FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Otto, M
AF Otto, Michael
TI Staphylococcus epidermidis - the 'accidental' pathogen
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Review
ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI;
ACCUMULATION-ASSOCIATED PROTEIN; CATHETER-ASSOCIATED INFECTION;
HORIZONTAL GENE-TRANSFER; FOREIGN-BODY INFECTION; QUORUM-SENSING SYSTEM;
FIBRINOGEN-BINDING PROTEIN; CASSETTE CHROMOSOME MEC; PHENOL-SOLUBLE
MODULINS
AB Although nosocomial infections by Staphylococcus epidermidis have gained much attention, this skin-colonizing bacterium has apparently evolved not to cause disease, but to maintain the commonly benign relationship with its host. Accordingly, S. epidermidis does not produce aggressive virulence determinants. Rather, factors that normally sustain the commensal lifestyle of S. epidermidis seem to give rise to additional benefits during infection. Furthermore, we are beginning to comprehend the roles of S. epidermidis in balancing the epithelial microflora and serving as a reservoir of resistance genes. In this Review, I discuss the molecular basis of the commensal and infectious lifestyles of S. epidermidis.
C1 NIAID, NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), NIAID, NIH, 9000 Rockville Pike Bldg,33 1W10, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the intramural research programme of the
National Institute of Allergy and Infectious Diseases.
NR 161
TC 412
Z9 430
U1 15
U2 108
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD AUG
PY 2009
VL 7
IS 8
BP 555
EP 567
DI 10.1038/nrmicro2182
PG 13
WC Microbiology
SC Microbiology
GA 471OY
UT WOS:000268069100009
PM 19609257
ER
PT J
AU Koonin, EV
Senkevich, TG
Dolja, VV
AF Koonin, Eugene V.
Senkevich, Tatiana G.
Dolja, Valerian V.
TI Compelling reasons why viruses are relevant for the origin of cells
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Letter
ID EVOLUTION; TREE; LIFE
C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Senkevich, Tatiana G.] NIAID, NIH, Viral Dis Lab, Bethesda, MD 20894 USA.
[Dolja, Valerian V.] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA.
[Dolja, Valerian V.] Oregon State Univ, Ctr Genome Res & Biocomp, Corvallis, OR 97331 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
NR 15
TC 17
Z9 17
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD AUG
PY 2009
VL 7
IS 8
DI 10.1038/nrmicro2108-c5
PG 2
WC Microbiology
SC Microbiology
GA 471OY
UT WOS:000268069100019
PM 19561624
ER
PT J
AU Petrie, RJ
Doyle, AD
Yamada, KM
AF Petrie, Ryan J.
Doyle, Andrew D.
Yamada, Kenneth M.
TI Random versus directionally persistent cell migration
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Review
ID SIGNAL-TRANSDUCTION PATHWAYS; ACTIN-DEPOLYMERIZING FACTOR; TYROSINE
KINASE ROR2; CONTACT GUIDANCE; LEADING-EDGE; FOCAL ADHESIONS; STRESS
FIBERS; GROWTH-FACTOR; RHO-GTPASES; RAC ACTIVATION
AB Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as the topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking, integrin co-receptors and actomyosin contraction converge on regulation of the Rho family of GTPases and the control of lamellipodial protrusions to promote directional migration.
C1 [Petrie, Ryan J.; Doyle, Andrew D.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Petrie, RJ (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM petrier@mail.nih.gov; kyamada@mail.nih.gov
OI Yamada, Kenneth/0000-0003-1512-6805
FU Intramural NIH HHS [Z01 DE000524-17]
NR 140
TC 373
Z9 377
U1 8
U2 93
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD AUG
PY 2009
VL 10
IS 8
BP 538
EP 549
DI 10.1038/nrm2729
PG 12
WC Cell Biology
SC Cell Biology
GA 473VM
UT WOS:000268238200015
PM 19603038
ER
PT J
AU Waldman, M
Austin, HA
AF Waldman, Meryl
Austin, Howard A., III
TI Controversies in the treatment of idiopathic membranous nephropathy
SO NATURE REVIEWS NEPHROLOGY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; METHYLPREDNISOLONE PLUS CHLORAMBUCIL;
MYCOPHENOLATE-MOFETIL TREATMENT; PROLIFERATIVE LUPUS NEPHRITIS;
PROGRESSIVE RENAL-FAILURE; 10-YEAR FOLLOW-UP; NEPHROTIC SYNDROME;
CYCLOSPORINE-A; LONG-TERM; PRIMARY GLOMERULONEPHRITIS
AB Optimum treatment of idiopathic membranous nephropathy is both controversial and challenging. The most extensively studied and frequently used immunosuppressive regimens for this disease comprise alkylating agents plus corticosteroids or ciclosporin. All of these treatment options have inherent problems: they are not effective in all patients, partial-rather than complete-remissions are common, adverse effects are worrisome, and relapses after treatment cessation remain problematic. Alternative immunosuppressive agents have been tested in an effort to overcome these unresolved issues. This paper reviews the available evidence regarding both established and new agents for the treatment of patients with idiopathic membranous nephropathy, with an emphasis on the results of the most recent clinical trials.
C1 [Waldman, Meryl; Austin, Howard A., III] NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Waldman, M (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10 Ctr Dr,Clin Res Ctr 5-2551, Bethesda, MD 20892 USA.
EM waldmanm@niddk.nih.gov
FU National institute of Diabetes and Digestive and Kidney Diseases, NIH
FX The authors are grateful to Drs James Balow and Monique Cho for their
critical reading of this manuscript. This work was supported by the
intramural research Program of the National institute of Diabetes and
Digestive and Kidney Diseases, NIH.
NR 94
TC 28
Z9 32
U1 0
U2 9
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 AUG
PY 2009
VL 5
IS 8
BP 469
EP 479
DI 10.1038/nrneph.2009.101
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA 476JY
UT WOS:000268437600010
PM 19581908
ER
PT J
AU Yun, SM
Moulaei, T
Lim, D
Bang, JK
Park, JE
Shenoy, SR
Liu, F
Kang, YH
Liao, CZ
Soung, NK
Lee, S
Yoon, DY
Lim, Y
Lee, DH
Otaka, A
Appella, E
McMahon, JB
Nicklaus, MC
Burke, TR
Yaffe, MB
Wlodawer, A
Lee, KS
AF Yun, Sang-Moon
Moulaei, Tinoush
Lim, Dan
Bang, Jeong K.
Park, Jung-Eun
Shenoy, Shilpa R.
Liu, Fa
Kang, Young H.
Liao, Chenzhong
Soung, Nak-Kyun
Lee, Sunhee
Yoon, Do-Young
Lim, Yoongho
Lee, Dong-Hee
Otaka, Akira
Appella, Ettore
McMahon, James B.
Nicklaus, Marc C.
Burke, Terrence R., Jr.
Yaffe, Michael B.
Wlodawer, Alexander
Lee, Kyung S.
TI Structural and functional analyses of minimal phosphopeptides targeting
the polo-box domain of polo-like kinase 1
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID CENP-A; PLK1; COMPLEX; DIVISION; CELLS
AB Polo-like kinase-1 (Plk1) has a pivotal role in cell proliferation and is considered a potential target for anticancer therapy. The noncatalytic polo-box domain (PBD) of Plk1 forms a phosphoepitope binding module for protein-protein interaction. Here, we report the identification of minimal phosphopeptides that specifically interact with the PBD of human PLK1, but not those of the closely related PLK2 and PLK3. Comparative binding studies and analyses of crystal structures of the PLK1 PBD in complex with the minimal phosphopeptides revealed that the C-terminal SpT dipeptide functions as a high-affinity anchor, whereas the N-terminal residues are crucial for providing specificity and affinity to the interaction. Inhibition of the PLK1 PBD by phosphothreonine mimetic peptides was sufficient to induce mitotic arrest and apoptotic cell death. The mode of interaction between the minimal peptide and PBD may provide a template for designing therapeutic agents that target PLK1.
C1 [Yun, Sang-Moon; Park, Jung-Eun; Kang, Young H.; Soung, Nak-Kyun; Lee, Sunhee; Lee, Dong-Hee; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Moulaei, Tinoush; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Lim, Dan; Yaffe, Michael B.] MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA.
[Lim, Dan; Yaffe, Michael B.] MIT, Ctr Canc Res, Dept Biol Engn, Cambridge, MA 02139 USA.
[Bang, Jeong K.] Korea Basic Sci Inst, Pusan, South Korea.
[Shenoy, Shilpa R.] NCI, Mol Targets Dev Program, SAIC Frederick, Frederick, MD 21701 USA.
[Liu, Fa; Liao, Chenzhong; Nicklaus, Marc C.; Burke, Terrence R., Jr.] NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[Lee, Sunhee; Yoon, Do-Young; Lim, Yoongho] Konkuk Univ, Dept Biosci & Biotechnol, Seoul, South Korea.
[Lee, Dong-Hee] Univ Seoul, Dept Life Sci, Seoul, South Korea.
[Otaka, Akira] Univ Tokushima, Grad Sch Pharmaceut Sci, Inst Hlth Biosci, Tokushima 770, Japan.
[Appella, Ettore] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[McMahon, James B.] NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kyunglee@mail.nih.gov
RI Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014;
OI Nicklaus, Marc/0000-0002-4775-7030
FU National Cancer Institute; National Institutes of Health [R01 GM60594];
Korea Basic Science Institute [N28079]; Korean Ministry of Education;
Japanese government; National Cancer Institute, National Institutes of
Health [N01-CO-12400, HHSN261200800001E]
FX We thank F.J. Gonzalez, C. Vinson and S. Garfield for critical reading
of the manuscript, and R. Erikson ( Harvard University) and W. Dai ( New
York University School of Medicine) for reagents and helpful
suggestions. This research was supported in part by the Intramural
Research Program of the National Cancer Institute ( E. A., J.B.M.,
M.C.N.,T. R. B., A. W. and K. S. L.), National Institutes of Health
grant R01 GM60594 (M.B.Y.), Korea Basic Science Institute project N28079
(J.K.B.), a Korean Ministry of Education grant ( D. H. L.) and a
Japanese government grant (A.O.). This project was funded in whole or in
part with federal funds from the National Cancer Institute, National
Institutes of Health, under contract N01-CO-12400 and HHSN261200800001E.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products or organizations imply
endorsement by the US government.
NR 23
TC 96
Z9 99
U1 1
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD AUG
PY 2009
VL 16
IS 8
BP 876
EP U104
DI 10.1038/nsmb.1628
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 480MJ
UT WOS:000268738700016
PM 19597481
ER
PT J
AU Sakurai, N
Kuroiwa, T
Ikeuchi, H
Hiramatsu, N
Takeuchi, S
Tomioka, M
Shigehara, T
Maeshima, A
Kaneko, Y
Hiromura, K
Kopp, JB
Nojima, Y
AF Sakurai, Noriyuki
Kuroiwa, Takashi
Ikeuchi, Hidekazu
Hiramatsu, Noriyuki
Takeuchi, Shigeru
Tomioka, Mai
Shigehara, Tetsuya
Maeshima, Akito
Kaneko, Yoriaki
Hiromura, Keiju
Kopp, Jeffery B.
Nojima, Yoshihisa
TI Fluvastatin prevents podocyte injury in a murine model of HIV-associated
nephropathy
SO NEPHROLOGY DIALYSIS TRANSPLANTATION
LA English
DT Article
DE fluvastatin; HIV-associated nephropathy; podocyte
ID RAT MODEL; OXIDATIVE STRESS; EXPRESSION; GLOMERULONEPHRITIS;
CERIVASTATIN; PRAVASTATIN; INHIBITION; EPITHELIUM; INFECTION; FIBROSIS
AB Background. Recent studies have reported that statins have renoprotective effects, independent from lowering plasma cholesterol. In this study, we examined whether statins were beneficial in a murine model of HIV-associated nephropathy (HIVAN).
Methods. We used conditional transgenic mice that express one of the HIV-1 accessory genes, vpr, selectively in podocytes using podocin promoter and the Tet-on system. These mice develop aggressive collapsing focal segmental glomerular sclerosis with massive proteinuria and deterioration of renal function within 4 weeks following heminephrectomy and doxycycline administration. Fluvastatin was administrated simultaneously with doxycycline, and the effect was compared with untreated controls after 4 weeks.
Results. Fluvastatin at 10 mg/kg/day significantly decreased urinary albumin excretion (87 versus 11 mg/day, P < 0.01) and glomerular sclerosis (2.4 versus 1.0, P < 0.01, assessed by semi-quantitative scoring: 0-4). Fluvastatin also decreased serum creatinine and total cholesterol, but these differences were not statistically significant (0.36 versus 0.32 mg/dl, P = 0.35; 492 versus 378 mg/dl, P = 0.11, respectively). Phenotypic changes in podocytes, as indicated by the downregulation of nephrin, Wilms' tumour 1 and synaptopodin, along with upregulation of proliferating cell nuclear antigen, were attenuated by fluvastatin, suggesting its protective effects against podocyte injuries. In cultured podocytes, angiotensin II treatment decreased nephrin expression to 13% of basal levels, which was reversed to 58% by adding fluvastatin.
Conclusions. In conclusion, fluvastatin was effective in treating experimental HIVAN. The beneficial effect of this drug might be caused, in part, by preserving nephrin expression in podocytes against angiotensin II-mediated injury.
C1 [Sakurai, Noriyuki; Kuroiwa, Takashi; Ikeuchi, Hidekazu; Hiramatsu, Noriyuki; Takeuchi, Shigeru; Tomioka, Mai; Shigehara, Tetsuya; Maeshima, Akito; Kaneko, Yoriaki; Hiromura, Keiju; Nojima, Yoshihisa] Gunma Univ, Grad Sch Med, Dept Med & Clin Sci, Gunma, Japan.
[Kopp, Jeffery B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA.
RP Kuroiwa, T (reprint author), Gunma Univ, Grad Sch Med, Dept Med & Clin Sci, Gunma, Japan.
EM tkuroiwa@med.gunma-u.ac.jp
OI Kopp, Jeffrey/0000-0001-9052-186X
FU Japanese Ministry of Education, Culture, Sports, Science and Technology
FX We thank Dr Stuart J. Shankland for providing the immortalized mouse
podocyte cell line. We also thank Ms Rumiko Koitabashi for her technical
assistance. This work is supported in part by a grant from the Japanese
Ministry of Education, Culture, Sports, Science and Technology.
NR 29
TC 14
Z9 14
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0931-0509
J9 NEPHROL DIAL TRANSPL
JI Nephrol. Dial. Transplant.
PD AUG
PY 2009
VL 24
IS 8
BP 2378
EP 2383
DI 10.1093/ndt/gfp012
PG 6
WC Transplantation; Urology & Nephrology
SC Transplantation; Urology & Nephrology
GA 472FN
UT WOS:000268115400015
PM 19188342
ER
PT J
AU Chio, A
Restagno, G
Brunetti, M
Ossola, I
Calvo, A
Mora, G
Sabatelli, M
Monsurro, MR
Battistini, S
Mandrioli, J
Salvi, F
Spataro, R
Schymick, J
Traynor, BJ
La Bella, V
AF Chio, Adriano
Restagno, Gabriella
Brunetti, Maura
Ossola, Irene
Calvo, Andrea
Mora, Gabriele
Sabatelli, Mario
Monsurro, Maria Rosaria
Battistini, Stefania
Mandrioli, Jessica
Salvi, Fabrizio
Spataro, Rossella
Schymick, Jennifer
Traynor, Bryan J.
La Bella, Vincenzo
CA ITALSGEN Consortium
TI Two Italian kindreds with familial amyotrophic lateral sclerosis due to
FUS mutation
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Amyotrophic lateral sclerosis; Genetics; FUS gene; Family pedigrees
ID GENE
AB Recently, fused in sarcoma/translated in liposarcoma (FUS/TLS) gene, located on chromosome 16p11.2, has been identified as a disease gene in familial amyotrophic lateral sclerosis (FALS). We have analyzed FUS/TLS in a cohort of 52 index cases from seven Italian regions with non-SOD1 and non-TARDBP FALS. We identified a heterozygous c.G1542C missense mutation in a family of northern Italian origin, and a heterozygous c.C1574T missense mutation in a family of Sicilian origin. Both variants are located in exon 15 encoding the RNA-recognition motif, and result in a substitution of an arginine with a serine in position 514 (p.R514S) and substitution of a proline with a leucine at position 525 (p.P525L), respectively. Overall, the two mutations accounted for 3.8% of 52 non-SOD1 and non-TDP43 index cases of FALS. The clinical phenotype was similar within each of the families, with a predominantly upper limb onset in the family carrying the p.R514S mutation and bulbar onset, with very young age and a rapid course in the family carrying the p.P525L mutation. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chio, Adriano; Calvo, Andrea] Univ Turin, ALS Ctr, Dept Neurosci, I-10126 Turin, Italy.
[Restagno, Gabriella; Brunetti, Maura; Ossola, Irene] OIRM S Anna, ASO, Dept Clin Pathol, Mol Genet Unit, Turin, Italy.
[Mora, Gabriele] Salvatore Maugeri Fdn, ALS Ctr, Milan, Italy.
[Sabatelli, Mario] Catholic Univ, Neurol Inst, Rome, Italy.
[Sabatelli, Mario] ICOMM Assoc ALS Res, Rome, Italy.
[Monsurro, Maria Rosaria] Univ Naples 2, Dept Neurol Sci, Naples, Italy.
[Battistini, Stefania] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy.
[Mandrioli, Jessica] Univ Modena, I-41100 Modena, Italy.
[Salvi, Fabrizio] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, Bologna, Italy.
[Spataro, Rossella; La Bella, Vincenzo] Univ Palermo, Dept Clin Neurosci, I-90133 Palermo, Italy.
[Schymick, Jennifer; Traynor, Bryan J.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Chio, A (reprint author), Univ Turin, ALS Ctr, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy.
EM achio@usa.net
RI Traynor, Bryan/G-5690-2010; Battistini, Stefania/N-2596-2015; Calvo,
Andrea/K-4141-2016; Spataro, Rossella/B-3656-2016; La Bella,
Vincenzo/H-4532-2012; MANDRIOLI, JESSICA/K-7235-2016;
OI Battistini, Stefania/0000-0003-2887-7624; Calvo,
Andrea/0000-0002-5122-7243; Spataro, Rossella/0000-0002-8910-3131;
MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli,
Mario/0000-0001-6635-4985; Chio, Adriano/0000-0001-9579-5341
FU Ministero della Salute, Ricerca Sanitaria Finalizzata; Fondazione Vialli
e Mauro for ALS, Torino; Regione Piemonte, Progetti Finalizzati; NIH;
National Institute on Aging [Z01-AG000949-02]
FX The work was supported by Ministero della Salute, Ricerca Sanitaria
Finalizzata 2007 (to AC, GR and GM); Fondazione Vialli e Mauro for ALS,
Torino (to AC and GM); and Regione Piemonte, Progetti Finalizzati (to
GR). This research was supported in part by the Intramural Research
Program of the NIH, National Institute on Aging (Z01-AG000949-02).
NR 6
TC 80
Z9 82
U1 0
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD AUG
PY 2009
VL 30
IS 8
BP 1272
EP 1275
DI 10.1016/j.neurobiolaging.2009.05.001
PG 4
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA 464TI
UT WOS:000267529500011
PM 19450904
ER
PT J
AU Cassano, T
Gaetani, S
Morgese, MG
Macheda, T
Laconca, L
Dipasquale, P
Taltavull, J
Shippenberg, TS
Cuomo, V
Gobbi, G
AF Cassano, Tommaso
Gaetani, Silvana
Morgese, Maria Grazia
Macheda, Teresa
Laconca, Leonardo
Dipasquale, Pasqua
Taltavull, Juan
Shippenberg, Toni S.
Cuomo, Vincenzo
Gobbi, Gabriella
TI Monoaminergic Changes in Locus Coeruleus and Dorsal Raphe Nucleus
Following Noradrenaline Depletion
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Locus coeruleus; Dorsal raphe; Noradrenaline; Serotonin; Dopamine; DSP-4
ID VENTRAL TEGMENTAL AREA; EXCITATORY AMINO-ACID; NORADRENERGIC NEURONS;
PARKINSONS-DISEASE; CEREBRAL-CORTEX; NOREPINEPHRINE NEURONS;
SEROTONERGIC NEURONS; ANTIDEPRESSANT DRUGS; NEUROTOXIN DSP4; FIRING
ACTIVITY
AB The goal of our study was to assess the monoaminergic changes in locus coeruleus (LC) and dorsal raphe nucleus (DRN) following noradrenaline (NA) depletion. Seven days after a single N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) intraperitoneal administration in mice, we observed a decrease of NA in both the LC and DRN, as well as in prefrontal cortex (PFC) and hippocampus (HIPP). Moreover, an increase of serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) was detected at LC level, while no change was found in DRN. DSP-4 also caused a significant decrease of dopamine (DA) tissue content in HIPP and DRN, without affecting the LC and the PFC. A decrease of DA metabolite, homovanillic acid (HVA), was found in the DRN of NA-depleted mice. These results highlight that the neurotoxic action of DSP-4 is not restricted to LC terminal projections but also involves NA depletion at the cell body level, where it is paralleled by adaptive changes in both serotonergic and dopaminergic systems.
C1 [Cassano, Tommaso; Morgese, Maria Grazia; Macheda, Teresa; Laconca, Leonardo] Univ Foggia, Dept Biomed Sci, I-71100 Foggia, Italy.
[Gaetani, Silvana; Dipasquale, Pasqua; Cuomo, Vincenzo] Univ Roma La Sapienza, Dept Physiol & Pharmacol V Erspamer, Rome, Italy.
[Taltavull, Juan; Shippenberg, Toni S.] NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, Baltimore, MD 21224 USA.
[Gobbi, Gabriella] McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
RP Cassano, T (reprint author), Univ Foggia, Dept Biomed Sci, Viale Luigi Pinto 1, I-71100 Foggia, Italy.
EM tommaso.cassano@unifg.it
RI Cuomo, Vincenzo/D-2772-2009; Gaetani, Silvana/D-3455-2009; cuomo,
vincenzo/J-6777-2012; Gobbi, Gabriella/I-2786-2013
FU Intramural NIH HHS [Z01 DA000504-01]
NR 57
TC 22
Z9 22
U1 1
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD AUG
PY 2009
VL 34
IS 8
BP 1417
EP 1426
DI 10.1007/s11064-009-9928-5
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 458RR
UT WOS:000267041700009
PM 19229609
ER
PT J
AU Goldstein, DS
Holmes, CS
Kaler, SG
AF Goldstein, David S.
Holmes, Courtney S.
Kaler, Stephen G.
TI Relative Efficiencies of Plasma Catechol Levels and Ratios for Neonatal
Diagnosis of Menkes Disease
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Menkes; Dopamine; Norepinephrine; Dopamine-beta-hydroxylase; DHPG;
DOPAC; Diagnosis
ID LIQUID-CHROMATOGRAPHY; ELECTROCHEMICAL DETECTION; TYROSINE-HYDROXYLASE;
MASS-SPECTROMETRY; DOPAMINE; 5-HYDROXYTRYPTAMINE; NOREPINEPHRINE;
PATIENT
AB Background Menkes disease is an X-linked recessive neurodevelopmental disorder resulting from mutation in a copper-transporting ATPase gene. Menkes disease can be detected by relatively high concentrations of dopamine (DA) and its metabolites compared to norepinephrine (NE) and its metabolites, presumably because dopamine-beta-hydroxylase (DBH) requires copper as a co-factor. The relative diagnostic efficiencies of levels of catechol analytes, alone or in combination, in neonates at genetic risk of Menkes disease have been unknown. Methods Plasma from 44 at-risk neonates less than 30 days old were assayed for DA, NE, and other catechols. Of the 44, 19 were diagnosed subsequently with Menkes disease, and 25 were unaffected. Results Compared to unaffected at-risk infants, those with Menkes disease had high plasma DA (P < 10(-6)) and low NE (P < 10(-6)) levels. Considered alone, neither DA nor NE levels had perfect sensitivity, whereas the ratio of DA:NE was higher in all affected than in all unaffected subjects (P = 2 x 10(-8)). Analogously, levels of the DA metabolite, dihydroxyphenylacetic acid (DOPAC), and the NE metabolite, dihydroxyphenylglycol (DHPG), were imperfectly sensitive, whereas the DOPAC:DHPG ratio was higher in all affected than in all unaffected subjects (P = 2 x 10(-4)). Plasma dihydroxyphenylalanine (DOPA) and the ratio of epinephrine (EPI):NE levels were higher in affected than in unaffected neonates (P = 0.0015; P = 0.013). Conclusions Plasma DA:NE and DOPAC:DHPG ratios are remarkably sensitive and specific for diagnosing Menkes disease in at-risk newborns. Affected newborns also have elevated DOPA and EPI:NE ratios, which decreased DBH activity alone cannot explain.
C1 [Goldstein, David S.; Holmes, Courtney S.] Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA.
[Kaler, Stephen G.] NICHHD, Unit Pediat Genet, Program Mol Med, NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Clin Neurosci Program, Div Intramural Res,NIH, Bldg 10 Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NINDS; NICHD
FX The research reported here was supported by the intramural programs of
the NINDS and NICHD.
NR 14
TC 16
Z9 16
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
J9 NEUROCHEM RES
JI Neurochem. Res.
PD AUG
PY 2009
VL 34
IS 8
BP 1464
EP 1468
DI 10.1007/s11064-009-9933-8
PG 5
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 458RR
UT WOS:000267041700014
PM 19234788
ER
PT J
AU Schmitt, JE
Lenroot, RK
Ordaz, SE
Wallace, GL
Lerch, JP
Evans, AC
Prom, EC
Kendler, KS
Neale, MC
Giedd, JN
AF Schmitt, J. Eric
Lenroot, Rhoshel K.
Ordaz, Sarah E.
Wallace, Gregory L.
Lerch, Jason P.
Evans, Alan C.
Prom, Elizabeth C.
Kendler, Kenneth S.
Neale, Michael C.
Giedd, Jay N.
TI Variance decomposition of MRI-based covariance maps using genetically
informative samples and structural equation modeling
SO NEUROIMAGE
LA English
DT Article
ID AUTOMATED 3-D EXTRACTION; CORTICAL THICKNESS; CEREBRAL-CORTEX; HUMAN
BRAIN; FUNCTIONAL CONNECTIVITY; VAL66MET POLYMORPHISM; SCHIZOPHRENIA;
MULTIVARIATE; NETWORKS; ADOLESCENTS
AB The role of genetics in driving intracortical relationships is an important question that has rarely been Studied in humans. In particular, there are no extant high-resolution imaging studies on genetic covariance. In this article, we describe a novel method that combines classical quantitative genetic methodologies for variance decomposition with recently developed semi-multivariate algorithms for high-resolution measurement of phenotypic covariance. Using these tools, we produced correlational maps of genetic and environmental (i.e. nongenetic) relationships between several regions of interest and the cortical surface in a large pediatric sample of 600 twins, siblings, and singletons. These analyses demonstrated high, fairly uniform, statistically significant genetic correlations between the entire cortex and global mean cortical thickness. In agreement with prior reports on phenotypic covariance using similar methods, we found that mean cortical thickness was most strongly correlated with association cortices. However, the present study suggests that genetics plays a large role in global brain patterning of cortical thickness in this manner. Further. using specific gyri with known high heritabilities as seed regions, we found a consistent pattern of high bilateral genetic correlations between structural homologues, with environmental correlations more restricted to the same hemisphere as the seed region, Suggesting that interhemispheric covariance is largely genetically mediated. These findings are consistent with the limited existing knowledge on the genetics of cortical variability as well as our prior multivariate studies on cortical gyri. Published by Elsevier Inc.
C1 [Lenroot, Rhoshel K.; Wallace, Gregory L.; Giedd, Jay N.] NIMH, Brain Imaging Unit, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Schmitt, J. Eric; Prom, Elizabeth C.; Kendler, Kenneth S.; Neale, Michael C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA.
[Ordaz, Sarah E.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Lerch, Jason P.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Evans, Alan C.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
RP Giedd, JN (reprint author), NIMH, Brain Imaging Unit, Child Psychiat Branch, Bldg 10,Room 4C110,10 Ctr Dr,MSC 1367, Bethesda, MD 20892 USA.
EM jg@nih.gov
RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015;
OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978;
Prom-Wormley, Elizabeth/0000-0001-9230-9723; Wallace,
Gregory/0000-0003-0329-5054
FU NIH [MH-65322, MH-20030, DA-18673]
FX This research was supported by NIH grants MH-65322, MH-20030, and
DA-18673.
NR 46
TC 25
Z9 25
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 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2009
VL 47
IS 1
BP 56
EP 64
DI 10.1016/j.neuroimage.2008.06.039
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 457YW
UT WOS:000266975300009
PM 18672072
ER
PT J
AU Horiguchi, H
Nakadomari, S
Misaki, M
Wandell, BA
AF Horiguchi, Hiroshi
Nakadomari, Satoshi
Misaki, Masaya
Wandell, Brian A.
TI Two temporal channels in human V1 identified using fMRI
SO NEUROIMAGE
LA English
DT Article
DE fMRI; Temporal channel; V1; Luminance; Uniform
ID HUMAN VISUAL-CORTEX; MACAQUE STRIATE CORTEX; MIDGET GANGLION-CELLS;
FUNCTIONAL MRI; BOLD RESPONSES; HUMAN RETINA; HUMAN-VISION; HUMAN BRAIN;
FIELD; DISCRIMINATION
AB Human visual sensitivity to a fairly broad class of dynamic stimuli can be modeled accurately using two temporal channels. Here, we analyze fMRI measurements of the temporal step response to spatially uniform stimuli to estimate these channels ill human primary Visual cortex (VI). In agreement with the psychophysical literature, the VI fMRI temporal responses are modeled accurately as a Mixture of two (transient and sustained) channels. We derive estimates of the relative contributions from these two channels at a range of eccentricities. We find that all portions of VI contain a significant transient response. The central visual field representation includes a significant sustained response, but the amplitude of the sustained channel signal declines with eccentricity. The sustained signals may reflect the emphasis on pattern recognition and color in the central Visual field; the dominant transient response in the Visual periphery may reflect responses in the human Visual attention system. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Horiguchi, Hiroshi; Wandell, Brian A.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
[Horiguchi, Hiroshi; Nakadomari, Satoshi] Jikei Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan.
[Nakadomari, Satoshi] Natl Rehabil Ctr Persons Disabil, Dept Funct Training 3, Tokorozawa, Saitama, Japan.
[Misaki, Masaya] Natl Inst Informat & Commun Technol, Kobe Adv ICT Res Ctr, Kobe, Hyogo, Japan.
[Misaki, Masaya] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Horiguchi, H (reprint author), Stanford Univ, Dept Psychol, Jordan Hall,Bldg 420, Stanford, CA 94305 USA.
EM hiroshih@stanford.edu
FU NEI NIH HHS [R01 EY003164-28A1, R01-EY03164, R01 EY003164]
NR 33
TC 7
Z9 7
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2009
VL 47
IS 1
BP 273
EP 280
DI 10.1016/j.neuroimage.2009.03.078
PG 8
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 457YW
UT WOS:000266975300030
PM 19361561
ER
PT J
AU Chang, SE
Kenney, MK
Loucks, TMJ
Poletto, CJ
Ludlow, CL
AF Chang, Soo-Eun
Kenney, Mary Kay
Loucks, Torrey M. J.
Poletto, Christopher J.
Ludlow, Christy L.
TI Common neural substrates support speech and non-speech vocal tract
gestures
SO NEUROIMAGE
LA English
DT Article
DE Sensory-motor interaction; Auditory dorsal stream; Functional magnetic
resonance imaging (fMRI); Speech production; Speech perception;
Non-speech
ID MOTOR CORTEX; PARKINSONS-DISEASE; MIRROR NEURONS; TEMPORAL-LOBE;
PREFRONTAL CORTEX; NONSPEECH SOUNDS; PREMOTOR CORTEX; LEXICAL ACCESS;
FMRI; INTEGRATION
AB The issue of whether speech is supported by the same neural substrates as non-speech vocal tract gestures has been contentious. In this fMRI study we tested whether producing non-speech vocal tract gestures in humans shares the same functional neuroanatomy as non-sense speech syllables. Production of non-speech vocal tract gestures, devoid of phonological content but similar to speech in that they had familiar acoustic and somatosensory targets, was compared to the production of speech syllables without meaning. Brain activation related to overt production was captured with BOLD fMRI using a sparse sampling design for both conditions. Speech and non-speech were compared using voxel-wise whole brain analyses, and ROI analyses focused on frontal and temporoparietal structures previously reported to support speech production. Results showed Substantial activation overlap between speech and non-speech function in regions. Although nonspeech gesture production showed greater extent and amplitude of activation in the regions examined, both speech and non-speech showed comparable left laterality, in activation for both target perception and production. These findings posit a more general role of the previously proposed "auditory dorsal stream" in the left hemisphere - to support the production of vocal tract gestures that are not limited to speech processing. Published by Elsevier Inc.
C1 [Chang, Soo-Eun; Kenney, Mary Kay; Loucks, Torrey M. J.; Poletto, Christopher J.; Ludlow, Christy L.] NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Ludlow, CL (reprint author), NINDS, Laryngeal & Speech Sect, Med Neurol Branch, NIH, 10 Ctr Dr,MSC 1416,Bldg 10,Room 5D38, Bethesda, MD 20892 USA.
EM ludlowc@ninds.nih.gov
OI Ludlow, Christy/0000-0002-2015-6171
FU Intramural Research Program in the National Institute of Neurological
Disorders and Stroke, NIH
FX This research was supported by the Intramural Research Program in the
National Institute of Neurological Disorders and Stroke, NIH.The authors
Wish to thank Richard Reynolds and Gang Chen for assistance during data
analyses and Sandra Martin for conducting speech and language testing.
NR 79
TC 37
Z9 37
U1 2
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD AUG 1
PY 2009
VL 47
IS 1
BP 314
EP 325
DI 10.1016/j.neuroimage.2009.03.032
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 457YW
UT WOS:000266975300035
PM 19327400
ER
PT J
AU Peckham, EL
Hallett, M
AF Peckham, Elizabeth L.
Hallett, Mark
TI Psychogenic Movement Disorders
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Psychogenic movement disorder; Functional movement disorder; Conversion;
Tremor; Medically unexplained symptoms; Dystonia
ID TRANSCRANIAL MAGNETIC STIMULATION; UNEXPLAINED MOTOR SYMPTOMS;
CONVERSION DISORDER; GAIT DISORDERS; FOLLOW-UP; FUNCTIONAL WEAKNESS;
SENSORY DISTURBANCE; CLINICAL-FEATURES; TREMOR; PARALYSIS
AB Psychogenic movement disorders (PMDs) represent a challenging dilemma for the treating neurologist. The terminology to classify this disorder is confusing and making the diagnosis is difficult. Once the diagnosis has been established, treatment options are limited, and the patient generally does not accept the diagnosis.
C1 [Peckham, Elizabeth L.] Neurol Specialists Dallas, Dallas, TX 75231 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Peckham, EL (reprint author), Neurol Specialists Dallas, 7515 Greenville Ave,Suite 500, Dallas, TX 75231 USA.
EM bethulrich@hotmail.com
FU Intramural NIH HHS [Z01 NS002667-23]
NR 74
TC 14
Z9 15
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0733-8619
J9 NEUROL CLIN
JI Neurol. Clin.
PD AUG
PY 2009
VL 27
IS 3
BP 801
EP +
DI 10.1016/j.ncl.2009.04.008
PG 20
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 477XE
UT WOS:000268551500011
PM 19555832
ER
PT J
AU Gozzi, M
Raymont, V
Solomon, J
Koenigs, M
Grafman, J
AF Gozzi, Marta
Raymont, Vanessa
Solomon, Jeffrey
Koenigs, Michael
Grafman, Jordan
TI Dissociable effects of prefrontal and anterior temporal cortical lesions
on stereotypical gender attitudes
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Ventromedial prefrontal cortex; Stereotypes; Implicit Association Test
ID HUMAN ORBITOFRONTAL CORTEX; IMPLICIT ASSOCIATION TEST; FRONTOTEMPORAL
DEMENTIA; SELF-CONCEPT; ACQUIRED SOCIOPATHY; NEURAL COMPONENTS; SOCIAL
COGNITION; FRONTAL DAMAGE; FUNCTIONAL MRI; HUMAN AMYGDALA
AB Clinical observations of patients with ventral frontal and anterior temporal cortical lesions reveal marked abnormalities in social attitudes. A previous study in seven patients with ventral prefrontal lesions provided the first direct experimental evidence for abnormalities in social attitudes using a well-established measure of gender stereotypes, the Implicit Association Test (IAT). Here, we were able to test whether these first findings could be reproduced in a larger sample of 154 patients with penetrating head injuries, and to determine the differential effects of ventromedial prefrontal (vmPFC) and ventrolateral prefrontal (vlPFC) cortical lesions on IAT performance. in addition, we investigated the role of the superior anterior temporal lobe (aTL), recently shown to represent conceptual social knowledge. First, we used a linear regression model to identify the role of each of the three regions, while controlling for the extent of damage to other regions. We found that larger lesions in either the vmPFC or the superior aTL were associated with increased stereotypical attitudes, whereas larger lesions in the vlPFC were associated with decreased stereotypical attitudes. Second, in a confirmatory analysis, we grouped patients by lesion location and compared their performance on the IAT with that of healthy volunteers. Compared to controls, patients with lesions in either the vmPFC or the superior aTL showed increased stereotypical attitudes, whereas patients with lesions in the vlPFC showed decreased stereotypical attitudes. The functional contributions of these regions in social attitudes are discussed. Published by Elsevier Ltd.
C1 [Gozzi, Marta; Raymont, Vanessa; Koenigs, Michael; Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Gozzi, Marta] Univ Milano Bicocca, Dipartimento Psicol, I-20126 Milan, Italy.
[Raymont, Vanessa] Natl Naval Med Ctr, Vietnam Head Injury Study, Henry M Jackson Fdn, Bethesda, MD 20889 USA.
[Raymont, Vanessa] Johns Hopkins Univ, Dept Radiol, Baltimore, MD 21287 USA.
[Solomon, Jeffrey] Med Numer Inc, Germantown, MD 20876 USA.
[Koenigs, Michael] Univ Wisconsin, Dept Psychiat, Madison, WI 53719 USA.
RP Grafman, J (reprint author), Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Natl Inst Hlth, Bldg 10,Room 7D43,MSC 1440, Bethesda, MD 20892 USA.
EM grafmanj@ninds.nih.gov
OI Grafman, Jordan H./0000-0001-8645-4457; Koenigs,
Michael/0000-0002-5799-4881
FU Intramural NIH HHS [Z01 NS002792-19]
NR 68
TC 21
Z9 22
U1 3
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD AUG
PY 2009
VL 47
IS 10
BP 2125
EP 2132
DI 10.1016/j.neuropsychologia.2009.04.002
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA 460LM
UT WOS:000267189200014
PM 19467362
ER
PT J
AU Cannella, N
Economidou, D
Kallupi, M
Stopponi, S
Heilig, M
Massi, M
Ciccocioppo, R
AF Cannella, Nazzareno
Economidou, Daina
Kallupi, Marsida
Stopponi, Serena
Heilig, Markus
Massi, Maurizio
Ciccocioppo, Roberto
TI Persistent Increase of Alcohol-Seeking Evoked by Neuropeptide S: an
Effect Mediated by the Hypothalamic Hypocretin System
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE neuropeptide S; alcohol; addiction; relapse; hypocretin-1/orexinA; rat
ID STRESS-INDUCED REINSTATEMENT; OREXIN NEURONS; FOOD-INTAKE; RATS;
ETHANOL; BEHAVIOR; EXTINCTION; STIMULI; RELAPSE; PEPTIDES
AB The association of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor for relapse risk in alcoholism. This study examined in rats the effects of a newly deorphanized neuropeptide receptor and its cognate ligand, Neuropeptide S (NPS), on ethanol consumption and reinstatement of ethanol-seeking by environmental cues previously associated with ethanol availability. In the self-administration experiments, the stable response rates observed for ethanol reinforcement were not modified by intracerebroventricular (ICV) injection of NPS (1.0 and 2.0 nmol per rat). In the reinstatement experiments, ethanol-associated cues induced robust rates of ethanol seeking, which were highly resistant to extinction over repeated sessions of reinstatement testing. ICV NPS treatment (1.0, 2.0 and 4.0 nmol per rat) resulted in a significant increase of ethanol seeking elicited by ethanol-associated cues. In contrast, NPS did not affect the reinstatement of responding to water-paired stimuli. Site-specific NPS injection (0.1 and 0.5 nmol per rat) into the lateral hypothalamus also reinstated extinguished responding to ethanol. This effect was selectively blocked by pre-treatment with the hypocretin-1/orexin-A antagonist SB-334867 (10 mg/kg, i.p.). At the dose tested, SB-334867 did not modify alcohol reinstatement per se. These results provide the first demonstration that activation of NPS receptors in the LH intensifies relapse to ethanol-seeking elicited by environmental conditioning factors. This effect is selective, and is mediated by activation of LH hypocretin neurones. Based on the present findings, we also predict that antagonism at NPS receptors could represent a novel pharmacological approach to alcohol relapse treatment. Neuropsychopharmacology (2009) 34, 2125-2134; doi:10.1038/npp.2009.37; published online 25 March 2009
C1 [Cannella, Nazzareno; Economidou, Daina; Kallupi, Marsida; Stopponi, Serena; Massi, Maurizio; Ciccocioppo, Roberto] Univ Camerino, Dept Pharmacol Sci & Expt Med, I-62032 Camerino, Italy.
[Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Ciccocioppo, R (reprint author), Univ Camerino, Dept Pharmacol Sci & Expt Med, Via Madonna delle Carceri, I-62032 Camerino, Italy.
EM roberto.ciccocioppo@unicam.it
OI Heilig, Markus/0000-0003-2706-2482; Kallupi,
Marsida/0000-0002-8688-709X; Cannella, Nazzareno/0000-0002-2891-8679
FU PRIN [2006]
FX Supported by Grant PRIN 2006 to (RC). We thank Alfredo Fiorelli and
Marino Cucculelli, for expert technical assistance, and Sheila Beatty
for linguistic revision of the paper.
NR 30
TC 51
Z9 52
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD AUG
PY 2009
VL 34
IS 9
BP 2125
EP 2134
DI 10.1038/npp.2009.37
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 471ZM
UT WOS:000268097200007
PM 19322167
ER
PT J
AU Freidlin, RZ
Ozarslan, E
Assaf, Y
Komlosh, ME
Basser, PJ
AF Freidlin, Raisa Z.
Oezarslan, Evren
Assaf, Yaniv
Komlosh, Michal E.
Basser, Peter J.
TI A multivariate hypothesis testing framework for tissue clustering and
classification of DTI data
SO NMR IN BIOMEDICINE
LA English
DT Article
DE DTI; diffusion tensor; tissue; region growing; clustering; segmentation;
classification; hypothesis testing; ROI; DWI; F-test
ID DIFFUSION TENSOR MRI; HUMAN BRAIN; SEGMENTATION; CONNECTIVITY; TRACKING;
NUCLEI; IMAGES; MODEL
AB The primary aim of this work is to propose and investigate the effectiveness of a novel unsupervised tissue clustering and classification algorithm for diffusion tensor MRI (DTI) data. The proposed algorithm utilizes information about the degree of homogeneity of the distribution of diffusion tensors within voxels. We adapt frameworks proposed by Hext and Snedecor, where the null hypothesis of diffusion tensors belonging to the same distribution is assessed by an F-test. Tissue type is classified according to one of the four possible diffusion models, the assignment of which is determined by a parsimonious model selection framework based on Schwarz Criterion. Both numerical phantoms and diffusion-weighted imaging (DWI) data obtained from excised rat and pig spinal cords are used to test and validate these tissue clustering and classification approaches. The unsupervised clustering method effectively identifies distinct regions of interest (ROIs) in phantoms and real experimental DTI data. Copyright (C) 2009 John Wiley & Sons, Ltd.
C1 [Freidlin, Raisa Z.] NIH, Biomed Imaging & Visualizat Sect, Computat Biosci & Engn Lab, Div Computat Biosci,Ctr Informat Technol, Bethesda, MD 20892 USA.
[Oezarslan, Evren; Komlosh, Michal E.; Basser, Peter J.] NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA.
[Assaf, Yaniv] Tel Aviv Univ, Dept Neurobiochem, Ramat Aviv, Israel.
RP Freidlin, RZ (reprint author), NIH, Biomed Imaging & Visualizat Sect, Computat Biosci & Engn Lab, Div Computat Biosci,Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
EM raisa@helix.nih.gov
RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011
OI Ozarslan, Evren/0000-0003-0859-1311;
FU Intramural Research Program of the National Institute of Child Health
and Development (NICHD); Center for Information Technology (CIT);
National Institutes of Health, Bethesda, Maryland
FX RZF thanks Kenneth Kempner for his support and encouragement. The
authors would like to thank Dr Carlo Pierpaoli and Dr Uri Nevo for
helpful discussions and Liz Salak for editing this paper. This research
was supported by the Intramural Research Program of the National
Institute of Child Health and Development (NICHD) and the Center for
Information Technology (CIT), National Institutes of Health, Bethesda,
Maryland.
NR 39
TC 4
Z9 4
U1 0
U2 5
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD AUG
PY 2009
VL 22
IS 7
BP 716
EP 729
DI 10.1002/nbm.1383
PG 14
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 486YE
UT WOS:000269236100004
PM 19593779
ER
PT J
AU Bock, NA
Kocharyan, A
Silva, AC
AF Bock, Nicholas A.
Kocharyan, Ara
Silva, Afonso C.
TI Manganese-enhanced MRI visualizes V1 in the non-human primate visual
cortex
SO NMR IN BIOMEDICINE
LA English
DT Article
DE manganese-enhanced MRI (MEMRI); visual cortex; marmoset; non-human
primate; Gennari stripe; cytochrome oxidase
ID CYTOCHROME-OXIDASE; BRAIN-FUNCTION; MUTANT MICE; MONKEY; TRANSPORT;
SYSTEM; MN; ORGANIZATION; PARVALBUMIN; TOXICITY
AB MRI at 7 Tesla has been used to investigate the accumulation of manganese in the occipital cortex of common marmoset monkeys (Callithrix jacchus) after administering four fractionated injections of 30 mg/kg MnCl(2)center dot 4H(2)O in the tail vein. We found a statistically significant decrease in T(1) in the primary (V1) and secondary (V2) areas of the visual cortex caused by an accumulation of manganese. The larger T, shortening in V1 (Delta T(1), = 640 ms) relative to V2 (AT, = 490 ms) allowed us to robustly detect the V1/V2 border in vivo using heavily T(1)-weighted MRI. Furthermore, the dorso-medial (DM) and middle-temporal (MT) areas of the visual pathway could be identified by their T(1)-weighted enhancement. We showed by comparison to histological sections stained for cytochrome oxidase (CO) activity that the extent of V1 is accurately identified throughout the visual cortex by manganese-enhanced MRI (MEMRI). This provides a means of visualizing functional cortical regions in vivo and could be used in longitudinal studies of phenomena such as cortical plasticity, and for non-destructive localization of cortical regions to guide in the implementation of functional techniques. Published in 2009 by John Wiley & Sons, Ltd.
C1 [Bock, Nicholas A.; Kocharyan, Ara; Silva, Afonso C.] Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Bock, NA (reprint author), Natl Inst Neurol Disorders & Stroke, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room BD109, Bethesda, MD 20892 USA.
EM bockn@mail.nih.gov
RI Silva, Afonso/A-7129-2009
FU Intramural NIH HHS [Z01 NS003041-01, Z01 NS003041-02, ZIA NS003041-03]
NR 37
TC 15
Z9 15
U1 0
U2 3
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD AUG
PY 2009
VL 22
IS 7
BP 730
EP 736
DI 10.1002/nbm.1384
PG 7
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 486YE
UT WOS:000269236100005
PM 19322808
ER
PT J
AU Semba, RD
Houston, DK
Ferrucci, L
Cappola, AR
Sun, K
Guralnik, JM
Fried, LP
AF Semba, Richard D.
Houston, Denise K.
Ferrucci, Luigi
Cappola, Anne R.
Sun, Kai
Guralnik, Jack M.
Fried, Linda P.
TI Low serum 25-hydroxyvitamin D concentrations are associated with greater
all-cause mortality in older community-dwelling women
SO NUTRITION RESEARCH
LA English
DT Article
DE Aging; Mortality; Survival; Vitamin D; Women
ID VITAMIN-D SUPPLEMENTATION; RANDOMIZED CONTROLLED-TRIALS; FRAILTY
SYNDROME; D DEFICIENCY; HEALTH; METAANALYSIS; ASSAY; RISK;
1,25-DIHYDROXYVITAMIN-D; PERFORMANCE
AB Vitamin D deficiency is associated with osteoporosis, poor muscle strength, falls, and fractures. The relationship between serum vitamin D concentrations and mortality in older community-dwelling women has not been well characterized. We hypothesized that women with lower 25-hydroxyvitamin D (25[OH]D) concentrations were at higher risk of mortality. We examined the association between serum 25[OH]D concentrations and all-cause mortality in a prospective, population-based study of 714 community-dwelling women, aged 70 to 79 years, the Women's Health and Aging Studies I and 11 in Baltimore, Md. The studies were originally designed to evaluate the causes and course of physical disability in older women living in the community. Vital status was determined through follow-up interviews and matching with the National Death Index. During a median of 72 months of follow-up, 100 (14%) of 714 women died. Women in the lowest quartile of 25(OH)D (<15.3 ng/mL or 38.2 nmol/L) were at higher risk of death (hazards ratio, 2.45; 95% confidence interval, 1.12-5.36; P = .02) compared to women in the highest quartile (>27.0 ng/mL or 67.4 nmol/L) of 25(OH)D in a multivariate Cox proportional hazards model adjusting for demographics, season, and conventional risk factors. Older community-dwelling women with low 25 (OH)D levels are at an increased risk of death. (C) 2009 Elsevier Inc. All rights reserved.
C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA.
Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA.
Wake Forest Univ, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
NIA, Longitudinal Studies Sect, Baltimore, MD 21225 USA.
Univ Penn, Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA.
NIA, Epidemiol & Demog Sect, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA.
EM rdsemba@jhmi.edu
FU National Institute on Aging [R01 AG027012]; NIH-NCRR; OPD-GCRC
[RR00722]; Intramural Research Program, National Institute on Aging,
National Institutes of Health
FX This work was supported by National Institute on Aging grant R01
AG027012, NIH-NCRR, OPD-GCRC grant RR00722, and the Intramural Research
Program, National Institute on Aging, National Institutes of Health.
NR 34
TC 41
Z9 41
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD AUG
PY 2009
VL 29
IS 8
BP 525
EP 530
DI 10.1016/j.nutres.2009.07.007
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 499WH
UT WOS:000270256900001
PM 19761886
ER
PT J
AU Shellhaas, CS
Gilbert, S
Landon, MB
Varner, MW
Leveno, KJ
Hauth, JC
Spong, CY
Caritis, SN
Wapner, RJ
Sorokin, Y
Miodovnik, M
O'Sullivan, MJ
Sibai, BM
Langer, O
Gabbe, SG
AF Shellhaas, Cynthia S.
Gilbert, Sharon
Landon, Mark B.
Varner, Michael W.
Leveno, Kenneth J.
Hauth, John C.
Spong, Catherine Y.
Caritis, Steve N.
Wapner, Ronald J.
Sorokin, Yoram
Miodovnik, Menachem
O'Sullivan, Mary J.
Sibai, Baha M.
Langer, Oded
Gabbe, Steven G.
CA Eunice Kennedy Shriver Natl Inst H
TI The Frequency and Complication Rates of Hysterectomy Accompanying
Cesarean Delivery
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID EMERGENCY PERIPARTUM HYSTERECTOMY; POSTPARTUM HYSTERECTOMY;
RISK-FACTORS; SECTION
AB OBJECTIVE: To estimate the frequency, indications, and complications of cesarean hysterectomy.
METHODS: This was a prospective, 2-year observational study at 13 academic medical centers conducted between January 1, 1999, and December 31, 2000, on all women who underwent a hysterectomy at the time of cesarean delivery. Data were abstracted from the medical record by study nurses. The outcomes included procedure frequency, indications, and complications.
RESULTS: A total of 186 cesarean hysterectomies (0.5%) were performed from a cohort of 39,244 women who underwent cesarean delivery. The leading indications for hysterectomy were placenta accreta (38%) and uterine atony (34%). Of the hysterectomy cases with a diagnosis recorded as accreta, 18% accompanied a primary cesarean delivery, and 82% had a prior procedure (P<.001). Of the hysterectomy cases with atony recorded as a diagnosis, 59% complicated primary cesarean delivery, whereas 41% had a prior cesarean (P<.001). Major maternal complications of cesarean hysterectomy included transfusion of red blood cells (84%) and other blood products (34%), fever (11%), subsequent laparotomy (4%), ureteral injury (3%), and death (1.6%). Accreta hysterectomy cases were more likely than atony hysterectomy cases to require ureteral stents (14% compared with 3%, P=.03) and to instill sterile milk into the bladder (23% compared with 8%, P=.02).
CONCLUSION: The rate of cesarean hysterectomy has declined modestly in the past decade. Despite the use of effective therapies and procedures to control hemorrhage at cesarean delivery, a small proportion of women continue to require hysterectomy to control hemorrhage from both uterine atony and placenta accreta. (Obstet Gynecol 2009;114:224-9)
C1 [Shellhaas, Cynthia S.] Ohio State Univ, Coll Med, Div Maternal Fetal Med, Dept Obstet, Columbus, OH 43210 USA.
Ohio State Univ, Dept Gynecol, Columbus, OH 43210 USA.
George Washington Univ, Ctr Biostat, Washington, DC USA.
Univ Utah, Salt Lake City, UT USA.
Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
Univ Alabama, Birmingham, AL USA.
Univ Pittsburgh, Pittsburgh, PA USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
Wayne State Univ, Detroit, MI USA.
Univ Cincinnati, Cincinnati, OH USA.
Univ Miami, Miami, FL USA.
Univ Tennessee, Memphis, TN USA.
Univ Texas San Antonio, San Antonio, TX USA.
Vanderbilt Univ, Nashville, TN USA.
RP Shellhaas, CS (reprint author), Ohio State Univ, Coll Med, Div Maternal Fetal Med, Dept Obstet, Room 550,935 W 12th Ave, Columbus, OH 43210 USA.
EM Cynthia.shellhaas@osumc.edu
RI Shellhaas, Cynthia/E-4077-2011; Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU NICHD NIH HHS [U10 HD027860, HD21410, HD21414, HD27860, HD27861,
HD27869, HD27915, HD27917, HD34116, HD34136, HD34208, HD34210, HD36801,
R24 HD050924, U01 HD036801, U10 HD021410, U10 HD021410-14, U10 HD027869,
U10 HD027905, U10 HD027915, U10 HD027917, U10 HD034116, U10 HD034122,
U10 HD034136, U10 HD034208, U10 HD036801, U10 HD040485, UG1 HD027869,
UG1 HD027915, UG1 HD034116, UG1 HD034208]
NR 23
TC 60
Z9 68
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD AUG
PY 2009
VL 114
IS 2
BP 224
EP 229
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 476DO
UT WOS:000268418200005
PM 19622981
ER
PT J
AU Purdue, MP
Severson, RK
Colt, JS
Stewart, P
De Roos, AJ
Cerhan, JR
Cozen, W
Davis, S
Hartge, P
Schenk, M
Blair, A
AF Purdue, M. P.
Severson, R. K.
Colt, J. S.
Stewart, P.
De Roos, A. J.
Cerhan, J. R.
Cozen, W.
Davis, S.
Hartge, P.
Schenk, M.
Blair, A.
TI Degreasing and risk of non-Hodgkin lymphoma
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID UNITED-STATES; OCCUPATION; EXPOSURES
AB Objective: To investigate the relationship between selected solvent-related workplace tasks (degreasing, painting, gluing, stripping paint, staining) and risk of non-Hodgkin lymphoma (NHL).
Methods: We analysed occupational data from a large population-based case-control study of NHL conducted in the USA. For participants reporting occupations with possible exposure to organic solvents, job-specific interview modules were administered to elicit in-depth information on solvent-related workplace tasks and other exposure-related factors (225 cases, 189 controls). Unconditional logistic regression models were fit to calculate odds ratios (ORs) and 95% CI for average frequency, maximal frequency and cumulative number of hours having performed each task. Individuals with jobs rated as unexposed to organic solvents in the workplace (180 cases, 213 controls) were used as a reference group.
Results: We observed an increased risk of NHL among subjects in the highest category of maximal degreasing frequency (>520 h/year: OR 2.1, 95% CI 0.9 to 4.9, trend test p = 0.02). We found similar associations for the highest levels of average frequency and, among men, cumulative number of hours. Other solvent-related tasks were not associated with NHL.
Conclusion: Findings from this case-control analysis of solvent-related tasks suggest that frequent degreasing work may be associated with an elevated risk of NHL.
C1 [Purdue, M. P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Severson, R. K.; Schenk, M.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
[De Roos, A. J.; Davis, S.] Univ Washington, Program Epidemiol, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[De Roos, A. J.; Davis, S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Cerhan, J. R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Cozen, W.] Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
RP Purdue, MP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, EPS 8114,6120 Execut Blvd, Bethesda, MD 20892 USA.
EM purduem@mail.nih.gov
RI Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Cerhan, James/0000-0002-7482-178X
FU National Institutes of Health (National Cancer Institute); National
Cancer Institute SEER [N01-PC-65064, N01-PC-67009, N01-CN-67008,
N01-CN-67010]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (National Cancer Institute) and by
National Cancer Institute SEER Contracts N01-PC-65064 (Detroit),
N01-PC-67009 (Seattle), N01-CN-67008 (Iowa) and N01-CN-67010 (Los
Angeles).
NR 13
TC 4
Z9 4
U1 0
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD AUG
PY 2009
VL 66
IS 8
BP 557
EP 560
DI 10.1136/oem.2008.040386
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 471ZQ
UT WOS:000268097600010
PM 19017696
ER
PT J
AU Smith, JA
Mackensen, F
Sen, HN
Leigh, JF
Watkins, AS
Pyatetsky, D
Tessler, HH
Nussenblatt, RB
Rosenbaum, JT
Reed, GF
Vitale, S
Smith, JR
Goldstein, DA
AF Smith, Janine A.
Mackensen, Friederike
Sen, H. Nida
Leigh, Julie F.
Watkins, Angela S.
Pyatetsky, Dmitry
Tessler, Howard H.
Nussenblatt, Robert B.
Rosenbaum, James T.
Reed, George F.
Vitale, Susan
Smith, Justine R.
Goldstein, Debra A.
TI Epidemiology and Course of Disease in Childhood Uveitis
SO OPHTHALMOLOGY
LA English
DT Article
ID PEDIATRIC UVEITIS; CHILDREN
AB Purpose: To describe the disease characteristics and visual outcome of pediatric uveitis.
Design: Retrospective, longitudinal observation.
Participants. Five hundred twenty-seven pediatric uveitis patients from the National Eye Institute, University of Illinois, Chicago, and Oregon Health Sciences University.
Methods: Retrospective chart review.
Main Outcome Measures: Demographics, uveitis disease characteristics, complications, treatments, and visual outcomes were determined at baseline and at 1-, 3-, 5-, and 10-year time points.
Results: The patient population was 54% female; 62.4% white, 12.5% black, 2.7% Asian, 2.1% multiracial, and 14.61% Hispanic. Median age at diagnosis was 9.4 years. The leading diagnoses were idiopathic uveitis (28.8%), juvenile idiopathic arthritis-associated uveitis (20.9%), and pars planitis (17.1%). Insidious onset (58%) and persistent duration (75.3%) were most common. Anterior uveitis was predominant (44.6%). Complications were frequent, and cystoid macular edema (odds ratio [OR] 2.94; P = 0.006) and hypotony (OR, 4.54; P = 0.026) had the most significant visual impact. Ocular surgery was performed in 18.9% of patients. The prevalence of legal blindness was 9.23% at baseline, 6.52% at 1 year, 3.17% at 3 years, 15.15% at 5 years, and 7.69% at 10 years. Posterior uveitis and panuveitis had more severe vision loss. Hispanic ethnicity was associated with a higher prevalence of infectious uveitis and vision loss at baseline.
Conclusions: The rate and spectrum of vision threatening complications of pediatric uveitis are significant. Prospective studies using standard outcome measures and including diverse populations are needed to identify children most at risk.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2009;116:1544-1551 (C) 2009 by the American Academy of Ophthalmology.
C1 [Smith, Janine A.] NEI, Natl Inst Hlth, Off Res Womens Hlth, Off Director,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Leigh, Julie F.; Pyatetsky, Dmitry; Tessler, Howard H.; Goldstein, Debra A.] Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA.
[Mackensen, Friederike; Watkins, Angela S.; Rosenbaum, James T.; Smith, Justine R.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA.
RP Smith, JA (reprint author), NEI, Natl Inst Hlth, Off Res Womens Hlth, Off Director,Dept Hlth & Human Serv, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA.
EM smithja2@od.nih.gov
FU Research to Prevent Blindness; National Eye Institute/National
Institutes of Health/Department of Health and Human Services
FX Supported in part by grants from Research to Prevent Blindness (Career
Development Award to JRS, unrestricted grant to Casey Eye Institute and
unrestricted grant to University of Illinois, DAG). Supported in part by
the intramural research program of the National Eye Institute/National
Institutes of Health/Department of Health and Human Services (JAS). The
funding organizations participated in conducting the study, data
collection, data management and data analysis for the manuscript
NR 12
TC 68
Z9 73
U1 1
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 AUG
PY 2009
VL 116
IS 8
BP 1544
EP 1551
DI 10.1016/j.ophtha.2009.05.002
PG 8
WC Ophthalmology
SC Ophthalmology
GA 480CT
UT WOS:000268710200021
PM 19651312
ER
PT J
AU Cheong, SC
Chandramouli, GVR
Saleh, A
Zain, RB
Lau, SH
Sivakumaren, S
Pathmanathan, R
Prime, SS
Teo, SH
Patel, V
Gutkind, JS
AF Cheong, S. C.
Chandramouli, G. V. R.
Saleh, A.
Zain, R. B.
Lau, S. H.
Sivakumaren, S.
Pathmanathan, R.
Prime, S. S.
Teo, S. H.
Patel, V.
Gutkind, J. S.
TI Gene expression in human oral squamous cell carcinoma is influenced by
risk factor exposure
SO ORAL ONCOLOGY
LA English
DT Article
DE Oral squamous cell carcinoma; Gene expression; Betel quid; Smoking; Risk
factors
ID HETEROTRIMERIC G-PROTEINS; CARBONIC-ANHYDRASE-XII; CANCER INVASION;
BREAST-CANCER; NECK-CANCER; PLASMINOGEN-ACTIVATOR; PROTEOLYTIC-ENZYMES;
SERINE-PROTEASE; G12 FAMILY; TRANSMEMBRANE
AB Oral squamous cell carcinoma (OSCC) is a world health problem and is associated with exposure to different risk factors. In the west, smoking and alcohol consumption are considered to be the main risk factors whilst in India and southeast Asia, betel quid (BQ) chewing is predominant. In this study, we compared the gene expression patterns of oral cancers associated with BQ chewing to those caused by smoking using Affymetrix microarrays. We found that 281 genes were differentially expressed between OSCC and normal oral mucosa regardless of aetiological factors including MMP1, PLAU, MAGE-D4, GNA12, IFITM3 and NMU. Further, we identified 168 genes that were differentially expressed between the BQ and smoking groups including CXCL-9, TMPRSS2, CA12 and RNF24. The expression of these genes was validated using qPCR using independent tissue samples. The results demonstrate that whilst common genes/pathways contribute to the development of oral cancer, there are also other gene expression changes that are specific to certain risk factors. The findings suggest that different carcinogens activate or inhibit specific pathways during cancer development and progression. These unique gene expression profiles should be taken into consideration when developing biomarkers for future use in prognostic or therapeutic applications. (C) 2008 Elsevier Ltd. All rights reserved.
C1 [Cheong, S. C.; Saleh, A.; Teo, S. H.] Subang Jaya Med Ctr, CARIF, Floor Outpatient Ctr 2, Subang Jaya 47500, Selangor, Malaysia.
[Chandramouli, G. V. R.] NIH, Lab Biosyst & Canc, Bethesda, MD 20892 USA.
[Zain, R. B.] Univ Malaya, Oral Canc Res & Coordinating Ctr, Kuala Lumpur, Malaysia.
[Lau, S. H.] Inst Med Res, Stomatol Unit, Kuala Lumpur 50588, Malaysia.
[Sivakumaren, S.; Pathmanathan, R.] Subang Jaya Med Ctr, Dept Pathol, Diagnost Lab, Subang Jaya 47500, Selangor, Malaysia.
[Prime, S. S.] Univ Bristol, Dept Oral & Dent Sci, Bristol BS8 1TH, Avon, England.
[Patel, V.] Natl Inst Craniofacial & Dent Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Cheong, SC (reprint author), Subang Jaya Med Ctr, CARIF, Floor Outpatient Ctr 2, Subang Jaya 47500, Selangor, Malaysia.
EM sokching.cheong@carif.com.my
RI Mohd Zain, Rosnah/C-1969-2009; Zain, Rosnah/B-8054-2010; Gutkind, J.
Silvio/A-1053-2009; Teo, Soo-hwang/H-2353-2014; Management Center,
Dental Research/C-2478-2013
FU Ministry of Science, Technology and Innovation (MOSTI) of Malaysia;
International Union against Cancer (UICC/ICRETT)
FX This study was funded by the Ministry of Science, Technology and
Innovation (MOSTI) of Malaysia and other sponsors of the Cancer Research
Initiatives Foundation 9. SCC was partially supported by the
International Union against Cancer (UICC/ICRETT). V. P. and J. S. G. are
supported by the intramural program, NIDCR. We are grateful to Dr.
Alfredo Molinolo for his assistance in the interpretation of
immunohistochemistry data. We thank our collaborating partners in the
Oral Cancer Research and Co-ordinating Centre, University of Malaya
(OCRCC) for providing clinical expertise, tissue and data
resource/banking facilities, in particular the Ministry of Health
Malaysia. CARIF is a non-profit research organisation. We are committed
to an understanding of cancer prevention, diagnosis and treatment
through a fundamental research programme.
NR 42
TC 34
Z9 36
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1368-8375
J9 ORAL ONCOL
JI Oral Oncol.
PD AUG
PY 2009
VL 45
IS 8
BP 712
EP 719
DI 10.1016/j.oraloncology.2008.11.002
PG 8
WC Oncology; Dentistry, Oral Surgery & Medicine
SC Oncology; Dentistry, Oral Surgery & Medicine
GA 472ER
UT WOS:000268112800014
PM 19147396
ER
PT J
AU Hart, TC
Hart, PS
AF Hart, T. C.
Hart, P. S.
TI Genetic studies of craniofacial anomalies: clinical implications and
applications
SO ORTHODONTICS & CRANIOFACIAL RESEARCH
LA English
DT Review
DE dental; diagnosis; genetic diseases; mutation; treatment
ID HEREDITARY GINGIVAL FIBROMATOSIS; CATHEPSIN-C GENE;
PAPILLON-LEFEVRE-SYNDROME; AMELOGENESIS IMPERFECTA; MUTATIONS; LOCUS;
IDENTIFICATION; PERIODONTITIS; PHENOTYPES; DISORDERS
AB Structured Abstract
Authors -
Hart TC, Hart PS
The objective of the study was to overview the role of genetic research in fostering translational studies of craniofacial diseases of dental interest. Background information is presented to illustrate influences affecting genetic research studies of Mendelian diseases. Genetic studies of amelogenesis imperfecta, dentinogenesis imperfecta, hereditary gingival fibromatosis and Papillon Lefevre syndrome are reviewed. Findings are presented to illustrate how translational applications of clinical and basic research may improve clinical care. Clinical and basic science research has identified specific genes and mutations etiologically responsible for amelogenesis imperfecta, dentinogenesis imperfecta, hereditary gingival fibromatosis and Papillon Lefevre syndrome. These findings are enabling researchers to understand how specific genetic alterations perturb normal growth and development of dental tissues. Identification of the genetic basis of these conditions is enabling clinicians and researchers to more fully understand the etiology and clinical consequences of these diseases of dental importance. Findings from genetic studies of dental diseases provide a basis for diagnostic genetic testing and development of therapeutic intervention strategies directed at the underlying disease etiology. These studies are advancing our understanding of the development of dental tissues in health and disease. The dental community must consider how to incorporate these developments into effective disease prevention paradigms to facilitate the diagnosis and treatment of individuals with genetic diseases.
C1 [Hart, T. C.] Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, Skeletal & Craniofacial Dis Branch, NIH, Bethesda, MD 20892 USA.
[Hart, P. S.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Hart, TC (reprint author), Natl Inst Dent & Craniofacial Res, Human Craniofacial Genet Sect, Skeletal & Craniofacial Dis Branch, NIH, Bldg 10,Room 5N-102,10 Ctr Dr, Bethesda, MD 20892 USA.
EM thart@mail.nih.gov
FU National Institute of Dental and Craniofacial Research [Z01-DE000711];
National Human Genome Research Institute of the National Institutes of
Health, Bethesda, MD
FX The authors were supported by the Intramural Research Programs of the
National Institute of Dental and Craniofacial Research (Z01-DE000711)
and the National Human Genome Research Institute of the National
Institutes of Health, Bethesda, MD. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institute of Dental and Craniofacial
Research, the National Human Genome Research Institute or the National
Institutes of Health.
NR 31
TC 14
Z9 15
U1 0
U2 4
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1601-6335
J9 ORTHOD CRANIOFAC RES
JI Orthod. Craniofac. Res.
PD AUG
PY 2009
VL 12
IS 3
BP 212
EP 220
PG 9
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 470JA
UT WOS:000267969800008
PM 19627523
ER
PT J
AU Parameswaran, N
O'Handley, RM
Grigg, ME
Wayne, A
Thompson, RCA
AF Parameswaran, N.
O'Handley, R. M.
Grigg, M. E.
Wayne, A.
Thompson, R. C. A.
TI Vertical transmission of Toxoplasma gondii in Australian marsupials
SO PARASITOLOGY
LA English
DT Article
DE Toxoplasma gondii; marsupial; vertical transmission; Australia;
congenital; toxoplasmosis
ID CONGENITAL TRANSMISSION; SERODIAGNOSIS; FULIGINOSUS; CALIFORNIA;
KANGAROOS; INFECTION; MELANOPS
AB To date, little is known about the dynamics of vertical transmission of Toxoplasma gondii in Australian marsupials. Studies in mice demonstrate that vertical transmission of T. gondii is common and that chronically infected mice can transmit T. gondii to successive generations. In this study, PCR and immunohistochemistry were used to detect T. gondii in chronically infected marsupial dams and their offspring. T. gondii was detected in the unfurred pouch young of 2 out of 10 chronically infected western grey kangaroos (Macropus fuliginosus) and in the unfurred pouch young of a brush-talied bettong (Bettongia penicillata). Results of the study suggest that vertical transmission of T. gondii can occur in chronically infected Australian marsupials.
C1 [Parameswaran, N.; Thompson, R. C. A.] Murdoch Univ, Sch Vet & Biomed Sci, WHO Collaborating Ctr Mol Epidemiol Parasit Infec, Murdoch, WA 6150, Australia.
[O'Handley, R. M.] Murdoch Univ, Environm Biotechnol CRC, Murdoch, WA 6150, Australia.
[Grigg, M. E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Wayne, A.] Dept Environm Conservat, Manjimup, WA 6258, Australia.
RP Parameswaran, N (reprint author), Murdoch Univ, Sch Vet & Biomed Sci, WHO Collaborating Ctr Mol Epidemiol Parasit Infec, Murdoch, WA 6150, Australia.
EM nevi.parameswaran@gmail.com
FU Australian Research Council, Department of Environment and Conservation,
Western Australia; NIH; NIAI
FX We wish to thank Glen Goudie and his team for their immense help with
collection of western grey kangaroo samples. This research was supported
by the Australian Research Council, Department of Environment and
Conservation, Western Australia and in part by the Intramural Research
Program of the NIH and NIAI (M. E. G.). M. E. G. is a Scholar of the
Canadian Institute for Advanced Research (CIFAR) Integrated Microbial
Biodiversity Program.
NR 22
TC 13
Z9 16
U1 3
U2 13
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0031-1820
J9 PARASITOLOGY
JI Parasitology
PD AUG
PY 2009
VL 136
IS 9
BP 939
EP 944
DI 10.1017/S0031182009006453
PG 6
WC Parasitology
SC Parasitology
GA 484JB
UT WOS:000269039400001
PM 19549348
ER
PT J
AU Goldstein, DS
Sewell, L
AF Goldstein, David S.
Sewell, LaToya
TI Olfactory dysfunction in pure autonomic failure: Implications for the
pathogenesis of Lewy body diseases
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Olfaction; Parkinson; Multiple system atrophy; Fluorodopa;
Fluorodopamine; PET; Biomarker
ID MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; ORTHOSTATIC HYPOTENSION;
ODOR IDENTIFICATION; NEURAL PATHWAYS; BODIES; DENERVATION; PATHOLOGY;
BRAIN; DEMENTIA
AB Background: Pure autonomic failure (PAF) and Parkinson disease (PD) both are Lewy body diseases, and both entail substantia nigra dopaminergic, locus ceruleus noradrenergic, and cardiac sympathetic denervation. Multiple system atrophy (MSA) is a non-Lewy body disease in which alpha-synuclein accumulates in glial cells, with central catecholamine deficiency but preserved cardiac sympathetic innervation in most patients. PD is associated with more severe and consistent olfactory dysfunction than in MSA; whether PAF entails olfactory dysfunction has been unknown. In this study we assessed olfactory function in PAF in comparison with the two other synucleinopathies and whether olfactory dysfunction correlates with neuroimaging evidence of cardiac noradrenergic or nigrostriatal dopaminergic denervation.
Method: The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 8 patients with PAF, 23 with PD, and 20 with MSA. 6-[(18)F]Fluorodopamine positron emission tomographic (PET) scanning was used to indicate cardiac noradrenergic innervation and the putamen:occipital cortex (PUT:OCC) and substantia nigra (SN):OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity to indicate nigrostriatal dopaminergic innervation.
Results: The PAF group had a low mean UPSIT score (22 +/- 3), similar to that in PD (20 +/- 2) and lower than in MSA (31 +/- 2, p = 0.004). Individual UPSIT scores correlated positively with cardiac 6-[(18)F]fluorodopamine-derived radioactivity (r = 0.63 in the septum, p < 0.0001; r = 0.64 in the free wall, p < 0.0001) but not with PUT:OCC or SN:OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity.
Discussion: in synucleinopathies, olfactory dysfunction is related to Lewy body pathology and cardiac sympathetic denervation, independently of parkinsonism or striatal dopamine deficiency. Published by Elsevier Ltd.
C1 [Goldstein, David S.] NINCDS, Clin Neurocardiol Sect, CNP, DIR,NIH, Bethesda, MD 20892 USA.
RP Goldstein, DS (reprint author), NINCDS, Clin Neurocardiol Sect, CNP, DIR,NIH, 10 Ctr Dr,MSC 1620,Bldg 10,Room 6N252, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NIH; National Institute of Neurological Disorders and Stroke
FX Dr. Peter Herscovitch was the Authorized User for administration of
6-[18F]fluorodopa and 6-[18F]fluorodopamine to
humans. Ms. Tereza Jenkins coordinated patient travel. Sandra Pechnik,
RN, assisted with clinical procedures and scheduling. Drs. Basil
Eldadah, Richard Imrich, and Yehonatan Sharabi served as post-doctoral
Fellows when the work was done. Mr. Takuya Sato, Mr. Oladi Bentho, Dr.
Jeffrey Moak, and Dr. Sheng-Ting Li carried out analyses of PET scans.
NR 30
TC 26
Z9 28
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD AUG
PY 2009
VL 15
IS 7
BP 516
EP 520
DI 10.1016/j.parkreldis.2008.12.009
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 483US
UT WOS:000268994500007
PM 19201246
ER
PT J
AU Henderson, WA
Shankar, R
Feld, JJ
Hadigan, CM
AF Henderson, Wendy A.
Shankar, Ravi
Feld, Jordan J.
Hadigan, Colleen M.
TI Symptomatic and Pathophysiologic Predictors of Hepatitis C Virus
Progression in Pediatric Patients
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE symptoms; fibrosis; cirrhosis; comorbidity; hepatitis C
ID CLINICAL SPECTRUM; CHILDHOOD-CANCER; CHILDREN; INFECTION; TRANSFUSION;
SURVIVORS; FEATURES; DISEASE; LIVER
AB Background: The slow progression of hepatitis C virus (HCV) infection could ultimately negatively impact pediatric patients during their lifespan. This study describes the symptomatic and pathophysiologic presentation of HCV infection in a cohort of pediatric outpatients.
Methods: HCV-positive patients were identified by diagnosis codes, from outpatient visits. Demographic and pathophysiologic indicators (comorbidities, reported symptoms, alanine transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV viral load, genotype, and liver biopsy results) were collected and analyzed.
Results: We reviewed 62 patients with HCV infection who were from 3 months and 19 years of age (M +/- SD, 12.5 +/- 5.8 years). Sixty percent presented with clinical symptoms of fatigue, Joint-abdominal pain, bruising/bleeding, or other non-specific symptoms. On liver biopsy (n=35) 80% had evidence of inflammation, 57% had fibrosis, and 9% had steatosis. All patients with steatosis or cirrhosis reported symptoms. Males were significantly more likely than women to be symptomatic (58.3% vs. 41.7%, P=0.04). Patients with symptoms were significantly older (M=13.5 +/- 5.2 vs. 8.9 +/- 5.5 years, P=0.003). There was a significant inverse relationship between viral load and symptoms (chi(2) = 4.7.5, P = 0.03). Patients with low viral load (<2 million copies) were 5 times more likely to have symptoms than those with high viral loads (P = 0.03). Significance was also noted between HCV genotype and ALT levels (chi(2) = 3.72, P = 0.05). There were no significant relationships between symptom status and race, comorbidities. alaninie transaminase, aspartate transaminase, gamma glutamyl transpeptidase, HCV genotype, or liver histology.
Conclusion: Pediatric patients with HCV can have significant symptoms and physiologic liver changes related to HCV.
C1 [Henderson, Wendy A.] NINR, Biobehav Unit, Symptoms Management Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA.
[Feld, Jordan J.] NIDDKD, Bethesda, MD 20892 USA.
[Hadigan, Colleen M.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Henderson, WA (reprint author), NINR, Biobehav Unit, Symptoms Management Branch, Intramural Res Program,NIH, 10 Ctr Dr,2-1339, Bethesda, MD 20892 USA.
EM hendersw@mail.nih.gov
OI Henderson, Wendy/0000-0003-3924-7118
FU National Institute of Nursing Research (NINR) Intramural Research
Program [P30NR03924]; National Institutes of Health (NIH); NIH Clinical
and Translational Fellowship [1TL1 RR 024155-01]
FX Supported by the National Institute of Nursing Research (NINR)
Intramural Research Program, National Institutes of Health (NIH), (to
W.A.H.) and the NINR funded Center for Research in Chronic Disorders
(P30NR03924) and additional support (to W.A.H.) was awarded for the NIH
Clinical and Translational Fellowship (1TL1 RR 024155-01), and endowed
scholarship from Dr. Corrine Barnes, and the Pennsylvania Higher
Education Funds.
NR 21
TC 6
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD AUG
PY 2009
VL 28
IS 8
BP 724
EP 727
DI 10.1097/INF.0b013e31819f1f71
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 477QG
UT WOS:000268533000013
PM 19593250
ER
PT J
AU Dornbusch, HJ
Manzoni, P
Roilides, E
Walsh, TJ
Groll, AH
AF Dornbusch, Hans Juergen
Manzoni, Paolo
Roilides, Emmanuel
Walsh, Thomas J.
Groll, Andreas H.
TI Invasive Fungal Infections in Children
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Editorial Material
DE fungus; opportunistic infections; antifungals
ID LIPOSOMAL AMPHOTERICIN-B; CLINICAL-PRACTICE GUIDELINES;
PEDIATRIC-PATIENTS; FLUCONAZOLE PROPHYLAXIS; BIRTH-WEIGHT; NEUTROPENIC
PATIENTS; DISEASES SOCIETY; RANDOMIZED-TRIAL; UNITED-STATES;
ASPERGILLOSIS
C1 [Dornbusch, Hans Juergen] Med Univ Graz, Dept Pediat & Adolescent Med, Div Pediat Hematol Oncol, Graz, Austria.
[Manzoni, Paolo] St Anna Hosp, Dept Neonatol, Turin, Italy.
[Manzoni, Paolo] St Anna Hosp, Neonatal Intens Care Unit, Turin, Italy.
[Roilides, Emmanuel] Aristotle Univ Thessaloniki, Dept Pediat 3, Sch Med, GR-54006 Thessaloniki, Greece.
[Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Groll, Andreas H.] Univ Childrens Hosp, Dept Pediat Hematol Oncol, Munster, Germany.
[Groll, Andreas H.] Univ Childrens Hosp, Ctr Bone Marrow Transplantat, Infect Dis Res Program, Munster, Germany.
RP Dornbusch, HJ (reprint author), Med Univ Graz, Dept Pediat & Adolescent Med, Div Pediat Hematol Oncol, Graz, Austria.
NR 55
TC 24
Z9 24
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD AUG
PY 2009
VL 28
IS 8
BP 734
EP 737
DI 10.1097/INF.0b013e3181b076b1
PG 4
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 477QG
UT WOS:000268533000015
PM 19633517
ER
PT J
AU Chernoff, M
Nachman, S
Williams, P
Brouwers, P
Heston, J
Hodge, J
Di Poalo, V
Deygoo, NS
Gadow, KD
AF Chernoff, Miriam
Nachman, Sharon
Williams, Paige
Brouwers, Pim
Heston, Jerry
Hodge, Janice
Di Poalo, Vinnie
Deygoo, Nagamah Sandra
Gadow, Kenneth D.
CA IMPAACT P1055 Study Team
TI Mental Health Treatment Patterns in Perinatally HIV-Infected Youth and
Controls
SO PEDIATRICS
LA English
DT Article; Proceedings Paper
CT 68th Annual Meeting of the Society-for-Applied-Anthropology
CY MAR 25-29, 2008
CL Memphis, TN
SP Soc Appl Anthropol
DE HIV; psychiatric disorders; treatment
ID PSYCHIATRIC-DISORDERS; PSYCHOTROPIC MEDICATION; SOCIAL SUPPORT; HAART
ERA; CHILDREN; ADOLESCENTS; HIV/AIDS
AB BACKGROUND: Youths perinatally infected with HIV often receive psychotropic medication and behavioral treatment for emotional and behavioral symptoms. We describe patterns of intervention for HIV-positive youth and youth in a control group in the United States.
METHODS: Three hundred nineteen HIV-positive youth and 256 controls, aged 6 to 17 years, enrolled in the International Maternal Adolescent AIDS Clinical Trials 1055, a prospective, 2-year observational study of psychiatric symptoms. One hundred seventy-four youth in the control group were perinatally exposed to HIV, and 82 youth were uninfected children living in households with HIV-positive members. Youth and their primary caregivers completed Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-referenced symptom-rating scales. Children's medication and behavioral psychiatric intervention histories were collected at entry. We evaluated the association of past or current psychiatric treatment with HIV status, baseline symptoms, and impairment by using multiple logistic regression, controlling for potential confounders.
RESULTS: HIV-positive youth and youth in the control group had a similar prevalence of psychiatric symptoms (61%) and impairment (14% to 15%). One hundred four (18%) participants received psychotropic medications (stimulants [14%], antidepressants [6%], and neuroleptic agents [4%]), and 127 (22%) received behavioral treatment. More HIV-positive youth than youth in the control group received psychotropic medication (23% vs 12%) and behavioral treatment (27% vs 17%). After adjusting for symptom class and confounders, HIV-positive children had twice the odds of children in the control group of having received stimulants and >4 times the odds of having received antidepressants. Caregiver-reported symptoms or impairment were associated with higher odds of intervention than reports by children alone.
CONCLUSIONS: HIV-positive children are more likely to receive mental health interventions than control-group children. Pediatricians and caregivers should consider available mental health treatment options for all children living in families affected by HIV. Pediatrics 2009; 124: 627-636
C1 [Chernoff, Miriam; Williams, Paige] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Williams, Paige] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Heston, Jerry] Child & Adolescent Psychiat Associates PLLC, Memphis, TN USA.
[Heston, Jerry] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Brouwers, Pim] NIMH, Ctr Mental Hlth Res AIDS, NIH, Rockville, MD 20857 USA.
[Gadow, Kenneth D.] SUNY Stony Brook, Sch Med, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA.
[Nachman, Sharon] SUNY Stony Brook, Sch Med, Dept Pediat, Stony Brook, NY 11794 USA.
[Di Poalo, Vinnie] Robert Wood Johnson Univ Hosp, Dept Pediat, Hazlet, NJ USA.
[Hodge, Janice] Frontier Sci & Technol Res Fdn Inc, IMPAACT Pediat Data Management, Amherst, NY USA.
[Deygoo, Nagamah Sandra] NYU, Sch Med, Dept Pediat, New York, NY USA.
RP Chernoff, M (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, 651 Huntington Ave, Boston, MA 02115 USA.
EM mchernoff@sdac.harvard.edu
FU NIAID NIH HHS [5 U01 AI-41110, U01 AI068632-03, U01 AI068632,
U01AI068632, 1 U01 AI-068616, U01 AI068616, U01 AI041110]
NR 30
TC 30
Z9 30
U1 1
U2 6
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2009
VL 124
IS 2
BP 627
EP 636
DI 10.1542/peds.2008-2441
PG 10
WC Pediatrics
SC Pediatrics
GA 475RC
UT WOS:000268377000025
PM 19596734
ER
PT J
AU Gonzalez, N
Mantey, SA
Pradhan, TK
Sancho, V
Moody, TW
Coy, DH
Jensen, RT
AF Gonzalez, Nieves
Mantey, Samuel A.
Pradhan, Tapas K.
Sancho, Veronica
Moody, Terry W.
Coy, David H.
Jensen, Robert T.
TI Characterization of putative GRP- and NMB-receptor antagonist's
interaction with human receptors
SO PEPTIDES
LA English
DT Article
DE Human; Gastrin-releasing peptide; Neuromedin B; Bombesin-related
peptide; Bombesin
ID GASTRIN-RELEASING-PEPTIDE; NEUROMEDIN-B-RECEPTOR; MAMMALIAN BOMBESIN
RECEPTORS; HUMAN ORPHAN RECEPTOR; CELL LUNG-CANCER; HIGH-AFFINITY;
ANTIMITOTIC ACTIVITY; PANCREATIC ACINAR; CARCINOMA CELLS; GROWTH-FACTORS
AB The mammalian bombesin (Bn) peptides neuromedin B (NMB) and gastrin-releasing peptide (GRP) actions are mediated by two receptors (NMB-receptor, GRP-receptor) which are widely distributed in the GI tract and CNS. From primarily animal studies NMB/GRP-receptor activation has physiological/pathophysiological effects in the CNS and GI tract including stimulating of growth of cancers and normal tissues. Whereas these Bn-receptors' effects have been extensively studied in nonhuman cells and animals, little is known of the physiological/pathological role(s) in humans, largely due to lack of potent antagonists. To address this issue we compared NMB/GRP-receptor affinity/potency of 10 chemical classes of putative antagonists (35 compounds) for human Bn-receptors by performing binding studies or assessing abilities to activate hGRP/hNMB-receptor [assessing phospholipase C activation] in four different cells containing native Bn-receptors or transfected receptors. From binding studies 23 were GRP-receptor-preferring, 4 were NMB-receptor, and 8 nonselective. For the hGRP-receptor-preferring analogues none showed hGRP-receptor agonist activity, but 13 were full or partial hNMB-receptor agonists at hNMB-receptors. For hNMB-receptor-preferring analogues none were agonists. Analogue #24 ([(3-Ph-Pr(6)), His(7), D-Ala(11), D-Pro(13), Psi(13-14), Phe(14)]Bn(6-14)NH(2)) and analogue #7 [D-Phe(6), Leu(13), Psi(CH(2)NH), Cpa(14)]Bn(6-14) were the most potent (0.2-1.4 nM) and selective (>10,000-fold) for the hGRP-receptor with analogue #7.5 [D-Tpi(6), Leu(13), Psi(CH(2)NH), Leu(14)]Bn(6-14)[RC-3095] (0.2-1.4 nM) slightly less selective. Analogue #34 (PD168368) had the highest affinity for hNMB-receptor (1.32-1.58 nM) and the greatest selectivity (2298-6952-fold) for the hNMB-receptor. These results demonstrate numerous putative hGRP/hNMB-receptor antagonists identified in nonhuman cells and/or animals have agonist activity at the hNMB-receptor. limiting their potential usefulness. However, a number were identified which were potent/selective for human Bn-receptors and should be useful for investigating their roles in human physiological/pathophysiological conditions. Published by Elsevier Inc.
C1 [Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
[Gonzalez, Nieves; Mantey, Samuel A.; Pradhan, Tapas K.; Sancho, Veronica; Jensen, Robert T.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Moody, Terry W.] NCI, NCI Off Director, CCR, Bethesda, MD 20892 USA.
[Moody, Terry W.] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Coy, David H.] Tulane Hlth Sci Ctr, Peptide Res Labs, Dept Med, New Orleans, LA 70112 USA.
RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bldg 10,Room 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
RI Gonzalez, Nieves/N-2199-2014
OI Gonzalez, Nieves/0000-0002-1551-2872
FU NIDDK; NCI, NIH
FX This work was partially supported by intramural funds of NIDDK and NCI,
NIH.
NR 67
TC 22
Z9 22
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
J9 PEPTIDES
JI Peptides
PD AUG
PY 2009
VL 30
IS 8
BP 1473
EP 1486
DI 10.1016/j.peptides.2009.05.007
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA 484IP
UT WOS:000269038200013
PM 19463875
ER
PT J
AU Siththanandan, VB
Tobacman, LS
Van Gorder, N
Homsher, E
AF Siththanandan, V. B.
Tobacman, L. S.
Van Gorder, N.
Homsher, E.
TI Mechanical and kinetic effects of shortened tropomyosin reconstituted
into myofibrils
SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
LA English
DT Article
DE Muscle mechanics; Regulation; Skeletal muscle; Mutation; Calcium
sensitivity
ID SKELETAL-MUSCLE FIBERS; THIN FILAMENT ACTIVATION; RABBIT PSOAS MUSCLE;
TROPONIN-TROPOMYOSIN; SINGLE MYOFIBRILS; ALPHA-TROPOMYOSIN; FORCE
GENERATION; INTERNAL DELETION; CARDIAC TROPONIN; BETA-TROPOMYOSIN
AB The effects of tropomyosin on muscle mechanics and kinetics were examined in skeletal myofibrils using a novel method to remove tropomyosin (Tm) and troponin (Tn) and then replace these proteins with altered versions. Extraction employed a low ionic strength rigor solution, followed by sequential reconstitution at physiological ionic strength with Tm then Tn. SDS-PAGE analysis was consistent with full reconstitution, and fluorescence imaging after reconstitution using Oregon-green-labeled Tm indicated the expected localization. Myofibrils remained mechanically viable: maximum isometric forces of myofibrils after sTm/sTn reconstitution (control) were comparable (similar to 84%) to the forces generated by non-reconstituted preparations, and the reconstitution minimally affected the rate of isometric activation (k (act)), calcium sensitivity (pCa(50)), and cooperativity (n (H)). Reconstitutions using various combinations of cardiac and skeletal Tm and Tn indicated that isoforms of both Tm and Tn influence calcium sensitivity of force development in opposite directions, but the isoforms do not otherwise alter cross-bridge kinetics. Myofibrils reconstituted with Delta 23Tm, a deletion mutant lacking the second and third of Tm's seven quasi-repeats, exhibited greatly depressed maximal force, moderately slower k (act) rates and reduced n (H). Delta 23Tm similarly decreased the cooperativity of calcium binding to the troponin regulatory sites of isolated thin filaments in solution. The mechanisms behind these effects of Delta 23Tm also were investigated using P (i) and ADP jumps. P (i) and ADP kinetics were indistinguishable in Delta 23Tm myofibrils compared to controls. The results suggest that the deleted region of tropomyosin is important for cooperative thin filament activation by calcium.
C1 [Siththanandan, V. B.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
[Siththanandan, V. B.; Homsher, E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA.
[Tobacman, L. S.; Van Gorder, N.] UIC, Dept Med, Chicago, IL 60612 USA.
[Tobacman, L. S.; Van Gorder, N.] UIC, Dept Physiol & Biophys, Chicago, IL 60612 USA.
RP Siththanandan, VB (reprint author), NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM siththanandanvb@nhlbi.nih.gov
FU NIH [AR30988, HL38834, HL63774]
FX The authors express their gratitude to J. Tidball (Physiological
Sciences Deptartment, UCLA) and T. Sakamoto (Laboratory of Molecular
Physiology, NHLBI, NIH) for their assistance in obtaining fluorescent
images, and also M. Regnier (Department of Bioengineering, University of
Washington) and R. Petraitiene (POB, NCI, NHLBI) for tissue samples.
Supported by NIH grants AR30988 (EH) and HL38834 (LST), and HL63774
(LST).
NR 44
TC 7
Z9 7
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0031-6768
EI 1432-2013
J9 PFLUG ARCH EUR J PHY
JI Pflugers Arch.
PD AUG
PY 2009
VL 458
IS 4
BP 761
EP 776
DI 10.1007/s00424-009-0653-3
PG 16
WC Physiology
SC Physiology
GA 465NA
UT WOS:000267592900012
PM 19255776
ER
PT J
AU Farnsworth, NR
Cassileth, B
Weaver, C
Birt, DF
Rosenthal, J
Raskin, I
Barrows, L
Capson, T
Cao, SG
AF Farnsworth, Norman R.
Cassileth, Barrie
Weaver, Connie
Birt, Diane F.
Rosenthal, Joshua
Raskin, Ilya
Barrows, Louis
Capson, Todd
Cao, Shugeng
TI Symposium proceedings for the 48(th) Annual Meeting, Society for
Economic Botany Lake Forest College, Chicago - June 4, 2007 Introduction
SO PHARMACEUTICAL BIOLOGY
LA English
DT Editorial Material
C1 [Farnsworth, Norman R.] Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res Womens Hlth, Chicago, IL 60612 USA.
[Cassileth, Barrie] Mem Sloan Kettering Canc Ctr, Integrat Med Serv, New York, NY 10021 USA.
[Weaver, Connie] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA.
[Birt, Diane F.] Iowa State Univ, Iowa Ctr Res Bot Dietary Supplements, Ames, IA 50011 USA.
[Rosenthal, Joshua] NIH, Div Int Training & Res, Bethesda, MD 20892 USA.
[Rosenthal, Joshua] NIH, ICBG Program, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Raskin, Ilya] Rutgers State Univ, Cook Coll, New Brunswick, NJ 08901 USA.
[Barrows, Louis] Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA.
[Capson, Todd] Smithsonian Trop Res Inst, Panama City, Panama.
[Cao, Shugeng] Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA.
RP Farnsworth, NR (reprint author), Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res Womens Hlth, 833 S Wood St, Chicago, IL 60612 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD AUG
PY 2009
VL 47
IS 8
BP 753
EP 753
DI 10.1080/13880200903013583
PG 1
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 490EN
UT WOS:000269481300016
ER
PT J
AU Farnsworth, NR
Mahady, GB
AF Farnsworth, Norman R.
Mahady, Gail B.
TI Research highlights from the UIC/NIH Center for Botanical Dietary
Supplements Research for Women's Health: Black cohosh from the field to
the clinic
SO PHARMACEUTICAL BIOLOGY
LA English
DT Article
CT 48th Annual Meeting of the Society-for-Economic-Botany
CY JUN 04-07, 2007
CL Lake Forest Coll, Chicago, IL
SP Soc Econ Bot
HO Lake Forest Coll
DE Actaea racemosa; block cohosh; botanical dietary supplements; estrogen;
menopause; multidisciplinary research; serotonin
ID HOPS HUMULUS-LUPULUS; CLOVER TRIFOLIUM-PRATENSE; MIXED COMPETITIVE
LIGAND; VITEX-AGNUS-CASTUS; MU-OPIATE RECEPTOR; INDUCED DNA-DAMAGE;
CIMICIFUGA-RACEMOSA; MASS-SPECTROMETRY; PARTIAL AGONIST; L.
AB In 1999, the Department of Medicinal Chemistry and Pharmacognosy at the College of Pharmacy, University of Illinois (UIC) at Chicago was funded to establish a Botanical Dietary Supplements Research Center from the National Institutes of Health (NIH). The emphasis of the UIC/NIH Center for Botanical Dietary Supplements Research (CBDSR) is botanical dietary supplements (BDS) for women's health. The Center's research has focused on BDS that may improve women's health and quality of life, specifically in the areas of menopause, premenstrual syndrome, and persistent urinary tract infections. Center investigators have overcome many challenges associated with botanical dietary supplements research, including acquiring and identifying plant species for investigation, isolating and identifying active constituents, elucidating the mechanisms of action of these botanicals, and conducting Phase I and Phase 11 clinical studies. Black cohosh [Actaea racemosa L. (Ranunculaceae)] has been used as a model to illustrate the steps involved in taking a botanical dietary supplement from the field, all the way to clinical trials. Bioassays are described that were necessary to elucidate the pertinent biological studies of plant extracts and their mechanisms of action. The Center has used an innovative multidisciplinary approach to this type of research, and thus has been very successful in fulfilling its specific aims.
C1 [Mahady, Gail B.] Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA.
[Farnsworth, Norman R.] NIH, Ctr Bot Dietary Supplements Res, Dept Med Chem & Pharmacognosy, Chicago, IL USA.
RP Mahady, GB (reprint author), Univ Illinois, Coll Pharm, Dept Pharm Practice, 833 S Wood St, Chicago, IL 60612 USA.
EM mahady@uic.edu
FU NCCIH NIH HHS [P50 AT000155, K01 AT002321-05, R21 AT001868-02, K01
AT002321, P50 AT000155-09, R21 AT001868]
NR 29
TC 4
Z9 4
U1 2
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD AUG
PY 2009
VL 47
IS 8
BP 755
EP 760
DI 10.1080/13880200902988637
PG 6
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 490EN
UT WOS:000269481300018
PM 20161501
ER
PT J
AU Rosenthal, J
Katz, F
AF Rosenthal, Joshua
Katz, Flora
TI Plant-based research among the International Cooperative Biodiversity
Groups
SO PHARMACEUTICAL BIOLOGY
LA English
DT Article
CT 48th Annual Meeting of the Society-for-Economic-Botany
CY JUN 04-07, 2007
CL Lake Forest Coll, Chicago, IL
SP Soc Econ Bot
HO Lake Forest Coll
DE ICBG; plant research; biodiversity conservation; drug discovery;
economic growth
ID IPOMOEA-SQUAMOSA; NATURAL-PRODUCTS; ALKALOIDS; LEAVES; DRUGS
AB The International Cooperative Biodiversity Groups (ICBG), administered by the Fogarty International Center, was created in 1992. By 2007, the program had completed three cycles of funding. In the last cycle (2003-2008), seven ICBGs were operating in biodiversity hotspots around the world with support from nine Institutes and Centers of the National Institutes of Health and from the National Science Foundation and the US Department of Agriculture. Accomplishments over the history of the program include discovery of numerous bioactive compounds, training of thousands of young scientists in the US and abroad, and the creation and enhancement of biodiversity protected areas around the world. Over the history of the ICBG program plant-based research has been a significant component of many projects. Over 10,000 species of tropical, temperate and arid lands plants from 350 plant families have been analyzed. While some of the research has been guided by ethnobotanical science, particularly science oriented toward botanical medicines, much has been focused around diversity-oriented collections, and some have used ecological principles to identify active compounds.While marine and microbial organisms have grown in importance among the natural products research community, plants will continue to play important roles for the foreseeable future.
C1 [Rosenthal, Joshua] NIH, Div Int Training & Res, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Rosenthal, J (reprint author), NIH, Div Int Training & Res, Fogarty Int Ctr, 31 Ctr Dr,MSC 2220, Bethesda, MD 20892 USA.
EM joshua_rosenthal@nih.gov
NR 25
TC 1
Z9 1
U1 0
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA
SN 1388-0209
J9 PHARM BIOL
JI Pharm. Biol.
PD AUG
PY 2009
VL 47
IS 8
BP 783
EP 787
DI 10.1080/13880200903015042
PG 5
WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy
GA 490EN
UT WOS:000269481300022
ER
PT J
AU Hall, SA
Link, CL
Hu, JC
Eggers, PW
McKinlay, JB
AF Hall, Susan A.
Link, Carol L.
Hu, Jim C.
Eggers, Paul W.
McKinlay, John B.
TI Drug Treatment of Urologic Symptoms: Estimating the Magnitude of Unmet
Need in the Community
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Hall, Susan A.; Link, Carol L.; McKinlay, John B.] New England Res Inst, Dept Epidemiol, Watertown, MA 02172 USA.
[Hu, Jim C.] Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA.
[Eggers, Paul W.] NIDDKD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2009
VL 18
BP S234
EP S234
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 483YQ
UT WOS:000269009900535
ER
PT J
AU Patrick, AR
Miller, M
Barber, CW
Wang, PS
Canning, CF
Schneeweiss, S
AF Patrick, Amanda R.
Miller, Matthew
Barber, Catherine W.
Wang, Philip S.
Canning, Claire F.
Schneeweiss, Sebastian
TI Identifying Intentional Self-Harm Hospitalizations when E-Codes Are
Incompletely Recorded
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Patrick, Amanda R.; Canning, Claire F.; Schneeweiss, Sebastian] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Miller, Matthew; Barber, Catherine W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Wang, Philip S.] NIMH, Bethesda, MD 20892 USA.
RI Schneeweiss, Sebastian/C-2125-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2009
VL 18
BP S44
EP S44
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 483YQ
UT WOS:000269009900100
ER
PT J
AU Batkai, S
Pacher, P
AF Batkai, Sandor
Pacher, Pal
TI Endocannabinoids and cardiac contractile function: Pathophysiological
implications
SO PHARMACOLOGICAL RESEARCH
LA English
DT Review
DE Cannabinoids; Cardiovascular disease; Cardiac function; Heart failure;
Cardiomyopathy; Cirrhosis; Doxorubicin
ID DOXORUBICIN-INDUCED CARDIOTOXICITY; CANNABINOID RECEPTOR ANTAGONISM;
ISCHEMIA-REPERFUSION INJURY; HEPATIC STELLATE CELLS; ACID AMIDE
HYDROLASE; CIRRHOTIC RATS; ENDOGENOUS CANNABINOIDS;
CARDIOVASCULAR-DISEASE; HEMODYNAMIC PROFILE; VANILLOID RECEPTORS
AB Endocannabinoids are part of a bioactive lipid signaling system, not only in the central nervous system but also in various peripheral organs. Accumulating evidence implicates dysregulation of the endocannabinoid system (ECS) in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, myocardial infarction, hemorrhagic or septic shock, heart failure and cardiovascular complications of liver cirrhosis. Even though the benefit of chronic cannabinoid 1 (CB1) receptor blockade with the currently available compounds may not outweigh the risks in chronic conditions such as obesity, modulation of the ECS may hold great therapeutic promise in various cardiovascular conditions/disorders. In this review we will discuss recent advances in understanding the role of CB, receptors and endocannabinoids in the regulation of cardiac function in cirrhotic carchomyopathy and in doxorubicin-induced heart failure. Published by Elsevier Ltd.
C1 [Batkai, Sandor] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA.
RP Batkai, S (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA.
EM sbatkai@mail.nih.gov; pacher@mail.nih.gov
RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai,
Sandor/H-7983-2014
OI Pacher, Pal/0000-0001-7036-8108;
FU Division of Intramural Clinical and Biological Research, NIAAA; NIH
FX This work was supported by the Division of Intramural Clinical and
Biological Research, NIAAA, NIH. Authors are indebted to George Kunos
for reading the manuscript and for valuable suggestions.
NR 81
TC 21
Z9 22
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD AUG
PY 2009
VL 60
IS 2
BP 99
EP 106
DI 10.1016/j.phrs.2009.04.003
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 472WQ
UT WOS:000268163900005
PM 19569260
ER
PT J
AU Machado-Vieira, R
Salvadore, G
DiazGranados, N
Zarate, CA
AF Machado-Vieira, Rodrigo
Salvadore, Giacomo
DiazGranados, Nancy
Zarate, Carlos A., Jr.
TI Ketamine and the next generation of antidepressants with a rapid onset
of action
SO PHARMACOLOGY & THERAPEUTICS
LA English
DT Review
DE Antidepressant; Depression; Glutamate; Ketamine; Rapid onset; Treatment
ID METHYL-D-ASPARTATE; MAJOR DEPRESSIVE DISORDER; NMDA-RECEPTOR ANTAGONIST;
EXCITATORY AMINO-ACIDS; TREATMENT-RESISTANT DEPRESSION; SEROTONIN
REUPTAKE INHIBITORS; ANTERIOR CINGULATE ACTIVITY;
GAMMA-AMINOBUTYRIC-ACID; STAR-ASTERISK-D; MOOD DISORDERS
AB Existing treatments for major depressive disorder (MOO) usually take weeks to months to achieve their antidepressant effects, and a significant number of patients do not have adequate improvement even after months of treatment. In addition, increased risk of suicide attempts is a major public health concern during the first month of standard antidepressant therapy. Thus, improved therapeutics that can exert their antidepressant effects within hours or a few days of their administration are urgently needed, as is a better understanding of the presumed mechanisms associated with these rapid antidepressant effects. In this context, the N-methyl-D-aspartate (NMDA) antagonist ketamine has consistently shown antidepressant effects within a few hours of its administration. This makes it a valuable research tool to identify biomarkers of response in order to develop the next generation of fast-acting antidepressants. In this review, we describe clinical, electrophysiological, biochemical, and imaging correlates as relevant targets in the study of the antidepressant response associated with ketamine, and their implications for the development of novel, fast-acting antidepressants. We also review evidence that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) to NMDA throughput may represent a convergent mechanism for the rapid antidepressant actions of ketamine. Overall, understanding the molecular basis of this work will likely lead to the ultimate development of improved therapeutics for MDD. Published by Elsevier Inc.
C1 [Zarate, Carlos A., Jr.] NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Zarate, CA (reprint author), NIMH, Expt Therapeut Mood & Anxiety Disorders Program, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, 10 Ctr Dr,Unit 7SE,Rm 7-3445, Bethesda, MD 20892 USA.
EM zaratec@mail.nih.gov
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190
FU National Institute of Mental Health (NIMH); NARSAD Award
FX Funding for this work was supported by the Intramural Research Program
of the National Institute of Mental Health (NIMH) and a NARSAD Award
(CAZ). Ioline Henter provided outstanding editorial assistance. A patent
application for the use of ketamine in depression has been submitted
listing Dr. Zarate among the inventors. Dr. Zarate has assigned his
rights on the patent to the US government.
NR 97
TC 141
Z9 153
U1 4
U2 30
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0163-7258
J9 PHARMACOL THERAPEUT
JI Pharmacol. Ther.
PD AUG
PY 2009
VL 123
IS 2
BP 143
EP 150
DI 10.1016/j.pharmthera.2009.02.010
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 470WC
UT WOS:000268011900001
PM 19397926
ER
PT J
AU Damiano, DL
Alter, KE
Chambers, H
AF Damiano, Diane L.
Alter, Katharine E.
Chambers, Henry
TI New Clinical and Research Trends in Lower Extremity Management for
Ambulatory Children with Cerebral Palsy
SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
LA English
DT Review
DE Physical therapy; Medication; Botulinum toxin; Gait; Orthopedic surgery;
Training; Spasticity
ID BOTULINUM-TOXIN-A; SELECTIVE DORSAL RHIZOTOMY; SONOGRAPHY-GUIDED
INJECTION; PLANOVALGUS FOOT DEFORMITY; AACPDM EVIDENCE REPORT; ONE-STAGE
CORRECTION; BODY-WEIGHT SUPPORT; LIMB STANCE PHASE; INTRATHECAL
BACLOFEN; DEROTATION OSTEOTOMY
AB Cerebral palsy (CP) is the most prevalent physical disability in childhood and includes a group of disorders with varying manifestations. This article focuses on current and future intervention strategies for improving mobility and participation during the lifespan for ambulatory children with CP. The provision and integration of physical therapy and medical and orthopedic surgery management focused primarily on the lower extremities are discussed here. Some of the newer trends are more intense and task-related exercise strategies, greater precision in tone identification and management, and a shift towards musculoskeletal surgery that focuses more on promoting dynamic bony alignment and less on releasing or lengthening tendons. Advances in basic and clinical science and technology development are changing existing paradigms and offering renewed hope for improved functioning for children with CP who face a lifelong disability with unique challenges at each stage in life.
C1 [Damiano, Diane L.; Alter, Katharine E.] NIH, Funct & Appl Biomech Sect, Ctr Clin, Bethesda, MD 20892 USA.
[Alter, Katharine E.] NICHHD, Dept Rehabil Med, NIH, Bethesda, MD 20892 USA.
[Chambers, Henry] Univ Calif San Diego, Dept Orthoped Surg, Rady Childrens Hosp, San Diego, CA 92123 USA.
RP Damiano, DL (reprint author), NIH, Funct & Appl Biomech Sect, Ctr Clin, 10 Ctr Dr,Room 1-1469, Bethesda, MD 20892 USA.
EM damianod@cc.nih.gov
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Intramural NIH HHS [Z99 CL999999]
NR 114
TC 28
Z9 30
U1 0
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1047-9651
EI 1558-1381
J9 PHYS MED REH CLIN N
JI Phys. Med. Rehabil. Clin. N. Am.
PD AUG
PY 2009
VL 20
IS 3
BP 469
EP +
DI 10.1016/j.pmr.2009.04.005
PG 25
WC Rehabilitation
SC Rehabilitation
GA 489QI
UT WOS:000269435800005
PM 19643348
ER
PT J
AU Berezhkovskii, AM
Pustovoit, MA
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Pustovoit, Mark A.
Bezrukov, Sergey M.
TI Entropic effects in channel-facilitated transport: Interparticle
interactions break the flux symmetry
SO PHYSICAL REVIEW E
LA English
DT Article
DE biotransport; Brownian motion; diffusion; entropy
ID PORE
AB We analyze transport through conical channels that is driven by the difference in particle concentrations on the two sides of the membrane. Because of the detailed balance, fluxes of noninteracting particles through the same channel, inserted into the membrane in two opposite orientations, are equal. We show that this flux symmetry is broken by particle-particle interactions so that one of the orientations can be much more efficient for transport under the same external conditions. The results are obtained analytically using a one-dimensional diffusion model and confirmed by three-dimensional Brownian dynamics simulations.
C1 [Berezhkovskii, Alexander M.] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Pustovoit, Mark A.] St Petersburg Nucl Phys Inst, Gatchina 188300, Russia.
[Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Phys & Struct Biol, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Berezhkovskii, AM (reprint author), NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA.
FU Russian Foundation [08-02-00314a]; Intramural Research Program of the
NIH
FX We are grateful to Adrian Parsegian, Alan Finkelstein, and Attila Szabo
for illuminating discussions. This work was supported by the Intramural
Research Program of the NIH, Center for Information Technology, and
Eunice Kennedy Shriver National Institute of Child Health and Human
Development. M. A. P. also thanks Russian Foundation for Basic Research
(Project No. 08-02-00314a) and the State Programs "Quantum
Macrophysics," "Strongly Correlated Electrons in Metals,
Superconductors, Semiconductors and Magnetic Materials," and " Neutron
Studies of Matter" for partial support.
NR 25
TC 22
Z9 22
U1 0
U2 3
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD AUG
PY 2009
VL 80
IS 2
AR 020904
DI 10.1103/PhysRevE.80.020904
PG 4
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 492EP
UT WOS:000269637800010
PM 19792070
ER
PT J
AU Miller, JC
AF Miller, Joel C.
TI Percolation and epidemics in random clustered networks
SO PHYSICAL REVIEW E
LA English
DT Article
DE complex networks; diseases; pattern clustering; percolation; random
processes
ID INFECTIOUS-DISEASES; RANDOM GRAPHS; MODELS; POPULATIONS
AB The social networks that infectious diseases spread along are typically clustered. Because of the close relation between percolation and epidemic spread, the behavior of percolation in such networks gives insight into infectious disease dynamics. A number of authors have studied percolation or epidemics in clustered networks, but the networks often contain preferential contacts in high degree nodes. We introduce a class of random clustered networks and a class of random unclustered networks with the same preferential mixing. Percolation in the clustered networks reduces the component sizes and increases the epidemic threshold compared to the unclustered networks.
C1 [Miller, Joel C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Miller, Joel C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Miller, JC (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA.
EM joel.c.miller.research@gmail.com
OI Miller, Joel/0000-0003-4426-0405
FU Department of Homeland Security; Fogarty International Center, National
Institutes of Health
FX This work was supported by the RAPIDD program of the Science and
Technology Directorate, Department of Homeland Security and the Fogarty
International Center, National Institutes of Health.
NR 19
TC 78
Z9 79
U1 2
U2 15
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 1539-3755
J9 PHYS REV E
JI Phys. Rev. E
PD AUG
PY 2009
VL 80
IS 2
AR 020901
DI 10.1103/PhysRevE.80.020901
PG 4
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA 492EP
UT WOS:000269637800007
PM 19792067
ER
PT J
AU Song, MO
Li, JY
Freedman, JH
AF Song, Min Ok
Li, Jianying
Freedman, Jonathan H.
TI Physiological and toxicological transcriptome changes in HepG2 cells
exposed to copper
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE signal transduction pathways; interactome; Gene Ontology; transition
metal; Cytoscape
ID GENE-EXPRESSION; OXIDATIVE STRESS; WILSON-DISEASE; LIVER-DISEASE; SERUM
COPPER; METALLOTHIONEIN EXPRESSION; HEPATOCELLULAR-CARCINOMA;
SACCHAROMYCES-CEREVISIAE; TROUT HEPATOCYTES; INDUCIBLE GENES
AB Song MO, Li J, Freedman JH. Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics 38: 386-401, 2009. First published June 23, 2009; doi: 10.1152/physiolgenomics.00083.2009.-Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 mu M copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-kappa B, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.
C1 [Song, Min Ok; Freedman, Jonathan H.] NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Li, Jianying] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Freedman, JH (reprint author), NIEHS, Mol Toxicol Lab, NIH, Mail Drop E1-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM freedma1@niehs.nih.gov
FU National Institute of Environmental Health Sciences [U19-ES-011375,
P42-ES-010356, Z01-ES-102045]; Intramural Research Program of the
National Institutes of Health
FX This work was supported (in part) by National Institute of Environmental
Health Sciences Grants U19-ES-011375, P42-ES-010356, and Z01-ES-102045
and by the Intramural Research Program of the National Institutes of
Health. RNA labeling, microarray hybridization, and data extraction were
performed by Cogenics (Morrisville, NC).
NR 72
TC 34
Z9 35
U1 1
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD AUG
PY 2009
VL 38
IS 3
BP 386
EP 401
DI 10.1152/physiolgenomics.00083.2009
PG 16
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 481AL
UT WOS:000268778600014
PM 19549813
ER
PT J
AU Balla, T
Szentpetery, Z
Kim, YJ
AF Balla, Tamas
Szentpetery, Zsofia
Kim, Yeun Ju
TI Phosphoinositide Signaling: New Tools and Insights
SO PHYSIOLOGY
LA English
DT Review
ID OXYSTEROL-BINDING-PROTEIN; PLECKSTRIN-HOMOLOGY-DOMAIN;
PHOSPHATIDYLINOSITOL TRANSFER PROTEIN; NEURONAL CALCIUM SENSOR-1;
CLATHRIN-COATED PITS; C VIRUS-REPLICATION; YEAST GOLGI-COMPLEX;
PHOSPHOLIPASE-C; PLASMA-MEMBRANE; LIVING CELLS
AB Phosphoinositides constitute only a small fraction of cellular phospholipids, yet their importance in the regulation of cellular functions can hardly be overstated. The rapid metabolic response of phosphoinositides after stimulation of certain cell surface receptors was the first indication that these lipids could serve as regulatory molecules. These early observations opened research areas that ultimately clarified the plasma membrane role of phosphoinositides in Ca2+ signaling. However, research of the last 10 years has revealed a much broader range of processes dependent on phosphoinositides. These lipids control organelle biology by regulating vesicular trafficking, and they modulate lipid distribution and metabolism more generally via their close relationship with lipid transfer proteins. Phosphoinositides also regulate ion channels, pumps, and transporters as well as both endocytic and exocytic processes. The significance of phosphoinositides found within the nucleus is still poorly understood, and a whole new research concerns the highly phosphorylated inositols that also appear to control multiple nuclear processes. The expansion of research and interest in phosphoinositides naturally created a demand for new approaches to determine where, within the cell, these lipids exert their effects. Imaging of phosphoinositide dynamics within live cells has become a standard cell biological method. These new tools not only helped us localize phosphoinositides within the cell but also taught us how tightly phosphoinositide control can be linked with distinct effector protein complexes. The recent progress allows us to understand the underlying causes of certain human diseases and design new strategies for therapeutic interventions.
C1 [Balla, Tamas; Szentpetery, Zsofia; Kim, Yeun Ju] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA.
RP Balla, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA.
EM ballat@mail.nih.gov
OI Balla, Tamas/0000-0002-9077-3335
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 191
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U1 3
U2 18
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
J9 PHYSIOLOGY
JI Physiology
PD AUG
PY 2009
VL 24
IS 4
BP 231
EP 244
DI 10.1152/physiol.00014.2009
PG 14
WC Physiology
SC Physiology
GA 482VM
UT WOS:000268917400004
PM 19675354
ER
PT J
AU Gallazzini, M
Burg, MB
AF Gallazzini, Morgan
Burg, Maurice B.
TI What's New About Osmotic Regulation of Glycerophosphocholine
SO PHYSIOLOGY
LA English
DT Review
ID NEUROPATHY TARGET ESTERASE; MDCK CELLS; CHOLINE PHOSPHODIESTERASE;
ORGANIC OSMOLYTES; RENAL-CELLS; PHOSPHATIDYLCHOLINE; GPC;
GLYCEROPHOSPHORYLCHOLINE; OSMOREGULATION; STABILITY
AB Glycerophosphocholine is an abundant renal medullary organic osmolyte that protects renal medullary cells from the high interstitial concentrations of NaCl and urea to which they are normally exposed. We consider the metabolism of glycerophosphocholine, its osmotic regulation, and the recently discovered molecular identity of the enzymes that osmoregulate its abundance.
C1 [Gallazzini, Morgan; Burg, Maurice B.] NHLBI, Dept Hlth & Human Serv, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA.
RP Gallazzini, M (reprint author), NHLBI, Dept Hlth & Human Serv, Kidney & Electrolyte Metab Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM maurice_burg@nih.gov
RI Gallazzini, Morgan/E-5465-2011
FU Intramural NIH HHS [ZIA HL001283-22]
NR 30
TC 20
Z9 20
U1 0
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1548-9213
J9 PHYSIOLOGY
JI Physiology
PD AUG
PY 2009
VL 24
IS 4
BP 245
EP 249
DI 10.1152/physiol.00009.2009
PG 5
WC Physiology
SC Physiology
GA 482VM
UT WOS:000268917400005
PM 19675355
ER
PT J
AU Elias, PM
Menon, G
Wetzel, BK
Williams, JW
AF Elias, Peter M.
Menon, Gopinathan
Wetzel, Bruce K.
Williams, John (Jack) W.
TI Evidence that stress to the epidermal barrier influenced the development
of pigmentation in humans
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Review
DE acidification; barrier function; melanocytes; permeability barrier;
pigmentation
ID STRATUM-CORNEUM LIPIDS; NERVE GROWTH-FACTOR; HUMAN-SKIN COLOR; SINGLE
NUCLEOTIDE POLYMORPHISMS; MELANOCYTE-STIMULATING HORMONE; UVB-INDUCED
ALTERATIONS; STEM-CELL FACTOR; PERMEABILITY BARRIER;
ULTRAVIOLET-RADIATION; VITAMIN-D
C1 [Elias, Peter M.] Univ Calif San Francisco, Dermatol Serv, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Elias, Peter M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Menon, Gopinathan] Calif Acad Sci, Dept Ornithol & Mammals, San Francisco, CA 94118 USA.
[Wetzel, Bruce K.] Natl Inst Gen Med Sci, Bethesda, MD USA.
[Williams, John (Jack) W.] Univ Wisconsin, Dept Geog, Madison, WI 53706 USA.
RP Elias, PM (reprint author), Univ Calif San Francisco, Dermatol Serv, Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
EM eliasp@derm.ucsf.edu
FU NIH [AR19098, AI059311]; Medical Research Service; Department of
Veterans Affairs, San Francisco, CA
FX This work was supported by NIH grants AR19098, AI059311, and the Medical
Research Service, Department of Veterans Affairs, San Francisco, CA.
Andrea Lucky, Ph.D., and Mary L. Williams, M.D. made many useful
suggestions. Ms. Joan Wakefield provided superb editorial assistance.
There are no conflicts of interests for any of the authors.
NR 146
TC 18
Z9 18
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2009
VL 22
IS 4
BP 420
EP 434
DI 10.1111/j.1755-148X.2009.00588.x
PG 15
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 470JB
UT WOS:000267969900009
PM 19508412
ER
PT J
AU Cronin, JC
Wunderlich, J
Loftus, SK
Prickett, TD
Wei, XM
Ridd, K
Vemula, S
Burrell, AS
Agrawal, NS
Lin, JC
Banister, CE
Buckhaults, P
Rosenberg, SA
Bastian, BC
Pavan, WJ
Samuels, Y
AF Cronin, Julia C.
Wunderlich, John
Loftus, Stacie K.
Prickett, Todd D.
Wei, Xiaomu
Ridd, Katie
Vemula, Swapna
Burrell, Allison S.
Agrawal, Neena S.
Lin, Jimmy C.
Banister, Carolyn E.
Buckhaults, Phillip
Rosenberg, Steven A.
Bastian, Boris C.
Pavan, William J.
Samuels, Yardena
TI Frequent mutations in the MITF pathway in melanoma
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE 5-7 MITF; SOX10; melanoma; mutations; p21; sequencing
ID SYNDROME TYPE-4 GENE; WAARDENBURG-SYNDROME; TUMOR PROGRESSION;
DOPACHROME-TAUTOMERASE; GENOMIC ANALYSES; HUMAN CANCER; DNA-BINDING;
N-RAS; SOX10; EXPRESSION
AB P>Microphthalmia-associated transcription factor (MITF) is involved in melanocyte cell development, pigmentation and neoplasia. To determine whether MITF is somatically mutated in melanoma, we compared the sequence of MITF from primary and metastatic lesions to patient-matched normal DNA. In the 50 metastatic melanoma tumor lines analysed, we discovered four samples that had genomic amplifications of MITF and four that had MITF mutations in the regions encoding the transactivation, DNA binding or basic, helix-loop-helix domains. Sequence analysis for SOX10, a transcription factor, which both acts upstream of MITF and synergizes with MITF, identified an additional three samples with frameshift or nonsense mutations. Microphthalmia-associated transcription factor and SOX10 were found to be mutated in a mutually exclusive fashion, possibly suggesting disruption in a common genetic pathway. Taken together we found that over 20% of the metastatic melanoma cases had alterations in the MITF pathway. We show that the MITF pathway is also altered in primary melanomas: 2/26 demonstrated mutations in MITF and 6/55 demonstrated mutations in SOX10. Our findings suggest that altered MITF function during melanomagenesis can be achieved by MITF amplification, MITF single base substitutions or by mutation of its regulator SOX10.
C1 [Cronin, Julia C.; Loftus, Stacie K.; Prickett, Todd D.; Wei, Xiaomu; Burrell, Allison S.; Agrawal, Neena S.; Pavan, William J.; Samuels, Yardena] NHGRI, Bethesda, MD 20892 USA.
[Wunderlich, John; Rosenberg, Steven A.] NCI, NIH, Bethesda, MD 20892 USA.
[Ridd, Katie; Vemula, Swapna; Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Ridd, Katie; Vemula, Swapna; Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA.
[Ridd, Katie; Vemula, Swapna; Bastian, Boris C.] Univ Calif San Francisco, UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD USA.
[Lin, Jimmy C.] Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD USA.
[Banister, Carolyn E.; Buckhaults, Phillip] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC USA.
RP Samuels, Y (reprint author), NHGRI, Bethesda, MD 20892 USA.
EM samuelsy@mail.nih.gov
FU National Human Genome Research Institute; National Cancer Institute;
National Institutes of Health
FX We thank Drs. Heinz Arnheiter, Tom Hornyak, and Paul Meltzer for their
helpful comments on the manuscript. Funded by the National Human Genome
Research Institute and National Cancer Institute, National Institutes of
Health.
NR 34
TC 74
Z9 75
U1 0
U2 8
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2009
VL 22
IS 4
BP 435
EP 444
DI 10.1111/j.1755-148X.2009.00578.x
PG 10
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 470JB
UT WOS:000267969900010
PM 19422606
ER
PT J
AU Solomon, DA
Kim, JS
Yang, XHR
Tucker, MA
Goldstein, AM
Samuels, Y
Waldman, T
AF Solomon, David A.
Kim, Jung-Sik
Yang, Xiaohong R.
Tucker, Margaret A.
Goldstein, Alisa M.
Samuels, Yardena
Waldman, Todd
TI Lack of inherited mutations of PTPRD in familial melanoma and
melanoma-astrocytoma syndrome
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Letter
DE receptor protein tyrosine phosphatase; p16(INK4a); germline mutation;
inherited susceptibility; chromosome 9p; familial melanoma
ID CUTANEOUS MALIGNANT-MELANOMA; NUCLEOTIDE POLYMORPHISM ARRAYS;
PROTEIN-TYROSINE PHOSPHATASES; HOMOZYGOUS DELETIONS; LUNG
ADENOCARCINOMA; PANCREATIC-CANCER; GENES; GENOME; TUMORS; 9P
C1 [Solomon, David A.; Kim, Jung-Sik; Waldman, Todd] Georgetown Univ, Sch Med, Dept Oncol, Lombardi Canc Ctr, Washington, DC USA.
[Yang, Xiaohong R.; Tucker, Margaret A.; Goldstein, Alisa M.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Samuels, Yardena] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Waldman, T (reprint author), Georgetown Univ, Sch Med, Dept Oncol, Lombardi Canc Ctr, Washington, DC USA.
EM waldmant@georgetown.edu
RI Tucker, Margaret/B-4297-2015
FU Intramural NIH HHS [Z01 HG200337-01]; NCI NIH HHS [R01 CA115699, R01
CA115699-04, P30 CA016672, R01 CA115699-05]
NR 24
TC 3
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1755-1471
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD AUG
PY 2009
VL 22
IS 4
BP 489
EP 491
DI 10.1111/j.1755-148X.2009.00587.x
PG 3
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA 470JB
UT WOS:000267969900016
PM 19500277
ER
PT J
AU Loulier, K
Lathia, JD
Marthiens, V
Relucio, J
Mughal, MR
Tang, SC
Coksaygan, T
Hall, PE
Chigurupati, S
Patton, B
Colognato, H
Rao, MS
Mattson, MP
Haydar, TF
Ffrench-Constant, C
AF Loulier, Karine
Lathia, Justin D.
Marthiens, Veronique
Relucio, Jenne
Mughal, Mohamed R.
Tang, Sung-Chun
Coksaygan, Turhan
Hall, Peter E.
Chigurupati, Srinivasulu
Patton, Bruce
Colognato, Holly
Rao, Mahendra S.
Mattson, Mark P.
Haydar, Tarik F.
Ffrench-Constant, Charles
TI beta 1 Integrin Maintains Integrity of the Embryonic Neocortical Stem
Cell Niche
SO PLOS BIOLOGY
LA English
DT Article
ID CEREBRAL CORTICAL SIZE; RADIAL GLIAL-CELLS; INTERKINETIC NUCLEAR
MIGRATION; CONGENITAL MUSCULAR-DYSTROPHY; PROGENITOR CELLS; ASYMMETRIC
INHERITANCE; MAMMALIAN NEUROGENESIS; NEUROEPITHELIAL CELLS; SIGNALING
PATHWAY; NEURAL PRECURSORS
AB During embryogenesis, the neural stem cells (NSC) of the developing cerebral cortex are located in the ventricular zone (VZ) lining the cerebral ventricles. They exhibit apical and basal processes that contact the ventricular surface and the pial basement membrane, respectively. This unique architecture is important for VZ physical integrity and fate determination of NSC daughter cells. In addition, the shorter apical process is critical for interkinetic nuclear migration (INM), which enables VZ cell mitoses at the ventricular surface. Despite their importance, the mechanisms required for NSC adhesion to the ventricle are poorly understood. We have shown previously that one class of candidate adhesion molecules, laminins, are present in the ventricular region and that their integrin receptors are expressed by NSC. However, prior studies only demonstrate a role for their interaction in the attachment of the basal process to the overlying pial basement membrane. Here we use antibody-blocking and genetic experiments to reveal an additional and novel requirement for laminin/integrin interactions in apical process adhesion and NSC regulation. Transient abrogation of integrin binding and signalling using blocking antibodies to specifically target the ventricular region in utero results in abnormal INM and alterations in the orientation of NSC divisions. We found that these defects were also observed in laminin alpha 2 deficient mice. More detailed analyses using a multidisciplinary approach to analyse stem cell behaviour by expression of fluorescent transgenes and multiphoton time-lapse imaging revealed that the transient embryonic disruption of laminin/integrin signalling at the VZ surface resulted in apical process detachment from the ventricular surface, dystrophic radial glia fibers, and substantial layering defects in the postnatal neocortex. Collectively, these data reveal novel roles for the laminin/integrin interaction in anchoring embryonic NSCs to the ventricular surface and maintaining the physical integrity of the neocortical niche, with even transient perturbations resulting in long-lasting cortical defects.
C1 [Loulier, Karine; Haydar, Tarik F.] Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA.
[Lathia, Justin D.; Marthiens, Veronique; Hall, Peter E.; Ffrench-Constant, Charles] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England.
[Lathia, Justin D.; Marthiens, Veronique; Hall, Peter E.; Ffrench-Constant, Charles] Univ Cambridge, Dept Med Genet, Cambridge CB2 1QP, England.
[Lathia, Justin D.; Hall, Peter E.; Ffrench-Constant, Charles] Univ Cambridge, Ctr Brain Repair, Cambridge CB2 1QP, England.
[Lathia, Justin D.; Mughal, Mohamed R.; Tang, Sung-Chun; Chigurupati, Srinivasulu; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Relucio, Jenne; Colognato, Holly] SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11794 USA.
[Coksaygan, Turhan] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Patton, Bruce] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA.
[Rao, Mahendra S.] Invitrogen Corp, Corp Res Labs, Carlsbad, CA USA.
[Rao, Mahendra S.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Loulier, K (reprint author), Childrens Natl Med Ctr, Ctr Neurosci, Washington, DC 20010 USA.
EM thaydar@cnmcresearch.org; cffc@ed.ac.uk
RI Mattson, Mark/F-6038-2012; Marthiens, Veronique/D-8673-2017; Loulier,
Karine/E-5529-2017;
OI Loulier, Karine/0000-0001-6216-2708; Haydar, Tarik/0000-0001-6772-3076;
Tang, Sung-Chun/0000-0003-3731-5973
FU National Institutes of Health-Cambridge Graduate Partnership Program;
Packard Foundation and Invitrogen Corporation; Wellcome Trust; Medical
Research Council and the Biotechnology; Biological Sciences Research
Council; National Institute on Aging Intramural Research Program;
Cellular Imaging Core of Mental Retardation and Developmental
Disabilities Research Center [P30HD40677]; [RO1 NS051852]
FX JDL is supported by the National Institutes of Health-Cambridge Graduate
Partnership Program. MSR is supported by the Packard Foundation and
Invitrogen Corporation. Cf-C and VM are supported by the Wellcome Trust.
Cf-C is also supported by the Medical Research Council and the
Biotechnology and Biological Sciences Research Council. This work was
supported by the National Institute on Aging Intramural Research
Program. KL and TFH are supported by grant RO1 NS051852 and the Cellular
Imaging Core of Mental Retardation and Developmental Disabilities
Research Center (P30HD40677). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 57
TC 88
Z9 89
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1544-9173
J9 PLOS BIOL
JI PLoS. Biol.
PD AUG
PY 2009
VL 7
IS 8
AR e1000176
DI 10.1371/journal.pbio.1000176
PG 16
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 486UW
UT WOS:000269226300014
PM 19688041
ER
PT J
AU Downey, CM
Horton, CR
Carlson, BA
Parsons, TE
Hatfield, DL
Hallgrimsson, B
Jirik, FR
AF Downey, Charlene M.
Horton, Chelsea R.
Carlson, Bradley A.
Parsons, Trish E.
Hatfield, Dolph L.
Hallgrimsson, Benedikt
Jirik, Frank R.
TI Osteo-Chondroprogenitor-Specific Deletion of the Selenocysteine tRNA
Gene, Trsp, Leads to Chondronecrosis and Abnormal Skeletal Development:
A Putative Model for Kashin-Beck Disease
SO PLOS GENETICS
LA English
DT Article
ID THYROID-HORMONE; THIOREDOXIN REDUCTASE; GROWTH-PLATE; BONE; SELENIUM;
MOUSE; SELENOPROTEINS; IODINE; DEFICIENCY; METABOLISM
AB Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA([Ser]Sec), required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome.
C1 [Downey, Charlene M.; Horton, Chelsea R.; Parsons, Trish E.; Hallgrimsson, Benedikt; Jirik, Frank R.] Univ Calgary, McCaig Inst Bone & Joint Hlth, Calgary, AB, Canada.
[Downey, Charlene M.; Horton, Chelsea R.; Jirik, Frank R.] Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB, Canada.
[Carlson, Bradley A.; Hatfield, Dolph L.] NCI, Mol Biol Selenium Sect, Lab Canc Prevent, Ctr Canc Res,Natl Inst Hlth, Bethesda, MD 20892 USA.
[Parsons, Trish E.; Hallgrimsson, Benedikt] Univ Calgary, Dept Cell Biol & Anat, Calgary, AB, Canada.
RP Downey, CM (reprint author), Univ Calgary, McCaig Inst Bone & Joint Hlth, Calgary, AB, Canada.
EM jirik@ucalgary.ca
RI Hallgrimsson, Benedikt/A-9616-2008
OI Hallgrimsson, Benedikt/0000-0002-7192-9103
FU Arthritis Society of Canada; Alberta Cancer Board; National Institutes
of Health National Cancer Institute Intramural Research Program; Center
for Cancer Research
FX This work was supported by grants from the Arthritis Society of Canada
and the Alberta Cancer Board (to FRJ) and in part by the National
Institutes of Health National Cancer Institute Intramural Research
Program and the Center for Cancer Research (to DLH). CD held an Alberta
Cancer Board Studentship and FRJ was the recipient of a Canada Research
Chairs award. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 41
TC 54
Z9 56
U1 0
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2009
VL 5
IS 8
AR e1000616
DI 10.1371/journal.pgen.1000616
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 516HS
UT WOS:000271533500030
PM 19696890
ER
PT J
AU Hancock, DB
Romieu, I
Shi, M
Sienra-Monge, JJ
Wu, H
Chiu, GY
Li, HL
del Rio-Navarro, BE
Willis-Owens, SAG
Weiss, ST
Raby, BA
Gao, H
Eng, C
Chapeia, R
Burchard, EG
Tang, H
Sullivan, PF
London, SJ
AF Hancock, Dana B.
Romieu, Isabelle
Shi, Min
Sienra-Monge, Juan-Jose
Wu, Hao
Chiu, Grace Y.
Li, Huiling
Estela del Rio-Navarro, Blanca
Willis-Owens, Saffron A. G.
Weiss, Scott T.
Raby, Benjamin A.
Gao, Hong
Eng, Celeste
Chapeia, Rocio
Burchard, Esteban G.
Tang, Hua
Sullivan, Patrick F.
London, Stephanie J.
TI Genome-Wide Association Study Implicates Chromosome 9q21.31 as a
Susceptibility Locus for Asthma in Mexican Children
SO PLOS GENETICS
LA English
DT Article
ID CASE-PARENT TRIADS; LINKAGE DISEQUILIBRIUM; CHILDHOOD ASTHMA;
PUERTO-RICAN; ADMIXTURE; GENES; RUNX3; AMERICAN; HOMOLOGS; PROTEINS
AB Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10 x 10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79 x 10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.
C1 [Hancock, Dana B.; London, Stephanie J.] Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Romieu, Isabelle] Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Shi, Min] Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Sienra-Monge, Juan-Jose; Estela del Rio-Navarro, Blanca] Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico.
[Wu, Hao; Li, Huiling; London, Stephanie J.] Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Chiu, Grace Y.] Westat Corp, Res Triangle Pk, NC USA.
[Willis-Owens, Saffron A. G.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Weiss, Scott T.; Raby, Benjamin A.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Weiss, Scott T.; Raby, Benjamin A.] Harvard Univ, Sch Med, Boston, MA USA.
[Gao, Hong; Tang, Hua] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Eng, Celeste; Burchard, Esteban G.] Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA.
[Chapeia, Rocio] Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
RP Hancock, DB (reprint author), Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
EM london2@niehs.nih.gov
RI Hancock, Dana/D-8577-2012;
OI Hancock, Dana/0000-0003-2240-3604; London, Stephanie/0000-0003-4911-5290
FU Intramural Research Program of the National Institute of Environmental
Health Sciences; National Institutes of Health; Department of Health and
Human Services [Z01ES049019]; National Council of Science and Technology
[26206-M]; National Center for Environmental Health at the Centers for
Disease Control; National Institute of General Medical Services
[GM073059]; National Institutes of Health [HL078885, HL088133, ES015794]
FX This research was supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health, Department of Health and Human Services (Z01ES049019).
Subject enrollment was supported in part by the National Council of
Science and Technology (grant 26206-M), Mexico. Dr. Romieu was supported
in part by the National Center for Environmental Health at the Centers
for Disease Control. Dr. Tang was supported in part by the National
Institute of General Medical Services grant GM073059. Dr. Burchard
received support from the National Institutes of Health (HL078885,
HL088133, ES015794), Flight Attendant Medical Research Institute
(FAMRI), RWJ Amos Medical Faculty Development Award, and the Sandler
Family Foundation. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 49
TC 102
Z9 107
U1 1
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1553-7390
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2009
VL 5
IS 8
AR e1000623
DI 10.1371/journal.pgen.1000623
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 516HS
UT WOS:000271533500037
PM 19714205
ER
PT J
AU Tripet, F
Clegg, S
Elnaiem, DE
Ward, RD
AF Tripet, Frederic
Clegg, Simon
Elnaiem, Dia-Eldin
Ward, Richard D.
TI Cooperative Blood-feeding and the Function and Implications of Feeding
Aggregations in the Sand Fly, Lutzomyia longipalpis (Diptera:
Psychodidae)
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID LEISHMANIA VIANNIA BRAZILIENSIS; AMERICAN VISCERAL LEISHMANIASIS;
MOSQUITO-MEDIATED ATTRACTION; CUTANEOUS LEISHMANIASIS; VASODILATORY
PEPTIDE; SALIVARY-GLANDS; HOST BEHAVIOR; MAXADILAN; SUCCESS; INFECTION
AB Given the importance that the evolution of cooperation bears in evolutionary biology and the social sciences, extensive theoretical work has focused on identifying conditions that promote cooperation among individuals. In insects, cooperative or altruistic interactions typically occur amongst social insects and are thus explained by kin selection. Here we provide evidence that in Lutzomia longipalpis, a small biting fly and an important vector of leishmaniasis in the New World, cooperative blood-feeding in groups of non-kin individuals results in a strong decrease in saliva expenditure. Feeding in groups also strongly affected the time taken to initiate a bloodmeal and its duration and ultimately resulted in greater fecundity. The benefits of feeding aggregations were particularly strong when flies fed on older hosts pre-exposed to sand fly bites, suggesting that flies feeding in groups may be better able to overcome their stronger immune response. These results demonstrate that, in L. longipalpis, feeding cooperatively maximizes the effects of salivary components injected into hosts to facilitate blood intake and to counteract the host immune defences. As a result, cooperating sand flies enjoy enormous fitness gains. This constitutes, to our knowledge, the first functional explanation for feeding aggregations in this species and potentially in other hematophagous insects and a rare example of cooperation amongst individuals of a nonsocial insects species. The evolution of cooperative group feeding in sand flies may have important implications for the epidemiology of leishmaniasis.
C1 [Tripet, Frederic; Clegg, Simon; Ward, Richard D.] Keele Univ, Sch Life Sci, Keele, Staffs, England.
[Elnaiem, Dia-Eldin] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Tripet, F (reprint author), Keele Univ, Sch Life Sci, Keele, Staffs, England.
EM f.tripet@biol.keele.ac.uk
RI Tripet, Frederic/M-6693-2015
OI Tripet, Frederic/0000-0002-7939-0712
FU Keele University
FX This work was supported by QR funding from Keele University to FT and
RW. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 42
TC 9
Z9 9
U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD AUG
PY 2009
VL 3
IS 8
AR e503
DI 10.1371/journal.pntd.0000503
PG 7
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA 486TL
UT WOS:000269220900009
PM 19688042
ER
PT J
AU Howard, G
Cushman, M
Prineas, RJ
Howard, VJ
Moy, CS
Sullivan, LM
D'Agostino, RB
McClure, LA
Pulley, L
Safford, MM
AF Howard, George
Cushman, Mary
Prineas, Ronald J.
Howard, Virginia J.
Moy, Claudia S.
Sullivan, Lisa M.
D'Agostino, Ralph B., Sr.
McClure, Leslie A.
Pulley, LeaVonne
Safford, Monika M.
TI Advancing the hypothesis that geographic variations in risk factors
contribute relatively little to observed geographic variations in heart
disease and stroke mortality
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Stroke; Coronary heart disease; Geography; Risk factors; Mortality
ID SOUTHEASTERN UNITED-STATES; HYPERTENSION; PREDICTION; PROFILE; BELT
AB Purpose. Geographic variation in risk factors may underlie geographic disparities in coronary heart disease (CHD) and stroke mortality.
Methods. Framingham CHD Risk Score (FCRS) and Stroke Risk Score (FSRS) were calculated for 25,770 stroke-free and 22,247 CHD-free participants from the REasons for Geographic And Racial Differences in Stroke cohort. Vital statistics provided age-adjusted CHD and stroke mortality rates. In an ecologic analysis, the age-adjusted, race-sex weighted, average state-level risk factor levels were compared to state-level mortality rates.
Results. There was no relationship between CHD and stroke mortality rates (r=0.04; p=0.78), but there was between CHD and stroke risk scores at the individual (r=0.68: p<0.0001) and state (r=0.64, p<0.0001) level. There was a stronger (p<0.0001) association between state-level FCRS and state-level CHD mortality (r=0.28, p=0.18), than between FSRS and stroke mortality (r=0.12, p=0.56).
Conclusions. weak associations between CHD and stroke mortality and strong associations between CHD and stroke risk scores suggest that geographic variation in risk factors may not underlie geographic variations in stroke and CHID mortality. The relationship between risk factor scores and mortality was stronger for CHID than stroke. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Howard, George; McClure, Leslie A.] Univ Alabama, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA.
[Cushman, Mary] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Prineas, Ronald J.] Wake Forest Univ, Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Howard, Virginia J.] Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Moy, Claudia S.; D'Agostino, Ralph B., Sr.] NINDS, NIH, Bethesda, MD 20892 USA.
[Sullivan, Lisa M.] Dept Biostat & Framingham Study, Boston, MA USA.
[Pulley, LeaVonne] Univ Arkansas Hlth Sci Univ, Dept Hlth Behav, Little Rock, AR USA.
[Safford, Monika M.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA.
[Safford, Monika M.] Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA.
RP Howard, G (reprint author), Univ Alabama, Sch Publ Hlth, Dept Biostat, 1665 Univ Blvd, Birmingham, AL 35294 USA.
EM ghoward@uab.edu
RI McClure, Leslie/P-2929-2015;
OI Sullivan, Lisa/0000-0003-0726-7149
FU National Institute of Neurological Disorders and Stroke [NS 041588]
FX The research reported in this article was supported by cooperative
agreement NS 041588 from the National Institute of Neurological
Disorders and Stroke.
NR 17
TC 22
Z9 23
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD AUG-SEP
PY 2009
VL 49
IS 2-3
BP 129
EP 132
DI 10.1016/j.ypmed.2009.03.004
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 503TF
UT WOS:000270562200011
PM 19285103
ER
PT J
AU Rapoport, SI
Igarashi, M
AF Rapoport, Stanley I.
Igarashi, Miki
TI Can the rat liver maintain normal brain DHA metabolism in the absence of
dietary DHA?
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article; Proceedings Paper
CT Workshop on DHA as a Required Nutrient
CY JUN, 2008
CL Columbia, MD
ID ALPHA-LINOLENIC ACID; POLYUNSATURATED FATTY-ACIDS; N-3 PUFA DEPRIVATION;
DOCOSAHEXAENOIC ACID; ADULT-RATS; NUTRITIONAL DEPRIVATION;
SIGNAL-TRANSDUCTION; PHOSPHOLIPASE A(2); PLASMA; CONVERSION
AB Background: Docosahexaenoic acid (DHA) is required for normal brain function. The concentration of DHA in the brain depends on both diet and liver metabolism.
Objective: To determine rat brain DHA concentration and consumption in relation to dietary n-3 (omega-3) polyunsaturated fatty acid (PUFA) content and liver secretion of DHA derived from circulating alpha-linolenic acid (alpha-LNA).
Design: Following weaning, male rats were fed for 15 weeks either: (1) a diet with a high DHA and alpha-LNA content, (2) an n-3 PUFA "adequate" diet containing 4.6% alpha-LNA but no DHA, or (3) an n-3 PUFA "deficient" diet containing 0.2% alpha-LNA and no DHA. Brain DHA consumption rates were measured following intravenous infusion in unanesthetized rats of [1-C-14]DHA, whereas liver and brain DHA synthesis rates were measured by infusing [1-C-14]alpha-LNA.
Results: Brain DHA concentrations equaled 17.6, 11.4 and 7.14 mu m/g in rats on diets 1, 2 and 3, respectively. With each diet, the rate of brain DHA synthesis from alpha-LNA was much less than the brain DHA consumption rate, whereas the liver synthesis-secretion rate was 5-10 fold higher. Higher elongase 2 and 5 and desaturase Delta 5 and Delta 6 activities in liver than in brain accounted for the higher liver DHA synthesis rates. Furthermore, these enzymes were transcriptionally upregulated in liver but not in brain of rats fed the deficient diet.
Conclusions: While DHA is essential to normal brain function, this need might be covered by dietary alpha-LNA when liver metabolic conversion machinery is intact and the diet has a high alpha-LNA content. Published by Elsevier Ltd.
C1 [Rapoport, Stanley I.; Igarashi, Miki] NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA.
RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 1S128,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sir@helix.nih.gov
FU Intramural NIH HHS [ZIA AG000399-05]
NR 52
TC 33
Z9 35
U1 0
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
EI 1532-2823
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD AUG-SEP
PY 2009
VL 81
IS 2-3
SI SI
BP 119
EP 123
DI 10.1016/j.plefa.2009.05.021
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 502NQ
UT WOS:000270467600005
PM 19540098
ER
PT J
AU Hibbeln, JR
Davis, JM
AF Hibbeln, Joseph R.
Davis, John M.
TI Considerations regarding neuropsychiatric nutritional requirements for
intakes of omega-3 highly unsaturated fatty acids
SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS
LA English
DT Article; Proceedings Paper
CT Workshop on DHA as a Required Nutrient
CY JUN, 2008
CL Columbia, MD
ID MAJOR DEPRESSIVE DISORDER; PLACEBO-CONTROLLED TRIAL; OMEGA-3-FATTY-ACID
DOCOSAHEXAENOIC ACID; POSTMORTEM ORBITOFRONTAL CORTEX; BLOOD-CELL
MEMBRANES; DOUBLE-BLIND; FISH CONSUMPTION; EICOSAPENTAENOIC ACID;
SEAFOOD CONSUMPTION; POSTPARTUM DEPRESSION
AB Background: Adverse neurodevelopmental and neuropsychiatric outcomes have been established as signs of nutrient deficiencies and may be applicable to insufficient dietary intakes of omega-3 highly unsaturated fatty acids (n-3 HUFAs).
Objective: Consider if statistical definitions for Daily Reference Intakes can be applied to n-3 HUFAs intakes during pregnancy for maternal and neurodevelopmental deficiencies.
Design: Data were prospectively collected from women during pregnancy and children up to age 8 years participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Statistical analyses took social and lifestyle factors into account.
Results: During pregnancy, n-3 HUFA intakes from seafood that putatively meet statistical definitions of an estimated average requirement ranged from 0.05 to 0.06 en% (111-139 mg/d/2000 Cal) for suboptimal fine motor control at 42 m and 0.065-0.08 en% (114-181 mg/d/2000 Cal) for suboptimal verbal IQ at age 8 years and 0.18-0.22 en% (389-486 mg/d/2000 Cal) for maternal depression at 32 weeks. Intakes of n-3 ranging from 0.2 to 0.41 en% (445-917 mg/d/2000 Cal) prevented both increased risk of maternal depression and adverse neurodevelopmental outcomes for children among 97.5% of the population. No upper limit for safety was found.
Conclusion: During pregnancy, a n-3 HUFA intake of 0.40 en% (900 mg/d/2000 Cal) from seafood is likely to meet the nutritional requirements for 97.5% of the mothers and children of this population. These considerations do not constitute DRI's for docosahexaenoic acid and n-3 HUFAs, but may contribute to their formulation. Published by Elsevier Ltd.
C1 [Hibbeln, Joseph R.] NIAAA, LMBB, NIH, Bethesda, MD 20892 USA.
[Davis, John M.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
RP Hibbeln, JR (reprint author), NIAAA, LMBB, NIH, 5625 Fishers Lane,Rm 3N-07,MSC 9410, Bethesda, MD 20892 USA.
EM jhibbeln@mail.nih.gov
FU Intramural NIH HHS; Medical Research Council [, G9815508]; Wellcome
Trust
NR 92
TC 23
Z9 24
U1 4
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0952-3278
J9 PROSTAG LEUKOTR ESS
JI Prostaglandins Leukot. Essent. Fatty Acids
PD AUG-SEP
PY 2009
VL 81
IS 2-3
BP 179
EP 186
DI 10.1016/j.plefa.2009.06.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology &
Metabolism
GA 502NQ
UT WOS:000270467600015
PM 19619995
ER
PT J
AU Orru, CD
Wilham, JM
Hughson, AG
Raymond, LD
McNally, KL
Bossers, A
Ligios, C
Caughey, B
AF Orru, Christina D.
Wilham, Jason M.
Hughson, Andrew G.
Raymond, Lynne D.
McNally, Kristin L.
Bossers, Alex
Ligios, Ciriaco
Caughey, Byron
TI Human variant Creutzfeldt-Jakob disease and sheep scrapie PrPres
detection using seeded conversion of recombinant prion protein
SO PROTEIN ENGINEERING DESIGN & SELECTION
LA English
DT Article
DE cerebral spinal fluid; CJD; diagnostics; prion; scrapie
ID IN-VITRO AMPLIFICATION; MISFOLDING CYCLIC AMPLIFICATION; CELL-FREE
FORMATION; RESISTANT STATE; ULTRASENSITIVE DETECTION;
CEREBROSPINAL-FLUID; PRPSC; BRAIN; FORM; BINDING
AB The pathological isoform of the prion protein (PrPres) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. Previously we showed that the quaking-induced conversion (QuIC) assay can detect sub-femtogram levels of PrPres in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (CSF) samples from normal and scrapie-infected hamsters. We now report the adaptation of the QuIC reaction to prion diseases of medical and agricultural interest: human variant Creutzfeldt-Jakob disease (vCJD) and sheep scrapie. PrPres-positive and -negative brain homogenates from humans and sheep were discriminated within 1-2 days with a sensitivity of 10-100 fg PrPres. More importantly, in as little as 22 h we were able to distinguish CSF samples from scrapie-infected and uninfected sheep. These results suggest the presence of prions in CSF from scrapie-infected sheep. This new method enables the relatively rapid and sensitive detection of human CJD and sheep scrapie PrPres and may facilitate the development of practical preclinical diagnostic and high-throughput interference tests.
C1 [Orru, Christina D.; Wilham, Jason M.; Hughson, Andrew G.; Raymond, Lynne D.; McNally, Kristin L.; Caughey, Byron] NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA.
[Orru, Christina D.] Univ Cagliari, Dept Biomed Sci & Technol, I-09042 Monserrato, Italy.
[Bossers, Alex] Cent Vet Inst Wageningen UR CVI, Dept Bacteriol, NL-8200 AB Lelystad, Netherlands.
[Bossers, Alex] TSEs, NL-8200 AB Lelystad, Netherlands.
[Ligios, Ciriaco] Expt Zooprophylact Inst Sardinia, I-07100 Sassari, Italy.
RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA.
EM bcaughey@nih.gov
OI Bossers, Alex/0000-0002-6586-717X
FU NIAID, NIH; Master and Back Program of the Regione Sardegna (Italy)
FX This research was funded by the Intramural Research Program of the
NIAID, NIH. C.D.O. was partially supported by the Master and Back
Program of the Regione Sardegna (Italy), J.M.W. was supported in part by
the Undergraduate Scholarship Program of the NIH.
NR 30
TC 35
Z9 36
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1741-0126
J9 PROTEIN ENG DES SEL
JI Protein Eng. Des. Sel.
PD AUG
PY 2009
VL 22
IS 8
BP 515
EP 521
DI 10.1093/protein/gzp031
PG 7
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 478KV
UT WOS:000268588100009
PM 19570812
ER
PT J
AU Tyagi, M
Shoemaker, BA
Bryant, SH
Panchenko, AR
AF Tyagi, Manoj
Shoemaker, Benjamin A.
Bryant, Stephen H.
Panchenko, Anna R.
TI Exploring functional roles of multibinding protein interfaces
SO PROTEIN SCIENCE
LA English
DT Article
DE protein-protein interaction; multibinding interfaces; promiscuous sites;
domain-domain interaction; conserved binding mode
ID NUCLEOTIDE EXCHANGE FACTOR; BINDING-SITES; STRUCTURAL BASIS; HOT-SPOTS;
SPECIFICITY; COMPLEXES; DETERMINANTS; EVOLUTIONARY; PROMISCUITY;
ASSOCIATION
AB Cellular processes are highly interconnected and many proteins are shared in different pathways. Some of these shared proteins or protein families may interact with diverse partners using the same interface regions; such multibinding proteins are the subject of our study. The main goal of our study is to attempt to decipher the mechanisms of specific molecular recognition of multiple diverse partners by promiscuous protein regions. To address this, we attempt to analyze the physicochemical properties of multibinding interfaces and highlight the major mechanisms of functional switches realized through multibinding. We find that only 5% of protein families in the structure database have multibinding interfaces, and multibinding interfaces do not show any higher sequence conservation compared with the background interface sites. We highlight several important functional mechanisms utilized by multibinding families. (a) Overlap between different functional pathways can be prevented by the switches involving nearby residues of the same interfacial region. (b) Interfaces can be reused in pathways where the substrate should be passed from one protein to another sequentially. (c) The same protein family can develop different specificities toward different binding partners reusing the same interface; and finally, (d) inhibitors can attach to substrate binding sites as substrate mimicry and thereby prevent substrate binding.
C1 [Tyagi, Manoj; Shoemaker, Benjamin A.; Bryant, Stephen H.; Panchenko, Anna R.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM panch@ncbi.nlm.nih.gov
RI Tyagi, Manoj/K-8438-2014
FU National Institutes of Health/DHHS (Intramural Research program of the
National Library of Medicine)
FX Grant sponsor: National Institutes of Health/DHHS (Intramural Research
program of the National Library of Medicine)
NR 47
TC 20
Z9 20
U1 0
U2 2
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0961-8368
J9 PROTEIN SCI
JI Protein Sci.
PD AUG
PY 2009
VL 18
IS 8
BP 1674
EP 1683
DI 10.1002/pro.181
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 482JM
UT WOS:000268882100011
PM 19591200
ER
PT J
AU Zhang, SQ
DeGraba, TJ
Wang, HH
Hoehn, GT
Gonzales, DA
Suffredini, AF
Ching, WK
Ng, MK
Zhou, XB
Wong, STC
AF Zhang, Shuqin
DeGraba, Thomas J.
Wang, Honghui
Hoehn, Gerard T.
Gonzales, Denise A.
Suffredini, Anthony F.
Ching, Wai-Ki
Ng, Michael K.
Zhou, Xiaobo
Wong, Stephen T. C.
TI A novel peak detection approach with chemical noise removal using
short-time FFT for prOTOF MS data
SO PROTEOMICS
LA English
DT Article
DE Adaptive short-time discrete Fourier transform; Complete linkage
hierarchical clustering; Peak alignment; Peak detection; Undecimated
wavelet transform
ID MASS-SPECTROMETRY DATA; PROTEIN IDENTIFICATION; WAVELET TRANSFORM;
QUANTIFICATION; ALGORITHM; SPECTRUM; MALDI
AB Peak detection is a pivotal first step in biomarker discovery from MS data and can significantly influence the results of downstream data analysis steps. We developed a novel automatic peak detection method for prOTOF MS data, which does not require a priori knowledge of protein masses. Random noise is removed by an undecimated wavelet transform and chemical noise is attenuated by an adaptive short-time discrete Fourier transform. Isotopic peaks corresponding to a single protein are combined by extracting an envelope over them. Depending on the SIN, the desired peaks in each individual spectrum are detected and those with the highest intensity among their peak clusters are recorded. The common peaks among all the spectra are identified by choosing an appropriate cut-off threshold in the complete linkage hierarchical clustering. To remove the 1 Da shifting of the peaks, the peak corresponding to the same protein is determined as the detected peak with the largest number among its neighborhood. We validated this method using a data set of serial peptide and protein calibration standards. Compared with MoverZ program, our new method detects more peaks and significantly enhances SIN of the peak after the chemical noise removal. We then successfully applied this method to a data set from prOTOF MS spectra of albumin and albumin-bound proteins from serum samples of 59 patients with carotid artery disease compared to vascular disease-free patients to detect peaks with S/N >= 2. Our method is easily implemented and is highly effective to define peaks that will be used for disease classification or to highlight potential biomarkers.
C1 [Zhang, Shuqin; Zhou, Xiaobo; Wong, Stephen T. C.] Harvard Univ, Sch Med, HCNR CBI, Boston, MA 02215 USA.
[Zhang, Shuqin; Zhou, Xiaobo; Wong, Stephen T. C.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Zhang, Shuqin] Fudan Univ, Sch Math Sci, Shanghai 200433, Peoples R China.
[DeGraba, Thomas J.] Natl Naval Med Ctr, Dept Neurol, Bethesda, MD USA.
[Wang, Honghui; Hoehn, Gerard T.; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gonzales, Denise A.; Ching, Wai-Ki] Univ Hong Kong, Dept Math, Hong Kong, Hong Kong, Peoples R China.
[Ng, Michael K.] Hong Kong Baptist Univ, Dept Math, Kowloon Tong, Hong Kong, Peoples R China.
[Zhou, Xiaobo; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Radiol, Houston, TX 77030 USA.
RP Zhou, XB (reprint author), Harvard Univ, Sch Med, HCNR CBI, Boston, MA 02215 USA.
EM XZhou@tmhs.org
RI Ng, Michael/B-7189-2009; HKBU, Mathematics/B-5086-2009;
OI NG, Michael/0000-0001-6833-5227
FU IBIS award (Zhou); TMHRI scholarship award (Zhou); Neurology Department,
National Naval Medical Center; NIH, Clinical Center
FX The opinions expressed herein are those of the authors and do not
necessarily reflect the policies of the Department of Health and Human
Services, the National Institutes of Health, or the Department of Navy.
The authors wish to thank Dr. Lisa Sapp (PerkinElmer) for acquiring all
prOTOF MS for clinical samples. This work is partially funded by IBIS
award (Zhou) and TMHRI scholarship award (Zhou). This research was
supported in part by the Neurology Department, National Naval Medical
Center and the Intramural Program of the NIH, Clinical Center. They also
thank Dominik Back for proofreading the manuscript.
NR 15
TC 6
Z9 6
U1 0
U2 3
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD AUG
PY 2009
VL 9
IS 15
BP 3833
EP 3842
DI 10.1002/pmic.200800030
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 489GO
UT WOS:000269408400006
PM 19681055
ER
PT J
AU Ginzburg, HM
AF Ginzburg, Harold M.
TI THIS ISSUE: Military Mental Health
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Ginzburg, Harold M.] Tulane Univ, Dept Psychiat & Neurol, Med Ctr, New Orleans, LA 70118 USA.
[Ginzburg, Harold M.] NIAID, Natl Inst Drug Abuse, Bethesda, MD USA.
RP Ginzburg, HM (reprint author), Tulane Univ, Dept Psychiat & Neurol, Med Ctr, New Orleans, LA 70118 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD AUG
PY 2009
VL 39
IS 8
BP 770
EP +
DI 10.3928/00485713-20090728-06
PG 3
WC Psychiatry
SC Psychiatry
GA 483EP
UT WOS:000268945500002
ER
PT J
AU Glantz, MD
Anthony, JC
Berglund, PA
Degenhardt, L
Dierker, L
Kalaydjian, A
Merikangas, KR
Ruscio, AM
Swendsens, J
Kessler, RC
AF Glantz, M. D.
Anthony, J. C.
Berglund, P. A.
Degenhardt, L.
Dierker, L.
Kalaydjian, A.
Merikangas, K. R.
Ruscio, A. M.
Swendsens, J.
Kessler, R. C.
TI Mental disorders as risk factors for later substance dependence:
estimates of optimal prevention and treatment benefits
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Mental disorders; prevention; substance dependence; treatment
ID NATIONAL-COMORBIDITY-SURVEY; ALCOHOL-USE DISORDERS; CHILDHOOD
PSYCHOPATHOLOGY INTERVENTIONS; REPLICATION NCS-R; AGE-OF-ONSET; ANXIETY
DISORDERS; PSYCHIATRIC COMORBIDITY; EPIDEMIOLOGIC SURVEY;
GENERAL-POPULATION; DRUG-ABUSE
AB Background. Although mental disorders have been shown to predict subsequent substance disorders, it is not known whether substance disorders could be cost-effectively prevented by large-scale interventions aimed at prior mental disorders. Although experimental intervention is the only way to resolve this uncertainty, a logically prior question is whether the associations of mental disorders with subsequent substance disorders are strong enough to justify mounting such an intervention. We investigated this question in this study using simulations to estimate the number of substance disorders that might be prevented under several hypothetical intervention scenarios focused on mental disorders.
Method. Data came from the National Comorbidity Survey Replication (NCS-R), a nationally representative US household survey that retrospectively assessed lifetime history and age of onset of DSM-IV mental and substance disorders. Survival analysis using retrospective age-of-onset reports was used to estimate associations of mental disorders with subsequent substance dependence. Simulations based on the models estimated effect sizes in several hypothetical intervention scenarios.
Results. Although successful intervention aimed at mental disorders might prevent some proportion of substance dependence, the number of cases of mental disorder that would have to be treated to prevent a single case of substance dependence is estimated to be so high that this would not be a cost-effective way to prevent substance dependence (in the range 76-177 for anxiety-mood disorders and 40-47 for externalizing disorders).
Conclusions. Treatment of prior mental disorders would not be a cost-effective way to prevent substance dependence. However, prevention of substance dependence might be considered an important secondary outcome of interventions for early-onset mental disorders.
C1 [Glantz, M. D.] Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD USA.
[Anthony, J. C.] Michigan State Univ, Sch Med, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Berglund, P. A.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Degenhardt, L.] Univ New S Wales, Natl Drug & Alcohol Res Ctr, Randwick, NSW, Australia.
[Dierker, L.] Wesleyan Univ, Dept Psychol, Middletown, CT USA.
[Kalaydjian, A.; Merikangas, K. R.] NIMH, Bethesda, MD 20892 USA.
[Ruscio, A. M.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA.
[Swendsens, J.] Natl Sci Res Ctr CNRS 5237, Bordeaux, France.
[Kessler, R. C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Glantz, MD (reprint author), 6001 Execut Blvd,Suite 5185,MSC 9589, Bethesda, MD 20892 USA.
EM mglantz@nida.nih.gov
RI Degenhardt, Louisa/D-4515-2012
OI Degenhardt, Louisa/0000-0002-8513-2218
FU Eli Lilly Company; Pfizer Inc.; Ortho-McNeil Pharmaceuticals Inc.;
Bristol-Myers Squibb
FX Professor Kessler has been a consultant for GlaxoSmithKline Inc., Pfizer
Inc., Wyeth-Ayerst, SanofiAventis, Kaiser Permanente, and Shire
Pharmaceuticals; has served on advisory boards for Eli Lilly & Company
and Wyeth-Ayerst; and has had research support for his epidemiological
studies from Eli Lilly & Company, Pfizer Inc., Ortho-McNeil
Pharmaceuticals Inc., and Bristol-Myers Squibb.
NR 79
TC 57
Z9 59
U1 3
U2 7
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD AUG
PY 2009
VL 39
IS 8
BP 1365
EP 1377
DI 10.1017/S0033291708004510
PG 13
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 472XC
UT WOS:000268165300015
PM 19046473
ER
PT J
AU Bar-Haim, Y
Fox, NA
Benson, B
Guyer, AE
Williams, A
Nelson, EE
Perez-Edgar, K
Pine, DS
Ernst, M
AF Bar-Haim, Yair
Fox, Nathan A.
Benson, Brenda
Guyer, Amanda E.
Williams, Amber
Nelson, Eric E.
Perez-Edgar, Koraly
Pine, Daniel S.
Ernst, Monique
TI Neural Correlates of Reward Processing in Adolescents With a History of
Inhibited Temperament
SO PSYCHOLOGICAL SCIENCE
LA English
DT Article
ID BEHAVIORAL-INHIBITION; NUCLEUS-ACCUMBENS; ANXIETY DISORDER; CHILDREN;
FACES; CONSTRUCTION; SENSITIVITY; ACTIVATION; FRAMEWORK; RESPONSES
AB Functional imaging data were acquired during performance of a reward-contingency task in a unique cohort of adolescents (ages 14-18 years) who were characterized since infancy on measures of temperamental behavioral inhibition. Neural activation was examined in striatal structures (nucleus accumbens, putamen, caudate) with a known role in facilitating response to salient reward-related cues. Adolescents with a history of behavioral inhibition, relative to noninhibited adolescents, showed increased activation in the nucleus accumbens when they believed their selection of an action would affect reward outcome. Neural responses did not differ between the two groups when participants made a prespecified response that they knew would result in reward or when they produced random motor responses that they knew would not be rewarded. These results link inhibited temperament and perturbed neural responses to reward-contingency cues.
C1 [Bar-Haim, Yair] Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel.
[Fox, Nathan A.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Benson, Brenda; Guyer, Amanda E.; Williams, Amber; Nelson, Eric E.; Pine, Daniel S.; Ernst, Monique] NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Perez-Edgar, Koraly] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
RP Bar-Haim, Y (reprint author), Tel Aviv Univ, Dept Psychol, IL-69978 Tel Aviv, Israel.
EM yair1@post.tau.ac.il
RI Nelson, Eric/B-8980-2008;
OI Nelson, Eric/0000-0002-3376-2453; Perez-Edgar,
Koraly/0000-0003-4051-9563
FU Intramural NIH HHS [ZIA MH002780-08, ZIA MH002781-08, ZIA MH002782-08];
NIMH NIH HHS [R01 MH074454, R01 MH074454-03]
NR 40
TC 69
Z9 69
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0956-7976
J9 PSYCHOL SCI
JI Psychol. Sci.
PD AUG
PY 2009
VL 20
IS 8
BP 1009
EP 1018
PG 10
WC Psychology, Multidisciplinary
SC Psychology
GA 480DV
UT WOS:000268713200013
PM 19594857
ER
PT J
AU Barrett, CE
Noble, P
Hanson, E
Pine, DS
Winslow, JT
Nelson, EE
AF Barrett, Catherine E.
Noble, Pamela
Hanson, Erin
Pine, Daniel S.
Winslow, James T.
Nelson, Eric E.
TI Early adverse rearing experiences alter steep-wake patterns and plasma
cortisol levels in juvenile rhesus monkeys
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Article
DE Circadian; Steep; Steep-wake cycle; Cortisol;
Hypothalamic-pituitary-adrenal axis; Rearing; Mood; Development
ID TRANSPORTER GENE VARIATION; PITUITARY-ADRENAL AXIS; CIRCADIAN-RHYTHMS;
NONHUMAN-PRIMATES; MAJOR DEPRESSION; AMYGDALA LESIONS; SLEEP DISORDERS;
MACACA-MULATTA; LIFE STRESS; HPA AXIS
AB Monkeys separated from their mothers soon after birth and raised with peers display many disturbances in emotional behavior that are similar to human mood and anxiety disorders. In addition to emotional disturbances, both mood and anxiety disorders are often characterized by disruptions in normal steep-wake cycles, a behavior that has not been well characterized in adversely reared non-human primates. Because polysomnographic measures are difficult to obtain in unrestrained monkeys we used 24-h actigraphy measures to assess probable steep-wake patterns in juvenile nursery- and mother-reared rhesus macaques (Macaca mulatto, N = 16) over several days in the home cage. In addition we assayed plasma cortisol in the morning, afternoon, and evening. Relative to mother-reared (MR) monkeys, actigraphic algorithms indicated that nursery-reared (NR) animals had shorter durations of nocturnal steep, earlier morning waking, and longer periods of steep during the active period, specifically in the mid morning. No shift in diurnal patterns of cortisol was observed, but NR animals displayed an overall elevation in cortisol. Finally a significant interaction was found between cortisol and actigraphic determination of steep efficiency in the two groups. A strong positive relationship (r(2) > 0.8) was found between mean cortisol levels and steep efficiency for the MR monkeys, but a significant negative relationship was found between these same variables for the NR monkeys, indicating a fundamentally different relationship between waking cortisol and actigraphy patterns in these two groups. Published by Elsevier Ltd.
C1 [Barrett, Catherine E.; Pine, Daniel S.; Winslow, James T.; Nelson, Eric E.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Noble, Pamela; Hanson, Erin; Winslow, James T.] NIMH, Primate Core Facil, Poolesville, MD 20842 USA.
RP Nelson, EE (reprint author), NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
EM en50k@nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 56
TC 20
Z9 20
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD AUG
PY 2009
VL 34
IS 7
BP 1029
EP 1040
DI 10.1016/j.psyneuen.2009.02.002
PG 12
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA 463ZD
UT WOS:000267471900010
PM 19268477
ER
PT J
AU Robinson, OJ
Sahakian, BJ
AF Robinson, Oliver J.
Sahakian, Barbara J.
TI Acute tryptophan depletion evokes negative mood in healthy females who
have previously experienced concurrent negative mood and tryptophan
depletion
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Serotonin; Mood; Females; Recurrence; Depression; Associative learning
ID PREVIOUS DEPRESSIVE EPISODES; STRESSFUL LIFE EVENTS; SEROTONIN
TRANSPORTER; MAJOR DEPRESSION; PLASMA TRYPTOPHAN; RAPID DEPLETION;
MONOAMINE DEPLETION; SEX-DIFFERENCES; FAMILY-HISTORY; NORMAL MALES
AB The majority of individuals who suffer an episode of depression go on to experience recurrences. We have proposed, based upon the observation that reducing serotonin via acute tryptophan depletion (ATD) is more likely to induce negative mood in recovered depressed individuals than never depressed individuals, that this may be because associations form between negative mood and reduced serotonin during an episode of depression (Robinson and Sahakian, Psychol Med 38:315-318, 2008b). Such associations would mean that subsequent reductions in serotonin are more likely to provoke depressed mood and hence trigger an episode of depression.
In this study, we tested this hypothesis by manipulating the mood state of healthy females undergoing ATD (or balanced placebo) on two separate testing sessions. On the first session, subjects received either negative or neutral mood induction, while on the second session all subjects received neutral mood induction.
Our findings demonstrate significant ATD-induced negative mood exclusively on the second visit of subjects who received both ATD and negative mood induction procedure on their first visit.
These findings may be explained by the formation of an association between the negative mood and reduced serotonin states during the first visit. As such, these findings provide preliminary support for the associative hypothesis of recurrence in depression.
Such associations might therefore explain the discrepancy between the effects of ATD in recovered- and never-depressed individuals and may, in turn, explain why an episode of depression increases the risk of subsequent episodes.
C1 [Robinson, Oliver J.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England.
[Robinson, Oliver J.; Sahakian, Barbara J.] Univ Cambridge, Addenbrookes Hosp, Behav & Clin Neurosci Inst, Cambridge CB2 2QQ, England.
[Robinson, Oliver J.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, POB 189,Level E4,Hills Rd, Cambridge CB2 2QQ, England.
EM oliver.j.robinson@googlemail.com
RI Robinson, Oliver/B-3646-2011
OI Robinson, Oliver/0000-0002-3100-1132
FU Wellcome Trust [076274/Z04/Z]; Medical Research Council
FX This work was conducted within the Behavioural and Clinical Neuroscience
Institute, which is co-funded by the Medical Research Council and the
Wellcome Trust. The research was funded by a programme grant from The
Wellcome Trust (grant number 076274/Z04/Z to TW Robbins, BJ Everitt, AC
Roberts and BJ Sahakian). We are grateful to Stuart Fuller and the staff
of the Wellcome Trust Clinical Research Facility, Addenbrooke's
Hospital, Cambridge. We thank Mike Franklin for analysis of plasma data.
OJR holds an MRC Research Studentship.
NR 66
TC 11
Z9 11
U1 4
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2009
VL 205
IS 2
BP 227
EP 235
DI 10.1007/s00213-009-1533-4
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 466UB
UT WOS:000267687200005
PM 19370340
ER
PT J
AU Suto, N
Ecke, LE
Wise, RA
AF Suto, Nobuyoshi
Ecke, Laurel E.
Wise, Roy A.
TI Control of within-binge cocaine-seeking by dopamine and glutamate in the
core of nucleus accumbens
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Cocaine; Nucleus accumbens; Dopamine; Glutamate; D1 receptor; D2
receptor; AMPA receptor; NMDA receptor
ID PROGRESSIVE RATIO SCHEDULE; MEDIAL PREFRONTAL CORTEX; INTRAVENOUS
COCAINE; INDUCED REINSTATEMENT; VENTRAL STRIATUM; REINFORCEMENT;
BEHAVIOR; SHELL; TRANSMISSION; NEURONS
AB Dopamine and glutamate are thought to interact in the ventral striatum and to play important roles there in the cocaine-seeking of cocaine-experienced animals.
We sought to determine the relative roles of the two transmitters in the two major zones of the nucleus accumbens (NAS), the core and shell subregions.
We assessed the effects of dopamine and glutamate receptor blockade in the core and shell on intravenous cocaine self-administration in rats. Trained animals were allowed to self-administer cocaine for an initial hour, and then D1-type or D2-type dopamine receptor blockers or NMDA-type or AMPA-type glutamate receptor blockers were infused by reverse microdialysis into one of the two regions for an additional 3 h of testing.
The D1-type antagonist SCH23390 and the D2-type antagonist raclopride each increased cocaine intake whereas the AMPA-type antagonist CNQX decreased responding when infused into the core. SCH23390 increased cocaine intake less strongly when infused into the shell, while raclopride and CNQX were each ineffective when infused into the shell. The NMDA-antagonist CPP failed to affect cocaine self-administration when infused into either site.
These findings implicate the core of NAS in the maintenance of established cocaine self-administration in trained animals, despite the fact that the reinforcement of responding in untrained animals appears to results from cocaine actions in the olfactory tubercle and medial shell and not the core of accumbens.
C1 [Suto, Nobuyoshi] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21131 USA.
[Suto, Nobuyoshi; Ecke, Laurel E.; Wise, Roy A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Suto, N (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, 55 Wade Ave, Baltimore, MD 21131 USA.
EM nsuto@mprc.umaryland.edu
FU Intramural Research Program; National Institute on Drug Abuse; National
Institutes of Health; Department of Health and Human Services
FX Supported by funding from the Intramural Research Program, National
Institute on Drug Abuse, National Institutes of Health, Department of
Health and Human Services. We thank Dr. Zhi-Bing You for technical
assistance with the reversedialysis technique, Drs. Marisela Morales and
Hui-Ling Wang for technical assistance with histology, and Eric
Thorndike for technical assistance with analyses of self-administration
data.
