FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Ward, RE
Boudreau, R
Caserotti, P
Harris, TB
Goodpaster, B
Cauley, JA
Newman, AB
Strotmeyer, ES
AF Ward, R. E.
Boudreau, R.
Caserotti, P.
Harris, T. B.
Goodpaster, B.
Cauley, J. A.
Newman, A. B.
Strotmeyer, E. S.
TI SENSORY AND MOTOR PERIPHERAL NERVE FUNCTION PREDICT LONGITUDINAL
LOWER-EXTREMITY QUADRICEPS STRENGTH
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Ward, R. E.; Boudreau, R.; Goodpaster, B.; Cauley, J. A.; Newman, A. B.; Strotmeyer, E. S.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Caserotti, P.] Univ So Denmark, Odense, Denmark.
[Harris, T. B.] NIA, Bethesda, MD 20892 USA.
RI Strotmeyer, Elsa/F-3015-2014
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 508
EP 508
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888203686
ER
PT J
AU Breslau, ES
Bellizzi, K
Schonberg, MA
AF Breslau, E. S.
Bellizzi, K.
Schonberg, M. A.
TI PREVALENCE OF MAMMOGRAPHY USE IN OLDER WOMEN BY 5-YEAR LIFE EXPECTANCY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Breslau, E. S.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Bellizzi, K.] Univ Connecticut, Storrs, CT USA.
[Schonberg, M. A.] Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 529
EP 530
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888203785
ER
PT J
AU Tolea, M
Simonsick, EM
AF Tolea, M.
Simonsick, E. M.
TI PERSONALITY CORRELATES OF EXCEPTIONAL HEALTH IN OLDER PARTICIPANTS IN
THE BALTIMORE LONGITUDINAL STUDY OF AGING (BLSA)
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tolea, M.] Univ Missouri, St Louis, MO 63121 USA.
[Simonsick, E. M.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 559
EP 559
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204056
ER
PT J
AU Nadkarni, NK
Nunley, KA
Aizenstein, H
Harris, TB
Yaffe, K
Brach, J
Newman, AB
Rosano, C
AF Nadkarni, N. K.
Nunley, K. A.
Aizenstein, H.
Harris, T. B.
Yaffe, K.
Brach, J.
Newman, A. B.
Rosano, C.
TI REGIONAL CEREBELLAR GREY MATTER VOLUME, PROCESSING SPEED AND GAIT
MEASURES
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Nadkarni, N. K.; Nunley, K. A.; Aizenstein, H.; Brach, J.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Nadkarni, N. K.; Rosano, C.] Pittsburgh Older Amer Independence Ctr, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 578
EP 578
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204134
ER
PT J
AU Tian, Q
Erickson, K
Simonsick, EM
Aizenstein, H
Glynn, NW
Yaffe, K
Newman, AB
Rosano, C
AF Tian, Q.
Erickson, K.
Simonsick, E. M.
Aizenstein, H.
Glynn, N. W.
Yaffe, K.
Newman, A. B.
Rosano, C.
TI ASSOCIATION BETWEEN ENDURANCE WALK CAPACITY AND INTEGRITY OF BRAIN
REGIONS IMPORTANT FOR PROCESSING SPEED IN VERY OLD ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tian, Q.; Erickson, K.; Aizenstein, H.; Glynn, N. W.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Simonsick, E. M.] NIA, Bethesda, MD 20892 USA.
[Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 579
EP 579
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204138
ER
PT J
AU Tian, Q
Simonsick, EM
Glynn, NW
Aizenstein, H
Yaffe, K
Harris, TB
Newman, AB
Rosano, C
AF Tian, Q.
Simonsick, E. M.
Glynn, N. W.
Aizenstein, H.
Yaffe, K.
Harris, T. B.
Newman, A. B.
Rosano, C.
TI FREE-LIVING PHYSICAL ACTIVITY AND BRAIN STRUCTURES IN OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Tian, Q.; Glynn, N. W.; Aizenstein, H.; Newman, A. B.; Rosano, C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Simonsick, E. M.; Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 579
EP 580
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204140
ER
PT J
AU Bellizzi, K
Breslau, ES
AF Bellizzi, K.
Breslau, E. S.
TI COLORECTAL CANCER SCREENING IN OLDER ADULTS BY 5 YEAR LIFE EXPECTANCY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Bellizzi, K.] UConn, HDFS, Storrs, CT USA.
[Breslau, E. S.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 582
EP 582
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204150
ER
PT J
AU Caserotti, P
Harris, TB
Puggaard, L
Rasmussen, C
Aagaard, P
AF Caserotti, P.
Harris, T. B.
Puggaard, L.
Rasmussen, C.
Aagaard, P.
TI POWER TRAINING IN OLDER ADULTS: MUSCLE MECHANICAL, MORPHOLOGICAL AND
FUNCTIONAL CHANGES
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Caserotti, P.; Puggaard, L.; Aagaard, P.] Univ So Denmark, Inst Sports Sci & Clin Biomech, Odense, Denmark.
[Caserotti, P.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Rasmussen, C.] Univ Aarhus, Inst Publ Hlth, Aarhus, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 608
EP 608
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204260
ER
PT J
AU Kim, DH
Patel, K
Newman, AB
Chaves, PH
Klein, R
Sarnak, M
Lipsitz, L
AF Kim, D. H.
Patel, K.
Newman, A. B.
Chaves, P. H.
Klein, R.
Sarnak, M.
Lipsitz, L.
TI BURDEN OF MICROVASCULAR AND MACROVASCULAR DISEASE AND FUNCTIONAL STATUS
IN COMMUNITY-DWELLING OLDER ADULTS: THE CARDIOVASCULAR HEALTH STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Kim, D. H.; Lipsitz, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Kim, D. H.; Lipsitz, L.] Hebrew SeniorLife, Boston, MA USA.
[Kim, D. H.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Patel, K.] NIA, Bethesda, MD 20892 USA.
[Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Chaves, P. H.] Johns Hopkins Univ, Baltimore, MD USA.
[Klein, R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Sarnak, M.] Tufts Med Ctr, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 623
EP 623
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204333
ER
PT J
AU Whitson, HE
Arnold, A
Mukamal, K
Kizer, JR
Siscovick, D
Thielke, SM
Hirsch, C
Zieman, S
AF Whitson, H. E.
Arnold, A.
Mukamal, K.
Kizer, J. R.
Siscovick, D.
Thielke, S. M.
Hirsch, C.
Zieman, S.
TI ASSOCIATION OF N-CARBOXYMETHYL-LISINE (CML) AND FRAILTY IN OLDER MEN AND
WOMEN: THE CARDIOVASCULAR HEALTH STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Whitson, H. E.] Duke, Internal Med, Durham, NC USA.
[Whitson, H. E.] Durham VA, Durham, NC USA.
[Arnold, A.; Siscovick, D.; Thielke, S. M.] Univ Washington, Seattle, WA 98195 USA.
[Mukamal, K.] Harvard Univ, Sch Med, Boston, MA USA.
[Kizer, J. R.] Cornell Weill Med Coll, New York, NY USA.
[Hirsch, C.] Univ Calif Davis, Davis, CA USA.
[Zieman, S.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 623
EP 623
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204334
ER
PT J
AU Chang, M
Snaedal, J
Einarsson, B
Saczynski, J
Gudnason, V
Launer, LJ
Harris, TB
Jonsson, PV
AF Chang, M.
Snaedal, J.
Einarsson, B.
Saczynski, J.
Gudnason, V.
Launer, L. J.
Harris, T. B.
Jonsson, P. V.
TI THE ASSOCIATION BETWEEN MID-LIFE PHYSICAL ACTIVITY AND LOWER EXTREMITY
FUNCTION IN OLDER ADULTS: ROLE OF COGNITIVE FUNCTION, AGE
GENE/ENVIRONMENT SUSCEPTIBILITY (AGES) - REYKJAVIK STUDY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Chang, M.; Snaedal, J.; Einarsson, B.; Jonsson, P. V.] Landspitali Univ Hosp, Geriatr Res Ctr, Reykjavik, Iceland.
[Snaedal, J.; Einarsson, B.; Gudnason, V.; Jonsson, P. V.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Saczynski, J.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[Saczynski, J.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA.
[Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Launer, L. J.; Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 626
EP 626
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204345
ER
PT J
AU Patel, K
AF Patel, K.
TI ASSOCIATION OF CHRONIC BACK PAIN AND BALANCE IMPAIRMENT WITH MOBILITY
LIMITATION AND PHYSICAL ACTIVITY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Patel, K.] NIA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 626
EP 627
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204348
ER
PT J
AU Deshpande, N
Metter, E
Guralnik, JM
Ferrucci, L
AF Deshpande, N.
Metter, E.
Guralnik, J. M.
Ferrucci, L.
TI FEAR OF FALLING IN OLDER PERSONS: INCIDENCE AND PROGRESSION OVER 3 YEARS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Deshpande, N.] Queens Univ, Kingston, ON, Canada.
[Metter, E.; Ferrucci, L.] NIA, Washington, DC USA.
[Guralnik, J. M.] Univ Maryland, College Pk, MD 20742 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 628
EP 628
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204352
ER
PT J
AU Kuo, J
Parisi, JM
Nahin, R
Fitzpatrick, A
Rapp, S
Lopez, OL
Snitz, B
Carlson, M
AF Kuo, J.
Parisi, J. M.
Nahin, R.
Fitzpatrick, A.
Rapp, S.
Lopez, O. L.
Snitz, B.
Carlson, M.
TI LATE-LIFE LIFESTYLE ACTIVITY AS A BUFFER FOR COGNITIVE DECLINE AND
FUNCTIONAL IMPAIRMENT
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Kuo, J.; Carlson, M.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA.
[Kuo, J.; Parisi, J. M.; Carlson, M.] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA.
[Nahin, R.] Natl Ctr Complementary & Alternat Med, Bethesda, MD USA.
[Fitzpatrick, A.] Univ Washington, Seattle, WA 98195 USA.
[Rapp, S.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Lopez, O. L.; Snitz, B.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 656
EP 656
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204494
ER
PT J
AU Murphy, RA
Patel, K
Kritchevsky, SB
Houston, DK
Tylavsky, FA
Cawthon, PM
Newman, AB
Harris, TB
AF Murphy, R. A.
Patel, K.
Kritchevsky, S. B.
Houston, D. K.
Tylavsky, F. A.
Cawthon, P. M.
Newman, A. B.
Harris, T. B.
TI ASSOCIATION OF CHANGES IN WEIGHT WITH BODY COMPOSITION AND MORTALITY IN
OLDER ADULTS: HEALTH ABC
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Murphy, R. A.; Patel, K.; Harris, T. B.] NIA, Bethesda, MD 20892 USA.
[Kritchevsky, S. B.; Houston, D. K.] Wake Forest Univ, Salem, NC USA.
[Tylavsky, F. A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Cawthon, P. M.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 658
EP 658
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204503
ER
PT J
AU Sanders, J
Boudreau, R
Penninx, B
Simonsick, EM
Kritchevsky, SB
Satterfield, S
Harris, TB
Newman, AB
AF Sanders, J.
Boudreau, R.
Penninx, B.
Simonsick, E. M.
Kritchevsky, S. B.
Satterfield, S.
Harris, T. B.
Newman, A. B.
TI ASSOCIATION OF A MODIFIED PHYSIOLOGIC INDEX WITH MORTALITY AND INCIDENT
DISABILITY
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Sanders, J.; Boudreau, R.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Penninx, B.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands.
[Simonsick, E. M.] Johns Hopkins Sch Med, Baltimore, MD USA.
[Simonsick, E. M.; Harris, T. B.] NIA, Baltimore, MD 21224 USA.
[Kritchevsky, S. B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Satterfield, S.] Univ Tennessee, Memphis, TN USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 658
EP 658
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204505
ER
PT J
AU Gomes, A
Dioufa, N
Price, N
Rolo, A
Mercken, E
Palmeira, C
De Cabo, R
Sinclair, DA
AF Gomes, A.
Dioufa, N.
Price, N.
Rolo, A.
Mercken, E.
Palmeira, C.
De Cabo, R.
Sinclair, D. A.
TI MEDICINES THAT MIMIC CALORIE RESTRICTION: HOW CLOSE ARE WE?
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Gomes, A.; Dioufa, N.; Price, N.; Sinclair, D. A.] Harvard Univ, Sch Med, Boston, MA USA.
[Gomes, A.; Rolo, A.; Palmeira, C.] Univ Coimbra, Coimbra, Portugal.
[Mercken, E.; De Cabo, R.] NIA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 667
EP 667
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204548
ER
PT J
AU Eggermont, L
Shi, L
Kiely, DK
Bean, JF
Guralnik, J
Shmerling, RH
Jones, R
Leveille, SG
AF Eggermont, L.
Shi, L.
Kiely, D. K.
Bean, J. F.
Guralnik, J.
Shmerling, R. H.
Jones, R.
Leveille, S. G.
TI PAIN CONTRIBUTES TO ONSET/WORSENING OF MOBILITY DIFFICULTY AND
PERFORMANCE DECLINE IN OLDER ADULTS
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Eggermont, L.] Vrije Univ Amsterdam, Deparment Neuropsychol, Amsterdam, Netherlands.
[Kiely, D. K.; Jones, R.] Harvard Univ, Dept Med, Hebrew SeniorLife, Inst Aging Res, Boston, MA USA.
[Jones, R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Med, Boston, MA 02215 USA.
[Shmerling, R. H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Rheumatol, Boston, MA 02215 USA.
[Guralnik, J.] NIA, Lab Epidemiol Demog & Biometry, Bathesda, MD USA.
[Bean, J. F.] Harvard Univ, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02115 USA.
[Shi, L.; Leveille, S. G.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
RI Bean, Jonathan/F-5798-2017
OI Bean, Jonathan/0000-0001-8385-8210
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 685
EP 686
PG 2
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204641
ER
PT J
AU Cohen, AA
Langer, FDB
Fried, LP
Ferrucci, L
AF Cohen, A. A.
Langer, F. Dusseault-Be
Fried, L. P.
Ferrucci, L.
TI MULTI-SYSTEM BIOMARKER ANALYSES IN TWO AGING POPULATIONS: SAME BIG
PICTURE, DIFFERENT DETAILS FOR WHAS AND INCHIANTI
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Cohen, A. A.] Ctr Hosp Univ Sherbrooke, Grp Rech PRIMUS, Sherbrooke, PQ, Canada.
[Cohen, A. A.; Langer, F. Dusseault-Be] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada.
[Fried, L. P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 700
EP 700
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204712
ER
PT J
AU Langer, FDB
Cohen, AA
Xue, Q
Fried, LP
Ferrucci, L
AF Langer, F. Dusseault-Be
Cohen, A. A.
Xue, Q.
Fried, L. P.
Ferrucci, L.
TI UNDERSTANDING THE AGING PROCESS USING PRINCIPAL COMPONENT ANALYSIS ON
LONGITUDINAL BIOMARKERS SUITES: INCHIANTI
SO GERONTOLOGIST
LA English
DT Meeting Abstract
C1 [Langer, F. Dusseault-Be; Cohen, A. A.] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada.
[Xue, Q.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Fried, L. P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
J9 GERONTOLOGIST
JI Gerontologist
PD NOV
PY 2012
VL 52
SU 1
BP 700
EP 700
PG 1
WC Gerontology
SC Geriatrics & Gerontology
GA 061ZG
UT WOS:000312888204711
ER
PT J
AU Chuang, ML
Gona, P
Hautvast, GLTF
Salton, CJ
Blease, SJ
Yeon, SB
Breeuwer, M
O'Donnell, CJ
Manning, WJ
AF Chuang, Michael L.
Gona, Philimon
Hautvast, Gilion L. T. F.
Salton, Carol J.
Blease, Susan J.
Yeon, Susan B.
Breeuwer, Marcel
O'Donnell, Christopher J.
Manning, Warren J.
TI Correlation of Trabeculae and Papillary Muscles With Clinical and
Cardiac Characteristics and Impact on CMR Measures of LV Anatomy and
Function
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE cardiac magnetic resonance; left ventricular ejection fraction;
papillary muscle; population study; trabeculae
ID VENTRICULAR NON-COMPACTION; MAGNETIC-RESONANCE; SYSTOLIC DYSFUNCTION;
MASS; HYPERTRABECULATION/NONCOMPACTION; REPRODUCIBILITY; CARDIOMYOPATHY;
NONCOMPACTION; DIAGNOSIS; FLASH
AB OBJECTIVES The goal of this study was to assess the relationship of left ventricular (LV) trabeculae and papillary muscles (TPM) with clinical characteristics in a community-based, free-living adult cohort and to determine the effect of TPM on quantitative measures of LV volume, mass, and ejection fraction (EF).
BACKGROUND Hypertrabeculation has been associated with adverse cardiovascular events, but the distribution and clinical correlates of the volume and mass of the TPM in a normal left ventricle have not been well characterized.
METHODS Short-axis cine cardiac magnetic resonance images, obtained using a steady-state free precession sequence from 1,494 members of the Framingham Heart Study Offspring cohort, were analyzed with software that automatically segments TPM. Absolute TPM volume, TPM as a fraction of end-diastolic volume (EDV) (TPM/EDV), and TPM mass as a fraction of LV mass were determined in all offspring and in a referent group of offspring free of clinical cardiovascular disease and hypertension.
RESULTS In the referent group (mean age 61 +/- 9 years; 262 men and 423 women), mean TPM was 23 +/- 3% of LV EDV in both sexes (p = 0.9). TPM/EDV decreased with age (p < 0.02) but was not associated with body mass index. TPM mass as a fraction of LV mass was inversely correlated with age (p < 0.0001), body mass index (p < 0.018), and systolic blood pressure (p < 0.0001). Among all 1,494 participants (699 men), LV volumes decreased 23%, LV mass increased 28%, and EF increased by 7.5 EF units (p < 0.0001) when TPM were considered myocardial mass rather than part of the LV blood pool.
CONCLUSIONS Global cardiac magnetic resonance LV parameters were significantly affected by whether TPM was considered as part of the LV blood pool or as part of LV mass. Our cross-sectional data from a healthy referent group of adults free of clinical cardiovascular disease demonstrated that TPM/EDV decreases with increasing age in both sexes but is not related to hypertension or obesity. (J Am Coll Cardiol Img 2012;5:1115-23) (C) 2012 by the American College of Cardiology Foundation
C1 [Chuang, Michael L.; Gona, Philimon; Blease, Susan J.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Chuang, Michael L.; Salton, Carol J.; Yeon, Susan B.; Manning, Warren J.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, Boston, MA 02215 USA.
[Chuang, Michael L.; O'Donnell, Christopher J.; Manning, Warren J.] Harvard Univ, Sch Med, Boston, MA USA.
[Gona, Philimon] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hautvast, Gilion L. T. F.; Breeuwer, Marcel] Philips Healthcare, Best, Netherlands.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Manning, Warren J.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA.
EM wmanning@bidmc.harvard.edu
FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01
HC 25195]; National Institutes of Health [RO1 HL70279]; Philips
Healthcare; Philips Medical Systems
FX This research was supported by the National Heart, Lung, and Blood
Institute's Framingham Heart Study (contract N01 HC 25195), a
subcontract from the National Institutes of Health (RO1 HL70279), and by
an unrestricted grant from Philips Healthcare. Drs. Hautvast and
Breeuwer are employees of Philips Healthcare. Dr. Manning has received
research support from Philips Medical Systems. All other authors have
reported that they have no relationships relevant to the contents of
this paper to disclose.
NR 20
TC 24
Z9 25
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD NOV
PY 2012
VL 5
IS 11
BP 1115
EP 1123
DI 10.1016/j.jcmg.2012.05.015
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 066VG
UT WOS:000313248600006
PM 23153911
ER
PT J
AU Daniels, MP
AF Daniels, Mathew P.
TI The role of agrin in synaptic development, plasticity and signaling in
the central nervous system
SO NEUROCHEMISTRY INTERNATIONAL
LA English
DT Review
DE Agrin; Brain; Synapse development; Synaptic activity; Synaptic
plasticity; Filopodia
ID NEUROMUSCULAR-JUNCTION FORMATION; CULTURED MUSCLE-CELLS; TYROSINE KINASE
MUSK; HIPPOCAMPAL-NEURONS; DENDRITIC FILOPODIA; CORTICAL-NEURONS;
DEFICIENT MICE; IN-VIVO; ACETYLCHOLINE-RECEPTORS; MESSENGER-RNA
AB Development of the neuromuscular junction (NMJ) requires secretion of specific isoforms of the proteoglycan agrin by motor neurons. Secreted agrin is widely expressed in the basal lamina of various tissues, whereas a transmembrane form is highly expressed in the brain. Expression in the brain is greatest during the period of synaptogenesis, but remains high in regions of the adult brain that show extensive synaptic plasticity. The well-established role of agrin in NMJ development and its presence in the brain elicited investigations of its possible role in synaptogenesis in the brain. Initial studies on the embryonic brain and neuronal cultures of agrin-null mice did not reveal any defects in synaptogenesis. However, subsequent studies in culture demonstrated inhibition of synaptogenesis by agrin antisense oligonucleotides or agrin siRNA. More recently, a substantial loss of excitatory synapses was found in the brains of transgenic adult mice that lacked agrin expression everywhere but in motor neurons. The mechanisms by which agrin influences synapse formation, maintenance and plasticity may include enhancement of excitatory synaptic signaling, activation of the "muscle-specific" receptor tyrosine kinase (MuSK) and positive regulation of dendritic filopodia. In this article I will review the evidence that agrin regulates synapse development, plasticity and signaling in the brain and discuss the evidence for the proposed mechanisms. Published by Elsevier Ltd.
C1 NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
RP Daniels, MP (reprint author), NHLBI, Electron Microscopy Core Facil, NIH, 50 Serv Rd W,Bldg 14E,Room 111B, Bethesda, MD 20892 USA.
EM danielsm2@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 66
TC 15
Z9 16
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0197-0186
J9 NEUROCHEM INT
JI Neurochem. Int.
PD NOV
PY 2012
VL 61
IS 6
BP 848
EP 853
DI 10.1016/j.neuint.2012.02.028
PG 6
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 068NY
UT WOS:000313374600007
PM 22414531
ER
PT J
AU Cui, F
Cole, HA
Clark, DJ
Zhurkin, VB
AF Cui, Feng
Cole, Hope A.
Clark, David J.
Zhurkin, Victor B.
TI Transcriptional activation of yeast genes disrupts intragenic nucleosome
phasing
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID HISTONE-DNA INTERACTIONS; SACCHAROMYCES-CEREVISIAE; MICROCOCCAL
NUCLEASE; RNA-POLYMERASE; GENOME-WIDE; CHROMATIN STRUCTURE; SEQUENCE
PATTERNS; EUKARYOTIC GENOME; HIGH-RESOLUTION; IN-VIVO
AB Nucleosomes often undergo extensive rearrangement when genes are activated for transcription. We have shown previously, using paired-end sequencing of yeast nucleosomes, that major changes in chromatin structure occur when genes are activated by 3-aminotriazole (3AT), an inducer of the transcriptional activator Gcn4. Here, we provide a global analysis of these data. At the genomic level, nucleosomes are regularly phased relative to the transcription start site. However, for a subset of 234 strongly induced genes, this phasing is much more irregular after induction, consistent with the loss of some nucleosomes and the re-positioning of the remaining nucleosomes. To address the nature of this rearrangement, we developed the inter-nucleosome distance auto-correlation (DAC) function. At long range, DAC analysis indicates that nucleosomes have an average spacing of 162 bp, consistent with the reported repeat length. At short range, DAC reveals a 10.25-bp periodicity, implying that nucleosomes in overlapping positions are rotationally related. DAC analysis of the 3AT-induced genes suggests that transcription activation coincides with rearrangement of nucleosomes into irregular arrays with longer spacing. Sequence analysis of the +1 nucleosomes belonging to the 45 most strongly activated genes reveals a distinctive periodic oscillation in the A/T-dinucleotide occurrence that is present throughout the nucleosome and extends into the linker. This unusual pattern suggests that the +1 nucleosomes might be prone to sliding, thereby facilitating transcription.
C1 [Cui, Feng; Zhurkin, Victor B.] NCI, Cell Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Cole, Hope A.; Clark, David J.] NICHHD, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Clark, DJ (reprint author), NICHHD, Program Genom Differentiat, NIH, Bldg 6A,Room 2A14,6 Ctr Dr,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM clarkda@mail.nih.gov; zhurkin@nih.gov
FU National Institutes of Health (Center for Cancer Research, National
Cancer Institute); National Institutes of Health (Program in Genomics of
Differentiation, National Institute for Child Health and Human
Development); National Institutes of Health
FX The Intramural Research Program of the National Institutes of Health
(Center for Cancer Research, National Cancer Institute; Program in
Genomics of Differentiation, National Institute for Child Health and
Human Development). Funding for open access charge: The Intramural
Research Program of the National Institutes of Health.
NR 60
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Z9 13
U1 2
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2012
VL 40
IS 21
BP 10753
EP 10764
DI 10.1093/nar/gks870
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 068EU
UT WOS:000313349100021
PM 23012262
ER
PT J
AU Meteyer, CU
Barber, D
Mandl, JN
AF Meteyer, Carol U.
Barber, Daniel
Mandl, Judith N.
TI Pathology in euthermic bats with white nose syndrome suggests a natural
manifestation of immune reconstitution inflammatory syndrome
SO VIRULENCE
LA English
DT Article
DE cave-hibernating bats; Geomyces destructans; hibernation-induced; immune
suppression; immune cell trafficking; immune reconstitution inflammatory
syndrome (IRIS); Myotis lucifugus; white nose syndrome
ID GEOMYCES-DESTRUCTANS; GROUND-SQUIRRELS; HIBERNATION; INFECTION; SYSTEM;
TEMPERATURE; RESPONSES; THERAPY
AB White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.
C1 [Meteyer, Carol U.] US Geol Survey, Natl Wildlife Hlth Ctr, Madison, WI USA.
[Barber, Daniel] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mandl, Judith N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Mandl, JN (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM mandlj@niaid.nih.gov
FU US. Geological Survey
FX Authors are grateful to Gregory Turner (Pennsylvania Game Commission),
Mick Valent (New Jersey Division of Fish and Wild-life) and Jackie
Kashmer (New Jersey Bat Sanctuary) for permission to use the photographs
in Figure 1 and Ann Rivers (Acadia Wildlife Foundation) for submitting
the Little Brown Bats from Maine. Diagnostic work was funded by the US.
Geological Survey. Use of trade or product names does not imply
endorsement by the US government.
NR 39
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Z9 24
U1 7
U2 80
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 2150-5594
J9 VIRULENCE
JI Virulence
PD NOV
PY 2012
VL 3
IS 7
BP 583
EP 588
DI 10.4161/viru.22330
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 067HU
UT WOS:000313285700006
PM 23154286
ER
PT J
AU Huang, CH
Nwe, K
Al Zaki, A
Brechbiel, MW
Tsourkas, A
AF Huang, Ching-Hui
Nwe, Kido
Al Zaki, Ajlan
Brechbiel, Martin W.
Tsourkas, Andrew
TI Biodegradable Polydisulfide Dendrimer Nanoclusters as MRI Contrast
Agents
SO ACS NANO
LA English
DT Article
DE gadolinium; magnetic resonance; nanoparticle; nanocluster; dendrimer;
biodegradable
ID NEPHROGENIC SYSTEMIC FIBROSIS; POROUS POLYMERSOMES; DRUG-DELIVERY;
GADOLINIUM; CLEARANCE; CORES; NANOPARTICLES; ENHANCEMENT; RELAXIVITY;
COMPLEXES
AB Gadolinium-conjugated dendrimer nanoclusters (DNCs) are a promising platform for the early detection of disease; however, their clinical utility is potentially limited due to safety concerns related to nephrogenic systemic fibrosis (NSF). In this paper, biodegradable DNCs were prepared with polydisulfide linkages between the individual dendrimers to facilitate excretion. Further, DNCs were labeled with premetalated Gd chelates to eliminate the risk of free Gd becoming entrapped in dendrimer cavities. The biodegradable polydisulfide DNCs possessed a circulation half-life of >1.6 h in mice and produced significant contrast enhancement in the abdominal aorta and kidneys for as long as 4h. The DNCs were reduced in circulation as a result of thiol-disulfide exchange, and the degradation products were rapidly excreted via renal filtration. These agents demonstrated effective and prolonged in vivo contrast enhancement and yet minimized Gd tissue retention. Biodegradable polydisulfide DNCs represent a promising biodegradable macromolecular MRI contrast agent for magnetic resonance angiography and can potentially be further developed into target-specific MRI contrast agents.
C1 [Huang, Ching-Hui; Al Zaki, Ajlan; Tsourkas, Andrew] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA.
[Nwe, Kido; Brechbiel, Martin W.] NCI, Riadioimmune Inorgan Chem Sect, Bethesda, MD 20892 USA.
RP Tsourkas, A (reprint author), Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA.
EM atsourk@seas.upenn.edu
RI Tsourkas, Andrew/A-1074-2007
OI Tsourkas, Andrew/0000-0001-7758-1753
FU National Institute of Health (NIH) [NIBIB/R01-EB012065,
NCI/R01-CA157766, NIBIB/R21-EB013226]; NIH, National Cancer Institute,
Center for Cancer Research
FX This research was supported in part by the National Institute of Health
(NIH) NIBIB/R01-EB012065 (A.T.), NCI/R01-CA157766 (A.T.),
NIBIB/R21-EB013226 (A.T.), and the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (M.B.).
NR 42
TC 40
Z9 40
U1 4
U2 108
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
J9 ACS NANO
JI ACS Nano
PD NOV
PY 2012
VL 6
IS 11
BP 9416
EP 9424
DI 10.1021/nn304160p
PG 9
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA 043CY
UT WOS:000311521700009
PM 23098069
ER
PT J
AU Wakano, C
Byun, JS
Di, LJ
Gardner, K
AF Wakano, Clay
Byun, Jung S.
Di, Li-Jun
Gardner, Kevin
TI The dual lives of bidirectional promoters (vol 1819, pg 688, 2012)
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Correction
C1 [Gardner, Kevin] NCI, Genet Branch, Bethesda, MD 20982 USA.
NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20982 USA.
