
Addonizio, L
Bernstein, D
Kirklin, JK
Naftel, DC
Webber, SA
AF Feingold, B.
Brooks, M. M.
Zeevi, A.
Ohmann, E. L.
Burckart, G. J.
Ferrell, R. E.
Chinnock, R.
Canter, C.
Addonizio, L.
Bernstein, D.
Kirklin, J. K.
Naftel, D. C.
Webber, S. A.
TI Association between Renal Function and Genetic Polymorphisms in
Pediatric Heart Transplant Recipients
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Meeting Abstract
CT 32nd Annual Meeting and Scientific Sessions of the
International-Society-for-Heart-and-Lung-Transplantation/Meeting of the
ISHLT Academy - Core Competencies in Mechanical Circulatory Support
CY APR 17-21, 2012
CL Prague, CZECH REPUBLIC
SP Int Soc Heart & Lung Transplantat (ISHLT), Int Soc Heart & Lung Transplantat Acad (ISHLT)
C1 [Feingold, B.; Ohmann, E. L.; Webber, S. A.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Brooks, M. M.; Zeevi, A.; Ferrell, R. E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Burckart, G. J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA.
[Chinnock, R.] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Canter, C.] Washington Univ, Sch Med, St Louis, MO USA.
[Addonizio, L.] Columbia Univ, New York, NY USA.
[Bernstein, D.] Stanford Univ, Palo Alto, CA 94304 USA.
[Kirklin, J. K.; Naftel, D. C.] Univ Alabama, Birmingham, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD APR
PY 2012
VL 31
IS 4
SU S
MA 139
BP S55
EP S56
PG 2
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 917VY
UT WOS:000302207900139
ER
PT J
AU Bromberg, JE
Augustson, EM
Backinger, CL
AF Bromberg, Julie E.
Augustson, Erik M.
Backinger, Cathy L.
TI Portrayal of Smokeless Tobacco in YouTube Videos
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Article
ID SMOKING INITIATION; MOVIE SMOKING; YOUNG-ADULTS; INFORMATION; WEB;
EXPOSURE; INTERNET
AB Videos of smokeless tobacco (ST) on YouTube are abundant and easily accessible, yet no studies have examined the content of ST videos. This study assesses the overall portrayal, genre, and messages of ST YouTube videos.
In August 2010, researchers identified the top 20 search results on YouTube by "relevance" and "view count" for the following search terms: "ST," "chewing tobacco," "snus," and "Skoal." After eliminating videos that were not about ST (n = 26), non-English (n = 14), or duplicate (n = 42), a final sample of 78 unique videos was coded for overall portrayal, genre, and various content measures.
Among the 78 unique videos, 15.4% were anti-ST, while 74.4% were pro-ST. Researchers were unable to determine the portrayal of ST in the remaining 10.3% of videos because they involved excessive or "sensationalized" use of the ST, which could be interpreted either positively or negatively, depending on the viewer. The most common ST genre was positive video diaries (or "vlogs"), which made up almost one third of the videos (29.5%), followed by promotional advertisements (20.5%) and anti-ST public service announcements (12.8%). While YouTube is intended for user-generated content, 23.1% of the videos were created by professional organizations.
These results demonstrate that ST videos on YouTube are overwhelmingly pro-ST. More research is needed to determine who is viewing these ST YouTube videos and how they may affect people's knowledge, attitudes, and behaviors regarding ST use.
C1 [Bromberg, Julie E.] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA.
RP Bromberg, JE (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4047, Bethesda, MD 20892 USA.
EM brombergje@mail.nih.gov
FU National Cancer Institute
FX This research was funded by the National Cancer Institute [Cancer
Research Training Award (CRTA) Program].
NR 35
TC 21
Z9 21
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD APR
PY 2012
VL 14
IS 4
BP 455
EP 462
DI 10.1093/ntr/ntr235
PG 8
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 919CM
UT WOS:000302298400010
PM 22080585
ER
PT J
AU Petibone, DM
Kulkarni, RM
Chang, CW
Chen, JJ
Morris, SM
AF Petibone, Dayton M.
Kulkarni, Rohan M.
Chang, Ching-Wei
Chen, James J.
Morris, Suzanne M.
TI Evaluation of p53 genotype on gene expression in the testis, liver, and
heart from male C57BL/6 mice
SO TRANSGENIC RESEARCH
LA English
DT Article
DE p53; Gene expression profiles; Transgenic mice; PCR arrays; Multivariate
analysis of variance
ID MALE GERM-CELLS; GENOTOXIC STRESS; APOPTOSIS; SPERMATOGENESIS; SPECTRUM;
DELETION; REPAIR; PCR
AB Our laboratory is conducting experiments designed to characterize the role of p53 in gene expression in the TSG-p53A (R) mouse model. In the study reported here, gene expression levels in tissue derived from the testis, liver, and heart of male, 8-9 week old, p53 wild-type (WT), heterozygous (HET) or knockout (KO) mice were determined utilizing a targeted qPCR 84-gene array. The heart, liver and testis were selected because of the unique function and rate of cell division of each tissue. The genes on the arrays were categorized into three Functional Gene Groups, Apoptosis, Cell-Cycle and DNA Repair. Differences in expression of the functional groups were determined by multivariate analysis of variance (MANOVA) and significant (P < 0.05) differences in their expression were found among the heart, liver and testis. Further, the expression of the Functional Gene Groups in each of these tissues was also significantly affected by p53 genotype. These data indicate that gene expression in unperturbed tissue is influenced by the status of p53 genotype, and relates, at least partially, to the function of the tissue.
C1 [Petibone, Dayton M.] NCTR, DGMT, HFT 120, Jefferson, AR 72079 USA.
[Petibone, Dayton M.; Kulkarni, Rohan M.; Morris, Suzanne M.] NCTR, FDA, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA.
[Chang, Ching-Wei; Chen, James J.] NCTR, FDA, Div Personalized Nutr & Med, Jefferson, AR 72079 USA.
RP Petibone, DM (reprint author), NCTR, DGMT, HFT 120, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM dayton.petibone@fda.hhs.gov
NR 25
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-8819
J9 TRANSGENIC RES
JI Transgenic Res.
PD APR
PY 2012
VL 21
IS 2
BP 257
EP 263
DI 10.1007/s11248-011-9526-6
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 918RW
UT WOS:000302269400003
PM 21656205
ER
PT J
AU Lee, LH
Blake, MS
AF Lee, Lucia H.
Blake, Milan S.
TI Effect of Increased CRM197 Carrier Protein Dose on Meningococcal C
Bactericidal Antibody Response
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID PNEUMOCOCCAL CONJUGATE VACCINE; RANDOMIZED CONTROLLED-TRIAL;
HAEMOPHILUS-INFLUENZAE; SEROGROUP-C; ACELLULAR PERTUSSIS; INACTIVATED
POLIO; HEALTHY INFANTS; HERD-IMMUNITY; B VACCINE;
CORYNEBACTERIUM-DIPHTHERIAE
AB New multivalent CRM197-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM197 coadministration with CRM197-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM197 carrier protein dose of similar to 50 mu g and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of >= 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM197 conjugate vaccine immunogenicity using alternative dosing schedules.
C1 [Lee, Lucia H.; Blake, Milan S.] US FDA, Ctr Biol Evaluat & Res, Washington, DC 20204 USA.
RP Lee, LH (reprint author), US FDA, Ctr Biol Evaluat & Res, Washington, DC 20204 USA.
EM Lucia.Lee@fda.hhs.gov
NR 53
TC 5
Z9 5
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD APR
PY 2012
VL 19
IS 4
BP 551
EP 556
DI 10.1128/CVI.05438-11
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 917FA
UT WOS:000302156700012
PM 22336285
ER
PT J
AU Florian, J
Garnett, CE
Nallani, SC
Rappaport, BA
Throckmorton, DC
AF Florian, J.
Garnett, C. E.
Nallani, S. C.
Rappaport, B. A.
Throckmorton, D. C.
TI A Modeling and Simulation Approach to Characterize Methadone QT
Prolongation Using Pooled Data From Five Clinical Trials in MMT Patients
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID TORSADES-DE-POINTES; INTERVAL PROLONGATION; MAINTENANCE THERAPY; CARDIAC
REPOLARIZATION; HOSPITALIZED-PATIENTS; RECEIVING METHADONE; DRUG-USERS;
PHARMACOKINETICS; RISK; POPULATION
AB Pharmacokinetic (PK)-pharmacodynamic modeling and simulation were used to establish a link between methadone dose, concentrations, and Fridericia rate-corrected QT (QTcF) interval prolongation, and to identify a dose that was associated with increased risk of developing torsade de pointes. A linear relationship between concentration and QTcF described the data from five clinical trials in patients on methadone maintenance treatment (MMT). A previously published population PK model adequately described the concentration time data, and this model was used for simulation. QTcF was increased by a mean (90% confidence interval (Cl)) of 17 (12, 22) ms per 1,000 ng/ml of methadone. Based on this model, doses >120 mg/day would increase the QTcF interval by >20 ms.The model predicts that 1-3% of patients would have Delta QTcF >60 ms, and 0.3-2.0% of patients would have QTcF >500 ms at doses of 160-200 mg/day. Our predictions are consistent with available observational data and support the need for electrocardiogram (ECG) monitoring and arrhythmia risk factor assessment in patients receiving methadone doses >120 mg/day.
C1 [Florian, J.; Garnett, C. E.; Nallani, S. C.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Rappaport, B. A.] US FDA, Div Anesthesia & Analgesia Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Throckmorton, D. C.] US FDA, Off Ctr Director, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Garnett, CE (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM christine.garnett@fda.hhs.gov
NR 47
TC 20
Z9 20
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2012
VL 91
IS 4
BP 666
EP 672
DI 10.1038/clpt.2011.273
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 913QF
UT WOS:000301891800018
PM 22378153
ER
PT J
AU Vieira, MLT
Zhao, P
Berglund, EG
Reynolds, KS
Zhang, L
Lesko, LJ
Huang, SM
AF Vieira, Md L. T.
Zhao, P.
Berglund, E. G.
Reynolds, K. S.
Zhang, L.
Lesko, L. J.
Huang, S-M
TI Predicting Drug Interaction Potential With a Physiologically Based
Pharmacokinetic Model: A Case Study of Telithromycin, a Time-Dependent
CYP3A Inhibitor
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID IN-VITRO; KETOLIDE ANTIBACTERIAL; SIMULATION; SINGLE; BIOAVAILABILITY;
CLARITHROMYCIN; PERSPECTIVE; METABOLISM; PAROXETINE; HMR-3647
AB Telithromycin is a substrate and an inhibitor of cytochrome P450 3A (CYP3A4), with dose- and time-dependent nonlinear pharmacokinetics (PK). We hypothesized that the time-dependent inhibition (TDI) of CYP3A4 was responsible for the nonlinear PK of telithromycin and then used physiologically based PK (PBPK) modeling and simulation to verify this mechanism. Telithromycin PBPK models integrating in vitro, in silico, and in vivo PK data ruled out the contribution of enzyme/transporter saturation and suggested that TDI is a plausible mechanism for PK nonlinearity. The model successfully predicted the clinical interaction with the CYP3A4 substrate midazolam, as verified by external data not used for the model-building (intravenous (i.v.) and oral (p.o.) midazolam area under the concentration-time curve (AUC) ratio with/without concurrent telithromycin administration: 3.26 and 6.72 predicted vs. 2.20 and 6.11 observed, respectively). Models assuming reversible inhibition failed to predict such strong CYP3A4 inhibition. In the absence of in vitro TDI data, a PBPK model can be used to incorporate TDI mechanisms based on nonlinear PK data to predict clinical drug-drug interactions.
C1 [Vieira, Md L. T.; Zhao, P.; Reynolds, K. S.; Zhang, L.; Lesko, L. J.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA.
[Vieira, Md L. T.] Univ Florida, Dept Pharmaceut, Gainesville, FL USA.
[Berglund, E. G.] Med Prod Agcy, Uppsala, Sweden.
RP Zhao, P (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA.
EM ping.zhao@fda.hhs.gov
FU CAPES; Center for Drug Evaluation and Research
FX We acknowledge the CAPES/Fulbright program for the doctoral scholarship
of M.d.L.T.V. and the US Food and Drug Administration (FDA) Critical
Path Initiative Project "Development of an Internal Drug Interaction
Database." This project was supported in part by an appointment to the
Research Participation Program at the Center for Drug Evaluation and
Research administered by the Oak Ridge Institute for Science and
Education through an interagency agreement between the US Department of
Energy and the FDA. Scientific discussions with Masoud Jamei (SimCYP,
Sheffield, UK), Amin Rostami-Hodjegan, and Malcolm Rowland (University
of Manchester, UK) were greatly appreciated. No official support or
endorsement by the FDA or Medical Products Agency (MPA) is intended or
should be inferred. As Associate Editors for Clinical Pharmacology &
Therapeutics, K.S.R. and S.-M.H. were not involved in the review or
decision process for this article. After the manuscript was accepted,
the authors received comments from Sharon Ripp (Pfizer Inc, CT, USA) via
personal communication on a publication containing in vitro TDI data for
telithromycin (Magee et al. J. Med. Chem. 52: 7446-7457, 2009). The
authors did not find this information when they conducted a literature
search. The reported CYP3A Kl and kinact values
12.4 mu mol/l and 2.4/h, respectively) suggest significant CYP3A
inhibition in vivo, which is consistent with the conclusion derived
using PBPK models in this manuscript.
NR 37
TC 17
Z9 19
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2012
VL 91
IS 4
BP 700
EP 708
DI 10.1038/clpt.2011.305
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 913QF
UT WOS:000301891800022
PM 22398966
ER
PT J
AU Hull, KM
Yim, S
AF Hull, K. M.
Yim, S.
TI Regulatory Aspects of New Medicines Targeted at Treatment of Autoimmune
Diseases
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID RHEUMATOID-ARTHRITIS
AB Autoimmune diseases comprise a diverse group of clinical disorders that result from the body's adaptive immune system reacting against its own tissues.(1) Conversely, autoinflammatory disorders encompass a more limited group of diseases distinguished by recurrent episodes of inflammation but in the absence of high-titer autoantibodies and antigen-specific T cells.(2) The past 15 years have seen a tremendous growth in the development of highly effective treatments for these diseases.
C1 [Hull, K. M.; Yim, S.] US FDA, Div Pulm Allergy & Rheumatol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Hull, KM (reprint author), US FDA, Div Pulm Allergy & Rheumatol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM keith.hull@fda.hhs.gov
NR 5
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2012
VL 91
IS 4
BP 739
EP 742
DI 10.1038/clpt.2012.5
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 913QF
UT WOS:000301891800027
PM 22398965
ER
PT J
AU de Souza, MV
Keller-Stanislawski, B
Blake, K
Hidalgo-Simon, A
Arlett, P
Dal Pan, G
AF de Souza, M. Vinhas
Keller-Stanislawski, B.
Blake, K.
Hidalgo-Simon, A.
Arlett, P.
Dal Pan, G.
TI Drug-Induced PML: A Global Agenda for a Global Challenge
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; MULTIPLE-SCLEROSIS PATIENTS;
JC VIRUS-DNA; NATALIZUMAB; ANTIBODIES; FLUID
AB The occurrence of severe adverse events such as progressive multifocal leukoencephalopathy (PML) has the potential to limit the benefits of highly efficacious medicines being developed to fulfill unmet clinical needs across therapeutic areas. Following an Expert meeting in London in July 2011 (http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500111562.pdf), a research agenda, highlighting methodological, clinical, and communication elements, to mitigate the risk and improve the management of drug-induced PML has been agreed upon.
C1 [de Souza, M. Vinhas; Blake, K.; Hidalgo-Simon, A.; Arlett, P.] European Med Agcy, Pharmacovigilance & Risk Management Sect, London, England.
[Keller-Stanislawski, B.] Fed Inst Vaccines & Biomed, Paul Ehrlich Inst, Safety Med Prod & Med Devices Unit, Langen, Germany.
[Dal Pan, G.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Hidalgo-Simon, A (reprint author), European Med Agcy, Pharmacovigilance & Risk Management Sect, London, England.
EM ana.hidalgo-simon@ema.europa.eu
NR 16
TC 8
Z9 8
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD APR
PY 2012
VL 91
IS 4
BP 747
EP 750
DI 10.1038/clpt.2012.4
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 913QF
UT WOS:000301891800029
ER
PT J
AU Valerio, LG
AF Valerio, Luis G., Jr.
TI Application of advanced in silico methods for predictive modeling and
information integration
SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
LA English
DT Editorial Material
DE computational toxicology; drug impurities; drug safety; genotoxicity; in
silico methods; in silico toxicology; QSAR; SAR
ID COMPUTATIONAL TOXICOLOGY; SAFETY; FOOD
AB Introduction: In silico predictive methods are well-known tools to the drug discovery process. In recent years, these tools have become of strategic interest to regulatory authorities to support risk-based approaches and to complement, and potentially strengthen evidence when considering product quality and safety of human pharmaceuticals.
Areas covered: This editorial reviews how chemically intelligent systems and computational models using structure-based assessments are important for providing predictive data on drug toxicity and safety liabilities considered at the FDA. The example of regulatory interest in application of in silico systems for mutagenicity predictions of drug impurities is discussed.
Expert opinion: The importance of information integration is emphasized toward the application of in silico predictive methods and enhancing data mining capabilities for safety signal detection. Modeling for cardiovascular drug safety based on human clinical trial data is one area of active testing of predictive technologies at the FDA. The FDA has taken appropriate steps in its strategies and initiatives aimed to enhance and support innovation for regulatory science and medical product development by developing and implementing the use of in silico predictive models and medical toxicity databases. This science priority area will ultimately help improve and protect public health.
C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51,Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM luis.valerio@fda.hhs.gov
NR 14
TC 4
Z9 4
U1 1
U2 4
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1742-5255
J9 EXPERT OPIN DRUG MET
JI Expert Opin. Drug Metab. Toxicol.
PD APR
PY 2012
VL 8
IS 4
BP 395
EP 398
DI 10.1517/17425255.2012.664636
PG 4
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 912YE
UT WOS:000301836700001
PM 22432718
ER
PT J
AU Warfel, JM
Beren, J
Kelly, VK
Lee, G
Merkel, TJ
AF Warfel, Jason M.
Beren, Joel
Kelly, Vanessa K.
Lee, Gloria
Merkel, Tod J.
TI Nonhuman Primate Model of Pertussis
SO INFECTION AND IMMUNITY
LA English
DT Article
ID BORDETELLA-PERTUSSIS; WHOOPING-COUGH; ADENYLATE-CYCLASE; TOXIN;
PROTECTION; ANTIBODIES; INFECTION; RESPONSES; KINETICS
AB Pertussis is a highly contagious, acute respiratory illness caused by the bacterial pathogen Bordetella pertussis. Despite nearly universal vaccine coverage, pertussis rates in the United States have been rising steadily over the last 20 years. Our failure to comprehend and counteract this important public health concern is due in large part to gaps in our knowledge of the disease and the mechanisms of vaccine-mediated protection. Important questions about pertussis pathogenesis and mechanisms of vaccine effectiveness remain unanswered due to the lack of an animal model that replicates the full spectrum of human disease. Because current animal models do not meet these needs, we set out to develop a nonhuman primate model of pertussis. We inoculated rhesus macaques and olive baboons with wild-type B. pertussis strains and evaluated animals for clinical disease. We found that only 25% of rhesus macaques developed pertussis. In contrast, 100% of inoculated baboons developed clinical pertussis. A strong anamnestic response was observed when convalescent baboons were infected 6 months following recovery from a primary infection. Our results demonstrate that the baboon provides an excellent model of clinical pertussis that will allow researchers to investigate pertussis pathogenesis and disease progression, evaluate currently licensed vaccines, and develop improved vaccines and therapeutics.
C1 [Warfel, Jason M.; Kelly, Vanessa K.; Lee, Gloria; Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Beren, Joel] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Merkel, TJ (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM tod.merkel@fda.hhs.gov
FU Food and Drug Administration; NIH/NIAID [Y1-AI-1727-01]; National
Institutes of Health National Center for Research Resources
[P40RR012317, 5R24RR016556-10]
FX This work was funded by the Food and Drug Administration and NIH/NIAID
through interagency agreement Y1-AI-1727-01. Baboons were obtained from
the Oklahoma Baboon Research Resource. The Oklahoma Baboon Research
Resource was supported by grants P40RR012317 and 5R24RR016556-10 from
the National Institutes of Health National Center for Research
Resources.
NR 30
TC 48
Z9 51
U1 2
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD APR
PY 2012
VL 80
IS 4
BP 1530
EP 1536
DI 10.1128/IAI.06310-11
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 914EL
UT WOS:000301931900024
PM 22252879
ER
PT J
AU Kimes, NE
Grim, CJ
Johnson, WR
Hasan, NA
Tall, BD
Kothary, MH
Kiss, H
Munk, AC
Tapia, R
Green, L
Detter, C
Bruce, DC
Brettin, TS
Colwell, RR
Morris, PJ
AF Kimes, Nikole E.
Grim, Christopher J.
Johnson, Wesley R.
Hasan, Nur A.
Tall, Ben D.
Kothary, Mahendra H.