NR 46
TC 24
Z9 24
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD AUG
PY 2009
VL 205
IS 3
BP 431
EP 439
DI 10.1007/s00213-009-1553-0
PG 9
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 472HE
UT WOS:000268120400008
PM 19436996
ER
PT J
AU Bialkowski, K
Szpila, A
Kasprzak, KS
AF Bialkowski, Karol
Szpila, Anna
Kasprzak, Kazimierz S.
TI Up-regulation of 8-oxo-dGTPase Activity of MTH1 Protein in the Brain,
Testes and Kidneys of Mice Exposed to Cs-137 gamma Radiation
SO RADIATION RESEARCH
LA English
DT Article
ID 5'-TRIPHOSPHATE PYROPHOSPHOHYDROLASE 8-OXO-DGTPASE; HUMAN MUTT HOMOLOG;
SINGLE NUCLEOTIDE POLYMORPHISM; GENE-ENCODING 8-OXO-DGTPASE; HMTH1
MESSENGER-RNA; INDUCED DNA-DAMAGE; OXIDATIVE STRESS; NUCLEOSIDE
TRIPHOSPHATASE; TRANSVERSION MUTATION; MUTAGENIC SUBSTRATE
AB Mammalian MTH1 protein is an antimutagenic (2'-deoxy) ribonucleoside 5'-triphosphate pyrophosphohydrolase that prevents the incorporation of oxidatively modified nucleotides into nucleic acids. It decomposes most specifically the miscoding products of oxidative damage to purine nucleic acid precursors (e.g. 8-oxo-dGTP, 2-oxo-dATP, 2-oxo-ATP, 8-oxo-GTP) that may cause point mutations or transcription errors when incorporated into DNA and RNA, respectively. The increased expression of MTH1 mRNA and MTH1 protein was previously proposed as a molecular marker of oxidative stress. Therefore, we hypothesized that increased 8-oxo-dGTPase activity of MTH1 protein in mouse organs could serve as a dose-dependent marker of exposure to ionizing radiation, which is known to induce oxidative stress. To test our hypothesis, we measured 8-oxo-dGTPase activity in six organs of male BL6 mice after exposure to 0, 10, 25 and 50 cGy and 1 Gy of Cs-137 gamma radiation given as a single whole-body dose (1 Gy/min). The mice were killed 4, 8 and 24 h after irradiation. A statistically significant induction of 8-oxo-dGTPase was found in brains, testes and kidneys but not in lungs, hearts or livers. Brains, which demonstrated the highest (4.3-fold) increase of 8-oxo-dGTPase activity, were shown to express similar to 50% higher levels of MTH1 protein. However, due to the lack of a simple positive correlation between the dose and the observed 8-oxo-dGTPase activity in brain, testes and kidneys, we conclude that measurements of 8-oxo-dGTPase activity in these organs may serve as a rough indicator rather than a quantifiable marker of radiation-induced oxidative stress. (C) 2009 by Radiation Research Society
C1 [Bialkowski, Karol; Szpila, Anna] Nicholas Copernicus Univ, Coll Med, Dept Clin Biochem, PL-85092 Bydgoszcz, Poland.
[Kasprzak, Kazimierz S.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA.
RP Bialkowski, K (reprint author), Nicholas Copernicus Univ, Coll Med, Dept Clin Biochem, St Karlowicza 24, PL-85092 Bydgoszcz, Poland.
EM karolb@cm.umk.pl
RI Bialkowski, Karol/E-2328-2014; Szpila, Anna/G-8402-2014
FU Polish State Committee for Scientific Research [41/6.PR UE/2007/7, 3P04A
06323]; Intramural Research Program of the U.S. NIH; National Cancer
Institute; Center for Cancer Research; ECNIS (European Cancer Risk,
Nutrition and Individual Susceptibility); European Union [513943]
FX This research was supported by grants 41/6.PR UE/2007/7 and 3P04A 06323
from the Polish State Committee for Scientific Research and the
Intramural Research Program of the U.S. NIH, National Cancer Institute,
Center for Cancer Research. KB and AS are partners of ECNIS (European
Cancer Risk, Nutrition and Individual Susceptibility), a network of
excellence operating within the European Union 6th Framework Program,
Priority 5: "Food Quality and Safety" (Contract No 513943). The authors
are thankful to Dr. Gary Pauly for his insightful critical comments on
this manuscript. KB has dedicated this work to the memory of Marek
Grechuta.
NR 51
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Z9 5
U1 0
U2 2
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD AUG
PY 2009
VL 172
IS 2
BP 187
EP 197
DI 10.1667/RR1636.1
PG 11
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 478WY
UT WOS:000268620600005
PM 19630523
ER
PT J
AU Lanz, C
Patterson, AD
Slavik, J
Krausz, KW
Ledermann, M
Gonzalez, FJ
Idle, JR
AF Lanz, Christian
Patterson, Andrew D.
Slavik, Josef
Krausz, Kristopher W.
Ledermann, Monika
Gonzalez, Frank J.
Idle, Jeffrey R.
TI Radiation Metabolomics. 3. Biomarker Discovery in the Urine of
Gamma-Irradiated Rats Using a Simplified Metabolomics Protocol of Gas
Chromatography-Mass Spectrometry Combined with Random Forests Machine
Learning Algorithm
SO RADIATION RESEARCH
LA English
DT Article
ID MICE; IDENTIFICATION; METABOLISM; PYRIMIDINES; EXPRESSION; INFECTION;
EXPOSURE; PURINES; KIDNEY; CANCER
AB Radiation metabolomics employing mass spectral technologies represents a plausible means of high-throughput minimally invasive radiation biodosimetry. A simplified metabolomics protocol is described that employs ubiquitous gas chromatography-mass spectrometry and open source software including random forests machine learning algorithm to uncover latent biomarkers of 3 Gy gamma radiation in rats. Urine was collected from six male Wistar rats and six sham-irradiated controls for 7 days, 4 prior to irradiation and 3 after irradiation. Water and food consumption, urine volume, body weight, and sodium, potassium, calcium, chloride, phosphate and urea excretion showed major effects from exposure to gamma radiation. The metabolomics protocol uncovered several urinary metabolites that were significantly up-regulated (glyoxylate, threonate, thymine, uracil, p-cresol) and down-regulated (citrate, 2-oxoglutarate, adipate, pimelate, suberate, azelaate) as a result of radiation exposure. Thymine and uracil were shown to derive largely from thymidine and 2'-deoxyuridine, which are known radiation biomarkers in the mouse. The radiation metabolomic phenotype in rats appeared to derive from oxidative stress and effects on kidney function. Gas chromatography-mass spectrometry is a promising platform on which to develop the field of radiation metabolomics further and to assist in the design of instrumentation for use in detecting biological consequences of environmental radiation release. (C) 2009 by Radiation Research Society
C1 [Lanz, Christian; Slavik, Josef; Ledermann, Monika; Idle, Jeffrey R.] Univ Bern, Inst Clin Pharmacol & Visceral Res, CH-3010 Bern, Switzerland.
[Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Idle, JR (reprint author), Univ Bern, Inst Clin Pharmacol & Visceral Res, Murtenstr 35, CH-3010 Bern, Switzerland.
EM jidle@ikp.unibe.ch
RI Patterson, Andrew/G-3852-2012;
OI Patterson, Andrew/0000-0003-2073-0070; Idle, Jeff/0000-0002-6143-1520
FU Columbia University Center for Medical Countermeasures against
Radiation; NIH (NIAID) [U19 A1067773-02]; National Cancer Institute
Intramural Research Program; Pharmacology Research Associate in Training
program; National Institute of General Medical Sciences
FX The authors wish to thank Professor Bernhard Lauterburg in Bern for his
support of this work and helpful discussions. The expert technical
assistance of Jurg Muller is also acknowledged. We thank Prof. Dr.
Bendicht, Wermuth, Director of the Zentrallabor, Inselspital, Bern, for
providing analyses of urinary urea and electrolytes. This work was
performed as part of the Columbia University Center for Medical
Countermeasures against Radiation (P.I. David Brenner) and funded by NIH
(NIAID) grant U19 A1067773-02 and also supported in part by the National
Cancer Institute Intramural Research Program. ADP is supported by the
Pharmacology Research Associate in Training program, National Institute
of General Medical Sciences. JRI is grateful to U.S. Smokeless Tobacco
Company for a grant for collaborative research.
NR 23
TC 55
Z9 59
U1 0
U2 18
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 AUG
PY 2009
VL 172
IS 2
BP 198
EP 212
DI 10.1667/RR1796.1
PG 15
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA 478WY
UT WOS:000268620600006
PM 19630524
ER
PT J
AU Luo, S
Wehr, NB
AF Luo, Shen
Wehr, Nancy B.
TI Protein carbonylation: avoiding pitfalls in the
2,4-dinitrophenylhydrazine assay
SO REDOX REPORT
LA English
DT Article
DE protein oxidation; carbonyl assay; nucleic acid; OxyBlot; bacteria;
oxidative stress
ID OXIDATIVELY MODIFIED PROTEINS; GLUTAMINE-SYNTHETASE; OXIDIZED PROTEINS;
CELLS; ACIDS
AB Protein carbonyl content is widely used as both a marker for oxidative stress and a measure of oxidative damage. Widely used methods for determination of protein carbonylation utilize the reaction of carbonyl groups with 2,4-dinitrophenylhydrazine (DNPH) to form protein-bound 2,4-dinitrophenylhydrazones. Hydrazones can be quantitated spectrophotometrically or, for greater sensitivity, detected immunochemically with anti-dinitrophenyl antibodies. Attention to methodology is important to avoid artifactual elevation in protein carbonyl measurements. We studied extracts of Escherichia coli to identify and eliminate such effects. Nucleic acid contamination caused serious artifactual increases in the protein carbonyl content determined by spectrophotometric techniques. Both in vitro synthesized DNA oligonucleotides and purified chromosomal DNA reacted strongly with 2,4-DNPH. Treatment of cell extracts with DNasee+RNase or with streptomycin sulfate to precipitate nucleic acids dramatically reduced the apparent carbonyl, while exposure to proteinase K did not. The commercial kit for immunochemical detection of protein carbonylation (OxyBlot (TM) from Chemicon/Millipore) recommends a high concentration of thiol in the homogenizing buffer. We found this recommendation leads to an artifactual doubling of the protein carbonyl, perhaps due to a thiol-stimulated Fenton reaction. Avoiding oxidizing conditions, removal of nucleic acids, and prompt assay of samples can prevent artifactual effects on protein carbonyl measurements.
C1 [Luo, Shen; Wehr, Nancy B.] NHLBI, Biochem Lab, Bethesda, MD 20892 USA.
RP Luo, S (reprint author), 8800 Rockville Pike,NIH Bldg 29A Room 2B24, Bethesda, MD 20892 USA.
EM shen.luo@fda.hhs.gov
FU National Heart, Lung, and Blood Institute; National Institutes of Health
FX The authors thank Dr Rodney L. Levine for very helpful discussions and
suggestions, and Dr Geumsoo Kim for the gifts of DNAl samples. This
research was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 23
TC 45
Z9 45
U1 7
U2 31
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1351-0002
J9 REDOX REP
JI Redox Rep.
PD AUG
PY 2009
VL 14
IS 4
BP 159
EP 166
DI 10.1179/135100009X392601
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 487RK
UT WOS:000269292300004
PM 19695123
ER
PT J
AU Pilotto, A
Matera, MG
Ferrucci, L
Sancarlo, D
Leandro, G
D'Onofrio, G
Seripa, D
Addante, F
Franceschi, M
Dallapiccola, B
AF Pilotto, Alberto
Matera, Maria G.
Ferrucci, Luigi
Sancarlo, Daniele
Leandro, Gioacchino
D'Onofrio, Grazia
Seripa, Davide
Addante, Filomena
Franceschi, Marilisa
Dallapiccola, Bruno
TI Association of Apolipoprotein E and Angiotensin Converting Enzyme Gene
Polymorphisms with the Multidimensional Impairment in Older Patients
SO REJUVENATION RESEARCH
LA English
DT Article
ID COMPREHENSIVE GERIATRIC ASSESSMENT; E GENOTYPES; PROGNOSTIC INDEX; HUMAN
LONGEVITY; FRAILTY; MORTALITY; DISEASE; CENTENARIANS; SARCOPENIA;
DEFICITS
AB The role of the apoliprotein E (APOE) and the angiotensin converting enzyme (ACE) polymorphisms on health and functional status deterioration in old age is still undefined. Recently, a Multidimensional Prognostic Index (MPI) for 1-year mortality derived from a Comprehensive Geriatric Assessment (CGA) was developed and validated in hospitalized elderly patients. The aim of this study was to investigate the possible association of the APOE and ACE gene polymorphisms with the multidimensional impairment, as evaluated by the MPI, in older patients. These polymorphisms were assessed in 1894 geriatric inpatients divided into three groups according to their MPI values: MPI-1 low risk (n = 988), MPI-2 moderate risk (n = 671), and MPI-3 severe risk of mortality (n = 235). A slight deviation from Hardy-Weinberg equilibrium was observed for the APOE genotypes. With the increasing of the MPI grade, a significant increase in the frequencies of epsilon 4 allele and the ACE D/D genotype was observed. The APOE epsilon 4(+) and ACE D/D genotypes were associated with severe MPI grade (APOE epsilon 4(+), odds ration [OR] = 1.79, 95% confidence interval [CI] 1.20-2.67; ACE D/D, OR = 1.42, 95% CI 1.05-1.92). The combined APOE epsilon 4(+) and ACE D/D genetic status was associated with higher MPI grade (OR = 2.85, 95% CI 1.75-4.65), without interaction. No significant associations between APOE and ACE polymorphisms and 2-year mortality were found. APOE and ACE genes might predispose individuals to health and functional status deterioration in old age, and their effect is additive.
C1 [Pilotto, Alberto; Matera, Maria G.; Sancarlo, Daniele; D'Onofrio, Grazia; Seripa, Davide; Addante, Filomena; Franceschi, Marilisa] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, I-71013 San Giovanni Rotondo, FG, Italy.
[Pilotto, Alberto; Matera, Maria G.; Sancarlo, Daniele; D'Onofrio, Grazia; Seripa, Davide; Addante, Filomena; Franceschi, Marilisa] IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Gerontol Geriatr Res Lab, I-71013 San Giovanni Rotondo, FG, Italy.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Harbor Hosp Ctr, Baltimore, MD 21224 USA.
[Leandro, Gioacchino] IRCCS Saverio De Bellis, Biostat & Gastroenterol Unit, Bari, Italy.
[Dallapiccola, Bruno] CSS Mendel Inst, Rome, Italy.
[Dallapiccola, Bruno] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy.
RP Pilotto, A (reprint author), IRCCS Casa Sollievo Sofferenza, Dept Med Sci, Geriatr Unit, Viale Cappuccini 1, I-71013 San Giovanni Rotondo, FG, Italy.
EM alberto.pilotto@operapadrepio.it
RI D'Onofrio, Grazia/K-9740-2016; Sancarlo, Daniele/C-1056-2017;
Dallapiccola, Bruno/K-8692-2016
OI D'Onofrio, Grazia/0000-0002-5905-6063; Sancarlo,
Daniele/0000-0001-9541-6364; Leandro, Gioacchino/0000-0001-6624-4532;
Dallapiccola, Bruno/0000-0002-5031-1013
FU Ministero della Salute, IRCCS Research Program
FX This work was supported by grants from Ministero della Salute, IRCCS
Research Program 2006-2008, Line 2: "Malattie di rilevanza sociale."
This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 32
TC 4
Z9 4
U1 1
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-1684
J9 REJUV RES
JI Rejuv. Res.
PD AUG
PY 2009
VL 12
IS 4
BP 239
EP 247
DI 10.1089/rej.2009.0858
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 508DV
UT WOS:000270908900002
PM 19653879
ER
PT J
AU Turner, KB
Yi-Brunozzi, HY
Brinson, RG
Marino, JP
Fabris, D
Le Grice, SFJ
AF Turner, Kevin B.
Yi-Brunozzi, Hye Young
Brinson, Robert G.
Marino, John P.
Fabris, Daniele
Le Grice, Stuart F. J.
TI SHAMS: Combining chemical modification of RNA with mass spectrometry to
examine polypurine tract-containing RNA/DNA hybrids
SO RNA-A PUBLICATION OF THE RNA SOCIETY
LA English
DT Article
DE retroviruses; polypurine tract; RNA/DNA hybrid; chemical modification;
mass spectrometry; NMR spectroscopy
ID SINGLE-NUCLEOTIDE RESOLUTION; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1
REVERSE-TRANSCRIPTASE; RETROTRANSPOSON TY3; CRYSTAL-STRUCTURE; PACKAGING
SIGNAL; NUCLEIC-ACIDS; DNA; SELECTION; COMPLEX
AB Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) has gained popularity as a facile method of examining RNA structure both in vitro and in vivo, exploiting accessibility of the ribose 2'-OH to acylation by N-methylisatoic anhydride (NMIA) in unpaired or flexible configurations. Subsequent primer extension terminates at the site of chemical modification, and these products are fractionated by high-resolution gel electrophoresis. When applying SHAPE to investigate structural features associated with the wild-type and analog-substituted polypurine tract (PPT)-containing RNA/DNA hybrids, their size (20-25 base pairs) rendered primer extension impractical. As an alternative method of detection, we reasoned that chemical modification could be combined with tandem mass spectrometry, relying on the mass increment of RNA fragments containing the NMIA adduct (M(r) = 133 Da). Using this approach, we demonstrate both specific modification of the HIV-1 PPT RNA primer and variations in its acylation pattern induced by replacing template nucleotides with a non-hydrogen-bonding thymine isostere. Our selective 2'-hydroxyl acylation analyzed by mass spectrometry strategy (SHAMS) should find utility when examining the structure of small RNA fragments or RNA/DNA hybrids where primer extension cannot be performed.
C1 [Yi-Brunozzi, Hye Young; Brinson, Robert G.; Le Grice, Stuart F. J.] NCI, RT Biochem Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
[Turner, Kevin B.; Fabris, Daniele] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA.
[Marino, John P.] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA.
[Marino, John P.] Natl Inst Stand & Technol, Rockville, MD 20850 USA.
RP Le Grice, SFJ (reprint author), NCI, RT Biochem Sect, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA.
EM legrices@mail.nih.gov
FU National Institutes of Health [GM59107, GM643208]; National Science
Foundation [CHE-0439067]; Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX This research was funded by National Institutes of Health grants GM59107
(to J. P. M.) and GM643208 (to D. F.), and grant CHE-0439067 from the
National Science Foundation ( to D. F.). S. F. J. L. G. was supported by
the intramural research program of the Center for Cancer Research,
National Cancer Institute, National Institutes of Health.
NR 40
TC 15
Z9 15
U1 2
U2 4
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI WOODBURY
PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA
SN 1355-8382
J9 RNA
JI RNA-Publ. RNA Soc.
PD AUG
PY 2009
VL 15
IS 8
BP 1605
EP 1613
DI 10.1261/rna.1615409
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 472IY
UT WOS:000268125000017
PM 19535461
ER
PT J
AU Kilts, T
Ameye, L
Syed-Picard, F
Ono, M
Berendsen, AD
Oldberg, A
Heegaard, AM
Bi, Y
Young, MF
AF Kilts, T.
Ameye, L.
Syed-Picard, F.
Ono, M.
Berendsen, A. D.
Oldberg, A.
Heegaard, A. -M.
Bi, Y.
Young, M. F.
TI Potential roles for the small leucine-rich proteoglycans biglycan and
fibromodulin in ectopic ossification of tendon induced by exercise and
in modulating rotarod performance
SO SCANDINAVIAN JOURNAL OF MEDICINE & SCIENCE IN SPORTS
LA English
DT Article
DE extracellular matrix; tendon; ectopic ossification; treadmill; rotarod
ID ABNORMAL COLLAGEN FIBRILS; MARROW STROMAL CELLS; II PROCOLLAGEN GENE;
DEFICIENT MICE; EXTRACELLULAR-MATRIX; TARGETED DISRUPTION; BONE;
OSTEOARTHRITIS; EXPRESSION; DECORIN
AB We present a detailed comparison of ectopic ossification (EO) found in tendons of biglycan (Bgn), fibromodulin (Fmod) single and double Bgn/Fmod-deficient (DKO) mice with aging. At 3 months, Fmod KO, Bgn KO and DKO displayed torn cruciate ligaments and EO in their quadriceps tendon, menisci and cruciate and patellar ligaments. The phenotype was the least severe in the Fmod KO, intermediate in the Bgn KO and the most severe in the DKO. This condition progressed with age in all three mouse strains and resulted in the development of large supernumerary sesmoid bones. To determine the role of exercise in the extent of EO, we subjected normal and DKO mice to a treadmill exercise 3 days a week for 4 weeks. In contrast to previous findings using more rigorous exercise regimes, the EO in moderately exercised DKO was decreased compared with unexercised DKO mice. Finally, DKO and Bgn KO mice tested using a rotarod showed a reduced ability to maintain their grip on a rotating cylinder compared with wild-type controls. In summary, we show (1) a detailed description of EO formed by Bgn, Fmod or combined depletion, (2) the role of exercise in modulating EO and (3) that Bgn and Fmod are critical in controlling motor function.
C1 [Kilts, T.; Syed-Picard, F.; Ono, M.; Berendsen, A. D.; Bi, Y.; Young, M. F.] NIDCR, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Ameye, L.] Nestle Res Ctr, Dept Nutr & Hlth, CH-1000 Lausanne, Switzerland.
[Oldberg, A.] Lund Univ, Dept Cell & Mol Biol, Lund, Sweden.
[Heegaard, A. -M.] Univ Copenhagen, Fac Pharmaceut Sci, Helsingor, Denmark.
RP Young, MF (reprint author), NIDCR, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, NIH, Bldg 30 Room 225, Bethesda, MD 20892 USA.
EM myoung@dir.nidcr.nih.gov
OI Syed-Picard, Fatima/0000-0002-8212-0254
FU Intramural Program of the National Institutes of Dental Research,
National Institutes of Health
FX This research was supported in part by the Intramural Program of the
National Institutes of Dental Research, National Institutes of Health.
NR 35
TC 14
Z9 14
U1 2
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0905-7188
J9 SCAND J MED SCI SPOR
JI Scand. J. Med. Sci. Sports
PD AUG
PY 2009
VL 19
IS 4
BP 536
EP 546
DI 10.1111/j.1600-0838.2009.00909.x
PG 11
WC Sport Sciences
SC Sport Sciences
GA 486JJ
UT WOS:000269192000010
PM 19422643
ER
PT J
AU Chamberlain, MC
Glantz, M
Groves, MD
Wilson, WH
AF Chamberlain, Marc C.
Glantz, Michael
Groves, Morris D.
Wilson, Wyndham H.
TI Diagnostic Tools for Neoplastic Meningitis: Detecting Disease,
Identifying Patient Risk, and Determining Benefit of Treatment
SO SEMINARS IN ONCOLOGY
LA English
DT Article
ID COMBINED-MODALITY THERAPY; CEREBROSPINAL-FLUID CYTOLOGY; METASTATIC
BREAST-CANCER; WHOLE-BRAIN RADIATION; ANGIOGENESIS-RELATED PROTEINS;
NERVOUS-SYSTEM INVOLVEMENT; ENDOTHELIAL GROWTH-FACTOR;
NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; LEPTOMENINGEAL METASTASES
AB Three methods are routinely used to diagnose neoplastic meningitis (NM): clinical signs and symptoms, cerebrospinal fluid (CSF) cytology, and magnetic resonance imaging (MRI) of the brain and spine. Clinical manifestations are often subtle or may be ascribed to other cancer complications, eg, treatment-related disorders or brain parenchymal metastases. CSF cytology has a high specificity (>95%), but its sensitivity is generally less than 50%. MRI sensitivity and specificity vary With the type of primary cancer, overall, MRI findings consistent with leptomeningeal disease are detected in fewer than 50% of NM patients. While most clinicians evaluate CSF cytology along with MRI and the clinical examination, underdiagnosis is a major problem, since many patients are both cytologically and radiographically negative. Failure to consider NM in the differential diagnosis magnifies the problem of underdiagnosis. CSF flow cytometry is particularly promising for evaluating NM from hematologic cancers, with a diagnostic sensitivity many fold greater than conventional cytology. Research has focused on identifying biochemical markers of tumor cells in the CSF. For example, molecules involved in CNS penetration (eg, matrix metalloproteinases and cathepsins), tumor cell tropism (eg, chemokines; CXCL8 and CCL18), and angiogenesis (eg, vascular endothelial growth factor) are elevated in the CSF of patients with NM. Evidence that some tumor types are more likely to infiltrate the CNS also has stimulated research into primary tumor markers predictive of CNS metastases. At present, there is no tumor marker or patient characteristic that reliably predicts the development of NM, and diagnosis still relies on suggestive signs and symptoms, positive CSF cytology, or a consistent MRI-all late manifestations of NM. Until techniques capable of detecting NM early are developed, increased awareness of the disease and standardized evaluation are likely to have the greatest impact on improving diagnosis and implementing earlier treatment. Semin Oncol 36 (Suppl 2):S35-S45 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Chamberlain, Marc C.] Univ Washington, Dept Neurol & Neurol Surg, Div Neurooncol, Seattle, WA 98109 USA.
[Glantz, Michael] Penn State Hershey Med Ctr, Dept Neurosurg, Hershey, PA USA.
[Groves, Morris D.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Chamberlain, MC (reprint author), Univ Washington, Dept Neurol & Neurol Surg, Div Neurooncol, 825 E Lake Ave E,Mail Stop G4-940, Seattle, WA 98109 USA.
EM chambemc@u.washington.edu
NR 56
TC 66
Z9 70
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD AUG
PY 2009
VL 36
IS 4
BP S35
EP S45
DI 10.1053/j.seminoncol.2009.05.005
PG 11
WC Oncology
SC Oncology
GA 482OX
UT WOS:000268899700005
PM 19660682
ER
PT J
AU Choudhary, S
Sudarshan, S
Choyke, PL
Prasad, SR
AF Choudhary, Shaile
Sudarshan, Sunil
Choyke, Peter L.
Prasad, Srinivasa R.
TI Renal Cell Carcinoma: Recent Advances in Genetics and Imaging
SO SEMINARS IN ULTRASOUND CT AND MRI
LA English
DT Article
ID HIPPEL-LINDAU-DISEASE; PARENCHYMAL SPARING SURGERY; TUMOR-SUPPRESSOR
PROTEIN; HOGG-DUBE-SYNDROME; HELICAL CT; PATHOLOGICAL CORRELATION;
HISTOLOGIC SUBTYPES; MESSENGER-RNA; KIDNEY CANCER; NEOPLASMS
AB Recent advances in molecular biology and cytogenetics have provided unique insights into the ontogeny, pathogenesis, and biological behavior of renal cell carcinoma. Renal cell carcinoma is now known to be a polymorphic malignant neoplasm consisting of several histologic subtypes demonstrating different biological profiles. Clear cell renal carcinoma, the most common histologic subtype, is predominantly associated with mutations involving the von Hippel-Lindau gene and elaboration of vascular and somatic growth factors. Clear cell renal cell carcinoma is thus typically hypervascular at imaging. By contrast, papillary renal cell carcinoma, the second most common subtype, is frequently hypovascular. Current molecular data on the biology of renal neoplasms have shown important diagnostic, therapeutic, and prognostic implications, Comprehensive knowledge of molecular pathways of carcinogenesis of renal cancers has allowed design of rational treatment protocols and posttreatment surveillance algorithms, thereby permitting optimal patient management. Semin Ultrasound CT MRI 30:315-325 (C) 2009 Elsevier Inc. All rights reserved.
C1 [Choudhary, Shaile; Prasad, Srinivasa R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA.
[Sudarshan, Sunil] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, San Antonio, TX 78229 USA.
[Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
RP Prasad, SR (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM prasads@uthscsa.edu
NR 61
TC 17
Z9 18
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0887-2171
J9 SEMIN ULTRASOUND CT
JI Semin. Ultrasound CT MRI
PD AUG
PY 2009
VL 30
IS 4
BP 315
EP 325
DI 10.1053/j.sult.2009.03.003
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 481CT
UT WOS:000268785400008
PM 19711643
ER
PT J
AU Alexander, MS
Anderson, KD
Biering-Sorensen, F
Blight, AR
Brannon, R
Bryce, TN
Creasey, G
Catz, A
Curt, A
Donovan, W
Ditunno, J
Ellaway, P
Finnerup, NB
Graves, DE
Haynes, BA
Heinemann, AW
Jackson, AB
Johnston, MV
Kalpakjian, CZ
Kleitman, N
Krassioukov, A
Krogh, K
Lammertse, D
Magasi, S
Mulcahey, MJ
Schurch, B
Sherwood, A
Steeves, JD
Stiens, S
Tulsky, DS
van Hedel, HJA
Whiteneck, G
AF Alexander, M. S.
Anderson, K. D.
Biering-Sorensen, F.
Blight, A. R.
Brannon, R.
Bryce, T. N.
Creasey, G.
Catz, A.
Curt, A.
Donovan, W.
Ditunno, J.
Ellaway, P.
Finnerup, N. B.
Graves, D. E.
Haynes, B. A.
Heinemann, A. W.
Jackson, A. B.
Johnston, M. V.
Kalpakjian, C. Z.
Kleitman, N.
Krassioukov, A.
Krogh, K.
Lammertse, D.
Magasi, S.
Mulcahey, M. J.
Schurch, B.
Sherwood, A.
Steeves, J. D.
Stiens, S.
Tulsky, D. S.
van Hedel, H. J. A.
Whiteneck, G.
TI Outcome measures in spinal cord injury: recent assessments and
recommendations for future directions
SO SPINAL CORD
LA English
DT Review
DE outcome tools; upper and lower limb; diagnostic tools; spinal cord
clinical trial targets; functional assessment; quality of life and
community participation
ID CLINICAL-TRIALS; ICCP PANEL; DATA SET; PSYCHOMETRIC PROPERTIES;
INDEPENDENCE MEASURE; VERSION III; PAIN SCALE; PARTICIPATION;
GUIDELINES; VALIDATION
AB Study design: Review by the spinal cord outcomes partnership endeavor (SCOPE), which is a broad-based international consortium of scientists and clinical researchers representing academic institutions, industry, government agencies, not-for-profit organizations and foundations.
Objectives: Assessment of current and evolving tools for evaluating human spinal cord injury (SCI) outcomes for both clinical diagnosis and clinical research studies.
Methods: a framework for the appraisal of evidence of metric properties was used to examine outcome tools or tests for accuracy, sensitivity, reliability and validity for human SCI.
Results: Imaging, neurological, functional, autonomic, sexual health, bladder/bowel, pain and psychosocial tools were evaluated. Several specific tools for human SCI studies have or are being developed to allow the more accurate determination for a clinically meaningful benefit (improvement in functional outcome or quality of life) being achieved as a result of a therapeutic intervention.
Conclusion: Significant progress has been made, but further validation studies are required to identify the most appropriate tools for specific targets in a human SCI study or clinical trial. Spinal Cord (2009) 47, 582-591; doi: 10.1038/sc.2009.18; published online 21 April 2009
C1 [Curt, A.; Krassioukov, A.; Steeves, J. D.] Univ British Columbia, ICORD, Vancouver, BC V5Z 1M9, Canada.
[Curt, A.; Krassioukov, A.; Steeves, J. D.] Vancouver Coastal Hlth, Vancouver, BC, Canada.
[Alexander, M. S.; Jackson, A. B.] Univ Alabama, Birmingham, AL USA.
[Anderson, K. D.] Univ Calif Irvine, Irvine, CA USA.
[Biering-Sorensen, F.] Rigshosp, Ctr Neurosci, DK-2100 Copenhagen, Denmark.
[Biering-Sorensen, F.] Univ Copenhagen, Copenhagen, Denmark.
[Blight, A. R.] Acorda Therapeut, Hawthorne, NY USA.
[Brannon, R.; Sherwood, A.] NIDRR, Washington, DC USA.
[Bryce, T. N.] Mt Sinai Sch Med, New York, NY USA.
[Creasey, G.] Stanford Univ, Palo Alto, CA 94304 USA.
[Catz, A.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel.
[Donovan, W.] Mem Hermann TIRR, Phys Med & Rehabil, Houston, TX USA.
[Ditunno, J.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Ellaway, P.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Finnerup, N. B.] Aarhus Univ Hosp, Danish Pain Res Ctr, DK-8000 Aarhus, Denmark.
[Graves, D. E.] Baylor Coll Med, Houston, TX 77030 USA.
[Haynes, B. A.] Alseres Pharmaceut, Hopkinton, MA USA.
[Heinemann, A. W.] Northwestern Univ, Sch Med, Chicago, IL USA.
[Heinemann, A. W.] Rehabil Inst Chicago, Chicago, IL 60611 USA.
[Johnston, M. V.] Univ Wisconsin, Milwaukee, WI 53201 USA.
[Kalpakjian, C. Z.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kleitman, N.] NINDS, NIH, Bethesda, MD 20892 USA.
[Lammertse, D.; Whiteneck, G.] Craig Hosp, Englewood, CO USA.
[Magasi, S.] Ctr Outcomes Res & Educ, Evanston, IL USA.
[Mulcahey, M. J.] Shriners Hosp Crippled Children, Philadelphia, PA USA.
[Schurch, B.; van Hedel, H. J. A.] Balgrist Hosp, Zurich, Switzerland.
[Stiens, S.] Vet Affairs Puget Sound Hlth Care, Seattle, WA USA.
[Tulsky, D. S.] Kessler Med Rehabil Res & Educ Ctr, W Orange, NJ USA.
RP Steeves, JD (reprint author), Univ British Columbia, ICORD, 818 W 10th Ave, Vancouver, BC V5Z 1M9, Canada.
EM steeves@icord.org
RI Heinemann, Allen /K-6283-2012;
OI Heinemann, Allen /0000-0003-2782-7326; Sherwood,
Arthur/0000-0002-0110-4317; Kleitman, Naomi/0000-0003-1089-0257;
Lammertse, Daniel/0000-0003-4590-2481; van Hedel,
Hubertus/0000-0002-9577-5049
FU ASIA; ICCP; ISCoS; our corporate partners
FX We are grateful for the support of ASIA, ICCP, ISCoS and our corporate
partners.
NR 61
TC 76
Z9 77
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1362-4393
J9 SPINAL CORD
JI Spinal Cord
PD AUG
PY 2009
VL 47
IS 8
BP 582
EP 591
DI 10.1038/sc.2009.18
PG 10
WC Clinical Neurology; Rehabilitation
SC Neurosciences & Neurology; Rehabilitation
GA 479TT
UT WOS:000268684500004
PM 19381157
ER
PT J
AU Fay, MP
Noubary, F
Saul, A
AF Fay, Michael P.
Noubary, Farzad
Saul, Allan
TI Robust Noninferiority Tests for Potency of a Test Drug Against a
Reference Drug
SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH
LA English
DT Article
DE Assay; Delta method; Fieller's Theorem; Inverse regression; Sandwich
variance estimator
AB In comparing test formulations of a drug product to reference formulations it is necessary to check that the test formulation has as much biologic activity as the reference within some indifference zone. A modern method for testing this relative potency is to fit a nonlinear model of the dose-response curve, constrained such that the dose-response of the test is modeled with the same function as the reference except for a multiplicative parameter on the dose. This method works well as long as the nonlinear model fits the data. Although tests of this fit are mentioned in the literature, how relative potency should be measured when those tests fail has not been addressed. We study the use of the sandwich estimator of variance for this noninferiority potency problem when the model does not fit the data. We focus on the simple linear model. Using the sandwich variance, the inferences are asymptotically valid even if the model does not hold. We discuss interpretation of the results under the misspecified linear model, and show by simulation that the method performs well in some practical cases. Finally, we give advice for designing a study that uses these methods.
C1 [Fay, Michael P.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Noubary, Farzad] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Fay, MP (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr MSC 7609, Bethesda, MD 20892 USA.
EM mfay@niaid.nih.gov; noubary@fas.harvard.edu; Allan.Saul@novartis.com
RI Saul, Allan/I-6968-2013
OI Saul, Allan/0000-0003-0665-4091
FU Intramural NIH HHS [Z99 AI999999]
NR 18
TC 0
Z9 0
U1 0
U2 1
PU AMER STATISTICAL ASSOC
PI ALEXANDRIA
PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA
SN 1946-6315
J9 STAT BIOPHARM RES
JI Stat. Biopharm. Res.
PD AUG
PY 2009
VL 1
IS 3
BP 291
EP 300
DI 10.1198/sbr.2009.0023
PG 10
WC Mathematical & Computational Biology; Statistics & Probability
SC Mathematical & Computational Biology; Mathematics
GA V17ZK
UT WOS:000207974900007
PM 19746196
ER
PT J
AU Xue, HP
Wu, S
Papadeas, ST
Spusta, S
Swistowska, AM
MacArthur, CC
Mattson, MP
Maragakis, NJ
Capecchi, MR
Rao, MS
Zeng, XM
Liu, Y
AF Xue, Haipeng
Wu, Sen
Papadeas, Sophia T.
Spusta, Steve
Swistowska, Anna Maria
MacArthur, Chad C.
Mattson, Mark P.
Maragakis, Nicholas J.
Capecchi, Mario R.
Rao, Mahendra S.
Zeng, Xianmin
Liu, Ying
TI A Targeted Neuroglial Reporter Line Generated by Homologous
Recombination in Human Embryonic Stem Cells
SO STEM CELLS
LA English
DT Article
DE Gene targeting; Neurogenesis; Gliogenesis; Basic helix-loop-helix
transcription factor; Olig2; Embryonic stem cell
ID DEVELOPING SPINAL-CORD; OLIGODENDROCYTE DIFFERENTIATION; MOTOR-NEURONS;
DIRECTED DIFFERENTIATION; GENETIC-MODIFICATION; PROGENITOR CELLS;
PRECURSOR CELLS; NEURAL CELLS; FACTOR OLIG2; IN-VIVO
AB In this study, we targeted Olig2, a basic helix-loop-helix transcription factor that plays an important role in motoneuron and oligodendrocyte development, in human embryonic stem cell (hESC) line BG01 by homologous recombination. One allele of Olig2 locus was replaced by a green fluorescent protein (GFP) cassette with a targeting efficiency of 5.7%. Targeted clone R-Olig2 (like the other clones) retained pluripotency, typical hESC morphology, and a normal parental karyotype 46,XY. Most importantly, GFP expression recapitulated endogenous Olig2 expression when R-Olig2 was induced by sonic hedgehog and retinoic acid, and GFP-positive cells could be purified by fluorescence-activated cell sorting. Consistent with previous reports on rodents, early GFP-expressing cells appeared biased to a neuronal fate, whereas late GFP-expressing cells appeared biased to an oligodendrocytic fate. This was corroborated by myoblast coculture, transplantation into the rat spinal cords, and whole genome expression profiling. The present work reports an hESC reporter line generated by homologous recombination targeting a neural lineage-specific gene, which can be differentiated and sorted to obtain pure neural progenitor populations. STEM CELLS 2009;27:1836-1846
C1 [Xue, Haipeng; MacArthur, Chad C.; Rao, Mahendra S.; Liu, Ying] Life Technol Corp, Primary & Stem Cell Syst, Carlsbad, CA 92008 USA.
[Xue, Haipeng; Mattson, Mark P.; Rao, Mahendra S.; Liu, Ying] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Wu, Sen; Capecchi, Mario R.] Univ Utah, Dept Human Genet, Howard Hughes Med Inst, Salt Lake City, UT USA.
[Papadeas, Sophia T.; Maragakis, Nicholas J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Spusta, Steve; Swistowska, Anna Maria] Buck Inst Age Res, Novato, CA USA.
RP Liu, Y (reprint author), Life Technol Corp, Primary & Stem Cell Syst, 5781 Van Allen Way, Carlsbad, CA 92008 USA.
EM ying.liu1@invitrogen.com
RI Mattson, Mark/F-6038-2012; Aksoy, Irene/O-2238-2013
OI Aksoy, Irene/0000-0003-4353-5876
FU Robert Packard Center for ALS Research award; National Institute on
Aging (NIH) Intramural Research Program; Intramural Research Training
Awards; California Institute for Regenerative Medicine [CL1-00501-1];
Larry L. Hillblom Foundation; Life Technologies Corporation.
FX We thank Dr. Y. Han for technical assistance and all members of our
laboratories for constant stimulating discussions. M. S. R. acknowledges
the contributions of Dr. S. Rao, which made undertaking this project
possible. This work was supported a by Robert Packard Center for ALS
Research award (to Y. L.), National Institute on Aging (NIH) Intramural
Research Program (M. S. R. and M. P. M.), Intramural Research Training
Awards (to Y. L.), California Institute for Regenerative Medicine Grant
CL1-00501-1 (to X. Z.), the Larry L. Hillblom Foundation (X. Z.), and
Life Technologies Corporation.
NR 54
TC 45
Z9 45
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1066-5099
J9 STEM CELLS
JI Stem Cells
PD AUG
PY 2009
VL 27
IS 8
BP 1836
EP 1846
DI 10.1002/stem.129
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 497HZ
UT WOS:000270050900015
PM 19544414
ER
PT J
AU Maas, R
Xanthakis, V
Polak, JF
Schwedhelm, E
Sullivan, LM
Benndorf, R
Schulze, F
Vasan, RS
Wolf, PA
Boger, RH
Seshadri, S
AF Maas, Renke
Xanthakis, Vanessa
Polak, Joseph F.
Schwedhelm, Edzard
Sullivan, Lisa M.
Benndorf, Ralf
Schulze, Friedrich
Vasan, Ramachandran S.
Wolf, Philip A.
Boeger, Rainer H.
Seshadri, Sudha
TI Association of the Endogenous Nitric Oxide Synthase Inhibitor ADMA With
Carotid Artery Intimal Media Thickness in the Framingham Heart Study
Offspring Cohort
SO STROKE
LA English
DT Article
DE carotid intimal medial thickness; epidemiology; risk factors
ID ASYMMETRIC DIMETHYLARGININE ADMA; STAGE RENAL-DISEASE;
MYOCARDIAL-INFARCTION; RISK-FACTOR; CARDIOVASCULAR HEALTH; VASCULAR
INJURY; PLASMA-LEVELS; OLDER-ADULTS; SHEAR-STRESS; FOLLOW-UP
AB Background and Purpose-Higher plasma concentrations of the endogenous nitric oxides synthase inhibitor asymmetrical dimethylarginine (ADMA) are associated with increased risk of cardiovascular and cerebrovascular events and death, presumably by promoting endothelial dysfunction and subclinical atherosclerosis. We hypothesized that plasma ADMA concentrations are positively related to common carotid artery intimal-media thickness (CCA-IMT) and to internal carotid (ICA)/bulb IMT.
Methods-We investigated the cross-sectional relations of plasma ADMA with CCA-IMT and ICA/bulb IMT in 2958 Framingham Heart Study participants (mean age, 58 years; 55% women).
Results-In unadjusted analyses, ADMA was positively related to both CCA-IMT (beta per SD increment, 0.012; P < 0.001) and ICA/bulb IMT (beta per SD increment, 0.059; P < 0.001). In multivariable analyses (adjusting for age, sex, systolic blood pressure, antihypertensive treatment, smoking status, diabetes, BMI, total-to-HDL cholesterol ratio, log C-reactive protein, and serum creatinine), plasma ADMA was not associated with CCA-IMT (P = 0.991), but remained significantly and positively related to ICA/bulb IMT (beta per SD increment, 0.0246; P = 0.002).
Conclusions-In our large community-based sample, we observed that higher plasma ADMA concentrations were associated with greater ICA/bulb IMT, but not with CCA-IMT. These data are consistent with the notion that ADMA promotes subclinical atherosclerosis in a site-specific manner, with a greater proatherogenic influence at known vulnerable sites in the arterial tree. (Stroke. 2009; 40: 2715-2719.)
C1 [Maas, Renke] Univ Erlangen Nurnberg, Inst Expt & Clin Pharmacol & Toxicol, Erlangen, Germany.
[Maas, Renke; Schwedhelm, Edzard; Benndorf, Ralf; Schulze, Friedrich; Boeger, Rainer H.] Univ Med Ctr Hamburg Eppendorf, Clin Pharmacol Unit, Inst Expt & Clin Pharmacol, Hamburg, Germany.
[Xanthakis, Vanessa; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Polak, Joseph F.] Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA USA.
[Sullivan, Lisa M.; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 E Concord St, Boston, MA 02118 USA.
EM suseshad@bu.edu
OI Seshadri, Sudha/0000-0001-6135-2622; Ramachandran,
Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149
FU National Institutes of Health/ National Heart, Lung, and Blood Institute
[N01- HC- 25195, N01HV28178, 2K24HL04334]; National Institute on Aging
[R01 AG16495, AG08122]
FX This work was supported by National Institutes of Health/ National
Heart, Lung, and Blood Institute Contract N01- HC- 25195, N01HV28178,
and 2K24HL04334, Dr Vasan), the National Institute on Aging ( R01
AG16495; AG08122, Dr Wolf; and AG033193, Dr Seshadri), the National
Institute of Neurological Disorders and Stroke ( R01 NS17950, Dr Wolf),
and the Deutsche Forschungsgemeinschaft grant ( Bo1431/ 4- 1, Dr Bo "
ger). The content is solely the responsibility of the authors and does
not necessarily represent the official views of NINDS, NHLBI, NIA, or
NIH.
NR 46
TC 28
Z9 29
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD AUG
PY 2009
VL 40
IS 8
BP 2715
EP 2719
DI 10.1161/STROKEAHA.109.552539
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 475UN
UT WOS:000268387000011
PM 19498184
ER
PT J
AU Hayes, LM
AF Hayes, Lindsay M.
TI Juvenile Suicide in Confinement-Findings from the First National Survey
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID BEHAVIOR; POPULATION; DETENTION; OFFENDERS; YOUTH
AB Findings from the first national survey on juvenile suicide in confinement are provided, and include the extent and distribution of juvenile suicides, as well as descriptive data on demographic characteristics of each victim, incident, and juvenile facility which sustained the suicide. Among the significant findings were that suicides were evenly distributed, i.e., the same number of deaths occurred within the first few days of confinement as occurred over many months of confinement; most deaths occurred during traditional waking hours; a strong association between room confinement and suicide was found, and no relationship between intoxication and suicide was found. Suicide prevention resources were found to be particularly lacking in juvenile detention centers that experienced suicides.
C1 Natl Ctr Inst & Alternat, Mansfield, MA 02048 USA.
RP Hayes, LM (reprint author), Natl Ctr Inst & Alternat, 40 Lantern Lane, Mansfield, MA 02048 USA.
EM lhayesta@msn.com
NR 29
TC 6
Z9 6
U1 1
U2 3
PU GUILFORD PUBLICATIONS INC
PI NEW YORK
PA 72 SPRING STREET, NEW YORK, NY 10012 USA
SN 0363-0234
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD AUG
PY 2009
VL 39
IS 4
BP 353
EP 363
PG 11
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA 483CV
UT WOS:000268940500001
PM 19792977
ER
PT J
AU Hui, TP
Modarres, R
Zheng, G
AF Hui, Terrence P.
Modarres, Reza
Zheng, Gang
TI Pseudo maximum likelihood estimates using ranked set sampling with
applications to estimating correlation
SO TEST
LA English
DT Article
DE Ranked set sampling; Concomitant variable; Bivariate normal
distribution; Pseudo maximum likelihood estimator
ID CORRELATION-COEFFICIENT; REGRESSION
AB Suppose theta is the parameter of interest and lambda is the nuisance parameter. When obtaining the maximum likelihood estimator (MLE) of theta in the presence of lambda requires intensive computation, the pseudo MLE of theta, based on a pseudo likelihood function, can be used. Gong and Samaniego (Ann. Stat. 9:861-869, 1981) proposed a pseudo MLE (PMLE) based on simple random samples. Ranked set sampling has been applied to the bivariate variables (X,Y) where measuring one of the variables is difficult or costly. In this paper, we obtain the pseudo MLE of the correlation coefficient from a bivariate normal distribution (X,Y) based on ranked set samples, assuming that Y is difficult or more expensive to measure and that the mean and variance of Y are the nuisance parameters. The PMLE is compared with three other estimators of the correlation coefficient. Simulations show that the PMLE is more (less) efficient than other estimators, depending on value of rho. Testing of soil contamination provides an example of the use of the methods.
C1 [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Modarres, Reza] George Washington Univ, Dept Stat, Washington, DC 20052 USA.
RP Zheng, G (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA.
EM zhengg@nhlbi.nih.gov
NR 14
TC 0
Z9 0
U1 1
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1133-0686
J9 TEST
JI Test
PD AUG
PY 2009
VL 18
IS 2
BP 365
EP 380
DI 10.1007/s11749-008-0096-8
PG 16
WC Statistics & Probability
SC Mathematics
GA 460DC
UT WOS:000267165800013
ER
PT J
AU Chavakis, E
Choi, EY
Chavakis, T
AF Chavakis, Emmanouil
Choi, Eun Young
Chavakis, Triantafyllos
TI Novel aspects in the regulation of the leukocyte adhesion cascade
SO THROMBOSIS AND HAEMOSTASIS
LA English
DT Review
DE Adhesion receptors; cell-cell interactions; endothelial cells;
inflammation; integrins
ID ENDOTHELIAL-CELL-INTERACTIONS; EXTRACELLULAR ADHERENCE PROTEIN;
NEUTROPHIL TRANSENDOTHELIAL MIGRATION; FUNCTION-ASSOCIATED ANTIGEN-1;
ISCHEMIA-REPERFUSION INJURY; INFLAMMATION IN-VIVO;
STAPHYLOCOCCUS-AUREUS; INTEGRIN ACTIVATION; CYTOPLASMIC DOMAIN; LFA-1
ACTIVATION
AB Leukocyte recruitment plays a major role in the immune response to infectious pathogens and during inflammatory and autoimmune disorders. The process of leukocyte extravasation from the blood into the inflamed tissue requires a complex cascade of adhesive events between the leukocytes and the endothelium including leukocyte rolling, adhesion and trans-endothelial migration. Leukocyte-endothelial interactions are mediated by tightly regulated binding interactions between adhesion receptors on both cells. In this regard, leukocyte adhesion onto the endothelium is governed by leukocyte integrins and their endothelial counter-receptors of the immunoglobulin superfamily. The present review will focus on novel aspects with respect to the modulation of the leukocyte adhesion cascade.
C1 [Choi, Eun Young; Chavakis, Triantafyllos] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Chavakis, Emmanouil] Goethe Univ Frankfurt, Dept Internal Med 3, Inst Cardiovasc Regenerat, Frankfurt, Germany.
RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Rm 5B17, Bethesda, MD 20892 USA.
EM chavakist@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010790-01, Z01 BC010663-03]
NR 133
TC 38
Z9 38
U1 1
U2 2
PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN
PI STUTTGART
PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY
SN 0340-6245
J9 THROMB HAEMOSTASIS
JI Thromb. Haemost.
PD AUG
PY 2009
VL 102
IS 2
BP 191
EP 197
DI 10.1160/TH08-12-0844
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 486LR
UT WOS:000269198500004
PM 19652868
ER
PT J
AU Engle, SK
Jordan, WH
Pritt, ML
Chiang, AY
Davis, MA
Zimmermann, JL
Rudmann, DG
Heinz-Taheny, KM
Irizarry, AR
Yamamoto, Y
Mendel, D
Schultze, AE
Cornwell, PD
Watson, DE
AF Engle, Steven K.
Jordan, William H.
Pritt, Michael L.
Chiang, Alan Y.
Davis, Myrtle A.
Zimmermann, John L.
Rudmann, Daniel G.
Heinz-Taheny, Kathleen M.
Irizarry, Armando R.
Yamamoto, Yumi
Mendel, David
Schultze, A. Eric
Cornwell, Paul D.
Watson, David E.
TI Qualification of Cardiac Troponin I Concentration in Mouse Serum Using
Isoproterenol and Implementation in Pharmacology Studies to Accelerate
Drug Development
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE troponin; biomarker; cardiac; necrosis; drug development; mouse
ID MYOCARDIAL INJURY; SIGNALING EVENTS; FLOW-CYTOMETRY; BIOMARKER; RELEASE;
PROTEIN; INFARCTION; TOXICITY; NECROSIS; ANIMALS
AB Cardiac troponin I is a useful biomarker of myocardial injury, but its use in mice and application to early drug discovery are not well described. The authors investigated the relationship between cTnI concentration in serum and histologic lesions in heart tissue from mice treated with isoproterenol (ISO). Cardiac TnI concentrations in serum increased in a dose-dependant manner and remained increased twenty-four to forty-eight hours after a single administration of isoproterenol. Increased cTnI concentration was of greater magnitude and longer duration than increased fatty acid binding protein 3 concentration, aspartate aminotransferase activity, and creatine kinase activity in serum. Isoproterenol-induced increases in cTnI concentrations were both greater and more sustained in BALB/c than in CD1 mice and correlated with incidence and severity of lesions observed in heart sections from both strains. In drug development studies in BALB/c mice with novel kinase inhibitors, cTnI concentration was a reliable stand-alone biomarker of cardiac injury and was used in combination with measurements of in vivo target inhibition to demonstrate an off-target contribution to cardiotoxicity. Additional attributes, including low cost and rapid turnaround time, made cTnI concentration in serum invaluable for detecting cardiotoxicity, exploring structure activity relationships, and prioritizing development of compounds with improved safety profiles early in drug discovery.
C1 [Engle, Steven K.; Jordan, William H.; Pritt, Michael L.; Chiang, Alan Y.; Davis, Myrtle A.; Zimmermann, John L.; Rudmann, Daniel G.; Heinz-Taheny, Kathleen M.; Irizarry, Armando R.; Yamamoto, Yumi; Mendel, David; Schultze, A. Eric; Cornwell, Paul D.; Watson, David E.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA.
[Davis, Myrtle A.] NCI, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Zimmermann, John L.] Vet Path Serv Inc, Mason, OH 45040 USA.
RP Engle, SK (reprint author), Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA.
EM Englesk@lilly.com; Davewatson@lilly.com
FU Eli Lilly and Company
FX The studies described in this article were funded by Eli Lilly and
Company. The authors have not declared any other conflicting interests.
NR 33
TC 15
Z9 16
U1 0
U2 6
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 AUG
PY 2009
VL 37
IS 5
BP 617
EP 628
DI 10.1177/0192623309339502
PG 12
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 476WF
UT WOS:000268476400006
PM 19549929
ER
PT J
AU Elmore, SA
Peddada, SD
AF Elmore, Susan A.
Peddada, Shyamal D.
TI Points to Consider on the Statistical Analysis of Rodent Cancer Bioassay
Data When Incorporating Historical Control Data
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE boxplot; IQR; lower quartile; median; range; upper quartile; historical
control data
ID INCREASED CARCINOGENICITY; CONTROL INFORMATION; TREND TESTS;
PROPORTIONS; MORTALITY
AB Researchers routinely use historical control data (HCD) when analyzing rodent carcinogenicity data obtained in a particular study. Although the concurrent control group is considered to be the most relevant group to compare with the dose groups, the HCD provides a broader perspective to assist in understanding the significance of the current study. The HCD is used to provide information about the incidences of spontaneous tumors and malignant systemic disorders such as lymphoma and leukemia. This article presents some possible ways of incorporating the HCD when analyzing data from a rodent cancer bioassay. Specifically, exploratory (informal) and formal statistical procedures for analyzing such data are reviewed. The boxplot is presented as an exploratory tool that describes the current data in the context of the distribution of the HCD. It will also identify potential outliers that would not be otherwise be flagged using standard methods such as the mean, standard deviation, and range. The various options for the statistical analysis of HCD presented here do not necessarily represent standard practice.
C1 [Elmore, Susan A.] NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Peddada, Shyamal D.] NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA.
RP Elmore, SA (reprint author), NIEHS, Natl Toxicol Program, Cellular & Mol Pathol Branch, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM elmore@niehs.nih.gov
RI Peddada, Shyamal/D-1278-2012
FU NIH; National Institute of Environmental Health Sciences [Z01
ES101744-04]
FX The authors wish to thank Ms. Elizabeth Ney of the National Institute of
Environmental Health Sciences (NIEHS) for preparation of the IQR and
boxplot figures and members of the Society of Toxicologic Pathology
Historical Control Data Working Group for helpful discussion and review.
This research was supported ( in part) by the Intramural Research
Program of the NIH, National Institute of Environmental Health Sciences
(Z01 ES101744-04). We also wish to thank Drs. Gregg Dinse (NIEHS), Grace
Kissling (NIEHS), Walter Piegorsch (U. Arizona) and John Peckham (EPL)
for their helpful comments which improved the presentation of this
manuscript.
NR 20
TC 14
Z9 15
U1 0
U2 12
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 AUG
PY 2009
VL 37
IS 5
BP 672
EP 676
DI 10.1177/0192623309339606
PG 5
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 476WF
UT WOS:000268476400011
PM 19516052
ER
PT J
AU Keenan, C
Elmore, S
Francke-Carroll, S
Kerlin, R
Peddada, S
Pletcher, J
Rinke, M
Schmidt, SP
Taylor, I
Wolf, DC
AF Keenan, Charlotte
Elmore, Susan
Francke-Carroll, Sabine
Kerlin, Roy
Peddada, Shyamal
Pletcher, John
Rinke, Matthias
Schmidt, Stephen Peter
Taylor, Ian
Wolf, Douglas C.
TI Potential for a Global Historical Control Database for Proliferative
Rodent Lesions
SO TOXICOLOGIC PATHOLOGY
LA English
DT Editorial Material
C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA.
[Elmore, Susan] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Francke-Carroll, Sabine] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Pletcher, John] Charles River, Frederick, MD 21701 USA.
[Rinke, Matthias] Bayer Schering Pharma AG, Wuppertal, Germany.
[Kerlin, Roy; Schmidt, Stephen Peter] Pfizer Inc, Groton, CT 06340 USA.
[Taylor, Ian] Huntingdon Life Sci, Eye IP23 7PX, Suffolk, England.
[Wolf, Douglas C.] US EPA, Res Triangle Pk, NC 27711 USA.
RP Keenan, C (reprint author), GlaxoSmithKline Inc, 709 Swedeland Rd,UE0360, King Of Prussia, PA 19406 USA.
EM charlotte.m.keenan@gsk.com
RI Peddada, Shyamal/D-1278-2012
FU Intramural NIH HHS
NR 3
TC 3
Z9 3
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 AUG
PY 2009
VL 37
IS 5
BP 677
EP 678
DI 10.1177/0192623309336155
PG 2
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 476WF
UT WOS:000268476400012
PM 19638441
ER
PT J
AU Keenan, C
Elmore, S
Francke-Carroll, S
Kemp, R
Kerlin, R
Peddada, S
Pletcher, J
Rinke, M
Schmidt, SP
Taylor, I
Wolf, DC
AF Keenan, Charlotte
Elmore, Susan
Francke-Carroll, Sabine
Kemp, Ramon
Kerlin, Roy
Peddada, Shyamal
Pletcher, John
Rinke, Matthias
Schmidt, Stephen Peter
Taylor, Ian
Wolf, Douglas C.
TI Best Practices for Use of Historical Control Data of Proliferative
Rodent Lesions
SO TOXICOLOGIC PATHOLOGY
LA English
DT Editorial Material
DE historical control data; rodent tumors; carcinogenicity studies; best
practices
ID NATIONAL TOXICOLOGY PROGRAM; SPRAGUE-DAWLEY RATS; DUAL CONTROL-GROUPS;
WISTAR RATS; BODY-WEIGHT; SPONTANEOUS TUMORS; B6C3F1 MICE; JOINT
PUBLICATION; REVISED GUIDES; NACAD GROUPS
C1 [Keenan, Charlotte] GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA.
[Elmore, Susan] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Francke-Carroll, Sabine] US FDA, CFSAN, College Pk, MD USA.
[Kemp, Ramon] Merck Res Labs, Riom, France.
[Kerlin, Roy; Schmidt, Stephen Peter] Pfizer Inc, Groton, CT 06340 USA.
[Pletcher, John] Charles River, Frederick, MD USA.
[Rinke, Matthias] Bayer Schering Pharma AG, Wuppertal, Germany.
[Wolf, Douglas C.] US EPA, Res Triangle Pk, NC 27711 USA.
RP Keenan, C (reprint author), GlaxoSmithKline Inc, 79 Swedeland Rd,UE0360, King Of Prussia, PA 19406 USA.
EM charlotte.m.keenan@gsk.com
RI Peddada, Shyamal/D-1278-2012
FU Intramural NIH HHS
NR 114
TC 43
Z9 44
U1 0
U2 7
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 AUG
PY 2009
VL 37
IS 5
BP 679
EP 693
DI 10.1177/0192623309336154
PG 15
WC Pathology; Toxicology
SC Pathology; Toxicology
GA 476WF
UT WOS:000268476400013
PM 19454599
ER
PT J
AU Walker, NJ
Bucher, JR
AF Walker, Nigel J.
Bucher, John R.
TI A 21st Century Paradigm for Evaluating the Health Hazards of Nanoscale
Materials?
SO TOXICOLOGICAL SCIENCES
LA English
DT Editorial Material
DE nanoparticles; risk assessment
ID WALL CARBON NANOTUBES; PULMONARY TOXICITY; NANOTECHNOLOGY;
NANOPARTICLES; NANOMATERIALS; SAFE
AB Over the past 5 years we have seen an increase in the attention focused on the assessment of the potential health risk posed by nanoscale materials. The diversity of these materials with respect to size, composition, and surface properties, and the rapid pace of their development and commercialization, poses significant challenges to traditional toxicity testing paradigms. At the same time the potential use of new high throughput "predictive "toxicity" strategies, such as that envisioned in the recent NRC report "Toxicity Testing in the 21st Century," have emerged as possible solutions to deal with the issue of how to assess the safety of the thousands of chemicals to which humans are potentially exposed. In this forum article we discuss how in some respects, the emergence of diverse engineered nanomaterials offers a tailor-made test case for the application of a new paradigm for assessing human heath risks. However, although this approach may have merit in the study of some specific nanomaterials, this approach does not consider the complexity involved in utilizing in vitro cell culture toxicology methods to evaluate the potential hazard of the wide array of current and future engineered nanomaterials.
C1 [Walker, Nigel J.; Bucher, John R.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Walker, NJ (reprint author), NIEHS, Natl Toxicol Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM walker3@niehs.nih.gov
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU Intramural NIH HHS
NR 21
TC 46
Z9 47
U1 1
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2009
VL 110
IS 2
BP 251
EP 254
DI 10.1093/toxsci/kfp106
PG 4
WC Toxicology
SC Toxicology
GA 469IM
UT WOS:000267889700001
PM 19468057
ER
PT J
AU Ellinger-Ziegelbauer, H
Fostel, JM
Aruga, C
Bauer, D
Boitier, E
Deng, SB
Dickinson, D
Le Fevre, AC
Fornace, AJ
Grenet, O
Gu, YZ
Hoflack, JC
Shiiyama, M
Smith, R
Snyder, RD
Spire, C
Tanaka, G
Aubrechtk, J
AF Ellinger-Ziegelbauer, Heidrun
Fostel, Jennifer M.
Aruga, Chinami
Bauer, Daniel
Boitier, Eric
Deng, Shibing
Dickinson, Donna
Le Fevre, Anne-Celine
Fornace, Albert J., Jr.
Grenet, Olivier
Gu, Yizhong
Hoflack, Jean-Christophe
Shiiyama, Masako
Smith, Roger
Snyder, Ronald D.
Spire, Catherine
Tanaka, Gotaro
Aubrechtk, Jiri
TI Characterization and Interlaboratory Comparison of a Gene Expression
Signature for Differentiating Genotoxic Mechanisms
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE gene expression; genetic toxicology; risk assessment
ID DISCRIMINATE RODENT CARCINOGENS; RISK-ASSESSMENT; HUMAN-CELLS;
DNA-DAMAGE; RELATIVE PREDICTIVITY; FUNCTIONAL GENOMICS; PROFILE
ANALYSIS; STRESS; IDENTIFICATION; INDUCTION
AB The genotoxicity testing battery is highly sensitive for detection of chemical carcinogens. However, it features a low specificity and provides only limited mechanistic information required for risk assessment of positive findings. This is especially important in case of positive findings in the in vitro chromosome damage assays, because chromosome damage may be also induced secondarily to cell death. An increasing body of evidence indicates that toxicogenomic analysis of cellular stress responses provides an insight into mechanisms of action of genotoxicants. To evaluate the utility of such a toxicogenomic analysis we evaluated gene expression profiles of TK6 cells treated with four model genotoxic agents using a targeted high density real-time PCR approach in a multilaboratory project coordinated by the Health and Environmental Sciences Institute Committee on the Application of Genomics in Mechanism-based Risk Assessment. We show that this gene profiling technology produced reproducible data across laboratories allowing us to conclude that expression analysis of a relevant gene set is capable of distinguishing compounds that cause DNA adducts or double strand breaks from those that interfere with mitotic spindle function or that cause chromosome damage as a consequence of cytotoxicity. Furthermore, our data suggest that the gene expression profiles at early time points are most likely to provide information relevant to mechanisms of genotoxic damage and that larger gene expression arrays will likely provide richer information for differentiating molecular mechanisms of action of genotoxicants. Although more compounds need to be tested to identify a robust molecular signature, this study confirms the potential of toxicogenomic analysis for investigation of genotoxic mechanisms.
C1 [Deng, Shibing; Dickinson, Donna; Aubrechtk, Jiri] Pfizer Global R&D, Groton, CT 06355 USA.
[Ellinger-Ziegelbauer, Heidrun] Bayer HealthCare, Special Toxicol, D-42096 Wuppertal, Germany.
[Fostel, Jennifer M.] NIEHS, Global Hlth Sector, SRA Int Inc, Res Triangle Pk, NC 27709 USA.
[Aruga, Chinami] Mitsubishi Tanabe Pharma Corp, Safety Res Lab, Kisaradu, Chiba 2920818, Japan.
[Bauer, Daniel; Grenet, Olivier] Novartis Pharma AG, CH-4002 Basel, Switzerland.
[Boitier, Eric; Le Fevre, Anne-Celine] Sanofi Aventis R&D, Drug Safety Evaluat, F-94403 Vitry Sur Seine, France.
[Fornace, Albert J., Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
[Gu, Yizhong; Smith, Roger; Snyder, Ronald D.] Schering Plough Res Inst, Summit, NJ 07901 USA.
[Hoflack, Jean-Christophe] F Hoffmann La Roche & Cie AG, CH-4070 Basel, Switzerland.
[Shiiyama, Masako] Meiji Seika Kaisha Ltd, Pharmaceut Res Ctr, Toxicol Lab, Yokohama, Kanagawa 2228567, Japan.
[Spire, Catherine] Toxicol Ctr, Biol SERVIER, F-45520 Gidy, France.
[Tanaka, Gotaro] Taiho Pharmaceut Co Ltd, Personalized Med Res Lab, Tokushima, Japan.
RP Aubrechtk, J (reprint author), Pfizer Global R&D, Eastern Point Rd, Groton, CT 06355 USA.
EM jiri.aubrecht@pfizer.com
OI Fornace, Albert/0000-0001-9695-085X
FU National Institute of Environmental Health Science [HHSN273200700046U]
FX Contributions by J. Fostel were supported by the Division of Intramural
research of the National Institute of Environmental Health Science,
under contract (HHSN273200700046U).
NR 54
TC 35
Z9 36
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
J9 TOXICOL SCI
JI Toxicol. Sci.
PD AUG
PY 2009
VL 110
IS 2
BP 341
EP 352
DI 10.1093/toxsci/kfp103
PG 12
WC Toxicology
SC Toxicology
GA 469IM
UT WOS:000267889700009
PM 19465456
ER
PT J
AU Liu, J
Qu, W
Kadiiska, MB
AF Liu, Jie
Qu, Wei
Kadiiska, Maria B.
TI Role of oxidative stress in cadmium toxicity and carcinogenesis
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Review
DE Cadmium; Reactive oxygen species; Spin-trapping technique; Chronic
toxicity; Adaptation; Malignant transformation
ID INDUCED MALIGNANT-TRANSFORMATION; PROSTATE EPITHELIAL-CELLS; INDUCED
HEPATOTOXICITY; GENE-EXPRESSION; APOPTOTIC RESISTANCE;
LIPID-PEROXIDATION; ELECTRON-TRANSFER; DNA METHYLATION; FREE-RADICALS;
NULL MICE
AB Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-kappa B, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis. Published by Elsevier Inc
C1 [Liu, Jie; Qu, Wei] NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Kadiiska, Maria B.] NIEHS, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA.
RP Liu, J (reprint author), NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, 111 TW Alexander Dr,MD F0-09, Res Triangle Pk, NC 27709 USA.
EM Liu6@niehs.nih.gov
FU NIH; National Cancer institute; Center for Cancer Research; National
Institute of Environmental Health Sciences
FX The authors thank Drs. Chikara Kojima and Larry Keefer for their
critical review of this manuscript. This review was supported, in part,
by the Intramural Research Program of the NIH, National Cancer
institute, Center for Cancer Research, and the National Institute of
Environmental Health Sciences.
NR 55
TC 274
Z9 283
U1 7
U2 85
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD AUG 1
PY 2009
VL 238
IS 3
BP 209
EP 214
DI 10.1016/j.taap.2009.01.029
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 472QS
UT WOS:000268147600004
PM 19236887
ER
PT J
AU Klaassen, CD
Liu, J
Diwan, BA
AF Klaassen, Curtis D.
Liu, Jie
Diwan, Bhalchandra A.
TI Metallothionein protection of cadmium toxicity
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Review
DE Cadmium; Metallothionein; Acute toxicity; Nephrotoxicity;
Carcinogenecity; MT polymorphism
ID WILD-TYPE MICE; NULL MICE; TISSUE DISTRIBUTION; TRANSGENIC MICE;
MESSENGER-RNA; CHRONIC CDCL2; RATS; ABSORPTION; CHLORIDE; LIVER
AB The discovery of the cadmium (Cd)-binding protein from horse kidney in 1957 marked the birth of research oil this low-molecular weight, cysteine-rich protein called metallothionein (MT) in Cd toxicology. MT plays minimal roles in the gastrointestinal absorption of Cd, but MT plays important roles in Cd retention in tissues and dramatically decreases biliary excretion of Cd. Cd-bound to MT is responsible for Cd accumulation in tissues and the long biological half-life of Cd in the body. Induction of MT protects against acute Cd-induced lethality, as well as acute toxicity to the liver and lung. Intracellular MT also plays important roles in ameliorating Cd toxicity following prolonged exposures, particularly chronic Cd-induced nephrotoxicity, osteotoxicity, and toxicity to the lung, liver, and immune system. There is an association between human and rodent Cd exposure and prostate cancers, especially in the portions where MT is poorly expressed. MT expression in Cd-induced tumors varies depending on the type and the stage of tumor development. For instance, high levels of MT are detected in Cd-induced sarcomas at the injection site, whereas the sarcoma metastases are devoid of MT. The use of MT-transgenic and MT-null mice has greatly helped define the role of MT in Cd toxicology, with the MT-null mice being hypersensitive and MT-transgenic mice resistant to Cd toxicity. Thus, MT is critical for protecting human health from Cd toxicity. There are large individual variations in MT expression, which might in turn predispose some people to Cd toxicity. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Klaassen, Curtis D.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
[Liu, Jie] NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Diwan, Bhalchandra A.] SAIC Frederick Inc, Basic Sci Program, NCI, Frederick, MD USA.
RP Klaassen, CD (reprint author), Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA.
EM cklaasse@kumc.edu
FU NIEHS [ES-013714, ES-09716, ES-09649]; NIH; National Cancer Institute;
Center for Cancer Research; National Institutes of Health
[HHSN261200800001E]
FX The authors thank Drs. Michael P. Waalkes, Wei Qu and Larry Keefer for
their critical review of this manuscript. This review was supported by
the NIEHS grants ES-013714, ES-09716, ES-09649 for Dr. Klaassen, and in
part by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research, and the federal funds from the
National Cancer Institute, National Institutes of Health, under contract
No. HHSN261200800001E.
NR 58
TC 231
Z9 249
U1 13
U2 80
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD AUG 1
PY 2009
VL 238
IS 3
BP 215
EP 220
DI 10.1016/j.taap.2009.03.026
PG 6
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 472QS
UT WOS:000268147600005
PM 19362100
ER
PT J
AU Prozialeck, WC
Edwards, JR
Lamar, PC
Liu, J
Vaidya, VS
Bonventre, JV
AF Prozialeck, Walter C.
Edwards, Joshua R.
Lamar, Peter C.
Liu, Jie
Vaidya, Vishal S.
Bonventre, Joseph V.
TI Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis
and apoptosis during the early stages of Cd-induced proximal tubule
injury
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Cadmium; Kim-1; Necrosis; Apoptosis; Proximal tubule
ID CADMIUM-INDUCED HEPATOTOXICITY; RENAL INJURY; CELL-DEATH; TOXIC METALS;
NEPHROTOXICITY; RATS; METALLOTHIONEIN; INTOXICATION; BIOMARKERS;
GENTAMICIN
AB Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 mu mol) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase (alpha-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, alpha-GST and LDH were not increased until 8-12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Prozialeck, Walter C.; Edwards, Joshua R.; Lamar, Peter C.] Midwestern Univ, Dept Pharmacol, Downers Grove, IL 60515 USA.
[Liu, Jie] NIEHS, NCI, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
[Vaidya, Vishal S.; Bonventre, Joseph V.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Renal Div, Boston, MA 02115 USA.
RP Prozialeck, WC (reprint author), Midwestern Univ, Dept Pharmacol, 555 31st St, Downers Grove, IL 60515 USA.
EM wprozi@midwestern.edu
FU NIH [ES 006478, DK 039773, DK 072831, DK 074099]; American Heart
Association [0535492T]; National Cancer Institute; Center for Cancer
Research
FX This work was Supported by NIH grants ES 006478 to W.C.P.; DK 039773, DK
072831 and DK 074099 to J.V.B., Scientist Development Grant 0535492T
from the American Heart Association to V.S.V. and by funds from the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research to J.L. The authors thank Peter Lamar for his
excellent technical assistance and Victoria Sears for her help in
preparing the manuscript.
NR 49
TC 43
Z9 48
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 AUG 1
PY 2009
VL 238
IS 3
BP 306
EP 314
DI 10.1016/j.taap.2009.01.016
PG 9
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 472QS
UT WOS:000268147600016
PM 19371613
ER
PT J
AU Martina, JA
Lelouvier, B
Puertollano, R
AF Martina, Jose A.
Lelouvier, Benjamin
Puertollano, Rosa
TI The Calcium Channel Mucolipin-3 is a Novel Regulator of Trafficking
Along the Endosomal Pathway
SO TRAFFIC
LA English
DT Article
DE autophagy; EGFR; endosomes; mucolipin; TRP
ID VARITINT-WADDLER MOUSE; CATION CHANNEL; AUTOPHAGIC VACUOLES; ENDOCYTIC
PATHWAYS; PROTEIN TRPML1; IV; MUTATION; RECEPTOR; DEAFNESS; CELLS
AB The varitint-waddler phenotype in mice is caused by gain-of-function mutations in mucolipin-3 (MCOLN3), a member of the mucolipin family of ion channels. These mice are characterized by defects in pigmentation, hearing loss and vestibular defects, suggesting that MCOLN3 might play a role in melanosome trafficking and hair cell maturation. Recent evidence has shown that MCOLN3 is a Ca(2+)-permeable channel and its activity is regulated by pH. Here we show that MCOLN3 primarily localizes to early and late endosomes in human epithelial cells. This distribution at the less acidic portions of the endocytic pathway is consistent with the reported inactivation of the channel by low pH. Furthermore, overexpression of MCOLN3 causes dramatic alterations in the endosomal pathway, including enlargement of Hrs-positive endosomes, delayed degradation of epidermal growth factor (EGF) and EGF receptor (EGFR) and defective autophagosome maturation, whereas depletion of endogenous MCOLN3 enhances EGFR degradation. Finally, we found that endosomal pH is higher in cells overexpressing MCOLN3 and propose a model in which Ca(2+) release from endosomes mediated by MCOLN3 might be important for efficient endosomal acidification. Therefore, MCOLN3 is a novel Ca(2+) channel that plays a crucial role in the regulation of cargo trafficking along the endosomal pathway.
C1 [Martina, Jose A.; Lelouvier, Benjamin; Puertollano, Rosa] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Puertollano, R (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM puertolr@mail.nih.gov
FU NIH, National Heart, Lung, and Blood Institute (NHLBI)
FX We appreciate the editorial advice of the NIH Fellows Editorial Board.
This project was supported by the Intramural Research Program of the
NIH, National Heart, Lung, and Blood Institute (NHLBI).
NR 61
TC 45
Z9 48
U1 2
U2 7
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-9219
J9 TRAFFIC
JI Traffic
PD AUG
PY 2009
VL 10
IS 8
BP 1143
EP 1156
DI 10.1111/j.1600-0854.2009.00935.x
PG 14
WC Cell Biology
SC Cell Biology
GA 467CU
UT WOS:000267714900016
PM 19497048
ER
PT J
AU Mondoro, TH
AF Mondoro, Traci Heath
TI Data safety monitoring boards: a word from a sponsor (NHLBI)
SO TRANSFUSION
LA English
DT Article
ID TRIALS
C1 [Mondoro, Traci Heath] NHLBI, Transfus Med & Cellular Therapeut Branch, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA.
RP Mondoro, TH (reprint author), 6701 Rockledge Dr,MSC 7950, Bethesda, MD 20892 USA.
EM mondorot@nhlbi.nih.gov
NR 7
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0041-1132
J9 TRANSFUSION
JI Transfusion
PD AUG
PY 2009
VL 49
IS 8
BP 1537
EP 1539
DI 10.1111/j.1537-2995.2009.02184.x
PG 3
WC Hematology
SC Hematology
GA 478LS
UT WOS:000268590400004
PM 19413736
ER
PT J
AU Roy, SW
Irimia, M
AF Roy, Scott William
Irimia, Manuel
TI Splicing in the eukaryotic ancestor: form, function and dysfunction
SO TRENDS IN ECOLOGY & EVOLUTION
LA English
DT Review
ID MESSENGER-RNA DECAY; INTRON-RICH GENES; GROUP-II INTRONS; SPLICEOSOMAL
INTRONS; EVOLUTIONARY CONSERVATION; GIARDIA-LAMBLIA; LEADER RNA; ORIGIN;
GENOME; SEQUENCES
AB Comparative genomics has begun to unravel the evolutionary history of transcript splicing in eukaryotes. The last common ancestor of modern eukaryotes is now known to have had at least moderately intron-dense genes and two complex spliceosomes. For other splicing-related phenomena the evolutionary history is less clear. We suggest that frequent mis-splicing is likely to be ancestral to eukaryotes, whereas trans-splicing and operon splicing are likely to be more recent. The origins of regulated splicing, alternative splicing and splicing of untranslated transcript regions are less certain. The data discussed underscore the significant genomic complexity of early eukaryotes, and should help to frame future questions about the origins of eukaryotic genome structure.
C1 [Roy, Scott William] Natl Inst Med, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Irimia, Manuel] Univ Barcelona, Fac Biol, Dept Genet, E-08028 Barcelona, Spain.
RP Roy, SW (reprint author), Natl Inst Med, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
EM royscott@ncbi.nlm.nih.gov; mirimia@gmail.com
RI Irimia, Manuel/E-3040-2010;
OI Irimia, Manuel/0000-0002-2179-2567
FU Spanish Ministerio de Educacion y Ciencia, through an FPI
[BFU2005-00252]; National Library of Medicine
FX M.I. was funded by the Spanish Ministerio de Educacion y Ciencia,
through an FPI grant (BFU2005-00252), and S.W.R. by the Intramural
Research Program of the National Library of Medicine at the National
Institutes of Health/DHHS. We thank Senda Jimenez-Delgado for critical
reading of the manuscript, and Eugene Koonin and Jordi GarciaFernandez
and their groups for intellectual support and stimulation, for financial
support and for fostering environments of open intellectual exploration
in their groups. Finally, we apologize to authors whose work and
hypotheses were not discussed owing to lack of space.
NR 95
TC 30
Z9 30
U1 1
U2 12
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0169-5347
J9 TRENDS ECOL EVOL
JI Trends Ecol. Evol.
PD AUG
PY 2009
VL 24
IS 8
BP 447
EP 455
DI 10.1016/j.tree.2009.04.005
PG 9
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 484NE
UT WOS:000269051400009
PM 19576657
ER
PT J
AU Biro, T
Toth, BI
Hasko, G
Paus, R
Pacher, P
AF Biro, Tamas
Toth, Balazs I.
Hasko, Gyoergy
Paus, Ralf
Pacher, Pal
TI The endocannabinoid system of the skin in health and disease: novel
perspectives and therapeutic opportunities
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID ALLERGIC CONTACT-DERMATITIS; CANNABINOID CB2 RECEPTORS; SENSORY
NERVE-FIBERS; TRANSDERMAL DELIVERY; HUMAN KERATINOCYTES; LIVER-DISEASES;
IN-VIVO; ANANDAMIDE; INFLAMMATION; INVOLVEMENT
AB The newly discovered endocannabinoid system (ECS; comprising the endogenous lipid mediators endocannabinoids present in virtually all tissues, their G-protein-coupled cannabinoid receptors, biosynthetic pathways and metabolizing enzymes) has been implicated in multiple regulatory functions both in health and disease. Recent studies have intriguingly suggested the existence of a functional ECS in the skin and implicated it in various biological processes (e.g. proliferation, growth, differentiation, apoptosis and cytokine, mediator or hormone production of various cell types of the skin and appendages, such as the hair follicle and sebaceous gland). It seems that the main physiological function of the cutaneous ECS is to constitutively control the proper and well-balanced proliferation, differentiation and survival, as well as immune competence and/or tolerance, of skin cells. The disruption of this delicate balance might facilitate the development of multiple pathological conditions and diseases of the skin (e.g. acne, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic sclerosis and cancer).
C1 [Biro, Tamas; Toth, Balazs I.] Univ Debrecen, Res Ctr Mol Med, Dept Physiol, H-4032 Debrecen, Hungary.
[Hasko, Gyoergy] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA.
[Paus, Ralf] Univ Lubeck, Univ Hosp Schleswig Holstein, Dept Dermatol, D-23538 Lubeck, Germany.
[Paus, Ralf] Univ Manchester, Sch Translat Med, Manchester M13 9PL, Lancs, England.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Rockville, MD 20892 USA.
RP Biro, T (reprint author), Univ Debrecen, Res Ctr Mol Med, Dept Physiol, H-4032 Debrecen, Hungary.
EM biro@phys.dote.hu; pacher@mail.nih.gov
RI Pacher, Pal/B-6378-2008; Toth, Balazs/K-1214-2013
OI Pacher, Pal/0000-0001-7036-8108;
FU Intramural Research Program of the National Institutes of
Health/National Institute on Alcohol Abuse and Alcoholism; Hungarian
Scientific Research Fund [63153]
FX This publication was supported by Intramural Research Program of the
National Institutes of Health/National Institute on Alcohol Abuse and
Alcoholism (www.nih.gov; www.niaaa.nih.gov; to P.P.) and by the
Hungarian Scientific Research Fund (www.otka.hu; OTKA 63153 to T.B.).
NR 71
TC 71
Z9 73
U1 1
U2 8
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD AUG
PY 2009
VL 30
IS 8
BP 411
EP 420
DI 10.1016/j.tips.2009.05.004
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 487PI
UT WOS:000269286700004
PM 19608284
ER
PT J
AU Pike, VW
AF Pike, Victor W.
TI PET radiotracers: crossing the blood-brain barrier and surviving
metabolism
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; P-GLYCOPROTEIN FUNCTION;
CENTRAL-NERVOUS-SYSTEM; 5-HT1A RECEPTOR RADIOLIGAND; PERIPHERAL
BENZODIAZEPINE-RECEPTORS; GLUTAMATE SUBTYPE-5 RECEPTORS; TEST-RETEST
REPRODUCIBILITY; IN-VIVO; DOPAMINE TRANSPORTER; MONKEY BRAIN
AB Radiotracers for imaging protein targets in the living human brain with positron emission tomography (PET) are increasingly useful in clinical research and in drug development. Such radiotracers must fulfill many criteria, among which an ability to enter brain adequately and reversibly without contamination by troublesome radio-metabolites is desirable for accurate measurement of the density of a target protein (e.g. neuroreceptor, transporter, enzyme or plaque). Candidate radiotracers can fail as a result of poor passive brain entry, rejection from brain by efflux transporters or undesirable metabolism. These issues are reviewed. Emerging PET radiotracers for measuring efflux transporter function and new strategies for ameliorating radiotracer metabolism are discussed. A growing understanding of the molecular features affecting the brain penetration, metabolism and efflux transporter sensitivity of prospective radiotracers should ultimately lead to their more rational and efficient design, and also to their greater efficacy.
C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, Room B3 C346A,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
FU National Institutes of Health (National Institute of Mental Health) [Z01
MH 002793]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (National Institute of Mental Health;
http://www.nimb.nih.gov), project number Z01 MH 002793. I thank members
of the Molecular Imaging Branch
(http://intramural.nimh.nih.gov/mood/proginfo/mib) for their
collaboration on topics discussed in this review.
NR 79
TC 199
Z9 200
U1 3
U2 34
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD AUG
PY 2009
VL 30
IS 8
BP 431
EP 440
DI 10.1016/j.tips.2009.05.005
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 487PI
UT WOS:000269286700006
PM 19616318
ER
PT J
AU Payvandi, L
Dyer, A
McPherson, D
Ades, P
Stein, J
Liu, K
Ferrucci, L
Criqui, MH
Guralnik, JM
Lloyd-Jones, D
Kibbe, MR
Liang, ST
Kane, B
Pearce, WH
Verta, M
McCarthy, WJ
Schneider, JR
Shroff, A
McDermott, MM
AF Payvandi, Laila
Dyer, Alan
McPherson, David
Ades, Philip
Stein, James
Liu, Kiang
Ferrucci, Luigi
Criqui, Michael H.
Guralnik, Jack M.
Lloyd-Jones, Donald
Kibbe, Melina R.
Liang, Susan T.
Kane, Bonnie
Pearce, William H.
Verta, Michael
McCarthy, Walter J.
Schneider, Joseph R.
Shroff, Adhir
McDermott, Mary M.
TI Physical activity during daily life and brachial artery flow-mediated
dilation in peripheral arterial disease
SO VASCULAR MEDICINE
LA English
DT Article
DE endothelial reactivity; intermittent claudication; peripheral arterial
disease; physical activity
ID ENDOTHELIAL FUNCTION; CARDIOVASCULAR EVENTS; VASCULAR REACTIVITY;
RISK-FACTORS; TASK-FORCE; ASSOCIATION; PREVALENCE; EXERCISE; GUIDELINES;
MORTALITY
AB We determined whether higher levels of physical activity in daily life are associated with better brachial artery flow-mediated dilation (FMD) among individuals with lower extremity peripheral arterial disease (PAD). Participants were 111 men and women with PAD (ankle-brachial index (ABI) <= 0.95) who completed baseline testing in the Study to Improve Leg Circulation (SILC). We evaluated FMD of the brachial artery at baseline and at 60 seconds following 4 minutes of suprasystolic blood pressure cuff inflation. Physical activity was measured continuously over 7 days using a vertical accelerometer (Caltrac) and a pedometer (Digiwalker). Adjusting for age, sex, race, ABI, cardiovascular risk factors and other potential confounders, higher levels of physical activity were associated with a greater percent change in brachial artery FMD at 60 seconds post cuff deflation for both Caltrac (1st tertile of activity +4.81% change; 2nd tertile +4.60% change; 3rd tertile +7.23% change; p-trend = 0.018) and the Digiwalker (1st tertile of activity +3.76% change; 2nd tertile +6.25% change; 3rd tertile +7.25% change; p-trend = 0.001). Similar findings were observed for absolute change in brachial artery FMD 60 seconds after cuff deflation. In conclusion, higher levels of physical activity during daily life are associated significantly and independently with better brachial artery FMD among individuals with PAD, even after adjusting for confounders. ClinicalTrials.gov Identifier: NCT00106327.
C1 [Payvandi, Laila; Dyer, Alan; Liu, Kiang; Lloyd-Jones, Donald; Kibbe, Melina R.; Kane, Bonnie; Pearce, William H.; McDermott, Mary M.] Northwestern Univ, Feinberg Sch Med, Evanston, IL 60208 USA.
[Ades, Philip] Univ Vermont, Burlington, VT 05405 USA.
[Stein, James] Univ Wisconsin, Madison, WI 53706 USA.
[Ferrucci, Luigi; Guralnik, Jack M.] NIA, Bethesda, MD 20892 USA.
[Criqui, Michael H.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Verta, Michael] Evanston NW Hosp, Evanston, IL USA.
[McCarthy, Walter J.] Rush Sch Med, Chicago, IL USA.
[Shroff, Adhir] Univ Illinois, Chicago, IL 60680 USA.
RP McDermott, MM (reprint author), 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
RI Lloyd-Jones, Donald/C-5899-2009
FU National Heart Lung and Blood Institute, NIH [R01-HL073351]
FX Supported by R01-HL073351 from the National Heart Lung and Blood
Institute, NIH.
NR 27
TC 27
Z9 29
U1 2
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
J9 VASC MED
JI Vasc. Med.
PD AUG 1
PY 2009
VL 14
IS 3
BP 193
EP 201
DI 10.1177/1358863X08101018
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 478DP
UT WOS:000268568300001
PM 19651668
ER
PT J
AU Walter-Rodriguez, B
Begnami, M
Quezado, M
AF Walter-Rodriguez, B.
Begnami, M.
Quezado, M.
TI Chordomas: evaluation of EGFR and c-METgenes expression
SO VIRCHOWS ARCHIV
LA English
DT Meeting Abstract
C1 [Walter-Rodriguez, B.; Begnami, M.; Quezado, M.] NCI, NIH, Bethesda, MD 20892 USA.
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 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD AUG
PY 2009
VL 455
BP 361
EP 361
PG 1
WC Pathology
SC Pathology
GA 474TT
UT WOS:000268307700979
ER
PT J
AU Quezado, M
Collins, TM
Merino, MJ
AF Quezado, M.
Collins, T. M.
Merino, M. J.
TI Phosphaturic mesenchymal tumors: what about them?
SO VIRCHOWS ARCHIV
LA English
DT Meeting Abstract
C1 [Quezado, M.; Collins, T. M.; Merino, M. J.] NCI, LP, NIH, Bethesda, MD 20892 USA.
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 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD AUG
PY 2009
VL 455
BP 364
EP 364
PG 1
WC Pathology
SC Pathology
GA 474TT
UT WOS:000268307700988
ER
PT J
AU Bahl, J
Vijaykrishna, D
Holmes, EC
Smith, GJD
Guan, Y
AF Bahl, Justin
Vijaykrishna, Dhanasekaran
Holmes, Edward C.
Smith, Gavin J. D.
Guan, Yi
TI Gene flow and competitive exclusion of avian influenza A virus in
natural reservoir hosts
SO VIROLOGY
LA English
DT Article
DE Evolution; Ecology; Population dynamics; Influenza A virus; Competition
ID NORTH-AMERICA; RNA VIRUSES; EVOLUTION; DUCKS; TRANSMISSION; LINEAGES;
ORIGIN; BIRDS; H6N2; SHOREBIRDS
AB Geographical separation of host species has shaped the avian influenza A virus gene pool into independently evolving Eurasian and American lineages, although phylogenetic evidence for gene flow and reassortment indicates that these lineages also mix on occasion, While the evolutionary dynamics of the avian influenza gene pool have been described, the consequences of gene flow on virus evolution and population structure in this system have not been investigated. Here we show that viral gene flow from Eurasia has led to the replacement of endemic avian influenza viruses in North America, likely through competition for susceptible hosts. This competition is characterized by changes in rates of nucleotide substitution and selection the discontinuous distribution of susceptible hosts may produce long periods of co-circulation of competing virus strains before lineage extinction occurs. These results also suggest that viral competition for host resources may be an important mechanism in disease emergence. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Bahl, Justin; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Guan, Yi] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, Pokfulam, Hong Kong, Peoples R China.
[Bahl, Justin; Vijaykrishna, Dhanasekaran; Smith, Gavin J. D.; Guan, Yi] Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Pokfulam, Hong Kong, Peoples R China.
[Holmes, Edward C.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Smith, GJD (reprint author), Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Emerging Infect Dis, 21 Sassoon Rd, Pokfulam, Hong Kong, Peoples R China.
EM gjsmith@hku.hk; yguan@hku.hk
RI Bahl, Justin/A-4728-2011; Vijaykrishna, Dhanasekaran/D-1011-2010;
OI Bahl, Justin/0000-0001-7572-4300; Vijaykrishna,
Dhanasekaran/0000-0003-3293-6279; Holmes, Edward/0000-0001-9596-3552;
Smith, Gavin JD/0000-0001-5031-468X
FU University Grants Committee [AoE/M-12/06]; National Institutes of Health
[HHSN266200700005C]
FX This work was supported by the Area of Excellence Scheme of the
University Grants Committee (Grant AoE/M-12/06) of the Hong Kong SAR
Government, the National Institutes of Health (NIAID contract
HHSN266200700005C), and the Li Ka Shing Foundation. GJDS is supported by
a career development award under NIAID contract HHSN266200700005C.
NR 51
TC 58
Z9 58
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 0042-6822
J9 VIROLOGY
JI Virology
PD AUG 1
PY 2009
VL 390
IS 2
BP 289
EP 297
DI 10.1016/j.virol.2009.05.002
PG 9
WC Virology
SC Virology
GA 473PA
UT WOS:000268218500016
PM 19501380
ER
PT J
AU Waheed, AA
Freed, EO
AF Waheed, Abdul A.
Freed, Eric O.
TI Lipids and membrane microdomains in HIV-1 replication
SO VIRUS RESEARCH
LA English
DT Review
DE HIV-1; Lipid rafts; Cholesterol; Sphingolipids; PI(4,5)P2; Entry;
Assembly; Budding; Inhibitors
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GPI-ANCHORED PROTEINS; TYPE-1 MATRIX
PROTEIN; DETERGENT-RESISTANT MEMBRANES; RESPIRATORY SYNCYTIAL VIRUS;
CELL PLASMA-MEMBRANES; MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA-VIRUS; B
METHYL-ESTER; VIRION-ASSOCIATED CHOLESTEROL
AB Several critical steps in the replication cycle of human immunodeficiency virus type 1 (HIV-1) - entry, assembly and budding - are complex processes that take place at the plasma membrane of the host cell. A growing body of data indicates that these early and late steps in HIV-1 replication take place in specialized plasma membrane microdomains, and that many of the viral and cellular components required for entry, assembly, and budding are concentrated in these microdomains. In particular, a number of studies have shown that cholesterol- and sphingolipid-enriched microdomains known as lipid rafts play important roles in multiple steps in the virus replication cycle. In this review, we provide an overview of what is currently known about the involvement of lipids and membrane microdomains in HIV-1 replication. Published by Elsevier B.V.
C1 [Waheed, Abdul A.; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA.
RP Waheed, AA (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Bldg 535,Rm 108,1050 Boyles St, Frederick, MD 21702 USA.
EM awaheed@ncifcrf.gov; efreed@nih.gov
FU NIH; National Cancer Institute, Center for Cancer Research; Intramural
AIDS Targeted Antiviral Program
FX We thank A. Ono and members of the Virus-Cell Interaction Section for
helpful discussions and critical reading of the manuscript, and A. Ono,
Q. Sattentau and C. Jolly for generously granting permission to
reproduce figures. The Freed laboratory is supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research and by the Intramural AIDS Targeted Antiviral Program.
We apologize to our colleagues whose work was not cited due to space
limitations.
NR 254
TC 87
Z9 88
U1 0
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD AUG
PY 2009
VL 143
IS 2
SI SI
BP 162
EP 176
DI 10.1016/j.virusres.2009.04.007
PG 15
WC Virology
SC Virology
GA 494BF
UT WOS:000269783400004
PM 19383519
ER
PT J
AU Chang, CM
Yu, KJ
Mbulaiteye, SM
Hildesheim, A
Bhatia, K
AF Chang, Cindy M.
Yu, Kelly J.
Mbulaiteye, Sam M.
Hildesheim, Allan
Bhatia, Kishor
TI The extent of genetic diversity of Epstein-Barr virus and its geographic
and disease patterns: A need for reappraisal
SO VIRUS RESEARCH
LA English
DT Review
DE EBV; Strain variation; Genetic diversity; Variants; Genotypes; EBNA1;
BZLF1; LMP1; ZP; 30 bp deletion; Xhol loss; EBV types 1 and 2; B98-5
ID LATENT MEMBRANE PROTEIN-1; NUCLEAR ANTIGEN 1; UNDIFFERENTIATED
NASOPHARYNGEAL CARCINOMA; CELL-IMMUNOCOMPROMISED INDIVIDUALS;
PERIPHERAL-BLOOD LYMPHOCYTES; REACTIVE LYMPHOID-TISSUE; AIDS-RELATED
LYMPHOMAS; AMINO-ACID CHANGES; SEQUENCE VARIATION; BURKITTS-LYMPHOMA
AB Epstein-Barr virus (EBV) is a ubiquitous, gamma-1 lymphotrophic virus etiologically linked to nasopharyngeal carcinoma (NPC) endemic to Southern China, and Burkitt lymphoma (BL), endemic to equatorial Africa, both of which are rare elsewhere in the world. Why EBV is associated with different malignancies in different geographic regions remains puzzling and may be related to EBV genotypic variability through specific disease and geographic associations. We review the literature on sequence variation in EBV genes, focusing on LMP-1, EBNA-1, and BZLF-1 and their distribution by geography and disease. Given the limitations of current studies, definitive conclusions regarding the link between EBV genotypes, disease and geography are not possible. We suggest that the true extent of EBV diversity is likely to be greater than is currently recognized. Additional studies conducted in carefully selected populations, that are sufficiently powered to provide robust estimates, and that utilize testing approaches that permit full characterization of viral diversity are needed to further our understanding of patterns of EBV genetic variation and their association with malignancies in different regions. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Chang, Cindy M.; Yu, Kelly J.; Mbulaiteye, Sam M.; Hildesheim, Allan; Bhatia, Kishor] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
RP Chang, CM (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 7074, Rockville, MD 20892 USA.
EM changcm@mail.nih.gov
RI Chang, Cindy/G-4514-2010; Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU Intramural NIH HHS [Z99 CA999999]
NR 160
TC 76
Z9 88
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
J9 VIRUS RES
JI Virus Res.
PD AUG
PY 2009
VL 143
IS 2
BP 209
EP 221
DI 10.1016/j.virusres.2009.07.005
PG 13
WC Virology
SC Virology
GA 494BF
UT WOS:000269783400008
PM 19596032
ER
PT J
AU Whitney, JB
Luedemann, C
Bao, S
Miura, A
Rao, SS
Mascola, JR
Letvin, NL
AF Whitney, James B.
Luedemann, Corinne
Bao, Saran
Miura, Ayako
Rao, Srinivas S.
Mascola, John R.
Letvin, Norman L.
TI Monitoring HIV vaccine trial participants for primary infection: studies
in the SIV/macaque model
SO AIDS
LA English
DT Article
DE acute HIV infection; HIV-1 infection monitoring; simian immunodeficiency
virus
ID DRIED BLOOD SPOTS; IMMUNODEFICIENCY-VIRUS RNA; VIRAL LOAD; WHOLE-BLOOD;
FILTER-PAPER; TYPE-1 RNA; T-CELLS; PLASMA; ASSAY; TRANSMISSION
AB Objectives: The ability to detect and quantify acute HIV-1 infection prior to seroconversion would be an important tool for use in HIV vaccine clinical efficacy trials. We have utilized the SIV/rhesus monkey model to evaluate whether samples more easily obtained than peripheral blood might be used for intensive monitoring of vaccine trial participants.
Methods: We have evaluated viral loads in peripheral blood, saliva, feces, and urine of five rhesus monkeys during primary SIV(mac251) infection by quantitative real-time PCR. As an alternative to the direct monitoring of frozen samples, we have also developed a fully quantitative viral load assay utilizing dried blood spots.
Results: Although all compartments were found to harbor viral RNA during primary infection, viral RNA could be detected in the peripheral compartments only when levels of plasma viremia exceed a threshold value of 10(4) RNA copies/ml. We found no direct correlation between viral burden in plasma and saliva, feces, or urine viral loads. Importantly, both dried saliva and whole blood spots can be used for viral detection. Quantitative whole blood or plasma spotting correlated well with viral burden in plasma during both the acute and set point phase of infection.
Conclusion: Dried blood spots are amenable to rapid quantitative viral load testing. Whole blood spotting has a significant logistical benefit as it requires low blood volumes and no blood processing. Saliva or dried saliva spots or both are potential candidates for acute phase diagnostic screening. These studies indicate the feasibility of intensive monitoring of HIV-1 vaccine trial participants for virus acquisition in resource-limited settings. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Whitney, James B.; Luedemann, Corinne; Miura, Ayako; Letvin, Norman L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Dept Med, Boston, MA 02215 USA.
[Whitney, James B.; Letvin, Norman L.] Harvard Univ, Sch Med, Boston, MA USA.
[Bao, Saran; Rao, Srinivas S.; Mascola, John R.; Letvin, Norman L.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Letvin, NL (reprint author), Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Dept Med, Res E Room 113,330 Brookline Ave, Boston, MA 02215 USA.
EM nletvin@bidmc.harvard.edu
FU Intramural Research Program of the Vaccine Research Center, NIAID;
Canadian Institutes of Health Research (CIHR)
FX This work was supported by the Intramural Research Program of the
Vaccine Research Center, NIAID. J.B.W was the recipient of a
postdoctoral fellowship from the Canadian Institutes of Health Research
(CIHR). J.B.W, S.S.R., J.R.M., and N.L.L. designed the study. J.B.W,
C.L., S.B., A.M. and S.S.R. conducted the experiment and collected all
experimental data. J.B.W and N.L.L. analyzed the data. J.B.W., J.R.M.
and N.L.L. wrote the manuscript.
NR 25
TC 9
Z9 9
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2009
VL 23
IS 12
BP 1453
EP 1460
DI 10.1097/QAD.0b013e32832b43d9
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 476CI
UT WOS:000268414300003
PM 19550289
ER
PT J
AU Tobian, AAR
Ssempijja, V
Kigozi, G
Oliver, AE
Serwadda, D
Makumbi, F
Nalugoda, FK
Iga, B
Reynolds, SJ
Wawer, MJ
Quinn, TC
Gray, RH
AF Tobian, Aaron A. R.
Ssempijja, Victor
Kigozi, Godfrey
Oliver, Amy E.
Serwadda, David
Makumbi, Frederick
Nalugoda, Frederick K.
Iga, Boaz
Reynolds, Steven J.
Wawer, Maria J.
Quinn, Thomas C.
Gray, Ronald H.
TI Incident HIV and herpes simplex virus type 2 infection among men in
Rakai, Uganda
SO AIDS
LA English
DT Article
DE herpes simplex virus type 2; HIV; male circumcision; risk factors;
Uganda
ID HUMAN-IMMUNODEFICIENCY-VIRUS; GENITAL HERPES; MALE CIRCUMCISION;
FACTORY-WORKERS; ACQUISITION; WOMEN; RISK; ASSOCIATION; PREVENTION;
PREVALENCE
AB Objective: Herpes simplex virus type 2 (HSV-2) infection is associated with an increased risk for acquiring HIV, but little is known about the temporal sequence of these infections.
Design: Six thousand three hundred ninety-six men were evaluated for serologic HSV-2 and HIV infections and behaviors during a male circumcision trial in Rakai, Uganda.
Methods: HIV and HSV-2 status were determined using enzyme-linked immunosorbent assays and confirmed by HIV-1 and HSV-2 western blots. A Poisson multivariable model was used to estimate adjusted incidence rate ratios of HIV acquisition associated with HSV-2 and other covariates.
Results: HIV incidence was 1.09/100 person-years and acquisition was associated with incident HSV-2 infection [adjusted incidence rate ratio (adjIRR) 5.28, 95% confidence interval (CI) 2.79-9.98], chronic HSV-2 infection (adjIRR 2.78, 95% Cl 1.64-5.68), genital ulcer disease, urethral discharge, genital washing after intercourse, being unmarried, and being uncircumcised. Sixteen men acquired both HIV and HSV-2 during the trial: four acquired HIV first, three acquired HSV-2 first, and [line acquired both infections in the same follow-up interval.
Conclusion: The findings suggest that unsafe sex places men at risk of both HIV and HSV-2 infections, and it is unclear whether HSV-2 acquisition is a cofactor for HIV infection or a marker of correlated sexual exposures. This reinforces the need for promotion of safe sex as the primary method of prevention of both viruses. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ssempijja, Victor; Nalugoda, Frederick K.; Iga, Boaz] Rakai Hlth Sci Program, Entebbe, Uganda.
[Kigozi, Godfrey; Serwadda, David; Makumbi, Frederick] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Reynolds, Steven J.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Reynolds, Steven J.; Quinn, Thomas C.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Dept Populat Family & Reprod Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
RP Quinn, TC (reprint author), Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn@jhmi.edu
FU National Institutes of Health [U1A151171]; Bill and Melinda Gates
Foundation [22006.02]; Fogarty International Center [5D43TW001508,
D43TW00015]; Intramural Research program of the National Institute of
Allergy and Infectious Diseases, NIH
FX The trials were funded by the National Institutes of Health
(#U1A151171), the Bill and Melinda Gates Foundation (#22006.02) and the
Fogarty International Center (#5D43TW001508 and #D43TW00015). This study
was supported by the Intramural Research program of the National
Institute of Allergy and Infectious Diseases, NIH.
NR 21
TC 33
Z9 34
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0269-9370
J9 AIDS
JI Aids
PD JUL 31
PY 2009
VL 23
IS 12
BP 1589
EP 1594
DI 10.1097/QAD.0b013e32832d4042
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 476CI
UT WOS:000268414300018
PM 19474649
ER
PT J
AU Garcia, MC
Ray, DM
Lackford, B
Rubino, M
Olden, K
Roberts, JD
AF Garcia, Melissa C.
Ray, Denise M.
Lackford, Brad
Rubino, Mark
Olden, Kenneth
Roberts, John D.
TI Arachidonic Acid Stimulates Cell Adhesion through a Novel p38 MAPK-RhoA
Signaling Pathway That Involves Heat Shock Protein 27
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GTP-BINDING PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; HETEROTRIMERIC
G-PROTEINS; KINASE-DEPENDENT PATHWAY; BREAST-CARCINOMA CELLS;
FACTOR-KAPPA-B; ACTIN CYTOSKELETON; PROSTATE-CANCER; CYCLOOXYGENASE-2
EXPRESSION; ACTIVATING PROTEIN
AB Rho GTPases are critical components of cellular signal transduction pathways. Both hyperactivity and overexpression of these proteins have been observed in human cancers and have been implicated as important factors in metastasis. We previously showed that dietary n-6 fatty acids increase cancer cell adhesion to extracellular matrix proteins, such as type IV collagen. Here we report that in MDA-MB-435 human melanoma cells, arachidonic acid activates RhoA, and inhibition of RhoA signaling with either C3 exoenzyme or dominant negative Rho blocked arachidonic acid-induced cell adhesion. Inhibition of the Rho kinase (ROCK) with either small molecule inhibitors or ROCK II-specific small interfering RNA (siRNA) blocked the fatty acid-induced adhesion. However, unlike other systems, inhibition of ROCK did not block the activation of p38 mitogen-activated protein kinase (MAPK); instead, Rho activation depended on p38 MAPK activity and the presence of heat shock protein 27 (HSP27), which is phosphorylated downstream of p38 after arachidonic acid treatment. HSP27 associated with p115RhoGEF in fatty acid-treated cells, and this association was blocked when p38 was inhibited. Furthermore, siRNA knockdown of HSP27 blocked the fatty acid-stimulated Rho activity. Expression of dominant negative p115-RhoGEF or p115RhoGEF-specific siRNA inhibited both RhoA activation and adhesion on type IV collagen, whereas a constitutively active p115RhoGEF restored the arachidonic acid stimulation in cells in which the p38 MAPK had been inhibited. These data suggest that n-6 dietary fatty acids stimulate a set of interactions that regulates cell adhesion through RhoA and ROCK II via a p38 MAPK-dependent association of HSP27 and p115RhoGEF.
C1 [Garcia, Melissa C.; Ray, Denise M.; Lackford, Brad; Rubino, Mark; Olden, Kenneth; Roberts, John D.] NIEHS, NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA.
RP Roberts, JD (reprint author), 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM roberts1@niehs.nih.gov
OI Garcia-Sherman, Melissa/0000-0003-1409-4397
FU National Institutes of Health (NIEHS)
FX This work was supported, in whole or in part, by the National Institutes
of Health Intramural Research Program of the National Institutes of
Health (NIEHS).
NR 76
TC 30
Z9 32
U1 0
U2 4
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 31
PY 2009
VL 284
IS 31
BP 20936
EP 20945
DI 10.1074/jbc.M109.020271
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474WV
UT WOS:000268316100057
PM 19506078
ER
PT J
AU Korzeniowski, MK
Popovic, MA
Szentpetery, Z
Varnai, P
Stojilkovic, SS
Balla, T
AF Korzeniowski, Marek K.
Popovic, Marko A.
Szentpetery, Zsofia
Varnai, Peter
Stojilkovic, Stanko S.
Balla, Tamas
TI Dependence of STIM1/Orai1-mediated Calcium Entry on Plasma Membrane
Phosphoinositides
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID LIGHT-CHAIN KINASE; PHOSPHATIDYLINOSITOL 4-KINASE; CHANNEL ACTIVATION;
ENDOTHELIAL-CELLS; HUMAN PLATELETS; CRAC CHANNELS; CA2+ CHANNELS; LIVING
CELLS; STIM1; ORAI1
AB Recent studies identified two main components of store-operated calcium entry (SOCE): the endoplasmic reticulum-localized Ca2+ sensor protein, STIM1, and the plasma membrane (PM)-localized Ca2+ channel, Orai1/CRACM1. In the present study, we investigated the phosphoinositide dependence of Orai1 channel activation in the PM and of STIM1 movements from the tubular to PM-adjacent endoplasmic reticulum regions during Ca2+ store depletion. Phosphatidylinositol 4,5-bisphosphate ( PtdIns( 4,5)P-2) levels were changed either with agonist stimulation or by chemically induced recruitment of a phosphoinositide 5-phosphatase domain to the PM, whereas PtdIns4P levels were decreased by inhibition or down-regulation of phosphatidylinositol 4-kinases (PI4Ks). Agonist-induced phospholipase C activation and PI4K inhibition, but not isolated PtdIns(4,5)P-2 depletion, substantially reduced endogenous or STIM1/Orai1-mediated SOCE without preventing STIM1 movements toward the PM upon Ca2+ store depletion. Patch clamp analysis of cells overexpressing STIM1 and Orai1 proteins confirmed that phospholipase C activation or PI4K inhibition greatly reduced I-CRAC currents. These results suggest an inositide requirement of Orai1 activation but not STIM1 movements and indicate that PtdIns4P rather than PtdIns(4,5)P-2 is a likely determinant of Orai1 channel activity.
C1 [Korzeniowski, Marek K.; Szentpetery, Zsofia; Balla, Tamas] NICHD, NIH, Sect Mol Signal Transduct, Program Dev Neurosci, Bethesda, MD 20892 USA.
[Popovic, Marko A.; Stojilkovic, Stanko S.] NICHD, NIH, Sect Cellular Signaling, Program Dev Neurosci, Bethesda, MD 20892 USA.
[Varnai, Peter] Semmelweis Univ, Fac Med, Dept Physiol, H-1094 Budapest, Hungary.
RP Balla, T (reprint author), NICHD, NIH, Sect Mol Signal Transduct, Program Dev Neurosci, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA.
EM ballat@mail.nih.gov
RI Korzeniowski, Marek/G-7214-2011;
OI Balla, Tamas/0000-0002-9077-3335
FU NICHD
FX This work was supported, in whole or in part, by a National Institutes
of Health grant from the Intramural Research Program of the NICHD.
NR 42
TC 66
Z9 67
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 31
PY 2009
VL 284
IS 31
BP 21027
EP 21035
DI 10.1074/jbc.M109.012252
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474WV
UT WOS:000268316100065
PM 19483082
ER
PT J
AU Herrick, DZ
Kuo, WW
Huang, H
Schwieters, CD
Ellena, JF
Cafiso, DS
AF Herrick, Dawn Z.
Kuo, Weiwei
Huang, Hao
Schwieters, Charles D.
Ellena, Jeffrey F.
Cafiso, David S.
TI Solution and Membrane-Bound Conformations of the Tandem C2A and C2B
Domains of Synaptotagmin 1: Evidence for Bilayer Bridging
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE site-directed spin labeling; EPR spectroscopy; membrane fusion;
protein-membrane interactions; calcium-binding protein
ID MOLECULAR-STRUCTURE DETERMINATION; SPIN-LABELED PROTEINS;
NEUROTRANSMITTER RELEASE; SIDE-CHAINS; DISTANCE MEASUREMENTS; EPR
SPECTROSCOPY; SNARE FUNCTION; T4 LYSOZYME; XPLOR-NIH; FUSION
AB Synaptotagmin 1 (syt1) is a synaptic vesicle membrane protein that functions as the Ca(2+) sensor in neuronal exocytosis. Here, site-directed spin labeling was used to generate models for the solution and membrane-bound structures of a soluble fragment of syt1 containing its two C2 domains, C2A and C2B. In solution, distance restraints between the two C2 domains of syt1 were measured using double electron-electron resonance and used in a simulated annealing routine to generate models for the structure of the tandem C2A-C2B fragment. The data indicate that the two C2 domains are flexibly linked and do not interact with each other in solution, with or without Ca(2+). However, the favored orientation is one where the Ca(2+)-binding loops are oriented in opposite directions. A similar approach was taken for membrane-associated C2A-C2B, combining both distances and bilayer depth restraints with simulated annealing. The restraints can only be satisfied if the Ca(2+) and membrane-binding surfaces of the domains are oriented in opposite directions so that C2A and C2B are docked to opposing bilayers. The result suggests that syt1 functions to bridge across the vesicle and plasma membrane surfaces in a Ca(2+)-dependent manner. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Herrick, Dawn Z.; Kuo, Weiwei; Huang, Hao; Ellena, Jeffrey F.; Cafiso, David S.] Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA.
[Herrick, Dawn Z.; Kuo, Weiwei; Huang, Hao; Ellena, Jeffrey F.; Cafiso, David S.] Univ Virginia, Biophys Program, Charlottesville, VA 22904 USA.
[Schwieters, Charles D.] Natl Inst Hlth, Div Computat Biosci, Bethesda, MD 20892 USA.
[Schwieters, Charles D.] Natl Inst Hlth, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Cafiso, DS (reprint author), Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA.
EM cafiso@virginia.edu
FU National Institutes of Health, National Institute of General Medical
Sciences [GM 072694]; Intramural Research Program of the National
Institutes of Health
FX This work was supported by a grant from the National Institutes of
Health, National Institute of General Medical Sciences, GM 072694, and
by the Intramural Research Program of the National Institutes of Health
(to C.D.S.).
NR 49
TC 33
Z9 33
U1 0
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 31
PY 2009
VL 390
IS 5
BP 913
EP 923
DI 10.1016/j.jmb.2009.06.007
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 477ZB
UT WOS:000268556400007
PM 19501597
ER
PT J
AU Grundy, GJ
Ramon-Maiques, S
Dimitriadis, EK
Kotova, S
Biertumpfel, C
Heymann, JB
Steven, AC
Gellert, M
Yang, W
AF Grundy, Gabrielle J.
Ramon-Maiques, Santiago
Dimitriadis, Emilios K.
Kotova, Svetlana
Biertuempfel, Christian
Heymann, J. Bernard
Steven, Alasdair C.
Gellert, Martin
Yang, Wei
TI Initial Stages of V(D)J Recombination: The Organization of RAG1/2 and
RSS DNA in the Postcleavage Complex
SO MOLECULAR CELL
LA English
DT Article
ID SINGLE ACTIVE-SITE; SYNAPTIC COMPLEX; CELL-CYCLE; ELECTRON-MICROSCOPY;
MUTATIONAL ANALYSIS; HAIRPIN FORMATION; RAG2 PROTEINS; AMINO-ACIDS;
SIGNAL ENDS; TRANSPOSITION
AB To obtain structural information on the early stages of V(D)J recombination, we isolated a complex of the core RAG1 and RAG2 proteins with DNA containing a pair of cleaved recombination signal sequences (RSS). Stoichiometric and molecular mass analysis established that this signal-end complex (SEC) contains two protomers each of RAG1 and RAG2. Visualization of the SEC by negative-staining electron microscopy revealed an anchor-shaped particle with approximate two-fold symmetry. Consistent with a parallel arrangement of DNA and protein subunits, the N termini of RAG1 and RAG2 are positioned at opposing ends of the complex, and the DNA chains beyond the RSS nonamer emerge from the same face of the complex, near the RAG1 N termini. These first images of the V(D)J recombinase in its post-cleavage state provide a framework for modeling RAG domains and their interactions with DNA.
C1 [Grundy, Gabrielle J.; Ramon-Maiques, Santiago; Biertuempfel, Christian; Gellert, Martin; Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.; Kotova, Svetlana] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA.
[Heymann, J. Bernard; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Gellert, M (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM gellert@helix.nih.gov; wei.yang@nih.gov
RI Yang, Wei/D-4926-2011; Heymann, Bernard/F-6825-2011;
OI Yang, Wei/0000-0002-3591-2195; Biertumpfel,
Christian/0000-0002-7528-6547; Heymann, Bernard/0000-0002-8872-5326
FU National Institutes of Health
FX We thank Drs. J.S. Wall and M.M. Simon of Brookhaven National Laboratory
for STEM data acquisition. S.R.-M. is indebted to Drs. N. Cheng, C.S.
Smith, U. Baxa, and D. Winkler for help with EM data acquisition, to
Drs. G. Effantin, N. Mizuno, and U. Baxa for guidance in image analysis,
and to Drs. M. Nowotny and J.Y. Lee for insightful discussions. We thank
C. Vander Kooi, P. Longo, J. McLellan, and D.J. Leahy for help in
establishing the mammalian expression system. S.R.-M. was a recipient of
a Human Frontiers Science Program fellowship. This work was supported by
the intramural research programs of the NIDDK, NIBIB, and NIAMS of the
National Institutes of Health.
NR 62
TC 23
Z9 23
U1 3
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD JUL 31
PY 2009
VL 35
IS 2
BP 217
EP 227
DI 10.1016/j.molcel.2009.06.022
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 479EY
UT WOS:000268643700010
PM 19647518
ER
PT J
AU Seol, Y
Stein, DL
Visscher, K
AF Seol, Yeonee
Stein, D. L.
Visscher, Koen
TI Phase Measurements of Barrier Crossings in a Periodically Modulated
Double-Well Potential
SO PHYSICAL REVIEW LETTERS
LA English
DT Article
ID STOCHASTIC RESONANCE; ACTIVATED ESCAPE; DRIVEN SYSTEMS; FLUCTUATIONS;
PARTICLE
AB We report on the experimental observation of the phase angle of a particle escaping over a periodically modulated potential barrier. Optical tweezers and back-focal plane position detection were used to record particle trajectories in the entire double-well potential. These measurements provide a sensitive test of theories proposed in the past decade of escape driven by random thermal noise from a periodically modulated potential. The observed phase shifts as a function of modulation frequency are consistent with those calculated using existing theories.
C1 [Seol, Yeonee] NHLBI, NIH, Bethesda, MD 20892 USA.
[Stein, D. L.] NYU, Dept Phys, New York, NY 10003 USA.
[Stein, D. L.] NYU, Dept Math, New York, NY 10003 USA.
[Visscher, Koen] Univ Arizona, Dept Phys, Tucson, AZ 85721 USA.
RP Seol, Y (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
FU NSF [PHY-0351964, PHY-0601179, PHY-0651077, PHY-0099484]
FX We thank Robert Maier for extensive discussions when the experiment was
being performed and Mark Dykman for helpful comments on the paper. D. L.
S. was supported in part by NSF Grants No. PHY-0351964, No. PHY-0601179,
and No. PHY-0651077. While at the University of Arizona, Y. S. was
supported in part by NSF No. PHY-0099484.
NR 25
TC 10
Z9 10
U1 0
U2 3
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 0031-9007
J9 PHYS REV LETT
JI Phys. Rev. Lett.
PD JUL 31
PY 2009
VL 103
IS 5
AR 050601
DI 10.1103/PhysRevLett.103.050601
PG 4
WC Physics, Multidisciplinary
SC Physics
GA 478WC
UT WOS:000268618300007
PM 19792473
ER
PT J
AU Dias-Ferreira, E
Sousa, JC
Melo, I
Morgado, P
Mesquita, AR
Cerqueira, JJ
Costa, RM
Sousa, N
AF Dias-Ferreira, Eduardo
Sousa, Joao C.
Melo, Irene
Morgado, Pedro
Mesquita, Ana R.
Cerqueira, Joao J.
Costa, Rui M.
Sousa, Nuno
TI Chronic Stress Causes Frontostriatal Reorganization and Affects
Decision-Making
SO SCIENCE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; DORSAL STRIATUM; HABIT
FORMATION; BASAL GANGLIA; CONTINGENCY; HIPPOCAMPAL; SENSITIVITY;
MORPHOLOGY; ADDICTION
AB The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision-making strategies, affecting the ability of stressed animals to perform actions on the basis of their consequences. Using two different operant tasks, we revealed that, in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action-outcome contingency. Furthermore, chronic stress caused opposing structural changes in the associative and sensorimotor corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex and the associative striatum and hypertrophy of the sensorimotor striatum. These data suggest that the relative advantage of circuits coursing through sensorimotor striatum observed after chronic stress leads to a bias in behavioral strategies toward habit.
C1 [Dias-Ferreira, Eduardo; Costa, Rui M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA.
[Dias-Ferreira, Eduardo; Sousa, Joao C.; Melo, Irene; Morgado, Pedro; Mesquita, Ana R.; Cerqueira, Joao J.; Sousa, Nuno] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, P-4710057 Braga, Portugal.
[Dias-Ferreira, Eduardo] Univ Coimbra, PhD Programme Expt Biol & Biomed PDBEB, Ctr Neurosci & Cell Biol, P-3004517 Coimbra, Portugal.
[Costa, Rui M.] Gulbenkian Inst Sci, Champalimaud Neurosci Programme, P-2780901 Oeiras, Portugal.
RP Costa, RM (reprint author), NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD 20852 USA.
EM costarui@mail.nih.gov; njcsousa@ecsaude.uminho.pt
RI Sousa, Nuno/C-2782-2009; Sousa, Joao/C-1048-2009; Cerqueira,
Joao/B-4579-2008; Morgado, Pedro/Q-1769-2015;
OI Sousa, Joao/0000-0003-3249-0035; Cerqueira, Joao/0000-0003-3155-2775;
Morgado, Pedro/0000-0003-3880-3258; Mesquita, Ana/0000-0002-9635-2355;
Costa, Rui/0000-0003-0495-8374; Sousa, Nuno/0000-0002-8755-5126
FU Bial Foundation [134/06]; ICV; Division of Intramural Clinical and Basic
Research, NIAAA, NIH
FX This work was supported by the Bial Foundation (134/06), the ICV, and
the Division of Intramural Clinical and Basic Research, NIAAA, NIH.
NR 30
TC 295
Z9 301
U1 4
U2 63
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 31
PY 2009
VL 325
IS 5940
BP 621
EP 625
DI 10.1126/science.1171203
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 477BY
UT WOS:000268493000053
PM 19644122
ER
PT J
AU Hodges, C
Bintu, L
Lubkowska, L
Kashlev, M
Bustamante, C
AF Hodges, Courtney
Bintu, Lacramioara
Lubkowska, Lucyna
Kashlev, Mikhail
Bustamante, Carlos
TI Nucleosomal Fluctuations Govern the Transcription Dynamics of RNA
Polymerase II
SO SCIENCE
LA English
DT Article
ID C-MYC; IN-VIVO; ELONGATION; GENE; DNA; TEMPLATES; MECHANISM; BARRIER;
BLOCK; END
AB RNA polymerase II (Pol II) must overcome the barriers imposed by nucleosomes during transcription elongation. We have developed an optical tweezers assay to follow individual Pol II complexes as they transcribe nucleosomal DNA. Our results indicate that the nucleosome behaves as a fluctuating barrier that locally increases pause density, slows pause recovery, and reduces the apparent pause-free velocity of Pol II. The polymerase, rather than actively separating DNA from histones, functions instead as a ratchet that rectifies nucleosomal fluctuations. We also obtained direct evidence that transcription through a nucleosome involves transfer of the core histones behind the transcribing polymerase via a transient DNA loop. The interplay between polymerase dynamics and nucleosome fluctuations provides a physical basis for the regulation of eukaryotic transcription.
C1 [Hodges, Courtney; Bustamante, Carlos] Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
[Hodges, Courtney; Bustamante, Carlos] Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
[Bintu, Lacramioara; Bustamante, Carlos] Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA.
[Lubkowska, Lucyna; Kashlev, Mikhail] NCI, Frederick Canc Res & Dev Ctr, NCI Ctr Canc Res, Frederick, MD 21702 USA.
[Bustamante, Carlos] Univ Calif Berkeley, Howard Hughes Med Inst, Dept Chem & Mol & Cell Biol, Berkeley, CA 94720 USA.
RP Hodges, C (reprint author), Univ Calif Berkeley, Jason L Choy Lab Single Mol Biophys, Berkeley, CA 94720 USA.
EM carlos@alice.berkeley.edu
FU NIH [GM32543]
FX Supported by NIH grant GM32543 (C.B.).
NR 25
TC 166
Z9 168
U1 7
U2 37
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 31
PY 2009
VL 325
IS 5940
BP 626
EP 628
DI 10.1126/science.1172926
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 477BY
UT WOS:000268493000054
PM 19644123
ER
PT J
AU Jaramillo-Gutierrez, G
Rodrigues, J
Ndikuyeze, G
Povelones, M
Molina-Cruz, A
Barillas-Mury, C
AF Jaramillo-Gutierrez, Giovanna
Rodrigues, Janneth
Ndikuyeze, Georges
Povelones, Michael
Molina-Cruz, Alvaro
Barillas-Mury, Carolina
TI Mosquito immune responses and compatibility between Plasmodium parasites
and anopheline mosquitoes
SO BMC MICROBIOLOGY
LA English
DT Article
ID DROSOPHILA MODEL; LIFE-CYCLE; FALCIPARUM; MALARIA; GAMBIAE; YOELII;
INFECTION; SELECTION; CULTURE; GENES
AB Background: Functional screens based on dsRNA-mediated gene silencing identified several Anopheles gambiae genes that limit Plasmodium berghei infection. However, some of the genes identified in these screens have no effect on the human malaria parasite Plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different Plasmodium species.
Results: Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P. berghei (Anka 2.34) and P. falciparum (3D7) infections. Orthologs of these genes, as well as LRIM1 and CTL4, were also silenced in An. stephensi (Nijmegen Sda500) females infected with P. yoelii (17XNL). For five of the six genes tested, silencing had the same effect on infection in the P. falciparum-An. gambiae and P. yoelii-An. stephensi parasite-vector combinations. Although silencing LRIM1 or CTL4 has no effect in An. stephensi females infected with P. yoelii, when An. gambiae is infected with the same parasite, silencing these genes has a dramatic effect. In An. gambiae (G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of P. yoelii, while CTL4 silencing enhances melanization.
Conclusion: There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different Plasmodium strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as P. yoelii (17XNL)-An. stephensi (Nijmegen Sda500), is more similar to that of P. falciparum (3D7)-An. gambiae (G3).
C1 [Jaramillo-Gutierrez, Giovanna; Rodrigues, Janneth; Ndikuyeze, Georges; Molina-Cruz, Alvaro; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Povelones, Michael] Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Cell & Mol Biol, London, England.
RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM gutierrgi@niaid.nih.gov; rodriguesj@niaid.nih.gov; gndiku1@towson.edu;
m.povelones@imperial.ac.uk; amolina-cruz@niaid.nih.gov;
cbarillas@niaid.nih.gov
FU Division of Intramural Research National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank Andre Laughinghouse, Kevin Lee, Tovi Lehman, and Robert Gwadz
for insectary support and NIAID Intramural editor Brenda Rae Marshall.
This research was supported by the Intramural Research Program of the
Division of Intramural Research National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 32
TC 35
Z9 35
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD JUL 30
PY 2009
VL 9
AR 154
DI 10.1186/1471-2180-9-154
PG 11
WC Microbiology
SC Microbiology
GA 492SX
UT WOS:000269680900002
PM 19643026
ER
PT J
AU Wang, B
Navath, RS
Romero, R
Kannan, S
Kannan, R
AF Wang, Bing
Navath, Raghavendra S.
Romero, Roberto
Kannan, Sujatha
Kannan, Rangaramanujam
TI Anti-inflammatory and anti-oxidant activity of anionic
dendrimer-N-acetyl cysteine conjugates in activated microglial cells
SO INTERNATIONAL JOURNAL OF PHARMACEUTICS
LA English
DT Article
DE Dendrimers; PAMAM; Drug delivery; Neuroinflammation; N-acetyl cysteine
ID DRUG-DELIVERY; NITRIC-OXIDE; IN-VITRO; PRETERM PARTURITION;
CELLULAR-TRANSPORT; RELEASE; INJURY; INFLAMMATION; MACROPHAGES;
INFECTION
AB Dendrimers are emerging as potential intracellular drug delivery vehicles. Understanding and improving the cellular efficacy of dendrimer-drug conjugates, can lead to significant in vivo benefits. This study explores efficacy of anionic polyamidoamine (PAMAM-COOH) dendrimer-N-acetyl cysteine (NAC) conjugates for applications in neuroinflammation. The anti-oxidative and anti-inflammatory effects of PAMAM-(COOH)(46)-(NAC)(18) conjugate is evaluated on microglial cells in vitro. Cell entry and localization of PAMAM-(COOH)(62)-(FITC)(2) conjugate in BV-2 microglial cells were assessed using flow cytometry and confocal microscopy. ELISA assays were used to evaluate markers of oxidative stress (ROS, NO) and inflammation (TNF-alpha) after stimulation of microglial cells with lipopolysaccharides (LPS), following treatment with increasing doses of free N-acetyl-L-cysteine (NAC) or PAMAM-(COOH)(46)-(NAC)(18) conjugate containing an equivalent molar concentration of NAC. Flow cytometry and confocal microscopy demonstrated the PAMAM-(COOH)(62)-(FITC)(2) conjugate entered BV-2 cells rapidly with significant increase in fluorescence within 15 min and localized mostly in the cytoplasm. PAMAM-(COOH)(46)-(NAC)(18) conjugate was non-toxic, and significantly reduced ROS, NO and TNF-alpha release by activated microglial cells after 24 h and 72 h stimulation of LPS following 3 h pre-treatment when compared to the same concentration of free NAC (P<0.05 or P<0.01). Anionic PAMAM dendrimer-NAC conjugate was synthesized with a glutathione sensitive linker for intracellular release. The non-toxic conjugate is a more effective anti-oxidant and anti-inflammatory agent when compared to free NAC in vitro. The conjugate showed significant efficacy even at the lowest dose (0.5 mM NAC), where the activity was comparable or better than that of free drug at 8 mM (16x higher dosage). The improved efficacy of the conjugate, when combined with the intrinsic neuroinflammation-targeting ability of the PAMAM dendrimers, may provide new opportunities for in vivo applications. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Navath, Raghavendra S.; Kannan, Rangaramanujam] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
[Wang, Bing; Kannan, Sujatha] Wayne State Univ, Dept Pediat Crit Care Med, Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Wang, Bing; Navath, Raghavendra S.; Romero, Roberto; Kannan, Rangaramanujam] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA.
RP Kannan, R (reprint author), Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA.
EM skannan@med.wayne.edu; rkannan@eng.wayne.edu
FU Intramural Research Program of the National Institute of Child Health
and Human Development; NIH; DHHS; Pediatric Critical Care Scientist
Development Program [NICHD-K08]
FX This study was supported by the Intramural Research Program of the
National Institute of Child Health and Human Development, NIH, DHHS, and
the Pediatric Critical Care Scientist Development Program NICHD-K08.
NR 32
TC 34
Z9 36
U1 2
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-5173
J9 INT J PHARMACEUT
JI Int. J. Pharm.
PD JUL 30
PY 2009
VL 377
IS 1-2
BP 159
EP 168
DI 10.1016/j.ijpharm.2009.04.050
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 476UK
UT WOS:000268471300022
PM 19463931
ER
PT J
AU Brooks, BR
Brooks, CL
Mackerell, AD
Nilsson, L
Petrella, RJ
Roux, B
Won, Y
Archontis, G
Bartels, C
Boresch, S
Caflisch, A
Caves, L
Cui, Q
Dinner, AR
Feig, M
Fischer, S
Gao, J
Hodoscek, M
Im, W
Kuczera, K
Lazaridis, T
Ma, J
Ovchinnikov, V
Paci, E
Pastor, RW
Post, CB
Pu, JZ
Schaefer, M
Tidor, B
Venable, RM
Woodcock, HL
Wu, X
Yang, W
York, DM
Karplus, M
AF Brooks, B. R.
Brooks, C. L., III
Mackerell, A. D., Jr.
Nilsson, L.
Petrella, R. J.
Roux, B.
Won, Y.
Archontis, G.
Bartels, C.
Boresch, S.
Caflisch, A.
Caves, L.
Cui, Q.
Dinner, A. R.
Feig, M.
Fischer, S.
Gao, J.
Hodoscek, M.
Im, W.
Kuczera, K.
Lazaridis, T.
Ma, J.
Ovchinnikov, V.
Paci, E.
Pastor, R. W.
Post, C. B.
Pu, J. Z.
Schaefer, M.
Tidor, B.
Venable, R. M.
Woodcock, H. L.
Wu, X.
Yang, W.
York, D. M.
Karplus, M.
TI CHARMM: The Biomolecular Simulation Program
SO JOURNAL OF COMPUTATIONAL CHEMISTRY
LA English
DT Review
DE biomolecular simulation; CHARMM program; molecular mechanics; molecular
dynamics; molecular modeling; biophysical computation; energy function
ID MOLECULAR-DYNAMICS SIMULATIONS; FREE-ENERGY CALCULATIONS; IMPLICIT
SOLVENT MODELS; EMPIRICAL FORCE-FIELD; MONTE-CARLO SIMULATIONS; BINDING
FREE-ENERGIES; PARTICLE-MESH EWALD; INTERMOLECULAR POTENTIAL FUNCTION;
CLASSICAL DRUDE OSCILLATOR; SIDE-CHAIN CONFORMATIONS
AB CHARMM (Chemistry at HARvard Molecular Mechanics) is a highly versatile and widely used molecular simulation program. It has been developed over the last three decades with a primary focus on molecules of biological interest, including proteins, peptides, lipids, nucleic acids, carbohydrates, and small molecule ligands, as they occur in solution, crystals, and membrane environments. For the study of such systems. the program provides a large suite of computational tools that include numerous conformational and path sampling methods, free energy estimators, molecular minimization, dynamics, and analysis techniques, and model-building capabilities. The CHARMM program is applicable to problems involving a much broader class of many-particle systems. Calculations with CHARMM can be performed using a number of different energy functions and models, from mixed quantum mechanical-molecular mechanical force fields, to all-atom classical potential energy functions with explicit solvent and various boundary conditions, to implicit solvent and membrane models. The program has been ported to numerous platforms in both serial and parallel architectures. This article provides an overview of the program as it exists today with an emphasis on developments since the publication of the original CHARMM article in 1983. (C) 2009 Wiley Periodicals, Inc. J Comput Chem 30: 1545-1614, 2009
C1 [Brooks, B. R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Brooks, C. L., III] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Brooks, C. L., III] Univ Michigan, Dept Biophys, Ann Arbor, MI 48109 USA.
[Mackerell, A. D., Jr.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Nilsson, L.] Karolinska Inst, Dept Biosci & Nutr, SE-14157 Huddinge, Sweden.
[Petrella, R. J.; Karplus, M.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Petrella, R. J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Roux, B.] Univ Chicago, Dept Biochem & Mol Biol, Gordon Ctr Integrat Sci, Chicago, IL 60637 USA.
[Won, Y.] Hanyang Univ, Dept Chem, Seoul 133792, South Korea.
[Karplus, M.] Univ Strasbourg, ISIS, Lab Chim Biophys, F-67000 Strasbourg, France.
RP Brooks, BR (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM brbrooks@helix.nih.gov; brookscl@umich.edu;
alex@outerbanks.umaryland.edu; Lennart.Nilsson@ki.se;
petrella@fas.harvard.edu; roux@uchicago.edu; won@hanyang.ac.kr;
marci@tammy.harvard.edu
RI Nilsson, Lennart/B-7208-2009; Pu, Jingzhi/C-4609-2011; Paci,
Emanuele/B-1893-2010; Woodc, Henry/D-9275-2011; Yang, Wei/H-5428-2011;
Caflisch, Amedeo/I-3459-2012; Bartels, Christian/D-1132-2013; Boresch,
Stefan/F-3467-2014;
OI MacKerell, Alex/0000-0001-8287-6804; Nilsson,
Lennart/0000-0002-5067-6397; Paci, Emanuele/0000-0002-4891-2768;
Bartels, Christian/0000-0002-6312-7450; Boresch,
Stefan/0000-0002-2793-6656; Woodcock, Henry/0000-0003-3539-273X
FU NIH [RR023920]; NSF; DOE; Accelrys; CNRS; NHLBI
FX In a multiauthor article. there is a leuitimate concern that the people
involved receive the credit that they deserve. In Peneral, this is not
possible Without listing the contributions of each individual, as some
journals are now requiring. For ail article of this length and
complexity, however, an), attempt at such specific attribution of credit
is impractical. All the authors contributed to the writing and rewriting
of significant portions of the text. The corresponding authors.
designated by asterisks, were also involved in planning the manuscript
and overseeing sections in the early stages of the writing. In both
groups (starred and unstarred), the listing is alphabetical. One author,
R.J. Petrella, needs to be mentioned individually because, in addition
to writing a significant portion of the article. he was instrumental in
transforming a large number of separate write-ups into what is very
nearly a unified whole.; The authors thank the referees for their
helpful comments and David A. Case for serving as the editor of the
paper. A number of people, other than those in the author list, have
read and commented on the manuscript. They include Kwangho Nam, Arjan
van der Vaart, loan Andricioaei, and Tom Darden.; In addition to all of
the authors of the paper, many other scientists have participated
significantly in the development of CHARMM through the years. See Table
3; this list is included with all distributions of the program (in
"charmm_main.src").; Support for the development of CHARMM, per se, and
for researchers concerned with CHARMM development, have come from many
sources. including NSF, NIH, DOE, Accelrys, and CNRS. It is not possible
to list all of the grants individually, but NIH grant RR023920 is
acknowledged for its direct support of the ongoing CHARMM conversion
project. Part of the research in the B.R. Brooks group was supported by
the Intramural Research Program of the NIH, NHLBI.
NR 721
TC 2780
Z9 2800
U1 57
U2 616
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0192-8651
EI 1096-987X
J9 J COMPUT CHEM
JI J. Comput. Chem.
PD JUL 30
PY 2009
VL 30
IS 10
SI SI
BP 1545
EP 1614
DI 10.1002/jcc.21287
PG 70
WC Chemistry, Multidisciplinary
SC Chemistry
GA 461LX
UT WOS:000267269600001
PM 19444816
ER
PT J
AU Ziolkowska, NE
Michejda, CJ
Bujacz, GD
AF Ziolkowska, Natasza E.
Michejda, Christopher J.
Bujacz, Grzegorz D.
TI Crystal structures of HIV-1 nonnucleoside reverse transcriptase
inhibitors: N-benzyl-4-methyl-benzimidazoles
SO JOURNAL OF MOLECULAR STRUCTURE
LA English
DT Article
DE AIDS; HIV-1; Reverse transcriptase inhibitor; Drug design; Crystal
structure
ID RESISTANCE MUTATIONS; BIOLOGICAL-ACTIVITY; WILD-TYPE; COMPLEX; DESIGN;
POTENT; RESOLUTION; MUTANT; 1H,3H-THIAZOLO<3,4-A>BENZIMIDAZOLES;
REPLICATION
AB HIV-1 nonnucleoside reverse transcriptase inhibitors are potentially specific and effective drugs in AIDS therapy. The presence of two aromatic systems with an angled orientation in the molecule of the inhibitor is crucial for interactions with HIV-1 RT. The inhibitor drives like a wedge into the cluster of aromatic residues of RT HIV-1 and restrains the enzyme in a conformation that blocks the chemical step of nucleotide incorporation. Structural studies provide useful information for designing new, more active inhibitors. The crystal structures of four NNRTIs are presented here. The investigated compounds are derivatives of N-benzyl-4-methyl-benzimidazole with various aliphatic and aromatic substituents at carbon 2 positions and a 2,6-dihalogeno-substituted N-benzyl moiety. Structural data reported here show that the conformation of the investigated compounds is relatively rigid. Such feature is important for the nonnucleoside inhibitor binding to HIV-1 reverse transcriptase. (C) 2009 Published by Elsevier B.V.
C1 [Ziolkowska, Natasza E.; Bujacz, Grzegorz D.] Tech Univ Lodz, Inst Tech Biochem, PL-90924 Lodz, Poland.
[Michejda, Christopher J.] NIH, Mol Aspects Drug Design Sect, Frederick, MD 21702 USA.
RP Bujacz, GD (reprint author), Tech Univ Lodz, Inst Tech Biochem, Stefanowskiego 4-10, PL-90924 Lodz, Poland.
EM gdbujacz@p.lodz.pl
FU Polish Committee for Scientific Research, KBN [4P05F 03114]
FX This work was supported by the Polish Committee for Scientific Research,
KBN, Grant no 4P05F 03114. Authors are grateful to Wieslaw Majzner for
his assistance in collecting data on CAD4 diffractometer and to Dr.
Tobias Walther for editorial suggestions.
NR 33
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0022-2860
J9 J MOL STRUCT
JI J. Mol. Struct.
PD JUL 30
PY 2009
VL 930
IS 1-3
BP 157
EP 161
DI 10.1016/j.molstruc.2009.05.007
PG 5
WC Chemistry, Physical
SC Chemistry
GA 475YH
UT WOS:000268403100026
ER
PT J
AU Polikov, VS
Su, EC
Ball, MA
Hong, JS
Reichert, WM
AF Polikov, Vadim S.
Su, Eric C.
Ball, Matthew A.
Hong, Jau-Shyong
Reichert, William M.
TI Control protocol for robust in vitro glial scar formation around
microwires: Essential roles of bFGF and serum in gliosis
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Glial scar; In vitro model; Neuroprosthetics; Brain machine interface;
Serum; bFGF; Neural precursor cells
ID NEURAL STEM-CELLS; OLIGODENDROCYTE PRECURSOR CELLS;
DOPAMINERGIC-NEURONS; INFLAMMATORY DAMAGE; FUNCTIONAL-NEURONS;
PLASMA-ALBUMIN; BRAIN-INJURY; ASTROCYTES; DIFFERENTIATION; MICROGLIA
AB Previously, we reported an in vitro cell culture model that recreates many of the hallmarks of glial scarring around electrodes used for recording in the brain; however, the model lacked the reproducibility necessary to establish a useful characterization tool. This methods paper describes a protocol, modeled on protocols typically used to culture neural stem/precursor cells, that generates a predictable positive control of an intense scarring reaction. Six independent cell culture variables (growth media, seeding density, bFGF addition day, serum concentration in treatment media, treatment day, and duration of culture) were varied systematically and the resulting scars were quantified. The following conditions were found to give the highest level of scarring: Neurobasal medium supplemented with 1327, 10% fetal bovine serum at treatment, 10 ng/ml b-FGF addition at seeding and at treatment, treatment at least 6 days after seeding and scar growth of at least 5 days. Seeding density did not affect scarring as long as at least 500,000 cells were seeded per well, but appropriate media, bFGF, and serum were essential for significant scar formation-insights that help validate the in vitro-based approach to understanding glial scarring. With the control protocol developed in this study producing a strong, reproducible glial scarring positive control with every dissection, this culture model is suitable for the in vitro study of the mechanisms behind glial scarring and neuroelectrode failure. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Polikov, Vadim S.; Su, Eric C.; Ball, Matthew A.; Reichert, William M.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA.
[Hong, Jau-Shyong] NIEHS, Neuropharmacol Grp, Res Triangle Pk, NC 27709 USA.
RP Reichert, WM (reprint author), Duke Univ, Dept Biomed Engn, Box 90281, Durham, NC 27708 USA.
EM reichert@duke.edu
FU [NS R21NS057131]
FX Our sincere thanks go to Dr. Theodore Slotkin of Duke University for his
help in explaining and recommending the various statistical methods used
to analyze the data. Dr. Slotkin teaches a graduate seminar called
Statistics for Basic Biomedical Scientists and freely and graciously
provides such help to current and former students. This work was
supported by NS R21NS057131.
NR 38
TC 12
Z9 13
U1 0
U2 7
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 2009
VL 181
IS 2
BP 170
EP 177
DI 10.1016/j.jneumeth.2009.05.002
PG 8
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 472SM
UT WOS:000268152400003
PM 19447137
ER
PT J
AU Atkin, SD
Patel, S
Kocharyan, A
Holtzclaw, LA
Weerth, SH
Schram, V
Pickel, J
Russell, JT
AF Atkin, Stan D.
Patel, Sundip
Kocharyan, Ara
Holtzclaw, Lynne A.
Weerth, Susanna H.
Schram, Vincent
Pickel, James
Russell, James T.
TI Transgenic mice expressing a cameleon fluorescent Ca2+ indicator in
astrocytes and Schwann cells allow study of glial cell Ca2+ signals in
situ and in vivo
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE YC 3.60 cameleon; Astrocytes; Schwann cells; Transgenic mice
ID GENETICALLY ENCODED INDICATORS; SYNAPTIC-TRANSMISSION;
NEURONAL-ACTIVITY; TEMPORAL EXPRESSION; NEURAL ACTIVITY; NERVOUS-SYSTEM;
CALCIUM WAVES; TROPONIN-C; GLUTAMATE; RECEPTORS
AB Glial cell Ca2+ signals play a key role in glial-neuronal and glial-glial network communication. Numerous studies have thus far utilized cell-permeant and injected Ca2+ indicator dyes to investigate glial Ca2+ signals in vitro and in situ. Genetically encoded fluorescent Ca2+ indicators have emerged as novel probes for investigating cellular Ca2+ signals. We have expressed one such indicator protein, the YC 3.60 cameleon, under the control of the S100 beta promoter and directed its expression predominantly in astrocytes and Schwann cells. Expression of YC 3.60 extended into the entire cellular cytoplasmic compartment and the fine terminal processes of protoplasmic astrocytes and Schwann cell Cajal bands. In the brain, all the cells known to express S100 beta in the adult or during development, expressed YC 3.60. While expression was most extensive in astrocytes, other glial cell types that express S100 beta, such as NG2 and CNP-positive oligodendrocyte progenitor cells (OP cells), microglia, and some of the large motor neurons in the brain stem, also contained YC 3.60 fluorescence. Using a variety of known in situ and in vivo assays, we found that stimuli known to elicit Ca2+ signals in astrocytes caused substantial and rapid Ca2+ signals in the YC 3.60-expressing astrocytes. In addition, forepaw stimulation while imaging astrocytes through a cranial window in the somatosensory cortex in live mice, revealed robust evoked and spontaneous Ca2+ signals. These results, for the first time, show that genetically encoded reporter is capable of recording activity-dependent Ca2+ signals in the astrocyte processes, and networks. Published by Elsevier B.V.
C1 [Russell, James T.] NICHD, Lab Cellular & Mol Neurophysiol, NIH, Sect Cell Biol & Signal Transduct, Bethesda, MD 20892 USA.
[Kocharyan, Ara] NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA.
[Schram, Vincent] NICHD Microscopy & Imaging Core, Bethesda, MD USA.
[Pickel, James] NIMH, NIMH Transgen Core Facil, Bethesda, MD 20892 USA.
RP Russell, JT (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Sect Cell Biol & Signal Transduct, Bldg 49,Room 5A-22,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA.
EM james@helix.nih.gov
FU National Institutes of Child Health and Human Development; National
Institutes of Health
FX We wish to thank Dr. Ramin Mollaaghababa for discussions and guidance in
the early phases of plasmid construction. We wish to thank Drs. josh
Lawrence, Newton Woo, and Ludovic Tricore for help in setting up the
Clampex software and integrating it with the Multiclamp. This work was
supported by funds from the intramural Research Program of the National
Institutes of Child Health and Human Development, National Institutes of
Health.
NR 57
TC 32
Z9 33
U1 0
U2 2
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 2009
VL 181
IS 2
BP 212
EP 226
DI 10.1016/j.jneumeth.2009.05.006
PG 15
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 472SM
UT WOS:000268152400007
PM 19454294
ER
PT J
AU Gautheron, V
Auffret, A
Mattson, MP
Mariani, J
Vernet-der Garabedian, B
AF Gautheron, Vanessa
Auffret, Alexandra
Mattson, Mark P.
Mariani, Jean
Vernet-der Garabedian, Beatrice
TI A new and simple approach for genotyping Alzheimer's disease
presenilin-1 mutant knock-in mice
SO JOURNAL OF NEUROSCIENCE METHODS
LA English
DT Article
DE Presenilin-1; Genotyping; SSCP; Knock-in; Alzheimer's disease
ID HIPPOCAMPAL-NEURONS; POLYACRYLAMIDE-GELS; DNA; POLYMORPHISMS; MUTATION;
SSCP; VULNERABILITY; APOPTOSIS; MODEL; BETA
AB The use of transgenic mice expressing point mutations demands that the detection of the different alleles is efficient and reliable. In addition, the multiplication of transgenes included in mouse models of human disease underlines the importance of correct controls and the fact that investigators need an accurate and rapid genotyping of the littermates generated. In this study, we demonstrate a powerful alternative for genotyping using presenilin-1 mutant knock-in (PS1M146KI) mice as an example.
Mutations in the presenilin-1 (PSI) gene are causally linked to many cases of early-onset inherited Alzheimer's disease (AD). PS1M146VKI mice that express the PS1M146V targeted allele at normal physiological levels and triple-transgenic model (3xTg-AD) derived from homozygous PS1M146VKI mice were generated to study the pathogenesis of AD. Genotyping PS1M146VKI line requires many steps and thus a large quantity of DNA. In PS1M146VKI mice, only three nucleotides are modified in the gene. Here we show that this small mutated DNA sequence can affect its secondary structure resulting in altered mobility that can be easily detected on a polyacrylamide gel, by the single-strand conformation polymorphism (SSCP) technique. Our results demonstrate that SSCP is a simple, accurate, repeatable and efficient method for the routine genotyping of this current AD model. This method could be easily applied to other transgenic mice. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Gautheron, Vanessa; Auffret, Alexandra; Mariani, Jean; Vernet-der Garabedian, Beatrice] Univ Paris 06, CNRS, Neurobiol Proc Adaptatifs NPA, Equipe Dev & Vieillissement Syst Nerveux,UMR 7102, F-75005 Paris, France.
[Mariani, Jean] Hop Charles Foix, AP HP, Unite Explorat Fonct, F-94200 Ivry, France.
[Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA.
RP Gautheron, V (reprint author), Univ Paris 06, CNRS, Neurobiol Proc Adaptatifs NPA, Equipe Dev & Vieillissement Syst Nerveux,UMR 7102, 9 Quai St Bernard, F-75005 Paris, France.
EM vgauther@snv.jussieu.fr; alexandraauffret@gmail.com;
mattsonm@grc.nia.nih.gov; jean.mariani@snv.jussieu.fr;
beatrice.vernet-dergarabedian@snv.jussieu.fr
RI Mattson, Mark/F-6038-2012
FU "Centre National de la Recherche Scientifique" (CNRS); Universite Pierre
et Marie Curie (UPMC); "Fondation de le la Recherche Medicale" (FRM);
"Fondation de la Recherche Sur le Cerveau" (FRC); NIH
FX This work was supported by funds from "Centre National de la Recherche
Scientifique" (CNRS), Universite Pierre et Marie Curie (UPMC),
"Fondation de le la Recherche Medicale" (FRM) and "Fondation de la
Recherche Sur le Cerveau" (FRC), and the Intramural Research Program of
the National Institute on Aging of the NIH. We thank the animal facility
of Universite Pierre et Marie Curie. We thank Mrs. S. Jezequel and
Mohamed Mughal for technical assistance, and Dr. Rachel Sherrard for her
critical reading of the paper.
NR 24
TC 3
Z9 3
U1 0
U2 0
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 2009
VL 181
IS 2
BP 235
EP 240
DI 10.1016/j.jneumeth.2009.05.009
PG 6
WC Biochemical Research Methods; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 472SM
UT WOS:000268152400009
PM 19465058
ER
PT J
AU Weintraub, D
Hoops, S
Shea, JA
Lyons, KE
Pahwa, R
Driver-Dunckley, ED
Adler, CH
Potenza, MN
Miyasaki, J
Siderowf, AD
Duda, JE
Hurtig, HI
Colcher, A
Horn, SS
Stem, MB
Voon, V
AF Weintraub, Daniel
Hoops, Staci
Shea, Judy A.
Lyons, Kelly E.
Pahwa, Rajesh
Driver-Dunckley, Erika D.
Adler, Charles H.
Potenza, Marc N.
Miyasaki, Janis
Siderowf, Andrew D.
Duda, John E.
Hurtig, Howard I.
Colcher, Amy
Horn, Stacy S.
Stem, Matthew B.
Voon, Valerie
TI Validation of the Questionnaire for Impulsive-Compulsive Disorders in
Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; impulse control disorders; dopamine dysregulation
syndrome; punding; pathological gambling
ID HEDONISTIC HOMEOSTATIC DYSREGULATION; DOPAMINE AGONISTS; PREVALENCE;
BEHAVIOR; ASSOCIATION
AB As no comprehensive assessment instrument for impulse control disorders (ICDs) in Parkinson's disease (PD) exists, the aim of this study was to design and assess the psychometric properties of a self-administered screening questionnaire for ICDs and other compulsive behaviors in PD. The Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease (QUIP) has 3 sections: Section 1 assesses four ICDs (involving gambling, sexual, buying, and eating behaviors), Section 2 other compulsive behaviors (punding, hobbyism, and walkabout), and Section 3 Compulsive medication use. For validation, a convenience sample of 157 PD patients at 4 movement disorders centers first completed the QUIP, and then was administered a diagnostic interview by a trained rater blinded to the QUIP results. A shortened instrument (QUIP-S) was then explored. The discriminant validity of the QUIP was high for each disorder or behavior (receiver operating characteristic area under the curve [ROC AUC]: gambling = 0.95, sexual behavior = 0.97, buying = 0.87, eating = 0.88, punding = 0.78, hobbyism = 0.93, walkabout = 0.79). On post hoc analysis, the QUIP-S ICD section had similar properties (ROC AUC: gambling = 0.95, sexual behavior = 0.96, buying = 0.87, eating = 0.88). When disorders/behaviors were combined, the sensitivity of the QUIP and QUIP-S to detect an individual with any disorder was 96 and 94%, respectively. Scores on the QUIP appear to be valid as a self-assessment screening instrument for a range of ICDs and other compulsive behaviors that occur in PD, and a shortened version may perform as well as the full version. A positive screen should be followed by a comprehensive, clinical interview to determine the range and severity of symptoms, as well as need for clinical management. (C) 2009 Movement Disorder Society
C1 [Weintraub, Daniel; Hoops, Staci] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Weintraub, Daniel; Siderowf, Andrew D.; Duda, John E.; Hurtig, Howard I.; Colcher, Amy; Horn, Stacy S.; Stem, Matthew B.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Weintraub, Daniel; Duda, John E.; Stem, Matthew B.] Philadelphia Vet Affairs Med Ctr, PADRECC, Philadelphia, PA USA.
[Weintraub, Daniel] Philadelphia Vet Affairs Med Ctr, MIRECC, Philadelphia, PA USA.
[Shea, Judy A.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Shea, Judy A.] Philadelphia Vet Affairs Med, CHERP, Philadelphia, PA USA.
[Lyons, Kelly E.; Pahwa, Rajesh] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Driver-Dunckley, Erika D.; Adler, Charles H.] Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA.
[Potenza, Marc N.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Miyasaki, Janis] Univ Toronto, Div Neurol, Toronto, ON, Canada.
[Voon, Valerie] NINDS, Bethesda, MD 20892 USA.
RP Weintraub, D (reprint author), 3615 Chestnut St,Room 330, Philadelphia, PA 19104 USA.
EM weintrau@mail.med.upenn.edu
OI Miyasaki, Janis/0000-0002-6372-6007
FU NIDA NIH HHS [R01 DA019039, R01 DA019039-05]; NIMH NIH HHS [K23
MH067894, K23 MH067894-05]
NR 31
TC 133
Z9 134
U1 3
U2 13
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUL 30
PY 2009
VL 24
IS 10
BP 1461
EP 1467
DI 10.1002/mds.22571
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 478UK
UT WOS:000268613600006
PM 19452562
ER
PT J
AU Silberberg, SD
Swartz, KJ
AF Silberberg, Shai D.
Swartz, Kenton J.
TI STRUCTURAL BIOLOGY Trimeric ion-channel design
SO NATURE
LA English
DT Editorial Material
ID P2X RECEPTORS; K+ CHANNEL; RESOLUTION
C1 [Silberberg, Shai D.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Silberberg, SD (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
EM shai.silberberg@nih.gov; kenton.swartz@nih.gov
FU Intramural NIH HHS [ZIA NS003018-03]
NR 14
TC 7
Z9 8
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 580
EP 581
DI 10.1038/460580a
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300035
PM 19641581
ER
PT J
AU Finkel, T
Deng, CX
Mostoslavsky, R
AF Finkel, Toren
Deng, Chu-Xia
Mostoslavsky, Raul
TI Recent progress in the biology and physiology of sirtuins
SO NATURE
LA English
DT Review
ID PANCREATIC BETA-CELLS; SIRT1 REGULATES APOPTOSIS; CALORIE RESTRICTION;
DEACETYLASE SIRT1; GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE;
INSULIN-SECRETION; LIFE-SPAN; TRANSCRIPTION FACTORS; LYSINE ACETYLATION
AB The sirtuins are a highly conserved family of NAD(+)-dependent enzymes that regulate lifespan in lower organisms. Recently, the mammalian sirtuins have been connected to an ever widening circle of activities that encompass cellular stress resistance, genomic stability, tumorigenesis and energy metabolism. Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live.
C1 [Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Finkel, Toren] NHLBI, Translat Med Branch, Bethesda, MD 20892 USA.
[Mostoslavsky, Raul] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
EM chuxiad@bdg10.niddk.nih.gov
RI deng, chuxia/N-6713-2016
FU NIH; Ellison Medical Foundation; Sidney Kimmel Cancer Research
Foundation; V Foundation
FX We apologize to our colleagues for being unable to cite all appropriate
references owing to space limitations. Highlighted references are a
subjective appraisal of some of the most interesting manuscripts
published in the last year. We are grateful to I. Rovira for help with
figures. This work was supported by NIH Intramural funds (T. F, C.-X.
D.), The Ellison Medical Foundation (T. F.), The Sidney Kimmel Cancer
Research Foundation (R. M.) and the V Foundation (R. M.).
NR 84
TC 679
Z9 703
U1 11
U2 110
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 30
PY 2009
VL 460
IS 7255
BP 587
EP 591
DI 10.1038/nature08197
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PK
UT WOS:000268454300041
PM 19641587
ER
PT J
AU Genovesio, A
Tsujimoto, S
Wise, SP
AF Genovesio, Aldo
Tsujimoto, Satoshi
Wise, Steven P.
TI Feature- and Order-Based Timing Representations in the Frontal Cortex
SO NEURON
LA English
DT Article
ID DURATION-DISCRIMINATION TASK; MONKEY PREFRONTAL NEURONS; TIME
PERCEPTION; ELAPSED TIME; TEMPORAL INFORMATION; STIMULUS-DURATION; BRAIN
ACTIVATION; PREMOTOR CORTEX; WORKING-MEMORY; BASAL GANGLIA
AB We examined activity in the frontal cortex as monkeys performed a duration-discrimination task. Two stimuli, one red and the other blue, appeared sequentially on a video screen-in either order. Later, both stimuli reappeared, and to receive a reward the monkeys had to choose the stimulus that had lasted longer during its initial presentation. Some neurons encoded stimulus duration, but a larger number of cells represented their relative duration, which was encoded in three ways: whether the first or second stimulus had lasted longer; whether the red or blue stimulus had lasted longer; or, less commonly, as the difference between the two durations. As the monkeys' choice approached, the signal encoding which stimulus (red or blue) had lasted longer increased as the order-based signal dissipated. By representing stimulus durations and relative durations-both bound to Stimulus features and event order-the frontal cortex could contribute to both temporal perception and episodic memory.
C1 [Genovesio, Aldo; Tsujimoto, Satoshi; Wise, Steven P.] NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
[Genovesio, Aldo] Univ Rome, Dept Physiol & Pharmacol, I-00185 Rome, Italy.
[Tsujimoto, Satoshi] Kobe Univ, Grad Sch Human Dev & Environm, Dev Cognit Neurosci Lab, Kobe, Hyogo 6578501, Japan.
RP Genovesio, A (reprint author), NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA.
EM aldo.genovesio@uniroma1.it
RI Tsujimoto, Satoshi/B-8223-2011
FU Division of Intramural Research of the National Institute of Mental
Health [Z01MH-01092]
FX This work was supported by the Division of Intramural Research of the
National Institute of Mental Health (Z01MH-01092). We thank Dr. Andrew
Mitz, Mr. James Fellows, and Ms. Ping Yu for technical support.
NR 36
TC 44
Z9 44
U1 0
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 30
PY 2009
VL 63
IS 2
BP 254
EP 266
DI 10.1016/j.neuron.2009.06.018
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 479IS
UT WOS:000268653500013
PM 19640483
ER
PT J
AU Flum, DR
Belle, SH
King, WC
Wahed, AS
Berk, P
Chapman, W
Pories, W
Courcoulas, A
McCloskey, C
Mitchell, J
Patterson, E
Pomp, A
Staten, MA
Yanovski, SZ
Thirlby, R
Wolfe, B
AF Flum, David Reed
Belle, Steven H.
King, Wendy C.
Wahed, Abdus S.
Berk, Paul
Chapman, William
Pories, Walter
Courcoulas, Anita
McCloskey, Carol
Mitchell, James
Patterson, Emma
Pomp, Alfons
Staten, Myrlene A.
Yanovski, Susan Z.
Thirlby, Richard
Wolfe, Bruce
CA LABS Consortium
TI Perioperative Safety in the Longitudinal Assessment of Bariatric
Surgery.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID GASTRIC BYPASS-SURGERY; MORTALITY RISK SCORE; MULTIVARIATE-ANALYSIS;
MORBID-OBESITY; OUTCOMES
AB Background: To improve decision making in the treatment of extreme obesity, the risks of bariatric surgical procedures require further characterization.
Methods: We performed a prospective, multicenter, observational study of 30-day outcomes in consecutive patients undergoing bariatric surgical procedures at 10 clinical sites in the United States from 2005 through 2007. A composite end point of 30-day major adverse outcomes (including death; venous thromboembolism; percutaneous, endoscopic, or operative reintervention; and failure to be discharged from the hospital) was evaluated among patients undergoing first-time bariatric surgery.
Results: There were 4776 patients who had a first-time bariatric procedure (mean age, 44.5 years; 21.1% men; 10.9% nonwhite; median body-mass index [the weight in kilograms divided by the square of the height in meters], 46.5). More than half had at least two coexisting conditions. A Roux-en-Y gastric bypass was performed in 3412 patients (with 87.2% of the procedures performed laparoscopically), and laparoscopic adjustable gastric banding was performed in 1198 patients; 166 patients underwent other procedures and were not included in the analysis. The 30-day rate of death among patients who underwent a Roux-en-Y gastric bypass or laparoscopic adjustable gastric banding was 0.3%; a total of 4.3% of patients had at least one major adverse outcome. A history of deep-vein thrombosis or pulmonary embolus, a diagnosis of obstructive sleep apnea, and impaired functional status were each independently associated with an increased risk of the composite end point. Extreme values of body-mass index were significantly associated with an increased risk of the composite end point, whereas age, sex, race, ethnic group, and other coexisting conditions were not.
Conclusions: The overall risk of death and other adverse outcomes after bariatric surgery was low and varied considerably according to patient characteristics. In helping patients make appropriate choices, short-term safety should be considered in conjunction with both the long-term effects of bariatric surgery and the risks associated with being extremely obese. (ClinicalTrials.gov number, NCT00433810.)
N Engl J Med 2009;361:445-54.
C1 [Flum, David Reed] Univ Washington, Surg Outcomes Res Ctr, Dept Surg, Seattle, WA 98195 USA.
[Belle, Steven H.; King, Wendy C.; Wahed, Abdus S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Berk, Paul] Columbia Univ, Med Ctr, New York, NY USA.
[Chapman, William; Pories, Walter] E Carolina Univ, Brody Sch Med, Greenville, NC USA.
[Courcoulas, Anita; McCloskey, Carol] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Mitchell, James] Neuropsychiat Res Inst, Fargo, ND USA.
[Patterson, Emma] Legacy Good Samaritan Hosp, Portland, OR USA.
[Pomp, Alfons] Cornell Univ, Med Ctr, New York, NY 10021 USA.
[Staten, Myrlene A.; Yanovski, Susan Z.] NIDDK, Bethesda, MD USA.
[Thirlby, Richard] Virginia Mason Med Ctr, Seattle, WA 98101 USA.
[Wolfe, Bruce] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Flum, DR (reprint author), Univ Washington, Surg Outcomes Res Ctr, Dept Surg, Box 356410, Seattle, WA 98195 USA.
EM sorce@u.washington.edu
OI King, Wendy/0000-0002-0740-0029; Wahed, Abdus/0000-0001-6911-7221
FU National Institute of Diabetes and Digestive and Kidney Diseases
[U01-DK066557, U01-DK66667, U01-DK66568, M01-RR-00037, U01-DK66471,
U01-DK66526, U01-DK66585, U01-DK66555]
FX Supported by grants from the National Institute of Diabetes and
Digestive and Kidney Diseases (U01-DK066557, to the Data Coordinating
Center; U01-DK66667, to Columbia University; U01-DK66568, to the
University of Washington, in collaboration with General Clinical
Research Center grant M01-RR-00037; U01-DK66471, to the Neuropsychiatric
Research Institute; U01DK66526, to East Carolina University;
U01-DK66585, to the University of Pittsburgh Medical Center; and
U01-DK66555, to Oregon Health and Science University).
NR 22
TC 586
Z9 603
U1 4
U2 15
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 30
PY 2009
VL 361
IS 5
BP 445
EP 454
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476LW
UT WOS:000268443900005
ER
PT J
AU Barrett, J
Blazar, BR
AF Barrett, John
Blazar, Bruce R.
TI Genetic Trickery -- Escape of Leukemia from Immune Attack.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID MYELOID LEUKEMIAS; TRANSPLANTATION
C1 [Barrett, John] NHLBI, Bethesda, MD 20892 USA.
[Blazar, Bruce R.] Univ Minnesota, Minneapolis, MN USA.
RP Barrett, J (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 5
TC 3
Z9 3
U1 0
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 30
PY 2009
VL 361
IS 5
BP 524
EP 525
DI 10.1056/NEJMe0903177
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476LW
UT WOS:000268443900016
PM 19641211
ER
PT J
AU Valentin, A
Chikhlikar, P
Patel, V
Rosati, M
Maciel, M
Chang, KH
Silvera, P
Felber, BK
Pavlakis, GN
August, JT
Marques, ETA
AF Valentin, Antonio
Chikhlikar, Priya
Patel, Vainav
Rosati, Margherita
Maciel, Milton
Chang, Kern-Hee
Silvera, Peter
Felber, Barbara K.
Pavlakis, George N.
August, J. Thomas
Marques, Ernesto T. A.
TI Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in
rhesus macaques reveals antigen-specific T-cell responses with distinct
phenotypes
SO VACCINE
LA English
DT Article
DE Central memory; Effector memory; CD4; CD8; T cells; IFN-gamma;
TNF-alpha; IL-2
ID IMMUNODEFICIENCY VIRUS CHALLENGE; NEUTRALIZING ANTIBODY-RESPONSE;
CLASS-II COMPARTMENT; MEMBRANE-PROTEIN; IMMUNE-RESPONSES; VACCINATION;
EXPRESSION; ELECTROPORATION; SEQUENCES; MONKEYS
AB Optimized DNA expression vectors encoding the native HIV-1 Gag ora fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4(+) T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4(+) responses with a phenotype of central memory-like T cells (CD28(+) CD45RA(-)), whereas the LAMP/Gag chimera induced CD4(+) responses with effector memory phenotype (CD28(-) CD45RA(-)). Antigen-specific T cells producing both IFN-gamma and TNF alpha were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity. Published by Elsevier Ltd.
C1 [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Valentin, Antonio; Patel, Vainav; Rosati, Margherita; Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA.
[Chikhlikar, Priya; Maciel, Milton; Chang, Kern-Hee; August, J. Thomas; Marques, Ernesto T. A.] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21210 USA.
[Marques, Ernesto T. A.] Johns Hopkins Univ, Sch Med, Dept Infect Dis, Baltimore, MD 21210 USA.
[Silvera, Peter] So Res Inst, Frederick, MD 21701 USA.
[Marques, Ernesto T. A.] Fundacao Oswaldo Cruz, FIOCRUZ, Inst Aggeu Magalhaes, BR-50670420 Recife, PE, Brazil.
RP Felber, BK (reprint author), NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, POB B,Bldg 535,Room 209, Frederick, MD 21702 USA.
EM felber@ncifcrf.gov; pavlakig@mail.nih.gov
RI Saude Publica, Inct/J-9544-2013; Marques, Ernesto/L-4514-2013; Marques,
Ernesto/L-4967-2013
OI Marques, Ernesto/0000-0003-3826-9358; Marques,
Ernesto/0000-0003-3826-9358
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research
FX We thank C. Bergamaschi and V. Kulkarni for discussions, K Nagashima for
electron microscopy, J. Bear and P. Roth for technical assistance, and
T. Jones for editorial assistance. We thank Jon Warren, VRP, DAIDS for
materials and support. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 35
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 0264-410X
J9 VACCINE
JI Vaccine
PD JUL 30
PY 2009
VL 27
IS 35
BP 4840
EP 4849
DI 10.1016/j.vaccine.2009.05.093
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 481QV
UT WOS:000268827500017
PM 19539586
ER
PT J
AU Canzian, F
Kaaks, R
Cox, DG
Henderson, KD
Henderson, BE
Berg, C
Bingham, S
Boeing, H
Buring, J
Calle, EE
Chanock, S
Clavel-Chapelon, F
Dossus, L
Feigelson, HS
Haiman, CA
Hankinson, SE
Hoover, R
Hunter, DJ
Isaacs, C
Lenner, P
Lund, E
Overvad, K
Palli, D
Pearce, CL
Quiros, JR
Riboli, E
Stram, DO
Thomas, G
Thun, MJ
Trichopoulos, D
van Gils, CH
Ziegler, RG
AF Canzian, Federico
Kaaks, Rudolf
Cox, David G.
Henderson, Katherine D.
Henderson, Brian E.
Berg, Christine
Bingham, Sheila
Boeing, Heiner
Buring, Julie
Calle, Eugenia E.
Chanock, Stephen
Clavel-Chapelon, Francoise
Dossus, Laure
Feigelson, Heather Spencer
Haiman, Christopher A.
Hankinson, Susan E.
Hoover, Robert
Hunter, David J.
Isaacs, Claudine
Lenner, Per
Lund, Eiliv
Overvad, Kim
Palli, Domenico
Pearce, Celeste Leigh
Quiros, Jose R.
Riboli, Elio
Stram, Daniel O.
Thomas, Gilles
Thun, Michael J.
Trichopoulos, Dimitrios
van Gils, Carla H.
Ziegler, Regina G.
TI Genetic polymorphisms of the GNRH1 and GNRHR genes and risk of breast
cancer in the National Cancer Institute Breast and Prostate Cancer
Cohort Consortium (BPC3)
SO BMC CANCER
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; MULTIETHNIC COHORT; ASSOCIATION; NUTRITION;
WOMEN; POPULATIONS; ESTROGENS; ANDROGENS; SAMPLE; HEALTH
AB Background: Gonadotropin releasing hormone (GNRH1) triggers the release of follicle stimulating hormone and luteinizing hormone from the pituitary. Genetic variants in the gene encoding GNRH1 or its receptor may influence breast cancer risk by modulating production of ovarian steroid hormones. We studied the association between breast cancer risk and polymorphisms in genes that code for GNRH1 and its receptor (GNRHR) in the large National Cancer Institute Breast and Prostate Cancer Cohort Consortium (NCI-BPC3).
Methods: We sequenced exons of GNRH1 and GNRHR in 95 invasive breast cancer cases. Resulting single nucleotide polymorphisms ( SNPs) were genotyped and used to identify haplotype-tagging SNPs (htSNPS) in a panel of 349 healthy women. The htSNPs were genotyped in 5,603 invasive breast cancer cases and 7,480 controls from the Cancer Prevention Study-II (CPS-II), European Prospective Investigation on Cancer and Nutrition ( EPIC), Multiethnic Cohort (MEC), Nurses' Health Study ( NHS), and Women's Health Study (WHS). Circulating levels of sex steroids ( androstenedione, estradiol, estrone and testosterone) were also measured in 4713 study subjects.
Results: Breast cancer risk was not associated with any polymorphism or haplotype in the GNRH1 and GNRHR genes, nor were there any statistically significant interactions with known breast cancer risk factors. Polymorphisms in these two genes were not strongly associated with circulating hormone levels.
Conclusion: Common variants of the GNRH1 and GNRHR genes are not associated with risk of invasive breast cancer in Caucasians.
C1 [Canzian, Federico; Kaaks, Rudolf; Dossus, Laure] German Canc Res Ctr, DKFZ, D-6900 Heidelberg, Germany.
[Cox, David G.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Henderson, Katherine D.; Henderson, Brian E.; Haiman, Christopher A.; Pearce, Celeste Leigh; Stram, Daniel O.] Univ So Calif, Los Angeles, CA USA.
[Henderson, Katherine D.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Berg, Christine; Chanock, Stephen; Hoover, Robert; Thomas, Gilles; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bingham, Sheila] MRC, Dunn Human Nutr Unit, Cambridge, England.
[Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
[Buring, Julie; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA.
[Calle, Eugenia E.; Feigelson, Heather Spencer; Thun, Michael J.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, INSERM, F-94805 Villejuif, France.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Lenner, Per] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway.
[Overvad, Kim] Aarhus Univ Hosp, Dept Clin Epidemiol, Aalborg, Denmark.
[Palli, Domenico] CSPO Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Quiros, Jose R.] Publ Hlth & Hlth Planning Directorate, Asturias, Spain.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, London, England.
[Trichopoulos, Dimitrios] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece.
[van Gils, Carla H.] Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
RP Canzian, F (reprint author), German Canc Res Ctr, DKFZ, D-6900 Heidelberg, Germany.
EM f.canzian@dkfz.de; r.kaaks@dkfz.de; cox@lyon.fnclcc.fr;
KHenderson@coh.org; brian.henderson@keck.usc.edu; bergc@mail.nih.gov;
sab@mrc-dunn.cam.ac.uk; boeing@mail.dife.de;
jburing@rics.bwh.harvard.edu; jeanne.calle@cancer.org;
chanocks@mail.nih.gov; clavel@igr.fr; l.dossus@dkfz.de;
Heather.S.Feigelson@kp.org; haiman@usc.edu;
sue.hankinson@channing.harvard.edu; hooverr@exchange.nih.gov;
david.hunter@channing.harvard.edu; isaacsc@georgetown.edu;
per.lenner@oc.umu.se; eiliv.lund@ism.uit.no; ko@dce.au.dk;
d.palli@cspo.it; pearce_l@ccnt.norccc.usc.edu; ramonqg@princast.es;
e.riboli@imperial.ac.uk; stram@usc.edu; thomasgi@mail.nih.gov;
michael.thun@cancer.org; dtrichop@hsph.harvard.edu;
C.vanGils@umcutrecht.nl; zieglerr@exchange.nih.gov
RI Clavel-Chapelon, Francoise/G-6733-2014; Cox, David/A-2023-2009; Dossus,
Laure/B-2875-2013
OI PALLI, Domenico/0000-0002-5558-2437; Cox, David/0000-0002-2152-9259;
Dossus, Laure/0000-0003-2716-5748
FU NCI [U01 CA098216, U01CA098233, U01CA098758, U01 CA098710]
FX We thank the participants in the component cohort studies. This work was
funded by NCI grants U01 CA098216 ( EPIC), U01CA098233 ( Harvard),
U01CA098758 (MEC) and U01 CA098710 (ACS). All co-authors of this paper
are members of the NCI Breast and Prostate Cancer Cohort Consortium
(BPC3).