RP Gardner, K (reprint author), NCI, Genet Branch, 41 Lib Dr,Rm D305, Bethesda, MD 20982 USA.
EM gardnerk@mail.nih.gov
RI Di, Li-jun/D-6160-2013
NR 1
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD NOV-DEC
PY 2012
VL 1819
IS 11-12
BP 1228
EP 1229
DI 10.1016/j.bbagrm.2012.06.003
PG 2
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 063AB
UT WOS:000312965700012
ER
PT J
AU Chow, GV
Marine, JE
Fleg, JL
AF Chow, Grant V.
Marine, Joseph E.
Fleg, Jerome L.
TI Epidemiology of Arrhythmias and Conduction Disorders in Older Adults
SO CLINICS IN GERIATRIC MEDICINE
LA English
DT Article
DE Aging; Arrhythmia; Atrial fibrillation; Atrial flutter; Conduction
disorders
ID BUNDLE-BRANCH BLOCK; APPARENTLY HEALTHY-VOLUNTEERS; 1ST-DEGREE
ATRIOVENTRICULAR-BLOCK; LONG-TERM PROGNOSIS; ATRIAL-FIBRILLATION;
HEART-RATE; CARDIAC-ARRHYTHMIAS; AMBULATORY ELECTROCARDIOGRAPHY;
SUPRAVENTRICULAR TACHYCARDIA; VENTRICULAR-TACHYCARDIA
AB Normal aging is associated with a multitude of changes in the cardiovascular system, including decreased compliance of blood vessels, mild concentric left ventricular hypertrophy, an increased contribution of atrial contraction to left ventricular filling, and a higher incidence of many cardiac arrhythmias, both bradyarrhythmias and tachyarrhythmias. Conduction disorders also become more common with age, and may either be asymptomatic, or cause hemodynamic changes requiring treatment. The epidemiology of common arrhythmias and conduction disorders in the elderly is reviewed.
C1 [Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Chow, Grant V.; Marine, Joseph E.] Johns Hopkins Univ, Sch Med, Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21287 USA.
RP Fleg, JL (reprint author), NHLBI, Div Cardiovasc Sci, Room 8150,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM flegj@nhlbi.nih.gov
FU Intramural NIH HHS [Z99 HL999999]
NR 66
TC 15
Z9 15
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0749-0690
EI 1879-8853
J9 CLIN GERIATR MED
JI Clin. Geriatr. Med.
PD NOV
PY 2012
VL 28
IS 4
BP 539
EP +
DI 10.1016/j.cger.2012.07.003
PG 16
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 058FI
UT WOS:000312619100002
PM 23101570
ER
PT J
AU Wang, E
Marincola, FM
AF Wang, E.
Marincola, F. M.
TI The Ying and Yang of the Tumour Microenvironment
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Wang, E.; Marincola, F. M.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 12
BP 8
EP 8
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000012
ER
PT J
AU Holbeck, S
Collins, JM
Doroshow, JH
AF Holbeck, S.
Collins, J. M.
Doroshow, J. H.
TI NCI-60 Combination Screening Matrix of Approved Anticancer Drugs
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Holbeck, S.; Collins, J. M.] NCI, Rockville, MD USA.
[Doroshow, J. H.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 5
Z9 5
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 27
BP 11
EP 11
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000025
ER
PT J
AU Paoloni, M
Webb, C
Mazcko, C
Cherba, D
Ehrhart, EJ
Lana, S
Fehling, H
Kingsley, C
Khanna, C
Trent, J
AF Paoloni, M.
Webb, C.
Mazcko, C.
Cherba, D.
Ehrhart, E. J.
Lana, S.
Fehling, H.
Kingsley, C.
Khanna, C.
Trent, J.
TI Prospective Molecular Profiling of Canine Cancers Provides a Comparative
Model for Evaluating Personalized Medicine Clinical Trials
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Paoloni, M.; Mazcko, C.; Khanna, C.] NCI, Comparatve Oncol Program, Bethesda, MD 20892 USA.
[Webb, C.; Cherba, D.] Van Andel Res Inst, Grand Rapids, MI USA.
[Ehrhart, E. J.; Lana, S.] Colorado State Univ, Ft Collins, CO 80523 USA.
[Fehling, H.] Clin Reference Lab, Lenexa, KS USA.
[Kingsley, C.; Trent, J.] TGEN, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 7
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 63
BP 21
EP 21
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000059
ER
PT J
AU Cook, KL
Schwartz, JL
Facey, COB
Jin, L
Zwart, A
Abu-Azab, M
Warri, A
Clarke, R
AF Cook, K. L.
Schwartz, J. L.
Facey, C. O. B.
Jin, L.
Zwart, A.
Abu-Azab, M.
Warri, A.
Clarke, R.
TI Un"Abl"ing Anti-estrogen Therapy Resistance in Estrogen Receptor-alpha
Positive Breast Cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Cook, K. L.; Schwartz, J. L.; Facey, C. O. B.; Jin, L.; Zwart, A.; Warri, A.; Clarke, R.] Georgetown Univ, Washington, DC USA.
[Abu-Azab, M.] NEI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 79
BP 26
EP 26
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000075
ER
PT J
AU Noonan, AM
Chen, J
Herrmann, M
Annunziata, CM
AF Noonan, A. M.
Chen, J.
Herrmann, M.
Annunziata, C. M.
TI Birinapant, a Novel Smac Mimetic, Activates Apoptosis in
NF-kappaB-dependent Gynecologic Cancer Cell Lines
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Noonan, A. M.; Annunziata, C. M.] NCI, Translat Genom Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Chen, J.; Herrmann, M.] NCI, Collaborat Prot Technol Resource Lab Cell Biol, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 97
BP 31
EP 31
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000093
ER
PT J
AU Song, G
Moore, S
Tarrant, T
Dobrovolskaia, M
Barrow, D
Kumar, P
Newman, S
Bae-Jump, V
Gehrig, P
Zamboni, W
AF Song, G.
Moore, S.
Tarrant, T.
Dobrovolskaia, M.
Barrow, D.
Kumar, P.
Newman, S.
Bae-Jump, V.
Gehrig, P.
Zamboni, W.
TI Relationship Between Complement Factors and CC Chemokines and the
Pharmacokinetics (PK) and Pharmacodynamics (PD) of PEGylated Liposomal
Doxorubicin (PLD) in Patients with Refractory Epithelial Ovarian Cancer
(EOC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Song, G.] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Tarrant, T.] Univ N Carolina, Dept Med, Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA.
[Dobrovolskaia, M.] NCI, SAIC Frederick Inc, Nanotechnol Characterizat Lab, Chapel Hill, NC USA.
[Barrow, D.] Univ N Carolina, Dent Res Ctr, Cytokine Anal Facil, Chapel Hill, NC 27599 USA.
[Kumar, P.; Newman, S.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Bae-Jump, V.; Gehrig, P.] Univ N Carolina, Div Gynecol Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Zamboni, W.] Univ N Carolina, UNC Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut,Inst Pharmac, Lineberger Comprehens Canc Ctr,Carolina Ctr Canc, Chapel Hill, NC USA.
NR 0
TC 1
Z9 1
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 126
BP 39
EP 40
PG 2
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000122
ER
PT J
AU He, M
Zuck, K
Shipley, S
Giddings, L
DeLloyd, T
Newman, D
AF He, M.
Zuck, K.
Shipley, S.
Giddings, L.
DeLloyd, T.
Newman, D.
TI Potent Spliceostatin Analogs Isolated From Pseudomonas by Manipulations
of Fermentation and Co-Culturing Conditions
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [He, M.; Giddings, L.; Newman, D.] NCI, DCTD, DTP, NPB, Frederick, MD USA.
[Zuck, K.; Shipley, S.; DeLloyd, T.] SAIC Frederick Inc, NPSG, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 216
BP 66
EP 66
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000212
ER
PT J
AU Pommier, Y
Reinhold, WC
Sunshine, M
Varma, SH
Kohn, KW
Doroshow, JH
AF Pommier, Y.
Reinhold, W. C.
Sunshine, M.
Varma, S. H.
Kohn, K. W.
Doroshow, J. H.
TI CellMiner: a Web-Based Suite of Genomic and Pharmacologic Tools to
Explore Transcript and Drug Patterns in the NCI-60 Cell Line Set
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Pommier, Y.; Reinhold, W. C.; Sunshine, M.; Varma, S. H.; Kohn, K. W.; Doroshow, J. H.] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 268
BP 82
EP 82
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000261
ER
PT J
AU Dexheimer, TS
Nguyen, GH
Rosenthal, AS
Bohr, VA
Harris, CC
Jadhav, A
Gileadi, O
Maloney, DJ
Simeonov, A
Hickson, ID
AF Dexheimer, T. S.
Nguyen, G. H.
Rosenthal, A. S.
Bohr, V. A.
Harris, C. C.
Jadhav, A.
Gileadi, O.
Maloney, D. J.
Simeonov, A.
Hickson, I. D.
TI A Small Molecule Inhibitor of the BLM Helicase That Modulates Chromosome
Stability in Human Cells
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Dexheimer, T. S.; Rosenthal, A. S.; Jadhav, A.; Maloney, D. J.; Simeonov, A.] Natl Ctr Adv Translat Sci, Div Priclin Innovat, Rockville, MD USA.
[Nguyen, G. H.; Harris, C. C.] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
[Bohr, V. A.] NIA, NIH, Baltimore, MD 21224 USA.
[Gileadi, O.] Univ Oxford, Struct Genom Consortium, Oxford, England.
[Hickson, I. D.] Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 276
BP 85
EP 85
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000269
ER
PT J
AU Pommier, Y
Huang, SH
Das, BB
Renaud, A
Zhang, Y
Takeda, SH
Doroshow, JH
AF Pommier, Y.
Huang, S. H.
Das, B. B.
Renaud, A.
Zhang, Y.
Takeda, S. H.
Doroshow, J. H.
TI Differential Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Pommier, Y.; Huang, S. H.; Das, B. B.; Renaud, A.; Zhang, Y.; Doroshow, J. H.] NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Takeda, S. H.] Kyoto Univ, Dept Radiat Genet, Kyoto, Japan.
NR 0
TC 0
Z9 0
U1 2
U2 15
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 284
BP 87
EP 87
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000277
ER
PT J
AU Abi-Habib, R
Kassab, E
Darwish, M
Timsah, Z
Liu, S
Leppla, S
Frankel, A
AF Abi-Habib, R.
Kassab, E.
Darwish, M.
Timsah, Z.
Liu, S.
Leppla, S.
Frankel, A.
TI Acute Myeloid Leukemia (AML) Cell Lines Are Sensitive to the Anthrax
Lethal Toxin (LeTx)-Mediated Inhibition of the MAPK Pathway
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Abi-Habib, R.; Kassab, E.; Darwish, M.; Timsah, Z.] Lebanese Amer Univ, Beirut, Lebanon.
[Liu, S.; Leppla, S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Frankel, A.] Scott & White Mem Hosp & Clin, Canc Res Inst, Temple, TX 76508 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 326
BP 100
EP 100
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000319
ER
PT J
AU Smith, M
Kang, M
Lock, R
Carol, H
Gorlick, R
Kolb, A
Maris, J
Keir, S
Kurmasheva, R
Houghton, P
AF Smith, M.
Kang, M.
Lock, R.
Carol, H.
Gorlick, R.
Kolb, A.
Maris, J.
Keir, S.
Kurmasheva, R.
Houghton, P.
TI Pediatric Preclinical Testing Program (PPTP) Stage 1 Evaluation of
Eribulin
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Smith, M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Kang, M.] Texas Tech Univ Hlth Sci Ctr, Ctr Canc, Lubbock, TX USA.
[Lock, R.; Carol, H.] Childrens Canc Inst, Leukemia Biol Program, Randwick, NSW, Australia.
[Gorlick, R.] Montefiore Med Ctr, Dept Pediat, Bronx, NY 10467 USA.
[Kolb, A.] Alfred I DuPont Hosp Children, Dept Oncol, Wilmington, DE USA.
[Maris, J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Keir, S.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA.
[Kurmasheva, R.; Houghton, P.] Nationwide Childrens Hosp, Ctr Childhood Canc & Blood Dis, Columbus, OH USA.
RI Carol, Hernan/F-5750-2013
OI Carol, Hernan/0000-0002-9443-8032
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 345
BP 105
EP 105
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000338
ER
PT J
AU Nagy, Z
Orosz, E
Kovacs, I
Torok, M
Biro, T
Blumberg, PM
Czifral, G
AF Nagy, Z.
Orosz, E.
Kovacs, I.
Toeroek, M.
Biro, T.
Blumberg, P. M.
Czifral, G.
TI Investigation of RasGRP3 Expression and Function in Human Breast Cancers
and Breast-derived Ductal Adenocarcinoma Cell Lines
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Nagy, Z.; Orosz, E.; Biro, T.; Czifral, G.] Univ Debrecen, Dept Physiol, Debrecen, Hungary.
[Kovacs, I.; Toeroek, M.] Gyula Kenezy Hosp, Dept Pathol, Debrecen, Hungary.
[Blumberg, P. M.] NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 381
BP 116
EP 116
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000374
ER
PT J
AU Hernandez, L
Kohlhammer, H
Staudt, L
Annunziata, CM
AF Hernandez, L.
Kohlhammer, H.
Staudt, L.
Annunziata, C. M.
TI Genome-wide shRNa Library Screen Identifies CASPASE 8 as a Gene
Sensitizing Ovarian Cancer Cells to IKK beta Inhibition
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Hernandez, L.; Annunziata, C. M.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Kohlhammer, H.; Staudt, L.] NCI, Metab Branch, Bethesda, MD 20892 USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 392
BP 119
EP 119
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000385
ER
PT J
AU Nafi, SM
Kong, A
Gijsen, M
Kramer-Marek, G
Capala, J
AF Nafi, S. Mohd
Kong, A.
Gijsen, M.
Kramer-Marek, G.
Capala, J.
TI Investigating the Role of HER4 in Relation to Trastuzumab Treatment and
Resistance in HER2 Positive Breast Cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Nafi, S. Mohd; Kong, A.; Gijsen, M.] Univ Oxford, Epidermal Growth Factor Grp, Weatherall Inst Mol Med, Oxford, England.
[Kramer-Marek, G.; Capala, J.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Mohd Nafi, Siti Norasikin/M-4548-2015
OI Mohd Nafi, Siti Norasikin/0000-0002-0642-0909
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 415
BP 126
EP 126
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000408
ER
PT J
AU Forest, A
Amatulli, M
Damoci, C
Ludwig, D
Baltes, N
Fiebig, H
Houghton, P
Smith, M
Benjamin, L
Novosyadlyy, R
AF Forest, A.
Amatulli, M.
Damoci, C.
Ludwig, D.
Baltes, N.
Fiebig, H.
Houghton, P.
Smith, M.
Benjamin, L.
Novosyadlyy, R.
TI Two Insulin Receptor Isoforms Confer Intrinsic Resistance to the
Antibody Against Insulin-like Growth Factor Receptor I
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Forest, A.; Amatulli, M.; Damoci, C.; Ludwig, D.; Benjamin, L.; Novosyadlyy, R.] Eli Lilly & Co, NYC, Indianapolis, IN USA.
[Baltes, N.; Fiebig, H.] Oncotest, Freiburg, Germany.
[Houghton, P.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 451
BP 140
EP 140
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000444
ER
PT J
AU Yang, SX
Kidwell, K
Costantino, JC
Mamounas, EP
Nguyen, D
Kim, C
Wolmark, N
Paik, S
AF Yang, S. X.
Kidwell, K.
Costantino, J. C.
Mamounas, E. P.
Nguyen, D.
Kim, C.
Wolmark, N.
Paik, S.
TI Prognostic Significance of pAKT Plus Estrogen Receptor Status in
Adjuvant Cytotoxic Treatment of Breast Cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Yang, S. X.; Nguyen, D.] NCI, NIH, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Kidwell, K.; Costantino, J. C.] Natl Surg Adjuvant Breast & Bowel Project, Dept Biostat, Pittsburgh, PA USA.
[Mamounas, E. P.] Aultman Hlth Fdn, Dept Oncol, Canton, OH USA.
[Kim, C.; Paik, S.] Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA.
[Wolmark, N.] Natl Surg Adjuvant Breast & Bowel Project, Div Surg, Pittsburgh, PA USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 478
BP 148
EP 148
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000471
ER
PT J
AU Parchment, RE
Kinders, RJ
Ji, J
Srivastava, AK
Ferry-Galow, K
Tomaszewski, JE
Doroshow, JH
AF Parchment, R. E.
Kinders, R. J.
Ji, J.
Srivastava, A. K.
Ferry-Galow, K.
Tomaszewski, J. E.
Doroshow, J. H.
TI Creating Clinical Target Validation Groups Via Quality Assured Transfer
of Robust Clinical Pharmacodynamic (PD) Assays From the National Cancer
Institute
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Parchment, R. E.; Kinders, R. J.; Srivastava, A. K.; Ferry-Galow, K.] Frederick Natl Lab Canc Res, Lab Human Toxicol & Pharmacol, Frederick, MD USA.
[Ji, J.] Frederick Natl Lab Canc Res, Natl Clin Target Validat Lab, Frederick, MD USA.
[Tomaszewski, J. E.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 493
BP 153
EP 153
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000486
ER
PT J
AU Kim, M
Annunziata, C
AF Kim, M.
Annunziata, C.
TI CHEK1 Cooperates with IKK epsilon to Promote Survival of Ovarian Cancer
Patients
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Kim, M.; Annunziata, C.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 534
BP 164
EP 164
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000526
ER
PT J
AU Kummar, S
Safgren, SL
Lindenberg, M
Kurdziel, K
Reid, JM
Streicher, H
Ames, MM
Jacobs, P
Collins, J
Doroshow, JH
AF Kummar, S.
Safgren, S. L.
Lindenberg, M.
Kurdziel, K.
Reid, J. M.
Streicher, H.
Ames, M. M.
Jacobs, P.
Collins, J.
Doroshow, J. H.
TI Phase I Trial of Z-endoxifen with Estrogen Receptor Imaging in Adults
with Refractory Hormone Receptor-positive Breast Cancer, Desmoid Tumors,
Gynecologic Tumors, or Other Hormone Receptor-Positive Solid Tumors
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Kummar, S.; Streicher, H.; Jacobs, P.; Collins, J.; Doroshow, J. H.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Lindenberg, M.; Kurdziel, K.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Safgren, S. L.; Reid, J. M.; Ames, M. M.] Mayo Clin, Dept Oncol, Rochester, MN USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 591
BP 181
EP 181
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000583
ER
PT J
AU Kummar, S
Anderson, L
Hill, K
Majerova, E
Allen, D
Horneffer, Y
Ivy, P
Harris, P
Doroshow, JH
Collins, J
AF Kummar, S.
Anderson, L.
Hill, K.
Majerova, E.
Allen, D.
Horneffer, Y.
Ivy, P.
Harris, P.
Doroshow, J. H.
Collins, J.
TI First-in-human Phase 0 Trial of Oral 5-iodo-2-pyrimidinone-2
'-deoxyribose (IPdR) in Patients with Advanced Malignancies
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Kummar, S.; Anderson, L.; Ivy, P.; Harris, P.; Doroshow, J. H.; Collins, J.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Allen, D.; Horneffer, Y.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hill, K.; Majerova, E.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 592
BP 181
EP 182
PG 2
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000584
ER
PT J
AU Cerna, D
Carter, D
Takebe, N
Coleman, CN
Yoo, S
AF Cerna, D.
Carter, D.
Takebe, N.
Coleman, C. N.
Yoo, S.
TI Radiosensitization of Glioma Cell Lines by a Novel Peptidomimetic of the
Second Mitochondria-derived Activator of Caspases (SMAC)
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Cerna, D.; Carter, D.] Frederick Natl Lab Canc Res, Mol Radiat Therapeut Branch Support, Frederick, MD USA.
[Takebe, N.] NCI, Canc Therapy Evaluat Program, Rockville, MD USA.
[Coleman, C. N.] NCI, Radiat Res Program, Rockville, MD USA.
[Yoo, S.] NCI, Mol Radiat Therapeut Branch, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 624
BP 192
EP 192
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000616
ER
PT J
AU Soto-Pantoja, D
Manso, GGM
Ridnour, LA
DeGraff, W
Wink, DA
Roberts, DD
AF Soto-Pantoja, D.
Manso, G. Gema Martin
Ridnour, L. A.
DeGraff, W.
Wink, D. A.
Roberts, D. D.
TI Radioprotection in Normal Tissue and Delayed Tumor Growth by Blockade of
CD47 Signaling is Associated with Selective Activation of Autophagy
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Meeting Abstract
CT 24th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer
Therapeutics
CY NOV 06-09, 2012
CL European Org Res & Treatment Canc (EORTC), Dublin, IRELAND
SP Natl Canc Inst (NCI), Amer Assoc Canc Res (AACR), Novartis Oncol, TAIHO, Johnson&Johnson, Janssen Pharmaceut Co
HO European Org Res & Treatment Canc (EORTC)
C1 [Soto-Pantoja, D.; Manso, G. Gema Martin; Roberts, D. D.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Ridnour, L. A.; DeGraff, W.; Wink, D. A.] NCI, Radiat Biol Branch, Bethesda, MD 20892 USA.
RI Roberts, David/A-9699-2008
OI Roberts, David/0000-0002-2481-2981
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2012
VL 48
SU 6
MA 622
BP 192
EP 192
PG 1
WC Oncology
SC Oncology
GA 060FX
UT WOS:000312763000614
ER
PT J
AU Bruce, I
Chan, CC
AF Bruce, Isaac
Chan, Chi-Chao
TI Interview with Chi-Chao Chan
SO FUTURE MEDICINAL CHEMISTRY
LA English
DT Editorial Material
C1 [Chan, Chi-Chao] NEI, NIH, Bethesda, MD 20892 USA.
EM chanc@nei.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 3
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1756-8919
J9 FUTURE MED CHEM
JI Future Med. Chem.
PD NOV
PY 2012
VL 4
IS 17
BP 2139
EP 2140
DI 10.4155/FMC.12.171
PG 2
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA 059AG
UT WOS:000312676200010
ER
PT J
AU Sallo, FB
Peto, T
Egan, C
Wolf-Schnurrbusch, UEK
Clemons, TE
Gillies, MC
Pauleikhoff, D
Rubin, GS
Chew, EY
Bird, AC
AF Sallo, Ferenc B.
Peto, Tunde
Egan, Catherine
Wolf-Schnurrbusch, Ute E. K.
Clemons, Traci E.
Gillies, Mark C.
Pauleikhoff, Daniel
Rubin, Gary S.
Chew, Emily Y.
Bird, Alan C.
CA MacTel Study Grp
TI The IS/OS Junction Layer in the Natural History of Type 2 Idiopathic
Macular Telangiectasia
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; JUXTAFOVEOLAR RETINAL TELANGIECTASIS;
CENTRAL SEROUS CHORIORETINOPATHY; FOVEAL PHOTORECEPTOR LAYER; FUNDUS
AUTOFLUORESCENCE; VISUAL FUNCTION; VEIN OCCLUSION; HOLE SURGERY;
MICROPERIMETRY; RESOLUTION
AB PURPOSE. To document the progression of a break in the photoreceptor inner segment/outer segment (IS/OS) junction layer and its functional correlates over time in the natural history of type 2 idiopathic macular telangiectasia (type 2 MacTel).
METHODS. Patients with at least 1 year of follow-up were selected from the MacTel Study. En face images were created by manual segmentation of the IS/OS junctional line in volume scans acquired using a spatial-domain optical coherence tomography retinal imaging unit. Retinal sensitivity thresholds were determined using a retinal microperimeter unit. Aggregate retinal sensitivity loss within IS/OS lesions was calculated. Changes over time in an area of IS/OS defects and retinal sensitivity were analyzed.
RESULTS. Thirty-nine eyes of 23 patients (mean age: 62.3 +/- 9.2 years) were analyzed. Mean follow-up time was 1.9 years (range: 1-3 years). Mean IS/OS break area at baseline was 0.575 mm(2) (SE = 0.092, 95% confidence interval [CI]: 0.394-0.756 mm(2)). The cluster-adjusted mean annual progression rate in IS/OS break area was 0.140 mm(2) (SE = 0.040, 95% CI: 0.062-0.218 mm(2), P < 0.001). Mean aggregate retinal sensitivity loss was at baseline 28.56 dB (SE = 5.43, 95% CI: 17.32-39.80 dB, n = 28), a positive correlation with IS/OS lesion area was present (P < 0.001). The mean annual rate of change in aggregate sensitivity loss was 5.14 dB (SE = 1.51, 95% CI: 2.19-8.10 dB, P < 0.001, n = 37), a significant correlation with lesion area increase was found (P = 0.006).
CONCLUSIONS. Both IS/OS break area and rate of enlargement correlate with aggregate retinal sensitivity loss in type 2 MacTel. En face OCT imaging of the IS/OS layer provides a functionally relevant method for documenting disease progression in type 2 MacTel. (Invest Ophthalmol Vis Sci. 2012; 53:7889-7895) DOI:10.1167/iovs.12-10765
C1 [Sallo, Ferenc B.] Moorfields Eye Hosp NHS Fdn Trust, Reading Ctr, Dept Res & Dev, Moorfields Eye Hosp, London EC1V 2PD, England.
[Sallo, Ferenc B.; Rubin, Gary S.] UCL, Inst Opthalmol, London, England.
[Sallo, Ferenc B.; Wolf-Schnurrbusch, Ute E. K.] Univ Bern, Univ Klin Augenheilkunde, Bern, Switzerland.
[Peto, Tunde] Moorfields Eye Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res, Biomed Res Ctr Ophthalmol, London, England.
[Peto, Tunde] UCL Inst Ophthalmol, London, England.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Gillies, Mark C.] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia.
[Pauleikhoff, Daniel] St Franziskus Hosp, Munster, Germany.
[Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 USA.
[Bird, Alan C.] Moorfields Eye Hosp, Div Inherited Eye Dis, London, England.
RP Sallo, FB (reprint author), Moorfields Eye Hosp NHS Fdn Trust, Reading Ctr, Dept Res & Dev, Moorfields Eye Hosp, 162 City Rd, London EC1V 2PD, England.
EM Ferenc.Sallo@moorfields.nhs.uk
RI gillies, mark/B-3242-2012; Rubin, Gary/A-4928-2009; Wolf,
Sebastian/B-8782-2008; Sahel, Jose-Alain/F-3172-2017
OI Rubin, Gary/0000-0002-2547-4953; Wolf, Sebastian/0000-0002-7467-7028;
FU Lowy Medical Research Institute (LMRI); National Institute for Health
Research
FX Supported by the Lowy Medical Research Institute (LMRI) and the National
Institute for Health Research. The LMRI also participated in the design
of the study and in the review and approval of the manuscript.
NR 40
TC 22
Z9 22
U1 0
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2012
VL 53
IS 12
BP 7889
EP 7895
DI 10.1167/iovs.12-10765
PG 7
WC Ophthalmology
SC Ophthalmology
GA 064EE
UT WOS:000313053500064
PM 23092925
ER
PT J
AU Parsa, N
AF Parsa, N.
TI Environmental Factors Inducing Human Cancers
SO IRANIAN JOURNAL OF PUBLIC HEALTH
LA English
DT Review
DE Environmental factors; Cancer causing genes; Human cancers
ID TUMOR-SUPPRESSOR GENE; LYMPHOMA CELL-LINES; PREVENT CANCER; RISK;
INFECTION; RADIATION; ONCOGENE; ALCOHOL; TRIAL
AB Background: An explosion of research has been done in discovering how human health is affected by environmental factors. I will discuss the impacts of environmental cancer causing factors and how they continue to cause multiple disruptions in cellular networking. Some risk factors may not cause cancer. Other factors initiate consecutive genetic mutations that would eventually alter the normal pathway of cellular proliferations and differentiation. Genetic mutations in four groups of genes; (Oncogenes, Tumor suppressor genes, Apoptosis genes and DNA repairing genes) play a vital role in altering the normal cell division. In recent years, molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development and utilizing these molecular techniques for cancer screening, diagnosis, prognosis and therapies. Inhibition of carcinogenic exposures wherever possible should be the goal of cancer prevention programs to reduce exposures from all environmental carcinogens.
C1 NIH, Bethesda, MD 20892 USA.
RP Parsa, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM nzparsa@yahoo.com
NR 35
TC 4
Z9 4
U1 7
U2 17
PU IRANIAN SCIENTIFIC SOCIETY MEDICAL ENTOMOLOGY
PI TEHRAN
PA SCHOOL PUBLIC HEALTH & INST HEALTH RESEARCH, TEHRAN UNIV MEDICAL
SCIENCES, P O BOX 6446-14155, TEHRAN, 00000, IRAN
SN 2251-6085
J9 IRAN J PUBLIC HEALTH
JI Iran J. Public Health
PD NOV
PY 2012
VL 41
IS 11
BP 1
EP 9
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 061SC
UT WOS:000312867300001
PM 23304670
ER
PT J
AU Casoni, F
Hutchins, BI
Donohue, D
Fornaro, M
Condie, BG
Wray, S
AF Casoni, Filippo
Hutchins, B. Ian
Donohue, Duncan
Fornaro, Michele
Condie, Brian G.
Wray, Susan
TI SDF and GABA interact to regulate axophilic migration of GnRH neurons
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE GABA; GIRK; GnRH; Motility; Neuronal migration; SDF
ID HORMONE-RELEASING HORMONE; CELL-DERIVED FACTOR-1-ALPHA;
GAMMA-AMINOBUTYRIC-ACID; LHRH NEURONS; INTERNEURON MIGRATION; OLFACTORY
EXPLANTS; KALLMANN-SYNDROME; CEREBRAL-CORTEX; KNOCKOUT MICE;
CLEFT-PALATE
AB Stromal derived growth factor (SDF-1) and gamma-aminobutyric acid (GABA) are two extracellular cues that regulate the rate of neuronal migration during development and may act synergistically. The molecular mechanisms of this interaction are still unclear. Gonadotropin releasing hormone-1 (GnRH) neurons are essential for vertebrate reproduction. During development, these neurons emerge from the nasal placode and migrate through the cribriform plate into the brain. Both SDF-1 and GABA have been shown to regulate the rate of GnRH neuronal migration by accelerating and slowing migration, respectively. As such, this system was used to explore the mechanism by which these molecules act to produce coordinated cell movement during development. In the present study, GABA and SDF-1 are shown to exert opposite effects on the speed of cell movement by activating depolarizing or hyperpolarizing signaling pathways, GABA via changes in chloride and SDF-1 via changes in potassium. GABA and SDF-1 were also found to act synergistically to promote linear rather than random movement. The simultaneous activation of these signaling pathways, therefore, results in tight control of cellular speed and improved directionality along the migratory pathway of GnRH neurons.