Kiss, Hajnalka
Munk, A. Christine
Tapia, Roxanne
Green, Lance
Detter, Chris
Bruce, David C.
Brettin, Thomas S.
Colwell, Rita R.
Morris, Pamela J.
TI Temperature regulation of virulence factors in the pathogen Vibrio
coralliilyticus
SO ISME JOURNAL
LA English
DT Article
DE Vibrio pathogens; coral disease; genome and proteome; quorum sensing;
global climate change; temperature
ID CORAL POCILLOPORA-DAMICORNIS; ACYL HOMOSERINE LACTONE; QUORUM SENSING
SIGNAL; CLIMATE-CHANGE; RTX TOXIN; ANTIMICROBIAL RESISTANCE; GENOME
SEQUENCE; TIME-SERIES; H-NS; CHOLERAE
AB Sea surface temperatures (SST) are rising because of global climate change. As a result, pathogenic Vibrio species that infect humans and marine organisms during warmer summer months are of growing concern. Coral reefs, in particular, are already experiencing unprecedented degradation worldwide due in part to infectious disease outbreaks and bleaching episodes that are exacerbated by increasing SST. For example, Vibrio coralliilyticus, a globally distributed bacterium associated with multiple coral diseases, infects corals at temperatures above 27 degrees C. The mechanisms underlying this temperature-dependent pathogenicity, however, are unknown. In this study, we identify potential virulence mechanisms using whole genome sequencing of V. coralliilyticus ATCC (American Type Culture Collection) BAA-450. Furthermore, we demonstrate direct temperature regulation of numerous virulence factors using proteomic analysis and bioassays. Virulence factors involved in motility, host degradation, secretion, antimicrobial resistance and transcriptional regulation are upregulated at the higher virulent temperature of 27 degrees C, concurrent with phenotypic changes in motility, antibiotic resistance, hemolysis, cytotoxicity and bioluminescence. These results provide evidence that temperature regulates multiple virulence mechanisms in V. coralliilyticus, independent of abundance. The ecological and biological significance of this temperature-dependent virulence response is reinforced by climate change models that predict tropical SST to consistently exceed 27 degrees C during the spring, summer and fall seasons. We propose V. coralliilyticus as a model Gram-negative bacterium to study temperature-dependent pathogenicity in Vibrio-related diseases. The ISME Journal (2012) 6, 835-846; doi: 10.1038/ismej.2011.154; published online 8 December 2011
C1 [Morris, Pamela J.] Univ S Carolina, Belle W Baruch Inst Marine & Coastal Sci, Baruch Marine Field Lab, Georgetown, SC 29442 USA.
[Grim, Christopher J.; Hasan, Nur A.; Colwell, Rita R.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20742 USA.
[Grim, Christopher J.; Colwell, Rita R.] Univ Maryland, Inst Adv Comp Studies, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Grim, Christopher J.; Tall, Ben D.; Kothary, Mahendra H.] US FDA, Laurel, MD USA.
[Johnson, Wesley R.] Ecosyst Solut Inc, Edgewater, MD USA.
[Kiss, Hajnalka; Munk, A. Christine; Tapia, Roxanne; Green, Lance; Detter, Chris; Bruce, David C.; Brettin, Thomas S.] Los Alamos Natl Lab, Biosci Div, Los Alamos, NM USA.
[Colwell, Rita R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Morris, PJ (reprint author), Univ S Carolina, Belle W Baruch Inst Marine & Coastal Sci, Baruch Marine Field Lab, POB 1630, Georgetown, SC 29442 USA.
EM pjmorris@belle.baruch.sc.edu
OI Tall, Ben/0000-0003-0399-3629
FU NSF [DEB 0516347, DEB 0964997]; NOAA OHHI; NOAA [SO660009]; NIH
[1R01A139129-01]
FX This work was supported by NSF Biodiversity Surveys and Inventories (DEB
0516347, DEB 0964997) to PJM, a NSF Foundation Graduate Research
Fellowship to NEK, the NOAA OHHI Distinguished Scholars program to RCC,
and NOAA (SO660009) and NIH (1R01A139129-01) to RRC. Sequencing support
was received from the Office of the Chief Scientist (USA), University of
Maryland Vibrio Genome Sequencing Project and the Los Alamos National
Laboratory. The Fellowship for Interpretation of Genomes (FIG, Argonne
National Laboratory) and the National Institute of Allergy and
Infectious Diseases (NIH) were instrumental in supporting the RAST and
the SEED data analysis environments. We thank Veronika Vonstein and Ross
Overbeek for their assistance with the RAST system, Lisa Kilpatrick
(NIST) and Kevin Schey/Jennifer Bethard (MUSC Mass Spectrometry
Facility) for the use of their facilities to perform the two-dimensional
liquid chromatography coupled with tandem mass spectrometry experiments,
and Jana Lee (Proteome Software) for assistance in using the Scaffold
software.
NR 66
TC 51
Z9 53
U1 6
U2 74
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1751-7362
J9 ISME J
JI ISME J.
PD APR
PY 2012
VL 6
IS 4
BP 835
EP 846
DI 10.1038/ismej.2011.154
PG 12
WC Ecology; Microbiology
SC Environmental Sciences & Ecology; Microbiology
GA 914JJ
UT WOS:000301945500013
PM 22158392
ER
PT J
AU Martinez, MN
Hunter, RP
AF Martinez, M. N.
Hunter, R. P.
TI Introduction to the bioequivalence theme issue
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA.
[Hunter, R. P.] Elanco Anim Hlth, Greenfield, IN USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA.
EM marilyn.martinez@fda.hhs.gov
OI Hunter, Robert/0000-0003-1224-2376
NR 2
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 1
EP 2
DI 10.1111/j.1365-2885.2012.01371.x
PG 2
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300001
PM 22413785
ER
PT J
AU Gehring, R
Martinez, M
AF Gehring, R.
Martinez, M.
TI Assessing product bioequivalence for extended-release formulations and
drugs with long half-lives
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID ORAL BIOAVAILABILITY; PHARMACOKINETICS; CEFOVECIN; DOGS
C1 [Martinez, M.] US FDA, Ctr Vet Med, Rockville, MD 20955 USA.
[Gehring, R.] Kansas State Univ, Coll Vet Med, Dept Clin Sci Agr Practices, Manhattan, KS 66506 USA.
RP Martinez, M (reprint author), US FDA, Ctr Vet Med, HFV 130, Rockville, MD 20955 USA.
EM marilyn.martinez@fda.hhs.gov
NR 9
TC 4
Z9 4
U1 1
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 3
EP 9
DI 10.1111/j.1365-2885.2012.01372.x
PG 7
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300002
PM 22413786
ER
PT J
AU Claxton, R
Cook, J
Endrenyi, L
Lucas, A
Martinez, MN
Sutton, SC
AF Claxton, R.
Cook, J.
Endrenyi, L.
Lucas, A.
Martinez, M. N.
Sutton, S. C.
TI Estimating product bioequivalence for highly variable veterinary drugs
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID SCALED AVERAGE BIOEQUIVALENCE; PATIENT VARIATION; BIOAVAILABILITY;
MEDICINE; DISSOLUTION; LIMITS; MODEL
C1 [Sutton, S. C.] Univ New England, Dept Pharmaceut Sci, Coll Pharm, Portland, ME 04103 USA.
[Claxton, R.] Schafer Vet Consultants, Ft Collins, CO USA.
[Cook, J.] Pfizer Inc, Clin Pharmacol, Specialty Care Business Unit, Groton, CT 06340 USA.
[Endrenyi, L.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada.
[Lucas, A.] Putney Inc, Portland, ME USA.
[Martinez, M. N.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA.
RP Sutton, SC (reprint author), Univ New England, Dept Pharmaceut Sci, Coll Pharm, Portland, ME 04103 USA.
EM ssutton1@une.edu
NR 24
TC 3
Z9 3
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 11
EP 16
DI 10.1111/j.1365-2885.2012.01376.x
PG 6
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300003
PM 22413787
ER
PT J
AU Bermingham, E
del Castillo, JRE
Lainesse, C
Pasloske, K
Radecki, S
AF Bermingham, E.
del Castillo, J. R. E.
Lainesse, C.
Pasloske, K.
Radecki, S.
TI Demonstrating bioequivalence using clinical endpoint studies
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID PHARMACOKINETIC EXPERIMENTS; DRUG DEVELOPMENT; GUIDELINES; SIMULATION;
RUMINANTS; EFFICACY; ECTOPARASITICIDES; TRIALS
C1 [Bermingham, E.] FDA Ctr Vet Med, Div Therapeut Drugs Nonfood Anim, Rockville, MD USA.
[del Castillo, J. R. E.] Univ Montreal, Dept Biomed Vet, St Hyacinthe, PQ, Canada.
[Lainesse, C.] Hlth Canada, Clin Evaluat Div, Vet Drugs Directorate, Ottawa, ON K1A 0L2, Canada.
[Pasloske, K.] Jurox Pty Ltd, Rutherford, NSW, Australia.
RP Bermingham, E (reprint author), FDA Ctr Vet Med, Div Therapeut Drugs Nonfood Anim, Rockville, MD USA.
EM eden.bermingham@fda.hhs.gov
RI del Castillo, Jerome/J-6976-2013
OI del Castillo, Jerome/0000-0001-5046-7926
NR 29
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 31
EP 37
DI 10.1111/j.1365-2885.2012.01366.x
PG 7
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300005
PM 22413789
ER
PT J
AU Toutain, PL
Modric, S
Bousquet-Melou, A
Sallovitz, JM
Lanusse, C
AF Toutain, P. -L.
Modric, S.
Bousquet-Melou, A.
Sallovitz, J. M.
Lanusse, C.
TI Should licking behavior be considered in the bioavailability evaluation
of transdermal products?
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID POUR-ON; CATTLE; IVERMECTIN; MOXIDECTIN; DORAMECTIN; CALVES;
BIOEQUIVALENCE; PROFILES; PLASMA; DRUGS
C1 [Toutain, P. -L.; Bousquet-Melou, A.] Univ Toulouse, INPT, ENVT, EIP,UPS, F-31076 Toulouse, France.
[Toutain, P. -L.; Bousquet-Melou, A.] INRA, UMR1331, F-31931 Toulouse, France.
[Modric, S.] US FDA, Ctr Vet Med, Rockville, MD USA.
[Sallovitz, J. M.; Lanusse, C.] Univ Nacl Ctr Prov Buenos Aires, Fac Ciencias Vet, Dept Fisiopatol, Farmacol Lab, Tandil, Argentina.
RP Toutain, PL (reprint author), Univ Toulouse, INPT, ENVT, EIP,UPS, 23 Chemin Capelles,BP 87614, F-31076 Toulouse, France.
EM pl.toutain@envt.fr
RI Toutain, Pierre-Louis/G-4540-2011
OI Toutain, Pierre-Louis/0000-0002-8846-8892
NR 20
TC 7
Z9 7
U1 0
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 39
EP 43
DI 10.1111/j.1365-2885.2012.01380.x
PG 5
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300006
PM 22413790
ER
PT J
AU Modric, S
Bermingham, E
Heit, M
Lainesse, C
Thompson, C
AF Modric, S.
Bermingham, E.
Heit, M.
Lainesse, C.
Thompson, C.
TI Considerations for extrapolating in vivo bioequivalence data across
species and routes
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID INTERSPECIES EXTRAPOLATION; INJECTED PHARMACEUTICALS;
GASTROINTESTINAL-TRACT; VETERINARY-MEDICINE; PATIENT VARIATION; DOSAGE
FORMS; PART II; RELEASE; ABSORPTION; CLEARANCE
C1 [Modric, S.; Bermingham, E.] US FDA, Ctr Vet Med, Rockville, MD 20886 USA.
[Heit, M.] Boehringer Ingelheim Vetmed, St Joseph, MO USA.
[Lainesse, C.] Hlth Canada, Vet Drugs Directorate, Ottawa, ON K1A 0L2, Canada.
[Thompson, C.] Eli Lilly & Co, Elanco Anim Hlth, Greenfield, IN USA.
RP Modric, S (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20886 USA.
EM sanja.modric@fda.hhs.gov
NR 32
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 45
EP 52
DI 10.1111/j.1365-2885.2012.01365.x
PG 8
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300007
PM 22413791
ER
PT J
AU Martinez, MN
Fahmy, R
AF Martinez, M. N.
Fahmy, R.
TI The scientific basis for establishing solubility criteria for veterinary
species
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID AQUEOUS DRUG SOLUBILITY; DISCOVERY; BIOAVAILABILITY; CLASSIFICATION;
PREDICTION
C1 [Martinez, M. N.; Fahmy, R.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA.
EM marilyn.martinez@fda.hhs.gov
NR 19
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0140-7783
EI 1365-2885
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 81
EP 86
DI 10.1111/j.1365-2885.2012.01370.x
PG 6
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300010
PM 22413794
ER
PT J
AU Martinez, MN
Papich, MG
AF Martinez, M. N.
Papich, M. G.
TI Drug solubility classification in the dog
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA.
[Papich, M. G.] N Carolina State Univ Raleigh, Dept Anat Physiol Sci & Radiol, Raleigh, NC USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV 130, Rockville, MD 20855 USA.
EM marilyn.martinez@fda.hhs.gov
FU Pfizer Animal Health, Bayer Animal Health; WB Saunders; Bayer
Corporation; Schering-Plough Animal Health; Pfizer Inc.; Morris Animal
Foundation; AAEP Foundation; Grayson Jockey Club
FX M.N.M. declares no conflicts of interest; M.G.P. has been a paid
consultant for the following companies or organizations: Pfizer Animal
Health, Bayer Corporation, Boehringer-Ingelheim, Putney Inc., Lilly
Companion Animal Health. The following companies have sponsored some of
his speaking activities: Pfizer Animal Health, Bayer Animal Health. He
has a financial agreement with the following publishers: Elsevier
(formerly WB Saunders): author of four veterinary drug books and
Blackwell Publishing: editor and author of a veterinary drug textbook.
Work in his laboratory has been funded by the following companies or
organizations: Bayer Corporation, Schering-Plough Animal Health, Pfizer
Inc., Morris Animal Foundation, AAEP Foundation, Grayson Jockey Club. He
serves on these boards or committees as a volunteer: Member of the
Council of Experts for the United States Pharmacopeia (USP), Member of
the CLSI (NCCLS), Veterinary Antimicrobial Susceptibility Testing
subcommittee (VAST).
NR 7
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 87
EP 91
DI 10.1111/j.1365-2885.2012.01373.x
PG 5
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300011
PM 22413795
ER
PT J
AU Martinez, MN
Apley, MD
AF Martinez, M. N.
Apley, M. D.
TI Drug solubility classification in the bovine
SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
LA English
DT Article
ID RUMINAL FERMENTATION; BEEF STEERS; DAIRY-COWS; DIGESTION
C1 [Martinez, M. N.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA.
[Apley, M. D.] Kansas State Univ, Coll Vet Med, PharmCATS Bioanalyt Serv, Manhattan, KS 66506 USA.
RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, HFV 130,7500 Standish Pl, Rockville, MD 20855 USA.
EM marilyn.martinez@fda.hhs.gov
NR 11
TC 4
Z9 4
U1 1
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0140-7783
J9 J VET PHARMACOL THER
JI J. Vet. Pharmacol. Ther.
PD APR
PY 2012
VL 35
SU 1
SI SI
BP 93
EP 97
DI 10.1111/j.1365-2885.2012.01369.x
PG 5
WC Pharmacology & Pharmacy; Veterinary Sciences
SC Pharmacology & Pharmacy; Veterinary Sciences
GA 907OX
UT WOS:000301428300012
PM 22413796
ER
PT J
AU Banugaria, SG
Patel, TT
Mackey, J
Das, S
Amalfitano, A
Rosenberg, AS
Charrow, J
Chen, YT
Kishnani, PS
AF Banugaria, Suhrad G.
Patel, Trusha T.
Mackey, Joanne
Das, Stuti
Amalfitano, Andrea
Rosenberg, Amy S.
Charrow, Joel
Chen, Y-T
Kishnani, Priya S.
TI Persistence of high sustained antibodies to enzyme replacement therapy
despite extensive immunomodulatory therapy in an infant with Pompe
disease: Need for agents to target antibody-secreting plasma cells
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Pompe disease; Antibodies; Immunomodulation; Cyclophosphamide;
Rituximab; Plasmapheresis
ID ACID ALPHA-GLUCOSIDASE; IMMUNE TOLERANCE INDUCTION; ALGLUCOSIDASE ALPHA;
CLINICAL-OUTCOMES; TERM; CHILDREN; TISSUES
AB With the advent of enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA, Myozyme (R)) for Pompe disease, the clinical course of the disease has changed. We have previously described the poor outcome in cross reactive immunologic material (CRIM)-negative and high-titer CRIM-positive (HTCP) patients secondary to high sustained antibody titers (HSAT) which effectively neutralize ERT efficacy. Various immunomodulation strategies are being explored to diminish the immune response to ERT. However, once HSAT are formed, tolerization therapy has uniformly failed to lower antibody titers. Here we describe a case in which immunomodulation over a prolonged period of 28 months with cyclophosphamide, intravenous immunoglobulin, plasmapheresis, increased doses of rhGAA and rituximab failed to lower antibody titers and resulted in continued clinical decline in an infantile Pompe disease patient treated with ERT. Thus, it appears that the failure to target the antibody-secreting plasma cells responsible for HSAT led to a failure of tolerance induction. This is the first report using this combination of agents over a very extensive period of time with no success. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Banugaria, Suhrad G.; Patel, Trusha T.; Mackey, Joanne; Das, Stuti; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA.
[Amalfitano, Andrea] Michigan State Univ, Dept Microbiol & Mol Genet, Coll Osteopath Med, E Lansing, MI 48824 USA.
[Amalfitano, Andrea] Michigan State Univ, Dept Pediat, Coll Osteopath Med, E Lansing, MI 48824 USA.
[Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Charrow, Joel] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Chen, Y-T] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
RP Kishnani, PS (reprint author), DUMC Box 103856,GSRB 1,4th Floor,905 LaSalle St, Durham, NC 27710 USA.
EM kishn001@mc.duke.edu
FU Synpac, Inc. (Durham, NC); Genzyme Corporation (Cambridge, MA); Genzyme
Corporation; Duke Clinical Research Unit (DCRU), National Center for
Research Resources [1UL1RR024128]; National Institutes of Health
FX The clinical trials in which this patient was enrolled were sponsored by
Synpac, Inc. (Durham, NC) and Genzyme Corporation (Cambridge, MA). The
clinical trials were supported by Genzyme Corporation and Grant
1UL1RR024128 from the Duke Clinical Research Unit (DCRU) Program,
National Center for Research Resources and the National Institutes of
Health. Priya S. Kishnani and Andrea Amalfitano have received
research/grant support from Genzyme Corporation. Joel Charrow is a
member of the Fabry and Gaucher Disease Registry Advisory Board for
Genzyme Corporation. Priya S. Kishnani is a member of the Pompe and
Gaucher Disease Registry Advisory Board for Genzyme Corporation. Joel
Charrow, Y-T Chen and Priya S. Kishnani and have received honoraria from
Genzyme Corporation. Alglucosidase alfa rhGAA, in the form of Genzyme's
product alglucosidase alfa, (Myozyme (R)/Lumizyme (R)) has been approved
by the US FDA and the European Union as therapy for Pompe disease. Duke
University and the inventors of the method of treatment and precursors
of the cell lines used to generate the enzyme (rhGAA) used commercially
have received royalties pursuant to the university's policy on
inventions, patents, and technology transfer. This potential conflict
for Duke University has been resolved through monetization. S. G.
Banugaria, T. T. Patel, S. Das, J. Mackey and A. S. Rosenberg have no
financial or proprietary interest in the materials presented herein.
NR 23
TC 28
Z9 28
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD APR
PY 2012
VL 105
IS 4
BP 677
EP 680
DI 10.1016/j.ymgme.2012.01.019
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 917OW
UT WOS:000302188700024
PM 22365055
ER
PT J
AU Kanungo, J
Cuevas, E
Ali, SF
Paule, MG
AF Kanungo, Jyotshnabala
Cuevas, Elvis
Ali, Syed F.
Paule, Merle G.
TI L-Carnitine rescues ketamine-induced attenuated heart rate and MAPK
(ERK) activity in zebrafish embryos
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE Heart rate; Ketamine; Zebrafish; L-Carnitine; MAPK/ERK; SAPK
ID GUINEA-PIG; MYOCARDIAL-INFARCTION; DIASTOLIC FUNCTION; PAPILLARY-MUSCLE;
GENE-EXPRESSION; MACACA-MULATTA; IN-VIVO; KINASE; CALCIUM; STIMULATION
AB Ketamine, an antagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptors, is a pediatric anesthetic. Ketamine has been shown to be neurotoxic and cardiotoxic in mammals. Here, we show that after 211 of exposure, 5 mM ketamine significantly reduced heart rate in 26 h old zebrafish embryos. In 52 h old embryos, I mM ketamine was effective after 2 h and 0.5 mM ketamine at 2011 of exposure. Ketamine also induced significant reductions in activated MAPK (ERK) levels. Treatment of the embryos with the ERK inhibitor, PD 98059, also significantly reduced heart rate whereas the p38/SAPK inhibitor, SB203580, was ineffective. Ketamine is known to inhibit lipolysis and a decrease of ATP content in the heart. Co-treatment with L-carnitine that enhances fatty acid metabolism effectively rescued ketamine-induced attenuated heart rate and ERK activity. These findings demonstrate that L-carnitine counteracts ketamine's negative effects on heart rate and ERK activity in zebrafish embryos. Published by Elsevier Inc.