NR 20
TC 3
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUL 29
PY 2009
VL 9
AR 257
DI 10.1186/1471-2407-9-257
PG 8
WC Oncology
SC Oncology
GA 489TV
UT WOS:000269446600001
PM 19640273
ER
PT J
AU Chen, YM
Gerwin, C
Sheng, ZH
AF Chen, Yan-Min
Gerwin, Claudia
Sheng, Zu-Hang
TI Dynein Light Chain LC8 Regulates Syntaphilin-Mediated Mitochondrial
Docking in Axons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID KINESIN HEAVY-CHAIN; COILED-COIL DOMAIN; CYTOPLASMIC DYNEIN;
INTERMEDIATE CHAIN; INTRACELLULAR-TRANSPORT; MYOSIN-V; PROTEIN;
SYNAPSES; COMPLEX; IDENTIFICATION
AB Mitochondria in the cell bodies of neurons are transported down neuronal processes in response to changes in local energy and metabolic states. Because of their extreme polarity, neurons require specialized mechanisms to regulate mitochondrial transport and retention in axons. Our previous studies using syntaphilin (snph) knock-out mice provided evidence that SNPH targets to axonal mitochondria and controls their mobility through its static interaction with microtubules (MTs). However, the mechanisms regulating SNPH-mediated mitochondrial docking remain elusive. Here, we report an unexpected role for dynein light chain LC8. Using proteomic biochemical and cell biological assays combined with time-lapse imaging in live snph wild-type and mutant neurons, we reveal that LC8 regulates axonal mitochondrial mobility by binding to SNPH, thus enhancing the SNPH-MT docking interaction. Using mutagenesis assays, we mapped a seven-residue LC8-binding motif. Through this specific interaction, SNPH recruits LC8 to axonal mitochondria; such colocalization is abolished when neurons express SNPH mutants lacking the LC8-binding motif. Transient LC8 expression reduces mitochondrial mobility in snph (+/+) but not (-/-) neurons, suggesting that the observed effect of LC8 depends on the SNPH-mediated docking mechanism. In contrast, deleting the LC8-binding motif impairs the ability of SNPH to immobilize axonal mitochondria. Furthermore, circular dichroism spectrum analysis shows that LC8 stabilizes an alpha-helical coiled-coil within the MT-binding domain of SNPH against thermal unfolding. Thus, our study provides new mechanistic insights into controlling mitochondrial mobility through a dynamic interaction between the mitochondrial docking receptor and axonal cytoskeleton.
C1 [Chen, Yan-Min; Gerwin, Claudia; Sheng, Zu-Hang] NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Sheng, ZH (reprint author), NINDS, Synapt Funct Sect, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 2B215,35 Convent Dr, Bethesda, MD 20892 USA.
EM shengz@ninds.nih.gov
RI CHEN, YANMIN/H-6124-2011
FU National Institute of Neurological Disorders and Stroke (NINDS)
Intramural Competitive Fellowship Award; Intramural Research Program of
NINDS; National Institutes of Health (NIH)
FX This work was supported by the National Institute of Neurological
Disorders and Stroke (NINDS) Intramural Competitive Fellowship Award
(Y.-M.C.) and the Intramural Research Program of NINDS, National
Institutes of Health (NIH) (Z.-H.S.). Y.-M.C. conducted the majority of
the cell biology and biochemical studies and manuscript writing; C. G.
performed some of the biochemical analysis. Z.-H. S. is a senior author
who was responsible for the project design and revised this manuscript.
The animal care and use in this study were in accordance with the NIH
guidelines and was approved by the NIH-NINDS-National Institute on
Deafness and Other Communication Disorders (NIDCD) Animal Care and Use
Committee.
NR 65
TC 33
Z9 34
U1 1
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 29
PY 2009
VL 29
IS 30
BP 9429
EP 9438
DI 10.1523/JNEUROSCI.1472-09.2009
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 476LX
UT WOS:000268444100003
PM 19641106
ER
PT J
AU Bosman, CA
Womelsdorf, T
Desimone, R
Fries, P
AF Bosman, Conrado A.
Womelsdorf, Thilo
Desimone, Robert
Fries, Pascal
TI A Microsaccadic Rhythm Modulates Gamma-Band Synchronization and Behavior
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID SACCADIC EYE-MOVEMENTS; PRIMARY VISUAL-CORTEX; OSCILLATORY NEURONAL
SYNCHRONIZATION; LATERAL GENICULATE-NUCLEUS; MACAQUE AREA V4; SPATIAL
ATTENTION; COVERT ATTENTION; AUDITORY-CORTEX; RESPONSES; POTENTIALS
AB Rhythms occur both in neuronal activity and in behavior. Behavioral rhythms abound at frequencies at or below 10 Hz. Neuronal rhythms cover a very wide frequency range, and the phase of neuronal low-frequency rhythms often rhythmically modulates the strength of higher-frequency rhythms, particularly of gamma-band synchronization (GBS). Here, we study stimulus-induced GBS in awake monkey areas V1 and V4 in relation to a specific form of spontaneous behavior, namely microsaccades (MSs), small fixational eye movements. We found that MSs occur rhythmically at a frequency of similar to 3.3 Hz. The rhythmic MSs were predicted by the phase of the 3.3 Hz rhythm in V1 and V4 local field potentials. In turn, the MSs modulated both visually induced GBS and the speed of visually triggered behavioral responses. Fast/slow responses were preceded by a specific temporal pattern of MSs. These MS patterns induced perturbations in GBS that in turn explained variability in behavioral response speed. We hypothesize that the 3.3 Hz rhythm structures the sampling and exploration of the environment through building and breaking neuronal ensembles synchronized in the gamma-frequency band to process sensory stimuli.
C1 [Bosman, Conrado A.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6525 EN Nijmegen, Netherlands.
[Desimone, Robert] Natl Inst Mental Hlth, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Desimone, Robert] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
RP Bosman, CA (reprint author), Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, Kapittelweg 29, NL-6525 EN Nijmegen, Netherlands.
EM c.bosman@donders.ru.nl
RI Fries, Pascal/E-3196-2010;
OI Fries, Pascal/0000-0002-4270-1468; Bosman, Conrado
A./0000-0003-2433-6126; Womelsdorf, Thilo/0000-0001-6921-4187
FU European Community's Seventh Framework Programme [FP7/2007-2013,
HEALTH-F2-2008-200728]; The Volkswagen Foundation [I/79876]; European
Science Foundation European Young Investigator Award Program; The
Netherlands Organization for Scientific Research [452-03-344]; National
Institute of Mental Health Intramural Research Program; National
Institute of Health [R01-EY017292]
FX This work was supported by Beca Presidente de la Rep blica, Gobierno de
Chile (C. A. B.), the European Community's Seventh Framework Programme
(FP7/2007-2013), Grant Agreement "BrainSynch" HEALTH-F2-2008-200728 (P.
F.), The Volkswagen Foundation Grant I/79876 (P. F.), the European
Science Foundation European Young Investigator Award Program (P. F.),
The Netherlands Organization for Scientific Research Grant 452-03-344
(P. F.), the National Institute of Mental Health Intramural Research
Program (R. D.), and National Institute of Health Grant R01-EY017292 (R.
D.). We thank J. H. Reynolds, A. E. Rorie, and A. F. Rossi for help
during the monkey experiments.
NR 68
TC 95
Z9 97
U1 1
U2 15
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 29
PY 2009
VL 29
IS 30
BP 9471
EP 9480
DI 10.1523/JNEUROSCI.1193-09.2009
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 476LX
UT WOS:000268444100007
PM 19641110
ER
PT J
AU Ma, JH
Gruschus, JM
Tjandra, N
AF Ma, Junhe
Gruschus, James M.
Tjandra, Nico
TI N-15-H-1 Scalar Coupling Perturbation: An Additional Probe for Measuring
Structural Changes Due to Ligand Binding
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID CROSS-CORRELATED RELAXATION; N-TERMINAL DOMAIN; DIPOLAR COUPLINGS;
RESIDUAL DIPOLAR; HYDROGEN-BONDS; ESCHERICHIA-COLI; NMR; PROTEINS;
CONSTANTS; IDENTIFICATION
AB Chemical shift perturbation mapping of backbone amides is one of the most widely employed techniques in biomolecular NMR, providing residue-by-residue information on interaction interfaces, ligand binding, and chemical modification sites, even for samples where poor solubility, short lifetime, or large size precludes more sophisticated experimental approaches. Significant changes can also occur in the amide one-bond (IN)-I-15-H-1 Scalar coupling constants for glutamine binding protein(GlnBP) due to ligand binding. Like chemical shift perturbations, large changes (>1 Hz) are seen near the site of glutamine binding, though perturbations also occur distant to the site. The coupling constant perturbations correlate with significant structural changes,especially changes in backbone hydrogen bonding. Thus, amide scalar coupling perturbation can serve as an adjunct to chemical shift perturbation, providing additional information on both short-range and longer-range, allosteric structural changes.
C1 [Ma, Junhe; Gruschus, James M.; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
FU NIH, National Heart,.Lung, and Blood Institute
FX This work was supported by the Intramural Research Program of the NIH,
National Heart,. Lung, and Blood Institute.
NR 21
TC 5
Z9 5
U1 0
U2 6
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 29
PY 2009
VL 131
IS 29
BP 9884
EP +
DI 10.1021/ja903552q
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 475WM
UT WOS:000268395000013
PM 19580276
ER
PT J
AU Rone, MB
Liu, J
Blonder, J
Ye, XY
Veenstra, TD
Young, JC
Papadopoulos, V
AF Rone, Malena B.
Liu, Jun
Blonder, Josip
Ye, Xiaoying
Veenstra, Timothy D.
Young, Jason C.
Papadopoulos, Vassilios
TI Targeting and Insertion of the Cholesterol-Binding Translocator Protein
into the Outer Mitochondrial Membrane
SO BIOCHEMISTRY
LA English
DT Article
ID PERIPHERAL BENZODIAZEPINE-RECEPTOR; ACUTE REGULATORY PROTEIN; LEYDIG
TUMOR-CELLS; IN-VITRO; 18 KDA; STEROID-BIOSYNTHESIS; MOLECULAR
CHAPERONES; CONTACT SITES; IMPORT; STEROIDOGENESIS
AB Translocator protein (18 kDa, TSPO), previously known as the peripheral-type benzodiazepine receptor, is an outer mitochondrial membrane (OMM) protein necessary for cholesterol import and steroid production. We reconstituted the mitochondrial targeting and insertion of TSPO into the OMM to analyze the signals and mechanisms required for this process. Initial Studies indicated the formation of a mitochondrial 66 kDa. complex through Blue Native-PAGE analysis. The formation of this complex was found to be dependent on the presence of ATP and the cytosolic chaperone Hsp90. Through mutational analysis we identified two areas necessary for TSPO targeting, import, and function: amino acids 103-108 (Schellman motif), which provide the necessary structural orientation for import, and the cholesterol-binding C-terminus required for insertion. Although the translocase of the outer mitochondrial membrane (TOM) complex proteins Tom22 and Tom40 were present in the OMM, the TOM complex did not interact with TSPO. In search of proteins involved in TSPO import, we analyzed complexes known to interact with TSPO by mass spectrometry. Formation of the 66 kDa complex Was found to be dependent on an identified protein, Metaxin 1, for formation and TSPO import. The level of import of TSPO into steroidogenic cell mitochondria was increased following treatment of the cells with cAMP. These findings suggest that the initial targeting of TSPO to mitochondria is dependent upon the presence of cytosolic chaperones interacting with the import receptor Tom70. The C-terminus plays an important role in targeting TSPO to mitochondria, whereas its import into the OMM is dependent upon the presence of the Schellman motif. Final integration of TSPO into the OMM occurs via its interaction with Metaxin 1. Import of TSPO into steroidogenic cell mitochondria is regulated by cAMP.
C1 [Rone, Malena B.; Papadopoulos, Vassilios] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ H3G 1A4, Canada.
[Rone, Malena B.; Liu, Jun; Papadopoulos, Vassilios] Georgetown Univ, Dept Biochem Mol & Cellular Biol, Med Ctr, Washington, DC 20007 USA.
McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada.
[Young, Jason C.; Papadopoulos, Vassilios] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada.
[Papadopoulos, Vassilios] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1A4, Canada.
[Blonder, Josip; Ye, Xiaoying; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Ft Detrick, MD 21702 USA.
RP Papadopoulos, V (reprint author), McGill Univ, Ctr Hlth, Res Inst, 1650 Cedar Ave,C10-148, Montreal, PQ H3G 1A4, Canada.
EM vassilios.Papadopoulos@mcgill.ca
OI Papadopoulos, Vassilios/0000-0002-1183-8568
FU National Institutes of Health [ES07747, HD37031]; Canada Research Chair
in Biochemical Pharmacology; Le Fonds de la recherche en sante du Quebec
FX This work was supported by National Institutes of Health Grant ES07747
and in part by Grant HD37031 (to V.P.). V.P. was also supported by a
Canada Research Chair in Biochemical Pharmacology. J.C.Y. holds a Canada
Research Chair in Molecular Chaperones. The Research Institute of MUHC
is supported by a Center grant from Le Fonds de la recherche en sante du
Quebec.
NR 52
TC 32
Z9 32
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 28
PY 2009
VL 48
IS 29
BP 6909
EP 6920
DI 10.1021/bi900854z
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 473AN
UT WOS:000268175600021
PM 19552401
ER
PT J
AU Brinson, RG
Turner, KB
Yi-Brunozzi, HY
Le Grice, SFJ
Fabris, D
Marino, JP
AF Brinson, Robert G.
Turner, Kevin B.
Yi-Brunozzi, Hye Young
Le Grice, Stuart F. J.
Fabris, Daniele
Marino, John P.
TI Probing Anomalous Structural Features in Polypurine Tract-Containing
RNA-DNA Hybrids with Neomycin B
SO BIOCHEMISTRY
LA English
DT Article
ID ION-CYCLOTRON RESONANCE; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSFORM
MASS-SPECTROMETRY; NUCLEIC-ACID LIGANDS; REVERSE-TRANSCRIPTASE;
NUCLEOCAPSID PROTEIN; CRYSTAL-STRUCTURE; BINDING; THERMODYNAMICS;
RECOGNITION
AB During (-)-strand DNA synthesis in retroviruses and Saccharomyces cerevisiae LTR retrotransposons, a purine rich region of the RNA template, known as the polypurine tract (PPT), is resistant to RNase H-mediated hydrolysis and subsequently serves as a primer for (+)-strand, DNA-dependent DNA synthesis. Although HIV-1 and Ty3 PPT sequences share no sequence similarity beyond the fact that both include runs of purine ribonucleotides, it has been suggested that these PPTs are processed by their cognate reverse transcriptases (RTs) through a common molecular mechanism. Here, we have used the aminoglycoside neomycin B (NB) to examine which structural features of the Ty3 PPT contribute to specific recognition and processing by its cognate RT. Using high-resolution NMR, direct infusion FTICR mass spectrometry, and isothermal titration calorimetry, we show that NB binds preferentially and selectively adjacent to the Ty3 3' PPT-U3 cleavage junction and in an upstream 5' region where the thumb subdomain of Ty3 RT putatively grips the substrate. Regions highlighted by NB oil the Ty3 PPT are similar to those previously identified oil the HIV-1 PPT sequence that are implicated as contact points for substrate binding by its RT. Our findings thus Support the notion that common structural features of lentiviral and LTR-retrotransposon PPTs facilitate the interaction with their cognate RT.
C1 [Brinson, Robert G.; Marino, John P.] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA.
[Brinson, Robert G.; Marino, John P.] NIST, Rockville, MD 20850 USA.
[Turner, Kevin B.; Fabris, Daniele] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA.
[Brinson, Robert G.; Yi-Brunozzi, Hye Young; Le Grice, Stuart F. J.] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA.
RP Marino, JP (reprint author), Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM fabris@umbc.edu; marino@umbi.umd.edu
FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM059107, R01 GM059107-09,
GM643208, GM59107]
NR 36
TC 11
Z9 11
U1 1
U2 2
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 28
PY 2009
VL 48
IS 29
BP 6988
EP 6997
DI 10.1021/bi900357j
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 473AN
UT WOS:000268175600028
PM 19449839
ER
PT J
AU Castle, PE
Rodriguez, AC
Burk, RD
Herrero, R
Wacholder, S
Alfaro, M
Morales, J
Guillen, D
Sherman, ME
Solomon, D
Schiffman, M
AF Castle, Philip E.
Cecilia Rodriguez, Ana
Burk, Robert D.
Herrero, Rolando
Wacholder, Sholom
Alfaro, Mario
Morales, Jorge
Guillen, Diego
Sherman, Mark E.
Solomon, Diane
Schiffman, Mark
CA PEG Grp
TI Short term persistence of human papillomavirus and risk of cervical
precancer and cancer: population based cohort study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID INCIDENCE TRENDS; SCREENING-TESTS; QUALITY-CONTROL; COSTA-RICA;
FOLLOW-UP; WOMEN; HPV; NEOPLASIA; DNA; INFECTION
AB Objective To evaluate the cumulative incidence of cervical intraepithelial neoplasia II or worse (grade II+) or cervical intraepithelial neoplasia grade III+ after short term persistence of prevalently detected carcinogenic human papillomavirus (HPV).
Design Population based cohort study.
Setting Guanacaste, Costa Rica.
Participants 2282 sexually active women actively followed after enrolment.
Main outcome measures Primary end points: three year and five year cumulative incidence of histologically confirmed cervical intraepithelial neoplasia grade II+ (n=70). Cervical specimens collected at each visit tested for more than 40 HPV genotypes. HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82 were considered the primary carcinogenic genotypes.
Results Women who tested positive for a carcinogenic HPV at enrolment and after about one year (9-21 months) (positive/positive) had a three year cumulative incidence of cervical intraepithelial neoplasia grade II+ of 17.0% (95% confidence interval 12.1% to 22.0%). Those who tested negative/positive (3.4%, 0.1% to 6.8%), positive/negative (1.2%,-0.2% to 2.5%), and negative/negative (0.5%, 0.1% to 0.9%) were at a significantly lower risk. There was little difference in the cumulative incidence of cervical intraepithelial neoplasia grade II+ between testing positive twice for any carcinogenic HPV genotype (same genotype or different genotypes) v testing positive twice for the same carcinogenic genotype (17.0% v 21.3%, respectively). Short term persistence of HPV 16 strongly predicted cervical intraepithelial neoplasia grade II+, with a three year cumulative incidence of 40.8% (26.4% to 55.1%). Similar patterns were observed for the five year cumulative incidence of grade II+ and for three year and five year cumulative incidence of grade III+.
Conclusions Short term persistence of a prevalently detected carcinogenic HPV infection, especially HPV 16, strongly predicts a subsequent diagnosis of cervical intraepithelial neoplasia II+ over the next few years.
C1 [Castle, Philip E.; Wacholder, Sholom; Sherman, Mark E.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Solomon, Diane] NCI, Canc Prevent Div, NIH, DHHS, Bethesda, MD 20892 USA.
[Cecilia Rodriguez, Ana; Herrero, Rolando; Alfaro, Mario; Morales, Jorge; Guillen, Diego] INCIEN SA Fdn, San Jose, Costa Rica.
[Burk, Robert D.] Yeshiva Univ Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA.
RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
EM castlep@mail.nih.gov
RI Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU National Institutes of Health [N01-CP-21081, N01-CP-33061, N01-CP-40542,
N01-CP-50535, N01-CP- 81023, CA78527]; National Cancer Institute;
National Institutes of Health, Department of Health and Human Services
FX This study was supported by the National Institutes of Health
(N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP- 81023,
intramural programme, CA78527 to RB). The Guanacaste cohort was partly
funded by the intramural research programme of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services. ACR was supported by an appointment to the senior fellowship
programme at the National Institutes of Health. The programme is
administered by the Oak Ridge Institute for Science and Education
through an interagency agreement between the US Department of Energy and
the National Institutes of Health. The sponsors had no role in the study
design, data collection, data analysis, data interpretation, or the
writing of the report.
NR 31
TC 99
Z9 105
U1 1
U2 1
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-8146
J9 BRIT MED J
JI Br. Med. J.
PD JUL 28
PY 2009
VL 339
AR b2569
DI 10.1136/bmj.b2569
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 479PG
UT WOS:000268672800004
PM 19638649
ER
PT J
AU Dhanantwari, P
Lee, E
Krishnan, A
Samtani, R
Yamada, S
Anderson, S
Lockett, E
Donofrio, M
Shiota, K
Leatherbury, L
Lo, CW
AF Dhanantwari, Preeta
Lee, Elaine
Krishnan, Anita
Samtani, Rajeev
Yamada, Shigehito
Anderson, Stasia
Lockett, Elizabeth
Donofrio, Mary
Shiota, Kohei
Leatherbury, Linda
Lo, Cecilia W.
TI Human Cardiac Development in the First Trimester A High-Resolution
Magnetic Resonance Imaging and Episcopic Fluorescence Image Capture
Atlas
SO CIRCULATION
LA English
DT Article
DE embryology; fetal development; human development; pregnancy trimester,
first
ID HUMAN HEART; INTERVENTRICULAR SEPTUM; EMBRYONIC HEART; SEPTATION;
MORPHOGENESIS; MYOCARDIUM; TRUNCUS; MUSCLE
C1 [Dhanantwari, Preeta; Lee, Elaine; Krishnan, Anita; Samtani, Rajeev; Yamada, Shigehito; Leatherbury, Linda; Lo, Cecilia W.] NHLBI, NIH, Dev Biol Lab, Bethesda, MD 20892 USA.
[Dhanantwari, Preeta; Krishnan, Anita; Donofrio, Mary; Leatherbury, Linda] Childrens Natl Med Ctr, Childrens Natl Heart Inst, Washington, DC 20010 USA.
[Lockett, Elizabeth] Natl Museum Hlth & Med, Human Dev Anat Ctr, Washington, DC USA.
[Yamada, Shigehito; Shiota, Kohei] Kyoto Univ, Grad Sch Med, Congenital Anomaly Res Ctr, Kyoto, Japan.
RP Lo, CW (reprint author), NHLBI, NIH, Dev Biol Lab, Bldg 10-6C-103, Bethesda, MD 20892 USA.
EM loc@nhlbi.nih.gov
FU Intramural NIH HHS [NIH0011060326, Z01 HL005701-06]; NHLBI NIH HHS [Z01
HL005701]
NR 29
TC 19
Z9 20
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 28
PY 2009
VL 120
IS 4
BP 343
EP U126
DI 10.1161/CIRCULATIONAHA.108.796698
PG 25
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 475RG
UT WOS:000268377500012
PM 19635979
ER
PT J
AU Lewandoski, M
Mackem, S
AF Lewandoski, Mark
Mackem, Susan
TI Limb Development: The Rise and Fall of Retinoic Acid
SO CURRENT BIOLOGY
LA English
DT Editorial Material
ID PECTORAL FIN BUD; MOUSE; INITIATION; OUTGROWTH; PATHWAY; PATTERN;
RALDH2; AXIS
AB Retinoic acid was thought to play a key instructive role during limb bud initiation and subsequent patterning. New results argue instead that its role is permissive: retinoic acid is essential only to antagonize early axial Fgf signals that otherwise inhibit the limb field.
C1 [Lewandoski, Mark; Mackem, Susan] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
RP Lewandoski, M (reprint author), NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
EM mlewandoski@mail.ncifcrf.gov; mackems@mail.nih.gov
NR 20
TC 11
Z9 12
U1 1
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD JUL 28
PY 2009
VL 19
IS 14
BP R558
EP R561
DI 10.1016/j.cub.2009.06.017
PG 4
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 477PE
UT WOS:000268530200012
PM 19640492
ER
PT J
AU Hu, KN
Tycko, R
AF Hu, Kan-Nian
Tycko, Robert
TI Zero-quantum frequency-selective recoupling of homonuclear dipole-dipole
interactions in solid state nuclear magnetic resonance
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
DE biological NMR; chemical shift; librational states; magic angle
spinning; molecular biophysics; proteins
ID TILTED ROTATING-FRAME; ANGLE-SPINNING NMR; DISTANCE MEASUREMENTS;
AMYLOID FIBRILS; L-THREONINE; SPECTROSCOPY; PEPTIDE; PROTEIN
AB We describe a method for measuring magnetic dipole-dipole interactions, and hence distances, between pairs of like nuclear spins in a many-spin system under magic-angle spinning (MAS). This method employs a homonuclear dipolar recoupling sequence that creates an average dipole-dipole coupling Hamiltonian under MAS with full zero-quantum symmetry, including both secular and flip-flop terms. Flip-flop terms are then attenuated by inserting rotor-synchronized periods of chemical shift evolution between recoupling blocks, leaving an effective Hamiltonian that contains only secular terms to a good approximation. Couplings between specific pairs of nuclear spins can then be selected with frequency-selective pi pulses. We demonstrate this technique, which we call zero-quantum shift evolution assisted homonuclear recoupling, in a series of one-dimensional and two-dimensional (13)C NMR experiments at 17.6 T and 40.00 kHz MAS frequency on uniformly (13)C-labeled L-threonine powder and on the helix-forming peptide MB(i+4)EK, synthesized with a pair of uniformly (13)C-labeled L-alanine residues. Experimental demonstrations include measurements of distances between (13)C sites that are separated by three bonds, placing quantitative constraints on both sidechain and backbone torsion angles in polypeptides.
C1 [Hu, Kan-Nian; Tycko, Robert] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), Natl Inst, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health;
Intramural AIDS Targeted Antiviral Program of the National Institutes of
Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health, and by the Intramural AIDS Targeted
Antiviral Program of the National Institutes of Health.
NR 36
TC 14
Z9 14
U1 0
U2 7
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUL 28
PY 2009
VL 131
IS 4
AR 045101
DI 10.1063/1.3176874
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 478UL
UT WOS:000268613700093
PM 19655922
ER
PT J
AU Najjar, SS
AF Najjar, Samer S.
TI Heart Failure With Preserved Ejection Fraction Failure to Preserve,
Failure of Reserve, and Failure on the Compliance Curve
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE contractility; heart failure; hypertension; pathophysiology
ID DIASTOLIC DYSFUNCTION; ABNORMALITIES; STIFFNESS
C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21225 USA.
RP Najjar, SS (reprint author), NIA, Intramural Res Program, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA.
EM NajjarSa@mail.nih.gov
FU Intramural NIH HHS [Z99 AG999999]
NR 18
TC 8
Z9 8
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 28
PY 2009
VL 54
IS 5
BP 419
EP 421
DI 10.1016/j.jacc.2009.05.011
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 475BG
UT WOS:000268329900006
PM 19628116
ER
PT J
AU Chaudhry, C
Plested, AJR
Schuck, P
Mayer, ML
AF Chaudhry, Charu
Plested, Andrew J. R.
Schuck, Peter
Mayer, Mark L.
TI Energetics of glutamate receptor ligand binding domain dimer assembly
are modulated by allosteric ions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE allosteric modulation; analytical ultracentrifugation; desensitization;
ion channels; thermodynamics
ID CRYSTAL-STRUCTURES; KAINATE RECEPTORS; K+ CHANNEL; D-SERINE;
DESENSITIZATION; MECHANISMS; AMPA; SUBUNIT; SELECTIVITY; CATIONS
AB The activity of many ligand-gated ion channels and cell surface receptors is modulated by small molecules and ions, but an understanding of the underlying molecular mechanisms is scarce. For kainate, but not AMPA subtype glutamate receptors, the binding of Na(+) and Cl(-) ions to discrete, electrostatically coupled sites in the extracellular ligand binding domain (LBD) dimer assembly regulates the rate of entry into the desensitized state, which occurs when the dimer interface ruptures and the channel closes. Studies on glutamate receptors have defined the LBD dimer assembly as a key functional unit that controls activation and desensitization. Here we use analytical ultracentrifugation to probe the energetic effects of allosteric ions on kainate receptor dimer stability in solution, using a GluR6 mutant that desensitizes slowly. Our results show that sodium and chloride ions modulate kainate receptor dimer affinity as much as 50-fold, and that removal of either Cl(-) or Na(+) disrupts the dimer. The applicability of a similar allosteric mechanism for modulation of delta2 glutamate receptors by Ca(2+) was also tested. Our results indicate that ions can contribute substantial free energy to active state stabilization in both these receptors, and provide quantitative measurements of the energetic consequences of allosteric ion binding to a ligand-gated ion channel.
C1 [Chaudhry, Charu; Plested, Andrew J. R.; Mayer, Mark L.] NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
EM mlm@helix.nih.gov
RI Mayer, Mark/H-5500-2013;
OI Schuck, Peter/0000-0002-8859-6966; Plested, Andrew/0000-0001-6062-0832
FU National Institute of Child Health and Human Development; National
Institutes of Health; Department of Health and Human Services; National
Institute of Biomedical Imaging and Bioengineering; Department of Health
and Human Services (P. S.); Helen Hay Whitney Foundation
FX We thank Carla Glasser for preparing cDNAs; Andrea Balbo for technical
assistance with AUC experiments; and the National Institute of
Neurological Disorders and Stroke DNA Sequencing Facility. This work was
supported by the intramural research programs of National Institute of
Child Health and Human Development, National Institutes of Health,
Department of Health and Human Services (M. L. M) and National Institute
of Biomedical Imaging and Bioengineering, National Institutes of Health,
Department of Health and Human Services (P. S.); and the Helen Hay
Whitney Foundation (C. C.).
NR 31
TC 32
Z9 32
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2009
VL 106
IS 30
BP 12329
EP 12334
DI 10.1073/pnas.0904175106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476KV
UT WOS:000268440200025
PM 19617541
ER
PT J
AU Liu, SL
Crown, D
Miller-Randolph, S
Moayeri, M
Wang, HL
Hu, HJ
Morley, T
Leppla, SH
AF Liu, Shihui
Crown, Devorah
Miller-Randolph, Sharmina
Moayeri, Mahtab
Wang, Hailun
Hu, Haijing
Morley, Thomas
Leppla, Stephen H.
TI Capillary morphogenesis protein-2 is the major receptor mediating
lethality of anthrax toxin in vivo
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE edema toxin; lethal toxin; tumor endothelium marker-8
ID INFANTILE SYSTEMIC HYALINOSIS; BACILLUS-ANTHRACIS; MONOCLONAL-ANTIBODY;
CELLULAR RECEPTOR; TUMOR ENDOTHELIUM; KINASE-KINASE; BINDING;
INTERNALIZATION; MUTATIONS; IDENTIFICATION
AB Anthrax toxin, a major virulence factor of Bacillus anthracis, gains entry into target cells by binding to either of 2 von Willebrand factor A domain-containing proteins, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2). The wide tissue expression of TEM8 and CMG2 suggest that both receptors could play a role in anthrax pathogenesis. To explore the roles of TEM8 and CMG2 in normal physiology, as well as in anthrax pathogenesis, we generated TEM8- and CMG2-null mice and TEM8/CMG2 double-null mice by deleting TEM8 and CMG2 transmembrane domains. TEM8 and CMG2 were found to be dispensable for mouse development and life, but both are essential in female reproduction in mice. We found that the lethality of anthrax toxin for mice is mostly mediated by CMG2 and that TEM8 plays only a minor role. This is likely because anthrax toxin has approximately 11-fold higher affinity for CMG2 than for TEM8. Finally, the CMG2-null mice are also shown to be highly resistant to B. anthracis spore infection, attesting to the importance of both anthrax toxin and CMG2 in anthrax infections.
C1 [Liu, Shihui; Crown, Devorah; Miller-Randolph, Sharmina; Moayeri, Mahtab; Wang, Hailun; Hu, Haijing; Morley, Thomas; Leppla, Stephen H.] NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
RP Liu, SL (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA.
EM shliu@niaid.nih.gov; sleppla@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX We thank Rasem Fattah for assistance in protein purification, Andrew
Griffin for assistance in genotyping, Thomas Bugge, Pradeep Gupta, and
Yogendra Singh for helpful discussion, and Brad St. Croix for TEM8
monoclonal antibodies and for sharing his unpublished work before
publication. This research was supported by the intramural research
program of the National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 32
TC 79
Z9 82
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2009
VL 106
IS 30
BP 12424
EP 12429
DI 10.1073/pnas.0905409106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476KV
UT WOS:000268440200041
PM 19617532
ER
PT J
AU Neumann, S
Huang, WW
Titus, S
Krause, G
Kleinau, G
Alberobello, AT
Zheng, W
Southall, NT
Inglese, J
Austin, CP
Celi, FS
Gavrilova, O
Thomas, CJ
Raaka, BM
Gershengorn, MC
AF Neumann, Susanne
Huang, Wenwei
Titus, Steve
Krause, Gerd
Kleinau, Gunnar
Alberobello, Anna Teresa
Zheng, Wei
Southall, Noel T.
Inglese, James
Austin, Christopher P.
Celi, Francesco S.
Gavrilova, Oksana
Thomas, Craig J.
Raaka, Bruce M.
Gershengorn, Marvin C.
TI Small-molecule agonists for the thyrotropin receptor stimulate thyroid
function in human thyrocytes and mice
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE 7TMR; G protein-coupled receptor; low-molecular-weight ligands;
radioiodide uptake; TSH receptor
ID LUTEINIZING-HORMONE RECEPTOR; PROTEIN-COUPLED RECEPTOR; RECOMBINANT
HUMAN TSH; CRYSTAL-STRUCTURE; FSH RECEPTOR; WEIGHT AGONIST;
HYPERTHYROIDISM; IDENTIFICATION; ANTAGONIST; ACTIVATION
AB Seven-transmembrane-spanning receptors (7TMRs) are prominent drug targets. However, small-molecule ligands for 7-transmembrane-spanning receptors for which the natural ligands are large, heterodimeric glycoprotein hormones, like thyroid-stimulating hormone (TSH; thyrotropin), have only recently been reported, and none are approved for human use. We have used quantitative high-throughput screening to identify a small-molecule TSH receptor (TSHR) agonist that was modified to produce a second agonist with increased potency. We show that these agonists are highly selective for human TSHR versus other glycoprotein hormone receptors and interact with the receptor's serpentine domain. A binding pocket within the transmembrane domain was defined by docking into a TSHR homology model and was supported by site-directed mutagenesis. In primary cultures of human thyrocytes, both TSH and the agonists increase mRNA levels for thyroglobulin, thyroperoxidase, sodium iodide symporter, and deiodinase type 2, and deiodinase type 2 enzyme activity. Moreover, oral administration of the agonist stimulated thyroid function in mice, resulting in increased serum thyroxine and thyroidal radioiodide uptake. Thus, we discovered a small molecule that activates human TSHR in vitro, is orally active in mice, and could be a lead for development of drugs to use in place of recombinant human TSH in patients with thyroid cancer.
C1 [Neumann, Susanne; Alberobello, Anna Teresa; Celi, Francesco S.; Raaka, Bruce M.; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Huang, Wenwei; Titus, Steve; Zheng, Wei; Southall, Noel T.; Inglese, James; Austin, Christopher P.; Thomas, Craig J.] NHGRI, Natl Inst Hlth Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Krause, Gerd; Kleinau, Gunnar] Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany.
[Gavrilova, Oksana] NIDDK, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU Intramural NIH HHS; NCRR NIH HHS [P41 RR-01081, P41 RR001081]
NR 44
TC 45
Z9 48
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2009
VL 106
IS 30
BP 12471
EP 12476
DI 10.1073/pnas.0904506106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476KV
UT WOS:000268440200049
PM 19592511
ER
PT J
AU Jacob, TC
Wan, Q
Vithlani, M
Saliba, RS
Succol, F
Pangalos, MN
Moss, SJ
AF Jacob, Tija C.
Wan, Qin
Vithlani, Mansi
Saliba, Richard S.
Succol, Francesca
Pangalos, Menelas N.
Moss, Stephen J.
TI GABA(A) receptor membrane trafficking regulates spine maturity
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE endocytosis; inhibition; phosphorylation
ID PHOSPHO-DEPENDENT BINDING; AP2 COMPLEX; PHOSPHORYLATION; ENDOCYTOSIS;
INHIBITION; MODULATION; CURRENTS; SUBUNIT; NEURONS; PSD-95
AB GABAA receptors (GABAARs), the principal sites of synaptic inhibition in the brain, are dynamic entities on the neuronal cell surface, but the role their membrane trafficking plays in shaping neuronal activity remains obscure. Here, weexamined this by using mutant receptor beta 3 subunits (beta 3S408/9A), which have reduced binding to the clathrin adaptor protein-2, a critical regulator of GABAAR endocytosis. Neurons expressing beta 3S408/9A subunits exhibited increases in the number and size of inhibitory synapses, together with enhanced inhibitory synaptic transmission due to reduced GABAAR endocytosis. Furthermore, neurons expressing beta 3S408/9A subunits had deficits in the number of mature spines and reduced accumulation of postsynaptic density protein-95 at excitatory synapses. This deficit in spine maturity was reversed by pharmacological blockade of GABAARs. Therefore, regulating the efficacy of synaptic inhibition by modulating GABAAR membrane trafficking may play a critical role in regulating spine maturity with significant implications for synaptic plasticity together with behavior.
C1 [Jacob, Tija C.; Vithlani, Mansi; Saliba, Richard S.; Moss, Stephen J.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02030 USA.
[Moss, Stephen J.] UCL, Dept Pharmacol, London WC1E 6BT, England.
[Succol, Francesca] Italian Inst Technol, I-16163 Genoa, Italy.
[Pangalos, Menelas N.] Wyeth Ayerst Res, Neurosci Discovery, Princeton, NJ 08852 USA.
[Wan, Qin] NEI, NIH, Bethesda, MD 20892 USA.
RP Moss, SJ (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02030 USA.
EM stephen.moss@tufts.edu
FU Medical Research Council; NINDS NIH HHS [P01 NS054900, P01NS054900]; PHS
HHS [NINDS 046478, NINDS 048045, NINDS 051195, NINDS 056359]; Wellcome
Trust
NR 20
TC 20
Z9 22
U1 0
U2 1
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2009
VL 106
IS 30
BP 12500
EP 12505
DI 10.1073/pnas.0903943106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476KV
UT WOS:000268440200054
PM 19617557
ER
PT J
AU Markovic, DS
Vinnakota, K
Chirasani, S
Synowitz, M
Raguet, H
Stock, K
Sliwa, M
Lehmann, S
Kalin, R
van Rooijeng, N
Holmbeck, K
Heppner, FL
Kiwit, J
Matyash, V
Lehnardt, S
Kaminska, B
Glass, R
Kettenmann, H
AF Markovic, D. S.
Vinnakota, K.
Chirasani, S.
Synowitz, M.
Raguet, H.
Stock, K.
Sliwa, M.
Lehmann, S.
Kaelin, R.
van Rooijeng, N.
Holmbeck, K.
Heppner, F. L.
Kiwit, J.
Matyash, V.
Lehnardt, S.
Kaminska, B.
Glass, R.
Kettenmann, H.
TI Gliomas induce and exploit microglial MT1-MMP expression for tumor
expansion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE brain tumor; invasion; metalloprotease; toll-like receptor
ID TOLL-LIKE RECEPTOR-4; GLIOBLASTOMA CELLS; UP-REGULATION; BRAIN-TUMORS;
IN-VITRO; INVASIVENESS; ACTIVATION; GENE; METALLOPROTEASE-2; INHIBITION
AB Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease- mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.
C1 [Markovic, D. S.; Vinnakota, K.; Chirasani, S.; Synowitz, M.; Raguet, H.; Stock, K.; Matyash, V.; Glass, R.; Kettenmann, H.] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
[Markovic, D. S.; Kiwit, J.] Helios Clin, Dept Neurosurg, D-13125 Berlin, Germany.
[Synowitz, M.] Charite Univ Med Berlin, Dept Neurosurg, D-13353 Berlin, Germany.
[Kaelin, R.; Heppner, F. L.] Charite Univ Med Berlin, Dept Neuropathol, D-13353 Berlin, Germany.
[Lehmann, S.; Lehnardt, S.] Charite Univ Med Berlin, Cecilie Vogt Clin Neurol, D-13353 Berlin, Germany.
[Sliwa, M.; Kaminska, B.] M Nencki Inst Expt Biol, Lab Transcript Regulat, PL-02093 Warsaw, Poland.
[van Rooijeng, N.] Vrije Univ Amsterdam, VU Univ Med Ctr, Fac Med, Dept Mol Cell Biol, NL-1081 BT Amsterdam, Netherlands.
[Holmbeck, K.] Natl Inst Dent & Craniofacial Res, Craniofacial Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA.
RP Glass, R (reprint author), Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany.
EM kettenmann@mdc-berlin.de
RI Kaminska, Bozena/B-2915-2014; Kaminska, Bozena/H-4592-2011
FU BMFT (German Ministry of Research and Technology); Deutsche
Forschungsgemeinschaft; National Institutes of Health/National Institute
of Neurological Disorders and Stroke [R01 NS046006]
FX We gratefully acknowledge Dr. Maciek Lipko's contribution of real- time
PCRs for MT1-MMP in rodent microglia. We thank Dr. Stefan Momma
(Frankfurt, Germany) for donating human glioma material, Dr. Jouko Lohi
(Helsinki, Finland) for donating MT1-MMP luciferase constructs, and
Irene Haupt for providing excellent technical help. This study was
supported by a joint German-Polish grant from BMFT (German Ministry of
Research and Technology), Deutsche Forschungsgemeinschaft, and National
Institutes of Health/National Institute of Neurological Disorders and
Stroke Grant R01 NS046006 (to F.L.H.).
NR 36
TC 126
Z9 130
U1 0
U2 12
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 28
PY 2009
VL 106
IS 30
BP 12530
EP 12535
DI 10.1073/pnas.0804273106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476KV
UT WOS:000268440200059
PM 19617536
ER
PT J
AU Simone, NL
Soule, BP
Ly, D
Saleh, AD
Savage, JE
DeGraff, W
Cook, J
Harris, CC
Gius, D
Mitchell, JB
AF Simone, Nicole L.
Soule, Benjamin P.
Ly, David
Saleh, Anthony D.
Savage, Jason E.
DeGraff, William
Cook, John
Harris, Curtis C.
Gius, David
Mitchell, James B.
TI Ionizing Radiation-Induced Oxidative Stress Alters miRNA Expression
SO PLOS ONE
LA English
DT Article
ID CELL-CYCLE PROGRESSION; MICRORNAOME DEREGULATION; TRANSCRIPTION FACTOR;
KAPPA-B; RESISTANCE; SIGNATURE
AB Background: MicroRNAs (miRNAs) are small, highly conserved, non-coding RNA that alter protein expression and regulate multiple intracellular processes, including those involved in the response to cellular stress. Alterations in miRNA expression may occur following exposure to several stress-inducing anticancer agents including ionizing radiation, etoposide, and hydrogen peroxide (H(2)O(2)).
Methodology/Principal Findings: Normal human fibroblasts were exposed to radiation, H(2)O(2), or etoposide at doses determined by clonogenic cell survival curves. Total RNA was extracted and miRNA expression was determined by microarray. Time course and radiation dose responses were determined using RT-PCR for individual miRNA species. Changes in miRNA expression were observed for 17 miRNA species following exposure to radiation, 23 after H(2)O(2) treatment, and 45 after etoposide treatment. Substantial overlap between the miRNA expression changes between agents was observed suggesting a signature miRNA response to cell stress. Changes in the expression of selected miRNA species varied in response to radiation dose and time. Finally, production of reactive oxygen species (ROS) increased with increasing doses of radiation and pre-treatment with the thiol antioxidant cysteine decreased both ROS production and the miRNA response to radiation.
Conclusions: These results demonstrate a common miRNA expression signature in response to exogenous genotoxic agents including radiation, H(2)O(2), and etoposide. Additionally, pre-treatment with cysteine prevented radiation-induced alterations in miRNA expression which suggests that miRNAs are responsive to oxidative stress. Taken together, these results imply that miRNAs play a role in cellular defense against exogenous stress and are involved in the generalized cellular response to genotoxic oxidative stress.
RP Simone, NL (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM simonen@mail.nih.gov
FU Intramural NIH HHS
NR 24
TC 141
Z9 149
U1 3
U2 23
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 JUL 27
PY 2009
VL 4
IS 7
AR e6377
DI 10.1371/journal.pone.0006377
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 475YV
UT WOS:000268404800009
PM 19633716
ER
PT J
AU Wu, FB
Matsuoka, Y
Mattson, MP
Yao, PJ
AF Wu, Fangbai
Matsuoka, Yasuji
Mattson, Mark P.
Yao, Pamela J.
TI The clathrin assembly protein AP180 regulates the generation of
amyloid-beta peptide
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Amyloid-beta peptide; APP; AP180; CALM; Clathrin assembly protein;
Neuron; Alzheimer's disease
ID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; IN-VIVO; CALM; LOCALIZATION;
TRAFFICKING; ENDOCYTOSIS; EXPRESSION; PATHOGENESIS; PATHWAYS
AB The overproduction and extracellular buildup of amyloid-beta peptide (A beta) is a critical step in the etiology of Alzheimer's disease. Recent data suggest that intracellular trafficking is of central importance in the production of A beta. Here we use a neuronal cell line to examine two structurally similar clathrin assembly proteins, AP180 and CALM. We show that RNA interference-mediated knockdown of AP180 reduces the generation of A beta 1-40 and AP1-42, whereas CALM knockdown has no effect on A beta generation. Thus AP180 is among the traffic controllers that oversee and regulate amyloid precursor protein processing pathways. Our results also suggest that AP180 and CALM, while similar in their domain structures and biochemical properties, are in fact dedicated to separate trafficking pathways in neurons.. Published by Elsevier Inc.
C1 [Wu, Fangbai; Mattson, Mark P.; Yao, Pamela J.] NIA, Neurosci Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Matsuoka, Yasuji] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yaopa@grc.nia.nih.gov
RI Mattson, Mark/F-6038-2012
FU Intramural Research Program of the National Institute on Aging of the
NIH [R01AG026478, K01AG022455]
FX This research was supported by the Intramural Research Program of the
National Institute on Aging of the NIH, and extramural grants
(R01AG026478 and K01AG022455 to Y.M,). We also thank Ms. Chiho
Hirata-Fukae for her technical assistance.
NR 28
TC 10
Z9 11
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD JUL 24
PY 2009
VL 385
IS 2
BP 247
EP 250
DI 10.1016/j.bbrc.2009.05.050
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 458PZ
UT WOS:000267037300023
PM 19450545
ER
PT J
AU Longo, MS
Carone, DM
Green, ED
O'Neill, MJ
O'Neill, RJ
AF Longo, Mark S.
Carone, Dawn M.
Green, Eric D.
O'Neill, Michael J.
O'Neill, Rachel J.
CA NISC Comparative Sequencing Progra
TI Distinct retroelement classes define evolutionary breakpoints
demarcating sites of evolutionary novelty
SO BMC GENOMICS
LA English
DT Article
ID DISTANTLY RELATED MARSUPIALS; DOUBLE-STRAND BREAKS; CHROMOSOME
EVOLUTION; KARYOTYPE RELATIONSHIPS; MAMMALIAN EVOLUTION; HUMAN GENOME;
MOUSE; REARRANGEMENTS; CENTROMERE; SEQUENCES
AB Background: Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined.
Results: To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, Macropus eugenii, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements.
Conclusion: Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials and eutherians that may have predisposed these genomic regions to large-scale chromosomal instability.
C1 [Longo, Mark S.; Carone, Dawn M.; O'Neill, Michael J.; O'Neill, Rachel J.] Univ Connecticut, Dept Mol & Cell Biol, Ctr Appl Genet & Technol, Storrs, CT 06269 USA.
[Green, Eric D.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Green, Eric D.; NISC Comparative Sequencing Progra] NHGRI, NISC, NIH, Bethesda, MD 20892 USA.
RP O'Neill, RJ (reprint author), Univ Connecticut, Dept Mol & Cell Biol, Ctr Appl Genet & Technol, Storrs, CT 06269 USA.
EM mark.longo@uconn.edu; dawn.carone@uconn.edu; egreen@nhgri.nih.gov;
michael.oneill@uconn.edu; rachel.oneill@uconn.edu
FU NIH; NSF
FX We thank C. Obergfell who helped maintain the cell lines used in this
study and provided thoughtful discussion on the methodology. We thank
the entire staff of the NIH Intramural Sequencing Center (NISC) for
their contributions to the sequencing of BAC clones. MJO was supported
by funding from the NIH and RJO by funding from the NSF.
NR 45
TC 22
Z9 23
U1 0
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 24
PY 2009
VL 10
AR 334
DI 10.1186/1471-2164-10-334
PG 14
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 490NU
UT WOS:000269508600001
PM 19630942
ER
PT J
AU Millet, C
Yamashita, M
Heller, M
Yu, LR
Veenstra, TD
Zhang, YE
AF Millet, Caroline
Yamashita, Motozo
Heller, Mary
Yu, Li-Rong
Veenstra, Timothy D.
Zhang, Ying E.
TI A Negative Feedback Control of Transforming Growth Factor-beta Signaling
by Glycogen Synthase Kinase 3-mediated Smad3 Linker Phosphorylation at
Ser-204
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TGF-BETA; UBIQUITIN LIGASE; TRANSCRIPTIONAL ACTIVATION;
CRYSTAL-STRUCTURE; BMP; DEGRADATION; PATHWAYS; DOMAIN; PROTEIN;
IDENTIFICATION
AB Through the action of its membrane-bound type I receptor, transforming growth factor-beta (TGF-beta) elicits a wide range of cellular responses that regulate cell proliferation, differentiation, and apoptosis. Many of these signaling responses are mediated by Smad proteins. As such, controlling Smad activity is crucial for proper signaling by TGF-beta and its related factors. Here, we show that TGF-beta induces phosphorylation at three sites in the Smad3 linker region in addition to the two C-terminal residues, and glycogen synthase kinase 3 is responsible for phosphorylation at one of these sites, namely Ser-204. Alanine substitution at Ser-204 and/or the neighboring Ser-208, the priming site for glycogen synthase kinase 3 in vivo activity, strengthened the affinity of Smad3 to CREB-binding protein, suggesting that linker phosphorylation may be part of a negative feedback loop that modulates Smad3 transcriptional activity. Thus, our findings reveal a novel aspect of the Smad3 signaling mechanism that controls the final amplitude of cellular responses to TGF-beta.
C1 [Millet, Caroline; Yamashita, Motozo; Heller, Mary; Zhang, Ying E.] NCI, Ctr Canc Res, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Yu, Li-Rong] US FDA, Natl Ctr Toxicol Res, Ctr Prote, Div Syst Toxicol, Jefferson, AR 72079 USA.
[Veenstra, Timothy D.] SAIC Frederick Inc, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA.
[Veenstra, Timothy D.] NCI, NIH, Frederick, MD 21702 USA.
RP Zhang, YE (reprint author), NCI, Ctr Canc Res, Cellular & Mol Biol Lab, NIH, 37 Convent Dr,Bldg 37,Rm 2056B, Bethesda, MD 20892 USA.
EM yingz@helix.nih.gov
RI Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU National Institutes of Health, NCI, Center for Cancer Research,
Intramural Research Program; NCI [N01-CO-12400]
FX This work was supported, in whole or in part, by the National Institutes
of Health, NCI, Center for Cancer Research, Intramural Research Program
and is funded in part by National Institutes of Health Contract
N01-CO-12400 from NCI.
NR 39
TC 40
Z9 42
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 24
PY 2009
VL 284
IS 30
BP 19808
EP 19816
DI 10.1074/jbc.M109.016667
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471ZO
UT WOS:000268097400007
PM 19458083
ER
PT J
AU Perrine, CL
Ganguli, A
Wu, P
Bertozzi, CR
Fritz, TA
Raman, J
Tabak, LA
Gerken, TA
AF Perrine, Cynthia L.
Ganguli, Anjali
Wu, Peng
Bertozzi, Carolyn R.
Fritz, Timothy A.
Raman, Jayalakshmi
Tabak, Lawrence A.
Gerken, Thomas A.
TI Glycopeptide-preferring Polypeptide GalNAc Transferase 10 (ppGalNAc
T10), Involved in Mucin-type O-Glycosylation, Has a Unique
GalNAc-O-Ser/Thr-binding Site in Its Catalytic Domain Not Found in
ppGalNAc T1 or T2
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACETYL-D-GALACTOSAMINE; N-ACETYLGALACTOSAMINYLTRANSFERASE FAMILY;
NEIGHBORING RESIDUE GLYCOSYLATION; PEPTIDE ACCEPTOR PREFERENCES;
UDP-GALNAC; TANDEM REPEAT; FUNCTIONAL-CHARACTERIZATION;
DROSOPHILA-MELANOGASTER; LINKED GLYCOSYLATION; STAUDINGER LIGATION
AB Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGalNAc Ts) that transfer GalNAc from UDP-GalNAc to the Ser and Thr residues of polypeptide acceptors. Some members of the family prefer previously glycosylated peptides (ppGalNAc T7 and T10), whereas others are inhibited by neighboring glycosylation (ppGalNAc T1 and T2). Characterizing their peptide and glycopeptide substrate specificity is critical for understanding the biological role and significance of each isoform. Utilizing a series of random peptide and glycopeptide substrates, we have obtained the peptide and glycopeptide specificities of ppGalNAc T10 for comparison with ppGalNAc T1 and T2. For the glycopeptide substrates, ppGalNAc T10 exhibited a single large preference for Ser/Thr-O-GalNAc at the +1 (C-terminal) position relative to the Ser or Thr acceptor site. ppGalNAc T1 and T2 revealed no significant enhancements suggesting Ser/Thr-O-GalNAc was inhibitory at most positions for these isoforms. Against random peptide substrates, ppGalNAc T10 revealed no significant hydrophobic or hydrophilic residue enhancements, in contrast to what has been reported previously for ppGalNAc T1 and T2. Our results reveal that these transferases have unique peptide and glycopeptide preferences demonstrating their substrate diversity and their likely roles ranging from initiating transferases to filling-in transferases.
C1 [Gerken, Thomas A.] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA.
[Perrine, Cynthia L.; Gerken, Thomas A.] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
[Gerken, Thomas A.] Case Western Reserve Univ, WA Bernbaum Ctr Cyst Fibrosis Res, Cleveland, OH 44106 USA.
[Ganguli, Anjali; Wu, Peng; Bertozzi, Carolyn R.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Bertozzi, Carolyn R.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
[Bertozzi, Carolyn R.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
[Bertozzi, Carolyn R.] Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA.
[Fritz, Timothy A.; Raman, Jayalakshmi; Tabak, Lawrence A.] NIDDK, Sect Biol Chem, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Gerken, TA (reprint author), Case Western Reserve Univ, Sch Med, Dept Pediat, BRB 823,2109 Adelbert Rd, Cleveland, OH 44106 USA.
EM txg2@cwru.edu
FU National Institutes of Health [CA-78834]; NCI [GM66047]; NIDDK
FX This work was supported, in whole or in part, by National Institutes of
Health Grants CA-78834 from NCI (to T. A. G.) and GM66047 (to C. R. B.)
and an NIDDK intramural program grant (to L. A. T.).
NR 51
TC 31
Z9 36
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 24
PY 2009
VL 284
IS 30
BP 20387
EP 20397
DI 10.1074/jbc.M109.017236
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471ZO
UT WOS:000268097400064
PM 19460755
ER
PT J
AU Bodner, CR
Dobson, CM
Bax, A
AF Bodner, Christina R.
Dobson, Christopher M.
Bax, Ad
TI Multiple Tight Phospholipid-Binding Modes of alpha-Synuclein Revealed by
Solution NMR Spectroscopy
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE alpha-helix; membrane binding; NOE; Parkinson's disease; SUV
ID DISEASE-LINKED MUTATIONS; A-BETA COMPONENT; NUCLEAR-MAGNETIC-RESONANCE;
CENTRAL-NERVOUS-SYSTEM; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; LEWY
BODIES; VESICLE PERMEABILIZATION; TRANSLATIONAL DIFFUSION; MEMBRANE
INTERACTIONS
AB 'In dopaminergic neurons, alpha-synuclein (alpha S) partitions between a disordered cytosolic state and a lipid-bound state. Binding of alpha S to membrane phospholipids is implicated in its functional role in synaptic regulation, but also impacts fibril formation associated with Parkinson's disease. We describe here a solution NMR study in which alpha S is added to small unilamellar vesicles of a composition mimicking synaptic vesicles; the results provide evidence for multiple distinct phospholipid-binding modes of US. Exchange between the free state and the lipid-bound alpha S state, and between different bound states is slow on the NMR timescale, being in the range of 1-10 s(-1). Partitioning of the binding modes is dependent on lipid/alpha S stoichiometry, and tight binding with slow-exchange kinetics is observed at stoichiometries as low as 2:1. In all lipid-bound states, a segment of residues starting at the N-terminus of alpha S adopts an alpha-helical conformation, while succeeding residues retain the characteristics of a random coil. The 40 C-terminal residues remain dynamically disordered, even at high-lipid concentrations, but can also bind to lipids to an extent that appears to be determined by the fraction of cis X-Pro peptide bonds in this region. While lipid-bound alpha S exhibits dynamic properties that preclude its direct observation by NMR, its exchange with the NMR-visible free form allows for its indirect characterization. Rapid amide-amide nuclear Overhauser enhancement buildup points to a large et-helical conformation, and a distinct increase in fluorescence anisotropy attributed to Tyr39 indicates an ordered environment for this "dark state." Titration of alpha S with increasing amounts of lipids suggests that the binding mode under high-lipid conditions remains qualitatively similar to that in the low-lipid case. The NMR data appear incompatible with the commonly assumed model where alpha S lies in an alpha-helical conformation on the membrane surface and instead suggest that considerable remodeling of the vesicles is induced by alpha S. Published by Elsevier Ltd.
C1 [Bodner, Christina R.; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Bodner, Christina R.; Dobson, Christopher M.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU Intramural NIH HHS [Z01 DK029047-01]; Wellcome Trust
NR 90
TC 127
Z9 127
U1 1
U2 29
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 24
PY 2009
VL 390
IS 4
BP 775
EP 790
DI 10.1016/j.jmb.2009.05.066
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 477KY
UT WOS:000268519200016
PM 19481095
ER
PT J
AU Upreti, VV
Eddington, ND
Moon, KH
Song, BJ
Lee, IJ
AF Upreti, Vijay V.
Eddington, Natalie D.
Moon, Kwan-Hoon
Song, Byoung Joon
Lee, Insong J.
TI Drug interaction between ethanol and 3,4-methylenedioxymethamphetamine
("ecstasy")
SO TOXICOLOGY LETTERS
LA English
DT Article
DE Ethanol; 3.4-Methylenedioxymethamphetamine; Acetaldehyde; Aldehyde
dehydrogenase; Drug interaction; Liver toxicity
ID MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; DISULFIRAM-ALCOHOL REACTION;
GLUTATHIONE-S-TRANSFERASE; SQUAMOUS-CELL CARCINOMA; RAT-LIVER;
ACETALDEHYDE METABOLISM; INDUCED TOXICITY; PROTEIN ADDUCTS; BLOOD; MDMA
AB Alcohol (ethanol) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are frequently co-abused, but recent findings indicate a harmful drug interaction between these two agents. In our previous study, we showed that MDMA exposure inhibits the activity of the acetaldehyde (ACH) metabolizing enzyme, aldehyde dehydrogenase2 (ALDH2). Based on this finding, we hypothesized that the co-administration of MDMA and ethanol would reduce the metabolism of ACH and result in increased accumulation of ACH. Rats were treated with MDMA or vehicle and then administered a single dose of ethanol. Liver ALDH2 activity decreased by 35% in the MDMA-treated rats compared to control rats. The peak concentration and the area under the concentration versus time curve of plasma ACH were 31% and 59% higher, respectively, in the MDMA-ethanol group compared to the ethanol-only group. In addition, the MDMA-ethanol group had 80% higher plasma transaminase levels than the ethanol-only group, indicating greater hepatocellular damage. Our results not only support a drug interaction between MDMA and ethanol but a novel underlying mechanism for the interaction. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
C1 [Upreti, Vijay V.; Eddington, Natalie D.; Lee, Insong J.] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA.
[Moon, Kwan-Hoon; Song, Byoung Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
RP Lee, IJ (reprint author), Coll Notre Dame Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21210 USA.
EM ilee@ndm.edu
FU National Institute of Alcohol Abuse and Alcoholism (NIAAA) Intramural
Research Fund
FX The authors, Kwan-Hoon Moon and Byoung-Joon Song were funded by National
Institute of Alcohol Abuse and Alcoholism (NIAAA) Intramural Research
Fund.
NR 51
TC 14
Z9 14
U1 1
U2 5
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 JUL 24
PY 2009
VL 188
IS 2
BP 167
EP 172
DI 10.1016/j.toxlet.2009.03.023
PG 6
WC Toxicology
SC Toxicology
GA 455CO
UT WOS:000266734400015
PM 19446252
ER
PT J
AU Sereti, I
AF Sereti, Irini
TI Where have all the T cells gone?
SO BLOOD
LA English
DT Editorial Material
ID EXPANSION
C1 NIH, Bethesda, MD 20892 USA.
RP Sereti, I (reprint author), NIH, Bethesda, MD 20892 USA.
NR 7
TC 4
Z9 4
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 JUL 23
PY 2009
VL 114
IS 4
BP 751
EP 752
DI 10.1182/blood-2009-04-217091
PG 4
WC Hematology
SC Hematology
GA 474BO
UT WOS:000268257400003
PM 19628713
ER
PT J
AU Landgren, O
Kristinsson, SY
Goldin, LR
Caporaso, NE
Blimark, C
Mellqvist, UH
Wahlin, A
Bjorkholm, M
Turesson, I
AF Landgren, Ola
Kristinsson, Sigurdur Y.
Goldin, Lynn R.
Caporaso, Neil E.
Blimark, Cecilie
Mellqvist, Ulf-Henrik
Wahlin, Anders
Bjorkholm, Magnus
Turesson, Ingemar
TI Risk of plasma cell and lymphoproliferative disorders among 14 621
first-degree relatives of 4458 patients with monoclonal gammopathy of
undetermined significance in Sweden
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MULTIPLE-MYELOMA FAMILIES;
NON-HODGKIN-LYMPHOMA; WALDENSTROM MACROGLOBULINEMIA; PRECURSOR DISEASES;
UNITED-STATES; POPULATION; PREVALENCE; AUTOIMMUNE; VETERANS
AB Familial clustering of the precursor condition, monoclonal gammopathy of undetermined significance (MGUS) has been observed in case reports and in smaller studies. Using population-based data from Sweden, we identified 4458 MGUS patients, 17 505 population-based controls, and first-degree relatives of patients (n = 14 621) and controls (n = 58 387) with the aim to assess risk of MGUS and lymphoproliferative malignancies among first-degree relatives of MGUS patients. Compared with relatives of controls, relatives of MGUS patients had increased risk of MGUS (relative risk [RR] = 2.8; 1.4-5.6), multiple myeloma (MM; RR = 2.9; 1.9-4.3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM; RR = 4.0; 1.5-11), and chronic lymphocytic leukemia (CLL; RR = 2.0; 1.2-2.3). Relatives of patients with IgG/IgA MGUS had a 4.0-fold (1.7-9.2), 2.9-fold (1.7-4.9), and 20-fold (2.3-170) elevated risk of developing MGUS, MM, and LPL/WM, respectively. Relatives of IgM MGUS patients had 5.0-fold (1.1-23) increased CLL risk and nonsignificant excess MM and LPL/WM risks. The results were very similar when we assessed risk by type of first-degree relative, age at MGUS (above/below 65 years), or sex. Risk of non-Hodgkin lymphoma or Hodgkin lymphoma was not increased among MGUS relatives. Among first-degree relatives of a nationwide MGUS cohort, we found elevated risks of MGUS, MM, LPL/WM, and CLL, supporting a role for germline susceptibility genes, shared environmental influences, or an interaction between both. (Blood. 2009; 114: 791-795)
C1 [Landgren, Ola] NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA.
[Landgren, Ola; Goldin, Lynn R.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Landgren, Ola; Kristinsson, Sigurdur Y.; Bjorkholm, Magnus] Karolinska Univ Hosp & Inst, Div Hematol, Dept Med, Stockholm, Sweden.
[Blimark, Cecilie; Mellqvist, Ulf-Henrik] Sahlgrens Univ Hosp, Dept Med, Sect Hematol & Coagulat, S-41345 Gothenburg, Sweden.
[Wahlin, Anders] Umea Univ Hosp, Sect Hematol, S-90185 Umea, Sweden.
[Turesson, Ingemar] Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden.
RP Landgren, O (reprint author), NCI, NIH, Ctr Canc Res, Med Oncol Branch, Bldg 10,Room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA.
EM landgreo@mail.nih.gov
RI Wahlin, Anders/F-6043-2013; Kristinsson, Sigurdur /M-2910-2015
OI Wahlin, Anders/0000-0001-6402-0463; Kristinsson, Sigurdur
/0000-0002-4964-7476
FU NIH; National Cancer Institute; Swedish Cancer Society; Stockholm County
Council; Karolinska Institutet Foundations
FX This research was supported by the Intramural Research Program of the
NIH (Bethesda, MD) and the National Cancer Institute (Bethesda, MD), and
by grants from the Swedish Cancer Society, Stockholm County Council, and
the Karolinska Institutet Foundations.
NR 32
TC 60
Z9 63
U1 0
U2 3
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 23
PY 2009
VL 114
IS 4
BP 791
EP 795
DI 10.1182/blood-2008-12-191676
PG 5
WC Hematology
SC Hematology
GA 474BO
UT WOS:000268257400013
PM 19182202
ER
PT J
AU Leich, E
Salaverria, I
Bea, S
Zettl, A
Wright, G
Moreno, V
Gascoyne, RD
Chan, WC
Braziel, RM
Rimsza, LM
Weisenburger, DD
Delabie, J
Jaffe, ES
Lister, A
Fitzgibbon, J
Staudt, LM
Hartmann, EM
Mueller-Hermelink, HK
Campo, E
Ott, G
Rosenwald, A
AF Leich, Ellen
Salaverria, Itziar
Bea, Silvia
Zettl, Andreas
Wright, George
Moreno, Victor
Gascoyne, Randy D.
Chan, Wing-Chung
Braziel, Rita M.
Rimsza, Lisa M.
Weisenburger, Dennis D.
Delabie, Jan
Jaffe, Elaine S.
Lister, Andrew
Fitzgibbon, Jude
Staudt, Louis M.
Hartmann, Elena M.
Mueller-Hermelink, Hans-Konrad
Campo, Elias
Ott, German
Rosenwald, Andreas
TI Follicular lymphomas with and without translocation t(14;18) differ in
gene expression profiles and genetic alterations
SO BLOOD
LA English
DT Article
ID B-CELL LYMPHOMA; SET ENRICHMENT ANALYSIS; BCL-2 PROMOTER; SURVIVAL;
REARRANGEMENT; T(14/18)(Q32,Q21); IDENTIFICATION; PATHOGENESIS;
BREAKPOINT; SIGNATURES
AB Follicular lymphoma (FL) is genetically characterized by the presence of the t(14; 18)(q32;q21) chromosomal translocation in approximately 90% of cases. In contrast to FL carrying the t(14; 18), their t(14; 18)-negative counterparts are less well studied about their immunohistochemical, genetic, molecular, and clinical features. Within a previously published series of 184 FLs grades 1 to 3A with available gene expression data, we identified 17 FLs lacking the t(14; 18). Comparative genomic hybridization and high-resolution single nucleotide polymorphism (SNP) array profiling showed that gains/amplifications of the BCL2 gene locus in 18q were restricted to the t(14; 18)-positive FL subgroup. A comparison of gene expression profiles showed an enrichment of germinal center B cell-associated signatures in t(14; 18)-positive FL, whereas activated B cell-like, NF kappa B, proliferation, and bystander cell signatures were enriched in t(14; 18)-negative FL. These findings were confirmed by immunohistochemistry in an independent validation series of 84 FLs, in which 32% of t(14; 18)-negative FLs showed weak or absent CD10 expression and 91% an increased Ki67 proliferation rate. Although overall survival did not differ between FL with and without t(14; 18), our findings suggest distinct molecular features of t(14; 18)-negative FL. (Blood. 2009; 114: 826-834)
C1 [Leich, Ellen; Zettl, Andreas; Hartmann, Elena M.; Mueller-Hermelink, Hans-Konrad; Ott, German; Rosenwald, Andreas] Univ Wurzburg, Inst Pathol, D-97080 Wurzburg, Germany.
[Salaverria, Itziar; Bea, Silvia; Campo, Elias] Univ Barcelona, Hosp Clin, Dept Pathol, Barcelona, Spain.
[Wright, George] NCI, Biometr Res Branch, Rockville, MD USA.
[Moreno, Victor] Univ Barcelona, Biostat & Bioinformat Unit, IDIBELL Catalan Inst Oncol, Barcelona, Spain.
[Gascoyne, Randy D.] Univ British Columbia, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada.
[Chan, Wing-Chung; Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, SW Oncol Grp, Portland, OR 97201 USA.
[Rimsza, Lisa M.] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Delabie, Jan] Norwegian Radium Hosp, Div Pathol, Oslo, Norway.
[Jaffe, Elaine S.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Lister, Andrew; Fitzgibbon, Jude] St Bartholomews Hosp, Canc Res UK, London, England.
[Staudt, Louis M.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Ott, German] Robert Bosch Krankenhaus, Inst Clin Pathol, Stuttgart, Germany.
[Ott, German] Inst Clin Pharmacol, Stuttgart, Germany.
RP Rosenwald, A (reprint author), Univ Wurzburg, Inst Pathol, Josef Schneider Str 2, D-97080 Wurzburg, Germany.
EM rosenwald@mail.uni-wuerzburg.de
RI Moreno, Victor/A-1697-2010; SALAVERRIA, ITZIAR/L-2246-2015; Bea,
Silvia/K-7699-2014;
OI Moreno, Victor/0000-0002-2818-5487; SALAVERRIA,
ITZIAR/0000-0002-2427-9822; Delabie, Jan/0000-0001-5023-0689; Bea,
Silvia/0000-0001-7192-2385; Campo, elias/0000-0001-9850-9793
FU Interdisciplinary Center for Clinical Research (IZKF); University of
Wurzburg, Germany; Robert-Bosch-Stiftung; Spanish Ministry of Science
[SAF 05/5855]; Instituto de Salud Carlos III; Red Tematica de
Investigacion del Cancer [2006RET2039]; National Cancer Institute (NCI)
[UO1-CA 114778]
FX This work was supported by the Interdisciplinary Center for Clinical
Research (IZKF), University of Wurzburg, Germany (A. R., E. L., and E.
H.); the Robert-Bosch-Stiftung (Stuttgart, Germany; G. O.); the Spanish
Ministry of Science (Madrid, Spain; SAF 05/5855; E. C.); the Instituto
de Salud Carlos III, Red Tematica de Investigacion del Cancer
(2006RET2039; E. C.); and the National Cancer Institute (NCI) Strategic
Partnering to Evaluate Cancer Signature (grant UO1-CA 114778).
NR 44
TC 67
Z9 70
U1 4
U2 8
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 23
PY 2009
VL 114
IS 4
BP 826
EP 834
DI 10.1182/blood-2009-01-198580
PG 9
WC Hematology
SC Hematology
GA 474BO
UT WOS:000268257400017
PM 19471018
ER
PT J
AU Hardwick, JM
Youle, RJ
AF Hardwick, J. Marie
Youle, Richard J.
TI SnapShot: BCL-2 Proteins
SO CELL
LA English
DT Editorial Material
C1 [Hardwick, J. Marie] Johns Hopkins, Baltimore, MD 21205 USA.
NINDS, NIH, Bethesda, MD 20892 USA.
RP Hardwick, JM (reprint author), Johns Hopkins, Baltimore, MD 21205 USA.
FU NIGMS NIH HHS [R01 GM077875, R01 GM077875-04]; NINDS NIH HHS [R01
NS037402]
NR 0
TC 38
Z9 43
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 23
PY 2009
VL 138
IS 2
BP 404
EP 404
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 474IM
UT WOS:000268277000020
PM 19632186
ER
PT J
AU Hardwick, JM
Youle, RJ
AF Hardwick, J. Marie
Youle, Richard J.
TI SnapShot: BCL-2 Proteins
SO CELL
LA English
DT Editorial Material
ID PROGRAMMED CELL-DEATH; APOPTOSIS; ELEGANS; BAX
C1 [Hardwick, J. Marie] Johns Hopkins, Baltimore, MD 21205 USA.
NINDS, NIH, Bethesda, MD 20892 USA.
RP Hardwick, JM (reprint author), Johns Hopkins, Baltimore, MD 21205 USA.
NR 10
TC 1
Z9 1
U1 0
U2 4
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
J9 CELL
JI Cell
PD JUL 23
PY 2009
VL 138
IS 2
AR 404.e1
DI 10.1016/j.cell.2009.07.003
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 474IM
UT WOS:000268277000021
ER
PT J
AU Ionov, M
Gordiyenko, N
Olchowik, E
Baram, N
Zijaev, K
Salakhutdinov, B
Bryszewska, M
Zamaraeva, M
AF Ionov, Maksim
Gordiyenko, Nataliya
Olchowik, Ewa
Baram, Nina
Zijaev, Khairulla
Salakhutdinov, Bakhtiyar
Bryszewska, Maria
Zamaraeva, Maria
TI The Immobilization of Gossypol Derivative on N-Polyvinylpyrrolidone
Increases its Water Solubility and Modifies Membrane-Active Properties
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID ANTIFERTILITY AGENT; RAT TESTIS; MITOCHONDRIA; PERMEABILITY;
(-)-GOSSYPOL; PARAMETERS; MECHANISM; APOPTOSIS; MOTILITY; FLUIDITY
AB The conjugate of the gossypol derivative megosin (1) with N-polyvinylpyrrolidone named rometin (2) was synthesized. The effects of 1 and 2 on the structure and permeability of human erythrocytes and rat liver mitochondria were compared. Compound 1 induced dose-dependent erythrocyte hemolysis and increased mitochondrial permeability, with concomitant changes in membrane structure as determined by ESR and fluorescence anisotropy methods. Immobilization of 1 on N-polyvinylpyrrolidone (compound 2) increased its water solubility and reduced the intensity of its effects oil erythrocyte membrane integrity and mitochondrial permeability, which correlated with a decrease in the membranes structural changes induced by the compound. Although the same concentrations of free and N-polyvinylpyrrolidone bound 1 were used, far less (14)C-labeled 1 was incorporated into the membranes from complex than free 1. The increase in water solubility and the reduction of membrane-active properties of 1 after immobilization oil N-polyvinylpyrrolidone could explain our previous observation of the decreased toxicity of 1.
C1 [Olchowik, Ewa; Zamaraeva, Maria] Univ Bialystok, Dept Biophys, PL-15950 Bialystok, Poland.
[Ionov, Maksim; Baram, Nina; Zijaev, Khairulla; Salakhutdinov, Bakhtiyar] Uzbek Acad Sci, Inst Bioorgan Chem, Tashkent 700135, Uzbekistan.
[Gordiyenko, Nataliya] NEI, NIH, Bethesda, MD 20892 USA.
[Ionov, Maksim; Bryszewska, Maria] Univ Lodz, Dept Gen Biophys, PL-90131 Lodz, Poland.
RP Zamaraeva, M (reprint author), Univ Bialystok, Dept Biophys, Swierkowa 20C, PL-15950 Bialystok, Poland.
EM m.zamaraeva@uwb.edu.pl
OI Bryszewska, Maria/0000-0003-4676-3743
NR 50
TC 7
Z9 7
U1 1
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUL 23
PY 2009
VL 52
IS 14
BP 4119
EP 4125
DI 10.1021/jm9002507
PG 7
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 472NX
UT WOS:000268139900010
PM 19603832
ER
PT J
AU Schultz, ZD
Pazos, IM
McNeil-Watson, FK
Lewis, EN
Levin, IW
AF Schultz, Zachary D.
Pazos, Ileana M.
McNeil-Watson, Fraser K.
Lewis, E. Neil
Levin, Ira W.
TI Magnesium-Induced Lipid Bilayer Microdomain Reorganizations:
Implications for Membrane Fusion
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID PHOSPHATIDYLSERINE-PHOSPHATIDYLCHOLINE VESICLES; LATERAL PHASE
SEPARATIONS; DYNAMIC LIGHT-SCATTERING; CALCIUM-INDUCED FUSION;
INFRARED-SPECTROSCOPY; PHOSPHOLIPID-BILAYERS; DOMAIN FORMATION; MODEL
MEMBRANES; CELL-MEMBRANES; STALK MODEL
AB Interactions between dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylserine (DPPS), combined both as binary lipid bilayer assemblies and separately, under the influence of divalent Mg(2+), a membrane bilayer fusogenic agent, are reported. Infrared vibrational spectroscopic analyses of the lipid acyl chain methylene symmetric stretching modes indicate that aggregates of the two phospholipid components exist as domains heterogeneously distributed throughout the binary bilayer system. In the presence of Mg(2+) DPPS maintains an ordered orthorhombic subcell gel phase structure through the phase transition temperature, while the DPPC component is only minimally perturbed with respect to the gel to liquid crystalline phase change. The addition of Mg(2+) induces a reorganization of the lipid domains in which the gel phase acyl chain planes rearrange from a hexagonal configuration toward a triclinic, parallel chain subcell. Examination of the acyl chain methylene deformation modes at low temperatures allows a determination of DPPS microdomain sizes, which decrease upon the addition of DPPC-d(62) in the absence of Mg(2+). On adding Mg(2+), a uniform DPPS domain size is observed in the binary mixtures, In either the presence or absence of Mg(2+), DPPC-d(62) aggregates remain in a configuration for which microdomain sizes are not spectroscopically measurable. Analysis of the acyl chain methylene deformation modes for DPPC-d(62) in the binary system suggests that clusters of the deuterated lipids are distributed throughout the DPPS matrix. Light scattering and fluorescence measurements indicate that Mg(2+) induces both the aggregation and the fusion of the lipid assemblies as a function of the ratio of DPPS to DPPC. The structural reorganizations of the lipid microdomains within the DPPS-DPPC bilayer are interpreted in the context of current concepts regarding lipid bilayer fusion.
C1 [Schultz, Zachary D.; Pazos, Ileana M.; Levin, Ira W.] NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
[McNeil-Watson, Fraser K.; Lewis, E. Neil] Malvern Instruments Inc, Novel Measurements Grp, Malvern WR14 1XZ, Worcs, England.
RP Levin, IW (reprint author), NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
EM iwl@helix.nih.gov
RI Schultz, Zachary/L-5724-2013
OI Schultz, Zachary/0000-0003-1741-8801
FU NIDDK intramural research program
FX We thank Dr. ShLiko Yoshikarni for assistance preparing vesicles
containing fluorescence indicators. This work was funded through the
NIDDK intramural research program.
NR 66
TC 17
Z9 17
U1 0
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUL 23
PY 2009
VL 113
IS 29
BP 9932
EP 9941
DI 10.1021/jp9011944
PG 10
WC Chemistry, Physical
SC Chemistry
GA 472NU
UT WOS:000268139600039
PM 19603842
ER
PT J
AU Keele, BF
Jones, JH
Terio, KA
Estes, JD
Rudicell, RS
Wilson, ML
Li, YY
Learn, GH
Beasley, TM
Schumacher-Stankey, J
Wroblewski, E
Mosser, A
Raphael, J
Kamenya, S
Lonsdorf, EV
Travis, DA
Mlengeya, T
Kinsel, MJ
Else, JG
Silvestri, G
Goodall, J
Sharp, PM
Shaw, GM
Pusey, AE
Hahn, BH
AF Keele, Brandon F.
Jones, James Holland
Terio, Karen A.
Estes, Jacob D.
Rudicell, Rebecca S.
Wilson, Michael L.
Li, Yingying
Learn, Gerald H.
Beasley, T. Mark
Schumacher-Stankey, Joann
Wroblewski, Emily
Mosser, Anna
Raphael, Jane
Kamenya, Shadrack
Lonsdorf, Elizabeth V.
Travis, Dominic A.
Mlengeya, Titus
Kinsel, Michael J.
Else, James G.
Silvestri, Guido
Goodall, Jane
Sharp, Paul M.
Shaw, George M.
Pusey, Anne E.
Hahn, Beatrice H.
TI Increased mortality and AIDS-like immunopathology in wild chimpanzees
infected with SIVcpz
SO NATURE
LA English
DT Article
ID GOMBE NATIONAL-PARK; IMMUNODEFICIENCY VIRUS-INFECTION; IMMUNE
ACTIVATION; HIV-INFECTION; T-CELLS; POPULATION; TRANSMISSION;
RESISTANCE; COMMUNITY; TANZANIA
AB African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2)(1,2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts(3). Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.
C1 [Keele, Brandon F.; Li, Yingying; Learn, Gerald H.; Shaw, George M.; Hahn, Beatrice H.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
[Rudicell, Rebecca S.; Hahn, Beatrice H.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA.
[Beasley, T. Mark] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA.
[Jones, James Holland] Stanford Univ, Dept Anthropol, Stanford, CA 94305 USA.
[Terio, Karen A.; Kinsel, Michael J.] Univ Illinois, Zool Pathol Program, Maywood, IL 60153 USA.
[Estes, Jacob D.] NCI, Sci Applicat Int Corp Frederick Inc, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
[Wilson, Michael L.] Univ Minnesota, Dept Anthropol, Minneapolis, MN 55455 USA.
[Wilson, Michael L.; Schumacher-Stankey, Joann; Wroblewski, Emily; Pusey, Anne E.] Univ Minnesota, Dept Ecol Evolut & Behav, Jane Goodall Inst Ctr Primate Studies, St Paul, MN 55108 USA.
[Mosser, Anna; Raphael, Jane; Kamenya, Shadrack] Jane Goodall Inst, Gombe Stream Res Ctr, Kigoma, Tanzania.
[Lonsdorf, Elizabeth V.] Lester E Fisher Ctr Study & Conservat Apes, Chicago, IL 60614 USA.
[Travis, Dominic A.] Lincoln Pk Zoo, Dept Conservat & Sci, Chicago, IL 60614 USA.
[Mlengeya, Titus] Tanzania Natl Pk, Arusha, Tanzania.
[Else, James G.] Emory Univ, Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA 30322 USA.
[Silvestri, Guido] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19107 USA.
[Goodall, Jane] Jane Goodall Inst, Arlington, VA 22203 USA.
[Sharp, Paul M.] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh EH9 3JT, Midlothian, Scotland.
RP Hahn, BH (reprint author), Univ Alabama, Dept Med, Birmingham, AL 35294 USA.
EM bhahn@uab.edu
RI Sharp, Paul/F-5783-2010;
OI Sharp, Paul/0000-0001-9771-543X; Jones, James/0000-0003-1680-6757
FU National Institutes of Health [R01 AI50529, R01 AI58715, U19 AI067854,
T32 GM008111]; National Cancer Institute [HHSN266200400088C]; UAB Center
for AIDS Research [P30 AI 27767]; Yerkes National Primate Research
Center [RR-00165]; National Science Foundation [DBS-9021946,
SBR-9319909, BSC-0452315, IIS-0431141, BSC-0648481]; Jane Goodall
Institute; Harris Steel Group; University of Minnesota; University of
Illinois; US Fish and Wildlife Service Great Ape Conservation Fund;
Windibrow, Arcus, Guthman and Davee Foundations; Lincoln Park Zoo;
Howard Hughes Medical Institute
FX We thank the field staff at the Gombe Stream Research Centre for
collecting behavioural data as well as urine and faecal samples from
wild chimpanzees; E. Kaaya for help with necropsies; A. Collins for
logistical support; the Tanzania Commission for Science and Technology,
the Tanzania Wildlife Research Institute, and the Tanzania National
Parks for permission to conduct research in Gombe; I. White for
discussions; L. Lowenstine for histological consultation; M. Salazar and
Y. Chen for technical assistance; and J. C. White for artwork and
manuscript preparation. This work was supported by grants from the
National Institutes of Health (R01 AI50529, R01 AI58715, U19 AI067854,
T32 GM008111), the National Cancer Institute (contract
HHSN266200400088C), the UAB Center for AIDS Research (P30 AI 27767), the
Yerkes National Primate Research Center (RR-00165), the National Science
Foundation (DBS-9021946, SBR-9319909, BSC-0452315, IIS-0431141,
BSC-0648481), the Jane Goodall Institute, the Harris Steel Group, the
University of Minnesota, the University of Illinois, the US Fish and
Wildlife Service Great Ape Conservation Fund, the Windibrow, Arcus,
Guthman and Davee Foundations, and the Lincoln Park Zoo. R. S. R. was
funded by a Howard Hughes Medical Institute Med-into-Grad Fellowship.
The content of this publication does not necessarily reflect the views
or policies of the US Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government.
NR 29
TC 172
Z9 174
U1 2
U2 62
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 23
PY 2009
VL 460
IS 7254
BP 515
EP 519
DI 10.1038/nature08200
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 474BK
UT WOS:000268257000039
PM 19626114
ER
PT J
AU Miller, FG
Truog, RD
AF Miller, Franklin G.
Truog, Robert D.
TI Controversies About Brain Death
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Truog, Robert D.] Harvard Univ, Sch Med, Boston, MA USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 5
TC 1
Z9 1
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 22
PY 2009
VL 302
IS 4
BP 380
EP 381
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472NQ
UT WOS:000268139200013
PM 19622812
ER
PT J
AU Dickert, N
Wendler, D
AF Dickert, Neal
Wendler, David
TI Ancillary Care Obligations of Medical Researchers
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID SICKLE-CELL-DISEASE; CLINICAL CARE; RESPONSIBILITIES
AB An investigator planning a study in Africa of the prevalence of pulmonary hypertension in children with severe malaria anticipates that she and her team will encounter significant unmet health needs during the course of the study. She recognizes that study procedures, particularly echocardiography, may identify and diagnose conditions that are not treatable within the local health system due to resource constraints. Aware that some of these needs may be serious, as well as difficult and costly to treat, she asks the bioethics consultation service for assistance in determining the extent to which she as an investigator has a responsibility to provide clinical care for conditions that she finds while conducting the study. This article reviews the issue of investigators' responsibilities to meet participants' needs for ancillary care and argues that investigators can have a responsibility to provide care for a wide range of health needs, including at times care for conditions not connected to the research question or study procedures. That responsibility, however, is significantly limited by the depth of the investigator's relationship with participants and the resource demands of providing such care. JAMA. 2009;302(4):424-428
C1 [Dickert, Neal] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Wendler, David] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Dickert, N (reprint author), Emory Univ, Sch Med, Div Cardiol, 1256 Briarcliff Rd,Bldg A,Ste 1 N,Mailstop 1256-0, Atlanta, GA 30322 USA.
EM njr@emory.edu
FU National Institutes of Health
FX Dr Dickert's participation in the initial Grand Rounds presentation was
supported by the National Institutes of Health.
NR 13
TC 18
Z9 18
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 22
PY 2009
VL 302
IS 4
BP 424
EP 428
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472NQ
UT WOS:000268139200025
PM 19622821
ER
PT J
AU Saha, S
Guillily, MD
Ferree, A
Lanceta, J
Chan, D
Ghosh, J
Hsu, CH
Segal, L
Raghavan, K
Matsumoto, K
Hisamoto, N
Kuwahara, T
Iwatsubo, T
Moore, L
Goldstein, L
Cookson, M
Wolozin, B
AF Saha, Shamol
Guillily, Maria D.
Ferree, Andrew
Lanceta, Joel
Chan, Diane
Ghosh, Joy
Hsu, Cindy H.
Segal, Lilach
Raghavan, Kesav
Matsumoto, Kunihiro
Hisamoto, Naoki
Kuwahara, Tomoki
Iwatsubo, Takeshi
Moore, Landon
Goldstein, Lee
Cookson, Mark
Wolozin, Benjamin
TI LRRK2 Modulates Vulnerability to Mitochondrial Dysfunction in
Caenorhabditis elegans
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID DISEASE-ASSOCIATED MUTATIONS; PARKINSONS-DISEASE; ALPHA-SYNUCLEIN;
KINASE-ACTIVITY; DOPAMINERGIC-NEURONS; PARAQUAT; DEGENERATION;
DROSOPHILA; PATHOLOGY; PINK1
AB Mutations in leucine-rich repeat kinase 2 (LRRK2) cause autosomal-dominant familial Parkinson's disease. We generated lines of Caenorhabditis elegans expressing neuronally directed human LRRK2. Expressing human LRRK2 increased nematode survival in response to rotenone or paraquat, which are agents that cause mitochondrial dysfunction. Protection by G2019S, R1441C, or kinase-dead LRRK2 was less than protection by wild-type LRRK2. Knockdown of lrk-1, the endogenous ortholog of LRRK2 in C. elegans, reduced survival associated with mitochondrial dysfunction. C. elegans expressing LRRK2 showed rapid loss of dopaminergic markers (DAT::GFP fluorescence and dopamine levels) beginning in early adulthood. Loss of dopaminergic markers was greater for the G2019S LRRK2 line than for the wild-type line. Rotenone treatment induced a larger loss of dopamine markers in C. elegans expressing G2019S LRRK2 than in C. elegans expressing wild-type LRRK2; however, loss of dopaminergic markers in the G2019S LRRK2 nematode lines was not statistically different from that in the control line. These data suggest that LRRK2 plays an important role in modulating the response to mitochondrial inhibition and raises the possibility that mutations in LRRK2 selectively enhance the vulnerability of dopaminergic neurons to a stressor associated with Parkinson's disease.
C1 [Saha, Shamol; Guillily, Maria D.; Ferree, Andrew; Lanceta, Joel; Chan, Diane; Hsu, Cindy H.; Segal, Lilach; Raghavan, Kesav; Wolozin, Benjamin] Boston Univ, Sch Med, Dept Pharmacol, Boston, MA 02118 USA.
[Ghosh, Joy; Goldstein, Lee] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Moore, Landon] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Wolozin, Benjamin] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Matsumoto, Kunihiro; Hisamoto, Naoki] Nagoya Univ, Dept Mol Biol, Inst Adv Res, Nagoya, Aichi 4648602, Japan.
[Kuwahara, Tomoki; Iwatsubo, Takeshi] Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo 1130033, Japan.
[Cookson, Mark] NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, Bethesda, MD 20892 USA.
RP Wolozin, B (reprint author), Boston Univ, Sch Med, Dept Pharmacol, 72 E Concord St,R614, Boston, MA 02118 USA.
EM bwolozin@bu.edu
OI Goldstein, Lee/0000-0001-8419-9800
FU National Institutes of Health (NIH)-National Institute of Environmental
Health Sciences [ES015567]; NIH-National Institute of Neurological
Disorders and Stroke [NS060872]; Alzheimer Association; Michael J. Fox
Foundation; Intramural Research Program of the NIH; National Institute
on Aging [1 Z01 AG000953]; NIH National Center for Research Resources
FX This work was supported by National Institutes of Health (NIH)-National
Institute of Environmental Health Sciences Grant ES015567, NIH-National
Institute of Neurological Disorders and Stroke Grant NS060872, the
Alzheimer Association, and the Michael J. Fox Foundation (all to B. W.).
This research was also supported in part by the Intramural Research
Program of the NIH, National Institute on Aging, Project 1 Z01 AG000953
(awarded to M. C.). Some nematode strains used in this work were
provided by the Caenorhabditis Genetics Center, which is funded by the
NIH National Center for Research Resources.
NR 48
TC 130
Z9 136
U1 2
U2 25
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 22
PY 2009
VL 29
IS 29
BP 9210
EP 9218
DI 10.1523/JNEUROSCI.2281-09.2009
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 473CE
UT WOS:000268181700007
PM 19625511
ER
PT J
AU Preis, SR
Pencina, MJ
Hwang, SJ
D'Agostino, RB
Savage, PJ
Levy, D
Fox, CS
AF Preis, Sarah Rosner
Pencina, Michael J.
Hwang, Shih-Jen
D'Agostino, Ralph B., Sr.
Savage, Peter J.
Levy, Daniel
Fox, Caroline S.
TI Trends in Cardiovascular Disease Risk Factors in Individuals With and
Without Diabetes Mellitus in the Framingham Heart Study
SO CIRCULATION
LA English
DT Article
DE diabetes mellitus; risk factors; cholesterol; blood pressure; obesity
ID PLACEBO-CONTROLLED TRIAL; BLOOD-PRESSURE; GLUCOSE CONTROL; MICROVASCULAR
COMPLICATIONS; UNITED-STATES; US ADULTS; TYPE-2; HYPERTENSION;
ATORVASTATIN; ASSOCIATION
AB Background-Individuals with diabetes mellitus are at 2-to 3-fold increased risk for cardiovascular disease (CVD) relative to those without diabetes. Our objective was to examine CVD risk factor level changes among individuals with and without type 2 diabetes mellitus from 1970 to 2005 in the Framingham Heart Study.
Methods and Results-We included 4195 participants (3990 with no diabetes and 205 with diabetes) 50 years of age and 3495 participants (3178 with no diabetes and 317 with diabetes) 60 years of age. Contemporaneous CVD risk factor levels were measured; linear regression models were used to assess the interaction between diabetes status and calendar year on CVD risk factor levels. Among 50-year-olds without diabetes mellitus, there was an increase in body mass index of 0.39 kg/m(2) per 10 years, whereas for those with diabetes, there was an increase of 2.52 kg/m2 (P value for the diabetes-by-calendar year interaction [P for interaction] < 0.001). For low-density lipoprotein cholesterol, the mean decrease was - 7.43 mg/dL per decade (nondiabetes) and - 15.5 mg/dL for diabetes (P for interaction = 0.002). For systolic blood pressure, the mean decrease was - 3.35 mm Hg per decade (nondiabetes) and - 3.50 mm Hg for diabetes (P for interaction = 0.97). The direction of the trends for those with diabetes relative to those without diabetes was similar for 60-year-olds.
Conclusions-Compared with individuals without diabetes mellitus, individuals with diabetes experienced a greater increase in body mass index, a greater decrease in low-density lipoprotein cholesterol, and a similar magnitude of decline in systolic blood pressure. Individuals with diabetes mellitus have not experienced the necessary declines in CVD risk factors to overcome their increased risk of CVD. Further efforts are needed to aggressively control CVD risk factors among individuals with diabetes mellitus. (Circulation. 2009; 120: 212-220.)
C1 [Preis, Sarah Rosner; Hwang, Shih-Jen; Levy, Daniel; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Preis, Sarah Rosner; Hwang, Shih-Jen; Savage, Peter J.; Levy, Daniel; Fox, Caroline S.] NHLBI, Ctr Populat Studies, NIH, Bethesda, MD 20892 USA.
[Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math, Boston, MA 02215 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Preis, Sarah/0000-0002-9360-4166
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC-25195]
FX This work was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study ( contract No. N01-HC-25195).
NR 34
TC 102
Z9 108
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 21
PY 2009
VL 120
IS 3
BP 212
EP U52
DI 10.1161/CIRCULATIONAHA.108.846519
PG 14
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 472EA
UT WOS:000268110900006
PM 19581493
ER
PT J
AU Lin, J
Steenbergen, C
Murphy, E
Sun, JH
AF Lin, Jeffrey
Steenbergen, Charles
Murphy, Elizabeth
Sun, Junhui
TI Estrogen Receptor-beta Activation Results in S-Nitrosylation of Proteins
Involved in Cardioprotection
SO CIRCULATION
LA English
DT Article
DE estrogen; ischemia; nitric oxide; reperfusion injury
ID ISCHEMIA-REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; ISCHEMIA/REPERFUSION
INJURY; FEMALE; HEART; SUSCEPTIBILITY; MICE; SEX
AB Background-It has been shown that the activation of estrogen receptor-beta (ER-beta) plays an important cardioprotective role against ischemia/reperfusion injury. However, the mechanism for this protection is not clear. We hypothesize that estrogen protects by ER-beta activation, which leads to S-nitrosylation (SNO) of key cardioprotective proteins.
Methods and Results-We treated ovariectomized C57BL/6J mice with the ER-beta selective agonist 2,2-bis(4-hydroxyphenyl)- proprionitrile (DPN), 17 beta-estradiol (E2), or vehicle using Alzet minipumps for 2 weeks. Isolated hearts were Langendorff perfused and subjected to ischemia and reperfusion. Compared with vehicle-treated hearts, DPN-and E2-treated hearts had significantly better postischemic functional recovery and decreased infarct size. To test the specificity of DPN, we treated ER-beta-knockout mice with DPN. However, no cardioprotective effect of DPN was found in ER-beta-knockout mice, indicating that the DPN-induced cardioprotection occurs through the activation of ER-beta. Using DyLight-maleimide fluors and a modified biotin switch method, we used a 2-dimensional DyLight fluorescence difference gel electrophoresis proteomic method to quantify differences in SNO of proteins. DPN-and E2-treated hearts showed an increase in SNO of a number of proteins. Interestingly, many of these proteins also had been shown to have increased SNO in preconditioned hearts. In addition, the DPN-induced cardioprotection and increased SNO were abolished by treatment with a nitric oxide synthase inhibitor.
Conclusion-The activation of ER-beta by DPN treatment leads to increased protein SNO and cardioprotection against ischemia/reperfusion injury, suggesting that long-term estrogen exposure protects hearts largely via activation of ER-beta and nitric oxide/SNO signaling. (Circulation. 2009; 120: 245-254.)
C1 [Murphy, Elizabeth; Sun, Junhui] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
[Lin, Jeffrey] Harvard Univ, Sch Med, Boston, MA USA.
[Steenbergen, Charles] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
RP Sun, JH (reprint author), NHLBI, Translat Med Branch, NIH, 10 Ctr Dr,Bldg10,Room 7N111, Bethesda, MD 20892 USA.
EM sun1@mail.nih.gov
RI Sun, Junhui/C-3499-2011
FU Sarnoff Foundation and Harvard Medical School; National Institutes of
Health [HL-39752]
FX Dr Lin was supported by the Sarnoff Foundation and Harvard Medical
School. Dr Steenbergen was supported in part by National Institutes of
Health grant HL- 39752. Drs Murphy and Sun were supported by the
National Institutes of Health Intramural Program.
NR 28
TC 68
Z9 72
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD JUL 21
PY 2009
VL 120
IS 3
BP 245
EP U157
DI 10.1161/CIRCULATIONAHA.109.868729
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 472EA
UT WOS:000268110900010
PM 19581491
ER
PT J
AU Finkel, T
Hwang, PM
AF Finkel, Toren
Hwang, Paul M.
TI The Krebs cycle meets the cell cycle: Mitochondria and the G(1)-S
transition
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Editorial Material
ID METABOLIC CHECKPOINT; PROGRESSION
C1 [Finkel, Toren; Hwang, Paul M.] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Finkel, T (reprint author), NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA.
EM finkelt@nih.gov
NR 11
TC 25
Z9 25
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2009
VL 106
IS 29
BP 11825
EP 11826
DI 10.1073/pnas.0906430106
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473BI
UT WOS:000268178400004
PM 19617546
ER
PT J
AU Chung, HS
Louis, JM
Eaton, WA
AF Chung, Hoi Sung
Louis, John M.
Eaton, William A.
TI Experimental determination of upper bound for transition path times in
protein folding from single-molecule photon-by-photon trajectories
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Alexa 488; fluorescence; FRET; maximum likelihood function; protein GB1
ID RESONANCE ENERGY-TRANSFER; PEPTIDE DYNAMICS; LOOP FORMATION; FRET;
SPECTROSCOPY; KINETICS; FLUORESCENCE; DIFFUSION; THERMODYNAMICS;
POLYPEPTIDES
AB Transition paths are a uniquely single-molecule property not yet observed for any molecular process in solution. The duration of transition paths is the tiny fraction of the time in an equilibrium single-molecule trajectory when the process actually happens. Here, we report the determination of an upper bound for the transition path time for protein folding from photon-by-photon trajectories. FRET trajectories were measured on single molecules of the dye-labeled, 56-residue 2-state protein GB1, immobilized on a glass surface via a biotin-streptavidin-biotin linkage. Characterization of individual emitted photons by their wavelength, polarization, and absolute and relative time of arrival after picosecond excitation allowed the determination of distributions of FRET efficiencies, donor and acceptor lifetimes, steady state polarizations, and waiting times in the folded and unfolded states. Comparison with the results for freely diffusing molecules showed that immobilization has no detectable effect on the structure or dynamics of the unfolded protein and only a small effect on the folding/unfolding kinetics. Analysis of the photon-by-photon trajectories yields a transition path time <200 mu s, >10,000 times shorter than the mean waiting time in the unfolded state (the inverse of the folding rate coefficient). Szabo's theory for diffusive transition paths shows that this upper bound for the transition path time is consistent with previous estimates of the Kramers preexponential factor for the rate coefficient, and predicts that the transition path time is remarkably insensitive to the folding rate, with only a 2-fold difference for rate coefficients that differ by 10(5)-fold.
C1 [Chung, Hoi Sung; Louis, John M.; Eaton, William A.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Chung, HS (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM chunghoi@niddk.nih.gov; eaton@helix.nih.gov
RI Chung, Hoi Sung/C-2624-2009
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. We thank Attila Szabo and Irina Gopich
for many helpful discussions and for sharing their unpublished
theoretical results, and Annie Aniana for technical assistance with
protein preparation.
NR 41
TC 142
Z9 143
U1 2
U2 36
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2009
VL 106
IS 29
BP 11837
EP 11844
DI 10.1073/pnas.0901178106
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473BI
UT WOS:000268178400007
PM 19584244
ER
PT J
AU Mitra, K
Wunder, C
Roysam, B
Lin, G
Lippincott-Schwartz, J
AF Mitra, Kasturi
Wunder, Christian
Roysam, Badrinath
Lin, Gang
Lippincott-Schwartz, Jennifer
TI A hyperfused mitochondrial state achieved at G(1)-S regulates cyclin E
buildup and entry into S phase
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE cell cycle; mitochondrial morphology; dynamin-related protein 1
ID CELL-CYCLE; LIVING CELLS; PROGRESSION; DYNAMICS; P53; MORPHOLOGY;
APOPTOSIS; MULTIPLE; FUSION
AB Mitochondria undergo fission-fusion events that render these organelles highly dynamic in cells. We report a relationship between mitochondrial form and cell cycle control at the G(1)-S boundary. Mitochondria convert from isolated, fragmented elements into a hyperfused, giant network at G(1)-S transition. The network is electrically continuous and has greater ATP output than mitochondria at any other cell cycle stage. Depolarizing mitochondria at early G(1) to prevent these changes causes cell cycle progression into S phase to be blocked. Inducing mitochondrial hyperfusion by acute inhibition of dynamin-related protein-1 (DRP1) causes quiescent cells maintained without growth factors to begin replicating their DNA and coincides with buildup of cyclin E, the cyclin responsible for G(1)-to-S phase progression. Prolonged or untimely formation of hyperfused mitochondria, through chronic inhibition of DRP1, causes defects in mitotic chromosome alignment and S-phase entry characteristic of cyclin E overexpression. These findings suggest a hyperfused mitochondrial system with specialized properties at G(1)-S is linked to cyclin E buildup for regulation of G(1)-to-S progression.
C1 [Mitra, Kasturi; Wunder, Christian; Lippincott-Schwartz, Jennifer] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
[Roysam, Badrinath; Lin, Gang] Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA.
RP Lippincott-Schwartz, J (reprint author), NIH, Cell Biol & Metab Branch, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov
OI Wunder, Christian/0000-0001-9091-0080
FU National Institutes of Health [R01EB005157]; National Science Foundation
[EEC-9986821]
FX We thank R. J. Youle, M. McNiven, C. Cardoso, Y. Wang, J. Chen, B.
Vogelstein, and J. Nunnari for reagents and S. Dwarkapuram for help in
the morphometric analysis and R. Hegde, R. J. Youle, C. Smith, M. Lilly,
A. Arnaoutov, and members of the Lippincott-Schwartz Laboratory for
valuable suggestions. B. R. acknowledges National Institutes of Health
Grant R01EB005157 and National Science Foundation Grant EEC-9986821.
NR 31
TC 204
Z9 205
U1 2
U2 17
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2009
VL 106
IS 29
BP 11960
EP 11965
DI 10.1073/pnas.0904875106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473BI
UT WOS:000268178400028
PM 19617534
ER
PT J
AU Seike, M
Goto, A
Okano, T
Bowman, ED
Schetter, AJ
Horikawa, I
Mathe, EA
Jen, J
Yang, P
Sugimura, H
Gemma, A
Kudoh, S
Croce, CM
Harris, CC
AF Seike, Masahiro
Goto, Akiteru
Okano, Tetsuya
Bowman, Elise D.
Schetter, Aaron J.
Horikawa, Izumi
Mathe, Ewy A.
Jen, Jin
Yang, Ping
Sugimura, Haruhiko
Gemma, Akihiko
Kudoh, Shoji
Croce, Carlo M.
Harris, Curtis C.
TI MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in
never-smokers
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE apoptosis; microRNA; microarray; EGFR-TKI; therapeutic target
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MICRORNA EXPRESSION; GEFITINIB RESISTANCE;
DOWN-REGULATION; MUTATIONS; RECEPTOR; GENE; PROGNOSIS; GROWTH; PROFILES
AB Fifteen percent of lung cancer cases occur in never-smokers and show characteristics that are molecularly and clinically distinct from those in smokers. Epidermal growth factor receptor (EGFR) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e. g., up-regulated miR-21) and unidentified (e. g., down-regulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs, including miR-21, were more remarkable in cases with EGFR mutations than in those without these mutations. A significant correlation between phosphorylated-EGFR (p-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggest that the EGFR signaling is a pathway positively regulating miR-21 expression. In the never-smoker-derived lung adenocarcinoma cell line H3255 with mutant EGFR and high levels of p-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker-derived adenocarcinoma cell line H441 with wildtype EGFR, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is enhanced further by the activated EGFR signaling pathway, plays a significant role in lung carcinogenesis in never-smokers, as well as in smokers, and is a potential therapeutic target in both EGFR-mutant and wild-type cases.
C1 [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43212 USA.
[Seike, Masahiro; Goto, Akiteru; Okano, Tetsuya; Bowman, Elise D.; Schetter, Aaron J.; Horikawa, Izumi; Mathe, Ewy A.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Seike, Masahiro; Okano, Tetsuya; Gemma, Akihiko; Kudoh, Shoji] Nippon Med Sch, Dept Pulm Med Infect & Oncol, Tokyo 1138602, Japan.
[Jen, Jin] Mayo Clin & Mayo Fdn, Div Pulm & Crit Care Med & Microarray Share Resou, Rochester, MN 55905 USA.
[Yang, Ping] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Sugimura, Haruhiko] Hamamatsu Univ Sch Med, Dept Pathol, Hamamatsu, Shizuoka 4313192, Japan.
RP Croce, CM (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43212 USA.
EM carlo.croce@osumc.edu; Curtis_Harris@nih.gov
FU National Institutes of Health, National Cancer Institute, and Center for
Cancer Research
FX We thank Dr. Kensuke Kumamoto for helpful discussions, Drs. Raymond T.
Jones, Andrew Borkowski, and Mark J. Krasna for sample collection and
pathology reports, and Audrey Salabes for interviewing the lung cancer
patients. This work was supported by the Intramural Research Program of
the National Institutes of Health, National Cancer Institute, and Center
for Cancer Research.
NR 50
TC 274
Z9 302
U1 1
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 21
PY 2009
VL 106
IS 29
BP 12085
EP 12090
DI 10.1073/pnas.0905234106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473BI
UT WOS:000268178400049
PM 19597153
ER
PT J
AU Li, JH
Sherman-Baust, CA
Tsai-Turton, M
Bristow, RE
Roden, RB
Morin, PJ
AF Li, Jianghong
Sherman-Baust, Cheryl A.
Tsai-Turton, Miyun
Bristow, Robert E.
Roden, Richard B.
Morin, Patrice J.
TI Claudin-containing exosomes in the peripheral circulation of women with
ovarian cancer
SO BMC CANCER
LA English
DT Article
ID TUMOR-DERIVED EXOSOMES; DIFFERENTIAL GENE-EXPRESSION; SQUAMOUS-CELL
CARCINOMA; TIGHT JUNCTION PROTEINS; REDUCED EXPRESSION; POTENTIAL
MARKERS; SEROUS PAPILLARY; CA125; OVEREXPRESSION; IDENTIFICATION
AB Background: The absence of highly sensitive and specific serum biomarkers makes mass screening for ovarian cancer impossible. The claudin proteins are frequently overexpressed in ovarian cancers, but their potential as prognostic, diagnostic, or detection markers remains unclear. Here, we have explored the possible use of these proteins as screening biomarkers for ovarian cancer detection.
Methods: Claudin protein shedding from cells was examined by immunoblotting of conditioned culture media. The presence of claudins in exosomes released from ovarian cancer cells was demonstrated by sucrose gradient separation and immunogold electron microscopy experiments. Claudin-4-containing exosomes in the plasma of ovarian cancer patients were evaluated in a pilot panel of 63 ovarian cancer patients and 50 healthy volunteers. The CA125 marker was also assessed in these samples and compared with claudin-4 positivity.
Results: We show that full-length claudins can be shed from ovarian cancer cells in culture and found in the media as part of small lipid vesicles known as exosomes. Moreover, 32 of 63 plasma samples from ovarian cancer patients exhibited the presence of claudin-4-containing exosomes. In contrast, only one of 50 samples from individuals without cancer exhibited claudin-4-positive exosomes. In our small panel, at a specificity of 98%, the claudin-4 and CA125 tests had sensitivities of 51% and 71%, respectively. The two tests did not appear to be independent and were strongly correlated.
Conclusion: Our work shows for the first time that claudin-4 can be released from ovarian cancer cells and can be detected in the peripheral circulation of ovarian cancer patients. The development of sensitive assays for the detection of claudin-4 in blood will be crucial in determining whether this approach can be useful, alone or in combination with other screening methods, for the detection of ovarian cancer.
C1 [Li, Jianghong; Sherman-Baust, Cheryl A.; Morin, Patrice J.] NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA.
[Tsai-Turton, Miyun; Roden, Richard B.; Morin, Patrice J.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Bristow, Robert E.; Roden, Richard B.] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA.
[Bristow, Robert E.; Roden, Richard B.] Johns Hopkins Med Inst, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA.
EM lijiang@grc.nia.nih.gov; shermanc@grc.nia.nih.gov; mtsaitu1@jhmi.edu;
rbristo1@jhmi.edu; roden@jhmi.edu; morinp@grc.nia.nih.gov
FU Intramural Research Program of the National institutes of Health,
National Institute on Aging
FX We thank members of our laboratory for helpful comments on the
manuscript. This research was supported entirely by the Intramural
Research Program of the National institutes of Health, National
Institute on Aging.
NR 48
TC 73
Z9 78
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUL 20
PY 2009
VL 9
AR 244
DI 10.1186/1471-2407-9-244
PG 11
WC Oncology
SC Oncology
GA 489TM
UT WOS:000269445600004
PM 19619303
ER
PT J
AU Munyeme, M
Rigouts, L
Shamputa, IC
Muma, JB
Tryland, M
Skjerve, E
Djonne, B
AF Munyeme, Musso
Rigouts, Leen
Shamputa, Isdore Chola
Muma, John Bwalya
Tryland, Morten
Skjerve, Eystein
Djonne, Berit
TI Isolation and characterization of Mycobacterium bovis strains from
indigenous Zambian cattle using Spacer oligonucleotide typing technique
SO BMC MICROBIOLOGY
LA English
DT Article
ID LIVESTOCK/WILDLIFE INTERFACE AREAS; FRAGMENT-LENGTH-POLYMORPHISM;
TUBERCULOSIS COMPLEX; MOLECULAR EPIDEMIOLOGY; GENETIC DIVERSITY;
RISK-FACTORS; DIFFERENTIATION; ANIMALS; MULTICENTER; PREVALENCE
AB Background: Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has remained a major source of concern to public health officials in Zambia. Previous investigations have used traditional epidemiological methods that are unable to identify the causative agent and from which dynamics of disease dispersion is difficult to discern. The objective of this study was to isolate, characterize and determine the genetic diversity and relatedness of M. bovis from major cattle rearing districts in Zambia by spoligotyping. A total of 695 carcasses were examined and 98 tissues had gross postmortem lesions compatible with BTB.
Results: Forty-two out of the ninety-eight suspected tissues examined had culture properties characteristic of mycobacteria from which 31 isolates yielded interpretable spoligotypes. This technique showed good discriminatory power (HGDI = 0.98), revealing 10 different spoligotype patterns. Twenty-seven isolates belonged to one cluster with more than 95% similarity and inside the cluster, one predominant spoligotype was found in 20 (64.5%) of the isolates tested. The highest number of spoligotypes was observed among samples from Namwala district. Spoligotypes from 26 (83.9%) of the isolates belonged to five spoligotypes that have been reported before while the remaining 5 (16.1%) isolates had unique spoligotypes that are being reported for the first time; these have been assigned numbers SB1763 to SB1767. Five of the 6 districts had the predominant spoligotype (SB0120).
Conclusion: The study has described the dispersion patterns of M. bovis in Zambian cattle for the first time and has identified 5 spoligotype patterns specific to Zambia. The observation of an overlap in the spoligotype pattern SB0120 in 5 of the 6 districts suggests the probability of sharing a common source of infection.
C1 [Munyeme, Musso; Muma, John Bwalya] Univ Zambia, Dept Dis Control, Sch Vet Med, Lusaka, Zambia.
[Rigouts, Leen; Shamputa, Isdore Chola] Inst Trop Med Prince Leopold, Mycobacteriol Unit, B-200 Antwerp, Belgium.
[Tryland, Morten] Norwegian Sch Vet Sci, Sect Arct Vet Med, Dept Food Safety & Infect Biol, N-9010 Tromso, Norway.
[Skjerve, Eystein] Norwegian Sch Vet Sci, Dept Food Safety & Infect Biol, N-0033 Oslo, Norway.
[Djonne, Berit] Natl Vet Inst, Dept Anim Hlth, N-0033 Oslo, Norway.
[Shamputa, Isdore Chola] NIAID, TB Res Sect, NIH, LCID, Bethesda, MD 20892 USA.
RP Munyeme, M (reprint author), Univ Zambia, Dept Dis Control, Sch Vet Med, POB 32379, Lusaka, Zambia.
EM munyeme@yahoo.co.uk; LRigouts@itg.be; shamputai@niaid.nih.gov;
jbwalya@lycos.com; morten.tryland@veths.no; eystein.skjerve@veths.no;
berit.djonne@vetinst.no
FU Norwegian Programme for Development, Research and Education (NUFU)
FX The technical support by School of Veterinary Medicine, Microbiology
Laboratories, Chest Diseases Laboratories (CDL), under the Center for
Disease Control (CDC), Lusaka Zambia and the Institute of Tropical
Medicine (ITM), Antwerp, Belgium are all highly appreciated. Special
thanks to Dr. Charles Maseka (Provincial Veterinary Officer, Southern
Province) H. M. Chimana (UNZA) and Charles Sikende the field Veterinary
Assistant.
NR 37
TC 11
Z9 11
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2180
J9 BMC MICROBIOL
JI BMC Microbiol.
PD JUL 20
PY 2009
VL 9
AR 144
DI 10.1186/1471-2180-9-144
PG 8
WC Microbiology
SC Microbiology
GA 479OF
UT WOS:000268669100001
PM 19619309
ER
PT J
AU Pierce, BL
Ballard-Barbash, R
Bernstein, L
Baumgartner, RN
Neuhouser, ML
Wener, MH
Baumgartner, KB
Gilliland, FD
Sorensen, BE
McTiernan, A
Ulrich, CM
AF Pierce, Brandon L.
Ballard-Barbash, Rachel
Bernstein, Leslie
Baumgartner, Richard N.
Neuhouser, Marian L.
Wener, Mark H.
Baumgartner, Kathy B.
Gilliland, Frank D.
Sorensen, Bess E.
McTiernan, Anne
Ulrich, Cornelia M.
TI Elevated Biomarkers of Inflammation Are Associated With Reduced Survival
Among Breast Cancer Patients
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; SERUM-AMYLOID-A; PHYSICAL-ACTIVITY LEVELS;
ACUTE-PHASE RESPONSE; CURATIVE RESECTION; CARCINOMA; PROGNOSIS
AB Purpose Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival.
Patients and Methods We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs.
Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07).
Conclusion Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.
C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Canc Prevent & Epidemiol Res Programs, Seattle, WA 98195 USA.
Univ Washington, Dept Epidemiol, Inst Publ Hlth Genet, Seattle, WA 98195 USA.
Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
City Hope Natl Med Ctr, Dept Canc Etiol, Duarte, CA 91010 USA.
Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA.
Univ Louisville, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
RP Ulrich, CM (reprint author), Fred Hutchinson Canc Ctr, Canc Prevent Res Program, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM nulrich@fhcrc.org
OI Pierce, Brandon/0000-0002-7829-952X
FU National Cancer Institute [N01-CN-75036-20, NO1-CN-05228, NO1-PC-67010,
U54-CA116847, R25-CA94880]; National Institutes of Health
[M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National
Institute of Child Health and Human Development [N01-HD-3-3175];
California Department of Health Services [050Q-8709-S1528]
FX Supported by National Cancer Institute Grants No. N01-CN-75036-20,
NO1-CN-05228, NO1-PC-67010, U54-CA116847, and R25-CA94880; National
Institutes of Health Grant No. M01-RR-00037; University of New Mexico
Grant No. NCRR M01-RR-0997; National Institute of Child Health and Human
Development Grant No. N01-HD-3-3175; and California Department of Health
Services Grant No. 050Q-8709-S1528.
NR 25
TC 274
Z9 279
U1 2
U2 16
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 JUL 20
PY 2009
VL 27
IS 21
BP 3437
EP 3444
DI 10.1200/JCO.2008.18.9068
PG 8
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100007
PM 19470939
ER
PT J
AU Korn, EL
Freidlin, B
Mooney, M
AF Korn, Edward L.
Freidlin, Boris
Mooney, Margaret
TI Stopping Trials Early for Positive Results: The Need to Know How Much
Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
C1 [Korn, Edward L.] Natl Canc Inst, Biometr Res Branch, Bethesda, MD USA.
Natl Canc Inst, Clin Investigat Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD USA.
RP Korn, EL (reprint author), Natl Canc Inst, Biometr Res Branch, Bethesda, MD USA.
NR 2
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 JUL 20
PY 2009
VL 27
IS 21
BP E30
EP E30
DI 10.1200/JCO.2009.23.8675
PG 1
WC Oncology
SC Oncology
GA 471II
UT WOS:000268049100033
ER
PT J
AU Kafadar, K
Prorok, PC
AF Kafadar, Karen
Prorok, Philip C.
TI Effect of length biased sampling of unobserved sojourn times on the
survival distribution when disease is screen detected
SO STATISTICS IN MEDICINE
LA English
DT Article
DE randomized screening trial; sojourn time; lead time; bivariate gamma
distribution; clinical duration; periodic screening; HIP trial
ID ESTIMATING LEAD TIME; NONPARAMETRIC-ESTIMATION; EMPIRICAL DISTRIBUTIONS;
BREAST-CANCER; MODELS; RATES; MORTALITY; NEOPLASMS; DENSITY; TRIALS
AB Data can arise as a length-biased sample rather than as a random sample; e.g. a sample of patients in hospitals or of network cable lines (experimental units with longer stays or longer lines have greater likelihoods of being sampled). The distribution arising from a single length-biased sampling (LBS) time has been derived (e.g. (The Statistical Analysis of Discrete Time Events. Oxford Press: London, 1972)) and applies when the observed outcome relates to the random variable subjected to LBS. Zelen (Breast Cancer: Trends in Research and Treatment. Raven Press: New York, 1976; 287-301) noted that cases of disease detected from a screening program likewise form a length-biased sample among all cases, since longer sojourn times afford greater likelihoods of being screen detected. In contrast to the samples on hospital stays and cable lines, however, the length-biased sojourns (preclinical durations) cannot be observed, although their subsequent clinical durations (survival times) are. This article quantifies the effect of LBS of the sojourn times (or pre-clinical durations) on the distribution of the observed clinical durations when cases undergo periodic screening for the early detection of disease. We show that, when preclinical and clinical durations are positively correlated, the mean, median, and quartiles of the distribution of the clinical duration from screen-detected cases can be substantially inflated-even in the absence of any benefit on survival from the screening procedure. Screening studies that report mean Survival time need to take account of the fact that, even in the absence of any real benefit, the mean survival among cases in the screen-detected group will be longer than that among interval cases or among cases that arise in the control arm, above and beyond lead time bias, simply by virtue of the LBS phenomenon. Published in 2009 by John Wiley & Sons, Ltd.
C1 [Kafadar, Karen] Indiana Univ, Dept Stat, Bloomington, IN 47408 USA.
[Prorok, Philip C.] NCI, Biometry Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kafadar, K (reprint author), Indiana Univ, Dept Stat, Bloomington, IN 47408 USA.
EM kkafadar@indiana.edu
FU Army Research Office [W911NF-05-1-0490]; National Science Foundation
[DMS-08-02295]
FX Contract/grant sponsor: National Science Foundation; contract/grant
number DMS-08-02295
NR 40
TC 7
Z9 7
U1 0
U2 4
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 0277-6715
J9 STAT MED
JI Stat. Med.
PD JUL 20
PY 2009
VL 28
IS 16
BP 2116
EP 2146
DI 10.1002/sim.3601
PG 31
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 464HD
UT WOS:000267495100003
PM 19424959
ER
PT J
AU Roelke, ME
Brown, MA
Troyer, JL
Winterbach, H
Winterbach, C
Hemson, G
Smith, D
Johnson, RC
Pecon-Slattery, J
Roca, AL
Alexander, KA
Klein, L
Martelli, P
Krishnasamy, K
O'Brien, SJ
AF Roelke, Melody E.
Brown, Meredith A.
Troyer, Jennifer L.
Winterbach, Hanlie
Winterbach, Christiaan
Hemson, Graham
Smith, Dahlem
Johnson, Randall C.
Pecon-Slattery, Jill
Roca, Alfred L.
Alexander, Kathleen A.
Klein, Lin
Martelli, Paolo
Krishnasamy, Karthiyani
O'Brien, Stephen J.
TI Pathological manifestations of feline immunodeficiency virus (FIV)
infection in wild African lions
SO VIROLOGY
LA English
DT Article
DE FIV; Lentivirus; Lions; Wild; Free-ranging; Pathology; Immune depletion
ID FREE-RANGING LIONS; HIV-INFECTION; PANTHERA-LEO; RHESUS MACAQUES;
DISEASE PROGRESSION; LENTIVIRUS INFECTION; PHYLOGENETIC ASPECTS; IMMUNE
DYSFUNCTION; PUMA LENTIVIRUSES; TERM SURVIVAL
AB Feline immunodeficiency virus (FIV) causes AIDS in the domestic cat (Felis catus) but has not been explicitly associated with AIDS pathology in any of the eight free-ranging species of Felidae that are endemic with circulating FIV strains. African lion (Panthera lea) populations are infected with lion-specific FIV strains (FIVple), yet there remains uncertainty about the degree to which FIV infection impacts their health. Reported CD4+ T-lymphocyte depletion in FIVple-infected lions and anecdotal reports of lion morbidity associated with FIV seroprevalence emphasize the concern as to whether FIVple is innocuous or pathogenic. Here we monitored clinical, biochemical, histological and serological parameters among FIVple-positive (N = 47) as compared to FIVple-negative (N = 17) lions anesthetized and sampled on multiple occasions between 1999 and 2006 in Botswana. Relative to uninfected lions, FIVple-infected lions displayed a significant elevation in the prevalence of AIDS-defining conditions: lymphadenopathy, gingivitis, tongue papillomas, dehydration, and poor coat condition, as well as displaying abnormal red blood cell parameters. depressed serum albumin, and elevated liver enzymes and gamma globulin. Spleen and lymph node biopsies from free-ranging FIVple-infected lions (N=9) revealed evidence of lymphoid depletion, the hallmark pathology documented in immunodeficiency virus infections of humans (HIV-1), macaques, and domestic cats. We conclude that over time FIVple infections in free-ranging lions can lead to adverse clinical, immunological, and pathological outcomes in some individuals that parallel sequelae caused by lentivirus infection in humans (HIV), Asian macaques (SIV) and domestic cats (FIVfca). (C) 2009 Elsevier Inc. All rights reserved.
C1 [Roelke, Melody E.; Troyer, Jennifer L.; Johnson, Randall C.; Roca, Alfred L.; O'Brien, Stephen J.] NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Winterbach, Hanlie; Winterbach, Christiaan] Tau Consultants, Maun, Botswana.
[Hemson, Graham] Wildlife Conservat Res Unit, Tubney, Oxon, England.
[Smith, Dahlem] NCI, Pathol Histol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Roca, Alfred L.] Univ Illinois, Dept Anim Sci, Urbana, IL 61801 USA.
[Alexander, Kathleen A.] Virginia Polytech Inst & State Univ, Dept Fisheries & Wildlife Sci, Blacksburg, VA USA.
[Klein, Lin] Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA.
[Martelli, Paolo] Ocean Pk Corp, Aberdeen, Hong Kong, Peoples R China.
[Krishnasamy, Karthiyani] SPCA, Wan Chai, Hong Kong, Peoples R China.
RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, SAIC Frederick Inc, Frederick, MD 21701 USA.
EM obrien@ncifcrf.gov
RI Alexander, Kathleen/A-9765-2010; Troyer, Jennifer/B-8415-2012; Johnson,
Randall/B-1517-2014
OI Alexander, Kathleen/0000-0001-7338-5341; Johnson,
Randall/0000-0001-7754-0847
FU Intramural NIH HHS [Z01 BC010537-05, Z99 CA999999]; NCI NIH HHS
[N01-CO-12400, N01CO12400]
NR 88
TC 30
Z9 30
U1 3
U2 18
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 JUL 20
PY 2009
VL 390
IS 1
BP 1
EP 12
DI 10.1016/j.virol.2009.04.011
PG 12
WC Virology
SC Virology
GA 473OX
UT WOS:000268218200001
PM 19464039
ER
PT J
AU Wawer, MJ
Makumbi, F
Kigozi, G
Serwadda, D
Watya, S
Nalugoda, F
Buwembo, D
Ssempijja, V
Kiwanuka, N
Moulton, LH
Sewankambo, NK
Reynolds, SJ
Quinn, TC
Opendi, P
Iga, B
Ridzon, R
Laeyendecker, O
Gray, RH
AF Wawer, Maria J.
Makumbi, Frederick
Kigozi, Godfrey
Serwadda, David
Watya, Stephen
Nalugoda, Fred
Buwembo, Dennis
Ssempijja, Victor
Kiwanuka, Noah
Moulton, Lawrence H.
Sewankambo, Nelson K.
Reynolds, Steven J.
Quinn, Thomas C.
Opendi, Pius
Iga, Boaz
Ridzon, Renee
Laeyendecker, Oliver
Gray, Ronald H.
TI Circumcision in HIV-infected men and its effect on HIV transmission to
female partners in Rakai, Uganda: a randomised controlled trial
SO LANCET
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DISCORDANT COUPLES; PREVENTION; AFRICA;
COHORT; KENYA; WOMEN
AB Background Observational studies have reported an association between male circumcision and reduced risk of HIV infection in female partners. We assessed whether circumcision in HIV-infected men would reduce transmission of the virus to female sexual partners.
Methods 922 uncircumcised, HIV-infected, asymptomatic men aged 15-49 years with CD4-cell counts 350 cells per mu L or more were enrolled in this unblinded, randomised controlled trial in Rakai District, Uganda. Men were randomly assigned by computer-generated randomisation sequence to receive immediate circumcision (intervention; n=474) or circumcision delayed for 24 months (control; n=448). HIV-uninfected female partners of the randomised men were concurrently enrolled (intervention, n=93; control, n=70) and followed up at 6, 12, and 24 months, to assess HIV acquisition by male treatment assignment (primary outcome). A modified intention-to-treat (ITT) analysis, which included all concurrently enrolled couples in which the female partner had at least one follow-up visit over 24 months, assessed female HIV acquisition by use of survival analysis and Cox proportional hazards modelling. This trial is registered with ClinicalTrials.gov, number NCT00124878.
Findings The trial was stopped early because of futility. 92 couples in the intervention group and 67 couples in the control group were included in the modified ITT analysis. 17 (18%) women in the intervention group and eight (12%) women in the control group acquired HIV during follow-up (p=0.36). Cumulative probabilities of female HIV infection at 24 months were 21.7% (95% Cl 12.7-33.4) in the intervention group and 13.4% (6.7-25.8) in the control group (adjusted hazard ratio 1.49, 95% CI 0.62-3.57; p=0.368).
Interpretation Circumcision of HIV-infected men did not reduce HIV transmission to female partners over 24 months; longer-term effects could not be assessed. Condom use after male circumcision is essential for HIV prevention.
C1 [Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA.
[Moulton, Lawrence H.] Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA.
[Makumbi, Frederick; Kigozi, Godfrey; Serwadda, David; Nalugoda, Fred; Buwembo, Dennis; Ssempijja, Victor; Kiwanuka, Noah; Sewankambo, Nelson K.; Opendi, Pius; Iga, Boaz] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Makumbi, Frederick; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
[Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda.
[Sewankambo, Nelson K.] Makerere Univ, Fac Med, Coll Hlth Sci, Kampala, Uganda.
[Reynolds, Steven J.; Quinn, Thomas C.; Laeyendecker, Oliver] Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA.
[Reynolds, Steven J.; Quinn, Thomas C.; Laeyendecker, Oliver] NIAID, NIH, Bethesda, MD 20892 USA.
[Ridzon, Renee] Bill & Melinda Gates Fdn, Seattle, WA USA.
RP Wawer, MJ (reprint author), Johns Hopkins Univ Bloomberg, Sch Publ Hlth, Dept Populat Family & Reprod Hlth, 615 N Wolfe St,Suite E4132, Baltimore, MD 21205 USA.
EM mwawer@jhsph.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker,
Oliver/0000-0002-6429-4760; Moulton, Lawrence/0000-0001-7041-7387
FU Bill & Melinda Gates Foundation [22006]
FX The trial was funded by the Bill & Melinda Gates Foundation as an
investigator-initiated grant (number 22006). Additional support for
laboratory analyses an training were provided, respectively, by the
Division of Intramural Research, National Institutes of Allergy and
Infectious Diseases, National Institutes of Health, and the Fogarty
International Center (grants SD43TW001508 and D43TW00015). The study was
conducted by the Rakai Health Sciences Program, a research collaboration
between the Uganda Virus Research Institute, and researchers at Makerere
and Johns Hopkins Universities. We thank the members of the data and
safety monitoring board, and the institutional review boards that
provided oversight (the Committee for Human Research, Johns Hopkins
Bloomberg School of Public Health, the Science and Ethics Committee of
the Uganda Virus Research Institute, and the We:;tern Institutional
Review Board). We are also grateful for the advice provided by the Rakai
community advisory board. We thank Edward Mbidde (Uganda Virus Research
Institute) for his support. Finally, we wish to express our gratitude to
the study participants whose commitment and cooperation made the study
possible.
NR 18
TC 169
Z9 174
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
J9 LANCET
JI Lancet
PD JUL 18
PY 2009
VL 374
IS 9685
BP 229
EP 237
DI 10.1016/S0140-6736(09)60998-3
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 474DP
UT WOS:000268263000031
PM 19616720
ER
PT J
AU Stanley, TL
Joy, T
Hadigan, CM
Liebau, JG
Makimura, H
Chen, CY
Thomas, BJ
Weise, SB
Robbins, GK
Grinspoon, SK
AF Stanley, Takara L.
Joy, Tisha
Hadigan, Colleen M.
Liebau, James G.
Makimura, Hideo
Chen, Cindy Y.
Thomas, Bijoy J.
Weise, Steven B.
Robbins, Gregory K.
Grinspoon, Steven K.
TI Effects of switching from lopinavir/ritonavir to atazanavir/ritonavir on
muscle glucose uptake and visceral fat in HIV-infected patients
SO AIDS
LA English
DT Article
DE atazanavir; glucose; HIV; intra-abdominal fat; lipids; lipodystrophy;
lopinavir
ID TWICE-DAILY LOPINAVIR/RITONAVIR; ONCE-DAILY ATAZANAVIR/RITONAVIR;
HORMONE-RELEASING FACTOR; PROTEASE INHIBITORS; INSULIN-RESISTANCE;
GROWTH-HORMONE; ADIPOCYTE DIFFERENTIATION; HIV-1-INFECTED PATIENTS;
ANTIRETROVIRAL THERAPY; SKELETAL-MUSCLE
AB Objective: To determine the effects of switching from lopinavir/ritonavir (LPV/r) to atazanavir/ritonavir (ATV/r) on muscle glucose uptake, glucose homeostasis, lipids, and body composition.
Methods: Fifteen HIV-infected men and women on a regimen containing LPV/r and with evidence of hyperinsulinemia and/or dyslipidemia were randomized to continue LPV/r or to switch to ATV/r (ATV 300 mg and ritonavir 100 mg daily) for 6 months. The primary endpoint was change in thigh muscle glucose uptake as measured by positron emission tomography. Secondary endpoints included abdominal visceral adipose tissue, fasting lipids, and safety parameters. The difference over time between treatment groups (treatment effect of ATV/r relative to LPV/r) was determined by repeated measures ANCOVA.
Results: After 6 months, anterior thigh muscle glucose uptake increased significantly (treatment effect +18.2 +/- 5.9 mu mol/kg per min, ATV/r vs. LPV/r, P=0.035), and visceral adipose tissue area decreased significantly in individuals who switched to ATV/r (treatment effect -31 +/- 11 cm(2), ATV/r vs. LPV/r, P=0.047). Switching to ATV/r significantly decreased triglyceride (treatment effect -182 +/- 64 mg/dl, ATV/r vs. LPV/r, P=0.02) and total cholesterol (treatment effect -23 +/- 8 mg/dl, ATV/r vs. LPV/r, P=0.01), whereas high-density lipoprotein and low-density lipoprotein did not change significantly. Fasting glucose also decreased significantly following switch to ATV/r (treatment effect -15 +/- 4 mg/dl, ATV/r vs. LPV/r, P=0.002).
Conclusion: Switching from LPV/r to ATV/r significantly increases glucose uptake by muscle, decreases abdominal visceral adipose tissue, improves lipid parameters, and decreases fasting glucose over 6 months. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
C1 [Stanley, Takara L.; Joy, Tisha; Liebau, James G.; Makimura, Hideo; Chen, Cindy Y.; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
[Robbins, Gregory K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Thomas, Bijoy J.; Weise, Steven B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Thomas, Bijoy J.; Weise, Steven B.] Harvard Univ, Sch Med, Boston, MA USA.
[Hadigan, Colleen M.] NIH, Bethesda, MD 20892 USA.
RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU NIH [M01-RR01066, 1 ULI RR025758-01, T32 HID052961-03, K01 AI062435, K24
DK064545-06]; Harvard Clinical and Translational Science Center;
National Center for Research Resources; Boehringer Ingelheim, Gilead;
Schering-Plough; Bristol Myers Squibb and Theratechnologies
FX Funding was provided by BMS in the form of an investigator initiated
research grant and NIH M01-RR01066 and 1 ULI RR025758-01, Harvard
Clinical and Translational Science Center, from the National Center for
Research Resources. NIH funding also provided by T32 HID052961-03
trainee support to TS., K01 AI062435 to G.R., and K24 DK064545-06 to
S.G. G.R. has received grant support from Boehringer Ingelheim, Gilead,
and Schering-Plough, and has been a consultant for Abbott Laboratories.
S.G. has received research support from Bristol Myers Squibb and
Theratechnologies and served as a consultant for Theratechnologies and
Serono, Inc.
NR 40
TC 31
Z9 32
U1 1
U2 2
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 2009
VL 23
IS 11
BP 1349
EP 1357
DI 10.1097/QAD.0b013e32832ba904
PG 9
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 470GJ
UT WOS:000267962900007
PM 19474651
ER
PT J
AU Liu, DF
Bryceson, YT
Meckel, T
Vasiliver-Shamis, G
Dustin, ML
Long, EO
AF Liu, Dongfang
Bryceson, Yenan T.
Meckel, Tobias
Vasiliver-Shamis, Gaia
Dustin, Michael L.
Long, Eric O.
TI Integrin-Dependent Organization and Bidirectional Vesicular Traffic at
Cytotoxic Immune Synapses
SO IMMUNITY
LA English
DT Article
ID CELL IMMUNOLOGICAL SYNAPSE; T-CELLS; RING JUNCTION; NK CELLS;
ACTIVATION; RECEPTORS; COSTIMULATION; POLARIZATION; RECOGNITION;
CONTRIBUTES
AB Cytotoxic lymphocytes kill target cells by releasing the content of secretory lysosomes at the immune synapse. To understand the dynamics and control of cytotoxic immune synapses, we imaged human primary, live natural killer cells on lipid bilayers carrying ligands of activation receptors. Formation of an organized synapse was dependent on the presence of the beta 2 integrin ligand ICAM-1. Ligands of coactivation receptors 2B4 and NKG2D segregated into central and peripheral regions, respectively. Lysosomal protein LAMP-1 that was exocytosed during degranulation accumulated in a large and spatially stable cluster, which overlapped with a site of membrane internalization. Lysosomal compartments reached the plasma membrane at focal points adjacent to centrally accumulated LAMP-1. Imaging of fixed cells revealed that perforin-containing granules were juxtaposed to an intracellular compartment where exocytosed LAMP-1 was retrieved. Thus, cytotoxic immune synapses include a central region of bidirectional vesicular traffic, which is controlled by integrin signaling.
C1 [Liu, Dongfang; Bryceson, Yenan T.; Meckel, Tobias; Long, Eric O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Bryceson, Yenan T.] Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden.
[Vasiliver-Shamis, Gaia; Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA.
[Vasiliver-Shamis, Gaia; Dustin, Michael L.] Skirball Inst Biomol Med, Program Mol Pathogenesis, New York, NY 10016 USA.
RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM elong@nih.gov
RI Meckel, Tobias/F-4372-2010; Liu, Dongfang/C-9618-2011; Long,
Eric/G-5475-2011;
OI Meckel, Tobias/0000-0003-0759-2072; Long, Eric/0000-0002-7793-3728;
Bryceson, Yenan/0000-0002-7783-9934; Dustin, Michael/0000-0003-4983-6389
FU National Institutes of Health; National Institute of Allergy and
Infectious Diseases
FX We thank T. Starr, A. Beal, Y. Sykulev, M. March, S. Radaev, J.
Brzostowski, and P. Tolar for advice and help. This work has been
supported by the Intramural Research Program of the National Institutes
of Health, National Institute of Allergy and Infectious Diseases.
NR 27
TC 90
Z9 90
U1 0
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1074-7613
J9 IMMUNITY
JI Immunity
PD JUL 17
PY 2009
VL 31
IS 1
BP 99
EP 109
DI 10.1016/j.immuni.2009.05.009
PG 11
WC Immunology
SC Immunology
GA 473PN
UT WOS:000268219900015
PM 19592272
ER
PT J
AU Yan, J
Menendez, D
Yang, XP
Resnick, MA
Jetten, AM
AF Yan, Jun
Menendez, Daniel
Yang, Xiao-Ping
Resnick, Michael A.
Jetten, Anton M.
TI A Regulatory Loop Composed of RAP80-HDM2-p53 Provides RAP80-enhanced p53
Degradation by HDM2 in Response to DNA Damage
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TUMOR SUPPRESSION; POSTTRANSLATIONAL MODIFICATIONS; DEPENDENT
PHOSPHORYLATION; TRANSCRIPTION-FACTOR; REPAIR PROTEINS; BREAST-CANCER;
BRCA1 PROTEIN; BINDING-SITES; HUMAN GENOME; RAP80
AB The ubiquitin interaction motif-containing protein RAP80 plays a key role in DNA damage response signaling. Using genomic and functional analysis, we established that the expression of the RAP80 gene is regulated in a DNA damage-responsive manner by the master regulator p53. This regulation occurs at the transcriptional level through a noncanonical p53 response element in the RAP80 promoter. Although it is inducible by p53, RAP80 is also able to regulate p53 through an association with both p53 and the E3 ubiquitin ligase HDM2, providing HDM2-dependent enhancement of p53 poly-ubiquitination. Depletion of RAP80 by small interfering RNA stabilizes p53, which, following DNA damage, results in an increased transactivation of several p53 target genes as well as greater apoptosis. Consistent with these observations, exogenous expression of RAP80 selectively inhibits p53-dependent transactivation of target genes in an mdm2-dependent manner in MEF cells. Thus, we identify a new DNA damage-associated role for RAP80. It can function in an autoregulatory loop consisting of RAP80, HDM2, and the p53 master regulatory network, implying an important role for this loop in genome stability and oncogenesis.
C1 [Menendez, Daniel; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA.
[Yan, Jun; Yang, Xiao-Ping; Jetten, Anton M.] NIEHS, Cell Biol Sect, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov; jetten@niehs.nih.gov
OI Jetten, Anton/0000-0003-0954-4445
FU National Institutes of Health [Z01 ES101586, Z01 ES065079]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants Z01 ES101586 ( to A. M. J.) and Z01 ES065079 ( to M. A.
R.).
NR 49
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U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2009
VL 284
IS 29
BP 19280
EP 19289
DI 10.1074/jbc.M109.013102
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300019
PM 19433585
ER
PT J
AU Kimple, AJ
Soundararajan, M
Hutsell, SQ
Roos, AK
Urban, DJ
Setola, V
Temple, BRS
Roth, BL
Knapp, S
Willard, FS
Siderovski, DP
AF Kimple, Adam J.
Soundararajan, Meera
Hutsell, Stephanie Q.
Roos, Annette K.
Urban, Daniel J.
Setola, Vincent
Temple, Brenda R. S.
Roth, Bryan L.
Knapp, Stefan
Willard, Francis S.
Siderovski, David P.
TI Structural Determinants of G-protein alpha Subunit Selectivity by
Regulator of G-protein Signaling 2 (RGS2)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GTPASE-ACTIVATING PROTEINS; MYOCARDIAL HYPERTROPHY; CIONA-INTESTINALIS;
SEQUENCE ALIGNMENT; PHOSPHOLIPASE-C; RECEPTOR; PRESSURE; ANXIETY;
DOMAIN; HYPERTENSION
AB "Regulator of G-protein signaling" (RGS) proteins facilitate the termination of G protein-coupled receptor (GPCR) signaling via their ability to increase the intrinsic GTP hydrolysis rate of G alpha subunits (known as GTPase-accelerating protein or "GAP" activity). RGS2 is unique in its in vitro potency and selectivity as a GAP for G alpha(q) subunits. As many vasoconstrictive hormones signal via G(q) heterotrimer-coupled receptors, it is perhaps not surprising that RGS2-deficient mice exhibit constitutive hypertension. However, to date the particular structural features within RGS2 determining its selectivity for G alpha(q) over G alpha(i/o) substrates have not been completely characterized. Here, we examine a trio of point mutations to RGS2 that elicits G alpha(i)-directed binding and GAP activities without perturbing its association with G alpha(q). Using x-ray crystallography, we determined a model of the triple mutant RGS2 in complex with a transition state mimetic form of G alpha(i) at 2.8-angstrom resolution. Structural comparison with unliganded, wild type RGS2 and of other RGS domain/G alpha complexes highlighted the roles of these residues in wild type RGS2 that weaken G alpha(i) subunit association. Moreover, these three amino acids are seen to be evolutionarily conserved among organisms with modern cardiovascular systems, suggesting that RGS2 arose from the R4-subfamily of RGS proteins to have specialized activity as a potent and selective G alpha(q) GAP that modulates cardiovascular function.
C1 [Kimple, Adam J.; Urban, Daniel J.; Setola, Vincent; Roth, Bryan L.; Willard, Francis S.; Siderovski, David P.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Hutsell, Stephanie Q.; Temple, Brenda R. S.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Setola, Vincent; Roth, Bryan L.] Univ N Carolina, NIMH, Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA.
[Siderovski, David P.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Temple, Brenda R. S.] Univ N Carolina, RL Juliano Struct Bioinformat Core Facil, Chapel Hill, NC 27599 USA.
[Soundararajan, Meera; Roos, Annette K.; Knapp, Stefan] Univ Oxford, Struct Genom Consortium, Oxford OX3 7DQ, England.
[Knapp, Stefan] Univ Oxford, Dept Clin Pharmacol, Oxford OX3 7DQ, England.
RP Siderovski, DP (reprint author), 4073 Genet Med Bldg,CB 7365, Chapel Hill, NC 27599 USA.
EM dsiderov@med.unc.edu
RI Roth, Bryan/F-3928-2010;
OI Knapp, Stefan/0000-0001-5995-6494
FU National Institutes of Health [R01 GM082892, T32 GM008570, T32 GM008719,
F30 MH074266]; American Heart Association Mid-Atlantic Affiliate Grant
[0815239E]
FX This work was supported, in whole or in part, by National Institutes of
Health Grants R01 GM082892 ( to D. P. S.), T32 GM008570 ( to S. Q. H.),
and T32 GM008719 and F30 MH074266 ( to A. J. K.). This work was also
supported by American Heart Association Mid-Atlantic Affiliate Grant
0815239E ( to D. J. U.).. S The on-line version of this article (
available at http://www.jbc.org) contains supplemental Figs. S1-S3 and
Tables S1 and S2.
NR 64
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U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2009
VL 284
IS 29
BP 19402
EP 19411
DI 10.1074/jbc.M109.024711
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300031
PM 19478087
ER
PT J
AU Yeung, ML
Houzet, L
Yedavalli, VSRK
Jeang, KT
AF Yeung, Man Lung
Houzet, Laurent
Yedavalli, Venkat S. R. K.
Jeang, Kuan-Teh
TI A Genome-wide Short Hairpin RNA Screening of Jurkat T-cells for Human
Proteins Contributing to Productive HIV-1 Replication
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTION; GENE; INTERFERENCE; ACTIVATION;
THERAPY; ESCAPE; TYPE-1; PPAR
AB Short interfering RNAs (siRNAs) have been used to inhibit HIV-1 replication. The durable inhibition of HIV-1 replication by RNA interference has been impeded, however, by a high mutation rate when viral sequences are targeted and by cytotoxicity when cellular genes are knocked down. To identify cellular proteins that contribute to HIV-1 replication that can be chronically silenced without significant cytotoxicity, we employed a shRNA library that targets 54,509 human transcripts. We used this library to select a comprehensive population of Jurkat T-cell clones, each expressing a single discrete shRNA. The Jurkat clones were then infected with HIV-1. Clones that survived viral infection represent moieties silenced for a human mRNA needed for virus replication, but whose chronic knockdown did not cause cytotoxicity. Overall, 252 individual Jurkat mRNAs were identified. Twenty-two of these mRNAs were secondarily verified for their contributions to HIV-1 replication. Five mRNAs, NRF1, STXBP2, NCOA3, PRDM2, and EXOSC5, were studied for their effect on steps of the HIV-1 life cycle. We discuss the similarities and differences between our shRNA findings for HIV-1 using a spreading infection assay in human Jurkat T-cells and results from other investigators who used siRNA-based screenings in HeLa or 293T cells.
C1 [Yeung, Man Lung; Houzet, Laurent; Yedavalli, Venkat S. R. K.; Jeang, Kuan-Teh] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Jeang, KT (reprint author), Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kj7e@nih.gov
RI Jeang, Kuan-Teh/A-2424-2008
FU NIAID; Office of the Director, NIH
FX This work was supported, in whole or in part, by National Institutes of
Health intramural research funds from NIAID. This work was also
supported by the IATAP program from the Office of the Director, NIH.
NR 35
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U1 1
U2 14
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 JUL 17
PY 2009
VL 284
IS 29
BP 19463
EP 19473
DI 10.1074/jbc.M109.010033
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300038
PM 19460752
ER
PT J
AU Kasiviswanathan, R
Longley, MJ
Chan, SSL
Copeland, WC
AF Kasiviswanathan, Rajesh
Longley, Matthew J.
Chan, Sherine S. L.
Copeland, William C.
TI Disease Mutations in the Human Mitochondrial DNA Polymerase Thumb
Subdomain Impart Severe Defects in Mitochondrial DNA Replication
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; TYPE-1 REVERSE-TRANSCRIPTASE; P55
ACCESSORY SUBUNIT; I KLENOW FRAGMENT; ALPERS-SYNDROME; POLG MUTATIONS;
FRAMESHIFT FIDELITY; ANGSTROM RESOLUTION; AUTOSOMAL-DOMINANT; NUCLEOSIDE
ANALOGS
AB Forty-five different point mutations in POLG, the gene encoding the catalytic subunit of the human mitochondrial DNA polymerase (pol gamma), cause the early onset mitochondrial DNA depletion disorder, Alpers syndrome. Sequence analysis of the C-terminal polymerase region of pol gamma revealed a cluster of four Alpers mutations at highly conserved residues in the thumb subdomain (G848S, c.2542g -> a; T851A, c.2551a -> g; R852C, c.2554c -> t; R853Q, c.2558g -> a) and two Alpers mutations at less conserved positions in the adjacent palm subdomain (Q879H, c.2637g -> t and T885S, c.2653a -> t). Biochemical characterization of purified, recombinant forms of pol gamma revealed that Alpers mutations in the thumb subdomain reduced polymerase activity more than 99% relative to the wild-type enzyme, whereas the palm subdomain mutations retained 50-70% wildtype polymerase activity. All six mutant enzymes retained physical and functional interaction with the pol gamma accessory subunit (p55), and none of the six mutants exhibited defects in misinsertion fidelity in vitro. However, differential DNA binding by these mutants suggests a possible orientation of the DNA with respect to the polymerase during catalysis. To our knowledge this study represents the first structure-function analysis of the thumb subdomain in pol gamma and examines the consequences of mitochondrial disease mutations in this region.
C1 [Kasiviswanathan, Rajesh; Longley, Matthew J.; Chan, Sherine S. L.; Copeland, William C.] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Copeland, WC (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr,Bldg 101,Rm E316, Res Triangle Pk, NC 27709 USA.
EM copelan1@niehs.nih.gov
RI Kasiviswanathan, Rajesh/D-2744-2012
FU National Institutes of Health Grant [ES 065078]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant ES 065078 ( Intramural Research Program of the NIEHS).
NR 54
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U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2009
VL 284
IS 29
BP 19501
EP 19510
DI 10.1074/jbc.M109.011940
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300042
PM 19478085
ER
PT J
AU Walmacq, C
Kireeva, ML
Irvin, J
Nedialkov, Y
Lubkowska, L
Malagon, F
Strathern, JN
Kashlev, M
AF Walmacq, Celine
Kireeva, Maria L.
Irvin, Jordan
Nedialkov, Yuri
Lubkowska, Lucyna
Malagon, Francisco
Strathern, Jeffrey N.
Kashlev, Mikhail
TI Rpb9 Subunit Controls Transcription Fidelity by Delaying NTP
Sequestration in RNA Polymerase II
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID STATE KINETIC-ANALYSIS; STRUCTURAL BASIS; SACCHAROMYCES-CEREVISIAE;
DRIVEN TRANSLOCATION; TRIGGER LOOP; IN-VIVO; DEPENDENT
RNA-POLYMERASE-(3D(POL)); RIBONUCLEOTIDE INCORPORATION; SEQUENCE
INSERTIONS; CLEAVAGE ACTIVITY
AB Rpb9 is a small non-essential subunit of yeast RNA polymerase II located on the surface on the enzyme. Deletion of the RPB9 gene shows synthetic lethality with the low fidelity rpb1-E1103G mutation localized in the trigger loop, a mobile element of the catalytic Rpb1 subunit, which has been shown to control transcription fidelity. Similar to the rpb1-E1103G mutation, the RPB9 deletion substantially enhances NTP misincorporation and increases the rate of mismatch extension with the next cognate NTP in vitro. Using pre-steady state kinetic analysis, we show that RPB9 deletion promotes sequestration of NTPs in the polymerase active center just prior to the phosphodiester bond formation. We propose a model in which the Rpb9 subunit controls transcription fidelity by delaying the closure of the trigger loop on the incoming NTP via interaction between the C-terminal domain of Rpb9 and the trigger loop. Our findings reveal a mechanism for regulation of transcription fidelity by protein factors located at a large distance from the active center of RNA polymerase II.
C1 [Walmacq, Celine; Kireeva, Maria L.; Irvin, Jordan; Nedialkov, Yuri; Lubkowska, Lucyna; Malagon, Francisco; Strathern, Jeffrey N.; Kashlev, Mikhail] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Nedialkov, Yuri] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA.
[Malagon, Francisco] Aarhus Univ, Inst Mol Biol, DK-8000 Aarhus, Denmark.
RP Kashlev, M (reprint author), NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM mkashlev@mail.ncifcrf.gov
RI Malagon, Francisco/A-7059-2013;
OI Irvin, Jordan/0000-0001-8504-5985
FU National Institutes of Health
FX This work was supported, in whole or in part, by the Intramural Research
Program of the National Institutes of Health through the NCI. The
contents of this publication do not necessarily reveal the views of the
policy of the Department of Health and Human Services, nor does mention
of trade names, commercial products, or organizations imply endorsement
of the U. S. government.
NR 59
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U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 17
PY 2009
VL 284
IS 29
BP 19601
EP 19612
DI 10.1074/jbc.M109.006908
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 469OE
UT WOS:000267908300052
PM 19439405
ER
PT J
AU Wojciechowski, R
Bailey-Wilson, JE
Stambolian, D
AF Wojciechowski, Robert
Bailey-Wilson, Joan E.
Stambolian, Dwight
TI Fine-mapping of candidate region in Amish and Ashkenazi families
confirms linkage of refractive error to a QTL on 1p34-p36
SO MOLECULAR VISION
LA English
DT Article
ID GENOME-WIDE SCAN; HIGH MYOPIA MAPS; OLD ORDER AMISH; OCULAR REFRACTION;
SUSCEPTIBILITY LOCUS; GENETIC-ASSOCIATION; CHROMOSOME 22Q12;
AFRICAN-AMERICAN; COMPLEX TRAITS; HERITABILITY
AB Purpose: A previous genome-wide study in Orthodox Ashkenazi Jewish pedigrees showed significant linkage of ocular refraction to a Quantitative Trait Locus (QTL) on 1p34-36.1. We carried out a fine-mapping study of this region in Orthodox Ashkenazi Jewish (ASHK) and Old Order Amish (OOA) families to confirm linkage and narrow the candidate region.
Methods: Families were recruited from ASHK and OOA American communities. The samples included: 402 individuals in 53 OOA families; and 596 members in 68 ASHK families. Families were ascertained to contain multiple myopic individuals. Genotyping of 1,367 SNPs was carried out within a 35cM (similar to 23.9 Mb) candidate QTL region on 1p34-36. Multipoint variance components (VC) and regression-based (REG) linkage analyses were carried out separately in OOA and ASHK groups, and in a combined analysis that included all families.
Results: Evidence of linkage of refractive error was found in both OOA (VC LOD=3.45, REG LOD=3.38 at similar to 59 cM) and ASHK families (VC LOD=3.12, REG LOD=4.263 at similar to 66 cM). Combined analyses showed three highly significant linkage peaks, separated by similar to 11 cM (or 10 Mb), within the candidate region.
Conclusion: In a fine-mapping linkage study of OOA and ASHK families, we have confirmed linkage of refractive error to a QTL on 1p. The area of linkage has been narrowed down to a gene-rich region at 1p34.2-35.1 containing similar to 124 genes.
C1 [Wojciechowski, Robert; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
RP Wojciechowski, R (reprint author), NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA.
EM robwoj@mail.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski,
Robert/0000-0002-9593-4652
FU U. S. Public Health National Eye Institute [EY12226]; National Human
Genome Research Institute, NIH; American Optometric Foundation; CIDR;
National Institutes of Health [N01-HG-65403]
FX This study was supported in part by U. S. Public Health National Eye
Institute grant EY12226 (D. S.) and in part by funds from the intramural
program of the National Human Genome Research Institute, NIH (J.E.B-W.,
R. W.). R.W. also received a William C. Ezell-CIBA Vision Fellowship
from the American Optometric Foundation. Genotyping services were
provided by the Center for Inherited Disease Research (CIDR). CIDR is
fully funded through a federal contract from the National Institutes of
Health to Johns Hopkins University (contract number N01-HG-65403). The
authors thank the families for their participation in the study. We are
also grateful to Dr. Reuvain Shanik and Rabbi Yitzchok Rozsansky for
their support enthusiasm in the Myopia Family Study. We are thankful to
the staff of the Amish Eye Clinic in Strasburg, PA, for their invaluable
help in study logistics and participant recruitment.
NR 43
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U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD JUL 17
PY 2009
VL 15
IS 145-48
BP 1398
EP 1406
PG 9
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA 493LX
UT WOS:000269739400004
PM 19626131
ER
PT J
AU Pitzer, VE
Viboud, C
Simonsen, L
Steiner, C
Panozzo, CA
Alonso, WJ
Miller, MA
Glass, RI
Glasser, JW
Parashar, UD
Grenfell, BT
AF Pitzer, Virginia E.
Viboud, Cecile
Simonsen, Lone
Steiner, Claudia
Panozzo, Catherine A.
Alonso, Wladimir J.
Miller, Mark A.
Glass, Roger I.
Glasser, John W.
Parashar, Umesh D.
Grenfell, Bryan T.
TI Demographic Variability, Vaccination, and the Spatiotemporal Dynamics of
Rotavirus Epidemics
SO SCIENCE
LA English
DT Article
ID UNITED-STATES; SPATIAL HIERARCHIES; TRAVELING-WAVES; SEASONALITY;
DIARRHEA; EFFICACY; MEASLES; SAFETY; GASTROENTERITIS; PROTECTION
AB Historically, annual rotavirus activity in the United States has started in the southwest in late fall and ended in the northeast 3 months later; this trend has diminished in recent years. Traveling waves of infection or local environmental drivers cannot account for these patterns. A transmission model calibrated against epidemiological data shows that spatiotemporal variation in birth rate can explain the timing of rotavirus epidemics. The recent large-scale introduction of rotavirus vaccination provides a natural experiment to further test the impact of susceptible recruitment on disease dynamics. The model predicts a pattern of reduced and lagged epidemics postvaccination, closely matching the observed dynamics. Armed with this validated model, we explore the relative importance of direct and indirect protection, a key issue in determining the worldwide benefits of vaccination.
C1 [Pitzer, Virginia E.; Grenfell, Bryan T.] Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA 16801 USA.
[Pitzer, Virginia E.; Viboud, Cecile; Alonso, Wladimir J.; Miller, Mark A.; Glass, Roger I.; Grenfell, Bryan T.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Simonsen, Lone] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20052 USA.
[Steiner, Claudia] US Dept HHS, Healthcare Cost & Utilizat Project, Ctr Delivery Org & Markets, Agcy Healthcare Res & Qual, Rockville, MD 20850 USA.
[Panozzo, Catherine A.; Glasser, John W.; Parashar, Umesh D.] Ctr Dis Control & Prevent, Epidemiol Branch, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA.
[Grenfell, Bryan T.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Grenfell, Bryan T.] Princeton Univ, Woodrow Wilson Sch, Princeton, NJ 08544 USA.
RP Pitzer, VE (reprint author), Penn State Univ, Ctr Infect Dis Dynam, State Coll, PA 16801 USA.
EM vep2@psu.edu
OI Pitzer, Virginia/0000-0003-1015-2289; Simonsen, Lone/0000-0003-1535-8526
FU NIH [R01 GM083983-01]; Bill and Melinda Gates Foundation; RAPIDD program
of the Science and Technology Directorate; U.S. Department of Homeland
Security
FX V.E.P and B.G. were supported by NIH (grant R01 GM083983-01) and the
Bill and Melinda Gates Foundation. V.E.P, B.G., and L.S. were also
supported by the RAPIDD program of the Science and Technology
Directorate, U.S. Department of Homeland Security, and the Fogarty
International Center, NIH. The findings and conclusions in this report
are those of the authors and do not necessarily represent the views of
the Centers for Disease Control and Prevention (CDC).
NR 30
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U1 2
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 JUL 17
PY 2009
VL 325
IS 5938
BP 290
EP 294
DI 10.1126/science.1172330
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 471DZ
UT WOS:000268036600037
PM 19608910
ER
PT J
AU Alousi, AM
Weisdorf, DJ
Logan, BR
Bolanos-Meade, J
Carter, S
DiFronzo, N
Pasquini, M
Goldstein, SC
Ho, VT
Hayes-Lattin, B
Wingard, JR
Horowitz, MM
Levine, JE
AF Alousi, Amin M.
Weisdorf, Daniel J.
Logan, Brent R.
Bolanos-Meade, Javier
Carter, Shelly
DiFronzo, Nancy
Pasquini, Marcelo
Goldstein, Steven C.
Ho, Vincent T.
Hayes-Lattin, Brandon
Wingard, John R.
Horowitz, Mary M.
Levine, John E.
CA Blood & Marrow Transplant Clin Tri
TI Etanercept, mycophenolate, denileukin, or pentostatin plus
corticosteroids for acute graft-versus-host disease: a randomized phase
2 trial from the Blood and Marrow Transplant Clinical Trials Network
SO BLOOD
LA English
DT Article; Proceedings Paper
CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint
Symposium
CY DEC 06-09, 2008
CL San Francisco, CA
SP Amer Soc Hematol (ASH), Sanofi Aventis U.S.
ID INITIAL THERAPY; CHRONIC GVHD; METHOTREXATE; CYCLOSPORINE; PROPHYLAXIS;
PREDNISONE; DIFTITOX; EFFICACY; STEROIDS; MODERATE
AB Acute graft-versus-host disease (aGVHD) is the primary limitation of allogeneic hematopoietic cell transplantation. Corticosteroids remain the standard initial therapy, yet only 25% to 41% of patients completely respond. This randomized, 4-arm, phase 2 trial was designed to identify the most promising agent(s) for initial therapy for aGVHD. Patients were randomized to receive methylprednisolone 2 mg/kg per day plus etanercept, mycophenolate mofetil (MMF), denileukin diftitox (denileukin), or pentostatin. Patients (n = 180) were randomized; their median age was 50 years (range, 7.5-70 years). Myeloablative conditioning represented 66% of transplants. Grafts were peripheral blood (61%), bone marrow (25%), or umbilical cord blood (14%); 53% were from unrelated donors. Patients who received MMF for prophylaxis (24%) were randomized to a non-MMF arm. At randomization, aGVHD was grade I to II (68%), III to IV (32%), and (53%) had visceral organ involvement. Day 28 complete response rates were etanercept 26%, MMF 60%, denileukin 53%, and pentostatin 38%. Corresponding 9-month overall survival was 47%, 64%, 49%, and 47%, respectively. Cumulative incidences of severe infections were as follows: etanercept 48%, MMF 44%, denileukin 62%, and pentostatin 57%. Efficacy and toxicity data suggest the use of MMF plus corticosteroids is the most promising regimen to compare against corticosteroids alone in a definitive phase 3 trial. This study is registered at http://www. clinicaltrials.gov as NCT00224874. (Blood. 2009; 114: 511-517)
C1 [Alousi, Amin M.] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA.
[Weisdorf, Daniel J.] Univ Minnesota, Dept Bone Marrow Transplant, Minneapolis, MN USA.
[Logan, Brent R.] Med Coll Wisconsin, Dept Populat Hlth, Milwaukee, WI 53226 USA.
[Bolanos-Meade, Javier] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Carter, Shelly] EMMES Corp, Rockville, MD USA.
[DiFronzo, Nancy] NHLBI, Transfus Med & Cellular Therapeut Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Pasquini, Marcelo] Med Coll Wisconsin, Dept Med, Div Neoplast Dis & Related Disorders, CIBMTR, Milwaukee, WI 53226 USA.
[Goldstein, Steven C.] Univ Penn, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Ho, Vincent T.] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA.
[Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA.
[Wingard, John R.] Univ Florida, Dept Med, Shands Canc Ctr, Gainesville, FL USA.
[Levine, John E.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA.
[Horowitz, Mary M.] Froedtert & Med Coll Wisconsin, Dept Med, Div Neoplast Dis & Related Disorders, Milwaukee, WI USA.
[Horowitz, Mary M.] Froedtert & Med Coll Wisconsin, CIBMTR, Milwaukee, WI USA.
RP Alousi, AM (reprint author), 1515 Holcombe Blvd,Unit 423, Houston, TX 77030 USA.
EM aalousi@mdanderson.org
OI Levine, John/0000-0002-9133-0800
FU NCI NIH HHS [U24 CA076518]; NHLBI NIH HHS [U10 HL069249, U10 HL069286,
U10 HL069294, U10 HL069301, U10 HL069330, U10 HL069348]
NR 24
TC 110
Z9 114
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 16
PY 2009
VL 114
IS 3
BP 511
EP 517
DI 10.1182/blood-2009-03-212290
PG 7
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800008
PM 19443659
ER
PT J
AU Johnson, LA
Morgan, RA
Dudley, ME
Cassard, L
Yang, JC
Hughes, MS
Kammula, US
Royal, RE
Sherry, RM
Wunderlich, JR
Lee, CCR
Restifo, NP
Schwarz, SL
Cogdill, AP
Bishop, RJ
Kim, H
Brewer, CC
Rudy, SF
VanWaes, C
Davis, JL
Mathur, A
Ripley, RT
Nathan, DA
Laurencot, CM
Rosenberg, SA
AF Johnson, Laura A.
Morgan, Richard A.
Dudley, Mark E.
Cassard, Lydie
Yang, James C.
Hughes, Marybeth S.
Kammula, Udai S.
Royal, Richard E.
Sherry, Richard M.
Wunderlich, John R.
Lee, Chyi-Chia R.
Restifo, Nicholas P.
Schwarz, Susan L.
Cogdill, Alexandria P.
Bishop, Rachel J.
Kim, Hung
Brewer, Carmen C.
Rudy, Susan F.
VanWaes, Carter
Davis, Jeremy L.
Mathur, Aarti
Ripley, Robert T.
Nathan, Debbie A.
Laurencot, Carolyn M.
Rosenberg, Steven A.
TI Gene therapy with human and mouse T-cell receptors mediates cancer
regression and targets normal tissues expressing cognate antigen
SO BLOOD
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; ADOPTIVE IMMUNOTHERAPY; METASTATIC
MELANOMA; TCR; AUTOIMMUNITY; RECOGNITION; PERSISTENCE
AB Gene therapy of human cancer using genetically engineered lymphocytes is dependent on the identification of highly reactive T-cell receptors (TCRs) with antitumor activity. We immunized transgenic mice and also conducted high-throughput screening of human lymphocytes to generate TCRs highly reactive to melanoma/melanocyte antigens. Genes encoding these TCRs were engineered into retroviral vectors and used to transduce autologous peripheral lymphocytes administered to 36 patients with metastatic melanoma. Transduced patient lymphocytes were CD45RA(-) and CD45RO(+) after ex vivo expansion. After infusion, the persisting cells displayed a CD45RA(+) and CD45RO(-) phenotype. Gene-engineered cells persisted at high levels in the blood of all patients 1 month after treatment, responding patients with higher ex vivo antitumor reactivity than nonresponders. Objective cancer regressions were seen in 30% and 19% of patients who received the human or mouse TCR, respectively. However, patients exhibited destruction of normal melanocytes in the skin, eye, and ear, and sometimes required local steroid administration to treat uveitis and hearing loss. Thus, T cells expressing highly reactive TCRs mediate cancer regression in humans and target rare cognate -antigen-containing cells throughout the body, a finding with important implications for the gene therapy of cancer. This trial was registered at www.ClinicalTrials.gov as NCI-07-C-0174 and NCI-07-C-0175. (Blood. 2009; 114: 535-546)
C1 [Johnson, Laura A.; Morgan, Richard A.; Dudley, Mark E.; Cassard, Lydie; Yang, James C.; Hughes, Marybeth S.; Kammula, Udai S.; Royal, Richard E.; Sherry, Richard M.; Wunderlich, John R.; Restifo, Nicholas P.; Schwarz, Susan L.; Cogdill, Alexandria P.; Davis, Jeremy L.; Mathur, Aarti; Ripley, Robert T.; Nathan, Debbie A.; Laurencot, Carolyn M.; Rosenberg, Steven A.] NCI, Surg Branch, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia R.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Bishop, Rachel J.] NEI, Off Clin Director, Bethesda, MD 20892 USA.
[Kim, Hung; Brewer, Carmen C.; Rudy, Susan F.; VanWaes, Carter] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Bethesda, MD USA.
RP Rosenberg, SA (reprint author), NCI, Surg Branch, Hatfield Clin Res Ctr, Bldg 10CRC, Bethesda, MD 20892 USA.
EM SAR@nih.gov
RI Restifo, Nicholas/A-5713-2008; Johnson, Laura/H-4861-2013; Lee,
Chyi-Chia/I-1938-2013;
OI Lee, Chyi-Chia/0000-0002-5306-7781; Cogdill,
Alexandria/0000-0001-8917-9462; Restifo, Nicholas P./0000-0003-4229-4580
NR 32
TC 571
Z9 587
U1 4
U2 52
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 16
PY 2009
VL 114
IS 3
BP 535
EP 546
DI 10.1182/blood-2009-03-211714
PG 12
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800012
PM 19451549
ER
PT J
AU Hinrichs, CS
Kaiser, A
Paulos, CM
Cassard, L
Sanchez-Perez, L
Heemskerk, B
Wrzesinski, C
Borman, ZA
Muranski, P
Restifo, NP
AF Hinrichs, Christian S.
Kaiser, Andrew
Paulos, Chrystal M.
Cassard, Lydie
Sanchez-Perez, Luis
Heemskerk, Bianca
Wrzesinski, Claudia
Borman, Zachary A.
Muranski, Pawel
Restifo, Nicholas P.
TI Type 17 CD8(+) T cells display enhanced antitumor immunity
SO BLOOD
LA English
DT Article
ID EFFECTOR; CANCER; DIFFERENTIATION; IMMUNOTHERAPY; EOMESODERMIN;
INDUCTION; REGRESSION; DISTINCT; THERAPY; TH17
AB Interleukin-17 (IL-17)-secreting CD8(+) T cells have been described, but they have not been thoroughly studied and they do not have a known role in cancer immunotherapy. We skewed CD8(+) T cells to secrete IL-17 through priming in Th17-polarizing conditions. IL-17-producing CD8(+) T cells demonstrated reduced expression of Eomes and diminished cytolytic differentiation in vitro. However, after adoptive transfer, these cells converted to interferon-gamma-producing effector cells and mediated regression of large, established tumors. This improved antitumor immunity was associated with increased expression of IL-7R-alpha, decreased expression of killer cell lectin-like receptor G1, and enhanced persistence of the transferred cells. This report is the first description of a cancer therapy with IL-17 secreting CD8(+) T cells. These findings have implications for the improvement of CD8(+) T cell-based adoptive immunotherapy. (Blood. 2009; 114: 596-599)
C1 [Muranski, Pawel] NCI, NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Heemskerk, Bianca] Netherlands Canc Inst, Dept Immunol, Amsterdam, Netherlands.
RP Muranski, P (reprint author), NCI, NIH, Clin Res Ctr, Rm 3-5816,10 Ctr Dr, Bethesda, MD 20892 USA.
EM Pawel_Muranski@nih.gov
RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010; Kaiser,
Andrew/C-2617-2012; Heemskerk, Bianca/C-4635-2012;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU NCI, Bethesda
FX This work was supported by the NCI, Bethesda, MD (through the intramural
program).
NR 24
TC 124
Z9 131
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 16
PY 2009
VL 114
IS 3
BP 596
EP 599
DI 10.1182/blood-2009-02-203935
PG 4
WC Hematology
SC Hematology
GA 471ML
UT WOS:000268061800019
PM 19471017
ER
PT J
AU Jiang, QF
Karata, K
Woodgate, R
Cox, MM
Goodman, MF
AF Jiang, Qingfei
Karata, Kiyonobu
Woodgate, Roger
Cox, Michael M.
Goodman, Myron F.
TI The active form of DNA polymerase V is UmuD ' C-2-RecA-ATP
SO NATURE
LA English
DT Article
ID SINGLE-STRANDED-DNA; ESCHERICHIA-COLI; RECA PROTEIN; UV-MUTAGENESIS;
REPLICATION; DEFICIENT; MUTATIONS; REPAIR; UMUC; PURIFICATION
AB DNA-damage-induced SOS mutations arise when Escherichia coli DNA polymerase (pol) V, activated by a RecA nucleoprotein filament (RecA*), catalyses translesion DNA synthesis. Here we address two longstanding enigmatic aspects of SOS mutagenesis, the molecular composition of mutagenically active pol V and the role of RecA*. We show that RecA* transfers a single RecA-ATP stoichiometrically from its DNA 39-end to free polV (UmuD'C-2) to form an active mutasome (polV Mut) with the composition UmuD'C-2-RecA-ATP. PolV Mut catalyses TLS in the absence of RecA* and deactivates rapidly upon dissociation from DNA. Deactivation occurs more slowly in the absence of DNA synthesis, while retaining RecA-ATP in the complex. Reactivation of polV Mut is triggered by replacement of RecA-ATP from RecA*. Thus, the principal role of RecA* in SOS mutagenesis is to transfer RecA-ATP to pol V, and thus generate active mutasomal complex for translesion synthesis.
C1 [Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA.
[Jiang, Qingfei; Goodman, Myron F.] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA.
[Karata, Kiyonobu; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
[Cox, Michael M.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA.
RP Goodman, MF (reprint author), Univ So Calif, Dept Biol Sci, Univ Pk, Los Angeles, CA 90089 USA.
EM mgoodman@usc.edu
RI JIANG, QINGFEI/K-3492-2012
FU National Institutes of Health [ES12259, R37GM21422, GM32335]; NICHD/NIH
FX This work was supported by National Institutes of Health grants to M. F.
G. (ES12259; R37GM21422) and M. M. C. (GM32335), and funds from the
NICHD/NIH Intramural Research Program to K. K. and R. W. The authors
thank R. Britt for preparation of the RecA E38KDC17 protein used in this
study. MALS data were collected using the USC NanoBiophysics Core
Facility, with the aid and cooperation of N. Chelyapov. Wethank J.
Bertram for his help in performing the MALS experiment and analysing the
data. We thank J. Petruska for his comments.
NR 25
TC 68
Z9 69
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 359
EP 363
DI 10.1038/nature08178
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000030
PM 19606142
ER
PT J
AU Harrison, DE
Strong, R
Sharp, ZD
Nelson, JF
Astle, CM
Flurkey, K
Nadon, NL
Wilkinson, JE
Frenkel, K
Carter, CS
Pahor, M
Javors, MA
Fernandez, E
Miller, RA
AF Harrison, David E.
Strong, Randy
Sharp, Zelton Dave
Nelson, James F.
Astle, Clinton M.
Flurkey, Kevin
Nadon, Nancy L.
Wilkinson, J. Erby
Frenkel, Krystyna
Carter, Christy S.
Pahor, Marco
Javors, Martin A.
Fernandez, Elizabeth
Miller, Richard A.
TI Rapamycin fed late in life extends lifespan in genetically heterogeneous
mice
SO NATURE
LA English
DT Article
ID INTERVENTIONS TESTING PROGRAM; CALORIC RESTRICTION; SIGNALING PATHWAY;
TOR; METABOLISM; EXTENSION; ELEGANS; DESIGN; TARGET; YEAST
AB Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruitflies(1-5); however, whether inhibition of mTOR signalling can extend lifespan in a mammalian species was unknown. Here we report that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age. On the basis of age at 90% mortality, rapamycin led to an increase of 14% for females and 9% for males. The effect was seen at three independent test sites in genetically heterogeneous mice, chosen to avoid genotype-specific effects on disease susceptibility. Disease patterns of rapamycin-treated mice did not differ from those of control mice. In a separate study, rapamycin fed to mice beginning at 270 days of age also increased survival in both males and females, based on an interim analysis conducted near the median survival point. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders. These findings have implications for further development of interventions targeting mTOR for the treatment and prevention of age-related diseases.
C1 [Harrison, David E.; Astle, Clinton M.; Flurkey, Kevin] Jackson Lab, Bar Harbor, ME 04609 USA.
[Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA.
[Strong, Randy; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Res Serv, Dept Pharmacol, San Antonio, TX 78229 USA.
[Strong, Randy; Sharp, Zelton Dave; Nelson, James F.; Fernandez, Elizabeth] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[Sharp, Zelton Dave] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78245 USA.
[Nelson, James F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA.
[Nadon, Nancy L.] NIA, Div Aging Biol, Bethesda, MD 20892 USA.
[Wilkinson, J. Erby] Univ Michigan, Sch Med, Unit Lab Anim Med, Ann Arbor, MI 48109 USA.
[Frenkel, Krystyna] NYU, Sch Med, New York, NY 10016 USA.
[Carter, Christy S.; Pahor, Marco] Wake Forest Univ, Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Winston Salem, Winston Salem, NC 27157 USA.