C1 [Casoni, Filippo; Hutchins, B. Ian; Donohue, Duncan; Fornaro, Michele; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Fornaro, Michele] Midwestern Univ, Dept Anat, Downers Grove, IL 60515 USA.
[Condie, Brian G.] Univ Georgia, Dept Genet, Athens, GA 30602 USA.
RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
EM wrays@ninds.nih.gov
RI Hutchins, Ian/A-5713-2009;
OI Hutchins, Ian/0000-0001-7657-552X; Fornaro, Michele/0000-0003-1852-9167;
wray, susan/0000-0001-7670-3915
FU Intramural Research Program of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke [ZIA
NS002824-21]; National Institutes of Health [R01MH064794]; Pharmacology
Research Associate (PRAT) Program of the National Institute of General
Medical Sciences, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Neurological
Disorders and Stroke [grant number ZIA NS002824-21]; and the National
Institutes of Health [grant number R01MH064794 to B.G.C.]. B.I.H. was
supported by the Pharmacology Research Associate (PRAT) Program of the
National Institute of General Medical Sciences, National Institutes of
Health. Deposited in PMC for release after 12 months.
NR 76
TC 19
Z9 20
U1 1
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
J9 J CELL SCI
JI J. Cell Sci.
PD NOV 1
PY 2012
VL 125
IS 21
BP 5015
EP 5025
DI 10.1242/jcs.101675
PG 11
WC Cell Biology
SC Cell Biology
GA 063GN
UT WOS:000312984300010
PM 22976302
ER
PT J
AU Morens, DM
Fauci, AS
AF Morens, David M.
Fauci, Anthony S.
TI Emerging Infectious Diseases in 2012: 20 Years after the Institute of
Medicine Report
SO MBIO
LA English
DT Article
ID PERPETUAL CHALLENGE; VIRUS; TRANSMISSION; EMERGENCE; INFLUENZA; SPREAD;
GENOME; DEATH
AB Twenty years ago (1992), a landmark Institute of Medicine report entitled "Emerging Infections: Microbial Threats to Health in the United States" underscored the important but often underappreciated concept of emerging infectious diseases (EIDs). A review of the progress made and setbacks experienced over the past 2 decades suggests that even though many new diseases have emerged, such as SARS (severe acute respiratory syndrome) and the 2009 pandemic influenza, significant advances have occurred in EID control, prevention, and treatment. Among many elements of the increase in the capacity to control EIDs are genomics-associated advances in microbial detection and treatment, improved disease surveillance, and greater awareness of EIDs and the complicated variables that underlie emergence. In looking back over the past 20 years, it is apparent that we are in a time of great change in which both the challenge of EIDs and our responses to them are being transformed. Recent advances support guarded optimism that further breakthroughs lie ahead.
C1 [Morens, David M.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Morens, DM (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dm270q@nih.gov
NR 33
TC 7
Z9 7
U1 0
U2 29
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2012
VL 3
IS 6
AR e00494-12
DI 10.1128/mBio.00494-12
PG 4
WC Microbiology
SC Microbiology
GA 064UK
UT WOS:000313100700031
ER
PT J
AU Wasmuth, JD
Pszenny, V
Haile, S
Jansen, EM
Gast, AT
Sher, A
Boyle, JP
Boulanger, MJ
Parkinson, J
Grigg, ME
AF Wasmuth, James D.
Pszenny, Viviana
Haile, Simon
Jansen, Emily M.
Gast, Alexandra T.
Sher, Alan
Boyle, Jon P.
Boulanger, Martin J.
Parkinson, John
Grigg, Michael E.
TI Integrated Bioinformatic and Targeted Deletion Analyses of the SRS Gene
Superfamily Identify SRS29C as a Negative Regulator of Toxoplasma
Virulence
SO MBIO
LA English
DT Article
ID SURFACE-ANTIGENS; PLASMODIUM-FALCIPARUM; TRYPANOSOMA-BRUCEI; GONDII;
FAMILY; OVERPRODUCTION; RECOMBINATION; TRANSCRIPTION; TACHYZOITES;
EXPRESSION
AB The Toxoplasma gondii SRS gene superfamily is structurally related to SRS29B (formerly SAG1), a surface adhesin that binds host cells and stimulates host immunity. Comparative genomic analyses of three Toxoplasma strains identified 182 SRS genes distributed across 14 chromosomes at 57 genomic loci. Eight distinct SRS subfamilies were resolved. A core 69 functional gene orthologs were identified, and strain-specific expansions and pseudogenization were common. Gene expression profiling demonstrated differential expression of SRS genes in a developmental-stage-and strain-specific fashion and identified nine SRS genes as priority targets for gene deletion among the tissue-encysting coccidia. A Delta sag1 Delta sag2A mutant was significantly attenuated in murine acute virulence and showed upregulated SRS29C (formerly SRS2) expression. Transgenic overexpression of SRS29C in the virulent RH parent was similarly attenuated. Together, these findings reveal SRS29C to be an important regulator of acute virulence in mice and demonstrate the power of integrated genomic analysis to guide experimental investigations.
IMPORTANCE Parasitic species employ large gene families to subvert host immunity to enable pathogen colonization and cause disease. Toxoplasma gondii contains a large surface coat gene superfamily that encodes adhesins and virulence factors that facilitate infection in susceptible hosts. We generated an integrated bioinformatic resource to predict which genes from within this 182-gene superfamily of adhesin-encoding genes play an essential role in the host-pathogen interaction. Targeted gene deletion experiments with predicted candidate surface antigens identified SRS29C as an important negative regulator of acute virulence in murine models of Toxoplasma infection. Our integrated computational and experimental approach provides a comprehensive framework, or road map, for the assembly and discovery of additional key pathogenesis genes contained within other large surface coat gene superfamilies from a broad array of eukaryotic pathogens.
C1 [Wasmuth, James D.; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 1X8, Canada.
[Wasmuth, James D.; Pszenny, Viviana; Gast, Alexandra T.; Grigg, Michael E.] NIAID, Mol Parasitol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Haile, Simon; Jansen, Emily M.; Grigg, Michael E.] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Sher, Alan] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Boyle, Jon P.] Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA.
[Boulanger, Martin J.] Univ Victoria, Dept Biochem & Microbiol, Victoria, BC, Canada.
[Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
[Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
RP Parkinson, J (reprint author), Hosp Sick Children, Program Mol Struct & Funct, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM john.parkinson@utoronto.ca; griggm@niaid.nih.gov
RI Parkinson, John/A-4424-2008
OI Parkinson, John/0000-0001-9815-1189
FU CIHR (MOP) [84556, 82915]; NIH; NIAID; Ontario MRI
FX This study was financially supported by the CIHR (MOP no. 84556 to J.P.
and M. E. G.), the Intramural Research Program of the NIH and NIAID (M.
E. G.), and the Ontario MRI (J.P.). M.J.B. was supported by the CIHR
(MOP no. 82915).
NR 36
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2012
VL 3
IS 6
AR e00321-12
DI 10.1128/mBio.00321-12
PG 13
WC Microbiology
SC Microbiology
GA 064UK
UT WOS:000313100700005
ER
PT J
AU Weinberger, AD
Wolf, YI
Lobkovsky, AE
Gilmore, MS
Koonin, EV
AF Weinberger, Ariel D.
Wolf, Yuri I.
Lobkovsky, Alexander E.
Gilmore, Michael S.
Koonin, Eugene V.
TI Viral Diversity Threshold for Adaptive Immunity in Prokaryotes
SO MBIO
LA English
DT Article
ID SINGLE-NUCLEOTIDE SUBSTITUTIONS; CRISPR RNA; SPONTANEOUS MUTATION;
STREPTOCOCCUS-THERMOPHILUS; BACTERIAL; FITNESS; EVOLUTION; SYSTEM; DNA;
RESISTANCE
AB Bacteria and archaea face continual onslaughts of rapidly diversifying viruses and plasmids. Many prokaryotes maintain adaptive immune systems known as clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (Cas). CRISPR-Cas systems are genomic sensors that serially acquire viral and plasmid DNA fragments (spacers) that are utilized to target and cleave matching viral and plasmid DNA in subsequent genomic invasions, offering critical immunological memory. Only 50% of sequenced bacteria possess CRISPR-Cas immunity, in contrast to over 90% of sequenced archaea. To probe why half of bacteria lack CRISPR-Cas immunity, we combined comparative genomics and mathematical modeling. Analysis of hundreds of diverse prokaryotic genomes shows that CRISPR-Cas systems are substantially more prevalent in thermophiles than in mesophiles. With sequenced bacteria disproportionately mesophilic and sequenced archaea mostly thermophilic, the presence of CRISPR-Cas appears to depend more on environmental temperature than on bacterial-archaeal taxonomy. Mutation rates are typically severalfold higher in mesophilic prokaryotes than in thermophilic prokaryotes. To quantitatively test whether accelerated viral mutation leads microbes to lose CRISPR-Cas systems, we developed a stochastic model of virus-CRISPR coevolution. The model competes CRISPR-Cas-positive (CRISPR-Cas +) prokaryotes against CRISPR-Cas-negative (CRISPR-Cas-) prokaryotes, continually weighing the antiviral benefits conferred by CRISPR-Cas immunity against its fitness costs. Tracking this cost-benefit analysis across parameter space reveals viral mutation rate thresholds beyond which CRISPR-Cas cannot provide sufficient immunity and is purged from host populations. These results offer a simple, testable viral diversity hypothesis to explain why mesophilic bacteria disproportionately lack CRISPR-Cas immunity. More generally, fundamental limits on the adaptability of biological sensors (Lamarckian evolution) are predicted.
IMPORTANCE A remarkable recent discovery in microbiology is that bacteria and archaea possess systems conferring immunological memory and adaptive immunity. Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (CRISPR-Cas) are genomic sensors that allow prokaryotes to acquire DNA fragments from invading viruses and plasmids. Providing immunological memory, these stored fragments destroy matching DNA in future viral and plasmid invasions. CRISPR-Cas systems also provide adaptive immunity, keeping up with mutating viruses and plasmids by continually acquiring new DNA fragments. Surprisingly, less than 50% of mesophilic bacteria, in contrast to almost 90% of thermophilic bacteria and Archaea, maintain CRISPR-Cas immunity. Using mathematical modeling, we probe this dichotomy, showing how increased viral mutation rates can explain the reduced prevalence of CRISPR-Cas systems in mesophiles. Rapidly mutating viruses outrun CRISPR-Cas immune systems, likely decreasing their prevalence in bacterial populations. Thus, viral adaptability may select against, rather than for, immune adaptability in prokaryotes.
C1 [Weinberger, Ariel D.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA.
[Weinberger, Ariel D.; Gilmore, Michael S.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Wolf, Yuri I.; Lobkovsky, Alexander E.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Weinberger, AD (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA 02114 USA.
EM ariel_weinberger@meei.harvard.edu; koonin@ncbi.nlm.nih.gov
FU NIH [AI072360]; U.S. Department of Health and Human Services (National
Library of Medicine, NIH)
FX We are grateful for the financial support from NIH grant AI072360 (to M.
S. G.) and an NIH F32 Postdoctoral Fellowship (to A. D. W.). A. E. L.,
Y.I.W., and E. V. K. were supported by intramural funding from the U.S.
Department of Health and Human Services (National Library of Medicine,
NIH). We thank the Kavli Institute of Theoretical Physics (KITP) for
hosting a cross-disciplinary workshop at which this collaboration began.
NR 62
TC 18
Z9 18
U1 2
U2 35
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD NOV-DEC
PY 2012
VL 3
IS 6
AR e00456-12
DI 10.1128/mBio.00456-12
PG 10
WC Microbiology
SC Microbiology
GA 064UK
UT WOS:000313100700027
PM 23221803
ER
PT J
AU Apolo, AB
Grossman, HB
Bajorin, D
Steinberg, G
Kamat, AM
AF Apolo, Andrea B.
Grossman, Herbert Barton
Bajorin, Dean
Steinberg, Gary
Kamat, Ashish M.
TI Practical use of perioperative chemotherapy for muscle-invasive bladder
cancer: Summary of session at the Society of Urologic Oncology annual
meeting
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Review
DE Bladder cancer; Neoadjuvant chemotherapy; Adjuvant chemotherapy;
Perioperative chemotherapy; Muscle invasive bladder cancer
ID TRANSITIONAL-CELL CARCINOMA; CISPLATIN-BASED CHEMOTHERAPY; GEMCITABINE
PLUS CISPLATIN; PHASE-III TRIAL; RADICAL CYSTECTOMY; NEOADJUVANT
CHEMOTHERAPY; UROTHELIAL CARCINOMA; RANDOMIZED-TRIAL; LYMPH-NODES; M-VAC
AB At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of 'suboptimal' chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multirnodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Grossman, Herbert Barton; Kamat, Ashish M.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Apolo, Andrea B.] NCI, Med Oncol Branch, Bethesda, MD 20014 USA.
[Bajorin, Dean] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10065 USA.
[Steinberg, Gary] Univ Chicago, Med Ctr, Urol Sect, Chicago, IL 60637 USA.
RP Kamat, AM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
EM akamat@mdanderson.org
FU NCI NIH HHS [P30 CA016672]
NR 64
TC 12
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD NOV-DEC
PY 2012
VL 30
IS 6
BP 772
EP 780
DI 10.1016/j.urolonc.2012.01.012
PG 9
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 056SI
UT WOS:000312511300004
PM 23218068
ER
PT J
AU Filson, CP
Miller, DC
Colt, JS
Ruterbusch, J
Linehan, WM
Chow, WH
Schwartz, K
AF Filson, Christopher P.
Miller, David C.
Colt, Joanne S.
Ruterbusch, Julie
Linehan, W. Marston
Chow, Wong-Ho
Schwartz, Kendra
TI Surgical approach and the use of lymphadenectomy and adrenalectomy among
patients undergoing radical nephrectomy for renal cell carcinoma
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Lymph node excision; Adrenalectomy; Renal cell carcinoma; Laparoscopy;
Neoplasm staging
ID LYMPH-NODE DISSECTION; CANCER; COMPONENT; TUMOR
AB Objectives: We assessed the influence of tumor size and surgical approach on the use of lymphadenectomy and adrenalectomy with radical nephrectomy.
Methods: We evaluated patients with renal cell carcinoma (RCC) enrolled in the U.S. Kidney Cancer Study, a case-control study in the metropolitan areas of Detroit and Chicago from 2002 to 2007. We identified patients who underwent open (URN) or laparoscopic radical nephrectomy (LRN). We used medical records and Surveillance, Epidemiology, and End Results (SEER) data to determine the proportion of patients who underwent lymphadenectomy or adrenalectomy. Bivariate analyses were performed to evaluate associations between tumor size, surgical approach, and receipt of lymphadenectomy or adrenalectomy.
Results: We identified 730 patients who underwent URN (427, 58%) or LRN (303, 42%) for RCC from 2002 to 2007. Among this group, 11% and 24% underwent lymphadenectomy or adrenalectomy, respectively. Lymphadenectomy was more common among patients treated from an open surgical approach (14.1% URN vs. 5.9% LRN, P < 0.01); this difference was most pronounced for cases with tumors between 4 and 7 cm (15.9% vs. 2.9%, P = 0.01). Patients treated with URN were also more likely to undergo adrenalectomy, with the greatest discrepancy among cases with tumors <= 4 cm (21.7% vs. 11.4%, P < 0.01).
Conclusions: Among patients undergoing radical nephrectomy for RCC, the use of lymphadenectomy and adrenalectomy is relatively uncommon and varies by tumor size and surgical approach. With an increasing number of patients with small tumors, the diffusion of laparoscopy, and the emergence of clinical trials evaluating systemic adjuvant therapies, our findings highlight important considerations for optimizing surgical management of patients with RCC. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Filson, Christopher P.; Miller, David C.] Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Miller, David C.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI 48105 USA.
[Colt, Joanne S.; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Ruterbusch, Julie; Schwartz, Kendra] Karmanos Canc Inst, Detroit, MI 48201 USA.
[Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Schwartz, Kendra] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI 48202 USA.
RP Miller, DC (reprint author), Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
EM dcmiller@umich.edu
OI Filson, Christopher/0000-0002-9353-871X; Filson,
Christopher/0000-0002-8184-7275
FU National Institutes of Health [NIH-N02-CP-11004, NIH-T32-DK007782]
FX This research was supported by the National Institutes of Health
Intramural Research Program (NIH-N02-CP-11004) and Training in Clinical
Investigation in Urology grant (NIH-T32-DK007782).
NR 18
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD NOV-DEC
PY 2012
VL 30
IS 6
BP 856
EP 863
DI 10.1016/j.urolonc.2010.08.024
PG 8
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 056SI
UT WOS:000312511300016
PM 21419672
ER
PT J
AU Gulley, JL
Emberton, M
Kurhanewicz, J
Choyke, P
AF Gulley, James L.
Emberton, Mark
Kurhanewicz, John
Choyke, Peter
TI Progress in prostate cancer imaging
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Prostate cancer; Imaging
AB There are multiple new technologies being developed for imaging of advanced prostate cancer. This Seminar article highlights several of these emerging modalities that were discussed at the Society of Urologic Oncology annual meeting in Bethesda, MD. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Gulley, James L.; Choyke, Peter] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Emberton, Mark] Univ Coll London Hosp, Div Surg & Intervent Sci, London, England.
[Kurhanewicz, John] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
RP Gulley, JL (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU NCI NIH HHS [R01 CA137207]
NR 0
TC 3
Z9 3
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD NOV-DEC
PY 2012
VL 30
IS 6
BP 938
EP 939
DI 10.1016/j.urolonc.2012.09.008
PG 2
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 056SI
UT WOS:000312511300028
PM 23218070
ER
PT J
AU Linehan, WM
Rathmell, WK
AF Linehan, W. Marston
Rathmell, W. Kimryn
TI Kidney cancer
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Article
DE Kidney cancer; Renal cancer
ID RENAL-CELL CARCINOMA; FUMARATE-HYDRATASE; GENETIC-BASIS; INHIBITOR;
PATHWAY
AB Over 65,000 Americans are diagnosed with kidney cancer each year and nearly 13,000 die of this disease. Kidney cancer is not a single disease, it is made up of a number of different types of cancer, each with a different histology, a different clinical course, responding differently to therapy and caused by a different gene. Study of the 13 genes that are known to cause kidney cancer has led to the understanding that kidney cancer is a metabolic disease. Recent discoveries of chromatin remodeling/histone modifying genes, such as PBRM1 and SETD2, have opened up new areas of intense interest in the study of the fundamental genetic basis of kidney cancer. New approaches to immunotherapy with agents such as the CTLA4 inhibitor, ipilumumab, have opened up promising new directions for clinical trials. A number of new agents targeting of VEGF receptor signaling and the mTOR pathways as well as novel approaches targeting HIF2 will hopefully provide the foundation for the development of effective forms of therapy for this disease. (C) 2012 Published by Elsevier Inc.
C1 [Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Rathmell, W. Kimryn] Univ N Carolina, Dept Med, Chapel Hill, NC 27514 USA.
[Rathmell, W. Kimryn] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM linehanm@mail.nih.gov
FU Intramural NIH HHS [ZIA BC011028-05, ZIA BC011038-05, ZIA BC011043-05]
NR 25
TC 7
Z9 8
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD NOV-DEC
PY 2012
VL 30
IS 6
BP 948
EP 951
DI 10.1016/j.urolonc.2012.08.021
PG 4
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 056SI
UT WOS:000312511300032
PM 23218074
ER
PT J
AU Ryugo, DK
Menotti-Raymond, M
AF Ryugo, David K.
Menotti-Raymond, Marilyn
TI Feline Deafness
SO VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE
LA English
DT Article
DE Auditory system; Brain; Cochlea; Congenital deafness; Genes; Synapse
ID AUDITORY BRAIN-STEM; MEDIAL SUPERIOR OLIVE; ANTEROVENTRAL COCHLEAR
NUCLEUS; SPIRAL GANGLION NEURONS; INTRACOCHLEAR ELECTRICAL-STIMULATION;
WAARDENBURG-HIRSCHSPRUNG-DISEASE; SENSORINEURAL HEARING-LOSS; NEONATALLY
DEAFENED CATS; ENDOTHELIN-B RECEPTOR; INFERIOR COLLICULUS
AB Cats have among the best hearing of all mammals in that they are extremely sensitive to a broad range of frequencies. The ear is a highly complex structure that is delicately balanced in terms of its biochemistry, types of receptors, ion channels, mechanical properties, and cellular organization. Sensorineural deafness is caused by "flawed" genes that are inherited from one or both parents. Hearing loss can also be acquired as a result of noise trauma from industrialized environment, viral infection, or blunt trauma. To date, it is not practical to intervene and attempt to correct these forms of deafness in cats.
C1 [Ryugo, David K.] Garvan Inst Med Res, Hearing Res Program, Sydney, NSW 2010, Australia.
[Menotti-Raymond, Marilyn] NCI, Frederick Natl Lab Canc Res, Lab Genom Divers, Frederick, MD 21702 USA.
RP Ryugo, DK (reprint author), Garvan Inst Med Res, Hearing Res Program, 384 Victoria St, Sydney, NSW 2010, Australia.
EM d.ryugo@garvan.org.au
RI Ryugo, David/G-1940-2012
OI Ryugo, David/0000-0002-5250-7503
FU NHMRC [1009842]; Garnett Passe and Rodney Williams Memorial Foundation;
NSW Office of Science and Medical Research; Curran Foundation; NIH/NIDCD
[DC004395]; National Cancer Institute, National Institutes of Health
[HHSN26120080001E]
FX D.K.R. is supported by NHMRC grant #1009842, The Garnett Passe and
Rodney Williams Memorial Foundation, NSW Office of Science and Medical
Research, the Curran Foundation, and NIH/NIDCD grant DC004395; M.M.R. is
supported with federal funds from the National Cancer Institute,
National Institutes of Health, under contract HHSN26120080001E. The
authors have nothing to disclose.
NR 135
TC 4
Z9 4
U1 2
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 0195-5616
J9 VET CLIN N AM-SMALL
JI Vet. Clin. N. Am.-Small Anim. Pract.
PD NOV
PY 2012
VL 42
IS 6
BP 1179
EP +
DI 10.1016/j.cvsm.2012.08.008
PG 30
WC Veterinary Sciences
SC Veterinary Sciences
GA 058ZZ
UT WOS:000312675500007
PM 23122176
ER
PT J
AU Liu, W
Phang, JM
AF Liu, Wei
Phang, James M.
TI Proline dehydrogenase (oxidase) in cancer
SO BIOFACTORS
LA English
DT Review
DE proline dehydrogenase; oxidase; reactive oxygen species; tumor
suppressor; oncogene; metabolic stress
ID PPAR-GAMMA; INDUCED APOPTOSIS; PYRROLINE-5-CARBOXYLIC ACID; P53-INDUCED
GENE-6; COLORECTAL-CANCER; TUMOR-SUPPRESSOR; OXIDIZED LDL; METABOLISM;
STRESS; CELLS
AB Proline dehydrogenase (oxidase, PRODH/POX), the first enzyme in the proline degradative pathway, plays a special role in tumorigenesis and tumor development. Proline metabolism catalyzed by PRODH/POX is closely linked with the tricarboxylic acid (TCA) cycle and urea cycle. The proline cycle formed by the interconversion of proline and ?1-pyrroline-5-carboxylate (P5C) between mitochondria and cytosol interlocks with pentose phosphate pathway. Importantly, by catalyzing proline to P5C, PRODH/POX donates electrons into the electron transport chain to generate ROS or ATP. In earlier studies, we found that PRODH/POX functions as a tumor suppressor to initiate apoptosis, inhibit tumor growth, and block the cell cycle, all by ROS signaling. It also suppresses hypoxia inducible factor signaling by increasing a-ketoglutarate. During tumor progression, PRODH/POX is under the control of various tumor-associated factors, such as tumor suppressor p53, inflammatory factor peroxisome proliferator-activated receptor gamma (PPAR?), onco-miRNA miR-23b*, and oncogenic transcription factor c-MYC. Recent studies revealed the two-sided features of PRODH/POX-mediated regulation. Under metabolic stress such as oxygen and glucose deprivation, PRODH/POX can be induced to serve as a tumor survival factor through ATP production or ROS-induced autophagy. The paradoxical roles of PRODH/POX can be understood considering the temporal and spatial context of the tumor. Further studies will provide additional insights into this protein and on its metabolic effects in tumors, which may lead to new therapeutic strategies.(C) 2012 International Union of Biochemistry and Molecular Biology, Inc.
C1 [Liu, Wei; Phang, James M.] NIH, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res,Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Phang, JM (reprint author), Frederick Natl Lab, 1050 Boyles St,Bldg 538,Rm 144, Frederick, MD 21702 USA.
EM phangj@mail.nih.gov
RI liu, wei /E-7340-2012
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; National Cancer Institute, NIH
[HHSN27612080001]
FX The work was supported by the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research. This project also
has been funded in part with Federal funds from the National Cancer
Institute, NIH, under contract no. HHSN27612080001. The content of this
review 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. The authors thank Dr. Ziqiang Zhu for his reading of the
manuscript.
NR 56
TC 18
Z9 18
U1 1
U2 28
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0951-6433
J9 BIOFACTORS
JI Biofactors
PD NOV-DEC
PY 2012
VL 38
IS 6
BP 398
EP 406
DI 10.1002/biof.1036
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 056YN
UT WOS:000312528300002
PM 22886911
ER
PT J
AU Callahan, R
Mudunuri, U
Bargo, S
Raafat, A
McCurdy, D
Boulanger, C
Lowther, W
Stephens, R
Luke, BT
Stewart, C
Wu, XL
Munroe, D
Smith, GH
AF Callahan, Robert
Mudunuri, Uma
Bargo, Sharon
Raafat, Ahmed
McCurdy, David
Boulanger, Corinne
Lowther, William
Stephens, Robert
Luke, Brian T.
Stewart, Claudia
Wu, Xiaolin
Munroe, David
Smith, Gilbert H.
TI Genes affected by mouse mammary tumor virus (MMTV) proviral insertions
in mouse mammary tumors are deregulated or mutated in primary human
mammary tumors
SO ONCOTARGET
LA English
DT Article
DE mouse mammary tumor virus; premalignant lesions; mammary tumors; genes;
human breast carcinomas; metastases
ID ENVELOPE PROTEIN; TRANSGENIC MICE; BREAST-CANCER; PATHWAYS; ACTIVATION;
EXPRESSION; FAMILY; TRANSPLANTATION; PROTOONCOGENES; PROGRESSION
AB The accumulation of mutations is a contributing factor in the initiation of premalignant mammary lesions and their progression to malignancy and metastasis. We have used a mouse model in which the carcinogen is the mouse mammary tumor virus (MMTV) which induces clonal premalignant mammary lesions and malignant mammary tumors by insertional mutagenesis. Identification of the genes and signaling pathways affected in MMTV-induced mouse mammary lesions provides a rationale for determining whether genetic alteration of the human orthologues of these genes/pathways may contribute to human breast carcinogenesis. A high-throughput platform for inverse PCR to identify MMTV-host junction fragments and their nucleotide sequences in a large panel of MMTV-induced lesions was developed. Validation of the genes affected by MMTV-insertion was carried out by microarray analysis. Common integration site (CIS) means that the gene was altered by an MMTV proviral insertion in at least two independent lesions arising in different hosts. Three of the new genes identified as CIS for MMTV were assayed for their capability to confer on HC11 mouse mammary epithelial cells the ability for invasion, anchorage independent growth and tumor development in nude mice. Analysis of MMTV induced mammary premalignant hyperplastic outgrowth (HOG) lines and mammary tumors led to the identification of CIS restricted to 35 loci. Within these loci members of the Wnt, Fgf and Rspo gene families plus two linked genes (Npm3 and Ddn) were frequently activated in tumors induced by MMTV. A second group of 15 CIS occur at a low frequency (2-5 observations) in mammary HOGs or tumors. In this latter group the expression of either Phf19 or Sdc2 was shown to increase HC11 cells invasion capability. Foxl1 expression conferred on HC11 cells the capability for anchorage-independent colony formation in soft agar and tumor development in nude mice. The published transcriptome and nucleotide sequence analysis of gene expression in primary human breast tumors was interrogated. Twenty of the human orthologues of MMTV CIS associated genes are deregulated and/or mutated in human breast tumors.
C1 [Callahan, Robert; Bargo, Sharon; Raafat, Ahmed; McCurdy, David; Boulanger, Corinne; Lowther, William; Smith, Gilbert H.] NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
[Mudunuri, Uma; Stephens, Robert; Luke, Brian T.; Stewart, Claudia; Wu, Xiaolin; Munroe, David] NCI, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Stewart, Claudia; Wu, Xiaolin; Munroe, David] NCI, Lab Mol Technol, SAIC Frederick Inc, Frederick, MD 21701 USA.
RP Callahan, R (reprint author), NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA.
EM rc54d@nih.gov
FU Intramural Research Program of the National Cancer Institute (NCI);
Center for Cancer Research (CCR) in the National Institutes of Health
(NIH); NCI, NIH [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute (NCI) and Center for Cancer Research
(CCR) in the National Institutes of Health (NIH), and in part with
federal funds from the NCI, NIH, under Contract No. HHSN261200800001E.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 37
TC 10
Z9 10
U1 0
U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV
PY 2012
VL 3
IS 11
BP 1320
EP 1334
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 056JE
UT WOS:000312483600013
PM 23131872
ER
PT J
AU Sourbier, C
Srivastava, G
Ghosh, MC
Ghosh, S
Yang, YF
Gupta, G
DeGraff, W
Krishna, MC
Mitchell, JB
Rouault, TA
Linehan, WM
AF Sourbier, Carole
Srivastava, Gaurav
Ghosh, Manik C.
Ghosh, Sanchari
Yang, Youfeng
Gupta, Gopal
DeGraff, William
Krishna, Murali C.