C1 [Kanungo, Jyotshnabala; Cuevas, Elvis; Ali, Syed F.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Kanungo, J (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM jyotshnabala.kanungo@fda.hhs.gov
FU National Center for Toxicological Research (NCTR)/US Food and Drug
Administration (FDA)
FX This work was supported by the National Center for Toxicological
Research (NCTR)/US Food and Drug Administration (FDA). We thank Melanie
Dumas for zebrafish breeding.
NR 65
TC 14
Z9 14
U1 3
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD APR
PY 2012
VL 33
IS 2
SI SI
BP 205
EP 212
DI 10.1016/j.reprotox.2011.10.004
PG 8
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA 917US
UT WOS:000302204700010
PM 22027688
ER
PT J
AU Jacob, CC
Von Tungeln, LS
Vanlandingham, M
Beland, FA
da Costa, GG
AF Jacob, Cristina C.
Von Tungeln, Linda S.
Vanlandingham, Michelle
Beland, Frederick A.
da Costa, Goncalo Gamboa
TI Pharmacokinetics of Melamine and Cyanuric Acid and Their Combinations in
F344 Rats
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE melamine; cyanuric acid; melamine cyanurate; pharmacokinetics
ID EXCRETION; CATS; DISPOSITION; ABSORPTION; TOXICITY; DOGS
AB The intentional adulteration of pet food with melamine and cyanuric acid has been implicated in the kidney failure and death of a large number of cats and dogs in the United States. Although individually these compounds present low toxicity in a range of experimental animals, coexposure can lead to the formation of melamine cyanurate crystals in the nephrons and eventual kidney failure. Given this mode of action, a good understanding of the pharmacokinetic profiles of melamine and cyanuric acid and their combinations is essential to define properly the risk associated with different exposure scenarios. Previous studies have investigated the individual pharmacokinetic profiles of melamine and cyanuric acid. In this work, we report a comparison between the pharmacokinetic profiles of melamine and cyanuric acid administered individually, administered simultaneously as the individual compounds, and administered as a preformed melamine cyanurate complex. Although the oral coadministration of 1 mg/kg body weight of melamine and cyanuric acid did not alter significantly the pharmacokinetic profiles in relation to those determined upon individual oral administration of each compound, the administration of equal amounts of each triazine as the preformed melamine cyanurate complex significantly altered the pharmacokinetics, with reduced bioavailability of both compounds, lower observed maximum serum concentrations, delayed peak concentrations, and prolonged elimination half lives. These results indicate that in order to estimate properly the combined nephrotoxic potential of melamine and cyanuric acid, the experimental design of toxicological experiments and the evaluation of animal or human exposure scenarios should consider the detailed mode of exposure, with particular emphasis on any possible ex vivo formation of melamine cyanurate.
C1 [Jacob, Cristina C.; Von Tungeln, Linda S.; Vanlandingham, Michelle; Beland, Frederick A.; da Costa, Goncalo Gamboa] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA.
RP da Costa, GG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 233,3900 NCTR Rd, Jefferson, AR 72079 USA.
EM goncalo.gamboa@fda.hhs.gov
RI Jacob, Cristina/A-3885-2015
OI Jacob, Cristina/0000-0003-2652-3865
FU Food and Drug Administration; National Institute of Environmental Health
Sciences [FDA IAG:224-07-0007, NIH Y1ES1027]
FX This study was supported through an interagency agreement between the
Food and Drug Administration and the National Toxicology Program at the
National Institute of Environmental Health Sciences (FDA
IAG:224-07-0007; NIH Y1ES1027).
NR 21
TC 17
Z9 18
U1 0
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD APR
PY 2012
VL 126
IS 2
BP 317
EP 324
DI 10.1093/toxsci/kfr348
PG 8
WC Toxicology
SC Toxicology
GA 915FD
UT WOS:000302008600004
PM 22228804
ER
PT J
AU Baylis, SA
Ma, L
Padley, DJ
Heath, AB
Yu, MW
AF Baylis, S. A.
Ma, L.
Padley, D. J.
Heath, A. B.
Yu, M. W.
CA Collaborative Study Grp
TI Collaborative study to establish a World Health Organization
International genotype panel for parvovirus B19 DNA nucleic acid
amplification technology (NAT)-based assays
SO VOX SANGUINIS
LA English
DT Article
DE nucleic acid amplification technique; parvovirus B19; standard
ID GENETIC DIVERSITY; IDENTIFICATION; STANDARD; PLASMA
AB Background and Objectives The aim of the collaborative study was to evaluate a panel of plasma samples containing different genotypes of parvovirus B19 (B19V) for use in nucleic acid amplification technology (NAT)-based assays.
Materials and Methods The panel of samples [Center for Biologics Evaluation and Research Parvovirus B19 Genotype Panel 1; National Institute for Biological Standards and Control (NIBSC) code number 09/110] comprises four different members, i.e. Member 1, Member 2, Member 3, and Member 4 (M1-M4); these represent genotypes 1, 2, 3a B19V, and a negative plasma control, respectively. Thirty-five laboratories from 13 different countries participated in the study. Participants assayed the panel members concurrently with the 2nd World Health Organization (WHO) International Standard for B19V DNA (NIBSC code 99/802) on four separate occasions.
Results A total of 44 sets of data were returned, 34 from quantitative assays and 10 from qualitative assays. The majority of assays used were in-house and based on real-time PCR. The results showed that all three genotypes were detected consistently by the majority of participants, although a small number of assays detected genotypes 2 and 3 less efficiently, or not at all. Real-time stability studies have indicated that the panel of B19V samples is stable under normal conditions of storage, i.e. <= -70 degrees C.
Conclusions The four-member panel is intended for use in evaluating the ability of NAT assays to detect different B19V genotypes (M1-M3). Based on the results of the collaborative study, the panel was established as the 1st WHO International Reference Panel for parvovirus B19 genotypes.
C1 [Baylis, S. A.] Paul Ehrlich Inst, D-63225 Langen, Germany.
[Ma, L.; Yu, M. W.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Padley, D. J.; Heath, A. B.] Natl Inst Biol Stand & Controls, S Mimms, Herts, England.
RP Baylis, SA (reprint author), Paul Ehrlich Inst, Paul Ehrlich Str 51-59, D-63225 Langen, Germany.
EM baysa@pei.de
OI Wenzel, Jurgen/0000-0001-8422-6581; Lappalainen,
Maija/0000-0001-5400-1250
FU CBER; CBER/FDA
FX We thank National Genetics Institute, CSL Behring GmbH, Baxter AG and
Talecris Biotherapeutics Inc. for providing materials and data essential
for formulating this panel. L.M. was supported by the Research
Participation Program at the CBER administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the U.S. Department of Energy and the FDA. We also thank Dr.
J.S. Finlayson for critical review of the manuscript and CBER/FDA for
the funding support.
NR 30
TC 11
Z9 13
U1 0
U2 5
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 APR
PY 2012
VL 102
IS 3
BP 204
EP 211
DI 10.1111/j.1423-0410.2011.01541.x
PG 8
WC Hematology
SC Hematology
GA 907SK
UT WOS:000301437900004
PM 21988191
ER
PT J
AU Weng, ZQ
Suda, M
Ohtani, K
Mei, N
Kawamoto, T
Nakajima, T
Wang, RS
AF Weng, Zuquan
Suda, Megumi
Ohtani, Katsumi
Mei, Nan
Kawamoto, Toshihiro
Nakajima, Tamie
Wang, Rui-Sheng
TI Differential genotoxic effects of subchronic exposure to ethyl tertiary
butyl ether in the livers of Aldh2 knockout and wild-type mice
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE ETBE; Genotoxic effect; Liver; Aldh2 knockout mice
ID ACCELERATOR MASS-SPECTROMETRY; ELECTROPHORESIS COMET ASSAY; GENE
TARGETING MOUSE; FISCHER-344 RATS; KINETIC-PROPERTIES; ORGANS LIVER;
BONE-MARROW; CD-1 MICE; IN-VITRO; DNA
AB Ethyl tertiary butyl ether (ETBE) is used as an additive to gasoline to reduce carbon monoxide emissions in some developed countries. So far, ETBE was not found with positive results in many genotoxic assays. This study is undertaken to investigate the modifying effects of deficiency of aldehyde dehydrogenase 2 (ALDH2) on the toxicity of ETBE in the livers of mice. Eight-week-old wild-type (WT) and Aldh2 knockout (KO) C57BL/6 mice of both sexes were exposed to 0, 500, 1,750, and 5,000 ppm ETBE for 6 h/day with 5 days per weeks for 13 weeks. Histopathology assessments and measurements of genetic effects in the livers were performed. Significantly increased accidences of centrilobular hypertrophy were observed in the livers of WT and KO mice of both sexes in 5,000 ppm group; there was a sex difference in centrilobular hypertrophy between male and female KO mice, with more severe damage in the males. In addition, DNA strand breaks, 8-hydroxyguanine DNA-glycosylase (hOGG1)-modified oxidative base modification, and 8-hydroxydeoxyguanosine as genetic damage endpoints were significantly increased in three exposure groups in KO male mice, while these genotoxic effects were only found in 5,000 ppm group of KO female mice. In WT mice, significant DNA damage was seen in 5,000 ppm group of male mice, but not in females. Thus, sex differences in DNA damage were found not only in KO mice, but also in WT mice. These results suggest that ALDH2 polymorphisms and sex should be taken into considerations in predicting human health effects of ETBE exposure.
C1 [Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Wang, Rui-Sheng] Japan Natl Inst Occupat Safety & Hlth, Div Hlth Effects Res, Kawasaki, Kanagawa 2148585, Japan.
[Mei, Nan] Natl Ctr Toxicol Res, Dept Genet & Mol Toxicol, Jefferson, AR 72079 USA.
[Kawamoto, Toshihiro] Univ Occupat & Environm Hlth, Dept Environm Hlth, Kitakyushu, Fukuoka 807, Japan.
[Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Dept Occupat & Environm Hlth, Nagoya, Aichi 4648601, Japan.
RP Wang, RS (reprint author), Japan Natl Inst Occupat Safety & Hlth, Div Hlth Effects Res, 6-21-1 Nagao, Kawasaki, Kanagawa 2148585, Japan.
EM wang@h.jniosh.go.jp
RI perumal, murugiah/D-1565-2012;
OI MEI, NAN/0000-0002-3501-9014
FU Japan National Institute of Occupational Safety and Health [P21-03]
FX This work was supported by Japan National Institute of Occupational
Safety and Health [Grand-in aid for Project Research P21-03].
NR 35
TC 6
Z9 6
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD APR
PY 2012
VL 86
IS 4
BP 675
EP 682
DI 10.1007/s00204-011-0779-x
PG 8
WC Toxicology
SC Toxicology
GA 912IZ
UT WOS:000301792400017
PM 22102104
ER
PT J
AU Bubalo, JS
Cherala, G
McCune, JS
Munar, MY
Tse, S
Maziarz, R
AF Bubalo, Joseph S.
Cherala, Ganesh
McCune, Jeannine S.
Munar, Myrna Y.
Tse, Sunny
Maziarz, Richard
TI Aprepitant Pharmacokinetics and Assessing the Impact of Aprepitant on
Cyclophosphamide Metabolism in Cancer Patients Undergoing Hematopoietic
Stem Cell Transplantation
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE Hematopoietic cell transplant; aprepitant; myeloablative regimen;
CYP450; pharmacokinetics; azole antifungals; cyclophosphamide;
sinusoidal obstruction syndrome
ID HUMAN LIVER-MICROSOMES; LIQUID-CHROMATOGRAPHY; IFOSFAMIDE ACTIVATION;
CYTOCHROME-P450 3A4; BIOACTIVATION; BUSULFAN; PLASMA; DEXAMETHASONE;
CHEMOTHERAPY; INHIBITOR
AB Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in cancer patients undergoing HSCT. Forty subjects were randomized to either aprepitant or placebo in addition to standard antiemetics. Aprepitant or placebo was started 1 hour before the first chemotherapy or radiation dose for HSCT conditioning and administered daily until 4 days after infusion of the hematopoietic cell graft (for a total of 10-12 days). Serial blood samples were collected for aprepitant and CY plus 2 important CY metabolites. The results indicate that aprepitant is well absorbed and does not auto-induce its metabolism. No significant drug interaction was observed with CY or its metabolites. A significant portion of the patients had subtherapeutic aprepitant concentrations; however, chemotherapy-induced nausea and vomiting were effectively managed. No dosage adjustment was necessary, and administration of aprepitant in HSCT at the prescribed dosage of 125 mg orally on day 1 and 80 mg orally on each consecutive day through day +4 after HSCT was well tolerated with no significant changes in CY pharmacokinetic parameters.
C1 [Cherala, Ganesh; Munar, Myrna Y.] Oregon State Univ, Dept Pharm Practice, Portland, OR 97239 USA.
[Bubalo, Joseph S.] Oregon Hlth & Sci Univ, Dept Pharm Serv, Portland, OR 97201 USA.
[Cherala, Ganesh; Munar, Myrna Y.] Oregon Hlth & Sci Univ, Coll Pharm, Portland, OR 97201 USA.
[McCune, Jeannine S.] Univ Washington, Dept Pharm, Seattle, WA 98195 USA.
[McCune, Jeannine S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Tse, Sunny] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA.
[Maziarz, Richard] Oregon Hlth & Sci Univ, Bone Marrow Transplant Program, Portland, OR 97201 USA.
RP Cherala, G (reprint author), Oregon State Univ, Dept Pharm Practice, 3303 SW Bond Ave,Mail Code CH12C, Portland, OR 97239 USA.
EM cheralag@ohsu.edu
RI Cherala, Ganesh/I-9210-2014
OI McCune, Jeannine/0000-0002-0795-497X; Cherala,
Ganesh/0000-0003-3678-0443
FU Merck and Co.; Merck Co, Inc.
FX Joseph Bubalo is on the Merck and Co Speakers Bureau and also received
clinical trial support as a grant from Merck and Co. This work is partly
funded by Merck & Co, Inc.
NR 27
TC 11
Z9 11
U1 0
U2 6
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0091-2700
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD APR
PY 2012
VL 52
IS 4
BP 586
EP 594
DI 10.1177/0091270011398243
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 914PP
UT WOS:000301964000014
PM 21415280
ER
PT J
AU Akiyama, T
Khan, AA
AF Akiyama, Tatsuya
Khan, Ashraf A.
TI Isolation and characterization of small qnrS1-carrying plasmids from
imported seafood isolates of Salmonella enterica that are highly similar
to plasmids of clinical isolates
SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY
LA English
DT Article
DE Salmonella enterica; plasmid-mediated quinolone resistance; imported
seafood
ID MEDIATED QUINOLONE RESISTANCE; MECHANISMS; PREVALENCE; EMERGENCE
AB Dissemination of plasmid-mediated quinolone resistance among pathogenic bacteria is a concern for public health because of decreased sensitivity to fluoroquinolones and increased potentials to develop high fluoroquinolone resistance. Two qnrS1-positive isolates of Salmonella enterica Corvallis (468) and Typhimurium (484) from imported seafood (Thailand and Vietnam) were tested for quinolone sensitivity using disk agar diffusion and the Sensititre (R) system. The presence of qnr genes, qnr-carrying plasmids, and mutations in the quinolone resistance determining regions were also determined. Minimal inhibitory concentrations of nalidixic acid for isolates 468 and 484 were 8 and 16 mu g mL-1, respectively, and those of ciprofloxacin were 1 and 2 mu g mL-1, respectively. Disk agar diffusion indicated that isolate 468 was moderately resistant to moxifloxacin, and isolate 484 was resistant to moxifloxacin and moderately resistant to norfloxacin. Isolates 468 and 484 carried a mutation on parC, but not on gyrA, gyrB, or parE. Sequences of qnrS1-carrying plasmids from isolates 468 and 484, sized 10 039 and 10 047 bp, were nearly identical (> 99% similarity) to each other and to published sequences of plasmids from clinical isolates of Salmonella Typhimurium isolated in the United Kingdom and Taiwan, indicating a dissemination of qnrS1-carrying plasmids among different serovars of Salmonella from geographically separated sources. This is the first complete sequence of a qnrS1-carrying plasmid from imported seafood isolate of S. enterica.
C1 [Akiyama, Tatsuya; Khan, Ashraf A.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Khan, AA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM ashraf.khan@fda.hhs.gov
RI Khan, Ashraf/E-8133-2013
FU National Center for Toxicological Research
FX We thank Drs. Carl E. Cerniglia, John B. Sutherland, and Marli Azevedo
for critical review of the manuscript, and Dr. Chorng-Ming Cheng for
providing Salmonella strains. We also want to thank Christine V.
Summage-West for technical support. This work was supported in part by
an appointment to the Postgraduate Research Program at the National
Center for Toxicological Research administered by the Oak Ridge
Institute for Science and Education through an interagency agreement
between the US Department of Energy and the US Food and Drug
Administration. The views presented in this article do not necessarily
reflect those of the US Food and Drug Administration.
NR 17
TC 6
Z9 6
U1 0
U2 3
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0928-8244
J9 FEMS IMMUNOL MED MIC
JI FEMS Immunol. Med. Microbiol.
PD APR
PY 2012
VL 64
IS 3
BP 429
EP 432
DI 10.1111/j.1574-695X.2011.00921.x
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 905PC
UT WOS:000301283700014
PM 22151215
ER
PT J
AU Burgos, JM
Schmitt, MP
AF Burgos, Jonathan M.
Schmitt, Michael P.
TI The ChrA Response Regulator in Corynebacterium diphtheriae Controls
Hemin-Regulated Gene Expression through Binding to the hmuO and hrtAB
Promoter Regions
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID 2-COMPONENT SIGNAL-TRANSDUCTION; BORDETELLA-PERTUSSIS; TOXIN REPRESSOR;
STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; VIRULENCE GENES;
RNA-POLYMERASE; IRON UPTAKE; SYSTEM; HEMOGLOBIN
AB Corynebacterium diphtheriae, the etiologic agent of diphtheria, utilizes heme and hemoglobin (Hb) as iron sources for growth. Heme-iron utilization involves HmuO, a heme oxygenase that degrades cytosolic heme, resulting in the release of heme-associated iron. Expression of the hmuO promoter is under dual regulation, in which transcription is repressed by DtxR and iron and activated by a heme source, such as hemin or Hb. Hemin-dependent activation is mediated primarily by the ChrAS two-component system, in which ChrS is a putative heme-responsive sensor kinase while ChrA is proposed to serve as a response regulator that activates transcription. It was recently shown that the ChrAS system similarly regulates the hrtAB genes, which encode an ABC transporter involved in the protection of C. diphtheriae from hemin toxicity. In this study, we characterized the phosphorelay mechanism in the ChrAS system and provide evidence for the direct regulation of the hmuO and hrtAB promoters by ChrA. A fluorescence staining method was used to show that ChrS undergoes autophosphorylation and that the phosphate moiety is subsequently transferred to ChrA. Promoter fusion studies identified regions upstream of the hmuO and hrtAB promoters that are critical for the heme-dependent regulation by ChrA. Electrophoretic mobility shift assays revealed that ChrA specifically binds at the hmuO and hrtAB promoter regions and that binding is phosphorylation dependent. A phosphorylation-defective mutant of ChrA [ChrA(D50A)] exhibited significantly diminished binding to the hmuO promoter region relative to that of wildtype ChrA. DNase I footprint analysis further defined the sequences in the hmuO and hrtAB promoters that are involved in ChrA binding, and this analysis revealed that the DtxR binding site at the hmuO promoter partially overlaps the binding site for ChrA. DNase I protection studies as well as promoter fusion analysis suggest that ChrA and DtxR compete for binding at the hmuO promoter. Collectively, these data demonstrate that the ChrA response regulator directly controls the expression of hmuO and the hrtAB genes and the binding activity of ChrA is dependent on phosphorylation by its cognate sensor kinase ChrS.
C1 [Burgos, Jonathan M.; Schmitt, Michael P.] US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20852 USA.
RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20852 USA.
EM michael.schmitt@fda.hhs.gov
NR 48
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 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD APR
PY 2012
VL 194
IS 7
BP 1717
EP 1729
DI 10.1128/JB.06801-11
PG 13
WC Microbiology
SC Microbiology
GA 906KT
UT WOS:000301344700009
PM 22287525
ER
PT J
AU Lionberger, RA
Raw, AS
Kim, SH
Zhang, XY
Yu, LX
AF Lionberger, Robert A.
Raw, Andre S.
Kim, Stephanie H.
Zhang, Xinyuan
Yu, Lawrence X.
TI Use of Partial AUC to Demonstrate Bioequivalence of Zolpidem Tartrate
Extended Release Formulations
SO PHARMACEUTICAL RESEARCH
LA English
DT Article
DE bioequivalence; modeling; modified-release; partial AUC; quality by
design
ID HIGHLY VARIABLE DRUGS; THERAPEUTIC EQUIVALENCE; PRODUCTS; ABSORPTION
AB FDA's bioequivalence recommendation for Zolpidem Tartrate Extended Release Tablets is the first to use partial AUC (pAUC) metrics for determining bioequivalence of modified-release dosage forms. Modeling and simulation studies were performed to aid in understanding the need for pAUC measures and also the proper pAUC truncation times.