[Javors, Martin A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA.
[Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA.
RP Harrison, DE (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM david.harrison@jax.org
RI Carter, Christy/A-6828-2011; Carter, Christy/E-6630-2011
FU NIA [AG022303, AG025707, AG022308, AG022307, AG13319]; Department of
Veterans Affairs; DoD [W81XWH-07-1-0605]
FX This work was supported by NIA grants AG022303 (R. A. M.), AG025707 and
AG022308 (D. E. H.), AG022307 (R. S.) and AG13319 (J. F. N. and R. S.),
and the Department of Veterans Affairs (R. A. M. and R. S.) and DoD
W81XWH-07-1-0605 (Z. D. S.). We wish to thank P. J. Krason, P. J.
Harrison, E. Adler, V. Diaz, J. Sewald, L. Burmeister, B. Kohler, M.
Han, M. Lauderdale and D. Jones for reliable technical assistance, S.
Pletcher and A. Galecki for statistical assistance, and H. Warner and S.
N. Austad for scientific counsel.
NR 30
TC 1408
Z9 1466
U1 32
U2 162
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 16
PY 2009
VL 460
IS 7253
BP 392
EP U108
DI 10.1038/nature08221
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470MO
UT WOS:000267979000038
PM 19587680
ER
PT J
AU Alexander, GM
Rogan, SC
Abbas, AI
Armbruster, BN
Pei, Y
Allen, JA
Nonneman, RJ
Hartmann, J
Moy, SS
Nicolelis, MA
McNamara, JO
Roth, BL
AF Alexander, Georgia M.
Rogan, Sarah C.
Abbas, Atheir I.
Armbruster, Blaine N.
Pei, Ying
Allen, John A.
Nonneman, Randal J.
Hartmann, John
Moy, Sheryl S.
Nicolelis, Miguel A.
McNamara, James O.
Roth, Bryan L.
TI Remote Control of Neuronal Activity in Transgenic Mice Expressing
Evolved G Protein-Coupled Receptors
SO NEURON
LA English
DT Article
ID CONDITIONAL EXPRESSION; IN-VIVO; G(I)-COUPLED RECEPTOR; MAMMALIAN
NEURONS; M-CHANNEL; OSCILLATIONS; INHIBITION; LIGAND
AB Examining the behavioral consequences of selective CNS neuronal activation is a powerful tool for elucidating mammalian brain function in health and disease. Newly developed genetic, pharmacological, and optical tools allow activation of neurons with exquisite spatiotemporal resolution; however, the inaccessibility to light of widely distributed neuronal populations and the invasiveness required for activation by light or infused ligands limit the utility of these methods. To overcome these barriers, we created transgenic mice expressing an evolved G protein-coupled receptor (hM3Dq) selectively activated by the pharmacologically inert, orally bioavailable drug clozapine-N-oxide (CNO). Here, we expressed hM3Dq in forebrain principal neurons. Local field potential and single-neuron recordings revealed that peripheral administration of CNO activated hippocampal neurons selectively in h1M3Dq-expressing mice. Behavioral correlates of neuronal activation included increased locomotion, stereotypy, and limbic seizures. These results demonstrate a powerful chemical-genetic tool for remotely controlling the activity of discrete populations of neurons in vivo.
C1 [Alexander, Georgia M.; Nicolelis, Miguel A.; McNamara, James O.] Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
[Abbas, Atheir I.] Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA.
[Roth, Bryan L.] Duke Univ, NIMH, Psychoact Drug Screening Program, Durham, NC 27710 USA.
[Roth, Bryan L.] Univ N Carolina, Sch Pharm, Dept Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Hartmann, John] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
[Rogan, Sarah C.; Armbruster, Blaine N.; Pei, Ying; Allen, John A.; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Moy, Sheryl S.; Roth, Bryan L.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Program Neurosci, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Roth, Bryan L.] Univ N Carolina, Carolina Integrated Chem Biol & Drug Discovery Ct, Chapel Hill, NC 27599 USA.
[Allen, John A.; Nonneman, Randal J.; Moy, Sheryl S.; Roth, Bryan L.] Univ N Carolina, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA.
RP McNamara, JO (reprint author), Duke Univ, Dept Neurobiol, Durham, NC 27710 USA.
EM jmc@neuro.duke.edu; bryan_roth@med.unc.edu
RI Roth, Bryan/F-3928-2010; Allen, John/D-6141-2011
FU National Institute of Neurological Disease and Stroke [NS060326,
NS049534, NS056217]; National Institute of General Medical Sciences
[GM07040-34, GM008719, GM007250, GM074554]; National Institute of Child
Health and Human Development [H0040127, HD03110]; National Institute of
Mental Health [MHO82441-02]; NARSAD Distinguished InvestigatorAward
FX This work was supported by the following awards from the National
Institutes of Health: NS060326 from the National Institute of
Neurological Disease and Stroke (G.M.A.), GM07040-34 and GM008719 from
the National Institute of General Medical Sciences (S.C.R.), GM007250
from the National Institute of General Medical Sciences (A.I.A.),
GM074554 from the National Institute of General Medical Sciences
(B.N.A.), H0040127 from the National Institute of Child Health and Human
Development (J.A.A.), HD03110 from the National Institute of Child
Health and Human Development (R.J.N., S.S.M.), NS049534 from the
National Institutes of Neurological Disorders and Stroke (M.A.N.),
NS056217 from the National Institute of Neurological Disease and Stroke
(J.O.M.), and MHO82441-02 from the National Institute of Mental Health
(B.L.R.). The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National
Institute of Health. This work is also supported by a NARSAD
Distinguished InvestigatorAward (B.L.R.).
NR 36
TC 255
Z9 255
U1 6
U2 49
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 16
PY 2009
VL 63
IS 1
BP 27
EP 39
DI 10.1016/j.neuron.2009.06.014
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA 473EX
UT WOS:000268189900006
PM 19607790
ER
PT J
AU Bromberg-Martin, ES
Hikosaka, O
AF Bromberg-Martin, Ethan S.
Hikosaka, Okihide
TI Midbrain Dopamine Neurons Signal Preference for Advance Information
about Upcoming Rewards
SO NEURON
LA English
DT Article
ID INTERTEMPORAL CHOICE; OBSERVING RESPONSES; DECISION-MAKING; UNCERTAINTY;
REINFORCEMENT; RESOLUTION; PREDICTION; ENCODE; ACQUISITION; MOTIVATION
AB The desire to know what the future holds is a powerful motivator in everyday life, but it is unknown how this desire is created by neurons in the brain. Here we show that when macaque monkeys are offered a water reward of variable magnitude, they seek advance information about its size. Furthermore, the same midbrain dopamine neurons that signal the expected amount of water also signal the expectation of information, in a manner that is correlated with the strength of the animal's preference. Our data show that single dopamine neurons process both primitive and cognitive rewards, and suggest that current theories of reward-seeking must be revised to include information-seeking.
C1 [Bromberg-Martin, Ethan S.; Hikosaka, Okihide] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Bromberg-Martin, Ethan S.] Brown Univ, Dept Neurosci, Brown NIH Grad Partnership Program, Providence, RI 02906 USA.
RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
EM oh@lsr.nei.nih.gov
FU intramural research program at the National Eye Institute
FX We thank M. Matsumoto, G. La Camera, B.J. Richmond, D. Sheinberg, and V.
Stuphorn for valuable discussions, and G. Tansey, D. Parker, M. Lawson,
B. Nagy, J.W. McClurkin, A.M. Nichols, T.W. Ruffner, L.P. Jensen, and
M.K. Smith for technical assistance. This work was supported by the
intramural research program at the National Eye Institute.
NR 62
TC 121
Z9 124
U1 3
U2 18
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
J9 NEURON
JI Neuron
PD JUL 16
PY 2009
VL 63
IS 1
BP 119
EP 126
DI 10.1016/j.neuron.2009.06.009
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 473EX
UT WOS:000268189900013
PM 19607797
ER
PT J
AU Morens, DM
Taubenberger, JK
Fauci, AS
AF Morens, David M.
Taubenberger, Jeffery K.
Fauci, Anthony S.
TI The Persistent Legacy of the 1918 Influenza Virus
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Morens, David M.; Taubenberger, Jeffery K.; Fauci, Anthony S.] NIAID, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 AI999999]
NR 5
TC 156
Z9 167
U1 1
U2 8
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 16
PY 2009
VL 361
IS 3
BP 225
EP 229
DI 10.1056/NEJMp0904819
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA 470LL
UT WOS:000267976100001
PM 19564629
ER
PT J
AU Weinberg, CR
AF Weinberg, Clarice R.
TI HPV Screening for Cervical Cancer in Rural India
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA.
FU Intramural NIH HHS [Z01 ES040006-11]
NR 1
TC 4
Z9 5
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 16
PY 2009
VL 361
IS 3
BP 305
EP 306
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 470LL
UT WOS:000267976100020
PM 19610159
ER
PT J
AU Troyer, RM
Propst, KL
Fairman, J
Bosio, CM
Dow, SW
AF Troyer, Ryan M.
Propst, Katie L.
Fairman, Jeff
Bosio, Catherine M.
Dow, Steven W.
TI Mucosal immunotherapy for protection from pneumonic infection with
Francisella tularensis
SO VACCINE
LA English
DT Article
DE Bacterial; Mucosa; Lung; Cytokines; Rodent
ID LIVE VACCINE STRAIN; INTRANASAL INTERLEUKIN-12 TREATMENT; LIPOSOME-DNA
COMPLEXES; IN-VIVO; LISTERIA-MONOCYTOGENES; REACTIVE NITROGEN;
IMMUNE-RESPONSE; INTRACELLULAR BACTERIA; RESPIRATORY-INFECTION; CATIONIC
LIPOSOMES
AB Previous studies have demonstrated that systemically administered immunotherapy can protect mice from systemic challenge with the bacterial pathogen Francisella tularensis. However, for protection from inhalational challenge with this bacterium, we wondered if mucosally administered immunotherapy might be more effective. Therefore, we administered cationic liposome-DNA complexes (CLDC), which are potent activators of innate immunity, intranasally (i.n.) and assessed the effectiveness of protection from lethal inhalational challenge with F tularensis. We found that pretreatment by i.n. administration of CLDC 24 h prior to bacterial challenge elicited nearly complete protection of BALB/c mice from lethal challenge with E tularensis LV5 strain. We also observed that mucosal CLDC immunotherapy provided a statistically significant increase in survival time in mice challenged with the highly virulent F tularensis Schu4 strain. Protection was associated with a significant reduction in bacterial burden in the lungs, liver, and spleen. Mucosal administration of CLDC elicited significantly increased expression of IL-12, IFN-gamma, TNF-alpha, IFN-beta and IFN-alpha genes in the lung as detected by real-time quantitative PCR. In vitro treatment of E tularensis infected macrophages with CLDC-elicited cytokines also significantly suppressed intracellular replication of E tularensis in infected macrophages. In vivo, depletion of NK cells prior to administration of CLDC completely abolished the protective effects of CLDC immunotherapy. CLDC-elicited protection was also dependent on induction of IFN-gamma production in vivo. We conclude therefore that activation of local pulmonary innate immune responses is capable of eliciting significant protection from inhalational exposure to a virulent bacterial pathogen. (C) 2009 Published by Elsevier Ltd.
C1 [Troyer, Ryan M.; Propst, Katie L.; Dow, Steven W.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Dow, Steven W.] Colorado State Univ, Dept Clin Sci, Ft Collins, CO 80523 USA.
[Fairman, Jeff] Juvaris BioTherapeut, Pleasanton, CA USA.
[Bosio, Catherine M.] NIAID, Intracellular Parasites Lab, NIH, Hamilton, MT USA.
RP Dow, SW (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
EM sdow@colostate.edu
RI Bosio, Catharine/D-7456-2015
FU National Institute of Allergy and Infectious Diseases SBIR [1 R43
A1060146-01 A2]
FX The authors thank Shayna Warner and Amber Troy for their excellent
technical contributions. Andrew Goodyear provided critical BSU training
and discussion.. This work was supported by a National Institute of
Allergy and Infectious Diseases SBIR grant (1 R43 A1060146-01 A2).
NR 61
TC 17
Z9 17
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 JUL 16
PY 2009
VL 27
IS 33
BP 4424
EP 4433
DI 10.1016/j.vaccine.2009.05.041
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 473OR
UT WOS:000268217600006
PM 19490961
ER
PT J
AU Gudmundsdotter, L
Nilsson, C
Brave, A
Hejdeman, B
Earl, P
Moss, B
Robb, M
Cox, J
Michael, N
Marovich, M
Biberfeld, G
Sandstrom, E
Wahren, B
AF Gudmundsdotter, Lindvi
Nilsson, Charlotta
Brave, Andreas
Hejdeman, Bo
Earl, Patricia
Moss, Bernard
Robb, Merlin
Cox, Josephine
Michael, Nelson
Marovich, Mary
Biberfeld, Gunnel
Sandstrom, Eric
Wahren, Britta
TI Recombinant Modified Vaccinia Ankara (MVA) effectively boosts DNA-primed
HIV-specific immune responses in humans despite pre-existing vaccinia
immunity
SO VACCINE
LA English
DT Article
DE HIV-1 vaccine; Modified Vaccinia virus Ankara (MVA); Pre-existing
immunity
ID CD8(+) T-CELL; VIRUS ANKARA; VACCINATION; VECTOR; IMMUNOGENICITY;
IMMUNIZATION; SMALLPOX; PROTEIN; SAFETY; GLYCOPROTEIN
AB The presence of vector-specific immune responses may hamper the induction of responses to a foreign antigen encoded by the vector. We evaluated the impact of pre-existing immunity to vaccinia virus on the induction of HIV-specific responses after immunization of healthy volunteers with a HIV-1 DNA prime-MVA boost vaccine. Following three priming immunizations with HIV-1 DNA plasmids, the volunteers were boosted with a single injection of recombinant MVA encoding HIV-1 proteins. Pre-existing immunity to vaccinia virus did not reduce the proportion of individuals who responded to HIV-1, but: did lower the magnitude of responses. Our results suggest that vaccinia-based vectors can be used to efficiently induce immune responses to vectored HIV-1 antigens, even in individuals with pre-existing immunity to vaccinia virus. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Gudmundsdotter, Lindvi; Nilsson, Charlotta; Brave, Andreas; Biberfeld, Gunnel; Wahren, Britta] Swedish Inst Infect Dis Control, Stockholm, Sweden.
[Gudmundsdotter, Lindvi; Nilsson, Charlotta; Brave, Andreas; Biberfeld, Gunnel; Wahren, Britta] Karolinska Inst, Stockholm, Sweden.
[Hejdeman, Bo; Sandstrom, Eric] Soder Sjukhuset, Stockholm, Sweden.
[Earl, Patricia; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Robb, Merlin; Michael, Nelson; Marovich, Mary] Walter Reed Army Inst Res, Dept Retroviral, Rockville, MD USA.
[Cox, Josephine] IAVI, New York, NY USA.
RP Gudmundsdotter, L (reprint author), Swedish Inst Infect Dis Control, Stockholm, Sweden.
EM L.gudmundsdotter@smi.se
FU European Union [INCO-DEV A4 ICFP501A4PR03, AVIP 503487]; Swedish
International Development Cooperation Agency (Sida); Department of
Research Cooperation (SAREC) [SWE-2004-120, HIV2004-000809, 2004:813];
Swedish Research Council (VetenskapsrAdet) [K2004-16x-07743-19]; Lakare
mot AIDS Forskningsfond [04-050301, 01-051101]; Division of Intramural
Research; National Institute of Allergy and Infectious Diseases;
National Institutes of Health; US Military HIV Research Program; Walter
Reed Army Institute of Research
FX This study was supported by the European Union (INCO-DEV A4
ICFP501A4PR03, AVIP 503487); Swedish International Development
Cooperation Agency (Sida); Department of Research Cooperation (SAREC)
(SWE-2004-120, HIV2004-000809, 2004:813); Swedish Research Council
(VetenskapsrAdet, K2004-16x-07743-19); Lakare mot AIDS Forskningsfond
(04-050301 and 01-051101). Construction of the HIV-1 modified vaccinia
virus Ankara was supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health and the US Military HIV Research Program. The
production costs were funded by the US Military HIV Research Program,
Walter Reed Army Institute of Research.
NR 33
TC 41
Z9 41
U1 0
U2 2
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 16
PY 2009
VL 27
IS 33
BP 4468
EP 4474
DI 10.1016/j.vaccine.2009.05.018
PG 7
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 473OR
UT WOS:000268217600013
PM 19450644
ER
PT J
AU Hodge, JW
Higgins, J
Schlom, J
AF Hodge, James W.
Higgins, Jack
Schlom, Jeffrey
TI Harnessing the unique local immunostimulatory properties of modified
vaccinia Ankara (MVA) virus to generate superior tumor-specific immune
responses and antitumor activity in a diversified prime and boost
vaccine regimen
SO VACCINE
LA English
DT Article
DE Modified vaccinia Ankara (MVA); Carcinoembryonic antigen (CEA);
Vaccinia; Costimulation
ID HUMAN DENDRITIC CELLS; ANTIGEN 5T4 TROVAX; CANCER-PATIENTS; PHASE-II;
T-CELLS; MICE; IMMUNOGENICITY; EXPRESSION; INDUCTION; INFECTION
AB Recombinant poxviruses expressing tumor-associated antigens (TAAs) are currently being evaluated in clinical trials as an approach to treat various cancers. We have previously generated poxviral vectors expressing a TAA and a TRlad of COstimulatory Molecules (B7-1, ICAM-1, and LFA-3; TRICOM) as transgenes, including replication competent recombinant vaccinia (rV) or replication-defective modified vaccinia Ankara (MVA), to prime tumor-specific immune responses, and a replication-defective recombinant fowlpox (rF) to boost these responses. MVA is a potentially safer, replication-defective form of vaccinia virus with unique immunostimulatory properties that could make it a superior priming vaccine. Here, an MVA vector encoding a tumor antigen (CEA) and TRICOM was utilized (rMVA). A single rMVA-CEA/TRICOM vaccination induced greater expression of several serum cytokines associated with enhanced T-cell immunity than that seen with vaccinia. We hypothesized that this effect might "pre-condition" the vaccination site for a more effective boost. An rMVA-CEA/TRICOM prime followed 7 days later (but not 30 days later) by an rf-CEA/TRICOM boost at the same injection site (but not at a distal site) induced more potent CEA-specific T-cell responses, and superior CEA-specific immunity and antitumor activity, than rV-CEA/TRICOM followed by rF-CEA/TRICOM. This preconditioning effect was also observed using a heterologous antigen model, where priming with rMVA-CEA/TRICOM followed 7 days later by rF-LacZ/TRICOM enhanced beta-gal-specific immunity compared to rF-LacZ/TRICOM only. The studies reported here show for the first time that priming with rMVA followed 7 days later by an rF boost at the same injection site, versus a distal site, generates superior tumor-specific immunity and antitumor activity. Published by Elsevier Ltd.
C1 [Hodge, James W.; Higgins, Jack; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA.
EM js141c@nih.gov
RI Hodge, James/D-5518-2015
OI Hodge, James/0000-0001-5282-3154
FU Intramural NIH HHS [Z01 BC010661-04]; NCI NIH HHS [Z01 BC010661-04]
NR 49
TC 18
Z9 18
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 JUL 16
PY 2009
VL 27
IS 33
BP 4475
EP 4482
DI 10.1016/j.vaccine.2009.05.017
PG 8
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 473OR
UT WOS:000268217600014
PM 19450631
ER
PT J
AU Villanueva, CM
Silverman, DT
Malats, N
Tardon, A
Garcia-Closas, R
Serra, C
Carrato, A
Fortuny, J
Rothman, N
Dosemeci, M
Kogevinas, M
AF Villanueva, Cristina M.
Silverman, Debra T.
Malats, Nuria
Tardon, Adonina
Garcia-Closas, Reina
Serra, Consol
Carrato, Alfredo
Fortuny, Joan
Rothman, Nathaniel
Dosemeci, Mustafa
Kogevinas, Manolis
TI Determinants of Quality of Interview and Impact on Risk Estimates in a
Case-Control Study of Bladder Cancer
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE data collection; environmental exposure; epidemiologic studies;
interviews as topic; methods; odds ratio; quality control;
questionnaires
ID VARIABILITY; QUESTIONS; SPAIN
AB The authors evaluated potential determinants of the quality of the interview in a case-control study of bladder cancer and assessed the effect of the interview quality on the risk estimates. The analysis included 1,219 incident bladder cancer cases and 1,271 controls recruited in Spain in 1998-2001. Information on etiologic factors for bladder cancer was collected through personal interviews, which were scored as unsatisfactory, questionable, reliable, or high quality by the interviewers. Eight percent of the interviews were unsatisfactory or questionable. Increasing age, lower socioeconomic status, and poorer self-perceived health led to higher proportions of questionable or unreliable interviews. The odds ratio for cigarette smoking, the main risk factor for bladder cancer, was 6.18 (95% confidence interval: 4.56, 8.39) overall, 3.20 (95% confidence interval: 1.13, 9.04) among unsatisfactory or questionable interviews, 6.86 (95% confidence interval: 4.80, 9.82) among reliable interviews, and 7.70 (95% confidence interval: 3.64, 16.30) among high-quality interviews. Similar trends were observed for employment in high-risk occupations, drinking water containing elevated levels of trihalomethanes, and use of analgesics. Higher quality interviews led to stronger associations compared with risk estimation that did not take the quality of interview into account. The collection of quality of interview scores and the exclusion of unreliable interviews probably reduce misclassification of exposure in observational studies.
C1 [Villanueva, Cristina M.] CREAL, Ctr Res Environm Epidemiol, Barcelona 08003, Spain.
[Villanueva, Cristina M.; Malats, Nuria; Kogevinas, Manolis] Hosp del Mar, IMIM, Municipal Inst Med Res, Barcelona, Spain.
[Villanueva, Cristina M.; Tardon, Adonina; Kogevinas, Manolis] CIBERESP, Barcelona, Spain.
[Silverman, Debra T.; Rothman, Nathaniel; Dosemeci, Mustafa] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Tardon, Adonina] Univ Oviedo, Oviedo, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, Tenerife, Spain.
[Serra, Consol] Univ Pompeu Fabra, Unit Res Occupat Hlth, Dept Expt & Hlth Sci, Barcelona, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Barcelona, Spain.
[Carrato, Alfredo] Hosp Gen Elche, Elche, Spain.
[Fortuny, Joan] Inst Catala Oncol, Barcelona, Spain.
[Kogevinas, Manolis] Univ Crete, Dept Social Med, Sch Med, Iraklion, Greece.
RP Villanueva, CM (reprint author), CREAL, Ctr Res Environm Epidemiol, Doctor Aiguader 88, Barcelona 08003, Spain.
EM cvillanueva@creal.cat
RI Serra, C/E-6879-2014; Malats, Nuria/H-7041-2015; Villanueva,
Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017
OI Serra, C/0000-0001-8337-8356; Malats, Nuria/0000-0003-2538-3784;
Villanueva, Cristina/0000-0002-0783-1259;
NR 17
TC 8
Z9 8
U1 1
U2 7
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 JUL 15
PY 2009
VL 170
IS 2
BP 237
EP 243
DI 10.1093/aje/kwp136
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 469HU
UT WOS:000267887900013
PM 19478234
ER
PT J
AU Robertson, KL
Thach, DC
AF Robertson, Kelly L.
Thach, Dzung C.
TI LNA flow-FISH: A flow cytometry-fluorescence in situ hybridization
method to detect messenger RNA using locked nucleic acid probes
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Fluorescence in situ hybridization (FISH); Flow cytometry; Locked
nucleic acid (LNA); messenger RNA (mRNA) detection; beta-Actin
ID INSITU HYBRIDIZATION; GENE-EXPRESSION; OLIGONUCLEOTIDE PROBES; HUMAN
TELOMERASE; RIBOSOMAL-RNA; DNA; DESIGN; CELLS; RECOGNITION; INHIBITION
AB We present a novel method using flow cytometry-fluorescence in situ hybridization (flow-FISH) to detect specific messenger RNA (mRNA) in Suspended cells using locked nucleic acid (LNA)-modified oligonucleotide probes. beta-Actin mRNA was targeted in whole A549 epithelial cells by hybridization with a biotinylated, LNA-modified probe. The LNA bound to beta-actin was then stained using phycoerythrin-conjugated streptavidin and detected by flow cytometry. Shifts in fluorescence signal intensity between the beta-actin LNA probe and a biotinylated, nonspecific control LNA were used to determine optimal conditions for this type of flow-FISH. Multiple conditions for permeabilization and hybridization were tested. and it was found that conditions using 3 mu g/ml of proteinase K for permeabilization and 90 min hybridization at 60 degrees C with buffer containing 50% formamide allow cells containing the LNA-bound mRNA to be detected and differentiated from the control LNA with high confidence (< 14% overlap between Curves). This combined method, called LNA flow-FISH, can be used for detection and quantification of other RNA species as well as for telomerase measurement and detection. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Robertson, Kelly L.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA.
[Thach, Dzung C.] NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Robertson, KL (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA.
EM kelly.robertson@nrl.navy.mil
NR 40
TC 27
Z9 28
U1 1
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUL 15
PY 2009
VL 390
IS 2
BP 109
EP 114
DI 10.1016/j.ab.2009.04.026
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 457QB
UT WOS:000266946000002
PM 19393610
ER
PT J
AU Edler, MC
Yang, GL
Jung, MK
Bai, RL
Bornmann, WG
Hamel, E
AF Edler, Michael C.
Yang, Guangli
Jung, M. Katherine
Bai, Ruoli
Bornmann, William G.
Hamel, Ernest
TI Demonstration of microtubule-like structures formed with (-)-rhazinilam
from purified tubulin outside of cells and a simple tubulin-based assay
for evaluation of analog activity
SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Article
DE Tubulin; (-)-rhazinilam; Rhazinilam analogs; Microtubule morphology;
GTP; Sedimentation assay; MCF-7 human breast carcinoma cells; Spiral
morphology of tubulin polymer; Vinblastine; Glutamate
ID ANTIMITOTIC AGENTS; INDUCED POLYMERIZATION; BRAIN TUBULIN; BINDING;
TAXOL; RHAZINILAM; DOLASTATIN-10; VINBLASTINE; MAYTANSINE; COLCHICINE
AB (-)-Rhazinilam was spontaneously generated from a natural product during isolation. In cultured cells, it causes microtubule bundle formation, like those caused by paclitaxel. With tubulin, (-)-rhazinilam causes formation of an aberrant spiral polymer. Using glutamate and GTP, we developed an assay for spiral formation and applied it to 17 new (+/-)-rhazinilam analogs with either a modified side chain or a different size D ring. There was reasonable correlation between spiral formation and inhibition of human MCF-7 breast carcinoma cell growth. Only one side chain analog was as active as (+/-)-rhazinilam. During these studies, we observed that omitting GTP from the reaction mixture caused a major change in the morphology of the (-)-rhazinilam-induced polymer, with half the observed polymer being microtubule-like and half being spirals. This mixed polymer slowly disassembled at 0 degrees C, but there was no apparent difference in the lability of the microtubules versus the spirals. Published by Elsevier Inc.
C1 [Edler, Michael C.; Bai, Ruoli; Hamel, Ernest] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Yang, Guangli; Bornmann, William G.] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst Canc Res, Organ Synth Core Facil, New York, NY 10021 USA.
[Jung, M. Katherine] NIAAA, Div Metab & Hlth Effects, NIH, Bethesda, MD 20892 USA.
RP Hamel, E (reprint author), NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bldg 469,Room 104, Frederick, MD 21702 USA.
EM hamele@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 28
TC 11
Z9 11
U1 1
U2 5
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 JUL 15
PY 2009
VL 487
IS 2
BP 98
EP 104
DI 10.1016/j.abb.2009.05.014
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 471QF
UT WOS:000268072500004
PM 19497297
ER
PT J
AU Ward, MM
Hendrey, MR
Malley, JD
Learch, TJ
Davis, JC
Reveille, JD
Weisman, MH
AF Ward, Michael M.
Hendrey, Matthew R.
Malley, James D.
Learch, Thomas J.
Davis, John C., Jr.
Reveille, John D.
Weisman, Michael H.
TI Clinical and Immunogenetic Prognostic Factors for Radiographic Severity
in Ankylosing Spondylitis
SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
LA English
DT Article
ID DISEASE EXPRESSION; RADIOLOGICAL MANIFESTATIONS; HLA-B27 HOMOZYGOSITY;
GENES; SUSCEPTIBILITY; INVOLVEMENT; PROGRESSION; PREDICTORS; MOBILITY;
FEATURES
AB Objective. To improve prognostic ability in ankylosing spondylitis (AS), we sought to identify demographic, clinical, and immunogenetic characteristics associated with radiographic severity in a large cohort of patients.
Methods. Patients with AS for >= 20 years were enrolled in a cross-sectional study (n = 398). Pelvic and spinal radiographs were scored using the Bath Ankylosing Spondylitis Radiology Index for the spine (BASRI-s), and radiographic severity was measured as the BASRI-s/duration of AS. Clinical factors and HLA-B, DR, DQ, and DP alleles associated with the highest quartile of the distribution of radiographic severity were identified by first using random forests and then using multivariable logistic regression modeling. Similar procedures were used to identify factors associated with the lowest quartile of radiographic severity.
Results. Radiographic severity (being in the top quartile of BASRI-s/duration of AS) was associated with older age at onset of AS (odds ratio [OR] 1.10 per year), male sex (OR 1.90), current smoker (OR 4.72), and the presence of HLA-B*4100 (OR 11.73), DRB1*0804 (OR 12.32), DQA1*0401 (OR 5.24), DQB1*0603 (OR 3.42), and DPB1*0202 (OR 23.36), whereas the presence of DRB1*0801 was strongly negatively associated (OR 0.03). Being in the lowest quartile of BASRI-s/duration of AS was also less likely among those with an older age at onset of AS (OR 0.94 per year), men (OR 0.281, and current smokers (OR 0.29).
Conclusion. The accuracy of the prognosis of radiographic severity in AS is improved by knowing the age at disease onset, sex, smoking history, and the presence of HLA-B*4100, DRB1*0804, DQA1*0401, DQB1*0603, DRB1*0801, and DPB1*0202 alleles.
C1 [Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Hendrey, Matthew R.] SRA Int Inc, Fairfax, VA USA.
[Learch, Thomas J.; Weisman, Michael H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Davis, John C., Jr.] Genentech Inc, San Francisco, CA 94080 USA.
[Davis, John C., Jr.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Reveille, John D.] Univ Texas Houston, Houston, TX USA.
RP Ward, MM (reprint author), NIAMSD, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
EM wardm1@mail.nih.gov
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases, NIH [R01-AR048465]; Cedars-Sinai
General Clinical Research Center [M01-RR00425]; University of Texas at
Houston General Clinical Research Center [M01-RR02558]; Rosalind Russell
Center for Arthritis Research at the University of California, San
Francisco
FX Supported in part by the Intramural Research Program of the National
Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, and
by the NIH/National Institute of Arthritis and Musculoskeletal and Skin
Diseases (grant R01-AR048465), Cedars-Sinai General Clinical Research
Center (grant M01-RR00425), University of Texas at Houston General
Clinical Research Center (grant M01-RR02558), and The Rosalind Russell
Center for Arthritis Research at the University of California, San
Francisco.
NR 39
TC 55
Z9 58
U1 1
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRIT RHEUM-ARTHR
JI Arthritis Rheum-Arthritis Care Res.
PD JUL 15
PY 2009
VL 61
IS 7
BP 859
EP 866
DI 10.1002/art.24585
PG 8
WC Rheumatology
SC Rheumatology
GA 472RZ
UT WOS:000268151100001
PM 19565552
ER
PT J
AU Gold, MS
Kobeissy, FH
Wang, KKW
Merlo, LJ
Bruijnzeel, AW
Krasnova, IN
Cadet, JL
AF Gold, Mark S.
Kobeissy, Firas H.
Wang, Kevin K. W.
Merlo, Lisa J.
Bruijnzeel, Adriaan W.
Krasnova, Irina N.
Cadet, Jean Lud
TI Methamphetamine- and Trauma-induced Brain Injuries: Comparative Cellular
and Molecular Neurobiological Substrates
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE alpha II-spectrin; brain injury; calpain; caspase; neuroproteomics;
neurotoxicity; methamphetamine; proteolysis; psychoproteomics
ID SPECTRIN BREAKDOWN PRODUCTS; ALPHA-II-SPECTRIN; MITOCHONDRIAL
PERMEABILITY TRANSITION; PROTEIN EXPRESSION PROFILE; CONTROLLED CORTICAL
IMPACT; RAT-BRAIN; ORBITOFRONTAL CORTEX; CEREBROSPINAL-FLUID; NEURONAL
APOPTOSIS; CALPAIN ACTIVATION
AB The use of methamphetamine (METH) is a growing public health problem, because its abuse is associated with long-term biochemical and structural effects on the human brain. Neurodegeneration is often observed in humans, because of mechanical injuries (e.g., traumatic brain injury [TBI]) and ischemic damage (strokes). In this review, we discuss recent findings documenting the fact that the psychostimulant drug METH can cause neuronal damage in several brain regions. The accumulated evidence from our laboratories and those of other investigators indicates that acute administration of METH leads to activation of calpain and caspase proteolytic systems. These systems are also involved in causing neuronal damage secondary to traumatic and ischemic brain injuries. Protease activation is accompanied by proteolysis of endogenous neuronal structural proteins (all-spectrin protein and microtubule-associated protein-tau), evidenced by the appearance of their breakdown products after these injuries. When taken together, these observations suggest that METH exposure, like TBI, can cause substantial damage to the brain by causing both apoptotic and necrotic cell death in the brains of METH addicts who use large doses of the drug during their lifetimes. Finally, because METH abuse is accompanied by functional and structural changes in the brain similar to those in TBI, METH addicts might experience greater benefit if their treatment involved greater emphasis on rehabilitation in conjunction with potential neuroprotective pharmacological agents such as calpain and caspase inhibitors similar to those used in TBI.
C1 [Gold, Mark S.; Kobeissy, Firas H.; Merlo, Lisa J.; Bruijnzeel, Adriaan W.] Univ Florida, McKnight Brain Inst, Dept Psychiat, Gainesville, FL 32610 USA.
[Gold, Mark S.] Univ Florida, McKnight Brain Inst, Coll Med, Dept Community Hlth & Family Med, Gainesville, FL 32610 USA.
[Gold, Mark S.; Kobeissy, Firas H.; Wang, Kevin K. W.] Univ Florida, McKnight Brain Inst, Ctr Neuroprote & Biomarkers Res, Gainesville, FL 32610 USA.
[Krasnova, Irina N.; Cadet, Jean Lud] Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA.
[Wang, Kevin K. W.] Banyan Biomarkers Inc, Alachua, FL USA.
RP Kobeissy, FH (reprint author), Univ Florida, McKnight Brain Inst, Dept Psychiat, POB 10015,100 S Newell Dr, Gainesville, FL 32610 USA.
EM firasko@ufl.edu
RI kobeissy, firas/E-7042-2017;
OI kobeissy, firas/0000-0002-5008-6944; Wang, Kevin/0000-0002-9343-6473
FU Donald Dizney Eminent Scholar Chair; Capebranch and Riverbranch
Endowments,. Department of Psychiatry at the University of Florida;
Department of Health and Human Services/National Institutes of Health
(NIH/Nations Institute of Drug Abuse (NIDA); NIDA [T32-DA-07313-10];
Department of Defense [DAMD17-03-1-0066]; NIH [R01 NS052831, R01 051,
431]
FX This work. was supported in part by the Donald Dizney Eminent Scholar
Chair, hell by Mark S. Gold, M.D., Distinguished Professor, at McKnight
Brain Institute, College of Medicine. and the Capebranch and Riverbranch
Endowments,. Department of Psychiatry at the University of Florida, Jean
Lud Cadet, M.D., and Irina A,. Krasnova, Ph.D., are supported by The
Intramural Research Program of the Department of Health and Human
Services/National Institutes of Health (NIH/Nations Institute of Drug
Abuse (NIDA). Lis J. Merlo, Ph.D., is supported in part by NIDA training
Grant T32-DA-07313-10 (PI: Cottler) on which she is a postdoctoral
research scholar. This work was supported in part by the Department of
Defense Grant DAMD17-03-1-0066 and NIH Grants R01 NS052831 and R01 051,
431. The authors report no biomedical financial interests or potential
conflicts of interest.
NR 103
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U1 2
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2009
VL 66
IS 2
BP 118
EP 127
DI 10.1016/j.biopsych.2009.02.021
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YO
UT WOS:000267470400004
PM 19345341
ER
PT J
AU Lu, L
Wang, X
Wu, P
Xu, CM
Zhao, M
Morales, M
Harvey, BK
Hoffer, BJ
Shaham, Y
AF Lu, Lin
Wang, Xi
Wu, Ping
Xu, Chunmei
Zhao, Mei
Morales, Marisela
Harvey, Brandon K.
Hoffer, Barry J.
Shaham, Yavin
TI Role of Ventral Tegmental Area Glial Cell Line-Derived Neurotrophic
Factor in Incubation of Cocaine Craving
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Drug self-administration; ERK; extinction; glial cell line-derived
neurotrophic factor; growth factors; reinstatement; relapse; ventral
tegmental area
ID ADENOASSOCIATED VIRAL VECTOR; SIGNAL-TRANSDUCTION CASCADE; MESOLIMBIC
DOPAMINE SYSTEM; MESSENGER-RNA EXPRESSION; IN-VIVO; PLACE PREFERENCE;
KNOCKOUT MICE; SYNAPTIC PLASTICITY; ALCOHOL-CONSUMPTION;
NUCLEUS-ACCUMBENS
AB Background: Ventral tegmental area (VTA) brain-derived neurotrophic factor (BDNF) contributes to time-dependent increases in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Here, we studied the role of glial cell line-derived neurotrophic factor (GDNF) in incubation of cocaine craving because, like BDNF, GDNF provides trophic support to midbrain dopamine neurons.
Methods: We first trained rats to self-administer intravenous cocaine for 10 days (6 hours/d, cocaine injections were paired with a tone-light cue). We then manipulated VTA GDNF function and assessed cue-induced cocaine seeking in extinction tests after withdrawal from cocaine.
Results: VTA injections of an adeno-associated virus (AAV) vector containing rat GDNF cDNA (5 x 10(8) viral genomes) on withdrawal Day 1 increased cue-induced cocaine seeking on withdrawal days 1 land 31; this effect was not observed after VTA injections of an AAV viral vector containing red fluorescent protein (RFP). Additionally, VTA, but not substantial nigra (SN), GDNF injections (1.25 mu g or 12.5 mu g/side) immediately after the last cocaine self-ad ministration session increased cue-induced drug seeking on withdrawal days 3 and 10; this effect was reversed by VTA injections of U0126, which inhibits the activity of extracellular signal-regulated kinases (ERK). Finally, interfering with VTA GDNF function by chronic delivery of anti-GDNF monoclonal neutralizing antibodies via minipumps (600 ng/side/d) during withdrawal Days 1-14 prevented the time-dependent increases in cue-induced cocaine seeking on withdrawal days 11 and 31.
Conclusions: Our results indicate that during the first weeks of withdrawal from cocaine self-administration, GDNF-dependent neuroadaptations in midbrain VTA neurons play an important role in the development of incubation of cocaine craving.
C1 [Lu, Lin; Wang, Xi; Wu, Ping; Xu, Chunmei; Zhao, Mei] Peking Univ, Natl Inst Drug Dependence, Beijing 100191, Peoples R China.
[Morales, Marisela; Harvey, Brandon K.; Hoffer, Barry J.; Shaham, Yavin] Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD USA.
RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, 38 Xueyuan Rd, Beijing 100191, Peoples R China.
EM linlu@bjmu.edu.cn
RI Harvey, Brandon/A-5559-2010; shaham, yavin/G-1306-2014
FU National Institute on Drug Abuse (National Institutes of Health, U.S.
Department of Health and Human Services); National Basic Research
Program of China [2007CB512302, 2009CB522004]; National High Technology
Research and Development Program of China [2006AA02Z4D1]; Natural
Science Foundation of China [30,670,713, 30,725,016]
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse (National Institutes of Health, U.S.
Department of Health and Human Services) and by the National Basic
Research Program of China (Grant Nos. 2007CB512302 and 2009CB522004),
the National High Technology Research and Development Program of China
(863 Program, Grant No. 2006AA02Z4D1), and the Natural Science
Foundation of China (Grant Nos. 30,670,713 and 30,725,016). We thank
Sarah Gray, Kristina Wihbey, Haifeng Zhai, Katie Zuchowski, and Doug
Howard for expert technical assistance and Dr. Dorit Ron for helpful
comments.
NR 86
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U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2009
VL 66
IS 2
BP 137
EP 145
DI 10.1016/j.biopsych.2009.02.009
PG 9
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YO
UT WOS:000267470400006
PM 19345340
ER
PT J
AU Moeller, SJ
Maloney, T
Parvaz, MA
Dunning, JP
Alia-Klein, N
Woicik, PA
Hajcak, G
Telang, F
Wang, GJ
Volkow, ND
Goldstein, RZ
AF Moeller, Scott J.
Maloney, Thomas
Parvaz, Muhammad A.
Dunning, Jonathan P.
Alia-Klein, Nelly
Woicik, Patricia A.
Hajcak, Greg
Telang, Frank
Wang, Gene-Jack
Volkow, Nora D.
Goldstein, Rita Z.
TI Enhanced Choice for Viewing Cocaine Pictures in Cocaine Addiction
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Choice behavior; cocaine addiction; craving; IAPS pictures reward;
neuropsychology; salience; unconscious motivation
ID DOPAMINE D2 RECEPTORS; NEUROANATOMICAL SPECIFICITY; ATTENTIONAL BIAS;
MONETARY REWARD; RHESUS-MONKEYS; USERS; FOOD; STRESS; CUES;
REINFORCEMENT
AB Background: Individuals with cocaine use disorder (CUD) chose cocaine over nondrug rewards. in two newly designed laboratory tasks with pictures, we document this modified choice outside of a cocaine administration paradigm.
Methods: Choice for viewing cocaine, pleasant, unpleasant, or neutral pictures-under explicit contingencies (choice made between two fully visible side-by-side images) and under more implicit contingencies (selections made between pictures hidden under flipped-over cards)-was examined in 20 CUD and 20 matched healthy control subjects. Subjects also provided self-reported ratings of each picture's pleasantness and arousal.
Results: Under both contingencies, CUD subjects chose to view more cocaine pictures than control subjects, group differences that were not fully explained by the self-reported picture ratings. Furthermore, whereas CUD subjects' choice for viewing cocaine pictures exceeded choice for viewing unpleasant pictures (but did not exceed choice for viewing pleasant pictures, in contrast to their self-reported ratings), healthy control subjects avoided viewing cocaine pictures as frequently as, or even more than, unpleasant pictures. Finally, CUD subjects with the most cocaine viewing selections, even when directly compared with selections of the pleasant pictures, also reported the most frequent recent cocaine use.
Conclusions: Enhanced drug-related choice in cocaine addiction can be demonstrated even for nonpharmacologic (pictorial) stimuli. This choice, which is modulated by alternative stimuli, partly transcends self-reports (possibly indicative of a disconnect in cocaine addiction between self-reports and objective behavior) to provide an objective marker of addiction severity. Neuroimaging studies are needed to establish the neural underpinnings of such enhanced cocaine-related choice.
C1 [Moeller, Scott J.] Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA.
[Maloney, Thomas; Parvaz, Muhammad A.; Dunning, Jonathan P.; Alia-Klein, Nelly; Woicik, Patricia A.; Telang, Frank; Wang, Gene-Jack; Goldstein, Rita Z.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Dunning, Jonathan P.; Hajcak, Greg] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Volkow, Nora D.] Natl Inst Drug Abuse, Directors Off, Bethesda, MD USA.
RP Moeller, SJ (reprint author), Univ Michigan, Dept Psychol, 3221 E Hall, Ann Arbor, MI 48109 USA.
EM smoeller@umich.edu
RI Moeller, Scott/L-5549-2016;
OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327
FU National Institute on Drug Abuse [1R01DA023579, R21DA02062]; General
Clinical Research Center [5-MO1-RR-10710]
FX This study was supported by grants from the National Institute on Drug
Abuse (to RZG, Grant Nos. 1R01DA023579 and R21DA02062) and General
Clinical Research Center (5-MO1-RR-10710)
NR 56
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U1 6
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2009
VL 66
IS 2
BP 169
EP 176
DI 10.1016/j.biopsych.2009.02.015
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YO
UT WOS:000267470400010
PM 19358975
ER
PT J
AU Zhu, PJ
Hobson, JP
Southall, N
Qiu, CP
Thomas, CJ
Lu, J
Inglese, J
Zheng, W
Leppla, SH
Bugge, TH
Austin, CP
Liu, S
AF Zhu, Ping Jun
Hobson, John P.
Southall, Noel
Qiu, Cunping
Thomas, Craig J.
Lu, Jiamo
Inglese, James
Zheng, Wei
Leppla, Stephen H.
Bugge, Thomas H.
Austin, Christopher P.
Liu, Shihui
TI Quantitative high-throughput screening identifies inhibitors of
anthrax-induced cell death
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Anthrax lethal factor; Quantitative high-throughput screening;
Niclosamide; Diphyllin; Anthrax; Endocytosis
ID RESPIRATORY SYNDROME CORONAVIRUS; ADP-RIBOSYLATING TOXINS; TUMOR-CELLS;
DIPHTHAMIDE; RECEPTORS; INFECTION; LIBRARIES; TARGET; ENTRY
AB Here, we report the results of a quantitative high-throughput screen (qHTS) measuring the endocytosis and translocation of a beta-lactamase-fused-lethal factor and the identification of small molecules capable of obstructing the process of anthrax toxin internalization. Several small molecules protect RAW264.7 macrophages and CHO cells from anthrax lethal toxin and protected cells from an LF-Pseudomonas exotoxin fusion protein and diphtheria toxin. Further efforts demonstrated that these compounds impaired the PA heptamer pre-pore to pore conversion in cells expressing the CMG2 receptor, but not the related TEM8 receptor, indicating that these compounds likely interfere with toxin internalization. (C) 2009 Published by Elsevier Ltd.
C1 [Lu, Jiamo; Leppla, Stephen H.; Liu, Shihui] NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA.
[Zhu, Ping Jun; Southall, Noel; Thomas, Craig J.; Inglese, James; Zheng, Wei; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, Natl Inst Hlth, Rockville, MD 20850 USA.
[Hobson, John P.; Qiu, Cunping; Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, 33 North Dr, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov; thomas.bugge@nih.gov; austinc@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU National Institute of Dental and Craniofacial Research; National
Institute of Allergy and Infectious Diseases; National Human Genome
Research Institute; NIAID; ICs; National Institutes of Health Roadmap
for Medical Research
FX We thank Carleen Klumpp and Sam Michael for assistance with the robotic
screen, and Adam Yasgar and Paul Shinn for assistance with compound
management. This research was supported by: the Intramural Research
Programs of the National Institute of Dental and Craniofacial Research,
National Institute of Allergy and Infectious Diseases, and National
Human Genome Research Institute; by the NIAID Support of Intramural
Biodefense Research from ICs other than NIAID, and by the Molecular
Libraries Initiative of the National Institutes of Health Roadmap for
Medical Research.
NR 27
TC 20
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U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2009
VL 17
IS 14
BP 5139
EP 5145
DI 10.1016/j.bmc.2009.05.054
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 469CM
UT WOS:000267873000034
PM 19540764
ER
PT J
AU Xu, H
Eck, PK
Baidoo, KE
Choyke, PL
Brechbiel, MW
AF Xu, Heng
Eck, Peter K.
Baidoo, Kwamena E.
Choyke, Peter L.
Brechbiel, Martin W.
TI Toward preparation of antibody-based imaging probe libraries for
dual-modality positron emission tomography and fluorescence imaging
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Molecular imaging; PET; SPECT; Optical imaging; Monoclonal antibody;
EGFR; HER2
ID MAGNETIC-RESONANCE; BREAST-CANCER; AGENT; RADIOIMMUNOTHERAPY;
INHIBITION; AFFIBODY; THERAPY; DESIGN
AB Two novel imaging agents trastuzumab-Cy5.5-CHX-A '' 1 and cetuximab-Cy7-CHX-A '' 2, bearing both a chelating moiety (CHX-A '') for sequestering metallic radionuclides ((86)Y or (111)In) and the near infrared dye Cy5.5/Cy7, were prepared by a novel modular synthetic strategy as examples of dual-labeled, anti-body-based imaging probe library. Fluorescent microscopy illustrated that 1 and 2 strongly bind to HER2-expressing cancer cells (e.g., NIH3T3-HER2(+), SKOV-3) and to EGFR-expressing cancer cells (e. g., A431), respectively, thereby demonstrating that the functionality of the targeting moiety is conserved. Hence, the described novel synthesis strategy can be applied to engineer other tumor-targeted monoclonal antibody based probes for multimodality imaging. Published by Elsevier Ltd.
C1 [Xu, Heng; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
[Eck, Peter K.; Choyke, Peter L.] NCI, Mol Imaging Program, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Natl Inst Hlth, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
OI Eck, Peter/0000-0003-2371-9774
FU NIH; National Cancer Institute; Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 29
TC 25
Z9 25
U1 4
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2009
VL 17
IS 14
BP 5176
EP 5181
DI 10.1016/j.bmc.2009.05.048
PG 6
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 469CM
UT WOS:000267873000039
PM 19505829
ER
PT J
AU Ko, HJ
Das, A
Carter, RL
Fricks, IP
Zhou, YX
Ivanov, AA
Melman, A
Joshi, BV
Kovac, P
Hajduch, J
Kirk, KL
Harden, TK
Jacobson, KA
AF Ko, Hyojin
Das, Arijit
Carter, Rhonda L.
Fricks, Ingrid P.
Zhou, Yixing
Ivanov, Andrei A.
Melman, Artem
Joshi, Bhalchandra V.
Kovac, Pavol
Hajduch, Jan
Kirk, Kenneth L.
Harden, T. Kendall
Jacobson, Kenneth A.
TI Molecular recognition in the P2Y(14) receptor: Probing the structurally
permissive terminal sugar moiety of uridine-5 '-diphosphoglucose
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE G protein-coupled receptor; Nucleotides; Pyrimidines; Phospholipase C;
Carbohydrates; Uracil
ID PROTEIN-COUPLED RECEPTORS; SELECTIVE AGONISTS; CRYSTAL-STRUCTURE;
PHOSPHOLIPASE-C; DENDRITIC CELLS; P2Y14 RECEPTOR; P2 RECEPTORS;
UDP-GLUCOSE; ADENOSINE; ANALOGS
AB The P2Y(14) receptor, a nucleotide signaling protein, is activated by uridine-5'-diphosphoglucose 1 and other uracil nucleotides. We have determined that the glucose moiety of 1 is the most structurally permissive region for designing analogues of this P2Y(14) agonist. For example, the carboxylate group of uridine-5'-diphosphoglucuronic acid proved to be suitable for flexible substitution by chain extension through an amide linkage. Functionalized congeners containing terminal 2-acylaminoethylamides prepared by this strategy retained P2Y(14) activity, and molecular modeling predicted close proximity of this chain to the second extracellular loop of the receptor. In addition, replacement of glucose with other sugars did not diminish P2Y(14) potency. For example, the [500] ribose derivative had an EC50 of 0.24 mu M. Selective monofluorination of the glucose moiety indicated a role for the 2 ''- and 6 ''- hydroxyl groups of 1 in receptor recognition. The beta-glucoside was twofold less potent than the native alpha-isomer, but methylene replacement of the 1 ''-oxygen abolished activity. Replacement of the ribose ring system with cyclopentyl or rigid bicyclo[3.1.0] hexane groups abolished activity. Uridine-5'-diphosphoglucose also activates the P2Y(2) receptor, but the 2-thio analogue and several of the potent modified-glucose analogues were P2Y(14)-selective. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Ko, Hyojin; Das, Arijit; Ivanov, Andrei A.; Joshi, Bhalchandra V.; Kovac, Pavol; Hajduch, Jan; Kirk, Kenneth L.; Jacobson, Kenneth A.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Carter, Rhonda L.; Fricks, Ingrid P.; Zhou, Yixing; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH [GM38213]; National Institute of Diabetes and Digestive and Kidney
Diseases
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Diabetes and Digestive and Kidney
Diseases. This work was supported by National Institutes of Health Grant
GM38213 to T. K. Harden.
NR 40
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U1 2
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2009
VL 17
IS 14
BP 5298
EP 5311
DI 10.1016/j.bmc.2009.05.024
PG 14
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 469CM
UT WOS:000267873000052
PM 19502066
ER
PT J
AU Zhao, XZ
Maddali, K
Marchand, C
Pommier, Y
Burke, TR
AF Zhao, Xue Zhi
Maddali, Kasthuraiah
Marchand, Christophe
Pommier, Yves
Burke, Terrence R., Jr.
TI Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric
arylamide functionality
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE HIV-1 integrase; Inhibit; Enantiomer; Arylamide; Diketoacid
ID VIRUS TYPE-1 INTEGRASE; TN5 TRANSPOSASE; BINDING MODE; RALTEGRAVIR;
DESIGN; POTENT; SAR
AB Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3( 2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer. The potency difference for enantiomers based on the isoindoline-1,3-dione ring system is less than for those derived from the isoindol-1-one ring system. Our findings provide useful information that should aid in understanding molecular binding interactions of DKA-derived IN inhibitors. Published by Elsevier Ltd.
C1 [Zhao, Xue Zhi; Burke, Terrence R., Jr.] NCI, Lab Med, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Maddali, Kasthuraiah; Marchand, Christophe; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Burke, TR (reprint author), NCI, Lab Med, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM tburke@helix.nih.gov
RI Zhao, Xue Zhi/N-9594-2014; Burke, Terrence/N-2601-2014
OI Zhao, Xue Zhi/0000-0003-1006-6364;
FU NIH, Center for Cancer Research, National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the NIH, Center for Cancer Research, National Cancer Institute.
NR 27
TC 23
Z9 24
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD JUL 15
PY 2009
VL 17
IS 14
BP 5318
EP 5324
DI 10.1016/j.bmc.2009.05.008
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 469CM
UT WOS:000267873000054
PM 19527935
ER
PT J
AU Bozdag, S
Close, TJ
Lonardi, S
AF Bozdag, Serdar
Close, Timothy J.
Lonardi, Stefano
TI A compartmentalized approach to the assembly of physical maps
SO BMC BIOINFORMATICS
LA English
DT Article
ID RICE GENOME; FINGERPRINTED CLONES; DRAFT SEQUENCE; SOFTWARE; L.;
EVOLUTION; CONTIGS; FPC; BAC
AB Background: Physical maps have been historically one of the cornerstones of genome sequencing and map-based cloning strategies. They also support marker assisted breeding and EST mapping. The problem of building a high quality physical map is computationally challenging due to unavoidable noise in the input fingerprint data.
Results: We propose a novel compartmentalized method for the assembly of high quality physical maps from fingerprinted clones. The knowledge of genetic markers enables us to group clones into clusters so that clones in the same cluster are more likely to overlap. For each cluster of clones, a local physical map is first constructed using FingerPrinted Contigs (FPC). Then, all the individual maps are carefully merged into the final physical map. Experimental results on the genomes of rice and barley demonstrate that the compartmentalized assembly produces significantly more accurate maps, and that it can detect and isolate clones that would induce "chimeric" contigs if used in the final assembly.
Conclusion: The software is available for download at http://www.cs.ucr.edu/similar to sbozdag/assembler/
C1 [Lonardi, Stefano] Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92521 USA.
[Bozdag, Serdar] NCI, NIH, Bethesda, MD 20892 USA.
[Close, Timothy J.] Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.
RP Lonardi, S (reprint author), Univ Calif Riverside, Dept Comp Sci & Engn, Riverside, CA 92521 USA.
EM bozdags@mail.nih.gov; timothy.close@ucr.edu; stelo@cs.ucr.edu
FU NSF [IIS-0447773, DBI-0321756]
FX This project was supported in part by NSF CAREER IIS-0447773, NSF
DBI-0321756 and USDA CSREES Barley-CAP ( visit [ 43] for more
information on this project).
NR 39
TC 1
Z9 1
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 15
PY 2009
VL 10
AR 217
DI 10.1186/1471-2105-10-217
PG 13
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 476OB
UT WOS:000268450800001
PM 19604400
ER
PT J
AU Nita-Lazar, M
Noonan, V
Rebustini, I
Walker, J
Menko, AS
Kukuruzinska, MA
AF Nita-Lazar, Mihai
Noonan, Vikki
Rebustini, Ivan
Walker, Janice
Menko, A. Sue
Kukuruzinska, Menko A.
TI Overexpression of DPAGT1 Leads to Aberrant N-Glycosylation of E-Cadherin
and Cellular Discohesion in Oral Cancer
SO CANCER RESEARCH
LA English
DT Article
ID LYMPH-NODE METASTASIS; ALPHA-CATENIN; TIGHT JUNCTIONS; BETA-CATENIN;
INVERSE CORRELATION; ADHESION; EXPRESSION; COMPLEX; MORPHOGENESIS;
INVASIVENESS
AB Cancer cells are frequently characterized by aberrant increases in protein N-glycosylation and by disruption of E-cadherin-mediated adherens junctions. The relationship between altered N-glycosylation and loss of E-cadherin adhesion in cancer, however, remains unclear. Previously, we reported that complex N-glycans on the extracellular domains of E-cadherin inhibited the formation of mature adherens junctions. Here, we examined whether dysregulated N-glycosylation was one of the underlying causes for cellular discohesion in oral cancer. We show that dense cultures of human salivary epidermoid carcinoma A253 cells exhibited elevated expression of DPAGT1, the gene that initiates protein N-glycosylation. Overexpression of DPAGT1 correlated with the production of E-cadherin-bearing complex N-glycans in nascent adherens junctions. Partial inhibition of DPAGT1 with small interfering RNA reduced the complex N-glycans of E-cadherin and increased the abundance of alpha-catenin and stabilizing proteins in adherens junctions. This was associated with the assembly of functional tight junctions. The inverse relationship between DPAGT1 expression and intercellular adhesion was a feature of oral squamous cell carcinoma. Oral squamous cell carcinomas displayed overexpression of DPAGT1 that correlated with diminished localization of E-cadherin and alpha-catenin at the sites of adherens junctions. Our studies show for the first time that DPAGT1 is an upstream regulator of E-cadherin N-glycosylation status and adherens junction composition and suggest that dysregulation of DPAGT1 causes disturbances in intercellular adhesion in oral cancer. [Cancer Res 2009;69(14):5673-80]
C1 [Nita-Lazar, Mihai; Kukuruzinska, Menko A.] Boston Univ, Med Ctr, Dept Mol & Cell Biol, Boston, MA 02118 USA.
[Noonan, Vikki] Boston Univ, Med Ctr, Dept Oral Pathol, Boston, MA 02118 USA.
[Rebustini, Ivan] Natl Inst Dent & Craniofacial Res, Matrix & Morphogenesis Unit, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA.
[Walker, Janice; Menko, A. Sue] Thomas Jefferson Univ, Dept Anat Pathol & Cell Biol, Philadelphia, PA 19107 USA.
RP Kukuruzinska, MA (reprint author), Boston Univ, Med Ctr, Dept Mol & Cell Biol, 72 E Concord St,E428, Boston, MA 02118 USA.
EM mkukuruz@bu.edu
RI Nita-Lazar, Mihai/Q-2206-2016;
OI Nita-Lazar, Mihai/0000-0002-5099-1311; Noonan, Vikki/0000-0003-4005-0275
FU NIH/NIDCR [5 RO1 DE010183, RO1 DE015304]; NIH/EY [R24 EY014798]
FX Grant support: NIH/NIDCR grants 5 RO1 DE010183 and RO1 DE015304 (MA
Kukuruzinska) and NIH/EY grant R24 EY014798 (A.S. Menko).
NR 47
TC 33
Z9 34
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2009
VL 69
IS 14
BP 5673
EP 5680
DI 10.1158/0008-5472.CAN-08-4512
PG 8
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300011
PM 19549906
ER
PT J
AU Hu, N
Wang, CY
Ng, D
Clifford, R
Yang, HH
Tang, ZZ
Wang, QH
Han, XY
Giffen, C
Goldstein, AM
Taylor, PR
Lee, MP
AF Hu, Nan
Wang, Chaoyu
Ng, David
Clifford, Robert
Yang, Howard H.
Tang, Ze-Zhong
Wang, Quan-Hong
Han, Xiao-You
Giffen, Carol
Goldstein, Alisa M.
Taylor, Philip R.
Lee, Maxwell P.
TI Genomic Characterization of Esophageal Squamous Cell Carcinoma from a
High-Risk Population in China
SO CANCER RESEARCH
LA English
DT Article
ID COPY NUMBER ALTERATIONS; HIGH-INCIDENCE AREA; GENE-EXPRESSION;
FAMILY-HISTORY; ALLELIC LOSS; PANCREATIC-CANCER; ANALYSIS REVEALS;
NORTHERN CHINA; HIGH-FREQUENCY; MESSENGER-RNA
AB Genomic instability plays an important role in most human cancers. To characterize genomic instability in esophageal squamous cell carcinoma (ESCC), we examined loss of heterozygosity (LOH), copy number (CN) loss, CN gain, and gene expression using the Affymetrix GeneChip Human Mapping 500K (n = 30 cases) and Human U133A (n = 17 cases) arrays in ESCC cases from a high-risk region of China. We found that genomic instability measures varied widely among cases and separated them into two groups: a high-frequency instability group (two-thirds of all cases with one or more instability category of >= 10%) and a low-frequency instability group (one-third of cases with instability of <10%). Genomic instability also varied widely across chromosomal arms, with the highest frequency of LOH on 9p (33% of informative single nucleotide polymorphisms), CN loss on 3p (33%), and CN gain on 3q (48%). Twenty-two LOH regions were identified: four on 9p, seven on 9q, four on 13q, two on 17p, and five on 17q. Three CN loss regions-3p12.3, 4p15.1, and 9p21.3-were detected. Twelve CN gain regions were found, including six on 3q, one on 7q, four on 8q, and one on 11q. One of the most gene-rich of these CN gain regions was 11q13.1-13.4, where 26 genes also had RNA expression data available. CN gain was significantly correlated with increased RNA expression in over 80% of these genes. Our findings show the potential utility of combining CN analysis and gene expression data to identify genes involved in esophageal carcinogenesis. [Cancer Res 2009;69(14):5908-17]
C1 [Taylor, Philip R.] NCI, Genet Epidemiol Branch, DCEG, EPS,NIH, Bethesda, MD 20892 USA.
[Clifford, Robert; Yang, Howard H.; Lee, Maxwell P.] NCI, Lab Populat Genet, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Tang, Ze-Zhong; Wang, Quan-Hong; Han, Xiao-You] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
[Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
RP Taylor, PR (reprint author), NCI, Genet Epidemiol Branch, DCEG, EPS,NIH, Room 7006,MSC 7236, Bethesda, MD 20892 USA.
EM ptaylor@mail.nih.gov; leemax@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Division of Cancer Epidemiology and Genetics; Center for Cancer Research
FX Intramural Research Program of the NIH, the National Cancer Institute,
the Division of Cancer Epidemiology and Genetics, and the Center for
Cancer Research.
NR 39
TC 31
Z9 36
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
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2009
VL 69
IS 14
BP 5908
EP 5917
DI 10.1158/0008-5472.CAN-08-4622
PG 10
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300039
PM 19584285
ER
PT J
AU Bian, YS
Terse, A
Du, J
Hall, B
Molinolo, A
Zhang, P
Chen, WJ
Flanders, KC
Gutkind, JS
Wakefield, LM
Kulkarni, AB
AF Bian, Yansong
Terse, Anita
Du, Juan
Hall, Bradford
Molinolo, Alfredo
Zhang, Pin
Chen, Wanjun
Flanders, Kathleen C.
Gutkind, J. Silvio
Wakefield, Lalage M.
Kulkarni, Ashok B.
TI Progressive Tumor Formation in Mice with Conditional Deletion of
TGF-beta Signaling in Head and Neck Epithelia Is Associated with
Activation of the PI3K/Akt Pathway
SO CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-BETA; SQUAMOUS-CELL CARCINOMA; COLON-CANCER; I RECEPTOR;
T-CELLS; ANGIOGENESIS; PROMOTES; CARCINOGENESIS; MUTATIONS;
TUMORIGENESIS
AB The precise role of transforming growth factor (TGF)-beta signaling in head and neck squamous cell carcinoma (SCC) is not yet fully understood. Here, we report generation of an inducible head- and neck-specific knockout mouse model by crossing TGF-beta receptor 1 (Tgfbr1) floxed mice with K14-CreER(lam) mice. By applying tamoxifen to oral cavity of the mouse to induce Cre expression, we were able to conditionally delete Tgfbr1 in the mouse head and neck epithelia. on tumor induction with 7,12-dimethylbenz(a)anthracene (DMBA), 45% of Tgfbr1 conditional knockout (cKO) mice (n = 42) developed SCCs in the head and neck area starting from 16 weeks after treatment. However, no tumors were observed in the control littermates. A molecular analysis revealed an enhanced proliferation and loss of apoptosis in the basal layer of the head and neck epithelia of Tgfbr1 cKO mice 4 weeks after tamoxifen and DMBA treatment. The most notable finding of our study is that the phosphoinositide 3-kinase (PI3K)/Akt pathway was activated in SCCs that developed in the Tgfbr1 cKO mice on inactivation of TGF-beta signaling through Smad2/3 and DMBA treatment. These observations suggest that activation of Smad-independent pathways may contribute cooperatively with inactivation of Smad-dependent pathways to promote head and neck carcinogenesis in these mice. Our results revealed the critical role of the TGF-beta signaling pathway and its crosstalk with the PI3K/Akt pathway in suppressing head and neck carcinogenesis. [Cancer Res 2009;69(14):5918-26]
C1 [Kulkarni, Ashok B.] Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Molinolo, Alfredo; Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA.
[Zhang, Pin; Chen, Wanjun] Natl Inst Dent & Craniofacial Res, Mucosal Immun Sect, Oral Immun & Infect Branch, Bethesda, MD 20892 USA.
[Flanders, Kathleen C.; Wakefield, Lalage M.] NCI, Canc Biol TGF Sect, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Kulkarni, AB (reprint author), Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Lab Cell & Dev Biol, NIH, 30 Convent Dr,Bldg 30,Room 130, Bethesda, MD 20892 USA.
EM ak40m@nih.gov
RI Gutkind, J. Silvio/A-1053-2009
FU Intramural Research Program, National Institute of Dental and
Craniofacial Research, NIH
FX Intramural Research Program, National Institute of Dental and
Craniofacial Research, NIH.
NR 49
TC 44
Z9 46
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2009
VL 69
IS 14
BP 5918
EP 5926
DI 10.1158/0008-5472.CAN-08-4623
PG 9
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300040
PM 19584284
ER
PT J
AU Olkhanud, PB
Baatar, D
Bodogai, M
Hakim, F
Gress, R
Anderson, RL
Deng, J
Xu, M
Briest, S
Biragyn, A
AF Olkhanud, Purevdorj B.
Baatar, Dolgor
Bodogai, Monica
Hakim, Fran
Gress, Ronald
Anderson, Robin L.
Deng, Jie
Xu, Mai
Briest, Susanne
Biragyn, Arya
TI Breast Cancer Lung Metastasis Requires Expression of Chemokine Receptor
CCR4 and Regulatory T Cells
SO CANCER RESEARCH
LA English
DT Article
ID GALACTOSIDE-BINDING PROTEIN; MYELOID SUPPRESSOR-CELLS; MAMMARY-CARCINOMA
4T1; AIRWAY HYPERREACTIVITY; CLINICAL-SIGNIFICANCE; HUMAN CD4(+);
BETA-GBP; NK CELLS; INFLAMMATION; EFFECTOR
AB Cancer metastasis is a leading cause of cancer morbidity and mortality. More needs to be learned about mechanisms that control this process. In particular, the role of chemokine receptors in metastasis remains controversial. Here, using a highly metastatic breast cancer (4T1) model, we show that lung metastasis is a feature of only a proportion of the tumor cells that express CCR4. Moreover, the primary tumor growing in mammary pads activates remotely the expression of TARC/CCL17 and MDC/CCL22 in the lungs. These chemokines acting through CCR4 attract both tumor and immune cells. However, CCR4-mediated chemotaxis was not sufficient to produce metastasis, as tumor cells in the lung were efficiently eliminated by natural killer (NK) cells. Lung metastasis required CCR4(+) regulatory T cells (Treg), which directly killed NK cells using beta-galactoside-binding protein. Thus, strategies that abrogate any part of this process should improve the outcome through activation of effector cells and prevention of tumor cell migration. We confirm this prediction by killing CCR4(+) cells through delivery of TARC-fused toxins or depleting Tregs and preventing lung metastasis. [Cancer Res 2009;69(14):5996-6004]
C1 [Olkhanud, Purevdorj B.; Baatar, Dolgor; Bodogai, Monica; Deng, Jie; Xu, Mai; Biragyn, Arya] NIA, Immunol Lab, Baltimore, MD 21224 USA.
[Anderson, Robin L.] Peter MacCallum Canc Ctr, Canc Biol Lab, Melbourne, Vic, Australia.
[Hakim, Fran; Gress, Ronald] Expt Transplantat & Immunol Branch, Bethesda, MD USA.
[Briest, Susanne] Univ Leipzig, Breast Canc Ctr, Leipzig, Germany.
RP Biragyn, A (reprint author), NIA, Immunol Lab, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA.
EM biragyna@mail.nih.gov
RI Anderson, Robin/I-2306-2013
FU Intramural Research Program of the National Institute on Aging (NIA),
NIH
FX Intramural Research Program of the National Institute on Aging (NIA),
NIH.
NR 47
TC 96
Z9 105
U1 0
U2 14
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2009
VL 69
IS 14
BP 5996
EP 6004
DI 10.1158/0008-5472.CAN-08-4619
PG 9
WC Oncology
SC Oncology
GA 475LJ
UT WOS:000268360300049
PM 19567680
ER
PT J
AU Zorov, DB
Juhaszova, M
Yaniv, Y
Nuss, HB
Wang, S
Sollott, SJ
AF Zorov, Dmitry B.
Juhaszova, Magdalena
Yaniv, Yael
Nuss, H. Bradley
Wang, Su
Sollott, Steven J.
TI Regulation and pharmacology of the mitochondrial permeability transition
pore
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Adenine nucleotide translocator; Cyclophilin D; Mitochondrial
voltage-dependent anion channel; Hexokinase; Creatine kinase;
Mitochondrial peripheral benzodiazepine receptor; Bcl-2; Glycogen
synthase kinase-3 beta
ID DEPENDENT ANION CHANNEL; RAT-LIVER MITOCHONDRIA; CA-2&-INDUCED MEMBRANE
TRANSITION; GLYCOGEN-SYNTHASE KINASE-3-BETA; ADENINE-NUCLEOTIDE
TRANSLOCATOR; HEXOKINASE-BINDING PROTEIN; SENSITIVE K+ CHANNELS;
CYTOCHROME-C RELEASE; CYCLOPHILIN-D; CYCLOSPORINE-A
AB The 'mitochondrial permeability transition', characterized by a sudden induced change of the inner mitochondrial membrane permeability for water as well as for small substances (< 1.5 kDa), has been known for three decades. Research interest in the entity responsible for this phenomenon, the 'mitochondrial permeability transition pore' (mPTP), has dramatically increased after demonstration that it plays a key role in the life and death decision in cells. Therefore, a better understanding of this phenomenon and its regulation by environmental stresses, kinase signalling, and pharmacological intervention is vital. The characterization of the molecular identity of the mPTP will allow identification of possible pharmacological targets and assist in drug design for its precise regulation. However, despite extensive research efforts, at this point the pore-forming core component(s) of the mPTP remain unidentified. Pivotal new genetic evidence has shown that components once believed to be core elements of the mPTP (namely mitochondrial adenine nucleotide translocator and cyclophilin D) are instead only mPTP regulators (or in the case of voltage-dependent anion channels, probably entirely dispensable). This review provides an update on the current state of knowledge regarding the regulation of the mPTP.
C1 [Zorov, Dmitry B.; Juhaszova, Magdalena; Yaniv, Yael; Nuss, H. Bradley; Wang, Su; Sollott, Steven J.] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Box 13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM sollotts@mail.nih.gov
RI Yaniv, Yael/B-3311-2015
OI Yaniv, Yael/0000-0002-5183-6284
FU National Institutes of Health, National Institute on Aging
FX This research was entirely supported by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging.
NR 142
TC 145
Z9 153
U1 1
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL 15
PY 2009
VL 83
IS 2
BP 213
EP 225
DI 10.1093/cvr/cvp151
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 463OF
UT WOS:000267440800007
PM 19447775
ER
PT J
AU Chaudhary, KR
Batchu, SN
Das, D
Suresh, MR
Falck, JR
Graves, JP
Zeldin, DC
Seubert, JM
AF Chaudhary, Ketul R.
Batchu, Sri Nagarjun
Das, Dipankar
Suresh, Mavanur R.
Falck, John R.
Graves, Joan P.
Zeldin, Darryl C.
Seubert, John M.
TI Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated
improved post-ischaemic recovery of heart contractile function
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE B-type natriuretic peptide; Epoxyeicosatrienoic acid;
Ischaemia-reperfusion; GSK-3 beta
ID SOLUBLE EPOXIDE HYDROLASE; GLYCOGEN-SYNTHASE KINASE-3-BETA;
PROTEIN-KINASE-C; K-ATP CHANNELS; ARACHIDONIC-ACID; GENE-EXPRESSION;
INDUCED CARDIOPROTECTION; ISCHEMIA-REPERFUSION; MYOCARDIAL-ISCHEMIA;
CARDIAC MYOCYTES
AB This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null).
Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naive hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C epsilon and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3 beta was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts.
Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.
C1 [Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Das, Dipankar; Suresh, Mavanur R.; Seubert, John M.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
[Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem & Pharmacol, Dallas, TX 75390 USA.
[Graves, Joan P.; Zeldin, Darryl C.] NIEHS NIH, Div Intramural Res, Res Triangle Pk, NC USA.
RP Seubert, JM (reprint author), Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
EM jseubert@pharmacy.ualberta.ca
OI Falck, John/0000-0002-9219-7845
FU NIH, National Institute of Environmental Health Sciences [Z01 ES025034];
Canadian Institutes of Health Research [MOP79465]; USPHS NIH [GM31278];
Robert A. Welch Foundation
FX J. M. S. is the recipient of a New Investigator Award from the Heart and
Stroke Foundation of Canada and a Health Scholar Award from the Alberta
Heritage Foundation for Medical Research. This work was supported by
Canadian Institutes of Health Research Grant (J. M. S., MOP79465) and in
part by the Intramural Research Program of the NIH, National Institute
of Environmental Health Sciences (Z01 ES025034), USPHS NIH (J. R. F.,
GM31278), and the Robert A. Welch Foundation (J. R. F.).
NR 43
TC 28
Z9 29
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL 15
PY 2009
VL 83
IS 2
BP 362
EP 370
DI 10.1093/cvr/cvp134
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 463OF
UT WOS:000267440800022
PM 19401302
ER
PT J
AU Kohn, KW
Aladjem, MI
Weinstein, JN
Pommier, Y
AF Kohn, Kurt W.
Aladjem, Mirit I.
Weinstein, John N.
Pommier, Yves
TI Network architecture of signaling from uncoupled helicase-polymerase to
cell cycle checkpoints and trans-lesion DNA synthesis
SO CELL CYCLE
LA English
DT Article
DE molecular interaction maps; checkpoints; signaling network; replication
stress; helicase-polymerase uncoupling; DNA damage; trans-lesion
synthesis; ATR; claspin; RPA
ID MOLECULAR INTERACTION MAPS; IN-VIVO; REPAIR; ATR; SYSTEMS; DAMAGE;
REPLICATION; DOMAINS; CHK1; FOCI
AB When replication is blocked by a template lesion or polymerase inhibitor while helicase continues unwinding the DNA, single stranded DNA (ssDNA) accumulates and becomes coated with RPA, which then initiates signals via PCNA mono-ubiquitination to activate trans-lesion polymerases and via ATR and Chk1 to inhibit Cdk2-dependent cell cycle progression. The signals are conveyed by way of a complex network of molecular interactions. To clarify those complexities, we have constructed a molecular interaction map (MIM) using a novel hierarchical assembly procedure. Molecules were arranged on the map in hierarchical levels according to interaction step distance from the DNA region of stalled replication. The hierarchical MIM allows us to disentangle the network's interlocking pathways and loops and to suggest functionally significant features of network architecture. The MIM shows how parallel pathways and multiple feedback loops can provide failsafe and robust switch-like responses to replication stress. Within the central level of hierarchy ATR and Claspin together appear to function as a nexus that conveys signals from many sources to many destinations. We noted a division of labor between those two molecules, separating enzymatic and structural roles. In addition, the network architecture disclosed by the hierarchical map, suggested a speculative model for how molecular crowding and the granular localization of network components in the cell nucleus can facilitate function.
C1 [Kohn, Kurt W.; Aladjem, Mirit I.; Weinstein, John N.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA.
EM kohnk@mail.nih.gov
RI Aladjem, Mirit/G-2169-2010
OI Aladjem, Mirit/0000-0002-1875-3110
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 21
TC 5
Z9 5
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 15
PY 2009
VL 8
IS 14
BP 2281
EP 2299
DI 10.4161/cc.8.14.9102
PG 19
WC Cell Biology
SC Cell Biology
GA 470IQ
UT WOS:000267968800033
PM 19556879
ER
PT J
AU Steeg, PS
Anderson, RL
Bar-Eli, M
Chambers, AF
Eccles, SA
Hunter, K
Itoh, K
Kang, YB
Matrisian, LM
Sleeman, JP
Theodorescu, D
Thompson, EW
Welch, DR
AF Steeg, Patricia S.
Anderson, Robin L.
Bar-Eli, Menashe
Chambers, Ann F.
Eccles, Suzanne A.
Hunter, Kent
Itoh, Kazuyuki
Kang, Yibin
Matrisian, Lynn M.
Sleeman, Jonathan P.
Theodorescu, Dan
Thompson, Erik W.
Welch, Danny R.
TI Preclinical Drug Development Must Consider the Impact on Metastasis
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID BREAST-CANCER; PULMONARY METASTASIS; LUNG METASTASIS; CELL-LINE;
PROGRESSION; INHIBITOR; TUMOR; INVASION; THERAPY
C1 [Steeg, Patricia S.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Anderson, Robin L.] Univ Melbourne, Metastasis Res Lab, Peter MacCallum Canc Inst, Dept Pathol, Melbourne, Vic, Australia.
[Bar-Eli, Menashe] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
[Chambers, Ann F.] Univ Western Ontario, Dept Oncol, London Reg Canc Program, London, ON, Canada.
[Eccles, Suzanne A.] Canc Res UK, Ctr Canc Therapeut, Inst Canc Res, Surrey, England.
[Hunter, Kent] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Itoh, Kazuyuki] Osaka Med Ctr Canc & Cardiovasc Dis, Dept Biol, Osaka, Japan.
[Kang, Yibin] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Matrisian, Lynn M.] Vanderbilt Univ, Nashville, TN USA.
[Sleeman, Jonathan P.] Heidelberg Univ, Univ Med Ctr, D-6800 Mannheim, Germany.
[Theodorescu, Dan] Univ Virginia, Charlottesville, VA USA.
[Thompson, Erik W.] Univ Melbourne, Dept Surg, St Vincents Hosp Melbourne, Melbourne, Vic 3010, Australia.
[Welch, Danny R.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA.
RP Steeg, PS (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 1122,900 Rockville Pike, Bethesda, MD 20892 USA.
EM steegp@mail.nih.gov
RI Sleeman, Jonathan/H-2515-2013; Anderson, Robin/I-2306-2013; Chambers,
Ann/L-6285-2015; Thompson, Erik/A-1425-2009
OI Chambers, Ann/0000-0002-9509-5123; Thompson, Erik/0000-0002-9723-4924
FU Intramural NIH HHS [Z01 SC000892-24]
NR 13
TC 25
Z9 25
U1 0
U2 3
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 2009
VL 15
IS 14
BP 4529
EP 4530
DI 10.1158/1078-0432.CCR-09-1363
PG 2
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400004
PM 25278743
ER
PT J
AU Zheng, CY
Cotrim, AP
Sunshine, AN
Sugito, T
Liu, LN
Sowers, A
Mitchel, JB
Baum, BJ
AF Zheng, Changyu
Cotrim, Ana P.
Sunshine, Abraham N.
Sugito, Takayuki
Liu, Lina
Sowers, Anastasia
Mitchel, James B.
Baum, Bruce J.
TI Prevention of Radiation-Induced Oral Mucositis after Adenoviral Vector -
Mediated Transfer of the Keratinocyte Growth Factor cDNA to Mouse
Submandibular Glands
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TRANSGENIC SECRETORY PROTEINS; GENE-TRANSFER; SALIVARY-GLANDS;
NECK-CANCER; EPITHELIAL-CELLS; PAROTID-GLANDS; LUNG INJURY;
CHEMOTHERAPY; HEAD; RADIOTHERAPY
AB Purpose: The study aims to evaluate if human keratinocyte growth factor (hKGF), secreted after transduction of murine salivary glands with adenoviral vectors, can prevent oral mucositis resulting from radiation.
Experimental Design: Two serotype 5 adenoviral vectors encoding hKGF were constructed: AdEF1 alpha-hKGF and AdLTR(2)EF1 alpha-hKGF. Female C3H mice, 8 weeks old, were irradiated by single (22.5 Gy) or fractionated (5 x 8 Gy for 5 days) doses to induce oral mucositis (ulcers on tongue). One day before irradiation, the above viral vectors or an empty vector, Adcontrol, was given (10(10) particles per gland) to both submandibular glands by retrograde ductal instillation. Each experiment included five groups: no irradiation and irradiation (+/-Adcontrol, AdEF1 alpha-hKGF, or AdLTR(2)EF1 alpha-hKGF). Blood, saliva, submandibular glands, and tongue were collected on day 7 for single-dose studies or day 10 for fractionated dosing. hKGF levels were measured by ELISA.
Results: In three separate single-dose irradiation experiments, lingual ulcers were dramatically reduced after either KGF-expressing vector. Similarly, in two separate fractionated irradiation experiments, the hKGF-expressing vectors completely prevented ulcer formation. QPCR data indicated that similar to 10(7) to 10(8) particles of each vector remained in the targeted submandibular glands at the terminal time. Transgenic hKGF protein was found at high levels in saliva, serum, and submandibular gland extracts.
Conclusions: hKGF gene transfer to salivary glands prevented radiation-induced oral mucositis in mice. This proof of concept study suggests that transgenic hKGF secreted from transduced salivary glands maybe useful clinically to prevent oral mucositis caused by radiation.
C1 [Zheng, Changyu] NIDCR, MPTB, NIH, Bethesda, MD 20892 USA.
[Sowers, Anastasia; Mitchel, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Sugito, Takayuki] Nagoya Univ, Sch Med, Dept Oral & Maxillofacial Surg, Nagoya, Aichi 466, Japan.
RP Baum, BJ (reprint author), NIDCR, MPTB, NIH, Bldg 10,Room 1N113,MSC 1190,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bbaum@dir.nidcr.nih.gov
FU Divisions of Intramural Research of the National Institute of Dental and
Craniofacial Research; National Cancer Institute
FX The Divisions of Intramural Research of the National Institute of Dental
and Craniofacial Research and the National Cancer Institute provided
support.
NR 44
TC 23
Z9 24
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2009
VL 15
IS 14
BP 4641
EP 4648
DI 10.1158/1078-0432.CCR-09-0819
PG 8
WC Oncology
SC Oncology
GA 482SG
UT WOS:000268908400017
PM 19584147
ER
PT J
AU Luo, TT
Xu, Y
Rangarajan, J
Hoffman, T
Hwang, YS
Schilling, T
Sargent, T
AF Luo, Ting Thalia
Xu, Yan
Rangarajan, Janaki
Hoffman, Trevor
Hwang, Yoo-Seok
Schilling, Thomas
Sargent, Thomas
TI The diverse functions of transcriptional factor AP2 (TFAP2) targets in
neural crest development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Luo, Ting Thalia; Xu, Yan; Rangarajan, Janaki; Hwang, Yoo-Seok; Sargent, Thomas] NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA.
[Hoffman, Trevor; Schilling, Thomas; Sargent, Thomas] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 20
BP 390
EP 391
DI 10.1016/j.ydbio.2009.05.027
PG 2
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900043
ER
PT J
AU Wang, H
Ge, GN
Ahn, S
AF Wang, Hui
Ge, Guannan
Ahn, Sohyun
TI The role of Gli3 in the neurogenesis of the forebrain
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Wang, Hui; Ge, Guannan; Ahn, Sohyun] NICHD, Unit Dev Neurogenet, PGD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 30
BP 394
EP 394
DI 10.1016/j.ydbio.2009.05.039
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900053
ER
PT J
AU Dawid, IB
Ro, H
AF Dawid, Igor B.
Ro, Hyunju
TI Regulation of dorsalventral axis formation by the control of protein
stability
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Dawid, Igor B.; Ro, Hyunju] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 41
BP 398
EP 398
DI 10.1016/j.ydbio.2009.05.051
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900064
ER
PT J
AU Tuan, RS
AF Tuan, Rocky S.
TI Adult stem cells and nanomaterials in skeletal tissue engineering and
regeneration
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 58
BP 405
EP 405
DI 10.1016/j.ydbio.2009.05.072
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900081
ER
PT J
AU Mishina, Y
Kaartinen, V
Komatsu, Y
AF Mishina, Yuji
Kaartinen, Vesa
Komatsu, Yoshihiro
TI BMP signaling through ACVR1 is crucial for establishment of the
leftright asymmetry via proper formation of node cilia in the mouse
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Mishina, Yuji; Komatsu, Yoshihiro] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Mishina, Yuji; Kaartinen, Vesa; Komatsu, Yoshihiro] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 117
BP 425
EP 425
DI 10.1016/j.ydbio.2009.05.138
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900139
ER
PT J
AU Naiche, LA
Holder, N
Lewandoski, MB
AF Naiche, L. A.
Holder, Nakisha
Lewandoski, Mark B.
TI Fibroblast growth factors (FGFs) are required to maintain the presomitic
mesoderm
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Naiche, L. A.; Holder, Nakisha; Lewandoski, Mark B.] NCI, Frederick, MD 21702 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 125
BP 427
EP 427
DI 10.1016/j.ydbio.2009.05.146
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900147
ER
PT J
AU Bharti, K
Gasper, M
Brucato, M
Arnheiter, H
AF Bharti, Kapil
Gasper, Melanie
Brucato, Martha
Arnheiter, Heinz
TI The role of PAX6 in the development of the retinal pigment epithelium
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Bharti, Kapil; Gasper, Melanie; Brucato, Martha; Arnheiter, Heinz] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 176
BP 440
EP 440
DI 10.1016/j.ydbio.2009.05.198
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900198
ER
PT J
AU Kitagaki, J
Ueda, Y
Chi, X
Costantini, F
Elder, C
Lewandoski, M
Perantoni, A
AF Kitagaki, Jirouta
Ueda, Yutaka
Chi, Xuan
Costantini, Frank
Elder, Cynthia
Lewandoski, Mark
Perantoni, Alan
TI Fgf8 is essential for development of the male reproductive tract
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Kitagaki, Jirouta; Ueda, Yutaka; Elder, Cynthia; Lewandoski, Mark] NCI, Frederick, MD 21701 USA.
[Chi, Xuan; Costantini, Frank] Columbia Univ, Med Ctr, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 186
BP 443
EP 443
DI 10.1016/j.ydbio.2009.05.209
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900208
ER
PT J
AU Chitnis, A
Matsuda, M
Dalle-Nogare, D
Heredia, D
AF Chitnis, Ajay
Matsuda, Miho
Dalle-Nogare, Damian
Heredia, David
TI Modeling the dynamic interactions that lead to the self-organization of
the lateral line system
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Chitnis, Ajay; Matsuda, Miho; Dalle-Nogare, Damian] NICHD, Mol Genet Lab, Bethesda, MD USA.
[Heredia, David] Univ Louisville, Dept Bioengn, Louisville, KY 40292 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 197
BP 446
EP 446
DI 10.1016/j.ydbio.2009.05.220
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900219
ER
PT J
AU Nie, S
Kee, Y
Bronner-Fraser, M
AF Nie, Shuyi
Kee, Yun
Bronner-Fraser, Marianne
TI Myosin-X is critical for the migratory ability of Xenopus cranial neural
crest cells
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Nie, Shuyi; Bronner-Fraser, Marianne] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Kee, Yun] NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 203
BP 447
EP 447
DI 10.1016/j.ydbio.2009.05.226
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900225
ER
PT J
AU Wang, X
Julien, D
Heinz, A
AF Wang, Xin
Julien, Debbache
Heinz, Arnheiter
TI Alternative splicing and cell cycle regulation in vertebrate pigment
cells
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Wang, Xin; Julien, Debbache; Heinz, Arnheiter] NINDS, Mammalian Dev Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 281
BP 468
EP 468
DI 10.1016/j.ydbio.2009.05.307
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900303
ER
PT J
AU Coate, TM
Crenshaw, EB
Kelley, MW
AF Coate, Thomas M.
Crenshaw, E. Bryan
Kelley, Matthew W.
TI Spiral ganglion neuron pathfinding requires Pou3f4 activity in the otic
mesenchyme during the development of the cochlea
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Coate, Thomas M.; Kelley, Matthew W.] NINDS, Sect Dev Neurosci, NIH, Bethesda, MD 20892 USA.
[Crenshaw, E. Bryan] Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 298
BP 473
EP 473
DI 10.1016/j.ydbio.2009.05.325
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900320
ER
PT J
AU Kim, MS
Kitagaki, J
Bollig, F
Englert, C
Perantoni, AO
Lee, SB
AF Kim, Myong Shin
Kitagaki, Jirouta
Bollig, Frank
Englert, Christoph
Perantoni, Alan O.
Lee, Sean B.
TI WID, a novel negative regulator of the MINT signaling pathway, is
important for kidney development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA.
Fritz Lipmann Inst, Leibniz Inst Age Res, Jena, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 338
BP 484
EP 484
DI 10.1016/j.ydbio.2009.05.367
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900358
ER
PT J
AU Morikawa, Y
Zehir, A
Maska, E
Deng, CX
Mishina, Y
Cserjesi, P
AF Morikawa, Yuka
Zehir, Ahmet
Maska, Emily
Deng, Chuxia
Mishina, Yuji
Cserjesi, Peter
TI The regulation of sympathetic nervous system development by
Smad4-dependent and -independent BMP pathways
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Morikawa, Yuka; Zehir, Ahmet; Maska, Emily; Cserjesi, Peter] Tulane Univ, Dept Cell & Mol Biol, New Orleans, LA 70118 USA.
[Deng, Chuxia] NIDDK, Mammalian Genet Sect, NIH, Bethesda, MD USA.
[Mishina, Yuji] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA.
RI Morikawa, Yuka/E-3092-2010
OI Morikawa, Yuka/0000-0002-4571-8409
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 352
BP 488
EP 488
DI 10.1016/j.ydbio.2009.05.382
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900372
ER
PT J
AU Knosp, WM
Hoffman, MP
Martin, GR
AF Knosp, Wendy M.
Hoffman, Matthew P.
Martin, Gail R.
TI Function of Sproutys in salivary gland branching morphogenesis
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Knosp, Wendy M.; Martin, Gail R.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA.
[Knosp, Wendy M.; Martin, Gail R.] Univ Calif San Francisco, CVRI, San Francisco, CA 94143 USA.
[Hoffman, Matthew P.] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 364
BP 491
EP 491
DI 10.1016/j.ydbio.2009.05.394
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900384
ER
PT J
AU Melani, M
Fujita, M
Castranova, D
Davis, A
Gore, A
Swift, M
Ryun-Cha, Y
Lo, BD
Weinstein, BM
AF Melani, Mariana
Fujita, Misato
Castranova, Daniel
Davis, Andrew
Gore, Aniket
Swift, Matthew
Ryun-Cha, Young
Lo, Brigid D.
Weinstein, Brant M.
TI A mutagenesis genetic screen to identify zebrafish embryos with defects
in vasculature development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Melani, Mariana; Fujita, Misato; Castranova, Daniel; Davis, Andrew; Gore, Aniket; Swift, Matthew; Ryun-Cha, Young; Lo, Brigid D.; Weinstein, Brant M.] NICHD, Mol Genet Lab, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 370
BP 493
EP 493
DI 10.1016/j.ydbio.2009.05.400
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900389
ER
PT J
AU Cohn, MJ
Yamaguchi, T
Seifert, AW
AF Cohn, Martin J.
Yamaguchi, Terry
Seifert, Ashley W.
TI Functional and phylogenetic analysis Fgf8 shows that Fgf8 is not
involved in external genital development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Cohn, Martin J.; Seifert, Ashley W.] Univ Florida, Dept Biol, Gainesville, FL USA.
[Yamaguchi, Terry] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 389
BP 497
EP 498
DI 10.1016/j.ydbio.2009.05.419
PG 2
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900408
ER
PT J
AU Joksimovic, M
Yun, BA
Raja, K
Angela, AM
Wendy, CW
Makoto, TM
McKay, RD
Rajeshwar, AB
AF Joksimovic, Milan
Yun, Beth A.
Raja, Kittappa
Angela, Anderegg M.
Wendy, Chang W.
Makoto, Taketo M.
McKay, Ronald D.
Rajeshwar, Awatramani B.
TI Wnt antagonism of Shh facilitates midbrain floor plate neurogenesis
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Joksimovic, Milan; Yun, Beth A.; Angela, Anderegg M.; Rajeshwar, Awatramani B.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA.
[Raja, Kittappa; Wendy, Chang W.; McKay, Ronald D.] NINDS, Mol Biol Lab, Bethesda, MD 20892 USA.
[Makoto, Taketo M.] Kyoto Univ, Grad Sch Med, Kyoto, Japan.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 422
BP 507
EP 508
DI 10.1016/j.ydbio.2009.05.449
PG 2
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900440
ER
PT J
AU Driver, EC
Sillers, L
Rose, M
Zoghbi, H
Kelley, M
AF Driver, Elizabeth C.
Sillers, Laura
Rose, Matthew
Zoghbi, Huda
Kelley, Matthew
TI The Atoh1-expressing cell lineage develops into both hair cells and
supporting cells
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Driver, Elizabeth C.; Sillers, Laura; Kelley, Matthew] NIDCD, Sect Dev Neurosc, NIH, Bethesda, MD USA.
[Rose, Matthew; Zoghbi, Huda] Baylor Coll Med, HHMI, Prog Dev Biol, Houston, TX 77030 USA.
OI Rose, Matthew/0000-0002-1148-4130
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 428
BP 509
EP 509
DI 10.1016/j.ydbio.2009.05.455
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900446
ER
PT J
AU Puligilla, C
Dabdoub, A
Kelley, MW
AF Puligilla, Chandrakala
Dabdoub, Alain
Kelley, Matthew W.
TI Molecular factors that regulate neuronal cell fate determination within
the developing inner ear
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Puligilla, Chandrakala; Dabdoub, Alain; Kelley, Matthew W.] NIDCD, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 429
BP 509
EP 509
DI 10.1016/j.ydbio.2009.05.456
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900447
ER
PT J
AU Gore, AV
Weinstein, BM
AF Gore, Aniket V.
Weinstein, Brant M.
TI R-Spondin mediated canonical Wnt signaling regulates angiogenesis in
zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Gore, Aniket V.; Weinstein, Brant M.] NIH, Mol Genet Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 448
BP 514
EP 514
DI 10.1016/j.ydbio.2009.05.475
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900466
ER
PT J
AU Singh, AP
Archer, TK
AF Singh, Ajeet P.
Archer, Trevor K.
TI SWI/SNF-BAF250A is remodeling chromatin in early embryogenesis and heart
development
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Singh, Ajeet P.; Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, LMC, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RI Singh, Ajeet/G-3935-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 450
BP 514
EP 514
DI 10.1016/j.ydbio.2009.05.477
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900468
ER
PT J
AU Gee, ST
Milgram, SL
Conlon, FL
Moody, SA
AF Gee, Stephen T.
Milgram, Sharon L.
Conlon, Frank L.
Moody, Sally A.
TI YAP is an important regulator of cellular differentiation
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Gee, Stephen T.; Milgram, Sharon L.] UNC, Dept Cell & Dev Biol, Chapel Hill, NC USA.
[Gee, Stephen T.; Milgram, Sharon L.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Conlon, Frank L.] UNC, Dept Genet, Chapel Hill, NC USA.
[Moody, Sally A.] George Washington Univ, Med Ctr, Dept Anat & Regenerat Biol, Washington, DC 20037 USA.
OI Moody, Sally/0000-0003-4192-1087
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 462
BP 518
EP 519
DI 10.1016/j.ydbio.2009.05.490
PG 2
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900480
ER
PT J
AU Znosko, W
Molina, G
Li, CJ
Tsang, W
Dawid, I
Tsang, M
AF Znosko, Wade
Molina, Gabriela
Li, Chengjian
Tsang, Warren
Dawid, Igor
Tsang, Michael
TI Pea3 ETS transcription factors function redundantly to regulate FGF
target genes and development in zebrafish
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Znosko, Wade; Molina, Gabriela; Li, Chengjian; Tsang, Warren; Tsang, Michael] Univ Pittsburgh, MMG, Pittsburgh, PA USA.
[Dawid, Igor] NICHD, LMG, NIH, Bethesda, MD USA.
RI TSANG, Michael/E-2758-2013
OI TSANG, Michael/0000-0001-6384-2422
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 461
BP 518
EP 518
DI 10.1016/j.ydbio.2009.05.489
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900479
ER
PT J
AU Duverger, O
Gentile, NB
Maddox, KM
Morasso, MI
AF Duverger, Olivier
Gentile, Nicole B.
Maddox, Katherine M.
Morasso, Maria I.
TI Conditional ablation of Dlx3 in cranial neural crest-derived cells
results in abnormal development of hair, teeth and craniofacial bone
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 [Duverger, Olivier; Gentile, Nicole B.; Maddox, Katherine M.; Morasso, Maria I.] NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 475
BP 522
EP 522
DI 10.1016/j.ydbio.2009.05.503
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900493
ER
PT J
AU Hwang, J
Kim, JS
Suh, J
Morasso, MI
AF Hwang, Joonsung
Kim, Joung-Soo
Suh, Jean
Morasso, Maria I.
TI Role of Dlx3 in hair cycling
SO DEVELOPMENTAL BIOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Meeting of the Society-for-Developmental-Biology
CY JUL 23-27, 2009
CL San Francisco, CA
SP Soc Dev Biol
C1 NIAMS, Dev Skin Biol Sect, NIH, Bethesda, MD USA.
Hanyang Univ, Dept Dermatol, Coll Med, Seoul 133791, South Korea.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD JUL 15
PY 2009
VL 331
IS 2
MA 476
BP 522
EP 522
DI 10.1016/j.ydbio.2009.05.504
PG 1
WC Developmental Biology
SC Developmental Biology
GA 467XW
UT WOS:000267777900494
ER
PT J
AU Koehler, D
Zakhartchenko, V
Froenicke, L
Stone, G
Stanyon, R
Wolf, E
Cremer, T
Brero, A
AF Koehler, Daniela
Zakhartchenko, Valeri
Froenicke, Lutz
Stone, Gary
Stanyon, Roscoe
Wolf, Eckhard
Cremer, Thomas
Brero, Alessandro
TI Changes of higher order chromatin arrangements during major genome
activation in bovine preimplantation embryos
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Chromosome territory; Nuclear architecture; Higher order chromatin
arrangements; Major genome activation; Preimplantation development
ID IN-SITU HYBRIDIZATION; GENE-EXPRESSION; NUCLEAR ARCHITECTURE;
DNA-REPLICATION; SATELLITE DNA; CELL-NUCLEI; ORGANIZATION; CHROMOSOMES;
MOUSE; INTERPHASE
AB Gene-dense chromosome territories (CTs) are typically located more interior, gene-poor CTs more peripheral in mammalian cell nuclei. Here, we show that this gene-density correlated CT positioning holds for the most gene-rich and gene-poor bovine chromosomes 19 and 20, respectively, in bovine fibroblast and lymphocyte nuclei. In order to determine the period at which this non-random CT order is established during development, we performed fluorescence in Situ hybridization, on three-dimensionally preserved bovine preimplantation embryos generated by in vitro fertilization and investigated the distribution of BTA 19 and 20 CTs. Radial arrangements of CTs 19 and 20 were the same up to the 8-cell stage. At the 10- to 16-cell stage, however, a significant difference became apparent with CTs 19 localized more internally and CTs 20 more peripherally. Since major genome activation in bovine embryos occurs at the 8- to 16-cell stage, our findings demonstrate a temporal correlation between transcriptional activation and a major rearrangement of chromatin topography in blastomere nuclei. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Koehler, Daniela; Cremer, Thomas] Ludwig Maximilians Univ Munchen, Div Anthropol & Human Genet, Bioctr, D-82152 Martinsried, Germany.
[Koehler, Daniela; Cremer, Thomas] Munich Ctr Integrated Prot Sci, D-81377 Munich, Germany.
[Zakhartchenko, Valeri; Wolf, Eckhard; Brero, Alessandro] Ludwig Maximilians Univ Munchen, Div Mol Anim Breeding & Biotechnol, D-81377 Munich, Germany.
[Zakhartchenko, Valeri; Wolf, Eckhard; Brero, Alessandro] Ludwig Maximilians Univ Munchen, Gene Ctr, Lab Funct Genome Anal LAFUGA, D-81377 Munich, Germany.
[Froenicke, Lutz] Univ Calif Davis, Sch Vet Med, Dept Populat Hlth & Reprod, Davis, CA 95616 USA.
[Stone, Gary] NCI, Frederick, MD 21701 USA.
[Stanyon, Roscoe] Dept Anim Biol & Genet, Lab Anthropol, Florence, Italy.
RP Cremer, T (reprint author), Ludwig Maximilians Univ Munchen, Div Anthropol & Human Genet, Bioctr, Grosshadernerstr 2, D-82152 Martinsried, Germany.
EM Thomas.Cremer@lrz.uni-muenchen.de; A.Brero@lrz.uni-muenchen.de
OI Zakhartchenko, Valeri/0000-0002-5974-9759; Stanyon,
Roscoe/0000-0002-7229-1092; Wolf, Eckhard/0000-0002-0430-9510
FU Deutsche Forschungsgemeinschaft [ZA 425/1, CR 59/26]; NIH; NCI; CCR
FX The present work is supported by the Deutsche Forschungsgemeinschaft (ZA
425/1 and CR 59/26). This project was funded in part by the Intramural
Research Program of the NIH, NCI, CCR.
NR 51
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U1 0
U2 3
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD JUL 15
PY 2009
VL 315
IS 12
BP 2053
EP 2063
DI 10.1016/j.yexcr.2009.02.016
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 457TL
UT WOS:000266956200006
PM 19254712
ER
PT J
AU Manisastry, SM
Zaal, KJM
Horowits, R
AF Manisastry, Shyam M.
Zaal, Kristien J. M.
Horowits, Robert
TI Myofibril assembly visualized by imaging N-RAP, alpha-actinin, and actin
in living cardiomyocytes
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Article
DE Myofibrillogenesis; Heart; Sarcomere
ID CULTURED CHICK CARDIOMYOCYTES; NEBULIN-RELATED PROTEIN; SKELETAL-MUSCLE
CELLS; STRIATED-MUSCLE; CARDIAC MYOFIBRILLOGENESIS; LIM PROTEIN; MOUSE
CARDIOMYOCYTES; PRECARDIAC MESODERM; NASCENT MYOFIBRILS; DYNAMICS
AB N-RAP is a striated muscle-specific scaffolding protein that organizes alpha-actinin and actin into symmetrical I-Z-I structures in developing myofibrils. Here we determined the order of events during myofibril assembly through time-lapse confocal microscopy of cultured embryonic chick cardiomyocytes coexpressing fluorescently tagged N-RAP and either alpha-actinin or actin. During de novo myofibril assembly, N-RAP assembled in fibrillar structures within the cell, with dots of alpha-actinin subsequently organizing along these structures. The initial fibrillar structures were reminiscent of actin fibrils, and coassembly of N-RAP and actin into newly formed fibrils supported this. The alpha-actinin dots subsequently broadened to Z-Iines that were wider than the underlying N-RAP fibril, and N-RAP fluorescence intensity decreased. FRAP experiments showed that most of the alpha-actinin dynamically exchanged during all stages of myofibril assembly. In contrast, less than 20% of the N-RAP in premyofibrils was exchanged during 10-20 min after photobleaching, but this value increased to 70% during myofibril maturation. The results show that N-RAP assembles into an actin containing scaffold before alpha-actinin recruitment; that the N-RAP scaffold is much more stable than the assembling structural components; that N-RAP dynamics increase as assembly progresses; and that N-RAP leaves the structure after assembly is complete. Published by Elsevier Inc.
C1 [Manisastry, Shyam M.; Zaal, Kristien J. M.; Horowits, Robert] NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Horowits, R (reprint author), NIAMSD, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1154,MSC 8024, Bethesda, MD 20892 USA.
EM horowits@helix.nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX This research was supported by the intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health. We thank Dr. Joseph Sanger (SUNY
Upstate Medical University, Syracuse, NY) for the generous gift of
expression plasmids for YFP-alpha-actinin and YFP-actin. We thank Drs.
George Patterson & Jennifer Lippincott-Schwartz (NICHD, NIH) for the
generous gift of the mCherry-C1 plasmid vector. Finally, we thank Drs.
Kuan Wang, Evelyn Ralston, and Garland Crawford (NIAMS, NIH) as well as
Dr. Matthew Daniels (NHLBI, NIH) for critical reading of the manuscript.
NR 47
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U1 1
U2 5
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
J9 EXP CELL RES
JI Exp. Cell Res.
PD JUL 15
PY 2009
VL 315
IS 12
BP 2126
EP 2139
DI 10.1016/j.yexcr.2009.02.006
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 457TL
UT WOS:000266956200013
PM 19233165
ER
PT J
AU Ranguelova, K
Mason, RP
AF Ranguelova, Kalina
Mason, Ronald P.
TI New insights into the detection of sulfur trioxide anion radical by spin
trapping: radical trapping versus nucleophilic addition
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE ESR spin trapping; DMPO; Sulfur-derived radicals; Kinetics; Free
radicals
ID N-OXIDE DMPO; HORSERADISH-PEROXIDASE; CATALYZED OXIDATION;
XANTHINE-OXIDASE; AQUEOUS-SOLUTION; SULFITE OXIDATION; CAUTIONARY NOTE;
RATE CONSTANTS; OXYGEN-UPTAKE; ION ADDITION
AB It has recently been demonstrated that (bi)sulfite (hydrated sulfur dioxide) reacts with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) via a nonradical, nucleophilic reaction, and further proposed that the radical adduct (DMPO/(center dot)SO(3)(-)) formation in biological systems is an artifact and not the result of spin trapping of sulfur trioxide anion radical ((center dot)SO(3)(-)). Here, the one-electron oxidation of (bi)sulfite catalyzed by horseradish peroxidase/H(2)O(2) has been reinvestigated by ESR spin trapping with DMPO and oxygen uptake studies to obtain further evidence for the radical reaction mechanism. In the case of ESR experiments, the signal of the DMPO/(center dot)SO(3)(-) radical adduct was detected, and the initial rate of its formation was calculated. Support for the radical pathway via (center dot)SO(3)(-) was obtained from the stoichiometry between the amount of consumed molecular oxygen and the amount of (bi)sulfite oxidized to sulfate (SO(4)(2-)). When DMPO was incubated with (bi)sulfite, oxygen consumption was completely inhibited owing to the efficiency of DMPO trapping. In the absence of DMPO, the initial rate of oxygen and H(2)O(2) consumption was determined to be half of the initial rate of DMPO/(center dot)SO(3)(-) radical adduct formation as determined by ESR, demonstrating that DMPO forms the radical adduct by trapping the (center dot)SO(3)(-) exclusively. We conclude that DMPO is not susceptible to artifacts arising from nonradical chemistry (nucleophilic addition) except when both (bi)sulfite and DMPO concentrations are at nonphysiological levels of at least 0.1 M and the incubations are for longer times. Published by Elsevier Inc.
C1 [Ranguelova, Kalina; Mason, Ronald P.] NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Ranguelova, K (reprint author), NIEHS, Pharmacol Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM RanguelovaK@niehs.nih.gov
FU National Institutes of Health; National Institute of Environmental
Health Sciences
FX We are grateful to Mrs. Mary Mason and Dr. Ann Motten for their editing
of the manuscript. Also, we acknowledge jean Corbett for the
purification of DMPO. This work was supported by the Intramural Research
Program of the National Institutes of Health and the National Institute
of Environmental Health Sciences.
NR 52
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD JUL 15
PY 2009
VL 47
IS 2
BP 128
EP 134
DI 10.1016/j.freeradbiomed.2009.04.006
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 460IL
UT WOS:000267181300002
PM 19362142
ER
PT J
AU Johnson, AD
Kavousi, M
Smith, AV
Chen, MH
Dehghan, A
Aspelund, T
Lin, JP
van Duijn, CM
Harris, TB
Cupples, LA
Uitterlinden, AG
Launer, L
Hofman, A
Rivadeneira, F
Stricker, B
Yang, Q
O'Donnell, CJ
Gudnason, V
Witteman, JC
AF Johnson, Andrew D.
Kavousi, Maryam
Smith, Albert V.
Chen, Ming-Huei
Dehghan, Abbas
Aspelund, Thor
Lin, Jing-Ping
van Duijn, Cornelia M.
Harris, Tamara B.
Cupples, L. Adrienne
Uitterlinden, Andre G.
Launer, Lenore
Hofman, Albert
Rivadeneira, Fernando
Stricker, Bruno
Yang, Qiong
O'Donnell, Christopher J.
Gudnason, Vilmundur
Witteman, Jacqueline C.
TI Genome-wide association meta-analysis for total serum bilirubin levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-HEART-DISEASE; ORGANIC CATION TRANSPORTER; UGT1A1-ASTERISK-28
ALLELE; OATP-C; GENE; POLYMORPHISMS; EXPRESSION; INHERITANCE; ROTTERDAM;
DESIGN
AB Variation in serum bilirubin is associated with altered cardiovascular disease risk and drug metabolism. We aimed to identify genetic contributors to variability in serum bilirubin levels by combining results from three genome-wide association studies (Framingham heart study, n = 3424; Rotterdam study, n = 3847; Age, Gene, Environment and Susceptibility-Reykjavik, n = 2193). Meta-analysis showed strong replication for a genetic influence on serum bilirubin levels of the UGT1A1 locus (P < 5 x 10(-324)) and a 12p12.2 locus. The peak signal in the 12p12.2 region was a non-synonymous SNP in SLCO1B1 (rs4149056, P = 6.7 x 10(-13)), which gives rise to a valine to alanine amino acid change leading to reduced activity for a hepatic transporter with known affinity for bilirubin. There were also suggestive associations with several other loci. The top variants in UGT1A1 and SLCO1B1 explain similar to 18.0 and similar to 1.0% of the variation in total serum bilirubin levels, respectively. In a conditional analysis adjusted for individual genotypes for the top UGT1A1 variant, the top SLCO1B1 variant remained highly significant (P = 7.3 x 10(-13)), but no other variants achieved genome-wide significance. In one of the largest genetic studies of bilirubin to date (n = 9464), we confirm the substantial genetic influence of UGT1A1 variants, consistent with past linkage and association studies, and additionally provide strong evidence of a role for allelic variation in SLCO1B1. Given the involvement of bilirubin in a number of physiological and disease processes, and the roles for UGT1A1 and SLCO1B1 in drug metabolism, these genetic findings have potential clinical importance. In analyses for association with gallbladder disease or gallstones, top bilirubin SNPs in UGT1A1 and SLCO1B1 were not associated.
C1 [Johnson, Andrew D.; Chen, Ming-Huei; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Kavousi, Maryam; Dehghan, Abbas; van Duijn, Cornelia M.; Uitterlinden, Andre G.; Hofman, Albert; Rivadeneira, Fernando; Stricker, Bruno; Witteman, Jacqueline C.] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.; Rivadeneira, Fernando; Stricker, Bruno] Erasmus MC Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Smith, Albert V.; Aspelund, Thor; Gudnason, Vilmundur] Iceland Heart Assoc, Reykjavik, Iceland.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Aspelund, Thor; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Lin, Jing-Ping] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Harris, Tamara B.; Launer, Lenore] Natl Inst Agings Age, Gene Environm Susceptibil Study, Reykjavik, Iceland.
[Cupples, L. Adrienne; Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Stricker, Bruno] Inspectorate Hlth Care, The Hague, Netherlands.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM codonnell@nih.gov
RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Johnson,
Andrew/G-6520-2013; Yang, Qiong/G-5438-2014; Gudnason,
Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015; Smith,
Albert/K-5150-2015;
OI Dehghan, Abbas/0000-0001-6403-016X; Aspelund, Thor/0000-0002-7998-5433;
Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira,
Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845;
Cupples, L. Adrienne/0000-0003-0273-7965
FU NHLBI NIH HHS [N01-HC-25195, N02-HL-6-4278]; NIA NIH HHS [N01-AG-12100]
NR 39
TC 113
Z9 115
U1 2
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2009
VL 18
IS 14
BP 2700
EP 2710
DI 10.1093/hmg/ddp202
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 463OJ
UT WOS:000267441200017
PM 19414484
ER
PT J
AU Sanna, S
Busonero, F
Maschio, A
McArdle, PF
Usala, G
Dei, M
Lai, S
Mulas, A
Piras, MG
Perseu, L
Masala, M
Marongiu, M
Crisponi, L
Naitza, S
Galanello, R
Abecasis, GR
Shuldiner, AR
Schlessinger, D
Cao, A
Uda, M
AF Sanna, Serena
Busonero, Fabio
Maschio, Andrea
McArdle, Patrick F.
Usala, Gianluca
Dei, Mariano
Lai, Sandra
Mulas, Antonella
Piras, Maria Grazia
Perseu, Lucia
Masala, Marco
Marongiu, Mara
Crisponi, Laura
Naitza, Silvia
Galanello, Renzo
Abecasis, Goncalo R.
Shuldiner, Alan R.
Schlessinger, David
Cao, Antonio
Uda, Manuela
TI Common variants in the SLCO1B3 locus are associated with bilirubin
levels and unconjugated hyperbilirubinemia
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GILBERTS-SYNDROME; GENE; FAMILY; TRANSPORTERS; THALASSEMIA; SLC21A6;
REGION; MAPS; MRP2
AB Bilirubin, resulting largely from the turnover of hemoglobin, is found in the plasma in two main forms: unconjugated or conjugated with glucuronic acid. Unconjugated bilirubin is transported into hepatocytes. There, it is glucuronidated by UGT1A1 and secreted into the bile canaliculi. We report a genome wide association scan in 4300 Sardinian individuals for total serum bilirubin levels. In addition to the two known loci previously involved in the regulation of bilirubin levels, UGT1A1 (P = 6.2 x 10(-62)) and G6PD (P = 2.5 x 10(-8)), we observed a strong association on chromosome 12 within the SLCO1B3 gene (P = 3.9 x 10(-9)). Our findings were replicated in an independent sample of 1860 Sardinians and in 832 subjects from the Old Order Amish (combined P < 5 x 10(-14)). We also show that SLC01B3 variants contribute to idiopathic mild unconjugated hyperbilirubinemia. Thus, SLC01B3 appears to be involved in the regulation of serum bilirubin levels in healthy individuals and in some bilirubin-related disorders that are only partially explained by other known gene variants.
C1 [Sanna, Serena; Busonero, Fabio; Maschio, Andrea; Usala, Gianluca; Dei, Mariano; Lai, Sandra; Mulas, Antonella; Piras, Maria Grazia; Perseu, Lucia; Masala, Marco; Marongiu, Mara; Crisponi, Laura; Naitza, Silvia; Cao, Antonio; Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy.
[McArdle, Patrick F.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Galanello, Renzo] Univ Cagliari, Pediat Clin, Osped Reg Microcitemie, Dipartimento Sci Biomed & Biotecnol, I-09121 Cagliari, Italy.
[Abecasis, Goncalo R.] Univ Michigan, Dept Stat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA.
RP Uda, M (reprint author), CNR, Ist Neurogenet & Neurofarmacol, I-09042 Cagliari, Italy.
EM manuela.uda@inn.cnr.it
RI Abecasis, Goncalo/B-7840-2010; Naitza, Silvia/D-5620-2017;
OI Mulas, Antonella/0000-0002-6856-1483; piras, maria
grazia/0000-0001-9004-0900; sanna, serena/0000-0002-3768-1749; MARONGIU,
MARA/0000-0002-7321-2384; Abecasis, Goncalo/0000-0003-1509-1825
FU National Institutes of Health [HL084729, HG002651, U01 HL72515];
National Institute of Aging [NO1-AG-1-2109]; SardiNIA ('ProgeNIA') team;
University of Michigan [263-MA-410953]; University of Maryland General
Clinical Research Center [M01 RR 16500]; Clinical Nutrition Research
Unit of Maryland [P30 DK072488]; Baltimore Veterans Administration
Medical Center Geriatrics Research
FX The work was supported by the following National Institutes of Health
grants: HL084729 to G. R. A., HG002651 to G. R. A., National Institute
of Aging contracts NO1-AG-1-2109 to the SardiNIA ('ProgeNIA') team and
263-MA-410953 to the University of Michigan ( G. R. A). The Old Order
Amish study was supported by National Institutes of Health research
grant U01 HL72515, the University of Maryland General Clinical Research
Center, grant M01 RR 16500, the Clinical Nutrition Research Unit of
Maryland P30 DK072488, and the Baltimore Veterans Administration Medical
Center Geriatrics Research.
NR 24
TC 83
Z9 86
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2009
VL 18
IS 14
BP 2711
EP 2718
DI 10.1093/hmg/ddp203
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 463OJ
UT WOS:000267441200018
PM 19419973
ER
PT J
AU Schumacher, J
Laje, G
Abou Jamra, R
Becker, T
Muhleisen, TW
Vasilescu, C
Mattheisen, M
Herms, S
Hoffmann, P
Hillmer, AM
Georgi, A
Herold, C
Schulze, TG
Propping, P
Rietschel, M
McMahon, FJ
Nothen, MM
Cichon, S
AF Schumacher, Johannes
Laje, Gonzalo
Abou Jamra, Rami
Becker, Tim
Muehleisen, Thomas W.
Vasilescu, Catalina
Mattheisen, Manuel
Herms, Stefan
Hoffmann, Per
Hillmer, Axel M.
Georgi, Alexander
Herold, Christine
Schulze, Thomas G.
Propping, Peter
Rietschel, Marcella
McMahon, Francis J.
Noethen, Markus M.
Cichon, Sven
TI The DISC locus and schizophrenia: evidence from an association study in
a central European sample and from a meta-analysis across different
European populations
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID MULTILOCUS GENOTYPE DATA; MAJOR MENTAL-ILLNESS; BIPOLAR DISORDER; GENES;
TRANSLOCATION; INFERENCE; GENETICS; LINKAGE; GENOME; RISK
AB Association studies, as well as the initial translocation family study, identified the gene Disrupted-In-Schizophrenia-1 (DISC1) as a risk factor for schizophrenia. DISC1 encodes a multifunctional scaffold protein involved in neurodevelopmental processes implicated in the etiology of schizophrenia. The present study explores the contribution of the DISC locus to schizophrenia using three different approaches: (i) systematic association mapping aimed at detecting DISC risk variants in a schizophrenia sample from a central European population (556 SNPs, n = 1621 individuals). In this homogenous sample, a circumscribed DISC1 interval in intron 9 was significantly associated with schizophrenia in females (P = 4 x 10(-5)) and contributed most strongly to early-onset cases (P = 9 x 10(-5)). The odds ratios (ORs) were in the range of 1.46-1.88. (ii) The same sample was used to test for the locus-specific SNP-SNP interaction most recently associated with schizophrenia. Our results confirm the SNP interplay effect between rs1538979 and rs821633 that significantly conferred disease risk in male patients with schizophrenia (P = 0.016, OR 1.57). (iii) In order to detect additional schizophrenia variants, a meta-analysis was performed using nine schizophrenia samples from different European populations (50 SNPs, n = 10 064 individuals maximum, n = 3694 minimum). We found evidence for a common schizophrenia risk interval within DISC1 intron 4-6 (P = 0.002, OR 1.27). The findings point to a complex association between schizophrenia and DISC, including the presence of different risk loci and SNP interplay effects. Furthermore, our phenotype-genotype results-including the consideration of sex-specific effects-highlight the value of homogenous samples in mapping risk genes for schizophrenia in general, and at the DISC locus in particular.
C1 [Schumacher, Johannes; Laje, Gonzalo; Schulze, Thomas G.; McMahon, Francis J.] NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Schumacher, Johannes; Abou Jamra, Rami; Mattheisen, Manuel; Propping, Peter; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany.
[Becker, Tim; Herold, Christine] Univ Bonn, Inst Med Biometry Informat & Epidemiol, D-5300 Bonn, Germany.
[Muehleisen, Thomas W.; Vasilescu, Catalina; Mattheisen, Manuel; Herms, Stefan; Hoffmann, Per; Hillmer, Axel M.; Noethen, Markus M.; Cichon, Sven] Univ Bonn, Dept Genom, Life & Brain Ctr, D-5300 Bonn, Germany.
[Georgi, Alexander; Schulze, Thomas G.; Rietschel, Marcella] Cent Inst Mental Hlth, Div Genet Epidemiol, D-6800 Mannheim, Germany.
RP Schumacher, J (reprint author), NIMH, Unit Genet Basis Mood & Anxiety Disorders, NIH, US Dept Hlth & Human Serv, 35 Convent Dr,Bldg 35,Room A202, Bethesda, MD 20892 USA.
EM schumacherj@mail.nih.gov
RI Herms, Stefan/J-1949-2014; Schulze, Thomas/H-2157-2013; Cichon,
Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Laje, Gonzalo/L-2654-2014;
Hillmer, Axel/N-2927-2014; Abou Jamra, Rami/I-4805-2015; Mattheisen,
Manuel/B-4949-2012; Schumacher, Johannes/F-4970-2015;
OI Georgi, Alexander/0000-0002-1499-8524; Herms,
Stefan/0000-0002-2786-8200; Cichon, Sven/0000-0002-9475-086X; Cichon,
Sven/0000-0002-9475-086X; Laje, Gonzalo/0000-0003-2763-3329; Hillmer,
Axel/0000-0002-3381-7266; Abou Jamra, Rami/0000-0002-1542-1399;
Mattheisen, Manuel/0000-0002-8442-493X; Schumacher,
Johannes/0000-0001-9217-6457; McMahon, Francis/0000-0002-9469-305X;
Nothen, Markus/0000-0002-8770-2464; Hoffmann, Per/0000-0002-6573-983X
FU National Genomic Network of the 'Bundesministerium fur Bildung und
Forschung; NIH/DFG Research Career Transition Award; NIMH Intramural
Research Program; Alfried Krupp von Bohlen und Halbach-Stiftung
FX This study was supported by the National Genomic Network of the
'Bundesministerium fur Bildung und Forschung' ( BMBF), a NIH/DFG
Research Career Transition Award to J. S., the Alfried Krupp von Bohlen
und Halbach-Stiftung to M. M. N. and the NIMH Intramural Research
Program to F. J. M.
NR 25
TC 49
Z9 51
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD JUL 15
PY 2009
VL 18
IS 14
BP 2719
EP 2727
DI 10.1093/hmg/ddp204
PG 9
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 463OJ
UT WOS:000267441200019
PM 19414483
ER
PT J
AU Schwarz, A
Sternberg, JM
Johnston, V
Medrano-Mercado, N
Anderson, JM
Hume, JCC
Valenzuela, JG
Schaub, GA
Billingsley, PF
AF Schwarz, Alexandra
Sternberg, Jeremy M.
Johnston, Valerie
Medrano-Mercado, Nora
Anderson, Jennifer M.
Hume, Jen C. C.
Valenzuela, Jesus G.
Schaub, Guenter A.
Billingsley, Peter F.
TI Antibody responses of domestic animals to salivary antigens of Triatoma
infestans as biomarkers for low-level infestation of triatomines
SO INTERNATIONAL JOURNAL FOR PARASITOLOGY
LA English
DT Article
DE Antibody responses; Chagas disease; Chickens; Guinea pigs; Salivary
proteins; Surveillance; Triatoma infestans; Cross-reactivity
ID PANSTRONGYLUS-MEGISTUS HEMIPTERA; MOSQUITO ANOPHELES-GAMBIAE;
BLOOD-FEEDING ARTHROPODS; CHAGAS-DISEASE CONTROL; LUTZOMYIA-LONGIPALPIS;
IMMUNE-RESPONSE; BRAZILIAN POPULATIONS; PROTRACTA HETEROPTERA;
RHODNIUS-PROLIXUS; TRYPANOSOMA-CRUZI
AB Hematophagous arthropods such as Triatoma infestans, the vector of Trypanosoma cruzi, elicit host-immune responses during feeding. Characterization of antibody responses to salivary antigens offers the potential to develop immunologically based monitoring techniques for exposure to re-emergent triatomine bug populations in peridomestic animals. IgG-antibody responses to the salivary antigens of T. infestans have been detected in chickens as soon as 2 days after the first exposure to five adult bugs. Chickens and guinea pigs regularly exposed to this number of triatomines showed a significantly lower anti-saliva antibody titre than animals exposed to 25 adults and fifth instars of four different T. infestans strains originating from Bolivia and from Northern Chile. Highly immunogenic salivary antigens of 14 and 21 kDa were recognised by all chicken sera and of 79 kDa by all guinea pig sera. Cross-reactivity studies using saliva or salivary gland extracts from different hematophagous species, e.g. different triatomines, bed bugs, mosquitoes, sand flies and ticks, as well as chicken sera exposed to triatomines and mosquitoes, demonstrated that the 14 and 21 kDa salivary antigens were only found in triatomines. Sera from peridomestic chickens and guinea pigs in sites of known T. infestans challenge in Bolivia also recognised the 14 and 21 kDa antigens. These represent promising epidemiological markers for the detection of small numbers of feeding bugs and hence may be a new tool for vector surveillance in Chagas disease control programs. (C) 2009 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
C1 [Schwarz, Alexandra; Sternberg, Jeremy M.; Johnston, Valerie] Univ Aberdeen, Sch Biol Sci, Aberdeen AB24 2TZ, Scotland.
[Schwarz, Alexandra; Schaub, Guenter A.] Ruhr Univ Bochum, Zool Parasitol Grp, Bochum, Germany.
[Medrano-Mercado, Nora] Univ Mayor de San Simon, Lab Chagas Dis & Immunoparasitol, Cochabamba, Bolivia.
[Anderson, Jennifer M.; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Unit, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Billingsley, Peter F.] Sanaria Inc, Entomol & Qual Syst, Rockville, MD USA.
[Hume, Jen C. C.] NIAID, Int Studies Malaria & Entomol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Schwarz, A (reprint author), Univ Aberdeen, Sch Biol Sci, Zool Bldg,Tillydrone Ave, Aberdeen AB24 2TZ, Scotland.
EM a.schwarz@abdn.ac.uk
OI Sternberg, Jeremy/0000-0002-1596-3622
FU University of Aberdeen, UK; Boehringer Ingelheim Fonds (BIF),
Heidesheim, Germany; German Academic Exchange Service (DAAD), Bonn,
Germany; 'Deutsche Forschungsgemeinschaft' [339113-1]; Humboldt
Foundation
FX The authors are very grateful to Sabine Kindermann, Holger
Schlierenkamp, Charles Soukou, Sonja Ortmann, Dr. Witold MOtze and Van
My Pham for their technical assistance and to Christian Meiser for the
introduction to the technology to obtain saliva of Triatorna infestans.
We thank Dr. Reiner Pospischil (Bayer CropScience, Monheim, Germany) for
providing Cirnex lectularius and Dr. Jose Jurberg (Departamento de
Entomologia, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil) for
providing the original stock of PanstronSylus megistus. A.S. was funded
by the University of Aberdeen, UK (Sixth Century Scholarship), the
Boehringer Ingelheim Fonds (BIF), Heidesheim, Germany (Travel award) and
the German Academic Exchange Service (DAAD), Bonn, Germany (Short term
scholarship). The support of the 'Deutsche Forschungsgemeinschaft'
(project Scha 339113-1) and the Humboldt Foundation to N.M.-M. is
gratefully acknowledged.
NR 52
TC 27
Z9 27
U1 0
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0020-7519
EI 1879-0135
J9 INT J PARASITOL
JI Int. J. Parasit.
PD JUL 15
PY 2009
VL 39
IS 9
BP 1021
EP 1029
DI 10.1016/j.ijpara.2009.01.010
PG 9
WC Parasitology
SC Parasitology
GA 465FX
UT WOS:000267569000009
PM 19248784
ER
PT J
AU Anderson, LA
Gadalla, S
Morton, LM
Landgren, O
Pfeiffer, R
Warren, JL
Berndt, SI
Ricker, W
Parsons, R
Engels, EA
AF Anderson, Lesley A.
Gadalla, Shahinaz
Morton, Lindsay M.
Landgren, Ola
Pfeiffer, Ruth
Warren, Joan L.
Berndt, Sonja I.
Ricker, Winnie
Parsons, Ruth
Engels, Eric A.
TI Population-based study of autoimmune conditions and the risk of specific
lymphoid malignancies
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE epidemiology; lymphoma; chronic lymphocytic leukemia; autoimmune; risk
ID NON-HODGKIN-LYMPHOMA; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
RHEUMATOID-ARTHRITIS; UNITED-STATES; PERNICIOUS-ANEMIA; CANCER-RISK;
LYMPHOPROLIFERATIVE DISORDERS; CHRONIC INFLAMMATION; MULTIPLE-MYELOMA;
HEMOLYTIC-ANEMIA
AB Some autoimmune conditions are associated with increased risk of lympboid malignancies, but information on specific malignancy subtypes is limited. From the U.S. Surveillance Epidemiology and End Results-Medicare database, we selected 44,350 lymphoid malignancy cases (>= 67 years) and 122,531 population-based controls. Logistic regression was used to derive odds ratios (ORs) comparing the prevalence of autoimmune conditions in cases and controls, by lymphoid malignancy subtype, adjusted for gender, age at malignancy/selection, year of malignancy/selection, race and number of physician claims. The strongest associations observed by non-Hodgkin lymphoma (NHL) subtypes were diffuse large B-cell lymphoma with rheumatoid arthritis (OR 1.4, 95% CI 1.2-1.5) and Sjogren syndrome (2.0, 1.5-2.8); T-cell lymphoma with hemolytic anemia (9.7, 4.3-22), psoriasis (3.1, 2.5-4.0), discoid lupus erythematosus (4.4, 2.3-8.4) and celiac disease (5.0, 2.4-14); and marginal zone lymphoma with Sjogren syndrome (6.6, 4.6-9.5), systemic lupus erythematosus (2.8, 1.7-4.7) and hemolytic anemia (7.4, 3.1-18). Hodgkin lymphoma was associated with systemic lupus erythematosus (3.5, 1.9-6.7). Multiple myeloma was associated only with pernicious anemia (1.5, 1.3-1.7). Several autoimmune conditions were associated with increased risk of lymphoid neoplasms, especially NHLs of diffuse large B-cell, marginal zone and T-cell subtypes. These results support a mechanism whereby chronic antigenic stimulation leads to lymphoid malignancy. Published 2009 UICC. This article is a US Government work, and, as such, is in the public domain in the United States of America.
C1 [Engels, Eric A.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol &Genet, Bethesda, MD 20892 USA.
[Anderson, Lesley A.] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Warren, Joan L.] Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA.
[Ricker, Winnie; Parsons, Ruth] Informat Management Serv Inc, Rockville, MD USA.
RP Engels, EA (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol &Genet, 6110 Execut Blvd,EPS 7076, Bethesda, MD 20892 USA.
EM engelse@mail.nih.gov
RI Pfeiffer, Ruth /F-4748-2011; Morton, Lindsay/B-5234-2015;
OI Morton, Lindsay/0000-0001-9767-2310; Anderson,
Lesley/0000-0002-1000-3649
FU Intramural NIH HHS [Z01 CP010150-08]
NR 48
TC 98
Z9 105
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0020-7136
J9 INT J CANCER
JI Int. J. Cancer
PD JUL 15
PY 2009
VL 125
IS 2
BP 398
EP 405
DI 10.1002/ijc.24287
PG 8
WC Oncology
SC Oncology
GA 460ZJ
UT WOS:000267231600019
PM 19365835
ER
PT J
AU Citrin, D
Mansueti, J
Likhacheva, A
Sciuto, L
Albert, PS
Rudy, SF
Cooley-Zgela, T
Cotrim, A
Solomon, B
Colevas, AD
Russo, A
Morris, JC
Herscher, L
Smith, S
Van Waes, C
AF Citrin, Deborah
Mansueti, John
Likhacheva, Anna
Sciuto, Linda
Albert, Paul S.
Rudy, Susan F.
Cooley-Zgela, Theresa
Cotrim, Ana
Solomon, Beth
Colevas, A. Dimitrios
Russo, Angelo
Morris, John C.
Herscher, Laurie
Smith, Sharon
Van Waes, Carter
TI LONG-TERM OUTCOMES AND TOXICITY OF CONCURRENT PACLITAXEL AND
RADIOTHERAPY FOR LOCALLY ADVANCED HEAD-AND-NECK CANCER
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the
American-Society-for-Therapeutic-Radiology-and-Oncology
CY OCT 28-NOV 01, 2007
CL Los Angeles, CA
SP Amer Soc Therapeut Radiol & Oncol
DE Paclitaxel; Radiotherapy; Toxicity; Head and neck
ID SQUAMOUS-CELL CARCINOMA; QUALITY-OF-LIFE; PHASE-I TRIAL;
RADIATION-THERAPY; STAGE-III; ACCELERATED RADIOTHERAPY; UNRESECTABLE
HEAD; RANDOMIZED-TRIAL; HYPERFRACTIONATED RADIOTHERAPY; CONCOMITANT
CHEMOTHERAPY
AB Purpose: To report the long-term outcomes and toxicity of a regimen of infusion paclitaxel delivered concurrently with radiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck.
Patients and Methods: Between 1995 and 1999, 35 patients with nonmetastatic, Stage III or IV squamous cell carcinoma of the head and neck were treated with three cycles of paclitaxel as a 120-h continuous infusion beginning on Days 1, 21, and 42, concurrent with radiotherapy. The initial 16 patients received 105 mg/m(2)/cycle, and the subsequent 19 patients received 120 mg/m(2)/cycle. External beam radiotherapy was delivered to a dose of 70.2-72 Gy at five fractions weekly. Patients were followed to evaluate the disease outcomes and late toxicity of this regimen.
Results: The median follow-up for all patients was 56.5 months. The median survival was 56.5 months, and the median time to local recurrence was not reached. Of the 35 patients, 15 (43%) developed hypothyroidism. Of the 33 patients who underwent percutaneous endoscopic gastrostomy tube placement, 11 were percutaneous endoscopic gastrostomy tube dependent until death or their last follow-up visit. Also, 5 patients (14%) required a tracheostomy until death, and 3 (9%) developed a severe esophageal stricture. All evaluated long-term survivors exhibited salivary hypofunction. Fibrosis in the radiation field occurred in 24 patients (69%).
Conclusion: The results of our study have shown that concurrent chemoradiotherapy with a 120-h infusion of paclitaxel provides long-term local control and survival in patients with squamous cell carcinoma of the head and neck. Xerostomia, hypothyroidism, esophageal and pharyngeal complications, and subcutaneous fibrosis were common long-term toxicities; however, the vast majority of toxicities were grade 1 or 2. Published by Elsevier Inc.
C1 [Citrin, Deborah; Mansueti, John; Likhacheva, Anna; Sciuto, Linda; Cooley-Zgela, Theresa; Russo, Angelo; Smith, Sharon] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Morris, John C.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rudy, Susan F.; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, NIH, Bethesda, MD USA.
[Cotrim, Ana] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Solomon, Beth] NIH, Speech Language Pathol Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Colevas, A. Dimitrios] Stanford Univ, Stanford Canc Ctr, Head & Neck Oncol Program, Stanford, CA 94305 USA.
[Herscher, Laurie] Suburban Hosp, Dept Radiat Oncol, Bethesda, MD USA.
[Albert, Paul S.] NCI, Biometr Res Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, 10 CRC,B2-3500, Bethesda, MD 20892 USA.
EM citrind@mail.nih.gov
FU Intramural NIH HHS [Z01 BC010850-01]
NR 27
TC 23
Z9 23
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2009
VL 74
IS 4
BP 1040
EP 1046
DI 10.1016/j.ijrobp.2008.09.053
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 464KY
UT WOS:000267505000010
PM 19117692
ER
PT J
AU Williams, KM
Chien, JW
Gladwin, MT
Pavletic, SZ
AF Williams, Kirsten M.
Chien, Jason W.
Gladwin, Mark T.
Pavletic, Steven Z.
TI Bronchiolitis Obliterans After Allogeneic Hematopoietic Stem Cell
Transplantation
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT
PROJECT; AIR-FLOW OBSTRUCTION; WORKING GROUP-REPORT; NONINFECTIOUS
PULMONARY COMPLICATIONS; LONG-TERM AZITHROMYCIN; LUNG TRANSPLANTATION;
CLINICAL-TRIALS; RISK-FACTORS
AB With improvements in supportive care, both long-term survival following allogeneic hematopoietic stem cell transplantations (HSCTs) and the indications for this procedure have increased. As a result, the number of patients living with long-term toxic effects due to HSCT has increased. A once rare condition of the donor immune cells attacking healthy host tissues, termed chronic graft-vs-host disease, has become a more common phenomenon. When chronic graft-vs-host disease affects the lung tissue, bronchiolitis obliterans syndrome ensues. Recent data suggest that bronchiolitis obliterans syndrome may affect up to 6% of HSCT recipients and dramatically alters survival, with overall survival of only 13% at 5 years. These statistics have not improved since the first presentation of this disease over 20 years ago. Challenges to the progress of medical management of bronchiolitis obliterans syndrome include difficulties and delays in diagnosis and a paucity of data on pathogenesis to direct new therapies. This article critically evaluates the current diagnostic criteria for bronchiolitis obliterans syndrome and reviews the epidemiology, pathogenesis, and available treatments. Improvements in survival will likely require early disease recognition, allowing for therapeutic modulation of disease prior to the development of irreversible airway obliteration. JAMA. 2009; 302(3):306-314 www.jama.com
C1 [Williams, Kirsten M.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Chien, Jason W.] Univ Washington, Div Clin Res, Fred Hutchinson Canc Res Ctr & Pulm & Crit Care, Seattle, WA 98195 USA.
[Gladwin, Mark T.] Univ Pittsburgh, Med Ctr, Div Pulm Allergy & Crit Care Med, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA USA.
RP Williams, KM (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10 CRC,Room 3-3288,10 Ctr Dr, Bethesda, MD 20892 USA.
EM williaki@mail.nih.gov
FU National Cancer Institute; National Institutes of Health; Intramural
Research Program; Center for Cancer Research; National Institutes of
Health [HL088201]
FX This project was supported in part by the National Cancer Institute,
National Institutes of Health, Intramural Research Program, Center for
Cancer Research. Dr Chien is supported by research grant HL088201 from
the National Institutes of Health.
NR 80
TC 93
Z9 97
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 15
PY 2009
VL 302
IS 3
BP 306
EP 314
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 470BR
UT WOS:000267948100024
PM 19602690
ER
PT J
AU Semsey, S
Krishna, S
Erdossy, J
Horvath, P
Orosz, L
Sneppen, K
Adhya, S
AF Semsey, Szabolcs
Krishna, Sandeep
Erdossy, Janos
Horvath, Peter
Orosz, Laszlo
Sneppen, Kim
Adhya, Sankar
TI Dominant Negative Autoregulation Limits Steady-State Repression Levels
in Gene Networks
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; POSITIVE FEEDBACK; GAL
REGULON; ISOREPRESSOR; MOTIFS; LOOPS
AB Many transcription factors repress transcription of their own genes. Negative autoregulation has been shown to reduce cell-cell variation in regulatory protein levels and speed up the response time in gene networks. In this work we examined transcription regulation of the galS gene and the function of its product, the GalS protein. We observed a unique operator preference of the GalS protein characterized by dominant negative autoregulation. We show that this pattern of regulation limits the repression level of the target genes in steady states. We suggest that transcription factors with dominant negative autoregulation are designed for regulating gene expression during environmental transitions.
C1 [Semsey, Szabolcs; Erdossy, Janos; Horvath, Peter; Orosz, Laszlo] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary.
[Krishna, Sandeep; Sneppen, Kim] Niels Bohr Inst, Ctr Models Life, DK-2100 Copenhagen, Denmark.
[Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Semsey, S (reprint author), Eotvos Lorand Univ, Dept Genet, Pazmany PS 1-C, H-1117 Budapest, Hungary.
EM semseys@yahoo.com
RI Semsey, Szabolcs/L-6329-2013;
OI Semsey, Szabolcs/0000-0002-4522-5495; Sneppen, Kim/0000-0001-9820-3567
FU NIH; National Cancer Institute; Center for Cancer Research,; 6th
European Community Framework Program; Danish National Research
Foundation; OTKA [PD75496]; Hungarian Academy of Sciences
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, by a Marie
Curie International Reintegration Grant within the 6th European
Community Framework Program, by the Danish National Research Foundation,
and by an OTKA PD75496 grant. S. S. is grateful for the Janos Bolyai
fellowship of the Hungarian Academy of Sciences.
NR 19
TC 12
Z9 12
U1 0
U2 0
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 15
PY 2009
VL 191
IS 14
BP 4487
EP 4491
DI 10.1128/JB.00056-09
PG 5
WC Microbiology
SC Microbiology
GA 462RH
UT WOS:000267372900001
PM 19429616
ER
PT J
AU Kouznetsova, A
Wang, H
Bellani, M
Camerini-Otero, RD
Jessberger, R
Hoog, C
AF Kouznetsova, Anna
Wang, Hong
Bellani, Marina
Camerini-Otero, R. Daniel
Jessberger, Rolf
Hoog, Christer
TI BRCA1-mediated chromatin silencing is limited to oocytes with a small
number of asynapsed chromosomes
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Meiosis; Oocytes; BRCA1; Meiotic silencing of unsynapsed chromatin
ID SYNAPTONEMAL COMPLEX; MEIOTIC CHROMOSOMES; MAMMALIAN MEIOSIS; DNA
RECOMBINATION; COHESIN SMC1-BETA; BODY FORMATION; MICE LACKING; FEMALE
MICE; MOUSE; SYNAPSIS
AB Transcriptional silencing of the sex chromosomes during male meiosis is regarded as a manifestation of a general mechanism active in both male and female germ cells, called meiotic silencing of unsynapsed chromatin (MSUC). MSUC is initiated by the recruitment of the tumor suppressor protein BRCA1 to the axes of unsynapsed chromosomes. We now show that Sycp3, a structural component of the chromosome axis, is required for localization of BRCA1 to unsynapsed pachytene chromosomes. Importantly, we find that oocytes carrying an excess of two to three pairs of asynapsed homologous chromosomes fail to recruit enough BRCA1 to the asynapsed axes to activate MSUC. Furthermore, loss of MSUC function only transiently rescues oocytes from elimination during early postnatal development. The fact that the BRCA1-dependent synapsis surveillance system cannot respond to higher degrees of asynapsis and is dispensable for removal of aberrant oocytes argues that MSUC has a limited input as a quality control mechanism in female germ cells.
C1 [Kouznetsova, Anna; Wang, Hong; Hoog, Christer] Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
[Bellani, Marina; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Jessberger, Rolf] Tech Univ Dresden, Inst Phys Chem, Sch Med, MTZ, D-01307 Dresden, Germany.
RP Hoog, C (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
EM christer.hoog@ki.se
FU Swedish Cancer Society; Swedish Research Council; Novo Nordisk
Foundation and Karolinska Institutet
FX We thank Ivana Novak for help with experiments on Smc1
beta-/- mice and Mary-Rose Hoja for the comments on the
manuscript. This work was supported by grants from the Swedish Cancer
Society, the Swedish Research Council, the Novo Nordisk Foundation and
Karolinska Institutet.
NR 34
TC 27
Z9 28
U1 0
U2 0
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD JUL 15
PY 2009
VL 122
IS 14
BP 2446
EP 2452
DI 10.1242/jcs.049353
PG 7
WC Cell Biology
SC Cell Biology
GA 474BQ
UT WOS:000268257600013
PM 19531582
ER
PT J
AU Metenou, S
Dembele, B
Konate, S
Dolo, H
Coulibaly, SY
Coulibaly, YI
Diallo, AA
Soumaoro, L
Coulibaly, ME
Sanogo, D
Doumbia, SS
Wagner, M
Traore, SF
Klion, A
Mahanty, S
Nutman, TB
AF Metenou, Simon
Dembele, Benoit
Konate, Siaka
Dolo, Housseini
Coulibaly, Siaka Y.
Coulibaly, Yaya I.
Diallo, Abdallah A.
Soumaoro, Lamine
Coulibaly, Michel E.
Sanogo, Dramane
Doumbia, Salif S.
Wagner, Marissa
Traore, Sekou F.
Klion, Amy
Mahanty, Siddhartha
Nutman, Thomas B.
TI Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine
Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected
Population
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID PLASMODIUM-FALCIPARUM MALARIA; TUMOR-NECROSIS-FACTOR; HUMAN LYMPHATIC
FILARIASIS; MURINE CEREBRAL MALARIA; SCHISTOSOMA-HAEMATOBIUM INFECTION;
ASCARIS-LUMBRICOIDES INFECTION; BLOOD-STAGE MALARIA; IMMUNE-RESPONSES;
T-CELLS; HELMINTH COINFECTION
AB The effect of filarial infections on malaria-specific immune responses was investigated in Malian villages coendemic for filariasis (Fit) and malaria. Cytokines were measured from plasma and Ag-stimulated whole blood from individuals with Wuchereria bancrofti and/or Mansonella perstans infections (Fil(+); n = 19) and those without evidence of filarial infection (Fil(-); n = 19). Plasma levels of IL-10 (geometric mean [GM], 22.8 vs 10.4) were higher in Fil(+) compared with Fil(-), whereas levels of IFN-inducible protein (IP)-10 were lower in Fil(+) (GM, 66.3 vs 110.0). Fil(+) had higher levels of spontaneously secreted IL-10 (GM, 59.3 vs 6.8 pg/ml) and lower levels of IL-2 (1.0 vs 1.2 pg/ml) than did Fil(-). Although there were no differences in levels of Staphylococcus aureus enterotoxin B-induced cytokines between the two groups, Fil(+) mounted lower IL-12p70 (GM, 1.11 vs 3.83 pg/ml; p = 0.007), IFN-gamma (GM, 5.44 vs 23.41 pg/ml; p = 0.009), and IP-10 (GM, 29.43 vs 281.7 pg/ml; p = 0.007) responses following malaria Ag (MalAg) stimulation compared with Fil(-). In contrast, Fil(+) individuals had a higher MalAg-specific IL-10 response (GM, 7318 pg/ml vs 3029 pg/ml; p = 0.006) compared with those without filarial infection. Neutralizing Ab to IL-10 (but not to TGF beta) reversed the down-regulated MalAg-specific IFN-gamma and IP-10 (p < 0.001) responses in Fil(+). Together, these data demonstrate that filarial infections modulate the Plasmodium falciparum-specific IL-12p70/IFN-gamma secretion pathways known to play a key role in resistance to malaria and that they do so in an IL-10-dependent manner. The Journal of Immunology, 2009, 183: 916-924.
C1 [Metenou, Simon; Klion, Amy; Mahanty, Siddhartha; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Dembele, Benoit; Konate, Siaka; Dolo, Housseini; Coulibaly, Siaka Y.; Coulibaly, Yaya I.; Diallo, Abdallah A.; Soumaoro, Lamine; Coulibaly, Michel E.; Sanogo, Dramane; Doumbia, Salif S.; Wagner, Marissa; Traore, Sekou F.] Univ Bamako, Filariasis Unit, Fac Med Pharm & Dent, Bamako, Mali.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room B1-03, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
RI Metenou, Simon/C-1101-2013;
OI Mery, Marissa/0000-0001-5819-6008; Klion, Amy/0000-0002-4986-5326;
Mahanty, Siddhartha/0000-0003-1068-0524
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 76
TC 37
Z9 37
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2009
VL 183
IS 2
BP 916
EP 924
DI 10.4049/jimmunol.0900257
PG 9
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600017
PM 19561105
ER
PT J
AU Perruche, S
Zhang, P
Maruyama, T
Bluestone, JA
Saas, P
Chen, WJ
AF Perruche, Sylvain
Zhang, Pin
Maruyama, Takashi
Bluestone, Jeffrey A.
Saas, Philippe
Chen, WanJun
TI Lethal Effect of CD3-Specific Antibody in Mice Deficient in TGF-beta 1
by Uncontrolled Flu-Like Syndrome
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; ANTI-CD3 MONOCLONAL-ANTIBODY;
TUMOR-NECROSIS-FACTOR; TGF-BETA; AUTOIMMUNE ENCEPHALOMYELITIS; ORAL
TOLERANCE; TRANSPLANTATION TOLERANCE; IMMUNE-RESPONSES; DENDRITIC CELLS
AB CD3-specific Ab therapy results in a transient, self-limiting, cytokine-associated, flu-like syndrome in experimental animals and in patients, but the underlying mechanism for this spontaneous resolution remains elusive. By using an in vivo model of CD3-specific Ab-induced flu-like syndrome, we show in this paper that a single injection of sublethal dose of the Ab killed all TGF-beta 1(-/-) Mice. The death of TGF-beta 1(-/-) mice was associated with occurrence of this uncontrolled flu-like syndrome, as demonstrated by a sustained storm of systemic inflammatory TNF and IFN-gamma cytokines. We present evidence that deficiency of professional phagocytes to produce TGF-beta 1 after apoptotic T cell clearance may be responsible, together with hypersensitivity of T cells to both activation and apoptosis, for the uncontrolled inflammation. These findings indicate a key role for TGF-beta 1 and phagocytes in protecting the recipients from lethal inflammation and resolving the flu-like syndrome after CD3-specific Ab treatment. The study may also provide a novel molecular mechanism explaining the early death in TGF-beta 1(-/-) mice. The Journal of Immunology, 2009, 183: 953-961.
C1 [Perruche, Sylvain; Zhang, Pin; Maruyama, Takashi; Chen, WanJun] Natl Inst Dent & Carniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA.
[Bluestone, Jeffrey A.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA.
[Saas, Philippe] Univ Franche Comte, INSERM UMR645, Estab Francais Sana Bourgogne Franche Comte, Inst Federatif Rech, F-25030 Besancon, France.
RP Chen, WJ (reprint author), Natl Inst Dent & Carniofacial Res, Mucosal Immunol Unit, Oral Infect & Immun Branch, NIH, 30 Convent Dr,Bldg 30,Room 304, Bethesda, MD 20892 USA.
EM wchen@mail.nih.gov
RI MaruYama, Takashi/N-5994-2014; SAAS, Philippe/M-3550-2015;
OI SAAS, Philippe/0000-0002-8857-9939
FU National Institutes of Health, National Institute of Dental and
Craniofacial Research; Institut National du Cancer [PL098]; Association
de Recherche contre le Cancer [3851]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research. P.S. is supported by grants froth the Institut
National du Cancer (PL098) and the Association de Recherche contre le
Cancer (3851).
NR 53
TC 7
Z9 7
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 JUL 15
PY 2009
VL 183
IS 2
BP 953
EP 961
DI 10.4049/jimmunol.0804076
PG 9
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600021
PM 19561097
ER
PT J
AU DeFord-Watts, LM
Tassin, TC
Becker, AM
Medeiros, JJ
Albanesi, JP
Love, PE
Wulfing, C
van Oers, NSC
AF DeFord-Watts, Laura M.
Tassin, Tara C.
Becker, Amy M.
Medeiros, Jennifer J.
Albanesi, Joseph P.
Love, Paul E.
Wuelfing, Christoph
van Oers, Nicolai S. C.
TI The Cytoplasmic Tail of the T Cell Receptor CD3 epsilon Subunit Contains
a Phospholipid-Binding Motif that Regulates T Cell Functions
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID INDUCED CONFORMATIONAL-CHANGE; TRANSGENIC MICE; ACTIVATION MOTIFS;
TCR-ZETA; CD3-EPSILON; MEMBRANE; SELECTION; SIGNAL; ITAM;
PHOSPHORYLATION
AB The CD3 epsilon subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3, termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P(3), and PI(4,5)P(2). Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 a localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 epsilon lipid-binding domain in T cell biology. The Journal of Immunology, 2009, 183: 1055-1064.
C1 [DeFord-Watts, Laura M.; Becker, Amy M.; Medeiros, Jennifer J.; Wuelfing, Christoph; van Oers, Nicolai S. C.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
[Tassin, Tara C.; Albanesi, Joseph P.] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA.
[van Oers, Nicolai S. C.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
[Wuelfing, Christoph] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA.
[Love, Paul E.] NICHHD, Lab Mammalian Genes & Dev, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP van Oers, NSC (reprint author), Univ Texas SW Med Ctr Dallas, Dept Immunol, Room NA2-200,6000 Harry Hines Blvd, Dallas, TX 75390 USA.
EM nicolai.vanoers@utsouthwestern.edu
FU National Institutes of Health [T32 A1005284, A142953, A171229]
FX This work was supported in part by grants from the National Institutes
of Health T32 A1005284 (to A.B. and L.D.), A142953, and A171229 (to
N.S.C.v.O.).
NR 33
TC 36
Z9 37
U1 1
U2 9
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 2009
VL 183
IS 2
BP 1055
EP 1064
DI 10.4049/jimmunol.0900404
PG 10
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600031
PM 19542373
ER
PT J
AU Petrovas, C
Chaon, B
Ambrozak, DR
Price, DA
Melenhorst, JJ
Hill, BJ
Geldmacher, C
Casazza, JP
Chattopadhyay, PK
Roederer, M
Douek, DC
Mueller, YM
Jacobson, JM
Kulkarni, V
Felber, BK
Pavlakis, GN
Katsikis, PD
Koup, RA
AF Petrovas, Constantinos
Chaon, Benjamin
Ambrozak, David R.
Price, David A.
Melenhorst, J. Joseph
Hill, Brenna J.
Geldmacher, Christof
Casazza, Joseph P.
Chattopadhyay, Pratip K.
Roederer, Mario
Douek, Daniel C.
Mueller, Yvonne M.
Jacobson, Jeffrey M.
Kulkarni, Viraj
Felber, Barbara K.
Pavlakis, George N.
Katsikis, Peter D.
Koup, Richard A.
TI Differential Association of Programmed Death-1 and CD57 with Ex Vivo
Survival of CD8(+) T Cells in HIV Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID FAS-MEDIATED APOPTOSIS; DISEASE PROGRESSION; PD-1 EXPRESSION;
CD95/FAS-INDUCED APOPTOSIS; VIRAL-INFECTION; ACTIVATION; RESPONSES;
RECEPTOR; TRANSLOCATION; LYMPHOCYTES
AB Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8(+) T cells. In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the "effector-memory" CD8(+) T cell population from HIV+ donors. High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-R alpha, high expression of CD95/Fas and high mitochondrial mass. Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8(+) T cells in HIV infection. CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1(L)CD57(H) phenotype exhibiting lower levels of cell death. The majority of HIV-specific CD8(+) T cells were found to express a PD-1(H)CD57(L) or PD-1(H)CD57(H) phenotype. No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8(+) T cells. Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8(+) T cells in HIV infection. The Journal of Immunology, 2009, 183: 1120-1132.
C1 [Petrovas, Constantinos; Chaon, Benjamin; Ambrozak, David R.; Geldmacher, Christof; Casazza, Joseph P.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA.
[Price, David A.; Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA.
[Chattopadhyay, Pratip K.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, Natl Inst Hlth, Bethesda, MD 20814 USA.
[Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales.
[Melenhorst, J. Joseph] NHLBI, Hematol Branch, Natl Inst Hlth, Bethesda, MD 20814 USA.
[Mueller, Yvonne M.; Jacobson, Jeffrey M.; Katsikis, Peter D.] Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19102 USA.
[Mueller, Yvonne M.; Jacobson, Jeffrey M.; Katsikis, Peter D.] Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19102 USA.
[Kulkarni, Viraj; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
[Pavlakis, George N.] NCI, Human Retrovirus Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA.
RP Petrovas, C (reprint author), NIAID, Vaccine Res Ctr, Natl Inst Hlth, 40 Convent Dr, Bethesda, MD 20892 USA.
EM petrovasc@mail.nih.gov; rk@mail.nih.gov
RI Chattopadhyay, Pratip/B-9227-2008; Price, David/C-7876-2013;
OI Mueller, Yvonne/0000-0002-4654-7509; Chattopadhyay,
Pratip/0000-0002-5457-9666; Price, David/0000-0001-9416-2737; Katsikis,
Peter/0000-0001-7690-5218
FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [,
G0501963]; NIAID NIH HHS [R01 AI046719, R01 AI046719-10, R01 AI46719]
NR 72
TC 64
Z9 65
U1 1
U2 6
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 2009
VL 183
IS 2
BP 1120
EP 1132
DI 10.4049/jimmunol.0900182
PG 13
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600038
PM 19564339
ER
PT J
AU Thaxton, JE
Romero, R
Sharma, S
AF Thaxton, Jessica E.
Romero, Roberto
Sharma, Surendra
TI TLR9 Activation Coupled to IL-10 Deficiency Induces Adverse Pregnancy
Outcomes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; NATURAL-KILLER-CELLS; UTERINE NK CELLS;
CPG-OLIGODEOXYNUCLEOTIDES; PRETERM BIRTH; BACTERIAL-DNA; GENE
POLYMORPHISMS; IMMUNE ACTIVATION; DENDRITIC CELLS; INNATE IMMUNITY
AB Pregnancy outcome is severely compromised by intrauterine infections and inflammation. Although the pregnant uterine microenvironment is replete with innate immune cells and TLR expression, the mechanisms that facilitate adverse effects of their activation are largely unknown. In this study, we mimic the activation of TLR9 with its pathogenic ligand hypomethylated CpG and demonstrate that IL-10 proficiency protects against CpG-induced pregnancy complications. We show that fetal resorption and preterm birth are rapidly induced in IL-10(-/-) mice by low doses of CpG (similar to 25 mu g/mouse) when injected i.p. on gestational day 6 or gestational day 14, respectively. In contrast, wild-type mice failed to experience such effects at comparable doses, but pups born at term displayed craniofacial/limb defects in response to higher doses (similar to 400 mu g/mouse). Pregnancy complications in IL-10(-/-) mice were associated with unexpected and robust TLR9-triggered activation and amplification of uterine neutrophil and macrophage subpopulations followed by their migration to the placental zone. Furthermore, a dramatic increase in serum levels of mouse KC and TNF-alpha production by uterine F4/80(+) cells, but not uterine NK or Gr-1(+)CD11b(+) cells, was observed. Depletion of F4/80+ macrophages or neutralization of TNF-a rescued pregnancy to term. Our results have important implications for IL-10-mediated "uterine tolerance" against CpG-driven innate immune activation. The Journal of Immunology, 2009, 183: 1144-1154.
C1 [Thaxton, Jessica E.; Sharma, Surendra] Brown Univ, Women & Infants Hosp, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02905 USA.
[Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Natl Inst Hlth, Dept Hlth & Human Serv, Detroit, MI 48201 USA.
RP Sharma, S (reprint author), Brown Univ, Women & Infants Hosp, Dept Pediat, Warren Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA.
EM ssharma@wihri.org
FU National Institutes of Health; National Center for Research Resources
[P20RR018728]
FX This work was supported in part by a grant from National Institutes of
Health, National Center for Research Resources (P20RR018728), The
Intramural Division of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health, and
Subcontract WSU05056 under National Instittue of Child Health and Human
Development Contract N01-HD-2-3342. J.E.T. was supported by a Superfund
Basic Research Program Award (P42ES013660) from the National Institute
of Environmental Health Sciences.
NR 60
TC 82
Z9 87
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 2009
VL 183
IS 2
BP 1144
EP 1154
DI 10.4049/jimmunol.0900788
PG 11
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600040
PM 19561095
ER
PT J
AU Schaljo, B
Kratochvill, F
Gratz, N
Sadzak, I
Sauer, I
Hammer, M
Vogl, C
Strobl, B
Muller, M
Blackshear, PJ
Poli, V
Lang, R
Murray, PJ
Kovarik, P
AF Schaljo, Barbara
Kratochvill, Franz
Gratz, Nina
Sadzak, Iwona
Sauer, Ines
Hammer, Michael
Vogl, Claus
Strobl, Birgit
Mueller, Mathias
Blackshear, Perry J.
Poli, Valeria
Lang, Roland
Murray, Peter J.
Kovarik, Pavel
TI Tristetraprolin Is Required for Full Anti-Inflammatory Response of
Murine Macrophages to IL-10
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; DUAL-SPECIFICITY PHOSPHATASE-1; MESSENGER-RNA
STABILITY; TNF-ALPHA PRODUCTION; AU-RICH ELEMENTS; GENE-EXPRESSION;
INFLAMMATORY RESPONSE; CHRONIC ENTEROCOLITIS; MAP KINASE; P38 MAPK
AB IL-10 is essential for inhibiting chronic and acute inflammation by decreasing the amounts of proinflammatory cytokines made by activated macrophages. IL-10 controls proinflammatory cytokine and chemokine production indirectly via the transcription factor Stat3. One of the most physiologically significant IL-10 targets is TNF-alpha, a potent proinflammatory mediator that is the target for multiple anti-TNF-alpha clinical strategies in Crohn's disease and rheumatoid arthritis. The anti-inflammatory effects of IL-10 seem to be mediated by several incompletely understood transcriptional and posttranscriptional mechanisms. In this study, we show that in LPS-activated bone marrow-derived murine macrophages, IL-10 reduces the mRNA and protein levels of TNF-a and IL-1 alpha in part through the RNA destabilizing factor tristetraprolin (TTP). TTP is known for its central role in destabilizing mRNA molecules containing class II AU-rich elements in 3' untranslated regions. We found that IL-10 initiates a Stat3-dependent increase of TTP expression accompanied by a delayed decrease of p38 MAPK activity. The reduction of p38 MAPK activity releases TTP from the p38 MAPK-mediated inhibition, thereby resulting in diminished mRNA and protein levels of proinflammatory cytokines. These findings establish that TTP is required for full responses of bone marrow-derived murine macrophages to IL-10. The Journal of Immunology, 2009, 183: 1197-1206.
C1 [Schaljo, Barbara; Kratochvill, Franz; Gratz, Nina; Sadzak, Iwona; Sauer, Ines; Kovarik, Pavel] Univ Vienna, Max F Perutz Labs, Dept Microbiol & Immunobiol, A-1030 Vienna, Austria.
[Vogl, Claus; Strobl, Birgit; Mueller, Mathias] Univ Vet Med Vienna, Inst Genet & Anim Breeding, Vienna, Austria.
[Strobl, Birgit; Mueller, Mathias] Univ Vet Med Vienna, Univ Ctr Biomodels Austria GmbH, Vienna, Austria.
[Blackshear, Perry J.] Natl Inst Environm Hlth Sci, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
[Poli, Valeria] Univ Turin, Dept Genet Biol & Biochem, Ctr Mol Biol, Turin, Italy.
[Hammer, Michael; Lang, Roland] Tech Univ Munich, Inst Med Microbiol & Immunol & Hyg, Munich, Germany.
[Hammer, Michael; Lang, Roland] Univ Hosp Erlangen, Inst Microbiol Immunol & Hyg, Erlangen, Germany.
[Murray, Peter J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA.
[Murray, Peter J.] St Jude Childrens Hosp, Dept Immunol, Memphis, TN 38105 USA.
RP Kovarik, P (reprint author), Univ Vienna, Max F Perutz Labs, Dept Microbiol & Immunobiol, Dr Bohr Gasse 9, A-1030 Vienna, Austria.
EM pavel.kovarik@univie.ac.at
RI Poli, Valeria/A-9215-2012; Lang, Roland/C-3287-2011; Kovarik,
Pavel/D-1184-2014;
OI Lang, Roland/0000-0003-0502-3677; Poli, Valeria/0000-0002-3739-3966;
Kovarik, Pavel/0000-0003-2956-0944; Strobl, Birgit/0000-0001-5716-3212
FU Austrian Science Fund (Fonds zur Forderungder Wissenschaftlichen
Forschung) [SFB F28, P16726-B14]; European Science Foundation [127-B03]
FX This study was supported by Austrian Science Fund (Fonds zur
Forderungder Wissenschaftlichen Forschung) Grants SFB F28 and
P16726-B14, European Science Foundation Grant 127-B03 (to P.K.),
Austrian Science Fund Fonds zur Forderungder Wissenschaftlichen
Forschung Grant SFB F28 and the Austrian Federal Ministry for Science
and Research Grant Bundesministerium fur Wissenschaft and Forschung
GZ200.112/1-V1/1/2004 (to M.M.), National Institutes of Health Grant
A1062921 (to P.J.M.), and Deutsche Forschungsgemcinschaft Grants
Sonderforschungsbereich 576/TP-A11 and LA 1262/4-1 (to R.L.).
NR 54
TC 57
Z9 60
U1 0
U2 3
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD JUL 15
PY 2009
VL 183
IS 2
BP 1197
EP 1206
DI 10.4049/jimmunol.0803883
PG 10
WC Immunology
SC Immunology
GA 468JD
UT WOS:000267812600045
PM 19542371
ER
PT J
AU Schiller, JT
Lowy, DR
AF Schiller, John T.
Lowy, Douglas R.
TI Immunogenicity Testing in Human Papillomavirus Virus-Like-Particle
Vaccine Trials
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
ID NEUTRALIZATION ASSAY; SUSTAINED EFFICACY; ANTIBODY-LEVELS; HPV VACCINES;
VLP VACCINE; YOUNG-WOMEN; FOLLOW-UP; TYPE-16; INFECTION; CYCLE
C1 [Schiller, John T.; Lowy, Douglas R.] NCI, Ctr Canc Res, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Schiller, JT (reprint author), NCI, Ctr Canc Res, Cellular Oncol Lab, Bldg 37,Rm 4106, Bethesda, MD 20892 USA.
EM schillej@mail.nih.gov
FU Intramural NIH HHS [ZIA BC010579-07]
NR 29
TC 53
Z9 57
U1 0
U2 5
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2009
VL 200
IS 2
BP 166
EP 171
DI 10.1086/599988
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 458RD
UT WOS:000267040300003
PM 19519255
ER
PT J
AU Babu, S
Bhat, SQ
Kumar, NP
Jayantasri, S
Rukmani, S
Kumaran, P
Gopi, PG
Kolappan, C
Kumaraswami, V
Nutman, TB
AF Babu, Subash
Bhat, Sajid Q.
Kumar, N. Pavan
Jayantasri, S.
Rukmani, S.
Kumaran, Paul
Gopi, P. G.
Kolappan, C.
Kumaraswami, V.
Nutman, Thomas B.
TI Human Type 1 and 17 Responses in Latent Tuberculosis Are Modulated by
Coincident Filarial Infection through Cytotoxic T Lymphocyte Antigen-4
and Programmed Death-1
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CHRONIC HELMINTH INFECTIONS; HUMAN LYMPHATIC FILARIASIS;
PARASITE-SPECIFIC ANERGY; VACCINE CVD 103-HGR;
MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSE; ASCARIS-LUMBRICOIDES;
SCHISTOSOMA-MANSONI; TETANUS VACCINATION; CELLS
AB Mycobacterium tuberculosis and filarial coinfection is highly prevalent, and the presence of a tissue-invasive helminth may modulate the predominant type 1 T helper (Th1; interferon [IFN]-gamma-mediated) response needed to control M. tuberculosis infection. By analyzing the cellular responses to mycobacterial antigens in patients who had latent tuberculosis with or without filarial infection, we were able to demonstrate that filarial infection coincident with M. tuberculosis infection significantly diminishes M. tuberculosis-specific Th1 (interleukin [IL]-12 and IFN-gamma) and type 17 T helper (Th17; IL-23 and IL-17) responses related to increased expression of cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1. Blockade of CTLA-4 restored production of both IFN-gamma and IL-17, whereas PD-1 blockade restored IFN-gamma production only. Thus, coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific Th1 and Th17 responses in latent tuberculosis, suggesting a mechanism by which concomitant filarial (and other systemic helminth) infections predispose to the development of active tuberculosis in humans.
C1 [Babu, Subash] NIH ICER, TB Res Ctr, Chennai 600031, Tamil Nadu, India.
[Babu, Subash] NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA.
[Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Babu, S (reprint author), NIH ICER, TB Res Ctr, Mayor VR Ramanathan Rd, Chennai 600031, Tamil Nadu, India.
EM sbabu@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX Intramural Research Program of the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 39
TC 57
Z9 57
U1 2
U2 4
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2009
VL 200
IS 2
BP 288
EP 298
DI 10.1086/599797
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 458RD
UT WOS:000267040300017
PM 19505258
ER
PT J
AU Dilks, DD
Baker, CI
Liu, YC
Kanwisher, N
AF Dilks, Daniel D.
Baker, Chris I.
Liu, Yicong
Kanwisher, Nancy
TI "Referred Visual Sensations": Rapid Perceptual Elongation after Visual
Cortical Deprivation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID PRIMATE STRIATE CORTEX; MACULAR DEGENERATION; BLIND SPOT; FUNCTIONAL
REORGANIZATION; RETINAL LESIONS; DYNAMIC CHANGES; PLASTICITY; CATS; V1;
CONNECTIONS
AB Visual perceptual distortion (i.e., elongation) has been demonstrated in a single case study after several months of cortical deprivation after a stroke. Here we asked whether similar perceptual elongation can be observed in healthy participants after deprivation and, crucially, how soon after deprivation this elongation occurs. To answer this question, we patched one eye, thus noninvasively and reversibly depriving bottom-up input to the region of primary visual cortex (V1) corresponding to the blind spot (BS) in the unpatched eye, and tested whether and how quickly elongation occurs after the onset of deprivation. Within seconds of eye patching, participants perceived rectangles adjacent to the BS to be elongated toward the BS. We attribute this perceptual elongation to rapid receptive field expansion within the deprived V1 as reported in electrophysiological studies after retinal lesions and refer to it as "referred visual sensations" (RVS). This RVS is too fast to be the result of structural changes in the cortex (e. g., the growth of new connections), instead implicating unmasking of preexisting connections as the underlying neural mechanism. These findings may shed light on other reported perceptual distortions, as well as the phenomena of "filling-in."
C1 [Dilks, Daniel D.; Liu, Yicong; Kanwisher, Nancy] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
[Baker, Chris I.] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
RP Dilks, DD (reprint author), MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA.
EM dilks@mit.edu
OI Baker, Chris/0000-0001-6861-8964
FU National Institutes of Health [EY016559]; Kirschstein National Research
Service [EY017507]; National Institute of Mental Health Intramural
Research Program
FX This work was supported by National Institutes of Health Grant EY016559
(N. K.), Kirschstein National Research Service Award EY017507 (D. D.
D.), and the National Institute of Mental Health Intramural Research
Program (C. I. B.). We thank Jonas Kubilius for help with data
collection and analyses, Brian Wandell for suggesting experiment 2, and
Aniruddha Das, David Ferster, Ken Nakayama, Mriganka Sur, Frank Tong,
and Gina Turrigiano for helpful comments on this manuscript.
NR 36
TC 11
Z9 11
U1 1
U2 5
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 15
PY 2009
VL 29
IS 28
BP 8960
EP 8964
DI 10.1523/JNEUROSCI.1557-09.2009
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 470YI
UT WOS:000268018000010
PM 19605633
ER
PT J
AU Abdala, APL
Rybak, IA
Smith, JC
Paton, JFR
AF Abdala, A. P. L.
Rybak, I. A.
Smith, J. C.
Paton, J. F. R.
TI Abdominal expiratory activity in the rat brainstem-spinal cord in situ:
patterns, origins and implications for respiratory rhythm generation
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Article
ID NEWBORN RATS; AUGMENTING NEURONS; BREATHING PATTERN; BOTZINGER-COMPLEX;
DECEREBRATE RAT; ROSTRAL MEDULLA; VENTRAL MEDULLA; MUSCLE-ACTIVITY;
NERVE ACTIVITY; HYPOXIA
AB We studied respiratory neural activity generated during expiration. Motoneuronal activity was recorded simultaneously from abdominal (AbN), phrenic (PN), hypoglossal (HN) and central vagus nerves from neonatal and juvenile rats in situ. During eupnoeic activity, low-amplitude post-inspiratory (post-I) discharge was only present in AbN motor outflow. Expression of AbN late-expiratory (late-E) activity, preceding PN bursts, occurred during hypercapnia. Biphasic expiratory (biphasic-E) activity with pre-inspiratory (pre-I) and post-I discharges occurred only during eucapnic anoxia or hypercapnic anoxia. Late-E activity generated during hypercapnia (7-10% CO2) was abolished with pontine transections or chemical suppression of retrotrapezoid nucleus/ventrolateral parafacial (RTN/vlPF). AbN late-E activity during hypercapnia is coupled with augmented pre-I discharge in HN, truncated PN burst, and was quiescent during inspiration. Our data suggest that the pons provides a necessary excitatory drive to an additional neural oscillatory mechanism that is only activated under conditions of high respiratory drive to generate late-E activity destined for AbN motoneurones. This mechanism may arise from neurons located in the RTN/vlPF or the latter may relay late-E activity generated elsewhere. We hypothesize that this oscillatory mechanism is not a necessary component of the respiratory central pattern generator but constitutes a defensive mechanism activated under critical metabolic conditions to provide forced expiration and reduced upper airway resistance simultaneously. Possible interactions of this oscillator with components of the brainstem respiratory network are discussed.
C1 [Abdala, A. P. L.; Paton, J. F. R.] Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol Heart Inst, Bristol BS8 1TD, Avon, England.
[Rybak, I. A.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19104 USA.
[Smith, J. C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Paton, JFR (reprint author), Univ Bristol, Sch Med Sci, Dept Physiol & Pharmacol, Bristol Heart Inst, Bristol BS8 1TD, Avon, England.
EM julian.f.r.paton@bristol.ac.uk
RI Abdala, Ana Paula/G-9104-2014;
OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913
FU National Institute of Neurological Disorders and Stroke (NINDS), NIH
[R01 NS057815]; Royal Society Wolfson Research Merit Award
FX This study was supported by the National Institute of Neurological
Disorders and Stroke (NINDS), NIH grant R01 NS057815 and in part by the
Intramural Research Program of the NIH, NINDS. J.F.R. Paton is the
recipient of a Royal Society Wolfson Research Merit Award.
NR 51
TC 83
Z9 84
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD JUL 15
PY 2009
VL 587
IS 14
BP 3539
EP 3559
DI 10.1113/jphysiol.2008.167502
PG 21
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 471FF
UT WOS:000268040500021
PM 19491247
ER
PT J
AU Grishaev, A
Yao, LS
Ying, JF
Pardi, A
Bax, A
AF Grishaev, Alexander
Yao, Lishan
Ying, Jinfa
Pardi, Arthur
Bax, Ad
TI Chemical Shift Anisotropy of Imino N-15 Nuclei in Watson-Crick Base
Pairs from Magic Angle Spinning Liquid Crystal NMR and Nuclear Spin
Relaxation
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID HYDROGEN-BONDS; TENSORS; COUPLINGS; ALIGNMENT; PHASE; MODEL
AB Knowledge of (IN)-I-15 chemical shift anisotropy is prerequisite both for quantitative interpretation of nuclear spin relaxation rates in terms of local dynamics and for the use of residual chemical shift anisotropy (RCSA) as a constraint in structure determination. Accurate measurement of the very small RCSA from the difference in N-15 chemical shift under isotropic and weakly aligning liquid crystaltine conditions is very sensitive to minute differences in sample conditions, such as pH or ionic strength. For this reason, chemical shifts were measured for the same solution, under static liquid crystalline alignment, and under magic angle spinning conditions where alignment relative to the magnetic field is removed. Measurements were made for 14 well-resolved G-N-1 and 6 U-N-3 N-15 nuclei in a sample of tRNA(val). Fitting these RCSA data together with N-15-H-1 dipole-CSA cross-correlated relaxation measurements to the recently refined structural model of tRNA(val) yields the magnitude, asymmetry, and orientation of the N-15 CSA tensors
C1 [Grishaev, Alexander; Yao, Lishan; Ying, Jinfa; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Pardi, Arthur] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Yao, Lishan /C-6961-2009; yao, lishan/H-3662-2012
OI yao, lishan/0000-0003-1797-922X
FU Intramural Research Program of the NIDDK; NIH [AI33098]
FX This work was supported in part by the Intramural Research Program of
the NIDDK, NIH and NIH Grant AI33098 (A.P.). We thank Werner Maas and
Jochem Struppe (Bruker Instruments) for help with the MAS measurements.