Mitchell, James B.
Rouault, Tracey A.
Linehan, W. Marston
TI Targeting HIF2 alpha Translation with Tempol in VHL-Deficient Clear Cell
Renal Cell Carcinoma
SO ONCOTARGET
LA English
DT Article
DE HIF; Tempol; RCC; VHL; IRP1; iron metabolism
ID VON-HIPPEL-LINDAU; HYPOXIA-INDUCIBLE FACTORS; TUMOR-SUPPRESSOR PROTEIN;
CARBONIC-ANHYDRASE IX; CANCER-CELLS; GENE; THERAPY; HIF-1-ALPHA;
HIF1-ALPHA; IDENTIFICATION
AB The tumor suppressor gene, Von Hippel-Lindau (VHL), is frequently mutated in the most common form of kidney cancer, clear cell renal cell carcinoma (CCRCC). In hypoxic conditions, or when there is a VHL mutation, the hypoxia inducible factors, HIF1 alpha and HIF2 alpha, are stabilized and transcribe a panel of genes associated with cancer such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). Recent studies in clear cell kidney cancer have suggested that HIF2 alpha, but not HIF1 alpha, is the critical oncoprotein in the VHL pathway. Therefore, targeting HIF2 alpha could provide a potential therapeutic approach for patients with advanced CCRCC. Since iron regulatory protein 1 (IRP1) is known to inhibit the translation of HIF2 alpha, we investigated whether Tempol, a stable nitroxide that activates IRP1 towards IRE-binding, might have a therapeutic effect on a panel of human CCRCC cells expressing both HIF1 alpha and HIF2 alpha. We first evaluated the protein expression of HIF1 alpha and HIF2 alpha in 15 different clear cell renal carcinoma cell lines established from patient tumors in our laboratory. Tempol decreased the expression of HIF2 alpha, and its downstream targets in all the cell lines of the panel. This effect was attributed to a dramatic increase of IRE-binding activity of IRP1. Several cell lines were found to have an increased IRP1 basal activity at 20% O-2 compared to 5% O-2, which may lower HIF2 alpha expression in some of the cell lines in a VHL-independent manner. Taken together our data identify Tempol as an agent with potential therapeutic activity targeting expression of HIF2 alpha in VHL-deficient clear cell kidney cancer and illustrate the importance of studying biochemical processes at relevant physiological O2 levels.
C1 [Sourbier, Carole; Srivastava, Gaurav; Ghosh, Sanchari; Yang, Youfeng; Gupta, Gopal; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Ghosh, Manik C.; Rouault, Tracey A.] NICHHD, Bethesda, MD 20892 USA.
[DeGraff, William; Krishna, Murali C.; Mitchell, James B.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM WML@nih.gov
FU Intramural NIH HHS [ZIA BC011028-05, ZIA BC011038-05, ZIE BC011023-05]
NR 33
TC 7
Z9 9
U1 0
U2 19
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD NOV
PY 2012
VL 3
IS 11
BP 1472
EP 1482
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 056JE
UT WOS:000312483600024
PM 23178531
ER
PT J
AU Pawlowski, J
Audic, S
Adl, S
Bass, D
Belbahri, L
Berney, C
Bowser, SS
Cepicka, I
Decelle, J
Dunthorn, M
Fiore-Donno, AM
Gile, GH
Holzmann, M
Jahn, R
Jirku, M
Keeling, PJ
Kostka, M
Kudryavtsev, A
Lara, E
Lukes, J
Mann, DG
Mitchell, EAD
Nitsche, F
Romeralo, M
Saunders, GW
Simpson, AGB
Smirnov, AV
Spouge, JL
Stern, RF
Stoeck, T
Zimmermann, J
Schindel, D
de Vargas, C
AF Pawlowski, Jan
Audic, Stephane
Adl, Sina
Bass, David
Belbahri, Lassaad
Berney, Cedric
Bowser, Samuel S.
Cepicka, Ivan
Decelle, Johan
Dunthorn, Micah
Fiore-Donno, Anna Maria
Gile, Gillian H.
Holzmann, Maria
Jahn, Regine
Jirku, Miloslav
Keeling, Patrick J.
Kostka, Martin
Kudryavtsev, Alexander
Lara, Enrique
Lukes, Julius
Mann, David G.
Mitchell, Edward A. D.
Nitsche, Frank
Romeralo, Maria
Saunders, Gary W.
Simpson, Alastair G. B.
Smirnov, Alexey V.
Spouge, John L.
Stern, Rowena F.
Stoeck, Thorsten
Zimmermann, Jonas
Schindel, David
de Vargas, Colomban
TI CBOL Protist Working Group: Barcoding Eukaryotic Richness beyond the
Animal, Plant, and Fungal Kingdoms
SO PLOS BIOLOGY
LA English
DT Article
ID INTERNAL TRANSCRIBED SPACER; DNA BARCODE; SPECIES IDENTIFICATION;
EVOLUTIONARY HISTORY; GENETIC-VARIATION; RDNA SEQUENCES; DIVERSITY;
DIATOMS; RBCL; MACROALGAE
C1 [Pawlowski, Jan; Holzmann, Maria; Kudryavtsev, Alexander] Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland.
[Audic, Stephane; Decelle, Johan; de Vargas, Colomban] Univ Paris 06, Stn Biol Roscoff, F-75252 Paris 05, France.
[Audic, Stephane; Decelle, Johan; de Vargas, Colomban] CNRS, Unite Mixte Rech 7144, F-75700 Paris, France.
[Adl, Sina] Univ Saskatchewan, Dept Soil Sci, Saskatoon, SK S7N 0W0, Canada.
[Bass, David; Berney, Cedric] Nat Hist Museum, Dept Life Sci, London SW7 5BD, England.
[Belbahri, Lassaad; Lara, Enrique; Mitchell, Edward A. D.] Univ Neuchatel, Lab Soil Biol, CH-2000 Neuchatel, Switzerland.
[Bowser, Samuel S.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA.
[Cepicka, Ivan] Charles Univ Prague, Dept Zool, Prague, Czech Republic.
[Dunthorn, Micah; Stoeck, Thorsten] Univ Kaiserslautern, Dept Ecol, Kaiserslautern, Germany.
[Fiore-Donno, Anna Maria] Ernst Moritz Arndt Univ Greifswald, Inst Bot & Landscape Ecol, Greifswald, Germany.
[Gile, Gillian H.] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS, Canada.
[Jahn, Regine; Zimmermann, Jonas] Free Univ Berlin, Bot Garten, Berlin, Germany.
[Jahn, Regine; Zimmermann, Jonas] Free Univ Berlin, Bot Museum Berlin Dahlem, Berlin, Germany.
[Jirku, Miloslav; Kostka, Martin; Lukes, Julius] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
[Keeling, Patrick J.] Univ British Columbia, Canadian Inst Adv Res, Dept Bot, Vancouver, BC, Canada.
[Kostka, Martin; Lukes, Julius] Univ S Bohemia, Fac Sci, Ceske Budejovice, Czech Republic.
[Kudryavtsev, Alexander; Smirnov, Alexey V.] St Petersburg State Univ, Dept Invertebrate Zool, St Petersburg, Russia.
[Mann, David G.] Royal Bot Garden Edinburgh, Edinburgh, Midlothian, Scotland.
[Nitsche, Frank] Univ Cologne, D-50931 Cologne, Germany.
[Romeralo, Maria] Uppsala Univ, Evolutionary Biol Ctr, Dept Systemat Biol, Uppsala, Sweden.
[Saunders, Gary W.] Univ New Brunswick, Dept Biol, Fredericton, NB E3B 6E1, Canada.
[Simpson, Alastair G. B.] Life Sci Ctr, Dept Biol, Halifax, NS, Canada.
[Spouge, John L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Computat Biol Branch, Bethesda, MD 20892 USA.
[Stern, Rowena F.] Sir Alister Hardy Fdn Ocean Sci, Plymouth, Devon, England.
[Zimmermann, Jonas] Univ Giessen, Giessen, Germany.
[Schindel, David] Natl Museum Nat Hist, Smithsonian Inst, Washington, DC 20560 USA.
RP Pawlowski, J (reprint author), Univ Geneva, Dept Genet & Evolut, Geneva, Switzerland.
EM Jan.Pawlowski@unige.ch; vargas@sb-roscoff.fr
RI Mitchell, Edward/B-7259-2013; Saunders, Gary/D-8767-2014; Jirku,
Miloslav/G-7823-2014; Mann, David/I-9018-2014; Kostka,
Martin/G-9770-2014; Lukes, Julius/H-6760-2012; Smirnov,
Alexey/K-3743-2013; Kudryavtsev, Alexander/J-2921-2013; Adl,
Sina/R-3187-2016;
OI Mitchell, Edward/0000-0003-0358-506X; Berney,
Cedric/0000-0001-8689-9907; Audic, Stephane/0000-0001-6193-4374;
Saunders, Gary/0000-0003-4813-6831; Mann, David/0000-0003-0522-6802;
Lukes, Julius/0000-0002-0578-6618; Smirnov, Alexey/0000-0002-9844-5344;
Kudryavtsev, Alexander/0000-0002-3818-3610; Simpson,
Alastair/0000-0002-4133-1709; Pawlowski, Jan/0000-0003-2421-388X; Lara,
Enrique/0000-0001-8500-522X
FU Consortium for the Barcoding of Life; European ERA-net program
BiodivErsA under the BioMarKs project; French ANR project [09-BLAN-0348
POSEIDON]; Swiss National Science Foundation [31003A-140766]
FX The initial phase of the Protist Working Group activities presented in
this paper were supported by the Consortium for the Barcoding of Life,
the European ERA-net program BiodivErsA, under the BioMarKs project, the
French ANR project 09-BLAN-0348 POSEIDON, and the Swiss National Science
Foundation 31003A-140766. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 56
TC 120
Z9 124
U1 4
U2 135
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2012
VL 10
IS 11
AR e1001419
DI 10.1371/journal.pbio.1001419
PG 5
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA 048CR
UT WOS:000311888300002
PM 23139639
ER
PT J
AU Miller, FG
AF Miller, Franklin G.
TI The Enduring Legacy of Sham-Controlled Trials of Internal Mammary Artery
Ligation
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Sham surgery; Risk-benefit assessment; Research ethics
ID STABLE CORONARY-DISEASE; ANGINA-PECTORIS; MYOCARDIAL REVASCULARIZATION;
PARKINSONS-DISEASE; RANDOMIZED-TRIAL; PLACEBO SURGERY; VERTEBROPLASTY;
FRACTURES; THERAPY; PCI
AB In 1959 and 1960 the results of two randomized controlled trials demonstrated that bilateral internal mammary artery ligation was no better than a sham intervention in the treatment of angina. These landmark trials were the first to use blinded placebo controls to evaluate invasive procedures. Revisiting the story of internal mammary artery ligation offers valuable insights into the ethics of sham-controlled trials and the implications of the placebo effect for thinking about risk-benefit assessment of sham procedures. (Prog Cardiovasc Dis 2012;55:246-250) Published by Elsevier Inc.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM fmiller@nih.gov
FU Intramural Research Program of the Clinical Center, NIH
FX This research was supported by the Intramural Research Program of the
Clinical Center, NIH.
NR 30
TC 11
Z9 11
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2012
VL 55
IS 3
BP 246
EP 250
DI 10.1016/j.pcad.2012.09.002
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 055RA
UT WOS:000312433100002
PM 23217427
ER
PT J
AU Sato, M
Freedman, A
Trovato, J
Zhan, M
Cunningham, F
Smith, WS
AF Sato, M.
Freedman, A.
Trovato, J.
Zhan, M.
Cunningham, F.
Smith, Weiss S.
TI IMPACT OF ERYTHROPOIESIS STIMULATING AGENTS ON SURVIVAL AMONG PATINETS
WITH COLORECTAL CANCER RECEIVING CHEMOTHERAPY
SO VALUE IN HEALTH
LA English
DT Meeting Abstract
C1 [Sato, M.; Trovato, J.; Smith, Weiss S.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA.
[Freedman, A.] NCI, Bethesda, MD 20892 USA.
[Zhan, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Cunningham, F.] Vet Hlth Adm Pharm Benefits Management Serv, Hine, IL 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 1098-3015
J9 VALUE HEALTH
JI Value Health
PD NOV
PY 2012
VL 15
IS 7
BP A653
EP A654
PG 2
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA 055JF
UT WOS:000312411102139
ER
PT J
AU Jensen, MB
Dunn, CA
Keijzers, G
Kulikowicz, T
Rasmussen, LJ
Croteau, DL
Bohr, VA
AF Jensen, Martin Borch
Dunn, Christopher A.
Keijzers, Guido
Kulikowicz, Tomasz
Rasmussen, Lene Juel
Croteau, Deborah L.
Bohr, Vilhelm A.
TI The helicase and ATPase activities of RECQL4 are compromised by
mutations reported in three human patients
SO AGING-US
LA English
DT Article
DE RecQ helicase; RECQL4; Rothmund-Thomson Syndrome; RAPADILINO Syndrome
ID ROTHMUND-THOMSON-SYNDROME; SYNDROME GENE-PRODUCT; DNA-REPLICATION;
GENOME STABILITY; SYNDROME PROTEIN; REPAIR; MAINTENANCE; CELLS;
INVOLVEMENT; MECHANISMS
AB RECQL4 is one of five members of the human RecQ helicase family, and is implicated in three syndromes displaying accelerating aging, developmental abnormalities and a predisposition to cancer. In this study, we purified three variants of RECQL4 carrying previously reported patient mutations. These three mutant proteins were analyzed for the known biochemical activities of RECQL4: DNA binding, unwinding of duplex DNA, ATP hydrolysis and annealing of simplex DNA. Further, the mutant proteins were evaluated for stability and recruitment to sites of laser-induced DNA damage. One mutant was helicase-dead, had marginal ATPase activity and may be structurally compromised, while the other two showed greatly reduced helicase and ATPase activities. The remaining biochemical activities and ability to recruit to damage sites were not significantly impaired for any of the mutants. Our findings demonstrate a consistent pattern of functional deficiency and provide further support for a helicase-dependent cellular function of RECQL4 in addition to its N-terminus-dependent role in initiation of replication, a function that may underlie the phenotype of RECQL4-linked disease.
C1 [Jensen, Martin Borch; Dunn, Christopher A.; Keijzers, Guido; Rasmussen, Lene Juel; Bohr, Vilhelm A.] Univ Copenhagen, Dept Cellular & Mol Med, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark.
[Kulikowicz, Tomasz; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), Univ Copenhagen, Dept Cellular & Mol Med, Ctr Healthy Aging, DK-2200 Copenhagen, Denmark.
EM vbohr@nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging;
Nordea Foundation
FX We would like to thank Dr. Takashi Tadokoro for help with the
thermostability assay, and Alfred May for help with micropoint laser
irradiation. We also thank Dr. Takashi Tadokoro and Dr. Evandro Fei Fang
for critical reading of this manuscript. This research was supported in
part by the Intramural Research Program of the NIH, National Institute
on Aging, as well as a grant from the Nordea Foundation.
NR 51
TC 7
Z9 7
U1 0
U2 4
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 NOV
PY 2012
VL 4
IS 11
BP 790
EP 802
PG 13
WC Cell Biology
SC Cell Biology
GA 053RE
UT WOS:000312289900010
PM 23238538
ER
PT J
AU Smith, DH
Feldstein, AC
Perrin, N
Rosales, AG
Mosen, DM
Liles, EG
Schneider, JL
Lafata, JE
Myers, RE
Glasgow, RE
AF Smith, David H.
Feldstein, Adrianne C.
Perrin, Nancy
Rosales, A. Gabriela
Mosen, David M.
Liles, Elizabeth G.
Schneider, Jennifer L.
Lafata, Jennifer E.
Myers, Ronald E.
Glasgow, Russell E.
TI Automated Telephone Calls to Enhance Colorectal Cancer Screening:
Economic Analysis
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Article
ID COST-EFFECTIVENESS ANALYSIS; NET BENEFIT REGRESSION; TRIAL; CARE;
INTERVENTIONS; FRAMEWORK; SYSTEM
AB Objectives: To estimate the cost-effectiveness of an automated telephone intervention for colorectal cancer screening from a managed care perspective, using data from a pragmatic randomized controlled trial.
Methods: Intervention patients received calls for fecal occult blood testing (FOBT) screening. We searched patients' electronic medical records for any screening (defined as FOBT, flexible sigmoidoscopy, double-contrast barium enema, or colonoscopy) during follow-up. Intervention costs included project implementation and management, telephone calls, patient identification, and tracking. Screening costs included FOBT (kits, mailing, and processing) and any completed screening tests during follow-up. We estimated the incremental cost-effectiveness ratio (ICER) of the cost per additional screen.
Results: At 6 months, average costs for intervention and control patients were $37 (25% screened) and $34 (19% screened), respectively. The ICER at 6 months was $42 per additional screen, less than half what other studies have reported. Cost-effectiveness probability was 0.49, 0.84, and 0.99 for willingness-to-pay thresholds of $40, $100, and $200, respectively. Similar results were seen at 9 months. A greater increase in FOBT testing was seen for patients aged >= 70 years (45/100 intervention, 33/100 control) compared with younger patients (25/100 intervention, 21/100 control). The intervention was dominant for patients aged >= 70 years and was $73 per additional screen for younger patients. It increased screening rates by about 6% and costs by $3 per patient.
Conclusions: At willingness to pay of $100 or more per additional screening test, an automated telephone reminder intervention can be an optimal use of resources. (Am J Manag Care, 2012;18(11):691-699)
C1 [Smith, David H.; Feldstein, Adrianne C.; Perrin, Nancy; Rosales, A. Gabriela; Mosen, David M.; Liles, Elizabeth G.; Schneider, Jennifer L.] Kaiser Permanence NW, Ctr Hlth Res, Portland, OR USA.
[Feldstein, Adrianne C.] Kaiser Permanence NW, NW Perrnanente, Portland, OR USA.
[Lafata, Jennifer E.] Henry Ford Hlth Syst, Detroit, MI USA.
[Myers, Ronald E.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Glasgow, Russell E.] NCI, Disseminat & Implementat Sci Div Canc Control & P, Bethesda, MD 20892 USA.
RP Smith, DH (reprint author), 3800 N Interstate Ave, Portland, OR 97227 USA.
EM david.h.smith@kpchr.org
OI Myers, Ronald E./0000-0002-8059-7390
FU National Cancer Institute [1R01CA132709]
FX Funding Source: National Cancer Institute (1R01CA132709).
NR 18
TC 6
Z9 6
U1 1
U2 6
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD NOV
PY 2012
VL 18
IS 11
BP 691
EP 699
PG 9
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 052VM
UT WOS:000312226900003
PM 23198712
ER
PT J
AU Morrison, DK
AF Morrison, Deborah K.
TI MAP Kinase Pathways
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID SCAFFOLD PROTEINS; MECHANISMS; CASCADES
C1 NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
RP Morrison, DK (reprint author), NCI, Lab Cell & Dev Signaling, Frederick, MD 21702 USA.
EM morrisod@mail.nih.gov
NR 17
TC 47
Z9 49
U1 1
U2 15
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD NOV
PY 2012
VL 4
IS 11
AR a011254
DI 10.1101/cshperspect.a011254
PG 5
WC Cell Biology
SC Cell Biology
GA 054MR
UT WOS:000312348400011
ER
PT J
AU Narendra, D
Walker, JE
Youle, R
AF Narendra, Derek
Walker, John E.
Youle, Richard
TI Mitochondrial Quality Control Mediated by PINK1 and Parkin: Links to
Parkinsonism
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID PINK1/PARKIN-MEDIATED MITOPHAGY; DEPOLARIZED MITOCHONDRIA;
ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; AXONAL-TRANSPORT; OXIDATIVE
STRESS; MTDNA MUTATIONS; DNA DELETIONS; NIGRA NEURONS; KINASE PINK1
AB Mutations in Parkin or PINK1 are the most common cause of recessive familial parkinsonism. Recent studies suggest that PINK1 and Parkin form a mitochondria quality control pathway that identifies dysfunctional mitochondria, isolates them from the mitochondrial network, and promotes their degradation by autophagy. In this pathway the mitochondrial kinase PINK1 senses mitochondrial fidelity and recruits Parkin selectively to mitochondria that lose membrane potential. Parkin, an E3 ligase, subsequently ubiquitinates outer mitochondrial membrane proteins, notably the mitofusins and Miro, and induces autophagic elimination of the impaired organelles. Here we review the recent rapid progress in understanding the molecular mechanisms of PINK1- and Parkin-mediated mitophagy and the identification of Parkin substrates suggesting how mitochondrial fission and trafficking are involved. We also discuss how defects in mitophagy may be linked to Parkinson's disease.
C1 [Narendra, Derek; Youle, Richard] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Narendra, Derek; Walker, John E.] MRC, Mitochondrial Biol Unit, Cambridge CB0 2XY, England.
RP Youle, R (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU intramural program at the NINDS; Medical Research Council; NIH
[1F30AG039185-01]
FX This review was supported by the intramural program at the NINDS (R.Y.
and D.N.), the Medical Research Council (J.E.W. and D.N.), and NIH grant
1F30AG039185-01 (D.N.). We thank Drs. Ian Fearnley, Joe Carroll, and
Shujing Ding for many helpful discussions and assistance in preparing
proteomics data for Tables 1 and 2 and Figure 2 of this review.
NR 94
TC 53
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U1 1
U2 23
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD NOV
PY 2012
VL 4
IS 11
AR a011338
DI 10.1101/cshperspect.a011338
PG 19
WC Cell Biology
SC Cell Biology
GA 054MR
UT WOS:000312348400012
ER
PT J
AU Ramos, E
Callier, SL
Rotimi, CN
AF Ramos, Edward
Callier, Shawneequa L.
Rotimi, Charles N.
TI Why personalized medicine will fail if we stay the course
SO PERSONALIZED MEDICINE
LA English
DT Article
DE diversity; ethnicity; genomic medicine; global populations; personalized
medicine
ID GENOME-WIDE ASSOCIATION; DIABETES SUSCEPTIBILITY GENES; ADVERSE
DRUG-REACTIONS; AFRICAN-AMERICANS; ETHICAL-ISSUES; WEST AFRICANS;
PHARMACOGENOMICS; VARIANTS; POPULATIONS; IMPACT
AB Genomic science and associated technologies are providing scientists and clinicians with novel insights that are transforming the delivery of healthcare and the overall well-being of society. However, these insights inform us that historical population sampling approaches for investigating rare and common genetic variations are not representative of the complex ancestral backgrounds of today's patients. In order for personalized medicine to be meaningful and applicable to the global populations, we will need to know how common and rare genetic variants found in different parts of the world influence health and drug response. This article demonstrates the importance of increasing ethnic and racial diversity among participants in genomic research, highlights areas of opportunity for improving our understanding of genomic diversity among populations, and provides examples of successful models that help to resolve these concerns.
C1 [Ramos, Edward; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Callier, Shawneequa L.] George Washington Univ, Dept Clin Res & Leadership, Sch Med & Hlth Sci, Washington, DC 20037 USA.
RP Ramos, E (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
EM ramose@mail.nih.gov
FU Intramural Research Program of the Center for Research on Genomics and
Global Health (CRGGH); Office of the Director, National Institute of
Diabetes and Digestive and Kidney diseases (NIDDK); National Human
Genome Research Institute (NHGRI) at the NIH [Z01HG200362]
FX This work was supported in part by the Intramural Research Program of
the Center for Research on Genomics and Global Health (CRGGH). The CRGGH
is supported by funds from the Office of the Director, National
Institute of Diabetes and Digestive and Kidney diseases (NIDDK) and
National Human Genome Research Institute (NHGRI) at the NIH
(Z01HG200362). The authors have no other relevant affiliations or
financial involvement with any organization or entity with a financial
interest in or financial conflict with the subject matter or materials
discussed in the manuscript apart from those disclosed.
NR 65
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Z9 12
U1 0
U2 10
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1741-0541
J9 PERS MED
JI Pers. Med.
PD NOV
PY 2012
VL 9
IS 8
BP 839
EP 847
DI 10.2217/PME.12.100
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 049JC
UT WOS:000311977800010
PM 23543886
ER
PT J
AU Arnold, JJ
Sharma, SD
Feng, JY
Ray, AS
Smidansky, ED
Kireeva, ML
Cho, A
Perry, J
Vela, JE
Park, Y
Xu, YL
Tian, Y
Babusis, D
Barauskus, O
Peterson, BR
Gnatt, A
Kashlev, M
Zhong, WD
Cameron, CE
AF Arnold, Jamie J.
Sharma, Suresh D.
Feng, Joy Y.
Ray, Adrian S.
Smidansky, Eric D.
Kireeva, Maria L.
Cho, Aesop
Perry, Jason
Vela, Jennifer E.
Park, Yeojin
Xu, Yili
Tian, Yang
Babusis, Darius
Barauskus, Ona
Peterson, Blake R.
Gnatt, Averell
Kashlev, Mikhail
Zhong, Weidong
Cameron, Craig E.
TI Sensitivity of Mitochondrial Transcription and Resistance of RNA
Polymerase II Dependent Nuclear Transcription to Antiviral
Ribonucleosides
SO PLOS PATHOGENS
LA English
DT Article
ID HEPATITIS-C-VIRUS; PURINE NUCLEOSIDE ANALOGS; MAMMALIAN MITOCHONDRIA;
DNA POLYMERASE; REPLICATION; TOXICITY; ELONGATION; INHIBITOR; REPLICON;
THERAPY
AB Ribonucleoside analogues have potential utility as anti-viral, -parasitic, -bacterial and -cancer agents. However, their clinical applications have been limited by off target effects. Development of antiviral ribonucleosides for treatment of hepatitis C virus (HCV) infection has been hampered by appearance of toxicity during clinical trials that evaded detection during preclinical studies. It is well established that the human mitochondrial DNA polymerase is an off target for deoxyribonucleoside reverse transcriptase inhibitors. Here we test the hypothesis that triphosphorylated metabolites of therapeutic ribonucleoside analogues are substrates for cellular RNA polymerases. We have used ribonucleoside analogues with activity against HCV as model compounds for therapeutic ribonucleosides. We have included ribonucleoside analogues containing 2'-C-methyl, 4'-methyl and 4'-azido substituents that are non-obligate chain terminators of the HCV RNA polymerase. We show that all of the anti-HCV ribonucleoside analogues are substrates for human mitochondrial RNA polymerase (POLRMT) and eukaryotic core RNA polymerase II (Pol II) in vitro. Unexpectedly, analogues containing 2'-C-methyl, 4'-methyl and 4'-azido substituents were inhibitors of POLRMT and Pol II. Importantly, the proofreading activity of TFIIS was capable of excising these analogues from Pol II transcripts. Evaluation of transcription in cells confirmed sensitivity of POLRMT to antiviral ribonucleosides, while Pol II remained predominantly refractory. We introduce a parameter termed the mitovir (mitochondrial dysfunction caused by antiviral ribonucleoside) score that can be readily obtained during preclinical studies that quantifies the mitochondrial toxicity potential of compounds. We suggest the possibility that patients exhibiting adverse effects during clinical trials may be more susceptible to damage by nucleoside analogs because of defects in mitochondrial or nuclear transcription. The paradigm reported here should facilitate development of ribonucleosides with a lower potential for toxicity.
C1 [Arnold, Jamie J.; Sharma, Suresh D.; Smidansky, Eric D.; Cameron, Craig E.] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
[Feng, Joy Y.; Ray, Adrian S.; Cho, Aesop; Perry, Jason; Vela, Jennifer E.; Park, Yeojin; Xu, Yili; Tian, Yang; Babusis, Darius; Barauskus, Ona; Zhong, Weidong] Gilead Sci Inc, Foster City, CA USA.
[Kireeva, Maria L.; Kashlev, Mikhail] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Peterson, Blake R.] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA.
[Gnatt, Averell] Univ Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA.
RP Arnold, JJ (reprint author), Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
EM jja5@psu.edu; cec9@psu.edu
RI SHARMA, Suresh/C-4431-2008; Peterson, Blake/O-2497-2016;
OI SHARMA, Suresh/0000-0002-8633-4145; Peterson, Blake/0000-0001-8251-3579;
Ray, Adrian/0000-0002-3508-3008
FU NIAID, NIH [AI045818]
FX This work was supported by grants from NIAID, NIH: AI045818 (CEC). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. The contents of
this publication do not necessarily reveal the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial product, or organizations imply endorsement by the U.
S. Government.
NR 50
TC 32
Z9 34
U1 0
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1003030
DI 10.1371/journal.ppat.1003030
PG 12
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100045
PM 23166498
ER
PT J
AU Kwon-Chung, KJ
Chang, YC
AF Kwon-Chung, Kyung J.
Chang, Yun C.
TI Aneuploidy and Drug Resistance in Pathogenic Fungi
SO PLOS PATHOGENS
LA English
DT Article
ID CANDIDA-GLABRATA ISOLATE; CRYPTOCOCCUS-NEOFORMANS; YEAST; CELLS;
VIRULENCE; HETERORESISTANCE; FLUCONAZOLE; ALBICANS; GENES
C1 [Kwon-Chung, Kyung J.; Chang, Yun C.] NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM june_kwon-chung@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This study was supported by funds from the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 32
TC 21
Z9 21
U1 0
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1003022
DI 10.1371/journal.ppat.1003022
PG 4
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100039
PM 23166494
ER
PT J
AU Nance, JP
Vannella, KM
Worth, D
David, C
Carter, D
Noor, S
Hubeau, C
Fitz, L
Lane, TE
Wynn, TA
Wilson, EH
AF Nance, J. Philip
Vannella, Kevin M.
Worth, Danielle
David, Clement
Carter, David
Noor, Shahani
Hubeau, Cedric
Fitz, Lori
Lane, Thomas E.
Wynn, Thomas A.
Wilson, Emma H.