Deconvolution techniques, In Vitro/In Vivo Correlations, and the CAT (Compartmental Absorption and Transit) model were used to predict the PK profiles for zolpidem. Models were validated using in-house data submitted to the FDA. Using dissolution profiles expressed by the Weibull model as input for the CAT model, dissolution spaces were derived for simulated test formulations.
The AUC(0-1.5) parameter was indicative of IR characteristics of early exposure and effectively distinguished among formulations that produced different pharmacodynamic effects. The AUC(1.5-t) parameter ensured equivalence with respect to the sustained release phase of Ambien CR. The variability of AUC(0-1.5) is higher than other PK parameters, but is reasonable for use in an equivalence test.
In addition to the traditional PK parameters of AUCinf and Cmax, AUC(0-1.5) and AUC(1.5-t) are recommended to provide bioequivalence measures with respect to label indications for Ambien CR: onset of sleep and sleep maintenance.
C1 [Lionberger, Robert A.; Raw, Andre S.; Kim, Stephanie H.; Zhang, Xinyuan; Yu, Lawrence X.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA.
RP Lionberger, RA (reprint author), US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 7519 Standish Pl, Rockville, MD 20855 USA.
EM Robert.Lionberger@fda.hhs.gov
RI Yu, Lawrence/L-6280-2016
NR 14
TC 13
Z9 13
U1 1
U2 8
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0724-8741
J9 PHARM RES-DORDR
JI Pharm. Res.
PD APR
PY 2012
VL 29
IS 4
BP 1110
EP 1120
DI 10.1007/s11095-011-0662-8
PG 11
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 909UQ
UT WOS:000301591100020
PM 22278753
ER
PT J
AU Musunuru, K
Roden, DM
Boineau, R
Bristow, MR
McCaffrey, TA
Newton-Cheh, C
Paltoo, DN
Rosenberg, Y
Wohlgemuth, JG
Zineh, I
Hasan, AAK
AF Musunuru, Kiran
Roden, Dan M.
Boineau, Robin
Bristow, Michael R.
McCaffrey, Timothy A.
Newton-Cheh, Christopher
Paltoo, Dina N.
Rosenberg, Yves
Wohlgemuth, Jay G.
Zineh, Issam
Hasan, Ahmed A. K.
TI Cardiovascular Pharmacogenomics: Current Status and Future
Directions-Report of a National Heart, Lung, and Blood Institute Working
Group
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE genetic polymorphisms; genetics; pharmacogenetics; pharmacogenetics
anticoagulants; pharmacogenetics cholesterol
ID ACUTE CORONARY SYNDROMES; GENOME-WIDE ASSOCIATION; TRP719ARG
POLYMORPHISM; MYOCARDIAL-INFARCTION; CYP2C19 GENOTYPE; WARFARIN;
CLOPIDOGREL; ANTICOAGULATION; EFFICACY; OUTCOMES
C1 [Musunuru, Kiran] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Musunuru, Kiran] Harvard Univ, Cambridge, MA 02138 USA.
[Roden, Dan M.] Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA.
[Boineau, Robin; Paltoo, Dina N.; Rosenberg, Yves; Hasan, Ahmed A. K.] NHLBI, Bethesda, MD 20892 USA.
[Bristow, Michael R.] Univ Colorado, Cardiovasc Inst, Aurora, CO USA.
[McCaffrey, Timothy A.] George Washington Univ, Med Ctr, Washington, DC 20037 USA.
[Newton-Cheh, Christopher] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[Wohlgemuth, Jay G.] Quest Diagnost Nichols Inst, San Juan Capistrano, CA USA.
[Zineh, Issam] US FDA, Silver Spring, MD USA.
RP Musunuru, K (reprint author), Harvard Univ, 7 Divin Ave, Cambridge, MA 02138 USA.
EM kiranmusunuru@gmail.com
FU National Heart, Lung, and Blood Institute; Personalized Medicine
Coalition; American College of Cardiology; American Medical Association;
Cheney Cardiovascular Institute at George Washington University
FX The Working Group meeting was underwritten by the National Heart, Lung,
and Blood Institute at the National Institutes of Health, Bethesda, MD.
The New Frontiers in Personalized Medicine: Cardiovascular Research and
Clinical Care was supported and/or cosponsored by the National Heart,
Lung, and Blood Institute; Personalized Medicine Coalition; American
College of Cardiology; American Medical Association; and the Cheney
Cardiovascular Institute at George Washington University.
NR 37
TC 5
Z9 5
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD APR
PY 2012
VL 1
IS 2
AR UNSP e000554
DI 10.1161/JAHA.111.000554
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 243QY
UT WOS:000326333200009
PM 23130127
ER
PT J
AU Zidan, AS
Rahman, Z
Khan, MA
AF Zidan, Ahmed S.
Rahman, Ziyaur
Khan, Mansoor A.
TI Chemometric evaluation of brompheniramine-tannate complexes
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE complexation; calorimetry (DSC); chemometrics; dissolution; infrared
spectroscopy; Raman spectroscopy
ID NEAR-INFRARED SPECTROSCOPY; QUANTITATIVE-ANALYSIS; RAMAN-SPECTROSCOPY;
MODEL SYSTEMS; TANNIC-ACID; NIR; IDENTIFICATION; OILS; CLASSIFICATION;
MULTIVARIATE
AB The objective of the current study was to evaluate the performance of Raman and near-infrared (NIR) techniques combined with chemometrics in characterizing the critical quality attributes of brompheniramine (BP)tannate complexes. Seven complexes were prepared and evaluated for chemical interactions, solubilities, dissolutions, and spatial distributions by NIR chemical imaging (CI). Principal component analysis (PCA) was applied before either partial least squares regression (PLSR) or principal component regression (PCR) models were developed. Complexation was confirmed by Fourier transform IR analysis to yield complexes of lower drug solubilities and sustained-release characteristics in alkaline media. PCA results showed better discrimination ability by NIR than by Raman spectroscopy. Compared with PCR, the PLSR predictions errors, calculated from the Raman and NIR data with second-derivative pretreatment, showed lesser values of 2.68, 0.37, 1.79, and 5.60 and 0.58, 0.25, 0.93, and 0.58 for complex solubilities in acidic and alkaline media and percentages dissolved after 1 and 20 h, respectively. In addition, good correlation (>0.95) was obtained for predicting the drug concentration using PLSR score images explaining the validity of the NIR-CI model for spatial quantitation of BP within its tannate complexes. In conclusion, the chemometric analysis of NIR and/or Raman spectra represented an innovative approach to determine the tannate complexation variability. (c) 2011 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:14501461, 2012
C1 [Zidan, Ahmed S.; Rahman, Ziyaur; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Zagazig, Egypt.
RP Khan, MA (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM Mansoor.Khan@fda.hhs.gov
RI Zidan, Ahmed/I-1147-2012;
OI Rahman, Ziyaur/0000-0002-0402-825X
FU Oak Ridge Institute for Science and Education (Oak Ridge, Tennessee)
FX The authors would like to thank the Oak Ridge Institute for Science and
Education (Oak Ridge, Tennessee) for supporting the post doctoral
research program. The findings and conclusions in this article have not
been formally disseminated by the US Food and Drug Administration and
should not be construed to represent any agency determination or policy.
NR 43
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3549
J9 J PHARM SCI-US
JI J. Pharm. Sci.
PD APR
PY 2012
VL 101
IS 4
BP 1450
EP 1461
DI 10.1002/jps.23030
PG 12
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 898EV
UT WOS:000300720200010
PM 22213440
ER
PT J
AU Serdarevic, F
Jones, RC
Weaver, KN
Black, SR
Ritger, KA
Guichard, F
Dombroski, P
Emanuel, BP
Miller, L
Gerber, SI
AF Serdarevic, F.
Jones, R. C.
Weaver, K. N.
Black, S. R.
Ritger, K. A.
Guichard, F.
Dombroski, P.
Emanuel, B. P.
Miller, L.
Gerber, S. I.
TI Multi-pathogen waterborne disease outbreak associated with a dinner
cruise on Lake Michigan
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Article
DE Outbreaks; water-borne infections
ID SHIPS
AB We report an outbreak associated with a dinner cruise on Lake Michigan. This took place on the same day as heavy rainfall, which resulted in 42.4 billion liters of rainwater and storm runoff containing highly diluted sewage being released into the lake. Of 72 cruise participants, 41 (57%) reported gastroenteritis. Stool specimens were positive for Shigella sonnei (n=3), Giardia (n=3), and Cryptosporidium (n=2). Ice consumption was associated with illness (risk ratio 2.2, P=0.011). S. sonnei was isolated from a swab obtained from the one of the boat's ice bins. Environmental inspection revealed conditions and equipment that could have contributed to lake water contaminating the hose used to load potable water onto the boat. Knowledge of water holding and distribution systems on boats, and of potential risks associated with flooding and the release of diluted sewage into large bodies of water, is crucial for public health guidance regarding recreational cruises.
C1 [Gerber, S. I.] Cook Cty Dept Publ Hlth, Communicable Dis Program, Oak Forest, IL 60452 USA.
[Serdarevic, F.; Jones, R. C.; Weaver, K. N.; Black, S. R.; Ritger, K. A.; Miller, L.] Chicago Dept Publ Hlth, Communicable Dis Program, Chicago, IL USA.
[Serdarevic, F.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA.
[Guichard, F.] Chicago Dept Publ Hlth, Food Protect Div, Chicago, IL USA.
[Dombroski, P.] Illinois Dept Publ Hlth, Div Labs, Springfield, IL 62761 USA.
[Emanuel, B. P.] US FDA, Consumer Safety Div, Chicago, IL USA.
RP Gerber, SI (reprint author), Cook Cty Dept Publ Hlth, Communicable Dis Program, 15900 S Cicero Ave,Bldg E-3rd Fl, Oak Forest, IL 60452 USA.
EM sgerber@ccdph.net
NR 5
TC 5
Z9 5
U1 1
U2 12
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 APR
PY 2012
VL 140
IS 4
BP 621
EP 625
DI 10.1017/S0950268811000896
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 899OE
UT WOS:000300824800008
PM 21676362
ER
PT J
AU Meng, FX
Hackenberg, M
Li, ZG
Yan, J
Chen, T
AF Meng, Fanxue
Hackenberg, Michael
Li, Zhiguang
Yan, Jian
Chen, Tao
TI Discovery of Novel MicroRNAs in Rat Kidney Using Next Generation
Sequencing and Microarray Validation
SO PLOS ONE
LA English
DT Article
ID CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; RNA-SEQ; MESSENGER-RNAS;
GENOME; IDENTIFICATION; ARABIDOPSIS; DATABASE; TARGETS; TOOL
AB MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of biological processes. The latest version of the miRBase database (Release 18) includes 1,157 mouse and 680 rat mature miRNAs. Only one new rat mature miRNA was added to the rat miRNA database from version 16 to version 18 of miRBase, suggesting that many rat miRNAs remain to be discovered. Given the importance of rat as a model organism, discovery of the completed set of rat miRNAs is necessary for understanding rat miRNA regulation. In this study, next generation sequencing (NGS), microarray analysis and bioinformatics technologies were applied to discover novel miRNAs in rat kidneys. MiRanalyzer was utilized to analyze the sequences of the small RNAs generated from NGS analysis of rat kidney samples. Hundreds of novel miRNA candidates were examined according to the mappings of their reads to the rat genome, presence of sequences that can form a miRNA hairpin structure around the mapped locations, Dicer cleavage patterns, and the levels of their expression determined by both NGS and microarray analyses. Nine novel rat hairpin precursor miRNAs (pre-miRNA) were discovered with high confidence. Five of the novel pre-miRNAs are also reported in other species while four of them are rat specific. In summary, 9 novel pre-miRNAs (14 novel mature miRNAs) were identified via combination of NGS, microarray and bioinformatics high-throughput technologies.
C1 [Meng, Fanxue; Li, Zhiguang; Yan, Jian; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Hackenberg, Michael] Univ Granada, Fac Ciencias, Dpto Genet, Granada, Spain.
RP Meng, FX (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM tao.chen@fda.hhs.gov
RI Hackenberg, Michael/A-2503-2009
OI Hackenberg, Michael/0000-0003-2248-3114
NR 68
TC 11
Z9 18
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 28
PY 2012
VL 7
IS 3
AR e34394
DI 10.1371/journal.pone.0034394
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 948FM
UT WOS:000304489000106
PM 22470567
ER
PT J
AU Ali, SF
Hussain, SM
Schlager, JJ
Trickler, WJ
AF Ali, Syed F.
Hussain, Saber M.
Schlager, John J.
Trickler, William J.
TI Engineered metallic nanoparticles and blood-brain-barrier
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Ali, Syed F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Hussain, Saber M.; Schlager, John J.; Trickler, William J.] US Air Force Res Lab, Appl Biotechnol Branch, HED AFRL, Dayton, OH 45433 USA.
EM Syed.ali@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 185-ENVR
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104969
ER
PT J
AU Battistel, MD
Shangold, M
Trinh, L
Shiloach, J
Freedberg, DI
AF Battistel, Marcos D.
Shangold, Michael
Trinh, Loc
Shiloach, Joseph
Freedberg, Daron I.
TI Hydrogen bonding, the foundations of helicity in a tetramer of alpha 2-8
sialic acid
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Battistel, Marcos D.; Shangold, Michael; Freedberg, Daron I.] US FDA, CBER, OVRR, Rockville, MD 20852 USA.
[Trinh, Loc] NIH, SBDPI, Bethesda, MD 20892 USA.
[Shiloach, Joseph] NIDDK, NIH, Bethesda, MD 20892 USA.
EM battiste@helix.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 131-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101194
ER
PT J
AU Borodina, Y
Callahan, L
Switzer, F
AF Borodina, Yulia
Callahan, Lawrence
Switzer, Frank
TI InChIs as building blocks for complex substance identifiers
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Borodina, Yulia; Callahan, Lawrence; Switzer, Frank] FDA, Off Commissioner, Silver Spring, MD 20993 USA.
EM yulia.borodina@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 111-CINF
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475103441
ER
PT J
AU Brorson, K
AF Brorson, Kurt
TI Quality by design, biopharmaceutical manufacture
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Brorson, Kurt] CDER FDA, Div Monoclonal Antibodies, Silve Spring, MD 20903 USA.
EM kurt.brorson@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 176-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100711
ER
PT J
AU Davis, EM
McDermott, MK
Benetatos, NM
Elabd, YA
AF Davis, Eric M.
McDermott, Martin K.
Benetatos, Nicholas M.
Elabd, Yossef A.
TI Drug delivery in biodegradable polymer coatings used in drug-eluting
medical devices: An infrared spectroscopic investigation
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Davis, Eric M.; Elabd, Yossef A.] Drexel Univ, Dept Chem & Biol Engn, Philadelphia, PA 19104 USA.
[McDermott, Martin K.; Benetatos, Nicholas M.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Device & Radiol Hlth, Silver Spring, MD 20903 USA.
EM emd64@drexel.edu
RI Elabd, Yossef/G-9866-2014
OI Elabd, Yossef/0000-0002-7790-9445
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 437-PMSE
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503204154
ER
PT J
AU Gendel, S
AF Gendel, Steven
TI Regulatory challenge of food allergens
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Gendel, Steven] US FDA, College Pk, MD 20740 USA.
EM steven.gendel@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 86-AGFD
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100044
ER
PT J
AU Lawless, MS
Zhang, JH
Zhuang, DC
Matthews, E
Waldman, M
Fraczkiewicz, R
AF Lawless, Michael S.
Zhang, Jinhua
Zhuang, Dechuan
Matthews, Edwin
Waldman, Marvin
Fraczkiewicz, Robert
TI Controlling specificity and sensitivity in artificial neural network
ensemble (ANNE) classification models
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Lawless, Michael S.; Zhang, Jinhua; Zhuang, Dechuan; Waldman, Marvin; Fraczkiewicz, Robert] Simulat Plus Inc, Lancaster, CA 93534 USA.
[Matthews, Edwin] US FDA, Ctr Food Safety & Nutr, Silver Spring, MD 20993 USA.
EM mlawless@simulations-plus.com
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 157-COMP
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475104351
ER
PT J
AU Madhavarao, C
Agarabi, C
Khan, M
Chen, C
Anderson, H
Johnson, G
AF Madhavarao, Chikkathur
Agarabi, Cyrus
Khan, Maliha
Chen, Claudia
Anderson, Howard
Johnson, Gibbes
TI Screening of supplements to increase output of a model therapeutic
enzyme protein and qualification in a parallel bioreactor system
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Madhavarao, Chikkathur; Khan, Maliha; Chen, Claudia; Anderson, Howard; Johnson, Gibbes] US FDA, Off Biotechnol Prod, Div Therapeut Proteins, Bethesda, MD 20014 USA.
[Agarabi, Cyrus] US FDA, Off Testing & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA.
EM cyrus.agarabi@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 271-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100802
ER
PT J
AU Miesegaes, G
Lute, S
Read, E
Dement-Brown, J
Brorson, K
AF Miesegaes, George
Lute, Scott
Read, Erik
Dement-Brown, Jessica
Brorson, Kurt
TI Comparison of adsorbtive membranes to traditional anion exchange
chromatography as an alternative purification step for monoclonal
antibodies
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Miesegaes, George; Lute, Scott; Read, Erik; Dement-Brown, Jessica; Brorson, Kurt] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20901 USA.
EM george.miesegaes@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 125-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100662
ER
PT J
AU Pohl, NL
Houser-Archeild, N
Benedict, R
Cipollo, JF
AF Pohl, Nichola L.
Houser-Archeild, Nadene
Benedict, Randy
Cipollo, John F.
TI Advances toward affinity proteomics strategies to target carbohydrate
dependant host pathogen interactions
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Houser-Archeild, Nadene; Cipollo, John F.] Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA.
[Pohl, Nichola L.; Benedict, Randy] Iowa State Univ, Ames, IA 50011 USA.
EM john.cipollo@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 66-CARB
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101132
ER
PT J
AU Pollack, SK
AF Pollack, Steven K.
TI From bed pans to deep brain stimulators: The polymer science of medical
devices
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 243rd National Spring Meeting of the American-Chemical-Society
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc
C1 [Pollack, Steven K.] US FDA, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA.
EM steven.pollack@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 443-POLY
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219JX
UT WOS:000324503204681
ER
PT J
AU Read, EK
Brorson, KA
AF Read, Erik K.
Brorson, Kurt A.
TI 2D HPLC-based process analytical technology for bioreactor control
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Read, Erik K.; Brorson, Kurt A.] US FDA, Off Biotechnol Prod, CDER FDA, Silver Spring, MD 20903 USA.
EM erik.read@fda.hhs.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 526-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475101058
ER
PT J
AU Uplekar, SD
Brorson, KA
LaCourse, WR
Moreira, AR
Rao, G
AF Uplekar, Shaunak D.
Brorson, Kurt A.
LaCourse, William R.
Moreira, Antonio R.
Rao, Govind
TI Comparability of monoclonal antibody titers and its glycosylation
profile produced in minibioreactors vs. bench scale bioreactors
SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Meeting Abstract
CT 11th International Biorelated Polymer Symposium / 243rd National Spring
Meeting of the American-Chemical-Society (ACS)
CY MAR 25-29, 2012
CL San Diego, CA
SP Amer Chem Soc, Div Polymer Chem Inc, Amer Chem Soc
C1 [Uplekar, Shaunak D.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA.
[Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA.
[LaCourse, William R.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
EM shaunak1@umbc.edu
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0065-7727
J9 ABSTR PAP AM CHEM S
JI Abstr. Pap. Am. Chem. Soc.
PD MAR 25
PY 2012
VL 243
MA 379-BIOT
PG 1
WC Chemistry, Multidisciplinary
SC Chemistry
GA 219AH
UT WOS:000324475100905
ER
PT J
AU Awotwe-Otoo, D
Agarabi, C
Faustino, PJ
Habib, MJ
Lee, S
Khan, MA
Shah, RB
AF Awotwe-Otoo, David
Agarabi, Cyrus
Faustino, Patrick J.
Habib, Muhammad J.
Lee, Sau
Khan, Mansoor A.
Shah, Rakhi B.
TI Application of quality by design elements for the development and
optimization of an analytical method for protamine sulfate
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Protamine sulfate; HPLC; Design of experiments; Box-Behnken;
Optimization
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYDROCHLORIDE; QUANTITATION;
PEPTIDES; PHASE
AB The purpose of this study was to develop a robust reverse phase-HPLC method for the separation of hydrolyzed protamine sulfate peptides using a quality by design approach.
A Plackett-Burman experimental design was utilized to screen the effects of mobile phase pH, flow rate, column temperature, injection volume and methanol concentration on peak resolution and USP tailing. Multivariate regression and Pareto ranking analyses showed that mobile phase pH, column temperature and injection volume were statistically significant (p<0.05) factors affecting the resolution and tailing of the peaks.