NR 20
TC 14
Z9 14
U1 1
U2 7
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 15
PY 2009
VL 131
IS 27
BP 9490
EP +
DI 10.1021/ja903244s
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA 473VT
UT WOS:000268239400011
PM 19537719
ER
PT J
AU Ryabov, Y
Suh, JY
Grishaev, A
Clore, GM
Schwieters, CD
AF Ryabov, Yaroslav
Suh, Jeong-Yong
Grishaev, Alexander
Clore, G. Marius
Schwieters, Charles D.
TI Using the Experimentally Determined Components of the Overall Rotational
Diffusion Tensor To Restrain Molecular Shape and Size in NMR Structure
Determination of Globular Proteins and Protein-Protein Complexes
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID N-TERMINAL DOMAIN; SMALL-ANGLE SCATTERING; MACROMOLECULAR STRUCTURE
DETERMINATION; RESIDUAL DIPOLAR COUPLINGS; X-RAY-SCATTERING; ENZYME-I;
PHOSPHOTRANSFERASE SYSTEM; STRUCTURE REFINEMENT; PHOSPHOCARRIER PROTEIN;
3-DIMENSIONAL STRUCTURES
AB This paper describes an approach for making use of the components of the experimentally determined rotational diffusion tensor derived from NMR relaxation measurements in macomolecular structure determination. The parameters of the rotational diffusion tensor describe the shape and size of the macromolecule or macromolecular complex, and are therefore complementary to traditional NMR restraints. The structural information contained in the rotational diffusion tensor is not dissimilar to that present in the small-angle region of solution X-ray scattering profiles. We demonstrate the utility of rotational diffusion tensor restraints for protein structure refinement using the N-terminal domain of enzyme I (EIN) as an example and validate the results by solution small-angle X-ray scattering. We also show how rotational diffusion tensor restraints can be used for docking complexes using the dimeric HIV-1 protease and the EIN-HPr complexes as examples. In the former case, the rotational diffusion tensor restraints are sufficient in their own right to determine the position of one subunit relative to another. In the latter case, rotational diffusion tensor restraints complemented by highly ambiguous distance restraints derived from chemical shift perturbation mapping and a hydrophobic contact potential are sufficient to correctly dock EIN to HPr. In each case, the cluster containing the lowest-energy structure corresponds to the correct solution.
C1 [Suh, Jeong-Yong; Grishaev, Alexander; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
[Ryabov, Yaroslav; Schwieters, Charles D.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov; charles.schwieters@nih.gov
RI Clore, G. Marius/A-3511-2008
OI Clore, G. Marius/0000-0003-3809-1027
FU National Research Council Research Associateship [0710430]; NIDDK
Intramural Research Program of the NIH; Office of the Director of the
NIH; NIH
FX We thank Dan Garrett and John Kuszewski for useful discussions. Y.R.
acknowledges a National Research Council Research Associateship (Award
No. 0710430). This work was supported by the NIDDK Intramural Research
Program of the NIH (to G.M.C.), the AIDS Targeted Antiviral Program of
the Office of the Director of the NIH (to G.M.C.), and the CIT
intramural research program of the NIH (to C.D.S.)
NR 56
TC 18
Z9 19
U1 0
U2 10
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 15
PY 2009
VL 131
IS 27
BP 9522
EP 9531
DI 10.1021/ja902336c
PG 10
WC Chemistry, Multidisciplinary
SC Chemistry
GA 473VT
UT WOS:000268239400021
PM 19537713
ER
PT J
AU Bermejo, GA
Strub, MP
Ho, C
Tjandra, N
AF Bermejo, Guillermo A.
Strub, Marie-Paule
Ho, Chien
Tjandra, Nico
TI Determination of the Solution-Bound Conformation of an Amino Acid
Binding Protein by NMR Paramagnetic Relaxation Enhancement: Use of a
Single Flexible Paramagnetic Probe with Improved Estimation of Its
Sampling Space
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS; ESCHERICHIA-COLI;
GLUTAMINE; H-1; RESOLUTION; ORIENTATION; DATABASE; SPECTRA
AB We demonstrate the feasibility of elucidating the bound ("closed") conformation of a periplasmic binding protein, the glutamine-binding protein (GlnBP), in solution, using paramagnetic relaxation enhancements (PREs) arising from a single paramagnetic group. GlnBP consists of two globular domains connected by a hinge. Using the ligand-free ("open") conformation as a starting point, conjoined rigid-body/torsion-angle simulated annealing calculations were performed using backbone (1)H(N)-PREs as a major source of distance information. Paramagnetic probe flexibility was accounted for via a multiple-conformer representation. A conventional approach where the entire PRE data set is enforced at once during simulated annealing yielded poor results due to inappropriate conformational sampling of the probe. On the other hand, significant improvements in coordinate accuracy were obtained by estimating the probe sampling space prior to structure calculation. Such sampling is achieved by refining the ensemble of probe conformers with intradomain PRIES only, keeping the protein backbone fixed in the open form. Subsequently, while constraining the probe to the previously found conformations, the domains are allowed to move relative to each other under the influence of the non-intradomain PREs, giving the hinge region torsional degrees of freedom. Thus, by partitioning the protocol into "probe sampling" and "backbone sampling" stages, structures significantly closer to the X-ray structure of ligand-bound GlnBP were obtained.
C1 [Bermejo, Guillermo A.; Strub, Marie-Paule; Tjandra, Nico] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Ho, Chien] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
RP Tjandra, N (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM tjandran@nhlbi.nih.gov
RI Ho, Chien/O-6112-2016
OI Ho, Chien/0000-0002-4094-9232
FU National Institutes of Health [GM-084614]; Intramural Research Program
of the NIH; National Heart, Lung, and Blood Institute
FX We thank James M. Gruschus for useful discussions. This work was
supported by the National Institutes of Health Grant GM-084614 to C.H.
and the Intramural Research Program of the NIH, National Heart, Lung,
and Blood Institute, to N.T.
NR 23
TC 23
Z9 23
U1 1
U2 5
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 15
PY 2009
VL 131
IS 27
BP 9532
EP 9537
DI 10.1021/ja902436g
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 473VT
UT WOS:000268239400022
PM 19583434
ER
PT J
AU Menashe, I
Anderson, WF
Jatoi, I
Rosenberg, PS
AF Menashe, Idan
Anderson, William F.
Jatoi, Ismail
Rosenberg, Philip S.
TI Underlying Causes of the Black-White Racial Disparity in Breast Cancer
Mortality: A Population-Based Analysis
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID UNITED-STATES; SURVIVAL; TRENDS; WOMEN; DIAGNOSIS; OBESITY; RATES; RACE;
AGE
AB In the United States, a black-to-white disparity in age-standardized breast cancer mortality rates emerged in the 1980s and has widened since then.
To further explore this racial disparity, black-to-white rate ratios (RRs(BW)) for mortality, incidence, hazard of breast cancer death, and incidence-based mortality (IBM) were investigated using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program on 244 786 women who were diagnosed with breast cancer from January 1990 through December 2003 and followed through December 2004. A counterfactual approach was used to examine the expected IBM RRs(BW), assuming equal distributions for estrogen receptor (ER) expression, and/or equal hazard rates of breast cancer death, among black and white women.
From 1990 through 2004, mortality RR(BW) was greater than 1.0 and widened over time (age-standardized breast cancer mortality rates fell from 36 to 29 per 100 000 for blacks and from 30 to 22 per 100 000 for whites). In contrast, incidence RR(BW) was generally less than 1.0. Absolute hazard rates of breast cancer death declined substantially for ER-positive tumors and modestly for ER-negative tumors but were persistently higher for blacks than whites. Equalizing the distributions of ER expression in blacks and whites decreased the IBM RR(BW) slightly. Interestingly, the black-to-white disparity in IBM RR(BW) was essentially eliminated when hazard rates of breast cancer death were matched within each ER category.
The black-to-white disparity in age-standardized breast cancer mortality was largely driven by the higher hazard rates of breast cancer death among black women, diagnosed with the disease, irrespective of ER expression, and especially in the first few years following diagnosis. Greater emphasis should be placed on identifying the etiology of these excess hazards and developing therapeutic strategies to address them.
C1 [Menashe, Idan; Anderson, William F.; Rosenberg, Philip S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Jatoi, Ismail] Uniformed Serv Univ Hlth Sci, Natl Naval Med Ctr, Breast Care Ctr, Bethesda, MD USA.
RP Menashe, I (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S,Rm 8047, Rockville, MD 20852 USA.
EM menashei@mail.nih.gov
FU National Institutes of Health; National Cancer Institute
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute
NR 31
TC 78
Z9 78
U1 0
U2 7
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 JUL 15
PY 2009
VL 101
IS 14
BP 993
EP 1000
DI 10.1093/jnci/djp176
PG 8
WC Oncology
SC Oncology
GA 472FE
UT WOS:000268114300011
PM 19584327
ER
PT J
AU Thiebaut, ACM
Jiao, L
Silverman, DT
Cross, AJ
Thompson, FE
Subar, AF
Hollenbeck, AR
Schatzkin, A
Stolzenberg-Solomon, RZ
AF Thiebaut, Anne C. M.
Jiao, Li
Silverman, Debra T.
Cross, Amanda J.
Thompson, Frances E.
Subar, Amy F.
Hollenbeck, Albert R.
Schatzkin, Arthur
Stolzenberg-Solomon, Rachael Z.
TI Dietary Fatty Acids and Pancreatic Cancer in the NIH-AARP Diet and
Health Study
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRES; RETIRED-PERSONS DIET;
NATIONAL-INSTITUTES; NUTRITIONAL FACTORS; INSULIN-RESISTANCE;
MEASUREMENT ERROR; BREAST-CANCER; AMERICAN-ASSOCIATION;
CONFIDENCE-INTERVALS; PROSTATE-CANCER
AB Previous research relating dietary fat, a modifiable risk factor, to pancreatic cancer has been inconclusive.
We prospectively analyzed the association between intakes of fat, fat subtypes, and fat food sources and exocrine pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study, a US cohort of 308 736 men and 216 737 women who completed a 124-item food frequency questionnaire in 1995-1996. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models, with adjustment for energy intake, smoking history, body mass index, and diabetes. Statistical tests were two-sided.
Over an average follow-up of 6.3 years, 865 men and 472 women were diagnosed with exocrine pancreatic cancer (45.0 and 34.5 cases per 100 000 person-years, respectively). After multivariable adjustment and combination of data for men and women, pancreatic cancer risk was directly related to the intakes of total fat (highest vs lowest quintile, 46.8 vs 33.2 cases per 100 000 person-years, HR = 1.23, 95% CI = 1.03 to 1.46; P(trend) = .03), saturated fat (51.5 vs 33.1 cases per 100 000 person-years, HR = 1.36, 95% CI = 1.14 to 1.62; P(trend) < .001), and monounsaturated fat (46.2 vs 32.9 cases per 100 000 person-years, HR = 1.22, 95% CI = 1.02 to 1.46; P(trend) = .05) but not polyunsaturated fat. The associations were strongest for saturated fat from animal food sources (52.0 vs 32.2 cases per 100 000 person-years, HR = 1.43, 95% CI = 1.20 to 1.70; P(trend) < .001); specifically, intakes from red meat and dairy products were both statistically significantly associated with increased pancreatic cancer risk (HR = 1.27 and 1.19, respectively).
In this large prospective cohort with a wide range of intakes, dietary fat of animal origin was associated with increased pancreatic cancer risk.
C1 [Thiebaut, Anne C. M.; Jiao, Li; Cross, Amanda J.; Schatzkin, Arthur; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Silverman, Debra T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Thompson, Frances E.; Subar, Amy F.] NCI, Appl Res Program, Div Canc Control & Populat Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Stolzenberg-Solomon, RZ (reprint author), 6120 Execut Blvd,Ste 320, Rockville, MD 20852 USA.
EM rs221z@nih.gov
FU National Institutes of Health; Division of Cancer Epidemiology and
Genetics; National Cancer Institute; Department of Health and Human
Services
FX Intramural Research Program of the National Institutes of Health,
Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services.
NR 71
TC 44
Z9 46
U1 0
U2 6
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 JUL 15
PY 2009
VL 101
IS 14
BP 1001
EP 1011
DI 10.1093/jnci/djp168
PG 11
WC Oncology
SC Oncology
GA 472FE
UT WOS:000268114300012
PM 19561318
ER
PT J
AU Milne, RL
Benitez, J
Nevanlinna, H
Heikkinen, T
Aittomaki, K
Blomqvist, C
Arias, JI
Zamora, MP
Burwinkel, B
Bartram, CR
Meindl, A
Schmutzler, RK
Cox, A
Brock, I
Elliott, G
Reed, MWR
Southey, MC
Smith, L
Spurdle, AB
Hopper, JL
Couch, FJ
Olson, JE
Wang, XS
Fredericksen, Z
Schurmann, P
Bremer, M
Hillemanns, P
Dork, T
Devilee, P
Van Asperen, CJ
Tollenaar, RAEM
Seynaeve, C
Hall, P
Czene, K
Liu, JJ
Li, YQ
Ahmed, S
Dunning, AM
Maranian, M
Pharoah, PDP
Chenevix-Trench, G
Beesley, J
Bogdanova, NV
Antonenkova, NN
Zalutsky, IV
Anton-Culver, H
Ziogas, A
Brauch, H
Justenhoven, C
Ko, YD
Haas, S
Fasching, PA
Strick, R
Ekici, AB
Beckmann, MW
Giles, GG
Severi, G
Baglietto, L
English, DR
Fletcher, O
Johnson, N
Silva, ID
Peto, J
Turnbull, C
Hines, S
Renwick, A
Rahman, N
Nordestgaard, BG
Bojesen, SE
Flyger, H
Kang, D
Yoo, KY
Noh, DY
Mannermaa, A
Kataja, V
Kosma, VM
Garcia-Closas, M
Chanock, S
Lissowska, J
Brinton, LA
Chang-Claude, J
Wang-Gohrke, S
Shen, CY
Wang, HC
Yu, JC
Chen, ST
Bermisheva, M
Nikolaeva, T
Khusnutdinova, E
Humphreys, MK
Morrison, J
Platte, R
Easton, DF
AF Milne, Roger L.
Benitez, Javier
Nevanlinna, Heli
Heikkinen, Tuomas
Aittomaki, Kristiina
Blomqvist, Carl
Ignacio Arias, Jose
Pilar Zamora, M.
Burwinkel, Barbara
Bartram, Claus R.
Meindl, Alfons
Schmutzler, Rita K.
Cox, Angela
Brock, Ian
Elliott, Graeme
Reed, Malcolm W. R.
Southey, Melissa C.
Smith, Letitia
Spurdle, Amanda B.
Hopper, John L.
Couch, Fergus J.
Olson, Janet E.
Wang, Xianshu
Fredericksen, Zachary
Schuermann, Peter
Bremer, Michael
Hillemanns, Peter
Doerk, Thilo
Devilee, Peter
Van Asperen, Christie J.
Tollenaar, Rob A. E. M.
Seynaeve, Caroline
Hall, Per
Czene, Kamila
Liu, Jianjun
Li, Yuqing
Ahmed, Shahana
Dunning, Alison M.
Maranian, Melanie
Pharoah, Paul D. P.
Chenevix-Trench, Georgia
Beesley, Jonathan
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Zalutsky, Iosif V.
Anton-Culver, Hoda
Ziogas, Argyrios
Brauch, Hiltrud
Justenhoven, Christina
Ko, Yon-Dschun
Haas, Susanne
Fasching, Peter A.
Strick, Reiner
Ekici, Arif B.
Beckmann, Matthias W.
Giles, Graham G.
Severi, Gianluca
Baglietto, Laura
English, Dallas R.
Fletcher, Olivia
Johnson, Nichola
Silva, Isabel dos Santos
Peto, Julian
Turnbull, Clare
Hines, Sarah
Renwick, Anthony
Rahman, Nazneen
Nordestgaard, Borge G.
Bojesen, Stig E.
Flyger, Henrik
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Garcia-Closas, Montserrat
Chanock, Stephen
Lissowska, Jolanta
Brinton, Louise A.
Chang-Claude, Jenny
Wang-Gohrke, Shan
Shen, Chen-Yang
Wang, Hui-Chun
Yu, Jyh-Cherng
Chen, Sou-Tong
Bermisheva, Marina
Nikolaeva, Tatjana
Khusnutdinova, Elza
Humphreys, Manjeet K.
Morrison, Jonathan
Platte, Radka
Easton, Douglas F.
CA kConFab Investigators
AOCS Grp
Breast Canc Assoc Consortium
TI Risk of Estrogen Receptor-Positive and -Negative Breast Cancer and
Single-Nucleotide Polymorphism 2q35-rs13387042
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS
AB A recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.
2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.
We found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P >= .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).
The rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
C1 [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Madrid 29029, Spain.
[Benitez, Javier] CIBERER, Madrid, Spain.
[Nevanlinna, Heli; Heikkinen, Tuomas] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, FIN-00290 Helsinki, Finland.
[Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Cent Hosp, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Cent Hosp, Helsinki, Finland.
[Ignacio Arias, Jose] Monte Naranco Hosp, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain.
[Burwinkel, Barbara] Univ Heidelberg, Dept Obstet & Gynecol, Heidelberg, Germany.
[Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, Munich, Germany.
[Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Ctr Clin, Cologne, Germany.
[Cox, Angela; Brock, Ian; Elliott, Graeme] Univ Sheffield, Inst Canc Studies, Sch Med, Sheffield, S Yorkshire, England.
[Reed, Malcolm W. R.] Univ Sheffield, Acad Unit Surg Oncol, Sch Med, Sheffield, S Yorkshire, England.
[Hopper, John L.; English, Dallas R.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Southey, Melissa C.; Smith, Letitia] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Olson, Janet E.; Fredericksen, Zachary] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Schuermann, Peter; Hillemanns, Peter; Doerk, Thilo; Bogdanova, Natalia V.; Bermisheva, Marina] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany.
[Bremer, Michael; Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Van Asperen, Christie J.] Leiden Univ, Dept Clin Genet, Med Ctr, Leiden, Netherlands.
[Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands.
[Seynaeve, Caroline] Erasmus MC Daniel den Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Liu, Jianjun; Li, Yuqing] Genome Inst Singapore, Human Genet Lab, Singapore, Singapore.
[Ahmed, Shahana; Dunning, Alison M.; Maranian, Melanie; Pharoah, Paul D. P.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D. P.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Spurdle, Amanda B.; Chenevix-Trench, Georgia; Beesley, Jonathan] Div Genet & Populat Hlth, Brisbane, Qld, Australia.
Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[kConFab Investigators; AOCS Grp] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Bogdanova, Natalia V.; Antonenkova, Natalia N.; Zalutsky, Iosif V.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Brauch, Hiltrud; Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Brauch, Hiltrud; Justenhoven, Christina] Univ Tubingen, Tubingen, Germany.
[Ko, Yon-Dschun] Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany.
[Haas, Susanne] Univ Bonn, Inst Pathol, D-5300 Bonn, Germany.
[Fasching, Peter A.; Strick, Reiner; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Erlangen, Germany.
[Ekici, Arif B.] Univ Hosp Erlangen, Inst Human Genet, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Gynecol & Obstet, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Giles, Graham G.; Severi, Gianluca; Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Fletcher, Olivia; Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Fletcher, Olivia; Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Canc Res UK Epidemiol & Genet Grp, London WC1, England.
[Turnbull, Clare; Hines, Sarah; Renwick, Anthony; Rahman, Nazneen] Sect Canc Genet, Sutton, Surrey, England.
[Peto, Julian] Inst Canc Res, Sutton, Surrey, England.
[Nordestgaard, Borge G.; Bojesen, Stig E.; Flyger, Henrik] Univ Copenhagen, Dept Clin Biochem, Herlev Univ Hosp, DK-1168 Copenhagen, Denmark.
[Nordestgaard, Borge G.; Bojesen, Stig E.; Flyger, Henrik] Univ Copenhagen, Dept Breast Surg, Herlev Univ Hosp, DK-1168 Copenhagen, Denmark.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Mannermaa, Arto; Kosma, Veli-Matti] Univ Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70211 Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Bioctr Kuopio, Kuopio, Finland.
[Kataja, Vesa] Vaasa Cent Hosp, Dept Oncol, Vaasa, Finland.
[Garcia-Closas, Montserrat; Chanock, Stephen] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Brinton, Louise A.] NCI, Hormonal & Reprod Epidemiol Branch, Rockville, MD USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Wang-Gohrke, Shan] Ulm Med Sch, Dept Gynecol & Obstet, Ulm, Germany.
[Shen, Chen-Yang; Wang, Hui-Chun] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Yu, Jyh-Cherng] Tri Serv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Chen, Sou-Tong] Changhua Christian Hosp, Dept Surg, Changhua, Taiwan.
[Bermisheva, Marina; Khusnutdinova, Elza] Russian Acad Sci, Inst Biochem & Genet, Ufa Sci Ctr, Ufa 450001, Russia.
[Nikolaeva, Tatjana] Russian Acad Med Sci, Dept Med Genet, Yakut Res Ctr, Yakutsk, Russia.
[Humphreys, Manjeet K.; Morrison, Jonathan; Platte, Radka; Easton, Douglas F.] Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.
RP Milne, RL (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Human Canc Genet Program, C Melchor Fernandez Almagro 3, Madrid 29029, Spain.
EM rmilne@cnio.es
RI Szeszenia-Dabrowska, Neonila/F-7190-2010; Dork, Thilo/J-8620-2012;
Bowtell, David/H-1007-2016; Bruning, Thomas/G-8120-2015; Khusnutdinova,
Elza/A-4810-2013; Rahman, Nazneen/D-2802-2013; Spurdle,
Amanda/A-4978-2011; Wang, Hui-Chun/C-5680-2009; Noh,
Dong-Young/G-5531-2011; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012;
Yoo, Keun-Young/J-5548-2012; Ekici, Arif/C-3971-2013; Rahman,
Nazneen/B-8890-2012; Smith, Letitia /J-9035-2014; Gonzalez-Neira,
Anna/C-5791-2015; Garcia-Closas, Montserrat /F-3871-2015; Brinton,
Louise/G-7486-2015
OI Dunning, Alison Margaret/0000-0001-6651-7166; Giles,
Graham/0000-0003-4946-9099; English, Dallas/0000-0001-7828-8188;
Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464;
Rahman, Nazneen/0000-0003-4376-0440; Czene, Kamila/0000-0002-3233-5695;
Lissowska, Jolanta/0000-0003-2695-5799; Nevanlinna,
Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798;
Cox, Angela/0000-0002-5138-1099; Spurdle, Amanda/0000-0003-1337-7897;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562
FU Cancer Research UK [10118, 10119, 10124, 11021, A10119, A10123, A10124,
C1287/A10118, C1287/A7497]; Intramural NIH HHS; Medical Research Council
[G0000934, G0700491]; NCI NIH HHS [CA69417, CA-95-011, CA102740-01A2,
CA116201, CA122340, CA128978, CA58860, CA69398, CA69446, CA69467,
CA69631, CA69638, CA92044, P50 CA116201]; Wellcome Trust [068545/Z/02]
NR 8
TC 78
Z9 80
U1 2
U2 10
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 JUL 15
PY 2009
VL 101
IS 14
BP 1012
EP 1018
DI 10.1093/jnci/djp167
PG 7
WC Oncology
SC Oncology
GA 472FE
UT WOS:000268114300013
PM 19567422
ER
PT J
AU Bagnato, F
Yao, B
Cantor, F
Merkle, H
Condon, E
Montequin, M
Moore, S
Quezado, M
Tkaczyk, D
McFarland, H
AF Bagnato, Francesca
Yao, Bing
Cantor, Fredric
Merkle, Hellmut
Condon, Ellen
Montequin, Marcela
Moore, Sandra
Quezado, Martha
Tkaczyk, Deborah
McFarland, Henry
TI Multisequence-imaging protocols to detect cortical lesions of patients
with multiple sclerosis: Observations from a post-mortem 3 Tesla imaging
study
SO JOURNAL OF THE NEUROLOGICAL SCIENCES
LA English
DT Article
DE Multiple sclerosis; Post-mortem imaging; 3-Tesla MRI; Cortical lesions;
Neurodegeneration; Inflammation
ID ATTENUATED INVERSION-RECOVERY; HIGH-FIELD MRI; SPIN-ECHO; BRAIN; TIME;
T1; PATHOLOGY; CONTRAST; MATTER; T2
AB Neocortical lesions (NLs) are an important component of multiple sclerosis (MS) pathology and may account for part of the physical and cognitive disability. Visualizing NLs of patients with MS using magnetic resonance imaging (MRI) poses several significant challenges. We optimized the inversion time (TI) of T(1)-based magnetization-prepared rapid acquisition gradient-echo (MPRAGE) images by suppressing the signal of the lesions and enhancing their appearance as hypo intensities, on the basis of the derived quantitative T(1) measurements. The latter were achieved by the means of 2D inversion recovery fast spin echo (IR-FSE), repeated using different inversion times (TI). Comparisons of detection of NLs by MPRAGE and dual echo T(2) weighted (T(2)W) and proton density (PD) W. Four coronal brain slices from a deceased MS patient and two coronal brain slices from two formerly healthy donors were imaged using a 3 Tesla magnet (3 T) equipped with a multi-channel coil. Based upon the averaged T1 values computed from the MS specimen as well as visual inspection, an optimal TI of 380 ms was selected for the MPRAGE image. No NLs were seen in the specimens of the two healthy donors.
Of the 40 total NLs observed, 8 (20%) were visible in all three sequences employed. Three (7.5%) NLs were visible only in the PDW image and 5 (12.5%) were seen only in the T(2)W image. Four NLs (10%) had clearly unique conspicuity in the MPRAGE image. Of those, 3 were retrospectively scored in the PDW image (1 NL) or in the T2W image (2 NLs). We conclude that for the detection of MS-related NLs, high-resolution T(1)-based MPRAGE and T(2)-W images offer complementary information and the combination of the two image sequences is crucial for increasing the sensitivity of detecting MS-induced NLs. Published by Elsevier B.V.
C1 [Bagnato, Francesca; Cantor, Fredric; McFarland, Henry] NINDS, Neuroimmunol Branch NIB, NIH, Bethesda, MD 20892 USA.
[Yao, Bing; Merkle, Hellmut] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Condon, Ellen; Montequin, Marcela; Moore, Sandra; Tkaczyk, Deborah] NIMH, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA.
RP Bagnato, F (reprint author), NINDS, Neuroimmunol Branch NIB, NIH, Bldg 10,Room 5C103,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bagnatof@ninds.nih.gov
FU Intramural Research Program of the NINDS, NIH
FX Mr Roger Stone from the NIB-NINDS is acknowledged for editing the
material. We are indebted to the nurses Ms Helen Griffith and Joan
Ohayon (NIB-NINDS-NIH), to the MRI technician Ms Shara Omar (NIMH-NIH)
and to Dr Jerzy Bodurzy (NIMH-NIH) for their assistance to the study.
This research was supported by the Intramural Research Program of the
NINDS, NIH.
NR 30
TC 15
Z9 15
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 2009
VL 282
IS 1-2
BP 80
EP 85
DI 10.1016/j.jns.2009.03.021
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 464IS
UT WOS:000267499200013
PM 19394970
ER
PT J
AU Feng, N
Sen, A
Nguyen, H
Vo, P
Hoshino, Y
Deal, EM
Greenberg, HB
AF Feng, N.
Sen, A.
Nguyen, H.
Vo, P.
Hoshino, Y.
Deal, E. M.
Greenberg, H. B.
TI Variation in Antagonism of the Interferon Response to Rotavirus NSP1
Results in Differential Infectivity in Mouse Embryonic Fibroblasts
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID REGULATORY FACTOR-3; I INTERFERON; CHILDREN; MICE; DEGRADATION;
DIARRHEA; ALPHA; CELLS; TRANSACTIVATION; ACTIVATION
AB Rotavirus NSP1 has been shown to function as an E3 ubiquitin ligase that mediates proteasome-dependent degradation of interferon (IFN) regulatory factors (IRF), including IRF3, -5, and -7, and suppresses the cellular type I IFN response. However, the effect of rotavirus NSP1 on viral replication is not well defined. Prior studies used genetic analysis of selected reassortants to link NSP1 with host range restriction in the mouse, suggesting that homologous and heterologous rotaviruses might use their different abilities to antagonize the IFN response as the basis of their host tropisms. Using a mouse embryonic fibroblast (MEF) model, we demonstrate that heterologous bovine (UK and NCDV) and porcine (OSU) rotaviruses fail to effectively degrade cellular IRF3, resulting in IRF3 activation and beta IFN (IFN-beta) secretion. As a consequence of this failure, replication of these viruses is severely restricted in IFN-competent wild-type, but not in IFN-deficient (IFN-alpha/beta/gamma receptor- or STAT1-deficient) MEFs. On the other hand, homologous murine rotaviruses (ETD or EHP) or the heterologous simian rotavirus (rhesus rotavirus [RRV]) efficiently degrade cellular IRF3, diminish IRF3 activation and IFN-beta secretion and are not replication restricted in wild-type MEFs. Genetic reassortant analysis between UK and RRV maps the distinctive phenotypes of IFN antagonism and growth restriction in wild-type MEFs to NSP1. Therefore, there is a direct relationship between the replication efficiencies of different rotavirus strains in MEFs and strain-related variations in NSP1-mediated antagonism of the type I IFN response.
C1 [Feng, N.; Sen, A.; Nguyen, H.; Vo, P.; Deal, E. M.; Greenberg, H. B.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
[Feng, N.; Sen, A.; Nguyen, H.; Vo, P.; Deal, E. M.; Greenberg, H. B.] Stanford Univ, Stanford, CA 94305 USA.
[Hoshino, Y.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Greenberg, HB (reprint author), VA Palo Alto Hlth Care Syst, 3801 Miranda Ave,MC154C, Palo Alto, CA 94304 USA.
EM hbgreen@stanford.edu
FU VA Merit Award; NIH [R01 AI021362-24, P30DK56339]
FX This study was supported in part by a VA Merit Award and NIH grants R01
AI021362-24 and P30DK56339.
NR 35
TC 32
Z9 35
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL 15
PY 2009
VL 83
IS 14
BP 6987
EP 6994
DI 10.1128/JVI.00585-09
PG 8
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300003
PM 19420080
ER
PT J
AU Kubo, M
Nishimura, Y
Shingai, M
Lee, W
Brenchley, J
Lafont, B
Buckler-White, A
Igarashi, T
Martin, MA
AF Kubo, Makoto
Nishimura, Yoshiaki
Shingai, Masashi
Lee, Wendy
Brenchley, Jason
Lafont, Bernard
Buckler-White, Alicia
Igarashi, Tatsuhiko
Martin, Malcolm A.
TI Initiation of Antiretroviral Therapy 48 Hours after Infection with
Simian Immunodeficiency Virus Potently Suppresses Acute-Phase Viremia
and Blocks the Massive Loss of Memory CD4(+) T Cells but Fails To
Prevent Disease
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIGH-FREQUENCY; GASTROINTESTINAL-TRACT; RHESUS MACAQUES;
MAMU-B-ASTERISK-08-POSITIVE MACAQUES; SIVMAC239 REPLICATION; HIV-1
INFECTION; SIV INFECTION; DEPLETION; MONKEYS; ESCAPE
AB We investigated whether a 28-day course of potent antiretroviral therapy, initiated at a time point ( 48 h postinoculation) following simian immunodeficiency virus (SIV) inoculation when the acquisition of a viral infection was virtually assured, would sufficiently sensitize the immune system and result in controlled virus replication when treatment was stopped. The administration of tenofovir 48 h after SIV inoculation to six Mamu-A*01-negative rhesus macaques did, in fact, potently suppress virus replication in all of the treated rhesus macaques, but plasma viral RNA rapidly became detectable in all six animals following its cessation. Unexpectedly, the viral set points in the treated monkeys became established at two distinct levels. Three controller macaques had chronic phase virus loads in the range of 1 x 10(3) RNA copies/ml, whereas three noncontroller animals had set points of 2 x 10(5) to 8 x 10(5) RNA copies/ml. All of the noncontroller monkeys died with symptoms of immunodeficiency by week 60 postinfection, whereas two of the three controller animals were alive at week 80. Interestingly, the three controller macaques each carried major histocompatibility complex class I alleles that previously were reported to confer protection against SIV, and two of these animals generated cytotoxic T-lymphocyte escape viral variants during the course of their infections.
C1 [Kubo, Makoto; Nishimura, Yoshiaki; Shingai, Masashi; Lee, Wendy; Brenchley, Jason; Lafont, Bernard; Buckler-White, Alicia; Igarashi, Tatsuhiko; Martin, Malcolm A.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 315A,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA.
EM malm@nih.gov
RI Lafont, Bernard/B-7236-2014
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health
FX We are indebted to Boris Skopets and Rahel Petros for their diligence
and assistance in the maintenance of our animals; Ronald Willey for
performing virus neutralization assays; Ranjini Iyengar and Robin
Kruthers for determining plasma viral RNA levels; Martha Vazquez and
Norbert Bischofberger, Gilead Science, Inc., for providing tenofovir;
and John Loffredo for providing information about protective MHC class I
alleles.; This work was supported by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 34
TC 11
Z9 12
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL 15
PY 2009
VL 83
IS 14
BP 7099
EP 7108
DI 10.1128/JVI.02522-08
PG 10
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300013
PM 19420078
ER
PT J
AU Wang, LS
Cheng, C
Ko, SY
Kong, WP
Kanekiyo, M
Einfeld, D
Schwartz, RM
King, CR
Gall, JGD
Nabel, GJ
AF Wang, Lingshu
Cheng, Cheng
Ko, Sung-Youl
Kong, Wing-Pui
Kanekiyo, Masaru
Einfeld, David
Schwartz, Richard M.
King, C. Richter
Gall, Jason G. D.
Nabel, Gary J.
TI Delivery of Human Immunodeficiency Virus Vaccine Vectors to the
Intestine Induces Enhanced Mucosal Cellular Immunity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID REPLICATION-DEFECTIVE ADENOVIRUS; CD8(+) T-CELLS;
GASTROINTESTINAL-TRACT; ORAL IMMUNIZATION; RHESUS-MONKEYS; GENE
DELIVERY; IN-VITRO; SIV INFECTION; EBOLA-VIRUS; MICE
AB Effective vaccines for human immunodeficiency virus type 1 (HIV-1) will likely need to stimulate protective immunity in the intestinal mucosa, where HIV-1 infection causes severe CD4(+) T-cell depletion. While replication-competent recombinant adenovirus (rAd) vectors can stimulate adenovirus-specific mucosal immunity after replication, oral delivery of replication-defective rAd vectors encoding specific immunogens has proven challenging. In this study, we have systematically identified barriers to effective gut delivery of rAd vectors and identified sites and strategies to induce potent cellular and humoral immunity. Vector-mediated gene transfer by rAd5 was susceptible to low-pH buffer, gastric and pancreatic proteases, and extracellular mucins. Using ex vivo organ explants, we found that transduction with rAd5 was highest in the ileum and colon among all intestinal segments. Transgene expression was 100-fold higher after direct surgical introduction into the ileum than after oral gavage, with rAd5 showing greater potency than the rAd35 or the rAd41 vector. A single immunization of rAd5 encoding HIV-1 gp140B to the ileum stimulated potent CD8(+) T-cell responses in the intestinal and systemic compartments, and these responses were further enhanced by intramuscular rAd5 boosting. These studies suggest that induction of primary immune responses by rAd5 gut immunization and subsequent systemic boosting elicits potent antigen-specific gut mucosal responses.
C1 [Wang, Lingshu; Cheng, Cheng; Ko, Sung-Youl; Kong, Wing-Pui; Kanekiyo, Masaru; Schwartz, Richard M.; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Einfeld, David; King, C. Richter; Gall, Jason G. D.] GenVec Inc, Gaithersburg, MD 20878 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC 3005,40 Convent Dr, Bethesda, MD 20892 USA.
EM gnabel@nih.gov
FU National Institutes of Health, Vaccine Research Center, NIAID; Bill and
Melinda Gates Foundation
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, Vaccine Research Center, NIAID, and by
the Bill and Melinda Gates Foundation.
NR 48
TC 17
Z9 18
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD JUL 15
PY 2009
VL 83
IS 14
BP 7166
EP 7175
DI 10.1128/JVI.00374-09
PG 10
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300019
PM 19420074
ER
PT J
AU Wyatt, LS
Earl, PL
Xiao, W
Americo, JL
Cotter, CA
Vogt, J
Moss, B
AF Wyatt, Linda S.
Earl, Patricia L.
Xiao, Wei
Americo, Jeffrey L.
Cotter, Catherine A.
Vogt, Jennifer
Moss, Bernard
TI Elucidating and Minimizing the Loss by Recombinant Vaccinia Virus of
Human Immunodeficiency Virus Gene Expression Resulting from Spontaneous
Mutations and Positive Selection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GENETICALLY-ENGINEERED POXVIRUSES; DEOXYRIBONUCLEIC-ACID POLYMERASE;
PROTECTIVE IMMUNITY; HEPATITIS-B; MVA; IMMUNOGENICITY; REPLICATION;
VACCINATION; MACAQUES; SEQUENCE
AB While characterizing modified vaccinia virus recombinants (rMVAs) containing human immunodeficiency virus env and gag-pol genes, we detected nonexpressing mutants by immunostaining individual plaques. In many cases, the numbers of mutants increased during successive passages, indicating strong selection pressure. This phenomenon provided an opportunity to investigate the formation of spontaneous mutations in vaccinia virus, which encodes its own cytoplasmic replication system, and a challenge to reduce the occurrence of mutations for vaccine production. Analysis of virus from individual plaques indicated that loss of expression was due to frameshift mutations, mostly by addition or deletion of a single nucleotide in runs of four to six Gs or Cs, and large deletions that included MVA DNA flanking the recombinant gene. Interruption of the runs of Gs and Cs by silent codon alterations and moving the recombinant gene to a site between essential, highly conserved MVA genes eliminated or reduced frameshifts and viable deletion mutants, respectively. The rapidity at which nonexpressing mutants accumulated depended on the individual env and gag-pol genes and their suppressive effects on virus replication. Both the extracellular and transmembrane domains contributed to the selection of nonexpressing Env mutants. Stability of an unstable Env was improved by swapping external or transmembrane domains with a more stable Env. Most dramatically, removal of the transmembrane and cytoplasmic domains stabilized even the most highly unstable Env. Understanding the causes of instability and taking preemptive actions will facilitate the development of rMVA and other poxviruses as human and veterinary recombinant vaccines.
C1 [Wyatt, Linda S.; Earl, Patricia L.; Xiao, Wei; Americo, Jeffrey L.; Cotter, Catherine A.; Vogt, Jennifer; Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 33 North Dr,MSC 3210, Bethesda, MD 20892 USA.
EM bmoss@niaid.nih.gov
FU National Institutes of Allergy and Infectious Diseases, National
Institutes of Health
FX This work was supported by the Intramural Program of the National
Institutes of Allergy and Infectious Diseases, National Institutes of
Health.
NR 37
TC 23
Z9 24
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 JUL 15
PY 2009
VL 83
IS 14
BP 7176
EP 7184
DI 10.1128/JVI.00687-09
PG 9
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300020
PM 19420086
ER
PT J
AU Geisbert, TW
Geisbert, JB
Leung, A
Daddario-DiCaprio, KM
Hensley, LE
Grolla, A
Feldmann, H
AF Geisbert, Thomas W.
Geisbert, Joan B.
Leung, Anders
Daddario-DiCaprio, Kathleen M.
Hensley, Lisa E.
Grolla, Allen
Feldmann, Heinz
TI Single-Injection Vaccine Protects Nonhuman Primates against Infection
with Marburg Virus and Three Species of Ebola Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ATTENUATED RECOMBINANT VACCINE; HEMORRHAGIC-FEVER; POSTEXPOSURE
PROTECTION; ADENOVIRUS VECTORS; CHALLENGE; OUTBREAK; CHILDREN; STRAINS;
DISEASE; ANGOLA
AB The filoviruses Marburg virus and Ebola virus cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (VSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Here, we performed a proof-of-concept study in order to determine the potential of having one single-injection vaccine capable of protecting nonhuman primates against Sudan ebolavirus (SEBOV), Zaire ebolavirus (ZEBOV), Cote d'Ivoire ebolavirus (CIEBOV), and Marburgvirus (MARV). In this study, 11 cynomolgus monkeys were vaccinated with a blended vaccine consisting of equal parts of the vaccine vectors VSV Delta G/SEBOVGP, VSV Delta G/ZEBOVGP, and VSV Delta G/MARVGP. Four weeks later, three of these animals were challenged with MARV, three with CIEBOV, three with ZEBOV, and two with SEBOV. Three control animals were vaccinated with VSV vectors encoding a nonfilovirus GP and challenged with SEBOV, ZEBOV, and MARV, respectively, and five unvaccinated control animals were challenged with CIEBOV. Importantly, none of the macaques vaccinated with the blended vaccine succumbed to a filovirus challenge. As expected, an experimental control animal vaccinated with VSV Delta G/ZEBOVGP and challenged with SEBOV succumbed, as did the positive controls challenged with SEBOV, ZEBOV, and MARV, respectively. All five control animals challenged with CIEBOV became severely ill, and three of the animals succumbed on days 12, 12, and 14, respectively. The two animals that survived CIEBOV infection were protected from subsequent challenge with either SEBOV or ZEBOV, suggesting that immunity to CIEBOV may be protective against other species of Ebola virus. In conclusion, we developed an immunization scheme based on a single-injection vaccine that protects nonhuman primates against lethal challenge with representative strains of all human pathogenic filovirus species.
C1 [Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA.
[Geisbert, Thomas W.; Geisbert, Joan B.; Daddario-DiCaprio, Kathleen M.] Boston Univ, Sch Med, Natl Emerging Infect Dis Labs Inst, Boston, MA 02118 USA.
[Geisbert, Thomas W.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Geisbert, Thomas W.; Daddario-DiCaprio, Kathleen M.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA.
[Geisbert, Thomas W.; Geisbert, Joan B.; Daddario-DiCaprio, Kathleen M.; Hensley, Lisa E.] USA, Div Virol, Med Res Inst Infect Dis, Ft Detrick, MD USA.
[Leung, Anders; Grolla, Allen; Feldmann, Heinz] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Feldmann, Heinz] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA.
RP Geisbert, TW (reprint author), Boston Univ, Sch Med, Dept Microbiol, 72 E Concord St,R514, Boston, MA 02118 USA.
EM geisbert@bu.edu
FU Defense Threat Reduction Agency [04-4-7J-012]; Canadian Institutes of
Health Research [MOP-39321]
FX Work on filoviruses at USAMRIID was funded by the Defense Threat
Reduction Agency (project number 04-4-7J-012). Work on filoviruses at
the NML was supported by PHAC and through a grant awarded to H. F. from
the Canadian Institutes of Health Research (MOP-39321).
NR 37
TC 111
Z9 117
U1 1
U2 21
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 15
PY 2009
VL 83
IS 14
BP 7296
EP 7304
DI 10.1128/JVI.00561-09
PG 9
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300032
PM 19386702
ER
PT J
AU Hensley, SE
Pinto, AK
Hickman, HD
Kastenmayer, RJ
Bennink, JR
Virgin, HW
Yewdell, JW
AF Hensley, Scott E.
Pinto, Amelia K.
Hickman, Heather D.
Kastenmayer, Robin J.
Bennink, Jack R.
Virgin, Herbert W.
Yewdell, Jonathan W.
TI Murine Norovirus Infection Has No Significant Effect on Adaptive
Immunity to Vaccinia Virus or Influenza A Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE-NOROVIRUS-1 INFECTION; RESPONSES; MICE; PROTEINS; ANTIBODY;
DISEASE; CELLS; HELP
AB Murine norovirus (MNV) is endemic in many research mouse colonies. Although MNV infections are typically asymptomatic in immunocompetent mice, the effects of MNV infection on subsequent experimental viral infections are poorly documented. Here, we infected C57BL/6 mice with MNV and then with either vaccinia virus or influenza A virus. MNV infection had no effect on CD8(+) T-cell or antibody responses to secondary viruses or to secondary virus-induced morbidity or mortality. While our findings suggest that MNV has little influence on host immunity in immunocompetent mice, we would urge caution regarding the potential effects of MNV on immune responses to viruses and other pathogens, which must be determined on a system-by-system basis.
C1 [Hensley, Scott E.; Hickman, Heather D.; Bennink, Jack R.; Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
[Pinto, Amelia K.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Kastenmayer, Robin J.] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), Bldg 33,Room 2E13,33 North Dr, Bethesda, MD 20892 USA.
EM jyewdell@mail.nih.gov
RI yewdell, jyewdell@nih.gov/A-1702-2012
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases [AI054483, AI065982]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases and grants
AI054483 and AI065982.
NR 14
TC 18
Z9 18
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 JUL 15
PY 2009
VL 83
IS 14
BP 7357
EP 7360
DI 10.1128/JVI.00623-09
PG 4
WC Virology
SC Virology
GA 462LO
UT WOS:000267354300038
PM 19403665
ER
PT J
AU Garcia, GL
Rericha, EC
Heger, CD
Goldsmith, PK
Parent, CA
AF Garcia, Gene L.
Rericha, Erin C.
Heger, Christopher D.
Goldsmith, Paul K.
Parent, Carole A.
TI The Group Migration of Dictyostelium Cells Is Regulated by Extracellular
Chemoattractant Degradation
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; ADENYLYL-CYCLASE; AMP
PHOSPHODIESTERASE; SIGNAL-TRANSDUCTION; MEDIATED ACTIVATION; LEUKOCYTE
MIGRATION; MOLECULAR-GENETICS; DISCOIDEUM; CHEMOTAXIS; CAMP
AB Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA(-) cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA(-) cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact.
C1 [Garcia, Gene L.; Parent, Carole A.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Garcia, Gene L.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA.
[Rericha, Erin C.] Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA.
[Heger, Christopher D.; Goldsmith, Paul K.] NCI, Antibody Prod & Purificat Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Parent, CA (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM parentc@mail.nih.gov
FU National Cancer Institute, National Institutes of Health and National
Institute of Standards and Technology Center for Theoretical and
Computational Materials Science [60NANB6D61200]; Burroughs Wellcome fund
FX We thank Richard Kessin for providing the pdsA- cells. In
addition, we thank the members of the Parent laboratory and the groups
of Alan Kimmel, Tian Jin, and Wolfgang Losert for many helpful
discussions and suggestions. This work was supported by the Intramural
Research Program at the Center for Cancer Research, National Cancer
Institute, National Institutes of Health and National Institute of
Standards and Technology Center for Theoretical and Computational
Materials Science grant 60NANB6D61200. E. C. R. is a recipient of a
Career Award at the Scientific Interface from the Burroughs Wellcome
fund.
NR 67
TC 22
Z9 23
U1 0
U2 1
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD JUL 15
PY 2009
VL 20
IS 14
BP 3295
EP 3304
DI 10.1091/mbc.E09-03-0223
PG 10
WC Cell Biology
SC Cell Biology
GA 470NL
UT WOS:000267981600012
PM 19477920
ER
PT J
AU Simon, KC
Chen, HL
Gao, X
Schwarzschild, MA
Ascherio, A
AF Simon, Kelly Claire
Chen, Honglei
Gao, Xiang
Schwarzschild, Michael A.
Ascherio, Alberto
TI Reproductive Factors, Exogenous Estrogen Use, and Risk of Parkinson's
Disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; estrogen; epidemiology; reproductive factors
ID POSTMENOPAUSAL HORMONE USE; BREAST-CANCER; INDUCED NEUROPROTECTION;
PREMENOPAUSAL WOMEN; CIGARETTE-SMOKING; AGE; GENDER; REPRODUCIBILITY;
PROGESTERONE; CAFFEINE
AB To determine if reproductive factors or exogenous estrogen are associated with risk of Parkinson's disease (PD), we conducted a prospective study with 22 years of follow-up among postmenopausal participants in the Nurses' Health Study. Relative risks (RRs) and 95% confidence intervals (CIs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Risk of PD was not significantly associated with any of the reproductive factors measured or exogenous estrogen use. Use of postmenopausal hormones, however, may modify the associations of smoking and caffeine intake with PD risk. The inverse relation between smoking and PD risk was attenuated among ever users of post-menopausal hormones (P for interaction = 0.05). Similar results were obtained for caffeine (P for interaction = 0.09). In exploratory analyses, women using progestin-only hormones were found to have an increased PD risk, but this result was based on a very small number of cases (n = 4). In this large longitudinal study, we found no evidence of a beneficial effect of exogenous or endogenous estrogens on risk of PD. The use of postmenopausal hormone use may interact with other risk factors, but findings are preliminary and need confirmation in other populations. (C) 2009 Movement Disorder Society
C1 [Simon, Kelly Claire; Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chen, Honglei] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ascherio, Alberto] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Simon, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,3rd Floor, Boston, MA 02115 USA.
EM ksimon@hsph.harvard.edu
OI Chen, Honglei/0000-0003-3446-7779
FU NIH/NINDS [ROI NS048517, T32 ES07069-26]; Intramural Research Program of
the National Institute of Environmental Health Sciences, the National
Institute of Health [ZOIES1019]; DOD [W81XWH-091-0881]
FX This work was funded by grant NIH/NINDS ROI NS048517 and training grant
T32 ES07069-26 and was in part supported by the Intramural Research
Program of the National Institute of Environmental Health Sciences, the
National Institute of Health (ZOIES1019) and DOD grant W81XWH-091-0881.
We thank Eilis O'Reilly for technical support. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 43
TC 30
Z9 30
U1 0
U2 4
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUL 15
PY 2009
VL 24
IS 9
BP 1359
EP 1365
DI 10.1002/mds.22619
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 478UH
UT WOS:000268613300015
PM 19424986
ER
PT J
AU Espay, AJ
Goldenhar, LM
Voon, V
Schrag, A
Burton, N
Lang, AE
AF Espay, Alberto J.
Goldenhar, Linda M.
Voon, Valerie
Schrag, Anette
Burton, Noel
Lang, Anthony E.
TI Opinions and Clinical Practices Related to Diagnosing and Managing
Patients with Psychogenic Movement Disorders: An International Survey of
Movement Disorder Society Members
SO MOVEMENT DISORDERS
LA English
DT Article
DE psychogenic movement disorders; medically unexplained symptoms; survey
ID RANDOMIZED CONTROLLED-TRIAL; CONVERSION DISORDER; SYMPTOMS
AB Five hundred and nineteen members of the Movement Disorder Society completed a 22-item questionnaire probing diagnostic and management issues in psychogenic movement disorders (PMD). When patients showed definite evidence of PMD with no other unexplained clinical features, approximately 20% said they informed patients of the diagnosis and requested no further neurological testing. The 51% who reported conducting standard neurological investigations to rule out organic causes before presenting the diagnosis to such patients had fewer years of fellowship training and fewer PMD patients seen per month. A non-PMD diagnosis was correlated with patients' normal social or personal functioning, little or no employment disruption, lack of non-physiologic findings, and lack of psychiatric history. Ongoing litigation was more predictive of the PMD diagnosis for US compared to non-US respondents. Two thirds of respondents, more commonly younger and academic clinician researchers, refer PMD patients to a psychiatrist or mental health specialist while also providing personal follow up. Physician reimbursement, insurability of PMD patients, and ongoing litigation interfered with managing PMD patients to a greater extent in the US compared to non-US countries. Acceptance of the diagnosis by the patient and identification and management of psychological stressors and concurrent psychiatric disorders were considered most important for predicting a favorable prognosis. These findings suggest that expert opinions and practices related to diagnosing and managing PMD patients differ among movement disorders neurologists. Some of the discrepancies may be accounted for by factors such as training, type of practice, volume of patients, and country of practice, but may also reflect absence of practice guidelines. (C) 2009 Movement Disorder Society
C1 [Espay, Alberto J.; Burton, Noel] Univ Cincinnati, Coll Med, Dept Neurol, Movement Disorders Ctr, Cincinnati, OH 45267 USA.
[Goldenhar, Linda M.] Univ Cincinnati, Coll Med, Off Med Educ Evaluat & Res, Cincinnati, OH 45267 USA.
[Voon, Valerie] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA.
[Schrag, Anette] Royal Free & Univ Coll Med Sch, Dept Clin Neurosci, London WC1E 6BT, England.
[Lang, Anthony E.] Univ Toronto, Div Neurol, Movement Disorders Div, Toronto, ON, Canada.
RP Espay, AJ (reprint author), Univ Cincinnati, Coll Med, Dept Neurol, Movement Disorders Ctr, 260 Stetson St,Suite 2300, Cincinnati, OH 45267 USA.
EM alberto.espay@uc.edu
RI Schrag, Anette/B-4181-2011;
OI Schrag, Anette/0000-0002-9872-6680; Espay, Alberto/0000-0002-3389-136X
NR 22
TC 57
Z9 57
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD JUL 15
PY 2009
VL 24
IS 9
BP 1366
EP 1374
DI 10.1002/mds.22618
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 478UH
UT WOS:000268613300016
PM 19425106
ER
PT J
AU Blasi, G
Popolizio, T
Taurisano, P
Caforio, G
Romano, R
Di Giorgio, A
Sambataro, F
Rubino, V
Latorre, V
Lo Bianco, L
Fazio, L
Nardini, M
Weinberger, DR
Bertolino, A
AF Blasi, Giuseppe
Popolizio, Teresa
Taurisano, Paolo
Caforio, Grazia
Romano, Raffaella
Di Giorgio, Annabella
Sambataro, Fabio
Rubino, Valeria
Latorre, Valeria
Lo Bianco, Luciana
Fazio, Leonardo
Nardini, Marcello
Weinberger, Daniel R.
Bertolino, Alessandro
TI Changes in prefrontal and amygdala activity during olanzapine treatment
in schizophrenia
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Amygdala; Antipsychotic drugs; Emotions; Functional magnetic resonance
imaging; Schizophrenia
ID WORKING-MEMORY TASK; FEARFUL FACES; FUNCTIONAL CONNECTIVITY; THREATENING
STIMULI; DOPAMINE MODULATION; EMISSION-TOMOGRAPHY; PERSONALITY STYLE;
NEURAL MECHANISMS; NEGATIVE EMOTION; BRAIN ACTIVITY
AB Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing. while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
C1 [Blasi, Giuseppe; Taurisano, Paolo; Caforio, Grazia; Romano, Raffaella; Di Giorgio, Annabella; Sambataro, Fabio; Rubino, Valeria; Latorre, Valeria; Lo Bianco, Luciana; Fazio, Leonardo; Nardini, Marcello; Bertolino, Alessandro] Univ Bari, Dept Neurol & Psychiat Sci, Sect Mental Disorders, Psychiat Neurosci Grp, I-70124 Bari, Italy.
[Popolizio, Teresa; Bertolino, Alessandro] IRCCS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy.
[Sambataro, Fabio; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiat, Piazza Giulio Cesare 9, I-70124 Bari, Italy.
EM a.bertolino@psichiat.uniba.it
RI Sambataro, Fabio/E-3426-2010; Fazio, Leonardo/J-4570-2012; Di Giorgio,
Annabella /D-7353-2017
OI Sambataro, Fabio/0000-0003-2102-416X; Fazio,
Leonardo/0000-0003-4000-974X; Di Giorgio, Annabella /0000-0001-7876-3495
FU Eli Lilly and Co.
FX This study was partially supported with an unrestricted grant from Eli
Lilly and Co. which was not involved in study design, data analysis, or
in reporting the experiment. We are thankful to Riccarda Lomuscio, BA,
for hell) with data acquisition, and to all subjects who have
participated in the study.
NR 66
TC 27
Z9 29
U1 4
U2 11
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD JUL 15
PY 2009
VL 173
IS 1
BP 31
EP 38
DI 10.1016/j.pscychresns.2008.09.001
PG 8
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YF
UT WOS:000267469400005
PM 19428222
ER
PT J
AU Alvarez, C
Wainer, IW
AF Alvarez, Covadonga
Wainer, Irving W.
TI Development of an automatic solid phase extraction and liquid
chromatography mass spectrometry method by using a monolithic column for
the analysis of Cyclosporin A in human plasma
SO TALANTA
LA English
DT Article
DE Cyclosporin A; Monolithic columns; LC-ESI-MS
ID WHOLE-BLOOD; SILICA COLUMNS; PERFORMANCE; THROUGHPUT; BIOANALYSIS;
SEPARATION; BEDS
AB A sensitive and specific and automated liquid chromatography-electrospray mass spectrometric (LC-ESI-MS) assay for the quantification of Cyclosporin A in human plasma was developed. Following a simple protein precipitation step, the supernatant was extracted on-line and directly injected into the system LC-ESI-MS. A relatively new type of monolithic column consisting of a silica rod with bimodal pore structure was used to achieve a retention time of 2.4 min with a very low backpressure at a flow rate of 1 ml/min. The assay was linear from 0.050 to 1.000 mu g/ml. The mean recovery was 91%. The mean inter-day and intra-day precisions were 1.85% and 2.83%, respectively. The combination of the automated solid phase extraction and the low retention time achieved with this columns increase the throughput and decrease the time of analysis of each sample. This technology is useful in order to improve the efficiency of the bioanalytical studies. Published by Elsevier B.V.
C1 [Wainer, Irving W.] NIH, Lab Bioanalyt Chem, Gerontol Res Ctr, Baltimore, MD 21224 USA.
[Alvarez, Covadonga] Univ Complutense Madrid, Fac Pharm, Dept Pharmaceut Technol, E-28040 Madrid, Spain.
RP Wainer, IW (reprint author), NIH, Lab Bioanalyt Chem, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM wainerir@grc.nia.nih.gov
FU National Institute on Aging/NIH (IWW)
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging/NIH (IWW). We would like to thank Dr.
Danuta Siluk for her help in preparing this manuscript and to Dr.
Michael Bayhamn for his technical support in the LC-MS system. We would
like to thank Merck for the kind gift of the Chromolith Performance RP
18-e column. We also thank the Complutense University and Madrid
Community Administration and its research group number 910939.
NR 17
TC 12
Z9 14
U1 4
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0039-9140
J9 TALANTA
JI Talanta
PD JUL 15
PY 2009
VL 79
IS 2
BP 280
EP 283
DI 10.1016/j.talanta.2009.03.054
PG 4
WC Chemistry, Analytical
SC Chemistry
GA 473OK
UT WOS:000268216900027
PM 19559878
ER
PT J
AU Neff, RT
Jindal, RM
Yoo, DY
Hurst, FP
Agodoa, LY
Abbott, KC
AF Neff, Robert T.
Jindal, Rahul M.
Yoo, David Y.
Hurst, Frank P.
Agodoa, Lawrence Y.
Abbott, Kevin C.
TI Analysis of USRDS: Incidence and Risk Factors for Pneumocystis jiroveci
Pneumonia
SO TRANSPLANTATION
LA English
DT Article
DE PCP; USRDS; Transplant infection
ID ORGAN-TRANSPLANT RECIPIENTS; CARINII-PNEUMONIA; RENAL-TRANSPLANTATION;
INFECTION; IMMUNOSUPPRESSION; PREVENTION; SIROLIMUS
AB Background. To investigate the effect of modern immunosuppression on the incidence, risk factors, morbidity, and mortality of Pneumocystis pneumonia (PCP) in recipients of kidney transplants.
Methods. We conducted a retrospective cohort study of 32,757 Medicare primary transplant recipients in the United States Renal Data System from January 1, 2000 through July 31, 2004. PCP infection was defined by Medicare claims using International Classification of Disease, 9th Revision codes. The incidence of PCP infections, graft loss, and death were measured.
Results. There were a total of 142 cases (cumulative incidence 0.4%) of PCP after kidney transplantation during the study period. By using multivariate analysis with Cox regression, expanded criteria donor, donation after cardiac death, and earlier year of transplant were associated with development of PCP disease. Induction immunosuppression and acute rejections were not associated with risk for PCP infections. However, based on adjusted hazard ratio (AHR), maintenance immunosuppression regimens containing the combination of tacrolimus and sirolimus (AHR 3.60, confidence interval [CI] 2.03-6.39), Neoral and mycophenolate mofetil (AHR 2.09, CI 1.31-3.31), and sirolimus and mycophenolate mofetil (AHR 2.77, Cl 1.40-5.47), were associated with development of PCP. As a time dependent variable, PCP was associated with an increased risk of both graft loss and death.
Conclusion. PCP infections are rare in the modern era of prophylaxis; however, these infections are a serious risk factor for graft loss and patient death, in particular, in patients who are on sirolimus as part of the immunosuppressive regimen. The median time to development of PCP after transplant was 0.80 +/- 0.95 years, suggesting a longer period of PCP prophylaxis.
C1 [Neff, Robert T.; Jindal, Rahul M.; Hurst, Frank P.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Organ Transplant Program, Washington, DC 20307 USA.
[Neff, Robert T.; Jindal, Rahul M.; Hurst, Frank P.; Abbott, Kevin C.] Walter Reed Army Med Ctr, Nephrol SVC, Washington, DC 20307 USA.
[Neff, Robert T.; Jindal, Rahul M.; Hurst, Frank P.; Abbott, Kevin C.] Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA.
[Jindal, Rahul M.] Brookdale Univ Hosp & Med Ctr, Dept Surg, Brooklyn, NY USA.
[Yoo, David Y.] Walter Reed Army Med Ctr, Med Serv, Washington, DC 20307 USA.
[Agodoa, Lawrence Y.] NIDDK, NIH, Bethesda, MD USA.
RP Jindal, RM (reprint author), Walter Reed Army Med Ctr, Organ Transplant Program, 6630 Georgia Ave, Washington, DC 20307 USA.
EM jindalr@msn.com
OI Abbott, Kevin/0000-0003-2111-7112
NR 17
TC 43
Z9 45
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD JUL 15
PY 2009
VL 88
IS 1
BP 135
EP 141
DI 10.1097/TP.0b013e3181aad256
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 468UJ
UT WOS:000267848000022
PM 19584693
ER
PT J
AU Wu, XW
Brooks, BR
AF Wu, Xiongwu
Brooks, Bernard R.
TI Isotropic periodic sum of electrostatic interactions for polar systems
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID MOLECULAR-DYNAMICS SIMULATIONS; ARTIFICIAL PERIODICITY;
DIELECTRIC-PROPERTIES; WATER; TRUNCATION; PROGRAM; FORCES; CHARMM
AB Isotropic periodic sum (IPS) is a method to calculate long-range interactions based on homogeneity of simulation systems. Long-range interactions are represented by interactions with isotropic periodic images of a defined local region and can be reduced to short ranged IPS potentials. The original electrostatic three-dimensional (3D)-IPS potential was derived based on a nonpolar homogeneous approximation and its application is limited to nonpolar or weak polar systems. This work derived a polar electrostatic 3D-IPS potential based on polar interactions. For the convenience of application, polynomial functions with rationalized coefficients are proposed for electrostatic and Lennard-Jones 3D-IPS potentials. Model systems of various polarities and several commonly used solvent systems are simulated to evaluate the 3D-IPS potentials. It is demonstrated that for polar systems the polar electrostatic 3D-IPS potential has much improved accuracy as compared to the nonpolar 3D-IPS potential. For homogeneous systems, the polar electrostatic 3D-IPS potential with a local region radius or cutoff distance of as small as 10 angstrom can satisfactorily reproduce energetic, structural, and dynamic properties from the particle-meshed-Ewald method. For both homogeneous and heterogeneous systems, the 3D-IPS/discrete fast Fourier transform method using either the nonpolar or the polar electrostatic 3D-IPS potentials results in very similar simulation results. (C) 2009 American Institute of Physics. [DOI: 10.1063/1.3160730]
C1 [Wu, Xiongwu; Brooks, Bernard R.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
RP Wu, XW (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
EM wuxw@nhlbi.nih.gov
NR 26
TC 29
Z9 29
U1 1
U2 6
PU AMER INST PHYSICS
PI MELVILLE
PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1,
MELVILLE, NY 11747-4501 USA
SN 0021-9606
J9 J CHEM PHYS
JI J. Chem. Phys.
PD JUL 14
PY 2009
VL 131
IS 2
AR 024107
DI 10.1063/1.3160730
PG 13
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 470NU
UT WOS:000267983100009
PM 19603970
ER
PT J
AU Lauer, MS
Skarlatos, SI
Bild, DE
AF Lauer, Michael S.
Skarlatos, Sonia I.
Bild, Diane E.
TI The Extramural Division of Cardiovascular Sciences of the National
Heart, Lung, and Blood Institute
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
C1 [Lauer, Michael S.; Skarlatos, Sonia I.; Bild, Diane E.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
RP Lauer, MS (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Room 10122, Bethesda, MD 20892 USA.
EM lauerm@nhlbi.nih.gov
RI Lauer, Michael/L-9656-2013
OI Lauer, Michael/0000-0002-9217-8177
FU NHLBI NIH HHS [R01 HL072771, P50 HL077107, R01 HL066004]
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 14
PY 2009
VL 54
IS 3
BP 265
EP 268
DI 10.1016/j.jacc.2009.04.025
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 467SJ
UT WOS:000267762400011
PM 19589441
ER
PT J
AU Sei, S
Mussio, JK
Yang, QE
Nagashima, K
Parchment, RE
Coffey, MC
Shoemaker, RH
Tomaszewski, JE
AF Sei, Shizuko
Mussio, Jodie K.
Yang, Quan-en
Nagashima, Kunio
Parchment, Ralph E.
Coffey, Matthew C.
Shoemaker, Robert H.
Tomaszewski, Joseph E.
TI Synergistic antitumor activity of oncolytic reovirus and
chemotherapeutic agents in non-small cell lung cancer cells
SO MOLECULAR CANCER
LA English
DT Article
ID INDUCED APOPTOSIS; TUMOR-CELLS; MITOTIC CHECKPOINT; PANCREATIC-CANCER;
INFECTION; THERAPY; PATHWAY; DEATH; GEMCITABINE; COMBINATION
AB Background: Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC).
Results: ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell lines examined, with the 50% effective dose, defined as the initial virus dose to achieve 50% cell killing after 48 hours of infection, ranging from 1.46 +/- 0.12 similar to 2.68 +/- 0.25 (mean +/- SD) log(10) pfu/cell. Chou-Talalay analysis of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine demonstrated strong synergistic effects on cell killing, but only in cell lines that were sensitive to these compounds. In contrast, the combination of ReoT3D and paclitaxel was invariably synergistic in all cell lines tested, regardless of their levels of sensitivity to either agent. Treatment of NSCLC cell lines with the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose) polymerase cleavage and caspase activity compared to single therapy, indicating enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated with the ReoT3D-paclitaxel combination showed increased proportions of mitotic and apoptotic cells, and a more pronounced level of caspase-3 activation was demonstrated in mitotically arrested cells.
Conclusion: These data suggest that the oncolytic activity of ReoT3D can be potentiated by taxanes and other chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively achieves synergy through accelerated apoptosis triggered by prolonged mitotic arrest.
C1 [Sei, Shizuko; Mussio, Jodie K.; Yang, Quan-en; Parchment, Ralph E.] NCI, Lab Human Toxicol & Pharmacol, SAIC Frederick, Frederick, MD 21701 USA.
[Nagashima, Kunio] NCI, Electron Microscope Lab, SAIC Frederick, Frederick, MD 21701 USA.
[Coffey, Matthew C.] Oncolyt Biotech Inc, Calgary, AB, Canada.
[Shoemaker, Robert H.] NCI, Dev Therapeut Program, Frederick, MD 21701 USA.
[Tomaszewski, Joseph E.] NCI, Div Canc Treatment & Diagnost, Bethesda, MD 20892 USA.
RP Sei, S (reprint author), NCI, Lab Human Toxicol & Pharmacol, SAIC Frederick, Frederick, MD 21701 USA.
EM seis@mail.nih.gov; mussiojk@mail.nih.gov; yangq2@mail.nih.gov;
nagashimak@mail.nih.gov; parchmentr@mail.nih.gov; MCoffey@oncolytics.ca;
shoemakr@mail.nih.gov; tomaszewsk@dtpepn.nci.nih.gov
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
Department of Health and Human Services; Developmental Therapeutics
Program; Division of Cancer Treatment; Diagnosis of the National Cancer
Institute
FX We would like to thank Drs. Jerry Collins, James Zwiebel, Yoshitatsu
Sei, and Kevin Harrington for advice and helpful discussions, and Mr. M.
Jason De la Cruz for technical assistance. This project has been funded
in whole or in part with federal funds from the National Cancer
Institute, National Institutes of Health, under contract N01-CO-12400.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U. S. Government. This research was supported in part
by the Developmental Therapeutics Program in the Division of Cancer
Treatment and Diagnosis of the National Cancer Institute.
NR 52
TC 51
Z9 51
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1476-4598
J9 MOL CANCER
JI Mol. Cancer
PD JUL 14
PY 2009
VL 8
AR 47
DI 10.1186/1476-4598-8-47
PG 15
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 486FZ
UT WOS:000269182900001
PM 19594950
ER
PT J
AU Harden, CL
Meador, KJ
Pennell, PB
Hauser, WA
Gronseth, GS
French, JA
Wiebe, S
Thurman, D
Koppel, BS
Kaplan, PW
Robinson, JN
Hopp, J
Ting, TY
Gidal, B
Hovinga, CA
Wilner, AN
Vazquez, B
Holmes, L
Krumholz, A
Finnell, R
Hirtz, D
Le Guen, C
AF Harden, C. L.
Meador, K. J.
Pennell, P. B.
Hauser, W. A.
Gronseth, G. S.
French, J. A.
Wiebe, S.
Thurman, D.
Koppel, B. S.
Kaplan, P. W.
Robinson, J. N.
Hopp, J.
Ting, T. Y.
Gidal, B.
Hovinga, C. A.
Wilner, A. N.
Vazquez, B.
Holmes, L.
Krumholz, A.
Finnell, R.
Hirtz, D.
Le Guen, C.
TI Practice Parameter update: Management issues for women with
epilepsy-Focus on pregnancy (an evidence-based review): Teratogenesis
and perinatal outcomes Report of the Quality Standards Subcommittee and
Therapeutics and Technology Assessment Subcommittee of the American
Academy of Neurology and American Epilepsy Society
SO NEUROLOGY
LA English
DT Review
ID ANTIEPILEPTIC DRUGS; IN-UTERO; MATERNAL EPILEPSY;
CONGENITAL-MALFORMATIONS; PSYCHOMOTOR DEVELOPMENT; ANTICONVULSANT DRUGS;
PRENATAL EXPOSURE; CHILDREN; INTELLIGENCE; VALPROATE
AB Objective: To reassess the evidence for management issues related to the care of women with epilepsy (WWE) during pregnancy.
Methods: Systematic review of relevant articles published between January 1985 and June 2007.
Results: It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine and possible compared to phenytoin or lamotrigine. Compared to untreated WWE, it is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. It is probable that antiepileptic drug (AED) polytherapy as compared to monotherapy regimens contributes to the development of MCMs and to reduced cognitive outcomes. For monotherapy, intrauterine exposure to VPA probably reduces cognitive outcomes. Further, monotherapy exposure to phenytoin or phenobarbital possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7.
Recommendations: If possible, avoidance of valproate (VPA) and antiepileptic drug (AED) polytherapy during the first trimester of pregnancy should be considered to decrease the risk of major congenital malformations (Level B). If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered to prevent reduced cognitive outcomes (Level B). If possible, avoidance of phenytoin and phenobarbital during pregnancy may be considered to prevent reduced cognitive outcomes (Level C). Pregnancy risk stratification should reflect that the offspring of women with epilepsy taking AEDs are probably at increased risk for being small for gestational age (Level B) and possibly at increased risk of 1-minute Apgar scores of <7 (Level C). Neurology(R) 2009; 73: 133-141
C1 [Harden, C. L.] Univ Miami, Miami, FL USA.
[Meador, K. J.; Pennell, P. B.] Emory Univ, Atlanta, GA 30322 USA.
[Hauser, W. A.] Columbia Univ, New York, NY USA.
[Gronseth, G. S.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[French, J. A.] NYU, Sch Med, New York, NY USA.
[Wiebe, S.] Univ Calgary, Calgary, AB T2N 1N4, Canada.
[Thurman, D.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Koppel, B. S.] New York Med Coll, New York, NY USA.
[Kaplan, P. W.] Johns Hopkins Univ, Baltimore, MD USA.
[Robinson, J. N.; Holmes, L.] Harvard Univ, Sch Med, Boston, MA USA.
[Hopp, J.; Ting, T. Y.; Krumholz, A.] Univ Maryland, Baltimore, MD 21201 USA.
[Gidal, B.] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA.
[Hovinga, C. A.] Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA.
[Finnell, R.] Texas A&M Univ, Hlth Sci Ctr, Houston, TX USA.
[Hirtz, D.] NINDS, Bethesda, MD 20892 USA.
[Le Guen, C.] Univ Penn, Philadelphia, PA 19104 USA.
RP Harden, CL (reprint author), Amer Acad Neurol, 1080 Montreal Ave, St Paul, MN 55116 USA.
EM guidelines@aan.com
RI French, Jacqueline/G-6795-2013
OI French, Jacqueline/0000-0003-2242-8027
FU NINDS NIH HHS [R01 NS038455, R01 NS038455-09]
NR 40
TC 125
Z9 128
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD JUL 14
PY 2009
VL 73
IS 2
BP 133
EP 141
DI 10.1212/WNL.0b013e3181a6b312
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 469XX
UT WOS:000267936400010
PM 19398681
ER
PT J
AU Lu, J
Kovach, JS
Johnson, F
Chiang, J
Hodes, R
Lonser, R
Zhuang, ZP
AF Lu, Jie
Kovach, John S.
Johnson, Francis
Chiang, Jeffrey
Hodes, Richard
Lonser, Russell
Zhuang, Zhengping
TI Inhibition of serine/threonine phosphatase PP2A enhances cancer
chemotherapy by blocking DNA damage induced defense mechanisms
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE DNA-damage responses; enhanced chemotherapy; PP2A inhibition
ID CONTROLLED TUMOR PROTEIN; CELLULAR SENESCENCE; MITOTIC CATASTROPHE; PLK1
DEPLETION; PHASE-II; TCTP; TEMOZOLOMIDE; THERAPY; PATHWAY; DEATH
AB A variety of mechanisms maintain the integrity of the genome in the face of cell stress. Cancer cell response to chemotherapeutic and radiation-induced DNA damage is mediated by multiple defense mechanisms including polo-like kinase 1 (Plk-1), protein kinase B (Akt-1), and/or p53 pathways leading to either apoptosis or cell cycle arrest. Subsequently, a subpopulation of arrested viable cancer cells may remain and recur despite aggressive and repetitive therapy. Here, we show that modulation (activation of Akt-1 and Plk-1 and repression of p53) of these pathways simultaneously results in paradoxical enhancement of the effectiveness of cytotoxic chemotherapy. We demonstrate that a small molecule inhibitor, LB-1.2, of protein phosphatase 2A (PP2A) activates Plk-1 and Akt-1 and decreases p53 abundance in tumor cells. Combined with temozolomide (TMZ; a DNA-methylating chemotherapeutic drug), LB-1.2 causes complete regression of glioblastoma multiforme (GBM) xenografts without recurrence in 50% of animals (up to 28 weeks) and complete inhibition of growth of neuroblastoma (NB) xenografts. Treatment with either drug alone results in only short-term inhibition/regression with all xenografts resuming rapid growth. Combined with another widely used anticancer drug, Doxorubicin (DOX, a DNA intercalating agent), LB-1.2 also causes marked GBM xenograft regression, whereas DOX alone only slows growth. Inhibition of PP2A by LB-1.2 blocks cell-cycle arrest and increases progression of cell cycle in the presence of TMZ or DOX. Pharmacologic inhibition of PP2A may be a general method for enhancing the effectiveness of cancer treatments that damage DNA or disrupt components of cell replication.
C1 [Lu, Jie; Lonser, Russell; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kovach, John S.] Lixte Biotechnol Holdings Inc, E Setauket, NY 11733 USA.
[Johnson, Francis] Chem Master Int Inc, Setauket, NY 11733 USA.
[Chiang, Jeffrey; Hodes, Richard] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Lonser, R (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,9000 Rockvillle Pike, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov; zhuangp@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health; National Institute of Neurological Disorders and
Stroke at the National Institutes of Health and Lixte Biotechnology
Holdings, Inc
FX This research was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health and a cooperative research and development
agreement between the National Institute of Neurological Disorders and
Stroke at the National Institutes of Health and Lixte Biotechnology
Holdings, Inc.
NR 30
TC 57
Z9 62
U1 1
U2 10
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2009
VL 106
IS 28
BP 11697
EP 11702
DI 10.1073/pnas.0905930106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470KD
UT WOS:000267972700050
PM 19564615
ER
PT J
AU Bassett, DS
Bullmore, ET
Meyer-Lindenberg, A
Apud, JA
Weinberger, DR
Coppola, R
AF Bassett, Danielle S.
Bullmore, Edward T.
Meyer-Lindenberg, Andreas
Apud, Jose A.
Weinberger, Daniel R.
Coppola, Richard
TI Cognitive fitness of cost-efficient brain functional networks
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE efficiency; graph theory; schizophrenia; working memory;
magnetoencephalography
ID WORKING-MEMORY; CORTICAL DYSFUNCTION; SCHIZOPHRENIA; OSCILLATIONS;
SYNCHRONY; ATTENTION; DYNAMICS; RANGE; MODEL; TASK
AB The human brain's capacity for cognitive function is thought to depend on coordinated activity in sparsely connected, complex networks organized over many scales of space and time. Recent work has demonstrated that human brain networks constructed from neuroimaging data have economical small-world properties that confer high efficiency of information processing at relatively low connection cost. However, it has been unclear how the architecture of complex brain networks functioning at different frequencies can be related to behavioral performance on cognitive tasks. Here, we show that impaired accuracy of working memory could be related to suboptimal cost efficiency of brain functional networks operating in the classical beta frequency band, 15-30 Hz. We analyzed brain functional networks derived from magnetoencephalography data recorded during working-memory task performance in 29 healthy volunteers and 28 people with schizophrenia. Networks functioning at higher frequencies had greater global cost efficiency than low-frequency networks in both groups. Superior task performance was positively correlated with global cost efficiency of the beta-band network and specifically with cost efficiency of nodes in left lateral parietal and frontal areas. These results are consistent with biophysical models highlighting the importance of beta-band oscillations for long-distance functional connections in brain networks and with pathophysiological models of schizophrenia as a dysconnection syndrome. More generally, they echo the saying that "less is more'': The information processing performance of a network can be enhanced by a sparse or low-cost configuration with disproportionately high efficiency.
C1 [Bassett, Danielle S.; Bullmore, Edward T.] Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 0QQ, England.
[Bassett, Danielle S.; Apud, Jose A.; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA.
[Coppola, Richard] NIMH, Magnetoencephalog Core Facil, NIH, Bethesda, MD 20892 USA.
[Bullmore, Edward T.] Addenbrookes Hosp, GlaxoSmithKline, Clin Unit Cambridge, Cambridge CB2 0QQ, England.
[Bassett, Danielle S.] Univ Cambridge, Dept Phys, Biol Soft Syst Sector, Cambridge CB2 1TN, England.
[Meyer-Lindenberg, Andreas] Cent Inst Mental Hlth, D-68072 Mannheim, Germany.
RP Bullmore, ET (reprint author), Univ Cambridge, Dept Psychiat, Behav & Clin Neurosci Inst, Cambridge CB2 0QQ, England.
EM etb23@cam.ac.uk
RI Bullmore, Edward/C-1706-2012; Meyer-Lindenberg, Andreas/H-1076-2011
OI Bullmore, Edward/0000-0002-8955-8283; Meyer-Lindenberg,
Andreas/0000-0001-5619-1123
FU National Institute of Biomedical Imaging and Bioengineering and the
National Institute of Mental Health (NIMH); Intramural Research Program
of the National Institutes of Health (NIH); Medical Research Council
FX This work was supported by a Human Brain Project grant from the National
Institute of Biomedical Imaging and Bioengineering and the National
Institute of Mental Health (NIMH), and by the Intramural Research
Program of the National Institutes of Health (NIH). The Behavioural and
Clinical Neurosciences Institute is supported by the Medical Research
Council and the Wellcome Trust. D. S. B. was supported by the NIH
Graduate Partnerships Program.
NR 41
TC 166
Z9 166
U1 3
U2 20
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 14
PY 2009
VL 106
IS 28
BP 11747
EP 11752
DI 10.1073/pnas.0903641106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 470KD
UT WOS:000267972700059
PM 19564605
ER
PT J
AU Kim, KP
Einstein, AJ
de Gonzalez, AB
AF Kim, Kwang Pyo
Einstein, Andrew J.
de Gonzalez, Amy Berrington
TI Coronary Artery Calcification Screening Estimated Radiation Dose and
Cancer Risk
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article
ID COMPUTED-TOMOGRAPHY; CARDIAC CT; ATHEROSCLEROSIS MESA; POOLED ANALYSIS;
EXPOSURE; ANGIOGRAPHY; MULTISLICE; HEART
AB Background: Multidetector computed tomography has been proposed as a tool for routine screening for coronary artery calcification in asymptomatic individuals. As proposed, such screening could involve tens of millions of individuals, but detailed estimates of radiation doses and potential risk of radiation-induced cancer are not currently available. We estimated organ-specific radiation doses and associated cancer risks from coronary artery calcification screening with multidetector computed tomography according to patient age, frequency of screening, and scan protocol.
Methods: Radiation doses delivered to adult patients were calculated from a range of available protocols using Monte Carlo radiation transport. Radiation risk models, derived using data from Japanese atomic bomb survivors and medically exposed cohorts, were used to estimate the excess lifetime risk of radiation-induced cancer.
Results: The radiation dose from a single coronary artery calcification computed tomographic scan varied more than 10-fold (effective dose range, 0.8-10.5 mSv) depending on the protocol. In general, higher radiation doses were associated with higher x-ray tube current, higher tube potential, spiral scanning with low pitch, and retrospective gating. The wide dose variation also resulted in wide variation in estimated radiation-induced cancer risk. Assuming screening every 5 years from the age of 45 to 75 years for men and 55 to 75 years for women, the estimated excess lifetime cancer risk using the median dose of 2.3 mSv was 42 cases per 100 000 men (range, 14-200 cases) and 62 cases per 100 000 women (range, 21-300 cases).
Conclusions: These radiation risk estimates can be compared with potential benefits from screening, when such estimates are available. Doses and therefore risks can be minimized by the use of optimized protocols.
C1 [Kim, Kwang Pyo; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Einstein, Andrew J.] Columbia Univ Coll Phys & Surg, Dept Med, Div Cardiol, New York, NY 10032 USA.
[Einstein, Andrew J.] Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 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
FU National Institutes of Health [5 KL2 RR024157-03]
FX Dr Einstein is supported in part by a National Institutes of Health K12
Institutional Career Development Award (5 KL2 RR024157-03).
NR 46
TC 128
Z9 132
U1 0
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9926
J9 ARCH INTERN MED
JI Arch. Intern. Med.
PD JUL 13
PY 2009
VL 169
IS 13
BP 1188
EP 1194
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473EN
UT WOS:000268188900005
PM 19597067
ER
PT J
AU Gurnev, PA
Harries, D
Parsegian, VA
Bezrukov, SM
AF Gurnev, Philip A.
Harries, Daniel
Parsegian, V. Adrian
Bezrukov, Sergey M.
TI The Dynamic Side of the Hofmeister Effect: A Single-Molecule Nanopore
Study of Specific Complex Formation
SO CHEMPHYSCHEM
LA English
DT Article
DE hydrophobic interactions; ion channels; kinetics; osmotic effect;
single-molecule studies
ID TRANSMEMBRANE PORE; CYCLODEXTRIN; WATER; PROTEIN; HYDRATION;
THERMODYNAMICS; ASSOCIATION; BINDING; CHANNEL
C1 [Harries, Daniel] Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
[Harries, Daniel] Hebrew Univ Jerusalem, Fritz Haber Res Ctr, IL-91904 Jerusalem, Israel.
[Gurnev, Philip A.; Parsegian, V. Adrian; Bezrukov, Sergey M.] NICHD, Lab Phys & Struct Biol, Program Phys Biol, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Harries, D (reprint author), Hebrew Univ Jerusalem, Inst Chem, IL-91904 Jerusalem, Israel.
EM doniel@huji.ac.il
RI Harries, Daniel/F-7016-2012
OI Harries, Daniel/0000-0002-3057-9485
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We are grateful to Donald Rau and Brian Todd for fruitful discussions
and for reading the manuscript. This study was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 26
TC 23
Z9 23
U1 0
U2 8
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1439-4235
J9 CHEMPHYSCHEM
JI ChemPhysChem
PD JUL 13
PY 2009
VL 10
IS 9-10
BP 1445
EP 1449
DI 10.1002/cphc.200900312
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA 469VF
UT WOS:000267928100015
PM 19504531
ER
PT J
AU Smith, C
Santi, M
Rajan, B
Rushing, EJ
Choi, MR
Rood, BR
Cornelison, R
MacDonald, TJ
Vukmanovic, S
AF Smith, Courtney
Santi, Mariarita
Rajan, Bhargavi
Rushing, Elisabeth J.
Choi, Mi Rim
Rood, Brian R.
Cornelison, Robert
MacDonald, Tobey J.
Vukmanovic, Stanislav
TI A novel role of HLA class I in the pathology of medulloblastoma
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
ID MHC CLASS-I; RENAL-CELL CARCINOMA; MAJOR HISTOCOMPATIBILITY COMPLEX;
CHILDHOOD BRAIN-TUMORS; DOWN-REGULATION; T-CELLS; SERUM
BETA(2)-MICROGLOBULIN; SIGNAL-TRANSDUCTION; FUNCTIONAL-ANALYSIS;
ANTIGEN-EXPRESSION
AB Background: MHC class I expression by cancer cells enables specific antigen recognition by the immune system and protection of the host. However, in some cancer types MHC class I expression is associated with an unfavorable outcome. We explored the basis of MHC class I association with unfavorable prognostic marker expression in the case of medulloblastoma.
Methods: We investigated expression of four essential components of MHC class I (heavy chain, beta 2m, TAPI and TAP2) in 10 medulloblastoma mRNA samples, a tissue microarray containing 139 medulloblastoma tissues and 3 medulloblastoma cell lines. Further, in medulloblastoma cell lines we evaluated the effects of HLA class I engagement on activation of ERK1/2 and migration in vitro.
Results: The majority of specimens displayed undetectable or low levels of the heavy chains. Medulloblastomas expressing high levels of HLA class I displayed significantly higher levels of anaplasia and c-myc expression, markers of poor prognosis. Binding of beta 2m or a specific antibody to open forms of HLA class I promoted phosphorylation of ERK1/2 in medulloblastoma cell line with high levels, but not in the cell line with low levels of HLA heavy chain. This treatment also promoted ERK1/2 activation dependent migration of medulloblastoma cells.
Conclusion: MHC class I expression in medulloblastoma is associated with anaplasia and c-myc expression, markers of poor prognosis. Peptide- and/or beta 2m-free forms of MHC class I may contribute to a more malignant phenotype of medulloblastoma by modulating activation of signaling molecules such as ERK1/2 that stimulates cell mobility.
C1 [Smith, Courtney; Rajan, Bhargavi; Choi, Mi Rim; Rood, Brian R.; MacDonald, Tobey J.; Vukmanovic, Stanislav] Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
[Santi, Mariarita] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA.
[Smith, Courtney; Rood, Brian R.; MacDonald, Tobey J.; Vukmanovic, Stanislav] George Washington Univ, Sch Med, Dept Pediat, Washington, DC 20052 USA.
[Rushing, Elisabeth J.] Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA.
[Cornelison, Robert] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Smith, Courtney] George Washington Univ, Inst Biomed Sci, Program Immunol, Washington, DC 20052 USA.
RP Vukmanovic, S (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol Res, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM smithco@mlhs.org; mariarita.santi@gmail.com; rajan_bhargavi@yahoo.com;
elisabeth.rushing@gmail.com; mirimchoi@yahoo.com; brood@cnmc.org;
rcorneli@mail.nih.gov; tmacdona@cnmc.org; svukmano@cnmc.org
RI MacDonald, Tobey/D-4554-2013
FU NIH [R01, CA111835]
FX Courtney Smith was a predoctoral student in the Immunology Program of
the Institute for Biomedical Sciences at the George Washington
University. This work is from a dissertation that was presented to the
above program in partial fulfillment of the requirements for the Ph. D.
degree. The authors thank Drs. Pan Zhengand Soldano Ferrone for
providing HC-10 and TAP-specific antibodies, respectively, Mary Rose for
the gift of primers for beta-actin and Thamara Abouantoun for the help
with Western blotting. These studies were supported in part by an R01
grant # CA111835 from NIH to TJM.
NR 63
TC 6
Z9 6
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 12
PY 2009
VL 7
AR 59
DI 10.1186/1479-5876-7-59
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 485TQ
UT WOS:000269147700001
PM 19594892
ER
PT J
AU Schultz, JM
Khan, SN
Ahmed, ZM
Riazuddin, S
Waryah, AM
Chhatre, D
Starost, MF
Ploplis, B
Buckley, S
Velasquez, D
Kabra, M
Lee, K
Hassan, MJ
Ali, G
Ansar, M
Ghosh, M
Wilcox, ER
Ahmad, W
Merlino, G
Leal, SM
Riazuddin, S
Friedman, TB
Morell, RJ
AF Schultz, Julie M.
Khan, Shaheen N.
Ahmed, Zubair M.
Riazuddin, Saima
Waryah, Ali M.
Chhatre, Dhananjay
Starost, Matthew F.
Ploplis, Barbara
Buckley, Stephanie
Velasquez, David
Kabra, Madhulika
Lee, Kwanghyuk
Hassan, Muhammad J.
Ali, Ghazanfar
Ansar, Muhammad
Ghosh, Manju
Wilcox, Edward R.
Ahmad, Wasim
Merlino, Glenn
Leal, Suzanne M.
Riazuddin, Sheikh
Friedman, Thomas B.
Morell, Robert J.
TI Noncoding Mutations of HGF Are Associated with Nonsyndromic Hearing
Loss, DFNB39
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; FACTOR-SCATTER FACTOR; AUTOSOMAL-RECESSIVE
DEAFNESS; AUDITORY SENSORY EPITHELIUM; DELAYED NEURONAL DEATH;
HEPARIN-BINDING SITE; FACTOR/SCATTER FACTOR; C-MET; INNER-EAR; IN-VIVO
AB A gene causing autosomal-recessive, nonsyndromic hearing loss, DFNB39, was previously mapped to an 18 Mb interval on chromosome 7q11.22-q21.12. We mapped an additional 40 consanguineous families segregating nonsyndromic hearing loss to the DFNB39 locus and refined the obligate interval to 1.2 Mb. The coding regions of all genes in this interval were sequenced, and no missense, nonsense, or frameshift mutations were found. We sequenced the noncoding sequences of genes, as well as noncoding genes, and found three mutations Clustered in intron 4 and exon 5 in the hepatocyte growth factor gene (HGF). Two intron 4 deletions occur in a highly conserved sequence that is part of the 3' Untranslated region of a previously undescribed short isoform of HGF The third mutation is a silent substitution, and we demonstrate that it affects splicing in vitro. HGF is involved in a wide variety of signaling pathways in many different tissues, yet these putative regulatory mutations cause a surprisingly specific phenotype, which is nonsydromic hearing loss. Two mouse models of Hgf dysregulation, one in which an Hgf transgene is ubiquitously overexpressed and the other a conditional knockout that deletes Hgf from a limited number of tissues, including the cochlea, result in deafness. Overexpression of HGF is associated with progressive degeneration of outer hair cells in the cochlea, whereas cochlear deletion of Hgf is associated with more general dysplasia.
C1 [Schultz, Julie M.; Ahmed, Zubair M.; Riazuddin, Saima; Chhatre, Dhananjay; Ploplis, Barbara; Buckley, Stephanie; Velasquez, David; Wilcox, Edward R.; Friedman, Thomas B.; Morell, Robert J.] NIH, Mol Genet Lab, Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
[Khan, Shaheen N.; Waryah, Ali M.; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan.
[Starost, Matthew F.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
[Kabra, Madhulika; Ghosh, Manju] All India Inst Med Sci, Dept Pediat, Genet Unit, New Delhi 110029, India.
[Lee, Kwanghyuk; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Hassan, Muhammad J.; Ali, Ghazanfar; Ansar, Muhammad; Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad 45320, Pakistan.
[Merlino, Glenn] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
RP Morell, RJ (reprint author), NIH, Mol Genet Lab, Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA.
EM morellr@nidcd.nih.gov
RI Ansar, Muhammad/H-5967-2011; Ali, Ghazanfar/J-9971-2012; Nasim Khan,
Shaheen/F-2135-2015; Ansar, Muhammad/F-4808-2015; Ahmad,
Wasim/E-9713-2015;
OI Ansar, Muhammad/0000-0001-5891-7063; Lee, Kwanghyuk/0000-0001-7781-9696;
Morell, Robert/0000-0003-1537-7356
FU Intramural NIH HHS; NHGRI NIH HHS [N01HG65403]; NIDCD NIH HHS [R01
DC03594, Z01 DC000039, 1 Z01 DC000039-11, R01 DC003594]
NR 81
TC 27
Z9 28
U1 0
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 10
PY 2009
VL 85
IS 1
BP 25
EP 39
DI 10.1016/j.ajhg.2009.06.003
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA 470RO
UT WOS:000267997600005
PM 19576567
ER
PT J
AU Zhao, WQ
Lacor, PN
Chen, H
Lambert, MP
Quon, MJ
Krafft, GA
Klein, WL
AF Zhao, Wei-Qin
Lacor, Pascale N.
Chen, Hui
Lambert, Mary P.
Quon, Michael J.
Krafft, Grant A.
Klein, William L.
TI Insulin Receptor Dysfunction Impairs Cellular Clearance of Neurotoxic
Oligomeric A beta
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID GROWTH-FACTOR-I; AMYLOID PRECURSOR PROTEIN; HIPPOCAMPAL SYNAPTIC
PLASTICITY; TYROSINE KINASE-ACTIVITY; LONG-TERM POTENTIATION;
CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE;
DEGRADING ENZYME; SIGNAL-TRANSDUCTION
AB Accumulation of amyloid beta (A beta) oligomers in the brain is toxic to synapses and may play an important role in memory loss in Alzheimer disease. However, how these toxins are built up in the brain is not understood. In this study we investigate whether impairments of insulin and insulin-like growth factor-1 (IGF-1) receptors play a role in aggregation of A beta. Using primary neuronal culture and immortal cell line models, we show that expression of normal insulin or IGF-1 receptors confers cells with abilities to reduce exogenously applied A beta oligomers (also known as ADDLs) to monomers. In contrast, transfection of malfunctioning human insulin receptor mutants, identified originally from patient with insulin resistance syndrome, or inhibition of insulin and IGF-1 receptors via pharmacological reagents increases ADDL levels by exacerbating their aggregation. In healthy cells, activation of insulin and IGF-1 receptor reduces the extracellular ADDLs applied to cells via seemingly the insulin-degrading enzyme activity. Although insulin triggers ADDL internalization, IGF-1 appears to keep ADDLs on the cell surface. Nevertheless, both insulin and IGF-1 reduce ADDL binding, protect synapses from ADDL synaptotoxic effects, and prevent the ADDL-induced surface insulin receptor loss. Our results suggest that dysfunctions of brain insulin and IGF-1 receptors contribute to A beta aggregation and subsequent synaptic loss.
C1 [Zhao, Wei-Qin; Lacor, Pascale N.; Lambert, Mary P.; Klein, William L.] Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA.
[Zhao, Wei-Qin] Blanchette Rockefeller Neurosci Inst, Rockville, MD 20680 USA.
[Krafft, Grant A.] Acumen Pharmaceut Inc, Livermore, CA 94080 USA.
[Chen, Hui; Quon, Michael J.] NIH, NCCAM, Bethesda, MD 20892 USA.
RP Zhao, WQ (reprint author), Merck & Co Inc, Alzheimers Res, Merck Res Labs, West Point, PA 19486 USA.
EM wei-qin_zhao@merck.com
OI Quon, Michael/0000-0002-9601-9915
FU National Institutes of Health [RO1-AG022547]; NIA; Intramural funding at
Blanchette Rockefeller Neurosciences Institute, Rockville, MD; American
Health Assistance Foundation; Alzheimer's Association; Acumen
Pharmaceuticals, Inc., South
FX This work was supported, in whole or in part, by National Institutes of
Health Grant RO1-AG022547 from NIA. This work was also supported by
Intramural funding at Blanchette Rockefeller Neurosciences Institute,
Rockville, MD, the American Health Assistance Foundation, the
Alzheimer's Association, Acumen Pharmaceuticals, Inc., South
NR 86
TC 82
Z9 84
U1 0
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 10
PY 2009
VL 284
IS 28
BP 18742
EP 18753
DI 10.1074/jbc.M109.011015
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BP
UT WOS:000267711500024
PM 19406747
ER
PT J
AU Kramer, BS
Hagerty, KL
Somerfield, MR
Schellhammer, P
AF Kramer, Barnett S.
Hagerty, Karen L.
Somerfield, Mark R.
Schellhammer, Paul
TI Three Considerations Before Advising 5-alpha-Reductase Inhibitors for
Chemoprevention Reply
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Letter
ID PROSTATE-CANCER; MORTALITY
C1 [Kramer, Barnett S.] Natl Inst Hlth, Bethesda, MD 20892 USA.
[Hagerty, Karen L.; Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA USA.
[Schellhammer, Paul] Eastern Virginia Med Sch, Sentara Med Grp, Norfolk, VA 23501 USA.
RP Kramer, BS (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA.
NR 9
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 JUL 10
PY 2009
VL 27
IS 20
BP E23
EP E23
DI 10.1200/JCO.2009.22.9997
PG 1
WC Oncology
SC Oncology
GA 468LZ
UT WOS:000267821400030
ER
PT J
AU Gardner, ER
Smith, NF
Figg, WD
Sparreboom, A
AF Gardner, Erin R.
Smith, Nicola F.
Figg, William D.
Sparreboom, Alex
TI Influence of the dual ABCB1 and ABCG2 inhibitor tariquidar on the
disposition of oral imatinib in mice
SO JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
LA English
DT Article
ID CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE;
IN-VITRO; MESYLATE; BRAIN; PHARMACOKINETICS; TRANSPORTERS; GLEEVEC;
XR9576
AB Background: Imatinib, a tyrosine kinase inhibitor currently approved for treatment of several malignancies, has been shown to be a substrate for multiple efflux-transporter proteins, including ABCB1 (P-glycoprotein) and ABCG2 (BCRP). The effect of inhibiting these transporters on tissue exposure to imatinib remains unclear.
Objective: To assess the role of these transporters on drug disposition, 50 mg/kg imatinib was administered to Balb/C mice, 30 minutes after receiving tariquidar (10 mg/kg), an inhibitor of both ABCB1 and ABCG2, or vehicle, via oral gavage.
Methods: Quantitative determination of imatinib in mouse plasma, liver and brain was performed using a newly-developed and validated liquid-chromatography-mass spectrometric method. Results: Exposure to imatinib was 2.2-fold higher in plasma, liver and brain in mice that received tariquidar, as compared to those that received the vehicle (P = 0.001). The peak plasma concentration did not increase substantially, suggesting that tariquidar is affecting the distribution, metabolism and/or excretion of imatinib, rather than absorption. Though tariquidar increased the absolute exposure of imatinib, the brain-to-plasma ratio of imatinib was unaffected.
Conclusion: This study suggests that intentional inhibition of ABCB1 and ABCG2 function at the blood-brain barrier is unlikely to significantly improve clinical outcome of imatinib with currently used dosing regimens.
C1 [Smith, Nicola F.; Figg, William D.; Sparreboom, Alex] NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Gardner, Erin R.] NCI, Clin Pharmacol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Sparreboom, Alex] St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM gardnerer@mail.nih.gov; smithni@mail.nih.gov; wdfigg@helix.nih.gov;
alex.sparreboom@stjude.org
RI Figg Sr, William/M-2411-2016
FU National Cancer Institute; National Institutes of Health [N01-CO-12400];
Center for Cancer Research
FX This work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 20
TC 11
Z9 11
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1756-9966
J9 J EXP CLIN CANC RES
JI J. Exp. Clin. Cancer Res.
PD JUL 10
PY 2009
VL 28
AR 99
DI 10.1186/1756-9966-28-99
PG 7
WC Oncology
SC Oncology
GA 485SZ
UT WOS:000269145900001
PM 19591692
ER
PT J
AU Shibata, Y
White, JF
Serrano-Vega, MJ
Magnani, F
Aloia, AL
Grisshammer, R
Tate, CG
AF Shibata, Yoko
White, Jim F.
Serrano-Vega, Maria J.
Magnani, Francesca
Aloia, Amanda L.
Grisshammer, Reinhard
Tate, Christopher G.
TI Thermostabilization of the Neurotensin Receptor NTS1
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE membrane protein; G-protein-coupled receptor; conformational
thermostabilization
ID PROTEIN-COUPLED RECEPTOR; CRYSTAL-STRUCTURE; BINDING-SITE;
ESCHERICHIA-COLI; MEMBRANE-PROTEIN; PURIFICATION; RHODOPSIN; ANTAGONIST;
RESOLUTION; EXPRESSION
AB Structural studies on G-protein-coupled receptors have been hampered for many years by their instability in detergent solution and by the number of potential conformations that receptors can adopt. Recently, the structures of the beta(1) and beta(2) adrenergic receptors and the adenosine A(2a) receptor were determined in the antagonist-bound state, a receptor conformation that is thought to be more stable than the agonist-bound state. In contrast to these receptors, the neurotensin (NT) receptor NTS1 is much less stable in detergent solution. We have therefore used a systematic mutational approach coupled with activity assays to identify receptor mutants suitable for crystallization, both alone and in complex with the peptide agonist NT. The best receptor mutant NTS1-7m contained four point mutations. It showed increased stability compared to the wild-type receptor, in the absence of ligand, after solubilization with a variety of detergents. In addition, NTS1-7m bound to NT was more stable than unliganded NTS1-7m. Of the four thermostabilizing mutations, only one residue (A86L) is predicted to be in the lipid environment. In contrast, 1260A appears to be buried within the transmembrane helix bundle, F342A may form a distant part of the putative ligand-binding site, whereas F358A is likely to be in a region that is important for receptor activation. NTS1-7m binds NT with a similar affinity for the wild-type receptor. However, agonist dissociation was slower, and NTS1-7m activated G-proteins poorly. The affinity of NTS1-7m for the antagonist SR48692 was also lower than that of the wildtype receptor. Thus, we have successfully stabilized NTS1 in an agonist-binding conformation that does not efficiently couple to G-proteins. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [White, Jim F.; Aloia, Amanda L.; Grisshammer, Reinhard] NINCDS, Membrane Prot Struct & Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Shibata, Yoko; Serrano-Vega, Maria J.; Magnani, Francesca; Tate, Christopher G.] MRC, Mol Biol Lab, Cambridge CB2 0QH, England.
RP Grisshammer, R (reprint author), NINCDS, Membrane Prot Struct & Funct Unit, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
EM rkgriss@helix.nih-gov; cgt@mrc-lmb.cam.ac.uk
RI Grisshammer, Reinhard/C-3089-2015;
OI Tate, Christopher/0000-0002-2008-9183
FU Pfizer Global Research; Development and the MRCT Development Gap Fund;
MRC; National Institutes of Health; National Institute of Neurological
Disorders and Stroke
FX This work was supported by a joint grant from Pfizer Global Research and
Development and the MRCT Development Gap Fund, in addition to core
funding from the MRC (YS., F.M., M.J.S.-V, and C.G.T.). The research
work of J.F.W., A.L.A., and R.G. was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Neurological Disorders and Stroke. We thank John K. Northup
(National Institute on Deafness and Other Communication Disorders,
National Institutes of Health, Department of Health and Human Services,
Rockville, MD 20850 USA) for providing purified G alpha q and G
beta1gamma1. The production of NTS1 in insect
cells was performed at the Protein Expression Laboratory, Advanced
Technology Program, SAIC-Frederick, Inc., National Cancer Institute,
Frederick, MD 21702, USA. DNA sequence analysis was performed by the
National Institute of Neurological Disorders and Stroke DNA Sequencing
Facility.
NR 49
TC 94
Z9 95
U1 0
U2 16
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
J9 J MOL BIOL
JI J. Mol. Biol.
PD JUL 10
PY 2009
VL 390
IS 2
BP 262
EP 277
DI 10.1016/j.jmb.2009.04.068
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 465XW
UT WOS:000267624600009
PM 19422831
ER
PT J
AU Muller, KM
Schillinger, F
Do, DH
Leopold, DA
AF Mueller, Kai-Markus
Schillinger, Frieder
Do, David H.
Leopold, David A.
TI Dissociable Perceptual Effects of Visual Adaptation
SO PLOS ONE
LA English
DT Article
ID TILTED LINES; CORTEX; ORIENTATION; CONTRAST; CURVATURE; RESPONSES;
DISCRIMINATION; REPRESENTATION; NORMALIZATION; MACAQUE
AB Neurons in the visual cortex are responsive to the presentation of oriented and curved line segments, which are thought to act as primitives for the visual processing of shapes and objects. Prolonged adaptation to such stimuli gives rise to two related perceptual effects: a slow change in the appearance of the adapting stimulus (perceptual drift), and the distortion of subsequently presented test stimuli (adaptational aftereffects). Here we used a psychophysical nulling technique to dissociate and quantify these two classical observations in order to examine their underlying mechanisms and their relationship to one another. In agreement with previous work, we found that during adaptation horizontal and vertical straight lines serve as attractors for perceived orientation and curvature. However, the rate of perceptual drift for different stimuli was not predictive of the corresponding aftereffect magnitudes, indicating that the two perceptual effects are governed by distinct neural processes. Finally, the rate of perceptual drift for curved line segments did not depend on the spatial scale of the stimulus, suggesting that its mechanisms lie outside strictly retinotopic processing stages. These findings provide new evidence that the visual system relies on statistically salient intrinsic reference stimuli for the processing of visual patterns, and point to perceptual drift as an experimental window for studying the mechanisms of visual perception.
RP Muller, KM (reprint author), NIMH, NIH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, Bethesda, MD 20892 USA.
EM leopoldd@mail.nih.gov
OI Leopold, David/0000-0002-1345-6360
FU Intramural NIH HHS [Z01 MH002898-02]
NR 63
TC 9
Z9 9
U1 0
U2 4
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 JUL 10
PY 2009
VL 4
IS 7
AR e6183
DI 10.1371/journal.pone.0006183
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 471DN
UT WOS:000268035300004
PM 19593384
ER
PT J
AU Garten, RJ
Davis, CT
Russell, CA
Shu, B
Lindstrom, S
Balish, A
Sessions, WM
Xu, XY
Skepner, E
Deyde, V
Okomo-Adhiambo, M
Gubareva, L
Barnes, J
Smith, CB
Emery, SL
Hillman, MJ
Rivailler, P
Smagala, J
de Graaf, M
Burke, DF
Fouchier, RAM
Pappas, C
Alpuche-Aranda, CM
Lopez-Gatell, H
Olivera, H
Lopez, I
Myers, CA
Faix, D
Blair, PJ
Yu, C
Keene, KM
Dotson, PD
Boxrud, D
Sambol, AR
Abid, SH
George, KS
Bannerman, T
Moore, AL
Stringer, DJ
Blevins, P
Demmler-Harrison, GJ
Ginsberg, M
Kriner, P
Waterman, S
Smole, S
Guevara, HF
Belongia, EA
Clark, PA
Beatrice, ST
Donis, R
Katz, J
Finelli, L
Bridges, CB
Shaw, M
Jernigan, DB
Uyeki, TM
Smith, DJ
Klimov, AI
Cox, NJ
AF Garten, Rebecca J.
Davis, C. Todd
Russell, Colin A.
Shu, Bo
Lindstrom, Stephen
Balish, Amanda
Sessions, Wendy M.
Xu, Xiyan
Skepner, Eugene
Deyde, Varough
Okomo-Adhiambo, Margaret
Gubareva, Larisa
Barnes, John
Smith, Catherine B.
Emery, Shannon L.
Hillman, Michael J.
Rivailler, Pierre
Smagala, James
de Graaf, Miranda
Burke, David F.
Fouchier, Ron A. M.
Pappas, Claudia
Alpuche-Aranda, Celia M.
Lopez-Gatell, Hugo
Olivera, Hiram
Lopez, Irma
Myers, Christopher A.
Faix, Dennis
Blair, Patrick J.
Yu, Cindy
Keene, Kimberly M.
Dotson, P. David, Jr.
Boxrud, David
Sambol, Anthony R.
Abid, Syed H.
George, Kirsten St.
Bannerman, Tammy
Moore, Amanda L.
Stringer, David J.
Blevins, Patricia
Demmler-Harrison, Gail J.
Ginsberg, Michele
Kriner, Paula
Waterman, Steve
Smole, Sandra
Guevara, Hugo F.
Belongia, Edward A.
Clark, Patricia A.
Beatrice, Sara T.
Donis, Ruben
Katz, Jacqueline
Finelli, Lyn
Bridges, Carolyn B.
Shaw, Michael
Jernigan, Daniel B.
Uyeki, Timothy M.
Smith, Derek J.
Klimov, Alexander I.
Cox, Nancy J.
TI Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1)
Influenza Viruses Circulating in Humans
SO SCIENCE
LA English
DT Article
ID A VIRUS; PHYLOGENETIC ANALYSIS; UNITED-STATES; NORTH-AMERICA; EVOLUTION;
PIGS; PATHOGENICITY; TRANSMISSION; EMERGENCE; INFECTION
AB Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).
C1 [Russell, Colin A.; Skepner, Eugene; de Graaf, Miranda; Burke, David F.; Smith, Derek J.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Garten, Rebecca J.; Davis, C. Todd; Shu, Bo; Lindstrom, Stephen; Balish, Amanda; Sessions, Wendy M.; Xu, Xiyan; Skepner, Eugene; Deyde, Varough; Okomo-Adhiambo, Margaret; Gubareva, Larisa; Barnes, John; Smith, Catherine B.; Emery, Shannon L.; Hillman, Michael J.; Rivailler, Pierre; Smagala, James; Pappas, Claudia; Guevara, Hugo F.; Belongia, Edward A.; Clark, Patricia A.; Beatrice, Sara T.; Donis, Ruben; Katz, Jacqueline; Finelli, Lyn; Bridges, Carolyn B.; Shaw, Michael; Jernigan, Daniel B.; Uyeki, Timothy M.; Klimov, Alexander I.; Cox, Nancy J.] Ctr Dis Control & Prevent CDC, WHO, Collaborating Ctr Influenza, Atlanta, GA 30333 USA.
[Russell, Colin A.; Smith, Derek J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[de Graaf, Miranda; Fouchier, Ron A. M.; Smith, Derek J.] Erasmus MC, Dept Virol, NL-3000 CA Rotterdam, Netherlands.
[Alpuche-Aranda, Celia M.; Lopez-Gatell, Hugo; Olivera, Hiram; Lopez, Irma] InDRE Prolongac Carpio, Mexico City 11340, DF, Mexico.
[Myers, Christopher A.; Faix, Dennis; Blair, Patrick J.] USN, Hlth Res Ctr, San Diego, CA 92152 USA.
[Yu, Cindy] Arizona State Publ Hlth Lab, Phoenix, AZ 85007 USA.
[Keene, Kimberly M.] Colorado Dept Publ Hlth & Environm, Denver, CO 80230 USA.
[Dotson, P. David, Jr.] Indiana State Dept Hlth Labs, Indianapolis, IN 46202 USA.
[Boxrud, David] Minnesota Dept Hlth, Publ Hlth Lab, St Paul, MN 55164 USA.
[Sambol, Anthony R.] Nebraska Publ Hlth Lab, Omaha, NE 68198 USA.
[Abid, Syed H.] Westchester Cty Dept Labs & Res Publ Hlth Labs, Valhalla, NY 10595 USA.
[George, Kirsten St.] New York State Dept Hlth, Wadsworth Ctr, Slingerlands, NY USA.
[Bannerman, Tammy] Ohio Dept Hlth Lab, Reynoldsburg, OH USA.
[Moore, Amanda L.] S Carolina Dept Hlth & Environm Control, Columbia, SC 29223 USA.
[Stringer, David J.] Dallas Cty Hlth & Human Serv, Dallas, TX 75207 USA.
[Blevins, Patricia] San Antonio Metro Hlth Dist, Brooks City Base, TX 78235 USA.
[Demmler-Harrison, Gail J.] Texas Childrens Hosp, Diagnost Virol Lab, Houston, TX 77030 USA.
[Ginsberg, Michele] San Diego Publ Hlth Lab, San Diego, CA 92186 USA.
[Kriner, Paula] Imperial Cty Publ Hlth Dept, El Centro, CA 92243 USA.
[Waterman, Steve] CDC, Border Infect Dis Surveillance Project, Atlanta, GA 30333 USA.
[Smole, Sandra] Massachusetts Dept Publ Hlth, William A Hinton State Lab Inst, Jamaica Plain, MA 02130 USA.
[Guevara, Hugo F.] Calif Dept Publ Hlth, Viral & Rickettsial Dis Lab, Richmond, CA 94804 USA.
[Belongia, Edward A.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA.
[Clark, Patricia A.] Michigan Dept Community Hlth, Lansing, MI 48906 USA.
[Beatrice, Sara T.] NYU, Dept Hlth & Mental Hyg, Publ Hlth Lab, New York, NY 10016 USA.
RP Smith, DJ (reprint author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England.
EM dsmith@zoo.cam.ac.uk; njc1@cdc.gov
RI Bannerman, Tammy/E-2694-2011; burke, david/C-2091-2013; Valle,
Ruben/A-7512-2013; Fouchier, Ron/A-1911-2014;
OI Fouchier, Ron/0000-0001-8095-2869; burke, david/0000-0001-8830-3951;
Russell, Colin/0000-0002-2113-162X
FU National Institute of Allergy and Infectious Diseases
[HHSN266200700010C]; International Federation of Pharmaceutical
Manufacturers and Associations [RG51953]; Research Fellowship from Clare
College, Cambridge; NIH [DP1-OD000490-01]; European Union [223498
EMPERIE]; Human Frontier Science Program [RG P0050/2008]
FX We thank the many individuals at the local, state, and national levels
for their enormous contributions to the surveillance of the 2009 A(H1N1)
virus; the entire CDC Influenza Division staff and emergency staff; the
maintainers of the GISAID EpiFluDB and NCBI GenBank/IVR, and the members
of the WHO Global Influenza Surveillance Network. The findings and
conclusions of this report are those of the authors and do not
necessarily represent the official position of the Centers for Disease
Control and Prevention. R.A.M.F. was supported by National Institute of
Allergy and Infectious Diseases under NIH contract HHSN266200700010C.
E.S. was supported in part by the International Federation of
Pharmaceutical Manufacturers and Associations through grant RG51953.
C.A.R. was supported in part by a Research Fellowship from Clare
College, Cambridge. D.J.S., C.A.R., E.S., and D.F.B. were supported by
an NIH Directors Pioneer Award, part of the NIH roadmap for medical
research, through grant DP1-OD000490-01, an FP7 grant, 223498 EMPERIE,
from the European Union, and program grant RG P0050/2008 from the Human
Frontier Science Program. GenBank accession numbers are listed in the
Supporting Online Material
NR 38
TC 1372
Z9 1481
U1 17
U2 217
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 10
PY 2009
VL 325
IS 5937
BP 197
EP 201
DI 10.1126/science.1176225
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468FK
UT WOS:000267802000046
PM 19465683
ER
PT J
AU Muranski, P
Restifo, NP
AF Muranski, Pawel
Restifo, Nicholas P.
TI Does IL-17 promote tumor growth?
SO BLOOD
LA English
DT Editorial Material
ID PLASTICITY; INTERLEUKIN-17; IMMUNITY; LINEAGE; CELLS
C1 [Muranski, Pawel; Restifo, Nicholas P.] NIH, Bethesda, MD 20892 USA.
RP Muranski, P (reprint author), NIH, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008; Muranski, Pawel/E-5572-2010;
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [ZIA BC010763-05]
NR 12
TC 18
Z9 21
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 9
PY 2009
VL 114
IS 2
BP 231
EP 232
DI 10.1182/blood-2009-04-215541
PG 4
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700003
PM 19589929
ER
PT J
AU Lan, Q
Morton, LM
Armstrong, B
Hartge, P
Menashe, I
Zheng, TZ
Purdue, MP
Cerhan, JR
Zhang, YW
Grulich, A
Cozen, W
Yeager, M
Holford, TR
Vajdic, CM
Davis, S
Leaderer, B
Kricker, A
Schenk, M
Zahm, SH
Chatterjee, N
Chanock, SJ
Rothman, N
Wang, SS
AF Lan, Qing
Morton, Lindsay M.
Armstrong, Bruce
Hartge, Patricia
Menashe, Idan
Zheng, Tongzhang
Purdue, Mark P.
Cerhan, James R.
Zhang, Yawei
Grulich, Andrew
Cozen, Wendy
Yeager, Meredith
Holford, Theodore R.
Vajdic, Claire M.
Davis, Scott
Leaderer, Brian
Kricker, Anne
Schenk, Maryjean
Zahm, Shelia H.
Chatterjee, Nilanjan
Chanock, Stephen J.
Rothman, Nathaniel
Wang, Sophia S.
TI Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a
pooled analysis of 3 population-based case-control studies
SO BLOOD
LA English
DT Article
ID SUSCEPTIBILITY; POLYMORPHISMS; MUTATIONS; VARIANTS; EPIDEMIOLOGY;
ASSOCIATION; EXPRESSION; HAPLOTYPES; IMMUNITY; FALSE
AB Caspases play a critical role in regulation of apoptosis, cell differentiation, inflammation, and innate immunity, and several are mutated or have altered expression in non-Hodgkin lymphoma (NHL). To study the impact of genetic variation in caspases on NHL risk, we analyzed tag single nucleotide polymorphisms (SNPs) in 12 caspase and related genes in 3 population-based case-control studies (1946 cases and 1808 controls). Gene-based analysis, adjusting for the number of tagSNPs genotyped in each gene, showed significant associations for CASP8, CASP9, and CASP1. SNP-based analysis showed that CASP8 rs6736233 (odds ratio (OR) (CG) = 1.21; OR (CC) = 2.13; P trend = .011); CASP9 rs4661636 (OR(CT) = 0.89; OR(TT) = 0.77; P trend = .011); and CASP1 rs1785882 (OR(AT) = 1.12; OR(AA) = 1.30; P trend = .0054) were significantly associated with NHL risk and consistent across studies. It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis. (Blood. 2009; 114: 264-267)
C1 [Lan, Qing; Morton, Lindsay M.; Hartge, Patricia; Menashe, Idan; Purdue, Mark P.; Zahm, Shelia H.; Chatterjee, Nilanjan; Chanock, Stephen J.; Rothman, Nathaniel; Wang, Sophia S.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA.
[Armstrong, Bruce; Kricker, Anne] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN USA.
[Grulich, Andrew] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia.
[Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA.
[Yeager, Meredith; Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Canc Res Ctr, Sydney, NSW, Australia.
[Davis, Scott] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Davis, Scott] Univ Washington, Seattle, WA 98195 USA.
[Schenk, Maryjean] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Schenk, Maryjean] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA.
EM qingl@mail.nih.gov
RI Morton, Lindsay/B-5234-2015; Armstrong, Bruce/K-9464-2015; Purdue,
Mark/C-9228-2016;
OI Morton, Lindsay/0000-0001-9767-2310; Armstrong,
Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108; Cerhan,
James/0000-0002-7482-178X; Vajdic, Claire/0000-0002-3612-8298
FU NIH (NCI); Public Health Service [N01-PC-65064, N01-PC-67008,
N01-PC-67009, N01-PC-67010, N02-PC-71105]; NIH [CA62006]; NCI; National
Health and Medical Research Council of Australia [990920]; Cancer
Council New South Wales; University of Sydney Medical Foundation
FX DNA extraction, genotyping, and statistical analysis for this project
were supported by the Intramural Research Program of NIH (NCI). The
NCI-SEER study was also supported by the Intramural Research Program of
NIH (NCI) and by the Public Health Service (contracts N01-PC-65064,
N01-PC-67008, N01-PC-67009, N01-PC-67010, and N02-PC-71105). The
Connecticut study was supported by NIH (grant CA62006; T. Z.) from the
NCI. The New South Wales study was supported by the National Health and
Medical Research Council of Australia (project grant 990920; B. A.), the
Cancer Council New South Wales, and the University of Sydney Medical
Foundation.
NR 25
TC 21
Z9 23
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 JUL 9
PY 2009
VL 114
IS 2
BP 264
EP 267
DI 10.1182/blood-2009-01-198697
PG 4
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700011
PM 19414860
ER
PT J
AU Di Mascio, M
Paik, CH
Carrasquillo, JA
Maeng, JS
Jang, BS
Shin, IS
Srinivasula, S
Byrum, R
Neria, A
Kopp, W
Catalfamo, M
Nishimura, Y
Reimann, K
Martin, M
Lane, HC
AF Di Mascio, Michele
Paik, Chang H.
Carrasquillo, Jorge A.
Maeng, Jin-Soo
Jang, Beom-Su
Shin, In Soo
Srinivasula, Sharat
Byrum, Russ
Neria, Achilles
Kopp, William
Catalfamo, Marta
Nishimura, Yoshiaki
Reimann, Keith
Martin, Malcolm
Lane, H. Clifford
TI Noninvasive in vivo imaging of CD4 cells in simian-human
immunodeficiency virus (SHIV)-infected nonhuman primates
SO BLOOD
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; HIV-1 INFECTION; BLOOD VOLUMES; LYMPH-NODES;
T-CELLS; B-CELL; LYMPHOCYTES; DISEASE; RETENTION; THERAPY
AB Since the earliest days of the HIV epidemic, the number of CD4(+) T cells per unit volume of blood has been recognized as a major prognostic factor for the development of AIDS in persons with HIV infection. It has also been generally accepted that approximately 2% of total body lymphocytes circulate in the blood. In the present study, we have used a nondepleting humanized anti-CD4 monoclonal antibody labeled with the gamma emitter indium-111 to visualize the CD4(+) T-cell pool in vivo in nonhuman primates with simian HIV infection. A strong correlation was noted between radiotracer uptake in spleen, tonsil, axillary lymph nodes, and peripheral blood CD4(+) T-cell counts (rho = 0.75, 0.93, and 0.85, respectively, P < .005). The relationship between radiotracer retention in lymphoid tissues and CD4(+) T-cell counts in the circulation was governed by an exponential law. These data provide an estimate for the total number of lymphocytes in the body as being between 1.9 and 2.9 x 10(12) and suggest that the partition between peripheral blood and lymphoid tissue is between 0.3% and 0.5%. (Blood. 2009; 114: 328-337)
C1 [Di Mascio, Michele; Catalfamo, Marta; Nishimura, Yoshiaki; Martin, Malcolm; Lane, H. Clifford] NIAID, NIH, Bethesda, MD 20817 USA.
[Paik, Chang H.; Maeng, Jin-Soo; Jang, Beom-Su; Shin, In Soo; Neria, Achilles] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Carrasquillo, Jorge A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Srinivasula, Sharat] NCI, SAIC Frederick Inc, Biostat Res Branch, Frederick, MD USA.
[Byrum, Russ] Bioqual, Rockville, MD USA.
[Kopp, William] NCI, Clin Serv Program, Frederick, MD 21701 USA.
[Reimann, Keith] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
RP Di Mascio, M (reprint author), NIAID, NIH, 6700A Rockledge Dr,Rm 5232, Bethesda, MD 20817 USA.
EM mdimascio@niaid.nih.gov
RI Carrasquillo, Jorge/E-7120-2010;
OI Carrasquillo, Jorge/0000-0002-8513-5734
FU National Cancer Institute; NIH [N01-CO-12400]; National Institute of
Allergy and Infectious Diseases (NIAID)
FX This work was supported in part by the National Cancer Institute, NIH
(contract N01-CO-12400) and in part by the National Institute of Allergy
and Infectious Diseases (NIAID).
NR 34
TC 26
Z9 26
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 9
PY 2009
VL 114
IS 2
BP 328
EP 337
DI 10.1182/blood-2008-12-192203
PG 10
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700018
PM 19417212
ER
PT J
AU Panaroni, C
Gioia, R
Lupi, A
Besio, R
Goldstein, SA
Kreider, J
Leikin, S
Vera, JC
Mertz, EL
Perilli, E
Baruffaldi, F
Villa, I
Farina, A
Casasco, M
Cetta, G
Rossi, A
Frattini, A
Marini, JC
Vezzoni, P
Forlino, A
AF Panaroni, Cristina
Gioia, Roberta
Lupi, Anna
Besio, Roberta
Goldstein, Steven A.
Kreider, Jaclynn
Leikin, Sergey
Vera, Juan Carlos
Mertz, Edward L.
Perilli, Egon
Baruffaldi, Fabio
Villa, Isabella
Farina, Aurora
Casasco, Marco
Cetta, Giuseppe
Rossi, Antonio
Frattini, Annalisa
Marini, Joan C.
Vezzoni, Paolo
Forlino, Antonella
TI In utero transplantation of adult bone marrow decreases perinatal
lethality and rescues the bone phenotype in the knockin murine model for
classical, dominant osteogenesis imperfecta
SO BLOOD
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; IV MOUSE MODEL; STROMAL CELLS; NONHEMATOPOIETIC
TISSUES; SELF-RENEWAL; COLLAGEN; MICE; DIFFERENTIATION; PROGENITORS;
CHILDREN
AB Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [alpha 1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P<.05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases. ( Blood. 2009; 114: 459-468)
C1 [Gioia, Roberta; Lupi, Anna; Besio, Roberta; Cetta, Giuseppe; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy.
[Panaroni, Cristina; Frattini, Annalisa; Vezzoni, Paolo] CNR, ITB, I-20133 Milan, Italy.
[Panaroni, Cristina; Frattini, Annalisa; Vezzoni, Paolo] Ist Clin Humanitas, Rozzano, Italy.
[Goldstein, Steven A.; Kreider, Jaclynn] Univ Michigan, Orthoped Res Labs, Ann Arbor, MI 48109 USA.
[Leikin, Sergey; Vera, Juan Carlos; Mertz, Edward L.] NICHD, Sect Phys Biochem, NICHHD, NIH, Bethesda, MD USA.
[Perilli, Egon; Baruffaldi, Fabio] Ist Ortoped Rizzoli, Lab Tecnol Med, Bologna, Italy.
[Villa, Isabella] Ist Sci San Raffaele, Bone Metab Unit, I-20132 Milan, Italy.
[Farina, Aurora; Casasco, Marco] Univ Pavia, Dept Expt Med, Sect Histol & Embryol, I-27100 Pavia, Italy.
[Marini, Joan C.] NICHD, Sect Connect Tissue Disorders, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RP Forlino, A (reprint author), Univ Pavia, Dept Biochem A Castellani, Sect Med & Pharm, Via Taramelli 3-B, I-27100 Pavia, Italy.
EM aforlino@unipv.it
RI Leikin, Sergey/A-5518-2008; Rossi, Antonio/E-9935-2012; Forlino,
Antonella/H-5385-2015
OI Leikin, Sergey/0000-0001-7095-0739; Forlino,
Antonella/0000-0002-6385-1182
FU MIUR [2006050235]; Consorzio Interuniversitario Biotecnologie; Progetto
Regione Lombardia-Universita; Fondazione Caripl; Fondazione Cariplo;
European Community [LSHM-CT-2007-037471]; NIH; NICHD
FX This work was supported by MIUR 2006 ( 2006050235), Consorzio
Interuniversitario Biotecnologie ( C. I. B.), Progetto Regione
Lombardia-Universita "Dalla Scienza dei Materiali alla Biomedicina
Molecolare," Fondazione Cariplo grant to A. Forlino, Fondazione Cariplo
N.O.B.E.L. Project to P. V., European Community (FP6,
LSHM-CT-2007-037471), Intramural Research Program of the NIH, NICHD and
NIH Director's Challenge Fund.
NR 51
TC 50
Z9 51
U1 4
U2 8
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 9
PY 2009
VL 114
IS 2
BP 459
EP 468
DI 10.1182/blood-2008-12-195859
PG 10
WC Hematology
SC Hematology
GA 471MK
UT WOS:000268061700032
PM 19414862
ER
PT J
AU Kim, C
Tai, CH
Lee, B
AF Kim, Changhoon
Tai, Chin-Hsien
Lee, Byungkook
TI Iterative refinement of structure-based sequence alignments by Seed
Extension
SO BMC BIOINFORMATICS
LA English
DT Article
ID PROTEIN-STRUCTURE ALIGNMENT; RELATE 2 SETS; INTEGRATED APPROACH;
ALGORITHM; PROFILES; DATABASE; CLASSIFICATION; ACCURACY; ROTATION;
VECTORS
AB Background: Accurate sequence alignment is required in many bioinformatics applications but, when sequence similarity is low, it is difficult to obtain accurate alignments based on sequence similarity alone. The accuracy improves when the structures are available, but current structure-based sequence alignment procedures still mis-align substantial numbers of residues. In order to correct such errors, we previously explored the possibility of replacing the residue-based dynamic programming algorithm in structure alignment procedures with the Seed Extension algorithm, which does not use a gap penalty. Here, we describe a new procedure called RSE (Refinement with Seed Extension) that iteratively refines a structure-based sequence alignment.
Results: RSE uses SE (Seed Extension) in its core, which is an algorithm that we reported recently for obtaining a sequence alignment from two superimposed structures. The RSE procedure was evaluated by comparing the correctly aligned fractions of residues before and after the refinement of the structure-based sequence alignments produced by popular programs. CE, DaliLite, FAST, LOCK2, MATRAS, MATT, TM-align, SHEBA and VAST were included in this analysis and the NCBI's CDD root node set was used as the reference alignments. RSE improved the average accuracy of sequence alignments for all programs tested when no shift error was allowed. The amount of improvement varied depending on the program. The average improvements were small for DaliLite and MATRAS but about 5% for CE and VAST. More substantial improvements have been seen in many individual cases. The additional computation times required for the refinements were negligible compared to the times taken by the structure alignment programs.
Conclusion: RSE is a computationally inexpensive way of improving the accuracy of a structure-based sequence alignment. It can be used as a standalone procedure following a regular structure-based sequence alignment or to replace the traditional iterative refinement procedures based on residue-level dynamic programming algorithm in many structure alignment programs.
C1 [Kim, Changhoon; Tai, Chin-Hsien; Lee, Byungkook] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kimchan@mail.nih.gov; taic@mail.nih.gov; bk@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 34
TC 10
Z9 10
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 9
PY 2009
VL 10
AR 210
DI 10.1186/1471-2105-10-210
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 476OA
UT WOS:000268450700001
PM 19589133
ER
PT J
AU Ghosh, AK
Leshchenko-Yashchuk, S
Anderson, DD
Baldridge, A
Noetzel, M
Miller, HB
Tie, YF
Wang, YF
Koh, Y
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Leshchenko-Yashchuk, Sofiya
Anderson, David D.
Baldridge, Abigail
Noetzel, Marcus
Miller, Heather B.
Tie, Yunfeng
Wang, Yuan-Fang
Koh, Yasuhiro
Weber, Irene T.
Mitsuya, Hiroaki
TI Design of HIV-1 Protease Inhibitors with Pyrrolidinones and
Oxazolidinones as Novel P1 '-Ligands To Enhance Backbone-Binding
Interactions with Protease: Synthesis, Biological Evaluation, and
Protein-Ligand X-ray Studies(infinity)
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID RESOLUTION CRYSTAL-STRUCTURES; DRUG-RESISTANT MUTANTS; VIRUS IN-VITRO;
HYDROGEN-BONDS; POTENT; THERAPY; ALKOXYCARBONYLATION; SAQUINAVIR;
INTERFACE; CARBONATE
AB Structure-based design,. synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors are described. In an effort to enhance interactions with protease backbone atoms, we have incorporated stereochemically defined methyl-2-pyrrolidonone and methyl oxazolidinone as the P1'-ligands. These ligands are designed to interact with Gly-27' carbonyl and Arg-8 side chain in the S1'-subsite of the HIV protease. We have investigated the potential of these ligands in combination with our previously developed bis-tetrahydrofuran (bis-THF) and cyclopentanyltetrahydrofuran (Cp-THF) as the P2-ligands. Inhibitor 19b with a (R)-aminomethyl-2-pyrrolidinone and a Cp-THF was shown to be the most potent compound. This inhibitor maintained near full potency against multi-PI-resistant clinical HIV-1 variants. A high resolution protein-ligand X-ray crystal structure of 19b-bound HIV-1 protease revealed that the P1'-pyrrolidinone heterocycle and the P2-Cp-ligand are involved in several critical interactions with the backbone atoms in the S1' and S2 subsites of HIV-1 protease.
C1 [Ghosh, Arun K.; Leshchenko-Yashchuk, Sofiya; Anderson, David D.; Baldridge, Abigail; Noetzel, Marcus; Miller, Heather B.] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA.
[Tie, Yunfeng; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol Mol Basis Dis, Atlanta, GA 30303 USA.
[Koh, Yasuhiro] Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 8608556, Japan.
[Koh, Yasuhiro; Mitsuya, Hiroaki] Kumamoto Univ, Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM053386, R01 GM053386-14, R01
GM062920, R01 GM062920-10, GM53386, GM62920, R01 GM062920-11A1, R37
GM053386, U01 GM062920]
NR 44
TC 36
Z9 38
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
J9 J MED CHEM
JI J. Med. Chem.
PD JUL 9
PY 2009
VL 52
IS 13
BP 3902
EP 3914
DI 10.1021/jm900303m
PG 13
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 466HJ
UT WOS:000267651900007
PM 19473017
ER
PT J
AU Ablin, RJ
Marincola, FM
Natali, PG
AF Ablin, Richard J.
Marincola, Francesco M.
Natali, Pier Giorgio
TI The "Excellence in Translational Medicine" and "Bedside-to-Bench" Awards
2007-08
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID GENE
C1 [Ablin, Richard J.] Univ Arizona, Coll Med, Dept Immunol, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Ablin, Richard J.] Univ Arizona, Coll Med, Dept Pathol, Arizona Canc Ctr, Tucson, AZ 85724 USA.
[Ablin, Richard J.] BIO5 Inst, Tucson, AZ 85724 USA.
[Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Natali, Pier Giorgio] Regina Elena Inst Canc Res, Immunol & Mol Pathol Lab, Rome, Italy.
RP Ablin, RJ (reprint author), Univ Arizona, Coll Med, Dept Immunol, Arizona Canc Ctr, Tucson, AZ 85724 USA.
EM ablinrj@email.arizona.edu; fmarincola@mail.cc.nih.gov;
natalipg2002@yahoo.it
NR 5
TC 0
Z9 3
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD JUL 9
PY 2009
VL 7
AR 57
DI 10.1186/1479-5876-7-57
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 485TO
UT WOS:000269147500001
PM 19589166
ER
PT J
AU Diaz, M
Daly, J
AF Diaz, Marilyn
Daly, Janssen
TI IMMUNOLOGY B cells break the rules
SO NATURE
LA English
DT Editorial Material
C1 [Diaz, Marilyn; Daly, Janssen] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Diaz, M (reprint author), NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
EM diaz@niehs.nih.gov; dalyj2@niehs.nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 184
EP 186
DI 10.1038/460184a
PG 3
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000024
PM 19587755
ER
PT J
AU Wang, JH
Gostissa, M
Yan, CT
Goff, P
Hickernell, T
Hansen, E
Difilippantonio, S
Wesemann, DR
Zarrin, AA
Rajewsky, K
Nussenzweig, A
Alt, FW
AF Wang, Jing H.
Gostissa, Monica
Yan, Catherine T.
Goff, Peter
Hickernell, Thomas
Hansen, Erica
Difilippantonio, Simone
Wesemann, Duane R.
Zarrin, Ali A.
Rajewsky, Klaus
Nussenzweig, Andre
Alt, Frederick W.
TI Mechanisms promoting translocations in editing and switching peripheral
B cells
SO NATURE
LA English
DT Article
ID END-JOINING PATHWAY; CHROMOSOMAL TRANSLOCATIONS; V(D)J RECOMBINATION;
RECEPTOR REVISION; BONE-MARROW; DNA BREAKS; LYMPHOCYTE DEVELOPMENT;
GENE-REGULATION; AID; EXPRESSION
AB Variable, diversity and joining gene segment (V(D) J) recombination assembles immunoglobulin heavy or light chain (IgH or IgL) variable region exons in developing bone marrow B cells, whereas class switch recombination (CSR) exchanges IgH constant region exons in peripheral B cells. Both processes use directed DNA double-strand breaks (DSBs) repaired by non-homologous end-joining (NHEJ). Errors in either V(D) J recombination or CSR can initiate chromosomal translocations, including oncogenic IgH locus (Igh) to c-myc (also known as Myc) translocations of peripheral B cell lymphomas. Collaboration between these processes has also been proposed to initiate translocations. However, the occurrence of V(D) J recombination in peripheral B cells is controversial. Here we show that activated NHEJ-deficient splenic B cells accumulate V(D) J-recombination-associated breaks at the lambda IgL locus (Igl), as well as CSR-associated Igh breaks, often in the same cell. Moreover, Igl and Igh breaks are frequently joined to form translocations, a phenomenon associated with specific Igh-Igl co-localization. Igh and c-myc also co-localize in these cells; correspondingly, the introduction of frequent c-myc DSBs robustly promotes Igh-c-myc translocations. Our studies show peripheral B cells that attempt secondary V(D) J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours.
C1 [Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Rajewsky, Klaus; Alt, Frederick W.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA.
[Wang, Jing H.; Gostissa, Monica; Yan, Catherine T.; Goff, Peter; Hickernell, Thomas; Hansen, Erica; Wesemann, Duane R.; Zarrin, Ali A.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
[Difilippantonio, Simone; Nussenzweig, Andre] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Wesemann, Duane R.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM alt@enders.tch.harvard.edu
RI Wang, Jing/M-7813-2015
OI Wang, Jing/0000-0003-4343-2527
FU National Insitutes of Health (NIH) [5P01CA92625]; Leukemia and Lymphoma
Society of America (LLS) SCORE; NCI
FX We thank Alt laboratory members for discussions, and Y. L. Chen, J. M.
Bianco and M. Moghimi for technical assistance. This work was supported
by the National Insitutes of Health (NIH) grant 5P01CA92625 and a
Leukemia and Lymphoma Society of America (LLS) SCORE grant to F. W. A.
and K. R. M. G. is and J. H. W. was a Special Fellow of the LLS. J. H.
W. and D. R. W. are supported by an NIH training grant and C. T. Y. was
supported by an NCI training grant. A. N. is supported by the Intramural
Research program of the NIH, NCI, Center for Cancer Research. F. W. A.
is an Investigator of the Howard Hughes Medical Institute.
NR 50
TC 87
Z9 90
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 9
PY 2009
VL 460
IS 7252
BP 231
EP U94
DI 10.1038/nature08159
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 467RV
UT WOS:000267761000035
PM 19587764
ER
PT J
AU Molloy, AM
Quadros, EV
Sequeira, JM
Troendle, JF
Scott, JM
Kirke, PN
Mills, JL
AF Molloy, Anne M.
Quadros, Edward V.
Sequeira, Jeffrey M.
Troendle, James F.
Scott, John M.
Kirke, Peadar N.
Mills, James L.
TI Lack of Association between Folate-Receptor Autoantibodies and
Neural-Tube Defects.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID DEFICIENCY SYNDROME; GENETIC RISK; AUTOIMMUNITY; PREGNANCY; CANCER;
ALPHA; WOMEN
AB Background: A previous report described the presence of autoantibodies against folate receptors in 75% of serum samples from women with a history of pregnancy complicated by a neural-tube defect, as compared with 10% of controls. We sought to confirm this finding in an Irish population, which traditionally has had a high prevalence of neural-tube defects.
Methods: We performed two studies. Study 1 consisted of analysis of stored frozen blood samples collected from 1993 through 1994 from 103 mothers with a history of pregnancy complicated by a neural-tube defect (case mothers), 103 mothers with a history of pregnancy but no complication by a neural-tube defect (matched with regard to number of pregnancies and sampling dates), 58 women who had never been pregnant, and 36 men. Study 2, conducted to confirm that the storage of samples did not influence the folate-receptor autoantibodies, included fresh samples from 37 case mothers, 22 control mothers, 10 women who had never been pregnant, and 9 men. All samples were assayed for blocking and binding autoantibodies against folate receptors.
Results: In Study 1, blocking autoantibodies were found in 17% of case mothers, as compared with 13% of control mothers (odds ratio, 1.54; 95% confidence interval [CI], 0.70 to 3.39), and binding autoantibodies in 29%, as compared with 32%, respectively (odds ratio, 0.82; 95% CI, 0.44 to 1.50). Study 2 showed similar results, indicating that sample degradation was unlikely.
Conclusions: The presence and titer of maternal folate-receptor autoantibodies were not significantly associated with a neural-tube defect-affected pregnancy in this Irish population.
N Engl J Med 2009;361:152-60.
C1 [Molloy, Anne M.; Scott, John M.] Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland.
[Molloy, Anne M.] Univ Dublin Trinity Coll, Sch Med, Dublin 2, Ireland.
[Kirke, Peadar N.] Hlth Res Board, Child Hlth Epidemiol Unit, Dublin, Ireland.
[Quadros, Edward V.; Sequeira, Jeffrey M.] SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA.
[Quadros, Edward V.; Sequeira, Jeffrey M.] SUNY Hlth Sci Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA.
[Troendle, James F.; Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
RP Molloy, AM (reprint author), Univ Dublin Trinity Coll, Sch Biochem & Immunol, Dublin 2, Ireland.
EM amolloy@tcd.ie
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3348]; Health Research Board, Ireland; National
Institutes of Health [HD051880]
FX Supported by the intramural research programs of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(N01-HD-3-3348) and the Health Research Board, Ireland, and a grant from
the National Institutes of Health (HD051880, to Dr. Quadros).
NR 16
TC 18
Z9 19
U1 0
U2 4
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2009
VL 361
IS 2
BP 152
EP 160
DI 10.1056/NEJMoa0803783
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900008
PM 19587340
ER
PT J
AU Nabel, GJ
AF Nabel, Gary J.
TI Protecting against Future Shock -- Inhalational Anthrax.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 2
TC 3
Z9 3
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2009
VL 361
IS 2
BP 191
EP 193
DI 10.1056/NEJMe0903259
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900015
PM 19587345
ER
PT J
AU Andriole, GL
Miller, AB
Berg, CD
AF Andriole, Gerald L.
Miller, Anthony B.
Berg, Christine D.
CA PLCO Project Team
TI Prostate-Cancer Screening REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Andriole, Gerald L.] Washington Univ, Sch Med, St Louis, MO 63110 USA.
[Miller, Anthony B.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Berg, Christine D.] NCI, Bethesda, MD 20892 USA.
RP Andriole, GL (reprint author), Washington Univ, Sch Med, St Louis, MO 63110 USA.
EM bergc@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2009
VL 361
IS 2
BP 204
EP 205
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900024
ER
PT J
AU Izmirlian, G
AF Izmirlian, Grant
TI Prostate-Cancer Screening
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 NCI, Bethesda, MD 20892 USA.
RP Izmirlian, G (reprint author), NCI, Bethesda, MD 20892 USA.
EM izmirlig@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 9
PY 2009
VL 361
IS 2
BP 204
EP 204
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 467OS
UT WOS:000267748900022
PM 19593853
ER
PT J
AU Li, Z
Venable, RM
Rogers, LA
Murray, D
Pastor, RW
AF Li, Zheng
Venable, Richard M.
Rogers, Laura A.
Murray, Diana
Pastor, Richard W.
TI Molecular Dynamics Simulations of PIP2 and PIP3 in Lipid Bilayers:
Determination of Ring Orientation, and the Effects of Surface Roughness
on a Poisson-Boltzmann Description
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID ELECTROSTATIC SEQUESTRATION; LIQUID/LIQUID INTERFACES;
NEUTRON-DIFFRACTION; COMPUTER-SIMULATION; INOSITOL LIPIDS; BASIC
PEPTIDES; MEMBRANES; BINDING; MODEL; PROTEINS
AB Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5) -trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted similar to 40 degrees with respect to the bilayer surface, as compared with 17 degrees for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Angstrom of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 angstrom, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of similar to 26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the -25 mV surfaces (17.1 +/- 0.1 angstrom for PIP2 and 19.4 +/- 0.3 angstrom for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 angstrom estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen.
C1 [Venable, Richard M.; Pastor, Richard W.] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA.
[Li, Zheng; Rogers, Laura A.; Murray, Diana] Columbia Univ, Dept Pharmacol, Presbyterian Hosp, New York, NY USA.
RP Pastor, RW (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM pastorr@nhlbi.nih.gov
RI li, zheng/B-2260-2010
FU Intramural Research Program of the National Heart. Lung and Blood
Institute; National Institutes of Health (NIH); National Institute of
General Medical Sciences [GM66147, GM71700]
FX This research was supported in part by the Intramural Research Program
of the National Heart. Lung and Blood Institute, National Institutes of
Health (NIH), and the National Institute of General Medical Sciences,
NIH (grant GM66147 and GM71700 to D.M.). This study utilized the
high-performance computational capabilities of the CIT Biowulf/LoBoS3
and NHLBI LOBOS clusters at the NIH, Bethesda, MD.
NR 52
TC 38
Z9 38
U1 1
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUL 8
PY 2009
VL 97
IS 1
BP 155
EP 163
DI 10.1016/j.bpj.2009.04.037
PG 9
WC Biophysics
SC Biophysics
GA 469BV
UT WOS:000267871000015
PM 19580753
ER
PT J
AU Michelman-Ribeiro, A
Mazza, D
Rosales, T
Stasevich, TJ
Boukari, H
Rishi, V
Vinson, C
Knutson, JR
McNally, JG
AF Michelman-Ribeiro, Ariel
Mazza, Davide
Rosales, Tilman
Stasevich, Timothy J.
Boukari, Hacene
Rishi, Vikas
Vinson, Charles
Knutson, Jay R.
McNally, James G.
TI Direct Measurement of Association and Dissociation Rates of DNA Binding
in Live Cells by Fluorescence Correlation Spectroscopy
SO BIOPHYSICAL JOURNAL
LA English
DT Article
ID LIVING CELLS; NUCLEAR PROTEINS; GLUCOCORTICOID-RECEPTOR; RECOVERY;
DYNAMICS; DIFFUSION; TRANSPORT; MEMBRANES; CHROMATIN; MOBILITY
AB Measurement of live-cell binding interactions is vital for understanding the biochemical reactions that drive cellular processes. Here, we develop, characterize, and apply a new procedure to extract information about binding to an immobile substrate from fluorescence correlation spectroscopy (FCS) autocorrelation data. We show that existing methods for analyzing such data by two-component diffusion fits can produce inaccurate estimates of diffusion constants and bound fractions, or even fail altogether to fit FCS binding data. By analyzing live-cell FCS measurements, we show that our new model can satisfactorily account for the binding interactions introduced by attaching a DNA binding domain to the dimerization domain derived from a site-specific transcription factor (the vitellogenin binding protein (VBP)). We find that our FCS estimates are quantitatively consistent with our fluorescence recovery after photobleaching (FRAP) measurements on the same VBP domains. However, due to the fast binding interactions introduced by the DNA binding domain, FCS generates independent estimates for the diffusion constant (6.7 +/- 2.4 mu m(2)/s) and the association (2 +/- 1.2 s(-1)) and dissociation (19 +/- 7 s(-1)) rates, whereas FRAP produces only a single, but a consistent, estimate, the effective-diffusion constant (4.4 +/- 1.4 mu m(2)/s), which depends on all three parameters. We apply this new FCS method to evaluate the efficacy of a potential anticancer drug that inhibits DNA binding of VBP in vitro and find that in vivo the drug inhibits DNA binding in only a subset of cells. In sum, we provide a straightforward approach to directly measure binding rates from FCS data.
C1 [Michelman-Ribeiro, Ariel; Mazza, Davide; Stasevich, Timothy J.; McNally, James G.] NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Rosales, Tilman; Knutson, Jay R.] NHLBI, NIH, Lab Mol Biophys, Bethesda, MD 20892 USA.
[Boukari, Hacene] NICHHD, NIH, Lab Cell Biophys, Bethesda, MD 20892 USA.
[Rishi, Vikas; Vinson, Charles] NCI, NIH, Lab Metab, Bethesda, MD 20892 USA.
RP McNally, JG (reprint author), NCI, NIH, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
EM mcnallyj@exchange.nih.gov
RI Mazza, Davide/F-9536-2011; Mazza, Davide/R-5340-2016
OI Mazza, Davide/0000-0003-2776-4142
FU National Institutes of Health; National Cancer Institute, and Center for
Cancer Research
FX This research was supported in part by the intramural program of the
National Institutes of Health, National Cancer Institute. and Center for
Cancer Research. Commercial names of materials and apparatus are
identified only to specify the experimental procedures. This does not
imply a recommendation by the National Institute of Standards and
Technology, nor does it imply that they are the best available for the
purpose.
NR 33
TC 69
Z9 69
U1 1
U2 15
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0006-3495
J9 BIOPHYS J
JI Biophys. J.
PD JUL 8
PY 2009
VL 97
IS 1
BP 337
EP 346
DI 10.1016/j.bpj.2009.04.027
PG 10
WC Biophysics
SC Biophysics
GA 469BV
UT WOS:000267871000034
PM 19580772
ER
PT J
AU Peterson, PN
Ambardekar, AV
Jones, PG
Krumholz, HM
Schelbert, E
Spertus, JA
Rumsfeld, JS
Masoudi, FA
AF Peterson, Pamela N.
Ambardekar, Amrut V.
Jones, Philip G.
Krumholz, Harlan M.
Schelbert, Erik
Spertus, John A.
Rumsfeld, John S.
Masoudi, Frederick A.
TI Increased Mortality among Survivors of Myocardial Infarction with Kidney
Dysfunction: the Contribution of Gaps in the use of Guideline-Based
Therapies
SO BMC CARDIOVASCULAR DISORDERS
LA English
DT Article
ID ACUTE CORONARY SYNDROMES; STAGE RENAL-DISEASE; CARDIOVASCULAR-DISEASE;
HEART-FAILURE; INSUFFICIENCY; OUTCOMES; ASSOCIATION; INHIBITORS;
ASPIRIN; EVENTS
AB Background: We assessed the degree to which differences in guideline-based medical therapy for acute myocardial infarction (AMI) contribute to the higher mortality associated with kidney disease.
Methods: In the PREMIER registry, we evaluated patients from 19 US centers surviving AMI. Cox regression evaluated the association between estimated glomerular filtration rate (GFR) and time to death over two years, adjusting for demographic and clinical variables. The contribution of variation in guideline-based medical therapy to differences in mortality was then assessed by evaluating the incremental change in the hazard ratios after further adjustment for therapy.
Results: Of 2426 patients, 26% had GFR >= 90, 44% had GFR = 60- < 90, 22% had GFR = 30- < 60, and 8% had GFR < 30 ml/min/1.73 m(2). Greater degrees of renal dysfunction were associated with greater 2-year mortality and lower rates of guideline-based therapy among eligible patients. For patients with severely decreased GFR, adjustment for differences in guideline-based therapy did not significantly attenuate the relationship with mortality (HR 3.82, 95% CI 2.39-6.11 partially adjusted; HR = 3.90, 95% CI 2.42-6.28 after adjustment for treatment differences).
Conclusion: Higher mortality associated with reduced GFR after AMI is not accounted for by differences in treatment factors, underscoring the need for novel therapies specifically targeting the pathophysiological abnormalities associated with kidney dysfunction to improve survival.
C1 [Peterson, Pamela N.; Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA.
[Peterson, Pamela N.; Ambardekar, Amrut V.; Rumsfeld, John S.; Masoudi, Frederick A.] Univ Colorado Denver, Aurora, CO USA.
[Jones, Philip G.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Schelbert, Erik] Natl Inst Hlth, Bethesda, MD USA.
[Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA.
[Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA.
RP Peterson, PN (reprint author), Denver Hlth Med Ctr, Denver, CO USA.
EM pamela.peterson@uchsc.edu; Amrut.Ambardekar@uchsc.edu;
pgjones@saint-lukes.org; Harlan.Krumholz@yale.edu;
Schelberteb@nhlbi.nih.gov; spertusj@umkc.edu; John.Rumsfeld@uchsc.edu;
Fred.Masoudi@uchsc.edu
OI Schelbert, Erik/0000-0003-0356-4437
NR 26
TC 4
Z9 4
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2261
J9 BMC CARDIOVASC DISOR
JI BMC Cardiovasc. Disord.
PD JUL 8
PY 2009
VL 9
AR 29
DI 10.1186/1471-2261-9-29
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 477AN
UT WOS:000268488400001
PM 19586550
ER
PT J
AU Sabatino, M
Stroncek, DF
Klein, H
Marincola, FM
Wang, E
AF Sabatino, Marianna
Stroncek, David F.
Klein, Harvey
Marincola, Francesco M.
Wang, Ena
TI Stem cells in melanoma development
SO CANCER LETTERS
LA English
DT Review
DE Melanoma stem cells; Cancer stem cells
ID ACUTE MYELOID-LEUKEMIA; GENETIC INSTABILITY; MALIGNANT-MELANOMA; CLONAL
ORIGIN; BREAST-CANCER; IDENTIFICATION; EXPRESSION; PROGENITOR; MODEL;
TUMORIGENESIS
AB Cutaneous melanoma is a significant health problem worldwide. Available treatments can induce objective tumor regression in a small percent of patients, but these responses are not always associated with improved long-term survival. The resistance of melanoma to therapy and its predestined recurrence are related to the genetic heterogeneity and genomic instability of the tumor. For many years these genetic alterations were thought to be linked to the accumulation of random mutations in functionally differentiated cells which transform them into malignant cells that have lost their ability to differentiate and have acquired drug resistance. In the last few years it has been largely demonstrated that melanoma as other solid tumors contains a subpopulation of cells (CSCs) considered the source of the primary tumor mass, of new tumor nodules and responsible for drug resistance and cancer recurrence.
In this review, we provide an overview of findings and advances in CSCs research that are relevant to the initiation, natural history, and the response to treatment of malignant melanoma. (C) 2008 Published by Elsevier Ireland Ltd.
C1 [Sabatino, Marianna; Stroncek, David F.; Klein, Harvey; Marincola, Francesco M.; Wang, Ena] NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Wang, E (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, 9000 Rockville Pike,Bldg 10 Room 1C711, Bethesda, MD 20892 USA.
EM ewang@mail.cc.nih.gov
FU Intramural NIH HHS [ZIA CL002118-04, ZIA CL002119-04]
NR 64
TC 10
Z9 11
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
J9 CANCER LETT
JI Cancer Lett.
PD JUL 8
PY 2009
VL 279
IS 2
BP 119
EP 125
DI 10.1016/j.canlet.2008.10.039
PG 7
WC Oncology
SC Oncology
GA 454RA
UT WOS:000266698900001
PM 19095348
ER
PT J
AU Cho, YW
Hong, SH
Jin, QH
Wang, LF
Lee, JE
Gavrilova, O
Ge, K
AF Cho, Young-Wook
Hong, SunHwa
Jin, Qihuang
Wang, Lifeng
Lee, Ji-Eun
Gavrilova, Oksana
Ge, Kai
TI Histone Methylation Regulator PTIP Is Required for PPAR gamma and C/EBP
alpha Expression and Adipogenesis
SO CELL METABOLISM
LA English
DT Article
ID LYSINE-4 METHYLTRANSFERASE COMPLEX; DEPENDENT KINASE INHIBITORS; BROWN
ADIPOSE-TISSUE; TRANSCRIPTIONAL CONTROL; GENE-EXPRESSION; CHROMATIN;
PROTEIN; COACTIVATOR; DEMETHYLASES; ISOFORMS
AB PPAR gamma and C/EBP alpha cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPAR gamma and C/EBP alpha expression during adipogenesis remain largely unclear. Here, we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPAR gamma and C/EBP alpha expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPAR gamma expression and PPAR gamma-stimulated C/EBP alpha expression. Further, PTIP is essential for induction of PPAR gamma and C/EBP alpha expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPAR gamma and C/EBP alpha promoters. Accordingly, PTIP(-/-) MEFs and preadipocytes all show striking defects in adipogenesis. Rescue of the adipogenesis defect in PTIP(-/-) MEFs requires coexpression of PPAR gamma and C/EBP alpha. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight. Thus, by regulating PPAR gamma and C/EBP alpha expression, PTIP plays a critical role in adipogenesis.
C1 [Cho, Young-Wook; Hong, SunHwa; Jin, Qihuang; Wang, Lifeng; Lee, Ji-Eun; Ge, Kai] NIDDKD, Nucl Receptor Biol Sect, CEB, NIH, Bethesda, MD 20892 USA.
[Gavrilova, Oksana] NIDDKD, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
RP Ge, K (reprint author), NIDDKD, Nucl Receptor Biol Sect, CEB, NIH, Bethesda, MD 20892 USA.
EM kaig@niddk.nih.gov
RI Lee, Ji-Eun/F-7891-2011; Cho, Young-Wook /F-8269-2011; Wang,
Lifeng/I-4888-2012;
OI Lee, Ji-Eun/0000-0002-3768-7016; Wang, Lifeng/0000-0003-4752-6547; Ge,
Kai/0000-0002-7442-5138
FU Intramural Research Program of the NIDDK; NIH
FX We thank G. Dressier for PTIP conditional KO mice; B. Kahn for aP2-Cre
mice line 1; G. Darlington for C/EBP alpha+/- and C/EBP
alpha-/- cell lines; D. Lane for 3T3Ll cell line; H. Yu, G.
Poy, W. Jou, and T. Chanturiya for technical assistance; and A.
McPherron for critical reading of the manuscript. This work was
supported by the Intramural Research Program of the NIDDK, NIH to K.G.
NR 33
TC 59
Z9 65
U1 0
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
J9 CELL METAB
JI Cell Metab.
PD JUL 8
PY 2009
VL 10
IS 1
BP 27
EP 39
DI 10.1016/j.cmet.2009.05.010
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA 469CX
UT WOS:000267874200007
PM 19583951
ER
PT J
AU Vasan, RS
Glazer, NL
Felix, JF
Lieb, W
Wild, PS
Felix, SB
Watzinger, N
Larson, MG
Smith, NL
Dehghan, A
Grosshennig, A
Schillert, A
Teumer, A
Schmidt, R
Kathiresan, S
Lumley, T
Aulchenko, YS
Konig, IR
Zeller, T
Homuth, G
Struchalin, M
Aragam, J
Bis, JC
Rivadeneira, F
Erdmann, J
Schnabel, RB
Dorr, M
Zweiker, R
Lind, L
Rodeheffer, RJ
Greiser, KH
Levy, D
Haritunians, T
Deckers, JW
Stritzke, J
Lackner, KJ
Volker, U
Ingelsson, E
O'Donnell, CJ
Heckbert, SR
Stricker, BH
Kullo, I
Ziegler, A
Reffelmann, T
Redfield, MM
Werdan, K
Mitchell, GF
Rice, K
Arnett, DK
Hofman, A
Gottdiener, JS
Uitterlinden, AG
Meitinger, T
Blettner, M
Friedrich, N
Wang, TJ
Psaty, BM
van Duijn, CM
Wichmann, HE
Munzel, T
Kroemer, HK
Benjamin, E
Rotter, JI
Witteman, JC
Schunkert, H
Schmidt, H
Volzke, H
Blankenberg, S
AF Vasan, Ramachandran S.
Glazer, Nicole L.
Felix, Janine F.
Lieb, Wolfgang
Wild, Philipp S.
Felix, Stephan B.
Watzinger, Norbert
Larson, Martin G.
Smith, Nicholas L.
Dehghan, Abbas
Grosshennig, Anika
Schillert, Arne
Teumer, Alexander
Schmidt, Reinhold
Kathiresan, Sekar
Lumley, Thomas
Aulchenko, Yurii S.
Koenig, Inke R.
Zeller, Tanja
Homuth, Georg
Struchalin, Maksim
Aragam, Jayashri
Bis, Joshua C.
Rivadeneira, Fernando
Erdmann, Jeanette
Schnabel, Renate B.
Doerr, Marcus
Zweiker, Robert
Lind, Lars
Rodeheffer, Richard J.
Greiser, Karin Halina
Levy, Daniel
Haritunians, Talin
Deckers, Jaap W.
Stritzke, Jan
Lackner, Karl J.
Voelker, Uwe
Ingelsson, Erik
O'Donnell, Christopher J.
Heckbert, Susan R.
Stricker, Bruno H.
Kullo, Iftikhar
Ziegler, Andreas
Reffelmann, Thorsten
Redfield, Margaret M.
Werdan, Karl
Mitchell, Gary F.
Rice, Kenneth
Arnett, Donna K.
Hofman, Albert
Gottdiener, John S.
Uitterlinden, Andre G.
Meitinger, Thomas
Blettner, Maria
Friedrich, Nele
Wang, Thomas J.
Psaty, Bruce M.
van Duijn, Cornelia M.
Wichmann, H. -Erich
Munzel, Thomas
Kroemer, Heyo K.
J. Benjamin, Emelia
Rotter, Jerome I.
Witteman, Jacqueline C.
Schunkert, Heribert
Schmidt, Helena
Voelzke, Henry
Blankenberg, Stefan
TI Genetic Variants Associated With Cardiac Structure and Function A
Meta-analysis and Replication of Genome-wide Association Data
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID LEFT-VENTRICULAR MASS; CONVERTING-ENZYME GENE; CORONARY HEART-DISEASE;
LEFT ATRIAL SIZE; ELDERLY COHORT; ECHOCARDIOGRAPHIC MEASUREMENTS;
ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR HEALTH;
SYSTOLIC DYSFUNCTION
AB Context Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease.
Objective To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples.
Design, Setting, and Participants Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms ( SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort.
Main Outcome Measures Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size.
Results In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining < 1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance).
Conclusions We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease. JAMA. 2009;302(2):168-178 www.jama.com
C1 [Vasan, Ramachandran S.; Smith, Nicholas L.; Lumley, Thomas; Bis, Joshua C.; Haritunians, Talin; Kullo, Iftikhar; Arnett, Donna K.; van Duijn, Cornelia M.; Witteman, Jacqueline C.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Vasan, Ramachandran S.; Witteman, Jacqueline C.] Boston Univ, Sch Med, Dept Med, Prevent Med Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Witteman, Jacqueline C.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Smith, Nicholas L.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Haritunians, Talin; Kullo, Iftikhar] NHLBI, Bethesda, MD 20892 USA.
[Felix, Janine F.; Rivadeneira, Fernando; Wichmann, H. -Erich] Univ Washington, Cardiovasc Hlth Study, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Felix, Janine F.; Rivadeneira, Fernando; Wichmann, H. -Erich] Univ Washington, Dept Med, Seattle, WA USA.
[Aulchenko, Yurii S.; Hofman, Albert] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Dehghan, Abbas; Ziegler, Andreas; Wichmann, H. -Erich] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wichmann, H. -Erich] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Dehghan, Abbas] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs, Off Res & Dev, Seattle, WA USA.
[Wichmann, H. -Erich] Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Grp Hlth, Seattle, WA 98101 USA.
[Gottdiener, John S.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA.
[Meitinger, Thomas] Univ Maryland Hosp, Div Cardiol, Baltimore, MD 21201 USA.
[Deckers, Jaap W.; Schunkert, Heribert] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA USA.
[Lieb, Wolfgang; Grosshennig, Anika; Koenig, Inke R.; Aragam, Jayashri; Reffelmann, Thorsten; Uitterlinden, Andre G.; Munzel, Thomas; Schmidt, Helena] Erasmus MC, Rotterdam Study, Dept Epidemiol, Rotterdam, Netherlands.
[Erdmann, Jeanette; Blettner, Maria] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Stritzke, Jan] Erasmus MC, Dept Cardiol, Rotterdam, Netherlands.
[Wild, Philipp S.; Schillert, Arne; Schnabel, Renate B.; Lackner, Karl J.; Voelzke, Henry] Med Univ Lubeck, MONICA KORA Med Clin 2, D-23538 Lubeck, Germany.
[Schillert, Arne; Teumer, Alexander; Zeller, Tanja; Redfield, Margaret M.] Med Univ Lubeck, Inst Med Biometry & Stat, D-23538 Lubeck, Germany.
[Kroemer, Heyo K.] Helmholtz Zentrum Munchen, Inst Epidemiol, Munich, Germany.
[Friedrich, Nele] Helmholtz Zentrum Munchen, Inst Human Genet, Munich, Germany.
[Kroemer, Heyo K.] German Res Ctr Environm Hlth, Neuherberg, Germany.
[Kroemer, Heyo K.] Univ Munich, Neuherberg, Germany.
[Friedrich, Nele] Tech Univ Munich, Munich, Germany.
[Felix, Stephan B.; Homuth, Georg; Doerr, Marcus; J. Benjamin, Emelia] Johannes Gutenberg Univ Mainz, Gutenberg Heart Study, Dept Med 2, Mainz, Germany.
[Voelker, Uwe] Johannes Gutenberg Univ Mainz, Dept Clin Chem & Lab Med, Mainz, Germany.
[Wang, Thomas J.] Johannes Gutenberg Univ Mainz, Inst Med Biometry Epidemiol & Informat, Mainz, Germany.
[Schmidt, Reinhold; Struchalin, Maksim; Ingelsson, Erik] Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Rotter, Jerome I.] Inst Pharmacol, Greifswald, Germany.
[Psaty, Bruce M.] Inst Community Med, Greifswald, Germany.
[Watzinger, Norbert; Schmidt, Reinhold; Struchalin, Maksim; Zweiker, Robert; Ingelsson, Erik; Werdan, Karl; Psaty, Bruce M.; Rotter, Jerome I.] Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany.
[Larson, Martin G.; Lind, Lars] Med Univ Graz, Austrian Stroke Prevent Study, Dept Internal Med, Div Cardiol, Graz, Austria.
[Kathiresan, Sekar] Med Univ Graz, Dept Neurol, Graz, Austria.
[Blankenberg, Stefan] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria.
[Rodeheffer, Richard J.] Uppsala Univ, Dept Med Sci, PIVUS Study, Uppsala, Sweden.
[O'Donnell, Christopher J.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Greiser, Karin Halina; Heckbert, Susan R.; Mitchell, Gary F.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Levy, Daniel; Stricker, Bruno H.] Inst Med Epidemiol Biostat & Informat, CARLA Study, Halle, Germany.
Univ Halle Wittenberg, Halle, Salle, Germany.
[Haritunians, Talin] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM vasan@bu.edu
RI Lieb, Wolfgang/C-1990-2012; Rice, Kenneth/A-4150-2013; Aulchenko,
Yurii/M-8270-2013; Schnabel, Renate/F-6527-2014; Meitinger,
Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Konig,
Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Erdmann,
Jeanette/P-7513-2014;
OI Dehghan, Abbas/0000-0001-6403-016X; Rice, Kenneth/0000-0001-5779-4495;
Aulchenko, Yurii/0000-0002-7899-1575; Rivadeneira,
Fernando/0000-0001-9435-9441; Ramachandran, Vasan/0000-0001-7357-5970;
Erdmann, Jeanette/0000-0002-4486-6231; Benjamin,
Emelia/0000-0003-4076-2336; Ziegler, Andreas/0000-0002-8386-5397
FU National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086,
N01-HC35129, N01HC-15103, N01-HC-55222, N01-HC-75150, N01-HC-45133, U01
HL080295, R01 HL087652]; National Center for Research Resources
[M01RR00069]; National Institute of Diabetes and Digestive and Kidney
Diseases [DK063491]; Netherlands Organization of Scientific Research NWO
[175.010.2005.011, 911.03.012]; Research Institute for Diseases in the
Elderly (RIDE); Netherlands Genomics Initiative (NGI)/NWO [050 60 810];
Erasmus Medical Center and Erasmus University, Rotterdam; Netherlands
organization for scientific research (NWO); Netherlands Organization for
Health Research and Development (ZonMw); Netherlands Heart Foundation;
Ministry of Education, Culture and Science; Ministry of Health, Welfare
and Sports, the European Commission; Municipality of Rotterdam; European
Union [LSHM-CT2006-037593]; National Genome Network [01GS0418,
01GR0466]; German Federal Ministry of Education and Research (BMBF);
Helmholtz Zentrum Munchen; National Research Center for Environmental
Health, Neuherberg, Germany; BMBF; Munich Center of Health Sciences;
National Heart, Lung, and Blood Institute's Framingham Heart Study
[N01-HC25195, 2K24HL04334, RO1HL080124, RO1HL077477, R01HL093328];
Affymetrix, Inc [N02-HL-6-4278]; government of RheinlandPfalz
[961-386261/733]; Boehringer Ingelheim; PHILIPS Medical Systems;
Gutenberg Heart Study; Federal Ministry of Education and Research,
Germany [A3 01GS0833]; Federal Ministry of Education and Research
[01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012]; Ministry of Cultural Affairs;
Social Ministry of the Federal State of Mecklenburg-West Pomerania;
Competence Network Heart Failure of the Federal Ministry of Education
and Research; Deutsche Forschungsgemeinschaft; Siemens Healthcare,
Erlangen, Germany; Federal State of Mecklenburg-West Pomerania; Austrian
Science Fund [P20545_P05]; [RO1 HL55502]
FX Cardiovascular Health Study: Contract numbers N01-HC-85079 through
N01-HC-85086, N01-HC35129, N01HC-15103, N01-HC-55222, N01-HC-75150,
N01-HC-45133, grant numbers U01 HL080295 and R01 HL087652 from the
National Heart, Lung, and Blood Institute. DNA handling and genotyping
was supported in part by National Center for Research Resources grant
M01RR00069 to the Cedars-Sinai General Clinical Research Center
Genotyping core and National Institute of Diabetes and Digestive and
Kidney Diseases grant DK063491 to the Southern California Diabetes
Endocrinology Research Center.; Rotterdam Study: The genome-wide
associations database of the Rotterdam Study was funded through the
Netherlands Organization of Scientific Research NWO (nr.
175.010.2005.011, 911.03.012) and the Research Institute for Diseases in
the Elderly ( RIDE). This study was supported by the Netherlands
Genomics Initiative (NGI)/NWO project number 050 60 810. The Rotterdam
Study is supported by the Erasmus Medical Center and Erasmus University,
Rotterdam; the Netherlands organization for scientific research (NWO),
the Netherlands Organization for Health Research and Development
(ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the
Netherlands Heart Foundation, the Ministry of Education, Culture and
Science, the Ministry of Health, Welfare and Sports, the European
Commission (DG XII), and the Municipality of Rotterdam. We thank Michael
Moorhouse, PhD, Department of Bioinformatics, and Pascal Arp, BSc, Mila
Jhamai, BSc, Marijn Verkerk, BSc, and Sander Bervoets, BSc, Department
of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands, for their
help in creating the database.; MONICA-KORA: The study was funded by the
European Union sponsored project Cardiogenics (LSHM-CT2006-037593), by
the National Genome Network (01GS0418 to Drs Schunkert and Erdmann;
01GR0466 to Dr Ziegler) and by the National Genome Network Plus
sponsored by the German Federal Ministry of Education and Research
(BMBF). The MONICA/KORA Augsburg studies were financed by the Helmholtz
Zentrum Munchen (former GSF) National Research Center for Environmental
Health, Neuherberg, Germany, and supported by grants from the BMBF and
Munich Center of Health Sciences ( MC Health) as part of LMU innovativ.;
Framingham Heart Study: This work was supported by the National Heart,
Lung, and Blood Institute's Framingham Heart Study (Contract No.
N01-HC25195) and its contract with Affymetrix, Inc for genotyping
services (Contract No. N02-HL-6-4278), and by grants from the National
Heart, Lung, and Blood Institute 2K24HL04334, RO1HL080124, RO1HL077477,
and R01HL093328 (all to Dr Vasan).; Gutenberg Heart Study: The Gutenberg
Heart Study is funded through the government of RheinlandPfalz
("Stiftung Rheinland Pfalz for Innovation," contract number AZ
961-386261/733), the research programs "Wissen schafft Zukunft" and
"Schwerpunkt Vaskul re Prevention" of the Johannes Gutenberg University
of Mainz and its contract with Boehringer Ingelheim and PHILIPS Medical
Systems including an unrestricted grant for the Gutenberg Heart Study.
Specifically, the research reported in this article was supported by the
National Genome Network " NGFNplus" ( contract number project A3
01GS0833) by the Federal Ministry of Education and Research, Germany.;
Study of Health in Pomerania ( SHIP): SHIP is funded by the Federal
Ministry of Education and Research ( grants No. 01ZZ9603, 01ZZ0103, and
01ZZ0403), the Ministry of Cultural Affairs as well as the Social
Ministry of the Federal State of Mecklenburg-West Pomerania.
Echocardiography in the 5-year follow-up was funded by the Competence
Network Heart Failure of the Federal Ministry of Education and Research,
and statistical analyses were supported by Deutsche
Forschungsgemeinschaft ( by grant SFB TR 19). Genome-wide data have been
supported by the Federal Ministry of Education and Research (grant No.
03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany,
and by the Federal State of Mecklenburg-West Pomerania.; Austrian Stroke
Prevention Study: Current analyses of the Austrian Stroke Prevention
Study are funded by the Austrian Science Fund Project P20545_P05
Genetics of cerebral small vessel disease (Dr H. Schmidt).; Mayo Clinic,
Olmsted County: Dr Rodheffer was supported in part by RO1 HL55502.
NR 59
TC 107
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U1 1
U2 7
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 JUL 8
PY 2009
VL 302
IS 2
BP 168
EP 178
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 466WU
UT WOS:000267696500026
PM 19584346
ER
PT J
AU Wittko, IM
Schanzer, A
Kuzmichev, A
Schneider, FT
Shibuya, M
Raab, S
Plate, KH
AF Wittko, Ina M.
Schaenzer, Anne
Kuzmichev, Andrey
Schneider, Fabian T.
Shibuya, Masabumi
Raab, Sabine
Plate, Karl H.
TI VEGFR-1 Regulates Adult Olfactory Bulb Neurogenesis and Migration of
Neural Progenitors in the Rostral Migratory Stream In Vivo
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE; STEM-CELLS; STIMULATES
NEUROGENESIS; SUBVENTRICULAR ZONE; GENERATED NEURONS; VASCULAR NICHE;
BLOOD-VESSELS; DENTATE GYRUS; BORN NEURONS
AB The generation of new neurons in the olfactory bulb (OB) persists into adulthood and is a multistep process that includes proliferation, fate choice, migration, survival, and differentiation. Neural precursor cells destined to form olfactory interneurons arise in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) to the OB. Recently, some factors classically known from their effects on the vascular system have been found to influence different steps of adult neurogenesis. In the present study, we report a modulatory function for the vascular endothelial growth factor receptor-1 (VEGFR-1) in adult olfactory neurogenesis. We identified expression of VEGFR-1 in GFAP-positive cells within regions involved in neurogenesis of the adult mouse brain. To determine functions for VEGFR-1 in adult neurogenesis, we compared neural progenitor cell proliferation, migration, and differentiation from wild-type and VEGFR-1 signaling-deficient mice (Flt-1TK(-/-) mice). Our data show that VEGFR-1 signaling is involved in the regulation of proliferation of neuronal progenitor cells within the SVZ, migration along the RMS, and in neuronal differentiation and anatomical composition of interneuron subtypes within the OB. RMS migration in Flt-1TK(-/-) mice was altered mainly as a result of increased levels of its ligand VEGF-A, which results in an increased phosphorylation of VEGFR-2 in neuronal progenitor cells within the SVZ and the RMS. This study reveals that proper RMS migration is dependent on endogenous VEGF-A protein.
C1 [Wittko, Ina M.; Schaenzer, Anne; Schneider, Fabian T.; Raab, Sabine; Plate, Karl H.] Univ Frankfurt, Sch Med, Inst Neurol, Edinger Inst,Neurosci Ctr, D-60528 Frankfurt, Germany.
[Wittko, Ina M.; Kuzmichev, Andrey] NINDS, Mol Biol Lab, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
[Shibuya, Masabumi] Tokyo Med & Dent Univ, Dept Mol Oncol, Bunkyo Ku, Tokyo 1138519, Japan.
RP Plate, KH (reprint author), Univ Frankfurt, Sch Med, Inst Neurol, Edinger Inst,Neurosci Ctr, Heinrich Hoffmann Str 7, D-60528 Frankfurt, Germany.