TI Chitinase Dependent Control of Protozoan Cyst Burden in the Brain
SO PLOS PATHOGENS
LA English
DT Article
ID ALTERNATIVELY ACTIVATED MACROPHAGES; TOXOPLASMA-GONDII INFECTION; ACIDIC
MAMMALIAN CHITINASE; CELL-MEDIATED-IMMUNITY; INDUCIBLE NITRIC-OXIDE;
CD4(+) T-CELLS; IFN-GAMMA; DIFFERENTIAL EXPRESSION; FUNCTIONAL
PLASTICITY; ALLERGIC INFLAMMATION
AB Chronic infections represent a continuous battle between the host's immune system and pathogen replication. Many protozoan parasites have evolved a cyst lifecycle stage that provides it with increased protection from environmental degradation as well as endogenous host mechanisms of attack. In the case of Toxoplasma gondii, these cysts are predominantly found in the immune protected brain making clearance of the parasite more difficult and resulting in a lifelong infection. Currently, little is known about the nature of the immune response stimulated by the presence of these cysts or how they are able to propagate. Here we establish a novel chitinase-dependent mechanism of cyst control in the infected brain. Despite a dominant Th1 immune response during Toxoplasma infection there exists a population of alternatively activated macrophages (AAM circle divide) in the infected CNS. These cells are capable of cyst lysis via the production of AMCase as revealed by live imaging, and this chitinase is necessary for protective immunity within the CNS. These data demonstrate chitinase activity in the brain in response to a protozoan pathogen and provide a novel mechanism to facilitate cyst clearance during chronic infections.
C1 [Nance, J. Philip; Worth, Danielle; David, Clement; Noor, Shahani; Wilson, Emma H.] Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA.
[Vannella, Kevin M.; Wynn, Thomas A.] NIAID, NIH, Bethesda, MD 20892 USA.
[Carter, David] Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA.
[Hubeau, Cedric; Fitz, Lori] Pfizer, Dept Inflammat & Immunol, Cambridge, MA USA.
[Lane, Thomas E.] Univ Calif Irvine, Inst Immunol, Dept Mol Biol & Biochem, Irvine, CA USA.
RP Wilson, EH (reprint author), Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA.
EM emmaw@ucr.edu
OI Nance, Phil/0000-0002-3369-0015
FU CRCC; UCR Division of Biomedical Sciences; UCR academic senate; NIH
[RNS071160A, RNS072298A, R01NS041249]; National Institute of Allergy and
Infectious Diseases/NIH
FX These studies were supported in part by grants to EHW from CRCC, the UCR
Division of Biomedical Sciences, the UCR academic senate and NIH
RNS071160A and RNS072298A and to TEL by NIH R01NS041249. TAW is
supported by the intramural research program of the National Institute
of Allergy and Infectious Diseases/NIH. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 91
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U1 0
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1002990
DI 10.1371/journal.ppat.1002990
PG 16
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100013
PM 23209401
ER
PT J
AU Perkins, MR
Ryschkewitsch, C
Liebner, JC
Monaco, MCG
Himelfarb, D
Ireland, S
Roque, A
Edward, HL
Jensen, PN
Remington, G
Abraham, T
Abraham, J
Greenberg, B
Kaufman, C
LaGanke, C
Monson, NL
Xu, XN
Frohman, E
Major, EO
Douek, DC
AF Perkins, Molly R.
Ryschkewitsch, Caroline
Liebner, Julia C.
Monaco, Maria Chiara G.
Himelfarb, Danielle
Ireland, Sara
Roque, Annelys
Edward, Heather L.
Jensen, Peter N.
Remington, Gina
Abraham, Thomas
Abraham, Jaspreet
Greenberg, Benjamin
Kaufman, Charles
LaGanke, Chris
Monson, Nancy L.
Xu, Xiaoning
Frohman, Elliot
Major, Eugene O.
Douek, Daniel C.
TI Changes in JC Virus-Specific T Cell Responses during Natalizumab
Treatment and in Natalizumab-Associated Progressive Multifocal
Leukoencephalopathy
SO PLOS PATHOGENS
LA English
DT Article
ID MULTIPLE-SCLEROSIS PATIENTS; PATIENTS RECEIVING NATALIZUMAB;
CEREBROSPINAL-FLUID; IMMUNE-RESPONSES; DISCREPANT FINDINGS;
MESSENGER-RNA; IN-VIVO; IL-15; PML; SERUM
AB Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients.
C1 [Perkins, Molly R.; Liebner, Julia C.; Himelfarb, Danielle; Roque, Annelys; Edward, Heather L.; Douek, Daniel C.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Perkins, Molly R.; Xu, Xiaoning] Univ Oxford, MRC Human Immunol Unit, Weatherall Inst Mol Med, Oxford, England.
[Ryschkewitsch, Caroline; Monaco, Maria Chiara G.; Jensen, Peter N.; Major, Eugene O.] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
[Ireland, Sara; Remington, Gina; Abraham, Thomas; Abraham, Jaspreet; Greenberg, Benjamin; Monson, Nancy L.; Frohman, Elliot] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75390 USA.
[Kaufman, Charles] Louisiana Neurol Consultants, Baton Rouge, LA USA.
[LaGanke, Chris] N Cent Neurol, Cullman, AL USA.
RP Perkins, MR (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM majorg@ninds.nih.gov; ddouek@mail.nih.gov
OI Greenberg, Benjamin/0000-0002-2091-8201; Ireland,
Sara/0000-0002-7811-197X
FU National Institute of Allergy and Infectious Diseases; National
Institute of Neurological Disorders and Stroke; Sanofi Aventis; Greater
Good Foundation; Biogen Idec; Elan; Applied Clinical Intelligence;
DioGenix; Guthy Jackson Charitable Foundation; Amplimmune; Accelerated
Cure Project; TEVA; Novartis; Acorda; Abbott; Genzyme
FX This work was supported by intramural funding from the National
Institute of Allergy and Infectious Diseases and the National Institute
of Neurological Disorders and Stroke. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.; I have read the journal's policy and
have the following conflicts: Dr. Greenberg has received honoraria from
the MSAA. He has received consulting fees from Sanofi Aventis, The
Greater Good Foundation, Biogen Idec, Elan, Applied Clinical
Intelligence and DioGenix. He holds equity in DioGenix, Inc. He receives
grant support from the Guthy Jackson Charitable Foundation, Amplimmune
and Accelerated Cure Project. Dr. Frohman has received speaker and
consulting fees from Biogen Idec, TEVA, Novartis, and Acorda; and
consulting fees from Abbott and Genzyme. This does not alter our
adherence to all PLoS Pathogens policies on sharing data and materials.
NR 41
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U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1003014
DI 10.1371/journal.ppat.1003014
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100033
PM 23144619
ER
PT J
AU Waki, K
Durell, SR
Soheilian, F
Nagashima, K
Butler, SL
Freed, EO
AF Waki, Kayoko
Durell, Stewart R.
Soheilian, Ferri
Nagashima, Kunio
Butler, Scott L.
Freed, Eric O.
TI Structural and Functional Insights into the HIV-1 Maturation Inhibitor
Binding Pocket
SO PLOS PATHOGENS
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; MAJOR HOMOLOGY REGION; GAG SPACER
PEPTIDE-1; CA-SP1 CLEAVAGE SITE; BETULINIC ACID; CAPSID PROTEIN;
MEMBRANE AFFINITY; HELICAL STRUCTURE; VIRAL PROTEASE; IN-VITRO
AB Processing of the Gag precursor protein by the viral protease during particle release triggers virion maturation, an essential step in the virus replication cycle. The first-in-class HIV-1 maturation inhibitor dimethylsuccinyl betulinic acid [PA-457 or bevirimat (BVM)] blocks HIV-1 maturation by inhibiting the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. A structurally distinct molecule, PF-46396, was recently reported to have a similar mode of action to that of BVM. Because of the structural dissimilarity between BVM and PF-46396, we hypothesized that the two compounds might interact differentially with the putative maturation inhibitor-binding pocket in Gag. To test this hypothesis, PF-46396 resistance was selected for in vitro. Resistance mutations were identified in three regions of Gag: around the CA-SP1 cleavage site where BVM resistance maps, at CA amino acid 201, and in the CA major homology region (MHR). The MHR mutants are profoundly PF-46396-dependent in Gag assembly and release and virus replication. The severe defect exhibited by the inhibitor-dependent MHR mutants in the absence of the compound is also corrected by a second-site compensatory change far downstream in SP1, suggesting structural and functional cross-talk between the HIV-1 CA MHR and SP1. When PF-46396 and BVM were both present in infected cells they exhibited mutually antagonistic behavior. Together, these results identify Gag residues that line the maturation inhibitor-binding pocket and suggest that BVM and PF-46396 interact differentially with this putative pocket. These findings provide novel insights into the structure-function relationship between the CA MHR and SP1, two domains of Gag that are critical to both assembly and maturation. The highly conserved nature of the MHR across all orthoretroviridae suggests that these findings will be broadly relevant to retroviral assembly. Finally, the results presented here provide a framework for increased structural understanding of HIV-1 maturation inhibitor activity.
C1 [Waki, Kayoko; Freed, Eric O.] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Durell, Stewart R.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Soheilian, Ferri; Nagashima, Kunio] NCI, Electron Microscope Lab, Adv Technol Program, SAIC Frederick,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Butler, Scott L.] Sandwich Labs, Pfizer Global Res & Dev, Sandwich, Kent, England.
RP Waki, K (reprint author), NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
EM efreed@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; Intramural
AIDS targeted Antiviral Program; National Cancer Institute, National
Institutes of Health [HHSN26120080001E]
FX Research in the Freed lab 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. This
project has also been funded in part with federal funds from the
National Cancer Institute, National Institutes of Health, under contract
HHSN26120080001E. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 65
TC 27
Z9 27
U1 1
U2 13
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1002997
DI 10.1371/journal.ppat.1002997
PG 19
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100018
PM 23144615
ER
PT J
AU Wang, X
Li, J
Schowalter, RM
Jiao, J
Buck, CB
You, JX
AF Wang, Xin
Li, Jing
Schowalter, Rachel M.
Jiao, Jing
Buck, Christopher B.
You, Jianxin
TI Bromodomain Protein Brd4 Plays a Key Role in Merkel Cell Polyomavirus
DNA Replication
SO PLOS PATHOGENS
LA English
DT Article
ID HOST MITOTIC CHROMOSOMES; T-ANTIGEN; ACETYLATED CHROMATIN; NUCLEAR
ANTIGEN; FACTOR-C; S-PHASE; CARCINOMA; INTERACTS; PROGRESSION;
INHIBITION
AB Merkel cell polyomavirus (MCV or MCPyV) is the first human polyomavirus to be definitively linked to cancer. The mechanisms of MCV-induced oncogenesis and much of MCV biology are largely unexplored. In this study, we demonstrate that bromodomain protein 4 (Brd4) interacts with MCV large T antigen (LT) and plays a critical role in viral DNA replication. Brd4 knockdown inhibits MCV replication, which can be rescued by recombinant Brd4. Brd4 colocalizes with the MCV LT/replication origin complex in the nucleus and recruits replication factor C (RFC) to the viral replication sites. A dominant negative inhibitor of the Brd4-MCV LT interaction can dissociate Brd4 and RFC from the viral replication complex and abrogate MCV replication. Furthermore, obstructing the physiologic interaction between Brd4 and host chromatin with the chemical compound JQ1(+) leads to enhanced MCV DNA replication, demonstrating that the role of Brd4 in MCV replication is distinct from its role in chromatin-associated transcriptional regulation. Our findings demonstrate mechanistic details of the MCV replication machinery; providing novel insight to elucidate the life cycle of this newly discovered oncogenic DNA virus.
C1 [Wang, Xin; Li, Jing; Jiao, Jing; You, Jianxin] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Schowalter, Rachel M.; Buck, Christopher B.] NCI, Tumor Virus Mol Biol Sect, Cellular Oncol Lab, Bethesda, MD 20892 USA.
RP Wang, X (reprint author), Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM jianyou@mail.med.upenn.edu
OI Buck, Christopher/0000-0003-3165-8094
FU HIV-Associated Malignancies Pilot Project Award (National Cancer
Institute), National Institutes of Health (NIH) [R01CA148768,
R01CA142723]; Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research
FX This work was supported by the HIV-Associated Malignancies Pilot Project
Award (National Cancer Institute), National Institutes of Health (NIH)
Grants R01CA148768 and R01CA142723 (to J.Y.) and the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 43
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U1 0
U2 14
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1003021
DI 10.1371/journal.ppat.1003021
PG 16
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100038
PM 23144621
ER
PT J
AU Wise, HM
Hutchinson, EC
Jagger, BW
Stuart, AD
Kang, ZH
Robb, N
Schwartzman, LM
Kash, JC
Fodor, E
Firth, AE
Gog, JR
Taubenberger, JK
Digard, P
AF Wise, Helen M.
Hutchinson, Edward C.
Jagger, Brett W.
Stuart, Amanda D.
Kang, Zi H.
Robb, Nicole
Schwartzman, Louis M.
Kash, John C.
Fodor, Ervin
Firth, Andrew E.
Gog, Julia R.
Taubenberger, Jeffery K.
Digard, Paul
TI Identification of a Novel Splice Variant Form of the Influenza A Virus
M2 Ion Channel with an Antigenically Distinct Ectodomain
SO PLOS PATHOGENS
LA English
DT Article
ID PROTEIN CYTOPLASMIC TAIL; M1 MESSENGER-RNA; MONOCLONAL-ANTIBODY;
MEMBRANE-PROTEINS; MATRIX PROTEIN-2; AVIAN INFLUENZA; TISSUE-CULTURE;
NUCLEAR EXPORT; NS1 PROTEIN; SEGMENT 2
AB Segment 7 of influenza A virus produces up to four mRNAs. Unspliced transcripts encode M1, spliced mRNA2 encodes the M2 ion channel, while protein products from spliced mRNAs 3 and 4 have not previously been identified. The M2 protein plays important roles in virus entry and assembly, and is a target for antiviral drugs and vaccination. Surprisingly, M2 is not essential for virus replication in a laboratory setting, although its loss attenuates the virus. To better understand how IAV might replicate without M2, we studied the reversion mechanism of an M2-null virus. Serial passage of a virus lacking the mRNA2 splice donor site identified a single nucleotide pseudoreverting mutation, which restored growth in cell culture and virulence in mice by upregulating mRNA4 synthesis rather than by reinstating mRNA2 production. We show that mRNA4 encodes a novel M2-related protein (designated M42) with an antigenically distinct ectodomain that can functionally replace M2 despite showing clear differences in intracellular localisation, being largely retained in the Golgi compartment. We also show that the expression of two distinct ion channel proteins is not unique to laboratory-adapted viruses but, most notably, was also a feature of the 1983 North American outbreak of H5N2 highly pathogenic avian influenza virus. In identifying a 14th influenza A polypeptide, our data reinforce the unexpectedly high coding capacity of the viral genome and have implications for virus evolution, as well as for understanding the role of M2 in the virus life cycle.
C1 [Wise, Helen M.; Hutchinson, Edward C.; Jagger, Brett W.; Stuart, Amanda D.; Kang, Zi H.; Firth, Andrew E.; Digard, Paul] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England.
[Wise, Helen M.; Digard, Paul] Univ Edinburgh, Roslin Inst, Easter Bush, Midlothian, Scotland.
[Jagger, Brett W.; Schwartzman, Louis M.; Kash, John C.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Gog, Julia R.] Univ Cambridge, Ctr Math Sci, DAMTP, Cambridge, England.
[Robb, Nicole; Fodor, Ervin] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England.
RP Wise, HM (reprint author), Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England.
EM paul.digard@roslin.ed.ac.uk
RI Digard, Paul/B-7717-2008; Hutchinson, Edward/M-7136-2016;
OI Digard, Paul/0000-0002-0872-9440; Hutchinson,
Edward/0000-0003-3673-9096; Firth, Andrew/0000-0002-7986-9520
FU UK Medical Research Council [G0700815, G0801931, G0700848]; Wellcome
Trust [088789, 075450]; National Institutes of Health-Oxford/Cambridge
Research Scholars Program; US National Institutes of Health; NIAID
FX This work was supported by grants from the UK Medical Research Council
(nos. G0700815 and G0801931 to PD, and G0700848 to EF), the Wellcome
Trust (no. 088789 to AEF and 075450 to ECH/PD), the National Institutes
of Health-Oxford/Cambridge Research Scholars Program (to BWJ, PD and
JKT) and in part by the intramural funds of the US National Institutes
of Health and NIAID (to JKT). The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 62
TC 77
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U1 3
U2 22
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD NOV
PY 2012
VL 8
IS 11
AR e1002998
DI 10.1371/journal.ppat.1002998
PG 14
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA 049PY
UT WOS:000311997100019
PM 23133386
ER
PT J
AU Roshandel, G
Semnani, S
Malekzadeh, R
Dawsey, SM
AF Roshandel, Gholamreza
Semnani, Shahryar
Malekzadeh, Reza
Dawsey, Sanford M.
TI Polycyclic Aromatic Hydrocarbons and Esophageal Squamous Cell Carcinoma
SO ARCHIVES OF IRANIAN MEDICINE
LA English
DT Review
DE Carcinogen; esophageal cancer; Iran; polycyclic aromatic hydrocarbons
ID WHITE BLOOD-CELLS; INDOOR AIR-POLLUTION; 1-HYDROXYPYRENE GLUCURONIDE
CONCENTRATIONS; URINARY HYDROXYLATED METABOLITES; HIGH-RISK POPULATION;
NORTH-EASTERN IRAN; COKE-OVEN WORKERS; PAH-DNA-ADDUCTS; GRANDE-DO-SUL;
OCCUPATIONAL-EXPOSURE
AB Esophageal cancer (EC) is the 8th most common cancer and the eh most frequent cause of cancer mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common type of EC. Exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested as a risk factor for developing ESCC. In this paper we will review different aspects of the relationship between PAH exposure and ESCC.
PAHs are a group of compounds that are formed by incomplete combustion of organic matter. Studies in humans have shown an association between PAH exposure and development of ESCC in many populations. The results of a recent case-control study in a high risk population in northeastern Iran showed a dramatic dose-response relationship between PAH content in non-tumor esophageal tissue (the target tissue for esophageal carcinogenesis) and ESCC case status, consistent with a causal role for PAH exposure in the pathogenesis of ESCC.
Identifying the main sources of exposure to PAHs may be the first and most important step in designing appropriate PAH-reduction interventions for controlling ESCC, especially in high risk areas. Coal smoke and drinking mate have been suggested as important modifiable sources of PAH exposure in China and Brazil, respectively. But the primary source of exposure to PAHs in other high risk areas for ESCC, such as northeastern Iran, has not yet been identified. Thus, environmental studies to determining important sources of PAH exposure should be considered as a high priority in future research projects in these areas.
C1 [Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20895 USA.
[Roshandel, Gholamreza; Semnani, Shahryar] Golestan Univ Med Sci, Golestan Res Ctr Gastroenterol & Hepatol, Gorgan, Iran.
[Roshandel, Gholamreza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran.
RP Dawsey, SM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320, Bethesda, MD 20895 USA.
EM dawseys@mail.nih.gov
RI Roshandel, gholamreza/N-2260-2016; Semnani, Shahryar/N-2270-2016;
OI Roshandel, gholamreza/0000-0002-5494-0722; Semnani,
Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics at the National Cancer Institute of the National Institutes of
Health
FX Preparation of this review was supported in part by the Intramural
Research Program of the Division of Cancer Epidemiology and Genetics at
the National Cancer Institute of the National Institutes of Health.
NR 141
TC 8
Z9 8
U1 1
U2 19
PU ACAD MEDICAL SCIENCES I R IRAN
PI TEHRAN
PA PO BOX 19395-5655, TEHRAN, 00000, IRAN
SN 1029-2977
J9 ARCH IRAN MED
JI Arch. Iran. Med.
PD NOV
PY 2012
VL 15
IS 11
BP 713
EP 722
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 049EQ
UT WOS:000311965400011
PM 23102250
ER
PT J
AU Cecchini, RS
Costantino, JP
Cauley, JA
Cronin, WM
Wickerham, DL
Bandos, H
Weissfeld, JL
Wolmark, N
AF Cecchini, Reena S.
Costantino, Joseph P.
Cauley, Jane A.
Cronin, Walter M.
Wickerham, D. Lawrence
Bandos, Hanna
Weissfeld, Joel L.
Wolmark, Norman
TI Baseline Mammographic Breast Density and the Risk of Invasive Breast
Cancer in Postmenopausal Women Participating in the NSABP Study of
Tamoxifen and Raloxifene (STAR)
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID SURGICAL ADJUVANT BREAST; AMERICAN WOMEN; BOWEL PROJECT; ROC CURVES; P-2
TRIAL; MODEL; VALIDATION; PREDICTION; MARKER; PREVENTION
AB Mammographic breast density is an established risk factor for breast cancer. However, results are inconclusive regarding its use in risk prediction models. The current study evaluated 13,409 postmenopausal participants in the NSABP Study of Tamoxifen and Raloxifene. A measure of breast density as reported on the entry mammogram report was extracted and categorized according to The American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) classifications. An increased risk of invasive breast cancer was associated with higher mammographic breast density (P < 0.001). The association remained significant after adjusting for age, treatment, and smoking history [HR 1.35, 95% confidence interval (CI): 1.16-1.58], as well as when added to a model including the Gail score (HR 1.33,95% CI: 1.14-1.55). At five years after random assignment, time-dependent area under the curve (AUC) improved from 0.63 for a model with Gail score alone to 0.64 when considering breast density and Gail score. Breast density was also significant when added to an abbreviated model tailored for estrogen receptor-positive breast cancers (P = 0.02). In this study, high BI-RADS breast density was significantly associated with increased breast cancer risk when considered in conjunction with Gail score but provided only slight improvement to the Gail score for predicting the incidence of invasive breast cancer. The BI-RADS breast composition classification system is a quick and readily available method for assessing breast density for risk prediction evaluations; however, its addition to the Gail model does not seem to provide substantial predictability improvements in this population of postmenopausal healthy women at increased risk for breast cancer. Cancer Prev Res; 5(11); 1321-9. (C) 2012 AACR.
C1 [Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Wickerham, D. Lawrence; Bandos, Hanna; Wolmark, Norman] NSABP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA.
[Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Wickerham, D. Lawrence; Bandos, Hanna; Wolmark, Norman] NSABP Operat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15213 USA.
[Cecchini, Reena S.; Costantino, Joseph P.; Cronin, Walter M.; Bandos, Hanna] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Cauley, Jane A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Wickerham, D. Lawrence; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Inst Canc, Pittsburgh, PA 15261 USA.
RP Cecchini, RS (reprint author), NSABP Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, 1 Sterling Plaza,201 N Craig St,Suite 350, Pittsburgh, PA 15213 USA.
EM cecchini@nsabp.pitt.edu
OI Cecchini, Reena/0000-0002-9075-9357; Cauley, Jane A/0000-0003-0752-4408
FU Public Health Service grants from the National Cancer Institute,
Department of Health and Human Services [U10-CA-12027, U10-CA-69651,
U10-CA-37377, U10-CA-69974]; Zeneca Pharmaceuticals, business unit of
ZENECA Inc.; Eli Lilly and Company
FX This work was supported by the Public Health Service grants
(U10-CA-12027, U10-CA-69651, U10-CA-37377, and U10-CA-69974) from the
National Cancer Institute, Department of Health and Human Services;
Zeneca Pharmaceuticals, a business unit of ZENECA Inc., and Eli Lilly
and Company
NR 38
TC 9
Z9 11
U1 0
U2 2
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 NOV
PY 2012
VL 5
IS 11
BP 1321
EP 1329
DI 10.1158/1940-6207.CAPR-12-0273
PG 9
WC Oncology
SC Oncology
GA 049VH
UT WOS:000312011000008
PM 23060039
ER
PT J
AU Widemann, BC
Kim, A
Fox, E
Baruchel, S
Adamson, PC
Ingle, AM
Bender, JG
Burke, M
Weigel, B
Stempak, D
Balis, FM
Blaney, SM
AF Widemann, Brigitte C.
Kim, AeRang
Fox, Elizabeth
Baruchel, Sylvain
Adamson, Peter C.
Ingle, Ashish M.
Bender, Julia Glade
Burke, Michael
Weigel, Brenda
Stempak, Diana
Balis, Frank M.
Blaney, Susan M.
TI A Phase I Trial and Pharmacokinetic Study of Sorafenib in Children with
Refractory Solid Tumors or Leukemias: A Children's Oncology Group Phase
I Consortium Report
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; FACTOR RECEPTOR INHIBITOR; ACUTE MYELOGENOUS
LEUKEMIA; RENAL-CELL CARCINOMA; DAYS ON/7 DAYS; RAF KINASE;
HEPATOCELLULAR-CARCINOMA; MULTIKINASE INHIBITOR; GROWTH; CANCER
AB Purpose: To determine the dose-limiting toxicities (DLT), maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of sorafenib in children with refractory extracranial solid tumors and evaluate the tolerability of the solid tumor MTD in children with refractory leukemias.
Experimental Design: Sorafenib was administered orally every 12 hours for consecutive 28-day cycles. Pharmacokinetics (day 1 and steady-state) and pharmacodynamics were conducted during cycle 1.
Results: Of 65 patients enrolled, 60 were eligible. In the solid tumor cohort (n = 49), 4 of 6 patients experienced a DLT [hypertension, pain, rash/urticaria, thrombocytopenia, alanine aminotransferase (ALT)/aspartate aminotransferase (AST)] at the starting dose (150 mg/m(2)/dose) which resulted in de-escalation to 105 mg/m(2)/dose. After eligibility criteria modification and dose re-escalation, the MTD was 200 mg/m(2)/dose for solid tumors and 150 mg/m(2)/dose for leukemias. Sorafenib exposure was highly variable between patients but was within the ranges reported in adults. The apparent sorafenib clearance increased with patient age. Diarrhea, rash, fatigue, and increased ALT/AST were the most common sorafenib-related toxicities. Stable disease for 4 or more cycles was observed in 14 solid tumor patients, and 2 patients with acute myeloid leukemia (AML) and FLT3 internal tandem duplication (FLT3ITD) experienced a decrease in bone marrow blasts to less than 5%.
Conclusions: The recommended phase II dose of sorafenib administered every 12 hours continuously for children with solid tumors is 200 mg/m(2)/dose and 150 mg/m(2)/dose for children with leukemias. Sorafenib toxicities and distribution in children are similar to adults. The activity of sorafenib in children with AML and FLT3ITD is currently being evaluated, and a phase II study for select solid tumors is ongoing. Clin Cancer Res; 18(21); 6011-22. (C) 2012 AACR.
C1 [Widemann, Brigitte C.; Kim, AeRang] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Kim, AeRang] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Fox, Elizabeth; Adamson, Peter C.; Balis, Frank M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Baruchel, Sylvain; Stempak, Diana] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Ingle, Ashish M.] Operat Ctr, Childrens Oncol Grp, Arcadia, CA USA.
[Bender, Julia Glade] Columbia Univ, Med Ctr, New York, NY USA.
[Burke, Michael; Weigel, Brenda] Univ Minnesota, Med Ctr Fairview, Minneapolis, MN USA.
[Blaney, Susan M.] Texas Childrens Canc Ctr, Houston, TX USA.
RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC,Room 1-5750, Bethesda, MD 20892 USA.
EM widemanb@mail.nih.gov
FU NIH, National Cancer Institute (NCI), Center for Cancer Research; Phase
I/Pilot Consortium Grant of the Children's Oncology Group from the NCI,
NIH, Bethesda, MD [U01 CA97452]
FX This research was in part supported by the Intramural Research Program
of the NIH, National Cancer Institute (NCI), Center for Cancer Research,
and by the Phase I/Pilot Consortium Grant U01 CA97452 of the Children's
Oncology Group from the NCI, NIH, Bethesda, MD.
NR 32
TC 37
Z9 38
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2012
VL 18
IS 21
BP 6011
EP 6022
DI 10.1158/1078-0432.CCR-11-3284
PG 12
WC Oncology
SC Oncology
GA 049YV
UT WOS:000312020400020
PM 22962440
ER
PT J
AU Lee, EQ
Puduvalli, VK
Reid, JM
Kuhn, JG
Lamborn, KR
Cloughesy, TF
Chang, SM
Drappatz, J
Yung, WKA
Gilbert, MR
Robins, HI
Lieberman, FS
Lassman, AB
McGovern, RM
Xu, JH
Desideri, S
Ye, XB
Ames, MM
Espinoza-Delgado, I
Prados, MD
Wen, PY
AF Lee, Eudocia Q.
Puduvalli, Vinay K.
Reid, Joel M.
Kuhn, John G.
Lamborn, Kathleen R.
Cloughesy, Timothy F.
Chang, Susan M.
Drappatz, Jan
Yung, W. K. Alfred
Gilbert, Mark R.
Robins, H. Ian
Lieberman, Frank S.
Lassman, Andrew B.
McGovern, Renee M.
Xu, Jihong
Desideri, Serena
Ye, Xiabu
Ames, Matthew M.
Espinoza-Delgado, Igor
Prados, Michael D.
Wen, Patrick Y.
TI Phase I Study of Vorinostat in Combination with Temozolomide in Patients
with High-Grade Gliomas: North American Brain Tumor Consortium Study
04-03
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SUBEROYLANILIDE HYDROXAMIC ACID; HISTONE DEACETYLASE INHIBITOR; ADJUVANT
TEMOZOLOMIDE; TRIAL; GLIOBLASTOMA; SAHA; RADIOTHERAPY; CONCOMITANT;
GROWTH; CANCER
AB Purpose: A phase I, dose-finding study of vorinostat in combination with temozolomide (TMZ) was conducted to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics in patients with high-grade glioma (HGG).
Experimental Design: This phase I, dose-finding, investigational study was conducted in two parts. Part 1 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days every 28 days. Part 2 was a dose-escalation study of vorinostat in combination with TMZ 150 mg/m(2)/day for 5 days of the first cycle and 200 mg/m(2)/day for 5 days of the subsequent 28-day cycles.
Results: In part 1, the MTD of vorinostat administered on days 1 to 7 and 15 to 21 of every 28-day cycle, in combination with TMZ, was 500 mg daily. Dose-limiting toxicities (DLT) included grade 3 anorexia, grade 3 ALT, and grade 5 hemorrhage in the setting of grade 4 thrombocytopenia. In part 2, the MTD of vorinostat on days 1 to 7 and 15 to 21 of every 28-day cycle, combined with TMZ, was 400 mg daily. No DLTs were encountered, but vorinostat dosing could not be escalated further due to thrombocytopenia. The most common serious adverse events were fatigue, lymphopenia, thrombocytopenia, and thromboembolic events. There were no apparent pharmacokinetic interactions between vorinostat and TMZ. Vorinostat treatment resulted in hyperacetylation of histones H3 and H4 in peripheral mononuclear cells.