A Box-Behnken experimental design with response surface methodology was then utilized to evaluate the main, interaction, and quadratic effects of these three factors on the selected responses. A desirability function applied to the optimized conditions predicted peak resolutions between 1.99 and 3.61 and tailing factor between 1.02 and 1.45 for the four peptide peaks of protamine sulfate with the following chromatographic conditions: an isocratic mobile phase consisting of 100 mM monosodium phosphate buffer pH 2.25, 1.8% acetonitrile and 0.3% methanol. The injection volume was 20 mu l, with a column temperature of 24 degrees C and a flow rate of 1.0 ml/min and a total run time of less than 25 min. The optimized chromatographic method was validated according to ICH Q2R1 guidelines and applied to separate and compare the peaks of protamine sulfate from five different sources. Analyses of the peptide peaks of the five protamine sulfate samples showed no significant differences in their compositions.
The results clearly showed that quality by design concept could be effectively applied to optimize an HPLC chromatographic method for protein analysis with the least number of experimental runs possible. Published by Elsevier B.V.
C1 [Awotwe-Otoo, David; Agarabi, Cyrus; Faustino, Patrick J.; Khan, Mansoor A.; Shah, Rakhi B.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
[Awotwe-Otoo, David; Habib, Muhammad J.] Howard Univ, Coll Pharm, Dept Pharmaceut Sci, Washington, DC 20059 USA.
[Lee, Sau] US FDA, Off Gener Drugs, Rockville, MD 20855 USA.
RP Shah, RB (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
EM rakhi.shah@fda.hhs.gov
NR 22
TC 32
Z9 35
U1 0
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 25
PY 2012
VL 62
BP 61
EP 67
DI 10.1016/j.jpba.2012.01.002
PG 7
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 902IQ
UT WOS:000301032200008
PM 22316620
ER
PT J
AU Duarte, JD
Zineh, I
Burkley, B
Gong, Y
Langaee, TY
Turner, ST
Chapman, AB
Boerwinkle, E
Gums, JG
Cooper-DeHoff, RM
Beitelshees, AL
Bailey, KR
Fillingim, RB
Kone, BC
Johnson, JA
AF Duarte, Julio D.
Zineh, Issam
Burkley, Ben
Gong, Yan
Langaee, Taimour Y.
Turner, Stephen T.
Chapman, Arlene B.
Boerwinkle, Eric
Gums, John G.
Cooper-DeHoff, Rhonda M.
Beitelshees, Amber L.
Bailey, Kent R.
Fillingim, Roger B.
Kone, Bruce C.
Johnson, Julie A.
TI Effects of genetic variation in H3K79 methylation regulatory genes on
clinical blood pressure and blood pressure response to
hydrochlorothiazide
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE Pharmacogenomics; Pharmacogenetics; hydrochlorothiazide; hypertension;
blood pressure; DOT1L; SIRT1; MLLT3; SGK1; histone methylation
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ANTIHYPERTENSIVE RESPONSE; ENAC-ALPHA;
REPRESSION; CHANNEL; HOME; TRANSCRIPTION; HYPERTENSION; HOMEOSTASIS;
ATENOLOL
AB Background: Nearly one-third of the United States adult population suffers from hypertension. Hydrochlorothiazide (HCTZ), one of the most commonly used medications to treat hypertension, has variable efficacy. The renal epithelial sodium channel (ENaC) provides a mechanism for fine-tuning sodium excretion, and is a major regulator of blood pressure homeostasis. DOT1L, MLLT3, SIRT1, and SGK1 encode genes in a pathway that controls methylation of the histone H3 globular domain at lysine 79 (H3K79), thereby modulating expression of the ENaC alpha subunit. This study aimed to determine the role of variation in these regulatory genes on blood pressure response to HCTZ, and secondarily, untreated blood pressure.
Methods: We investigated associations between genetic variations in this candidate pathway and HCTZ blood pressure response in two separate hypertensive cohorts (clinicaltrials.gov NCT00246519 and NCT00005520). In a secondary, exploratory analysis, we measured associations between these same genetic variations and untreated blood pressure. Associations were measured by linear regression, with only associations with P <= 0.01 in one cohort and replication by P <= 0.05 in the other cohort considered significant.
Results: In one cohort, a polymorphism in DOT1L (rs2269879) was strongly associated with greater systolic (P = 0.0002) and diastolic (P = 0.0016) blood pressure response to hydrochlorothiazide in Caucasians. However, this association was not replicated in the other cohort. When untreated blood pressure levels were analyzed, we found directionally similar associations between a polymorphism in MLLT3 (rs12350051) and greater untreated systolic (P < 0.01 in both cohorts) and diastolic (P < 0.05 in both cohorts) blood pressure levels in both cohorts. However, when further replication was attempted in a third hypertensive cohort and in smaller, normotensive samples, significant associations were not observed.
Conclusions: Our data suggest polymorphisms in DOT1L, MLLT3, SIRT1, and SGK1 are not likely associated with blood pressure response to HCTZ. However, a possibility exists that rs2269879 in DOT1L could be associated with HCTZ response in Caucasians. Additionally, exploratory analyses suggest rs12350051 in MLLT3 may be associated with untreated blood pressure in African-Americans. Replication efforts are needed to verify roles for these polymorphisms in human blood pressure regulation.
C1 [Duarte, Julio D.; Zineh, Issam; Burkley, Ben; Gong, Yan; Langaee, Taimour Y.; Gums, John G.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Ctr Pharmacogen, Gainesville, FL 32610 USA.
[Duarte, Julio D.; Zineh, Issam; Burkley, Ben; Gong, Yan; Langaee, Taimour Y.; Gums, John G.; Cooper-DeHoff, Rhonda M.; Johnson, Julie A.] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32610 USA.
[Duarte, Julio D.] Univ Illinois, Dept Pharm Practice, Chicago, IL 60612 USA.
[Zineh, Issam] US FDA, Off Clin Pharmacol, Off Translat Sci CDER, Silver Spring, MD 20993 USA.
[Turner, Stephen T.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA.
[Chapman, Arlene B.] Emory Univ, Dept Med, Div Renal, Atlanta, GA 30322 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Human Genet Ctr, Houston, TX 77030 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA.
[Beitelshees, Amber L.] Univ Maryland, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Bailey, Kent R.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN 55905 USA.
[Fillingim, Roger B.] Univ Florida, Dept Community Dent & Behav Sci, Gainesville, FL 32610 USA.
[Kone, Bruce C.] Univ Florida, Div Nephrol Hypertens & Renal Transplantat, Gainesville, FL 32610 USA.
[Kone, Bruce C.] Univ Texas Hlth Sci Ctr, Div Renal Dis & Hypertens, Houston, TX 77030 USA.
RP Duarte, JD (reprint author), Univ Florida, Ctr Pharmacogen, Gainesville, FL 32610 USA.
EM juliod@uic.edu
FU NIH [HL74735, HL53335, R01 DK075065, R01 HL064691, R01 NS42754, K23
HL091120, T32 DK007518]; Mayo Foundation; National Institutes of Health
(Bethesda, MD) [U01 GM074492]; Pharmacogenetics Research Network; NIH
National Center for Research Resources [M01 RR00082, UL1 RR029890, UL1
RR025008, M01 RR00039, UL1 RR024150]
FX GERA: This work was supported by NIH grants HL74735, HL53335, and the
Mayo Foundation.; PEAR: This work is supported by a grant from the
National Institutes of Health (Bethesda, MD), grant U01 GM074492, funded
as part of the Pharmacogenetics Research Network. This work is also
supported by the following grants from the NIH National Center for
Research Resources: grant M01 RR00082 and UL1 RR029890 to the University
of Florida, grants UL1 RR025008 and M01 RR00039 to Emory University, and
UL1 RR024150 to Mayo Clinic.; This research was also supported by NIH
grants R01 DK075065 (B. C. K.), R01 HL064691 (J.A.J.), R01 NS42754 (R.
L. F.), K23 HL091120 (A. L. B.), and T32 DK007518 (J.D.D.). While Dr.
Zineh is an employee of the FDA, no official FDA endorsement of this
manuscript is intended nor should be inferred.
NR 31
TC 8
Z9 8
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD MAR 22
PY 2012
VL 10
AR 56
DI 10.1186/1479-5876-10-56
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 921QY
UT WOS:000302493400001
PM 22440088
ER
PT J
AU Simhadri, VR
Andersen, JF
Calvo, E
Choi, SC
Coligan, JE
Borrego, F
AF Simhadri, Venkateswara R.
Andersen, John F.
Calvo, Eric
Choi, Seung-Chul
Coligan, John E.
Borrego, Francisco
TI Human CD300a binds to phosphatidylethanolamine and phosphatidylserine,
and modulates the phagocytosis of dead cells
SO BLOOD
LA English
DT Article
ID RECEPTOR IRP60 CD300A; IMMUNOGLOBULIN-LIKE RECEPTORS; INHIBITORY
RECEPTOR; APOPTOTIC CELLS; ANNEXIN-V; GENERAL FEATURE; NK CELLS;
B-CELLS; CLEARANCE; IDENTIFICATION
AB CD300a is an immunoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 family of paired activating/inhibitory receptors. It has been shown that its ligation inhibits activation signals on cells of both myeloid and lymphoid lineages. The ligands for CD300a have not been identified. Here, we show that a CD300a-Ig fusion protein specifically binds to apoptotic cells that are evolutionary apart, such as human and insect cells, suggesting that the ligand has to be conserved. Using surface plasmon resonance, ultracentrifugation, ELISA, and reporter cell assays, we identified phosphatidylethanolamine (PE) and phosphatidylserine (PS), 2 phospholipids that translocate to the outer leaflet of the plasma membrane of dead cells, as the ligands for CD300a. Mutational and structural modeling studies identified residues that are involved in the binding of CD300a to PE and PS and that form a cavity where the hydrophilic heads of PE and PS, can penetrate. CD300a down-regulates the uptake of apoptotic cells by macrophages and its ectopic expression in CD300a-negative cell lines also decreased the engulfment of dead cells. Collectively, our results indicate that PE and PS are ligands for CD300a, and that this interaction plays an important role in regulating the removal of dead cells. (Blood. 2012; 119(12): 2799-2809)
C1 [Simhadri, Venkateswara R.; Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA.
[Andersen, John F.; Calvo, Eric] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Choi, Seung-Chul; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bdg 29B,Rm 3NN18,29 Lincoln Dr,HFD-123, Bethesda, MD 20892 USA.
EM francisco.borrego@fda.hhs.gov
OI Calvo, Eric/0000-0001-7880-2730
FU Food and Drug Administration; National Institute of Allergy and
Infectious Diseases
FX This work was funded by the intramural programs of the Food and Drug
Administration and the National Institute of Allergy and Infectious
Diseases.
NR 50
TC 55
Z9 56
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 MAR 22
PY 2012
VL 119
IS 12
BP 2799
EP 2809
DI 10.1182/blood-2011-08-372425
PG 11
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700017
PM 22302738
ER
PT J
AU Enose-Akahata, Y
Abrams, A
Johnson, KR
Maloney, EM
Jacobson, S
AF Enose-Akahata, Yoshimi
Abrams, Anna
Johnson, Kory R.
Maloney, Elizabeth M.
Jacobson, Steven
TI Quantitative differences in HTLV-I antibody responses: classification
and relative risk assessment for asymptomatic carriers and ATL and
HAM/TSP patients from Jamaica
SO BLOOD
LA English
DT Article
ID VIRUS TYPE-I; T-CELL LEUKEMIA; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS;
PROVIRAL DNA LOAD; PERIPHERAL-BLOOD; NATURAL-HISTORY; LEUKEMIA/LYMPHOMA;
DISEASE; LYMPHOCYTES; INFECTION
AB Adult T-cell leukemia (ATL) and human T-cell lymphotropic virus type I (HTLV-I)associated myelopathy/tropical spastic paraparesis (HAM/TSP) are known to be caused by HTLV-I infection. However, current methods used to determine HTLV-I infection do not differentiate between HTLV-I asymptomatic carriers (ACs) and ATL and HAM/TSP patients. Using the luciferase immunoprecipitation system, a highly sensitive, quantitative technology that can efficiently detect HTLV-I Ab responses, we examined Ab responses for HTLV-I in serum/plasma samples from 439 subjects in Jamaica, including HTLVI- seronegative donors, ACs, and ATL and HAM/TSP patients. The Ab responses of HTLV-I-infected subjects differed significantly from those of seronegative donors for all 3 immunodominant proteins, Gag, Env, and Tax. HAM/TSP patients had significantly higher Ab responses for Gag and Env compared with ACs, and Ab responses for all 3 Ags were higher in HAM/TSP patients than in ATL patients. Moreover, immunoreactivities for HTLV-I Ags as determined by the luciferase immunoprecipitation system could distinguish HAM/TSP patients from ACs at a true-positive rate of 85.42% and from ATL patients at a true-positive rate of 75.00%, and modeled in conjunction with subject information to distinguish HAM/TSP patients from ACs (odds ratio=14.12) and from ATL patients (odds ratio=7.00). The relative risk assessment resulting from these significant differences between Ab responses in HTLVI-infected groups may be a useful diagnostic tool in the future. (Blood. 2012; 119(12): 2829-2836)
C1 [Enose-Akahata, Yoshimi; Abrams, Anna; Jacobson, Steven] NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
[Johnson, Kory R.] NINDS, Informat Technol & Bioinformat Program, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Maloney, Elizabeth M.] US FDA, Div Epidemiol 2, Off Surveillance & Epidemiol, Silver Spring, MD USA.
RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA.
EM jacobsons@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke, NIH
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke, NIH.
NR 46
TC 11
Z9 11
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 MAR 22
PY 2012
VL 119
IS 12
BP 2829
EP 2836
DI 10.1182/blood-2011-11-390807
PG 8
WC Hematology
SC Hematology
GA 916RU
UT WOS:000302121700020
PM 22318200
ER
PT J
AU Laksanalamai, P
Jackson, SA
Mammel, MK
Datta, AR
AF Laksanalamai, Pongpan
Jackson, Scott A.
Mammel, Mark K.
Datta, Atin R.
TI High Density Microarray Analysis Reveals New Insights into Genetic
Footprints of Listeria monocytogenes Strains Involved in Listeriosis
Outbreaks
SO PLOS ONE
LA English
DT Article
ID FEBRILE GASTROENTERITIS; COMPARATIVE GENOMICS; ESCHERICHIA-COLI;
IDENTIFICATION; VIRULENCE; DIVERSIFICATION; ELECTROPHORESIS;
RECOMBINATION; EVOLUTIONARY; DIVERSITY
AB Listeria monocytogenes, a foodborne bacterial pathogen, causes invasive and febrile gastroenteritis forms of listeriosis in humans. Both invasive and febrile gastroenteritis listeriosis is caused mostly by serotypes 1/2a, 1/2b and 4b strains. The outbreak strains of serotype 1/2a and 4b could be further classified into several epidemic clones but the genetic bases for the diverse pathophysiology have been unsuccessful. DNA microarray provides an important tool to scan the entire genome for genetic signatures that may distinguish the L. monocytogenes strains belonging to different outbreaks. We have designed a pan-genomic microarray chip (Listeria GeneChip) containing sequences from 24 L. monocytogenes strains. The chip was designed to identify the presence/absence of genomic sequences, analyze transcription profiles and identify SNPs. Analysis of the genomic profiles of 38 outbreak strains representing 1/2a, 1/2b and 4b serotypes, revealed that the strains formed distinct genetic clusters adhering to their serotypes and epidemic clone types. Although serologically 1/2a and 1/b strains share common antigenic markers microarray analysis revealed that 1/2a strains are further apart from the closely related 1/2b and 4b strains. Within any given serotype and epidemic clone type the febrile gastroenteritis and invasive strains can be further distinguished based on several genetic markers including large numbers of phage genome, and intergenic sequences. Our results showed that the microarray-based data can be an important tool in characterization of L. monocytogenes strains involved in both invasive and gastroenteritis outbreaks. The results for the first time showed that the serotypes and epidemic clones are based on extensive pan-genomic variability and the 1/2b and 4bstrains are more closely related to each other than the 1/2a strains. The data also supported the hypothesis that the strains causing these two diverse outbreaks are genotypically different and this finding might be important in understanding the pathophysiology of this organism.
C1 [Laksanalamai, Pongpan; Jackson, Scott A.; Mammel, Mark K.; Datta, Atin R.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
RP Laksanalamai, P (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA.
EM atin.datta@fda.hhs.gov
NR 43
TC 9
Z9 10
U1 1
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 21
PY 2012
VL 7
IS 3
AR e32896
DI 10.1371/journal.pone.0032896
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939YN
UT WOS:000303857100007
PM 22457724
ER
PT J
AU Derrick, SC
Dao, D
Yang, A
Kolibab, K
Jacobs, WR
Morris, SL
AF Derrick, Steven C.
Dao, Dee
Yang, Amy
Kolibab, Kris
Jacobs, William R.
Morris, Sheldon L.
TI Formulation of a mmaA4 Gene Deletion Mutant of Mycobacterium bovis BCG
in Cationic Liposomes Significantly Enhances Protection against
Tuberculosis
SO PLOS ONE
LA English
DT Article
ID BACILLUS-CALMETTE-GUERIN; CD4 T-CELLS; ORAL VACCINATION; CHALLENGE;
INFECTION; CHILDREN; MEMORY; METAANALYSIS; EFFICACY; VACCINES
AB A new vaccination strategy is urgently needed for improved control of the global tuberculosis (TB) epidemic. Using a mouse aerosol Mycobacterium tuberculosis challenge model, we investigated the protective efficacy of a mmaA4 gene deletion mutant of Mycobacterium bovis BCG (Delta mmaA4BCG) formulated in dimethyl dioctadecyl ammonium bromide (DDA) - D(+) trehalose 6,6 dibenenate (TDB) (DDA/TDB) adjuvant. In previous studies, deletion of the mmaA4 gene was shown to reduce the suppression of IL-12 production often seen after mycobacterial infections. While the non-adjuvanted Delta mmaA4BCG strain did not protect mice substantially better than conventional BCG against a tuberculous challenge in four protection experiments, the protective responses induced by the Delta mmaA4BCG vaccine formulated in DDA/TDB adjuvant was consistently increased relative to nonadjuvanted BCG controls. Furthermore, the Delta mmaA4BCG-DDA/TDB vaccine induced significantly higher frequencies of multifunctional (MFT) CD4 T cells expressing both IFN gamma and TNF alpha (double positive) or IFN gamma, TNF alpha and IL-2 (triple positive) than CD4 T cells derived from mice vaccinated with BCG. These MFT cells were characterized by having higher IFN gamma and TNF alpha median fluorescence intensity (MFI) values than monofunctional CD4 T cells. Interestingly, both BCG/adjuvant and Delta mmaA4BCG/adjuvant formulations induced significantly higher frequencies of CD4 T cells expressing TNF alpha and IL-2 than nonadjuvanted BCG or Delta mmaA4BCG vaccines indicating that BCG/adjuvant mixtures may be more effective at inducing central memory T cells. Importantly, when either conventional BCG or the mutant were formulated in adjuvant and administered to SCID mice or immunocompromised mice depleted of IFN gamma, significantly lower vaccine-derived mycobacterial CFU were detected relative to immunodeficient mice injected with non-adjuvanted BCG. Overall, these data suggest that immunization with the Delta mmaA4BCG/adjuvant formulation may be an effective, safe, and relatively inexpensive alternative to vaccination with conventional BCG.
C1 [Derrick, Steven C.; Yang, Amy; Kolibab, Kris; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
[Dao, Dee; Jacobs, William R.] Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA.
RP Derrick, SC (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
EM steven.derrick@fda.hhs.gov
FU Howard Hughes Medical Institute
NR 37
TC 10
Z9 11
U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 19
PY 2012
VL 7
IS 3
AR e32959
DI 10.1371/journal.pone.0032959
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 939TA
UT WOS:000303836500016
PM 22442674
ER
PT J
AU DeGrasse, JA
AF DeGrasse, Jeffrey A.
TI A Single-Stranded DNA Aptamer That Selectively Binds to Staphylococcus
aureus Enterotoxin B
SO PLOS ONE
LA English
DT Article
ID LINKED IMMUNOSORBENT-ASSAY; FOOD; ENZYME; PATHOGENS; MILK;
IDENTIFICATION; CONFIRMATION; BIOSENSORS; EVOLUTION; PRODUCTS
AB The bacterium Staphylococcus aureus is a common foodborne pathogen capable of secreting a cocktail of small, stable, and strain-specific, staphylococcal enterotoxins (SEs). Staphylococcal food poisoning (SFP) results when improperly handled food contaminated with SEs is consumed. Gastrointestinal symptoms of SFP include emesis, diarrhea and severe abdominal pain, which manifest within hours of ingesting contaminated food. Immuno-affinity based methods directly detect, identify, and quantify several SEs within a food or clinical sample. However, the success of these assays depends upon the availability of a monoclonal antibody, the development of which is non-trivial and costly. The current scope of the available immuno-affinity based methods is limited to the classical SEs and does not encompass all of the known or emergent SEs. In contrast to antibodies, aptamers are short nucleic acids that exhibit high affinity and specificity for their targets without the high-costs and ethical concerns of animal husbandry. Further, researchers may choose to freely distribute aptamers and develop assays without the proprietary issues that increase the per-sample cost of immuno-affinity assays. This study describes a novel aptamer, selected in vitro, with affinity to staphylococcal enterotoxin B (SEB) that may be used in lieu of antibodies in SE detection assays. The aptamer, designated APT(SEB1), successfully isolates SEB from a complex mixture of SEs with extremely high discrimination. This work sets the foundation for future aptamer and assay development towards the entire family of SEs. The rapid, robust, and low-cost identification and quantification of all of the SEs in S. aureus contaminated food is essential for food safety and epidemiological efforts. An in vitro generated library of SE aptamers could potentially allow for the comprehensive and cost-effective analysis of food samples that immuno-affinity assays currently cannot provide.