EM karl-heinz.plate@kgu.de
FU Deutsche Forschungsgemeinschaft [PL158/5-3, SPP 1109]; German Israeli
Foundation (GIF) [I-740]; Division of Intramural Research
Program/National Institute of Neurological Disorders and Stroke-National
Institutes of Health
FX This work was supported by the Deutsche Forschungsgemeinschaft (Project
PL158/5-3, SPP 1109) and the German Israeli Foundation (GIF I-740). A.
K. was supported by the Division of Intramural Research Program/National
Institute of Neurological Disorders and Stroke-National Institutes of
Health. We are grateful to R. D. G. McKay for support, valuable
discussions, and laboratory space. We express thanks to H. Rohrer and V.
Taylor for helpful discussions, to J.D. Boyd and S. Mommafor critically
reading this manuscript, and to A. Beckert, M. Damm, J. Drynski, and C.
Schneider for excellent technical assistance. Wethank G. Breier for the
gift of the VEGFR-1 in situ hybridization cDNA probe.
NR 49
TC 62
Z9 64
U1 0
U2 6
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 8
PY 2009
VL 29
IS 27
BP 8704
EP 8714
DI 10.1523/JNEUROSCI.5527-08.2009
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 468KY
UT WOS:000267818400011
PM 19587277
ER
PT J
AU Berezin, MY
Guo, K
Teng, B
Edwards, WB
Anderson, CJ
Vasalatiy, O
Gandjbakhche, A
Griffiths, GL
Achilefu, S
AF Berezin, Mikhail Y.
Guo, Kevin
Teng, Bao
Edwards, W. Barry
Anderson, Carolyn J.
Vasalatiy, Olga
Gandjbakhche, Amir
Griffiths, Gary L.
Achilefu, Samuel
TI Radioactivity-Synchronized Fluorescence Enhancement Using a Radionuclide
Fluorescence-Quenched Dye
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID ENERGY-TRANSFER; COPPER; SENSORS; METALS; HEAVY
AB We demonstrate the first evidence of radioactivity-synchronized fluorescence quenching of a near-infrared tight-emitting dye by a radionuclide, (64)Cu, and subsequent fluorescence enhancement upon (64)Cu decay to the daughter isotopes (64)Ni and (64)Zn. The dynamic switch from high radioactivity and low fluorescence to Low radioactivity and high fluorescence is potentially useful for developing complementary multimodal imaging and detection platforms for chemical, environmental, and biomedical applications as well as for unraveling the mechanisms of meta-induced dynamic fluorescence changes.
C1 [Berezin, Mikhail Y.; Guo, Kevin; Edwards, W. Barry; Anderson, Carolyn J.; Achilefu, Samuel] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Teng, Bao; Vasalatiy, Olga; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, NIH, Bethesda, MD 20892 USA.
[Gandjbakhche, Amir] Eunice Shriver NICHD, Phys Biol Program, NIH, Bethesda, MD 20892 USA.
[Achilefu, Samuel] Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA.
RP Achilefu, S (reprint author), Washington Univ, Sch Med, Dept Radiol, 4525 Scott Ave, St Louis, MO 63110 USA.
EM achilefus@mir.wustl.edu
RI Achilefu, Samuel/A-3681-2012; Berezin, Mikhail/B-4102-2009;
OI Achilefu, Samuel/0000-0002-3133-6717
FU NIH [R01 CA109754, R33 CA123537, R33 CA 100972, U54 CA136398, U54
CA119342]
FX This study was support in part by the NIH extramural grants R01
CA109754, R33 CA123537, R33 CA 100972, U54 CA136398, and U54 CA119342,
the NIH Roadmap for Medical Research as the funding source for the IPDC,
and the Intramural Research Program of Eunice Shriver NICHD.
NR 21
TC 20
Z9 20
U1 1
U2 8
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 8
PY 2009
VL 131
IS 26
BP 9198
EP +
DI 10.1021/ja903685b
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA 466AT
UT WOS:000267633300031
PM 19514722
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI Do Methodological Flaws Invalidate a Randomized Trial of Lifestyle
Modification Programs in Obese Patients?
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 NCI, Bethesda, MD 20892 USA.
RP Berger, VW (reprint author), NCI, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [Z99 CA999999]
NR 3
TC 1
Z9 1
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 7
PY 2009
VL 151
IS 1
BP 70
EP 70
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 470BF
UT WOS:000267946100011
PM 19581650
ER
PT J
AU Tycko, R
Sciarretta, KL
Orgel, JPRO
Meredith, SC
AF Tycko, Robert
Sciarretta, Kimberly L.
Orgel, Joseph P. R. O.
Meredith, Stephen C.
TI Evidence for Novel beta-Sheet Structures in Iowa Mutant beta-Amyloid
Fibrils
SO BIOCHEMISTRY
LA English
DT Article
ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE;
CEREBRAL-HEMORRHAGE; ROTATING SOLIDS; EXPERIMENTAL CONSTRAINTS; DISTANCE
MEASUREMENTS; MOLECULAR-LEVEL; IN-VITRO; PEPTIDE
AB Asp23-to-Asn mutation within the coding sequence of beta-amyloid, called the Iowa mutation, is associated with early onset, familial Alzheimer's disease and cerebral amyloid angiopathy, in which patients develop neuritic plaques and massive vascular deposition predominantly of the mutant peptide. We examined the mutant peptide, D23N-A beta 40, by electron microscopy, X-ray diffraction, and solid-state NMR spectroscopy. D23N-A beta 40 forms Fibrils considerably faster than the wild-type peptide (k = 3.77 x 10(-3) min(-1) and 1.07 x 10(-4) min(-1) for D23N-A beta 40 and the wild-type peptide WT-A beta 40, respectively) and without a lag phase. Electron microscopy shows that D23N-A beta 40 forms fibrils with multiple morphologies. X-ray fiber diffraction shows a cross-beta pattern, with a sharp reflection at 4.7 angstrom and a broad reflection at 9.4 angstrom, which is notably smaller than the value for WT-A beta 40 fibrils (10.4 angstrom). Solid-state NMR measurements indicate molecular level polymorphism of the fibrils, with only a minority of D23N-A beta 40 fibrils containing the in-register, parallel P-sheet structure commonly found in WT-A beta 40 fibrils and most other amyloid fibrils. Antiparallel beta-sheet structures in the majority of fibrils are indicated by measurements of intermolecular distances through (13)C-(13)C and (15)N-(13)C dipole-dipole couplings. An intriguing possibility exists that there is a relationship between the aberrant structure of D23N-A beta 40 fibrils and the unusual vasculotropic clinical picture in these patients.
C1 [Meredith, Stephen C.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Meredith, Stephen C.] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA.
[Tycko, Robert] NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA.
[Sciarretta, Kimberly L.] Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA.
[Orgel, Joseph P. R. O.] IIT, Pritzker Inst Biomed Sci & Engn, BioCAT & uCoSM, Chicago, IL 60616 USA.
[Orgel, Joseph P. R. O.] IIT, CSRRI, Chicago, IL 60616 USA.
[Orgel, Joseph P. R. O.] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA.
RP Meredith, SC (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM scmeredi@uchicago.edu
RI ID, BioCAT/D-2459-2012
FU NIH [NS042852]; Alzheimer's Association [IIRG-06-27794]; NIH
Cardiovascular Pathophysiology Training [HL07237]; NSF [MCB-0644015];
National Institute of Diabetes and Digestive and Kidney Diseases;
National Institutes of Health; U.S. Department of Energy, Basic Energy
Sciences, Office of Science [W-31-109-ENG-38]; National Institutes of
Health-supported Research Center [RR-08630]
FX We acknowledge support from the NIH (NS042852, S.C.M.) and the
Alzheimer's Association (IIRG-06-27794, S.C.M.) and from NIH
Cardiovascular Pathophysiology Training Grant, (HL07237, K.L.S.) and NSF
(MCB-0644015 CAREER, J.P.R.O.O.). This work was supported in part by the
Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health. Use
of the Advanced Photon Source was supported by the U.S. Department of
Energy, Basic Energy Sciences, Office of Science, under Contract
W-31-109-ENG-38. BioCAT is a National Institutes of Health-supported
Research Center RR-08630.
NR 55
TC 88
Z9 89
U1 1
U2 25
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD JUL 7
PY 2009
VL 48
IS 26
BP 6072
EP 6084
DI 10.1021/bi9002666
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 465TA
UT WOS:000267609100005
PM 19358576
ER
PT J
AU Worschech, A
Chen, NH
Yu, YA
Zhang, Q
Pos, Z
Weibel, S
Raab, V
Sabatino, M
Monaco, A
Liu, H
Monsurro, V
Buller, RM
Stroncek, DF
Wang, E
Szalay, AA
Marincola, FM
AF Worschech, Andrea
Chen, Nanhai
Yu, Yong A.
Zhang, Qian
Pos, Zoltan
Weibel, Stephanie
Raab, Viktoria
Sabatino, Marianna
Monaco, Alessandro
Liu, Hui
Monsurro, Vladia
Buller, R. Mark
Stroncek, David F.
Wang, Ena
Szalay, Aladar A.
Marincola, Francesco M.
TI Systemic treatment of xenografts with vaccinia virus GLV-1h68 reveals
the immunologic facet of oncolytic therapy
SO BMC GENOMICS
LA English
DT Article
ID MESSENGER-RNA AMPLIFICATION; GENE-EXPRESSION; IN-VIVO; THYMIDINE KINASE;
BREAST-TUMORS; IMMUNE CELLS; CANCER; CARCINOMA; REJECTION; MELANOMA
AB Background: GLV-1h68 is an attenuated recombinant vaccinia virus (VACV) that selectively colonizes established human xenografts inducing their complete regression.
Results: Here, we explored xenograft/VACV/host interactions in vivo adopting organism-specific expression arrays and tumor cell/VACV in vitro comparing VACV replication patterns. There were no clear-cut differences in vitro among responding and non-responding tumors, however, tumor rejection was associated in vivo with activation of interferon-stimulated genes (ISGs) and innate immune host's effector functions (IEFs) correlating with VACV colonization of the xenografts. These signatures precisely reproduce those observed in humans during immune-mediated tissue-specific destruction (TSD) that causes tumor or allograft rejection, autoimmunity or clearance of pathogens. We recently defined these common pathways in the "immunologic constant of rejection" hypothesis (ICR).
Conclusion: This study provides the first prospective validation of a universal mechanism associated with TSD. Thus, xenograft infection by oncolytic VACV, beyond offering a promising therapy of established cancers, may represent a reliable pre-clinical model to test therapeutic strategies aimed at modulating the central pathways leading to TSD; this information may lead to the identification of principles that could refine the treatment of cancer and chronic infection by immune stimulation or autoimmunity and allograft rejection through immune tolerance.
C1 [Worschech, Andrea; Chen, Nanhai; Yu, Yong A.; Zhang, Qian; Weibel, Stephanie; Raab, Viktoria; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA.
[Worschech, Andrea; Weibel, Stephanie; Raab, Viktoria; Szalay, Aladar A.] Univ Wurzburg, Virchow Ctr Expt Biomed, Wurzburg, Germany.
[Worschech, Andrea; Weibel, Stephanie; Raab, Viktoria; Szalay, Aladar A.] Univ Wurzburg, Inst Biochem, D-8700 Wurzburg, Germany.
[Worschech, Andrea; Pos, Zoltan; Sabatino, Marianna; Monaco, Alessandro; Liu, Hui; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Buller, R. Mark] St Louis Univ, Sch Med, Dept Mol Microbiol & Immunol, St Louis, MO USA.
[Stroncek, David F.] NIH, Cellular Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA.
[Monsurro, Vladia] Univ Verona, Sch Med, Immunol Sect, Dept Pathol, I-37100 Verona, Italy.
RP Szalay, AA (reprint author), Genelux Corp, San Diego Sci Ctr, San Diego, CA USA.
EM worschecha@mail.nih.gov; nchen@genelux.com; tony@genelux.com;
qian@genelux.com; posz@cc.nih.gov; stephanie.weibel@gmx.de;
viktoriaraab@yahoo.de; sabatinom@cc.nih.gov; monacoal@cc.nih.gov;
liuh6@cc.nih.gov; vladia.monsurro@univr.it; mark.buller@gmail.com;
DStroncek@cc.nih.gov; Ewang@cc.nih.gov; aaszalay@genelux.com;
Fmarincola@mail.cc.nih.gov
RI Worschech, Andrea/I-3919-2012; Pos, Zoltan/C-3623-2014; Monaco,
Alessandro/O-5338-2015
OI Worschech, Andrea/0000-0002-4303-8653; Pos, Zoltan/0000-0002-2574-7616;
Monaco, Alessandro/0000-0002-9941-7003
FU Genelux Corporation
FX The authors would like to thank Mr. T. Trevino for the excellent work
with provision of all cell culture materials, Ms. M. Jing for tumor size
determination and tumor harvesting (both from Genelux Corporation), and
Ms. J. Langbein for excellent technical support (University of
Wurzburg). We also thank Genelux Corporation for the custom-designed
vaccinia virus chip by Affymetrix, and for a research grant supporting
all cell culture and animal tumor model experiments. Ms. S. Weibel and
Ms. V. Raab are recipients of postdoctoral fellowship and graduate
stipend, respectively, awarded to the University of Wurzburg by Genelux
Corporation. Ms. A. Worschech, visitor at NIH, is a graduate student in
Dr. Szalay's laboratory in the Department of Biochemistry, University of
Wurzburg, Germany, and is supported by a graduate stipend and foreign
travel grant from Genelux Corporation.
NR 66
TC 34
Z9 34
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD JUL 7
PY 2009
VL 10
AR 301
DI 10.1186/1471-2164-10-301
PG 22
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 480RV
UT WOS:000268755400001
PM 19583830
ER
PT J
AU Yadavalli, VK
Forbes, JG
Wang, K
AF Yadavalli, Vamsi K.
Forbes, Jeffrey G.
Wang, Kuan
TI Nanomechanics of Full-Length Nebulin: An Elastic Strain Gauge in the
Skeletal Muscle Sarcomere
SO LANGMUIR
LA English
DT Article
ID ATOMIC-FORCE MICROSCOPY; SINGLE-MOLECULE; MECHANICAL STABILITY;
RECOGNITION EVENTS; MEMBRANE-PROTEIN; STRIATED-MUSCLE; FILAMENT LENGTH;
THIN-FILAMENTS; COILED-COIL; ACTIN
AB Nebulin, a family of giant modular proteins (MW 700-800 kDa), acts as a F-actin thin filament ruler and calcium-linked regulator of actomyosin interaction. The nanomechanics of full length, native rabbit nebulin was investigated with an atomic force microscope by tethering, bracketing, and stretching full-length molecules via pairs of site-specific antibodies that were attached covalently, one to a protein resistant self-assembled monolayer of oligoethylene glycol and the other to the cantilever. Using this new nanomechanics platform that enables the identification of single molecule events via an unbiased analysis of detachment force and distance of all force curves, we showed that nebulin is elastic and extends to similar to 1 mu m by external force up to an antibody detachment force of similar to 300-400 pN. Upon stretching, nebulin unravels and yields force spectra with craggy mountain range profiles with variable numbers and heights of force peaks. The peak spacings, analyzed by the model-independent, empirical Hilbert-Huang transform method, displayed underlying periodicities at similar to 15 and similar to 22 nm that may result from the unfolding of one or more nebulin modules between force peaks. Nebulin may act as an elastic strain gauge that interacts optimally with actin only under appropriate strain and stress. This stretch to match protein ruler may also exert a compressive force that stabilizes thin filaments against stress during contraction. We propose that the elasticity of nebulin is integral and essential in the muscle sarcomere.
C1 [Yadavalli, Vamsi K.; Forbes, Jeffrey G.; Wang, Kuan] NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, K (reprint author), NIAMS, LMB, NIH, B50 Rm1523, Bethesda, MD 20892 USA.
EM wangk@mail.nih.gov
OI Yadavalli, Vamsi/0000-0002-8879-1948
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin Diseases; National Institutes of Health;
Department of Health and Human Services
FX We thank Gustavo Gutierrez-Cruz for technical assistance in preparing
nebulin and Dr. Norden Huang for his insights in adaptive data analysis.
We thank the reviewers of this manuscript for their insightful comments.
This work was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases,
National Institutes of Health, and Department of Health and Human
Services.
NR 80
TC 7
Z9 7
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0743-7463
J9 LANGMUIR
JI Langmuir
PD JUL 7
PY 2009
VL 25
IS 13
BP 7496
EP 7505
DI 10.1021/la9009898
PG 10
WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science,
Multidisciplinary
SC Chemistry; Materials Science
GA 464UR
UT WOS:000267533800052
PM 19463013
ER
PT J
AU Kiyatkin, EA
Sharma, HS
AF Kiyatkin, E. A.
Sharma, H. S.
TI PERMEABILITY OF THE BLOOD-BRAIN BARRIER DEPENDS ON BRAIN TEMPERATURE
SO NEUROSCIENCE
LA English
DT Article
DE brain hyperthermia; blood-brain barrier; acute astrocytic activation;
edema
ID NORMOTENSIVE YOUNG-RATS; CENTRAL-NERVOUS-SYSTEM; GLIAL-CELLS;
METHAMPHETAMINE INTOXICATION; HEAT-STRESS; IN-VITRO; HYPERTHERMIA;
EDEMA; INJURY; HYPOTHERMIA
AB Increased permeability of the blood-brain barrier (BBB) has been reported in different conditions accompanied by hyperthermia, but the role of brain temperature per se in modulating brain barrier functions has not been directly examined. To delineate the contribution of this factor, we examined albumin immunoreactivity in several brain structures (cortex, hippocampus, thalamus and hypothalamus) of pentobarbital-anesthetized rats (50 mg/kg i.p.), which were passively warmed to different levels of brain temperature (32-42 degrees C). Similar brain structures were also examined for the expression of glial fibrillary acidic protein (GFAP), an index of astrocytic activation, water and ion content, and morphological cell abnormalities. Data were compared with those obtained from drug-free awake rats with normal brain temperatures (36-37 degrees C). The numbers of albumin- and GFAP-positive cells strongly correlate with brain temperature, gradually increasing from similar to 38.5 degrees C and plateauing at 41-42 degrees C. Brains maintained at hyperthermia also showed larger content of brain water and Na(+), K(+) and Cl(-) as well as structural abnormalities of brain cells, all suggesting acute brain edema. The latter alterations were seen at similar to 39 degrees C, gradually progressed with temperature increase, and peaked at maximum hyperthermia. Temperature-dependent changes in albumin immunoreactivity tightly correlated with GFAP immunoreactivity, brain water, and numbers of abnormal cells; they were found in each tested area, but showed some structural specificity. Notably, a mild BBB leakage, selective glial activation, and specific cellular abnormalities were also found in the hypothalamus and piriform cortex during extreme hypothermia (32-33 degrees C); in contrast to hyperthermia these changes were associated with decreased levels of brain water, Na(+) and K(+), suggesting acute brain dehydration. Therefore, brain temperature per se is an important factor in regulating BBB permeability, alterations in brain water homeostasis, and subsequent structural abnormalities of brain cells. Published by Elsevier Ltd on behalf of IBRO.
C1 [Kiyatkin, E. A.; Sharma, H. S.] Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Sharma, H. S.] Uppsala Univ, Univ Hosp, Dept Surg Sci, Lab Cerebrovasc Res, SE-75185 Uppsala, Sweden.
RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
RI Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016
FU NIDA-NIH; Laerdal Foundation; NIDA Distinguished International Scientist
Collaboration Award (NIH)
FX This study was supported by the Intramural Research Program of NIDA-NIH,
the Laerdal Foundation, and 2007 NIDA Distinguished International
Scientist Collaboration Award (NIH) awarded to Hari S. Sharma. The
authors greatly appreciate technical assistance of P. Leon Brown, David
Bae and Michael S. Smirnov (NIDA-IRP) as well as Mari-Anne Carlsson and
Inga Horte (Uppsala University). We wish to thank Drs. Barry Hoffer and
Roy A. Wise for support of this study and the valuable comments on the
matter of this manuscript.
NR 56
TC 62
Z9 70
U1 2
U2 11
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 JUL 7
PY 2009
VL 161
IS 3
BP 926
EP 939
DI 10.1016/j.neuroscience.2009.04.004
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 455VE
UT WOS:000266794300026
PM 19362131
ER
PT J
AU Li, G
Xie, HC
Ning, H
Lu, W
Low, D
Citrin, D
Kaushal, A
Zach, L
Camphausen, K
Miller, RW
AF Li, Guang
Xie, Huchen
Ning, Holly
Lu, Wei
Low, Daniel
Citrin, Deborah
Kaushal, Aradhana
Zach, Leor
Camphausen, Kevin
Miller, Robert W.
TI A novel analytical approach to the prediction of respiratory diaphragm
motion based on external torso volume change
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
ID 4-DIMENSIONAL COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; TUMOR MOTION;
ORGAN MOTION; RADIOTHERAPY; TRACKING; LUNG; CT; SURFACE; MARKERS
AB An analytical approach to predict respiratory diaphragm motion should have advantages over a correlation-based method, which cannot adapt to breathing pattern changes without re-calibration for a changing correlation and/or linear coefficient. To quantitatively calculate the diaphragm motion, a new expandable 'piston' respiratory (EPR) model was proposed and tested using 4DCT torso images of 14 patients. The EPR model allows two orthogonal lung motions (with a few volumetric constraints): (1) the lungs expand (Delta V(EXP)) with the same anterior height variation as the thoracic surface, and (2) the lungs extend (Delta V(EXT)) with the same inferior distance as the volumetrically equivalent 'piston' diaphragm. A volume conservation rule (VCR) established previously (Li et al 2009 Phys. Med. Biol. 54 1963-78) was applied to link the external torso volume change (TVC) to internal lung volume change (LVC) via lung air volume change (AVC). As the diaphragm moves inferiorly, the vacant space above the diaphragm inside the rib cage should be filled by lung tissue with a volume equal to Delta V(EXT) (=LVC - Delta V(EXP)), while the volume of non-lung tissues in the thoracic cavity should conserve. It was found that Delta V(EXP) accounted for 3-24% of the LVC in these patients. The volumetric shape of the rib cage, characterized by the variation of cavity volume per slice over the piston motion range, deviated from a hollow cylinder by -1.1% to 6.0%, and correction was made iteratively if the variation is > 3%. The predictions based on the LVC and TVC (with a conversion factor) were compared with measured diaphragm displacements (averaged from six pivot points), showing excellent agreements (0.2 +/- 0.7 mm and 0.2 +/- 1.2 mm, respectively), which are within clinically acceptable tolerance. Assuming motion synchronization between the piston and points of interest along the diaphragm, point motion was estimated but at higher uncertainty (similar to 10% +/- 4%). This analytical approach provides a patient-independent technique to calculate the patient-specific diaphragm motion, using the anatomical and respiratory volumetric constraints.
C1 [Li, Guang; Xie, Huchen; Ning, Holly; Citrin, Deborah; Kaushal, Aradhana; Zach, Leor; Camphausen, Kevin; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Lu, Wei; Low, Daniel] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA.
RP Li, G (reprint author), NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM ligeorge@mail.nih.gov
OI Li, Guang/0000-0002-9022-2883
FU NIH [NIH R01CA096679, NIH R01CA116712]
FX This research was supported in part by NIH intramural funding and by NIH
extramural funding for DL and WL ( NIH R01CA096679 & NIH R01CA116712).
NR 44
TC 12
Z9 12
U1 0
U2 3
PU IOP PUBLISHING LTD
PI BRISTOL
PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUL 7
PY 2009
VL 54
IS 13
BP 4113
EP 4130
DI 10.1088/0031-9155/54/13/010
PG 18
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 459UW
UT WOS:000267137200010
PM 19521009
ER
PT J
AU Wong, V
Case, DA
Szabo, A
AF Wong, Vance
Case, David A.
Szabo, Attila
TI Influence of the coupling of interdomain and overall motions on NMR
relaxation
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE rotation; diffusion; spin
ID MAGNETIC-RESONANCE RELAXATION; MODEL-FREE APPROACH; ROTATIONAL
DIFFUSION; GLOBULAR-PROTEINS; CHEMICAL EXCHANGE; INTERNAL MOTION;
NUCLEAR; MACROMOLECULES; DYNAMICS; SPECTROSCOPY
AB Most theoretical models for NMR relaxation in liquids assume that overall rotational motion can be described as rotational diffusion with a single diffusion tensor. Such models cannot handle motions (such as between "closed" and "open" states of an enzyme, or between conformers of a partially disordered system) where the shape of the molecule (and hence its rotational diffusion behavior) fluctuates. We provide here a formalism for dealing with such problems. The model involves jumps between discrete conformers with different overall diffusion tensors, and a master (rate) equation to describe the transitions between these conformers. Numerical examples are given for a two-site jump model where global and local motions are concerted, showing how the rate of conformational transitions (relative to the rate of rotational diffusion) affects the observed relaxation parameters.
C1 [Wong, Vance; Case, David A.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
[Wong, Vance; Case, David A.] Rutgers State Univ, BioMaPS Inst, Piscataway, NJ 08854 USA.
[Szabo, Attila] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Case, DA (reprint author), Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA.
EM case@biomaps.rutgers.edu
RI Szabo, Attila/H-3867-2012
FU National Institutes of Health [GM45811]; National Institute of Diabetes
and Digestive and Kidney Diseases
FX We thank Irina Gopich and Dennis Torchia for their input. This work was
supported by National Institutes of Health Grant GM45811, and by the
Intramural Research Program of the National Institutes of Health,
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 29
TC 35
Z9 35
U1 1
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2009
VL 106
IS 27
BP 11016
EP 11021
DI 10.1073/pnas.0809994106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100029
PM 19541602
ER
PT J
AU McKay, MM
Ritt, DA
Morrison, DK
AF McKay, Melissa M.
Ritt, Daniel A.
Morrison, Deborah K.
TI Signaling dynamics of the KSR1 scaffold complex
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE ERK cascade; protein scaffolds; signal tranduction
ID MAP KINASE PATHWAY; ACTIVATION IN-VIVO; PHOSPHORYLATION SITES;
MASS-SPECTROMETRY; 14-3-3 BINDING; GENE ENCODES; C-ELEGANS; RAS; MEK;
SUPPRESSOR
AB Scaffold proteins contribute to the spatiotemporal control of MAPK signaling and KSR1 is an ERK cascade scaffold that localizes to the plasma membrane in response to growth factor treatment. To better understand the molecular mechanisms of KSR1 function, we examined the interaction of KSR1 with each of the ERK cascade components, Raf, MEK, and ERK. Here, we identify a hydrophobic motif within the proline-rich sequence (PRS) of MEK1 and MEK2 that is required for constitutive binding to KSR1 and find that MEK binding and residues in the KSR1 CA1 region enable KSR1 to form a ternary complex with B-Raf and MEK following growth factor treatment that enhances MEK activation. We also find that docking of active ERK to the KSR1 scaffold allows ERK to phosphorylate KSR1 and B-Raf on feedback S/TP sites. Strikingly, feedback phosphorylation of KSR1 and B-Raf promote their dissociation and result in the release of KSR1 from the plasma membrane. Together, these findings provide unique insight into the signaling dynamics of the KSR1 scaffold and reveal that through regulated interactions with Raf and ERK, KSR1 acts to both potentiate and attenuate ERK cascade activation, thus regulating the intensity and duration of ERK cascade signaling emanating from the plasma membrane during growth factor signaling.
C1 [McKay, Melissa M.; Ritt, Daniel A.; Morrison, Deborah K.] NCI, Lab Cell & Dev Signaling, Ctr Canc Res, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
EM dmorrison@ncifcrf.gov
FU National Institutes of Health; National Cancer Institute
FX We thank Dr. Michael Weber for generously providing valuable reagents
and Suzanne Specht for excellent technical assistance. This research was
supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute.
NR 34
TC 70
Z9 75
U1 1
U2 8
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2009
VL 106
IS 27
BP 11022
EP 11027
DI 10.1073/pnas.0901590106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100030
PM 19541618
ER
PT J
AU Jerlhag, E
Egecioglu, E
Landgren, S
Salome, N
Heilig, M
Moechars, D
Datta, R
Perrissoud, D
Dickson, SL
Engel, JA
AF Jerlhag, Elisabet
Egecioglu, Emil
Landgren, Sara
Salome, Nicolas
Heilig, Markus
Moechars, Diederik
Datta, Rakesh
Perrissoud, Daniel
Dickson, Suzanne L.
Engel, Jorgen A.
TI Requirement of central ghrelin signaling for alcohol reward
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE appetite; ethanol; GHS-R1A; mesolimbic dopamine system; reinforcing
ID HORMONE SECRETAGOGUE RECEPTOR; STIMULATES LOCOMOTOR-ACTIVITY;
CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS; DOPAMINE-OVERFLOW;
FOOD-INTAKE; RATS; APPETITE; ETHANOL; BRAIN
AB The stomach-derived hormone ghrelin interacts with key CNS circuits regulating energy balance and body weight. Here we provide evidence that the central ghrelin signaling system is required for alcohol reward. Central ghrelin administration (to brain ventricles or to tegmental areas involved in reward) increased alcohol intake in a 2-bottle (alcohol/water) free choice limited access paradigm in mice. By contrast, central or peripheral administration of ghrelin receptor (GHS-R1A) antagonists suppressed alcohol intake in this model. Alcohol-induced locomotor stimulation, accumbal dopamine release and conditioned place preference were abolished in models of suppressed central ghrelin signaling: GHS-R1A knockout mice and mice treated with 2 different GHS-R1A antagonists. Thus, central ghrelin signaling, via GHS-R1A, not only stimulates the reward system, but is also required for stimulation of that system by alcohol. Our data suggest that central ghrelin signaling constitutes a potential target for treatment of alcohol-related disorders.
C1 [Jerlhag, Elisabet; Landgren, Sara; Engel, Jorgen A.] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Pharmacol Sect, SE-40530 Gothenburg, Sweden.
[Egecioglu, Emil; Salome, Nicolas; Dickson, Suzanne L.] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Sect Physiol Endocrinol, SE-40530 Gothenburg, Sweden.
[Heilig, Markus] NIAAA, Bethesda, MD 20892 USA.
[Moechars, Diederik] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium.
[Datta, Rakesh] Ipsen Biomeasure Inc, Milford, MA 01757 USA.
[Perrissoud, Daniel] Aeterna Zentaris, D-60314 Frankfurt, Germany.
RP Jerlhag, E (reprint author), Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Pharmacol Sect, SE-40530 Gothenburg, Sweden.
EM elisabet.jerlhag@pharm.gu.se
NR 44
TC 179
Z9 179
U1 2
U2 24
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2009
VL 106
IS 27
BP 11318
EP 11323
DI 10.1073/pnas.0812809106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100081
PM 19564604
ER
PT J
AU Horovitz, SG
Braun, AR
Carr, WS
Picchioni, D
Balkin, TJ
Fukunaga, M
Duyn, JH
AF Horovitz, Silvina G.
Braun, Allen R.
Carr, Walter S.
Picchioni, Dante
Balkin, Thomas J.
Fukunaga, Masaki
Duyn, Jeff H.
TI Decoupling of the brain's default mode network during deep sleep
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE EEG; fMRI; resting state; connectivity; consciousness
ID RESTING HUMAN BRAIN; CAT VISUAL-CORTEX; FUNCTIONAL CONNECTIVITY; BOLD
SIGNAL; SPONTANEOUS FLUCTUATIONS; COGNITIVE NEUROSCIENCE; STATE;
CONSCIOUSNESS; FMRI; ARCHITECTURE
AB The recent discovery of a circuit of brain regions that is highly active in the absence of overt behavior has led to a quest for revealing the possible function of this so-called default-mode network (DMN). A very recent study, finding similarities in awake humans and anesthetized primates, has suggested that DMN activity might not simply reflect ongoing conscious mentation but rather a more general form of network dynamics typical of complex systems. Here, by performing functional MRI in humans, it is shown that a natural, sleep-induced reduction of consciousness is reflected in altered correlation between DMN network components, most notably a reduced involvement of frontal cortex. This suggests that DMN may play an important role in the sustenance of conscious awareness.
C1 [Horovitz, Silvina G.] Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Horovitz, Silvina G.; Fukunaga, Masaki; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Braun, Allen R.] Natl Inst Deafness & Other Commun Disorders, Language Sect, Voice Speech & Language Branch, NIH, Bethesda, MD 20892 USA.
[Carr, Walter S.] USN, Med Res Ctr, Silver Spring, MD 20910 USA.
[Picchioni, Dante; Balkin, Thomas J.] Walter Reed Army Inst Res, Dept Behav Biol, Silver Spring, MD 20910 USA.
RP Horovitz, SG (reprint author), Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM silvina.horovitz@nih.gov
RI Duyn, Jozef/F-2483-2010; Sanguansri, Luz/B-6630-2011; Fukunaga,
Masaki/F-6441-2013
OI Sanguansri, Luz/0000-0003-1908-7604; Fukunaga,
Masaki/0000-0003-1010-2644
FU Intramural NIH HHS
NR 47
TC 249
Z9 254
U1 7
U2 31
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2009
VL 106
IS 27
BP 11376
EP 11381
DI 10.1073/pnas.0901435106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100091
PM 19549821
ER
PT J
AU Liu, QH
Zheng, YM
Korde, AS
Yadav, VR
Rathore, R
Wess, J
Wang, YX
AF Liu, Qing-Hua
Zheng, Yun-Min
Korde, Amit S.
Yadav, Vishal R.
Rathore, Rakesh
Wess, Juergen
Wang, Yong-Xiao
TI Membrane depolarization causes a direct activation of G protein-coupled
receptors leading to local Ca2+ release in smooth muscle
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE muscarinic receptors; ryanodine receptors
ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; INDUCED CALCIUM-RELEASE; RYANODINE
RECEPTORS; MICE LACKING; INOSITOL TRISPHOSPHATE; VASCULAR MYOCYTES;
CELLS; CONTRACTION; SPARKS; CURRENTS
AB Membrane depolarization activates voltage-dependent Ca2+ channels (VDCCs) inducing Ca2+ release via ryanodine receptors (RyRs), which is obligatory for skeletal and cardiac muscle contraction and other physiological responses. However, depolarization-induced Ca2+ release and its functional importance as well as underlying signaling mechanisms in smooth muscle cells (SMCs) are largely unknown. Here we report that membrane depolarization can induce RyR-mediated local Ca2+ release, leading to a significant increase in the activity of Ca2+ sparks and contraction in airway SMCs. The increased Ca2+ sparks are independent of VDCCs and the associated extracellular Ca2+ influx. This format of local Ca2+ release results from a direct activation of G protein-coupled, M-3 muscarinic receptors in the absence of exogenous agonists, which causes activation of Gq proteins and phospholipase C, and generation of inositol 1,4,5-triphosphate (IP3), inducing initial Ca2+ release through IP3 receptors and then further Ca2+ release via RyR2 due to a local Ca2+-induced Ca2+ release process. These findings demonstrate an important mechanism for Ca2+ signaling and attendant physiological function in SMCs.
C1 [Liu, Qing-Hua; Zheng, Yun-Min; Korde, Amit S.; Yadav, Vishal R.; Rathore, Rakesh; Wang, Yong-Xiao] Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA.
[Wess, Juergen] NIDDK, Mol Signalling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Wang, YX (reprint author), Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA.
EM wangy@mail.ame.edu
OI Korde, Amit/0000-0003-0702-290X
FU National Institutes of Health (NIH) [R01HL071000]; NIH Intramural
Research Program; American Lung Association Research [19994]; American
Heart Association (AHA) Scientist Development [0630236N, 0730242N]; AHA
Established Investigator Award [0340160N]
FX This work was supported by National Institutes of Health (NIH)
R01HL071000 (Y.-X.W.), NIH Intramural Research Program (J.W.), American
Lung Association Research Grant 19994 (Q.-H. L.), American Heart
Association (AHA) Scientist Development Grant 0630236N (Y.-M.Z.) and
0730242N (Q.-H.L.), and AHA Established Investigator Award 0340160N
(Y.-X.W.).
NR 32
TC 42
Z9 43
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 7
PY 2009
VL 106
IS 27
BP 11418
EP 11423
DI 10.1073/pnas.0813307106
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 468DX
UT WOS:000267796100098
PM 19549818
ER
PT J
AU Okoye, A
Park, H
Rohankhedkar, M
Coyne-Johnson, L
Lum, R
Walker, JM
Planer, SL
Legasse, AW
Sylwester, AW
Piatak, M
Lifson, JD
Sodora, DL
Villinger, F
Axthelm, MK
Schmitz, JE
Picker, LJ
AF Okoye, Afam
Park, Haesun
Rohankhedkar, Mukta
Coyne-Johnson, Lia
Lum, Richard
Walker, Joshua M.
Planer, Shannon L.
Legasse, Alfred W.
Sylwester, Andrew W.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Sodora, Donald L.
Villinger, Francois
Axthelm, Michael K.
Schmitz, Joern E.
Picker, Louis J.
TI Profound CD4(+)/CCR5(+) T cell expansion is induced by CD8(+) lymphocyte
depletion but does not account for accelerated SIV pathogenesis
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; INFECTED RHESUS-MONKEYS; HIV-1 INFECTION;
IN-VIVO; VIRAL REPLICATION; GASTROINTESTINAL-TRACT; IMMUNE-RESPONSES;
IFN-GAMMA; CD4(+); MACAQUES
AB Depletion of CD8(+) lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8(+) lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8(+) lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4(+) effector memory T (T-EM) cells and, to a lesser extent, transitional memory T (T-TrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4(+)/CCR5(+) SIV "target" cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8(+) lymphocytes in SIV. RMs led to a sustained increase in the number of potential CD4(+) SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4(+) T-EM cell proliferation of CD8(+) lymphocyte-depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4(+) T-EM and T-TrM cell proliferation, it did not recapitulate the viral dynamics of CD8(+) lymphocyte depletion. These data suggest that CD8(+) lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.
C1 [Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M.; Sylwester, Andrew W.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA.
[Picker, Louis J.] Oregon Hlth & Sci Univ, Dept Pathol, Beaverton, OR 97006 USA.
[Walker, Joshua M.; Picker, Louis J.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Beaverton, OR 97006 USA.
[Okoye, Afam; Park, Haesun; Rohankhedkar, Mukta; Coyne-Johnson, Lia; Lum, Richard; Walker, Joshua M.; Planer, Shannon L.; Legasse, Alfred W.; Sylwester, Andrew W.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA.
[Piatak, Michael, Jr.; Lifson, Jeffrey D.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Sodora, Donald L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Villinger, Francois] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Villinger, Francois] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Schmitz, Joern E.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA.
RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA.
EM pickerl@ohsu.edu
FU NIH [R37-AI054292, P51-RR00163, U42-RR016025, U24-RR018107,
RO1-AI065335]; National Cancer Institute [HHSN266200400088C]
FX This work was supported by NIH grants R37-AI054292 (to L. J. Picker),
P51-RR00163 (to L. J. Picker and M. K. Axthelm), U42-RR016025 and
U24-RR018107 (to M. K. Axthelm), and RO1-AI065335 (to J. E. Schmitz),
and by National Cancer Institute funds under contract no.
HHSN266200400088C (to J. D. Lifson and M. Piatak).
NR 58
TC 46
Z9 46
U1 0
U2 1
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD JUL 6
PY 2009
VL 206
IS 7
BP 1575
EP 1588
DI 10.1084/jem.20090356
PG 14
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 467KW
UT WOS:000267738700013
PM 19546246
ER
PT J
AU Araya, R
Hu, XZ
Heron, J
Enoch, MA
Evans, J
Lewis, G
Nutt, D
GoIdman, D
AF Araya, Ricardo
Hu, Xianzhang
Heron, Jon
Enoch, Mary-Anne
Evans, Jonathan
Lewis, Glyn
Nutt, David
GoIdman, David
TI Effects of Stressful Life Events, Maternal Depression and 5-HTTLPR
Genotype on Emotional Symptoms in Pre-Adolescent Children
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE genotype; environment; interactions; depression; ALSPAC
ID SEROTONIN TRANSPORTER GENE; GENERALIZED ANXIETY DISORDER;
DIFFICULTIES-QUESTIONNAIRE SDQ; CORTICOTROPIN-RELEASING-FACTOR; MAJOR
DEPRESSION; PSYCHOMETRIC PROPERTIES; PSYCHIATRIC-DISORDER; ENVIRONMENT
INTERACTION; ADOLESCENT DEPRESSION; POLYMORPHISM 5-HTTLPR
AB There has been a large but inconsistent literature on interactions between the 5-HTTLPR polymorphism of the serotonin transporter gene and adversity on emotional disorders. We investigated these interactions in 4,334 children from a birth longitudinal cohort: the Avon Longitudinal Study of Parents and Children (ALSPAC). We measured emotional symptoms at 7 years with the Strengths and Difficulties Questionnaire. Mothers rated stressful life events between ages 5 and 7 years. Maternal depression was defined as a score >= 12 on the Edinburgh Postnatal Depression Scale at 2 or 8 months postnatally. Triallelic genoptyping of the 5-HTTLPR polymorphism was performed. We found strong associations between stressful life events (OR 1.19; 1.12-1.26; P < 0.01) and maternal postnatal depression (OR 1.91; 1.63-2.24; P < 0.01) with emotional symptoms in the children. There were no main 5-HTTLPR genotype effects or significant interactions between genotype and life events or maternal postnatal depression on emotional symptoms. There was marginal evidence (P = 0.08) for an interaction between stressful life events and genotype in boys only, with those in the low and high 5-HTTLPR expression groups showing stronger associations. In these 7-year-old children, we did not replicate previously reported G x E interactions between 5-HTTLPR and life events for emotional symptoms. Gene by environment interactions may be developmentally dependent and show variation depending on the type and levels of exposure and sex. Young cohorts are essential to improve our understanding of the impact of development on gene and environment interactions. (C) 2008 Wiley-Liss, Inc.
C1 [Araya, Ricardo; Evans, Jonathan; Lewis, Glyn; Nutt, David] Univ Bristol, Acad Unit Psychiat, Bristol BS6 6JL, Avon, England.
[Hu, Xianzhang; Enoch, Mary-Anne; GoIdman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
[Heron, Jon] Univ Bristol, ALSPAC, Bristol BS6 6JL, Avon, England.
RP Araya, R (reprint author), Univ Bristol, Acad Unit Psychiat, Cotham House,Cotham Hill, Bristol BS6 6JL, Avon, England.
EM r.araya@bris.ac.uk
RI Lewis, Glyn/E-9944-2012; Heron, Jon/D-5884-2011; Goldman,
David/F-9772-2010;
OI Lewis, Glyn/0000-0001-5205-8245; Heron, Jon/0000-0001-6199-5644; Evans,
Jonathan/0000-0003-3171-640X; Goldman, David/0000-0002-1724-5405; nutt,
david/0000-0002-1286-1401
FU Wellcome Trust; University of Bristol; National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health, USA
FX We are extremely grateful to all the families who took part in this
study, the midwives for their help in recruiting them, and the whole
ALSPAC team, which includes interviewers, computer and laboratory
technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses. The UK Medical Research Council, the
Wellcome Trust and the University of Bristol provide core support for
ALSPAC. This publication is the work of the authors and R Araya will
serve as guarantor for the contents of this paper. The Intramural
Research Program of the National Institute on Alcohol Abuse and
Alcoholism, National Institutes of Health, USA specifically funded this
research.
NR 79
TC 38
Z9 39
U1 2
U2 10
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL 5
PY 2009
VL 150B
IS 5
BP 670
EP 682
DI 10.1002/ajmg.b.30888
PG 13
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 464BZ
UT WOS:000267481100006
PM 19016475
ER
PT J
AU Goes, FS
Willour, VL
Zandi, PP
Belmonte, PL
MacKinnon, DF
Mondimore, FM
Schweizer, B
Gershon, ES
McMahon, FJ
Potash, JB
AF Goes, Fernando S.
Willour, Virginia L.
Zandi, Peter P.
Belmonte, Pamela L.
MacKinnon, Dean F.
Mondimore, Francis M.
Schweizer, Barbara
Gershon, Elliot S.
McMahon, Francis J.
Potash, James B.
CA Bipolar Disorder Phenome Grp
NIMH Genetics Initiative Bipolar
TI Family-Based Association Study of Neuregulin 1 With Psychotic Bipolar
Disorder
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE Neuregulin 1; bipolar disorder; psychosis; mood-incongruent psychosis;
genetic association
ID NO SIGNIFICANT ASSOCIATION; GENOME-WIDE ASSOCIATION; AT-RISK HAPLOTYPE;
SUSCEPTIBILITY GENE; CANDIDATE GENES; SCHIZOAFFECTIVE DISORDER;
DIAGNOSTIC INTERVIEW; SCOTTISH POPULATION; ROSCOMMON FAMILY;
SCHIZOPHRENIA
AB The Neuregulin 1 gene (NRG1) has been associated with schizophrenia, and, to a lesser extent, with bipolar disorder (BP). We investigated the association of NRG1 with BP in a large family sample, and then performed analyses according to the presence of psychotic features or mood-incongruent psychotic features. We genotyped 116 tagSNPs and four Icelandic "core" SNPs in 1,199 subjects from 314 nuclear families. Of 515 BP offspring, 341 had psychotic features, and 103 had mood-incongruent psychotic features. In single-marker and sliding window haplotype analyses using FBAT, there was little association using the standard BP or mood-incongruent psychotic BP phenotypes, but stronger signals were seen in the psychotic BP phenotype. The most significant associations with psychotic BP were in haplotypes within the 5' "core" region. The strongest global P-value was across three SNPs: NRG241930-NRG243177-rs7819063 (P = 0.0016), with an undertransmitted haplotype showing an individual P = 0.0007. The most significant individual haplotype was an undertransmitted two-allele subset of the above (NRG243177-rs7819063, P = 0.0004). Additional associations with psychotic BP were found across six SNPs in a 270 kb central region of the gene. The most 3' of these, rs7005606 (P = 0.0029), is located similar to 4 kb from the type I NRG1 isoform promoter. In sum, our study suggests that NRG1 may be specifically associated with the psychotic subset of BP; however, our results should be interpreted cautiously since they do not meet correction for multiple testing and await independent replication. (C) 2009 Wiley-Liss, Inc.
C1 [Goes, Fernando S.; Willour, Virginia L.; Belmonte, Pamela L.; MacKinnon, Dean F.; Mondimore, Francis M.; Schweizer, Barbara; Potash, James B.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Gershon, Elliot S.] Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA.
[McMahon, Francis J.] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Mood & Anxiety Program, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Potash, JB (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Meyer 4-119,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jpotash@jhmi.edu
OI McMahon, Francis/0000-0002-9469-305X
FU NIMH [R01 MH042243, R01 MH-061613]; National Alliance for Research on
Schizophrenia and Depression; Stanley Medical Research Institute;
Alexander Wilson Schweizer Fellowship; Margaret Price Investigatorships
FX Bederow, MA; NIMH Intramural Research Program, Betesda, M.D.,
1Z01MH002810-01, F. McMahon, M.D., L. Kassem, PsyD, S. Detera-Wadleigh,
Ph.D., L. Austin, Ph.D., D.L. Murphy, M.D.
NR 67
TC 23
Z9 23
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL 5
PY 2009
VL 150B
IS 5
BP 693
EP 702
DI 10.1002/ajmg.b.30895
PG 10
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 464BZ
UT WOS:000267481100008
PM 19127563
ER
PT J
AU Bienvenu, OJ
Wang, Y
Shugart, YY
Welch, JM
Grados, MA
Fyer, AJ
Rauch, SL
McCracken, JT
Rasmussen, SA
Murphy, DL
Cullen, B
Valle, D
Hoehn-Saric, R
Greenberg, BD
Pinto, A
Knowles, JA
Piacentini, J
Pauls, DL
Liang, KY
Willour, VL
Riddle, M
Samuels, JF
Feng, G
Nestadt, G
AF Bienvenu, O. J.
Wang, Y.
Shugart, Y. Y.
Welch, J. M.
Grados, M. A.
Fyer, A. J.
Rauch, S. L.
McCracken, J. T.
Rasmussen, S. A.
Murphy, D. L.
Cullen, B.
Valle, D.
Hoehn-Saric, R.
Greenberg, B. D.
Pinto, A.
Knowles, J. A.
Piacentini, J.
Pauls, D. L.
Liang, K. Y.
Willour, V. L.
Riddle, M.
Samuels, J. F.
Feng, G.
Nestadt, G.
TI Sapap3 and Pathological Grooming in Humans: Results From the OCD
Collaborative Genetics Study
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE genes; Dlgap3; obsessive-compulsive disorder; nail biting;
trichotillomania
ID OBSESSIVE-COMPULSIVE DISORDER; SPECTRUM DISORDERS; PEDIATRIC PROBANDS;
ANXIETY DISORDERS; TRANSPORTER GENE; LINKAGE ANALYSIS; MESSENGER-RNA;
TRICHOTILLOMANIA; FAMILY; ASSOCIATION
AB SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had cortico-striatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies. We conducted family-based association analyses using the FBAT and GenAssoc statistical packages. Thirty-two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P < 0.05) with at least one GD (genotypic relative risks: 1.6-3.3), and all three haplotypes were nominally associated with at least one GD (permuted P < 0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association. (C) 2008 Wiley-Liss, Inc.
C1 [Bienvenu, O. J.; Wang, Y.; Grados, M. A.; Cullen, B.; Hoehn-Saric, R.; Willour, V. L.; Riddle, M.; Samuels, J. F.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA.
[Shugart, Y. Y.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Welch, J. M.; Feng, G.] Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA.
[Fyer, A. J.; Knowles, J. A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Fyer, A. J.; Knowles, J. A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Rauch, S. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Boston, MA USA.
[McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles Sch Med, Los Angeles, CA 90024 USA.
[Rasmussen, S. A.; Greenberg, B. D.; Pinto, A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA.
[Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA.
[Valle, D.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
[Pauls, D. L.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Liang, K. Y.] Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
RP Bienvenu, OJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 115, Baltimore, MD 21287 USA.
EM jbienven@jhmi.edu
RI Piacentini, John/C-4645-2011; Citations, TLC SAB/C-4006-2011; Liang,
Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017;
OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905
FU NIH [MH50125, RR00052, NS42609, MH64543, MH66284]
FX NIH grants MH50125, RR00052, NS42609, MH64543, and MH66284 supported
this study. The authors thank the many families who have participated in
the OCD Collaborative Genetics Study (OCGS); the Obsessive-Compulsive
Foundation; Ann Pulver, PhD, Kathleen Merikangas, PhD, David Houseman,
MD, and Alec Wilson, PhD, for consultation; and clinicians and
coordinators at each OCGS site: Providence (Maria Mancebo, PhD, Richard
Marsland, RN, and Shirley Yen, PhD); New York (Renee Goodwin, PhD,
Joshua Lipsitz, PhD, and Jessica Page, PsyD); Baltimore (Laura Eisen,
BS, Karan Lamb, PsyD, Tracey Lichner, PhD, Yung-mei Leong, PhD, and
Krista Vermillion, BA); Boston (Dan Geller, MD, Anne Chosak, PhD,
Michelle Wedig, BS, Evelyn Stewart, MD, Michael Jenike, MD, Beth
Gershuny, PhD, and Sabine Wilhelm, PhD); Bethesda (Lucy Justement, Diane
Kazuba, V. Holland LaSalle-Ricci, and Theresa B. DeGuzman); and Los
Angeles (R. Lindsey Bergman, PhD, Susanna Chang, PhD, Audra Langley,
PhD, and Amanda Pearlman, BA).
NR 63
TC 70
Z9 75
U1 2
U2 12
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4841
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD JUL 5
PY 2009
VL 150B
IS 5
BP 710
EP 720
DI 10.1002/ajmg.b.30897
PG 11
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA 464BZ
UT WOS:000267481100010
PM 19051237
ER
PT J
AU Karata, K
Vidal, AE
Woodgate, R
AF Karata, Kiyonobu
Vidal, Antonio E.
Woodgate, Roger
TI Construction of a circular single-stranded DNA template containing a
defined lesion
SO DNA REPAIR
LA English
DT Article
DE Translesion DNA synthesis; Mutagenesis; DNA repair; Cyclobutane
pyrimidine dimer; UV-light; Y-family DNA polymerase
ID XERODERMA-PIGMENTOSUM; CIS-SYN; POLYMERASES; MUTAGENESIS; MUTATIONS
AB We report a concise and efficient method to make a circular single-stranded DNA containing a defined DNA lesion. In this protocol, phagemid DNA containing Uracil is used as a template to synthesize a complementary DNA strand using T7 DNA polymerase and an oligonucleotide primer including a site-specific DNA lesion. The ligated lesion-containing strand can be recovered after the phage-derived template DNA is degraded by treatment with E coli Uracil DNA glycosylase and Exonucleases I and III. The resulting product is a circular single-stranded DNA containing a defined DNA lesion suitable for in vitro translesion replication assays. Published by Elsevier B.V.
C1 [Karata, Kiyonobu; Vidal, Antonio E.; Woodgate, Roger] NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA.
RP Woodgate, R (reprint author), 9800 Med Ctr Dr,Bldg C,Room 320, Bethesda, MD 20892 USA.
EM woodgate@nih.gov
OI Vidal, Antonio/0000-0001-9491-8901
FU NIH/NICHD; Japan Society for the Promotion of Science; Programa Ramon y
Cajal (Ministerio de Ciencia e Innovacion, Spain)
FX This work was supported by funds from the NIH/NICHD Intramural Research
Program. K.K. was also a recipient of a research fellowship from the
Japan Society for the Promotion of Science. A.V. was supported by funds
of the Programa Ramon y Cajal (Ministerio de Ciencia e Innovacion,
Spain).
NR 16
TC 5
Z9 5
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD JUL 4
PY 2009
VL 8
IS 7
BP 852
EP 856
DI 10.1016/j.dnarep.2009.03.006
PG 5
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 471VL
UT WOS:000268086300009
PM 19386556
ER
PT J
AU Kempen, JH
Daniel, E
Dunn, JP
Foster, CS
Gangaputra, S
Hanish, A
Helzlsouer, KJ
Jabs, DA
Kacmaz, RO
Levy-Clarke, GA
Liesegang, TL
Newcomb, CW
Nussenblatt, RB
Pujari, SS
Rosenbaum, JT
Suhler, EB
Thorne, JE
AF Kempen, John H.
Daniel, Ebenezer
Dunn, James P.
Foster, C. Stephen
Gangaputra, Sapna
Hanish, Asaf
Helzlsouer, Kathy J.
Jabs, Douglas A.
Kacmaz, R. Oktay
Levy-Clarke, Grace A.
Liesegang, Teresa L.
Newcomb, Craig W.
Nussenblatt, Robert B.
Pujari, Siddharth S.
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
TI Overall and cancer related mortality among patients with ocular
inflammation treated with immunosuppressive drugs: retrospective cohort
study
SO BRITISH MEDICAL JOURNAL
LA English
DT Article
ID NATIONAL DEATH INDEX; RHEUMATOID-ARTHRITIS; FOLLOW-UP; RISK;
MALIGNANCIES; CYCLOPHOSPHAMIDE; CYCLOSPORINE; ETANERCEPT; DISEASES;
THERAPY
AB Context Whether immunosuppressive treatment adversely affects survival is unclear.
Objective To assess whether immunosuppressive drugs increase mortality.
Design Retrospective cohort study evaluating overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort's mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.
Setting Five tertiary ocular inflammation clinics.
Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.
Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.
Main outcome measures Overall mortality, cancer mortality.
Results Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval [CI] 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio [HR] 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).
Conclusions Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.
C1 [Kempen, John H.] Univ Penn, Scheie Eye Inst, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
[Kempen, John H.; Daniel, Ebenezer] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Kempen, John H.; Hanish, Asaf; Newcomb, Craig W.] Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Daniel, Ebenezer; Dunn, James P.; Gangaputra, Sapna; Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Helzlsouer, Kathy J.; Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen; Kacmaz, R. Oktay] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Gangaputra, Sapna] Univ Wisconsin, Dept Ophthalmol, Fundus Photograph Reading Ctr, Madison, WI USA.
[Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Ctr Prevent & Res Mercy, Baltimore, MD USA.
[Jabs, Douglas A.; Kacmaz, R. Oktay] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] St Lukes Cataract & Laser Inst, Tarpon Springs, FL USA.
[Liesegang, Teresa L.; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
RP Kempen, JH (reprint author), Univ Penn, Scheie Eye Inst, Ocular Inflammat Serv, Philadelphia, PA 19104 USA.
FU National Eye Institute [EY014943]
FX This study was supported primarily by National Eye Institute Grant
EY014943 (JHK). Additional support was provided by Research to Prevent
Blindness and the Paul and Evanina Mackall Foundation. JHK is an RPB
James S Adams Special Scholar Award recipient. DAJ and JTR are Research
to Prevent Blindness Senior Scientific Investigator Award recipients.
JET is an RPB Harrington Special Scholar Award recipient. GALC was
previously supported by and RBN continues to be supported by intramural
funds of the National Eye Institute. None of the sponsors had any role
in the design and conduct of the report; collection, management,
analysis, and interpretation of the data; or in the preparation, review,
and approval of this manuscript.
NR 26
TC 1
Z9 1
U1 1
U2 3
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-8146
J9 BRIT MED J
JI Br. Med. J.
PD JUL 3
PY 2009
VL 339
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 466RB
UT WOS:000267679000003
ER
PT J
AU Zhang, YW
Jones, TL
Martin, SE
Caplen, NJ
Pommier, Y
AF Zhang, Yong-Wei
Jones, Tamara L.
Martin, Scott E.
Caplen, Natasha J.
Pommier, Yves
TI Implication of Checkpoint Kinase-dependent Up-regulation of
Ribonucleotide Reductase R2 in DNA Damage Response
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TOPOISOMERASE-I INHIBITORS; DOUBLE-STRAND BREAKS; S-PHASE CHECKPOINT;
CANCER-CELL-LINES; PROTEIN-KINASE; MULTIDRUG-RESISTANCE; CLEAVABLE
COMPLEXES; REPLICATION STRESS; CARCINOMA CELLS; CAMPTOTHECIN
AB To investigate drug mechanisms of action and identify molecular targets for the development of rational drug combinations, we conducted synthetic small interfering RNA (siRNA)-based RNAi screens to identify genes whose silencing affects anti-cancer drug responses. Silencing of RRM1 and RRM2, which encode the large and small subunits of the human ribonucleotide reductase complex, respectively, markedly enhanced the cytotoxicity of the topoisomerase I inhibitor camptothecin (CPT). Silencing of RRM2 was also found to enhance DNA damage as measured by histone gamma-H2AX. Further studies showed that CPT up-regulates both RRM1 and RRM2 mRNA and protein levels and induces the nuclear translocation of RRM2. The checkpoint kinase 1 (Chk1) was up-regulated and activated in response to CPT, and CHEK1 down-regulation by siRNA and small molecule inhibitors of Chk1 blocked RRM2 induction by CPT. CHEK1 siRNA also suppressed E2F1 up-regulation by CPT, and silencing of E2F1 suppressed the up-regulation of RRM2. Silencing of ATR or ATM and inhibition of ATM activity by KU-55933 blocked Chk1 activation and RRM2 up-regulation. This study links the known components of CPT-induced DNA damage response with proteins required for the synthesis of dNTPs and DNA repair. Specifically, we propose that upon DNA damage, Chk1 activation, mediated by ATM and ATR, up-regulates RRM2 expression through the E2F1 transcription factor. Upregulation in RRM2 expression levels coupled with its nuclear recruitment suggests an active role for ribonucleotide reductase in the cellular response to CPT-mediated DNA damage that could potentially be exploited as a strategy for enhancing the efficacy of topoisomerase I inhibitors.
C1 [Zhang, Yong-Wei; Pommier, Yves] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA.
[Jones, Tamara L.; Martin, Scott E.; Caplen, Natasha J.] NCI, Gene Silencing Sect, Genet Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), Bldg 37,Rm 5068,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM pommier@nih.gov
RI ZHANG, YONGWEI/E-6252-2012; Caplen, Natasha/H-2768-2016
OI Caplen, Natasha/0000-0002-0001-9460
FU National Institutes of Health Intramural Research Program; Center for
Cancer Research, NCI
FX This research was supported, in whole or in part, by the National
Institutes of Health Intramural Research Program, Center for Cancer
Research, NCI.
NR 66
TC 56
Z9 57
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2009
VL 284
IS 27
BP 18085
EP 18095
DI 10.1074/jbc.M109.003020
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BW
UT WOS:000267712400020
PM 19416980
ER
PT J
AU Guzman-Hernandez, ML
Vazquez-Macias, A
Carretero-Ortega, J
Hernandez-Garcia, R
Garcia-Regalado, A
Hernandez-Negrete, I
Reyes-Cruz, G
Gutkind, JS
Vazquez-Prado, J
AF Luisa Guzman-Hernandez, Maria
Vazquez-Macias, Aleida
Carretero-Ortega, Jorge
Hernandez-Garcia, Ricardo
Garcia-Regalado, Alejandro
Hernandez-Negrete, Ivette
Reyes-Cruz, Guadalupe
Silvio Gutkind, J.
Vazquez-Prado, Jose
TI Differential Inhibitor of G beta gamma Signaling to AKT and ERK Derived
from Phosducin-like Protein EFFECT ON SPHINGOSINE 1-PHOSPHATE-INDUCED
ENDOTHELIAL CELL MIGRATION AND IN VITRO ANGIOGENESIS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID NUCLEOTIDE EXCHANGE FACTOR; ENDOTHELIAL-CELL CHEMOTAXIS; HEPATOCYTE
GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; SPHINGOSINE 1-PHOSPHATE;
DICTYOSTELIUM-DISCOIDEUM; COUPLED RECEPTORS; ACTIVATION; COMPLEX;
TRANSDUCIN
AB Differential inhibitors of G beta gamma-effector regions are required to dissect the biological contribution of specific G beta gamma-initiated signaling pathways. Here, we characterize PhLP-M1-G149, a G beta gamma-interacting construct derived from phosducin-like protein 1 (PhLP) as a differential inhibitor of G beta gamma, which, in endothelial cells, prevented sphingosine 1-phosphate- induced phosphorylation of AKT, glycogen synthase kinase 3 beta, cell migration, and tubulogenesis, while having no effect on ERK phosphorylation or hepatocyte growth factor-dependent responses. This construct attenuated the recruitment of phosphoinositide 3-kinase gamma (PI3K gamma) to the plasma membrane and the signaling to AKT in response to G beta gamma overexpression. In coimmunoprecipitation experiments, PhLP-M1-G149 interfered with the interaction between PI3K gamma and G beta gamma. Other PhLP- derived constructs interacted with G beta gamma but were not effective inhibitors of G beta gamma signaling to AKT or ERK. Our results indicate that PhLP-M1-G149 is a suitable tool to differentially modulate the G beta gamma-initiated pathway linking this heterodimer to AKT, endothelial cell migration, and in vitro angiogenesis. It can be also useful to further characterize the molecular determinants of the G beta gamma-PI3K gamma interaction.
C1 [Vazquez-Prado, Jose] Natl Polytech Inst, CINVESTAV IPN, Dept Pharmacol, Ctr Res & Adv Studies, Mexico City 14740, DF, Mexico.
[Luisa Guzman-Hernandez, Maria; Vazquez-Macias, Aleida; Carretero-Ortega, Jorge; Hernandez-Garcia, Ricardo; Hernandez-Negrete, Ivette; Vazquez-Prado, Jose] Inst Politecn Nacl, Ctr Res & Adv Studies, Dept Pharmacol, Mexico City 07000, DF, Mexico.
[Luisa Guzman-Hernandez, Maria; Vazquez-Macias, Aleida; Carretero-Ortega, Jorge; Hernandez-Garcia, Ricardo; Hernandez-Negrete, Ivette; Vazquez-Prado, Jose] Inst Politecn Nacl, Ctr Res & Adv Studies, Dept Cell Biol, Mexico City 07000, DF, Mexico.
[Silvio Gutkind, J.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Vazquez-Prado, J (reprint author), Natl Polytech Inst, CINVESTAV IPN, Dept Pharmacol, Ctr Res & Adv Studies, Av Inst Politcn Nacl 2508,Col San Pedro Zacatenco, Mexico City 14740, DF, Mexico.
EM jvazquez@cinvestav.mx
RI Gutkind, J. Silvio/A-1053-2009; VAZQUEZ-PRADO, JOSE/C-1630-2017;
OI Hernandez Negrete, Ivette/0000-0003-1097-0038
FU National Institutes of Health [R01TW006664]; Fogarty International
Center; the Consejo Nacional de Ciencia y Tecnologia [61127, 45957]
FX This work was supported, in whole or in part, by National Institutes of
Health Grant R01TW006664 ( to J. V. P.) from the Fogarty International
Center. This work was also supported by the Consejo Nacional de Ciencia
y Tecnologia ( CONACyT, Grant 61127 to J. V. P. and Grant 45957 to G. R.
C.).
NR 55
TC 5
Z9 5
U1 0
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2009
VL 284
IS 27
BP 18334
EP 18346
DI 10.1074/jbc.M109.008839
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BW
UT WOS:000267712400046
PM 19403526
ER
PT J
AU Suhasini, AN
Sommers, JA
Mason, AC
Voloshin, ON
Camerini-Otero, RD
Wold, MS
Brosh, RM
AF Suhasini, Avvaru N.
Sommers, Joshua A.
Mason, Aaron C.
Voloshin, Oleg N.
Camerini-Otero, R. Daniel
Wold, Marc S.
Brosh, Robert M., Jr.
TI FANCJ Helicase Uniquely Senses Oxidative Base Damage in Either Strand of
Duplex DNA and Is Stimulated by Replication Protein A to Unwind the
Damaged DNA Substrate in a Strand-specific Manner
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BREAST-CANCER; ESCHERICHIA-COLI; ANEMIA PATHWAY; GENOMIC STABILITY;
MAMMALIAN-CELLS; BINDING PROTEIN; THYMINE GLYCOL; WRN HELICASE; HUMAN
RECQ1; REPAIR
AB FANCJ mutations are genetically linked to the Fanconi anemia complementation group J and predispose individuals to breast cancer. Understanding the role of FANCJ in DNA metabolism and how FANCJ dysfunction leads to tumorigenesis requires mechanistic studies of FANCJ helicase and its protein partners. In this work, we have examined the ability of FANCJ to unwind DNA molecules with specific base damage that can be mutagenic or lethal. FANCJ was inhibited by a single thymine glycol, but not 8-oxoguanine, in either the translocating or nontranslocating strands of the helicase substrate. In contrast, the human RecQ helicases (BLM, RECQ1, and WRN) display strand-specific inhibition of unwinding by the thymine glycol damage, whereas other DNA helicases (DinG, DnaB, and UvrD) are not significantly inhibited by thymine glycol in either strand. In the presence of replication protein A (RPA), but not Escherichia coli single-stranded DNA-binding protein, FANCJ efficiently unwound the DNA substrate harboring the thymine glycol damage in the nontranslocating strand; however, inhibition of FANCJ helicase activity by the translocating strand thymine glycol was not relieved. Strand-specific stimulation of human RECQ1 helicase activity was also observed, and RPA bound with high affinity to single-stranded DNA containing a single thymine glycol. Based on the biochemical studies, we propose a model for the specific functional interaction between RPA and FANCJ on the thymine glycol substrates. These studies are relevant to the roles of RPA, FANCJ, and other DNA helicases in the metabolism of damaged DNA that can interfere with basic cellular processes of DNA metabolism.
C1 [Suhasini, Avvaru N.; Sommers, Joshua A.; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, Baltimore, MD 21224 USA.
[Mason, Aaron C.; Wold, Marc S.] Univ Iowa, Dept Biochem, Carver Coll Med, Iowa City, IA 52242 USA.
[Voloshin, Oleg N.; Camerini-Otero, R. Daniel] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, Biomed Res Ctr, NIH, 251 Bayview Blvd,Ste 100,Rm 06B125, Baltimore, MD 21224 USA.
EM BroshR@mail.nih.gov
RI Wold, Marc/F-5806-2010
FU National Institutes of Health Research [GM44721]; NIA; NIDDK National
Institutes of Health Intramural Research Program; Fanconi Anemia
Research Fund
FX This work was supported, in whole or in part, by National Institutes of
Health Research Grant GM44721 (to M. S. W.) and the NIA and NIDDK
National Institutes of Health Intramural Research Program. This work was
also supported by the Fanconi Anemia Research Fund (to R. M. B.).
NR 48
TC 33
Z9 33
U1 0
U2 0
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2009
VL 284
IS 27
BP 18458
EP 18470
DI 10.1074/jbc.M109.012229
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BW
UT WOS:000267712400057
PM 19419957
ER
PT J
AU Mathew, S
Fu, LZ
Fiorentino, M
Matsuda, H
Das, B
Shi, YB
AF Mathew, Smita
Fu, Liezhen
Fiorentino, Maria
Matsuda, Hiroki
Das, Biswajit
Shi, Yun-Bo
TI Differential Regulation of Cell Type-specific Apoptosis by Stromelysin-3
A POTENTIAL MECHANISM VIA THE CLEAVAGE OF THE LAMININ RECEPTOR DURING
TAIL RESORPTION IN XENOPUS LAEVIS
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID MATRIX-METALLOPROTEINASE STROMELYSIN-3; HORMONE RESPONSE GENES;
THYROID-HORMONE; XENOPUS-LAEVIS; AMPHIBIAN METAMORPHOSIS; FROG
METAMORPHOSIS; BREAST-CARCINOMA; EXTRACELLULAR-MATRIX; MOUSE
STROMELYSIN-3; EXPRESSION PATTERN
AB Matrix metalloproteinases (MMPs) have been extensively studied because of their functional attributes in development and diseases. However, relatively few in vivo functional studies have been reported on the roles of MMPs in postembryonic organ development. Amphibian metamorphosis is a unique model for studying MMP function during vertebrate development because of its dependence on thyroid hormone (T3) and the ability to easily manipulate this process with exogenous T3. The MMP stromelysin-3 (ST3) is induced by T3, and its expression correlates with cell death during metamorphosis. We have previously shown that ST3 is both necessary and sufficient for larval epithelial cell death in the remodeling intestine. To investigate the roles of ST3 in other organs and especially on different cell types, we have analyzed the effect of transgenic overexpression of ST3 in the tail of premetamorphic tadpoles. We report for the first time that ST3 expression, in the absence of T3, caused significant muscle cell death in the tail of premetamorphic transgenic tadpoles. On the other hand, only relatively low levels of epidermal cell death were induced by precocious ST3 expression in the tail, contrasting what takes place during natural and T3-induced metamorphosis when ST3 expression is high. This cell type-specific apoptotic response to ST3 in the tail suggests distinct mechanisms regulating cell death in different tissues. Furthermore, our analyses of laminin receptor, an in vivo substrate of ST3 in the intestine, suggest that laminin receptor cleavage may be an underlying mechanism for the cell type-specific effects of ST3.
C1 [Mathew, Smita; Fu, Liezhen; Fiorentino, Maria; Matsuda, Hiroki; Das, Biswajit; Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, LGRD, PCRM,NIH, Rockville, MD 20852 USA.
RP Fu, LZ (reprint author), NICHD, Sect Mol Morphogenesis, LGRD, PCRM,NIH, Bldg 18T,Rm 106, Rockville, MD 20852 USA.
EM fuliez@helix.nih.gov; shi@helix.nih.gov
OI Fiorentino, Maria R/0000-0001-5318-7313
FU National Institutes of Health NICHD Intramural Research Program
FX This work was supported, in whole or in part, by the National Institutes
of Health NICHD Intramural Research Program.
NR 65
TC 14
Z9 14
U1 0
U2 1
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 3
PY 2009
VL 284
IS 27
BP 18545
EP 18556
DI 10.1074/jbc.M109.017723
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467BW
UT WOS:000267712400065
PM 19429683
ER
PT J
AU Yang, Y
Aisa, HA
Ito, Y
AF Yang, Yi
Aisa, Haji Akber
Ito, Yoichiro
TI Flat-twisted tubing: Novel column design for spiral high-speed
counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Spiral tube assembly; Flat-twisted tubing; High-speed counter-current
chromatography; Retention of the stationary phase; Resolution;
Separation of DNP-amino acid, dipeptide and protein
ID RESOLUTION
AB The original spiral tube assembly for high-speed counter-current chromatography (HSCCC) is further improved by a new tube configuration called "flat-twisted tubing" which was made by extruding the tube (1.6 mm 1.D.) through a narrow slot followed by twisting along its axis forming about I cm twisted screw pitch. This modification interrupts the laminar How of the mobile phase through the tube and continuously mixes the two phases through the column. The performance of this spiral tube assembly was tested by three types of two-phase solvent systems with different polarities each with a set of suitable test samples such as DNP-amino acids, dipeptides and proteins at the optimal elution modes. In general all these test samples yielded higher resolution with the lower mobile phase than the upper mobile phase. In the most hydrophobic two-phase solvent system composed of hexane-ethyl acetate-methanol-0.1 M hydrochloric acid (1:1:1:1, v/v/v/v), DNP-amino acids were separated with Rs-a (peak resolution based on the same Column capacity adjusted for comparison) at 4.40 and 73% of stationary phase retention at a flow rate of 0.5 ml/min with the lower mobile phase. In the polar solvent system composed of 1 butanol-acetic acid-water (4:1:5, v/v/v), dipeptide samples were resolved with Rs-a at 4.06, compared to 2.79 with the cross-pressed tube assembly at 45% stationary phase retention, each at a flow rate of 1 ml/min. Finally in the aqueous-aqueous polymer phase systems composed of polyethylene glycol 1000 - dibasic potassium phosphate each 12.5% (w/w) in water, protein samples were resolved with Rs-a at 2.53 compared to 1.10 with the cross-pressed tube assembly at 52% of stationary phase retention,each at a now rate of 1 ml/min. These results indicate that the present system substantially improves the partition efficiency with a satisfactory level of stationary phase retention by the lower mobile phase. Published by Elsevier B.V.
C1 [Yang, Yi; Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Yang, Yi; Aisa, Haji Akber] Chinese Acad Sci, Xinjiang Tech Inst Phys & Chem, Xinjiang Key Lab Plant Resources & Nat Prod Chem, Urumqi 830011, Peoples R China.
[Yang, Yi] Chinese Acad Sci, Grad Univ, Beijing 100049, Peoples R China.
RP Ito, Y (reprint author), NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 8N230, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 9
TC 23
Z9 23
U1 0
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD JUL 3
PY 2009
VL 1216
IS 27
BP 5265
EP 5271
DI 10.1016/j.chroma.2009.05.024
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 465CT
UT WOS:000267559800014
PM 19486987
ER
PT J
AU Barsh, GS
Anderson, TM
Vonholdt, BM
Candille, SI
Musiani, M
Stahler, DR
Leonard, JA
Padhukasahasram, B
Randi, E
Bustamante, CD
Ostrander, EA
Tang, H
Wayne, RK
AF Barsh, Gregory S.
Anderson, Tovi M.
Vonholdt, Bridgett M.
Candille, Sophie I.
Musiani, Marco
Stahler, Daniel R.
Leonard, Jennifer A.
Padhukasahasram, Badri
Randi, Ettore
Bustamante, Carlos D.
Ostrander, Elaine A.
Tang, Hua
Wayne, Robert K.
TI How the Gray Wolf Got Its Color Response
SO SCIENCE
LA English
DT Letter
C1 [Barsh, Gregory S.; Anderson, Tovi M.; Candille, Sophie I.; Tang, Hua] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Vonholdt, Bridgett M.; Stahler, Daniel R.; Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 91302 USA.
[Musiani, Marco] Univ Calgary, Fac Environm Design, Calgary, AB T2N 1N4, Canada.
[Leonard, Jennifer A.] Uppsala Univ, Dept Evolutionary Biol, S-75236 Uppsala, Sweden.
[Padhukasahasram, Badri; Bustamante, Carlos D.] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14853 USA.
[Randi, Ettore] INFS, I-40064 Ozzano Dell Emilia, BO, Italy.
[Ostrander, Elaine A.] NHGRI, Bethesda, MD 20892 USA.
RP Barsh, GS (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
EM gbarsh@stanford.edu
RI CSIC, EBD Donana/C-4157-2011; Leonard, Jennifer/A-7894-2010
OI CSIC, EBD Donana/0000-0003-4318-6602; Leonard,
Jennifer/0000-0003-0291-7819
NR 0
TC 0
Z9 1
U1 1
U2 20
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD JUL 3
PY 2009
VL 325
IS 5936
BP 34
EP 34
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 465NL
UT WOS:000267594000018
ER
PT J
AU Trainor, CD
Mas, C
Archambault, P
Di Lello, P
Omichinski, JG
AF Trainor, Cecelia D.
Mas, Caroline
Archambault, Patrick
Di Lello, Paola
Omichinski, James G.
TI GATA-1 associates with and inhibits p53
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA-1; DNA-BINDING DOMAIN; BETA-GLOBIN LOCUS;
ERYTHROID-DIFFERENTIATION; HEMATOPOIETIC-CELLS; MAMMALIAN-CELLS;
ZINC-FINGER; IN-VIVO; EXPRESSION; PU.1
AB In addition to orchestrating the expression of all erythroid-specific genes, GATA-1 controls the growth, differentiation, and survival of the erythroid lineage through the regulation of genes that manipulate the cell cycle and apoptosis. The stages of mammalian erythropoiesis include global gene inactivation, nuclear condensation, and enucleation to yield circulating erythrocytes, and some of the genes whose expression are altered by GATA-1 during this process are members of the p53 pathway. In this study, we demonstrate a specific in vitro interaction between the transactivation domain of p53 (p53TAD) and a segment of the GATA-1 DNA-binding domain that includes the carboxyl-terminal zinc-finger domain. We also show by immunoprecipitation that the native GATA-1 and p53 interact in erythroid cells and that activation of p53-responsive promoters in an erythroid cell line can be inhibited by the overexpression of GATA-1. Mutational analysis reveals that GATA-1 inhibition of p53 minimally requires the segment of the GATA-1 DNA-binding domain that interacts with p53TAD. This inhibition is reciprocal, as the activation of a GATA-1 responsive promoter can be inhibited by p53. Based on these findings, we conclude that inhibition of the p53 pathway by GATA-1 may be essential for erythroid cell development and survival. ( Blood. 2009; 114: 165-173)
C1 [Trainor, Cecelia D.] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Mas, Caroline; Archambault, Patrick; Di Lello, Paola; Omichinski, James G.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
RP Trainor, CD (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Rm 208, Bethesda, MD 20892 USA.
EM ceceliat@mail.nih.gov; jg.omichinski@umontreal.ca
RI di lello, paola/C-8605-2013
FU Canadian Institutes of Health Research [MOP-135604]; National Institute
of Diabetes and Digestive and Kidney Diseases; National Institutes of
Health
FX This work was supported by Canadian Institutes of Health Research Grant
MOP-135604 ( Ottawa, ON; to J. G. O.) and by National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health ( Bethesda, MD). The microcalorimeter for the ITC experiments was
purchased with funds from National Sciences and Engineering Research
Council ( Ottawa, ON).
NR 50
TC 16
Z9 20
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 2
PY 2009
VL 114
IS 1
BP 165
EP 173
DI 10.1182/blood-2008-10-180489
PG 9
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800026
PM 19411634
ER
PT J
AU Tanno, T
Porayette, P
Sripichai, O
Noh, SJ
Byrnes, C
Bhupatiraju, A
Lee, YT
Goodnough, JB
Harandi, O
Ganz, T
Paulson, RF
Miller, JL
AF Tanno, Toshihiko
Porayette, Prashanth
Sripichai, Orapan
Noh, Seung-Jae
Byrnes, Colleen
Bhupatiraju, Ajoy
Lee, Y. Terry
Goodnough, Julia B.
Harandi, Omid
Ganz, Tomas
Paulson, Robert F.
Miller, Jeffery L.
TI Identification of TWSG1 as a second novel erythroid regulator of
hepcidin expression in murine and human cells
SO BLOOD
LA English
DT Article
ID TWISTED-GASTRULATION; BETA-THALASSEMIA; IRON HOMEOSTASIS; BMP
ANTAGONIST; COOLEY-ANEMIA; MOUSE MODEL; ERYTHROPOIESIS; HEMOJUVELIN;
GENES; LIVER
AB In thalassemia and other iron loading anemias, ineffective erythropoiesis and erythroid signaling molecules are thought to cause inappropriate suppression of a small peptide produced by hepatocytes named hepcidin. Previously, it was reported that the erythrokine GDF15 is expressed at very high levels in thalassemia and suppresses hepcidin expression. In this study, erythroblast expression of a second molecule named twisted gastrulation (TWSG1) was explored as a potential erythroid regulator of hepcidin. Transcriptome analyses suggest TWSG1 is produced during the earlier stages of erythropoiesis. Hepcidin suppression assays demonstrated inhibition by TWSG1 as measured by quantitative polymerase chain reaction (PCR) in dosed assays (1-1000 ng/mL TWSG1). In human cells, TWSG1 suppressed hepcidin indirectly by inhibiting the signaling effects and associated hepcidin up-regulation by bone morphogenic proteins 2 and 4 (BMP2/BMP4). In murine hepatocytes, hepcidin expression was inhibited by murine Twsg1 in the absence of additional BMP. In vivo studies of Twsg1 expression were performed in healthy and thalassemic mice. Twsg1 expression was significantly increased in the spleen, bone marrow, and liver of the thalassemic animals. These data demonstrate that twisted gastrulation protein interferes with BMP-mediated hepcidin expression and may act with GDF15 to dysregulate iron homeostasis in thalassemia syndromes. (Blood. 2009;114:181-186)
C1 [Tanno, Toshihiko; Sripichai, Orapan; Noh, Seung-Jae; Byrnes, Colleen; Bhupatiraju, Ajoy; Lee, Y. Terry; Miller, Jeffery L.] NIDDKD, Mol Med Branch, NIDDK, NIH, Bethesda, MD 20892 USA.
[Porayette, Prashanth; Harandi, Omid; Paulson, Robert F.] Penn State Univ, Dept Vet Biomed Sci, Ctr Mol Immunol & Infect Dis, University Pk, PA 16802 USA.
[Goodnough, Julia B.; Ganz, Tomas] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Goodnough, Julia B.; Ganz, Tomas] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA.
RP Miller, JL (reprint author), NIDDKD, Mol Med Branch, NIDDK, NIH, Bldg 10,Rm 9N311,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jm7f@nih.gov
FU Intramural Research Program of the National Institutes of Health;
National Institute of Diabetes and Digestive and Kidney Diseases (
Bethesda, MD).
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases ( Bethesda, MD).
NR 24
TC 193
Z9 204
U1 1
U2 7
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 2
PY 2009
VL 114
IS 1
BP 181
EP 186
DI 10.1182/blood-2008-12-195503
PG 6
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800028
PM 19414861
ER
PT J
AU Aerbajinai, W
Zhu, JQ
Kumkhaek, C
Chin, K
Rodgers, GP
AF Aerbajinai, Wulin
Zhu, Jianqiong
Kumkhaek, Chutima
Chin, Kyung
Rodgers, Griffin P.
TI SCF induces gamma-globin gene expression by regulating downstream
transcription factor COUP-TFII
SO BLOOD
LA English
DT Article
ID STEM-CELL FACTOR; FACTOR NF-Y; FETAL-HEMOGLOBIN; PROTEIN PHOSPHATASE;
EPSILON-GLOBIN; BINDING; ERYTHROPOIESIS; KIT; DIFFERENTIATION;
ACTIVATION
AB Increased fetal hemoglobin expression in adulthood is associated with acute stress erythropoiesis. However, the mechanisms underlying gamma-globin induction during the rapid expansion of adult erythroid progenitor cells have not been fully elucidated. Here, we examined COUP-TFII as a potential repressor of gamma-globin gene after stem cell factor (SCF) stimulation in cultured human adult erythroid progenitor cells. We found that COUP-TFII expression is suppressed by SCF through phosphorylation of serine/threonine phosphatase (PP2A) and correlated well with fetal hemoglobin induction. Furthermore, down-regulation of COUP-TFII expression with small interfering RNA (siRNA) significantly increases the gamma-globin expression during the erythroid maturation. Moreover, SCF-increased expression of NF-YA associated with redox regulator Ref-1 and cellular reducing condition enhances the effect of SCF on gamma-globin expression. Activation of Erk1/2 plays a critical role in SCF modulation of downstream transcriptional factor COUP-TFII, which is involved in the regulation of gamma-globin gene induction. Our data show that SCF stimulates Erk1/2 MAPK signaling pathway, which regulates the downstream repressor COUP-TFII by inhibiting serine/threonine phosphatase 2A activity, and that decreased COUP-TFII expression resulted in gamma-globin reactivation in adult erythropoiesis. These observations provide insight into the molecular pathways that regulate gamma-globin augmentation during stress erythropoiesis. (Blood. 2009;114:187-194)
C1 [Aerbajinai, Wulin; Zhu, Jianqiong; Kumkhaek, Chutima; Chin, Kyung; Rodgers, Griffin P.] NHLBI, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Rodgers, GP (reprint author), NHLBI, Mol & Clin Hematol Branch, NIH, Bldg 10,Rm 9N-113A, Bethesda, MD 20892 USA.
EM gr5n@nih.gov
NR 38
TC 19
Z9 21
U1 1
U2 5
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 2
PY 2009
VL 114
IS 1
BP 187
EP 194
DI 10.1182/blood-2008-07-170712
PG 8
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800029
PM 19401563
ER
PT J
AU Hsieh, MM
Fitzhugh, CD
Tisdale, JF
AF Hsieh, Matthew M.
Fitzhugh, Courtney D.
Tisdale, John F.
TI Incidence of second cancers after allogeneic hematopoietic stem cell
transplantation using reduced-dose radiation
SO BLOOD
LA English
DT Letter
ID ATOMIC-BOMB SURVIVORS; SOLID CANCERS
C1 [Hsieh, Matthew M.] NIH, Bethesda, MD 20892 USA.
RP Hsieh, MM (reprint author), NIH, 9000 Rockville Pike,Bldg 10,9N 116, Bethesda, MD 20892 USA.
EM matthewhs@mail.nih.gov
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 2
PY 2009
VL 114
IS 1
BP 225
EP 225
PG 1
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800036
PM 19574484
ER
PT J
AU Rizzo, JD
Curtis, RE
Deeg, HJ
Travis, LB
AF Rizzo, J. Douglas
Curtis, Rochelle E.
Deeg, H. Joachim
Travis, Lois B.
TI Solid cancers after allogeneic hematopoietic cell transplantation
Response
SO BLOOD
LA English
DT Letter
C1 [Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
[Curtis, Rochelle E.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Travis, Lois B.] James P Wilmot Canc Ctr, Rochester, NY USA.
RP Rizzo, JD (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM rizzo@mcw.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD JUL 2
PY 2009
VL 114
IS 1
BP 225
EP 226
DI 10.1182/blood-2009-04-210187
PG 4
WC Hematology
SC Hematology
GA 468CA
UT WOS:000267789800037
ER
PT J
AU Chakrabarti, S
Panchenko, AR
AF Chakrabarti, Saikat
Panchenko, Anna R.
TI Ensemble approach to predict specificity determinants: benchmarking and
validation
SO BMC BIOINFORMATICS
LA English
DT Article
ID FUNCTIONAL SPECIFICITY; DETERMINING RESIDUES; SEQUENCE ALIGNMENTS;
PROTEIN FAMILIES; DIVERGENCE; SERVER; COMMON
AB Background: It is extremely important and challenging to identify the sites that are responsible for functional specification or diversification in protein families. In this study, a rigorous comparative benchmarking protocol was employed to provide a reliable evaluation of methods which predict the specificity determining sites. Subsequently, three best performing methods were applied to identify new potential specificity determining sites through ensemble approach and common agreement of their prediction results.
Results: It was shown that the analysis of structural characteristics of predicted specificity determining sites might provide the means to validate their prediction accuracy. For example, we found that for smaller distances it holds true that the more reliable the prediction method is, the closer predicted specificity determining sites are to each other and to the ligand.
Conclusion: We observed certain similarities of structural features between predicted and actual subsites which might point to their functional relevance. We speculate that majority of the identified potential specificity determining sites might be indirectly involved in specific interactions and could be ideal target for mutagenesis experiments.
C1 [Chakrabarti, Saikat; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Chakrabarti, S (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM chakraba@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov
FU National Library of Medicine at National Institutes of Health/Department
of Health and Human Services
FX Mikhail S. Gelfand is acknowledged for kindly providing the alignments
of IDH_ IMDH family. The authors also thank Iain M. Wallace for
providing the alignments of serine protease, nucleotidyl cyclase and
LDH_ MDH families. This work was supported by the Intramural Research
Program of the National Library of Medicine at National Institutes of
Health/Department of Health and Human Services.
NR 30
TC 19
Z9 19
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1471-2105
J9 BMC BIOINFORMATICS
JI BMC Bioinformatics
PD JUL 2
PY 2009
VL 10
AR 207
DI 10.1186/1471-2105-10-207
PG 11
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA 476NZ
UT WOS:000268450600002
PM 19573245
ER
PT J
AU Best, RB
Hummer, G
AF Best, Robert B.
Hummer, Gerhard
TI Optimized Molecular Dynamics Force Fields Applied to the Helix-Coil
Transition of Polypeptides
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID ALANINE-BASED PEPTIDES; QUANTUM-MECHANICAL CALCULATIONS; VARYING CHAIN
LENGTHS; FOLDING SPEED LIMIT; ALPHA-HELIX; DIPOLAR COUPLINGS; BIOLOGICAL
MOLECULES; POTENTIAL FUNCTIONS; CIRCULAR-DICHROISM; SPIN RELAXATION
AB Obtaining the correct balance of secondary structure propensities is a central priority in protein force-field development. Given that current force fields differ significantly in their alpha-helical propensities, a correction to match experimental results would be highly desirable. We have determined simple backbone energy corrections for two force fields to reproduce the fraction of helix measured in short peptides at 300 K. As validation, we show that the optimized force fields produce results in excellent agreement with nuclear magnetic resonance experiments for folded proteins and short peptides not used in the optimization. However. despite the agreement at ambient conditions, the dependence of the helix content on temperature is too weak, a problem shared with other force fields. A fit of the Lifson-Roig helix-coil theory shows that both the enthalpy and entropy of helix formation are too small: the helix extension parameter w agrees well with experiment, but its entropic and enthalpic components are both only about half the respective experimental estimates. Our structural and thermodynamic analyses point toward the physical origins of these shortcomings in current force fields, and suggest ways to address them in future force-field development.
C1 [Best, Robert B.] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Hummer, Gerhard] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM rbb24@cam.ac.uk
RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016
OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543
FU Royal Society University Research Fellowship; National Institute of
Diabetes and Digestive and Kidney Diseases, National Institutes of
Health
FX We would like to thank Alex MacKerell for sharing with us the
LMP2/cc-pVQZ-//MP2/6-31g* energy surface for alanine dipeptide. R.B.B.
is supported by a Royal Society University Research Fellowship, This
work was supported in part by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, and made use of the biowulf cluster at
NIH, the Cambridge HPC facility (Darwin), and local clusters in the
Cambridge Chemistry department. We would like to thank Jeetain Mittal
and Nick Fawzi for helpful comments on the manuscript.
NR 85
TC 312
Z9 313
U1 11
U2 79
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1520-6106
J9 J PHYS CHEM B
JI J. Phys. Chem. B
PD JUL 2
PY 2009
VL 113
IS 26
BP 9004
EP 9015
DI 10.1021/jp901540t
PG 12
WC Chemistry, Physical
SC Chemistry
GA 462VF
UT WOS:000267384400026
PM 19514729
ER
PT J
AU Park, JI
Venteicher, AS
Hong, JY
Choi, J
Jun, S
Shkreli, M
Chang, W
Meng, ZJ
Cheung, P
Ji, H
McLaughlin, M
Veenstra, TD
Nusse, R
McCrea, PD
Artandi, SE
AF Park, Jae-Il
Venteicher, Andrew S.
Hong, Ji Yeon
Choi, Jinkuk
Jun, Sohee
Shkreli, Marina
Chang, Woody
Meng, Zhaojing
Cheung, Peggie
Ji, Hong
McLaughlin, Margaret
Veenstra, Timothy D.
Nusse, Roel
McCrea, Pierre D.
Artandi, Steven E.
TI Telomerase modulates Wnt signalling by association with target gene
chromatin
SO NATURE
LA English
DT Article
ID BETA-CATENIN; REVERSE-TRANSCRIPTASE; ANTEROPOSTERIOR AXIS; TRANSIENT
ACTIVATION; CELL-PROLIFERATION; XENOPUS EMBRYOS; STEM-CELLS; IN-VIVO;
MICE; MOUSE
AB Stem cells are controlled, in part, by genetic pathways frequently dysregulated during human tumorigenesis. Either stimulation of Wnt/beta-catenin signalling or overexpression of telomerase is sufficient to activate quiescent epidermal stem cells in vivo, although the mechanisms by which telomerase exerts these effects are not understood. Here we show that telomerase directly modulates Wnt/beta-catenin signalling by serving as a cofactor in a beta-catenin transcriptional complex. The telomerase protein component TERT (telomerase reverse transcriptase) interacts with BRG1 (also called SMARCA4), a SWI/SNF-related chromatin remodelling protein, and activates Wnt-dependent reporters in cultured cells and in vivo. TERT serves an essential role in formation of the anterior-posterior axis in Xenopus laevis embryos, and this defect in Wnt signalling manifests as homeotic transformations in the vertebrae of Tert(-/-) mice. Chromatin immunoprecipitation of the endogenous TERT protein from mouse gastrointestinal tract shows that TERT physically occupies gene promoters of Wnt-dependent genes. These data reveal an unanticipated role for telomerase as a transcriptional modulator of the Wnt/beta-catenin signalling pathway.
C1 [Park, Jae-Il; Venteicher, Andrew S.; Choi, Jinkuk; Jun, Sohee; Shkreli, Marina; Chang, Woody; Cheung, Peggie; Artandi, Steven E.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Venteicher, Andrew S.; Artandi, Steven E.] Stanford Univ, Sch Med, Biophys Program, Stanford, CA 94305 USA.
[Choi, Jinkuk; Artandi, Steven E.] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA.
[Hong, Ji Yeon; Ji, Hong; McCrea, Pierre D.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Meng, Zhaojing; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[McLaughlin, Margaret] MIT, Koch Inst Integrat Canc Biol, Cambridge, MA 02139 USA.
[McLaughlin, Margaret] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Nusse, Roel] Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Dev Biol, Stanford, CA 94305 USA.
RP Artandi, SE (reprint author), Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
EM sartandi@stanford.edu
OI PARK, JAE-IL/0000-0002-0737-2654
FU Stanford Comprehensive Cancer Center Fellowship; NCI [CA111691,
CA125453]; California Breast Cancer Research Program
FX We thank P. Chu of the Stanford Comparative Medicine Histology Research
Core Laboratory for technical assistance. Wethank F. Ishikawa for
Xenopus TERT plasmid, G. Crabtree for antibodies and plasmids, T. Jacks
for ROSACreER T2 mice, and K. Park for constructive comments. J.-I. P.
was supported by a Stanford Comprehensive Cancer Center Fellowship. This
work was supported by NCI grants CA111691 and CA125453 and by a grant
from the California Breast Cancer Research Program to S. E. A.
NR 50
TC 297
Z9 312
U1 1
U2 36
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD JUL 2
PY 2009
VL 460
IS 7251
BP 66
EP U77
DI 10.1038/nature08137
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 464XW
UT WOS:000267545200030
PM 19571879
ER
PT J
AU Biancotto, A
Grivel, JC
Lisco, A
Vanpouille, C
Markham, PD
Gallo, RC
Margolis, LB
Lusso, P
AF Biancotto, Angelique
Grivel, Jean-Charles
Lisco, Andrea
Vanpouille, Christophe
Markham, Phillip D.
Gallo, Robert C.
Margolis, Leonid B.
Lusso, Paolo
TI Evolution of SIV toward RANTES resistance in macaques rapidly
progressing to AIDS upon coinfection with HHV-6A
SO RETROVIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE; HUMAN-HERPESVIRUS
6; SMALL-MOLECULE; PRIMARY INFECTION; LYMPHOCYTES-T; HIV; TYPE-1;
HUMAN-HERPESVIRUS-6; CELLS
AB Background: Progression to AIDS is often associated with the evolution of HIV-1 toward increased virulence and/or pathogenicity. Evidence suggests that a virulence factor for HIV-1 is resistance to CCR5-binding chemokines, most notably RANTES, which are believed to play a role in HIV-1 control in vivo. HIV-1 can achieve RANTES resistance either by phenotypic switching from an exclusive CCR5 usage to an expanded coreceptor specificity, or by the acquisition of alternative modalities of CCR5 usage. An infectious agent that might promote the evolution of HIV-1 toward RANTES resistance is human herpesvirus 6A (HHV-6A), which is frequently reactivated in HIV-1-infected patients and is a potent RANTES inducer in lymphoid tissue.
Results: SIV isolates obtained from pig-tailed macaques (M. nemestrina) after approximately one year of single infection with SIV(smE660) or dual infection with SIV(smE660) and HHV-6A(GS) were characterized for their growth capacity and sensitivity to HHV6A- and RANTES-mediated inhibition in human or macaque lymphoid tissues ex vivo. Four out of 4 HHV-6A-coinfected macaques, all of which progressed to full-blown AIDS within 2 years of infection, were found to harbor SIV variants with a reduced sensitivity to both HHV-6A and RANTES, despite maintaining an exclusive CCR5 coreceptor specificity; viruses derived from two of these animals replicated even more vigorously in the presence of exogenous HHV-6A or RANTES. The SIV variants that emerged in HHV-6A-coinfected macaques showed an overall reduced ex vivo replication capacity that was partially reversed upon addition of exogenous RANTES, associated with suppressed IL-2 and enhanced IFN-gamma production. In contrast, SIV isolates obtained from two singly-infected macaques, none of which progressed to AIDS, maintained HHV-6A/RANTES sensitivity, whereas the only AIDS progressor among singly-infected macaques developed an SIV variant with partial HHV-6A/RANTES resistance and increased replication capacity, associated with expanded coreceptor usage.
Conclusion: These results provide in vivo evidence of SIV evolution toward RANTES resistance in macaques rapidly progressing to AIDS. RANTES resistance may represent a common virulence factor allowing primate immunodeficiency retroviruses to evade a critical mechanism of host antiviral defense.
C1 [Biancotto, Angelique; Grivel, Jean-Charles; Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid B.] NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA.
[Biancotto, Angelique] NHLBI, Ctr Human Immunol, Hematol Branch, Bethesda, MD 20892 USA.
[Markham, Phillip D.] Adv Biosci Labs, Kensington, MD 20895 USA.
[Gallo, Robert C.] Univ Maryland, Inst Human Virol, Inst Biotechnol, Baltimore, MD 21202 USA.
[Lusso, Paolo] Ist Sci San Raffaele, DIBIT, Unit Human Virol, I-20132 Milan, Italy.
[Lusso, Paolo] Univ Cagliari, Sch Med, Dept Med Sci, I-09149 Cagliari, Italy.
[Lusso, Paolo] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Margolis, LB (reprint author), NICHHD, Lab Mol & Cellular Biophys, Bethesda, MD 20892 USA.
EM biancoa@nhlbi.nih.gov; grivelj@cc1.nichd.nih.gov; liscoa@mail.nih.gov;
vanpouic@mail.nih.gov; Phillip.MARKHAM@ablinc.com;
snallo@ihv.umaryland.edu; margolil@mail.nih.gov; plusso@niaid.nih.gov
FU NIH; NICHD; EU [BMH4CT961301]; ISS Italian AIDS Program [40B.57, 50C.
17, 50D.17, 50F.23]
FX We are grateful to Dr. M. Santi and the entire staff of the Department
of Anatomic Pathology of Children's National Medical Center in
Washington, DC, for their generous assistance in obtaining human tonsil
tissues. This research was supported in part by the Intramural Research
Program of the NICHD, NIH, Bethesda, MD, the EU Biomed-2 Programme,
Brussels (grant no. BMH4CT961301 to P. L.), and the ISS Italian AIDS
Program, Rome (grants no. 40B.57, 50C. 17, 50D.17 and 50F.23 to P. L.).
NR 34
TC 6
Z9 6
U1 0
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T
4LB, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD JUL 2
PY 2009
VL 6
AR 61
DI 10.1186/1742-4690-6-61
PG 11
WC Virology
SC Virology
GA 475ZN
UT WOS:000268406600001
PM 19573243
ER
PT J
AU Bryant, NA
Rash, AS
Russell, CA
Ross, J
Cooke, A
Bowman, S
MacRae, S
Lewis, NS
Paillot, R
Zanoni, R
Meier, H
Griffiths, LA
Daly, JM
Tiwari, A
Chambers, TM
Newton, JR
Elton, DM
AF Bryant, Neil A.
Rash, Adam S.
Russell, Colin A.
Ross, Julie
Cooke, Annie
Bowman, Samantha
MacRae, Shona
Lewis, Nicola S.
Paillot, Romain
Zanoni, Reto
Meier, Hanspeter
Griffiths, Lowri A.
Daly, Janet M.
Tiwari, Ashish
Chambers, Thomas M.
Newton, J. Richard
Elton, Debra M.
TI Antigenic and genetic variations in European and North American equine
influenza virus strains (H3N8) isolated from 2006 to 2007
SO VETERINARY MICROBIOLOGY
LA English
DT Article
DE Equine influenza virus; H3N8; Surveillance; Vaccine strain selection
ID A VIRUSES; NS1 PROTEIN; RESPIRATORY-DISEASE; UNITED-KINGDOM; EVOLUTION;
HEMAGGLUTININ; VACCINE; HORSES; PROTECTION; NEWMARKET
AB Equine influenza virus (EIV) surveillance is important in the management of equine influenza. It provides data on circulating and newly emerging strains for vaccine strain selection. To this end, antigenic characterisation by haemaggluttination inhibition (HI) assay and phylogenetic analysis was carried out on 28 EIV strains isolated in North America and Europe during 2006 and 2007. In the UK, 20 viruses were isolated from 28 nasopharyngeal swabs that tested positive by enzyme-linked immunosorbent assay. All except two of the UK viruses were characterised as members of the Florida sublineage with similarity to A/eq/Newmarket/5/03 (clade 2). One isolate, A/eq/Cheshire/1/06, was characterised as an American lineage strain similar to viruses isolated up to 10 years earlier. A second isolate, A/eq/Lincolnshire/1/07 was characterised as a member of the Florida sublineage (clade 1) with similarity to A/eq/Wisconsin/03. Furthermore. A/eq/Lincolnshire/1/06 was a member of the Florida sublineage (clade 2) by haemagglutinin (HA) gene sequence, but appeared to be a member of the Eurasian lineage by the non-structural gene (NS) sequence suggesting that reassortment had occurred. A/eq/Switzerland/P112/07 was characterised as a member of the Eurasian lineage, the first time since 2005 that isolation of a virus from this lineage has been reported. Seven viruses from North America were classified as members of the Florida sublineage (clade 1), similar to A/eq/Wisconsin/03. In conclusion, a variety of antigenically distinct EIVs continue to circulate worldwide. Florida sublineage clade 1 viruses appear to predominate in North America, clade 2 viruses in Europe. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Bryant, Neil A.; Rash, Adam S.; Ross, Julie; Cooke, Annie; Bowman, Samantha; MacRae, Shona; Paillot, Romain; Griffiths, Lowri A.; Daly, Janet M.; Newton, J. Richard; Elton, Debra M.] Anim Hlth Trust, Ctr Prevent Med, Newmarket CB8 7UU, Suffolk, England.
[Russell, Colin A.; Lewis, Nicola S.] Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England.
[Zanoni, Reto] Univ Bern, Inst Vet Virol, CH-3012 Bern, Switzerland.
[Meier, Hanspeter] Univ Bern, Equine Clin, Dept Clin Vet Med, Vetsuisse Fac, CH-3012 Bern, Switzerland.
[Tiwari, Ashish; Chambers, Thomas M.] Univ Kentucky, Gluck Equine Res Ctr, Dept Vet Sci, Lexington, KY 40546 USA.
[Russell, Colin A.; Lewis, Nicola S.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Bryant, NA (reprint author), Anim Hlth Trust, Ctr Prevent Med, Lanwades Pk, Newmarket CB8 7UU, Suffolk, England.
EM neil.bryant@aht.org.uk
RI Daly, Janet/G-9797-2011; Cooke, Anne/E-8709-2012;
OI Rash, Adam/0000-0002-2627-4873; Russell, Colin/0000-0002-2113-162X;
Daly, Janet/0000-0002-1912-4500
FU Horserace Betting Levy Board (HBLB); Animal Health Trust; Clare College;
University of Cambridge; NIH [DP1-OD000490-01]; Cambridge Infectious
Diseases Consortium as part of the DEFRA Veterinary Training and
Research Initiative
FX We would like to thank Toni-Ann Hammond for excellent technical support
for EIV diagnostics, Schering Plough Animal Health and Intervet for
subsidising the EIV surveillance programme and Prof. Alan Guthrie
(University of Pretoria, SA) for providing us with
A/eq/South-Africa/4/03. Study was supported by the Horserace Betting
Levy Board (HBLB) and the Animal Health Trust. C.A.R. was supported by a
research fellowship from Clare College, University of Cambridge and by
the NIH Director's Pioneer Award program, part of the NIH roadmap to
medical research, through grant number DP1-OD000490-01. N.S.L. was
supported by the Cambridge Infectious Diseases Consortium as part of the
DEFRA Veterinary Training and Research Initiative.
NR 47
TC 83
Z9 87
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1135
J9 VET MICROBIOL
JI Vet. Microbiol.
PD JUL 2
PY 2009
VL 138
IS 1-2
BP 41
EP 52
DI 10.1016/j.vetmic.2009.03.004
PG 12
WC Microbiology; Veterinary Sciences
SC Microbiology; Veterinary Sciences
GA 467XY
UT WOS:000267778100006
PM 19346084
ER
PT J
AU Summers, R
AF Summers, Ronald
TI The Elephant in the Room: Bowel Preparation for CT Colonography
SO ACADEMIC RADIOLOGY
LA English
DT Editorial Material
ID VIRTUAL COLONOSCOPY; CATHARTIC PREPARATION; PATIENT ACCEPTANCE;
COLORECTAL POLYPS; CLEANSING METHOD; COLONIC POLYPS; FEASIBILITY;
PREFERENCES; REGIMENS; FLUID
C1 NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
RP Summers, R (reprint author), NIH, Radiol & Imaging Sci Dept, Ctr Clin, Bldg 10,Room 1C368X MSC 1182, Bethesda, MD 20892 USA.
EM rms@nih.gov
FU Intramural NIH HHS [Z01 CL040003-05]
NR 28
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
J9 ACAD RADIOL
JI Acad. Radiol.
PD JUL
PY 2009
VL 16
IS 7
BP 777
EP 779
DI 10.1016/j.acra.2009.04.001
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 462WN
UT WOS:000267388900001
PM 19505655
ER
PT J
AU Ogawa, M
Kosaka, N
Choyke, PL
Kobayashi, H
AF Ogawa, Mikako
Kosaka, Nobuyuki
Choyke, Peter L.
Kobayashi, Hisataka
TI H-Type Dimer Formation of Fluorophores: A Mechanism for Activatable, in
Vivo Optical Molecular Imaging
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID XANTHENE DYES; FLUORESCENCE PROBES; CANCER METASTASES; BODIPY; CONJUGATE
AB In vivo molecular imaging with target-specific activatable "smart" probes, which yield fluorescence only at the intended target, enables sensitive and specific cancer detection. Dimerization and fluorescence quenching has been shown to occur in concentrated aqueous solutions of various fluorophores. Here, we hypothesized that fluorophore dimerization and quenching after conjugation to targeting proteins can occur at low concentration. This dimerization can be exploited as a mechanism for fluorescence activation. Rhodamine derivatives were conjugated to avidin and trastuzumab, which target D-galactose receptor and HER2/neu antigen, respectively. After conjugation, a large proportion of R6G and TAMRA formed H-type dinners, even at low concentrations, but could be fully dequenched upon dissociation of the dinners to monomers. To demonstrate the fluorescence activation effect during in vivo fluorescence endoscopic molecular imaging, a highly quenched probe, avidin-TAMRA, or a minimally quenched probe, avidin-Alexa488, was administered into mice with ovarian metastases to the peritoneum. The tumors were clearly visualized with avidin-TAMRA, with low background fluorescence; in contrast, the background fluorescence was high for avidin-Alexa488. Thus, H-dimer formation as a mechanism of fluorescence quenching could be used to develop fluorescence activatable probes for in vivo molecular imaging.
C1 [Ogawa, Mikako; Kosaka, Nobuyuki; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
FU National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research. We thank Prof. Yasuteru Urano, the University of Tokyo,
for his kind suggestion and calculation of HOMO values. We also thank to
Drs. Masatoshi Takahashi, Brian J. Field, and Masayuki Nishimura in the
Shimadzu Scientific Instruments, Inc., Columbia, MD for their great
assistance for performing the various mass spectroscopy analyses of the
Av-TAMRA conjugate.
NR 26
TC 87
Z9 87
U1 2
U2 36
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD JUL
PY 2009
VL 4
IS 7
BP 535
EP 546
DI 10.1021/cb900089j
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 473TS
UT WOS:000268233000006
PM 19480464
ER
PT J
AU Magracheva, E
Kozlov, S
Stewart, CL
Wlodawer, A
Zdanov, A
AF Magracheva, Eugenia
Kozlov, Serguei
Stewart, Colin L.
Wlodawer, Alexander
Zdanov, Alexander
TI Structure of the lamin A/C R482W mutant responsible for dominant
familial partial lipodystrophy (FPLD)
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION
COMMUNICATIONS
LA English
DT Article
ID C-TERMINAL DOMAIN; NUCLEAR LAMIN; MUTATIONS; SOFTWARE; COMMON
AB Proteins of the A-type lamin family, which consists of two members, lamin A and lamin C, are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A-type lamins have recently become the focus of extensive functional studies as a consequence of the linking of at least eight congenital diseases to mutations in the lamin A/C gene (LMNA). This spectrum of pathologies, which mostly manifest themselves as dominant traits, includes muscle dystrophies, dilated cardiomyopathies, the premature aging syndrome Hutchinson-Guilford progeria and familial partial lipodystrophy (FPLD). The crystal structure of the lamin A/C mutant R482W, a variant that causes FPLD, has been determined at 1.5 angstrom resolution. A completely novel aggregation state of the C-terminal globular domain and the position of the mutated amino-acid residue suggest means by which the mutation may affect lamin A/C-protein and protein-DNA interactions.
C1 [Magracheva, Eugenia; Zdanov, Alexander] NCI, Basic Res Program SAIC Frederick, Frederick, MD 21702 USA.
[Kozlov, Serguei; Stewart, Colin L.] NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA.
[Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA.
RP Zdanov, A (reprint author), NCI, Basic Res Program SAIC Frederick, Frederick, MD 21702 USA.
EM zdanov@ncifcrf.gov
FU NIH; National Cancer Institute, [NO1-CO-12400]
FX project was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research and with Federal
funds from the National Cancer Institute, NIH under Contract No.
NO1-CO-12400. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the US Government.
NR 14
TC 11
Z9 11
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1744-3091
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun.
PD JUL
PY 2009
VL 65
BP 665
EP 670
DI 10.1107/S1744309109020302
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA 464TM
UT WOS:000267530000003
PM 19574635
ER
PT J
AU Wu, FB
Yao, PJ
AF Wu, Fangbai
Yao, Pamela J.
TI Clathrin-mediated endocytosis and Alzheimer's disease: An update
SO AGEING RESEARCH REVIEWS
LA English
DT Review
DE Alzheimer's disease; Endocytosis; Clathrin; APP processing
ID AMYLOID PRECURSOR PROTEIN; COATED VESICLES; SYNAPTIC VESICLE; IN-VIVO;
ASSEMBLY PROTEIN; NUMB; CELL; PATHOGENESIS; TRAFFICKING; EXPRESSION
AB Thanks to new evidence we are now a step closer to understanding how neurons produce amyloid-beta peptide (A beta)-the chief culprit of Alzheimer's disease. As importance of clathrin-mediated endocytosis to normal neurons has become clearer, so has its role in pathology of neurological disorders. Here we update recent evidence that endocytosis plays a central role in the production of A beta in neurons. Published by Elsevier Ireland Ltd.
C1 [Wu, Fangbai; Yao, Pamela J.] NIA, Neurosci Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM yaopa@grc.nia.nih.gov
FU NIH/NIA
FX This research was supported by the Intramural Research Program of the
NIH/NIA.
NR 30
TC 33
Z9 36
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1568-1637
J9 AGEING RES REV
JI Ageing Res. Rev.
PD JUL
PY 2009
VL 8
IS 3
BP 147
EP 149
DI 10.1016/j.arr.2009.03.002
PG 3
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA 467DY
UT WOS:000267718800001
PM 19491039
ER
PT J
AU Purushotham, A
Schug, TT
Li, XL
AF Purushotham, Aparna
Schug, Thaddeus T.
Li, Xiaoling
TI SIRT1 performs a balancing act on the tight-rope toward longevity
SO AGING-US
LA English
DT Article
DE SIRT1; PPAR alpha; hepatic fatty acid oxidation; PGC-1 alpha;
gluconeogenesis
ID METABOLIC SYNDROME; HEPATIC STEATOSIS; ADIPOSE-TISSUE; OBESITY; DIET;
PGC-1-ALPHA; HOMEOSTASIS; GLUCOSE; PROTEIN; HEALTH
AB Our recent study defined a new role for SIRT1 as a regulator of hepatic lipid metabolism. In the liver a major target of this sirtuin is the PPAR alpha/PGC-1 alpha signaling axis. Ablation of SIRT1 in the liver results in disrupted fatty acid oxidation, increased cellular stress, and elevations in proinflammatory cytokines. However, contrary to previous studies, we observed no changes in glucose production in the absence of SIRT1, despite impaired PGC-1 alpha signaling. These findings point toward the involvement of other players in SIRT1-regulated hepatic metabolism. Here we discuss our findings, and comment on some of the controversy surrounding this protein in the current literature.
C1 [Purushotham, Aparna; Schug, Thaddeus T.; Li, Xiaoling] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Li, XL (reprint author), NIEHS, Lab Signal Transduct, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM lix3@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences [Z01 ES102205]
FX We thank Drs. Sailesh Surapureddi and Anton Jetten for critical reading
of the manuscript; Dr. Frederic Alt at Harvard Medical School for
providing the SIRT1 exon 4 floxed allele; and NIEHS Multimedia Services
Department for the cartoon graph of Figure 2. This work was supported by
the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences to X.L. (Z01 ES102205).
NR 24
TC 11
Z9 11
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUL
PY 2009
VL 1
IS 7
BP 669
EP 673
PG 5
WC Cell Biology
SC Cell Biology
GA 579UQ
UT WOS:000276401400008
PM 20157548
ER
PT J
AU Venuti, P
de Falco, S
Esposito, G
Bornstein, MH
AF Venuti, P.
de Falco, S.
Esposito, G.
Bornstein, Marc H.
TI Mother-Child Play: Children With Down Syndrome and Typical Development
SO AJIDD-AMERICAN JOURNAL ON INTELLECTUAL AND DEVELOPMENTAL DISABILITIES
LA English
DT Article
ID SYMBOLIC PLAY; YOUNG-CHILDREN; EMOTIONAL AVAILABILITY; PRETENSE PLAY;
LANGUAGE; TODDLERS; PATTERNS; EXPLORATION; ATTENTION; BEHAVIOR
AB Child solitary and collaborative mother-child play with 21 children with Down syndrome and 33 mental-age-matched typically developing children were compared. In solitary play, children with Down syndrome showed less exploratory but similar symbolic play compared to typically developing children. From solitary to collaborative play, children with Down syndrome increased their exploratory play, attaining the same level as typically developing children. Pretense significantly increased from solitary to collaborative play only in typically developing children. Differences between mothers' play in the two groups mirrored those between their children. Both groups showed similar attunement and synchrony. Mothers contribute to the play development of children with Down syndrome through their own adaptation to their children's limitations and potentialities.
C1 [Venuti, P.; de Falco, S.; Esposito, G.] Univ Trent, Trento, Italy.
[Bornstein, Marc H.] NICHHD, Bethesda, MD USA.
RP de Falco, S (reprint author), Univ Trent, Dept Cognit Sci & Educ, Via Matteo Del Ben 5, I-38068 Rovereto, TN, Italy.
EM simona.defalco@unitn.it
RI Esposito, Gianluca/B-1374-2012
OI Esposito, Gianluca/0000-0002-9442-0254
FU Intramural NIH HHS [Z99 HD999999]
NR 56
TC 15
Z9 15
U1 3
U2 14
PU AMER ASSOC INTELLECTUAL DEVELOPMENTAL DISABILITIES
PI WASHINGTON
PA 444 N CAPITOL ST, NW STE 846, WASHINGTON, DC 20001-1512 USA
SN 1944-7515
J9 AJIDD-AM J INTELLECT
JI AJIDD-Am. J. Intellect. Dev. Disabil.
PD JUL
PY 2009
VL 114
IS 4
BP 274
EP 288
DI 10.1352/1944-7558-114.4:274-288
PG 15
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 469SQ
UT WOS:000267921200005
PM 19642713
ER
PT J
AU DeStefano, AL
Seshadri, S
Beiser, A
Atwood, LD
Massaro, JM
Au, R
Wolf, PA
DeCarli, C
AF DeStefano, Anita L.
Seshadri, Sudha
Beiser, Alexa
Atwood, Larry D.
Massaro, Joe M.
Au, Rhoda
Wolf, Philip A.
DeCarli, Charles
TI Bivariate Heritability of Total and Regional Brain Volumes The
Framingham Study
SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS
LA English
DT Article
DE heritability; quantitative MRI; brain volume; white matter
hyperintensity
ID WHITE-MATTER HYPERINTENSITY; STROKE RISK PROFILE; TRAIT LINKAGE
ANALYSIS; COGNITIVE PERFORMANCE; GENETIC INFLUENCES; HEART-DISEASE; MALE
TWINS; MRI; MORPHOLOGY; SCHIZOPHRENIA
AB Heritability and genetic and environmental correlations of total and regional brain volumes were estimated from a large, generally healthy, community-based sample, to determine if there are common elements to the genetic influence of brain volumes and white matter hyperintensity (WMH) volume. There were 1538 Framingham Heart Study participants with brain volume measures from quantitative magnetic resonance imaging who were free of stroke and other neurologic disorders that might influence brain volumes and who were members of families with at least 2 Framingham Heart Study participants. Heritability was estimated using variance component methodology and adjusting for the components of the Framingham stroke risk profile. Genetic and environmental correlations between traits were obtained from bivariate analysis. Heritability estimates ranging from 0.46 to 0.60 were observed for total brain, WMH, hippocampal, temporal lobe, and lateral ventricular volumes. Moderate, yet significant, heritability was observed for the other measures. Bivariate analyses demonstrated that relationships between brain volume measures, except for WMH, reflected both moderate to strong shared genetic and shared environmental influences. This study confirms strong genetic effects on brain and WMH volumes. These data extend current knowledge by showing that these 2 different types of magnetic resonance imaging measures do not share underlying genetic or environmental influences.
C1 [DeStefano, Anita L.; Beiser, Alexa; Atwood, Larry D.; Massaro, Joe M.] Boston Univ Publ Hlth, Dept Biostat, Boston, MA USA.
[DeStefano, Anita L.; Seshadri, Sudha; Beiser, Alexa; Atwood, Larry D.; Au, Rhoda; Wolf, Philip A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Massaro, Joe M.] Boston Univ, Dept Math & Stat, Boston, MA 02118 USA.
[Seshadri, Sudha; Atwood, Larry D.; Massaro, Joe M.; Au, Rhoda; Wolf, Philip A.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA.
RP DeStefano, AL (reprint author), Boston Univ, Dept Biostat, Sch Publ Hlth, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM adestef@bu.edu
FU National Heart, Lung, and Blood Institute's Framingham Heart Study;
National Institutes of Health [N01-HC-25195]; NIA [5RO1-AG16495,
5RO1-AG08122]; NINDS [5R01-NS17950]; Boston University Alzheimer's
Disease Center [P30 AG13846]
FX Supported by the National Heart, Lung, and Blood Institute's Framingham
Heart Study; National Institutes of Health (NIH/NHLBI contract
N01-HC-25195) and grants NIA no. 5RO1-AG16495, NIA no. 5RO1-AG08122. and
NINDS no. 5R01-NS17950; and Boston University Alzheimer's Disease Center
P30 AG13846.
NR 35
TC 13
Z9 13
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0893-0341
J9 ALZ DIS ASSOC DIS
JI Alzheimer Dis. Assoc. Dis.
PD JUL-SEP
PY 2009
VL 23
IS 3
BP 218
EP 223
PG 6
WC Clinical Neurology; Pathology
SC Neurosciences & Neurology; Pathology
GA 495QO
UT WOS:000269909300007
PM 19812462
ER
PT J
AU Willenbring, ML
Massey, SH
Gardner, MB
AF Willenbring, Mark L.
Massey, Suena H.
Gardner, Maureen B.
TI Helping Patients Who Drink Too Much: An Evidence-Based Guide for Primary
Care Physicians
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID INTEGRATED OUTPATIENT TREATMENT; NATIONAL EPIDEMIOLOGIC SURVEY;
RANDOMIZED CONTROLLED-TRIAL; ILL ALCOHOLIC MEN; UNITED-STATES;
DEPENDENCE; RECOVERY; INTERVENTIONS; METAANALYSIS; DEPRESSION
AB Excessive alcohol consumption is a leading cause of preventable morbidity and mortality, but few heavy drinkers receive treatment. Primary care physicians are in a position to address heavy drinking and alcohol use disorders with patients, and can do so quickly and effectively. The National Institute on Alcohol Abuse and Alcoholism has published a guide for physicians that offers an evidence-based approach to screening, assessing, and treating alcohol use disorders in general health care settings. Screening can be performed by asking patients how many heavy drinking days they have per week. Assessing patients' willingness to change their drinking behaviors can guide treatment. Treatment recommendations should be presented in a clear, nonjudgmental way. Patients who are not alcohol-dependent may opt to reduce drinking to lower risk levels. Patients with alcohol dependence should receive pharmacotherapy and brief behavioral support, as well as disease management for chronic relapsing dependence. All patients with alcohol dependence should be encouraged to participate in community support groups. (Am Fam Physician. 2009; 80 (1):44-50. Copyright (C) 2009 American Academy of Family Physicians.)
C1 [Willenbring, Mark L.] NIAAA, Div Treatment & Recovery Res, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Willenbring, Mark L.; Massey, Suena H.] George Washington Univ, Sch Med, Washington, DC USA.
RP Willenbring, ML (reprint author), NIAAA, Div Treatment & Recovery Res, NIH, US Dept Hlth & Human Serv, 5635 Fishers Ln,Room 2047, Bethesda, MD 20892 USA.
EM mlw@niaaa.nih.gov
NR 27
TC 50
Z9 50
U1 1
U2 3
PU AMER ACAD FAMILY PHYSICIANS
PI KANSAS CITY
PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA
SN 0002-838X
J9 AM FAM PHYSICIAN
JI Am. Fam. Physician
PD JUL 1
PY 2009
VL 80
IS 1
BP 44
EP 50
PG 7
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 467WJ
UT WOS:000267773500006
PM 19621845
ER
PT J
AU Grorodeski, EZ
Ishwaran, H
Blackstone, EH
Lauer, MS
AF Grorodeski, Eiran Z.
Ishwaran, Hemant
Blackstone, Eugene H.
Lauer, Michael S.
TI Quantitative electrocardiographic measures and long-term mortality in
exercise test patients with clinically normal resting electrocardiograms
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CORONARY-HEART-DISEASE; LEFT-VENTRICULAR HYPERTROPHY; T-WAVE
ABNORMALITIES; CARDIOVASCULAR MORTALITY; ALL-CAUSE; HYPERTENSIVE
PATIENTS; PREDICT MORTALITY; RISK PREDICTION; ARTERY-DISEASE; RATE
RECOVERY
AB Background Currently, the only function of the resting electrocardiogram (ECG) in patients referred for exercise testing is to determine whether imaging is mandated. It is unknown if subtle ECG findings in those patients with clinically normal resting ECGs have prognostic significance.
Methods We performed a single-center cohort study of 18,964 patients without known cardiovascular disease who had a clinically normal resting ECG and who underwent treadmill exercise testing for evaluation of suspected coronary artery disease. Eleven quantitative ECG measures relating to heart rate, conduction, left ventricular mass, or repolarization were collected digitally. The primary outcome was all-cause mortality. The prognostic importance of a composite ECG score was assessed by measuring its impact on the c-index (analogous to area under receiver operating characteristic curve) and by measures of reclassification.
Results During a median follow-up of 10.7 years, 1,585 patients died. The 4 most predictive digital ECG variables were higher ventricular rate, more leftward QRS axis, more downward ST-segment deviation, and longer QT interval. The ECG score was independently associated with mortality (75th vs 25th percentile hazard ratio 1.36, 95% confidence interval 1.25-1.49, P < .0001). The ECG score had modest impact on discrimination (change in c-index 0.04) and reclassification of risk (3.0% decrease of relative integrated discrimination improvement, P < .001).
Conclusions Subtle ECG findings relating to heart rate, conduction, left ventricular mass, or repolarization in patients with clinically normal ECGs referred for exercise testing may provide modest additional prognostic information over and above clinical and exercise measures. (Am Heart J 2009; 158:61-70.)
C1 [Lauer, Michael S.] NHLBI, Div Prevent & Populat Sci, Rockledge Ctr 2, Bethesda, MD 20892 USA.
[Ishwaran, Hemant] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Grorodeski, Eiran Z.; Blackstone, Eugene H.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA.
RP Lauer, MS (reprint author), NHLBI, Div Prevent & Populat Sci, Rockledge Ctr 2, 6701 Rockledge Dr,Room 10122, Bethesda, MD 20892 USA.
EM lauerm@nhibi.nih.gov
RI Lauer, Michael/L-9656-2013;
OI Lauer, Michael/0000-0002-9217-8177; Gorodeski, Eiran/0000-0003-3756-8831
NR 40
TC 0
Z9 0
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD JUL
PY 2009
VL 158
IS 1
BP 61
EP U7
DI 10.1016/j.ahj.2009.04.015
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465ZU
UT WOS:000267630600009
ER
PT J
AU Fleischmann, KE
Orav, EJ
Lamas, GA
Mangione, CM
Schron, EB
Lee, KL
Goldman, L
AF Fleischmann, Kirsten E.
Orav, E. John
Lamas, Gervasio A.
Mangione, Carol M.
Schron, Eleanor B.
Lee, Kerry L.
Goldman, Lee
CA MOST Investigators
TI Atrial fibrillation and quality of life after pacemaker implantation for
sick sinus syndrome: Data from the Mode Selection Trial (MOST)
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID HEALTH SURVEY SF-36; ATRIOVENTRICULAR JUNCTION; NODE DYSFUNCTION;
CATHETER ABLATION; CANADIAN TRIAL; FOLLOW-UP; OUTCOMES; MANAGEMENT;
VALIDITY
AB Background In the Mode Selection Trial (MOST) of 2,010 patients with sinus node dysfunction, dual-chamber-paced patients had less atrial fibrillation (AF) and heart failure and had slightly improved health-related quality of life (QOL) compared with rate modulated right ventricular-paced patients. Our objective was to assess the impact of AF on QOL within MOST.
Methods We analyzed serial QOL measures (Short Form-36, Specific Activity Scale, time trade-off) in 3 groups: (1) those without AF; (2) those with paroxysmal AF (PAF), but not chronic AF (CAF); and (3) those with CAF We carried forward the lost known QOL before crossover for all subsequent time points in patients randomized to rate modulated right ventricular pacing who crossed over to dual-chamber pacing for severe pacemaker syndrome.
Results Three hundred seventeen patients (15.8%) had AF in the year after implantation, 206 patients within 3 months (191 PAF, 15 CAF), and another 159 (124 PAF, 35 CAF) between 3 and 12 months. There were no significant differences among groups in individual Short Form-36 subscales or time trade-off scores at 12 months as compared with baseline or 3 months. Cardiovascular health status was better at 12 months as compared with baseline or 3 months in those without AF.
Conclusions Atrial fibrillation after pacemaker implantation in elderly patients with sick sinus syndrome was not a major determinant of QOL. However, there was a trend toward better cardiovascular functional status in patients without AF. (Am Heart J 2009;158:78-83.)
C1 [Fleischmann, Kirsten E.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Orav, E. John] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Orav, E. John] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Lamas, Gervasio A.] Columbia Univ, Mt Sinai Med Ctr, Div Cardiol, Miami Beach, FL USA.
[Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Schron, Eleanor B.] NHLBI, Bethesda, MD 20892 USA.
[Lee, Kerry L.] Duke Univ, Sch Med, Durham, NC USA.
[Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA.
[Goldman, Lee] Columbia Univ, Coll Phys & Surg, New York, NY USA.
RP Fleischmann, KE (reprint author), Box 0124,505 Parnassus Ave, San Francisco, CA 94143 USA.
EM fleischm@medicine.ucsf.edu
FU National Heart, Lung, and Blood Institute [UO1 HL 49804, UO1 HL 53973,
UO1 HL 55981]; NIH, National Institute of Aging [P30 AG-21684]
FX Dr Lamas reports receiving research grants and acting as a consultant
and speaker for Medtronic; a speaker and consultant for Astra-Zeneca
(Wilmington, DE) and CVf (Foster City, CA); a consultant for Astellas
(Tokyo, Japan); and a speaker for Novartis (Washington, DC) and
GlaxoSmith-Kline (Philadelphia, PA). Dr Fleischmann has participated in
CME and QI initiatives sponsored by Pfizer.
NR 26
TC 3
Z9 4
U1 0
U2 3
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 JUL
PY 2009
VL 158
IS 1
BP 78
EP 83
DI 10.1016/j.ahj.2009.02.023
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 465ZU
UT WOS:000267630600012
PM 19540395
ER
PT J
AU Pop-Busui, R
Lombardero, M
Lavis, V
Forker, A
Green, J
Korytkowski, M
Sobel, BE
Jones, TLZ
AF Pop-Busui, Rodica
Lombardero, Manuel
Lavis, Victor
Forker, Alan
Green, Jennifer
Korytkowski, Mary
Sobel, Burton E.
Jones, Teresa L. Z.
CA BARI 2D Study Grp
TI Relation of Severe Coronary Artery Narrowing to Insulin or
Thiazolidinedione Use in Patients With Type 2 Diabetes Mellitus (from
the Bypass Angioplasty Revascularization Investigation 2 Diabetes Study)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID INTRAVASCULAR ULTRASOUND; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE;
PIOGLITAZONE; RISK; ROSIGLITAZONE; METFORMIN; TRIAL; ATHEROSCLEROSIS;
MORTALITY
AB Patients with diabetes continue to die of coronary artery disease (CAD) at rates 2 to 4 times higher than patients without diabetes, despite advances in treatment of cardiovascular disease. The role of glycemic control therapies, independent of their glucose-lowering effects, on cardiovascular disease is a recurring question. We examined the association of glycemic control therapies with extent of CAD as measured by coronary angiogram obtained at baseline in 1,803 subjects in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial who had type 2 diabetes mellitus, documented moderate to severe CAD, and no previous cardiac revascularization procedures. The association between glycemic control therapy use recorded at baseline and percent coronary artery stenosis and myocardial jeopardy index was analyzed by multiple regression models. Insulin use at study entry was associated with 23% fewer highly stenotic lesions (>= 70%) (p < 0.001) and a significantly lower myocardial jeopardy index compared with subjects not on insulin, despite a worse cardiac risk factor profile, more unstable angina, and increased inflammatory markers in insulin users. Subjects taking thiazolidinediones (TZDs) for >= 6 months had 17% fewer highly stenotic lesions (p = 0.02) and significantly lower C-reactive protein, fibrinogen, and plasminogen activator inhibitor-1 levels compared with those not taking TZDs. In conclusion, this cross-sectional study of patients with type 2 diabetes mellitus and CAD showed that treatment with insulin or TZDs was associated with fewer highly stenotic lesions, independent of disease duration, glycemic control, and other risk factors. (c) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:52-58)
C1 [Jones, Teresa L. Z.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Pop-Busui, Rodica] Univ Michigan, Dept Internal Med, Div Metab, Ann Arbor, MI 48109 USA.
[Lombardero, Manuel] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Korytkowski, Mary] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Lavis, Victor] Univ Texas MD Anderson Canc Ctr, Div Internal Med, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA.
[Forker, Alan] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Forker, Alan] Univ Missouri, Kansas City, MO 64110 USA.
[Green, Jennifer] Duke Univ, Med Ctr, Dept Med, Div Endocrinol, Durham, NC 27710 USA.
[Sobel, Burton E.] Univ Vermont, Burlington, VT USA.
RP Jones, TLZ (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA.
EM jonest@extra.niddk.nih.gov
FU National Heart, Lung and Blood Institute (Bethesda, Maryland) [U01
HL061746, U01 HL061748, U01 HL063804]; National Institute of Diabetes
and Digestive and Kidney Diseases (Bethesda, Maryland) [HL061744];
National Institutes of Health, Bethesda, Maryland [R01 HL71306]
FX The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI
2D) trial is funded by Grants U01 HL061746, U01 HL061748, and U01
HL063804 from the National Heart, Lung and Blood Institute (Bethesda,
Maryland) and receives substantial funding (Grant HL061744) from the
National Institute of Diabetes and Digestive and Kidney Diseases
(Bethesda, Maryland). BARI 2D receives significant supplemental funding
from GlaxoSmithKline, Lantheus Medical Imaging, Inc. (formerly
BristolMyers Squibb Medical Imaging, Inc.), Astellas Pharma US, Inc.,
Merck, & Co., Inc.. Abbott Laboratories. Inc., and Pfizer, Inc., and
generous financial support from Abbott Laboratories, Ltd.. MediSense
Products, Bayer Diagnostics, Becton, Dickinson, & Company, J.R. Carlson
Laboratories. Inc., Centocor, Inc., Eli Lilly and Company, LipoScience,
Inc.. Merck Sante. Novartis Pharmaceuticals Corporation, and Novo
Nordisk, Inc. The BARI 2D trial is co-ordinated by the Epidemiology Data
Center, Graduate School of Public Health, University of Pittsburgh,
Pittsburgh. Pennsylvania. Dr. Sobel received Grant R01 HL71306 from the
National Institutes of Health, Bethesda, Maryland.
NR 28
TC 6
Z9 6
U1 0
U2 0
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2009
VL 104
IS 1
BP 52
EP 58
DI 10.1016/j.amjcard.2009.02.046
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100011
PM 19576321
ER
PT J
AU Schnabel, RB
Larson, MG
Yamamoto, JF
Kathiresan, S
Rong, J
Levy, D
Keaney, JF
Wang, TJ
Vasan, RS
Benjamin, EJ
AF Schnabel, Renate B.
Larson, Martin G.
Yamamoto, Jennifer F.
Kathiresan, Sekar
Rong, Jian
Levy, Daniel
Keaney, John F., Jr.
Wang, Thomas J.
Vasan, Ramachandran S.
Benjamin, Emelia J.
TI Relation of Multiple Inflammatory Biomarkers to Incident Atrial
Fibrillation
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID C-REACTIVE PROTEIN; OSTEOPROTEGERIN LEVELS; PLASMA OSTEOPROTEGERIN;
DIABETIC-PATIENTS; INTERLEUKIN-6; METAANALYSIS; HEART; RISK;
THROMBOGENESIS; POPULATION
AB Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myelo-peroxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events. (c) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;104:92-96)
C1 [Schnabel, Renate B.; Larson, Martin G.; Yamamoto, Jennifer F.; Rong, Jian; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.] Natl Heart Lung Blood Inst, Framingham Study, Framingham, MA USA.
[Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Dept Med 2, Mainz, Germany.
[Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA USA.
[Yamamoto, Jennifer F.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Kathiresan, Sekar; Wang, Thomas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA.
[Kathiresan, Sekar] Broad Inst Harvard, Cambridge, MA USA.
[Kathiresan, Sekar] MIT, Cambridge, MA 02139 USA.
[Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Keaney, John F., Jr.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Med Dept, Boston, MA 02118 USA.
[Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Prevent Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
RP Benjamin, EJ (reprint author), Natl Heart Lung Blood Inst, Framingham Study, Framingham, MA USA.
EM melia@bu.edu
OI Larson, Martin/0000-0002-9631-1254; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Institutes of Health/National Heart, Lung, Blood Institute
[N01-HC-25195, 6R01-NS 17950]; National Institutes of Health [HL064753,
HL076784, AG028321, R01HL71039]; National Institutes of Health Research
Career Award [K24 HL04334]; Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship [SCHN 1149/1-1]; Doris Duke
Charitable Foundation Clinical Scientist Development Award
[1K231-11-083102]
FX This study was supported by National Institutes of Health/National
Heart, Lung, Blood Institute Grants N01-HC-25195 and 6R01-NS 17950, and
National Institutes of Health Grants HL064753. HL076784, and AG028321
(E. J. Benjamin), 1 R01HL71039 (R. S. Vasan), Bethesda, Maryland;
National Institutes of Health Research Career Award K24 HL04334 (R. S.
Vasan), Bethesda, Maryland Deutsche Forschungsgemeinschaft (German
Research Foundation) Research Fellowship SCHN 1149/1-1 (R. B. Schnabel),
Bonn, Germany; and Grant 1K231-11-083102, Doris Duke Charitable
Foundation Clinical Scientist Development Award (S. Kathiresan), New
York, New York.
NR 28
TC 68
Z9 71
U1 0
U2 6
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2009
VL 104
IS 1
BP 92
EP 96
DI 10.1016/j.amjcard.2009.02.053
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 469JX
UT WOS:000267895100016
PM 19576326
ER
PT J
AU Bailey, RL
Miller, PE
Mitchell, DC
Hartman, TJ
Lawrence, FR
Sempos, CT
Smiciklas-Wright, H
AF Bailey, Regan L.
Miller, Paige E.
Mitchell, Diane C.
Hartman, Terryl J.
Lawrence, Frank R.
Sempos, Christopher T.
Smiciklas-Wright, Helen
TI Dietary screening tool identifies nutritional risk in older adults
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID QUALITY-OF-LIFE; SUPPLEMENT USE; VEGETABLE INTAKE; PRIMARY-CARE; HEALTH;
PATTERNS; COHORT; QUESTIONNAIRE; PREVENTION; PHYSICIANS
AB Background: No rapid methods exist for screening overall dietary intakes in older adults.
Objective: The purpose of this study was to develop and evaluate a scoring system for a diet screening tool to identify nutritional risk in community-dwelling older adults.
Design: This cross-sectional study in older adults (n = 204) who reside in rural areas examined nutrition status by using an in-person interview, biochemical measures, and four 24-h recalls that included the use of dietary supplements.
Results: The dietary screening tool was able to characterize 3 levels of nutritional risk: at risk, possible risk, and not at risk. Individuals classified as at nutritional risk had significantly lower indicators of diet quality (Healthy Eating Index and Mean Adequacy Ratio) and intakes of protein, most micronutrients, dietary fiber, fruit, and vegetables. The at-risk group had higher intakes of fats and oils and refined grains. The at-risk group also had the lowest serum vitamin B-12, folate, beta-cryptoxanthin, lutein, and zeaxanthin concentrations. The not-at-nutritional-risk group had significantly higher lycopene and beta-carotene and lower homocysteine and methylmalonic acid concentrations.
Conclusion: The dietary screening tool is a simple and practical tool that can help to detect nutritional risk in older adults. Am J Clin Nutr 2009;90:177-83.
C1 [Bailey, Regan L.; Sempos, Christopher T.] Off Dietary Supplements, NIH, Bethesda, MD 20892 USA.
[Miller, Paige E.; Mitchell, Diane C.; Hartman, Terryl J.; Smiciklas-Wright, Helen] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Lawrence, Frank R.] Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA.
RP Bailey, RL (reprint author), Off Dietary Supplements, NIH, 6100 Execut Blvd 2B03, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
FU NIH [R21AG023179-01A1]; USDA [58-1950-6019, 58-1950-4-401]; National
Institute on Aging [T32AG00048]
FX Supported by NIH grant no. R21AG023179-01A1, USDA grant no.
58-1950-6019, USDA grant no. 58-1950-4-401, and National Institute on
Aging training grant no. T32AG00048.
NR 45
TC 22
Z9 25
U1 1
U2 10
PU AMER SOC CLINICAL NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998
USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD JUL 1
PY 2009
VL 90
IS 1
BP 177
EP 183
DI 10.3945/ajcn.2008.27268
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 462RK
UT WOS:000267373200024
PM 19458013
ER
PT J
AU Gualco, G
Chioato, L
Weiss, LM
Harrington, WJ
Bacchi, CE
AF Gualco, Gabriela
Chioato, Lucimara
Weiss, Lawrence M.
Harrington, William J., Jr.
Bacchi, Carlos E.
TI Analysis of Human T-Cell Lymphotropic Virus in CD25+ Anaplastic Large
Cell Lymphoma in Children
SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY
LA English
DT Article
DE Malignant lymphoma; T-cell lymphoma; Anaplastic large cell lymphoma;
HTLV-1; Virus-related lymphomas; CD25; Child
ID CLASSICAL HODGKINS LYMPHOMA; LEUKEMIA/LYMPHOMA; EXPRESSION; HTLV-1;
GENE; BRAZIL; CHILDHOOD; LEUKEMIA; PROJECT; PROTEIN
AB Anaplastic large cell lymphoma (ALCL) is recognized as 2 distinct diseases: anaplastic lymphoma kinase (ALK)+ ALCL and ALK- ALCL. ALK+ ALCL occurs in younger patients and has a better prognosis. Human T-cell lymphotropic virus (HTLV-1) is linked to the development of adult T-cell leukemia/lymphoma (ATLL), which frequently expresses CD25. CD25 is significantly expressed in childhood ALCL. In Brazil, HTLV-1 infection is endemic, and vertical transmission is responsible for spread to children. Of HTLV-1 carriers, 90% or more remain asymptomatic. Some cases of adult HTLV-1-related lymphomas have characteristics of ALCL but are considered CD30+ ATLL subtypes. No similar cases have been described in children.
We analyzed 33 cases of pediatric ALCL, CD25+ and CD25-, for proviral HTLV-1 DNA. All cases corresponded to the common histologic ALCL ope and were CD30+ in virtually all neoplastic cells. ALK expression was observed in 31 (94%) of 33 cases; CD25 was positive in 2 7 (82%), including 1 ALK- ALCL case. There was a strong positive correlation between ALK and CD25 expression. None of the cases showed proviral HTLV-1 DNA. ALCL in children has no relationship with HTLV-1; the frequent CD25 e,expression must be explained by a mechanism different from that in ATLL.
C1 [Weiss, Lawrence M.] City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA.
[Harrington, William J., Jr.] Fogarty Int Ctr AIDS & TB Program, Sylvester Canc Ctr, Miami, FL USA.
[Harrington, William J., Jr.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
RP Bacchi, CE (reprint author), Rua Major Leonidas Cardoso 739, BR-18602010 Botucatu, SP, Brazil.
FU National Cancer Institute, Bethesda, MD [R01CA082274-08]
FX Supported in part by grant R01CA082274-08 from the National Cancer
Institute, Bethesda, MD (Dr Harrington).
NR 34
TC 9
Z9 9
U1 0
U2 0
PU AMER SOC CLINICAL PATHOLOGY
PI CHICAGO
PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA
SN 0002-9173
J9 AM J CLIN PATHOL
JI Am. J. Clin. Pathol.
PD JUL
PY 2009
VL 132
IS 1
BP 28
EP 33
DI 10.1309/AJCP6Q7QMUVGMVMF
PG 6
WC Pathology
SC Pathology
GA 460SC
UT WOS:000267206400005
PM 19864230
ER
PT J
AU Prentice, RL
Manson, JE
Langer, RD
Anderson, GL
Pettinger, M
Jackson, RD
Johnson, KC
Kuller, LH
Lane, DS
Wactawski-Wende, J
Brzyski, R
Allison, M
Ockene, J
Sarto, G
Rossouw, JE
AF Prentice, Ross L.
Manson, JoAnn E.
Langer, Robert D.
Anderson, Garnet L.
Pettinger, Mary
Jackson, Rebecca D.
Johnson, Karen C.
Kuller, Lewis H.
Lane, Dorothy S.
Wactawski-Wende, Jean
Brzyski, Robert
Allison, Matthew
Ockene, Judith
Sarto, Gloria
Rossouw, Jacques E.
TI Benefits and Risks of Postmenopausal Hormone Therapy When It Is
Initiated Soon After Menopause
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE clinical trial; cohort studies; estrogens; estrogen replacement therapy;
hormone replacement therapy; medroxyprogesterone 17-acetate;
postmenopause; progestins
ID ESTROGEN PLUS PROGESTIN; CONJUGATED EQUINE ESTROGENS;
CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIAL;
CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; BREAST-CANCER; VENOUS
THROMBOSIS; WOMEN
AB The authors further analyzed results from the Women's Health Initiative randomized trials (1993-2004) of conjugated equine estrogens, with or without medroxyprogesterone acetate, focusing on health benefits versus risks among women who initiated hormone therapy soon after menopause. Data from the Women's Health Initiative observational study (1993-2004) were included in some analyses for additional precision. Results are presented here for incident coronary heart disease, stroke, venous thromboembolism, breast cancer, colorectal cancer, endometrial cancer, or hip fracture; death from other causes; a summary global index; total cancer; and total mortality. Hazard ratios for breast cancer and total cancer were comparatively higher (P < 0.05) among women who initiated hormone therapy soon after menopause, for both regimens. Among these women, use of conjugated equine estrogens appeared to produce elevations in venous thromboembolism and stroke and a reduction in hip fracture. Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism, stroke, and hip fracture but also included evidence of longer-term elevations in breast cancer, total cancer, and the global index. These analyses provide little support for the hypothesis of favorable effects among women who initiate postmenopausal estrogen use soon after menopause, either for coronary heart disease or for health benefits versus risk indices considered.
C1 [Prentice, Ross L.; Anderson, Garnet L.; Pettinger, Mary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Manson, JoAnn E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Manson, JoAnn E.] Harvard Univ, Sch Med, Boston, MA USA.
[Langer, Robert D.] Geisinger Hlth Syst, Outcomes Res Inst, Danville, PA USA.
[Jackson, Rebecca D.] Ohio State Univ, Coll Med, Dept Internal Med, Div Endocrinol, Columbus, OH 43210 USA.
[Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Kuller, Lewis H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Lane, Dorothy S.] SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Sch Publ Hlth & Hlth Profess, Buffalo, NY USA.
[Brzyski, Robert] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
[Allison, Matthew] Univ Calif San Diego, Dept Family & Prevent Med, Sch Med, La Jolla, CA 92093 USA.
[Ockene, Judith] Univ Massachusetts, Sch Med, Dept Prevent & Behav Med, Worcester, MA USA.
[Sarto, Gloria] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Rossouw, Jacques E.] NHLBI, Bethesda, MD 20892 USA.
RP Prentice, RL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA.
EM rprentic@fhcrc.org
OI Allison, Matthew/0000-0003-0777-8272
FU NCI NIH HHS [CA53996, P01 CA053996]
NR 26
TC 111
Z9 115
U1 0
U2 7
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 JUL 1
PY 2009
VL 170
IS 1
BP 12
EP 23
DI 10.1093/aje/kwp115
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 463NZ
UT WOS:000267440200002
PM 19468079
ER
PT J
AU Weiss, A
Sutin, AR
Duberstein, PR
Friedman, B
Bagby, RM
Costa, PT
AF Weiss, Alexander
Sutin, Angelina R.
Duberstein, Paul R.
Friedman, Bruce
Bagby, R. Michael
Costa, Paul T., Jr.
TI The Personality Domains and Styles of the Five-Factor Model are Related
to Incident Depression in Medicare Recipients Aged 65 to 100
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article
DE Major depression; minor depression; Neuroticism; Conscientiousness;
aging; personality styles; Medicare recipients
ID PRIMARY-CARE PATIENTS; INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW;
RANDOMIZED CONTROLLED-TRIAL; LATE-LIFE DEPRESSION; 6-YEAR FOLLOW-UP;
NEO-PI-R; MAJOR DEPRESSION; CONSENSUS STATEMENT; MENTAL-DISORDERS;
DSM-IV
AB Objectives: Few prospective studies have examined personality and depression in older adults. The authors investigated whether the Five-Factor Model of personality traits Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness-and trait combinations ( styles) are related to incident major or minor depression. Participants/Setting: Prospective data were gathered on a community sample of 512 older adults with disability and a history of significant health care utilization who were enrolled in a Medicare Demonstration Project. Measurements: Depression and personality traits and styles were assessed at baseline; depression was assessed again at approximately 12 and 22 months. Design: Participants who developed incident major depression were compared with those free of depression at all three assessments. Similar analyses were done for minor depression. Results: High Neuroticism and low Conscientiousness were risk factors for both major and minor depression. Combinations of high Neuroticism with low or high Extraversion or high Openness conferred risk for major depression. Other novel findings for major depression revealed new trait combinations of low Conscientiousness with low or high Extraversion, high Openness, or low Agreeableness. Three trait combinations, all involving low Conscientiousness, predicted risk for minor depression: high Neuroticism, high Agreeableness, and low Openness. Conclusion: The present findings highlight the importance of examining combinations of personality traits or personality styles when identifying those who are most at-risk for geriatric depression. Since other personality domains may modify the risk related to high Neuroticism and low Conscientiousness, the prevention, diagnosis, and treatment of depression could be greatly improved by assessing older patients not only on all five domains of personality but in terms of their combinations. (Am J Geriatr Psychiatry 2009; 17:591-601)
C1 [Costa, Paul T., Jr.] NIA, NIH, Biomed Res Ctr, IRP,Lab Personal & Cognit,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
[Weiss, Alexander] Univ Edinburgh, Dept Psychol, Sch Philosophy Psychol & Language Sci, Edinburgh, Midlothian, Scotland.
[Duberstein, Paul R.] Univ Rochester, Med Ctr, Lab Personal & Dev, Rochester, NY 14642 USA.
[Friedman, Bruce] Univ Rochester, Med Ctr, Dept Community & Prevent Med, Rochester, NY 14642 USA.
[Friedman, Bruce] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
[Bagby, R. Michael] Ctr Addict & Mental Hlth, Dept Clin Res, Toronto, ON, Canada.
RP Costa, PT (reprint author), NIA, NIH, Biomed Res Ctr, IRP,Lab Personal & Cognit,Dept Hlth & Human Serv, 251 Bayview Blvd,Suite 100,Room 04B335, Baltimore, MD 21224 USA.
EM Costap@mail.nih.gov
OI Costa, Paul/0000-0003-4375-1712
FU Intramural NIH HHS [Z01 AG000184-19]; NIMH NIH HHS [K01 MH064718, K01
MH64718-01, K24 MH072712, K24MH072712]; PHS HHS [CMS 95-C-90467]
NR 57
TC 38
Z9 38
U1 3
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1064-7481
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD JUL
PY 2009
VL 17
IS 7
BP 591
EP 601
PG 11
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 465KJ
UT WOS:000267582500007
PM 19554673
ER
PT J
AU Hebert-Magee, S
Lee-Stroka, H
Langeberg, A
Sandler, SG
AF Hebert-Magee, Shantel
Lee-Stroka, Hallie
Langeberg, Al
Sandler, S. Gerald
TI Anti-G presenting as a blood transfusion error
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Letter
C1 [Hebert-Magee, Shantel; Sandler, S. Gerald] Georgetown Univ Hosp, Dept Pathol, Washington, DC 20007 USA.
[Lee-Stroka, Hallie; Langeberg, Al] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sandler, S. Gerald] Georgetown Univ Hosp, Dept Lab Med, Washington, DC 20007 USA.
RP Hebert-Magee, S (reprint author), Georgetown Univ Hosp, Dept Pathol, Washington, DC 20007 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0361-8609
J9 AM J HEMATOL
JI Am. J. Hematol.
PD JUL
PY 2009
VL 84
IS 7
BP 466
EP 467
DI 10.1002/ajh.21437
PG 2
WC Hematology
SC Hematology
GA 467DT
UT WOS:000267718000023
PM 19484733
ER
PT J
AU Boudreau, EA
Johnson, KP
Jackman, AR
Blancato, J
Huizing, M
Bendavid, C
Jones, M
Chandrasekharappa, SC
Lewy, AJ
Smith, ACM
Magenis, RE
AF Boudreau, Eilis A.
Johnson, Kyle P.
Jackman, Angela R.
Blancato, Jan
Huizing, Marjan
Bendavid, Claude
Jones, MaryPat
Chandrasekharappa, Settara C.
Lewy, Alfred J.
Smith, Ann C. M.
Magenis, R. Ellen
TI Review of Disrupted Sleep Patterns in Smith-Magenis Syndrome and Normal
Melatonin Secretion in a Patient With an Atypical Interstitial 17p11.2
Deletion
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE melatonin; Smith-Magenis syndrome; sleep; interstitial deletion 17p11.2;
array CGH
ID SYNDROME DEL 17P11.2; CIRCADIAN-RHYTHM; LIGHT; HUMANS; PHASE;
DISTURBANCES; MUTATIONS; PROFILES; BEHAVIOR; COMPLEX
AB Smith-Magenis syndrome (SMS) is a disorder characterized by multiple congenital anomalies and behavior problems, including abnormal sleep patterns. It is most commonly due to a 3.5 Mb interstitial deletion of chromosome 17 band p11.2. Secretion of melatonin, a hormone produced by the pineal gland, is the body's signal for nighttime darkness. Published reports of 24-hr melatonin secretion patterns in two independent SMS cohorts (US and France) document an inverted endogenous melatonin pattern in virtually all cases (96%), suggesting that this finding is pathognomic for the syndrome. We report on a woman with SMS due to an atypical large proximal deletion (similar to 6Mb; -TNFRSFproteinB) of chromosome band (17)(p11.2p11.2) who presents with typical sleep disturbances but a normal pattern of melatonin secretion. We further describe a melatonin light suppression test in this patient. This is the second reported patient with a normal endogenous melatonin rhythm in SMS associated with an atypical large deletion. These two patients are significant because they suggest that the sleep disturbances in SMS cannot be solely attributed to the abnormal diurnal melatonin secretion versus the normal nocturnal pattern. (C) 2009 Wiley-Liss, Inc.
C1 [Boudreau, Eilis A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Johnson, Kyle P.; Jackman, Angela R.; Lewy, Alfred J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA.
[Blancato, Jan; Smith, Ann C. M.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Huizing, Marjan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Bendavid, Claude] Univ Rennes, Fac Med, CNRS UMR 6061, Inst Genet & Dev Rennes, Rennes, France.
[Jones, MaryPat; Chandrasekharappa, Settara C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Smith, Ann C. M.] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Magenis, R. Ellen] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA.
RP Boudreau, EA (reprint author), Dept Vet Affairs, Med Ctr, Portland Div, 3710 SW US Vet Hosp Rd,Box 1034, Portland, OR 97207 USA.
EM boudreau@ohsu.edu
OI Jackman, Angela/0000-0002-1784-9700
FU Intramural NIH HHS; NICHD NIH HHS [R01 HD042125-05, R01 HD042125]
NR 40
TC 22
Z9 24
U1 0
U2 2
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2009
VL 149A
IS 7
BP 1382
EP 1391
DI 10.1002/ajmg.a.32846
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 467VA
UT WOS:000267770000003
PM 19530184
ER
PT J
AU Becerik, S
Cogulu, D
Emingil, G
Han, T
Hart, PS
Hart, TC
AF Becerik, Sema
Cogulu, Dilsah
Emingil, Guelnur
Han, Ted
Hart, P. Suzanne
Hart, Thomas C.
TI Exclusion of Candidate Genes in Seven Turkish Families With Autosomal
Recessive Amelogenesis Imperfecta
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE autosomal recessive amelogenesis imperfecta; AMBN; AMELX; ENAM; FAM83H;
KLK4; MMP20; TUFT1
ID FAM83H MUTATIONS; ENAM MUTATIONS; OPEN-BITE; NEPHROCALCINOSIS;
CLASSIFICATION; NOMENCLATURE; PHENOTYPE; FEATURES
AB Amelogenesis imperfectas (AI) are a group of inherited defects of dental enamel formation that show both clinical and genetic heterogeneity. Seven Turkish families segregating autosomal recessive AI (ARAI) were evaluated for evidence of a genetic etiology of AI for the seven major candidate gene loci (AMBN, AMELX, ENAM, FAM83H, KLK4, MMP20, and TUFT1). Dental and periodontal characteristics of the affected members of these families were also described. The mean scores of DMFS and dfs indices were 9.7 and 9.6, respectively. The mean PPD was 2.2 min and the percentage of the sites with plaque and BOP were 87.8% and 72.4%, respectively. The exons and intron/exon junctions of the candidate genes were sequenced and no gene mutations were identified in any individuals. These findings support the existence of an additional gene(s) that are etiologic for ARAI in these families. (C) 2009 Wiley-Liss, Inc.
C1 [Becerik, Sema; Emingil, Guelnur] Ege Univ, Dept Periodontol, Sch Dent, TR-35100 Izmir, Turkey.
[Cogulu, Dilsah] Ege Univ, Dept Pedodont, Sch Dent, TR-35100 Izmir, Turkey.
[Han, Ted; Hart, Thomas C.] NIDCR, Human & Craniofacial Genet Sect, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA.
[Hart, P. Suzanne] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Becerik, S (reprint author), Ege Univ, Dept Periodontol, Sch Dent, TR-35100 Izmir, Turkey.
EM sema.cinar@ege.edu.tr
FU Intramural NIH HHS [Z99 HG999999]
NR 38
TC 7
Z9 8
U1 1
U2 6
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2009
VL 149A
IS 7
BP 1392
EP 1398
DI 10.1002/ajmg.a.32885
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 467VA
UT WOS:000267770000004
PM 19530186
ER
PT J
AU Schell-Apacik, CC
Ertl-Wagner, B
Panzel, A
Klausener, K
Rausch, G
Muenke, M
von Voss, H
Hehr, U
AF Schell-Apacik, Chayirn Can
Ertl-Wagner, Birgit
Panzel, Axel
Klausener, Kerstin
Rausch, Gisbert
Muenke, Maximilian
von Voss, Hubertus
Hehr, Ute
TI Maternally Inherited Heterozygous Sequence Change in the Sonic Hedgehog
Gene in a Male Patient with Bilateral Closed-Lip Schizencephaly and
Partial Absence of the Corpus Callosum
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Letter
ID GERMLINE MUTATIONS; EMX2
C1 [Schell-Apacik, Chayirn Can] Practice Human Genet, D-14050 Berlin, Germany.
[Schell-Apacik, Chayirn Can; von Voss, Hubertus] Univ Munich, Inst Social Pediat & Adolescent Med, Munich, Germany.
[Ertl-Wagner, Birgit] Univ Munich, Inst Clin Radiol, Munich, Germany.
[Panzel, Axel] DRK Childrens Hosp, Dept Neuropediat, Berlin, Germany.
[Klausener, Kerstin] Hosp Frankfurt Oder, Inst Radiol, Frankfurt, Germany.
[Rausch, Gisbert] Hosp Frankfurt Oder, Childrens Ctr, Frankfurt, Germany.
[Muenke, Maximilian] NHGRI, NIH, Bethesda, MD 20892 USA.
[Hehr, Ute] Ctr Human Genet, Regensburg, Germany.
RP Schell-Apacik, CC (reprint author), Practice Human Genet, Spandauer Damm 130, D-14050 Berlin, Germany.
EM schell-apacik@gmx.de
FU Intramural NIH HHS [Z99 HG999999]
NR 11
TC 5
Z9 5
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 1552-4825
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2009
VL 149A
IS 7
BP 1592
EP 1594
DI 10.1002/ajmg.a.32940
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 467VA
UT WOS:000267770000041
PM 19533790
ER
PT J
AU Kanapuru, B
Ershler, WB
AF Kanapuru, Bindu
Ershler, William B.
TI Inflammation, Coagulation, and the Pathway to Frailty
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Coagulation; Cytokines; D-dimer; Frailty; Inflammation; Interleukin-6;
Sarcopenia; Tumor necrosis factor-alpha
ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; NECROSIS-FACTOR-ALPHA; C-REACTIVE
PROTEIN; RECOMBINANT HUMAN INTERLEUKIN-6; PERIPHERAL ARTERIAL-DISEASE;
CARDIOVASCULAR RISK-FACTORS; DWELLING ELDERLY PERSONS;
CORONARY-HEART-DISEASE; DEGRADATION PRODUCT-D; DISABLED OLDER WOMEN
AB There are inevitable physiologic changes associated with advancing age, yet for some people these changes are exaggerated, and as a result a phenotype emerges recognized as "frailty." Why some people become frail and others do not remains incompletely understood. Although chronic illnesses are common among frail elderly persons, some will develop all of the phenotypic features without a diagnosed underlying disease. It has been recognized that certain proinflammatory cytokines and coagulation factors are elevated to a greater extent in those who are frail than in age-matched nonfrail individuals. In this review, we provide an overview of current research in the biology of frailty with particular emphasis on the role of inflammatory pathways and disordered coagulation in its pathogenesis. Published by Elsevier Inc. The American Journal of Medicine (2009) 122, 605-613
C1 [Kanapuru, Bindu; Ershler, William B.] NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Ershler, WB (reprint author), Harbor Hosp, NIA, 3001 S Hanover St, Baltimore, MD USA.
EM ershlerwi@mail.nih.gov
FU Intramural Research Program, National Institute on Aging (National
Institutes of Health)
FX This work was supported by the Intramural Research Program, National
Institute on Aging (National Institutes of Health).
NR 98
TC 66
Z9 67
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2009
VL 122
IS 7
BP 605
EP 613
DI 10.1016/j.amjmed.2009.01.030
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 462HF
UT WOS:000267341000004
PM 19559159
ER
PT J
AU Parikh, NI
Hwang, SJ
Ingelsson, E
Benjamin, EJ
Fox, CS
Vasan, RS
Murabito, JM
AF Parikh, Nisha I.
Hwang, Shih-Jen
Ingelsson, Erik
Benjamin, Emelia J.
Fox, Caroline S.
Vasan, Ramachandran S.
Murabito, Joanne M.
TI Breastfeeding in Infancy and Adult Cardiovascular Disease Risk Factors
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Body mass index; Breastfeeding; Early nutrition; High-density
lipoprotein cholesterol; Infancy; Lactation; Risk factors
ID BODY-MASS INDEX; BLOOD-PRESSURE; SOCIOECONOMIC-STATUS; CHILDHOOD
OBESITY; PHYSICAL-ACTIVITY; MILK LEPTIN; LATER LIFE; FRAMINGHAM;
CHOLESTEROL; GROWTH
AB BACKGROUND: Public health recommendations advocate breastfeeding in infancy as a means to reduce obesity in later life. Several prior studies relating breastfeeding to cardiovascular risk factors have been limited by lack of adjustment for maternal and participant confounding factors.
METHODS: We ascertained breastfeeding history via questionnaire from mothers enrolled in the Framingham Offspring Study. In their young to middle-aged adult children enrolled in the Framingham Third Generation, we examined the relations between maternal breastfeeding history (yes, no) and cardiovascular risk factors, including body mass index (BMI), high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, fasting blood glucose, and systolic and diastolic blood pressure levels. We applied generalized estimating equations to account for sibling correlations and adjusted for maternal and participant lifestyle, education, and cardiovascular risk factors.
RESULTS: In Third Generation participants (n = 962, mean age = 41 years, 54% were women), 26% of their mothers reported breastfeeding. Compared with non-breastfed individuals, breastfed adult participants had lower multivariable-adjusted BMI (26.1 kg/m(2) vs 26.9 kg/m(2), P = .04) and higher HDL cholesterol levels (HDL 56.6 mg/dL vs 53.7 mg/dL, P = .01). On additional adjustment for BMI, the association between breastfeeding and HDL cholesterol was attenuated (P = .09). Breastfeeding was not associated with total cholesterol, triglycerides, fasting blood glucose, systolic blood pressure, or diastolic blood pressure.
CONCLUSION: Breastfeeding in infancy is inversely associated with adult BMI and positively associated with HDL cholesterol. Associations between breastfeeding and BMI may mediate the association between breastfeeding and HDL cholesterol. (C) 2009 Elsevier Inc. All rights reserved. The American Journal of Medicine (2009) 122, 656-663
C1 [Parikh, Nisha I.; Hwang, Shih-Jen; Ingelsson, Erik; Benjamin, Emelia J.; Fox, Caroline S.; Vasan, Ramachandran S.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Parikh, Nisha I.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA.
[Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Epidemiol Sect, Boston, MA USA.
[Fox, Caroline S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
RP Murabito, JM (reprint author), 73 Mt Wayte Ave,2, Framingham, MA 01702 USA.
EM murabito@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran,
Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336
FU National Institute of Health/National Heart, Lung, and Blood Institute
[N01-HC-25195, 2K24 HL 04334]
FX Supported by a National Institute of Health/National Heart, Lung, and
Blood Institute, contract N01-HC-25195, 2K24 HL 04334 (RSV).
NR 52
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Z9 33
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD JUL
PY 2009
VL 122
IS 7
BP 656
EP U80
DI 10.1016/j.amjmed.2008.11.034
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 462HF
UT WOS:000267341000013
PM 19559168
ER
PT J
AU Hassan, S
Ferrario, C
Saragovi, U
Quenneville, L
Gaboury, L
Baccarelli, A
Salvucci, O
Basik, M
AF Hassan, Saima
Ferrario, Cristiano
Saragovi, Uri
Quenneville, Louise
Gaboury, Louis
Baccarelli, Andrea
Salvucci, Ombretta
Basik, Mark
TI The Influence of Tumor-Host Interactions in the Stromal Cell-Derived
Factor-1/CXCR4 Ligand/Receptor Axis in Determining Metastatic Risk in
Breast Cancer
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CHEMOKINE RECEPTOR CXCR4; EXPRESSION; GROWTH; INHIBITION; RECURRENCE;
SPECIMENS; SURVIVAL; MARKER
AB The chemokine stromal cell-derived factor-1 (SDF-1) may function to attract CXCR4-expressing cancer cells to metastatic organs. We have previously demonstrated that low plasma SDF-1, a host-derived marker, increases distant metastatic risk in breast cancer. We therefore hypothesized that tumors over-expressing the SDF-1 receptor CXCR4 have an enhanced ability to metastasize in patients with low plasma SDF-1 levels. In this study, we determined the prognostic significance of activated CXCR4, or phosphorylated CXCR4 (p-CXCR4), and CXCR7, another receptor for SDF-1. immunohistochemistry was performed on a tissue microarray built using 237 samples from the same cohort of patients for which we measured plasma SDF-1 levels. We found that the prognostic value of p-CXCR4 expression (hazard ratio or HR, 3.95; P = 0.004) was superior to total CXCR4 expression (HR, 3.20; P = 0.03). The rate of breast cancer-specific mortality was much higher in patients with both high p-CXCR4 expression and low plasma SDF-1 levels (HR, 5.96; P < 0.001) than either low plasma SDF-1 (HR, 3.59; P = 0.01) or high p-CXCR4 expression (HR, 3.83; P = 0.005) alone. The added prognostic value of low plasma SDF-1 was only effective in patients with high p-CXCR4 expression, and as such, provides clinical validation for modulation of the metastatic potential of tumor cells by an inherent host-derived metastatic risk factor. (Am J Pathol 2009, 175:66-73; DOI: 10.2353/ajpath.2009.080948)
C1 [Hassan, Saima; Ferrario, Cristiano; Saragovi, Uri; Basik, Mark] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Oncol, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Hassan, Saima; Basik, Mark] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Surg, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Quenneville, Louise] McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Pathol, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
[Saragovi, Uri] McGill Univ, Dept Pharm & Therapeut, Montreal, PQ H3T 1E2, Canada.
[Gaboury, Louis] Univ Montreal, Inst Res Immunol & Canc, Dept Pathol, Montreal, PQ, Canada.
[Baccarelli, Andrea] Univ Milan, Ctr Mol & Genet Epidemiol, Dept Environm & Occupat Hlth, Milan, Italy.
[Baccarelli, Andrea] IRCCS Maggiore Policlin Hosp, Milan, Italy.
[Salvucci, Ombretta] NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Basik, M (reprint author), McGill Univ, Sir Mortimer B Davis Jewish Gen Hosp, Dept Oncol, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada.
EM markbasik@gmail.com
OI Baccarelli, Andrea/0000-0002-3436-0640
FU Canadian Breast Cancer Research Alliance [14598]; Fonds de la recherche
en sante du Quebec Reseau de Recherche sur le Cancer
FX Supported by Canadian Breast Cancer Research Alliance grant 14598 (to
M.B.) and Fonds de la recherche en sante du Quebec Reseau de Recherche
sur le Cancer for the tumor bank.
NR 30
TC 35
Z9 35
U1 0
U2 3
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD JUL
PY 2009
VL 175
IS 1
BP 66
EP 73
DI 10.2353/ajpath.2009.080948
PG 8
WC Pathology
SC Pathology
GA 464MG
UT WOS:000267508600007
PM 19497995
ER
PT J
AU Csiszar, A
Labinskyy, N
Pinto, JT
Ballabh, P
Zhang, HR
Losonczy, G
Pearson, K
de Cabo, R
Pacher, P
Zhang, CH
Ungvari, Z
AF Csiszar, Anna
Labinskyy, Nazar
Pinto, John T.
Ballabh, Praveen
Zhang, Hanrui
Losonczy, Gyorgy
Pearson, Kevin
de Cabo, Rafael
Pacher, Pal
Zhang, Cuihua
Ungvari, Zoltan
TI Resveratrol induces mitochondrial biogenesis in endothelial cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE vasoprotection; histone deacetylase; endothelial dysfunction; diabetes;
obesity
ID SMALL-MOLECULE ACTIVATORS; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA;
KAPPA-B ACTIVATION; OXIDATIVE STRESS; LIFE-SPAN; POLYPHENOLIC
PHYTOALEXIN; CARDIAC DYSFUNCTION; CALORIC RESTRICTION; PROTEIN-KINASE
AB Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 297: H13-H20, 2009. First published May 8, 2009; doi:10.1152/ajpheart.00368.2009.-Pathways that regulate mitochondrial biogenesis are potential therapeutic targets for the amelioration of endothelial dysfunction and vascular disease. Resveratrol was shown to impact mitochondrial function in skeletal muscle and the liver, but its role in mitochondrial biogenesis in endothelial cells remains poorly defined. The present study determined whether resveratrol induces mitochondrial biogenesis in cultured human coronary arterial endothelial cells (CAECs). In CAECs resveratrol increased mitochondrial mass and mitochondrial DNA content, upregulated protein expression of electron transport chain constituents, and induced mitochondrial biogenesis factors (proliferator-activated receptor-coactivator-1 alpha, nuclear respiratory factor-1, mitochondrial transcription factor A). Sirtuin 1 (SIRT1) was induced, and endothelial nitric oxide (NO) synthase (eNOS) was upregulated in a SIRT1-dependent manner. Knockdown of SIRT1 (small interfering RNA) or inhibition of NO synthesis prevented resveratrol-induced mitochondrial biogenesis. In aortas of type 2 diabetic (db/db) mice impaired mitochondrial biogenesis was normalized by chronic resveratrol treatment, showing the in vivo relevance of our findings. Resveratrol increases mitochondrial content in endothelial cells via activating SIRT1. We propose that SIRT1, via a pathway that involves the upregulation of eNOS, induces mitochondrial biogenesis. Resveratrol induced mitochondrial biogenesis in the aortas of type 2 diabetic mice, suggesting the potential for new treatment approaches targeting endothelial mitochondria in metabolic diseases.
C1 [Csiszar, Anna; Labinskyy, Nazar; Ungvari, Zoltan] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Pinto, John T.] New York Med Coll, Dept Biochem, Valhalla, NY 10595 USA.
[Ballabh, Praveen] New York Med Coll, Dept Cell Biol & Anat & Pediat, Valhalla, NY 10595 USA.
[Zhang, Hanrui; Zhang, Cuihua] Univ Missouri, Dept Internal Med Med Pharmacol & Physiol & Nutr, Columbia, MO USA.
[Losonczy, Gyorgy; Ungvari, Zoltan] Semmelweis Univ, Dept Pulmonol, H-1085 Budapest, Hungary.
[Pearson, Kevin; de Cabo, Rafael] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA.
[Pacher, Pal] NIAAA, Lab Physiol Studies, Sect Oxidat Stress Tissue Injury, NIH, Bethesda, MD USA.
[Ungvari, Zoltan] Univ Oklahoma, Hlth Sci Ctr, Dept Geriatr Med, Reynolds Oklahoma Ctr Aging, Oklahoma City, OK USA.
RP Ungvari, Z (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
EM anna_csiszar@nymc.edu; zoltan_ungvari@nymc.edu
RI Pacher, Pal/B-6378-2008; de Cabo, Rafael/J-5230-2016;
OI Pacher, Pal/0000-0001-7036-8108; de Cabo, Rafael/0000-0002-3354-2442;
Zhang, Hanrui/0000-0001-8655-938X; , rafael/0000-0003-2830-5693
FU American Diabetes Association; American Heart Association [110350047A];
American Federation for Aging Research; National Institutes of Health
(NIH) [HL-077256, HL-43023, CA-111842, RO1-HL077566, RO1-HL085119];
Hungarian Science Fund [OTKA 68758]; Intramural Research Program
FX This work was supported by grants from the American Diabetes Association
(to Z. Ungvari); the American Heart Association (Grant 110350047A to C.
Zhang); the American Federation for Aging Research (to A. Csiszar);
National Institutes of Health (NIH) Grants HL-077256 and HL-43023 (to Z.
Ungvari), CA-111842 (to J. Pinto), and RO1-HL077566 and RO1-HL085119 (to
C. Zhang); the Hungarian Science Fund (OTKA 68758 to G. Losonczy); and
the Intramural Research Program of NIH (to P. Pacher and R. de Cabo).
NR 47
TC 184
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U1 0
U2 18
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP H13
EP H20
DI 10.1152/ajpheart.00368.2009
PG 8
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 464GI
UT WOS:000267492900004
PM 19429820
ER
PT J
AU Zhang, YF
El-Sikhry, H
Chaudhary, KR
Batchu, SN
Shayeganpour, A
Jukar, TO
Bradbury, JA
Graves, JP
DeGraff, LM
Myers, P
Rouse, DC
Foley, J
Nyska, A
Zeldin, DC
Seubert, JM
AF Zhang, Yunfang
El-Sikhry, Haitham
Chaudhary, Ketul R.
Batchu, Sri Nagarjun
Shayeganpour, Anooshirvan
Jukar, Taibeh Orujy
Bradbury, J. Alyce
Graves, Joan P.
DeGraff, Laura M.
Myers, Page
Rouse, Douglas C.
Foley, Julie
Nyska, Abraham
Zeldin, Darryl C.
Seubert, John M.
TI Overexpression of CYP2J2 provides protection against doxorubicin-induced
cardiotoxicity
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE cytochrome P-450 2J2; heart; function
ID ANKYRIN REPEAT PROTEIN; INDUCED CARDIAC INJURY; INDUCED HEART-FAILURE;
NECROSIS-FACTOR-ALPHA; INDUCED CELL-DEATH; EPOXYEICOSATRIENOIC ACIDS;
OXIDATIVE STRESS; HUMAN MYOCARDIUM; TRANSGENIC MICE; CARP GENE
AB Zhang Y, El-Sikhry H, Chaudhary KR, Batchu SN, Shayeganpour A, Jukar TO, Bradbury JA, Graves JP, DeGraff LM, Myers P, Rouse DC, Foley J, Nyska A, Zeldin DC, Seubert JM. Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol 297: H37-H46, 2009. First published May 8, 2009; doi:10.1152/ajpheart.00983.2008.-Human cytochrome P-450 (CYP)2J2 is abundant in heart and active in biosynthesis of epoxyeicosatrienoic acids (EETs). Recently, we demonstrated that these eicosanoid products protect myocardium from ischemia-reperfusion injury. The present study utilized transgenic (Tr) mice with cardiomyocyte-specific overexpression of human CYP2J2 to investigate protection toward toxicity resulting from acute (0, 5, or 15 mg/kg daily for 3 days, followed by 24-h recovery) or chronic (0, 1.5, or 3.0 mg/kg biweekly for 5 wk, followed by 2-wk recovery) doxorubicin (Dox) administration. Acute treatment resulted in marked elevations of serum lactate dehydrogenase and creatine kinase levels that were significantly greater in wild-type (WT) than CYP2J2 Tr mice. Acute treatment also resulted in less activation of stress response enzymes in CYP2J2 Tr mice (catalase 750% vs. 300% of baseline, caspase- 3 235% vs. 165% of baseline in WT vs. CYP2J2 Tr mice). Moreover, CYP2J2 Tr hearts exhibited less Dox-induced cardiomyocytes apoptosis (measured by TUNEL) compared with WT hearts. After chronic treatment, comparable decreases in body weight were observed in WT and CYP2J2 Tr mice. However, cardiac function, assessed by measurement of fractional shortening with M-mode transthoracic echocardiography, was significantly higher in CYP2J2 Tr than WT hearts after chronic Dox treatment (WT 37 +/- 2%, CYP2J2 Tr 47 +/- 1%). WT mice also had larger increases in beta-myosin heavy chain and cardiac ankryin repeat protein compared with CYP2J2 Tr mice. CYP2J2 Tr hearts had a significantly higher rate of Dox metabolism than WT hearts (2.2 +/- 0.25 vs. 1.6 +/- 0.50 ng.min(-1).100 mu g protein(-1)). In vitro data from H9c2 cells demonstrated that EETs attenuated Dox-induced mitochondrial damage. Together, these data suggest that cardiac-specific overexpression of CYP2J2 limited Dox-induced toxicity.