Conclusion: Vorinostat in combination with temozolomide is well tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in newly diagnosed glioblastoma is underway. Clin Cancer Res; 18(21); 6032-9. (C) 2012 AACR.
C1 [Lee, Eudocia Q.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Puduvalli, Vinay K.; Yung, W. K. Alfred; Gilbert, Mark R.; Xu, Jihong] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Reid, Joel M.; McGovern, Renee M.; Ames, Matthew M.] Mayo Clin, Ctr Comprehens Canc, Rochester, MN USA.
[Kuhn, John G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Lamborn, Kathleen R.; Chang, Susan M.; Prados, Michael D.] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Drappatz, Jan; Lieberman, Frank S.] Univ Pittsburgh, Med Ctr, Ctr Canc, Pittsburgh, PA USA.
[Robins, H. Ian] Univ Wisconsin, Madison, WI USA.
[Lassman, Andrew B.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Desideri, Serena; Ye, Xiabu] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Wen, PY (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,SW 430, Boston, MA 02215 USA.
EM pwen@partners.org
RI Puduvalli, Vinay/A-2411-2016; Gilbert, Mark/J-7494-2016
OI Gilbert, Mark/0000-0003-2556-9722
FU NIH [U01 CA062399]; Merck; UpToDate; DEMOS Publishers; Genentech;
Celgene; Schering; Abbott; Campus Bio; Eisai; GSK;
Merck/Schering-Plough; Novartis; Kyowa Hakko Kirin Pharma; Keryx; Sigma
Tau; Amgen; AstraZeneca; Esai; Sanofi-Aventis; Genzyme; Medimmune;
Vascular Biogenics
FX E. Q. Lee is on advisory board for Novartis and has royalties from
UpToDate and DEMOS Publishers. Vinay K. Puduvalli has a research grant
support from Merck, Genentech, and Celgene and is on advisory board for
Novartis. Joel M. Reid has a funding from Merck for PK analysis. T. F.
Cloughesy is a consultant/advisory member of Merck, Roche, Merck Sorano,
Celgene, and Novartis, has honoraria from speakers bureau from Merck,
and honoraria from ad board from Genentech and Roche. Susan M. Chang has
a research support from Schering. Mark R. Gilbert is on advisory boards
of Merck, Genentech and Abbott and has honoraria from Merck, Genentech
and Abbott. H. Ian Robins is a consultant/advisory board member of
Genentech and Abbott. Andrew B. Lassman is a consultant/advisory board
member, is a Speaker, and has research funding from Abbott, Campus Bio,
Eisai, Genentech, GSK, Merck/Schering-Plough, Novartis, Kyowa Hakko
Kirin Pharma, Keryx, Sigma Tau. R. M. McGovern and Matthew M. Ames have
funding from Merck for PK analysis. Patrick Y. Wen is a consultant/
advisory board member of Novartis and Merck, is a paid speaker for
Merck, has research support from Amgen, AstraZeneca, Esai,
Sanofi-Aventis, Genentech, Genzyme, Novartis, Medimmune, Vascular
Biogenics, and has royalties from UpToDate and DEMOS Publishers. No
potential conflicts of interest were disclosed by other authors.; This
study was sponsored by NIH Grant number U01 CA062399. Funding for
pharmacokinetic analysis was provided by Merck.
NR 14
TC 20
Z9 22
U1 1
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2012
VL 18
IS 21
BP 6032
EP 6039
DI 10.1158/1078-0432.CCR-12-1841
PG 8
WC Oncology
SC Oncology
GA 049YV
UT WOS:000312020400022
PM 22923449
ER
PT J
AU Matsui, S
Simon, R
Qu, PP
Shaughnessy, JD
Barlogie, B
Crowley, J
AF Matsui, Shigeyuki
Simon, Richard
Qu, Pingping
Shaughnessy, John D., Jr.
Barlogie, Bart
Crowley, John
TI Developing and Validating Continuous Genomic Signatures in Randomized
Clinical Trials for Predictive Medicine
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MULTIPLE-MYELOMA; BREAST-CANCER; EXPRESSION; SURVIVAL; CLASSIFICATION;
SELECTION; DESIGN; GENES; MODEL; BIAS
AB Purpose: It is highly challenging to develop reliable diagnostic tests to predict patients' responsiveness to anticancer treatments on clinical endpoints before commencing the definitive phase III randomized trial. Development and validation of genomic signatures in the randomized trial can be a promising solution. Such signatures are required to predict quantitatively the underlying heterogeneity in the magnitude of treatment effects.
Experimental Design: We propose a framework for developing and validating genomic signatures in randomized trials. Codevelopment of predictive and prognostic signatures can allow prediction of patient-level survival curves as basic diagnostic tools for treating individual patients.
Results: We applied our framework to gene-expression microarray data from a large-scale randomized trial to determine whether the addition of thalidomide improves survival for patients with multiple myeloma. The results indicated that approximately half of the patients were responsive to thalidomide, and the average improvement in survival for the responsive patients was statistically significant. Cross-validated patient-level survival curves were developed to predict survival distributions of individual future patients as a function of whether or not they are treated with thalidomide and with regard to their baseline prognostic and predictive signature indices.
Conclusion: The proposed framework represents an important step toward reliable predictive medicine. It provides an internally validated mechanism for using randomized clinical trials to assess treatment efficacy for a patient population in a manner that takes into consideration the heterogeneity in patients' responsiveness to treatment. It also provides cross-validated patient-level survival curves that can be used for selecting treatments for future patients. Clin Cancer Res; 18(21); 6065-73. (C) 2012 AACR.
C1 [Matsui, Shigeyuki] Inst Stat Math, Dept Data Sci, Tachikawa, Tokyo 1908562, Japan.
[Simon, Richard] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD USA.
[Shaughnessy, John D., Jr.; Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
RP Matsui, S (reprint author), Inst Stat Math, Dept Data Sci, 10-3 Midori Cho, Tachikawa, Tokyo 1908562, Japan.
EM smatsui@ism.ac.jp
FU NCI NIH HHS [P01 CA055819]
NR 24
TC 11
Z9 12
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2012
VL 18
IS 21
BP 6065
EP 6073
DI 10.1158/1078-0432.CCR-12-1206
PG 9
WC Oncology
SC Oncology
GA 049YV
UT WOS:000312020400026
PM 22927484
ER
PT J
AU Giacoia, GP
Taylor-Zapata, P
Zajicek, A
AF Giacoia, George P.
Taylor-Zapata, Perdita
Zajicek, Anne
TI Eunice Kennedy Shriver National Institute of Child Health and Human
Development Pediatrics Formulation Initiative: Proceedings from the
Second Workshop on Pediatric Formulations
SO CLINICAL THERAPEUTICS
LA English
DT Editorial Material
DE pediatric formulations; drug delivery systems; novel formulations
ID DRUG-DELIVERY; YOUNG-CHILDREN; BEVACIZUMAB; MEDICINES; EFFICACY; SAFETY
AB Background: The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) organized a workshop held in November 2011 to address knowledge gaps that limit the availability of adequate pediatric formulations. This workshop was used as a means to identify the types of research innovations needed and to stimulate research efforts designed to improve the availability of pediatric formulations and the technologies required to make these formulations.
Methods: Information for this article was gathered from the proceedings of the Second US PFI Workshop sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development in Bethesda, Maryland, on November 1 and 2, 2011, as well as from post-workshop discussions. The workshop preparation began with formation of 4 working groups: Biopharmaceutics, Biopharmaceutics Classification System (BCS), New Technology and Drug Delivery Systems, and Taste and Flavor.
Results: The recommendations of the 4 working groups will form the basis for the development of a blueprint to guide future research efforts. The pediatric-specific problems identified include the heterogeneity of the population, the small size of the pediatric drug market, the limited number of new formulations for the large number of off-patent and unlabeled drugs, and the lack of universal agreement on how to define appropriate formulations for different ages and stages of development. There was consensus on the need to develop a universal technology platform for flexible pediatric dosage forms, transforming an empirical process into a science-based platform. A number of problems affect the availability of drugs in the developing world. Age-appropriate solid oral pediatric medicines for common diseases can have a global impact. Success on a global scale depends on the commitment of policy makers, regulators, scientists, pharmaceutical companies, sponsors, government, and research foundations to address gaps in knowledge and solve public health issues related to the availability of formulations in the developing world.
Conclusions: Solutions to the worldwide lack of appropriate pediatric formulations will require the development of a road map and the commitment of policy makers, regulators, scientists, pharmaceutical sponsors, academic institutions, governments, and research foundations. The development of a universal, cost-effective platform using existing or developing innovative technology that produces flexible pediatric dosage forms remains an important but elusive goal. (Clin Ther. 2012;34: S1-S10) Published by Elsevier HS Journals, Inc.
C1 [Giacoia, George P.; Taylor-Zapata, Perdita; Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pharmacol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Giacoia, GP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pharmacol Branch, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Room 4A01C MSC 7510, Bethesda, MD 20892 USA.
EM giacoiag@exchange.nih.gov
NR 28
TC 12
Z9 13
U1 1
U2 11
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
J9 CLIN THER
JI Clin. Ther.
PD NOV
PY 2012
VL 34
IS 11
BP S1
EP S10
DI 10.1016/j.clinthera.2012.09.013
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 051GS
UT WOS:000312114900007
PM 23149008
ER
PT J
AU Zhang, XM
Qi, QB
Zhang, CL
Hu, FB
Sacks, FM
Qi, L
AF Zhang, Xiaomin
Qi, Qibin
Zhang, Cuilin
Hu, Frank B.
Sacks, Frank M.
Qi, Lu
TI FTO Genotype and 2-Year Change in Body Composition and Fat Distribution
in Response to Weight-Loss Diets The POUNDS LOST Trial
SO DIABETES
LA English
DT Article
ID VISCERAL ADIPOSE-TISSUE; GENE-EXPRESSION; COMMON VARIANT; ADULT OBESITY;
MASS INDEX; ASSOCIATION; RS9939609; HUMANS; WOMEN; INTERVENTION
AB Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902. Diabetes 61:3005-3011, 2012
C1 [Zhang, Xiaomin; Qi, Qibin; Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Zhang, Xiaomin] Huazhong Univ Sci & Technol, Dept Occupat & Environm Hlth, Wuhan 430074, Peoples R China.
[Zhang, Xiaomin] Huazhong Univ Sci & Technol, Key Lab Environm & Hlth, Tongji Med Coll, Minist Educ,Sch Publ Hlth, Wuhan 430074, Peoples R China.
[Zhang, Cuilin] Eunice Kennedy Shrivel Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA.
[Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Hu, Frank B.; Sacks, Frank M.; Qi, Lu] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
RP Qi, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM nhlqi@channing.harvard.edu
FU National Heart, Lung, and Blood Institute [HL071981]; National Institute
of Diabetes and Digestive and Kidney Diseases [DK091718]; General
Clinical Research Center [RR-02635]; Boston Obesity Nutrition Research
Center [DK46200]; American Heart Association [0730094N]; Eunice Kennedy
Shriver National Institute of Child Health & Human Development, National
Institutes of Health; National Natural Science Foundation of China
[NNSFC 30972453]
FX This study was supported by grants from the National Heart, Lung, and
Blood Institute (HL071981), the National Institute of Diabetes and
Digestive and Kidney Diseases (DK091718), the General Clinical Research
Center (RR-02635), and the Boston Obesity Nutrition Research Center
(DK46200). L.Q. was a recipient of the American Heart Association
Scientist Development Award (0730094N). C.Z. was supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health & Human Development, National Institutes of
Health. X.Z. was supported by the National Natural Science Foundation of
China (NNSFC 30972453).
NR 39
TC 39
Z9 39
U1 0
U2 6
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2012
VL 61
IS 11
BP 3005
EP 3011
DI 10.2337/db11-1799
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 050GQ
UT WOS:000312041600040
PM 22891219
ER
PT J
AU Howson, JMM
Cooper, JD
Smyth, DJ
Walker, NM
Stevens, H
She, JX
Eisenbarth, GS
Rewers, M
Todd, JA
Akolkar, B
Concannon, P
Erlich, HA
Julier, C
Morahan, G
Nerup, J
Nierras, C
Pociot, F
Rich, SS
AF Howson, Joanna M. M.
Cooper, Jason D.
Smyth, Deborah J.
Walker, Neil M.
Stevens, Helen
She, Jin-Xiong
Eisenbarth, George S.
Rewers, Marian
Todd, John A.
Akolkar, Beena
Concannon, Patrick
Erlich, Henry A.
Julier, Cecile
Morahan, Grant
Nerup, Jorn
Nierras, Concepcion
Pociot, Flemming
Rich, Stephen S.
CA Type 1 Diabet Genetics Consortium
TI Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1
Diabetes
SO DIABETES
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CTLA4 GENES; CLASS-I; HLA-B; PTPN22;
SUSCEPTIBILITY; VARIANTS; GENOTYPE; MELLITUS; DISEASES
AB The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 x 10(-6) and 2.5 x 10(-5), respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 X 10(-5)). No evidence of differential risk by sex was obtained at any loci (P >= 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease. Diabetes 61:3012-3017, 2012
C1 [Howson, Joanna M. M.; Cooper, Jason D.; Smyth, Deborah J.; Walker, Neil M.; Stevens, Helen; Todd, John A.] Univ Cambridge, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Dept Med Genet, Cambridge, England.
[She, Jin-Xiong] Georgia Hlth Sci Univ, Ctr Biotechnol & Genom Med, Augusta, GA USA.
[Eisenbarth, George S.; Rewers, Marian] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Akolkar, Beena] NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD USA.
[Concannon, Patrick] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA.
[Concannon, Patrick; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Erlich, Henry A.] Roche Mol Syst, Pleasanton, CA USA.
[Julier, Cecile] Univ Paris 07, Paris, France.
[Morahan, Grant] Univ Western Australia, Ctr Diabet Res, Western Australian Inst Med Res, Perth, WA 6009, Australia.
[Morahan, Grant] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia.
[Nerup, Jorn] Steno Diabet Ctr, DK-2820 Gentofte, Denmark.
[Nerup, Jorn] Hagedorn Res Inst, Gentofte, Denmark.
[Nierras, Concepcion] Juvenile Diabet Res Fdn, New York, NY USA.
[Pociot, Flemming] Glostrup Cty Hosp, Glostrup Res Inst, Glostrup, Denmark.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA.
RP Howson, JMM (reprint author), Univ Cambridge, Wellcome Trust Diabet & Inflammat Lab, Cambridge Inst Med Res, Juvenile Diabet Res Fdn,Dept Med Genet, Cambridge, England.
EM joanna.howson@cimr.cam.ac.uk
RI Todd, John/A-3542-2010;
OI Walker, Neil/0000-0001-9796-7688; smyth, deborah/0000-0002-6330-2669;
Concannon, Patrick/0000-0002-5801-1859; Pociot,
Flemming/0000-0003-3274-5448
FU National Institute of Diabetes and Digestive and Kidney Diseases;
National Institute of Allergy and Infectious Diseases; National Human
Genome Research Institute; National Institute of Child Health and Human
Development; Juvenile Diabetes Research Foundation International (JDRF);
Wellcome Trust (WT) [076113]; National Institute for Health Research
Cambridge Biomedical Centre; WT Strategic Award [079895]; JDRF; [U01
DK-062418]
FX This research uses resources provided by the T1DGC, a collaborative
clinical study sponsored by the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institute of Allergy and
Infectious Diseases, National Human Genome Research Institute, National
Institute of Child Health and Human Development, and Juvenile Diabetes
Research Foundation International (JDRF) and is supported by U01
DK-062418. This work was funded by the JDRF, the Wellcome Trust (WT),
under award 076113, and by the National Institute for Health Research
Cambridge Biomedical Centre. The Cambridge Institute for Medical
Research (CIMR) is in receipt of a WT Strategic Award (079895). T1DGC
supplied samples.
NR 29
TC 24
Z9 25
U1 1
U2 10
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD NOV
PY 2012
VL 61
IS 11
BP 3012
EP 3017
DI 10.2337/db11-1694
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 050GQ
UT WOS:000312041600041
PM 22891215
ER
PT J
AU Katz, DM
Berger-Sweeney, JE
Eubanks, JH
Justice, MJ
Neul, JL
Pozzo-Miller, L
Blue, ME
Christian, D
Crawley, JN
Giustetto, M
Guy, J
Howell, CJ
Kron, M
Nelson, SB
Samaco, RC
Schaevitz, LR
St Hillaire-Clarke, C
Young, JL
Zoghbi, HY
Mamounas, LA
AF Katz, David M.
Berger-Sweeney, Joanne E.
Eubanks, James H.
Justice, Monica J.
Neul, Jeffrey L.
Pozzo-Miller, Lucas
Blue, Mary E.
Christian, Diana
Crawley, Jacqueline N.
Giustetto, Maurizio
Guy, Jacky
Howell, C. James
Kron, Miriam
Nelson, Sacha B.
Samaco, Rodney C.
Schaevitz, Laura R.
St Hillaire-Clarke, Coryse
Young, Juan L.
Zoghbi, Huda Y.
Mamounas, Laura A.
TI Preclinical research in Rett syndrome: setting the foundation for
translational success
SO DISEASE MODELS & MECHANISMS
LA English
DT Review
ID MECP2 MUTANT MICE; SEVERE MENTAL-RETARDATION; CPG-BINDING PROTEIN-2;
NEUROTROPHIC FACTOR EXPRESSION; MOUSE MODEL; BEHAVIORAL-PHENOTYPE;
RESPIRATORY-FUNCTION; SYNAPTIC PLASTICITY; SOCIAL INTERACTIONS;
PYRAMIDAL NEURONS
AB In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (N H), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.
C1 [Katz, David M.; Christian, Diana; Howell, C. James; Kron, Miriam] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44120 USA.
[Berger-Sweeney, Joanne E.; Schaevitz, Laura R.] Tufts Univ, Dept Biol, Medford, MA 02155 USA.
[Eubanks, James H.] Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada.
[Justice, Monica J.; Neul, Jeffrey L.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Neul, Jeffrey L.; Samaco, Rodney C.; Zoghbi, Huda Y.] Texas Childrens Hosp, Jan & Dan Duncan Neurol Res Inst, Houston, TX 77030 USA.
[Pozzo-Miller, Lucas] Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA.
[Blue, Mary E.] Hugo W Moser Res Inst Kennedy Krieger, Baltimore, MD 21209 USA.
[Crawley, Jacqueline N.] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
[Giustetto, Maurizio] Univ Turin, Dept Neurosci, I-10126 Turin, Italy.
[Giustetto, Maurizio] Univ Turin, Natl Inst Neurosci Italy, I-10126 Turin, Italy.
[Guy, Jacky] Univ Edinburgh, Edinburgh EH9 3JR, Midlothian, Scotland.
[Nelson, Sacha B.] Brandeis Univ, Shapiro Sci Ctr, Waltham, MA 02454 USA.
[St Hillaire-Clarke, Coryse; Mamounas, Laura A.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA.
[Young, Juan L.] Hussman Inst Human Genom, Miami, FL 33136 USA.
[Zoghbi, Huda Y.] Howard Hughes Med Inst, Houston, TX 77030 USA.
RP Katz, DM (reprint author), Case Western Reserve Univ, Sch Med, Dept Neurosci, 10900 Euclid Ave, Cleveland, OH 44120 USA.
EM david.katz@case.edu; hzoghbi@bcm.edu; mamounal@ninds.nih.gov
OI Nelson, Sacha/0000-0002-0108-8599; Christian, Diana/0000-0002-1799-0771;
Neul, Jeffrey/0000-0002-5628-5872; Giustetto,
Maurizio/0000-0003-1323-4060
FU National Institute of Neurological Disorders and Stroke (NINDS); Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD); International Rett Syndrome Research Foundation (IRSF); Rett
Syndrome Research Trust (RSRT); NINDS [NS-057398, NS-065027]; Rett
Syndrome Research Trust; International Rett Syndrome Foundation (ANGEL)
[2608]; ANGEL award [2583]; Canadian Institutes of Health [MOP-106481];
Fondazione Telethon
FX Support for the September 2011 workshop on which this paper reports
('Setting Priorities for Therapy Development in Rett Syndrome') was
provided by the National Institute of Neurological Disorders and Stroke
(NINDS), the Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD), the International Rett Syndrome Research
Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT). Grant
support includes NINDS (NS-057398 to D.M.K. and NS-065027 to L.P.-M.),
Rett Syndrome Research Trust (to M.J.J.), the International Rett
Syndrome Foundation (ANGEL award 2608 to M.J.J. and ANGEL award 2583 to
D.M.K.) and Canadian Institutes of Health (MOP-106481 to J.H.E.).
NR 141
TC 64
Z9 64
U1 0
U2 23
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD NOV
PY 2012
VL 5
IS 6
BP 733
EP 745
DI 10.1242/dmm.011007
PG 13
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA 047RT
UT WOS:000311859700006
PM 23115203
ER
PT J
AU Qi, QB
Menzaghi, C
Smith, S
Liang, LM
de Rekeneire, N
Garcia, ME
Lohman, KK
Miljkovic, I
Strotmeyer, ES
Cummings, SR
Kanaya, AM
Tylavsky, FA
Satterfield, S
Ding, JZ
Rimm, EB
Trischitta, V
Hu, FB
Liu, YM
Qi, L
AF Qi, Qibin
Menzaghi, Claudia
Smith, Shelly
Liang, Liming
de Rekeneire, Nathalie
Garcia, Melissa E.
Lohman, Kurt K.
Miljkovic, Iva
Strotmeyer, Elsa S.
Cummings, Steve R.
Kanaya, Alka M.
Tylavsky, Frances A.
Satterfield, Suzanne
Ding, Jingzhong
Rimm, Eric B.
Trischitta, Vincenzo
Hu, Frank B.
Liu, Yongmei
Qi, Lu
TI Genome-wide association analysis identifies TYW3/CRYZ and NDST4 loci
associated with circulating resistin levels
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; LINKED-IMMUNOSORBENT-ASSAY; INSULIN-RESISTANCE;
PLASMA RESISTIN; SERUM RESISTIN; HEART-DISEASE; ADIPONECTIN LEVELS;
HORMONE RESISTIN; GENETIC-VARIANTS; MESSENGER-RNA
AB Resistin is a polypeptide hormone that was reported to be associated with insulin resistance, inflammation and risk of type 2 diabetes and cardiovascular disease. We conducted a genome-wide association (GWA) study on circulating resistin levels in individuals of European ancestry drawn from the two independent studies: the Nurses Health Study (n 1590) and the Health, Aging and Body Composition Study (n 1658). Single-nucleotide polymorphisms (SNPs) identified in the GWA analysis were replicated in an independent cohort of Europeans: the Gargano Family Study (n 659). We confirmed the association with a previously known locus, the RETN gene (19p13.2), and identified two novel loci near the TYW3/CRYZ gene (1p31) and the NDST4 gene (4q25), associated with resistin levels at a genome-wide significant level, best represented by SNP rs3931020 (P 6.37 10(12)) and SNP rs13144478 (P 6.19 10(18)), respectively. Gene expression quantitative trait loci analyses showed a significant cis association between the SNP rs3931020 and CRYZ gene expression levels (P 3.68 10(7)). We also found that both of these two SNPs were significantly associated with resistin gene (RETN) mRNA levels in white blood cells from 68 subjects with type 2 diabetes (both P 0.02). In addition, the resistin-rising allele of the TYW3/CRYZ SNP rs3931020, but not the NDST4 SNP rs13144478, showed a consistent association with increased coronary heart disease risk [odds ratio 1.18 (95 CI, 1.031.34); P 0.01]. Our results suggest that genetic variants in TYW3/CRYZ and NDST4 loci may be involved in the regulation of circulating resistin levels. More studies are needed to verify the associations of the SNP rs13144478 with NDST4 gene expression and resistin-related disease.
C1 [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC 27157 USA.
[Qi, Qibin; Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Liang, Liming; Rimm, Eric B.; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Menzaghi, Claudia; Trischitta, Vincenzo] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy.
[Garcia, Melissa E.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[de Rekeneire, Nathalie] Yale Univ, Sch Med, Dept Geriatr, New Haven, CT USA.
[Miljkovic, Iva; Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Cummings, Steve R.; Kanaya, Alka M.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Tylavsky, Frances A.; Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Rimm, Eric B.; Hu, Frank B.; Qi, Lu] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Trischitta, Vincenzo] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy.
RP Liu, YM (reprint author), Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
EM yoliu@wakehealth.edu; nhlqi@channing.harvard.edu
RI Strotmeyer, Elsa/F-3015-2014; Trischitta, Vincenzo/K-1487-2016;
OI Trischitta, Vincenzo/0000-0003-1174-127X; Miljkovic,
Iva/0000-0002-3155-9777; Strotmeyer, Elsa/0000-0002-4093-6036; Menzaghi,
Claudia/0000-0002-7438-8955
FU NHS; HPFS [DK091718, HL071981, U01HG004399, HL71981, HL073168, DK58845,
DK46200]; American Heart Association Scientist Development Award
[0730094N]; Merck Research Laboratories, North Wales, PA, USA; NIH/NIA
[N01AG62101, N01AG62103, N01AG62106]; NIA [1R01AG032098-01A1]; National
Institutes of Health [HHSN268200782096C]; Intramural Research Program of
the NIH, National Institute on Aging; Accordo Programma Quadro in
Materia di Ricerca Scientifica nella Regione Puglia-PST, Italian
Ministry of Health [RC2011, RC2012]; EFSD/Pfizer
FX This research in the NHS and HPFS is supported by grants DK091718,
HL071981, U01HG004399, HL71981, HL073168, U01HG004399, DK58845 and
DK46200. L. Q. is a recipient of the American Heart Association
Scientist Development Award (0730094N). The genotyping of the HPFS and
NHS CHD GWAS was supported by an unrestricted grant from Merck Research
Laboratories, North Wales, PA, USA. This research in the Health ABC was
supported by NIH/NIA contracts N01AG62101, N01AG62103 and N01AG62106.
The genome-wide association study in the Health ABC was funded by NIA
grant 1R01AG032098-01A1 to Wake Forest University Health Sciences, and
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 The Johns Hopkins University,
contract number HHSN268200782096C. This research was supported in part
by the Intramural Research Program of the NIH, National Institute on
Aging. Part of the research described in this paper was supported by
Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione
Puglia-PST 2006, an Italian Ministry of Health grant (RC2011 and
RC2012), an EFSD/Pfizer grant (C. M.).
NR 43
TC 8
Z9 8
U1 5
U2 11
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 NOV 1
PY 2012
VL 21
IS 21
BP 4774
EP 4780
DI 10.1093/hmg/dds300
PG 7
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 025DN
UT WOS:000310165500015
PM 22843503
ER
PT J
AU Boraska, V
Jeroncic, A
Colonna, V
Southam, L
Nyholt, DR
Rayner, NW
Perry, JRB
Toniolo, D
Albrecht, E
Ang, W
Bandinelli, S
Barbalic, M
Barroso, I
Beckmann, JS
Biffar, R
Boomsma, D
Campbell, H
Corre, T
Erdmann, J
Esko, T
Fischer, K
Franceschini, N
Frayling, TM
Girotto, G
Gonzalez, JR
Harris, TB
Heath, AC
Heid, IM
Hoffmann, W
Hofman, A
Horikoshi, M
Zhao, JH
Jackson, AU
Hottenga, JJ
Jula, A
Kahonen, M
Khaw, KT
Kiemeney, LA
Klopp, N
Kutalik, Z
Lagou, V
Launer, LJ
Lehtimaki, T
Lemire, M
Lokki, ML
Loley, C
Luan, JA
Mangino, M
Leach, IM
Medland, SE
Mihailov, E
Montgomery, GW
Navis, G
Newnham, J
Nieminen, MS
Palotie, A
Panoutsopoulou, K
Peters, A
Pirastu, N
Polasek, O
Rehnstrom, K
Ripatti, S
Ritchie, GRS
Rivadeneira, F
Robino, A
Samani, NJ
Shin, SY
Sinisalo, J
Smit, JH
Soranzo, N
Stolk, L
Swinkels, DW
Tanaka, T
Teumer, A
Tonjes, A
Traglia, M
Tuomilehto, J
Valsesia, A
van Gilst, WH
van Meurs, JBJ
Smith, AV
Viikari, J
Vink, JM
Waeber, G
Warrington, NM
Widen, E
Willemsen, G
Wright, AF
Zanke, BW
Zgaga, L
Boehnke, M
d'Adamo, AP
de Geus, E
Demerath, EW
den Heijer, M
Eriksson, JG
Ferrucci, L
Gieger, C
Gudnason, V
Hayward, C
Hengstenberg, C
Hudson, TJ
Jarvelin, MR
Kogevinas, M
Loos, RJF
Martin, NG
Metspalu, A
Pennell, CE
Penninx, BW
Perola, M
Raitakari, O
Salomaa, V
Schreiber, S
Schunkert, H
Spector, TD
Stumvoll, M
Uitterlinden, AG
Ulivi, S
van der Harst, P
Vollenweider, P
Volzke, H
Wareham, NJ
Wichmann, HE
Wilson, JF
Rudan, I
Xue, YL
Zeggini, E
AF Boraska, Vesna
Jeroncic, Ana
Colonna, Vincenza
Southam, Lorraine
Nyholt, Dale R.
Rayner, Nigel William
Perry, John R. B.
Toniolo, Daniela
Albrecht, Eva
Ang, Wei
Bandinelli, Stefania
Barbalic, Maja
Barroso, Ines
Beckmann, Jacques S.
Biffar, Reiner
Boomsma, Dorret
Campbell, Harry
Corre, Tanguy
Erdmann, Jeanette
Esko, Tonu
Fischer, Krista
Franceschini, Nora
Frayling, Timothy M.
Girotto, Giorgia
Gonzalez, Juan R.
Harris, Tamara B.
Heath, Andrew C.
Heid, Iris M.
Hoffmann, Wolfgang
Hofman, Albert
Horikoshi, Momoko
Zhao, Jing Hua
Jackson, Anne U.