C1 US FDA, Spect & Mass Spectrometry Branch, Div Analyt Chem, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP DeGrasse, JA (reprint author), US FDA, Spect & Mass Spectrometry Branch, Div Analyt Chem, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM jeffrey.degrasse@fda.hhs.gov
RI DeGrasse, Jeffrey/J-1151-2014
OI DeGrasse, Jeffrey/0000-0003-3178-6301
FU Food and Drug Administration (FDA)
FX This work was supported by intramural funding to the Food and Drug
Administration (FDA). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
TC 38
Z9 41
U1 7
U2 80
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 MAR 16
PY 2012
VL 7
IS 3
AR e33410
DI 10.1371/journal.pone.0033410
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RV
UT WOS:000303309100042
PM 22438927
ER
PT J
AU Mohan, KVK
Devadas, K
Rao, SS
Hewlett, I
Atreya, C
AF Mohan, Ketha V. K.
Devadas, Krishnakumar
Rao, Shilpakala Sainath
Hewlett, Indira
Atreya, Chintamani
TI Identification of XMRV Infection-Associated microRNAs in Four Cell Types
in Culture
SO PLOS ONE
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER;
BLOOD-CELLS; RETROVIRUS; HIV-1; EXPRESSION; CARCINOMA; CONTAMINATION;
INDIVIDUALS
AB Introduction: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC) and chronic fatigue syndrome (CFS) in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA), which regulate gene expression, were so far not identified in cells infected with XMRV in culture.
Methods: Two prostate cell lines (LNCaP and DU145) and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock-and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray.
Results: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs). miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types.
Discussion: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.
C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Devadas, Krishnakumar; Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Mohan, KVK (reprint author), US FDA, Sect Cell Biol, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
EM chintamani.atreya@fda.hhs.gov
FU Center for Biologics Evaluation and Research
FX SSR is a recipient of a postdoctoral fellowship at the Center for
Biologics Evaluation and Research administered by the Oak Ridge
Institute for Science and Education through an intra-agency agreement
between the U.S. Department of Energy and the U.S. Food and Drug
Administration. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 56
TC 3
Z9 3
U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 16
PY 2012
VL 7
IS 3
AR e32853
DI 10.1371/journal.pone.0032853
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RV
UT WOS:000303309100016
PM 22438885
ER
PT J
AU Sun, C
Fang, H
Xie, T
Auth, RD
Patel, N
Murray, PR
Snoy, PJ
Frucht, DM
AF Sun, Chen
Fang, Hui
Xie, Tao
Auth, Roger D.
Patel, Nayana
Murray, Patrick R.
Snoy, Philip J.
Frucht, David M.
TI Anthrax Lethal Toxin Disrupts Intestinal Barrier Function and Causes
Systemic Infections with Enteric Bacteria
SO PLOS ONE
LA English
DT Article
ID BACILLUS-ANTHRACIS; KAPPA-B; CELLS; ACTIVATION
AB A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK) signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT) has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs). Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis.
C1 [Sun, Chen; Fang, Hui; Xie, Tao; Auth, Roger D.; Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
[Patel, Nayana; Murray, Patrick R.] NIH, Dept Lab Med, Warren Magnusen Clin Ctr, Bethesda, MD 20892 USA.
[Snoy, Philip J.] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
RP Sun, C (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA.
EM david.frucht@fda.hhs.gov
FU United States government
FX The United States government provided the funding to support this work.
The information presented in this manuscript reflects the work of the
authors and does not necessarily represent the policy of the United
States Food and Drug Administration. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 33
TC 9
Z9 9
U1 0
U2 7
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 MAR 16
PY 2012
VL 7
IS 3
AR e33583
DI 10.1371/journal.pone.0033583
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 932RV
UT WOS:000303309100061
PM 22438953
ER
PT J
AU Donoghue, M
Lemery, SJ
Yuan, WS
He, K
Sridhara, R
Shord, S
Zhao, H
Marathe, A
Kotch, L
Jee, J
Wang, Y
Zhou, L
Adams, WM
Jarral, V
Pilaro, A
Lostritto, R
Gootenberg, JE
Keegan, P
Pazdur, R
AF Donoghue, Martha
Lemery, Steven J.
Yuan, Weishi
He, Kun
Sridhara, Rajeshwari
Shord, Stacy
Zhao, Hong
Marathe, Anshu
Kotch, Lori
Jee, Josephine
Wang, Ying
Zhou, Liang
Adams, William M.
Jarral, Vaishali
Pilaro, Anne
Lostritto, Richard
Gootenberg, Joseph E.
Keegan, Patricia
Pazdur, Richard
TI Eribulin Mesylate for the Treatment of Patients with Refractory
Metastatic Breast Cancer: Use of a "Physician's Choice" Control Arm in a
Randomized Approval Trial
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HALICHONDRIN B ANALOG; PHASE-II; ANTHRACYCLINE; TUBULIN; TAXANE; E7389
AB This work describes the considerations that led to the approval by the U. S. Food and Drug Administration (FDA), on November 15, 2010, of eribulin mesylate (Halaven; Eisai, Inc.) for the treatment of patients with refractory metastatic breast cancer. The FDA review focused primarily on the results of a single randomized, open-label, multicenter trial of 762 patients with refractory locally advanced or metastatic breast cancer. The patients were randomized to receive eribulin or any single-agent treatment of the physician's choice, selected prior to randomization. The FDA's approval of eribulin mesylate was based on demonstration of a statistically significant prolongation of overall survival (OS) in patients who had been randomized to receive eribulin. The median OS was 13.1 months in the eribulin arm compared with 10.6 months in the control arm [HR 0.81 (95% CI, 0.66-0.99); P = 0.041]. Treatment with eribulin did not show a statistically significant treatment effect [HR 0.87 (95% CI, 0.71-1.05)] on progression-free survival as determined by independent review. This approval highlights the appropriate use of an innovative trial design and shows that improvement in OS is an achievable endpoint in the setting of advanced breast cancer. On the basis of the different conclusions arising from the OS and progression-free survival results, investigators should consider using OS as a primary endpoint in clinical trials for refractory breast cancer. Clin Cancer Res; 18(6); 1496-505. (C)2012 AACR.
C1 [Donoghue, Martha] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Div Oncol Prod 2, Silver Spring, MD 20993 USA.
[Yuan, Weishi; He, Kun; Sridhara, Rajeshwari] US FDA, Off Biostat, Silver Spring, MD 20993 USA.
[Shord, Stacy; Zhao, Hong; Marathe, Anshu] US FDA, Off Clin Pharmacol, Silver Spring, MD 20993 USA.
[Jee, Josephine; Wang, Ying; Zhou, Liang; Adams, William M.; Lostritto, Richard] US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Donoghue, M (reprint author), US FDA, Off Hematol & Oncol Prod, Off New Drugs, Div Oncol Prod 2, Bldg 22,Room 2135,10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM martha.donoghue@fda.hhs.gov
NR 23
TC 11
Z9 13
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 MAR 15
PY 2012
VL 18
IS 6
BP 1496
EP 1505
DI 10.1158/1078-0432.CCR-11-2149
PG 10
WC Oncology
SC Oncology
GA 910VW
UT WOS:000301672400004
PM 22282463
ER
PT J
AU Baird-Heinz, HE
Van Schoick, AL
Pelsor, FR
Ranivand, DL
Hungerford, LL
AF Baird-Heinz, Hope E.
Van Schoick, A'ndrea L.
Pelsor, Francis R.
Ranivand, D. Lauren
Hungerford, Laura L.
TI A systematic review of the safety of potassium bromide in dogs
SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION
LA English
DT Review
ID DIETARY CHLORIDE CONTENT; RAT-THYROID GLAND; SODIUM-BROMIDE; IDIOPATHIC
EPILEPSY; ANTICONVULSANT THERAPY; ANTIEPILEPTIC DRUG; TOXICOSIS BROMISM;
ENDOCRINE SYSTEM; SPECIAL EMPHASIS; HUMAN VOLUNTEERS
AB Objective-To critically evaluate and summarize available information on the safety of potassium bromide in dogs.
Design-Systematic review. Sample-111 references reporting safety information relevant to potassium bromide published between 1938 and 2011.
Procedures-PubMed searches without date limitations were conducted with the terms "potassium bromide" and "sodium bromide" in December 2009 and October 2011. Additional articles were identified through examination of article reference lists and book chapters on seizures in dogs and pharmacology.
Results-Reversible neurologic signs were the most consistently reported toxicoses and were generally associated with adjunctive potassium bromide treatment or high serum bromide concentrations. Dermatologic and respiratory abnormalities were rare in dogs. Insufficient information was available to assess the effects of potassium bromide on behavior or to determine the incidence of vomiting, weight gain, polyphagia, pancreatitis, polyuria, polydipsia, or reproductive abnormalities associated with potassium bromide administration. Evidence suggested that administration of potassium bromide with food may alleviate gastrointestinal irritation and that monitoring for polyphagia, thyroid hormone abnormalities, and high serum bromide concentrations may be beneficial.
Conclusions and Clinical Relevance-Results suggested that potassium bromide is not an appropriate choice for treatment of every dog with seizures and that practitioners should tailor therapeutic regimens and clinical monitoring to each dog. Abrupt dietary changes or fluid therapy may compromise seizure control or increase the likelihood of adverse events. Availability of an appropriately labeled, approved potassium bromide product could provide better assurance for veterinarians and their clients of the quality, safety, and effectiveness of the product for veterinary use. (J Am Vet Med Assoc 2012;240:705-715)
C1 [Baird-Heinz, Hope E.; Van Schoick, A'ndrea L.; Pelsor, Francis R.; Ranivand, D. Lauren; Hungerford, Laura L.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA.
[Hungerford, Laura L.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
RP Hungerford, LL (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA.
EM laura.hungerford@fda.hhs.gov
NR 137
TC 13
Z9 13
U1 2
U2 32
PU AMER VETERINARY MEDICAL ASSOC
PI SCHAUMBURG
PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA
SN 0003-1488
J9 JAVMA-J AM VET MED A
JI JAVMA-J. Am. Vet. Med. Assoc.
PD MAR 15
PY 2012
VL 240
IS 6
BP 705
EP 715
PG 11
WC Veterinary Sciences
SC Veterinary Sciences
GA 908CN
UT WOS:000301468100027
PM 22380809
ER
PT J
AU Reed, JL
Scott, DE
Bray, M
AF Reed, Jennifer L.
Scott, Dorothy E.
Bray, Mike
TI Eczema Vaccinatum
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID ATOPIC-DERMATITIS; SMALLPOX VACCINATION; SKIN INFLAMMATION; PROGRESSIVE
VACCINIA; UNITED-STATES; MOUSE MODEL; VIRUS; DISEASE; COMPLICATIONS;
CELLS
AB Eczema vaccinatum (EV) is a complication of smallpox vaccination that can occur in persons with eczema/atopic dermatitis (AD), in which vaccinia virus disseminates to cause an extensive rash and systemic illness. Because persons with eczema are deferred from vaccination, only a single, accidentally transmitted case of EV has been described in the medical literature since military vaccination was resumed in the United States in 2002. To enhance understanding of EV, we review its history during the era of universal vaccination and discuss its relationship to complications in persons with other diseases or injuries of the skin. We then discuss current concepts of the pathophysiology of AD, noting how defective skin barrier function, epidermal hyperplasia, and abnormal immune responses favor the spread of poxviral infection, and identify a number of unanswered questions about EV. We conclude by considering how its occurrence might be minimized in the event of a return to universal vaccination.
C1 [Reed, Jennifer L.; Scott, Dorothy E.] US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA.
[Bray, Mike] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Reed, JL (reprint author), US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM 345,NIH Bldg 29,Rm 302, Rockville, MD 20892 USA.
EM jennifer.reed@fda.hhs.gov
FU Food and Drug Administration, Center for Biologics Evaluation and
Research
FX This work is supported by the Food and Drug Administration, Center for
Biologics Evaluation and Research operating funds. These findings and
conclusions have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 59
TC 17
Z9 17
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD MAR 15
PY 2012
VL 54
IS 6
BP 832
EP 840
DI 10.1093/cid/cir952
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 899CK
UT WOS:000300790900017
PM 22291103
ER
PT J
AU Pinsky, PF
Gallas, B
AF Pinsky, Paul F.
Gallas, B.
TI Enriched designs for assessing discriminatory performance - analysis of
bias and variance
SO STATISTICS IN MEDICINE
LA English
DT Article
DE AUC; bias; enrichment; inverse probability weighting; sensitivity;
variance
ID VERIFICATION BIAS; BREAST-CANCER; CURVE; AREA
AB In evaluating discriminatory performance of a new modality in a screening setting, a logistical constraint is that the prevalence of the disease of interest is typically very low. This implies that under a standard study design large numbers of subjects have to be evaluated using the new modality. However, if a predicate modality exists in clinical practice, one can base inclusion into the study of the new modality on the clinical results from the predicate to enrich the population of diseased subjects in the study. If this enrichment is not accounted for when estimating sensitivity, specificity, and area under the ROC curve, these naive estimates may be substantially biased compared with expected performance in the intended use population. We derive expressions for the magnitude of this bias in terms of correlations of modality scores. When such estimates are corrected for the sampling weights using inverse probability weighting, the variances of the estimates of the above quantities are affected. We derive here analytic expressions for these variances. For a fixed number of diseased subjects, differential sampling increases the variance of the (corrected) estimates, all other things being equal. However, differential sampling also increases the number with disease for fixed total study size, which decreases the variance of the sensitivity and area under the ROC curve estimates, all other things being equal. The balance of these two effects determines the gain in efficiency when using enrichment and corrected estimates. These principles are illustrated with a simulation study motivated by the Digital Mammographic Imaging Screening Trial study, a trial of digital versus screen film mammography. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Pinsky, Paul F.; Gallas, B.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
RP Pinsky, PF (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
EM pp4f@nih.gov
OI Gallas, Brandon/0000-0001-7332-1620
NR 9
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD MAR 15
PY 2012
VL 31
IS 6
BP 501
EP 515
DI 10.1002/sim.4432
PG 15
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 894MD
UT WOS:000300429900001
PM 22095795
ER
PT J
AU Stramer, SL
Collins, C
Nugent, T
Wang, X
Fuschino, M
Heitman, JW
Law, J
Krysztof, DE
Kiely, N
Todd, D
Vermeulen, NMJ
Harrington, K
Kamel, H
Kelvin, DJ
Busch, MP
George, KS
Hewlett, IK
Linnen, JM
Norris, PJ
AF Stramer, Susan L.
Collins, Cynthia
Nugent, Thomas
Wang, Xue
Fuschino, Meghan
Heitman, John W.
Law, Jacqueline
Krysztof, David E.
Kiely, Nancy
Todd, Deborah
Vermeulen, Nicolaas M. J.
Harrington, Karen
Kamel, Hany
Kelvin, David J.
Busch, Michael P.
George, Kirsten St.
Hewlett, Indira K.
Linnen, Jeffrey M.
Norris, Philip J.
CA NHLBI Retrovirus Epidemiology
TI Sensitive Detection Assays for Influenza RNA Do Not Reveal Viremia in US
Blood Donors
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID BINOMIAL CONFIDENCE-INTERVALS; RESPIRATORY SYNCYTIAL VIRUS; REVERSE
TRANSCRIPTION-PCR; PANDEMIC H1N1 2009; A H5N1; ASIAN INFLUENZA;
INCUBATION PERIOD; VIRAL LOAD; INFECTION; FERRETS
AB Background. There have been anecdotal reports of influenza viremia since the 1960s. We present an assessment of the prevalence of seasonal and 2009 H1N1 influenza viremia (via RNA testing) in blood donor populations using multiple sensitive detection assays.
Methods. Several influenza RNA amplification assays, including transcription-mediated amplification (TMA) and 2 reverse-transcription polymerase chain reaction (RT-PCR) assays, were evaluated and used to test donor samples. Retrospective samples from 478 subjects drawn at sites with high influenza activity were tested. Prospective samples were collected from 1004 blood donors who called their donation center within 3 days of donation complaining of influenza-like illness (ILI). The plasma collected on the day of donation for these subjects was tested.
Results. Of the repository samples, 2 of 478 plasma samples were initially reactive but not repeat reactive by influenza TMA. Of blood donors reporting ILI symptoms postdonation, 1 of 1004 samples was TMA initially reactive but not repeat reactive; all samples were nonreactive by RT-PCR testing.
Conclusions. Targeting blood donor populations most likely to have influenza infection, we failed to detect influenza RNA in 1482 donor samples, with most tested by 3 different RNA assays. Seasonal influenza does not appear to pose a significant contamination threat to the blood supply.
C1 [Heitman, John W.; Law, Jacqueline; Busch, Michael P.; Norris, Philip J.] Blood Syst Res Inst, San Francisco, CA 94118 USA.
[Stramer, Susan L.; Krysztof, David E.] Amer Red Cross Sci Support Off, Gaithersburg, MD USA.
[Collins, Cynthia; Nugent, Thomas; Harrington, Karen; Linnen, Jeffrey M.] Gen Probe, San Diego, CA USA.
[Wang, Xue; Hewlett, Indira K.] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD USA.
[Fuschino, Meghan; George, Kirsten St.] Wadsworth Ctr, Albany, NY USA.
[Kiely, Nancy; Kamel, Hany] Blood Syst Inc, Scottsdale, AZ USA.
[Todd, Deborah] Westat Corp, Rockville, MD USA.
[Vermeulen, Nicolaas M. J.] Epoch Biosci, Bothell, WA USA.
[Kelvin, David J.] Univ Hlth Network, Toronto, ON, Canada.
[Busch, Michael P.; Norris, Philip J.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Norris, Philip J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Norris, PJ (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA.
EM pnorris@bloodsystems.org
FU NHLBI [N01-HB-57181]
FX This work was supported by NHLBI contract N01-HB-57181.
NR 50
TC 7
Z9 7
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD MAR 15
PY 2012
VL 205
IS 6
BP 886
EP 894
DI 10.1093/infdis/jir863
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 898FU
UT WOS:000300724100005
PM 22293429
ER
PT J
AU Jeannot, E
Boorman, GA
Kosyk, O
Bradford, BU
Shymoniak, S
Tumurbaatar, B
Weinman, SA
Melnyk, SB
Tryndyak, V
Pogribny, IP
Rusyn, I
AF Jeannot, Emmanuelle
Boorman, Gary A.
Kosyk, Oksana
Bradford, Blair U.
Shymoniak, Svitlana
Tumurbaatar, Batbayar
Weinman, Steven A.
Melnyk, Stepan B.
Tryndyak, Volodymyr
Pogribny, Igor P.
Rusyn, Ivan
TI Increased incidence of aflatoxin B1-induced liver tumors in hepatitis
virus C transgenic mice
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE aflatoxin B1; hepatitis C virus; liver; mouse
ID UNFOLDED PROTEIN RESPONSE; HEPATOCELLULAR-CARCINOMA; CORE PROTEIN;
MITOCHONDRIAL-DNA; OXIDATIVE STRESS; KNOCKOUT MICE; RISK-FACTORS; MOUSE
MODEL; STEATOSIS; HCV
AB Viral hepatitis and aflatoxin B1 (AFB1) exposure are common risk factors for hepatocellular carcinoma (HCC). The incidence of HCC in individuals coexposed to hepatitis C (HCV) or B virus and AFB1 is greater than could be explained by the additive effect; yet, the mechanisms are poorly understood because of the lack of an animal model. Our study investigated the outcomes and mechanisms of combined exposure to HCV and AFB1. We hypothesized that HCV transgenic (HCV-Tg; expressing core, E1, E2 and p7, nucleotides 3422771) mice will be prone to hepatocarcinogenesis when exposed to AFB1. Neonatal (7 days old) HCV-Tg or C57BL/6J wild-type (WT) mice were exposed to AFB1 (6 mu g/g bw) or tricaprylin vehicle (15 mu l/g bw), and male offspring were followed for up to 12 months. No liver lesions were observed in vehicle-treated WT or HCV-Tg mice. Tumors (adenomas or carcinomas) and preneoplastic lesions (hyperplasia or foci) were observed in 22.5% (9 of 40) of AFB1-treated WT mice. In AFB1-treated HCV-Tg mice, the incidence of tumorous or pretumorous lesions was significantly elevated (50%, 18 of 36), with the difference largely due to a 2.5-fold increase in the incidence of adenomas (30.5 vs. 12.5%). Although oxidative stress and steatohepatitis were observed in both AFB1-treated groups, molecular changes indicative of the enhanced inflammatory response and altered lipid metabolism were more pronounced in HCV-Tg mice. In summary, HCV proteins core, E1, E2 and p7 are sufficient to reproduce the cocarcinogenic effect of HCV and AFB1, which is a known clinical phenomenon.