C1 [Zhang, Yunfang; El-Sikhry, Haitham; Chaudhary, Ketul R.; Batchu, Sri Nagarjun; Shayeganpour, Anooshirvan; Jukar, Taibeh Orujy; Seubert, John M.] Univ Alberta, Fac Pharm & Pharmaceut Sci, Edmonton, AB T6G 2N8, Canada.
[Graves, Joan P.; DeGraff, Laura M.; Myers, Page; Rouse, Douglas C.; Foley, Julie; Nyska, Abraham; Zeldin, Darryl C.] Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC USA.
[Nyska, Abraham] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[Rouse, Douglas C.] Duke Univ, Med Ctr, Durham, NC USA.
RP Seubert, JM (reprint author), Univ Alberta, Fac Pharm & Pharmaceut Sci, 3126 Dent Pharm Ctr, Edmonton, AB T6G 2N8, Canada.
EM jseubert@pharmacy.ualberta.ca
FU Canadian Institutes of Health Research [MOP79465]; Intramural Research
Program of the National Institute of Environmental Health Sciences
[Z01-ES-025034]; Heart and Stroke Foundation of Canada; Alberta Heritage
Foundation for Medical Research
FX This work was supported by a Canadian Institutes of Health Research
Grant (MOP79465, J. M. Seubert) and by the Intramural Research Program
of the National Institute of Environmental Health Sciences
(Z01-ES-025034). J. M. Seubert is the recipient of a New Investigator
Award from the Heart and Stroke Foundation of Canada and a Health
Scholar Award from the Alberta Heritage Foundation for Medical Research.
NR 65
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U1 0
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP H37
EP H46
DI 10.1152/ajpheart.00983.2008
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 464GI
UT WOS:000267492900007
PM 19429816
ER
PT J
AU Xu, D
Perez, RE
Rezaiekhaligh, MH
Bourdi, M
Truog, WE
AF Xu, Dong
Perez, Ricardo E.
Rezaiekhaligh, Mohammad H.
Bourdi, Mohammed
Truog, William E.
TI Knockdown of ERp57 increases BiP/GRP78 induction and protects against
hyperoxia and tunicamycin-induced apoptosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE endoplasmic reticulum stress; unfolded protein response; lung injury;
bronchopulmonary dysplasia; immunoglobulin heavy chain-binding protein
ID ENDOPLASMIC-RETICULUM STRESS; IN-GEL DIGESTION; CELL-DEATH;
BRONCHOPULMONARY DYSPLASIA; ENDOTHELIAL-CELLS; OXIDATIVE STRESS;
DISULFIDE-ISOMERASE; EPITHELIAL-CELLS; LUNG; CALRETICULIN
AB Xu D, Perez RE, Rezaiekhaligh MH, Bourdi M, Truog WE. Knockdown of ERp57 increases BiP/GRP78 induction and protects against hyperoxia and tunicamycin-induced apoptosis. Am J Physiol Lung Cell Mol Physiol 297: L44-L51, 2009. First published May 1, 2009; doi: 10.1152/ajplung.90626.2008.-Supplemental oxygen therapy (hyperoxia) in preterm babies with respiratory stress is associated with lung injury and the development of bronchopulmonary dysplasia. Endoplasmic reticulum (ER) homeostasis plays critical roles in maintaining cellular functions such as protein synthesis, folding, and secretion. Interruption of ER homeostasis causes ER stress and triggers the unfolded protein response, which can lead to apoptosis in persistently stressed cells. ERp57 is an ER protein and is associated with calreticulin and calnexin in protein glycosylation. In this study, we found hyperoxia downregulated ERp57 in neonatal rat lungs and cultured human endothelial cells. Transient transfection of ERp57 small interfering RNA significantly knocked down ERp57 expression and reduced hyperoxia- or tunicamycin-induced apoptosis in human endothelial cells. Apoptosis was decreased from 26.8 to 9.9% in hyperoxia-exposed cells and from 37.8 to 5.0% in tunicamycin-treated cells. The activation of caspase-3 induced by hyperoxia or tunicamycin was diminished and immunoglobulin heavy chain-binding protein/glucose-regulated protein 78-kDa (BiP/GRP78) induction was increased in ERp57 knockdown cells. Overexpression of ERp57 exacerbated hyperoxia- or tunicamycin-induced apoptosis in human endothelial cells. Apoptosis was increased from 10.1 to 14.3% in hyperoxia-exposed cells and from 14.0 to 21.2% in tunicamycin-treated cells. Overexpression of ERp57 also augmented tunicamycin-induced caspase-3 activation and reduced BiP/GRP78 induction. Our results demonstrate that ERp57 can regulate apoptosis in human endothelial cells. It appears that knockdown of ERp57 confers cellular protection against hyperoxia- or tunicamycin-induced apoptosis by inhibition of caspase-3 activation and stimulation of BiP/GRP78 induction.
C1 [Xu, Dong] Univ Missouri, Sch Med, Childrens Mercy Hosp & Clin,Neonatol Res Lab, Pediat Res Ctr,Dept Pediat,Sect Neonatal Perinata, Kansas City, MO 64108 USA.
[Bourdi, Mohammed] NHLBI, Mol & Cellular Toxicol Sect, NIH, Bethesda, MD 20892 USA.
RP Xu, D (reprint author), Univ Missouri, Sch Med, Childrens Mercy Hosp & Clin,Neonatol Res Lab, Pediat Res Ctr,Dept Pediat,Sect Neonatal Perinata, 4th Floor,2401 Gillham Rd, Kansas City, MO 64108 USA.
EM xud@umkc.edu
FU Children's Mercy Hospital, Kansas City (D. Xu)
FX This research work was supported by the Clinical Scholar Award and the
Katherine B. Richardson Grants from Children's Mercy Hospital, Kansas
City (D. Xu).
NR 56
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U1 1
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUL
PY 2009
VL 297
IS 1
BP L44
EP L51
DI 10.1152/ajplung.90626.2008
PG 8
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 474ID
UT WOS:000268276100006
PM 19411306
ER
PT J
AU Schenck, AP
Peacock, SC
Klablinde, CN
Lapin, P
Coan, JF
Brown, ML
AF Schenck, Anna P.
Peacock, Sharon C.
Klablinde, Carrie N.
Lapin, Pauline
Coan, Jim F.
Brown, Martin L.
TI Trends in Colorectal Cancer Test Use in the Medicare Population,
1998-2005
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SCREENING PROCEDURES; PREVENTIVE SERVICES; UNITED-STATES; COLON-CANCER;
BENEFICIARIES; DISPARITIES; REIMBURSEMENT; COLONOSCOPY; GUIDELINES;
ENROLLEES
AB Background: Colorectal cancer (CRC) screening has been covered under the Medicare program since 1998. No prior study has addressed the question of the completeness of CRC screening in the entire Medicare cohort.
Methods: In 2008, CRC test-use rates were analyzed for the national fee-for-service Medicare population using Medicare enrollment and claims data from 1998 through 2005. Annual test-use rates were calculated for fecal occult blood testing, sigmoidoscopy, barium enema, and colonoscopy for each year by the demographic characteristics of enrollees. A current-in-Medicare rate was calculated to assess the percentage of enrollees with CRC testing according to recommended intervals.
Results: Colonoscopy rates have increased every year since the introduction of CRC screening coverage. Test-use rates for all other test modalities have steadily decreased. The percentage of Medicare enrollees receiving appropriate tests has slowly increased. In 2005, 47% of enrollees aged >= 65 years and 33% of enrollees aged 50-64 years had claims indicating that they had been tested according to recommended intervals.
Conclusions: CRC test-use rates in the Medicare population are low. Disparities are apparent by age, race/ethnicity, gender, disability, income, and geographic residence. Much work remains to be done to increase testing to acceptable levels. (Am J Prev Med 2009;37(1):1-7) (C) 2009 American Journal of Preventive Medicine
C1 [Schenck, Anna P.; Peacock, Sharon C.] Carolinas Ctr Med Excellence, Cary, NC 27518 USA.
[Klablinde, Carrie N.; Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Lapin, Pauline; Coan, Jim F.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA.
RP Schenck, AP (reprint author), Carolinas Ctr Med Excellence, 100 Regency Forest,Suite 200, Cary, NC 27518 USA.
EM aschenck@ncqio.sdps.org
FU Centers for Medicare & Medicaid Services (CMS) [500-02-NC03]; National
Cancer Institute (NCI) [YI-PC-1007]
FX The analyses on which this publication is based were performed under
Contract No. 500-02-NC03 (Utilization and Quality Control Peer Review
Organization for the State of North Carolina), sponsored by the Centers
for Medicare & Medicaid Services (CMS) with collaboration from the
National Cancer Institute (NCI) under inter-agency agreement
#YI-PC-1007. The content of this publication does not necessarily
reflect the views or policies of CMS, NCI, or The Carolinas Center for
Medical Excellence. The opinions expressed in this paper are those of
the authors.
NR 31
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2009
VL 37
IS 1
BP 1
EP 7
DI 10.1016/j.amepre.2009.03.009
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 462IE
UT WOS:000267343800001
PM 19423273
ER
PT J
AU Klabunde, CN
Lanier, D
Nadel, MR
McLeod, C
Yuan, GG
Vernon, SW
AF Klabunde, Carrie N.
Lanier, David
Nadel, Marion R.
McLeod, Caroline
Yuan, Gigi
Vernon, Sally W.
TI Colorectal Cancer Screening by Primary Care Physicians Recommendations
and Practices, 2006-2007
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SERVICES TASK-FORCE; PATIENT PREFERENCES; PREVENTIVE SERVICES;
NATIONAL-SURVEY; MEDICARE ENROLLEES; AMERICAN-COLLEGE; OLDER AMERICANS;
UNITED-STATES; COLONOSCOPY; GUIDELINES
AB Background: Primary care physicians (hereafter, physicians) play a critical role in the delivery of colorectal cancer (CRC) screening in the U.S. This study describes the CRC screening recommendations and practices of U.S. physicians and compares them to findings from a 1999-2000 national provider survey.
Methods: Data from 1266 physicians responding to the 2006-2007 National Survey of Primary Care Physicians' Recommendations and Practices for Breast, Cervical, Colorectal, and Lung Cancer Screening (cooperation rate=75%) were analyzed in 2008. Descriptive statistics were used to examine physicians' CRC screening recommendations and practices as well as the office systems used to support screening activities. Sample weights were applied in the analyses to obtain national estimates.
Results: Ninety-five percent of physicians routinely recommend screening colonoscopy to asymptomatic, average-risk patients; 80% recommend fecal occult blood testing (FOBT). Only a minority recommend sigmoidoscopy, double-contrast barium enema, computed tomographic colonography, or fecal DNA testing. Fifty-six percent recommend two screening modalities; 17% recommend one. Nearly all physicians who recommend endoscopy refer their patients for the procedure. Four percent perform sigmoidoscopy, a 25-percentage-point decline from 1999-2000. Although 61% of physicians reported that their practice had guidelines for CRC screening, only 30% use provider reminders; 15% use patient reminders.
Conclusions: Physicians' CRC screening recommendations and practices have changed substantially since 1999-2000. Colonoscopy is now the most frequently recommended test. Most physicians do not recommend the full menu of test options prescribed in national guidelines. Few perform sigmoidoscopy. Office systems to support CRC screening are lacking in many physicians' practices. Given ongoing changes in CRC screening technologies and guidelines, the continued monitoring of physicians' CRC screening recommendations and practices is imperative. (Am J Prev Med 2009;37(1):8-16) Published by Elsevier Inc. on behalf of American journal of Preventive Medicine
C1 [Klabunde, Carrie N.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[McLeod, Caroline] Westat Corp, Rockville, MD USA.
[Yuan, Gigi] Information Management Serv Inc, Silver Spring, MD USA.
[Nadel, Marion R.] CDC, Div Canc Prevent & Control, Atlanta, GA 30333 USA.
[Vernon, Sally W.] Univ Texas Houston, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX USA.
RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd, Bethesda, MD 20892 USA.
EM klabundc@mail.nih.gov
FU National Cancer Institute [N02-PC-51308]; Agency for Healthcare Research
and Quality [Y3-PC-5019-01, Y3-PC-5019-02]; CDC [Y3-PC-6017-01]
FX Funding support for this study was provided by the National Cancer
Institute (contract number N02-PC-51308); the Agency for Healthcare
Research and Quality (inter-agency agreement number Y3-PC-5019-01 and
Y3-PC-5019-02); and the CDC (inter-agency agreement number
Y3-PC-6017-01).
NR 45
TC 113
Z9 119
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2009
VL 37
IS 1
BP 8
EP 16
DI 10.1016/j.amepre.2009.03.008
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 462IE
UT WOS:000267343800002
PM 19442479
ER
PT J
AU Shavers, VL
Underwood, W
Moser, RP
AF Shavers, Vickie L.
Underwood, Willie
Moser, Richard P.
TI Race/Ethnicity and the Perception of the Risk of Developing Prostate
Cancer
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID AFRICAN-AMERICAN MEN
AB Background: Although the higher risk of prostate cancer for African-American men is well known in the medical community, it is not clear how prevalent this knowledge is among African-American men themselves. Both the side effects of treatment and the lack of a demonstrated mortality benefit of routine screening with the prostate-specific antigen test among men in the general population have increased the focus on patient participation in decision making about prostate cancer screening.
Methods: Data on 1075 male respondents to the 2003 Health Information National Trends Study were collected from October 2002 to April 2003 and analyzed in 2008 to examine the associations among race/ethnicity, demographic characteristics, and the perception of the risk of developing prostate cancer for African-American, Hispanic, and non-Hispanic white men aged >= 45 years without a history of prostate cancer.
Results: Nearly 50% of African-American men, 47.4% of Hispanic men, and 43.3% of non-Hispanic white men perceived their likelihood of getting prostate cancer as somewhat or very low. Nearly 18% of African-American men, 21.6% of Hispanic men, and 12.9% of non-Hispanic white men perceived themselves to be more likely to get prostate cancer than the average man of the same age.
Conclusions: Despite statistics to the contrary, few African-American men perceived themselves to have a higher-than-average risk of prostate cancer, while a higher percentage of Hispanic men perceived their risk to be higher than that of the average man of the same age. These findings suggest that all men, but particularly African-American and Hispanic men, could benefit from information regarding their specific risk of developing prostate cancer before making a decision about prostate cancer screening. (Am J Prev Med 2009;37(1):64-67) (C) 2009 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine.
C1 [Shavers, Vickie L.] NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA.
[Moser, Richard P.] NCI, Behav Res Program, Bethesda, MD 20892 USA.
[Underwood, Willie] Roswell Pk Canc Inst, Dept Urol Oncol, Buffalo, NY 14263 USA.
RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, 6130 Execut Blvd,MSC 7344 EPN Room 4005, Bethesda, MD 20892 USA.
EM shaversv@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 16
TC 17
Z9 17
U1 5
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD JUL
PY 2009
VL 37
IS 1
BP 64
EP 67
DI 10.1016/j.amepre.2009.03.007
PG 4
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 462IE
UT WOS:000267343800010
PM 19423272
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI The Randomized Controlled Trial as a Demonstration Project: An Ethical
Perspective
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID CLINICAL-RESEARCH; EQUIPOISE
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
NR 5
TC 14
Z9 14
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD JUL
PY 2009
VL 166
IS 7
BP 743
EP 745
DI 10.1176/appi.ajp.2009.09040538
PG 3
WC Psychiatry
SC Psychiatry
GA 465RF
UT WOS:000267603800001
PM 19570933
ER
PT J
AU Misior, AM
Deshpande, DA
Loza, MJ
Pascual, RM
Hipp, JD
Penn, RB
AF Misior, Anna M.
Deshpande, Deepak A.
Loza, Matthew J.
Pascual, Rodolfo M.
Hipp, Jason D.
Penn, Raymond B.
TI Glucocorticoid- and Protein Kinase A-Dependent Transcriptome Regulation
in Airway Smooth Muscle
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE airway smooth muscle; protein kinase A; glucocorticoid; gene expression;
G protein-coupled receptors
ID GENE-EXPRESSION; CELL-PROLIFERATION; EXTRACELLULAR-MATRIX; COUPLED
RECEPTORS; OLIGONUCLEOTIDE ARRAYS; ASTHMA; CAMP; DEXAMETHASONE; GROWTH;
ACTIVATION
AB Glucocorticoids (GCs) and protein kinase A (PKA)-activating agents (beta-adrenergic receptor agonists) are mainstream asthma therapies based on their ability to prevent or reverse excessive airway smooth muscle (ASM) constriction. Their abilities to regulate another important feature of asthma-excessive ASM growth-are poorly understood. Recent studies have suggested that GCs render agents of inflammation such as IL-1 beta and TNF-alpha mitogenic to ASM, via suppression of (antimitogenic) induced cyclooxygenase-2-dependent PKA activity. To further explore the mechanistic basis of these observations, we assessed the effects of epidermal growth factor and IL-1 beta stimulation, and the modulatory effects of GC treatment and PKA inhibition, on the ASM transcriptome by microarray analysis. Results demonstrate that ASM stimulated with IL-1 beta, in a manner that is often cooperative with stimulation with epidermal growth factor, exhibit a profound capacity to function as immunomodulatory cells. Moreover, results implicate an important role for induced autocrine/paracrine factors (many whose regulation was minimally affected by GCs or PKA inhibition) as regulators of both airway inflammation and ASM growth. Induction of numerous chemokines, in conjunction with regulation of proteases and agents of extracellular matrix remodeling, is suggested as an important mechanism promoting upregulated G protein-coupled receptor signaling capable of stimulating ASM growth. Additional functional assays suggest that intracellular PKA plays a critical role in suppressing the promitogenic effects of induced autocrine factors in ASM. Finally, identification and comparison of GC- and PKA-sensitive genes in ASM provide insight into the complementary effects of beta-agonist/GC combination therapies, and suggest specific genes as important targets for guiding the development of new generations of GCs and adjunct asthma therapies.
C1 [Misior, Anna M.; Deshpande, Deepak A.; Loza, Matthew J.; Pascual, Rodolfo M.; Penn, Raymond B.] Wake Forest Univ Hlth Sci, Dept Internal Med, Winston Salem, NC 27103 USA.
[Misior, Anna M.; Deshpande, Deepak A.; Loza, Matthew J.; Pascual, Rodolfo M.; Penn, Raymond B.] Wake Forest Univ Hlth Sci, Ctr Human Genom, Winston Salem, NC 27103 USA.
[Hipp, Jason D.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Penn, RB (reprint author), Wake Forest Univ, Hlth Sci Ctr, Ctr Human Genom, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM rpenn@wfubmc.edu
FU National Institutes of Health [HL58506]; GlaxoSmithKline
FX This study was funded by National Institutes of Health grant HL58506 (to
R.B.P.) and an independent investigator grant from GlaxoSmithKline (to
R.B.P.).
NR 54
TC 21
Z9 23
U1 1
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA
SN 1044-1549
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL
PY 2009
VL 41
IS 1
BP 24
EP 39
DI 10.1165/rcmb.2008-0266OC
PG 16
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 461YA
UT WOS:000267309000006
PM 19059887
ER
PT J
AU Costello, RB
AF Costello, Rebecca B.
TI Vitamin D and Health in the 21st Century: Federal Initiatives to Advance
Research
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article; Proceedings Paper
CT Symposium on Nutrition and Cardiovascular Disease held at the Annual
Scientific Session of the Southern-Society-for-Clinical-Investigation
CY FEB 12-14, 2009
CL New Orleans, LA
SP Southern Soc Clin Investigat
DE Dietary supplements; Vitamin D; Cardiovascular; National Institutes of
Health
ID PARATHYROID-HORMONE LEVELS; CONGESTIVE-HEART-FAILURE; METABOLIC
SYNDROME; 25-HYDROXYVITAMIN-D LEVELS; SERUM 25-HYDROXYVITAMIN-D; D
SUPPLEMENTATION; US POPULATION; D DEFICIENCY; RISK; PREVALENCE
AB The role for dietary supplements for health maintenance and disease prevention is receiving increasingly more attention in the public media as well as in academic institutions and research centers. The mission of the National Institutes of Health Office of Dietary Supplements is to support and promote the science on the benefits and risks of dietary supplements. To this end, Office of Dietary Supplements supports a number of initiatives to advance the evidence base on vitamin D. These initiatives include an evidence-based review on the relationship of vitamin D and calcium intakes to nutrient status indicators and health outcomes; developing and validating analytical methods for measuring vitamin D in biological fluids and foods; support for continued collection of vitamin D status indicators through the National Health and Nutrition Examination Survey; and funding for National Institutes of Health grants on vitamin D and related health outcomes. Taken together, these programs address research gaps and needs to further the science and exploration of the role of vitamin D in health.
C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
RP Costello, RB (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,3B01, Bethesda, MD 20892 USA.
EM costellb@od.nih.gov
NR 40
TC 3
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0002-9629
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD JUL
PY 2009
VL 338
IS 1
BP 34
EP 39
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472QT
UT WOS:000268147700007
PM 19593101
ER
PT J
AU Rothman, RB
Baumann, MH
AF Rothman, Richard B.
Baumann, Michael H.
TI Appetite Suppressants, Cardiac Valve Disease and Combination
Pharmacotherapy
SO AMERICAN JOURNAL OF THERAPEUTICS
LA English
DT Review
DE amphetamine; obesity; cardiac valve disease; fenfluramine; ephedrine;
addiction
ID VALVULAR HEART-DISEASE; CENTRAL-NERVOUS-SYSTEM; NEUROTRANSMITTER
TRANSPORTERS; WEIGHT-LOSS; IN-VITRO; 5-HT2B RECEPTORS; ANORECTIC DRUGS;
D-FENFLURAMINE; DIET PILLS; RAT-BRAIN
AB The prevalence of obesity in the United States is a major health problem associated with significant morbidity, mortality, and economic burden. Although obesity and drug addiction are typically considered distinct clinical entities, both diseases involve dysregulation of biogenic amine neuron systems in the brain. Thus, research efforts to develop medications for treating drug addiction can contribute insights into the pharmacotherapy for obesity. Here, we review the neurochemical mechanisms of selected stimulant medications used in the treatment of obesity and issues related to fenfluramine-associated cardiac valvulopathy. In particular, we discuss the evidence that cardiac valve disease involves activation of mitogenic serotonin 213 (5-HT(2B)) receptors by norfenfluramine, the major metabolite of fenfluramine. Advances in medication discovery suggest that novel molecular entities that target 2 different neurochemical mechanisms, that is, "combination pharmacotherapy," will yield efficacious antiobesity medications with reduced adverse side effects.
C1 [Rothman, Richard B.; Baumann, Michael H.] Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RP Rothman, RB (reprint author), Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Suite 4500,Triad Bldg,333 Cassell Dr, Baltimore, MD 21224 USA.
EM rrothman@mail.nih.gov
FU National Institutes of Health; National Institute on Drug Abuse.
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Drug Abuse.
NR 81
TC 21
Z9 22
U1 1
U2 6
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-AUG
PY 2009
VL 16
IS 4
BP 354
EP 364
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 475LS
UT WOS:000268361300015
PM 19092640
ER
PT J
AU Tian, F
Hu, XZ
Wu, X
Jiang, H
Pan, HN
Marini, AM
Lipsky, RH
AF Tian, Feng
Hu, Xian-Zhang
Wu, Xuan
Jiang, Hong
Pan, Hongna
Marini, Ann M.
Lipsky, Robert H.
TI Dynamic chromatin remodeling events in hippocampal neurons are
associated with NMDA receptor-mediated activation of Bdnf gene promoter
1
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Tian, Feng; Lipsky, Robert H.] NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20814 USA.
[Hu, Xian-Zhang; Wu, Xuan; Jiang, Hong; Pan, Hongna; Marini, Ann M.] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20892 USA.
[Tian, Feng] NCI, Sect Canc Genet, Genet Branch, NIH, Bethesda, MD USA.
[Lipsky, Robert H.] Inova Fairfax Hosp, Dept Neurosci, Falls Church, VA 22030 USA.
[Lipsky, Robert H.] George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 15
EP 16
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800050
ER
PT J
AU Szyf, M
Meaney, MJP
Turecki, G
Hallet, M
Hertzman, C
Power, C
Suderman, M
Hallett, M
Borghol, N
Provencal, N
McGowan, P
Suomi, SJ
Tremblay, R
AF Szyf, M.
Meaney, M. J. P.
Turecki, G.
Hallet, M.
Hertzman, C.
Power, C.
Suderman, M.
Hallett, M.
Borghol, N.
Provencal, N.
McGowan, P.
Suomi, S. J.
Tremblay, R.
TI Epigenetic mechanisms mediating the long-term impact on behavior of the
social environment in early life
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Szyf, M.; Borghol, N.; Provencal, N.] McGill Univ, Dept Pharmacol, Montreal, PQ H3A 2T5, Canada.
[Meaney, M. J. P.; Turecki, G.; McGowan, P.] Douglas Hosp, Res Ctr, Dept Psychiat, Montreal, PQ, Canada.
[Hallet, M.; Suderman, M.; Hallett, M.] Univ British Columbia, McGill Ctr Bioinformat, Vancouver, BC V5Z 1M9, Canada.
[Hertzman, C.] Univ British Columbia, Dept Hlth Care & Epidemiol, Vancouver, BC V6T 1W5, Canada.
[Power, C.] UCL, Inst Child Hlth, London, England.
[Suomi, S. J.] NICHHD, Comparat Ethol Lab, Poolesville, MD USA.
[Tremblay, R.] Univ Montreal, Montreal, PQ, Canada.
NR 0
TC 2
Z9 2
U1 1
U2 9
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 16
EP 17
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800053
ER
PT J
AU Lee, SB
Park, JH
Park, MH
AF Lee, Seung Bum
Park, Jong Hwan
Park, Myung Hee
TI The effect of hypusine modification and acetylation on the intracellular
localization of eIF5A
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Lee, Seung Bum; Park, Jong Hwan; Park, Myung Hee] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 54
EP 54
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800185
ER
PT J
AU Love, DC
Krause, MM
Hanover, JA
AF Love, Dona C.
Krause, Michael M.
Hanover, John A.
TI O-GlcNAc: friend or foe in feast or famine
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Love, Dona C.; Krause, Michael M.; Hanover, John A.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 60
EP 60
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800205
ER
PT J
AU Marini, AM
Jiang, XY
Tian, F
Du, Y
Copeland, NG
Jenkins, NA
Wu, X
Pan, HN
Xu, K
Kenney, H
Egan, SE
Harris, A
Turley, H
Lipsky, RH
AF Marini, Ann M.
Jiang, Xueying
Tian, Feng
Du, Yang
Copeland, Neal G.
Jenkins, Nancy A.
Wu, Xuan
Pan, Hongna
Xu, Ke
Kenney, Heather
Egan, Sean E.
Harris, Adrian
Turley, Helen
Lipsky, Robert H.
TI Basic helix loop helix B2: a new candidate for targeting the brain
against ischemia?
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Marini, Ann M.; Wu, Xuan; Pan, Hongna] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA.
[Jiang, Xueying; Tian, Feng; Kenney, Heather; Lipsky, Robert H.] NIAAA, Mol Genet Sect, NIH, Bethesda, MD USA.
[Xu, Ke] NIAAA, Sect Human Genet, Neurogenet Lab, NIH, Bethesda, MD USA.
[Du, Yang; Copeland, Neal G.; Jenkins, Nancy A.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Egan, Sean E.] Univ Toronto, Hosp Sick Children, Program Canc Res, Toronto, ON M5G 1X8, Canada.
[Egan, Sean E.] Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada.
[Egan, Sean E.] Univ Toronto, Dept Mol Med Genet, Toronto, ON, Canada.
[Harris, Adrian; Turley, Helen] Univ Oxford, John Radcliffe Hosp, Mol Oncol Lab, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 68
EP 69
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800233
ER
PT J
AU Wolf, R
Howard, OMZ
Dong, HF
Voscopoulos, C
Boeshans, K
Winston, J
Divi, R
Gunsior, M
Goldsmith, P
Ahvazi, B
Chavakis, T
Oppenheim, J
Yuspa, SH
AF Wolf, Ronald
Howard, O. M. Zack
Dong, Hui-Fang
Voscopoulos, Christopher
Boeshans, Karen
Winston, Jason
Divi, Rao
Gunsior, Michele
Goldsmith, Paul
Ahvazi, Bijan
Chavakis, Triantafyllos
Oppenheim, Joost
Yuspa, Stuart H.
TI S100A7 (psoriasin) and S100A15 (Koebnerisin) are almost identical in
sequence but highly distinct in function: implications for disease
pathogenesis
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Wolf, Ronald; Voscopoulos, Christopher; Winston, Jason; Divi, Rao; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Howard, O. M. Zack; Oppenheim, Joost] NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dong, Hui-Fang] NCI, SAIC Frederick, Div Basic Sci & Cellular Immunol, Bethesda, MD 20892 USA.
[Boeshans, Karen; Ahvazi, Bijan] NIAMS, Xray Crystallog Facil, NIH, Bethesda, MD USA.
[Gunsior, Michele; Goldsmith, Paul] NCI, Antibody & Prot Purificat Unit, Ctr Canc Res, Bethesda, MD 20892 USA.
[Chavakis, Triantafyllos] NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Howard, O M Zack/B-6117-2012
OI Howard, O M Zack/0000-0002-0505-7052
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 78
EP 78
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800264
ER
PT J
AU Boasso, A
Vaccari, M
Fuchs, D
Hardy, AW
Tsai, WP
Tryniszewska, E
Shearer, GM
Franchini, G
AF Boasso, Adriano
Vaccari, Monica
Fuchs, Dietmar
Hardy, Andrew W.
Tsai, Wen-Po
Tryniszewska, Elzbieta
Shearer, Gene M.
Franchini, Genoveffa
TI HIV-induced tryptophan catabolism: pathogenic mechanism and target for
immunotherapy
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Boasso, Adriano] Univ London Imperial Coll Sci Technol & Med, Dept Immunol, Chelsea & Westminster Hosp, London, England.
[Vaccari, Monica; Tsai, Wen-Po; Tryniszewska, Elzbieta; Franchini, Genoveffa] NCI, Anim Models & Retroviral Vaccines Sect, NIH, Bethesda, MD 20892 USA.
[Fuchs, Dietmar] Innsbruck Med Univ, Div Biol Chem Bioctr, Innsbruck, Austria.
[Hardy, Andrew W.; Shearer, Gene M.] NCI, Expt Immunol Branch, CCR, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 89
EP 89
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800303
ER
PT J
AU Su, TP
Hayashi, T
AF Su, Tsung-Ping
Hayashi, Teruo
TI Molecular chaperones in ER-mitochondrial calcium signaling
SO AMINO ACIDS
LA English
DT Meeting Abstract
C1 [Su, Tsung-Ping; Hayashi, Teruo] NIDA, Cellular Pathobiol Sect, CNRB, IRP,NIH,DHHS, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD JUL
PY 2009
VL 37
IS 1
SU S
BP 119
EP 120
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 468MN
UT WOS:000267823800410
ER
PT J
AU Motabar, O
Shi, ZD
Goldin, E
Liu, K
Southall, N
Sidransky, E
Austin, CP
Griffiths, GL
Zheng, W
AF Motabar, Omid
Shi, Zhen-Dan
Goldin, Ehud
Liu, Ke
Southall, Noel
Sidransky, Ellen
Austin, Christopher P.
Griffiths, Gary L.
Zheng, Wei
TI A new resorufin-based alpha-glucosidase assay for high-throughput
screening
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE alpha-Glucosidase; Enzyme assay; Assay optimization; Assay
miniaturization; High-throughput screening (HTS); Pompe disease
ID DISEASE TYPE-II; GLYCOGENOSIS TYPE-II; FIBROBLASTS; EXPRESSION;
MUTATIONS; LIBRARIES
AB Mutations in alpha-glucosidase cause accumulation of glycogen in lysosomes, resulting in Pompe disease, a lysosomal storage disorder. Small molecule chaperones that bind to enzyme proteins and correct the misfolding and mistrafficking of mutant proteins have emerged as a new therapeutic approach for the lysosomal storage disorders. In addition, alpha-glucosidase is a therapeutic target for type II diabetes, and alpha-glucosidase inhibitors have been used in the clinic as alternative treatments for this disease. We have developed a new fluorogenic substrate for the alpha-glucosidase enzyme assay, resorufin alpha-D-glucopyranoside. The enzyme reaction product of this new Substrate emits at a peak of 590 nm, reducing the interference from fluorescent compounds seen with the existing fluorogenic substrate, 4-methylumbelliferyl-alpha-D-glucopyranoside. Also, the enzyme kinetic assay can be carried out continuously without the addition Of Stop Solution due to the lower pK(a) of the product of this substrate. Therefore, this new fluorogenic substrate is a useful tool for the alpha-glucosidase enzyme assay and will facilitate compound screening for the development of new therapies for Pompe disease. Published by Elsevier Inc.
C1 [Motabar, Omid; Liu, Ke; Southall, Noel; Austin, Christopher P.; Zheng, Wei] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
[Motabar, Omid; Goldin, Ehud; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Shi, Zhen-Dan; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Zheng, W (reprint author), NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Southall, Noel/H-8991-2012; Zheng, Wei/J-8889-2014
OI Southall, Noel/0000-0003-4500-880X; Zheng, Wei/0000-0003-1034-0757
FU National Institutes of Health (NIH); National Human Genome Research
Institute
FX This research was supported by the Molecular Libraries Initiative of the
National Institutes of Health (NIH) Roadmap for Medical Research and the
Intramural Research Programs of the National Human Genome Research
Institute. The authors thank Paul Shinn for assistance with compound
management.
NR 24
TC 14
Z9 17
U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD JUL 1
PY 2009
VL 390
IS 1
BP 79
EP 84
DI 10.1016/j.ab.2009.04.010
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 452XD
UT WOS:000266573600012
PM 19371716
ER
PT J
AU Alone, DP
Rodriguez, JC
Noland, CL
Nash, HA
AF Alone, Debasmita P.
Rodriguez, Jason C.
Noland, Cameron L.
Nash, Howard A.
TI Impact of Gene Copy Number Variation on Anesthesia in Drosophila
melanogaster
SO ANESTHESIOLOGY
LA English
DT Article
ID CATION CHANNEL; GENOME; MUTATIONS; POLYMORPHISM; NUCLEOTIDE; SELECTION;
VARIANTS; REVEAL; REGION
AB Background Chromosomal deletions and duplications, which result in halving or doubling of copy number in a block of genes, are an important source of variation between Individuals. Phenotypic effects of copy number variation are commonly observed, but effects on sensitivity to volatile anesthetics have not been assessed in any organism.
Methods: The potency with which halothane depresses the righting reflex of fruit flies was measured in congenic Drosophila strains, each of which was heterozygous for a deletion of average size 400 kb. Over 200 strains were examined, thereby scanning approximately half of the fly genome.
Results: Although the vast majority of deletion heterozygotes were indistinguishable from the control, eight had significantly altered sensitivity to halothane. Genetic tests supported the hypothesis that the change in anesthetic sensitivity was the result of reduction in copy number and not adventitious mutations in the strains. Among the eight outliers, the difference in halothane potency ranged from a 25% increase to a 15% decrease. Changes of similar magnitude but distinctive patterns were found when these lines were tested with enflurane, isoflurane, and sevoflurane.
Conclusions: Variation in gene copy number has a significant Impact on anesthetic sensitivity in Drosophila melanogaster. The level of transcription of a few genes must thus be limiting for a normal response to volatiles. Coupling between gene copy and gene expression is universal, and the components of the fly's nervous system are highly conserved, therefore, this work provides a rationale for investigating the clinical impact of copy number variation.
C1 [Nash, Howard A.] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Nash, HA (reprint author), NIMH, Mol Biol Lab, Bldg 35,Room 1B-1002,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM howardnash@mail.nih.gov
FU National Institute of Mental Health, Bethesda, Maryland
FX Supported by the Intramural Program of the National Institute of Mental
Health, Bethesda, Maryland.
NR 42
TC 6
Z9 6
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0003-3022
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUL
PY 2009
VL 111
IS 1
BP 15
EP 24
PG 10
WC Anesthesiology
SC Anesthesiology
GA 462IY
UT WOS:000267346200006
PM 19546691
ER
PT J
AU Takaku, T
Calado, RT
Kajigaya, S
Young, NS
AF Takaku, Tomoiku
Calado, Rodrigo T.
Kajigaya, Sachiko
Young, Neal S.
TI Interleukin-23 receptor (IL-23R) gene polymorphisms in acquired aplastic
anemia
SO ANNALS OF HEMATOLOGY
LA English
DT Article
DE Aplastic anemia; IL-23R; Autoimmune disease; Polymorphism
ID INFLAMMATORY-BOWEL-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE
ASSOCIATION; CROHNS-DISEASE; IL23R GENE; T-CELLS; INTERFERON; IL12B;
IL-12; PATHOPHYSIOLOGY
AB Acquired aplastic anemia (AA) is a rare disease with a complex pathogenesis. In most cases, T cell-mediated immune destruction of hematopoietic cells results in peripheral blood pancytopenia and bone marrow hypoplasia. A subset of the heterodimeric interleukin-23 receptor gene (IL-23R) is significantly associated with autoimmune-mediated diseases. To examine whether IL-23R single nucleotide polymorphisms (SNPs) might contribute to AA, we selected three IL-23R SNPs with amino acid changes (rs11209026: p.Arg381Gln; rs41313262: p.Val362Ile; and rs11465797: p.Thr175Asn) and compared their frequencies in 279 AA patients and 184 ethnically matched healthy controls. The three SNP prevalences were similar between the AA patients and controls. The Arg381Gln variant, which has a strong protective effect against inflammatory bowel disease, showed no association with AA. Furthermore, IL-23 levels in sera were measured in the AA patients and in controls, and there were no significant differences among them. Our results indicate that these three IL-23R SNPs and serum IL-23 level have no apparent impact on susceptibility to AA.
C1 [Takaku, Tomoiku; Calado, Rodrigo T.; Kajigaya, Sachiko; Young, Neal S.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Takaku, T (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,Room 3E 5216,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM takakut@nhlbi.nih.gov
RI Calado, Rodrigo/G-2619-2011
FU National Institutes of Health (NIH)
FX This work was supported by the National Institutes of Health (NIH)
Intramural Research Program. The authors are grateful to Colin Wu for
the assistance with the statistical analysis.
NR 33
TC 7
Z9 7
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-5555
J9 ANN HEMATOL
JI Ann. Hematol.
PD JUL
PY 2009
VL 88
IS 7
BP 653
EP 657
DI 10.1007/s00277-008-0666-6
PG 5
WC Hematology
SC Hematology
GA 448KA
UT WOS:000266260300008
PM 19165485
ER
PT J
AU Paisan-Ruiz, C
Washecka, N
Nath, P
Singleton, AB
Corder, EH
AF Paisan-Ruiz, Coro
Washecka, Nicole
Nath, Priti
Singleton, Andrew B.
Corder, Elizabeth H.
TI Parkinson's Disease and Low Frequency Alleles Found Together Throughout
LRRK2
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Genetic epidemiology; Parkinson's disease; LRRK2; low frequency alleles;
grade-of-membership analysis
ID ALZHEIMERS-DISEASE; GENE VARIANTS; MEMBERSHIP; GENOTYPE; GRADE;
ASSOCIATION; INTEGRATION; PROFILES; RISK; LOCI
AB P>Mutations within LRRK2, most notably p.G2019S, cause Parkinson's disease (PD) in rare monogenic families, and sporadic occurrences in diverse populations. We investigated variation throughout LRRK2 (84 SNPs; genotype or diplotype found for 49 LD blocks) for 275 cases (European ancestry, onset at age 60 or older) and 275 neurologically healthy control subjects (NINDS Neurogenetics Repository). Three grade-of-membership groups, i.e. genetic risk sets, were identified that exactly matched many subjects (cases: 46, 4, 137; controls: 0, 178, 0), and distinguished 94% of the subjects (i.e. > 50% likeness to one set). Set I, affected, carried certain low frequency alleles located in multiple functional domains. Set II was unaffected. Set III, also affected, resembled set II except for slightly elevated frequencies of minor alleles not defining set I. We conclude that certain low frequency alleles distributed throughout LRRK2 are a genetic background to a third of cases, defining a distinct subset.
C1 [Corder, Elizabeth H.] Matrix Genom Inc, Santa Fe, NM 87507 USA.
[Paisan-Ruiz, Coro] UCL Inst Neurol, Mol Neurosci Dept, London WC1N 3BG, England.
[Paisan-Ruiz, Coro] UCL Inst Neurol, Reta Lila Weston Labs, London WC1N 3BG, England.
[Washecka, Nicole; Nath, Priti; Singleton, Andrew B.] NIA, Neurogenet Lab, Mol Genet Sect, NIH, Bethesda, MD 20892 USA.
[Singleton, Andrew B.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
RP Corder, EH (reprint author), Matrix Genom Inc, 3900 Paseo Sol, Santa Fe, NM 87507 USA.
EM elizabeth-corder@hotmail.com
RI Paisan-Ruiz, Coro/C-2912-2009; Singleton, Andrew/C-3010-2009
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health, Department of Health and Human Services [Z01
AG000957-06.]
FX This work was supported in part by the Intramural Research Program of
the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services, project Z01 AG000957-06.
NR 30
TC 10
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JUL
PY 2009
VL 73
BP 391
EP 403
DI 10.1111/j.1469-1809.2009.00524.x
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 457II
UT WOS:000266921300001
PM 19489756
ER
PT J
AU Stanescu, H
Wolfsberg, TG
Moreland, RT
Ayub, MH
Erickson, E
Westbroek, W
Huizing, M
Gahl, WA
Helip-Wooley, A
AF Stanescu, Horia
Wolfsberg, Tyra G.
Moreland, R. Travis
Ayub, Mariam H.
Erickson, Elizabeth
Westbroek, Wendy
Huizing, Marjan
Gahl, William A.
Helip-Wooley, Amanda
TI Identifying Putative Promoter Regions of Hermansky-Pudlak Syndrome Genes
by Means of Phylogenetic Footprinting
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Hermansky-Pudlak syndrome; lysosome-related organelle; phylogenetic
footprinting; promoter; mutation analysis
ID LYSOSOME-RELATED ORGANELLES; BIOGENESIS; PROTEINS; COMPLEX;
IDENTIFICATION; TRAFFICKING; MUTATIONS; SEQUENCES; ELEMENTS; GENOME
AB P>HPS is an autosomal recessive disorder characterized by oculocutaneous albinism and prolonged bleeding. Eight human genes are described resulting in the HPS subtypes 1-8. Certain HPS proteins combine to form Biogenesis of Lysosome-related Organelles Complexes (BLOCs), thought to function in the formation of intracellular vesicles such as melanosomes, platelet dense bodies, and lytic granules. Specifically, BLOC-2 contains the HPS3, HPS5 and HPS6 proteins. We used phylogenetic footprinting to identify conserved regions in the upstream sequences of HPS3, HPS5 and HPS6. These conserved regions were verified to have in vitro transcription activation activity using luciferase reporter assays. Transcription factor binding site analyses of the regions identified 52 putative sites shared by all three genes. When analysis was limited to the conserved footprints, seven binding sites were found shared among all three genes: Pax-5, AIRE, CACD, ZF5, Zic1, E2F and Churchill. The HPS3 conserved upstream region was sequenced in four patients with decreased fibroblast HPS3 RNA levels and only one HPS3 mutation in the coding exons and surrounding exon/intron boundaries; no mutation was found. These findings illustrate the power of phylogenetic footprinting for identifying potential regulatory regions in non-coding sequences and define the first putative promoter elements for any HPS genes.
C1 [Stanescu, Horia; Ayub, Mariam H.; Erickson, Elizabeth; Westbroek, Wendy; Huizing, Marjan; Gahl, William A.; Helip-Wooley, Amanda] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Wolfsberg, Tyra G.; Moreland, R. Travis] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Helip-Wooley, A (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA.
EM ahwooley@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute; National Institutes of Health, Bethesda, Maryland, USA
FX The authors appreciate the advice and assistance of Richard Hess, Robert
Kleta, Elliot Margulies and Anthony Antonelllis. This research was
supported by the Intramural Research Program of the National Human
Genome Research Institute, National Institutes of Health, Bethesda,
Maryland, USA.
NR 29
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JUL
PY 2009
VL 73
BP 422
EP 428
DI 10.1111/j.1469-1809.2009.00525.x
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 457II
UT WOS:000266921300004
PM 19523149
ER
PT J
AU She, DW
Zhang, H
Li, ZH
AF She, Dewei
Zhang, Hong
Li, Zhaohai
TI Testing Hardy-Weinberg Equilibrium using Family Data from Complex
Surveys
SO ANNALS OF HUMAN GENETICS
LA English
DT Article
DE Complex sampling; Hardy-Weinberg Equilibrium; inbreeding coefficient;
Pearson chi(2) based test; Rao-Scott first order correction
ID DISEQUILIBRIUM COEFFICIENT; STATISTICS; ASSOCIATION; HOMOGENEITY
AB P>Genetic data collected during the second phase of the Third National Health and Nutrition Examination Survey (NHANES III) enable us to investigate the association of a wide variety of health factors with regard to genetic variation. The classic question when looking into the genetic variations in a population is whether the population is in the state of Hardy-Weinberg Equilibrium (HWE). Our objective was to develop test procedures using family data from complex surveys such as NHANES III. We developed six Pearson chi(2) based tests for a diallelic locus of autosomal genes. The finite sample properties of the proposed test procedures were evaluated via Monte Carlo simulation studies and the Rao-Scott first order corrected test was recommended. Test procedures were applied to three loci from NHANES III genetic databases, i.e., ADRB2, TGFB1, and VDR. HWE was shown to hold at 0.05 level for all three loci when only families with genotypic information available for two parents and for one or more children were used in the analysis.
C1 [Li, Zhaohai] George Washington Univ, Dept Stat, Stat Program, Washington, DC 20052 USA.
[She, Dewei] EMMES Corp, Rockville, MD 20850 USA.
[Zhang, Hong] Univ Sci & Technol China, Dept Stat & Finance, Hefei 230026, Anhui, Peoples R China.
[Zhang, Hong; Li, Zhaohai] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Li, ZH (reprint author), George Washington Univ, Dept Stat, Stat Program, 2140 Penn Ave,NW, Washington, DC 20052 USA.
EM zli@gwu.edu
FU National Natural Science Foundation of China; Chinese Academy of
Science; Outstanding Overseas Chinese Scholars Fund of Chinese Academy
of Sciences
FX The authors thank Mr. Christopher Sanders and Dr. Geraldine McQuillan
from the National Center for Health Statistics of the Centers for
Disease Control and Prevention for preparing the NHANES III genetic data
for us. This work was supported in part by the National Natural Science
Foundation of China, the Knowledge Innovation Program of the Chinese
Academy of Science, and the Outstanding Overseas Chinese Scholars Fund
of Chinese Academy of Sciences.
NR 24
TC 5
Z9 5
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD JUL
PY 2009
VL 73
BP 449
EP 455
DI 10.1111/j.1469-1809.2009.00528.x
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 457II
UT WOS:000266921300007
PM 19489753
ER
PT J
AU Fang, F
Kamel, F
Lichtenstein, P
Bellocco, R
Sparen, P
Sandler, DP
Ye, WM
AF Fang, Fang
Kamel, Freya
Lichtenstein, Paul
Bellocco, Rino
Sparen, Par
Sandler, Dale P.
Ye, Weimin
TI Familial Aggregation of Amyotrophic Lateral Sclerosis
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID SUPEROXIDE-DISMUTASE; PARKINSONS-DISEASE; SOD1 MUTATION; IDENTIFICATION;
PATIENT; RISK; TWIN; ALS
AB Objective: To assess the relative risk for amyotrophic lateral sclerosis (ALS) in families of ALS patients.
Methods: We conducted a cohort study based on the Swedish Multi-Generation Register in 1961 to 2005. Among 6,671 probands (first ALS case in the family), 1,909 full siblings, 13,947 children, and 5,405 spouses were identified (exposed group). Other persons in the Multi-Generation Register, who were siblings, children, or spouses to persons without ALS, served as the reference group. Relative risks for ALS among the exposed group, compared with the reference group, were calculated from Poisson regression models. Concurrence of ALS within twins was assessed in 86,441 twin pairs registered in the Swedish Twin Register.
Results: Nine cases of ALS were noted among the siblings and 37 cases among the children of the probands, giving a 17-fold risk among the siblings (95% confidence interval, 8.1-30.4) and a 9-fold risk among the children (95% confidence interval, 6.2-12.0), compared with the reference group. Siblings and children had a greater excess risk if the proband was diagnosed at a younger age, and the excess risks decreased with increasing age at diagnosis of the proband (p < 0.001). Spouses had no significantly increased risk (p = 0.27). Two cases were identified among the cotwins of ALS probands, giving a relative risk of 32 (95% confidence interval, 5.2-102.6).
Interpretation: The siblings and children of ALS patients have an about 10-fold risk for ALS compared with the reference group. The excess risks vary with both age and kinship, indicating a major genetic role in familial ALS.
C1 [Fang, Fang; Lichtenstein, Paul; Bellocco, Rino; Sparen, Par; Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Fang, Fang; Kamel, Freya; Sandler, Dale P.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA.
[Bellocco, Rino] Univ Milano Bicocca, Dept Stat, Milan, Italy.
RP Fang, F (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, S-17177 Stockholm, Sweden.
EM fang.fang@ki.se
RI Ye, Weimin/A-5939-2008;
OI lichtenstein, paul/0000-0003-3037-5287; Fang, Fang/0000-0002-3310-6456;
Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018
FU Intramural NIH HHS [NIH0013887932, Z01 ES049005-16]; NIEHS NIH HHS [201
ES49005-15]
NR 21
TC 27
Z9 27
U1 0
U2 0
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0364-5134
J9 ANN NEUROL
JI Ann. Neurol.
PD JUL
PY 2009
VL 66
IS 1
BP 94
EP 99
DI 10.1002/ana.21580
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 481XY
UT WOS:000268847600015
PM 19670447
ER
PT J
AU Moriyama, B
Henning, SA
Neuhauser, MM
Danner, RL
Walsh, TJ
AF Moriyama, Brad
Henning, Stacey A.
Neuhauser, Melinda M.
Danner, Robert L.
Walsh, Thomas J.
TI Continuous-infusion beta-Lactam Antibiotics During Continuous Venovenous
Hemofiltration for the Treatment of Resistant Gram-Negative Bacteria
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE Acinetobacter baumannii; beta-lactam; continuous infusion; continuous
venovenous hemofiltration; Pseudomonas aeruginosa
ID RENAL REPLACEMENT THERAPY; CRITICALLY-ILL PATIENTS;
PSEUDOMONAS-AERUGINOSA INFECTION; SINGLE-DOSE PHARMACOKINETICS; RABBIT
ENDOCARDITIS MODEL; IN-VITRO; CYSTIC-FIBROSIS; CLAVULANIC ACID;
INTERMITTENT INFUSION; ANTIMICROBIAL AGENTS
AB OBJECTIVE: To describe the rationale, principles, and dosage calculations for continuous-infusion beta-lactam antibiotics to treat multidrug-resistant bacteria in patients undergoing continuous venovenous hemofiltration (CVVH).
DATA SOURCES: A MEDLINE search (1968-November 2008) of the English-language literature was performed using the terms continuous infusion and Pseudomonas or Acinetobacter, hemofiltration or CVVH or hemodiafiltration or CVVHDF or continuous renal replacement therapy or pharmacokinetics; and terms describing different beta-lactam antibiotics.
STUDY SELECTION AND DATA EXTRACTION: In vitro, in vivo, and human studies were evaluated that used continuous-infusion beta-lactam antibiotics to treat Pseudomonas aeruginosa and Acinetobacter baumannii infections. Studies were reviewed that described the pharmacokinetics of beta-lactam antibiotics during CVVH as well as other modalities of continuous renal replacement therapy.
DATA SYNTHESIS: Continuous infusion of beta-lactam antibiotics, maintaining drug concentrations 4-5 times higher than the minimum inhibitory concentration, is a promising approach for managing infections caused by P. aeruginosa and A. baumannii. Safe yet effective continuous infusion therapy is made difficult by the occurrence of acute renal failure and the need for renal replacement therapy. Case series and pharmacokinetic properties indicate that several beta-lactam antimicrobials that have been studied for continuous infusion, such as cefepime, ceftazidime, piperacillin, ticarcillin, clavulanic acid, and tazobactam, are significantly cleared by hemofiltration. Methodology and formulas are provided that allow practitioners to calculate dosage regimens and reach target drug concentrations for continuous beta-lactam antibiotic infusions during CVVH based on a literature review, pharmacokinetic principles, and our experience at the National Institutes of Health Clinical Center.
CONCLUSIONS: Continuous infusion of beta-lactam antibiotics may be a useful treatment strategy for multidrug-resistant gram-negative infections in the intensive care unit. Well-established pharmacokinetic and pharmacodynamic principles can be used to safely reach and maintain steady-state target concentrations of beta-lactam antibiotics in critical illness complicated by acute renal failure requiring CVVH.
C1 [Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Moriyama, Brad; Henning, Stacey A.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
[Neuhauser, Melinda M.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA.
[Danner, Robert L.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Walsh, TJ (reprint author), CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA.
EM walsht@mail.nih.gov
FU National Institutes of Health
FX This work was supported in part by the intramural research program of
the National Institutes of Health.
NR 87
TC 9
Z9 10
U1 0
U2 1
PU HARVEY WHITNEY BOOKS CO
PI CINCINNATI
PA PO BOX 42696, CINCINNATI, OH 45242 USA
SN 1060-0280
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD JUL-AUG
PY 2009
VL 43
IS 7-8
BP 1324
EP 1337
DI 10.1345/aph.1L638
PG 14
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 477IM
UT WOS:000268512700020
PM 19584386
ER
PT J
AU Alexander, HR
Bartlett, DL
Libutti, SK
Pingpank, JF
Fraker, DL
Royal, R
Steinberg, SM
Helsabeck, CB
Beresneva, TH
AF Alexander, H. Richard, Jr.
Bartlett, David L.
Libutti, Steven K.
Pingpank, James F.
Fraker, Douglas L.
Royal, Richard
Steinberg, Seth M.
Helsabeck, Cynthia B.
Beresneva, Tatiana H.
TI Analysis of Factors Associated with Outcome in Patients Undergoing
Isolated Hepatic Perfusion for Unresectable Liver Metastases from
Colorectal Center
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; PLUS IRINOTECAN; FLUOROURACIL-LEUCOVORIN; CANCER;
OXALIPLATIN; THERAPY; CETUXIMAB; TRIAL
AB To define the indications for hyperthermic isolated hepatic perfusion (IHP) in patients with unresectable liver metastases (LM) from colorectal cancer (CRC) with particular focus on IHP's utility as a second-line option for patients whose tumors have progressed following combination systemic chemotherapy treatment.
From June 1994 through July 2005, 120 patients with unresectable CRC LM underwent IHP with melphalan (n = 69), tumor necrosis factor (TNF) (n = 10) or both (n = 41). Hepatic arterial infusion (HAI) with floxuridine started 6-8 weeks post IHP in 46 (38%). Patients were followed for toxicity, radiographic response, and overall survival (OS). Wilcoxon rank-sum and Fisher's exact tests were used to compare parameters by response category; survival and hepatic progression-free survival were calculated by the Kaplan-Meier method.
Of 79 males and 41 females, 96 (80%) received prior chemotherapy. There were five (4%) operative/treatment mortalities. There were 69 responses in 114 evaluable patients (61%). Total melphalan dose and combination melphalan/TNF were each associated with response; age, preoperative carcinoembryonic antigen (CEA), prior chemotherapy for established LM, tumor burden, and post-IHP HAI therapy were not. Median overall survival was 17.4 months and 2-year survival was 34%. Factors found to be independently related to survival were preoperative CEA < 30 ng/mL and use of post-IHP HAI (P < 0.015).
IHP results in marked tumor regression and prolonged survival in patients with CRC LM. Continued development of IHP in this clinical setting is warranted.
C1 [Alexander, H. Richard, Jr.] Univ Maryland, Sch Med, Dept Surg Surg Oncol, Baltimore, MD 21201 USA.
[Alexander, H. Richard, Jr.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Alexander, H. Richard, Jr.; Bartlett, David L.; Libutti, Steven K.; Pingpank, James F.; Fraker, Douglas L.; Royal, Richard; Helsabeck, Cynthia B.; Beresneva, Tatiana H.] NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Alexander, HR (reprint author), Univ Maryland, Sch Med, Dept Surg Surg Oncol, Baltimore, MD 21201 USA.
EM HRAlexander@smail.umaryland.edu
FU Center for Cancer Research; NCI, Bethesda; University of Maryland
Marlene; Stewart Greenebaum Cancer Center, Baltimore, Maryland
FX This work was supported by the Center for Cancer Research, NCI,
Bethesda, and the University of Maryland Marlene and Stewart Greenebaum
Cancer Center, Baltimore, Maryland.
NR 26
TC 20
Z9 20
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD JUL
PY 2009
VL 16
IS 7
BP 1852
EP 1859
DI 10.1245/s10434-009-0482-9
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA 458AO
UT WOS:000266982900020
PM 19434456
ER
PT J
AU Fotiou, S
Trimble, EL
Papakonstantinou, K
Kondi-Pafiti, A
Panoskaltsis, T
Deliconstantinos, G
Creatsas, G
AF Fotiou, Stelios
Trimble, Edward L.
Papakonstantinou, Katerina
Kondi-Pafiti, Agatha
Panoskaltsis, Theo
Deliconstantinos, George
Creatsas, George
TI Complete Pelvic Lymphadenectomy in Patients with Clinical Early, Grade I
and II Endometrioid Corpus Cancer
SO ANTICANCER RESEARCH
LA English
DT Article
DE Endometrial cancer; favorable histological characteristics; complete
pelvic lymphadenectomy; pelvic nodal involvement
ID FROZEN-SECTION; LYMPH-NODES; STAGE-I; CARCINOMA; MANAGEMENT; HISTOLOGY;
ACCURACY; CTF
AB Aim: To investigate the risk of pelvic lymph node metastasis in patients with a preoperative diagnosis of early endometrial cancer with favorable histological characteristics, assessed by complete pelvic lymphadenectomy. Patients and Methods: A total of 108 patients with clinical early endometrioid grade I or II endometrial carcinoma underwent complete pelvic lymphadenectomy between 2001-2007. Only cases with at least 15 nodes histologically examined were included. All operations were performed by the same team. The preoperative tumor histology was compared with the final pathological findings. The incidence of pelvic nodal involvement was estimated in relation to the final grade and depth of myometrial invasion in halves. Results: The median age of patients was 63 years. In the final histology, 10 tumors (9.3%) of non-endometrioid histology were found. The discordance between pre- and postoperative tumor grade was 32.4%, with 24.1% being upgraded. Nine patients (8.3%) had poorly differentiated tumors and 23 (21.3%) deep (>50%) myometrial invasion in the final pathology. A total of 11 patients (10.2%) had pelvic nodal metastasis. The rate of lymph node metastasis in relation to final grade I and II and myometrial invasion was as follows: grade 1, 1.8% (inner half 0%, outer half 14.3%); grade 11, 15.9% (inner half 12.1% outer half 27.3%). Overall 19.4% of patients were upstaged at surgery. Conclusion: A significant proportion of patients presenting with early endometrial cancer of optimal characteristics will have a more advanced disease at surgical staging. Complete pelvic lymphadenectomy may increase the possibility of detecting metastatic disease in the lymph nodes.
C1 [Fotiou, Stelios; Papakonstantinou, Katerina; Panoskaltsis, Theo; Deliconstantinos, George; Creatsas, George] Univ Athens, Aretaie Hosp, Sch Med, Dept Obstet & Gynecol 2, Athens 1528, Greece.
[Kondi-Pafiti, Agatha] Univ Athens, Aretaie Hosp, Sch Med, Dept Pathol, Athens 1528, Greece.
[Trimble, Edward L.] NCI, Bethesda, MD 20892 USA.
RP Papakonstantinou, K (reprint author), Univ Athens, Aretaie Hosp, Sch Med, Dept Obstet & Gynecol 2, 76Vas Sofias Ave, Athens 1528, Greece.
EM Foste@otenet.gr; k_papakon@yahoo.gr
NR 24
TC 4
Z9 9
U1 0
U2 0
PU INT INST ANTICANCER RESEARCH
PI ATHENS
PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22,
ATHENS 19014, GREECE
SN 0250-7005
J9 ANTICANCER RES
JI Anticancer Res.
PD JUL
PY 2009
VL 29
IS 7
BP 2781
EP 2785
PG 5
WC Oncology
SC Oncology
GA 472BM
UT WOS:000268104100053
PM 19596961
ER
PT J
AU Sionov, E
Chang, YC
Garraffo, HM
Kwon-Chung, KJ
AF Sionov, Edward
Chang, Yun C.
Garraffo, H. Martin
Kwon-Chung, Kyung J.
TI Heteroresistance to Fluconazole in Cryptococcus neoformans Is Intrinsic
and Associated with Virulence
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID RESISTANT CANDIDA-ALBICANS; DRUG-RESISTANCE; AZOLE RESISTANCE;
ITRACONAZOLE RESISTANCE; ASPERGILLUS-FUMIGATUS; ANTIFUNGAL AGENTS;
PETITE MUTANTS; IN-VIVO; MECHANISMS; AIDS
AB In 1999, heteroresistance to triazoles was reported in Cryptococcus neoformans strains isolated from an azole therapy failure case of cryptococcosis in an AIDS patient and in a diagnostic strain from a non-AIDS patient. In this study, we analyzed 130 strains of C. neoformans isolated from clinical and environmental sources before 1979, prior to the advent of triazoles, and 16 fluconazole (FLC)-resistant strains isolated from AIDS patients undergoing FLC maintenance therapy during 1990 to 2000. All strains isolated prior to 1979 manifested heteroresistance (subset of a population that grows in the presence of FLC) at concentrations between 4 and 64 mu g/ml, and all 16 FLC-resistant AIDS isolates manifested heteroresistance at concentrations between 16 and 128 mu g/ml. Upon exposure to stepwise increases in the concentration of FLC, subpopulations that could grow at higher concentrations emerged. Repeated transfer on drug-free media caused the highly resistant subpopulations to revert to the original level of heteroresistance. The reversion pattern fell into four categories based on the number of transfers required. The strains heteroresistant at >= 32 mu g/ml were significantly more resistant to other xenobiotics and were also more virulent in mice than were those heteroresistant at <= 8 mu g/ml. During FLC treatment of mice infected by strains with low levels of heteroresistance, subpopulations exhibiting higher levels of heteroresistance emerged after a certain period of time. The ABC transporter AFR1, known to efflux FLC, was unrelated to the heteroresistance mechanism. Our study showed that heteroresistance to azole is universal and suggests that heteroresistance contributes to relapse of cryptococcosis during azole maintenance therapy.
C1 [Sionov, Edward; Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Garraffo, H. Martin] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
EM June_Kwon-Chung@nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX This study was supported by funds from the intramural program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 57
TC 48
Z9 48
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD JUL
PY 2009
VL 53
IS 7
BP 2804
EP 2815
DI 10.1128/AAC.00295-09
PG 12
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 462LL
UT WOS:000267354000016
PM 19414582
ER
PT J
AU Spellberg, B
Andes, D
Perez, M
Anglim, A
Bonilla, H
Mathisen, GE
Walsh, TJ
Ibrahim, AS
AF Spellberg, Brad
Andes, David
Perez, Mario
Anglim, Anne
Bonilla, Hector
Mathisen, Glenn E.
Walsh, Thomas J.
Ibrahim, Ashraf S.
TI Safety and Outcomes of Open-Label Deferasirox Iron Chelation Therapy for
Mucormycosis
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID AGENT; DEFEROXAMINE; ZYGOMYCOSIS; MANAGEMENT
AB We sought to describe the safety profile of open-label, adjunctive deferasirox iron chelation therapy in eight patients with biopsy-proven mucormycosis. Deferasirox was administered for an average of 14 days (range, 7 to 21) at 5 to 20 mg/kg of body weight/day. The only adverse effects attributable to deferasirox were rashes in two patients. Deferasirox treatment was not associated with changes in renal or liver function, complete blood count, or transplant immunosuppressive levels. Thus, deferasirox appears safe as an adjunctive therapy for mucormycosis.
C1 [Spellberg, Brad; Ibrahim, Ashraf S.] Harbor Univ Calif LosAngeles, Div Infect Dis, Los Angeles Biomed Res Inst, Med Ctr, Torrance, CA USA.
[Spellberg, Brad; Ibrahim, Ashraf S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Andes, David] Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA.
[Andes, David] Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA.
[Perez, Mario] Univ So Calif, Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90033 USA.
[Anglim, Anne] Long Beach Publ Dept Hlth, Long Beach, CA USA.
[Bonilla, Hector] Summa Hlth Syst, Akron, OH USA.
[Mathisen, Glenn E.] Olive View UCLA, Med Ctr, Div Infect Dis, Sylmar, CA USA.
[Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Spellberg, B (reprint author), 1124 W Carson St,RB2, Torrance, CA 90502 USA.
EM bspellberg@labiomed.org
RI a, a/M-9467-2013
FU NIAID NIH HHS [R01 AI072052, R21 AI064716, K08 AI060641, R01 AI063503]
NR 13
TC 43
Z9 43
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 JUL
PY 2009
VL 53
IS 7
BP 3122
EP 3125
DI 10.1128/AAC.00361-09
PG 4
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 462LL
UT WOS:000267354000064
PM 19433555
ER
PT J
AU Sotelo-Silveira, JR
Lepanto, P
Elizondo, V
Horjales, S
Palacios, F
Martinez-Palma, L
Marin, M
Beckman, JS
Barbeito, L
AF Sotelo-Silveira, Jose R.
Lepanto, Paola
Elizondo, Victoria
Horjales, Sofia
Palacios, Florencia
Martinez-Palma, Laura
Marin, Monica
Beckman, Joseph S.
Barbeito, Luis
TI Axonal Mitochondrial Clusters Containing Mutant SOD1 in Transgenic
Models of ALS
SO ANTIOXIDANTS & REDOX SIGNALING
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PERIAXOPLASMIC RIBOSOMAL PLAQUES; CU,ZN
SUPEROXIDE-DISMUTASE; MOTOR-NEURON DEGENERATION; MYELINATED AXONS;
SPINAL-CORD; TRANSPORT; MICE; PROTEIN; NEUROFILAMENTS
AB We studied the subcellular distribution of mitochondria and superoxide dismutase-1 (SOD1) in whole mounts of microdissected motor axons of rats expressing the ALS-linked SOD1-G93A mutation. The rationale was to determine whether physical interactions between the enzyme and mitochondria were linked to the axonopathy of motor fibers occurring in amyotrophic lateral sclerosis (ALS). Mitochondria and SOD1 displayed a homogeneous distribution along motor axons both in nontransgenic rats and in those overexpressing wild-type SOD1. In contrast, axons from SOD1-G93A rats (older than 35 days) showed accumulation of mitochondria in discrete clusters located at regular intervals. Most of SOD1 immunoreactivity was enriched in these clusters and colocalized with mitochondria, suggesting a recruitment of SOD1-G93A to the organelle. The SOD1/mitochondrial clusters were abundant in motor axons but scarcely seen in sensory axons. Clusters also were stained for neuronal nitric oxide synthase, nitrotyrosine, and cytochrome c. The later also was detected surrounding clusters. Ubiquitin colocalized with clusters only at late stages of the disease. The cytoskeleton was not overtly altered in clusters. These results suggest that mutant SOD1 and defective mitochondria create localized dysfunctional domains in motor axons, which may lead to progressive axonopathy in ALS. Antioxid. Redox Signal. 11, 1535-1545.
C1 [Sotelo-Silveira, Jose R.; Lepanto, Paola; Elizondo, Victoria; Martinez-Palma, Laura; Barbeito, Luis] Inst Invest Biol Clemente Estable, Dept Cell & Mol Neurobiol, Montevideo, Uruguay.
[Sotelo-Silveira, Jose R.; Horjales, Sofia; Palacios, Florencia; Marin, Monica] Fac Ciencias, Dept Cell & Mol Biol, Montevideo, Uruguay.
[Beckman, Joseph S.] Oregon State Univ, Environm Hlth Sci Ctr, Corvallis, OR 97331 USA.
Inst Pasteur Montevideo, Montevideo, Uruguay.
RP Sotelo-Silveira, JR (reprint author), NCI, Lab Mol Technol, ATP, SAIC, Frederick, MD 21701 USA.
EM soteloj@mail.nih.gov; barbeito@pasteur.edu.uy
FU ALSA [963]; PEW Latin American Fellowship in Biomedical Sciences; CSIC;
PDT-CONICYT; PEDECIBA; NIEHS Core Center [ES00240, NS058628, AT002034]
FX We thank the Department of Proteins and Nucleic Acids and the confocal
microscopy core of the IIBCE for their support. Thanks to Pak Chan for
the wtSOD-expressing rats. This work was funded by ALSA grant 963 and
PEW Latin American Fellowship in Biomedical Sciences, to Jose Sotelo,
and in part by Uruguayan agencies like CSIC, PDT-CONICYT, and PEDECIBA.
Part of this work was made possible by access to the Cell Imaging and
Analysis Core of the NIEHS Core Center (ES00240) and support from grants
NS058628 and AT002034. Special thanks to Pablo Diaz and Andres de Leon
for genotyping animals used in this study.; JRSS performed research for
Figs. 2-9; JRSS and LB designed research; PL and VE contributed to Figs.
2, 6, 8, and 9; LMP contributed to Fig. 7; SH, FP, and MM performed
research for Fig. 1; JSB contributed to Fig. 4; JRSS, JSB, and LB
analyzed data and wrote the article.
NR 39
TC 32
Z9 33
U1 0
U2 0
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 2009
VL 11
IS 7
BP 1535
EP 1546
DI 10.1089/ars.2009.2614
PG 13
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 450AJ
UT WOS:000266373100005
PM 19344250
ER
PT J
AU Rosenberg, HF
Dyer, KD
Domachowske, JB
AF Rosenberg, Helene F.
Dyer, Kimberly D.
Domachowske, Joseph B.
TI Respiratory viruses and eosinophils: Exploring the connections
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE Respiratory syncytial virus; Pneumoviruses; Cytokines; Hypersensitivity;
Vaccine
ID VACCINE-ENHANCED DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS;
FORMALIN-INACTIVATED RSV; AIRWAY EPITHELIAL-CELLS; CORONAVIRUS SARS-COV;
SYNCYTIAL VIRUS; INFLUENZA-VIRUS; PNEUMONIA VIRUS; HOST-DEFENSE;
IN-VITRO
AB In this review, we consider the role played by eosinophilic leukocytes in the pathogenesis and pathophysiology of respiratory virus infection. The vast majority of the available information on this topic focuses on respiratory syncytial virus (RSV: Family Paramyxoviridae, genus Pneumovirus), an important pediatric pathogen that infects infants worldwide. There is no vaccine currently available for RSV. A formalin-inactivated RSV vaccine used in a trial in the 1960s elicited immunopathology in response to natural RSV infection: this has been modeled experimentally, primarily in inbred mice and cotton rats. Eosinophils are recruited to the lung tissue in response to formalin-inactivated RSV vaccine antigens in humans and in experimental models. but they may or may not be involved in promoting the severe clinical sequelae observed. Pulmonary eosinophilia elicited in response to primary RSV infection has also been explored: this response is particularly evident in the youngest human infants and in neonatal mouse models. Although pulmonary eosinophilia is nearly always perceived in a negative light, the specific role played by virus-elicited eosinophils - negative, positive or neutral bystander - remain unclear. Lastly, we consider the data that focus on the role of eosinophils in promoting virus clearance and antiviral host defense, and conclude with a recent study that explores the role of eosinophils themselves as targets of virus infection. Published by Elsevier B.V.
C1 [Rosenberg, Helene F.; Dyer, Kimberly D.] NIAID, EBS, LAD, NIH, Bethesda, MD 20892 USA.
[Domachowske, Joseph B.] SUNY Upstate Med Univ, Div Infect Dis, Dept Pediat, Syracuse, NY USA.
RP Rosenberg, HF (reprint author), NIAID, EBS, LAD, NIH, Bldg 10,Room 11C215,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hrosenberg@niaid.nih.gov
FU Division of Intramural Research (DIR); National Institute of Allergy and
Infectious Diseases; Children's Miracle Network of Greater NewYork
FX Research in Dr. Rosenberg's laboratory is supported by the Division of
Intramural Research (DIR) of the National Institute of Allergy and
Infectious Diseases. Research in Dr. Domachowske's laboratory is
supported by the Children's Miracle Network of Greater NewYork.
NR 113
TC 32
Z9 33
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD JUL
PY 2009
VL 83
IS 1
BP 1
EP 9
DI 10.1016/j.antiviral.2009.04.005
PG 9
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 464BP
UT WOS:000267480100001
PM 19375458
ER
PT J
AU Kash, JC
AF Kash, John C.
TI Applications of high-throughput genomics to antiviral research: Evasion
of antiviral responses and activation of inflammation during fulminant
RNA virus infection
SO ANTIVIRAL RESEARCH
LA English
DT Review
DE 1918 Influenza virus; Influenza; Ebola virus; Filovirus; Interferon;
Host response evasion
ID SPANISH INFLUENZA-VIRUS; ACUTE-RESPIRATORY-SYNDROME; INTERFERON
REGULATORY FACTOR-3; INNATE IMMUNE-RESPONSES; EBOLA-VIRUS;
GENE-EXPRESSION; PANDEMIC INFLUENZA; I INTERFERON; H5N1 VIRUS; A VIRUSES
AB Host responses can contribute to the severity of viral infection, through the failure of innate antiviral mechanisms to recognize and restrict the pathogen, the development of intense systemic inflammation leading to circulatory failure or through tissue injury resulting from overly exuberant cell-mediated immune responses. High-throughput genomics methods are now being used to identify the biochemical pathways underlying ineffective or damaging host responses in a number of acute and chronic viral infections. This article reviews recent gene expression studies of 1918 H1N1 influenza and Ebola hemorrhagic fever in cell culture and animal models, focusing on how genomics experiments can be used to increase our understanding of the mechanisms that permit those viruses to cause rapidly overwhelming infection. Particular attention is paid to how evasion of type I IFN responses in infected cells might contribute to over-activation of inflammatory responses. Reviewing recent research and describing how future studies might be tailored to understand the relationship between the infected cell and its environment, this article discusses how the rapidly growing field of high-throughput genomics can contribute to a more complete understanding of severe, acute viral infections and identify novel targets for therapeutic intervention. Published by Elsevier B.V.
C1 NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Kash, JC (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA.
EM kashj@niaid.nih.gov
FU Intramural Research Program; NIH; NIAID
FX I would like to thank Drs. Mike Bray and Jeffery Taubenberger at
NIH/NIAID for helpful discussions and suggestions. This work was
supported by the Intramural Research Program of the NIH and the NIAID.
NR 99
TC 8
Z9 10
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-3542
J9 ANTIVIR RES
JI Antiviral Res.
PD JUL
PY 2009
VL 83
IS 1
BP 10
EP 20
DI 10.1016/j.antiviral.2009.04.004
PG 11
WC Pharmacology & Pharmacy; Virology
SC Pharmacology & Pharmacy; Virology
GA 464BP
UT WOS:000267480100002
PM 19375457
ER
PT J
AU Gualco, G
Chioato, L
Harrington, WJ
Weiss, LM
Bacchi, CE
AF Gualco, Gabriela
Chioato, Lucimara
Harrington, William J., Jr.
Weiss, Lawrence M.
Bacchi, Carlos E.
TI Primary and Secondary T-cell Lymphomas of the Breast Clinico-pathologic
Features of 11 Cases
SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY
LA English
DT Article
DE malignant lymphoma; breast T-cell lymphoma; extranodal; non-Hodgkin
lymphoma; immunohistochemistry
ID NON-HODGKINS-LYMPHOMA; IMPLANTS; CLASSIFICATION; ADJACENT; CANCER; MASS
AB Breast involvement by non-Hodgkin lymphomas is rare, and exceptional for T-cell lymphomas; we studied the morphologic, immunophenotypic, and clinical features of 11 patients with T-cell non-Hodgkin lymphomas involving the breast. Four cases fulfilled the definition criteria for primary breast lymphomas, 3 females and 1 male, with a median age of 51 years. One primary breast lymphomas was T-cell lymphoma unspecified, other was subcutaneous panniculitis-like T-cell lymphoma, and 2 cases were anaplastic large cell lymphomas. One of the anaplastic large cell lymphoma cases was found surrounding a silicone breast implant and presented as clinically as mastitis; whereas the other case occurred in a man. T-cell lymphoma secondarily involved the breast in 7 patients, all women and 1 bilateral, with a median age of 29 years. These secondary breast lymphomas occurred as part of widespread nodal or leukemic disease. Three patients had adult T-cell leukemia/lymphoma, including the patient with bilateral lesions, 3 others had precursor T-lymphoblastic lymphoma/leukemia, and the other presented with a peripheral-T-cell lymphoma nonotherwise specified type. Breast T-cell lymphomas are very infrequent and are morphologically and clinically heterogeneous.
C1 [Gualco, Gabriela; Chioato, Lucimara; Bacchi, Carlos E.] Consultoria Patol, BR-18602010 Sao Paulo, Brazil.
[Harrington, William J., Jr.] Univ Miami, Miller Sch Med, Dept Hematol, Miami, FL 33136 USA.
[Harrington, William J., Jr.] Fogarty Int Ctr AIDS & TB Program, Sylvester Canc Ctr, Miami, FL USA.
[Weiss, Lawrence M.] City Hope Natl Med Ctr, Div Pathol, Duarte, CA 91010 USA.
RP Bacchi, CE (reprint author), Consultoria Patol, Rua Major Leonidas Cardoso 739, BR-18602010 Sao Paulo, Brazil.
EM bacchi@consultoriapatologia.com.br
FU NCI NIH HHS [R01 CA121935, R01 CA121935-03, R01 CA112217-03]
NR 33
TC 32
Z9 32
U1 0
U2 0
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 2009
VL 17
IS 4
BP 301
EP 306
PG 6
WC Anatomy & Morphology; Medical Laboratory Technology; Pathology
SC Anatomy & Morphology; Medical Laboratory Technology; Pathology
GA 464AR
UT WOS:000267477100006
PM 19318917
ER
PT J
AU Lahiri, P
Li, HL
AF Lahiri, Partha
Li, Huilin
TI An adaptive hierarchical Bayes quality measurement plan
SO APPLIED STOCHASTIC MODELS IN BUSINESS AND INDUSTRY
LA English
DT Article
CT 6th International Satellite Symposium on Business and Industrial
Statistics
CY AUG 18-20, 2007
CL Sao Miguel, PORTUGAL
DE parametric bootstrap; empirical Bayes; estimating equations
AB The quality of a production process is often judged by a quality assurance audit, which is essentially a structured system of sampling inspection plan. The defects of sampled products are assessed and compared with a quality standard, which is determined from a tradeoff among manufacturing costs, operating costs and customer needs. In this paper, we propose a new hierarchical Bayes quality measurement plan that assumes an implicit prior for the hyperparameters. The resulting posterior means and variances are obtained adaptively using a parametric bootstrap method. (C) Published in 2009 by John Wiley & Sons, Ltd.
C1 [Lahiri, Partha] Univ Maryland, College Pk, MD 20742 USA.
NCI, Bethesda, MD 20892 USA.
RP Lahiri, P (reprint author), Univ Maryland, 1218 Lefrak Hall, College Pk, MD 20742 USA.
EM plahiri@survey.umd.edu
NR 11
TC 0
Z9 0
U1 0
U2 1
PU JOHN WILEY & SONS LTD
PI CHICHESTER
PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND
SN 1524-1904
J9 APPL STOCH MODEL BUS
JI Appl. Stoch. Models. Bus. Ind.
PD JUL-AUG
PY 2009
VL 25
IS 4
BP 468
EP 477
DI 10.1002/asmb.778
PG 10
WC Operations Research & Management Science; Mathematics, Interdisciplinary
Applications; Statistics & Probability
SC Operations Research & Management Science; Mathematics
GA 492JK
UT WOS:000269651200005
ER
PT J
AU Treutlein, J
Cichon, S
Ridinger, M
Wodarz, N
Soyka, M
Zill, P
Maier, W
Moessner, R
Gaebel, W
Dahmen, N
Fehr, C
Scherbaum, N
Steffens, M
Ludwig, KU
Frank, J
Wichmann, HE
Schreiber, S
Dragano, N
Sommer, WH
Leonardi-Essmann, F
Lourdusamy, A
Gebicke-Haerter, P
Wienker, TF
Sullivan, PF
Nothen, MM
Kiefer, F
Spanagel, R
Mann, K
Rietschel, M
AF Treutlein, Jens
Cichon, Sven
Ridinger, Monika
Wodarz, Norbert
Soyka, Michael
Zill, Peter
Maier, Wolfgang
Moessner, Rainald
Gaebel, Wolfgang
Dahmen, Norbert
Fehr, Christoph
Scherbaum, Norbert
Steffens, Michael
Ludwig, Kerstin U.
Frank, Josef
Wichmann, H. Erich
Schreiber, Stefan
Dragano, Nico
Sommer, Wolfgang H.
Leonardi-Essmann, Fernando
Lourdusamy, Anbarasu
Gebicke-Haerter, Peter
Wienker, Thomas F.
Sullivan, Patrick F.
Noethen, Markus M.
Kiefer, Falk
Spanagel, Rainer
Mann, Karl
Rietschel, Marcella
TI Genome-wide Association Study of Alcohol Dependence
SO ARCHIVES OF GENERAL PSYCHIATRY
LA English
DT Article
ID CONVERGENT FUNCTIONAL GENOMICS; AFFECTED SIB PAIR; BIPOLAR-DISORDER;
LINKAGE DISEQUILIBRIUM; COMMON VARIANTS; CANDIDATE GENES; GENETICS;
RISK; POPULATION; DISEASE
AB Context: Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder.
Objective: To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset.
Design: The GWAS tested 524 396 single-nucleotide polymorphisms (SNPs). All SNPs with P < 10(-4) were subjected to the follow-up study. In addition, nominally significant SNPs from genes that had also shown expression changes in rat brains after long-term alcohol consumption were selected for the follow-up step.
Setting: Five university hospitals in southern and central Germany.
Participants: The GWAS included 487 male inpatients with alcohol dependence as defined by the DSM-IV and an age at onset younger than 28 years and 1358 population-based control individuals. The follow-up study included 1024 male inpatients and 996 age-matched male controls. All the participants were of German descent.
Main Outcome Measures: Significant association findings in the GWAS and follow-up study with the same alleles.
Results: The GWAS produced 121 SNPs with nominal P < 10(-4). These, together with 19 additional SNPs from homologues of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, 2 closely linked intergenic SNPs met genome-wide significance (rs7590720, P=9.72 X 10(-9); rs1344694, P=1.69 X 10(-8)). They are located on chromosome region 2q35, which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including the CDH13 and ADH1C genes, that have been reported to be associated with alcohol dependence.
Conclusions: This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.
C1 [Scherbaum, Norbert] Univ Duisburg Essen, Hosp Essen, Essen, Germany.
[Wichmann, H. Erich] Helmholtz Ctr, Inst Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Univ Munich, Inst Med Data Management Biometr & Epidemiol, Chair Epidemiol, Munich, Germany.
[Schreiber, Stefan] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany.
[Schreiber, Stefan] Univ Kiel, Dept Gen Internal Med, Kiel, Germany.
[Dragano, Nico] Univ Dusseldorf, Dept Med Sociol, Heinz Nixdorf Risk Factors Evaluat Coronary Calci, Dusseldorf, Germany.
[Sommer, Wolfgang H.] NIAAA, Bethesda, MD USA.
[Lourdusamy, Anbarasu] Univ Camerino, Dipartimento Med Sperimentale & Sanita Pubbl, I-62032 Camerino, Italy.
[Sullivan, Patrick F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
RP Rietschel, M (reprint author), Univ Heidelberg, Dept Genet Epidemiol Psychiat, Cent Inst Mental Hlth Mannheim, J5, D-68159 Mannheim, Germany.
EM marcella.rietschel@zi-mannheim.de
RI Schreiber, Stefan/B-6748-2008; Wodarz, Norbert/E-1805-2011; Lourdusamy,
Anbarasu/G-3387-2011; Cichon, Sven/H-8803-2013; Cichon,
Sven/B-9618-2014; Lourdusamy, Anbarasu/P-6606-2014; Kiefer,
Falk/E-8325-2012;
OI Schreiber, Stefan/0000-0003-2254-7771; Cichon, Sven/0000-0002-9475-086X;
Cichon, Sven/0000-0002-9475-086X; Lourdusamy,
Anbarasu/0000-0002-1978-6301; Sommer, Wolfgang/0000-0002-5903-6521;
Steffens, Michael/0000-0002-6445-8593
FU German Federal Ministry of Education and Research [NGFN2, NGFN-Plus FKZ
01GS0117, 01GS08152, FKZ EB01011300, 01EB0410]; Sixth Framework Program
of the European Commission [IMAGENIP-13250]; Alfried Krupp von Bohlen
und Halbach-Stiftung; Heinz Nixdorf Foundation
FX This work was supported by grants from the German Federal Ministry of
Education and Research: NGFN2 and NGFN-Plus FKZ 01GS0117 and 01GS08152
(Drs Mann, Nothen, Rietschel, Schreiber, Spanagel, and Wichmann) and
grants FKZ EB01011300 and 01EB0410 (Drs Mann and Spanagel), and by a
grant from the Sixth Framework Program of the European Commission:
Integrated Project IMAGENIP-13250 (Drs Mann, Rietschel, and Spanagel).
Drs Cichon and Nthen received support from the Alfried Krupp von Bohlen
und Halbach-Stiftung. The Heinz Nixdorf RECALL study was supported by a
grant from the Heinz Nixdorf Foundation.
NR 89
TC 196
Z9 200
U1 5
U2 18
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-990X
J9 ARCH GEN PSYCHIAT
JI Arch. Gen. Psychiatry
PD JUL
PY 2009
VL 66
IS 7
BP 773
EP 784
PG 12
WC Psychiatry
SC Psychiatry
GA 467EI
UT WOS:000267720200012
PM 19581569
ER
PT J
AU Pearlman, RB
Golchet, PR
Feldmann, MG
Yannuzzi, LA
Cooney, MJ
Thorne, JE
Folk, JC
Ryan, EH
Agarwal, A
Barnes, KC
Becker, KG
Jampol, LM
AF Pearlman, Robert B.
Golchet, Pamela R.
Feldmann, Marni G.
Yannuzzi, Lawrence A.
Cooney, Michael J.
Thorne, Jennifer E.
Folk, James C.
Ryan, Edwin H.
Agarwal, Anita
Barnes, Kathleen C.
Becker, Kevin G.
Jampol, Lee M.
TI Increased Prevalence of Autoimmunity in Patients With White Spot
Syndromes and Their Family Members
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID PLACOID PIGMENT EPITHELIOPATHY; JUVENILE RHEUMATOID-ARTHRITIS; OCCULT
OUTER RETINOPATHY; MULTIPLE-SCLEROSIS; MULTIFOCAL CHOROIDITIS;
GENETIC-ANALYSIS; CROHNS-DISEASE; GRANULOMATOSIS; CHOROIDOPATHY;
ASSOCIATION
AB Objective: To determine whether there is an increased prevalence of systemic autoimmune diseases in both patients with white spot syndromes (WSS) and their family members.
Methods: Patients with WSS at participating institutions were asked to complete a questionnaire reporting their own medical histories as well as any autoimmune diseases among their first-and second-degree relatives.
Results: As of January 1, 2008, 114 questionnaires had been collected, providing medical histories of 114 patients with WSS and 1098 family members. The number of patients with WSS with self-reported systemic autoimmune diseases was 26 (23%). Of 1098 relatives, 106 (10%) had at least 1 autoimmune disease. Systemic autoimmunity was more prevalent in female relatives (13%) as compared with male relatives (6%). In addition, the prevalence of autoimmunity was significantly higher among first-degree relatives (13%) than second-degree relatives (8%). Patients who themselves had systemic autoimmune diseases showed a greater prevalence of systemic autoimmunity among their families as compared with the families of patients without systemic autoimmune diseases.
Conclusions: Our data indicate that there is an increased prevalence of systemic autoimmunity in both patients with WSS and their first-and second-degree relatives. This suggests that WSS occur in families with inherited immune dysregulation that predisposes to autoimmunity.
C1 [Pearlman, Robert B.; Golchet, Pamela R.; Feldmann, Marni G.; Jampol, Lee M.] Northwestern Univ, Dept Ophthalmol, Chicago, IL 60611 USA.
[Yannuzzi, Lawrence A.; Cooney, Michael J.] Manhattan Eye & Ear Infirm, New York, NY USA.
[Barnes, Kathleen C.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Becker, Kevin G.] NIH, Baltimore, MD USA.
[Folk, James C.] Univ Iowa, Dept Ophthalmol, Iowa City, IA 52242 USA.
[Ryan, Edwin H.] Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA.
[Agarwal, Anita] Vanderbilt Univ, Dept Ophthalmol, Nashville, TN USA.
RP Jampol, LM (reprint author), Northwestern Univ, Dept Ophthalmol, 645 N Michigan Ave,Ste 440, Chicago, IL 60611 USA.
EM l-jampol@northwestern.edu
OI Becker, Kevin/0000-0002-6794-6656
FU Prevent Blindness Inc; Macula Foundation, Inc, New York; Macula Society;
National Institute on Aging; National Institutes of Health
FX This work was supported in part by an unrestricted grant from Research
to Prevent Blindness Inc, by the Macula Foundation, Inc, New York, by a
grant from the Macula Society, and by the Intramural Research Program,
National Institute on Aging, National Institutes of Health.
NR 26
TC 7
Z9 7
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD JUL
PY 2009
VL 127
IS 7
BP 869
EP 874
PG 6
WC Ophthalmology
SC Ophthalmology
GA 470CK
UT WOS:000267950500005
PM 19597107
ER
PT J
AU Madeo, AC
Manichaikul, A
Reynolds, JC
Sarlis, NJ
Pryor, SP
Shawker, TH
Griffith, AJ
AF Madeo, Anne C.
Manichaikul, Ani
Reynolds, James C.
Sarlis, Nicholas J.
Pryor, Shannon P.
Shawker, Thomas H.
Griffith, Andrew J.
TI Evaluation of the Thyroid in Patients With Hearing Loss and Enlarged
Vestibular Aqueducts
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID GENOTYPE-PHENOTYPE CORRELATION; PENDRED-SYNDROME; IODINE DEFICIENCY;
REFERENCE VALUES; PDS GENE; GOITER; DEAFNESS; VOLUME; ULTRASOUND;
MUTATIONS
AB Objective: To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss.
Design: Prospective cohort survey.
Setting: National Institutes of Health Clinical Center, a federal biomedical research facility.
Patients: The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss.
Main Outcome Measures: Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 (123I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin.
Results: Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P <= .001) greater percentage of (123)I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles.
Conclusions: Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.
C1 [Pryor, Shannon P.; Griffith, Andrew J.] NIDCD, Otolaryngol Branch, NIH, Bethesda, MD 20892 USA.
[Madeo, Anne C.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Sarlis, Nicholas J.] NIDDK, Warren G Magnuson Clin Ctr, Clin Endocrinol Branch, Bethesda, MD USA.
[Manichaikul, Ani] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
RP Griffith, AJ (reprint author), NIDCD, Otolaryngol Branch, NIH, 9000 Rockville Pike,Bldg 5RC Room 1A13-MSC3320, Bethesda, MD 20892 USA.
EM griffita@nidcd.nih.gov
RI Manichaikul, Ani/B-7726-2009; Madeo, Anne/K-2880-2012;
OI Manichaikul, Ani/0000-0002-5998-795X
FU Intramural NIH HHS [ZIA DC000060-09]; NIDCD NIH HHS [Z01 DC000064, Z01
DC000060]
NR 25
TC 11
Z9 12
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD JUL
PY 2009
VL 135
IS 7
BP 670
EP 676
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 472MZ
UT WOS:000268137400009
PM 19620588
ER
PT J
AU Hingson, RW
AF Hingson, Ralph W.
TI The Legal Drinking Age and Underage Drinking in the United States
SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE
LA English
DT Article
ID DATING VIOLENCE VICTIMIZATION; HIGH-SCHOOL-STUDENTS; IV ALCOHOL-ABUSE;
PREVENTIVE INTERVENTIONS; RISK BEHAVIORS; FATAL CRASHES; ONSET;
INVOLVEMENT; DEPENDENCE; TRIAL
C1 NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Ln,Rm 2077, Bethesda, MD 20892 USA.
EM rhingson@mail.nih.gov
RI Miles, Bronte/B-2562-2012
NR 61
TC 4
Z9 4
U1 4
U2 5
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 JUL
PY 2009
VL 163
IS 7
BP 598
EP 600
PG 3
WC Pediatrics
SC Pediatrics
GA 467EK
UT WOS:000267720400001
PM 19581541
ER
PT J
AU Ling, SM
Conwit, RA
Ferrucci, L
Metter, EJ
AF Ling, Shari M.
Conwit, Robin A.
Ferrucci, Luigi
Metter, E. Jeffrey
TI Age-Associated Changes in Motor Unit Physiology: Observations From the
Baltimore Longitudinal Study of Aging
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Aging; Muscles; Rehabilitation
ID ALL-CAUSE MORTALITY; MUSCLE STRENGTH; SKELETAL-MUSCLES; FIRING RATE;
DECOMPOSITION; MEN; PREDICTORS; MOBILITY; QUALITY; WOMEN
AB Age-associated changes in motor unit physiology: observations from the Baltimore Longitudinal Study of Aging.
Objective: To examine motor unit characteristics (size and firing rate) associated with aging.
Design: Cross-sectional, observational.
Setting: Community.
Participants: Baltimore Longitudinal Study of Aging participants (N=102), aged 22.2 to 94.1 years, were studied.
Interventions: Not applicable.
Main Outcome Measures: Surface-represented motor unit size and firing rate were collected from the vastus medialis during knee extension at 10%, 20%, 30%, and 50% of each subject's maximum isometric voluntary contraction (MVC).
Results: MVC declined with older age (P<.0001). Adjusting for differences in MVC, both firing rate and motor unit size per newton force generated began to increase in the 6th decade of life. Motor unit size increased per newton force to a greater extent than firing rate. Those over the age of 75 years also activated significantly larger motor units per unit force (P=.04). Relative to force generated, the average firing rate began increasing at 57.8 +/- 3.4 years and between 50.2 and 56.4 years (+/- 4y) for motor unit size.
Conclusions: The size of motor units and firing rates used to achieve a given force changes with age, particularly after middle age. Whether these changes precede, follow, or occur concurrent to age-related modifications in muscle structure and contractile properties or sarcopenia is not known.
C1 [Ling, Shari M.; Ferrucci, Luigi; Metter, E. Jeffrey] NIA, Clin Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Conwit, Robin A.] NINDS, Intramural Res Program, Bethesda, MD 20892 USA.
RP Ling, SM (reprint author), Harbor Hosp, Clin Res Branch, 5th Fl,3001 S Hanover St, Baltimore, MD 21225 USA.
EM lingsh@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Institute on Aging.
NR 23
TC 15
Z9 15
U1 1
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD JUL
PY 2009
VL 90
IS 7
BP 1237
EP 1240
DI 10.1016/j.apmr.2008.09.565
PG 4
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 470SA
UT WOS:000267999000022
PM 19577038
ER
PT J
AU Shimada, H
Narumi, R
Nagano, M
Yasutake, A
Waalkes, MP
Imamura, Y
AF Shimada, Hideaki
Narumi, Rika
Nagano, Masaaki
Yasutake, Akira
Waalkes, Michael P.
Imamura, Yorishige
TI Strain difference of cadmium-induced testicular toxicity in inbred
Wistar-Imamichi and Fischer 344 rats
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Cd; Testicular toxicity; Strain difference; Rat; Zn
ID ISOLATED INTERSTITIAL-CELLS; INDUCED HEPATOTOXICITY; ZINC;
METALLOTHIONEIN; TESTES; MICE; RESISTANCE; PRETREATMENT; TOLERANCE;
CARCINOGENESIS
AB Previously, we reported that Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl(2), sc and killed 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathological and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), the testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, the testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that the testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats.
C1 [Shimada, Hideaki; Narumi, Rika] Kumamoto Univ, Fac Educ, Kumamoto 8608555, Japan.
[Nagano, Masaaki; Yasutake, Akira] Natl Inst Minamata Dis, Biochem Sect, Kumamoto 8670008, Japan.
[Waalkes, Michael P.] NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA.
[Imamura, Yorishige] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan.
RP Shimada, H (reprint author), Kumamoto Univ, Fac Educ, 2-40-1 Kurokami, Kumamoto 8608555, Japan.
EM hshimada@gpo.kumamoto-u.ac.jp
FU NIH, National Cancer Institute, and Center for Cancer Reasearh
FX This research was supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, and Center for Cancer Reasearh.
NR 28
TC 8
Z9 8
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD JUL
PY 2009
VL 83
IS 7
BP 647
EP 652
DI 10.1007/s00204-009-0442-y
PG 6
WC Toxicology
SC Toxicology
GA 466KL
UT WOS:000267661000005
PM 19479238
ER
PT J
AU Fan, YY
Huang, ZT
Li, L
Wu, MH
Yu, T
Koup, RA
Bailer, RT
Wu, CY
AF Fan, Yan-Ying
Huang, Zi-Tong
Li, Li
Wu, Man-Hui
Yu, Tao
Koup, Richard A.
Bailer, Robert T.
Wu, Chang-You
TI Characterization of SARS-CoV-specific memory T cells from recovered
individuals 4 years after infection
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID ACUTE RESPIRATORY SYNDROME; T(H)1 CELLS; CORONAVIRUS; RESPONSES;
VACCINE; CD4(+); GENERATION; PROTEIN; EFFECTOR; SUBSETS
AB SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-gamma was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8(+) T cells produced IFN-gamma, whereas memory CD4(+) T cells produced IFN-gamma, IL-2 or TNF-alpha. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.
C1 [Fan, Yan-Ying; Li, Li; Wu, Chang-You] Sun Yat Sen Univ, Key Lab Trop Dis Control Res, Minist Educ, Dept Immunol,Zhongshan Sch Med, Guangzhou 510080, Guangdong, Peoples R China.
[Huang, Zi-Tong; Wu, Man-Hui; Yu, Tao] Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510120, Peoples R China.
[Koup, Richard A.; Bailer, Robert T.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Wu, CY (reprint author), Sun Yat Sen Univ, Key Lab Trop Dis Control Res, Minist Educ, Dept Immunol,Zhongshan Sch Med, 74 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China.
EM changyou_wu@yahoo.com
RI Fan, Yanying/F-9208-2014
FU National "863'' Project [2007AA02Z415]; Scientific Technology Program of
Guangdong Province [2006B36005005]; Science and Technology Program of
Guangzhou [2008J1-C141-3]
FX This study was supported by grants from National "863'' Project (No.
2007AA02Z415), Scientific Technology Program of Guangdong Province (No.
2006B36005005) and the Science and Technology Program of Guangzhou (No.
2008J1-C141-3). We sincerely thank the individuals who donated their
blood for this study.
NR 21
TC 12
Z9 12
U1 0
U2 1
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0304-8608
J9 ARCH VIROL
JI Arch. Virol.
PD JUL
PY 2009
VL 154
IS 7
BP 1093
EP 1099
DI 10.1007/s00705-009-0409-6
PG 7
WC Virology
SC Virology
GA 466RK
UT WOS:000267680000008
PM 19526193
ER
PT J
AU Butler, J
Kalogeropoulos, A
Georgiopoulou, V
de Rekeneire, N
Rodondi, N
Smith, AL
Hoffmann, U
Kanaya, A
Newman, AB
Kritchevsky, SB
Vasan, RS
Wilson, PWF
Harris, TB
AF Butler, Javed
Kalogeropoulos, Andreas
Georgiopoulou, Vasiliki
de Rekeneire, Nathalie
Rodondi, Nicolas
Smith, Andrew L.
Hoffmann, Udo
Kanaya, Alka
Newman, Anne B.
Kritchevsky, Stephen B.
Vasan, Ramachandran S.
Wilson, Peter W. F.
Harris, Tamara B.
CA Hlth ABC Study
TI Serum Resistin Concentrations and Risk of New Onset Heart Failure in
Older Persons The Health, Aging, and Body Composition (Health ABC) Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE heart failure; elderly; resistin
ID INSULIN-RESISTANCE; PLASMA RESISTIN; CARDIOVASCULAR EVENTS;
MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; MULTIPLE IMPUTATION;
ISCHEMIC-STROKE; ADIPOSE-TISSUE; OBESITY; ATHEROSCLEROSIS
AB Objective-Resistin is associated with inflammation and insulin resistance and exerts direct effects on myocardial cells including hypertrophy and altered contraction. We investigated the association of serum resistin concentrations with risk for incident heart failure (HF) in humans.
Methods and Results-We studied 2902 older persons without prevalent HF (age, 73.6 +/- 2.9 years; 48.1% men; 58.8% white) enrolled in the Health, Aging, and Body Composition (Health ABC) Study. Correlation between baseline serum resistin concentrations (20.3 +/- 10.0 ng/mL) and clinical variables, biochemistry panel, markers of inflammation and insulin resistance, adipocytokines, and measures of adiposity was weak (all rho <0.25). During a median follow-up of 9.4 years, 341 participants (11.8%) developed HF. Resistin was strongly associated with risk for incident HF in Cox proportional hazards models controlling for clinical variables, biomarkers, and measures of adiposity (HR, 1.15 per 10.0 ng/mL in adjusted model; 95% CI, 1.05 to 1.27; P = 0.003). Results were comparable across sex, race, diabetes mellitus, and prevalent and incident coronary heart disease subgroups. In participants with available left ventricular ejection fraction at HF diagnosis (265 of 341; 77.7%), association of resistin with HF risk was comparable for cases with reduced versus preserved ejection fraction.
Conclusions-Serum resistin concentrations are independently associated with risk for incident HF in older persons. (Arterioscler Thromb Vasc Biol. 2009; 29: 1144-1149.)
C1 [Butler, Javed; Kalogeropoulos, Andreas; Georgiopoulou, Vasiliki; Smith, Andrew L.; Wilson, Peter W. F.] Emory Univ, Atlanta, GA 30322 USA.
[de Rekeneire, Nathalie] Epictr, Paris, France.
[Rodondi, Nicolas] Univ Lausanne, CH-1015 Lausanne, Switzerland.
[Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Kalogeropoulos, Andreas] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Butler, J (reprint author), Emory Univ Hosp, Div Cardiol, 1364 Clifton Rd NE,Suite AT 430, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Kalogeropoulos, Andreas/A-9494-2009; Newman, Anne/C-6408-2013;
OI Kritchevsky, Stephen/0000-0003-3336-6781; Kalogeropoulos,
Andreas/0000-0002-1284-429X; Newman, Anne/0000-0002-0106-1150;
Ramachandran, Vasan/0000-0001-7357-5970
FU National Institute of Aging, National Institutes of Health, Bethesda Md;
[N01-AG-6-2101]; [N01-AG-62103]; [N01-AG-6-2106]; [2K24 HL04334]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Aging, National Institutes of Health,
Bethesda Md, and by grants N01-AG-6-2101, N01-AG-62103, and
N01-AG-6-2106. Dr Vasan was supported by a research career award 2K24
HL04334.
NR 31
TC 41
Z9 42
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP 1144
EP U236
DI 10.1161/ATVBAHA.109.186783
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500025
PM 19372460
ER
PT J
AU Anzinger, JJ
Chang, J
Leyva, FJ
Kruth, HS
AF Anzinger, Joshua J.
Chang, Janet
Leyva, Francisco J.
Kruth, Howard S.
TI Native Low-Density Lipoprotein Uptake by Macrophage Colony-Stimulating
Factor Differentiated Macrophages Is Mediated by Macropinocytosis and
Micropinocytosis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Anzinger, Joshua J.; Chang, Janet; Leyva, Francisco J.; Kruth, Howard S.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E43
EP E43
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500197
ER
PT J
AU Idelman, G
Chatterjee, T
Netzer, N
Neltner, B
Haggerty, C
Gardner, K
Hui, D
Deepe, G
Weintraub, N
AF Idelman, Gila
Chatterjee, Tapan
Netzer, Nir
Neltner, Bonnie
Haggerty, Cynthia
Gardner, Kevin
Hui, David
Deepe, George
Weintraub, Neal
TI Insulin Growth Factor-1 Influences Proinflammatory Phenotype of T Cells:
Possible Implication in Atherogenesis
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Idelman, Gila; Chatterjee, Tapan; Neltner, Bonnie; Hui, David; Deepe, George; Weintraub, Neal] Univ Cincinnati, Cincinnati, OH USA.
[Netzer, Nir] GenoSmart Ltd, Ness Ziona, Israel.
[Haggerty, Cynthia; Gardner, Kevin] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E25
EP E25
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500108
ER
PT J
AU Mohanraj, R
Mukhopadhyay, P
Batkai, S
Mukhopadhyay, B
Patel, V
Pacher, P
AF Mohanraj, Rajesh
Mukhopadhyay, Partha
Batkai, Sandor
Mukhopadhyay, Bani
Patel, Vivek
Pacher, Pal
TI Pharmacological Inhibition of Xanthine Oxidase Attenuates the
Development of Diabetic Cardiomyopathy
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Mohanraj, Rajesh; Mukhopadhyay, Partha; Batkai, Sandor; Mukhopadhyay, Bani; Patel, Vivek; Pacher, Pal] NIAAA, NIH, Rockville, MD 20852 USA.
RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E128
EP E128
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500617
ER
PT J
AU Zabalawi, M
Wilhelm, AJ
Thomas, MJ
Owen, J
Bhat, S
Remaley, AT
Sorci-Thomas, MG
AF Zabalawi, Manal
Wilhelm, Ashley J.
Thomas, Michael J.
Owen, John
Bhat, Shaila
Remaley, Alan T.
Sorci-Thomas, Mary G.
TI Treatment with ApoA-I Reverses Inflammation and Cholesterol Deposition
in the Skin and Lymph Nodes of LDLr-/-, ApoA-I-/- Mice
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc, Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Zabalawi, Manal; Wilhelm, Ashley J.; Thomas, Michael J.; Owen, John; Bhat, Shaila; Sorci-Thomas, Mary G.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E26
EP E26
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500112
ER
PT J
AU Zhu, XW
Owen, JS
Wilson, M
Thomas, MJ
Hiltbold, E
Fessler, MB
Parks, JS
AF Zhu, Xuewei
Owen, John S.
Wilson, Martha
Thomas, Michael J.
Hiltbold, Elizabeth
Fessler, Michael B.
Parks, John S.
TI Macrophage ABCA1 Functions as an Inhibitor of Inflammation Through
Modulation of Cellular Free Cholesterol Content
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Meeting Abstract
CT 10th Annual Conference on Arteriosclerosis, Thrombosis and Vascular
Biology
CY APR 29-MAY 01, 2009
CL Washington, DC
SP Amer Heart Assoc Council Arteriosclerosis, Thrombosis & Vasc Biol
C1 [Zhu, Xuewei; Owen, John S.; Wilson, Martha; Thomas, Michael J.; Hiltbold, Elizabeth; Parks, John S.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Fessler, Michael B.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD JUL
PY 2009
VL 29
IS 7
BP E63
EP E63
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 459LA
UT WOS:000267102500289
ER
PT J
AU Richards, TJ
Eggebeen, A
Gibson, K
Yousem, S
Fuhrman, C
Gochuico, BR
Fertig, N
Oddis, CV
Kaminski, N
Rosas, IO
Ascherman, DP
AF Richards, Thomas J.
Eggebeen, Aaron
Gibson, Kevin
Yousem, Samuel
Fuhrman, Carl
Gochuico, Bernadette R.
Fertig, Noreen
Oddis, Chester V.
Kaminski, Naftali
Rosas, Ivan O.
Ascherman, Dana P.
TI Characterization and Peripheral Blood Biomarker Assessment of Anti-Jo-1
Antibody-Positive Interstitial Lung Disease
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID TRANSFER-RNA-SYNTHETASE; IDIOPATHIC PULMONARY-FIBROSIS;
POLYMYOSITIS-DERMATOMYOSITIS; INFLAMMATORY MYOPATHIES;
CLINICAL-FEATURES; AUTOANTIBODIES; PNEUMONIA; PROGNOSIS; MYOSITIS
AB Objective. Using a combination of clinical, radiographic, functional, and serum protein biomarker assessments, this study was aimed at defining the prevalence and clinical characteristics of interstitial lung disease (ILD) in a large cohort of patients with anti-Jo-1 antibodies.
Methods. A review of clinical records, pulmonary function test results, and findings on imaging studies determined the existence of ILD in anti-Jo-1 antibody-positive individuals whose data were accumulated in the University of Pittsburgh Myositis Database from 1982 to 2007. Multiplex enzyme-linked immunosorbent assays (ELISAs) for serum inflammation markers, cytokines, chemokines, and matrix metalloproteinases in different patient subgroups were performed to assess the serum proteins associated with anti-Jo-1. antibody-positive ILD.
Results. Among the 90 anti-Jo-1 antibody-positive individuals with sufficient clinical, radiographic, and/or pulmonary function data, 77 (86%) met the criteria for ILD. While computed tomography scans revealed a variety of patterns suggestive of underlying usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia, a review of the histopathologic abnormalities in a subset of patients undergoing open lung biopsy or transplantation or whose lung tissue was obtained at autopsy (n = 22) demonstrated a preponderance of UIP and diffuse alveolar damage. Analysis by multiplex ELISA yielded statistically significant associations between anti-Jo-1 antibody-positive ILD and elevated serum levels of C-reactive protein (CRP), CXCL9, and CXCL10, which distinguished this disease entity from idiopathic pulmonary fibrosis and anti-signal recognition particle antibody-positive myositis. Recursive partitioning further demonstrated that combinations of these and other serum protein biomarkers can distinguish these disease subgroups at high levels of sensitivity and specificity.
Conclusion. In this large cohort of anti-Jo-1 antibody-positive individuals, the incidence of ILD approached 90%. Multiplex ELISA demonstrated disease-specific associations between anti-Jo-1 antibody-positive ILD and serum levels of CRP as well as the interferon-gamma-inducible chemokines CXCL9 and CXCL10, highlighting the potential of this approach to define biologically active molecules contributing to the pathogenesis of myositis-associated ILD.
C1 [Ascherman, Dana P.] Univ Pittsburgh, Sch Med, Dept Med, Div Clin Immunol & Rheumatol, Pittsburgh, PA 15261 USA.
[Gochuico, Bernadette R.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rosas, Ivan O.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Rosas, Ivan O.] Harvard Univ, Sch Med, Boston, MA USA.
RP Ascherman, DP (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Clin Immunol & Rheumatol, BST S707,3500 Terrace St, Pittsburgh, PA 15261 USA.
EM irosas@rics.bwh.harvard.edu; ascher@pitt.edu
OI Kaminski, Naftali/0000-0001-5917-4601
FU NIH [HL-0894932, HL-073745, HL-087030, K08-AR-047891]; Arthritis
Foundation Arthritis Investigator
FX Drs. Richards and Kaminski's work was supported by NIH grants HL-0894932
and HL-073745. Dr. Gibson's work was supported by NIH grant HL-0894932.
Dr. Kaminski holds the Dorothy P. and Richard P. Simmons Endowed Chair
for Interstitial Lung Disease at the University of Pittsburgh. Dr.
Rosas' work was supported by NIH grant HL-087030. Dr. Ascherman's work
was supported by NIH grant K08-AR-047891; he also is recipient of an
Arthritis Foundation Arthritis Investigator Award.
NR 41
TC 44
Z9 53
U1 1
U2 1
PU WILEY-LISS
PI HOBOKEN
PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 0004-3591
J9 ARTHRITIS RHEUM
JI Arthritis Rheum.
PD JUL
PY 2009
VL 60
IS 7
BP 2183
EP 2192
DI 10.1002/art.24631
PG 10
WC Rheumatology
SC Rheumatology
GA 470HN
UT WOS:000267965900036
PM 19565490
ER
PT J
AU Tian, LW
Lan, Q
Yang, D
He, XZ
Yu, ITS
Hammond, SK
AF Tian, Linwei
Lan, Qing
Yang, Dong
He, Xingzhou
Yu, Ignatius T. S.
Hammond, S. Katharine
TI Effect of chimneys on indoor air concentrations of PM10 and
benzo[a]pyrene in Xuan Wei, China
SO ATMOSPHERIC ENVIRONMENT
LA English
DT Article
DE Coal; Indoor air pollution; Chimney; PM10; Benzo[a]pyrene
ID LUNG-CANCER; RETROSPECTIVE COHORT; IMPROVED COOKSTOVES; STOVE
IMPROVEMENT; COAL; POLLUTION; MORTALITY; EMISSIONS; EXPOSURE; RISK
AB This paper reports the effect of chimneys in reducing indoor air pollution in a lung cancer epidemic area of rural China. Household indoor air pollution concentrations were measured during unvented burning (chimneys blocked) and vented burning (chimneys open) of bituminous coal in Xuan Wei, China. Concentrations of particulate matter with an aerodynamic diameter of 10 mu m or less (PM10) and of benzo[a]pyrene (BaP) were measured in 43 homes during normal activities. The use of chimneys led to significant decreases in indoor air concentrations of particulate matter with an aerodynamic diameter of 10 mu m or less (PM10) by 66% and of benzo[a]pyrene (BaP) by 84%. The average BaP content of PM10 also decreased by 55% with the installation of a chimney. The reduction of indoor pollution levels by the installation of a chimney supports the epidemiology findings on the health benefits of stove improvement. However, even in the presence of a chimney, the indoor air concentrations for both PM10 and BaP still exceeded the indoor air quality standards of China. Movement up the energy ladder to cleaner liquid or gaseous fuels is probably the only sustainable indoor air pollution control measure. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Tian, Linwei; Yu, Ignatius T. S.] Chinese Univ Hong Kong, Sch Publ Hlth, Shatin, Hong Kong, Peoples R China.
[Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Yang, Dong] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[He, Xingzhou] Chinese Acad Prevent Med, Inst Environm Hlth & Engn, Beijing, Peoples R China.
[Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
RP Tian, LW (reprint author), Chinese Univ Hong Kong, Prince Wales Hosp, Sch Publ Hlth, Shatin, Hong Kong, Peoples R China.
EM linweit@cuhk.edu.hk
RI Tian, Linwei/A-9736-2009; Yu, Ignatius Tak Sun/A-9936-2008
OI Tian, Linwei/0000-0002-4739-1534;
NR 15
TC 10
Z9 14
U1 0
U2 18
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1352-2310
J9 ATMOS ENVIRON
JI Atmos. Environ.
PD JUL
PY 2009
VL 43
IS 21
BP 3352
EP 3355
DI 10.1016/j.atmosenv.2009.04.004
PG 4
WC Environmental Sciences; Meteorology & Atmospheric Sciences
SC Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences
GA 464TJ
UT WOS:000267529600008
ER
PT J
AU Dumbacher, JP
Menon, GK
Daly, JW
AF Dumbacher, John P.
Menon, Gopinathan K.
Daly, John W.
TI SKIN AS A TOXIN STORAGE ORGAN IN THE ENDEMIC NEW GUINEAN GENUS PITOHUI
SO AUK
LA English
DT Article
DE batrachotoxin; chemical defense; feathers; Hooded Pitohui; Pitohui
dichrous; skin
ID AVIAN EPIDERMAL DIFFERENTIATION; POISON FROGS DENDROBATIDAE;
STRATUM-CORNEUM LIPIDS; PERMEABILITY BARRIER; NA+ CHANNELS; FUNCTIONAL
CONSIDERATIONS; BATRACHOTOXIN ALKALOIDS; CHEMICAL DEFENSE; PASSERINE
BIRDS; DART FROGS
AB Several bird species in the endemic New Guinean genus Pitohui contain potent defensive toxins of the batrachotoxin family of steroidal alkaloid neurotoxins. We surveyed toxin concentrations in various tissues of Hooded Pitohui (Pitohui dichrous) using radioligand binding assays. The highest concentrations were found in the skin and feathers, on the outside of the birds, where predators or parasites are likely to encounter toxins. Significant levels of toxins also were found in skeletal muscle, heart, and liver. Muscle and liver would normally be poisoned by batrachotoxins; thus, Hooded Pitohuis must be insensitive to the toxins. The presence of toxins in internal organs further argues against the hypothesis that Hooded Pitohuis merely apply toxins topically to skin and feathers. Finally, we used scanning and transmission electron microscopy to examine skin and feathers for unusual morphological or histological adaptations for storing and secreting toxins. The skin of Hooded Pitohuis appears to have typical dermal and epidermal morphology, and we speculate on possible ways in which this species may sequester and secrete toxins using typical avian skin structural features, unique among vertebrates. Received 10 November 2008, accepted 16 January 2009.
C1 [Dumbacher, John P.; Menon, Gopinathan K.] Calif Acad Sci, Dept Birds & Mammals, San Francisco, CA 94118 USA.
[Dumbacher, John P.] Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA.
[Daly, John W.] NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Dumbacher, JP (reprint author), Calif Acad Sci, Dept Birds & Mammals, 55 Mus Concourse Dr,Golden Gate Pk, San Francisco, CA 94118 USA.
EM jdumbacher@calacademy.org
FU National Geographic Society [5082-93]; National Science Foundation
[DEB-0452732]; University of Chicago Hinds Fund; National Institutes of
Health (NIH; through the National Institute of Diabetes and Digestive
and Kidney Diseases [NIDDK]); University of Chicago; Christensen
Research Institute of Madang
FX We thank W. L. Padget, H. M. Garraffo, C. R. Creveling, and T. F. Spande
for help with BTX assays; and S. J. Pruett-Jones, S. A. Arnold, J.
Bergelson, M. Wade, and M. Kreitman for research guidance and for
reading earlier drafts. We thank A. M. Dufty, Jr., S. G. Sealy, and an
anonymous reviewer for helpful comments in review. For help in the field
and permits to collect, we thank the Papua New Guinea (PNG) Department
of Environment and Conservation and the PNG National Museum and Art
Gallery. For funding and support, we thank the National Geographic
Society (grant no. 5082-93), National Science Foundation (grant
DEB-0452732), University of Chicago Hinds Fund, and fellowships from the
National Institutes of Health (NIH; through the National Institute of
Diabetes and Digestive and Kidney Diseases [NIDDK]), William Ramey
Harper Fellowship, GAAN Ecology Fellowship (University of Chicago),
Christensen Research Institute of Madang, and Christensen Fund. Research
at NIH was supported by NIDDK intramural funds. Our coauthor, John W.
Daly, a tireless worker and a wonderful mentor throughout this research,
died of pancreatic cancer on 5 March 2008, while this paper was in
review.
NR 55
TC 10
Z9 10
U1 3
U2 45
PU AMER ORNITHOLOGISTS UNION
PI LAWRENCE
PA ORNITHOLOGICAL SOC NORTH AMER PO BOX 1897, LAWRENCE, KS 66044-8897 USA
SN 0004-8038
J9 AUK
JI AUK
PD JUL
PY 2009
VL 126
IS 3
BP 520
EP 530
DI 10.1525/auk.2009.08230
PG 11
WC Ornithology
SC Zoology
GA 484BY
UT WOS:000269019500006
ER
PT J
AU Narendra, D
Tanaka, A
Suen, DF
Youle, RJ
AF Narendra, Derek
Tanaka, Atsushi
Suen, Der-Fen
Youle, Richard J.
TI Parkin-induced mitophagy in the pathogenesis of Parkinson disease
SO AUTOPHAGY
LA English
DT Article
DE autophagy; mitochondria; Pink1; E3 ligase; ubiquitin; Park2; Park6
ID MITOCHONDRIAL DYSFUNCTION; AUTOPHAGY; DROSOPHILA-PINK1; DEGENERATION;
DEGRADATION; PATHOLOGY; MUTANTS; MUSCLE; PINK1; BRAIN
AB Knockout of the ubiquitin ligase Parkin, the gene product of the Parkinson associated Park2, leads to loss of mitochondrial integrity and function in Drosophila melanogaster. Although Parkin is primarily cytosolic, we have found that Parkin is selectively recruited to dysfunctional mitochondria with low membrane potential and subsequently promotes their autophagy. Here we report that Parkin recruitment is voltage-dependent and independent of changes in ATP or pH. These findings suggest that Parkin promotes mitophagy of dysfunctional mitochondria following loss of mitochondrial membrane potential and implicates the targeted elimination of mitochondria in the pathogenesis of Parkinson disease.
C1 [Narendra, Derek; Tanaka, Atsushi; Suen, Der-Fen; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Narendra, Derek] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr,2C-917, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU NIH; JSPS
FX This work was supported by the NIH intramural program and JSPS Research
Fellowship for Japanese Biomedical and Behavioral Researchers (A.T.).
NR 23
TC 111
Z9 118
U1 0
U2 10
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD JUL 1
PY 2009
VL 5
IS 5
BP 706
EP 708
PG 3
WC Cell Biology
SC Cell Biology
GA 473KQ
UT WOS:000268205300013
PM 19377297
ER
PT J
AU Takikita, S
Myerowitz, R
Schreiner, C
Baum, R
Raben, N
Plotz, PH
AF Takikita, Shoichi
Myerowitz, Rachel
Schreiner, Cynthia
Baum, Rebecca
Raben, Nina
Plotz, Paul H.
TI The values and limits of an in vitro model of Pompe disease The best
laid schemes o' mice an' men ...
SO AUTOPHAGY
LA English
DT Editorial Material
DE lysosomal storage; glycogen; Pompe disease; myotubes; Atg7
AB In Pompe disease, a lysosomal glycogen storage disorder, cardiac and skeletal muscle abnormalities are responsible for premature death and severe weakness. Swollen glycogen-filled lysosomes, the expected pathology, are accompanied in skeletal muscle by a secondary pathology massive accumulation of autophagic debris-that appears to contribute greatly to the weakness. We have tried to reproduce these defects in murine, Pompe myotubes derived from either primary myoblasts or myoblasts with extended proliferative capacity. The cells accumulated large lysosomes filled with glycogen, but, to our disappointment, did not have autophagic buildup even though basal autophagy was intact. When we suppressed autophagy by knocking down Atg7, we found that glycogen uptake by lysosomes was not affected, suggesting that macroautophagy is not the major pathway for glycogen delivery to lysosomes. But two apparently incidental observations-a peculiar distribution of both microinjected dextran and of small acidic structures adjacent to the interior membrane of large alkalinized glycogen-containing lysosomes-raised the possibility that glycogen traffics to the lysosomes by microautophagy or/and by the engulfment of small lysosomes by large ones. The cultured myotubes, therefore, appear to be a useful model for studying the mechanisms involved in glycogen accumulation in Pompe disease and to test substrate deprivation approaches.
C1 [Takikita, Shoichi; Myerowitz, Rachel; Schreiner, Cynthia; Baum, Rebecca; Raben, Nina; Plotz, Paul H.] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA.
[Myerowitz, Rachel] St Marys Coll Maryland, St Marys City, MD 20686 USA.
RP Takikita, S (reprint author), NIAMS NIH, Bethesda, MD 20892 USA.
EM takikitas@mail.nih.gov
FU Intramural NIH HHS [Z01 AR041099-16, Z99 AR999999]
NR 0
TC 7
Z9 8
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD JUL 1
PY 2009
VL 5
IS 5
BP 729
EP 731
PG 3
WC Cell Biology
SC Cell Biology
GA 473KQ
UT WOS:000268205300021
PM 19571661
ER
PT J
AU Tan, YK
Vu, HA
Kusuma, CM
Wu, AG
AF Tan, Yian Kim
Vu, Hao A.
Kusuma, Caroline M.
Wu, Aiguo
TI Implications of autophagy in anthrax pathogenicity
SO AUTOPHAGY
LA English
DT Editorial Material
DE anthrax; lethal factor; lethal toxin; protective antigen; autophagy;
Bacillus anthracis
AB The etiological agent for anthrax is Bacillus anthracis, which produces lethal toxin (IT) that exerts a myriad of effects on many immune cells. In our previous study, it was demonstrated that IT and protective antigen (PA) induce autophagy in mammalian cells. Preliminary results suggest that autophagy may function as a cellular defense mechanism against LT-mediated toxemia. This degradation pathway may also be relevant to other aspects of the immune response in both innate and adaptive immunity. Understanding the role of autophagy in response to anthrax infection and the possibility of modulating this degradation pathway as potential countermeasures are subjects for further investigation.
C1 [Tan, Yian Kim] DSO Natl Labs, Singapore, Singapore.
[Vu, Hao A.] NIH, Natl Biosafety & Biocontainment Training Program, Bethesda, MD 20892 USA.
[Kusuma, Caroline M.] AFG Biosolut Inc, Gaithersburg, MD USA.
RP Wu, AG (reprint author), 8211 Terminal Rd,Suite 1000, Lorton, VA 22079 USA.
EM awu5@gmu.edu
NR 0
TC 4
Z9 4
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD JUL 1
PY 2009
VL 5
IS 5
BP 734
EP 735
PG 2
WC Cell Biology
SC Cell Biology
GA 473KQ
UT WOS:000268205300023
PM 19395870
ER
PT J
AU Pellegrino, D
Shiva, S
Angelone, T
Gladwin, MT
Tota, B
AF Pellegrino, Daniela
Shiva, Sruti
Angelone, Tommaso
Gladwin, Mark T.
Tota, Bruno
TI Nitrite exerts potent negative inotropy in the isolated heart via
eNOS-independent nitric oxide generation and cGMP-PKG pathway activation
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article; Proceedings Paper
CT Experimental Biology 2008 Annual Meeting
CY APR 05-09, 2008
CL San Diego, CA
SP Amer Soc Pharmacol & Expt Therapeut, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Biochem & Mol Biol, Amer Assoc Immunologists, Amer Assoc Anatomists, Amer Physiol Soc
DE Nitrite; Nitric oxide; Heart; Langendorff rat heart; PKG; cGMP; NOS
ID VIVO ISCHEMIA-REPERFUSION; CYCLIC-GMP; IN-VIVO; HYPOXIC CONDITIONS; CA2+
CURRENT; NO; REDUCTION; DEOXYHEMOGLOBIN; PROTECTS; KINETICS
AB The ubiquitous anion nitrite (NO2-) has recently emerged as an endocrine storage form of nitric oxide (NO) and a signalling molecule that mediates a number of biological responses. Although the role of NO in regulating cardiac function has been investigated in depth, the physiological signalling effects of nitrite on cardiac function have only recently been explored. We now show that remarkably low concentrations of nitrite (1 nM) significantly modulate cardiac contractility in isolated and perfused Langendorff rat heart. In particular, nitrite exhibits potent negative inotropic and lusitropic activities as evidenced by a decrease in left ventricular pressure and relaxation, respectively. Furthermore, we demonstrate that the nitrite-dependent effects are mediated by NO formation but independent of NO synthase (NOS) activity. Specifically, nitrite infusion in the Langendorff system produces NO and cGMP/PKG-dependent negative inotropism, as evidenced by the formation of cellular iron-nitrosyl complexes and inhibition of biological effect by NO scavengers and by PKG inhibitors. These data are consistent with the hypothesis that nitrite represents an eNOS-independent source of NO in the heart which modulates cardiac contractility through the NO-cGMP/PKG pathway. The observed high potency of nitrite supports a physiological function of nitrite as a source of cardiomyocyte NO and a fundamental signalling molecule in the heart. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Shiva, Sruti; Gladwin, Mark T.] NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA.
[Angelone, Tommaso; Tota, Bruno] Univ Calabria, Dept Cell Biol, I-87030 Commenda Di Rende, Italy.
[Pellegrino, Daniela] Univ Calabria, Dept Pharmacobiol, I-87030 Commenda Di Rende, Italy.
RP Gladwin, MT (reprint author), NHLBI, Pulm & Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bldg 10 CRC,Room 5-5140,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA.
EM mgladwin@nih.gov; tota@unical.it
OI Angelone, Tommaso/0000-0001-7797-7862
NR 40
TC 13
Z9 13
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2009
VL 1787
IS 7
BP 818
EP 827
DI 10.1016/j.bbabio.2009.02.007
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 467VU
UT WOS:000267772000007
PM 19248761
ER
PT J
AU Switzer, CH
Flores-Santana, W
Mancardi, D
Donzelli, S
Basudhar, D
Ridnour, LA
Miranda, KM
Fukuto, JM
Paolocci, N
Wink, DA
AF Switzer, Christopher H.
Flores-Santana, Wilmarie
Mancardi, Daniele
Donzelli, Sonia
Basudhar, Debashree
Ridnour, Lisa A.
Miranda, Katrina M.
Fukuto, Jon M.
Paolocci, Nazareno
Wink, David A.
TI The emergence of nitroxyl (HNO) as a pharmacological agent
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article; Proceedings Paper
CT Experimental Biology 2008 Annual Meeting
CY APR 05-09, 2008
CL San Diego, CA
SP Amer Soc Pharmacol & Expt Therapeut, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Biochem & Mol Biol, Amer Assoc Immunologists, Amer Assoc Anatomists, Amer Physiol Soc
DE Nitroxyl; Nitric oxide; Heart failure; Ischemia reperfusion injury
ID NITRIC-OXIDE SYNTHASE; NO-CENTER-DOT; ANGELIS SALT;
SUPEROXIDE-DISMUTASE; RESISTANCE ARTERIES; CARDIAC-MUSCLE; CATHEPSIN-B;
IN-VIVO; INHIBITION; ANION
AB Once a virtually unknown nitrogen oxide, nitroxyl (HNO) has emerged as a potential pharmacological agent. Recent advances in the understanding of the chemistry of HNO has led to the an understanding of HNO biochemistry which is vastly different from the known chemistry and biochemistry of nitric oxide (NO), the one-electron oxidation product of HNO. The cardiovascular roles of NO have been extensively studied, as NO is a key modulator of vascular tone and is involved in a number of vascular related pathologies. HNO displays unique cardiovascular properties and has been shown to have positive lusitropic and ionotropic effects in failing hearts without a chronotropic effect. Additionally, HNO causes a release of CGRP and modulates calcium channels such as ryanodine receptors. HNO has shown beneficial effects in ischemia reperfusion injury, as HNO treatment before ischemia-reperfusion reduces infarct size. In addition to the cardiovascular effects observed, HNO has shown initial promise in the realm of cancer therapy. HNO has been demonstrated to inhibit GAPDH, a key glycolytic enzyme. Due to the Warburg effect, inhibiting glycolysis is an attractive target for inhibiting tumor proliferation. Indeed, HNO has recently been shown to inhibit tumor proliferation in mouse xenografts. Additionally, HNO inhibits tumor angiogenesis and induces cancer cell apoptosis. The effects seen with HNO donors are quite different from NO donors and in some cases are opposite. The chemical nature of HNO explains how HNO and NO, although closely chemically related, act so differently in biochemical systems. This also gives insight into the potential molecular motifs that may be reactive towards HNO and opens up a novel field of pharmacological development. Published by Elsevier B.V.
C1 [Switzer, Christopher H.; Flores-Santana, Wilmarie; Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Mancardi, Daniele] Univ Turin, Inst Expt & Clin Pharmacol, I-10124 Turin, Italy.
[Donzelli, Sonia] Univ Hosp Hamburg Eppendorf, Dept Neurol, D-27109 Hamburg, Germany.
[Basudhar, Debashree; Miranda, Katrina M.] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA.
[Fukuto, Jon M.] Calif State Univ, Dept Chem, Rohnert Pk, CA 94928 USA.
[Paolocci, Nazareno] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Paolocci, Nazareno] Univ Perugia, Gen Pathol & Immunol Sect, Dept Clin & Expt Med, I-06100 Perugia, Italy.
RP Wink, DA (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3-B35, Bethesda, MD 20892 USA.
EM wink@mail.nih.gov
RI Miranda, Katrina/B-7823-2009; Switzer, Christopher/D-9203-2013;
OI MANCARDI, Daniele/0000-0003-3809-6047; Paolocci,
Nazareno/0000-0001-7011-997X
FU Intramural NIH HHS [Z01 SC007281-14]
NR 58
TC 64
Z9 64
U1 2
U2 16
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2009
VL 1787
IS 7
BP 835
EP 840
DI 10.1016/j.bbabio.2009.04.015
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 467VU
UT WOS:000267772000009
PM 19426703
ER
PT J
AU Mancardi, D
Penna, C
Merlino, A
Del Soldato, P
Wink, DA
Pagliaro, P
AF Mancardi, Daniele
Penna, Claudia
Merlino, Annalisa
Del Soldato, Piero
Wink, David A.
Pagliaro, Pasquale
TI Physiological and pharmacological features of the novel gasotransmitter:
Hydrogen sulfide
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Article; Proceedings Paper
CT Experimental Biology 2008 Annual Meeting
CY APR 05-09, 2008
CL San Diego, CA
SP Amer Soc Pharmacol & Expt Therapeut, Amer Soc Investigat Pathol, Amer Soc Nutr, Amer Soc Biochem & Mol Biol, Amer Assoc Immunologists, Amer Assoc Anatomists, Amer Physiol Soc
DE Hydrogen sulfide; Cardioprotection; Gasotransmitter; Ischemic
preconditioning; Nitric oxide
ID ISCHEMIA-REPERFUSION INJURY; CYSTATHIONINE-BETA-SYNTHASE; CYTOCHROME-C
OXIDASE; ANIMATION-LIKE STATE; K-ATP CHANNELS; NITRIC-OXIDE;
MYOCARDIAL-ISCHEMIA; CARBON-MONOXIDE; ENDOTHELIAL-CELLS;
HEMORRHAGIC-SHOCK
AB Hydrogen sulfide (H2S) has been known for hundreds of years because of its poisoning effect. Once the basal bio-production became evident its pathophysiological role started to be investigated in depth. H2S is a gas that can be formed by the action of two enzymes, cystathionine gamma-lyase and cystathionine beta-synthase, both involved in the metabolism of cysteine. It has several features in common with the other two well known "gasotransmitters" (nitric oxide and carbon monoxide) in the biological systems. These three gasses share some biological targets; however, they also have dissimilarities. For instance, the three gases target heme-proteins and open K-ATP channels: H2S as NO is an antioxidant, but in contrast to the latter molecule, H2S does not directly form radicals. In the last years H2S has been implicated in several physiological and pathophysiological processes such as long term synaptic potentiation, vasorelaxation, pro-and anti-inflammatory conditions, cardiac inotropism regulation, cardioprotection, and several other physiological mechanisms. We will focus on the biological role of H2S as a molecule able to trigger cell signaling. Our attention will be particularly devoted on the effects in cardiovascular system and in cardioprotection. We will also provide available information on H2S-donating drugs which have so far been tested in order to conjugate the beneficial effect of H2S with other pharmaceutical properties. (C) 2009 Elsevier B.V. All rights reserved.
C1 [Mancardi, Daniele; Penna, Claudia; Merlino, Annalisa; Pagliaro, Pasquale] Univ Turin, Dept Clin & Biol Sci, I-10043 Orbassano, TO, Italy.
[Del Soldato, Piero] CTG Pharma, Milan, Italy.
[Wink, David A.] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
[Pagliaro, Pasquale] INRC, Bologna, Italy.
RP Mancardi, D (reprint author), Univ Turin, Dipartimento Sci Clin & Biol, Osped S Luigi, Reg Gonzole 10, I-10043 Orbassano, TO, Italy.
EM daniele.mancardi@unito.it
RI Pagliaro, Pasquale/E-5239-2010;
OI MANCARDI, Daniele/0000-0003-3809-6047
FU Intramural NIH HHS [Z01 BC010899-01]
NR 106
TC 89
Z9 100
U1 0
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD JUL
PY 2009
VL 1787
IS 7
BP 864
EP 872
DI 10.1016/j.bbabio.2009.03.005
PG 9
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 467VU
UT WOS:000267772000013
PM 19285949
ER
PT J
AU Wolff, J
AF Wolff, J.
TI Plasma membrane tubulin
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Review
DE Microtubule; Integral membrane protein; Linker; Electrostatic; Receptor;
Channel
ID MICROTUBULE-ASSOCIATED PROTEIN-2; D-ASPARTATE RECEPTOR; DIGLYCERIDE
KINASE-ACTIVITY; DEPENDENT ANION CHANNEL; COLCHICINE-BINDING-SITE;
URCHIN EMBRYONIC CILIA; STATHMIN-LIKE DOMAIN; ALPHA-BETA-TUBULIN;
RAT-BRAIN TUBULIN; COATED VESICLES
AB The association of tubulin with the plasma membrane comprises multiple levels of penetration into the bilayer: from integral membrane protein, to attachment via palmitoylation, to surface binding, and to microtubules attached by linker proteins to proteins in the membrane. Here we discuss the soundness and weaknesses of the chemical and biochemical evidence marshaled to support these associations, as well as the mechanisms by which tubulin or microtubules may regulate functions at the plasma membrane. Published by Elsevier B.V.
C1 NIDDK, Lab Biochem & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Wolff, J (reprint author), NIDDK, Lab Biochem & Genet, Natl Inst Hlth, Bethesda, MD 20892 USA.
EM wolffj@mail.nih.gov
NR 290
TC 36
Z9 36
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JUL
PY 2009
VL 1788
IS 7
BP 1415
EP 1433
DI 10.1016/j.bbamem.2009.03.013
PG 19
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 458HJ
UT WOS:000267006200001
PM 19328773
ER
PT J
AU Polgar, O
Ediriwickrema, LS
Robey, RW
Sharma, A
Hegde, RS
Li, YF
Xia, D
Ward, Y
Dean, M
Ozvegy-Laczka, C
Sarkadi, B
Bates, SE
AF Polgar, Orsolya
Ediriwickrema, Lilangi S.
Robey, Robert W.
Sharma, Ajay
Hegde, Ramanujan S.
Li, Yongfu
Xia, Di
Ward, Yvona
Dean, Michael
Ozvegy-Laczka, Csilla
Sarkadi, Balazs
Bates, Susan E.
TI Arginine 383 is a crucial residue in ABCG2 biogenesis
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE ABCG2; ABC transporter; Membrane protein; Mutagenesis; Biogenesis
ID MULTIDRUG-RESISTANCE TRANSPORTER; BREAST-CANCER CELLS;
SUBSTRATE-SPECIFICITY; ENDOPLASMIC-RETICULUM; INSECT CELLS; ACQUIRED
MUTATIONS; FUMITREMORGIN-C; ATP HYDROLYSIS; P-GLYCOPROTEIN; MRP1 ABCC1
AB ABCG2 is an ATP-binding cassette half-transporter initially identified in multidrug-resistant cancer cell lines and recently suggested to play an important role in pharmacokinetics. Here we report studies of a conserved arginine predicted to localize near the cytoplasmic side of TM1. First, we determined the effect of losing charge and bulk at this position via substitutions with glycine and alanine. The R383G mutant when transfected into HEK cells was not detectable on immunoblot or by functional assay, while the R383A mutant exhibited detectable but significantly decreased levels compared to wild-type, partial retention in the ER and altered glycosylation. Efflux of the ABCG2-substrates mitoxantrone and pheophorbide a was observed. Our experiments suggested rapid degradation of the R383A mutant by the proteasome via a kifunensine-insensitive pathway. Interestingly, overnight treatment of the R383A mutant with mitoxantrone assisted in protein maturation as evidenced by a shift to the N-glycosylated form. The R383A mutant when expressed in insect cells, though detected on the surface, had no measurable ATPase activity. In addition, substitution with the positively charged lysine resulted in significantly decreased protein expression levels in HEK cells, while retaining function. In conclusion, arginine 383 is a crucial residue for ABCG2 biogenesis. where even the most conservative mutations have a large impact. Published by Elsevier B.V.
C1 [Polgar, Orsolya; Ediriwickrema, Lilangi S.; Robey, Robert W.; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Sharma, Ajay; Hegde, Ramanujan S.] NIH, Cell Biol & Metab Branch, Bethesda, MD 20892 USA.
[Li, Yongfu; Xia, Di] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Ward, Yvona] NICHHD, Cell & Canc Biol Branch, Natl Canc Inst, Bethesda, MD 20892 USA.
[Dean, Michael] NCI, Human Genet Sect, Lab Genom Div, Frederick, MD 21702 USA.
[Ozvegy-Laczka, Csilla; Sarkadi, Balazs] Hungarian Acad Sci, Natl Med Ctr, Inst Haematol & Immunol, Membrane Res Grp, H-1113 Budapest, Hungary.
RP Bates, SE (reprint author), NCI, Med Oncol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM sebates@helix.nih.gov
RI Dean, Michael/G-8172-2012; Sarkadi, Balazs/I-5024-2013;
OI Dean, Michael/0000-0003-2234-0631; Hegde, Ramanujan/0000-0001-8338-852X
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 66
TC 12
Z9 12
U1 0
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD JUL
PY 2009
VL 1788
IS 7
BP 1434
EP 1443
DI 10.1016/j.bbamem.2009.04.016
PG 10
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 458HJ
UT WOS:000267006200002
PM 19406100
ER
PT J
AU Bras, JM
Singleton, A
AF Bras, Jose Miguel
Singleton, Andrew
TI Genetic susceptibility in Parkinson's disease
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Review
DE Parkinson's disease; Synuclein; Tau; Glucocerebrosidase
ID LRRK2 GLY2385ARG VARIANT; ALPHA-SYNUCLEIN PROMOTER; GLUCOCEREBROSIDASE
GENE; RISK-FACTOR; CHINESE POPULATION; GAUCHER-DISEASE; MAPT H1;
NORWEGIAN POPULATION; PROTEASE HTRA2/OMI; LOCUS TRIPLICATION
AB It is hoped that an understanding of the genetic basis of Parkinson's disease (PD) will lead to an appreciation of the molecular pathogenesis of disease, which in turn will highlight potential points of therapeutic intervention. It is also hoped that such an understanding will allow identification of individuals at risk for disease prior to the onset of motor symptoms. A large amount of work has already been performed in the identification of genetic risk factors for PD and some of this work, particularly those efforts that focus on genes implicated in monogenic forms of PD, have been successful, although hard won. A new era of gene discovery has begun, with the application of genome wide association studies; these promise to facilitate the identification of common genetic risk loci for complex genetic diseases. This is the first of several high throughput technologies that promise to shed light on the (likely) myriad genetic factors involved in this complex, late-onset neurodegenerative disorder. Published by Elsevier B.V
C1 [Bras, Jose Miguel; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bras, Jose Miguel] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Singleton, Andrew] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
RP Singleton, A (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Bras,
Jose/A-1428-2011
FU Intramural Research Program of the National Institute on Aging; National
Institutes of Health; Department of Health and Human Services
[ZOI-AG000957-05]; Portuguese FCT [SFRH/BD/29647/2006]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; Annual Report number
ZOI-AG000957-05 and Portuguese FCT grant #SFRH/BD/29647/2006.
NR 69
TC 23
Z9 23
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD JUL
PY 2009
VL 1792
IS 7
BP 597
EP 603
DI 10.1016/j.bbadis.2008.11.008
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 470FI
UT WOS:000267960200003
PM 19063963
ER
PT J
AU Kosaka, N
Ogawa, M
Choyke, PL
Karassina, N
Corona, C
McDougall, M
Lynch, DT
Hoyt, CC
Levenson, RM
Los, GV
Kobayashi, H
AF Kosaka, Nobuyuki
Ogawa, Mikako
Choyke, Peter L.
Karassina, Natasha
Corona, Cesear
McDougall, Mark
Lynch, David T.
Hoyt, Clifford C.
Levenson, Richard M.
Los, Georgyi V.
Kobayashi, Hisataka
TI In Vivo Stable Tumor-Specific Painting in Various Colors Using
Dehalogenase-Based Protein-Tag Fluorescent Ligands
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID IMMUNOFLUORESCENCE; TECHNOLOGY; TISSUE
AB In vivo fluorescence cancer imaging is an important tool in understanding tumor growth and therapeutic monitoring and can be performed either with endogenously produced fluorescent proteins or with exogenously introduced fluorescent probes bound to targeting molecules. However, endogenous fluorescence proteins cannot be altered after transfection, thus requiring rederivation of cell lines for each desired color, while exogenously targeted fluorescence probes are limited by the heterogeneous expression of naturally occurring cellular targets. In this study, we adapted the dehalogenase-based protein-Tag (HaloTag) system to in vivo cancer imaging, by introducing highly expressed HaloTag receptors (HaloTagR) in cancer cells coupled with a range of externally injected fluorophore-conjugated dehalogenase-reactive reactive linkers. Tumor nodules arising from a single transfected cell line were stably labeled with fluorescence varying in emission spectra front green to near-infrared. After establishing and validating a SHIN3 cell line stably transfected with HaloTagR (HaloTagR-SHIN3), in vivo spectral fluorescence imaging Studies were performed in live animals using a peritoneal dissemination model. The tumor nodules arising from HaloTagR-SHIN3 could be successfully labeled by four different fluorophore-conjugated HaloTag-ligands each emitting light at different wavelengths. These fluorophores could be alternated on serial imaging sessions permitting assessment of interval growth. Fluorescence was retained in histological specimens after fixation. Thus, this tagging system proves versatile both for in vivo and in vitro imaging without requiring modification of the underlying cell line. Thus, this strategy can overcome some of the limitations associated with the use of endogenous fluorescent proteins and exogenous targeted optical agents in current use.
C1 [Kosaka, Nobuyuki; Ogawa, Mikako; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Karassina, Natasha; Corona, Cesear; McDougall, Mark; Los, Georgyi V.] Promega Corp, Madison, WI 53711 USA.
Cambridge Res & Instrumentat, Woburn, MA 01801 USA.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room 1B40,MSC1088,10 Ctr Dr, Bethesda, MD 20892 USA.
EM georgyi.los@promega.com; kobayash@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 14
TC 27
Z9 28
U1 0
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD JUL
PY 2009
VL 20
IS 7
BP 1367
EP 1374
DI 10.1021/bc9001344
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 472NB
UT WOS:000268137700011
PM 19514716
ER
PT J
AU Ramakrishnan, B
Boeggeman, E
Manzoni, M
Zhu, ZY
Loomis, K
Puri, A
Dimitrov, DS
Qasba, PK
AF Ramakrishnan, Boopathy
Boeggeman, Elizabeth
Manzoni, Maria
Zhu, Zhongyu
Loomis, Kristin
Puri, Anu
Dimitrov, Dimiter S.
Qasba, Pradman K.
TI Multiple Site-Specific in Vitro Labeling of Single-Chain Antibody
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID N-ACETYLGALACTOSAMINYLTRANSFERASES; MONOCLONAL-ANTIBODIES;
CANCER-THERAPY; UDP-GALNAC; PROTEINS; IDENTIFICATION; GLYCOSYLATION;
CONJUGATION; RESIDUES
AB For multiple site-specific conjugations of bioactive molecules to a single-chain antibody (scFv) molecule, we have constructed a human anti HER2 receptor, scFv, with a C-terminal fusion polypeptide containing 1, 3, or 17 threonine (Thr) residues. The C-terminal extended fusion polypeptides of these recombinant scFv fusion proteins are used as the acceptor substrate for human polypeptide-alpha-N-acetylgalactosaminyltransferase II (h-ppGalNAc-T2) that transfers either GalNAc or 2-keto-Gal. a modified galactose with a chemical handle. from their respective UDP-sugars to the side-chain hydroxyl group of the Thr residue(s). The recombinant scFv fusion proteins are expressed in E. coli as inclusion bodies and in vitro refolded and glycosylated with h-ppGaINAc-T2. Upon protease cleavage. the MALDI-TOF spectra of the glycosylated C-terminal fusion polypeptides showed that the glycosylated scFv fusion protein with a single Thr residue is fully glycosylated with a single 2-keto-Gal, whereas the glycosylated scFv fusion protein with 3 and 17 Thr residues is found as all equal mixture of 2-3 and 5-8 2-keto-Gal glycosylated fusion proteins, respectively. These fusion scFv proteins with the modified galactose are then conjugated with a fluorescence probe, Alexa488, that carries an orthogonal reactive group. The fluorescence labeled scFv proteins bind specifically to a human breast. cancer cell line (SK-BR-3) that overexpresses the HER2 receptor, indicating that the in vitro folded scFv fusion proteins are biologically active and the presence of conjugated multiple Alexa488 probes in their C-terminal end does not interfere with their binding to the antigen.
C1 [Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Manzoni, Maria; Qasba, Pradman K.] NCI, Struct Glycobiol Sect, CCRNP, CCR, Frederick, MD 21702 USA.
[Zhu, Zhongyu; Dimitrov, Dimiter S.] NCI, Prot Interact Grp, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Loomis, Kristin; Puri, Anu] NCI, Membrane Struct & Funct Sect, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Ramakrishnan, Boopathy; Boeggeman, Elizabeth; Zhu, Zhongyu] NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, CCRNP, CCR, Bldg 469,Room 221, Frederick, MD 21702 USA.
EM qasba@helix.nih.gov
FU National Cancer Institute, National Institutes of Health [N01-C0-12400];
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX We thank Dr. John T. Simpson, Protein Chemistry Laboratory,
NCI-Frederick, for the mass spectroscopic analysis of the samples. This
project has been funded in part with Federal funds from the National
Cancer Institute, National Institutes of Health, under contract no.
N01-C0-12400. The content of this publication does not necessarily
reflect the view or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government. This research
was supported [in part] by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 22
TC 13
Z9 14
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD JUL
PY 2009
VL 20
IS 7
BP 1383
EP 1389
DI 10.1021/bc900149r
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 472NB
UT WOS:000268137700013
PM 19507852
ER
PT J
AU Nwe, K
Xu, H
Regino, CAS
Bernardo, M
Ileva, L
Riffle, L
Wong, KJ
Brechbiel, MW
AF Nwe, Kido
Xu, Heng
Regino, Celeste Aida S.
Bernardo, Marcelino
Ileva, Lilia
Riffle, Lisa
Wong, Karen J.
Brechbiel, Martin W.
TI A New Approach in the Preparation of Dendrimer-Based Bifunctional
Diethylenetriaminepentaacetic Acid MR Contrast Agent Derivatives
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID ACUTE-RENAL-FAILURE; WATER EXCHANGE-RATE; MAGNETIC-RESONANCE; GADOLINIUM
COMPLEXES; PROTEIN-BINDING; PAMAM DENDRIMER; HIGH RELAXIVITY; CHLORIDE;
DYNAMICS; ANTIBODY
AB In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (134) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 Suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production Of Such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.
C1 [Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Regino, Celeste Aida S.; Bernardo, Marcelino; Wong, Karen J.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa] NCI, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room 1B40,10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 38
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U1 2
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD JUL
PY 2009
VL 20
IS 7
BP 1412
EP 1418
DI 10.1021/bc900057z
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 472NB
UT WOS:000268137700017
PM 19555072
ER
PT J
AU Hariri, AR
Gorka, A
Hyde, LW
Kimak, M
Halder, I
Ducci, F
Ferrell, RE
Goldman, D
Manuck, SB
AF Hariri, Ahmad R.
Gorka, Adam
Hyde, Luke W.
Kimak, Mark
Halder, Indrani
Ducci, Francesca
Ferrell, Robert E.
Goldman, David
Manuck, Stephen B.
TI Divergent Effects of Genetic Variation in Endocannabinoid Signaling on
Human Threat- and Reward-Related Brain Function
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Amygdala; endocannabinoids; fMRI; genetics; individual differences;
reward; threat; ventral striatum
ID ACID AMIDE HYDROLASE; CB1 CANNABINOID RECEPTORS; PROBLEM DRUG-USE;
AMYGDALA REACTIVITY; KNOCKOUT MICE; INDIVIDUAL-DIFFERENCES; ANANDAMIDE
HYDROLYSIS; MISSENSE MUTATION; NEURAL MECHANISMS; IMAGING GENETICS
AB Background: Fatty acid amide hydrolase (FAAH) is a key enzyme in regulating endocannabinoid (eCB) signaling. A common single nucleotide polymorphism (C385A) in the human FAAH gene has been associated with increased risk for addiction and obesity.
Methods: Using imaging genetics in 82 healthy adult volunteers, we examined the effects of FAAH C385A on threat- and reward-related human brain function.
Results: Carriers of FAAH 385A, associated with reduced enzyme and possibly increased eCB signaling, had decreased threat-related amygdala reactivity but increased reward-related ventral striatal reactivity in comparison with C385 homozygotes. Similarly divergent effects of FAAH C385A genotype were manifest at the level of brain-behavior relationships. The 385A carriers showed decreased correlation between amygdala reactivity and trait anxiety but increased correlation between ventral striatal reactivity and delay discounting, an index of impulsivity.
Conclusions: Our results parallel pharmacologic and genetic dissection of eCB signaling, are consistent with the psychotropic effects of Delta(9)-tetrahydrocannabinol, and highlight specific neural mechanisms through which variability in eCB signaling impacts complex behavioral processes related to risk for addiction and obesity.
C1 [Hariri, Ahmad R.] Univ Pittsburgh, Dev Imaging Genet Program, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Hariri, Ahmad R.; Gorka, Adam; Hyde, Luke W.; Manuck, Stephen B.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15213 USA.
[Kimak, Mark; Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA.
[Ducci, Francesca; Goldman, David] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
RP Hariri, AR (reprint author), Univ Pittsburgh, Dev Imaging Genet Program, Dept Psychiat, Pittsburgh, PA 15213 USA.
EM haririar@upmc.edu
RI Goldman, David/F-9772-2010; Hariri, Ahmad/D-5761-2011; Hyde,
Luke/I-2279-2012
OI Goldman, David/0000-0002-1724-5405;
FU National institutes of Health (NIH) [HL040962, MH072837]; National
Alliance for Research on Schizophrenia and Depression (NARSAD); National
Institute on Alcohol Abuse and Alcoholism (NIAAA)
FX This work was supported by National institutes of Health (NIH) Grants
HL040962 to SBM and MH072837 to ARH, as well as a National Alliance for
Research on Schizophrenia and Depression (NARSAD) Young Investigator
Award to ARH. IH is supported by the intramural research program of
National Institute on Alcohol Abuse and Alcoholism (NIAAA).
NR 65
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U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 1
PY 2009
VL 66
IS 1
BP 9
EP 16
DI 10.1016/j.biopsych.2008.10.047
PG 8
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YK
UT WOS:000267469900003
PM 19103437
ER
PT J
AU Grillon, C
Pine, DS
Lissek, S
Rabin, S
Bonne, O
Vythilingam, M
AF Grillon, Christian
Pine, Daniel S.
Lissek, Shmuel
Rabin, Stephanie
Bonne, Omer
Vythilingam, Meena
TI Increased Anxiety During Anticipation of Unpredictable Aversive Stimuli
in Posttraumatic Stress Disorder but not in Generalized Anxiety Disorder
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Anticipatory anxiety; anxiety; fear-potentiated startle; generalized
anxiety disorder; predictability; PTSD; startle; threat
ID FEAR-POTENTIATED STARTLE; CORTICOTROPIN-RELEASING-FACTOR; VIETNAM
VETERANS; PANIC DISORDER; NORADRENERGIC FUNCTION; SUSTAINED ANXIETY;
ACOUSTIC STARTLE; POLICE OFFICERS; CONTEXTUAL FEAR; BED NUCLEUS
AB Background: Uncontrollability and unpredictability are key concepts related to re-experiencing, avoidance, and hypervigilance symptoms of posttraumatic stress disorder (PTSD). However, little is known about the differential sensitivity of PTSD individuals to unpredictable stressors, relative to either healthy individuals or individuals with other anxiety disorders. This study tested the hypothesis that elevated anxious reactivity, specifically for unpredictable aversive events, is a psychophysiological correlate of PTSD.
Methods: Sixteen patients with PTSD (34.5 +/- 12.4 years) were compared with 18 patients with generalized anxiety disorder (GAD) (34.0 +/- 10.5 years) and 34 healthy control subjects (30.2 +/- 8.5 years). Participants were exposed to three conditions: one in which predictable aversive stimuli were signaled by a cue, a second in which aversive stimuli were administered unpredictably, and a third in which no aversive stimuli were anticipated. Startle magnitude was used to assess anxious responses to the threat cue and to contexts associated with each condition.
Results: Posttraumatic stress disorder and GAD patients showed normative enhancement of fear to the predictable threat cue, but the PTSD group displayed elevated anxiety during the unpredictable condition compared with participants with GAD and healthy control subjects.
Conclusions: Anxious reactivity to unpredictable aversive events was heightened in PTSD but not in GAD and healthy subjects. Prior works also found signs of increased reactivity to unpredictable threat in panic disorder (PD), suggesting that PTSD and PD may involve shared vulnerability. As such, the current results inform understandings of classification, pathophysiology, and psychopharmacology of anxiety disorders, generally, and PTSD and panic disorder specifically.
C1 [Grillon, Christian] NIMH, MAP, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Bonne, Omer] Hadassah Hebrew Univ Med Ctr, Dept Psychiat, Jerusalem, Israel.
RP Grillon, C (reprint author), NIMH, MAP, NIH, Mood & Anxiety Disorders Program, 15K N Dr,Bldg 15K,Room 113,MSC 2670, Bethesda, MD 20892 USA.
EM Christian.grillon@nih.gov
OI Rabin, Stephanie/0000-0002-8282-0867
FU Intramural NIH HHS [Z01 MH002798-06]
NR 55
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 1
PY 2009
VL 66
IS 1
BP 47
EP 53
DI 10.1016/j.biopsych.2008.12.028
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YK
UT WOS:000267469900008
PM 19217076
ER
PT J
AU Fujimura, Y
Yasuno, F
Farris, A
Liow, JS
Geraci, M
Drevets, W
Pine, DS
Ghose, S
Lerner, A
Hargreaves, R
Burns, HD
Morse, C
Pike, VW
Innis, RB
AF Fujimura, Yota
Yasuno, Fumihiko
Farris, Amanda
Liow, Jeih-San
Geraci, Marilla
Drevets, Wayne
Pine, Daniel S.
Ghose, Subroto
Lerner, Alicja
Hargreaves, Richard
Burns, H. Donald
Morse, Cheryl
Pike, Victor W.
Innis, Robert B.
TI Decreased Neurokinin-1 (Substance P) Receptor Binding in Patients with
Panic Disorder: Positron Emission Tomographic Study with [F-18]SPA-RQ
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE NK1; receptor; panic attack; panic disorder; positron emission
tomography (PET); substance P
ID HUMAN BRAIN; NK1 RECEPTORS; ANTAGONIST; STRESS; PET; ANXIETY; PHOBIA
AB Background: Positron emission tomography (PET) can localize and quantify neurokinin-1 (NK1) receptors in brain using the nonpeptide antagonist radioligand, [F-18]SPA-RQ. We sought to determine if patients with panic disorder have altered density of INK, receptors in brain because of their history of recurrent panic attacks. We also sought to determine if a drug-induced panic attack releases substance P in brain, as measured by decreased binding of [F-18]SPA-RQ.
Methods: Positron emission tomography scans with [F-18]SPA-RQ were performed in 14 patients with panic disorder and 14 healthy subjects. Of these two groups, 7 patients and 10 healthy subjects were scanned twice, once at baseline and once after injection of doxapram, a drug that induces panic attacks.
Results: NK1 receptor binding in patients (n = 14) compared with that in healthy subjects (n = 14) was significantly decreased by 12% to 21% in all brain regions. Doxapram effectively produced panic attacks in 6 of 7 patients with panic disorder but only 2 of 10 healthy subjects. Doxapram caused no significant change of [F-18]SPA-RQ binding in either patients or healthy subjects.
Conclusions: Although induction of a panic attack has no significant effect on [F-18]SPA-RQ binding to NK1 receptors, patients with panic disorder have widespread reduction of NK1 receptor binding in brain.
C1 [Fujimura, Yota] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Geraci, Marilla; Drevets, Wayne; Pine, Daniel S.] NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Ghose, Subroto] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Hargreaves, Richard; Burns, H. Donald] Merck Res Labs, West Point, PA USA.
RP Fujimura, Y (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 31,Room B2-B37,31 Ctr Dr, Bethesda, MD 20892 USA.
EM FujimuraY@mail.nih.gov
RI Ghose, Subroto/J-6732-2016
FU Intramural NIH HHS [Z01 MH002852-04]; NIMH NIH HHS [Z01 MH002852]
NR 19
TC 23
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U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 1
PY 2009
VL 66
IS 1
BP 94
EP 97
DI 10.1016/j.biopsych.2008.12.027
PG 4
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 463YK
UT WOS:000267469900015
PM 19200949
ER
PT J
AU Dorsey, SG
Leitch, CC
Renn, CL
Lessans, S
Smith, BA
Wang, XM
Dionne, RA
AF Dorsey, Susan G.
Leitch, Carmen C.
Renn, Cynthia L.
Lessans, Sherrie
Smith, Barbara A.
Wang, Xiao M.
Dionne, Raymond A.
TI Genome-Wide Screen Identifies Drug-Induced Regulation of the Gene Giant
Axonal Neuropathy (Gan) in a Mouse Model of Antiretroviral-Induced
Painful Peripheral Neuropathy
SO BIOLOGICAL RESEARCH FOR NURSING
LA English
DT Article
DE microarray; painful peripheral neuropathy; chronic pain; gigaxonin;
giant axonal neuropathy; HIV/AIDS; HAART; NRTI
ID SENSORY NEUROPATHY; CLINICAL-FEATURES; TOXIC NEUROPATHY; RISK-FACTORS;
THERAPY; EPIDEMIOLOGY; DENSITY; AIDS
AB Painful peripheral neuropathy is a debilitating complication of the treatment of HIV with nucleoside reverse transcriptase inhibitors (NRTIs). Patients are living longer with these drugs; however many develop excruciating, unremitting, and often treatment-limiting neuropathy that is resistant to conventional pain management therapies. Improving patient comfort and quality of life is paramount and depends on a clearer understanding of this devastating side effect. The mechanisms underlying the development of NRTI-induced neuropathy, however, remain unclear. Using a mouse model of NRTI-induced neuropathy, the authors conducted an unbiased whole-genome microarray screen to identify molecular targets in the spinal dorsal horn, which is the location where integration of ascending sensory transmission and descending modulatory effects Occur. Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy. Gan1 has not been previously linked to nerve pathologies in other populations. In this study, downregulation of the Gan1 gene and the gene protein product, gigaxonin, was validated via quantitative polymerase chain reaction ([qPCR] gene expression) and Western blot analyses (protein level). Our report is the first to suggest that Gan1 might be a novel molecular target in the development of NRTI-induced peripheral neuropathy with implications for new therapeutic approaches to preventing or reducing a significant side effect of HIV treatment.
C1 [Dorsey, Susan G.; Leitch, Carmen C.; Renn, Cynthia L.; Lessans, Sherrie; Smith, Barbara A.] Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA.
[Wang, Xiao M.; Dionne, Raymond A.] NINR, Bethesda, MD 20892 USA.
RP Dorsey, SG (reprint author), Univ Maryland, Sch Nursing, 655 W Lombard St,Room 764, Baltimore, MD 21201 USA.
EM sdorsey@son.umaryland.edu
FU NINR [R01 NR010207]; American Pain Society; NINR Intramural Funds
FX This study was funded by NINR R01 NR010207 (SGD), American Pain Society
(SGD), NINR Intramural Funds (XMW, RAD).
NR 32
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U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1099-8004
J9 BIOL RES NURS
JI Biol. Res. Nurs.
PD JUL
PY 2009
VL 11
IS 1
BP 7
EP 16
DI 10.1177/1099800409332726
PG 10
WC Nursing
SC Nursing
GA 464SX
UT WOS:000267528200002
PM 19398414
ER
PT J
AU Gupta, V
Tomblyn, M
Pedersen, TL
Atkins, HL
Battiwalla, M
Gress, RE
Pollack, MS
Storek, J
Thompson, JC
Tiberghien, P
Young, JAH
Ribaud, P
Horowitz, MM
Keating, A
AF Gupta, Vikas
Tomblyn, Marcie
Pedersen, Tanya L.
Atkins, Harry L.
Battiwalla, Minoo
Gress, Ronald E.
Pollack, Marilyn S.
Storek, Jan
Thompson, Jill C.
Tiberghien, Pierre
Young, Jo-Anne H.
Ribaud, Patricia
Horowitz, Mary M.
Keating, Armand
TI Allogeneic Hematopoietic Cell Transplantation in Human Immunodeficiency
Virus-Positive Patients with Hematologic Disorders: A Report from the
Center for International Blood and Marrow Transplant Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Human immunodeficiency virus; Bone marrow transplantation; Malignancy;
Allogeneic
ID ACTIVE ANTIRETROVIRAL THERAPY; HIGH-DOSE THERAPY; HIV-ASSOCIATED
LYMPHOMA; ACUTE MYELOID-LEUKEMIA; NON-HODGKIN-LYMPHOMA; PROGENITOR
CELLS; INFECTION; CANCER; AIDS; RISK
AB The role of allogeneic hematopoietic cell transplantation (alloHCT) in human immunodeficiency virus (HIV)-positive patients is not known. Using the Center for International Blood and Marrow Transplant Research database, we retrospectively evaluated 23 HIV-positive patients undergoing matched sibling donor (n = 19) or unrelated donor (n = 4) alloHCT between 1987 and 2003. The median age at alloHCT was 32 years. Indications for alloHCT were diverse and included malignant (n = 21) and nonmalignant (n = 2) hematologic disorders. Nine patients (39%) underwent transplantation after 1996, the approximate year that highly active antiretroviral therapy became standard treatment. The median time to neutrophil engraftment was 16 days (range, 7 to 30 days), and the cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD) at 100 days, chronic GVHD (cGVHD), and survival at 2 years were 30% (95% confidence interval [CI] = 14% to 50%), 28% (95% CI = 12% to 48%), and 30% (95% CI = 14% to 50%), respectively. At a median follow-up of 59 months, 6 patients were alive. Survival appears to be better in the patients undergoing alloHCT after 1996; 4 of these 9 patients survived, compared with only 2 of 14 those undergoing transplantation before 1996. These data suggest that alloHCT is feasible for selected HIV-positive patients with malignant and nonmalignant disorders. Prospective studies are needed to evaluate the safety and efficacy of this modality in specific diseases in these patients.
C1 [Gupta, Vikas] Univ Toronto, Princess Margaret Hosp, Blood & Marrow Transplant Program, Div Haematol, Toronto, ON M5G 2M9, Canada.
[Tomblyn, Marcie; Young, Jo-Anne H.] Univ Minnesota, Med Ctr, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA.
[Pedersen, Tanya L.; Thompson, Jill C.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Atkins, Harry L.] Ottawa Hosp, Ottawa, ON, Canada.
[Battiwalla, Minoo] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA.
[Gress, Ronald E.] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Pollack, Marilyn S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[Storek, Jan] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Tiberghien, Pierre] Univ Franche Comte, Etab Francais Sang, INSERM, U645, F-25030 Besancon, France.
[Ribaud, Patricia] Univ Paris 07, Hop St Louis, Serv Greffe Moelle Osseuse, Paris, France.
[Horowitz, Mary M.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA.
RP Gupta, V (reprint author), Univ Toronto, Princess Margaret Hosp, Blood & Marrow Transplant Program, Div Haematol, Suite 5-217,610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM vikas.gupta@uhn.on.ca
RI Young, Jo-Anne/G-2617-2013
OI Young, Jo-Anne/0000-0003-4182-341X
FU National Marrow Donor Program; Health Resources and Services
Administration [240-97-0036, 23 1-02-0007]; National Cancer Institute
[U24-CA76518]; AABB; Aetna; American International Group; American
Society for Blood and Marrow Transplantation; Amgen; Astellas Pharma US;
Baxter International; Bayer HealthCare Pharmaceuticals; BioOne; Blood
Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow
Foundation; Bristol-Myers Squibb; Cangene; Celgene; CellGenix; Cerus;
Cubist Pharmaceuticals; Cylex; CytoTherm; DOR BloPharma; Dvnal Biotech;
EKR Therapeutics; Enzon Pharmaceuticals; Gainbro BCT; Gamida Cell;
Genzyme; Gift of Life Bone Marrow Foundation; GlaxoSmithKfine;
Histogenetics; HKS Medical Information Systems; Hospira; Infectious
Diseases Society of America; Kiadis Pharma; Krin Brewerv Co, Merck
Company; Medical College of Wisconsin; MGI Pharma; Millennium
Pharmaceuticals; Miller Pharmacal Group; Millmian USA; Miltenvi Biotec;
MultiPlan; Nature Publishing Group; Oncology Nursing Society; Osiris
Therapeutics; Pall Life Sciences; PDL BioPharma; Pfizer; Pharinion;
Roche Laboratories; Schering Plough; Society for Healthcare Epidemiology
of America; StemCyte; SternSoft Software; SuperGen; Svsrnex; Teva
Pharmaceutical Industries; Marrow Foundation; TFIERAKOS; University of
Colorado Cord Blood Bank; ViaCell; Vidacare; ViraCor Laboratories;
ViroPharma; Wellpoint; Office of Naval Research
FX This project was supported by funding from the National Marrow Donor
Program and the Health Resources and Services Administration (Contracts
240-97-0036 and 23 1-02-0007, to the National Marrow Donor Program). The
views expressed in this article do not reflect the official policy or
position of the Health Resources and Services Administration or the
National Marrow Donor Program. The authors thank the data managers at
the participating transplantation centers, whose diligence in obtaining
and reporting the data made this study possible. The CIBMTR is supported
by Public Health Service Grant U24-CA76518 from the National Cancer
Institute, the National Institute of Allergy and Infectious Diseases,
and the National Heart, Lung and Blood Institute; the Office of Naval
Research, the Health Resources and Services Administration; and grants
from AABB, Aetna, American International Group, American Society for
Blood and Marrow Transplantation, Amgen, an anonymous donation to the
Medical College of Wisconsin; Astellas Pharma US, Baxter International,
Bayer HealthCare Pharmaceuticals, BioOne, Blood Center of Wisconsin,
Blue Cross and Blue Shield Association, Bone Marrow Foundation,
Bristol-Myers Squibb, Cangene, Celgene, CellGenix, Cerus, Cubist
Pharmaceuticals, Cylex, CytoTherm, DOR BloPharma, Dvnal Biotech, EKR
Therapeutics, Enzon Pharmaceuticals, Gainbro BCT, Gamida Cell, Genzyme,
Gift of Life Bone Marrow Foundation, GlaxoSmithKfine, Histogenetics, HKS
Medical Information Systems, Hospira, Infectious Diseases Society of
America; Kiadis Pharma; Krin Brewerv Co, Merck & Company, Medical
College of Wisconsin, MGI Pharma, Millennium Pharmaceuticals, Miller
Pharmacal Group, Millmian USA, Miltenvi Biotec, MultiPlan, National
Marrow Donor Program, Nature Publishing Group, Oncology Nursing Society,
Osiris Therapeutics, Pall Life Sciences, PDL BioPharma, Pfizer,
Pharinion, Roche Laboratories, Schering Plough, Society for Healthcare
Epidemiology of America, StemCyte, SternSoft Software, SuperGen,
Svsrnex, Teva Pharmaceutical Industries, The Marrow Foundation,
TFIERAKOS, University of Colorado Cord Blood Bank, ViaCell, Vidacare,
ViraCor Laboratories, ViroPharma, and Wellpoint. The views expressed in
this article do not reflect the official policy or position of the
National Institutes of Health, the Department of the Navy, the
Department of Defense, or any other agency of the US Government.
NR 35
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U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2009
VL 15
IS 7
BP 864
EP 871
DI 10.1016/j.bbmt.2009.03.023
PG 8
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 465MD
UT WOS:000267588300013
PM 19539219
ER
PT J
AU Le, Q
Shenoy, A
Koklanaris, E
Childs, R
Barrett, AJ
Savani, BN
AF Le, Quan
Shenoy, Aarthi
Koklanaris, Eleftheria
Childs, Richard
Barrett, A. John
Savani, Bipin N.
TI Lamivudine Prophylaxis and Hepatitis B Vaccination for Prevention of
Hepatitis B Virus Reverse Seroconversion in Long-Term Survivors after
Allogeneic Stem Cell Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Letter
ID VIRAL REACTIVATION; CHRONIC GVHD; RECIPIENTS; INFECTION
C1 [Le, Quan; Shenoy, Aarthi; Koklanaris, Eleftheria; Childs, Richard; Barrett, A. John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplantat Sect, Nashville, TN USA.
RP Le, Q (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA HL006105-02]
NR 8
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD JUL
PY 2009
VL 15
IS 7
BP 886
EP 887
DI 10.1016/j.bbmt.2009.03.024
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 465MD
UT WOS:000267588300016
PM 19539222
ER
PT J
AU Yin, YM
Wang, S
Sun, YJ
Matt, Y
Colburn, NH
Shu, YQ
Han, X
AF Yin, Yongmei
Wang, Shui
Sun, Yujie
Matt, Young
Colburn, Nancy H.
Shu, Yongqian
Han, Xiao
TI JNK/AP-1 pathway is involved in tumor necrosis factor-alpha induced
expression of vascular endothelial growth factor in MCF7 cells
SO BIOMEDICINE & PHARMACOTHERAPY
LA English
DT Article
DE AP-1; JNK; MCF7; VEGF
ID NF-KAPPA-B; C-JUN; PROLONGED ACTIVATION; SIGNAL-TRANSDUCTION; AP-1;
KINASES; TRANSCRIPTION; CANCER; VEGF; KERATINOCYTES
AB Vascular endothelial growth factor (VEGF) has been implicated in breast tumor angiogenesis. And tumor necrosis factor-alpha (TNF-alpha) is a positive regulator of VEGF. This study was aimed to identify the signalling pathway of TNF-alpha in VEGF expression regulation in breast cancer cell line MCF7. Using luciferase reporter assays, we demonstrated that TNF-alpha significantly increased activator protein-1 (AP-1) transcriptional activity in the MCF7 cells. The expression of the AP-1 family members c-Jun, c-Fos and JunB and phosphorylation levels of c-Jun were upregulated by TNF-alpha, whereas other AP-1 family members Fra-1, Fra-2, and JunD were unaffected. The activation of AP-1 was associated with the formation of p-c-Jun-c-Jun and p-c-Jun-JunB homodimers. Furthermore, the phosphorylation levels of c-Jun N-terminal kinase (JNK) but not P38 and ERK were elevated by TNF-alpha in MCF7 cells. TNF-alpha potently upregulated the mRNA and protein levels of VEGF, which were significantly reversed by JNK inhibitor SP600125. Finally using chromatin immunoprecipitation (CHIP) assays, we found that p-c-Jun bound to the VEGF promoter and regulated VEGF transcription directly. These data suggest that the pro-inflammatory cytokine TNF-alpha is a critical regulator of VEGF expression in breast cancer cells, at least partially via a JNK and AP-1 dependent pathway. (C) 2009 Elsevier Masson SAS. All rights reserved.
C1 [Yin, Yongmei; Shu, Yongqian] Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, Nanjing 210029, Peoples R China.
[Sun, Yujie; Han, Xiao] Nanjing Med Univ, Key Lab Human Funct Genom Jiangsu Prov, Nanjing 210029, Peoples R China.
[Matt, Young; Colburn, Nancy H.] Ctr Canc Res, Lab Cancer Prevent, Natl Canc Inst, Frederick, MD 21702 USA.
[Wang, Shui] Nanjing Med Univ, Affiliated Hosp 1, Dept Gen Surg, Nanjing 210029, Peoples R China.
RP Shu, YQ (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Oncol, 300 Guangzhou Rd, Nanjing 210029, Peoples R China.
EM shuyongqian@csco.org.cn; hanxiao@njmu.edu.cn
FU National Natural Science Foundation of China [30772474, 30771041];
Special Funds for Major State Basic Research Program of China
[2006CB503908]; Jiangsu Provincial Natural Science Foundation
[BK2008477]
FX This work was supported by grants from the National Natural Science
Foundation of China (30772474 and 30771041), the Special Funds for Major
State Basic Research Program of China (973 Program, 2006CB503908) to X.
Han and Jiangsu Provincial Natural Science Foundation (NO. BK2008477).