Hottenga, Jouke-Jan
Jula, Antti
Kahonen, Mika
Khaw, Kay-Tee
Kiemeney, Lambertus A.
Klopp, Norman
Kutalik, Zoltan
Lagou, Vasiliki
Launer, Lenore J.
Lehtimaki, Terho
Lemire, Mathieu
Lokki, Marja-Liisa
Loley, Christina
Luan, Jian'an
Mangino, Massimo
Leach, Irene Mateo
Medland, Sarah E.
Mihailov, Evelin
Montgomery, Grant W.
Navis, Gerjan
Newnham, John
Nieminen, Markku S.
Palotie, Aarno
Panoutsopoulou, Kalliope
Peters, Annette
Pirastu, Nicola
Polasek, Ozren
Rehnstrom, Karola
Ripatti, Samuli
Ritchie, Graham R. S.
Rivadeneira, Fernando
Robino, Antonietta
Samani, Nilesh J.
Shin, So-Youn
Sinisalo, Juha
Smit, Johannes H.
Soranzo, Nicole
Stolk, Lisette
Swinkels, Dorine W.
Tanaka, Toshiko
Teumer, Alexander
Tonejes, Anke
Traglia, Michela
Tuomilehto, Jaakko
Valsesia, Armand
van Gilst, Wiek H.
van Meurs, Joyce B. J.
Smith, Albert Vernon
Viikari, Jorma
Vink, Jacqueline M.
Waeber, Gerard
Warrington, Nicole M.
Widen, Elisabeth
Willemsen, Gonneke
Wright, Alan F.
Zanke, Brent W.
Zgaga, Lina
Boehnke, Michael
d'Adamo, Adamo Pio
de Geus, Eco
Demerath, Ellen W.
den Heijer, Martin
Eriksson, Johan G.
Ferrucci, Luigi
Gieger, Christian
Gudnason, Vilmundur
Hayward, Caroline
Hengstenberg, Christian
Hudson, Thomas J.
Jarvelin, Marjo-Riitta
Kogevinas, Manolis
Loos, Ruth J. F.
Martin, Nicholas G.
Metspalu, Andres
Pennell, Craig E.
Penninx, Brenda W.
Perola, Markus
Raitakari, Olli
Salomaa, Veikko
Schreiber, Stefan
Schunkert, Heribert
Spector, Tim D.
Stumvoll, Michael
Uitterlinden, Andre G.
Ulivi, Sheila
van der Harst, Pim
Vollenweider, Peter
Volzke, Henry
Wareham, Nicholas J.
Wichmann, H-Erich
Wilson, James F.
Rudan, Igor
Xue, Yali
Zeggini, Eleftheria
CA Wellcome Trust Case Control
TI Genome-wide meta-analysis of common variant differences between men and
women
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID HUMAN SEX-RATIO; ASSOCIATION; SIMULATION; DISEASE; BIRTH; TIME
AB The male-to-female sex ratio at birth is constant across world populations with an average of 1.06 (106 male to 100 female live births) for populations of European descent. The sex ratio is considered to be affected by numerous biological and environmental factors and to have a heritable component. The aim of this study was to investigate the presence of common allele modest effects at autosomal and chromosome X variants that could explain the observed sex ratio at birth. We conducted a large-scale genome-wide association scan (GWAS) meta-analysis across 51 studies, comprising overall 114 863 individuals (61 094 women and 53 769 men) of European ancestry and 2 623 828 common (minor allele frequency 0.05) single-nucleotide polymorphisms (SNPs). Allele frequencies were compared between men and women for directly-typed and imputed variants within each study. Forward-time simulations for unlinked, neutral, autosomal, common loci were performed under the demographic model for European populations with a fixed sex ratio and a random mating scheme to assess the probability of detecting significant allele frequency differences. We do not detect any genome-wide significant (P 5 10(8)) common SNP differences between men and women in this well-powered meta-analysis. The simulated data provided results entirely consistent with these findings. This large-scale investigation across approximate to 115 000 individuals shows no detectable contribution from common genetic variants to the observed skew in the sex ratio. The absence of sex-specific differences is useful in guiding genetic association study design, for example when using mixed controls for sex-biased traits.
C1 [Boraska, Vesna; Colonna, Vincenza; Southam, Lorraine; Rayner, Nigel William; Barroso, Ines; Palotie, Aarno; Panoutsopoulou, Kalliope; Rehnstrom, Karola; Ritchie, Graham R. S.; Shin, So-Youn; Soranzo, Nicole; Xue, Yali; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Boraska, Vesna; Rudan, Igor] Univ Split, Sch Med, Dept Med Biol, Split, Croatia.
[Jeroncic, Ana] Univ Split, Sch Med, Dept Res Biomed & Hlth, Split, Croatia.
[Polasek, Ozren] Univ Split, Sch Med, Dept Publ Hlth, Split, Croatia.
[Colonna, Vincenza] Natl Res Council CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.
[Nyholt, Dale R.; Medland, Sarah E.; Montgomery, Grant W.; Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Rayner, Nigel William; Perry, John R. B.; Horikoshi, Momoko; Lagou, Vasiliki] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Rayner, Nigel William; Horikoshi, Momoko; Lagou, Vasiliki] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Perry, John R. B.; Frayling, Timothy M.] Univ Exeter, Peninsula Med Sch, Exeter EX4 4QJ, Devon, England.
[Perry, John R. B.; Mangino, Massimo; Soranzo, Nicole; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Toniolo, Daniela; Corre, Tanguy; Traglia, Michela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Ang, Wei; Newnham, John; Warrington, Nicole M.; Pennell, Craig E.] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Barbalic, Maja] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Cambridge, England.
[Zhao, Jing Hua; Luan, Jian'an; Loos, Ruth J. F.; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Beckmann, Jacques S.; Kutalik, Zoltan; Valsesia, Armand] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne Hosp, CHU Vaudois, Serv Med Genet, Lausanne, Switzerland.
[Biffar, Reiner] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany.
[Hoffmann, Wolfgang; Volzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Boomsma, Dorret; Hottenga, Jouke-Jan; Vink, Jacqueline M.; Willemsen, Gonneke; de Geus, Eco] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Campbell, Harry; Zgaga, Lina; Wilson, James F.; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Erdmann, Jeanette; Schunkert, Heribert] Med Univ Lubeck, Med Klin 2, Lubeck, Germany.
[Erdmann, Jeanette; Schunkert, Heribert] Deutsch Zentrum Herz Kreislauf Forsch ev DZHK, Lubeck, Germany.
[Loley, Christina] Med Univ Lubeck, Inst Med Biometrie & Stat, D-23538 Lubeck, Germany.
[Esko, Tonu; Fischer, Krista; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Girotto, Giorgia; Pirastu, Nicola; Robino, Antonietta; d'Adamo, Adamo Pio] Univ Trieste, IRCCS Burlo Garofolo Trieste, Inst Maternal & Child Hlth, I-34127 Trieste, Italy.
[Gonzalez, Juan R.; Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Gonzalez, Juan R.; Kogevinas, Manolis] CIBER Epidemiol Salud & Publ CIBERESP, Barcelona, Spain.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Heid, Iris M.] Univ Regensburg, Med Ctr, Inst Epidemiol & Prevent Med, Regensburg, Germany.
[Heid, Iris M.; Wichmann, H-Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Rivadeneira, Fernando; Stolk, Lisette; van Meurs, Joyce B. J.; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hofman, Albert; Rivadeneira, Fernando; Stolk, Lisette; van Meurs, Joyce B. J.; Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, Rotterdam, Netherlands.
[Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Populat Studies Unit, Turku, Finland.
[Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland.
[Khaw, Kay-Tee] Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England.
[Kiemeney, Lambertus A.; den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6525 ED Nijmegen, Netherlands.
[Swinkels, Dorine W.] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, NL-6525 ED Nijmegen, Netherlands.
[den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6525 ED Nijmegen, Netherlands.
[Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Klopp, Norman] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Unit Mol Epidemiol, Neuherberg, Germany.
[Kutalik, Zoltan; Valsesia, Armand] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Lemire, Mathieu; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Palotie, Aarno; Rehnstrom, Karola; Ripatti, Samuli; Widen, Elisabeth; Perola, Markus] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland.
[Leach, Irene Mateo; van Gilst, Wiek H.; van der Harst, Pim] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Navis, Gerjan] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands.
[Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
[Nieminen, Markku S.; Sinisalo, Juha] Univ Helsinki, Cent Hosp, Div Cardiol, Cardiovasc Lab, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, Aarno] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Ritchie, Graham R. S.] European Bioinformat Inst, Cambridge, England.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.
[Smit, Johannes H.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst,Ctr Neurogen & Cognit Res, Amsterdam, Netherlands.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, EMGO Inst,Inst Neurosci, Amsterdam, Netherlands.
[Tanaka, Toshiko] NIA, Clin Res Branch, NIH, Baltimore, MD 21250 USA.
[Teumer, Alexander] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.
[Tonejes, Anke; Stumvoll, Michael] Univ Leipzig, Dept Med, Leipzig, Germany.
[Tonejes, Anke; Stumvoll, Michael] Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki 00271, Finland.
[Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid 28046, Spain.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.
[Valsesia, Armand] Ludwig Inst Canc Res, Lausanne, Switzerland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland.
[Waeber, Gerard; Vollenweider, Peter] CHU Vaudois, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Zanke, Brent W.] Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41000, Croatia.
[Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Eriksson, Johan G.; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Chron Dis Epidemiol & Prevent Unit, Helsinki, Finland.
[Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Unit Publ Hlth Genom, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Univ Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA.
[Hengstenberg, Christian] Med Klin & Poliklin 2, Regensburg, Germany.
[Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Kogevinas, Manolis] IMIM Hosp Mar Res Inst, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
[Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
[Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany.
[Ulivi, Sheila] Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy.
[Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Palotie, Aarno] Univ Cent Hosp Helsinki, Helsinki, Finland.
RP Boraska, V (reprint author), Wellcome Trust Sanger Inst, Morgan Bldg,Wellcome Trust Genome Campus, Cambridge CB10 1HH, England.
EM vboraska@mefst.hr
RI Colonna, Vincenza/H-2021-2014; Erdmann, Jeanette/P-7513-2014; Jeroncic,
Ana/D-6191-2017; Boraska Perica, Vesna/D-8230-2017; Study,
Raine/G-9547-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Polasek,
Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Peters, Annette/A-6117-2011; Rudan, Igor/I-1467-2012;
Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Kogevinas, Manolis/C-3918-2017; Swinkels,
D.W./H-8098-2014; Warrington, Nicole/P-4868-2014; Pirastu,
Nicola/G-4358-2011; Medland, Sarah/C-7630-2013; Nyholt,
Dale/C-8384-2013; Beckmann, Jacques S /A-9772-2008; Ulivi,
Sheila/H-3700-2013; Colaus, PsyColaus/K-6607-2013; Lagou,
Vasiliki/N-8451-2013; d'Adamo, Adamo Pio/G-4064-2011; Kiemeney,
Lambertus/D-3357-2009; Schreiber, Stefan/B-6748-2008
OI Sinisalo, Juha/0000-0002-0169-5137; Martin,
Nicholas/0000-0003-4069-8020; Colonna, Vincenza/0000-0002-3966-0474;
Erdmann, Jeanette/0000-0002-4486-6231; Soranzo,
Nicole/0000-0003-1095-3852; Gieger, Christian/0000-0001-6986-9554;
Rivadeneira, Fernando/0000-0001-9435-9441; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; Girotto, Giorgia/0000-0003-4507-6589;
Eriksson, Johan/0000-0002-2516-2060; Newnham, John/0000-0001-9983-7457;
Jeroncic, Ana/0000-0003-1621-1956; Pirastu, Nicola/0000-0002-5363-3886;
Zeggini, Eleftheria/0000-0003-4238-659X; Zgaga,
Lina/0000-0003-4089-9703; Ritchie, Graham/0000-0002-6456-9736; Esko,
Tonu/0000-0003-1982-6569; Gudnason, Vilmundur/0000-0001-5696-0084;
Ripatti, Samuli/0000-0002-0504-1202; Wilson, James
F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; de Geus,
Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; Rudan,
Igor/0000-0001-6993-6884; Smith, Albert/0000-0003-1942-5845; mangino,
massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550;
Warrington, Nicole/0000-0003-4195-775X; Medland,
Sarah/0000-0003-1382-380X; Beckmann, Jacques S /0000-0002-9741-1900;
Ulivi, Sheila/0000-0003-3606-835X; d'Adamo, Adamo
Pio/0000-0001-9367-4909; Kiemeney, Lambertus/0000-0002-2368-1326;
Schreiber, Stefan/0000-0003-2254-7771
FU Wellcome Trust [076113, 098051]; NIH [N01-AG-1-2100, LM010098, HL65234,
HL67466, RR018787]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament);
National Heart, Lung, and Blood Institute [HHSN26820 1100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN26820 1100010C, HHSN268201100011C, HHSN2682011
00012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome
Research Institute [U01HG004402]; National Institutes of Health
[HHSN268200625226C]; National Institutes of Health and NIH Roadmap for
Medical Research [UL1RR025005]; Intramural Research Program of the NIH,
National Institute on Aging; MedStar Research Institute;
GlaxoSmithKline; Faculty of Biology and Medicine of Lausanne,
Switzerland; Swiss National Science Foundation [33CSCO-122661]; Medical
Research Council (UK); Republic of Croatia Ministry of Science,
Education and Sports research [108-1080315-0302]; Republic of Croatia
Ministry of Science, Education and Sports [108-1080315-0302]; European
Commission [LSHG-CT-2006-018947]; Spanish Ministry of Science and
Innovation [MTM2008-02457]; Fondo de Investigaciones Santarias
[97/0035-01, 99/0034-01, 99/0034-02]; Hospital Universitario de
Albacete; Consejeria de Sanidad; FWO (Fund for Scientific Research)
[G.0402.00]; University of Antwerp; Flemish Health Ministry; Sociedad
Espanola de Neumologia y Cirugia Toracica (SEPAR), Public Health Service
[R01 HL62633-01]; Consell Interdepartamental de Recerca i Innovacio
Tecnologica (CIRIT) [1999SGR 00241]; Red Respira Instituto de Salud
Carlos III (ISCIII); FP7 programs (ENGAGE, OPENGENE); Estonian
Government [SF0180142s08]; Estonian Research Roadmap through Estonian
Ministry of Education and Research, Center of Excellence in Genomics
(EXCEGEN); University of Tartu [SP1GVARENG]; Estonian Science Foundation
[EstSF ETF9353]; European Community [HEALTH-F4-2007-201413]; Medical
Research Council UK; Cancer Research UK; Deutsche
Forschungsgemeinschaft; German Federal Ministry of Education and
Research (BMBF); EU [LSHM-CT-2006-037593]; ENGAGE [201413]; CARDomics
[01KU0908A]; DZHK (Deutsches Zentrum fur Herz-Kreislauf-Forschung -
German Centre for Cardiovascular Research); BMBF (German Ministry of
Education and Research); U.S. National Institute on Aging [263 MD 9164,
263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; Intramural
research program of the National Institute on Aging, National Institutes
of Health, Baltimore, Maryland; Sir Henry Wellcome Postdoctoral
Fellowship [092447/Z/10/Z]; Regione FVG [L.26.2008]; Compagnia di San
Paolo, Torino, Italy; Fondazione Cariplo, Italy; Ministry of Health,
Ricerca Finalizzata and Telethon, Italy; State of Bavaria; German
National Genome Research Network [NGFN-2, NGFNPlus: 01GS0823]; Munich
Center of Health Sciences (MC Health) as part of LMUinnovativ; Radboud
University Nijmegen Medical Centre; Genetic Association Information
Network (GAIN) of the Foundation for the US National Institutes of
Health; GAIN; NIMH [MH081802]; Netherlands Heart Foundation [90.313,
86.083, 88.042, 2006B140, 2006T003]; Netherlands Organization for
Scientific Research [904-61-090]; Genetics of individual differences in
smoking initiation and persistence [NWO 985-10-002]; Resolving cause and
effect in the association between exercise and well-being [904-61-193];
Twin family database for behaviour genomics studies [480-04-004]; Twin
research focusing on behaviour [400-05-717]; Genetic determinants of
risk behaviour in relation to alcohol use and alcohol use disorder
[Addiction-31160008]; Genotype/phenotype database for behaviour genetic
and genetic epidemiological studies [911-09-032]; Spinozapremie [SPI
56-464-14192]; CMSB: Center for Medical Systems Biology (NWO Genomics);
BBMRI -NL: Biobanking and Biomolecular Resources Research
Infrastructure; VU University; Institute for Health and Care Research
(EMGO+) and Neuroscience Campus Amsterdam (NCA); European Science
Foundation (ESF): Genomewide analyses of European twin and population
cohorts [EU/QLRT-2001-01254]; European Community's Seventh Framework
Program [HEALTH-F4-2007-201413]; European Science Council (ERC) Genetics
of Mental Illness [230374]; Rutgers University Cell and DNA Repository
cooperative agreement [NIMH U24 MH068457-06]; Collaborative study of the
genetics of DZ twinning [NIH R01D0042157-01A]; Genetic Association
Information Network; Pfizer Inc.; Affymetrix Inc.; Abbott Laboratories;
Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Twin
family database for behaviour genomics studies [480-04-004]; Chief
Scientist Office of the Scottish Government; Royal Society; European
Union [LSHG-CT-2006-018947]; Dutch Kidney Foundation [E033]; EU project
grant GENECURE [FP-6 LSHM CT 2006 037697]; NWO VENI [91676170]; Dutch
Inter University Cardiology Institute Netherlands (ICIN); Australian
National Health and Medical Research Council (NHMRC) [241944, 339462,
389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485,
552498]; Australian Research Council (ARC) [A7960034, A79906588,
A79801419, DP0770096, DP0212016, DP0343921]; FP-5 GenomEUtwin Project
[QLG2-CT-2002-01254]; U.S. National Institutes of Health (NIH) [AA07535,
AA10248, AA13320, AA13321, AA13326, AA14041, MH66206]; Netherlands
Scientific Organization [NWO 480-05-003]; NHMRC [619667]; ARC Future
Fellowship [FT0991022, FT110100548]; National Health and Medical
Research Council of Australia [403981, 003209]; Canadian Institutes of
Health Research [MOP-82893]; Netherlands Organisation of Scientific
Research NWO Investments; Research Institute for Diseases in the
Elderly; Netherlands Genomics Initiative (NGI) Netherlands Consortium of
Healthy Aging (NCHA); EC; Erasmus Medical Center and Erasmus University,
Rotterdam, Netherlands Organization for the Health Research and
Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission (DG XII); Municipality of
Rotterdam; German Bundesministerium fuer Forschung und Technology;
Federal Ministry of Education and Research; Ministry of Cultural
Affairs; Social Ministry of the Federal State of Mecklenburg-West
Pomerania; Greifswald Approach to Individualized Medicine (GANI_MED);
Siemens Healthcare, Erlangen, Germany; Federal State of Mecklenburg-
West Pomerania; Interdisciplinary Centre for Clinical Research at the
University of Leipzig; German Diabetes Association; BIF; DHFD, Diabetes
Hilfs-und Forschungsfonds Deutschland; ENGAGE (European Network for
Genetic and Genomic Epidemiology) Consortium, the European Community;
European Community's Seventh Framework Programme; European Union FP-5
GenomEUtwin Project; Framework 6 Project EUroClot; National Institute
for Health Research (NIHR) comprehensive Biomedical Research Centre;
Academy of Finland; Social Insurance Institution of Finland; University
Hospital Medical; Turku University Hospitals; Finnish Foundation of
Cardiovascular Research Emil Aaltonen Foundation; Tampere Tuberculosis
Foundation; Unity Through Knowledge Fund CONNECTIVITY PROGRAM; National
Foundation for Science, Higher Education and Technological Development
of the Republic of Croatia
FX WTCCC: This study makes use of data generated by the Wellcome Trust Case
Control Consortium. A full list of the investigators who contributed to
the generation of the data is available in the Supplementary Material
and at www.wtccc.org.uk. Funding for the project was provided by the
Wellcome Trust under award 076113.; AGES: The researchers are indebted
to the participants for their willingness to participate in the study.
This study has been funded by NIH contract N01-AG-1-2100, the NIA
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament). The study is
approved by the Icelandic National Bioethics Committee, VSN: 00-063.;
ARIC: The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN26820 1100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN26820
1100010C, HHSN268201100011C, and HHSN2682011 00012C), R01HL087641,
R01HL59367 and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and National Institutes of Health contract
HHSN268200625226C. The authors thank the staff and participants of the
ARIC study for their important contributions. Infrastructure was partly
supported by Grant Number UL1RR025005, a component of the National
Institutes of Health and NIH Roadmap for Medical Research.; BLSA: The
BLSA was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging. A portion of that support was through
a R&D contract with MedStar Research Institute.; CoLaus: The authors
express their gratitude to the participants in the Lausanne CoLaus study
and to the investigators who have contributed to the recruitment. We
would like to thank Drs Vincent Mooser and Dawn Waterworth from
GlaxoSmithKline for helpful comments and for their continuous support
for the CoLaus project. Part of the computation has been performed on
the Vital-IT cluster (www.vital-it.ch). We are grateful to Dr. Toby
Johnson and Pr. Sven Bergmann for statistical discussions. The CoLaus
study was supported by research grants from GlaxoSmithKline; the Faculty
of Biology and Medicine of Lausanne, Switzerland; and the Swiss National
Science Foundation (grant no: 33CSCO-122661). Gerard Waeber and Peter
Vollenweider received an unrestricted grant from GSK to build the CoLaus
study.; CROATIA-Korcula: We would like to acknowledge the staff of
several institutions in Croatia that supported the field work, including
but not limited to The University of Split and Zagreb Medical Schools
and Croatian Institute for Public Health. The SNP genotyping for the
CROATIA-Korcula cohort was performed in Helmholtz Zentrum Munchen,
Neuherberg, Germany. The CROATIA-Korcula study was funded by grants from
the Medical Research Council (UK), and Republic of Croatia Ministry of
Science, Education and Sports research (108-1080315-0302).;
CROATIA-Split: We would like to acknowledge the staff of several
institutions in Croatia that supported the field work, including but not
limited to The University of Split and Zagreb Medical Schools and
Croatian Institute for Public Health. The SNP genotyping for the
CROATIA-Split cohort was performed by AROS Applied Biotechnology,
Aarhus, Denmark. The CROATIA-Split study is funded by grants from the
Medical Research Council (UK) and Republic of Croatia Ministry of
Science, Education and Sports research grants to I. R.
(108-1080315-0302).; CROATIA-Vis: We would like to acknowledge the staff
of several institutions in Croatia that supported the field work,
including but not limited to The University of Split and Zagreb Medical
Schools, Institute for Anthropological Research in Zagreb and Croatian
Institute for Public Health. The SNP genotyping for the CROATIA-Vis
cohort was performed in the core genotyping laboratory of the Wellcome
Trust Clinical Research Facility at the Western General Hospital,
Edinburgh, Scotland, UK. The CROATIA-Vis study was funded by grants from
the Medical Research Council (UK), European Commission Framework 6
project EUROSPAN (Contract No. LSHG-CT-2006-018947) and Republic of
Croatia Ministry of Science, Education and Sports research grants
(108-1080315-0302).; ECHRS-Spain: Spanish Ministry of Science and
Innovation grant MTM2008-02457; Fondo de Investigaciones Santarias
grants 97/0035-01, 99/0034-01 and 99/0034-02; Hospital Universitario de
Albacete; Consejeria de Sanidad; FWO (Fund for Scientific Research)
grant G.0402.00; University of Antwerp; the Flemish Health Ministry;
Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR), Public
Health Service grant R01 HL62633-01; Consell Interdepartamental de
Recerca i Innovacio Tecnologica (CIRIT) grant 1999SGR 00241; Red Respira
Instituto de Salud Carlos III (ISCIII).; EGCUT: EGCUT received financial
support from FP7 programs (ENGAGE, OPENGENE), targeted financial support
from Estonian Government SF0180142s08, Estonian Research Roadmap through
Estonian Ministry of Education and Research, Center of Excellence in
Genomics (EXCEGEN) and University of Tartu (SP1GVARENG). The work of K.
F. was supported by Estonian Science Foundation grant EstSF ETF9353. We
acknowledge EGCUT technical personnel, especially Mr V. Soo and S. Smit.
Data analyzes were carried out in part in the High Performance Computing
Center of University of Tartu.; ENGAGE: This research was supported
through funds from The European Community's Seventh Framework Programme
(FP7/2007-2013), ENGAGE Consortium, grant agreement
HEALTH-F4-2007-201413.; EPIC-Obesity: The EPIC Norfolk Study is funded
by program grants from the Medical Research Council UK and Cancer
Research UK.; GerMIFS: Supported by the Deutsche Forschungsgemeinschaft
and the German Federal Ministry of Education and Research (BMBF) in the
context of the German National Genome Research Network (NGFN-2 and
NGFN-plus), the FP6 and FP7 EU funded integrated projects Cardiogenics
(LSHM-CT-2006-037593) and ENGAGE (201413), and the bi-national BMBF/ANR
funded project CARDomics (01KU0908A). Supported by the DZHK (Deutsches
Zentrum fur Herz-Kreislauf-Forschung - German Centre for Cardiovascular
Research) and by the BMBF (German Ministry of Education and Research).;
HBCS: Helsinki Birth Cohort Study has been supported by grants from the
Academy of Finland (Grant No. 120315 and 129287 to EW, 1129457 and
1216965 to KR, 120386 and 125876 to JGE), the Finnish Diabetes Research
Society, Folkhalsan Research Foundation, Novo Nordisk Foundation, Finska
Lakaresallskapet, the European Science Foundation (EuroSTRESS), the
Wellcome Trust (Grant No. 89061/Z/09/Z and 089062/Z/09/Z), Samfundet
Folkhalsan, Finska Lakaresallskapet and the Signe and Ane Gyllenberg
foundation.; InCHIANTI: We thank the Intramural Research Program of the
NIH, National Institute on Aging who are responsible for the InCHIANTI
samples. We also thank the InCHIANTI participants. The InCHIANTI study
baseline (1998-2000) was supported as a 'targeted project'
(ICS110.1/RF97.71) by the Italian Ministry of Health and in part by the
U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD
821336); the InCHIANTI Follow-up 1 (2001-2003) was funded by the U.S.
National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111);
the InCHIANTI Followups 2 and 3 studies (2004-2010) were financed by the
U.S. National Institute on Aging (Contract: N01-AG-5-0002); supported in
part by the Intramural research program of the National Institute on
Aging, National Institutes of Health, Baltimore, Maryland. JRBP is
funded by a Sir Henry Wellcome Postdoctoral Fellowship (092447/Z/10/Z).;
INGI-CARLANTINO and INGI-FVG: The study was funded Regione FVG
(L.26.2008). We thank Laura Esposito, Angela D'Eustacchio and Emmanouil
Athanasakis for technical support. We are very grateful to the municipal
administrators for their collaboration on the project and for logistic
support. We would like to thank all participants to this study.;
INGI-VB: We thank the inhabitants of the VB that made this study
possible, the local administrations, the Tortona and Genova archdiocese
and the ASL-22, Novi Ligure (Al) for support. We also thank Cinzia Sala
and Clara Camaschella for data collection supervision and organization
of the clinical data collection, Fiammetta Vigano for technical help,
Corrado Masciullo and Massimiliano Cocca for building the analysis
platform. The research was supported by funds from Compagnia di San
Paolo, Torino, Italy; Fondazione Cariplo, Italy and Ministry of Health,
Ricerca Finalizzata 2008 and Telethon, Italy to DT. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.; KORA: The KORA authors acknowledge
the contribution of Peter Lichtner, Gertrud Eckstein, Guido Fischer and
all members of the Helmholtz Center Munich genotyping staff for
generating the SNP data, as well as all members of field staffs who were
involved in the planning and conduction of the KORA Augsburg studies.
The KORA research platform was initiated and financed by the Helmholtz
Center Munich, German Research Center for Environmental Health, which is
funded by the German Federal Ministry of Education and Research (BMBF)
and by the State of Bavaria. Part of this work was financed by the
German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823).
Our research was supported within the Munich Center of Health Sciences
(MC Health) as part of LMUinnovativ.; NBS: We thank the participants
from the Municipality of Nijmegen for their continued support to the
Nijmegen Biomedical Study. The study was partly funded by an investment
grant of the Radboud University Nijmegen Medical Centre.; NESDA:
Neuroscience Campus Amsterdam; EMGO+ Institute for Health and Care
Research; NIMH R01 MH059160; Geestkracht program of ZonMW (10-000-1002);
matching funds from universities and mental health care institutes
involved in NESDA. Genotyping was funded by the Genetic Association
Information Network (GAIN) of the Foundation for the US National
Institutes of Health, and analysis was supported by grants from GAIN and
the NIMH (MH081802).; NTR: We thank the twins and their families for
their participation.; NTR1: Funding was obtained from the Netherlands
Heart Foundation (90.313, 86.083 and 88.042), the Netherlands
Organization for Scientific Research (NWO: MagW/ZonMW): Genetic basis of
anxiety and depression (904-61-090); Genetics of individual differences
in smoking initiation and persistence (NWO 985-10-002); Resolving cause
and effect in the association between exercise and well-being
(904-61-193); Twin family database for behaviour genomics studies
(480-04-004); Twin research focusing on behaviour (400-05-717); Genetic
determinants of risk behaviour in relation to alcohol use and alcohol
use disorder (Addiction-31160008); Genotype/phenotype database for
behaviour genetic and genetic epidemiological studies (911-09-032);
Spinozapremie (SPI 56-464-14192); CMSB: Center for Medical Systems
Biology (NWO Genomics); NBIC/BioAssist/RK/2008.024); BBMRI -NL:
Biobanking and Biomolecular Resources Research Infrastructure; the VU
University: Institute for Health and Care Research (EMGO+) and
Neuroscience Campus Amsterdam (NCA); the European Science Foundation
(ESF): Genomewide analyses of European twin and population cohorts
(EU/QLRT-2001-01254); European Community's Seventh Framework Program
(FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science
Council (ERC) Genetics of Mental Illness (230374); Rutgers University
Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06);
Collaborative study of the genetics of DZ twinning (NIH
R01D0042157-01A); the Genetic Association Information Network, a
public-private partnership between the NIH and Pfizer Inc., Affymetrix
Inc. and Abbott Laboratories.; NTR2: Funding is acknowledged from the
Netherlands Organization for Scientific Research (NWO: MagW/ZonMW): Twin
family database for behaviour genomics studies (480-04-004); Twin
research focusing on behaviour (400-05-717); Genetic determinants of
risk behaviour in relation to alcohol use (Addiction-31160008);
Genotype/phenotype database for behaviour genetic and genetic
epidemiological studies (911-09-032); Spinozapremie (SPI 56-464-14192);
CMSB: Center for Medical Systems Biology (NWO Genomics);
NBIC/BioAssist/RK/2008.024); BBMRI -NL: Biobanking and Biomolecular
Resources Research Infrastructure; European Science Foundation (ESF):
Genomewide analyses of European twin and population cohorts
(EU/QLRT-2001-01254); European Community's Seventh Framework Program
(FP7/2007-2013): ENGAGE (HEALTH-F4-2007-201413); the European Science
Council (ERC) Genetics of Mental Illness (230374); Rutgers University
Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06).;
ORCADES: ORCADES DNA extractions were performed at the Wellcome Trust
Clinical Research Facility in Edinburgh. We would like to acknowledge
the invaluable contributions of Lorraine Anderson and the research
nurses in Orkney, the administrative team in Edinburgh and the people of
Orkney. ORCADES was supported by the Chief Scientist Office of the
Scottish Government, the Royal Society and the European Union framework
program 6 EUROSPAN project (contract no. LSHG-CT-2006-018947). PREVEND:
PREVEND genetics is supported by the Dutch Kidney Foundation (Grant
E033), The Netherlands Heart Foundation (Grant 2006B140, 2006T003),
National Institutes of Health (grant LM010098, HL65234, HL67466,
RR018787) and the EU project grant GENECURE (FP-6 LSHM CT 2006 037697).