C1 [Jeannot, Emmanuelle; Kosyk, Oksana; Bradford, Blair U.; Shymoniak, Svitlana; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
[Boorman, Gary A.] Covance, Vienna, VA USA.
[Tumurbaatar, Batbayar; Weinman, Steven A.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA.
[Melnyk, Stepan B.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Tryndyak, Volodymyr; Pogribny, Igor P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
EM iir@unc.edu
RI Rusyn, Ivan/S-2426-2016
FU National Institutes of Health [ES005948, AA016258, ES010126, AA012863]
FX Grant sponsor: National Institutes of Health; Grant numbers: ES005948,
AA016258, ES010126, AA012863
NR 44
TC 13
Z9 13
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD MAR 15
PY 2012
VL 130
IS 6
BP 1347
EP 1356
DI 10.1002/ijc.26140
PG 10
WC Oncology
SC Oncology
GA 878IV
UT WOS:000299250700012
PM 21500192
ER
PT J
AU Hoelzer, K
Pouillot, R
Dennis, S
AF Hoelzer, Karin
Pouillot, Regis
Dennis, Sherri
TI Animal models of listeriosis: a comparative review of the current state
of the art and lessons learned
SO VETERINARY RESEARCH
LA English
DT Review
ID PREGNANT GUINEA-PIGS; MONOCYTOGENES-INDUCED STILLBIRTHS; MICROVASCULAR
ENDOTHELIAL-CELLS; MESSENGER-RNA EXPRESSION; NONHUMAN PRIMATE MODEL;
CENTRAL-NERVOUS-SYSTEM; PROTECTIVE T-CELLS; E-CADHERIN; INTRAGASTRIC
INOCULATION; ORAL INFECTION
AB Listeriosis is a leading cause of hospitalization and death due to foodborne illness in the industrialized world. Animal models have played fundamental roles in elucidating the pathophysiology and immunology of listeriosis, and will almost certainly continue to be integral components of the research on listeriosis. Data derived from animal studies helped for example characterize the importance of cell-mediated immunity in controlling infection, allowed evaluation of chemotherapeutic treatments for listeriosis, and contributed to quantitative assessments of the public health risk associated with L. monocytogenes contaminated food commodities. Nonetheless, a number of pivotal questions remain unresolved, including dose-response relationships, which represent essential components of risk assessments. Newly emerging data about species-specific differences have recently raised concern about the validity of most traditional animal models of listeriosis. However, considerable uncertainty about the best choice of animal model remains. Here we review the available data on traditional and potential new animal models to summarize currently recognized strengths and limitations of each model. This knowledge is instrumental for devising future studies and for interpreting current data. We deliberately chose a historical, comparative and cross-disciplinary approach, striving to reveal clues that may help predict the ultimate value of each animal model in spite of incomplete data.
C1 [Hoelzer, Karin; Pouillot, Regis; Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20707 USA.
RP Hoelzer, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20707 USA.
EM Karin.Hoelzer@fda.hhs.gov
RI Pouillot, Regis/E-8103-2010
OI Pouillot, Regis/0000-0002-6107-5212
NR 251
TC 12
Z9 12
U1 1
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 0928-4249
EI 1297-9716
J9 VET RES
JI Vet. Res.
PD MAR 14
PY 2012
VL 43
AR 18
DI 10.1186/1297-9716-43-18
PG 27
WC Veterinary Sciences
SC Veterinary Sciences
GA 965CP
UT WOS:000305744000001
PM 22417207
ER
PT J
AU de Filippis, I
de Lemos, APS
Hostetler, JB
Wollenberg, K
Sacchi, CT
Harrison, LH
Bash, MC
Prevots, DR
AF de Filippis, Ivano
de Lemos, Ana Paula S.
Hostetler, Jessica B.
Wollenberg, Kurt
Sacchi, Claudio T.
Harrison, Lee H.
Bash, Margaret C.
Prevots, D. Rebecca
TI Molecular Epidemiology of Neisseria meningitidis Serogroup B in Brazil
SO PLOS ONE
LA English
DT Article
ID MENINGOCOCCAL DISEASE; FACTOR-H; VACCINE CANDIDATE; SAO-PAULO; PROTEIN;
DIVERSITY; STRAINS; NADA; PORA; IDENTIFICATION
AB Background: Neisseria meningitidis serogroup B has been predominant in Brazil, but no broadly effective vaccine is available to prevent endemic meningococcal disease. To understand genetic diversity among serogroup B strains in Brazil, we selected a nationally representative sample of clinical disease isolates from 2004, and a temporally representative sample for the state of Sao Paulo (1988-2006) for study (n = 372).
Methods: We performed multi-locus sequence typing (MLST) and sequence analysis of five outer membrane protein (OMP) genes, including novel vaccine targets fHbp and nadA.
Results: In 2004, strain B:4:P1.15,19 clonal complex ST-32/ET-5 (cc32) predominated throughout Brazil; regional variation in MLST sequence type (ST), fetA, and porB was significant but diversity was limited for nadA and fHbp. Between 1988 and 1996, the Sao Paulo isolates shifted from clonal complex ST-41/44/Lineage 3 (cc41/44) to cc32. OMP variation was associated with but not predicted by cc or ST. Overall, fHbp variant 1/subfamily B was present in 80% of isolates and showed little diversity. The majority of nadA were similar to reference allele 1.
Conclusions: A predominant serogroup B lineage has circulated in Brazil for over a decade with significant regional and temporal diversity in ST, fetA, and porB, but not in nadA and fHbp.
C1 [de Filippis, Ivano] Oswaldo Cruz Fdn FIOCRUZ, Natl Qual Control Inst INCQS, Rio De Janeiro, Brazil.
[de Filippis, Ivano; Bash, Margaret C.] US FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD 20014 USA.
[de Filippis, Ivano; Prevots, D. Rebecca] NIAID, Epidemiol Unit, Lab Clin Infect Dis, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[de Lemos, Ana Paula S.] IAL, Dept Bacteriol, Sao Paulo, Brazil.
[Hostetler, Jessica B.] JCVI, Rockville, MD USA.
[Wollenberg, Kurt] NIAID, Off Cyberinfrastruct & Computat Biol OCICB, NIH, Bethesda, MD 20892 USA.
[Sacchi, Claudio T.] Inst Adolfo Lutz Registro, Dept Immunol, Sao Paulo, Brazil.
[Harrison, Lee H.] Univ Pittsburgh, Infect Dis Epidemiol Res Unit, Pittsburgh, PA USA.
RP de Filippis, I (reprint author), Oswaldo Cruz Fdn FIOCRUZ, Natl Qual Control Inst INCQS, Rio De Janeiro, Brazil.
EM rprevots@niaid.nih.gov
FU Division of Intramural Research; Office of Global Research; National
Institute of Allergy and Infectious Disease (NIAID), National Institutes
of Health (NIH) [N01-AI30071]; Center for Biologics Evaluation and
Research (CBER), Food and Drug Administration (FDA); NIAID [K24
AI52788]; Fogarty International Center, NIH [D43TW006592]; Fundacao de
Amparo a Pesquisa (FAPESP) [07/00462-3]; Sanofi Pasteur; Novartis;
Merck; Wyeth; GlaxoSmithKline
FX This work was supported by the Division of Intramural Research, and the
Office of Global Research, the National Institute of Allergy and
Infectious Disease (NIAID), National Institutes of Health (NIH); the
Center for Biologics Evaluation and Research (CBER), Food and Drug
Administration (FDA); a career development award to Dr. Harrison, NIAID
(K24 AI52788); a Fogarty International Center Global Infectious Diseases
Research Training Program grant, NIH, to the University of Pittsburgh
(D43TW006592); and by a grant from the Fundacao de Amparo a Pesquisa
(FAPESP), to Sao Paulo, Brazil (07/00462-3). Microbial sequencing was
supported through a contract to the J. Craig Venter Institute
(N01-AI30071) from NIAID, NIH. Ivano de Filippis was a postdoctoral
fellow at the NIH and FDA at the time this work was conducted. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.; Dr. Harrison
receives research funding from Sanofi Pasteur; he has received
consulting fees and speaking honoraria from Sanofi Pasteur, Novartis,
Merck, Wyeth, and GlaxoSmithKline. This does not alter the authors'
adherence to all the PLoS ONE policies on sharing data and materials.
None of the other authors have competing interests.
NR 39
TC 14
Z9 14
U1 0
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD MAR 14
PY 2012
VL 7
IS 3
AR e33016
DI 10.1371/journal.pone.0033016
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 931EO
UT WOS:000303198600037
PM 22431994
ER
PT J
AU Yin, JJ
Fu, PP
Lutterodt, H
Zhou, YT
Antholine, WE
Wamer, W
AF Yin, Jun-Jie
Fu, Peter P.
Lutterodt, Herman
Zhou, Yu-Ting
Antholine, William E.
Wamer, Wayne
TI Dual Role of Selected Antioxidants Found in Dietary Supplements:
Crossover between Anti- and Pro-Oxidant Activities in the Presence of
Copper
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE antioxidant; electron spin resonance; Fenton-like reaction; hydroxyl
radical; copper
ID HYDROXYL RADICAL FORMATION; LOW-DENSITY-LIPOPROTEIN; OXIDATIVE STRESS;
ASCORBIC-ACID; CATALYZED OXIDATION; HYDROGEN-PEROXIDE; PROTEIN
OXIDATION; FENTON CHEMISTRY; HUMAN-DISEASE; DNA-DAMAGE
AB Overproduction of reactive oxygen species (ROS) in vivo can result in damage associated with many aging-associated diseases. Defenses against ROS that have evolved include antioxidant enzymes, such as superoxide dismutases, peroxidases, and catalases, which can scavenge ROS. In addition, endogenous and dietary antioxidants play an important role in moderating damage associated with ROS. In this study, we use four common dietary antioxidants to demonstrate that, in the presence of copper (cupric sulfate and cupric gluconate) and physiologically relevant levels of hydrogen peroxide, these antioxidants can also act as pro-oxidants by producing hydroxyl radicals. Using electron spin resonance (ESR) spin trapping techniques, we demonstrate that the level of hydroxyl radical formation is a function of the pH of the medium and the relative amounts of antioxidant and copper. On the basis of the level of hydroxyl radical formation, the relative pro-oxidant potential of these antioxidants is cysteine > ascorbate > EGCG > GSH. It has been reported that copper sequestered by protein ligands, as happens in vivo, loses its redox activity (diminishing/abolishing the formation of free radicals). However, in the presence of hydrogen peroxide, cysteine and GSH efficiently react with cupric sulfate sequestered with bovine serum albumin to generate hydroxyl radicals. Overall, the results demonstrate that in the presence of copper, endogenous and dietary antioxidants can also exhibit pro-oxidative activity.
C1 [Yin, Jun-Jie; Zhou, Yu-Ting; Wamer, Wayne] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Lutterodt, Herman] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA.
[Antholine, William E.] Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 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 perumal, murugiah/D-1565-2012; Zhou, Yuting/I-9125-2012; Yin, Jun Jie
/E-5619-2014
FU NIBIB NIH HHS [P41 EB001980]
NR 69
TC 23
Z9 25
U1 3
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD MAR 14
PY 2012
VL 60
IS 10
BP 2554
EP 2561
DI 10.1021/jf204724w
PG 8
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 907GY
UT WOS:000301407000020
PM 22339379
ER
PT J
AU Fardin-Kia, AR
Handy, SM
Rader, JI
AF Fardin-Kia, Ali Reza
Handy, Sara M.
Rader, Jeanne I.
TI Characterization of Pine Nuts in the U.S. Market, Including Those
Associated with "Pine Mouth", by GC-FID
SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
LA English
DT Article
DE pine nuts; "pine mouth"; diagnostic index; DI; SLB-IL 111 column; Delta
5-unsaturated polymethylene-interrupted fatty acids
ID FATTY-ACID-COMPOSITION; DELTA-5-OLEFINIC ACIDS; SEED LIPIDS;
TRIACYLGLYCEROLS; PINACEAE; TAXONOMY; OILS
AB Taste disturbances following consumption of pine nuts, referred to as "pine mouth", have been reported by consumers in the United States and Europe. Nuts of Pinus armandii have been associated with pine mouth, and a diagnostic index (DI) measuring the content of Delta 5-unsaturated fatty acids relative to that of their fatty acid precursors has been proposed for identifying nuts from this species. A 100 m SLB-IL 111 GC column was used to improve fatty acid separations, and 45 pine nut samples were analyzed, including pine mouth-associated samples. This study examined the use of a DI for the identification of mixtures of pine nut species and showed the limitation of morphological characteristics for species identification. DI values for many commercial samples did not match those of known reference species, indicating that the majority of pine nuts collected in the U.S. market, including those associated with pine mouth, are mixtures of nuts from different Pinus species.
C1 [Fardin-Kia, Ali Reza; Handy, Sara M.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA.
RP Fardin-Kia, AR (reprint author), ORS CFSAN FDA, 5100 Paint Branch Pkwy HFS-715, College Pk, MD 20740 USA.
EM alireza.fardinkia@fda.hhs.gov
RI Handy, Sara/C-6195-2008
NR 29
TC 3
Z9 3
U1 3
U2 15
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0021-8561
J9 J AGR FOOD CHEM
JI J. Agric. Food Chem.
PD MAR 14
PY 2012
VL 60
IS 10
BP 2701
EP 2711
DI 10.1021/jf205188m
PG 11
WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science &
Technology
SC Agriculture; Chemistry; Food Science & Technology
GA 907GY
UT WOS:000301407000037
PM 22339292
ER
PT J
AU Zhuang, M
Wang, W
De Feo, CJ
Vassell, R
Weiss, CD
AF Zhuang, Min
Wang, Wei
De Feo, Christopher J.
Vassell, Russell
Weiss, Carol D.
TI Trimeric, Coiled-coil Extension on Peptide Fusion Inhibitor of HIV-1
Influences Selection of Resistance Pathways
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; TERMINAL HEPTAD REPEAT; ENVELOPE
GLYCOPROTEIN; SIV GP41; TRANSMEMBRANE GLYCOPROTEIN; CROSS-RESISTANCE;
ATOMIC-STRUCTURE; MEMBRANE-FUSION; ENTRY INHIBITOR; CORE STRUCTURE
AB Peptides corresponding to N- and C-terminal heptad repeat regions (HR1 and HR2, respectively) of viral fusion proteins can block infection of viruses in a dominant negative manner by interfering with refolding of the viral HR1 and HR2 to form a six-helix bundle (6HB) that drives fusion between viral and host cell membranes. The 6HB of the HIV gp41 (endogenous bundle) consists of an HR1 coiled-coil trimer with grooves lined by antiparallel HR2 helices. HR1 peptides form coiled-coil oligomers that may bind to gp41 HR2 as trimers to form a heterologous 6HB (inhibitor bundle) or to gp41 HR1 as monomers or dimers to form a heterologous coiled coil. To gain insights into mechanisms of Env entry and inhibition by HR1 peptides, we compared resistance to a peptide corresponding to 36 residues in gp41 HR1 (N36) and the same peptide with a coiled-coil trimerization domain fused to its N terminus (IZN36) that stabilizes the trimer and increases inhibitor potency (Eckert, D. M., and Kim, P. S. (2001) Proc. Nat. Acad. Sci. U. S. A. 98, 11187-11192). Whereas N36 selected two genetic pathways with equal probability, each defined by an early mutation in either HR1 or HR2, IZN36 preferentially selected the HR1 pathway. Both pathways conferred cross-resistance to both peptides. Each HR mutation enhanced the thermostability of the endogenous 6HB, potentially allowing the virus to simultaneously escape inhibitors targeting either gp41 HR1 or HR2. These findings inform inhibitor design and identify regions of plasticity in the highly conserved gp41 that modulate virus entry and escape from HR1 peptide inhibitors.
C1 [Weiss, Carol D.] NIH, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA.
[Zhuang, Min] Harbin Med Univ, Dept Microbiol, Harbin 150086, Heilongjiang, Peoples R China.
RP Weiss, CD (reprint author), NIH, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, US FDA, Bldg 29,Rm 532,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM carol.weiss@fda.hhs.gov
RI Ghartouchent, malek/B-9088-2012; Weiss, Carol/F-6438-2011
OI Weiss, Carol/0000-0002-9965-1289
FU National Institutes of Health; United States Food and Drug
Administration
FX This work was supported in part by the National Institutes of Health
Intramural AIDS Targeted Antiviral Program (to C. D. W.). This work was
also supported in part by institutional funds from the United States
Food and Drug Administration.
NR 44
TC 8
Z9 8
U1 0
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD MAR 9
PY 2012
VL 287
IS 11
BP 8297
EP 8309
DI 10.1074/jbc.M111.324483
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 906MN
UT WOS:000301349400044
PM 22235115
ER
PT J
AU Hong, T
Gurian, PL
Huang, Y
Haas, CN
AF Hong, Tao
Gurian, Patrick L.
Huang, Yin
Haas, Charles N.
TI Prioritizing Risks and Uncertainties from Intentional Release of
Selected Category A Pathogens
SO PLOS ONE
LA English
DT Article
ID AIRBORNE PASTEURELLA-TULARENSIS; BACILLUS-ANTHRACIS SPORES; PANDEMIC
INFLUENZA; QUANTITATIVE PCR; FRANCISELLA-TULARENSIS; RELATIVE HUMIDITY;
AEROSOL SURVIVAL; WARFARE AGENTS; INFECTION; VIRUS
AB This paper synthesizes available information on five Category A pathogens (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Variola major and Lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. An integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite contact exposure as well as inhalational exposure, and 3) includes an uncertainty analysis to identify key input uncertainties, which may inform future research directions. The findings provide a framework for developing the many different environmental standards that are needed for making risk-informed response decisions, such as when prophylactic antibiotics should be distributed, and whether or not a contaminated area should be cleaned up. The approach is based on the assumption of uniform mixing in environmental compartments and is thus applicable to areas sufficiently removed in time and space from the initial release that mixing has produced relatively uniform concentrations. Results indicate that when pathogens are released into the air, risk from inhalation is the main component of the overall risk, while risk from ingestion (dermal contact for B. anthracis) is the main component of the overall risk when pathogens are present on surfaces. Concentrations sampled from untracked floor, walls and the filter of heating ventilation and air conditioning (HVAC) system are proposed as indicators of previous exposure risk, while samples taken from touched surfaces are proposed as indicators of future risk if the building is reoccupied. A Monte Carlo uncertainty analysis is conducted and input-output correlations used to identify important parameter uncertainties. An approach is proposed for integrating these quantitative assessments of parameter uncertainty with broader, qualitative considerations to identify future research priorities.
C1 [Hong, Tao] US EPA, Natl Exposure Res Lab, Athens, GA USA.
[Gurian, Patrick L.; Haas, Charles N.] Drexel Univ, Dept Civil Architectural & Environm Engn, Philadelphia, PA 19104 USA.
[Huang, Yin] US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA.
RP Hong, T (reprint author), US EPA, Natl Exposure Res Lab, Athens, GA USA.
EM hongtao510@gmail.com
RI Gurian, Patrick/A-8365-2013; Haas, Charles/G-8830-2011
OI Gurian, Patrick/0000-0001-7456-9740; Haas, Charles/0000-0002-9255-9930
FU Center for Advancing Microbial Risk Assessment; United States
Environmental Protection Agency; United States Department of Homeland
Security, under Science to Achieve Results (STAR) [R83236201]
FX This research was funded through the Center for Advancing Microbial Risk
Assessment, supported by the United States Environmental Protection
Agency and United States Department of Homeland Security, under the
Science to Achieve Results (STAR) grant program (grant
number:R83236201). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 61
TC 10
Z9 10
U1 0
U2 17
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 MAR 6
PY 2012
VL 7
IS 3
AR e32732
DI 10.1371/journal.pone.0032732
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 928XD
UT WOS:000303021100025
PM 22412915
ER
PT J
AU Gryniewicz-Ruzicka, CM
Rodriguez, JD
Arzhantsev, S
Buhse, LF
Kauffman, JF
AF Gryniewicz-Ruzicka, Connie M.
Rodriguez, Jason D.
Arzhantsev, Sergey
Buhse, Lucinda F.
Kauffman, John F.
TI Libraries, classifiers, and quantifiers: A comparison of chemometric
methods for the analysis of Raman spectra of contaminated pharmaceutical
materials
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE Rapid screening; Raman spectroscopy; Spectral library; SIMCA; PLS
ID DIETHYLENE GLYCOL; SPECTROSCOPY; GLYCERIN
AB In this study, pharmaceutical grade sorbitol was used as a model system for comparison of Raman based library spectral correlation methods with more sophisticated methods of chemometric data analysis. Both crystallizing sorbitol (CS) and non-crystallizing sorbitol (NCS) from several manufacturers were examined. The Raman spectrum of each sample was collected and identified by correlation with a spectral library that included the CS spectrum but not the NCS spectrum. The average hit quality index (HQI) for the measured NCS spectra and the library CS spectrum was 0.966 whereas the average HQ! for the measured CS spectra was 0.991. Both HQIs exceeded the 0.950 threshold that is commonly used for material verification. To enhance the discrimination between CS and NCS, a CS/NCS classification model was constructed using soft independent modeling of class analogies (SIMCA). SIMCA was able to positively identify CS and NCS solutions with no mis-classifications. When CS was adulterated with low levels (0-5%) of ethylene glycol (EG) and diethylene glycol (DEG), the HQ! values of the measured spectra and the CS library spectrum were still above 0.950. When the CS SIMCA model was applied to adulterated CS spectra, it determined that CS samples with adulterant levels as low as 2% were outside of the CS class. A quantitative PLS model was also applied to EG adulterated CS and resulted in a detection limit of 0.9% for EG. The results obtained from these studies highlight the importance of selecting an appropriate data analysis process for the detection of low level adulterants in pharmaceutical raw materials using Raman spectroscopic screening methods. Published by Elsevier B.V.