NR 31
TC 23
Z9 27
U1 1
U2 5
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0753-3322
J9 BIOMED PHARMACOTHER
JI Biomed. Pharmacother.
PD JUL
PY 2009
VL 63
IS 6
BP 429
EP 435
DI 10.1016/j.biopha.2009.04.045
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 476GG
UT WOS:000268426200007
PM 19553068
ER
PT J
AU Skoumbourdis, AP
LeClair, CA
Stefan, E
Turjanski, AG
Maguire, W
Titus, SA
Huang, R
Auld, DS
Inglese, J
Austin, CP
Michnick, SW
Xia, MH
Thomas, CJ
AF Skoumbourdis, Amanda P.
LeClair, Christopher A.
Stefan, Eduard
Turjanski, Adrian G.
Maguire, William
Titus, Steven A.
Huang, Ruili
Auld, Douglas S.
Inglese, James
Austin, Christopher P.
Michnick, Stephen W.
Xia, Menghang
Thomas, Craig J.
TI Exploration and optimization of substituted triazolothiadiazines and
triazolopyridazines as PDE4 inhibitors
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE PDE4; PDE4 inhibitor; Triazolothiadiazines; Triazolopyridazines; Asthma;
COPD
ID FRAGMENT COMPLEMENTATION ASSAYS; CRYSTAL-STRUCTURE; BIOLOGICAL
EVALUATION; ANXIOLYTIC ACTIVITY; DERIVATIVES; COMPLEX;
PHOSPHODIESTERASE-4; SELECTIVITY; MECHANISM; BINDING
AB An expansion of structure-activity studies on a series of substituted 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine PDE4 inhibitors and the introduction of a related [1,2,4]triazolo[4,3-b]pyridazine based inhibitor of PDE4 is presented. The development of SAR included strategic incorporation of known substituents on the critical catachol diether moiety of the 6-phenyl appendage on each heterocyclic core. From these studies, (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (10) and (R)-3-(2,5-dimethoxyphenyl)-6-(4-methoxy-3-(tetrahydrofuran-3-yloxy)phenyl)-[1,2,4]triazolo[4,3-b]pyridazine (18) were identified as highly potent PDE4A inhibitors. Each of these analogues was submitted across a panel of 21 PDE family members and was shown to be highly selective for PDE4 isoforms (PDE4A, PDE4B, PDE4C, PDE4D). Both 10 and 18 were then evaluated in divergent cell-based assays to assess their relevant use as probes of PDE4 activity. Finally, docking studies with selective ligands (including 10 and 18) were undertaken to better understand this chemotypes ability to bind and inhibit PDE4 selectively. (C) 2009 Published by Elsevier Ltd.
C1 [Skoumbourdis, Amanda P.; LeClair, Christopher A.; Maguire, William; Titus, Steven A.; Huang, Ruili; Auld, Douglas S.; Inglese, James; Austin, Christopher P.; Xia, Menghang; Thomas, Craig J.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA.
[Stefan, Eduard; Michnick, Stephen W.] Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada.
[Turjanski, Adrian G.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
RP Thomas, CJ (reprint author), NHGRI, NIH Chem Genom Ctr, NIH, 9800 Med Ctr Dr,MSC 3370, Bethesda, MD 20892 USA.
EM craigt@nhgir.nih.gov
OI Stefan, Eduard/0000-0003-3650-4713
FU Molecular Libraries Initiative of the National Institutes of Health
Roadmap for Medical Research; National Human Genome Research Institute;
National Institute of Dental and Craniofacial Research
FX We thank Ms. Allison Peck for critical reading of this manuscript. This
research was supported by the Molecular Libraries Initiative of the
National Institutes of Health Roadmap for Medical Research, the
Intramural Research Program of the National Human Genome Research
Institute and the National Institute of Dental and Craniofacial
Research.
NR 27
TC 20
Z9 20
U1 0
U2 6
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 1
PY 2009
VL 19
IS 13
BP 3686
EP 3692
DI 10.1016/j.bmcl.2009.01.057
PG 7
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 456EG
UT WOS:000266822800072
PM 19464886
ER
PT J
AU Talamo, GP
Ibrahim, S
Claxton, D
Tricot, GJ
Fink, LM
Zangari, M
AF Talamo, Giampaolo P.
Ibrahim, Sulfi
Claxton, David
Tricot, Guido J.
Fink, Louis M.
Zangari, Maurizio
TI Hypercoagulable states in patients with multiple myeloma can affect the
thalidomide-associated venous thromboembolism
SO BLOOD COAGULATION & FIBRINOLYSIS
LA English
DT Article
DE deep vein thrombosis; multiple myeloma; thalidomide
ID THROMBOSIS
AB The therapeutic use of thalidomide in patients with multiple myeloma is often complicated by the development of venous thromboembolism. The objective of the present study was to identify hypercoagulable states associated with development of venous thromboembolism in thalidomide-treated multiple myeloma patients. We screened 49 consecutive multiple myeloma patients treated with thalidomide at baseline for hypercoagulability. With a median follow-up of 11 months, 10 of 49 multiple myeloma patients developed a thrombotic episode. Laboratory assays revealed an underlying abnormality in nine of the 10 patients; hypercoagulable screenings were normal in 36 of the 39 patients who did not develop venous thromboembolism (P<0.0001). Our retrospective study results suggest that the multiple myeloma patients with thromboembolic complications during treatment with thalidomide have a frequent concomitant underlying thrombophilic state. Blood Coagul Fibrinolysis 20:337-339 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Talamo, Giampaolo P.; Ibrahim, Sulfi; Claxton, David] Penn State Milton S Hershey Med Ctr, Div Hematol Oncol, Hershey, PA USA.
[Fink, Louis M.] NCI, Las Vegas, NV USA.
[Tricot, Guido J.; Zangari, Maurizio] Univ Utah, Div Hematol, Blood Marrow Transplant & Myeloma Program, Salt Lake City, UT USA.
RP Zangari, M (reprint author), 30 N 1900 E,SOM Room 5C402, Salt Lake City, UT 84132 USA.
EM Maurizio.zangari@hsc.utah.edu
NR 8
TC 7
Z9 8
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0957-5235
J9 BLOOD COAGUL FIBRIN
JI Blood Coagul. Fibrinolysis
PD JUL
PY 2009
VL 20
IS 5
BP 337
EP 339
DI 10.1097/MBC.0b013e32832b27e6
PG 3
WC Hematology
SC Hematology
GA 466AP
UT WOS:000267632900005
PM 19367157
ER
PT J
AU Gafni, RI
Baron, J
AF Gafni, Rachel I.
Baron, Jeffrey
TI Adolescence and bone health debate. Bone mass acquisition during
adolescence may not influence risk of osteoporosis in late adulthood
SO BONE
LA English
DT Meeting Abstract
CT 5th International Conference on Childrens Bone Health
CY JUN 23-26, 2009
CL Cambridge, ENGLAND
C1 [Gafni, Rachel I.; Baron, Jeffrey] NICHHD, Sect Growth & Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
[Gafni, Rachel I.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 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 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2009
VL 45
BP S49
EP S49
DI 10.1016/j.bone.2009.04.016
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 458PV
UT WOS:000267036900013
ER
PT J
AU Hangartner, TN
Short, DF
Zemel, BS
Gilsanz, V
Kalkwarf, HJ
Lappe, JM
Oberfield, S
Shepherd, JA
Winer, K
AF Hangartner, T. N.
Short, D. F.
Zemel, B. S.
Gilsanz, V.
Kalkwarf, H. J.
Lappe, J. M.
Oberfield, S.
Shepherd, J. A.
Winer, K.
TI Fitting of BMD with consideration of confounding parameters
SO BONE
LA English
DT Meeting Abstract
CT 5th International Conference on Childrens Bone Health
CY JUN 23-26, 2009
CL Cambridge, ENGLAND
C1 [Hangartner, T. N.; Short, D. F.] Wright State Univ, Dayton, OH 45435 USA.
[Zemel, B. S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Gilsanz, V.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Kalkwarf, H. J.] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA.
[Lappe, J. M.] Creighton Univ, Omaha, NE 68178 USA.
[Oberfield, S.] Columbia Univ, New York, NY USA.
[Shepherd, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Winer, K.] NICHHD, Bethesda, MD 20892 USA.
RI Zemel, Babette/D-1117-2009
NR 1
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 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2009
VL 45
BP S87
EP S87
DI 10.1016/j.bone.2009.04.124
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 458PV
UT WOS:000267036900116
ER
PT J
AU Panaroni, C
Gioia, R
Lupi, A
Besio, R
Goldstein, SA
Leikin, S
Mertz, EL
Villa, I
Rossi, A
Frattini, A
Marini, JC
Vezzoni, P
Forlino, A
AF Panaroni, C.
Gioia, R.
Lupi, A.
Besio, R.
Goldstein, S. A.
Leikin, S.
Mertz, E. L.
Villa, I.
Rossi, A.
Frattini, A.
Marini, J. C.
Vezzoni, P.
Forlino, A.
TI In utero transplantation rescues bone phenotype in the osteogenesis
imperfecta murine model BrtIIV
SO BONE
LA English
DT Meeting Abstract
CT 5th International Conference on Childrens Bone Health
CY JUN 23-26, 2009
CL Cambridge, ENGLAND
C1 [Panaroni, C.; Frattini, A.; Vezzoni, P.] ITB CNR, Milan, Italy.
[Panaroni, C.; Gioia, R.; Lupi, A.; Besio, R.; Rossi, A.; Forlino, A.] Univ Pavia, I-27100 Pavia, Italy.
[Goldstein, S. A.] Univ Michigan, Ann Arbor, MI USA.
[Leikin, S.; Mertz, E. L.] NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA.
[Villa, I.] Ist Sci San Raffaele, Bone Metab Unit, Milan, Italy.
[Marini, J. C.] NICHD, Sect Connect Tissue Disorders, NIH, Bethesda, MD USA.
RI Rossi, Antonio/E-9935-2012; Forlino, Antonella/H-5385-2015
OI Forlino, Antonella/0000-0002-6385-1182
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD JUL
PY 2009
VL 45
BP S54
EP S55
DI 10.1016/j.bone.2009.04.033
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 458PV
UT WOS:000267036900027
ER
PT J
AU Neumann, J
Bras, J
Deas, E
O'Sullivan, SS
Parkkinen, L
Lachmann, RH
Li, A
Holton, J
Guerreiro, R
Paudel, R
Segarane, B
Singleton, A
Lees, A
Hardy, J
Houlden, H
Revesz, T
Wood, NW
AF Neumann, Juliane
Bras, Jose
Deas, Emma
O'Sullivan, Sean S.
Parkkinen, Laura
Lachmann, Robin H.
Li, Abi
Holton, Janice
Guerreiro, Rita
Paudel, Reema
Segarane, Badmavady
Singleton, Andrew
Lees, Andrew
Hardy, John
Houlden, Henry
Revesz, Tamas
Wood, Nicholas W.
TI Glucocerebrosidase mutations in clinical and pathologically proven
Parkinson's disease
SO BRAIN
LA English
DT Article
DE Parkinson's disease; GBA; Gaucher's disease; neuropathology
ID LEWY BODY DISORDERS; GAUCHER-DISEASE; GENE-MUTATIONS; ASHKENAZI-JEWS;
VISUAL HALLUCINATIONS; RISK-FACTOR; DIAGNOSIS; ONSET; ASSOCIATION;
FREQUENCIES
AB Mutations in the glucocerebrosidase gene (GBA) are associated with Gaucher's disease, the most common lysosomal storage disorder. Parkinsonism is an established feature of Gaucher's disease and an increased frequency of mutations in GBA has been reported in several different ethnic series with sporadic Parkinson's disease. In this study, we evaluated the frequency of GBA mutations in British patients affected by Parkinson's disease. We utilized the DNA of 790 patients and 257 controls, matched for age and ethnicity, to screen for mutations within the GBA gene. Clinical data on all identified GBA mutation carriers was reviewed and analysed. Additionally, in all cases where brain material was available, a neuropathological evaluation was performed and compared to sporadic Parkinson's disease without GBA mutations. The frequency of GBA mutations among the British patients (33/790 = 4.18%) was significantly higher (P = 0.01; odds ratio = 3.7; 95% confidence interval = 1.12-12.14) when compared to the control group (3/257 = 1.17%). Fourteen different GBA mutations were identified, including three previously undescribed mutations, K7E, D443N and G193E. Pathological examination revealed widespread and abundant alpha-synuclein pathology in all 17 GBA mutation carriers, which were graded as Braak stage of 5-6, and had McKeith's limbic or diffuse neocortical Lewy body-type pathology. Diffuse neocortical Lewy body-type pathology tended to occur more frequently in the group with GBA mutations compared to matched Parkinson's disease controls. Clinical features comprised an early onset of the disease, the presence of hallucinations in 45% (14/31) and symptoms of cognitive decline or dementia in 48% (15/31) of patients. This study demonstrates that GBA mutations are found in British subjects at a higher frequency than any other known Parkinson's disease gene. This is the largest study to date on a non-Jewish patient sample with a detailed genotype/phenotype/pathological analyses which strengthens the hypothesis that GBA mutations represent a significant risk factor for the development of Parkinson's disease and suggest that to date, this is the most common genetic factor identified for the disease.
C1 [Neumann, Juliane; Deas, Emma; O'Sullivan, Sean S.; Parkkinen, Laura; Lachmann, Robin H.; Li, Abi; Holton, Janice; Paudel, Reema; Segarane, Badmavady; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Neumann, Juliane; Deas, Emma; O'Sullivan, Sean S.; Parkkinen, Laura; Lachmann, Robin H.; Li, Abi; Holton, Janice; Paudel, Reema; Segarane, Badmavady; Lees, Andrew; Hardy, John; Houlden, Henry; Revesz, Tamas; Wood, Nicholas W.] Reta Lila Weston Inst, Inst Neurol, London, England.
[Neumann, Juliane] Charite Univ Med Berlin, Int Grad Program Med Neurosci, Berlin, Germany.
[Bras, Jose; Guerreiro, Rita; Singleton, Andrew] NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bras, Jose; Guerreiro, Rita] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
RP Wood, NW (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq House,Queen Sq, London WC1N 3BG, England.
EM n.wood@ion.ucl.ac.uk
RI Wood, Nicholas/C-2505-2009; Hardy, John/C-2451-2009; Singleton,
Andrew/C-3010-2009; Bras, Jose/D-3366-2009; Deas, Emma/A-6755-2010;
Bras, Jose/A-1428-2011; Holton, Janice/F-6831-2011; O'Sullivan,
Sean/C-9333-2012; Lees, Andrew/A-6605-2009; Guerreiro, Rita/A-1327-2011;
Houlden, Henry/C-1532-2008; Revesz, Tamas/A-8732-2010
OI Wood, Nicholas/0000-0002-9500-3348; Holton, Janice/0000-0002-3882-5249;
O'Sullivan, Sean/0000-0002-0583-7956; Houlden,
Henry/0000-0002-2866-7777; Revesz, Tamas/0000-0003-2501-0259
FU Intramural NIH HHS; Medical Research Council [G0400000, G0701075,
G108/638]; Parkinson's UK [G-0612, G-0907, G-0909]
NR 48
TC 218
Z9 223
U1 1
U2 21
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2009
VL 132
BP 1783
EP 1794
DI 10.1093/brain/awp044
PN 7
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 463OE
UT WOS:000267440700016
PM 19286695
ER
PT J
AU Simunovic, F
Yi, M
Wang, YL
Macey, L
Brown, LT
Krichevsky, AM
Andersen, SL
Stephens, RM
Benes, FM
Sonntag, KC
AF Simunovic, Filip
Yi, Ming
Wang, Yulei
Macey, Laurel
Brown, Lauren T.
Krichevsky, Anna M.
Andersen, Susan L.
Stephens, Robert M.
Benes, Francine M.
Sonntag, Kai C.
TI Gene expression profiling of substantia nigra dopamine neurons: further
insights into Parkinson's disease pathology
SO BRAIN
LA English
DT Article
DE Parkinson's disease; microarray; laser microdissection; pathogenesis;
dopamine
ID CELL-DEATH; UBIQUITIN-PROTEASOME; OXIDATIVE STRESS; ALPHA-SYNUCLEIN;
PROTEIN; RECEPTORS; BRAIN; INVOLVEMENT; MECHANISMS; PATHWAYS
AB Parkinson's disease is caused by a progressive loss of the midbrain dopamine (DA) neurons in the substantia nigra pars compacta. Although the main cause of Parkinson's disease remains unknown, there is increasing evidence that it is a complex disorder caused by a combination of genetic and environmental factors, which affect key signalling pathways in substantia nigra DA neurons. Insights into pathogenesis of Parkinson's disease stem from in vitro and in vivo models and from postmortem analyses. Recent technological developments have added a new dimension to this research by determining gene expression profiles using high throughput microarray assays. However, many of the studies reported to date were based on whole midbrain dissections, which included cells other than DA neurons. Here, we have used laser microdissection to isolate single DA neurons from the substantia nigra pars compacta of controls and subjects with idiopathic Parkinson's disease matched for age and postmortem interval followed by microarrays to analyse gene expression profiling. Our data confirm a dysregulation of several functional groups of genes involved in the Parkinson's disease pathogenesis. In particular, we found prominent down-regulation of members of the PARK gene family and dysregulation of multiple genes associated with programmed cell death and survival. In addition, genes for neurotransmitter and ion channel receptors were also deregulated, supporting the view that alterations in electrical activity might influence DA neuron function. Our data provide a 'molecular fingerprint identity' of late-stage Parkinson's disease DA neurons that will advance our understanding of the molecular pathology of this disease.
C1 [Simunovic, Filip; Macey, Laurel; Brown, Lauren T.; Sonntag, Kai C.] Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA.
[Yi, Ming; Stephens, Robert M.] NCI, SAIC Frederick Inc, Adv Technol Program, Adv Biomed Comp Ctr, Frederick, MD 21702 USA.
[Wang, Yulei] Appl Biosyst Inc, Foster City, CA 94404 USA.
[Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Andersen, Susan L.] Harvard Univ, McLean Hosp, Sch Med, Lab Dev Neuropsychopharmacol, Belmont, MA 02478 USA.
[Benes, Francine M.] Harvard Univ, Sch Med, McLean Hosp, Program Neurosci, Belmont, MA 02478 USA.
[Benes, Francine M.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
RP Sonntag, KC (reprint author), Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, MRC 223,115 Mill St, Belmont, MA 02478 USA.
EM ksonntag@mclean.harvard.edu
FU PHS HHS [NINDS N5057460]
NR 64
TC 128
Z9 132
U1 3
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD JUL
PY 2009
VL 132
BP 1795
EP 1809
DI 10.1093/brain/awn323
PN 7
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 463OE
UT WOS:000267440700017
PM 19052140
ER
PT J
AU Neuhausen, SL
Ozcelik, H
Southey, MC
John, EM
Godwin, AK
Chung, W
Iriondo-Perez, J
Miron, A
Santella, RM
Whittemore, A
Andrulis, IL
Buys, SS
Daly, MB
Hopper, JL
Seminara, D
Senie, RT
Terry, MB
AF Neuhausen, Susan L.
Ozcelik, Hilmi
Southey, Melissa C.
John, Esther M.
Godwin, Andrew K.
Chung, Wendy
Iriondo-Perez, Jeniffer
Miron, Alexander
Santella, Regina M.
Whittemore, Alice
Andrulis, Irene L.
Buys, Saundra S.
Daly, Mary B.
Hopper, John L.
Seminara, Daniela
Senie, Ruby T.
Terry, Mary Beth
CA Breast Canc Family Registry
TI BRCA1 and BRCA2 mutation carriers in the Breast Cancer Family Registry:
an open resource for collaborative research
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Biospecimen repository; Breast cancer; BRCA1; BRCA2
ID SENSITIVE GEL-ELECTROPHORESIS; UNKNOWN CLINICAL-SIGNIFICANCE; SEQUENCE
VARIANTS; TRUNCATING BRCA1; RISK; WOMEN; PREVALENCE
AB The Breast Cancer Family Registry is a resource for interdisciplinary and translational studies of the genetic epidemiology of breast cancer. This resource is available to researchers worldwide for collaborative studies. Herein, we report the results of testing for germline mutations in BRCA1 and BRCA2. We have tested 4,531 probands for mutations in BRCA1 and 4,084 in BRCA2. Deleterious mutations in BRCA1 and BRCA2 were identified for 9.8% of probands tested [233/4,531 (5.1%) for BRCA1 and 193/4,084 (4.7%) for BRCA2]. Of 1,385 Ashkenazi Jewish women tested for only the three founder mutations, 17.4% carried a deleterious mutation. In total, from the proband and subsequent family testing, 1,360 female mutation carriers (788 in BRCA1, 566 in BRCA2, 6 in both BRCA1 and BRCA2) have been identified. The value of the resource has been greatly enhanced by determining the germline BRCA1 and BRCA2 mutation statuses of nearly 6,000 probands.
C1 [Neuhausen, Susan L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
[Ozcelik, Hilmi] Mt Sinai Hosp, Div Epidemiol & Biostat, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[John, Esther M.] No Calif Canc Ctr, Fremont, CA USA.
[Godwin, Andrew K.; Daly, Mary B.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Chung, Wendy] Columbia Univ, Dept Pediat & Med, New York, NY USA.
[Iriondo-Perez, Jeniffer] Res Triangle Inst, Raleigh, NC USA.
[Miron, Alexander] Dana Farber Canc Ctr, Dept Canc Biol, Boston, MA USA.
[Santella, Regina M.; Senie, Ruby T.; Terry, Mary Beth] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Whittemore, Alice] Stanford Univ, Sch Med, Palo Alto, CA 94304 USA.
[Andrulis, Irene L.] Mt Sinai Hosp, Ontario Canc Genet Network, Fred A Litwin Ctr Canc Genet, Canc Care Ontario,Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Buys, Saundra S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Hopper, John L.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia.
[Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Clin & Genet Epidemiol Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Seminara, Daniela] Breast Canc Family Registry, Bethesda, MD USA.
RP Neuhausen, SL (reprint author), Univ Calif Irvine, Dept Epidemiol, Irvine, CA 92697 USA.
EM sneuhaus@uci.edu
RI Andrulis, Irene/E-7267-2013
FU National Cancer Institute; National Institutes of Health [CA-95-011];
Breast Cancer Family Registry and Principal Investigators [U01 CA69467];
Columbia University [U01 CA69398]; Fox Chase Cancer Center [U01
CA69631]; Huntsman Cancer Institute [U01 CA69446]; Northern California
Cancer Center [U01 CA69417]; University of Melbourne [U01 CA69638];
Research Triangle Institute Informatics Support Center [RFP
N02PC45022-46]; National Health and Medical Research Council (NHMRC);
Victorian Breast Cancer Research Consortium (VBCRC); Ovarian Cancer
SPORE [P50 CA83638]
FX This work was supported by the National Cancer Institute, National
Institutes of Health under RFA # CA-95-011 and through cooperative
agreements with members of the Breast Cancer Family Registry and
Principal Investigators, including Cancer Care Ontario (U01 CA69467),
Columbia University (U01 CA69398), Fox Chase Cancer Center (U01
CA69631), Huntsman Cancer Institute (U01 CA69446), Huntsman Cancer
Institute (U01 CA69446), Northern California Cancer Center (U01
CA69417), University of Melbourne (U01 CA69638), and Research Triangle
Institute Informatics Support Center (RFP No. N02PC45022-46). Mutation
testing in Australia was supported by grants from the National Health
and Medical Research Council (NHMRC) and the Victorian Breast Cancer
Research Consortium (VBCRC). Mutation testing at Fox Chase Cancer Center
was in part supported by an Ovarian Cancer SPORE grant (P50 CA83638).
Mutation testing in Ontario was supported in part by Cancer Care
Ontario. We wish to thank members of the Ontario Cancer Genetics Network
for their contributions to the study. MCS is a Senior Research Fellow of
the NHMRC and JLH is an Australia Fellow and a VBCRC Group Leader. The
content of this manuscript does not necessarily reflect the views or
policies of the National Cancer Institute or any of the collaborating
centers in the Breast CFR, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government or the
Breast CFR.
NR 24
TC 30
Z9 30
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2009
VL 116
IS 2
BP 379
EP 386
DI 10.1007/s10549-008-0153-8
PG 8
WC Oncology
SC Oncology
GA 458BR
UT WOS:000266988000018
PM 18704680
ER
PT J
AU Eng-Wong, J
Perkins, SN
Bondy, M
Li, DH
Singletary, SE
Nunez, N
Hursting, S
Chang, S
AF Eng-Wong, Jennifer
Perkins, Susan N.
Bondy, Melissa
Li, Donghui
Singletary, Sonya Eva
Nunez, Nomeli
Hursting, Stephen
Chang, Shine
TI Premenopausal Breast Cancer: Estrogen Receptor Status and Insulin-Like
Growth Factor-I (IGF-I), Insulin-Like Growth Factor Binding Protein-3
(IGFBP-3), and Leptin
SO BREAST JOURNAL
LA English
DT Letter
ID OBESITY; RISK
C1 [Eng-Wong, Jennifer] NCI, Bethesda, MD 20892 USA.
[Perkins, Susan N.; Nunez, Nomeli] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA.
[Bondy, Melissa; Chang, Shine] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Singletary, Sonya Eva] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Hursting, Stephen] Univ Texas Austin, Div Nutr Sci, Austin, TX 78712 USA.
[Hursting, Stephen] Univ Texas MD Anderson Canc Ctr, Austin, TX USA.
RP Eng-Wong, J (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM je95@georgetown.edu
NR 7
TC 6
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1075-122X
J9 BREAST J
JI Breast J.
PD JUL-AUG
PY 2009
VL 15
IS 4
BP 426
EP 428
DI 10.1111/j.1524-4741.2009.00753.x
PG 3
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 467CP
UT WOS:000267714400020
PM 19601950
ER
PT J
AU Soliman, AS
Banerjee, M
Lo, AC
Ismail, K
Hablas, A
Seifeldin, IA
Ramadan, M
Omar, HG
Fokuda, A
Harford, JB
Merajver, SD
AF Soliman, Amr S.
Banerjee, Mousumi
Lo, An-Chi
Ismail, Kadry
Hablas, Ahmed
Seifeldin, Ibrahim A.
Ramadan, Mohamed
Omar, Hoda G.
Fokuda, Aya
Harford, Joe B.
Merajver, Sofia D.
TI High Proportion of Inflammatory Breast Cancer in the Population-Based
Cancer Registry of Gharbiah, Egypt
SO BREAST JOURNAL
LA English
DT Letter
C1 [Soliman, Amr S.; Lo, An-Chi; Fokuda, Aya] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Ismail, Kadry; Hablas, Ahmed; Seifeldin, Ibrahim A.; Ramadan, Mohamed] Gharbiah Populat Based Canc Registry, Tanta, Egypt.
[Omar, Hoda G.] Tanta Canc Ctr, Tanta, Egypt.
[Harford, Joe B.] NCI, Off Int Affairs, Bethesda, MD 20892 USA.
[Merajver, Sofia D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
RP Soliman, AS (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA.
EM asoliman@umich.edu
FU NCI NIH HHS [5 P30 CA46592, CA77612, K07 CA090241, K07 CA90241, P30
CA046592, R01 CA077612, R03 CA117350, R25 CA112383]
NR 6
TC 14
Z9 14
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1075-122X
J9 BREAST J
JI Breast J.
PD JUL-AUG
PY 2009
VL 15
IS 4
BP 432
EP 434
DI 10.1111/j.1524-4741.2009.00755.x
PG 3
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 467CP
UT WOS:000267714400022
PM 19601951
ER
PT J
AU Ahn, J
Moore, SC
Albanes, D
Huang, WY
Leitzmann, MF
Hayes, RB
AF Ahn, J.
Moore, S. C.
Albanes, D.
Huang, W-Y
Leitzmann, M. F.
Hayes, R. B.
CA Prostate Lung Colorectal & Ovarian
TI Height and risk of prostate cancer in the prostate, lung, colorectal,
and ovarian cancer screening trial
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE height; prostate cancer; aggressiveness
ID BODY-MASS INDEX; NORWEGIAN MEN; UNITED-STATES; FOLLOW-UP;
PHYSICAL-ACTIVITY; SIZE; ANTHROPOMETRY; NUTRITION; COHORTS; WEIGHT
AB BACKGROUND: The relationship between prostate cancer and height is uncertain.
METHODS: We prospectively examined the association of height with prostate cancer among 34268 men in the prostate, lung, colorectal, and ovarian cancer trial. Anthropometry was assessed at baseline and 2144 incident prostate cancer cases were identified upto 8.9 years of follow-up.
RESULTS: Overall, tallness was not associated with the risk of prostate cancer or with the risk of non-aggressive disease, but the risk for aggressive prostate cancer tended to be greater in taller men (Gleason score >> 7 or stage XIII; P trend 0.05; relative risk (RR) for 190 cm + vs << 170 cm = 1.39, 95% confidence interval (95% CI): 0.96-2.01). This association was largely limited to men below the age of 65 years (P trend = 0.008; RR for 190 cm + vs << 170 cm = 1.76, 95% CI: 1.06-2.93; P for interaction = 0.009), although the number of cases was small and risk estimates were somewhat unstable.
CONCLUSION: The results of this large prospective prostate cancer screening trial suggest that tallness is associated with increased risk for younger onset aggressive prostate cancer. British Journal of Cancer (2009) 101, 522-525. doi:10.1038/sj.bjc.6605159 www.bjcancer.com Published online 30 June 2009 (C) 2009 Cancer Research UK
C1 [Ahn, J.] NYU, Div Epidemiol, Dept Environm Med, Sch Med, New York, NY 10016 USA.
[Ahn, J.; Moore, S. C.; Albanes, D.; Huang, W-Y] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20852 USA.
[Leitzmann, M. F.] Univ Regensburg, Dept Epidemiol & Prevent Med, D-93053 Regensburg, Germany.
RP Ahn, J (reprint author), NYU, Div Epidemiol, Dept Environm Med, Sch Med, 650 1st Ave, New York, NY 10016 USA.
EM Jiyoung.Ahn@NYUMC.org
RI Albanes, Demetrius/B-9749-2015; Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Hayes, Richard/0000-0002-0918-661X
FU Division of Cancer Prevention; National Cancer Institute; NIH; DHHS
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS. The authors thank Drs.
Christine Berg and Philip Prorok, Division of Cancer Prevention,
National Cancer Institute, the Screening Center investigators and the
staff of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer
Screening Trial, Mr Tom Riley and staff, Information Management
Services, Inc., Ms Barbara O'Brien and staff, Westat, Inc. Most
importantly, we acknowledge the study participants for their
contributions to making this study possible.
NR 29
TC 5
Z9 5
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUL
PY 2009
VL 101
IS 3
BP 522
EP 525
DI 10.1038/sj.bjc.6605159
PG 4
WC Oncology
SC Oncology
GA 476KP
UT WOS:000268439500022
PM 19568244
ER
PT J
AU Masjedi, K
Bruze, M
Hindsen, M
Minang, J
Ahlborg, N
AF Masjedi, K.
Bruze, M.
Hindsen, M.
Minang, J.
Ahlborg, N.
TI Is the variability of nickel patch test reactivity over time associated
with fluctuations in the systemic T-cell reactivity to nickel?
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
DE contact allergy; cytokine; enzyme-linked immunospot assay; patch test
ID ALLERGIC CONTACT-DERMATITIS; IN-VITRO; TRUE TEST(TM); REPRODUCIBILITY;
TH1-TYPE; TH2-TYPE; ELICITS
AB Background Patch test reactivity to nickel varies over time. To what extent this variation is associated with fluctuations in the T-cell reactivity to nickel is not known.
Objectives Our aim was to investigate the relationship between variation over time in the patch test and the systemic T-cell reactivity to nickel.
Methods Patients (n = 15) with a history of contact allergy to nickel were subjected to three consecutive patch tests at 3-month intervals, utilizing NiSO(4) at 10 concentrations ranging from 0.0032% to 12.5%. Prior to each patch test, blood mononuclear cells were analysed for T-cell reactivity to nickel by interleukin (IL)-4 and IL-13 enzyme-linked immunospot assay.
Results Eleven patients reacted positively in all three patch tests, two patients reacted in one or two tests and two remained negative. All 13 positive patients displayed variability over time, in terms of the lowest dose of nickel to which they responded. Also the cytokine response to nickel varied over time but the patients' mean cytokine response was positively correlated with their mean patch test reactivity (r(s) = 0.70, P < 0.01 for IL-4; r(s) = 0.78, P < 0.001 for IL-13). However, although the changes over time in patch test reactivity and the cytokine responses to nickel displayed a similar pattern in many patients, there was no significant correlation between the individuals' variation over time in vivo and in vitro.
Conclusions The overall magnitude of the T-cell reactivity to nickel and the patch test reactivity are closely associated but fluctuations in the systemic T-cell reactivity cannot be singled out as the major cause of longitudinal variability in nickel patch test reactivity.
C1 [Masjedi, K.; Ahlborg, N.] Mabtech, Nacka Strand, Sweden.
[Masjedi, K.; Minang, J.; Ahlborg, N.] Stockholm Univ, Dept Immunol, S-10691 Stockholm, Sweden.
[Bruze, M.; Hindsen, M.] Lund Univ, Univ Hosp, Dept Occupat & Environm Dermatol, Malmo, Sweden.
[Minang, J.] NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Masjedi, K (reprint author), Mabtech, Nacka Strand, Sweden.
EM khosro@mabtech.com
FU Swedish Agency for Innovation Systems (VINNOVA); Swedish Research
Council
FX This work was supported by the Swedish Agency for Innovation Systems
(VINNOVA) and an industrial PhD student grant from the Swedish Research
Council (K.M.). The authors thank Karin K. Olsson, Malmo University
Hospital, for collecting blood samples and Jan-Olov Persson, Stockholm
University, for advice on statistics.
NR 24
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-0963
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2009
VL 161
IS 1
BP 102
EP 109
DI 10.1111/j.1365-2133.2009.09182.x
PG 8
WC Dermatology
SC Dermatology
GA 459SF
UT WOS:000267128500014
PM 19438434
ER
PT J
AU Goldin, LR
Bjorkholm, M
Kristinsson, SY
Turesson, I
Landgren, O
AF Goldin, Lynn R.
Bjorkholm, Magnus
Kristinsson, Sigurdur Y.
Turesson, Ingemar
Landgren, Ola
TI Highly increased familial risks for specific lymphoma subtypes
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE non-Hodgkin lymphoma; diffuse large B-cell lymphoma; follicular
lymphoma; Hodgkin lymphoma; familial risk
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; SUSCEPTIBILITY LOCI;
CANCER DATABASE; CLASSIFICATION; AGGREGATION; DISORDERS; NEOPLASMS;
SCREEN; TUMORS
AB P>Studies have shown that familial risk contributes to aetiology of lymphomas. Using large population registries from Sweden, we evaluated risk of lymphoma subtypes among first-degree relatives of 2668 follicular lymphoma (FL) patients, 2517 diffuse large B-cell lymphoma (DLBCL) patients, and 6963 Hodgkin lymphoma (HL) patients compared to first-degree relatives of controls. Relatives were at the highest risk for developing the same lymphoma subtype as the case. DLBCL was increased 10-fold among relatives of DLBCL patients, FL was increased fourfold among relatives of FL patients and HL was increased fourfold among relatives of HL patients. These results imply that germline susceptibility genes are specific to lymphoma subtype.
C1 [Goldin, Lynn R.; Landgren, Ola] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Bjorkholm, Magnus; Kristinsson, Sigurdur Y.; Landgren, Ola] Karolinska Univ Hosp Solna, Dept Med, Div Haematol, Stockholm, Sweden.
[Bjorkholm, Magnus; Kristinsson, Sigurdur Y.; Landgren, Ola] Karolinska Inst, Stockholm, Sweden.
[Turesson, Ingemar] Malmo Univ Hosp, Sect Haematol, Dept Med, Malmo, Sweden.
RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Executive Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA.
EM goldinl@mail.nih.gov
RI Fuller, Stephen/C-1200-2009; Kristinsson, Sigurdur /M-2910-2015
OI Kristinsson, Sigurdur /0000-0002-4964-7476
FU NIH; NCI; Swedish Cancer Society; Stockholm County Council; Karolinska
Institutet Foundations
FX This research was supported by the Intramural Research Program of the
NIH, NCI and by grants from the Swedish Cancer Society, Stockholm County
Council, and the Karolinska Institutet Foundations. The authors thank
Ms. Shiva Ayobi, The National Board of Health and Welfare, Stockholm,
Sweden; Ms. Susanne Dahllof, Statistics Sweden, and Ms. Emily
Steplowski, Information Management Services, Silver Spring, MD, for
important efforts in the development of this database.
NR 15
TC 39
Z9 39
U1 0
U2 1
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2009
VL 146
IS 1
BP 91
EP 94
DI 10.1111/j.1365-2141.2009.07721.x
PG 4
WC Hematology
SC Hematology
GA 457IL
UT WOS:000266921600011
PM 19438470
ER
PT J
AU Kim, SY
Wan, XL
Helman, LJ
AF Kim, Su Young
Wan, Xiaolin
Helman, Lee J.
TI Targeting IGF-1R in the treatment of sarcomas: past, present and future
SO BULLETIN DU CANCER
LA English
DT Article
DE IGF family; IGF-1R antibody; sarcomas; clinical trials; mechanisms of
resistance
ID FACTOR-I-RECEPTOR; GASTROINTESTINAL STROMAL TUMORS; EWINGS-SARCOMA;
THERAPEUTIC TARGET; GROWTH; PATHWAY; CANCER; INHIBITION; CELLS; IGF2
AB The use of multimodality therapy has resulted in markedly improved cure rates for patients with sarcomas in the past 25 years. However, for virtually all patients with metastatic or recurrent disease, survival remains dismal. The important role that members of the insulin-like growth factor (IGF) family play in tumorigenesis has been known for decades. But it has only been in the last five years, that humanized and fully human antibodies targeting insulin-like growth factor receptor 1 (IGF-1R) have been developed. The use of these agents in clinical trials has been accompanied by several dramatic responses in patients with recurrent and refractory sarcomas. In this review, we will focus on preclinical highlights in the past, current clinic trials and discuss some exciting research opportunities to foster advances in the future.
C1 [Kim, Su Young; Wan, Xiaolin; Helman, Lee J.] NCI, Pediat Oncol Branch, Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Kim, SY (reprint author), NCI, Pediat Oncol Branch, Natl Inst Hlth, 10 Ctr Dr,CRC 1W-3750, Bethesda, MD 20892 USA.
EM kimsuyou@mail.nih.gov
NR 30
TC 14
Z9 14
U1 0
U2 1
PU JOHN LIBBEY EUROTEXT LTD
PI MONTROUGE
PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE
SN 0007-4551
J9 B CANCER
JI Bull. Cancer
PD JUL-AUG
PY 2009
VL 96
IS 7-8
BP E52
EP E60
DI 10.1684/bdc.2009.0915
PG 9
WC Oncology
SC Oncology
GA 484NP
UT WOS:000269052900002
PM 19617179
ER
PT J
AU English, BC
Price, DK
Figg, WD
AF English, Bevin C.
Price, Douglas K.
Figg, William D.
TI VEGF inhibition and metastasis Possible implications for antiangiogenic
therapy
SO CANCER BIOLOGY & THERAPY
LA English
DT Editorial Material
DE angiogenesis; VEGF; sunitinib; DC101; hypoxia; metastasis; invasiveness
ID TUMOR ANGIOGENESIS; GROWTH; RECEPTOR; HYPOXIA; CANCER
C1 [English, Bevin C.; Price, Douglas K.; Figg, William D.] NCI, Mol Pharmacol Sect, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP English, BC (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, NIH, 9000 Rockville Pike,Bldg 10 Room 5A07,MSC 1910, Bethesda, MD 20892 USA.
EM englishbclitwill@mail.nih.gov
RI Figg Sr, William/M-2411-2016
NR 8
TC 2
Z9 3
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4047
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD JUL 1
PY 2009
VL 8
IS 13
BP 1212
EP 1213
DI 10.4161/cbt.8.13.8918
PG 2
WC Oncology
SC Oncology
GA 486TC
UT WOS:000269220000005
ER
PT J
AU Kilfoy, BA
Zheng, TZ
Holford, TR
Han, XS
Ward, MH
Sjodin, A
Zhang, YQ
Bai, YN
Zhu, CR
Guo, GL
Rothman, N
Zhang, YW
AF Kilfoy, Briseis A.
Zheng, Tongzhang
Holford, Theodore R.
Han, Xuesong
Ward, Mary H.
Sjodin, Andreas
Zhang, Yaqun
Bai, Yana
Zhu, Cairong
Guo, Grace L.
Rothman, Nathaniel
Zhang, Yawei
TI International patterns and trends in thyroid cancer incidence, 1973-2002
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE International trends; Thyroid cancer; Papillary thyroid cancer
ID POLYCHLORINATED-BIPHENYLS; REPRODUCTIVE FACTORS; HORMONAL FACTORS; BIRTH
COHORT
AB During the past several decades, an increasing incidence of thyroid cancer has been reported in many parts of the world. To date, no study has compared the trends in thyroid cancer incidence across continents. We examined incidence data from cancer incidence in five continents (CI5) over the 30-year period 1973-2002 from 19 populations in the Americas, Asia, Europe, and Oceania. Thyroid cancer rates have increased from 1973-1977 to 1998-2002 for most of the populations except Sweden, in which the incidence rates decreased about 18% for both males and females. The average increase was 48.0% among males and 66.7% among females. More recently, the age-adjusted international thyroid cancer incidence rates from 1998 to 2002 varied 5-fold for males and nearly 10-fold for females by geographic region. Considerable variation in thyroid cancer incidence was present for every continent but Africa, in which the incidence rates were generally low. Our analysis of published CI5 data suggests that thyroid cancer rates increased between 1973 and 2002 in most populations worldwide, and that the increase does not appear to be restricted to a particular region of the world or by the underlying rates of thyroid cancer.
C1 [Kilfoy, Briseis A.; Zheng, Tongzhang; Holford, Theodore R.; Han, Xuesong; Zhang, Yaqun; Bai, Yana; Zhu, Cairong; Zhang, Yawei] Yale Univ, Yale Sch Publ Hlth, New Haven, CT 06520 USA.
[Kilfoy, Briseis A.; Ward, Mary H.; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, US Dept Hlth & Human Serv, Rockville, MD USA.
[Sjodin, Andreas] Ctr Dis Control & Prevent CDC, DLS, OATB, NCEH, Atlanta, GA 30341 USA.
[Zhang, Yaqun] Gansu Prov Design & Res Inst Environm Sci, Lanzhou, Gansu, Peoples R China.
[Bai, Yana] Lanzhou Univ, Sch Publ Hlth, Lanzhou, Gansu, Peoples R China.
[Zhu, Cairong] Sichuan Univ, Sch Publ Hlth, Chengdu 610064, Sichuan, Peoples R China.
[Guo, Grace L.] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA.
RP Zhang, YW (reprint author), Yale Univ, Yale Sch Publ Hlth, 60 Coll St,LEPH 440,POB 208034, New Haven, CT 06520 USA.
EM yawei.zhang@yale.edu
RI Aschebrook-Kilfoy, Briseis/A-2537-2012; Sjodin, Andreas/F-2464-2010
FU National Institutes of Health [TU2CA105666, 2043TW007864-01]
FX This research was supported by the National Institutes of Health
training grant TU2CA105666 and National Institutes of Health Fogarty
training grant 2043TW007864-01.
NR 25
TC 250
Z9 272
U1 6
U2 32
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2009
VL 20
IS 5
BP 525
EP 531
DI 10.1007/s10552-008-9260-4
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 449OP
UT WOS:000266340200003
PM 19016336
ER
PT J
AU Meinhold, CL
de Gonzalez, AB
Albanes, D
Weinstein, SJ
Taylor, PR
Virtamo, J
Stolzenberg-Solomon, RZ
AF Meinhold, Cari L.
de Gonzalez, Amy Berrington
Albanes, Demetrius
Weinstein, Stephanie J.
Taylor, Philip R.
Virtamo, Jarmo
Stolzenberg-Solomon, Rachael Z.
TI Predictors of fasting serum insulin and glucose and the risk of
pancreatic cancer in smokers
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Insulin resistance; Pancreatic cancer; Lifestyle factors; Nutrition;
Anthropometry
ID GLYCEMIC LOAD; NUTRITIONAL FACTORS; MULTIETHNIC COHORT; METABOLIC
SYNDROME; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; DIRECT INTERVIEWS;
DIETARY FACTORS; KOREAN MEN; WOMEN
AB A history of type 2 diabetes is one of few consistent risk factors for pancreatic cancer. Potentially modifiable factors related to fasting insulin and glucose concentrations may influence pancreatic cancer risk.
Multiple linear regression models were used to identify anthropometric, clinical, behavioral, and dietary factors associated with fasting insulin and glucose in a subcohort of non-diabetics in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 366). Hazards ratios (HRs) and 95% confidence intervals (CIs) were calculated among the larger cohort (n = 27,035).
During follow-up (median 16.1 years), 305 participants developed pancreatic cancer. Fasting insulin and/or glucose were positively associated with body mass index (BMI), height, and dietary total and saturated fat and inversely associated with serum high-density lipoprotein cholesterol (HDL) and dietary available carbohydrates, sucrose, and alcohol. Comparing highest to lowest quintiles, total fat (HR = 1.54, 95% CI 1.05-2.25, p-trend = 0.01) and saturated fat (HR = 1.38, 95% CI 0.97-1.98, p-trend = 0.06) were positively associated and available carbohydrates (HR = 0.63, 95% CI 0.44-0.90, p-trend = 0.01), particularly sucrose (HR = 0.62, 95% CI 0.43-0.89, p-trend = 0.09), were inversely associated with risk of pancreatic cancer. BMI, HDL, height, and alcohol were not associated with pancreatic cancer risk.
Dietary fat is associated with higher fasting insulin concentrations and may increase pancreatic cancer risk in smokers.
C1 [Meinhold, Cari L.; Albanes, Demetrius; Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Meinhold, Cari L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Virtamo, Jarmo] Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland.
RP Meinhold, CL (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM meinholdc@mail.nih.gov
RI Albanes, Demetrius/B-9749-2015; Kitahara, Cari/R-8267-2016
FU NIH; National Cancer Institute; U. S. Public Health Service
[N01-CN-45165, N01-RC-45035]; National Cancer Institute [N01-RC-37004];
Department of Health and Human Services
FX This research was supported in part by the Intramural Research Program
of the NIH and the National Cancer Institute. Additionally, this
research was supported by U. S. Public Health Service contracts
N01-CN-45165, N01-RC-45035, and N01-RC-37004 from the National Cancer
Institute, Department of Health and Human Services. We thank Dr.
Elizabeth Platz and Dr. Kala Visvanathan of the Johns Hopkins School of
Public Health for helpful comments during preparation of this
manuscript.
NR 58
TC 9
Z9 9
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2009
VL 20
IS 5
BP 681
EP 690
DI 10.1007/s10552-008-9281-z
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 449OP
UT WOS:000266340200020
PM 19083105
ER
PT J
AU Leitzmann, MF
Koebnick, C
Moore, SC
Danforth, KN
Brinton, LA
Hollenbeck, AR
Schatzkin, A
Lacey, JV
AF Leitzmann, Michael F.
Koebnick, Corinna
Moore, Steven C.
Danforth, Kim N.
Brinton, Louise A.
Hollenbeck, Albert R.
Schatzkin, Arthur
Lacey, James V.
TI Prospective study of physical activity and the risk of ovarian cancer
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Physical activity; Cancer; Prospective study
ID LARGE COHORT; FOLLOW-UP; WOMEN; LIFE; HEALTH; BREAST
AB Available studies on physical activity and ovarian cancer have produced inconsistent findings, with some previous studies reporting a positive association between vigorous physical activity and ovarian cancer risk.
We prospectively investigated the relations of self-reported moderate and vigorous physical activity to ovarian cancer in a cohort of 96,216 US women aged 51-72 years at baseline, followed from 1996-1997 to 31 December 2003.
During seven years of follow-up, we documented 309 cases of epithelial ovarian carcinoma. In analyses adjusted for age, the relative risks (RRs) of ovarian cancer for individual and joint combinations of moderate and vigorous physical activity such as entirely inactive, neither moderate nor vigorous physical activity, moderate physical activity only, vigorous physical activity only, and both moderate and vigorous physical activity were 0.88, 1.0 (reference), 0.89, 1.05, and 1.08 (95% confidence interval (CI) = 0.81-1.43, respectively. After multivariate adjustment, the relation was essentially unchanged (RR comparing women with both moderate and vigorous physical activity to those with neither moderate nor vigorous physical activity = 1.10; 95% CI = 0.82-1.48). The null association between physical activity and ovarian cancer persisted in subgroups of women as defined by body mass index, parity, oral contraceptive use, menopausal hormone therapy, family history of ovarian cancer, and other variables (all p values for interaction > 0.05).
Neither moderate nor vigorous physical activity showed a statistically significant association with ovarian cancer in this large cohort of women.
C1 [Leitzmann, Michael F.; Koebnick, Corinna; Moore, Steven C.; Schatzkin, Arthur] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Koebnick, Corinna] So Calif Permanente Med Grp, Oakland, CA USA.
[Danforth, Kim N.; Brinton, Louise A.; Lacey, James V.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
RP Leitzmann, MF (reprint author), Univ Regensburg, Inst Epidemiol & Prevent Med, Franz Josef Struass Allee 11, D-93053 Regensburg, Germany.
EM michael.leitzmann@klinik.uni-regensburg.de
RI Brinton, Louise/G-7486-2015; Koebnick, Corinna/P-4767-2016; Moore,
Steven/D-8760-2016
OI Brinton, Louise/0000-0003-3853-8562; Koebnick,
Corinna/0000-0001-8274-0309; Moore, Steven/0000-0002-8169-1661
FU Intramural NIH HHS [Z01 CP010196-02]
NR 34
TC 18
Z9 19
U1 1
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2009
VL 20
IS 5
BP 765
EP 773
DI 10.1007/s10552-008-9291-x
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 449OP
UT WOS:000266340200029
PM 19116765
ER
PT J
AU Rohrmann, S
Linseisen, J
Vrieling, A
Boffetta, P
Stolzenberg-Solomon, RZ
Lowenfels, AB
Jensen, MK
Overvad, K
Olsen, A
Tjonneland, A
Boutron-Ruault, MC
Clavel-Chapelon, F
Fagherazzi, G
Misirli, G
Lagiou, P
Trichopoulou, A
Kaaks, R
Bergmann, MM
Boeing, H
Bingham, S
Khaw, KT
Allen, N
Roddam, A
Palli, D
Pala, V
Panico, S
Tumino, R
Vineis, P
Peeters, PHM
Hjartaker, A
Lund, E
Cornejo, MLR
Agudo, A
Arriola, L
Sanchez, MJ
Tormo, MJ
Gurrea, AB
Lindkvist, B
Manjer, J
Johansson, I
Ye, WM
Slimani, N
Duell, EJ
Jenab, M
Michaud, DS
Mouw, T
Riboli, E
Bueno-de-Mesquita, HB
AF Rohrmann, Sabine
Linseisen, Jakob
Vrieling, Alina
Boffetta, Paolo
Stolzenberg-Solomon, Rachael Z.
Lowenfels, Albert B.
Jensen, Majken K.
Overvad, Kim
Olsen, Anja
Tjonneland, Anne
Boutron-Ruault, Marie-Christine
Clavel-Chapelon, Francoise
Fagherazzi, G.
Misirli, Gesthimani
Lagiou, Pagona
Trichopoulou, Antonia
Kaaks, Rudolf
Bergmann, Manuela M.
Boeing, Heiner
Bingham, Sheila
Khaw, Kay-Tee
Allen, Naomi
Roddam, Andrew
Palli, Domenico
Pala, Valeria
Panico, Salvatore
Tumino, Rosario
Vineis, Paolo
Peeters, Petra H. M.
Hjartaker, Anette
Lund, Eiliv
Redondo Cornejo, Ma Luisa
Agudo, Antonio
Arriola, Larraitz
Sanchez, Maria-Jose
Tormo, Maria-Jose
Barricarte Gurrea, Aurelio
Lindkvist, Bjorn
Manjer, Jonas
Johansson, Ingegerd
Ye, Weimin
Slimani, Nadia
Duell, Eric J.
Jenab, Mazda
Michaud, Dominique S.
Mouw, Traci
Riboli, Elio
Bueno-de-Mesquita, H. Bas
TI Ethanol intake and the risk of pancreatic cancer in the European
prospective investigation into cancer and nutrition (EPIC)
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Ethanol; Pancreatic cancer; Epidemiology; EPIC
ID DIETARY-INTAKE MEASUREMENTS; LIFE-STYLE FACTORS; BEVERAGE CONSUMPTION;
ALCOHOL-CONSUMPTION; COFFEE CONSUMPTION; CIGARETTE-SMOKING; MALE
SMOKERS; COHORT; EPIDEMIOLOGY; PROJECT
AB To examine the association of baseline and lifetime ethanol intake with cancer of the pancreas in the European Prospective Investigation into Cancer and Nutrition (EPIC).
Included in this analysis were 478,400 subjects, of whom detailed information on the intake of alcoholic beverages at baseline and over lifetime was collected between 1992 and 2000. During a median follow-up time of 8.9 years, 555 non-endocrine pancreatic cancer cases were observed. Multivariate Cox proportional hazard models were used to examine the association of ethanol intake at recruitment and average lifetime ethanol intake and pancreatic cancer adjusting for smoking, height, weight, and history of diabetes.
Overall, neither ethanol intake at recruitment (relative risk (RR) = 0.94, 95% confidence interval (CI) 0.69-1.27 comparing 30+ g/d vs. 0.1-4.9 g/d) nor average lifetime ethanol intake (RR = 0.95, 95% CI 0.65-1.39) was associated with pancreatic cancer risk. High lifetime ethanol intake from spirits/liquor at recruitment tended to be associated with a higher risk (RR = 1.40, 95% CI 0.93-2.10 comparing 10+ g/d vs. 0.1-4.9 g/d), but no associations were observed for wine and beer consumption.
These results suggest no association of alcohol consumption with the risk of pancreatic cancer.
C1 [Rohrmann, Sabine; Linseisen, Jakob; Kaaks, Rudolf] German Canc Res Ctr, Div Clin Epidemiol, D-69120 Heidelberg, Germany.
[Vrieling, Alina; Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth Environm RIVM, Bilthoven, Netherlands.
[Vrieling, Alina; Peeters, Petra H. M.] Univ Med Ctr Utrecht, Julius Ctr, Utrecht, Netherlands.
[Boffetta, Paolo; Slimani, Nadia; Duell, Eric J.; Jenab, Mazda] IARC WHO, Lyon, France.
[Stolzenberg-Solomon, Rachael Z.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA.
[Lowenfels, Albert B.] New York Med Coll, Valhalla, NY 10595 USA.
[Jensen, Majken K.; Overvad, Kim] Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark.
[Olsen, Anja; Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Francoise; Fagherazzi, G.] Univ Paris 11, Inst Gustave Roussy, INSERM, ERI20, Villejuif, France.
[Misirli, Gesthimani; Lagiou, Pagona; Trichopoulou, Antonia] Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece.
[Bergmann, Manuela M.; Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Bingham, Sheila] MRC, Dunn Human Nutr Unit, Cambridge, England.
[Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[Allen, Naomi; Roddam, Andrew] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Pala, Valeria] Natl Canc Inst, Nutr Epidemiol Unit, I-20133 Milan, Italy.
[Panico, Salvatore] Univ Naples Federico 2, Dept Clin & Expt Med, Naples, Italy.
[Tumino, Rosario] Azienda Osped Civile MP Arezzo, Canc Registry, Ragusa, Italy.
[Peeters, Petra H. M.; Michaud, Dominique S.; Mouw, Traci; Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Publ Hlth, London, England.
[Hjartaker, Anette] Canc Registry Norway, Insititute Populat Based Canc Res, Oslo, Norway.
[Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway.
[Redondo Cornejo, Ma Luisa] Hlth & Hlth Serv Council Asturias, Publ Hlth Directorate, Asturias, Spain.
[Agudo, Antonio] Catalan Inst Oncol, Unit Nutr Environm & Canc, Barcelona, Spain.
[Arriola, Larraitz] Basque Govt, Publ Hlth Dept Gipuzkoa, Gipuzkoa, Spain.
[Arriola, Larraitz; Sanchez, Maria-Jose; Tormo, Maria-Jose; Barricarte Gurrea, Aurelio] CIBERESP, Murcia, Spain.
[Sanchez, Maria-Jose] Andalusian Sch Publ Hlth, Granada, Spain.
[Tormo, Maria-Jose] Murcia Reg Hlth Council, Dept Epidemiol, Murcia, Spain.
[Barricarte Gurrea, Aurelio] Publ Hlth Inst Navarra, Pamplona, Spain.
[Lindkvist, Bjorn] Sahlgrens Univ Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Gothenburg, Sweden.
[Manjer, Jonas] Malmo Univ Hosp, Dept Surg, Malmo, Sweden.
[Johansson, Ingegerd] Umea Univ Hosp, Dept Odontol, S-90185 Umea, Sweden.
[Ye, Weimin] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
RP Rohrmann, S (reprint author), German Canc Res Ctr, Div Clin Epidemiol, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM s.rohrmann@dkfz.de
RI Hjartaker, Anette/D-6220-2011; Rohrmann, Sabine/D-2113-2012; Ye,
Weimin/A-5939-2008; Boutron Ruault, Marie-Christine/G-3705-2013;
Boutron, Marie-Christine/K-8168-2013; Linseisen, Jakob/B-5353-2014;
Clavel-Chapelon, Francoise/G-6733-2014; Michaud, Dominique/I-5231-2014;
SANCHEZ-PEREZ, MARIA JOSE/D-1087-2011; Boutron-Ruault,
Marie-Christine/H-3936-2014; Vrieling, Alina/A-2725-2016; Panico,
Salvatore/K-6506-2016
OI Arriola, Larraitz/0000-0001-8487-7181; Agudo,
Antonio/0000-0001-9900-5677; PALLI, Domenico/0000-0002-5558-2437; Duell,
Eric J/0000-0001-5256-0163; Linseisen, Jakob/0000-0002-9386-382X;
SANCHEZ-PEREZ, MARIA JOSE/0000-0003-4817-0757; Panico,
Salvatore/0000-0002-5498-8312
FU European Commission; Deutsche Krebshilfe; Deutsches
Krebsforschungszentrum; German Federal Ministry of Education and
Research; Danish Cancer Society; Health Research Fund (FIS) of the
Spanish Ministry of Health; Spanish Regional Governments of Andalucia,
Asturias, Basque Country, Murcia and Navarra; ISCIII Network RCESP
(C03/09), Spain; Cancer Research UK; Medical Research Council, United
Kingdom; Stroke Association, United Kingdom; British Heart Foundation;
Department of Health, United Kingdom; Food Standards Agency, United
Kingdom; Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek
Ministry of Education; Italian Association for Research on Cancer
(AIRC); Italian National Research Council, Fondazione-Istituto Banco
Napoli, Italy; Compagnia di San Paolo; Dutch Ministry of Public Health,
Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society;
Swedish Scientific Council; Regional Government of Skane, Sweden;
Norwegian Cancer Society; Research Council of Norway; French League
against Cancer (LNCC); National Institute for Health and Medical
Research (INSERM), France; Mutuelle Generale de l'Education Nationale
(MGEN), France; 3 M Co, France; Gustave Roussy Institute (IGR), France;
General Councils of France
FX European Commission: Public Health and Consumer Protection Directorate
1993-2004; Research Directorate-General 2005-; Deutsche Krebshilfe,
Deutsches Krebsforschungszentrum, German Federal Ministry of Education
and Research; Danish Cancer Society; Health Research Fund (FIS) of the
Spanish Ministry of Health, Spanish Regional Governments of Andalucia,
Asturias, Basque Country, Murcia and Navarra; the ISCIII Network RCESP
(C03/09), Spain; Cancer Research UK; Medical Research Council, United
Kingdom; Stroke Association, United Kingdom; British Heart Foundation;
Department of Health, United Kingdom; Food Standards Agency, United
Kingdom; Wellcome Trust, United Kingdom; Greek Ministry of Health; Greek
Ministry of Education; Italian Association for Research on Cancer
(AIRC); Italian National Research Council, Fondazione-Istituto Banco
Napoli, Italy; Compagnia di San Paolo; Dutch Ministry of Public Health,
Welfare and Sports; World Cancer Research Fund; Swedish Cancer Society;
Swedish Scientific Council; Regional Government of Skane, Sweden;
Norwegian Cancer Society; Research Council of Norway; French League
against Cancer (LNCC); National Institute for Health and Medical
Research (INSERM), France; Mutuelle Generale de l'Education Nationale
(MGEN), France; 3 M Co, France; Gustave Roussy Institute (IGR), France;
and General Councils of France
NR 40
TC 29
Z9 30
U1 0
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD JUL
PY 2009
VL 20
IS 5
BP 785
EP 794
DI 10.1007/s10552-008-9293-8
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 449OP
UT WOS:000266340200031
PM 19145468
ER
PT J
AU Robey, RW
Obrzut, T
Shukla, S
Polgar, O
Macalou, S
Bahr, JC
Di Pietro, A
Ambudkar, SV
Bates, SE
AF Robey, Robert W.
Obrzut, Tomasz
Shukla, Suneet
Polgar, Orsolya
Macalou, Sira
Bahr, Julian C.
Di Pietro, Attilio
Ambudkar, Suresh V.
Bates, Susan E.
TI Becatecarin (rebeccamycin analog, NSC 655649) is a transport substrate
and induces expression of the ATP-binding cassette transporter, ABCG2,
in lung carcinoma cells
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Becatecarin; Rebecamycin derivative; ABCG2; Drug-resistance;
Topoisomerase inhibitor
ID CANCER RESISTANCE PROTEIN; TOPOISOMERASE-I INHIBITORS; BREAST-CANCER;
PHASE-II; MULTIDRUG TRANSPORTER; P-GLYCOPROTEIN; INDOLOCARBAZOLE
COMPOUND; CONFERS RESISTANCE; IMATINIB MESYLATE; DRUG-RESISTANCE
AB ABCG2 overexpression has been linked to resistance to topoisomerase inhibitors, leading us to examine the potential interaction between ABCG2 and becatecarin.
Interaction with ABCG2 was determined by ATPase assay, competition of [(125)I]iodoarylazidoprazosin (IAAP) photolabeling and flow cytometry. Cellular resistance was measured in 4-day cytotoxicity assays. ABCG2 expression was measured by fluorescent-substrate transport assays and immunoblot.
Becatecarin competed [(125)I]-IAAP labeling of ABCG2, stimulated ATPase activity and, at concentrations greater than 10 mu M, inhibited ABCG2-mediated transport. Becatecarin-selected A549 Bec150 lung carcinoma cells were 3.1-, 15-, 8-, and 6.8-fold resistant to becatecarin, mitoxantrone, SN-38 and topotecan, respectively. A549 Bec150 cells transported the ABCG2 substrates pheophorbide a, mitoxantrone and BODIPY-prazosin and displayed increased staining with the anti-ABCG2 antibody 5D3 compared to parental cells. Increased ABCG2 expression was confirmed by immunoblot.
Our results suggest that becatecarin is transported by ABCG2 and can induce ABCG2 expression in cancer cells.
C1 [Macalou, Sira; Di Pietro, Attilio] Univ Lyon, CNRS, Inst Biol & Chim Prot, UMR5086, F-69367 Lyon 07, France.
[Robey, Robert W.; Obrzut, Tomasz; Polgar, Orsolya; Bahr, Julian C.; Bates, Susan E.] NIH, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Shukla, Suneet; Ambudkar, Suresh V.] NIH, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Robey, RW (reprint author), 9000 Rockville Pike,Bldg 10 Rm 13N248, Bethesda, MD 20892 USA.
EM robeyr@mail.nih.gov
RI shukla, suneet/B-4626-2012
FU NIH, National Cancer Institute, Center for Cancer Research; French
Region Rhone-Alpes
FX We thank Dr. Krishnamachary Nandigama for providing crude membranes of
ABCG2-expressing High Five insect cells. This research was supported by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. S. M. was recipient of an Explora'Doc
fellowship from the French Region Rhone-Alpes, in the frame of a
collaboration between A.D.P. and S.E.B.
NR 37
TC 10
Z9 11
U1 0
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD JUL
PY 2009
VL 64
IS 3
BP 575
EP 583
DI 10.1007/s00280-008-0908-2
PG 9
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 458QP
UT WOS:000267038900015
PM 19132374
ER
PT J
AU Kato, I
Cichon, M
Yee, CL
Land, S
Korczak, JF
AF Kato, Ikuko
Cichon, Michelle
Yee, Cecilia L.
Land, Susan
Korczak, Jeannette F.
TI African American-preponderant single nucleotide polymorphisms (SNPs) and
risk of breast cancer
SO CANCER EPIDEMIOLOGY
LA English
DT Article
DE Breast cancer; African American; SNP; Case-control study; Estrogen
ID ESTROGEN METABOLISM; WHITE WOMEN; POPULATION STRATIFICATION; CYP1B1
POLYMORPHISM; GENE POLYMORPHISMS; ASSOCIATION; HSD17B1; SMOKING;
INCREASES; ENZYMES
AB Background: African American women more often present with more aggressive types of breast cancer than Caucasian women, but little is known whether genetic polymorphisms specific to or disproportionate in African Americans are associated with their risk of breast cancer. Methods: A population-based case-control study was conducted including 194 cases identified through the Metropolitan Detroit Cancer Surveillance System and 189 controls recruited through random digit dialing to examine polymorphisms in genes involved in estrogen metabolism and action. Results: The African American-specific CYP1A1 5639C allele was associated with an increased risk of breast cancer (odds ratio (OR) = 2.34, 95% confidence interval (CI) 1.23-4.44) and this association with the CYP1A1 5639 locus was dependent on another polymorphism in the CYP3A4 gene (P = 0.043 for the interaction). In addition, African American-predominant CYP1B1 432 Val allele was significantly more often found in the cases than in the controls overall and the HSD17B1 312 Gly allele was specifically associated with premenopausal breast cancer risk (OR = 3.00, 95%CI 1.29-6.99). Conclusion: These observations need to be confirmed in larger studies due to the limited statistical power of the study based on a small number of cases. (C) 2009 Elsevier LtdPublished by Elsevier Ltd. All rights reserved.
C1 [Kato, Ikuko; Cichon, Michelle; Yee, Cecilia L.; Land, Susan; Korczak, Jeannette F.] Wayne State Univ, Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA.
[Kato, Ikuko] Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48201 USA.
[Land, Susan] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA.
[Korczak, Jeannette F.] NCI, Div Extramural Act, Bethesda, MD 20892 USA.
RP Kato, I (reprint author), 110 E Warren Ave, Detroit, MI 48201 USA.
EM katoi@karmanos.org
FU Susan G. Komen for the Cure [POP0100608, POP0504545]; NIH [R01-CA93817]
FX This research was supported by grants from Susan G. Komen for the Cure,
POP0100608 and POP0504545, and from NIH R01-CA93817.
NR 38
TC 19
Z9 19
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD JUL
PY 2009
VL 33
IS 1
BP 24
EP 30
DI 10.1016/j.canep.2009.04.009
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 494VF
UT WOS:000269846400005
PM 19679043
ER
PT J
AU Giambartolomei, C
Mueller, CM
Greene, MH
Korde, LA
AF Giambartolomei, Claudia
Mueller, Christine M.
Greene, Mark H.
Korde, Larissa A.
TI A mini-review of familial ovarian germ cell tumors: An additional
manifestation of the familial testicular germ cell tumor syndrome
SO CANCER EPIDEMIOLOGY
LA English
DT Review
DE Ovarian germ cell tumor; Familial; Epidemiology; Testicular germ cell
tumor; Genetic predisposition; SEER
ID 2 SIBLINGS; CANCER; RISK; DYSGERMINOMA; DYSGENESIS; EXPRESSION;
GENETICS; BROTHER; BIOLOGY; GONADS
AB Introduction While testicular germ cell tumors (TGCTs) are the most common malignancy in young men, germ cell tumors in women are uncommon. Familial clustering, epidemiologic evidence of increased risk with family or personal history of TGCT, and associations with genitourinary tract anomalies suggest an underlying genetic predisposition to TGCT, but traditional linkage studies have yet to identify a highly penetrant TGCT cancer susceptibility gene. In this paper, we investigate the familial occurrence of testicular and ovarian germ cell tumors. Methods We report a family in which a TGCT and an ovarian germ cell tumor (OGCT) occurred in two siblings, summarize the existing literature on familial occurrences of OGCT, either alone or in combination with extragonadal or TGCTs, and compare the incidence of familial and sporadic testicular and ovarian GCTs. Sporadic GCT data were obtained from the US Surveillance Epidemiology and End Results (SEER) registry. Results We identified 16 reports of OGCT occurring in conjunction with either ovarian, testicular or extragonadal GCT. In these familial cases, the mean age at onset of female dysgerminoma was younger than that noted in the general population (age 17 vs. age 24, p = 0.01). In SEER, the incidence of TGCT was 15 times higher than that of OGCT. Histologic distributions in males and females showed distinctly different patterns. Discussion Although the incidence of OGCTs in the general population is quite low, its occurrence in multiple members of the same family and in families with TGCT suggests that a gene conferring susceptibility to GCTs may exist in some families. Published by Elsevier Ltd.
C1 [Giambartolomei, Claudia; Mueller, Christine M.; Greene, Mark H.; Korde, Larissa A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
RP Korde, LA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd Rm 7030, Rockville, MD 20852 USA.
EM larissa.korde@gmail.com
FU National Cancer Institute; Westat [NO2-CP-11019-50, NO2-CP-65504-50]
FX This work was funded by the Intramural Research Program of the National
Cancer Institute, and supported by resource contracts with Westat
(NO2-CP-11019-50 and NO2-CP-65504-50). The authors would like to
acknowledge the contributions of Claudia Soho, Jennifer Loud, and June
Peters to the CGB Familial Testicular Cancer study. We also offer
special thanks to our study participants, whose commitment has made this
research possible.
NR 36
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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 1877-7821
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD JUL
PY 2009
VL 33
IS 1
BP 31
EP 36
DI 10.1016/j.canep.2009.04.015
PG 6
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 494VF
UT WOS:000269846400006
PM 19679044
ER
PT J
AU Wu, HY
Rusiecki, JA
Zhu, KM
Potter, J
Devesa, SS
AF Wu, Hongyu
Rusiecki, Jennifer A.
Zhu, Kangmin
Potter, John
Devesa, Susan S.
TI Stomach Carcinoma Incidence Patterns in the United States by Histologic
Type and Anatomic Site
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GASTRIC CARDIA CARCINOMAS; HELICOBACTER-PYLORI; CANCER INCIDENCE;
CHANGING PATTERNS; MORTALITY TRENDS; ESOPHAGEAL; METAANALYSIS; DIFFUSE;
WHITES; ADENOCARCINOMAS
AB Background: Using data from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results program, we analyzed stomach carcinoma incidence patterns by both histologic type and anatomic site.
Methods: We calculated age-adjusted (2000 U.S. standard) rates for 1978 to 2005, and for five time periods from 1978-1983 through 2001-2005 according to histologic type and anatomic site, separately and jointly. We also analyzed rates by race, gender, and age group.
Results: During 1978 to 2005, more than 54,000 stomach carcinoma cases were diagnosed among residents of the nine Surveillance, Epidemiology, and End Results areas. Total stomach carcinoma rates declined by 34% from the 1978-1983 to the 2001-2005 time periods. By histologic type, intestinal rates decreased consistently, whereas those for diffuse rates increased through 2000 and declined in recent years. By anatomic site, cardia rates increased during earlier years and then decreased, whereas rates for all other sites declined. When considered jointly by histologic type and anatomic site, intestinal carcinoma rates decreased for all sites except the cardia; diffuse rates increased through 2000 and decreased in recent years for all sites except the overlapping/nonspecified sites. Both diffuse and intestinal rates were lowest among whites, intermediate among blacks, and highest among the other, primarily Asian, races, with only modest gender differences for the diffuse type. In contrast, cardia carcinoma rates were highest among whites and were notably higher among males, especially whites among whom the male/female rate ratio was five to one.
Conclusions: Stomach carcinoma incidence patterns differ by histologic type, anatomic site, race, gender, and age, suggesting that etiologic heterogeneity should be pursued in future research. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1945-52)
C1 [Devesa, Susan S.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Wu, Hongyu; Zhu, Kangmin; Potter, John] US Mil Canc Inst, Walter Reed Army Med Ctr, Washington, DC USA.
[Rusiecki, Jennifer A.; Zhu, Kangmin] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
RP Devesa, SS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8048, Rockville, MD 20850 USA.
EM devesas@mail.nih.gov
FU National Cancer Institute; NIH; The United States Military Cancer
Institute via the Uniformed Services University; Henry M. Jackson
Foundation
FX Intramural Research Program of the National Cancer Institute, the NIH
and The United States Military Cancer Institute via the Uniformed
Services University, of the Health Sciences under the auspices of the
Henry M. Jackson Foundation for the Advancement of Military Medicine.
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U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2009
VL 18
IS 7
BP 1945
EP 1952
DI 10.1158/1055-9965.EPI-09-0250
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 471LR
UT WOS:000268059700001
PM 19531677
ER
PT J
AU Sanderson, SC
O'Neill, SC
White, DB
Bepler, G
Bastian, L
Lipkus, IM
McBride, CM
AF Sanderson, Saskia C.
O'Neill, Suzanne C.
White, Della Brown
Bepler, Gerold
Bastian, Lori
Lipkus, Isaac M.
McBride, Colleen M.
TI Responses to Online GSTM1 Genetic Test Results among Smokers Related to
Patients with Lung Cancer: A Pilot Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SMOKING-CESSATION TREATMENT; AFRICAN-AMERICAN SMOKERS; NICOTINE
DEPENDENCE; RISK; SUSCEPTIBILITY; IMPACT; FEEDBACK; MOTIVATION; PROGRAM;
ANALOG
AB Providing smokers with personal genetic test results indicating increased lung cancer risk may increase uptake of effective smoking cessation services. Using the internet may increase reach and enable real-time assessment of how people process genetic risk information away from the clinic setting. We therefore explored smokers' responses to Web-delivered GSTM1 genetic test results indicating higher or lower lung cancer risk. Participants were smokers (n = 44) biologically related to patients with newly diagnosed lung cancer. Measures were assessed at baseline, before and immediately after receipt of online genetic test results, and at 6-month follow-up. Outcomes included accurate comprehension of results, regret about being tested, cessation-related cognitions (e.g., perceived response efficacy), and uptake of free smoking cessation services (nicotine replacement therapy, printed self-help materials, telephone counseling sessions). Twenty-two "relative smokers" received a GSTM1-missing (higher risk) and 22 a GSTM1-present (lower risk) result. All relative smokers with GSTM1-missing results and 55% of those with GSTM1-present results accurately interpreted their results. No relative smokers regretted having taken the test. Relative smokers receiving GSTM1-missing results reported lower confidence that quitting could reduce lung cancer risk (perceived response efficacy) than those receiving GSTM1-present results. There were no other significant between-group differences. Uptake of smoking cessation services was high (e.g., 91% nicotine replacement therapy uptake). Genetic test results may not influence uptake of free smoking cessation services because of ceiling effects. Further research is needed to determine the risks and benefits of Web-based disclosure of genetic test results. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1953-61)
C1 [Sanderson, Saskia C.] Mt Sinai Sch Med, Icahn Med Inst, Dept Genet & Genom Sci, New York, NY 10029 USA.
[O'Neill, Suzanne C.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[White, Della Brown; McBride, Colleen M.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
[Bepler, Gerold] H Lee Moffitt Comprehens Canc Ctr, Tampa, FL USA.
[Lipkus, Isaac M.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
RP Sanderson, SC (reprint author), Mt Sinai Sch Med, Icahn Med Inst, Dept Genet & Genom Sci, Floor 14,1425 Madison Ave, New York, NY 10029 USA.
EM saskia.sanderson@mssm.edu
FU National Human Genome Research Institute (NHGRI); NIH; National Cancer
Institute; NHGRI [U01CA09622]
FX Intramural Research program of the National Human Genome Research
Institute (NHGRI), NIH, and National Cancer Institute and NHGRI grant
U01CA09622. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Cancer
Institute, NHGRI, or NIH.
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2009
VL 18
IS 7
BP 1953
EP 1961
DI 10.1158/1055-9965.EPI-08-0620
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 471LR
UT WOS:000268059700002
PM 19567511
ER
PT J
AU Li, CI
Mathes, RW
Malone, KE
Daling, JR
Bernstein, L
Marchbanks, PA
Strom, BL
Simon, MS
Press, MF
Deapen, D
Burkman, RT
Folger, SG
McDonald, JA
Spirtas, R
AF Li, Christopher I.
Mathes, Robert W.
Malone, Kathleen E.
Daling, Janet R.
Bernstein, Leslie
Marchbanks, Polly A.
Strom, Brian L.
Simon, Michael S.
Press, Michael F.
Deapen, Dennis
Burkman, Ronald T.
Folger, Suzanne G.
McDonald, Jill A.
Spirtas, Robert
TI Relationship between Migraine History and Breast Cancer Risk among
Premenopausal and Postmenopausal Women
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID REPRODUCTIVE LIFE EVENTS; COLLABORATIVE REANALYSIS; PREVALENCE;
HEADACHE; AURA
AB Both migraine and breast cancer are hormonally mediated diseases, and it is biologically plausible that women with a history of migraine may have a reduced breast cancer risk. However, this relationship has only been assessed in a single relatively small study that was unable to assess the effect of migraine triggers, which are also well-established breast cancer risk factors (e.g., use of alcohol and exogenous hormones), on the inverse association observed. Utilizing data on 4,568 breast cancer cases and 4,678 controls who participated in a multicenter population-based case-control study in the United States, we evaluated the association between migraine history and breast cancer risk using unconditional logistic regression. Migraine history data were obtained from structured in-person interviews. Women with a history of migraine had a reduced risk of breast cancer [odds ratio, 0.74; 95% confidence interval (CI), 0.66-0.82]. This risk did not differ by menopausal status, age at migraine diagnosis, use of prescription migraine medications, or when analyses were restricted to women who avoided various migraine triggers (including alcohol, exogenous hormones, and smoking). These data support a previous finding that a history of migraine may be associated with a reduced risk of breast cancer. It extends the prior report in observing that this relationship holds for both premenopausal and postmenopausal women and is independent of exposure to common migraine triggers. (Cancer Epidemol Biomarkers Prev 2009;18(7):2030-4)
C1 [Li, Christopher I.; Mathes, Robert W.; Malone, Kathleen E.; Daling, Janet R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Div Canc Etiol, Los Angeles, CA USA.
[Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
[Deapen, Dennis] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Deapen, Dennis] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Marchbanks, Polly A.; Folger, Suzanne G.; McDonald, Jill A.] Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA.
[Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Strom, Brian L.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA.
[Burkman, Ronald T.] Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA.
[Spirtas, Robert] NICHHD, NIH, Contracept & Reprod Branch, Ctr Populat Res,Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Li, CI (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-C308,POB 19024, Seattle, WA 98109 USA.
EM cili@fhcrc.org
FU National Institute of Child Health and Human Development; National
Cancer Institute [N01-HD-2-3168]; Fred Hutchinson Cancer Research Center
[N01-HD-2-3166]; Karmanos Cancer Institute at Wayne State University
[N01-HD-03-3-3174]; University of Pennsylvania [N01-HD-3-3176];
University of Southern California [N01-HD-3-3175]; Centers for Disease
Control and Prevention [Y01-HD-7022]
FX National Institute of Child Health and Human Development, with
additional support from the National Cancer Institute, through contracts
with Emory University (N01-HD-2-3168), Fred Hutchinson Cancer Research
Center (N01-HD-2-3166), Karmanos Cancer Institute at Wayne State
University (N01-HD-03-3-3174), the University of Pennsylvania
(N01-HD-3-3176), and the University of Southern California
(N01-HD-3-3175); and through an intraagency agreement with the Centers
for Disease Control and Prevention (Y01-HD-7022). The Centers for
Disease Control contributed additional staff and computer support. The
findings and conclusions in this article are those of the authors and do
not necessarily represent the views of the Centers for Disease Control
and Prevention. The collection of cancer incidence data in California
used in this publication (University of Southern California Los Angeles
County portion of this study) was also supported by the California
Department of Health Services as part of the statewide cancer reporting
program mandated by the California Health and Safety Code Section
103885. The ideas and opinions expressed herein are those of the
authors, and no endorsement by the State of California, Department of
Health Services, is intended or should be inferred.
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PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2009
VL 18
IS 7
BP 2030
EP 2034
DI 10.1158/1055-9965.EPI-09-0291
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 471LR
UT WOS:000268059700012
PM 19589913
ER
PT J
AU Spector, D
Mishel, M
Skinner, CS
DeRoo, LA
VanRiper, M
Sandler, DP
AF Spector, Denise
Mishel, Merle
Skinner, Celette Sugg
DeRoo, Lisa A.
VanRiper, Marcia
Sandler, Dale P.
TI Breast Cancer Risk Perception and Lifestyle Behaviors Among White and
Black Women With a Family History of the Disease
SO CANCER NURSING
LA English
DT Article
DE Breast cancer; Family history; Lifestyle behaviors; Risk perception
ID 1ST-DEGREE RELATIVES; QUALITATIVE RESEARCH; PREVENTION; PREDICTORS;
NUTRITION; TAMOXIFEN; AWARENESS; CHOICES
AB Although researchers have Investigated the relationships between perceived risk and behavioral risk factors for breast cancer, few qualitative studies have addressed the meaning of risk and its impact on decision making regarding lifestyle behaviors. This qualitative study explored factors involved in the formulation of perceived breast cancer risk and associations between risk perception and lifestyle behaviors in white and black women with a family history of breast cancer. Eligible participants were North Carolina residents in the Sister Study, a nationwide study of risk factors for breast cancer among women who have at least 1 sister diagnosed with breast cancer. Personal interviews were conducted with 32 women. Although most had heightened perceived risk, almost 20% considered themselves below-to-average risk. Participants with moderate-to-high perceived risk were more likely to report an affected sister and mother, a first-degree relative's diagnosis within 4 years, and death of a first-degree relative from breast cancer. Many women were unaware of associations between lifestyle behaviors and breast cancer risk. Only one-third of the women reported healthy lifestyle changes because of family history; dietary change was most frequently reported. Findings may be important for cancer nurses involved in developing breast cancer education programs for women with a family history of breast cancer.
C1 [Spector, Denise; Mishel, Merle; VanRiper, Marcia] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
[Skinner, Celette Sugg] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Behav & Commun Sci, Dallas, TX 75390 USA.
[DeRoo, Lisa A.; Sandler, Dale P.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
RP Spector, D (reprint author), 318 Sunset Creek Circle, Chapel Hill, NC 27516 USA.
EM dspector@email.unc.edu
OI Sandler, Dale/0000-0002-6776-0018
FU National Institute of Nursing Research and the National Center on
Minority Health and Health Disparities [P20 NR 8369]; American Cancer
Society, Doctoral Degree Scholarship in Cancer Nursing [DSCN-07-132-01];
National Institute of Health, National Institute of Environmental Health
Sciences [Z01 ES044005-10]
FX The Center for Innovations in Health Disparities Research from the
National Institute of Nursing Research and the National Center on
Minority Health and Health Disparities provided the funds to conduct
this research under grant P20 NR 8369. The First author was supported by
the American Cancer Society through a Doctoral Degree Scholarship in
Cancer Nursing (grant no. DSCN-07-132-01). This research was also
supported in part by the Intramural Program of the National Institute of
Health, National Institute of Environmental Health Sciences (Z01
ES044005-10).
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U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0162-220X
J9 CANCER NURS
JI Cancer Nurs.
PD JUL-AUG
PY 2009
VL 32
IS 4
BP 299
EP 308
PG 10
WC Oncology; Nursing
SC Oncology; Nursing
GA 465MK
UT WOS:000267589300006
PM 19444084
ER
PT J
AU Wang, Y
Zhang, ZQ
Garbow, JR
Rowland, DJ
Lubet, RA
Sit, D
Law, F
You, M
AF Wang, Yian
Zhang, Zhongqiu
Garbow, Joel R.
Rowland, Doug J.
Lubet, Ronald A.
Sit, Daniel
Law, Francis
You, Ming
TI Chemoprevention of Lung Squamous Cell Carcinoma in Mice by a Mixture of
Chinese Herbs
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID RANDOMIZED-TRIAL; BETA-CAROTENE; VITAMIN-A; CANCER; MODELS; EFFICACY;
MATRINE
AB Antitumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal and lung cancers. We have recently developed a new mouse model for lung squamous cell carcinomas (SCC). In this study, lung SCC mouse model was characterized using small-animal imaging techniques (magnetic resonance imaging and computed tomography). ATB decreased lung SCC significantly (3.1-fold; P<0.05) and increased lung hyperplastic lesions by 2.4-fold (P<0.05). This observation suggests that ATB can block hyperplasia from progression to SCC. ATB tissue distribution was determined using matrine as a marker chemical. We found that ATB is rapidly absorbed and then distributes to various tissues including the lung. These results indicate that ATB is a potent chemopreventive agent against the development of mouse lung SCCs.
C1 [Wang, Yian; Zhang, Zhongqiu; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Wang, Yian; Zhang, Zhongqiu; You, Ming] Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA.
[Garbow, Joel R.; Rowland, Doug J.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Lubet, Ronald A.] NCI, Chemoprevent Branch, Bethesda, MD 20892 USA.
[Sit, Daniel; Law, Francis] Simon Fraser Univ, Dept Biol Sci, Burnaby, BC V5A 1S6, Canada.
RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Eulcid Ave,4950 Childrens Pl, St Louis, MO 63110 USA.
EM youm@wudosis.wustl.edu
RI Rowland, Douglas/F-3104-2014
OI Rowland, Douglas/0000-0001-8059-6905
FU United States Public Health Service [R01 AT003203, N01-CN-25104];
NIH/National Cancer Institute Small Animal Imaging Resource Program [R24
CA83060]; Alvin J. Siteman Cancer Center at Washington University in St.
Louis; National Cancer Institute Comprehensive Cancer Center [P30
CA91842]
FX United States Public Health Service Grants R01 AT003203 & N01-CN-25104 (
M. You), an NIH/National Cancer Institute Small Animal Imaging Resource
Program grant (R24 CA83060); and the Alvin J. Siteman Cancer Center at
Washington University in St. Louis, a National Cancer Institute
Comprehensive Cancer Center (P30 CA91842).
NR 21
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U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD JUL
PY 2009
VL 2
IS 7
BP 634
EP 640
DI 10.1158/1940-6207.CAPR-09-0052
PG 7
WC Oncology
SC Oncology
GA 467MQ
UT WOS:000267743400006
PM 19584077
ER
PT J
AU Horvath, A
Korde, L
Greene, MH
Libe, R
Osorio, P
Faucz, FR
Raffin-Sanson, ML
Tsang, KM
Drori-Herishanu, L
Patronas, Y
Remmers, EF
Nikita, ME
Moran, J
Greene, J
Nesterova, M
Merino, M
Bertherat, J
Stratakis, CA
AF Horvath, Anelia
Korde, Larissa
Greene, Mark H.
Libe, Rossella
Osorio, Paulo
Faucz, Fabio Rueda
Raffin-Sanson, Marie Laure
Tsang, Kit Man
Drori-Herishanu, Limor
Patronas, Yianna
Remmers, Elaine F.
Nikita, Maria Eleni
Moran, Jason
Greene, Joseph
Nesterova, Maria
Merino, Maria
Bertherat, Jerome
Stratakis, Constantine A.
TI Functional Phosphodiesterase 11A Mutations May Modify the Risk of
Familial and Bilateral Testicular Germ Cell Tumors
SO CANCER RESEARCH
LA English
DT Article
ID CANCER; GENE; PDE11A; HYPERPLASIA; PROTEIN; MEN
AB Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 nonsynonymous substitutions in 20 patients from 15 families: four (R52T, F258Y, G291R, and V820M) were newly recognized, three (R804H, R867G, and M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P = 0.0002), present in 19% of the families of our cohort. Most variants,were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of the involvement of a PDE gene in TGCT, although the cyclic AMP signaling pathway has been investigated extensively in reproductive organ function and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT. [Cancer Res 2009;69(13):5301-6]
C1 [Horvath, Anelia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PDEGEN, NIH, CRC, Bethesda, MD 20892 USA.
[Korde, Larissa; Greene, Mark H.] NCI, Clin Genet Branch, Bethesda, MD 20892 USA.
[Merino, Maria] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Remmers, Elaine F.] NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA.
[Libe, Rossella; Bertherat, Jerome] Univ Paris 05, Inst Natl Sante & Rech Med, U567, Paris, France.
[Libe, Rossella; Bertherat, Jerome] Univ Paris 05, Hop Cochin, CNRS, Inst Cochin,UMR8104, Paris, France.
[Raffin-Sanson, Marie Laure] Inst Cochin, Dept Endocrinol Metab & Canc, Inst Natl Sante & Rech Med, U567, Paris, France.
[Osorio, Paulo; Faucz, Fabio Rueda] Pontificia Univ Catolica Parana, Mol Genet Lab, Curitiba, Parana, Brazil.
[Raffin-Sanson, Marie Laure] Hop Ambroise Pare, Dept Endocrinol, Boulogne Billancourt, France.
[Raffin-Sanson, Marie Laure] Univ Versailles, St Quentin en Yvelines, France.
RP Horvath, A (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, PDEGEN, NIH, CRC, 10 Ctr Dr,Room 1-3330, Bethesda, MD 20892 USA.
EM horvatha@gmail.nih.gov
RI Faucz, Fabio/C-1607-2009
FU NCI; Plan Hospitalier de Recherche Clinique [AOR 01093]; M.L.
Raffin-Sanson and the Agence Nationale de la Recherche
[ANR-06-MRAR-002]; Westat, Inc., Rockville, MD [02-C-0178,
N02-CP-11019-50, N02-CP-65504]; NIH [Z01-HD-000642-04]; National
Institute of Arthritis, Musculoskeletal and Skin Diseases
FX We thank Dr. Maria Dufau (Section on Molecular Endocrinology, Program on
Developmental Endocrinology and Genetics, National Institute of Child
Health and Human Development. NIH) for the generous donation of the
MLTC-1 cell line; the dedication, hard work meticulous attention to
detail, unflagging kindness, and support of study participants provided
by clinical research staff from NCI (Jennifer Loud, CRNP,
2,4-dinitrophenot or 2,4-dinitrophenyl; June Peters, MS; Phuong Mai, MD;
Christine Mueller, DO) and Westat (Ron Kase, MS; Rissah Watkins, MPH;
Ann Carr, MS); and to the FTC family members who contributed their time,
energy, and biological samples, without which this study could never
have been done.
NR 20
TC 45
Z9 47
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2009
VL 69
IS 13
BP 5301
EP 5306
DI 10.1158/0008-5472.CAN-09-0884
PG 6
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800006
PM 19549888
ER
PT J
AU Pinnix, CC
Lee, JT
Liu, ZJ
McDaid, R
Balint, K
Beverly, LJ
Brafford, PA
Xiao, M
Himes, B
Zabierowski, SE
Yashiro-Ohtani, Y
Nathanson, KL
Bengston, A
Pollock, PM
Weeraratna, AT
Nickoloff, BJ
Pear, WS
Capobianco, AJ
Herlyn, M
AF Pinnix, Chelsea C.
Lee, John T.
Liu, Zhao-Jun
McDaid, Ronan
Balint, Klara
Beverly, Levi J.
Brafford, Patricia A.
Xiao, Min
Himes, Benjamin
Zabierowski, Susan E.
Yashiro-Ohtani, Yumi
Nathanson, Katherine L.
Bengston, Ana
Pollock, Pamela M.
Weeraratna, Ashani T.
Nickoloff, Brian J.
Pear, Warren S.
Capobianco, Anthony J.
Herlyn, Meenhard
TI Active Notch1 Confers a Transformed Phenotype to Primary Human
Melanocytes
SO CANCER RESEARCH
LA English
DT Article
ID HUMAN-MELANOMA CELLS; E-CADHERIN; NEOPLASTIC TRANSFORMATION; MURINE
MELANOCYTES; MALIGNANT-MELANOMA; GROWTH-FACTOR; IN-VITRO; EXPRESSION;
PROGRESSION; DIFFERENTIATION
AB The importance of mitogen-activated protein kinase signaling in melanoma is underscored by the prevalence of activating mutations in N-Ras and B-Raf, yet clinical development of inhibitors of this pathway has been largely ineffective, suggesting that alternative oncogenes may also promote melanoma. Notch is an interesting candidate that has only been correlated with melanoma development and progression; a thorough assessment of tumor-initiating effects of activated Notch on human melanocytes would clarify the mounting correlative evidence and perhaps identify a novel target for an otherwise untreatable disease. Analysis of a substantial panel of cell lines and patient lesions showed that Notch activity is significantly higher in melanomas than their nontransformed counterparts. The use of a constitutively active, truncated Notch transgene construct (N(IC)) was exploited to determine if Notch activation is a "driving" event in melanocytic transformation or instead a "passenger" event associated with melanoma progression. N(IC)-infected melanocytes displayed increased proliferative capacity and biological features more reminiscent of melanoma, such as dysregulated cell adhesion and migration. Gene expression analyses supported these observations and aided in the identification of MCAM, an adhesion molecule associated with acquisition of the malignant phenotype, as a direct target of Notch trans-activation. N(IC)-positive melanocytes grew at clonal density, proliferated in limiting media conditions, and also exhibited anchorage-independent growth, suggesting that Notch alone is a transforming oncogene in human melanocytes, a phenomenon not previously described for any melanoma oncogene. This new information yields valuable insight into the basic epidemiology of melanoma and launches a realm of possibilities for drug intervention in this deadly disease. [Cancer Res 2009;69(13):5312-20]
C1 [Pinnix, Chelsea C.; Lee, John T.; Liu, Zhao-Jun; McDaid, Ronan; Balint, Klara; Beverly, Levi J.; Brafford, Patricia A.; Xiao, Min; Himes, Benjamin; Zabierowski, Susan E.; Capobianco, Anthony J.; Herlyn, Meenhard] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Pinnix, Chelsea C.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Nathanson, Katherine L.] Univ Penn, Dept Med, Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Yashiro-Ohtani, Yumi; Pear, Warren S.] Univ Penn, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Bengston, Ana; Pollock, Pamela M.] Translat Genom Res Inst, Phoenix, AZ USA.
[Weeraratna, Ashani T.] NIA, NIH, Baltimore, MD 21224 USA.
[Nickoloff, Brian J.] Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA.
RP Herlyn, M (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St,Room 489, Philadelphia, PA 19104 USA.
EM herlynm@wistar.org
OI Nathanson, Katherine/0000-0002-6740-0901
FU NIH [CA76674, CA25874, CA10815, CA93372, CA47159, CA80999, CA098101,
CA117881, GM071695]
FX We thank Drs. B. Keith and L. Brass for helpful discussions, J. Hayden
for imaging assistance, Sherry Yang for assistance with Notch receptor
real-time PCR experiments, and Gan Zhang for his expertise and aid in
processing the microarray data.
NR 41
TC 73
Z9 74
U1 2
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2009
VL 69
IS 13
BP 5312
EP 5320
DI 10.1158/0008-5472.CAN-08-3767
PG 9
WC Oncology
SC Oncology
GA 466VP
UT WOS:000267691800008
PM 19549918
ER
PT J
AU Unoki, M
Kumamoto, K
Takenoshita, S
Harris, CC
AF Unoki, Motoko
Kumamoto, Kensuke
Takenoshita, Seiichi
Harris, Curtis C.
TI Reviewing the current classification of inhibitor of growth family
proteins
SO CANCER SCIENCE
LA English
DT Review
ID CANDIDATE TUMOR-SUPPRESSOR; CELL-CYCLE ARREST; HISTONE H3K4ME3
RECOGNITION; PHD FINGER PROTEINS; ALTERNATIVE TRANSCRIPTS; ING1 GENE;
REPLICATIVE SENESCENCE; DEACETYLASE COMPLEX; PLANT HOMEODOMAIN; GENOMIC
STRUCTURE
AB Inhibitor of growth (ING) family proteins have been defined as candidate tumor suppressors for more than a decade. Recent emerging results using siRNA and knockout mice are expanding the previous understanding of this protein family. The results of ING1 knockout mouse experiments revealed that ING1 has a protective effect on apoptosis. Our recent results showed that ING2 is overexpressed in colorectal cancer, and induces colon cancer cell invasion through an MMP13-dependent pathway. Knockdown of ING2 by siRNA induces premature senescence in normal human fibroblast cells, and apoptosis or cell cycle arrest in various adherent cancer cells. Taken together, these results suggest that ING2 may also have roles in cancer progression and/or malignant transformation under some conditions. Additionally, knockdown of ING4 and ING5 by siRNA shows an inhibitory effect on the transition from G(2)/M to G(1) phase and DNA replication, respectively, suggesting that these proteins may play roles during cell proliferation in some context. ING family proteins may play dual roles, similar to transforming growth factor-beta, which has tumor suppressor-like functions in normal epithelium and also oncogenic functions in invasive metastatic cancers. In the present article, we briefly review ING history and propose a possible interpretation of discrepancies between past and recent data. (Cancer Sci 2009; 100: 1173-1179)
C1 [Unoki, Motoko; Kumamoto, Kensuke; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Unoki, Motoko] RIKEN, Inst Phys & Chem Res, Lab Biomarker, Tokyo, Japan.
[Kumamoto, Kensuke; Takenoshita, Seiichi] Fukushima Med Univ, Sch Med, Dept Surg 2, Fukushima, Japan.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM curtis_harris@nih.gov
FU Intramural NIH HHS [Z01 BC005795-13, Z01 BC010875-01]
NR 78
TC 27
Z9 33
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1347-9032
J9 CANCER SCI
JI Cancer Sci.
PD JUL
PY 2009
VL 100
IS 7
BP 1173
EP 1179
DI 10.1111/j.1349-7006.2009.01183.x
PG 7
WC Oncology
SC Oncology
GA 458AL
UT WOS:000266982000005
PM 19432890
ER
PT J
AU Yasuda, M
Nishizawa, T
Ohigashi, H
Tanaka, T
Hou, DX
Colburn, NH
Murakami, A
AF Yasuda, Michiko
Nishizawa, Takashi
Ohigashi, Hajime
Tanaka, Takuji
Hou, De-Xing
Colburn, Nancy H.
Murakami, Akira
TI Linoleic acid metabolite suppresses skin inflammation and tumor
promotion in mice: possible roles of programmed cell death 4 induction
SO CARCINOGENESIS
LA English
DT Article
ID INHIBITS AP-1 TRANSACTIVATION; ACTIVATOR PROTEIN-1 ACTIVITY;
COLON-CARCINOMA CELLS; NF-KAPPA-B; MOUSE SKIN; JB6 CELLS; NEOPLASTIC
TRANSFORMATION; GENERATION INHIBITOR; OXIDATIVE STRESS; GROWTH-FACTOR
AB (+/-)-13-Hydroxy-10-oxo-trans-11-octadecenoic acid (13-HOA) is one of the lipoxygenase metabolites of linoleic acid (LA) from corn germ. Recently, we reported that this metabolite suppressed the expression of lipopolysaccharide-induced proinflammatory genes in murine macrophages by disrupting mitogen-activated protein kinases and Akt pathways. In this study, we investigated the inhibitory effects of 13-HOA on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in ears and skin, as well as tumor promotion in female ICR mice. Pretreatment with 13-HOA (1600 nmol) inhibited ear edema formation by 95% (P < 0.05) in an inflammation test and reduced tumor incidence and the number of tumors per mouse by 40 and 64% (P < 0.05 each), respectively, in a two-stage skin carcinogenesis model. Histological examinations revealed that it decreased epidermal thickness, the number of infiltrated leukocytes and cell proliferation index. Furthermore, 13-HOA (8-40 mu M) suppressed TPA-induced anchorage-independent growth of JB6 mouse epidermal cells by 70-100%, whereas LA was virtually inactive. 13-HOA (40 mu M) inhibited TPA-induced activator protein-1 transactivation but not extracellular signal-regulated kinase1/2 activation. Interestingly, 13-HOA (40 mu M and 1600 nmol in JB6 cells and mouse skin, respectively) induced expression of programmed cell death 4 (Pdcd4), a novel tumor suppressor protein. To our knowledge, this is the first report of a food factor that is able to induce Pdcd4 expression. Collectively, our results indicate that 13-HOA may be a novel anti-inflammatory and antitumor chemopreventive agent with a unique mode of action.
C1 [Yasuda, Michiko; Nishizawa, Takashi; Ohigashi, Hajime; Murakami, Akira] Kyoto Univ, Div Food Sci & Biotechnol, Grad Sch Agr, Kyoto 6068502, Japan.
[Tanaka, Takuji] Kanazawa Med Univ, Dept Oncol Pathol, Uchinada, Ishikawa 9200293, Japan.
[Hou, De-Xing] Kagoshima Univ, Dept Biochem Sci & Technol, Fac Agr, Kagoshima 8900065, Japan.
[Colburn, Nancy H.] NCI, Gene Regulat Sect, Lab Canc Prevent, Ctr Canc Res, Frederick, MD 21702 USA.
RP Murakami, A (reprint author), Kyoto Univ, Div Food Sci & Biotechnol, Grad Sch Agr, Kyoto 6068502, Japan.
EM cancer@kais.kyoto-u.ac.jp
RI Hou, De-Xing/C-9296-2011;
OI Yasuda, Michiko/0000-0002-8984-6138
FU Ministry of Health, Labor and Welfare of Japan
FX Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and
Welfare of Japan (A. M. and T. T.).
NR 50
TC 10
Z9 10
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD JUL
PY 2009
VL 30
IS 7
BP 1209
EP 1216
DI 10.1093/carcin/bgp106
PG 8
WC Oncology
SC Oncology
GA 466MK
UT WOS:000267666100018
PM 19414503
ER
PT J
AU Lee, HS
Daar, IO
AF Lee, Hyun-Shik
Daar, Ira O.
TI EphrinB reverse signaling in cell-cell adhesion Is it just par for the
course?
SO CELL ADHESION & MIGRATION
LA English
DT Article
DE ephrin; Eph; cell-cell adhesion; Par-6; tight junctions
AB Cell-cell adhesion is a critical process for the formation and maintenance of tissue patterns during development, as well as invasion and metastasis of cancer cells. Although great strides have been made regarding our understanding of the processes that play a role in cell-cell adhesion, the precise mechanisms by which diverse signaling events regulate cell and tissue architecture is poorly understood. In this commentary we will focus on the Eph/ephrin signaling system, and specifically how the ephrinB1 transmembrane ligand for Eph receptor tyrosine kinases sends signals affecting cell-cell junctions. In a recent study using the epithelial cells of early stage Xenopus embryos, we have shown that loss-or gain-of function of ephrinB1 can disrupt cell-cell contacts and tight junctions. This study reveals a mechanism where ephrinB1 competes with active Cdc42 for binding to Par-6, a scaffold protein central to the Par polarity complex (Par-3/Par-6/Cdc42/aPKC) and disrupts the localization of tight junction-associated proteins (ZO-1, Cingulin) at tight junctions. This competition reduces aPKC activity critical to maintaining and/or forming tight junctions. Finally, phosphorylation of ephrinB1 on specific tyrosine residues can block the interaction between ephrinB1 and Par-6 at tight junctions, and restore tight junction formation. Recent evidence indicates that de-regulation of forward signaling through EphB receptors may play a role in metastatic progression in colon cancer. In light of the new data showing an effect of ephrinB reverse signaling on tight junctions, an additional mechanism can be hypothesized where de-regulation of ephrinB1 expression or phosphorylation may also impact metastatic progression.
C1 [Lee, Hyun-Shik; Daar, Ira O.] NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Daar, IO (reprint author), NCI, Lab Cell & Dev Signaling, Bldg 560,Room 22-3, Frederick, MD 21702 USA.
EM daar@ncifcrf.gov
RI Lee, Hyun-Shik/G-3555-2011;
OI Daar, Ira/0000-0003-2657-526X
NR 41
TC 13
Z9 13
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6918
J9 CELL ADHES MIGR
JI Celll Adhes. Migr.
PD JUL-SEP
PY 2009
VL 3
IS 3
BP 250
EP 255
DI 10.4161/cam.3.3.8211
PG 6
WC Cell Biology
SC Cell Biology
GA V21VF
UT WOS:000208234400003
PM 19276658
ER
PT J
AU Okun, E
Lathia, JD
Mattson, MP
AF Okun, Eitan
Lathia, Justin D.
Mattson, Mark P.
TI Adhesion- and migration-related side effects of phosphothioated CpG
oligodeoxynucleotides
SO CELL ADHESION & MIGRATION
LA English
DT Article
DE ECM; CpG; toll-like receptors; neurons; adhesion; phosphothioated;
oligodeoxynucleotides
AB Nucleic acid oligodeoxynucleotides (ODN) are increasingly used in biological research and in clinics where they are used for both diagnostic and therapeutic purposes. In order to increase the stability and efficacy of ODNs, various chemical modifications have been applied to create nucleic acid derivatives that are not recognized by endogenous nucleic acid cleavage mechanisms. One of the most common and cost-effective modifications is the phosphothioate (PTO) modification. The PTO modification is implemented mainly in antisense ODN, but also in ODN that were shown to activate members of the toll-like receptor (TLR) family such as TLR3 (poly-I:C), TLR8 (ssRNA) and TLR9 (CpG). We recently found that PTO-ODN aimed at activating TLR9 induce a non-TLR9-specific detachment phenotype in a growth-substrate dependent manner. Moreover, we found that unmodified and PTO-modified TLR ligands induce distinct patterns of gene expression in cultured neural cells. These findings suggest that PTO-ODN can cause nonspecific effects on cell adhesion that could compromise interpretation of data from experiments using PTO-ODN.
C1 [Okun, Eitan; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Lathia, Justin D.] Cleveland Clin Fdn, Dept Stem Cell Biol & Regenerat Med, Lerner Res Inst, Cleveland, OH 44195 USA.
RP Okun, E (reprint author), NIA, Neurosci Lab, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM okune@mail.nih.gov
RI Mattson, Mark/F-6038-2012
NR 10
TC 5
Z9 5
U1 0
U2 1
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1933-6918
J9 CELL ADHES MIGR
JI Celll Adhes. Migr.
PD JUL-SEP
PY 2009
VL 3
IS 3
BP 272
EP 274
DI 10.4161/cam.3.3.8692
PG 3
WC Cell Biology
SC Cell Biology
GA V21VF
UT WOS:000208234400008
PM 19458479
ER
PT J
AU Korzeniowski, MK
Szanda, G
Balla, T
Spat, A
AF Korzeniowski, Marek K.
Szanda, Gergoe
Balla, Tamas
Spaet, Andras
TI Store-operated Ca2+ influx and subplasmalemmal mitochondria
SO CELL CALCIUM
LA English
DT Article
DE Mitochondria; Calcium; Store-operated calcium entry; STIM1
ID PLASMA-MEMBRANE; CALCIUM-RELEASE; CRAC CHANNEL; CYTOSOLIC CA2+;
INSULIN-SECRETION; STIM1; CELLS; ENTRY; ORAI1; ER
AB Calcium depletion of the endoplasmic reticulum (ER) induces oligomerisation, puncta formation and translocation of the ER Ca2+ sensor proteins, STIM1 and -2 into plasma membrane (PM)-adjacent regions of the ER, where they activate the Orai1, -2 or -3 proteins present in the opposing PM. These proteins form ion channels through which store-operated Ca2+ influx (SOC) occurs. Calcium ions exert negative feedback on SOC. Here we examined whether subplasmalemmal mitochondria, which reduce this feed-back by Ca2+ uptake, are located within or out of the high-Ca2+ microdomains (HCMDs) formed between the ER and plasmalemmal Orai1 channels. For this purpose, COS-7 cells were cotransfected with Orai1, STIM1 labelled with YFP or mRFP and the mitochondrially targeted Ca2+ sensitive fluorescent protein inverse-Pericam. Depletion of ER Ca2+ with ATP + thapsigargin (in Ca2+-free medium) induced the appearance of STIM1 puncta in the <= 100 nm wide subplasmalemmal space, as examined with TIRE Mitochondria were located either in the gaps between STIM1-tagged puncta or in remote, STIM1-free regions. After addition of Ca2+ mitochondrial Ca2+ concentration increased irrespective of the mitochondrion-STIM1 distance. These observations indicate that mitochondria are exposed to Ca2+ diffused laterally from the HCMDs formed between the PM and the subplasmalemmal ER. (C) 2009 Elsevier Ltd. All rights reserved.
C1 [Szanda, Gergoe; Spaet, Andras] Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary.
[Korzeniowski, Marek K.; Balla, Tamas] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA.
[Spaet, Andras] Hungarian Acad Sci, Lab Neurobiochem & Mol Physiol, Budapest, Hungary.
RP Spat, A (reprint author), Semmelweis Univ, Dept Physiol, POB 259, H-1444 Budapest, Hungary.
EM spat@eok.sote.hu
RI Korzeniowski, Marek/G-7214-2011;
OI Balla, Tamas/0000-0002-9077-3335
FU National Institute of Child Health and Human Development of the National
Institutes of Health
FX Mt-inverse-Pericam was kindly gifted by Prof. A. Miyawaki (Saitama,
Japan). The confocal imaging was performed at the Microscopy & Imaging
Core of the National Institute of Child Health and Human Development,
NIH with the kind assistance of Drs. Vincent Schram and James T.
Russell. This research was supported in part by the Intramural Research
Program of the National Institute of Child Health and Human Development
of the National Institutes of Health.
NR 48
TC 18
Z9 18
U1 1
U2 7
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0143-4160
J9 CELL CALCIUM
JI Cell Calcium
PD JUL
PY 2009
VL 46
IS 1
BP 49
EP 55
DI 10.1016/j.ceca.2009.04.002
PG 7
WC Cell Biology
SC Cell Biology
GA 474MT
UT WOS:000268288900005
PM 19427033
ER
PT J
AU Koonin, EV
Aravind, L
AF Koonin, Eugene V.
Aravind, L.
TI Comparative genomics, evolution and origins of the nuclear envelope and
nuclear pore complex
SO CELL CYCLE
LA English
DT Editorial Material
C1 [Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov; aravind@ncbi.nlm.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 5
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2009
VL 8
IS 13
BP 1984
EP 1985
DI 10.4161/cc.8.13.8829
PG 2
WC Cell Biology
SC Cell Biology
GA 465RG
UT WOS:000267603900011
PM 19550152
ER
PT J
AU Wang, S
Pashtan, I
Tsutsumi, S
Xu, WP
Neckers, L
AF Wang, Suiquan
Pashtan, Itai
Tsutsumi, Shinji
Xu, Wanping
Neckers, Len
TI Cancer cells harboring MET gene amplification activate alternative
signaling pathways to escape MET inhibition but remain sensitive to
Hsp90 inhibitors
SO CELL CYCLE
LA English
DT Article
DE c-Met; Hsp90; 17-AAG; TKI; oncogene switching
ID TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR TRANSACTIVATION;
SMALL-MOLECULE INHIBITOR; GROWTH-FACTOR; LUNG-CANCER; C-MET;
ACQUIRED-RESISTANCE; BREAST-CANCER; TUMOR-GROWTH; IN-VIVO
AB Hepatocyte growth factor/scatter factor (HGF/SF) receptor c-Met is implicated in growth, invasion and metastasis of many tumors. Tumor cells harboring MET gene amplification are initially sensitive to c-Met tyrosine kinase inhibitors (TKI), but escape from long-term treatment has not been investigated. C-Met is a client of heat shock protein 90 (Hsp90) and is destabilized by Hsp90 inhibitors, suggesting that these drugs may inhibit tumors driven by MET amplification, although tumor escape under these conditions also has not been explored. Here, we evaluated the initial inhibitory effects of, and the likelihood of escape from, the Hsp90 inhibitor 17-allylamino-17-demethoxy-geldanamycin (17-AAG) and the c-Met TKI SU11274, using two cell lines harboring MET gene amplification. 17-AAG inhibited cell growth in both cell lines and induced substantial apoptosis, whereas SU11274 was only growth inhibitory in one cell line. In both cell lines, c-Met-dependent Akt, Erk and/or STAT3 signaling, as well as activation of the EGFR family, resumed shortly after treatment with c-Met TKI despite sustained c-Met inhibition. PKC delta upregulation may participate in reactivation of c-Met downstream signaling in both cell lines. In contrast to c-Met TKI, 17-AAG destabilized c-Met protein and durably blocked reactivation of downstream signaling pathways and EGFR family members. Our data demonstrate that downstream signaling in tumor cells overexpressing c-Met is not stably suppressed by c-Met TKI, even though c-Met remains fully inhibited. In contrast, Hsp90 inhibitors provide long-lasting suppression of c-Met-dependent signaling, and these drugs should be further evaluated in tumors driven by MET gene amplification.
C1 [Wang, Suiquan; Pashtan, Itai; Tsutsumi, Shinji; Xu, Wanping; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Neckers, L (reprint author), 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM neckers@nih.gov
NR 40
TC 20
Z9 20
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2009
VL 8
IS 13
BP 2050
EP 2056
DI 10.4161/cc.8.13.8861
PG 7
WC Cell Biology
SC Cell Biology
GA 465RG
UT WOS:000267603900022
PM 19502802
ER
PT J
AU De Siervi, A
De Luca, P
Moiola, C
Gueron, G
Tongbai, R
Chandramouli, GVR
Haggerty, C
Dzekunova, I
Petersen, D
Kawasaki, E
Kil, WJ
Camphausen, K
Longo, D
Gardner, K
AF De Siervi, Adriana
De Luca, Paola
Moiola, Cristian
Gueron, Geraldine
Tongbai, Ron
Chandramouli, G. V. R.
Haggerty, Cynthia
Dzekunova, Inna
Petersen, David
Kawasaki, Ernest
Kil, Whoon Jong
Camphausen, Kevin
Longo, Dan
Gardner, Kevin
TI Identification of new Rel/NF kappa B regulatory networks by focused
genome location analysis
SO CELL CYCLE
LA English
DT Article
DE ATM; ChIP/chip; Ets; NF kappa B; T-cells
ID DOUBLE-STRAND BREAKS; GENE-EXPRESSION; C-REL; TRANSCRIPTION FACTORS;
DNA-REPAIR; ATM; ACTIVATION; CELLS; CANCER; LIFE
AB NF kappa B is an inducible transcription factor that controls kinetically complex patterns of gene expression. Several studies reveal multiple pathways linking NF kappa B to the promotion and progression of various cancers. Despite extensive interest and characterization, many NF kappa B controlled genes still remain to be identified. We used chromatin immunoprecipitation combined with microarray technology (ChIP/chip) to investigate the dynamic interaction of NF kappa B with the promoter regions of 100 genes known to be expressed in mitogen-induced T-cells. Six previously unrecognized NF kappa B controlled genes (ATM, EP300, TGF beta, Selectin, MMP-1 and SFN) were identified. Each gene is induced in mitogen-stimulated T-cells, repressed by pharmacological NF kappa B blockade, reduced in cells deficient in the p50 NF kappa B subunit and dramatically repressed by RNAi specifically designed against cRel. A coregulatory role for Ets transcription factors in the expression of the NF kappa B controlled genes was predicted by comparative promoter analysis and confirmed by ChIP and by functional disruption of Ets. NF kappa B deficiency produces a deficit in ATM function and DNA repair indicating an active role for NF kappa B in maintaining DNA integrity. These results define new potential targets and transcriptional networks governed by NF kappa B and provide novel functional insights for the role of NF kappa B in genomic stability, cell cycle control, cell-matrix and cell-cell interactions during tumor progression.
C1 [De Siervi, Adriana; De Luca, Paola; Moiola, Cristian; Gueron, Geraldine] Univ Buenos Aires, Dept Biol Chem, Sch Sci, CONICET,FCEyN,UBA, Buenos Aires, Argentina.
[De Siervi, Adriana; Tongbai, Ron; Chandramouli, G. V. R.; Haggerty, Cynthia; Gardner, Kevin] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
[Dzekunova, Inna; Petersen, David; Kawasaki, Ernest] NCI, Microarray Facil, Bethesda, MD 20892 USA.
[Kil, Whoon Jong; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Longo, Dan] NIA, Immunol Lab, Bethesda, MD 20892 USA.
RP De Siervi, A (reprint author), Univ Buenos Aires, Dept Biol Chem, Sch Sci, CONICET,FCEyN,UBA, Intendente Guiraldes 2160,Ciudad Univ,Pab II,2nd, Buenos Aires, Argentina.
EM adesiervi@qb.fcen.uba.ar; gardnerk@mail.nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
National Institute on Aging
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute and the National Institute on Aging.
NR 43
TC 17
Z9 17
U1 0
U2 2
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD JUL 1
PY 2009
VL 8
IS 13
BP 2093
EP 2100
DI 10.4161/cc.8.13.8926
PG 8
WC Cell Biology
SC Cell Biology
GA 465RG
UT WOS:000267603900027
PM 19502793
ER
PT J
AU Wehrly, TD
Chong, A
Virtaneva, K
Sturdevant, DE
Child, R
Edwards, JA
Brouwer, D
Nair, V
Fischer, ER
Wicke, L
Curda, AJ
Kupko, JJ
Martens, C
Crane, DD
Bosio, CM
Porcella, SF
Celli, J
AF Wehrly, Tara D.
Chong, Audrey
Virtaneva, Kimmo
Sturdevant, Dan E.
Child, Robert
Edwards, Jessica A.
Brouwer, Dedeke
Nair, Vinod
Fischer, Elizabeth R.
Wicke, Luke
Curda, Alissa J.
Kupko, John J., III
Martens, Craig
Crane, Deborah D.
Bosio, Catharine M.
Porcella, Stephen F.
Celli, Jean
TI Intracellular biology and virulence determinants of Francisella
tularensis revealed by transcriptional profiling inside macrophages
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID GENE-EXPRESSION; SALMONELLA-ENTERICA; SECRETION SYSTEM;
MYCOBACTERIUM-TUBERCULOSIS; INTRAMACROPHAGE GROWTH; MURINE MACROPHAGES;
BACTERIAL PATHOGEN; REACTIVE NITROGEN; BRUCELLA-ABORTUS;
EPITHELIAL-CELLS
AB The highly infectious bacterium Francisella tularensis is a facultative intracellular pathogen, whose virulence requires proliferation inside host cells, including macrophages. Here we have performed a global transcriptional profiling of the highly virulent F. tularensis ssp. tularensis Schu S4 strain during its intracellular cycle within primary murine macrophages, to characterize its intracellular biology and identify pathogenic determinants based on their intracellular expression profiles. Phagocytosed bacteria rapidly responded to their intracellular environment and subsequently altered their transcriptional profile. Differential gene expression profiles were revealed that correlated with specific intracellular locale of the bacteria. Upregulation of general and oxidative stress response genes was a hallmark of the early phagosomal and late endosomal stages, while induction of transport and metabolic genes characterized the cytosolic replication stage. Expression of the Francisella Pathogenicity Island (FPI) genes, which are required for intracellular proliferation, increased during the intracellular cycle. Similarly, 27 chromosomal loci encoding putative hypothetical, secreted, outer membrane proteins or transcriptional regulators were identified as upregulated. Among these, deletion of FTT0383, FTT0369c or FTT1676 abolished the ability of Schu S4 to survive or proliferate intracellularly and cause lethality in mice, therefore identifying novel determinants of Francisella virulence from their intracellular expression profile.
C1 [Wehrly, Tara D.; Chong, Audrey; Child, Robert; Edwards, Jessica A.; Brouwer, Dedeke; Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Crane, Deborah D.; Bosio, Catharine M.] NIAID, Immun Pulm Pathogens Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
[Virtaneva, Kimmo; Sturdevant, Dan E.; Wicke, Luke; Curda, Alissa J.; Kupko, John J., III; Martens, Craig; Porcella, Stephen F.] NIAID, Genom Unit, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Nair, Vinod; Fischer, Elizabeth R.] NIAID, Electron Microscopy Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA.
RP Celli, J (reprint author), NIAID, Tularemia Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM jcelli@niaid.nih.gov
RI Bosio, Catharine/D-7456-2015
FU NIH, National Institute of Allergy and Infectious Diseases
FX We are grateful to Rick Lyons and Francis Nano for the gift of strains
and antibodies, to Leigh Knodler for critical reading of the manuscript
and helpful suggestions, and to Tregei Starr for her help with
generating the Delta FTT0369c mutant of Schu S4. This work was supported
by the Intramural Research Program of the NIH, National Institute of
Allergy and Infectious Diseases.
NR 66
TC 101
Z9 101
U1 0
U2 5
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1462-5814
J9 CELL MICROBIOL
JI Cell Microbiol.
PD JUL
PY 2009
VL 11
IS 7
BP 1128
EP 1150
DI 10.1111/j.1462-5822.2009.01316.x
PG 23
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 453TW
UT WOS:000266636800012
PM 19388904
ER
PT J
AU Luo, R
Ha, VL
Hayashi, R
Randazzo, PA
AF Luo, Ruibai
Ha, Vi Luan
Hayashi, Ryo
Randazzo, Paul A.
TI Arf GAP2 is positively regulated by coatomer and cargo
SO CELLULAR SIGNALLING
LA English
DT Article
DE ADP-ribosylation factor; GTPase-activating protein; COPI; Golgi; p24
Cargo protein
ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; NUCLEOTIDE-EXCHANGE
FACTORS; GOLGI-COMPLEX; COPI VESICLES; ACTIN CYTOSKELETON; TRANSPORT
VESICLES; KINETIC-ANALYSIS; SORTING SIGNALS; COATED VESICLES
AB Arf GAP2 is one of four Arf GAPs that function in the Golgi apparatus. We characterized the kinetics of Arf GAP2 and its regulation. Purified Arf GAP2 had little activity compared to purified Arf GAP1. Of the potential regulators we examined, coatomer had the greatest effect, stimulating activity one to two orders of magnitude. The effect was biphasic, with half-maximal activation observed at 50 nM coatomer and activation peaking at approximate to 150 nM coatomer. Activation by coatomer was greater for Arf GAP2 than has been reported for Arf GAP1. The effects of phosphoinositides and changes in vesicle curvature on GAP activity were small compared to coatomer; however, both increased coatomer-dependent activity. Peptides from p24 cargo proteins increased Arf GAP2 activity by an additional 2- to 4-fold. The effect of cargo peptide was dependent on coatomer. Overexpressing the cargo protein p25 decreased cellular Arfl.GTP levels. The differential sensitivity of Arf GAP1 and Arf GAP2 to coatomer could coordinate their activities. Based on the common regulatory features of Arf GAP1 and 2, we propose a mechanism for cargo selection in which GTP hydrolysis triggered by cargo binding to the coat protein is coupled to coat polymerization. Published by Elsevier Inc.
C1 [Luo, Ruibai; Ha, Vi Luan; Randazzo, Paul A.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Hayashi, Ryo] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
RP Randazzo, PA (reprint author), Bldg 37,Room 2042, Bethesda, MD 20892 USA.
EM randazzo@helix.nih.gov
FU Intramural NIH HHS [Z01 BC007365-13, Z99 CA999999]
NR 59
TC 14
Z9 16
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD JUL
PY 2009
VL 21
IS 7
BP 1169
EP 1179
DI 10.1016/j.cellsig.2009.03.006
PG 11
WC Cell Biology
SC Cell Biology
GA 449QO
UT WOS:000266345300015
PM 19296914
ER
PT J
AU Pommier, Y
AF Pommier, Yves
TI DNA Topoisomerase I Inhibitors: Chemistry, Biology, and Interfacial
Inhibition
SO CHEMICAL REVIEWS
LA English
DT Review
ID RING-MODIFIED CAMPTOTHECIN; DOUBLE-STRAND BREAKS; ANTICANCER ALKALOID
CAMPTOTHECIN; CLEAVAGE COMPLEXES; PHOSPHODIESTERASE TDP1; COVALENT
COMPLEXES; NITRATED INDENOISOQUINOLINES; SPINOCEREBELLAR ATAXIA;
ANTITUMOR-ACTIVITY; CELL-LINES
C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU National Cancer Institute Intramural Program; Center for Cancer Research
FX Our studies are supported by the National Cancer Institute Intramural
Program, Center for Cancer Research. We wish to thank Dr. Kurt W. Kohn
for long term collaboration and many insights. We also wish to thank the
past and current members of the Laboratory of Molecular Pharmacology for
their dedication and enthusiasm over the years.
NR 139
TC 309
Z9 320
U1 12
U2 69
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
J9 CHEM REV
JI Chem. Rev.
PD JUL
PY 2009
VL 109
IS 7
BP 2894
EP 2902
DI 10.1021/cr900097c
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA 471WW
UT WOS:000268090000004
PM 19476377
ER
PT J
AU Tofilon, PJ
Camphausen, K
AF Tofilon, Philip J.
Camphausen, Kevin
TI Molecular Targets for Tumor Radiosensitization
SO CHEMICAL REVIEWS
LA English
DT Review
ID GROWTH-FACTOR RECEPTOR; HISTONE DEACETYLASE INHIBITORS; DEPENDENT
PROTEIN-KINASE; STRAND BREAK REPAIR; PHASE-I TRIAL; DNA-DAMAGE RESPONSE;
CARCINOMA-CELL-LINES; ADVANCED PANCREATIC-CANCER; CHAIN ANTIBODY
FRAGMENT; ERBB SIGNALING NETWORK
C1 [Tofilon, Philip J.] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, Tampa, FL 33612 USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, CRC, Bethesda, MD 20892 USA.
RP Tofilon, PJ (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM philip.tofilon@moffitt.org
FU Intramural NIH HHS [ZIA SC010372-10]
NR 175
TC 24
Z9 26
U1 2
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
J9 CHEM REV
JI Chem. Rev.
PD JUL
PY 2009
VL 109
IS 7
BP 2974
EP 2988
DI 10.1021/cr800504x
PG 15
WC Chemistry, Multidisciplinary
SC Chemistry
GA 471WW
UT WOS:000268090000008
PM 19338375
ER
PT J
AU Cragg, GM
Grothaus, PG
Newman, DJ
AF Cragg, Gordon M.
Grothaus, Paul G.
Newman, David J.
TI Impact of Natural Products on Developing New Anti-Cancer Agents
SO CHEMICAL REVIEWS
LA English
DT Review
ID DIVERSITY-ORIENTED-SYNTHESIS; HISTONE DEACETYLASE INHIBITORS;
PROTEIN-STRUCTURE SIMILARITY; SOLID-PHASE SYNTHESIS; COMPOUND LIBRARY
DEVELOPMENT; ARYL-HYDROCARBON RECEPTOR; NATIONAL-CANCER-INSTITUTE;
POTENT ANTITUMOR-ACTIVITY; MICROORGANISM STREPTOMYCES-AVERMITILIS;
CYANOBACTERIUM LYNGBYA-MAJUSCULA
C1 [Cragg, Gordon M.; Grothaus, Paul G.; Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Fairview Ctr, Frederick, MD 21702 USA.
RP Newman, DJ (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Fairview Ctr, Suite 206,POB B, Frederick, MD 21702 USA.
EM newmand@mail.nih.gov
NR 337
TC 505
Z9 516
U1 8
U2 137
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
J9 CHEM REV
JI Chem. Rev.
PD JUL
PY 2009
VL 109
IS 7
BP 3012
EP 3043
DI 10.1021/cr900019j
PG 32
WC Chemistry, Multidisciplinary
SC Chemistry
GA 471WW
UT WOS:000268090000010
PM 19422222
ER
PT J
AU Miller, TW
Isenberg, JS
Roberts, DD
AF Miller, Thomas W.
Isenberg, Jeff S.
Roberts, David D.
TI Molecular Regulation of Tumor Angiogenesis and Perfusion via Redox
Signaling
SO CHEMICAL REVIEWS
LA English
DT Review
ID ENDOTHELIAL-GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; VASCULAR
SMOOTH-MUSCLE; SOLUBLE GUANYLATE-CYCLASE; PROTEIN-TYROSINE PHOSPHATASES;
HEME OXYGENASE-1 EXPRESSION; ACTIVATED RECEPTOR-GAMMA;
EXTRACELLULAR-SUPEROXIDE DISMUTASE; PLASMA THROMBOSPONDIN LEVELS;
CYSTATHIONINE BETA-SYNTHASE
C1 [Miller, Thomas W.; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Hemostasis & Vasc Biol Res Inst, Pittsburgh, PA 15260 USA.
[Isenberg, Jeff S.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2A33,10 Ctr Dr MSC1500, Bethesda, MD 20892 USA.
EM droberts@helix.nih.gov
RI Roberts, David/A-9699-2008; Miller, Thomas/G-1215-2011
OI Roberts, David/0000-0002-2481-2981; Miller, Thomas/0000-0001-8645-2785
FU Intramural NIH HHS [ZIA SC009172-21, ZIA SC009174-21]; NCI NIH HHS [K22
CA128616]
NR 418
TC 63
Z9 68
U1 1
U2 8
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0009-2665
J9 CHEM REV
JI Chem. Rev.
PD JUL
PY 2009
VL 109
IS 7
BP 3099
EP 3124
DI 10.1021/cr8005125
PG 26
WC Chemistry, Multidisciplinary
SC Chemistry
GA 471WW
UT WOS:000268090000013
PM 19374334
ER
PT J
AU Kozikowski, AP
Chen, YH
Subhasish, T
Lewin, NE
Blumberg, PM
Zhong, ZY
D'Annibale, MA
Wang, WL
Shen, Y
Langley, B
AF Kozikowski, Alan P.
Chen, Yihua
Subhasish, Tapadar
Lewin, Nancy E.
Blumberg, Peter M.
Zhong, Zhenyu
D'Annibale, Melissa A.
Wang, Weng-Long
Shen, Yong
Langley, Brett
TI Searching for Disease Modifiers-PKC Activation and HDAC Inhibition-A
Dual Drug Approach to Alzheimer's Disease that Decreases A beta
Production while Blocking Oxidative Stress
SO CHEMMEDCHEM
LA English
DT Article
DE Alzheimer's disease; amyloid beta; HDAC inhibition; neuroprotection; PKC
activation
ID PROTEIN-KINASE-C; HISTONE DEACETYLASE INHIBITORS; AMYLOID PRECURSOR
PROTEIN; BIOLOGICAL EVALUATION; CORTICAL-NEURONS; FIBROBLASTS; BRAIN;
MODULATORS; SECRETION; ALPHA
AB Alzheimer's disease (AD) is a well-studied neurodegenerative process characterized by the presence of amyloid plaques and neurofibrillary tangles. In this study, a series of protein kinase C (PKC) activators were investigated, some of which also exhibit histone deacetylase (HDAC) inhibitory activity, under the hypothesis that such compounds might provide a new path forward in the discovery of drugs for the treatment of AD. The PKC-activating properties of these drugs were expected to enhance the alpha-secretase pathway in the processing of amyloid precursor protein (APP), while their HDAC inhibition was anticipated to confer neuroprotective activity. We found that benzolactams 9 and 11-14 caused a concentration-dependent increase in sAPP alpha, and decrease in beta-amyloid (A beta) production in the concentration range of 0.1-10 mu M, consistent with a shift of APP metabolism toward the alpha-secretase-processing pathway. Moreover, compounds 9-14 showed neuroprotective effects in the 10-20 mu M range in the homocysteate (HCA) cortical neuron model of oxidative stress. In parallel, we found that the most neuroprotective compounds caused increased levels of histone acetylation (H4), thus indicating their likely ability to inhibit HDAC activity. As the majority of the compounds studied also show nanomolar binding affinities for PKC, we conclude that it is possible to design, de novo, agents that combine both PKC-activating properties along with HDAC inhibitory properties. Such agents would be capable of modulating amyloid processing while showing neuroprotection. These findings may offer a new approach to therapies that exhibit disease-modifying effects, as opposed to symptomatic relief, in the treatment of AD.
C1 [Kozikowski, Alan P.; Chen, Yihua; Subhasish, Tapadar; Wang, Weng-Long] Univ Illinois, Coll Pharm, Drug Discovery Program, Chicago, IL 60612 USA.
[Lewin, Nancy E.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Zhong, Zhenyu; Shen, Yong] Sun Hlth Res Inst, Haldeman Lab Mol & Cellular Neurobiol, Sun City, AZ 85351 USA.
[D'Annibale, Melissa A.; Langley, Brett] Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA.
[Langley, Brett] Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA.
RP Kozikowski, AP (reprint author), Univ Illinois, Coll Pharm, Drug Discovery Program, 833 S Wood St, Chicago, IL 60612 USA.
EM kozikowa@uic.edu; bcl2002@med.cornell.edu
RI Chen, Yihua/A-4323-2013
OI Chen, Yihua/0000-0003-1733-7980
FU National Institutes of Health [RO1AG022941, RO1AG025888]; National
Cancer Institute; Center for Cancer Research; Adelson Medical Research
Foundation; Burke Foundation
FX This work is supported by the National Institutes of Health grants
RO1AG022941 (A.P.K) and RO1AG025888 (Y.S.), and in part by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research. Support also
comes from the Adelson Medical Research Foundation (B.L.) and Burke
Foundation (B.L.). We thank Dr. Rang He and Ms. Kathryn MCLaughlin for
assistance in the preparation of the manuscript.
NR 52
TC 31
Z9 32
U1 1
U2 12
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1860-7179
J9 CHEMMEDCHEM
JI ChemMedChem
PD JUL
PY 2009
VL 4
IS 7
BP 1095
EP 1105
DI 10.1002/cmdc.200900045
PG 11
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 469JG
UT WOS:000267893000009
PM 19396896
ER
PT J
AU Tse, T
Williams, RJ
Zarin, DA
AF Tse, Tony
Williams, Rebecca J.
Zarin, Deborah A.
TI Reporting "Basic Results" in ClinicalTrials.gov
SO CHEST
LA English
DT Editorial Material
ID CLINICAL-TRIALS; REGISTRATION; DISCLOSURE
C1 [Tse, Tony; Williams, Rebecca J.; Zarin, Deborah A.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA.
RP Zarin, DA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM dzarin@mail.nih.gov
FU Intramural NIH HHS
NR 12
TC 58
Z9 58
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2009
VL 136
IS 1
BP 295
EP 303
DI 10.1378/chest.08-3022
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 467YG
UT WOS:000267779000042
PM 19584212
ER
PT J
AU Tse, T
Williams, RJ
Zarin, DA
AF Tse, Tony
Williams, Rebecca J.
Zarin, Deborah A.
TI Update on Registration of Clinical Trials in ClinicalTrials.gov
SO CHEST
LA English
DT Editorial Material
C1 [Tse, Tony; Williams, Rebecca J.; Zarin, Deborah A.] NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, Bethesda, MD 20894 USA.
RP Zarin, DA (reprint author), NIH, Lister Hill Natl Ctr Biomed Commun, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM dzarin@mail.nih.gov
NR 4
TC 16
Z9 16
U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2009
VL 136
IS 1
BP 304
EP 305
DI 10.1378/chest.09-1219
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 467YG
UT WOS:000267779000043
PM 19584213
ER
PT J
AU King, CS
Collen, J
Holley, AB
Greenburg, D
Hnatiuk, O
AF King, Christopher S.
Collen, Jacob
Holley, Aaron B.
Greenburg, David
Hnatiuk, Oleh
TI Discordance in Spirometric Interpretations Using Different Reference
Equations Response
SO CHEST
LA English
DT Letter
C1 [King, Christopher S.] Walter Reed Army Med Ctr, Dept Med, Washington, DC 20350 USA.
[Greenburg, David] Madigan Army Med Ctr, Seattle, WA USA.
[Hnatiuk, Oleh] NHLBI, Bethesda, MD 20892 USA.
RP King, CS (reprint author), Walter Reed Army Med Ctr, Dept Med, 6900 Georgia Ave, Washington, DC 20350 USA.
EM christopher.king@amedd.army.mil
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD JUL
PY 2009
VL 136
IS 1
BP 325
EP 325
DI 10.1378/chest.09-0820
PG 1
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 467YG
UT WOS:000267779000059
ER
PT J
AU Guyer, AE
McClure-Tone, EB
Shiffrin, ND
Pine, DS
Nelson, EE
AF Guyer, Amanda E.
McClure-Tone, Erin B.
Shiffrin, Nina D.
Pine, Daniel S.
Nelson, Eric E.
TI Probing the Neural Correlates of Anticipated Peer Evaluation in
Adolescence
SO CHILD DEVELOPMENT
LA English
DT Article
ID GENERALIZED ANXIETY DISORDER; PREFRONTAL CORTEX ACTIVATION;
GENDER-DIFFERENCES; SEX-DIFFERENCES; SOCIAL-ANXIETY; FACIAL EXPRESSIONS;
BEHAVIOR PROBLEMS; BRAIN ENGAGEMENT; REWARD VALUE; ANGRY FACES
AB Neural correlates of social-cognition were assessed in 9- to- 17-year-olds (N = 34) using functional magnetic resonance imaging. Participants appraised how unfamiliar peers they had previously identified as being of high or low interest would evaluate them for an anticipated online chat session. Differential age- and sex-related activation patterns emerged in several regions previously implicated in affective processing. These included the ventral striatum, hippocampus, hypothalamus, and insula. In general, activation patterns shifted with age in older relative to younger females but showed no association with age in males. Relating these neural response patterns to changes in adolescent social-cognition enriches theories of adolescent social development through enhanced neurobiological understanding of social behavior.
C1 [Guyer, Amanda E.; Shiffrin, Nina D.; Pine, Daniel S.; Nelson, Eric E.] NIMH, Bethesda, MD 20892 USA.
[McClure-Tone, Erin B.] Georgia State Univ, Atlanta, GA 30303 USA.
RP Guyer, AE (reprint author), NIMH, 15K North Dr,Room 208, Bethesda, MD 20892 USA.
EM amandaguyer@mail.nih.gov
RI Nelson, Eric/B-8980-2008
OI Nelson, Eric/0000-0002-3376-2453
FU Intramural NIH HHS [ZIA MH002782-08, ZIA MH002780-08, ZIA MH002781-08];
NIMH NIH HHS [R00 MH080076, K99 MH080076]
NR 78
TC 85
Z9 85
U1 4
U2 17
PU WILEY-BLACKWELL PUBLISHING, INC
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0009-3920
J9 CHILD DEV
JI Child Dev.
PD JUL-AUG
PY 2009
VL 80
IS 4
BP 1000
EP 1015
PG 16
WC Psychology, Educational; Psychology, Developmental
SC Psychology
GA 471IV
UT WOS:000268051200005
PM 19630890
ER
PT J
AU Peng, YY
Liu, HL
Tang, M
Cai, LS
Pike, V
AF Peng Yiyuan
Liu Hanliang
Tang Min
Cai Lisheng
Pike, Victor
TI Highly Efficient N-Monomethylation of Primary Aryl Amines
SO CHINESE JOURNAL OF CHEMISTRY
LA English
DT Article
DE N-monomethylation; N-methylaniline; N-methyl acetanilide; methyl iodide;
ethylene glycol
ID PRIMARY AROMATIC-AMINES; TYROSINE-PHOSPHATASE INHIBITOR;
SODIUM-BOROHYDRIDE; HETEROAROMATIC AMINES; ALKYLATION; MONOALKYLATION;
REARRANGEMENT; DEPHOSTATIN; ACETYLATION; METHYLATION
AB A highly efficient method for specific synthesis of N-monomethylarylamines is presented. Anilines were treated with acetic anhydride and triethylamine in dry CH(2)Cl(2) to give the corresponding acetamides. The subsequent N-monomethylation of acetyl aryl amines with methyl iodide and NaH in THF introduced methyl group. Acid hydrolysis of the N-methyl acetanilides in ethylene glycol generated the corresponding N-methyl-N-aryl amines in high yields. This method was also used to synthesize (E)-2-bromo-5-(4-methylaminostyryl)pyridine that may be useful as an amyloid imaging agent for Alzheimer's disease.
C1 [Peng Yiyuan; Liu Hanliang; Tang Min] Jiangxi Normal Univ, Dept Chem, Jiangxi Key Lab Green Chem, Nanchang 330027, Jiangxi, Peoples R China.
[Cai Lisheng; Pike, Victor] NIMH, Positron Emiss Tomog Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Peng, YY (reprint author), Jiangxi Normal Univ, Dept Chem, Jiangxi Key Lab Green Chem, Nanchang 330027, Jiangxi, Peoples R China.
EM yiyuanpeng@yahoo.com
FU National Natural Science Foundation of China [20462003, 20862009];
National Natural Science Foundation of Jiangxi Province [2008GQH0026]
FX Project supported by the National Natural Science Foundation of China (
Nos. 20462003, 20862009) and the National Natural Science Foundation of
Jiangxi Province (No. 2008GQH0026).
NR 39
TC 9
Z9 10
U1 0
U2 16
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY
SN 1001-604X
J9 CHINESE J CHEM
JI Chin. J. Chem.
PD JUL
PY 2009
VL 27
IS 7
BP 1339
EP 1344
PG 6
WC Chemistry, Multidisciplinary
SC Chemistry
GA 478YR
UT WOS:000268625200022
ER
PT J
AU Bondy, CA
Cheng, C
AF Bondy, Carolyn A.
Cheng, Clara
TI Monosomy for the X chromosome
SO CHROMOSOME RESEARCH
LA English
DT Article
DE Turner syndrome; X-monosomy; dosage compensation; X inactivation;
pseudoautosomal gene; epigenetics; chromosomal interaction
ID TURNER-SYNDROME; GENE-EXPRESSION; DOSAGE COMPENSATION; GROWTH-HORMONE;
SHORT STATURE; CELL-LINES; INACTIVATION; PHENOTYPE; FEMALE; SEX
AB Dosage compensation serves to equalize X chromosome gene expression in mammalian males and females and involves extensive silencing of the 2nd X chromosome in females. If dosage compensation mechanisms completely suppressed the 2nd X chromosome, then actual physical loss of this "eXtra" chromosome should have few consequences. However, X monosomy has major effects upon normal development, fertility and longevity in humans and some other species. This article reviews observations and arguments attempting to explain the phenotypic effects of X monosomy in humans and other mammals in terms of X chromosome gene dosage.
C1 [Bondy, Carolyn A.; Cheng, Clara] NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA.
RP Bondy, CA (reprint author), NIH, CRC 1-3330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bondyc@mail.nih.gov
FU NICHD, NIH
FX This work was supported by the intramural research programme of the
NICHD, NIH.
NR 57
TC 16
Z9 16
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
J9 CHROMOSOME RES
JI Chromosome Res.
PD JUL
PY 2009
VL 17
IS 5
BP 649
EP 658
DI 10.1007/s10577-009-9052-z
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 502HQ
UT WOS:000270448800006
PM 19802705
ER
PT J
AU Douglas, PS
Taylor, A
Bild, D
Bonow, R
Greenland, P
Lauer, M
Peacock, F
Udelson, J
AF Douglas, Pamela S.
Taylor, Allen
Bild, Diane
Bonow, Robert
Greenland, Philip
Lauer, Michael
Peacock, Frank
Udelson, James
TI Outcomes Research in Cardiovascular Imaging
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiovascular imaging; chest pain diagnosis; clinical trials
ID CORONARY-ARTERY-DISEASE; ABDOMINAL AORTIC-ANEURYSM; COMPUTED-TOMOGRAPHY
ANGIOGRAPHY; ISCHEMIC MITRAL REGURGITATION; INCREMENTAL PROGNOSTIC
VALUE; HEART-ASSOCIATION COMMITTEE; RANDOMIZED CONTROLLED TRIAL; ACUTE
MYOCARDIAL-INFARCTION; INTIMA-MEDIA THICKNESS; ACUTE CARDIAC ISCHEMIA
AB In July of 2008. the National Heart, Lung, and Blood Institute convened experts in noninvasive cardiovascular imaging, outcomes research, statistics, and clinical trials to develop recommendations for future randomized controlled trials of the use of imaging in: 1) screening the asymptomatic patient for coronary artery disease; 2) assessment of patients with stable angina; 3) identification of acute coronary syndromes in the emergency room; and 4) assessment of heart failure patients with chronic coronary artery disease with reduced left ventricular ejection fraction. This Study highlights several possible trial design,, for each clinical situation. (Circ Cardiovasc Imaging. 2009;2:339-348.)
C1 [Douglas, Pamela S.] Duke Univ, Med Ctr, Div Cardiovasc Med, Durham, NC USA.
[Taylor, Allen] Washington Hosp Ctr, Cardiovasc Res Inst, Dept Med, Washington, DC 20010 USA.
[Bild, Diane] NHLBI, NIH, Div Prevent & Populat Sci, Bethesda, MD 20892 USA.
[Lauer, Michael] NHLBI, NIH, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Bonow, Robert; Greenland, Philip] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Peacock, Frank] Cleveland Clin, Cleveland, OH 44106 USA.
[Udelson, James] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
RP Douglas, PS (reprint author), 7022 N Pavilion DUMC,POB 17969, Durham, NC 27715 USA.
EM pamela.douglas@duke.edu
NR 70
TC 11
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JUL
PY 2009
VL 2
IS 4
BP 339
EP 348
DI 10.1161/CIRCIMGING.108.123999
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 471SE
UT WOS:000268077800009
PM 19808615
ER
PT J
AU Louie, GH
Reveille, JD
Ward, MM
AF Louie, G. H.
Reveille, J. D.
Ward, M. M.
TI Challenges comparing functional limitations in rheumatoid arthritis and
ankylosing spondylitis
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Review
DE Rheumatoid arthritis; ankylosing spondylitis; physical function;
functional limitation
ID HEALTH-ASSESSMENT QUESTIONNAIRE; QUALITY-OF-LIFE; DISEASE-ACTIVITY
INDEXES; DIRECT MEDICAL COSTS; PSORIATIC-ARTHRITIS; RISK-FACTORS;
INTERNATIONAL CLASSIFICATION; GENERAL-POPULATION; DISABILITY INDEX; WORK
DISABILITY
AB Whether physical functioning in patients with rheumatoid arthritis (RA) differs from that in patients with ankylosing spondylitis (AS) is presently uncertain. Such a comparison poses challenges, not only because the two diseases differ in the domains of functioning affected, but also because of the different instruments used to measure functional limitations. Limiting our analysis to studies using similar self-report questionnaires, we examined published observational studies of unselected cohorts of patients with RA and patients with AS to compare and contrast the severity of functional limitations. Available studies from a few direct comparisons, and mostly indirect comparions, suggested that patients with RA are generally more severely limited in physical functioning throughout the disease course than patients with AS. Since mose studies did not adjust adequately for potentially important confounders. Such as age, gender, comorbidity, and disease duration, reported differences in functional disability between patients with RA and patients with AS must be interpreted cautiously.
C1 [Louie, G. H.; Ward, M. M.] NIAMSD, Intramural Res Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Reveille, J. D.] Univ Texas Hlth Sci Ctr Houston, Div Rheumatol & Clin Immunogenet, Houston, TX USA.
RP Ward, MM (reprint author), NIAMS, NIH, Bldg 10 CRC Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA AR041153-05]
NR 106
TC 9
Z9 9
U1 0
U2 1
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2009
VL 27
IS 4
BP S83
EP S91
PG 9
WC Rheumatology
SC Rheumatology
GA 507ZL
UT WOS:000270895600016
PM 19822052
ER
PT J
AU Miura, K
Zhou, H
Diouf, A
Moretz, SE
Fay, MP
Miller, LH
Martin, LB
Pierce, MA
Ellis, RD
Mullen, GED
Long, CA
AF Miura, Kazutoyo
Zhou, Hong
Diouf, Ababacar
Moretz, Samuel E.
Fay, Michael P.
Miller, Louis H.
Martin, Laura B.
Pierce, Mark A.
Ellis, Ruth D.
Mullen, Gregory E. D.
Long, Carole A.
TI Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than
Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting
Plasmodium falciparum Growth, as Determined by the In Vitro Growth
Inhibition Assay
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID APICAL MEMBRANE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; MALARIA VACCINE
CANDIDATE; BLOOD-STAGE VACCINE; MONTANIDE ISA 720; IMMUNOGENICITY TRIAL;
KENYAN CHILDREN; CLINICAL-TRIAL; AMA1 VACCINE; SAFETY
AB Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 (MSP1(42)) are leading malaria vaccine candidates. Several preclinical and clinical trials have been conducted, and an in vitro parasite growth inhibition assay has been used to evaluate the biological activities of the resulting antibodies. In a U.S. phase 1 trial with AMA1-C1/Alhydrogel plus CPG 7909, the vaccination elicited anti-AMA1 immunoglobulin G (IgG) which showed up to 96% inhibition. However, antibodies induced by MSP1(42)-C1/Alhydrogel plus CPG 7909 vaccine showed less than 32% inhibition in vitro. To determine whether anti-MSP1(42) IgG had less growth-inhibitory activity than anti-AMA1 IgG in vitro, the amounts of IgG that produced 50% inhibition of parasite growth (Ab(50)) were compared for rabbit and human antibodies. The Ab(50)s of rabbit and human anti-MSP1(42) IgGs were significantly higher (0.21 and 0.62 mg/ml, respectively) than those of anti-AMA1 IgGs (0.07 and 0.10 mg/ml, respectively) against 3D7 parasites. Ab(50) data against FVO parasites also demonstrated significant differences. We further investigated the Ab(50)s of mouse and monkey anti-AMA1 IgGs and showed that there were significant differences between the species (mouse, 0.28 mg/ml, and monkey, 0.14 mg/ml, against 3D7 parasites). Although it is unknown whether growth-inhibitory activity in vitro reflects protective immunity in vivo, this study showed that the Ab(50) varies with both antigen and species. Our data provide a benchmark for antibody levels for future AMA1- or MSP1(42)-based vaccine development efforts in preclinical and clinical trials.
C1 [Miura, Kazutoyo; Miller, Louis H.; Martin, Laura B.; Pierce, Mark A.; Ellis, Ruth D.; Mullen, Gregory E. D.] NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA.
[Zhou, Hong; Diouf, Ababacar; Moretz, Samuel E.; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20817 USA.
RP Miura, K (reprint author), 12441 Parklawn Dr,Twinbrook 2,Room 107, Rockville, MD 20852 USA.
EM kmiura@niaid.nih.gov; clong@niaid.nih.gov
RI Martin, Laura/N-1789-2013;
OI Martin, Laura/0000-0002-4431-4381; Fay, Michael P./0000-0002-8643-9625
FU National Institute of Allergy and Infectious Diseases; NIH; PATH/Malaria
Vaccine Initiative
FX We are very grateful to all volunteers who participated in the clinical
trials. We also appreciate John Treanor, Anna Durbin, Joanne Margason,
Ev Tierney, and Allan Saul for contributions to the human trials. We are
also very grateful to Lynn Lambert and her team for meticulous execution
of animal immunization studies.; The studies were supported by the
intramural program of the National Institute of Allergy and Infectious
Diseases, NIH, and the GIA Reference Center was supported by the
PATH/Malaria Vaccine Initiative.
NR 34
TC 50
Z9 50
U1 0
U2 0
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 JUL 1
PY 2009
VL 16
IS 7
BP 963
EP 968
DI 10.1128/CVI.00042-09
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 467OH
UT WOS:000267747700001
PM 19439523
ER
PT J
AU Parra, M
Yang, AL
Lim, J
Kolibab, K
Derrick, S
Cadieux, N
Perera, LP
Jacobs, WR
Brennan, M
Morris, SL
AF Parra, Marcela
Yang, Amy L.
Lim, JaeHyun
Kolibab, Kristopher
Derrick, Steven
Cadieux, Nathalie
Perera, Liyanage P.
Jacobs, William R.
Brennan, Michael
Morris, Sheldon L.
TI Development of a Murine Mycobacterial Growth Inhibition Assay for
Evaluating Vaccines against Mycobacterium tuberculosis
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; IN-VITRO; INTRACELLULAR GROWTH;
PROTECTIVE IMMUNITY; INTERFERON-GAMMA; CALMETTE-GUERIN; INFECTION; MICE;
BCG
AB The development and characterization of new tuberculosis (TB) vaccines has been impeded by the lack of reproducible and reliable in vitro assays for measuring vaccine activity. In this study, we developed a murine in vitro mycobacterial growth inhibition assay for evaluating TB vaccines that directly assesses the capacity of immune splenocytes to control the growth of Mycobacterium tuberculosis within infected macrophages. Using this in vitro assay, protective immune responses induced by immunization with five different types of TB vaccine preparations (Mycobacterium bovis BCG, an attenuated M. tuberculosis mutant strain, a DNA vaccine, a modified vaccinia virus strain Ankara [MVA] construct expressing four TB antigens, and a TB fusion protein formulated in adjuvant) can be detected. Importantly, the levels of vaccine-induced mycobacterial growth-inhibitory responses seen in vitro after 1 week of coculture correlated with the protective immune responses detected in vivo at 28 days postchallenge in a mouse model of pulmonary tuberculosis. In addition, similar patterns of cytokine expression were evoked at day 7 of the in vitro culture by immune splenocytes taken from animals immunized with the different TB vaccines. Among the consistently upregulated cytokines detected in the immune cocultures are gamma interferon, growth differentiation factor 15, interleukin-21 (IL-21), IL-27, and tumor necrosis factor alpha. Overall, we have developed an in vitro functional assay that may be useful for screening and comparing new TB vaccine preparations, investigating vaccine-induced protective mechanisms, and assessing manufacturing issues, including product potency and stability.
C1 [Parra, Marcela; Yang, Amy L.; Lim, JaeHyun; Kolibab, Kristopher; Derrick, Steven; Cadieux, Nathalie; Brennan, Michael; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Perera, Liyanage P.] Ctr Canc Res, Metab Branch, Natl Canc Inst, Bethesda, MD USA.
[Jacobs, William R.] Albert Einstein Coll Med, Howard Hughes Med Inst, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Brennan, Michael] Aeras Global TB Vaccine Fdn, Rockville, MD USA.
RP Morris, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA.
EM sheldon.morris@fda.hhs.gov
FU National Institute of Allergy and Infectious Diseases; National
Institutes of Health; Department of Health and Human Services [IAA
224-06-1322]
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 IAA
224-06-1322.
NR 36
TC 32
Z9 33
U1 0
U2 0
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 JUL 1
PY 2009
VL 16
IS 7
BP 1025
EP 1032
DI 10.1128/CVI.00067-09
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 467OH
UT WOS:000267747700010
PM 19458207
ER
PT J
AU Russo, AL
Jedlicka, K
Wernick, M
McNally, D
Kirk, M
Sproull, M
Smith, S
Shankavaram, U
Kaushal, A
Figg, WD
Dahut, W
Citrin, D
Bottaro, DP
Albert, PS
Tofilon, PJ
Camphausen, K
AF Russo, Andrea L.
Jedlicka, Kimberly
Wernick, Meredith
McNally, Debbie
Kirk, Melissa
Sproull, Mary
Smith, Sharon
Shankavaram, Uma
Kaushal, Aradhana
Figg, William D.
Dahut, William
Citrin, Deborah
Bottaro, Donald P.
Albert, Paul S.
Tofilon, Philip J.
Camphausen, Kevin
TI Urine Analysis and Protein Networking Identify Met as a Marker of
Metastatic Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HEPATOCYTE GROWTH-FACTOR; C-MET; ANDROGEN RECEPTOR; ANTIGEN LEVEL;
CELL-LINE; EXPRESSION; SERUM; PROGRESSION; INDUCTION; CARCINOMA
AB Purpose: Metastatic prostate cancer is a major cause of death of men in the United States. Expression of met, a receptor tyrosine kinase, has been associated with progression of prostate cancer.
Experimental Design: To investigate met as a biomarker of disease progression, urinary met was evaluated via ELISA in men with localized (n = 75) and metastatic (n = 81) prostate cancer. Boxplot analysis was used to compare the distribution of met values between each group. We estimated a receiver operating characteristic curve and the associated area under the curve to summarize the diagnostic accuracy of met for distinguishing between localized and metastatic disease. Protein-protein interaction networking via yeast two-hybrid technology supplemented by Ingenuity Pathway Analysis and Human Interactome was used to elucidate proteins and pathways related to met that may contribute to progression of disease.
Results: Met distribution was significantly different between the metastatic group and the group with localized prostate cancer and people with no evidence of cancer (P < 0.0001). The area under the curve for localized and metastatic disease was 0.90, with a 95% confidence interval of 0.84 to 0.95. Yeast two-hybrid technology, Ingenuity Pathway Analysis, and Human Interactome identified 89 proteins that interact with met, of which 40 have previously been associated with metastatic prostate cancer.
Conclusion: Urinary met may provide a noninvasive biomarker indicative of metastatic prostate cancer and may be a central regulator of multiple pathways involved in prostate cancer progression.
C1 [Russo, Andrea L.; Wernick, Meredith; McNally, Debbie; Kirk, Melissa; Sproull, Mary; Smith, Sharon; Shankavaram, Uma; Kaushal, Aradhana; Citrin, Deborah; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD USA.
[Russo, Andrea L.] NCI, HHMI NIH Res Scholars Program, Howard Hughes Med Inst, NIH, Bethesda, MD 20892 USA.
[Jedlicka, Kimberly; Bottaro, Donald P.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Figg, William D.; Dahut, William] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Albert, Paul S.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Tofilon, Philip J.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA.
RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD USA.
EM camphauk@mail.nih.gov
RI Bottaro, Donald/F-8550-2010; Figg Sr, William/M-2411-2016
OI Bottaro, Donald/0000-0002-5057-5334;
FU Intramural Research Program of the NIH; National Cancer Institute;
Howard Hughes Medical Institute through the Howard Hughes Medical
Institute-NIH Research Scholars Program
FX Intramural Research Program of the NIH, National Cancer Institute and by
the Howard Hughes Medical Institute through the Howard Hughes Medical
Institute-NIH Research Scholars Program.
NR 27
TC 22
Z9 23
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 JUL 1
PY 2009
VL 15
IS 13
BP 4292
EP 4298
DI 10.1158/1078-0432.CCR-09-0599
PG 7
WC Oncology
SC Oncology
GA 482SF
UT WOS:000268908300009
PM 19549766
ER
PT J
AU Xiao, Y
Gao, XG
Maragh, S
Telford, WG
Tona, A
AF Xiao, Yan
Gao, Xiugong
Maragh, Samantha
Telford, William G.
Tona, Alessandro
TI Cell Lines as Candidate Reference Materials for Quality Control of ERBB2
Amplification and Expression Assays in Breast Cancer
SO CLINICAL CHEMISTRY
LA English
DT Article
ID IN-SITU HYBRIDIZATION; HER-2/NEU EXPRESSION; ESTROGEN-RECEPTOR; HER2;
IMMUNOHISTOCHEMISTRY; QUANTITATION; C-ERBB-2; STANDARD; DISEASE; N9831
AB BACK(;ROUND: Human epidermal growth factor receptor 2 (HER2) is an important biomarker whose status plays a pivotal role in therapeutic decision-making for breast cancer patients and in determining their clinical outcomes. Ensuring the accuracy and reproducibility of HER2 assays by immunohistochemistry (IHC) and by fluorescence in situ hybridization (FISH) requires a reliable standard for monitoring assay sensitivity and specificity, and for assessing methodologic variation. A prior NIST workshop addressed this need by reaching a consensus to create cell lines as reference materials for HER2 testing.
METHODS: Breast carcinoma cell lines SK-BR-3 and MCF-7 were characterized quantitatively by IHC with chicken anti-HER2 IgY antibody and by FISH with biotinylated bacterial artificial chromosome DNA probes; both assays used quantum dots as detectors. Formalin-fixed and paraffin-embedded (FFPE) cell blocks were prepared and tested for suitability as candidate reference materials by IHC and FISH with commercially available reagents. IHC and FISH results were also compared with those obtained by laser-scanning cytometry and real-time PCR, respectively.
RESULTS: MCF-7 cells had typical numbers of gene copies and very low production of HER2 protein, whereas SK-BR-3 cells contained approximately 10-fold more copies of the gene and exhibited approximately 15-fold higher amounts of HER2 protein than MCF-7 cells. FFPE SK-BR-3 cells showed results similar to those for fresh SK-BR-3 cells.
CONCLUSIONS: SK-BR-3 and MCF-7 are suitable as candidate reference materials in QC of HER2 testing. Coupled with the associated assay platforms, they provide valuable controls for quantitative measurement of HER2 amplification and production in breast cancer samples, irrespective of the antibody/probe or detector used. (C) 2009 American Association for Clinical Chemistry
C1 [Xiao, Yan] Natl Inst Stand & Technol, DNA Measurements Grp, Div Biochem Sci, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA.
[Tona, Alessandro] Sci Applicat Int Corp, Arlington, VA USA.
[Gao, Xiugong] Translabion, Clarksburg, MD USA.
[Telford, William G.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Xiao, Y (reprint author), Natl Inst Stand & Technol, DNA Measurements Grp, Div Biochem Sci, Chem Sci & Technol Lab, 100 Bur Dr, Gaithersburg, MD 20899 USA.
EM yan.xiao@nist.gov
NR 23
TC 15
Z9 16
U1 1
U2 7
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2009
VL 55
IS 7
BP 1307
EP 1315
DI 10.1373/clinchem.2008.120576
PG 9
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 463VI
UT WOS:000267460200011
PM 19443566
ER
PT J
AU Solomon, BD
Potocki, L
Oyer, CE
Muenke, M
AF Solomon, Benjamin D.
Potocki, Lorraine
Oyer, Calvin E.
Muenke, Maximilian
TI Holoprosencephaly in an 8.5-week triploidy gestation
SO CLINICAL DYSMORPHOLOGY
LA English
DT Article
C1 [Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA.
[Potocki, Lorraine] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Potocki, Lorraine] Texas Childrens Hosp, Houston, TX 77030 USA.
[Oyer, Calvin E.] Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI 02912 USA.
[Oyer, Calvin E.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
RP Muenke, M (reprint author), NHGRI, NIH, Med Genet Branch, Bldg 35,Room 1B-203, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU National Human Genome Research Institute; National Institutes of Health
FX This work was supported (in part) by the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health.
NR 10
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0962-8827
J9 CLIN DYSMORPHOL
JI Clin. Dysmorphol.
PD JUL
PY 2009
VL 18
IS 3
BP 166
EP 167
DI 10.1097/MCD.0b013e32832a9e90
PG 2
WC Genetics & Heredity
SC Genetics & Heredity
GA 459NR
UT WOS:000267110300013
PM 19357506
ER
PT J
AU Timmers, HJLM
Eisenhofer, G
Carrasquillo, JA
Chen, CC
Whatley, M
Ling, A
Adams, KT
Pacak, K
AF Timmers, Henri J. L. M.
Eisenhofer, Graeme
Carrasquillo, Jorge A.
Chen, Clara C.
Whatley, Millie
Ling, Alexander
Adams, Karen T.
Pacak, Karel
TI Use of 6-[F-18]-fluorodopamine positron emission tomography (PET) as
first-line investigation for the diagnosis and localization of
non-metastatic and metastatic phaeochromocytoma (PHEO)
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID LYMPH-NODES; I-123 METAIODOBENZYLGUANIDINE; BIOCHEMICAL-DIAGNOSIS;
PARAGANGLIOMA; SCINTIGRAPHY; PLASMA; CATECHOLAMINES; SUPERIORITY;
BENIGN; SIZE
AB P>Objective
Imaging modalities available for the localization of phaeochromocytoma (PHEO) include computed tomography (CT), magnetic resonance imaging (MRI), [I-123]- or [I-131]-labelled metaiodobenzylguanidine (I-123/131-MIBG) scintigraphy and 6-[F-18]-fluorodopamine (F-18-FDA) positron emission tomography (PET). Our aim was to investigate the yield of F-18-FDA PET vs. biochemical testing and other imaging techniques to establish the diagnosis and location of PHEO.
Patients and measurements
The study included 99 consecutive patients (35 Males, 64 Females, mean +/- SD age 46 center dot 4 +/- 13 center dot 4 years), who underwent F-18-FDA PET, biochemical testing (plasma catecholamines and free metanephrines) and CT and/or MRI. The majority (78%) also underwent I-123/131-MIBG.
Results
In total 26 patients had non-metastatic PHEO, 34 patients had metastatic PHEO, and PHEO was ruled out in 39 patients. Investigations to rule out or confirm PHEO yielded the following sensitivity/specificity: plasma metanephrines 97/95%, F-18-FDA 92/90%, I-123-MIBG 83/100%, I-123/131-MIBG 70/100%, CT 100/41%, MRI 98/60%. Sensitivities for localizing non-metastatic PHEO on a per-lesion base were: CT 97%, MRI 92%, F-18-FDA 78%, I-123-MIBG 78% and I-123/131-MIBG 76%. Sensitivities for detecting metastases on a per-patient base were: CT and MRI 100%, F-18-FDA 97%, I-123-MIBG 85% and I-123/131-MIBG 65%.
Conclusion
For tumour localization, F-18-FDA PET and I-123/131-MIBG scintigraphy perform equally well in patients with non-metastatic PHEO, but metastases are better detected by F-18-FDA PET than by I-123/131-MIBG.
C1 [Timmers, Henri J. L. M.; Adams, Karen T.; Pacak, Karel] NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bethesda, MD 20892 USA.
[Timmers, Henri J. L. M.] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Eisenhofer, Graeme] Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany.
[Eisenhofer, Graeme] Univ Dresden, Dept Med, Dresden, Germany.
[Carrasquillo, Jorge A.; Chen, Clara C.; Whatley, Millie] NIH, Dept Nucl Med, Bethesda, MD USA.
[Ling, Alexander] NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), NICHD, Sect Med Neuroendocrinol, Reprod & Adult Endocrinol Program, NIH, Bldg 10,CRC,Room 1E-3140,10 Ctr Dr MSC-1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
RI Carrasquillo, Jorge/E-7120-2010;
OI Carrasquillo, Jorge/0000-0002-8513-5734
FU Intramural Research Program of the NICHD/NIH
FX This research was supported by the Intramural Research Program of the
NICHD/NIH.
NR 24
TC 40
Z9 41
U1 0
U2 4
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0300-0664
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD JUL
PY 2009
VL 71
IS 1
BP 11
EP 17
DI 10.1111/j.1365-2265.2008.03496.x
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 457IQ
UT WOS:000266922100003
PM 19138315
ER
PT J
AU Jones, KL
Seward, RJ
Ben-Menachem, G
Glickstein, LJ
Costello, CE
Steere, AC
AF Jones, Kathryn L.
Seward, Robert J.
Ben-Menachem, Gil
Glickstein, Lisa J.
Costello, Catherine E.
Steere, Allen C.
TI Strong IgG antibody responses to Borrelia burgdorferi glycolipids in
patients with Lyme arthritis, a late manifestation of the infection
SO CLINICAL IMMUNOLOGY
LA English
DT Article
DE Lyme disease; Bacterial infection; Borrelia burgdorferi; Antibodies;
Glycolipid antigens
ID T-CELLS; CHOLESTERYL GALACTOSIDE; DISEASE; RECOMBINANT; ANTIGENS;
PEPTIDE; VACCINE
AB In this study, the membrane lipids of B. burgdorferi were separated into 16 fractions; the components in each fraction were identified, and the immunogenicity of each fraction was determined by ELISA using sera from Lyme disease patients. Only the 2 glycolipids, acylated cholesteryl galactoside (ACG, BbGL-I) and monogalactosyl diacylglycerol (MgaID, BbGL-II), were immunogenic. Early in the infection, 24 of 84 patients (29%) who were convalescent from erythema migrans and 19 of the 35 patients (54%) with neuroborreliosis had weak IgG responses to purified MgaID, and a smaller percentage of patients had early responses to synthetic ACG. However, almost all of 75 patients with Lyme arthritis, a late disease manifestation, had strong IgG reactivity with both glycolipids. Thus, almost all patients with Lyme arthritis have strong IgG antibody responses to B. burgdorferi glycolipid antigens. (C) 2009 Elsevier Inc. All rights reserved.
C1 [Jones, Kathryn L.; Seward, Robert J.; Glickstein, Lisa J.; Steere, Allen C.] Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Med Sch, Boston, MA 02114 USA.
[Ben-Menachem, Gil] NICHHD, NIH, Bethesda, MD 20892 USA.
[Seward, Robert J.; Costello, Catherine E.] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA.
RP Steere, AC (reprint author), Harvard Univ, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Med Sch, 55 Fruit St,Charlestown Navy Yard 149-8301, Boston, MA 02114 USA.
EM asteere@partners.org
OI Costello, Catherine/0000-0003-1594-5122; Jones,
Kathryn/0000-0003-3815-5713
FU National Institutes of Health [RO1 AR-20358, P41 RR10888, S10 RR 15942,
AR-007258]; English, Bonter, Mitchell Foundation; Eshe Fund;
Lyme/Arthritis Research Fund at Massachusetts General Hospital; Walter
J. and Lille A. Berbecker Foundation
FX We thank Dr. Nitin Damle in Wakefield, Rhode Island, and Dr. Vijay
Sikand in East Lyme, Connecticut, for obtaining serum samples from
patients with erythema migrans, Mr. Vincent Poszgay for making the
synthetic preparation of ACG (BbGL-I), Dr. Rachel Schneerson for
providing the preparation for our study, Ms. Gail McHugh for help in the
processing and storage of serum samples, Ms. Colleen Squires for
assistance with the preparation of this manuscript, and Dr. Shiv Pillai
for helpful discussions. This work was supported by funding from the
National Institutes of Health (RO1 AR-20358 to ACS and P41 RR10888 and
S10 RR 15942 to CEC), the English, Bonter, Mitchell Foundation, the Eshe
Fund, and the Lyme/Arthritis Research Fund at Massachusetts General
Hospital. K.L.J. received support from a scholarship from the Walter J.
and Lille A. Berbecker Foundation for the study of Lyme disease, and
from the National Institutes of Health training grant AR-007258.
NR 29
TC 11
Z9 12
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD JUL
PY 2009
VL 132
IS 1
BP 93
EP 102
DI 10.1016/j.clim.2009.03.510
PG 10
WC Immunology
SC Immunology
GA 457SY
UT WOS:000266954900010
PM 19342303
ER
PT J
AU Mermel, LA
Allon, M
Bouza, E
Craven, DE
Flynn, P
O'Grady, NP
Raad, II
Rijnders, BJA
Sherertz, RJ
Warren, DK
AF Mermel, Leonard A.
Allon, Michael
Bouza, Emilio
Craven, Donald E.
Flynn, Patricia
O'Grady, Naomi P.
Raad, Issam I.
Rijnders, Bart J. A.
Sherertz, Robert J.
Warren, David K.
TI Clinical Practice Guidelines for the Diagnosis and Management of
Intravascular Catheter-Related Infection: 2009 Update by the Infectious
Diseases Society of America
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Review
ID BLOOD-STREAM INFECTION; STAPHYLOCOCCUS-AUREUS BACTEREMIA; CENTRAL VENOUS
CATHETER; CRITICALLY-ILL PATIENTS; VANCOMYCIN-RESISTANT ENTEROCOCCUS;
ANTIBIOTIC LOCK TECHNIQUE; LIPOSOMAL AMPHOTERICIN-B; SUPPURATIVE
PERIPHERAL THROMBOPHLEBITIS; COAGULASE-NEGATIVE STAPHYLOCOCCI;
SERRATIA-MARCESCENS BACTEREMIA
C1 [Mermel, Leonard A.] Brown Univ, Warren Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA.
[Allon, Michael] Univ Alabama Birmingham Hosp, Birmingham, AL USA.
[Craven, Donald E.] Tufts Univ, Sch Med, Lahey Clin Med Ctr, Burlington, MA USA.
[Flynn, Patricia] St Jude Childrens Res Hosp, Childrens Infect Def Ctr, Memphis, TN 38105 USA.
[O'Grady, Naomi P.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Raad, Issam I.] Univ Texas MD Anderson Canc Ctr, Infect Dis Sect, Houston, TX 77030 USA.
[Sherertz, Robert J.] Wake Forest Univ, Bowman Gray Sch Med, Infect Dis Sect, Winston Salem, NC USA.
[Warren, David K.] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA.
[Bouza, Emilio] Hosp Gen Gregorio Maranon, Serv Microbiol Clin & E Infecciosas, Madrid, Spain.
[Rijnders, Bart J. A.] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
RP Mermel, LA (reprint author), Rhode Isl Hosp, Div Infect Dis, 593 Eddy St, Providence, RI 02903 USA.
EM lmermel@lifespan.org
RI Bouza, Emilio/D-8661-2014;
OI Bouza, Emilio/0000-0001-6967-9267; Warren, David/0000-0001-8679-8241
FU NIDDK NIH HHS [U01 DK058968]
NR 284
TC 964
Z9 1029
U1 9
U2 65
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 JUL 1
PY 2009
VL 49
IS 1
BP 1
EP 45
DI 10.1086/599376
PG 45
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 455ND
UT WOS:000266766500001
PM 19489710
ER
PT J
AU Vinh, DC
Shea, YR
Sugui, JA
Parrilla-Castellar, ER
Freeman, AF
Campbell, JW
Pittaluga, S
Jones, PA
Zelazny, A
Kleiner, D
Kwon-Chung, KJ
Holland, SM
AF Vinh, Donald C.
Shea, Yvonne R.
Sugui, Janyce A.
Parrilla-Castellar, Edgardo R.
Freeman, Alexandra F.
Campbell, J. William
Pittaluga, Stefania
Jones, Pamela A.
Zelazny, Adrian
Kleiner, David
Kwon-Chung, Kyung J.
Holland, Steven M.
TI Invasive Aspergillosis Due to Neosartorya udagawae
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B;
IMMUNOCOMPROMISED PATIENTS; IN-VITRO; FUMIGATUS; FISCHERI; TRANSPLANT;
INFECTION; THERAPY
AB Background. Invasive aspergillosis (IA) is most commonly caused by the morphospecies Aspergillus fumigatus. However, genetic-based methods indicate that organisms phenotypically identified as A. fumigatus actually constitute a mold complex, designated Aspergillus section fumigati subgenus fumigati.
Methods. Multilocus sequencing and analysis was performed on fungi identified as A. fumigatus from the clinical culture collection maintained at the National Institutes of Health from 2000 through 2008, with a focus on the internal transcribed spacer 1 and 2 regions of ribosomal DNA (rDNA), beta-tubulin, and rodlet A genes. We reviewed the medical records, radiology, and histopathology of corresponding patients. To confirm identification of Neosartorya udagawae isolates, mating studies were performed with reference strains. Antifungal susceptibility testing was performed by broth microdilution and read at 48 hours.
Results. Thirty-six cases of infection attributed to A. fumigatus were identified; 4 were caused by N. udagawae (3 in patients with chronic granulomatous disease and 1 in a patient with myelodysplastic syndrome). Disease due to N. udagawae was chronic, with a median duration of 35 weeks, compared with a median duration of 5.5 weeks for patients with chronic granulomatous disease who had infection due to A. fumigatus sensu stricto (P < .05 Mann-Whitney U test). Infection spread across anatomical planes in a contiguous manner and was refractory to standard therapy. Two of the 4 patients died. N. udagawae demonstrated relatively higher minimum inhibitory concentrations to various agents, compared with those demonstrated by contemporary A. fumigatus sensu stricto isolates.
Conclusions. To our knowledge, this is the first report documenting infection due to N. udagawae. Clinical manifestations were distinct from those of typical IA. Fumigati-mimetics with inherent potential for antifungal resistance are agents of IA. Genetic identification of molds should be considered for unusual or refractory IA.
C1 [Holland, Steven M.] NIAID, Sect Immunopathogenesis, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sugui, Janyce A.; Kwon-Chung, Kyung J.] NIAID, Sect Mol Microbiol, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Shea, Yvonne R.; Jones, Pamela A.; Zelazny, Adrian] NIH, Microbiol Serv, Dept Lab Med, Bethesda, MD 20892 USA.
[Parrilla-Castellar, Edgardo R.; Pittaluga, Stefania; Kleiner, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.] NCI, Lab Clin Infect Dis, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA.
[Campbell, J. William] St Lukes Hosp, Dept Med, Div Infect Dis, Chesterfield, MO USA.
RP Holland, SM (reprint author), NIAID, Sect Immunopathogenesis, Lab Clin Infect Dis, NIH, Bldg 10CRC,Rm B3-4141,MSC 1684, Bethesda, MD 20892 USA.
EM smh@nih.gov
OI VINH, DONALD/0000-0003-1347-7767; Kleiner, David/0000-0003-3442-4453
FU Canadian Institutes of Health Research fellowship; National Institutes
of Health Supplemental Visiting fellowship; Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health [N01-CO-12400]; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]
FX Canadian Institutes of Health Research fellowship (to D. C. V.);
National Institutes of Health Supplemental Visiting fellowship (to D. C.
V.); Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health (N01-CO-12400); and
National Cancer Institute, National Institutes of Health
(HHSN261200800001E).
NR 42
TC 59
Z9 59
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2009
VL 49
IS 1
BP 102
EP 111
DI 10.1086/599345
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 455ND
UT WOS:000266766500010
PM 19489714
ER
EF