C1 [Gryniewicz-Ruzicka, Connie M.; Rodriguez, Jason D.; Arzhantsev, Sergey; Buhse, Lucinda F.; Kauffman, John F.] FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA.
RP Gryniewicz-Ruzicka, CM (reprint author), FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA.
EM connie.ruzicka@fda.hhs.gov
NR 34
TC 13
Z9 14
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD MAR 5
PY 2012
VL 61
BP 191
EP 198
DI 10.1016/j.jpba.2011.12.002
PG 8
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 886NS
UT WOS:000299861700026
PM 22206890
ER
PT J
AU Leroy, Z
Broder, K
Menschik, D
Shimabukuro, T
Martin, D
AF Leroy, Z.
Broder, K.
Menschik, D.
Shimabukuro, T.
Martin, D.
TI Febrile seizures after 2010-2011 influenza vaccine in young children,
United States: A vaccine safety signal from the vaccine adverse event
reporting system
SO VACCINE
LA English
DT Article
DE Febrile seizure; Trivalent influenza vaccine; Vaccine safety;
Post-marketing surveillance
ID IMMUNIZATION
AB During the 2010-2011 influenza season, the Centers for Disease Control and Prevention and the Food and Drug Administration conducted enhanced vaccine safety monitoring for possible febrile seizures in all trivalent influenza vaccine (TIV) products in the United States using the Vaccine Adverse Event Reporting System (VAERS). We used Empirical Bayesian data mining techniques to assess disproportionate reporting after TIV and reviewed febrile seizure reports in children aged <5 years. On November 23, 2010, the combination of the coding term "febrile convulsion" and the Fluzone (R) TIV product exceeded a predetermined threshold in the VAERS database. By December 10, we confirmed 43 reports of febrile seizure following TIV in children aged 6-23 months. Clinical features of most reports were consistent with typical uncomplicated febrile seizures, and all children recovered. Further epidemiologic assessment of a possible association between TIV and febrile seizures was undertaken in a separate, population-based vaccine safety monitoring system. Published by Elsevier Ltd.
C1 [Leroy, Z.; Broder, K.; Shimabukuro, T.] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Hlth Care Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
[Menschik, D.; Martin, D.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
RP Leroy, Z (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Hlth Care Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA.
EM ezv6@cdc.gov
NR 18
TC 21
Z9 22
U1 0
U2 4
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 MAR 2
PY 2012
VL 30
IS 11
BP 2020
EP 2023
DI 10.1016/j.vaccine.2011.12.042
PG 4
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 924AM
UT WOS:000302662800015
PM 22361303
ER
PT J
AU Broder, KR
Martin, DB
Vellozzi, C
AF Broder, Karen R.
Martin, David B.
Vellozzi, Claudia
TI In the heat of a signal: Responding to a vaccine safety signal for
febrile seizures after 2010-11 influenza vaccine in young children,
United States
SO VACCINE
LA English
DT Editorial Material
C1 [Broder, Karen R.; Vellozzi, Claudia] Ctr Dis Control & Prevent CDC, Immunizat Safety Off, Div HealthCare Qual Promot, Natl Ctr Emerging & Zoonor Infect Dis, Atlanta, GA USA.
[Martin, David B.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA.
RP Broder, KR (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mail Stop D-26, Atlanta, GA 30333 USA.
EM kbroder@cdc.gov
NR 19
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-410X
J9 VACCINE
JI Vaccine
PD MAR 2
PY 2012
VL 30
IS 11
BP 2032
EP 2034
DI 10.1016/j.vaccine.2011.12.040
PG 3
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 924AM
UT WOS:000302662800017
PM 22361305
ER
PT J
AU Zhang, ZW
Albert, PS
Simons-Morton, B
AF Zhang, Zhiwei
Albert, Paul S.
Simons-Morton, Bruce
TI MARGINAL ANALYSIS OF LONGITUDINAL COUNT DATA IN LONG SEQUENCES: METHODS
AND APPLICATIONS TO A DRIVING STUDY
SO ANNALS OF APPLIED STATISTICS
LA English
DT Article
DE Correlation; generalized estimating equation; multiple outputation;
overdispersion; random effect; separated blocks; within-cluster
resampling
ID ESTIMATING EQUATIONS; REGRESSION-MODEL; TIME-SERIES; BINARY DATA;
JACKKNIFE; VARIANCE
AB Most of the available methods for longitudinal data analysis are designed and validated for the situation where the number of subjects is large and the number of observations per subject is relatively small. Motivated by the Naturalistic Teenage Driving Study (NTDS), which represents the exact opposite situation, we examine standard and propose new methodology for marginal analysis of longitudinal count data in a small number of very long sequences. We consider standard methods based on generalized estimating equations, under working independence or an appropriate correlation structure, and find them unsatisfactory for dealing with time-dependent covariates when the counts are low. For this situation, we explore a within-cluster resampling (WCR) approach that involves repeated analyses of random subsamples with a final analysis that synthesizes results across subsamples. This leads to a novel WCR method which operates on separated blocks within subjects and which performs better than all of the previously considered methods. The methods are applied to the NTDS data and evaluated in simulation experiments mimicking the NTDS.
C1 [Zhang, Zhiwei] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
[Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA.
RP Zhang, ZW (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM zhiwei.zhang@fda.hhs.gov; albertp@mail.nih.gov; mortonb@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH),
Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX Supported by the Intramural Research Program of the National Institutes
of Health (NIH), Eunice Kennedy Shriver National Institute of Child
Health and Human Development. The computation was facilitated by the
Biowulf cluster computer system made available by the Center for
Information-Technology at the NIH.
NR 24
TC 2
Z9 2
U1 1
U2 7
PU INST MATHEMATICAL STATISTICS
PI CLEVELAND
PA 3163 SOMERSET DR, CLEVELAND, OH 44122 USA
SN 1932-6157
J9 ANN APPL STAT
JI Ann. Appl. Stat.
PD MAR
PY 2012
VL 6
IS 1
BP 27
EP 54
DI 10.1214/11-AOAS507
PG 28
WC Statistics & Probability
SC Mathematics
GA 991QJ
UT WOS:000307716000002
PM 27087885
ER
PT J
AU Welle, CG
Krauthamer, V
AF Welle, Cristin G.
Krauthamer, Victor
TI FDA Regulation of Invasive Neural Recording Electrodes: A Daunting Task
for Medical Innovators
SO IEEE PULSE
LA English
DT Article
ID DEVICE REGULATION
C1 [Welle, Cristin G.; Krauthamer, Victor] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
RP Welle, CG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
EM cristin.welle@fda.hhs.gov; victor.krauthamer@fda.hhs.gov
OI Welle, Cristin/0000-0001-8735-0983
FU DARPA, Microsystems Technology Office [FDA-DARPA224-10-6006]
FX This work was supported in part by the DARPA, Microsystems Technology
Office, through an Interagency Agreement with the FDA
(FDA-DARPA224-10-6006).
NR 4
TC 2
Z9 2
U1 0
U2 3
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD MAR-APR
PY 2012
VL 3
IS 2
BP 37
EP 41
DI 10.1109/MPUL.2011.2181022
PG 5
WC Engineering, Biomedical
SC Engineering
GA 992UY
UT WOS:000307806600010
PM 22481744
ER
PT J
AU Azevedo, MSP
Zhang, W
Wen, K
Gonzalez, AM
Saif, LJ
Yousef, AE
Yuan, L
AF Azevedo, M. S. P.
Zhang, W.
Wen, K.
Gonzalez, A. M.
Saif, L. J.
Yousef, A. E.
Yuan, L.
TI Lactobacillus acidophilus and Lactobacillus reuteri modulate cytokine
responses in gnotobiotic pigs infected with human rotavirus
SO BENEFICIAL MICROBES
LA English
DT Article
DE lactic acid bacteria; probiotics; cytokines; human rotavirus;
gnotobiotic pigs
ID LACTIC-ACID BACTERIA; HUMAN DENDRITIC CELLS; ACUTE DIARRHEA; PROBIOTIC
LACTOBACILLI; IMMUNE-RESPONSES; ORAL TOLERANCE; CHILDREN; MODEL;
COLONIZATION; PROTECTION
AB Probiotic lactic acid bacteria (LAB) have been shown to alleviate inflammation, enhance the immunogenicity of rotavirus vaccines, or reduce the severity of rotavirus diarrhoea. Although the mechanisms are not clear, the differential Th1/Th2/Th3-driving capacities and modulating effects on cytokine production of different LAB strains may be the key. Our goal was to delineate the influence of combining two probiotic strains of Lactobacillus acidophilus and Lactobacillus reuteri on the development of cytokine responses in neonatal gnotobiotic pigs infected with human rotavirus (HRV). We demonstrated that HRV alone, or HRV plus LAB, but not LAB alone, initiated serum cytokine responses, as indicated by significantly higher concentrations of IFN-alpha, IFN-gamma, IL-12, and IL-10 at post-inoculation day (PID) 2 in the HRV only and LAB+HRV+ pigs compared to LAB only and LAB-HRV-pigs. Peak cytokine responses coincided with the peak of HRV replication. LAB further enhanced the Th1 and Th2 cytokine responses to HRV infection as indicated by significantly higher concentrations of IL-12, IFN-gamma, IL-4 and IL-10 in the LAB+HRV+ pigs compared to the LAB-HRV+ pigs. The LAB+HRV+ pigs maintained relatively constant concentrations of TGF-beta compared to the HRV only group which had a significant increase at PID 2 and decrease at PID 7, suggesting a regulatory role of LAB in maintaining gut homeostasis. At PID 28, cytokine secreting cell (CSC) responses, measured by ELISpot, showed increased Th1 (IL-12, IFN-gamma) CSC numbers in the LAB+HRV+ and LAB-HRV+ groups compared to LAB only and LAB-HRV- pigs, with significantly increased IL-12 CSCs in spleen and PBMCs and IFN-gamma CSCs in spleen of the LAB+HRV+ group. Thus, HRV infection alone, but not LAB alone was effective in inducing cytokine responses but LAB significantly enhanced both Th1 and Th2 cytokines in HRV-infected pigs. LAB may also help to maintain immunological homeostasis during HRV infection by regulating TGF-beta production.
C1 [Azevedo, M. S. P.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA.
[Zhang, W.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Entomol, Wooster, OH 44691 USA.
[Wen, K.; Yuan, L.] Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Ctr Mol Med & Infect Dis, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA.
[Gonzalez, A. M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA.
[Saif, L. J.] Ohio State Univ, Ohio Agr Res & Dev Ctr, Dept Vet Prevent Med, Food Anim Hlth Res Program, Wooster, OH 44691 USA.
[Yousef, A. E.] Ohio State Univ, Coll Food Agr & Environm Sci, Dept Food Sci & Technol, Columbus, OH 43210 USA.
RP Azevedo, MSP (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM lyuan@vt.edu
RI Yousef, Ahmed/E-4358-2011; Wen, Ke /K-7101-2013
FU National Institutes of Health [1R21AT002524, R01AI033561]; Ohio
Agricultural Research and Development Center, Ohio State University
[OHOA1208]
FX This work was supported by grants from the National Institutes of Health
(1R21AT002524 to LY and R01AI033561 to LJS) and Ohio Agricultural
Research and Development Center, Ohio State University (OHOA1208 to LY).
We thank Dr. Juliette Hanson and Mr. Rich McCormmick for animal care and
veterinary clinical assistance, respectively. Salaries and research
support were provided by state and federal funds appropriated to OARDC
of The Ohio State University.
NR 40
TC 15
Z9 18
U1 0
U2 13
PU WAGENINGEN ACADEMIC PUBLISHERS
PI WAGENINGEN
PA PO BOX 220, WAGENINGEN, 6700 AE, NETHERLANDS
SN 1876-2883
J9 BENEF MICROBES
JI Benef. Mirbobes
PD MAR
PY 2012
VL 3
IS 1
BP 33
EP 42
DI 10.3920/BM2011.0041
PG 10
WC Microbiology; Nutrition & Dietetics
SC Microbiology; Nutrition & Dietetics
GA 969VL
UT WOS:000306087400005
PM 22348907
ER
PT J
AU Wu, KM
Powley, MW
Ghantous, H
AF Wu, Kuei-Meng
Powley, Mark W.
Ghantous, Hanan
TI Timing of Carcinogenicity Studies and Predictability of Genotoxicity for
Tumorigenicity in Anti-HIV Drug Development
SO INTERNATIONAL JOURNAL OF TOXICOLOGY
LA English
DT Article
DE carcinogenicity; genotoxicity; predictability; timing
ID ENZYME-INDUCTION; TESTS
AB The timing of carcinogenicity studies in parallel with the clinical development of anti-human immunodeficiency virus (HIV) drugs has been flexible for most cases in the past. This includes postponement of the initiation of the studies and submission of final audited reports to the US Food and Drug Administration (FDA) for a new drug application (NDA) approval. We address this regulatory practice for anti-HIV drugs for which, in the past, there had been no effective treatment. We also examine the correlation of genotoxicity data with carcinogenicity data for the varied subclasses of anti-HIV drugs. We suggest that this regulatory policy regarding the timing of carcinogenicity testing does not compromise the safety standards of FDA's drug evaluation and the approval process. The policy does facilitate availability of these agents to meet the medical needs of the target population. Our analysis on the profile of carcinogenicity findings of anti-HIV drugs shows trends of class effects. Additionally, both carcinogenicity and genotoxicity data show significant correlations, which provide useful insights into issues involving these 2 important areas of toxicological investigations.
C1 [Wu, Kuei-Meng; Powley, Mark W.; Ghantous, Hanan] US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
RP Wu, KM (reprint author), US FDA, Div Antiviral Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
EM kueimeng.wu@fda.hhs.gov
NR 22
TC 2
Z9 3
U1 0
U2 0
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.
PD MAR-JUN
PY 2012
VL 31
IS 3
BP 211
EP 221
DI 10.1177/1091581812439585
PG 11
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 953QH
UT WOS:000304885600001
PM 22550047
ER
PT J
AU Chiang, HM
Xia, QS
Zou, XJ
Wang, C
Wang, SG
Miller, BJ
Howard, PC
Yin, JJ
Beland, FA
Yu, HT
Fu, PP
AF Chiang, Hsiu-mei
Xia, Qingsu
Zou, Xiaoju
Wang, Cheng
Wang, Shuguang
Miller, Barbara J.
Howard, Paul C.
Yin, Jun Jie
Beland, Frederick A.
Yu, Hongtao
Fu, Peter P.
TI Nanoscale ZnO Induces Cytotoxicity and DNA Damage in Human Cell Lines
and Rat Primary Neuronal Cells
SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY
LA English
DT Article
DE ZnO Nanoparticles; Cytotoxicity; Reactive Oxygen Species; DNA Damage
ID ZINC-OXIDE NANOPARTICLES; HUMAN SKIN KERATINOCYTES; OXIDATIVE STRESS;
COMPARATIVE TOXICITY; PARTICLE SOLUBILITY; BULK ZNO; NANOMATERIALS;
WATER; SUSPENSIONS; CHALLENGES
AB The toxic effects of ZnO nanoparticles (nano-ZnO) (1-100 mu g/mL) suspended in DMEM were examined in human A549 cells, HepG2 cells, human skin fibroblast cells, human skin keratinocytes, and rat primary neuronal cells for 24 h. Nano-ZnO induced dose dependent cytotoxicity and damaged cell membranes. Cell death was not mediated by reactive oxygen species (ROS) or apoptosis. Nano-ZnO induced DNA damage in rat primary neuronal cells, human fibroblasts, and A549 cells. The cytotoxicity of nano-ZnO in DMEM supplemented with 10% FBS, instead of serum free DMEM, was also examined in the A549 cells, human skin fibroblast cells, and human skin keratinocytes. The levels of cytotoxicity induced were similar to those tested without FBS; in addition, ROS was observed. These results indicate that the cause of cytotoxicity is medium dependent and imply that cellular growth conditions may play a significant role in induction of cytotoxicity and DNA damage by nano-ZnO.
C1 [Chiang, Hsiu-mei; Xia, Qingsu; Wang, Shuguang; Beland, Frederick A.; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zou, Xiaoju; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Wang, Shuguang; Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA.
[Miller, Barbara J.; Howard, Paul C.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Yin, Jun Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
RP Fu, PP (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RI Chiang, Hsiu-Mei/L-8150-2013; Yin, Jun Jie /E-5619-2014
NR 42
TC 26
Z9 27
U1 2
U2 25
PU AMER SCIENTIFIC PUBLISHERS
PI VALENCIA
PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA
SN 1533-4880
J9 J NANOSCI NANOTECHNO
JI J. Nanosci. Nanotechnol.
PD MAR
PY 2012
VL 12
IS 3
BP 2126
EP 2135
DI 10.1166/jnn.2012.5758
PG 10
WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials
Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA 955RX
UT WOS:000305039700057
PM 22755030
ER
PT J
AU Mossoba, MM
Kramer, JKG
Azizian, H
Kraft, J
Delmonte, P
Kia, ARF
Bueso, FJ
Rader, JI
Lee, JK
AF Mossoba, Magdi M.
Kramer, John K. G.
Azizian, Hormoz
Kraft, Jana
Delmonte, Pierluigi
Kia, Ali-Reza Fardin
Bueso, Francisco J.
Rader, Jeanne I.
Lee, Jung K.
TI Application of a Novel, Heated, Nine-Reflection ATR Crystal and a
Portable FTIR Spectrometer to the Rapid Determination of Total Trans Fat
SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY
LA English
DT Article
DE Fats and oils; Spectroscopy; Lipid chemistry; Lipid analysis
ID CORONARY-HEART-DISEASE; INFRARED-SPECTROSCOPY; REGULATORY COMPLIANCE;
UNITED-STATES; ISOMERS; FOODS; RISK
AB Since trans fat labeling requirements became mandatory in the US and many other countries, there has been a need for rapid and accurate analytical methodologies that can facilitate compliance with the various regulations. The determination of total trans fatty acids by mid-infrared (IR) spectroscopy is a widely used procedure that was standardized and validated as AOCS Official Method Cd 14e-09 (negative second derivative infrared spectroscopic method for the rapid (5 min) determination of total isolated trans fat) in 2009. The C-H out-of-plane deformation mid-IR band observed at 966 cm(-1) is uniquely characteristic of isolated (non-conjugated) double bonds with trans configuration. AOCS Official Method Cd 14e-09, the most recent attenuated total reflection-Fourier transform IR (ATR-FTIR) official method, entails the measurement of the height of the negative second derivative of the trans absorption band. In the present study, the performance of a novel, portable FTIR system equipped with a heated 9-bounce diamond ATR crystal was evaluated and compared to that of a conventional benchtop single-bounce ATR-FTIR spectrometer. The introduction of the 9-bounce diamond ATR crystal resulted in the lowering of the limit of quantification of trans fat, as a percentage of the total fat, from approximately 2 to 0.34%. The data collected from accurately weighed gravimetric standards and 28 unknown test samples ranging in trans fat content from about 0.5 to 54%, as a percentage of the total fat, indicated that this IR official method and the use of the new 9-bounce portable ATR-FTIR instrumentation could lead to a five-fold enhancement in sensitivity relative to single-bounce systems. Implementing these changes would facilitate regulatory compliance and verification of fat and oil samples for trans fat content in the US and other countries, since all of the published regulations (e. g., "0 g trans fat per serving'') have levels of trans fat, as percentage of total fat, that exceed 0.34%.
C1 [Mossoba, Magdi M.; Delmonte, Pierluigi; Kia, Ali-Reza Fardin; Bueso, Francisco J.; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr CFSAN, College Pk, MD 20740 USA.
[Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada.
[Azizian, Hormoz] NIR Technol Inc, Oakville, ON, Canada.
[Kraft, Jana] Univ Vermont, Coll Agr & Life Sci, Burlington, VT USA.
[Lee, Jung K.] US FDA, Off Food Def Commun & Emergency Response, CFSAN, College Pk, MD 20740 USA.
RP Mossoba, MM (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr CFSAN, Mail Stop HFS 717,Room BE 012,5100 Paint Branch P, College Pk, MD 20740 USA.
EM magdi.mossoba@fda.hhs.gov; JKGKramer@roger.com
NR 24
TC 8
Z9 9
U1 0
U2 18
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0003-021X
J9 J AM OIL CHEM SOC
JI J. Am. Oil Chem. Soc.
PD MAR
PY 2012
VL 89
IS 3
BP 419
EP 429
DI 10.1007/s11746-011-1930-9
PG 11
WC Chemistry, Applied; Food Science & Technology
SC Chemistry; Food Science & Technology
GA 959DK
UT WOS:000305291600007
ER
EF