P.vd.H is supported by NWO VENI grant 91676170 and Dutch Inter
University Cardiology Institute Netherlands (ICIN). QIMR: We thank the
twins and their families for their participation. We also thank Dixie
Statham, Ann Eldridge, Marlene Grace, Kerrie McAloney (sample
collection); Anjali Henders, Megan Campbell, Lisa Bowdler and Steven
Crooks (sample and DNA processing); Scott Gordon, David Smyth, Harry
Beeby, and Daniel Park (IT support). We also acknowledge David Duffy,
Peter Visscher, Margaret Wright, Pamela Madden and Wendy Slutske for
their funding contributions. Genotype imputation was carried out on the
Genetic Cluster Computer. Funding was provided by the Australian
National Health and Medical Research Council (NHMRC grants 241944,
339462, 389927, 389875, 389891, 389892, 389938, 442915, 442981, 496739,
552485, 552498), the Australian Research Council (ARC grants A7960034,
A79906588, A79801419, DP0770096, DP0212016, DP0343921), the FP-5
GenomEUtwin Project (QLG2-CT-2002-01254), and the U.S. National
Institutes of Health (NIH grants AA07535, AA10248, AA13320, AA13321,
AA13326, AA14041, MH66206). The Genetic Cluster Computer is financially
supported by the Netherlands Scientific Organization (NWO 480-05-003).
G. W. M. was supported by an NHMRC Fellowship (619667), D.R.N.
(FT0991022) and S. E. M. (FT110100548) were supported by an ARC Future
Fellowship. RAINE: The authors are grateful to the Raine Study
participants and their families and to the Raine Study research staff
for cohort coordination and data collection. The authors gratefully
acknowledge the NH&MRC for their long term contribution to funding the
study over the last 20 years and also the following Institutions for
providing funding for Core Management of the Raine Study: The University
of Western Australia (UWA), Raine Medical Research Foundation, UWA
Faculty of Medicine, Dentistry and Health Sciences, The Telethon
Institute for Child Health Research and Women and Infants Research
Foundation. The authors gratefully acknowledge the assistance of the
Western Australian DNA Bank (National Health and Medical Research
Council of Australia National Enabling Facility). The authors also
acknowledge the support of the National Health and Medical Research
Council of Australia (Grant ID 403981 and ID 003209) and the Canadian
Institutes of Health Research (Grant ID MOP-82893).; RS: We thank Pascal
Arp, Mila Jhamai, Marijn Verkerk, and Lisbeth Herrera for their help in
creating the GWAS database. The authors are grateful to the study
participants, the staff from the Rotterdam Study and the participating
general practitioners and pharmacists. We would like to thank Dr. Tobias
A. Knoch, Karol Estrada, Luc V. de Zeeuw, Anis Abuseiris and Rob de
Graaf as well as their institutions the Erasmus Computing Grid,
Rotterdam, The Netherlands, and especially the national German MediGRID
and Services@MediGRID part of the German D-Grid for access to their grid
resources. The generation and management of GWAS genotype data for the
Rotterdam Study is supported by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012).
This study is funded by the Research Institute for Diseases in the
Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)
Netherlands Consortium of Healthy Aging (NCHA) project nr. 050-060-810,
and funding from the European Commission (HEALTH-F2-2008-201865, GEFOS;
HEALTH-F2-2008-35627, TREAT-OA). The Rotterdam Study is funded by
Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands
Organization for the Health Research and Development (ZonMw), the
Research Institute for Diseases in the Elderly (RIDE), the Ministry of
Education, Culture and Science, the Ministry for Health, Welfare and
Sports, the European Commission (DG XII) and the Municipality of
Rotterdam. German MediGRID and Services@MediGRID are part of the German
D-Grid and are both funded by the German Bundesministerium fuer
Forschung und Technology under grants # 01 AK 803 A-H and # 01 IG 07015
G.; SHIP: We thank all staff members and participants of the SHIP study,
as well as all of the genotyping staff for generating the SHIP SNP data
set. The genetic data analysis workflow was created using the Software
InforSense. Genetic data were stored using the database Cache
(InterSystems). SHIP is part of the Community Medicine Research net of
the University of Greifswald, Germany, which 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, and the
network 'Greifswald Approach to Individualized Medicine (GANI_MED)'
funded by the Federal Ministry of Education and Research (grant
03IS2061A). 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 the Federal State of
Mecklenburg- West Pomerania. The University of Greifswald is a member of
the 'Center of Knowledge Interchange' program of the Siemens AG.; SORBS:
We thank all those who participated in the study. Sincere thank is given
to Peter Kovacs who was significantly involved in the planning and
procedure of the Sorbs study. We also thank Knut Krohn (Microarray Core
Facility of the Interdisciplinary Centre for Clinical Research,
University of Leipzig) for the genotyping support and Inga Prokopenko
and Nigel W. Rayner (WTCHG, University of Oxford, UK) for the excellent
analytical and bioinformatics support. This work was supported by grants
from the Interdisciplinary Centre for Clinical Research at the
University of Leipzig (B27 to A. T.) from the German Diabetes
Association (to A. T.), a Travel Grant from BIF (to A. T.) and by the
DHFD, Diabetes Hilfs-und Forschungsfonds Deutschland. The work of
Vasiliki Lagou was funded through the ENGAGE (European Network for
Genetic and Genomic Epidemiology) Consortium, the European Community's
Seventh Framework Programme (HEALTH-F4-2007-201413).; TwinsUK: We thank
the staff from the TwinsUK, the DNA Collections and Genotyping
Facilities at the Wellcome Trust Sanger Institute for sample
preparation; Quality Control of the Twins UK cohort for genotyping (in
particular Amy Chaney, Radhi Ravindrarajah, Douglas Simpkin, Cliff
Hinds, and Thomas Dibling); Paul Martin and Simon Potter of the DNA and
Genotyping Informatics teams for data handling; Le Centre National de
Genotypage, France, led by Mark Lathrop, for genotyping; Duke
University, North Carolina, USA, led by David Goldstein, for genotyping;
and the Finnish Institute of Molecular Medicine, Finnish Genome Center,
University of Helsinki, led by Aarno Palotie. The authors declare they
have no conflicts of interest. The study was funded by the Wellcome
Trust; European Community's Seventh Framework Programme
(FP7/2007-2013)/grant agreement HEALTH-F2-2008-ENGAGE and the European
Union FP-5 GenomEUtwin Project (QLG2-CT-2002-01254) and Framework 6
Project EUroClot. The study also receives support from the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership
with King's College London.; YFS: The Cardiovascular Risk in Young Finns
study (YFS) is supported by the Academy of Finland (grant no. 117797,
121584 and 126925), the Social Insurance Institution of Finland,
University Hospital Medical funds to Tampere, and Turku University
Hospitals, the Finnish Foundation of Cardiovascular Research Emil
Aaltonen Foundation (T. L), and Tampere Tuberculosis Foundation.; V. B.
is supported by Unity Through Knowledge Fund CONNECTIVITY PROGRAM
('Gaining Experience' Grant 2A), The National Foundation for Science,
Higher Education and Technological Development of the Republic of
Croatia (BRAIN GAIN-Postdoc fellowship) and the Wellcome Trust (098051).
E.Z. is supported by the Wellcome Trust (098051). Funding to pay the
Open Access publication charges for this article was provided by the
Wellcome Trust (098051).
NR 32
TC 9
Z9 9
U1 0
U2 29
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 NOV 1
PY 2012
VL 21
IS 21
BP 4805
EP 4815
DI 10.1093/hmg/dds304
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 025DN
UT WOS:000310165500018
PM 22843499
ER
PT J
AU Blanch-Hartigan, D
AF Blanch-Hartigan, Danielle
TI An effective training to increase accurate recognition of patient
emotion cues
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Emotion recognition; Training; Emotion cue; Medical education; Accuracy
ID MEDICAL-STUDENTS; COMMUNICATION-SKILLS; NONVERBAL-COMMUNICATION;
INTERPERSONAL SENSITIVITY; INTERVIEWING SKILLS; SELF-ASSESSMENT;
CANCER-PATIENTS; PRIMARY-CARE; SATISFACTION; PHYSICIANS
AB Objective: For healthcare providers, accurate perception of patients, particularly accurate recognition of patient emotions, is an ability associated with better patient care and more satisfied patients. Despite the importance of accurately recognizing patient cues for provider-patient communication, research on clinically relevant training programs is limited. The effectiveness of a multi-component training program designed to enhance emotion cue recognition ability was experimentally assessed.
Methods: The comprehensive training included raising awareness about the importance of emotion cues in healthcare interactions, providing instruction on increasing emotion cue recognition accuracy, and practicing emotion recognition while receiving feedback. Undergraduate participants were randomly assigned to one of five training conditions or an untrained control condition to experimentally test the efficacy of the comprehensive training and each training component.
Results: Participants were significantly more accurate on a standardized test of patient emotion cue recognition in the comprehensive condition, as compared to those participants in the control condition, with Practice with Feedback emerging as the most effective component.
Conclusions: Results suggest that a 30-min emotion recognition training intervention can significantly improve emotion recognition accuracy.
Practice implications: The results can be used to guide development and implementation of future research and programs aimed at increasing providers' emotion recognition. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
RP Blanch-Hartigan, D (reprint author), NCI, Canc Prevent Fellowship Program, Execut Plaza S,Suite 150E,6120 Execut Blvd,MSC 71, Bethesda, MD 20892 USA.
EM danielleblanch@gmail.com
NR 48
TC 8
Z9 8
U1 2
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD NOV
PY 2012
VL 89
IS 2
BP 274
EP 280
DI 10.1016/j.pec.2012.08.002
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 046LO
UT WOS:000311766700009
PM 22906744
ER
PT J
AU Kent, EE
Arora, NK
Rowland, JH
Bellizzi, KM
Forsythe, LP
Hamilton, AS
Oakley-Girvan, I
Beckjord, EB
Aziz, NM
AF Kent, Erin E.
Arora, Neeraj K.
Rowland, Julia H.
Bellizzi, Keith M.
Forsythe, Laura P.
Hamilton, Ann S.
Oakley-Girvan, Ingrid
Beckjord, Ellen B.
Aziz, Noreen M.
TI Health information needs and health-related quality of life in a diverse
population of long-term cancer survivors
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Cancer survivorship; Information needs; Self-efficacy; Quality of care;
Health-related quality of life
ID BREAST-CANCER; SOCIAL SUPPORT; SELF-EFFICACY; CARE PLANS; PREVALENCE;
CHALLENGE; LITERACY; IMPACT
AB Objective: To investigate health information needs and their association with health-related quality of life (HRQOL) in a diverse, population-based sample of long-term cancer survivors.
Methods: We analyzed health information needs from 1197 cancer survivors 4-14 years post-diagnosis drawn from two cancer registries in California. Multivariable regression models were used to identify factors associated with endorsement of total number and different categories of needs. The relationship between number of needs and HRQOL and effect modification by confidence for obtaining information was examined.
Results: Survivors reported a high prevalence of unmet information needs in the following categories: side effects & symptoms: 75.8%; tests & treatment: 71.5%; health promotion: 64.5%; interpersonal & emotional: 60.2%; insurance: 39.0%; and sexual functioning & fertility: 34.6%. Survivors who were younger, non-White, and did not receive but wanted a written treatment summary reported a higher number of needs. Number of information needs was inversely related to mental well-being, particularly for those with low confidence for obtaining information (P < 0.05).
Conclusion: These patterns suggest disparities in access to important health information in long-term survivors and that affect HRQOL Practice Implications: Findings suggest a need for tailored interventions to equip survivors with comprehensive health information and to bolster skills for obtaining information. Published by Elsevier Ireland Ltd.
C1 [Kent, Erin E.; Arora, Neeraj K.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, Bethesda, MD 20892 USA.
[Kent, Erin E.; Forsythe, Laura P.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Kent, Erin E.; Rowland, Julia H.; Forsythe, Laura P.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Bellizzi, Keith M.] Univ Connecticut, Storrs, CT USA.
[Hamilton, Ann S.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Oakley-Girvan, Ingrid] Canc Prevent Inst Calif, Fremont, CA USA.
[Beckjord, Ellen B.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Aziz, Noreen M.] NINR, NIH, Bethesda, MD 20892 USA.
RP Kent, EE (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci,NIH, 6130 Execut Blvd,Room 4020, Bethesda, MD 20892 USA.
EM Erin.Kent@nih.gov
FU NCI SEER [N01-PC-35136, N01-PC-35139]
FX This study was supported under NCI SEER contract numbers: N01-PC-35136,
N01-PC-35139 (http://cancercontrol.cancer.gov/ocs/focus.html). The
authors would like to acknowledge Ms. Gretchen Keel (Information
Management Services, Inc., Rockville, MD) for her assistance with data
analysis on this project. This study has been presented in part at a
poster at the 2011 American Association of Cancer Research Science of
Cancer Health Disparities Meeting, on September 19, 2011, in Washington,
DC.
NR 46
TC 38
Z9 38
U1 0
U2 19
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD NOV
PY 2012
VL 89
IS 2
BP 345
EP 352
DI 10.1016/j.pec.2012.08.014
PG 8
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 046LO
UT WOS:000311766700019
PM 23021856
ER
PT J
AU Li, JX
Ferraris, JD
Yu, DN
Singh, T
Izumi, Y
Wang, GH
Gucek, M
Burg, MB
AF Li, Jinxi
Ferraris, Joan D.
Yu, Danni
Singh, Taruna
Izumi, Yuichiro
Wang, Guanghui
Gucek, Marjan
Burg, Maurice B.
TI Proteomic analysis of high NaCl-induced changes in abundance of nuclear
proteins
SO PHYSIOLOGICAL GENOMICS
LA English
DT Article
DE NFAT5; hypertonicity; nucleoskeleton; DDX5/DDX17; 14-3-3
ID QUANTITATIVE PROTEOMICS; BINDING PROTEIN; DNA-DAMAGE; HEAT-SHOCK; CELLS;
TRANSCRIPTION; STRESS; ACTIVATION; UREA; PHOSPHORYLATION
AB Li J, Ferraris JD, Yu D, Singh T, Izumi Y, Wang G, Gucek M, Burg MB. Proteomic analysis of high NaCl-induced changes in abundance of nuclear proteins. Physiol Genomics 44: 1063-1071, 2012. First published September 18, 2012; doi: 10.1152/physiolgenomics.00068.2012.-Mammalian cells are normally stressed by high interstitial NaCl in the renal medulla and by lesser elevation of NaCl in several other tissues. High NaCl damages proteins and DNA and can kill cells. Known protective responses include nuclear translocation of the transcription factor NFAT5 and other proteins. In order better to understand the extent and significance of changes in nuclear protein abundance, we extracted nuclear and cytoplasmic proteins separately from HEK293 cells and measured by LC-MS/MS (iTRAQ) changes of abundance of proteins in the extracts in response to high NaCl at three time points: 1 h, 8 h, and adapted for two passages. We confidently identified a total of 3,190 proteins; 163 proteins changed significantly at least at one time point in the nucleus. We discerned the biological significance of the changes by Gene Ontology and protein network analysis. Proteins that change in the nucleus include ones involved in protein folding and localization, microtubule-based process, regulation of cell death, cytoskeleton organization, DNA metabolic process, RNA processing, and cell cycle. Among striking changes in the nucleus, we found a decrease of all six 14-3-3 isoforms; dynamic changes of "cytoskeletal" proteins, suggestive of nucleoskeletal reorganization; rapid decrease of tubulins; and dynamic changes of heat shock proteins. Identification of these changes of nuclear protein abundance enhances our understanding of high NaCl-induced cellular stress, and provides leads to previously unknown damages and protective responses.
C1 [Li, Jinxi; Ferraris, Joan D.; Yu, Danni; Singh, Taruna; Izumi, Yuichiro; Wang, Guanghui; Gucek, Marjan; Burg, Maurice B.] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
RP Burg, MB (reprint author), NIH, Bldg 10,Rm 6N260, Bethesda, MD 20892 USA.
EM maurice_burg@nih.gov
FU IRP of the NHLBI
FX This research was supported by the IRP of the NHLBI.
NR 35
TC 6
Z9 6
U1 3
U2 13
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1094-8341
J9 PHYSIOL GENOMICS
JI Physiol. Genomics
PD NOV
PY 2012
VL 44
IS 21
BP 1063
EP 1071
DI 10.1152/physiolgenomics.00068.2012
PG 9
WC Cell Biology; Genetics & Heredity; Physiology
SC Cell Biology; Genetics & Heredity; Physiology
GA 032FU
UT WOS:000310699800006
PM 22991206
ER
PT J
AU Walker, A
Pao, M
Nguyen, N
AF Walker, Audrey
Pao, Maryland
Ngoc Nguyen
TI Pediatric Psychosomatic Medicine: Creating a Template for Training
SO PSYCHOSOMATICS
LA English
DT Article
ID PREVALENCE; DISORDERS; HEALTH; CHILD
AB There is a critical public health problem in the United States today, the problem of childhood psychiatric disorders in youngsters with physical illnesses. Currently there is a pressing need for well-trained pediatric psychosomatic medicine practitioners as well as advanced training in the field. Yet, this training does not currently exist. This article will present the innovative Montefiore Medical Center/Albert Einstein College of Medicine (MMC/AECOM) program as a model for a training curriculum, clinical training experience, and clinical research training setting in this important and rapidly expanding area of need in pediatric mental health. (Psychosomatics 2012; 53:532-540)
C1 [Walker, Audrey] Montefiore Med Ctr, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
[Pao, Maryland] NIMH, Clin Res Ctr, Bethesda, MD 20892 USA.
[Ngoc Nguyen] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Psychiat, Bronx, NY USA.
RP Walker, A (reprint author), Montefiore Med Ctr, Dept Psychiat & Behav Sci, 3331 Bainbridge Ave, Bronx, NY 10467 USA.
EM auwalker@montefiore.org
FU Intramural NIH HHS [ZIA MH002922-04]
NR 8
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 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD NOV-DEC
PY 2012
VL 53
IS 6
BP 532
EP 540
PG 9
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 049KC
UT WOS:000311980900004
PM 22658325
ER
PT J
AU Dyda, F
Chandler, M
Hickman, AB
AF Dyda, Fred
Chandler, Michael
Hickman, Alison Burgess
TI The emerging diversity of transpososome architectures
SO QUARTERLY REVIEWS OF BIOPHYSICS
LA English
DT Review
ID EUKARYOTIC TRANSPOSABLE ELEMENTS; CLEAVAGE SYNAPTIC COMPLEX; DNA STRAND
TRANSFER; V(D)J RECOMBINATION; ESCHERICHIA-COLI; MU-TRANSPOSOSOME;
MOLECULAR ARCHITECTURE; RETROVIRAL INTEGRATION; PARAMECIUM-TETRAURELIA;
PIGGYBAC TRANSPOSASE
AB DNA transposases are enzymes that catalyze the movement of discrete pieces of DNA from one location in the genome to another. Transposition occurs through a series of controlled DNA strand cleavage and subsequent integration reactions that are carried out by nucleoprotein complexes known as transpososomes. Transpososomes are dynamic assemblies which must undergo conformational changes that control DNA breaks and ensure that, once started, the transposition reaction goes to completion. They provide a precise architecture within which the chemical reactions involved in transposon movement occur, but adopt different conformational states as transposition progresses. Their components also vary as they must, at some stage, include target DNA and sometimes even host-encoded proteins. A very limited number of transpososome states have been crystallographically captured, and here we provide an overview of the various structures determined to date. These structures include examples of DNA transposases that catalyze transposition by a cut-and-paste mechanism using an RNaseH-like nuclease catalytic domain, those that transpose using only single-stranded DNA substrates and targets, and the retroviral integrases that carry out an integration reaction very similar to DNA transposition. Given that there are a number of common functional requirements for transposition, it is remarkable how these are satisfied by complex assemblies that are so architecturally different.
C1 [Dyda, Fred; Hickman, Alison Burgess] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chandler, Michael] CNRS, Lab Microbiol & Genet Mol, F-31062 Toulouse, France.
RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM fred.dyda@nih.gov
OI Chandler, Michael/0000-0002-0292-6662
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), Bethesda MD; CNRS (France); ANR; European
contract [LSHM-CT-2005-019023]
FX This work was supported at the NIH by the Intramural Program of the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), Bethesda MD and in France by continuous intramural funding from
the CNRS (France) and, in its later stages, by ANR grant Mobigen (M.C.),
and by European contract LSHM-CT-2005-019023 (M.C.).
NR 118
TC 18
Z9 18
U1 2
U2 21
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-5835
J9 Q REV BIOPHYS
JI Q. Rev. Biophys.
PD NOV
PY 2012
VL 45
IS 4
BP 493
EP 521
DI 10.1017/S0033583512000145
PG 29
WC Biophysics
SC Biophysics
GA 050NA
UT WOS:000312058800003
PM 23217365
ER
PT J
AU Candotti, F
Shaw, KL
Muul, L
Carbonaro, D
Sokolic, R
Choi, C
Schurman, SH
Garabedian, E
Kesserwan, C
Jagadeesh, GJ
Fu, PY
Gschweng, E
Cooper, A
Tisdale, JF
Weinberg, KI
Crooks, GM
Kapoor, N
Shah, A
Abdel-Azim, H
Yu, XJ
Smogorzewska, M
Wayne, AS
Rosenblatt, HM
Davis, CM
Hanson, C
Rishi, RG
Wang, XY
Gjertson, D
Yang, OO
Balamurugan, A
Bauer, G
Ireland, JA
Engel, BC
Podsakoff, GM
Hershfield, MS
Blaese, RM
Parkman, R
Kohn, DB
AF Candotti, Fabio
Shaw, Kit L.
Muul, Linda
Carbonaro, Denise
Sokolic, Robert
Choi, Christopher
Schurman, Shepherd H.
Garabedian, Elizabeth
Kesserwan, Chimene
Jagadeesh, G. Jayashree
Fu, Pei-Yu
Gschweng, Eric
Cooper, Aaron
Tisdale, John F.
Weinberg, Kenneth I.
Crooks, Gay M.
Kapoor, Neena
Shah, Ami
Abdel-Azim, Hisham
Yu, Xiao-Jin
Smogorzewska, Monika
Wayne, Alan S.
Rosenblatt, Howard M.
Davis, Carla M.
Hanson, Celine
Rishi, Radha G.
Wang, Xiaoyan
Gjertson, David
Yang, Otto O.
Balamurugan, Arumugam
Bauer, Gerhard
Ireland, Joanna A.
Engel, Barbara C.
Podsakoff, Gregory M.
Hershfield, Michael S.
Blaese, R. Michael
Parkman, Robertson
Kohn, Donald B.
TI Gene therapy for adenosine deaminase-deficient severe combined immune
deficiency: clinical comparison of retroviral vectors and treatment
plans
SO BLOOD
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; MARROW TRANSPLANT RECIPIENTS;
HEMATOPOIETIC STEM-CELLS; EXPRESSION; MURINE; ADA; VIRUS; EFFICACY;
DISEASE; IL-7
AB We conducted a gene therapy trial in 10 patients with adenosine deaminase (ADA)-deficient severe combined immunodeficiency using 2 slightly different retroviral vectors for the transduction of patients' bone marrow CD34(+) cells. Four subjects were treated without pretransplantation cytoreduction and remained on ADA enzyme-replacement therapy (ERT) throughout the procedure. Only transient (months), low-level (< 0.01%) gene marking was observed in PBMCs of 2 older subjects (15 and 20 years of age), whereas some gene marking of PBMC has persisted for the past 9 years in 2 younger subjects (4 and 6 years). Six additional subjects were treated using the same gene transfer protocol, but after withdrawal of ERT and administration of low-dose busulfan (65-90 mg/m(2)). Three of these remain well, off ERT (5, 4, and 3 years postprocedure), with gene marking in PBMC of 1%-10%, and ADA enzyme expression in PBMC near or in the normal range. Two subjects were restarted on ERT because of poor gene marking and immune recovery, and one had a subsequent allogeneic hematopoietic stem cell transplantation. These studies directly demonstrate the importance of providing nonmyeloablative pretransplantation conditioning to achieve therapeutic benefits with gene therapy for ADA-deficient severe combined immunodeficiency. (Blood. 2012;120(18):3635-3646)
C1 [Candotti, Fabio; Muul, Linda; Sokolic, Robert; Schurman, Shepherd H.; Garabedian, Elizabeth; Kesserwan, Chimene; Jagadeesh, G. Jayashree] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Shaw, Kit L.; Carbonaro, Denise; Choi, Christopher; Fu, Pei-Yu; Gschweng, Eric; Kohn, Donald B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Cooper, Aaron] Univ Calif Los Angeles, David Geffen Sch Med, Mol Biol Interdept PhD Program, Los Angeles, CA 90095 USA.
[Tisdale, John F.] NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Weinberg, Kenneth I.] Stanford Sch Med, Dept Pediat, Stanford, CA USA.
[Crooks, Gay M.; Gjertson, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA.
[Kapoor, Neena; Shah, Ami; Abdel-Azim, Hisham; Yu, Xiao-Jin; Smogorzewska, Monika; Ireland, Joanna A.; Parkman, Robertson] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Res Immunol Bone Marrow Transplant,Dept Pedia, Los Angeles, CA 90033 USA.
[Rosenblatt, Howard M.] Dell Childrens Med Ctr Cent Texas, Austin, TX USA.
[Wayne, Alan S.] NCI, Hematol Dis Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Davis, Carla M.; Hanson, Celine] Texas Childrens Hosp, Dept Pediat, Sect Allergy & Immunol, Houston, TX 77030 USA.
[Wang, Xiaoyan; Gjertson, David] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA.
[Rishi, Radha G.] Arizona Allergy Associates, Scottsdale, AZ USA.
[Yang, Otto O.; Balamurugan, Arumugam] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA.
[Bauer, Gerhard] Calif State Univ Sacramento, Davis Sch Med, Dept Internal Med, Div Hematol Oncol, Sacramento, CA 95819 USA.
[Engel, Barbara C.] Childrens Hosp, Philadelphia Res Inst, Philadelphia, PA 19104 USA.
[Podsakoff, Gregory M.] Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA USA.
[Podsakoff, Gregory M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA USA.
[Hershfield, Michael S.] Duke Univ, Sch Med, Dept Biochem, Durham, NC USA.
[Blaese, R. Michael] Immune Deficiency Fdn, Towson, MD USA.
[Kohn, Donald B.] Univ Calif Los Angeles, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA.
RP Kohn, DB (reprint author), 3163 Terasaki Life Sci Bldg,610 Charles E Young D, Los Angeles, CA 90095 USA.
EM dkohn@mednet.ucla.edu
RI Kohn, Donald/N-5085-2016;
OI Kohn, Donald/0000-0003-1840-6087; Schurman,
Shepherd/0000-0002-9133-7906; Cooper, Aaron/0000-0003-4588-2513
FU Clinical Research Award from the Saban Research Institute of Children's
Hospital Los Angeles, a Distinguished Clinical Scientist Award from the
Doris Duke Charitable Foundation; NHLBI SCOR grant [1P50 HL54850]; FDA
[1 RO1 FD003005]; UCLA GCRC [MO1 RR000865]; Sigma-Tau Pharmaceuticals;
NHGRI; NIDDK; NCI
FX This study was supported by the following awards: a Clinical Research
Award from the Saban Research Institute of Children's Hospital Los
Angeles, a Distinguished Clinical Scientist Award (2000-654) from the
Doris Duke Charitable Foundation, an NHLBI SCOR grant to R. Parkman
(1P50 HL54850), and FDA 1 RO1 FD003005. The Clinical Gene Therapy Core
Laboratory of the CHLA/USC General Clinical Research Center (MO1 RR0043)
was vital to performance of this trial and the UCLA GCRC also helped
support this study (MO1 RR000865). Sigma-Tau Pharmaceuticals provides
research grant support to M.S.H. This study was also supported in part
by intramural funds of NHGRI, NIDDK, and NCI.; M.S.H. receives grant
support from Sigma-Tau Pharmaceuticals. The remaining authors declare no
competing financial interests.
NR 40
TC 95
Z9 98
U1 5
U2 28
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2012
VL 120
IS 18
BP 3635
EP 3646
DI 10.1182/blood-2012-02-400937
PG 12
WC Hematology
SC Hematology
GA 044MW
UT WOS:000311624800007
PM 22968453
ER
PT J
AU Gil, MP
Ploquin, MJY
Watford, WT
Lee, SH
Kim, K
Wang, X
Kanno, Y
O'Shea, JJ
Biron, CA
AF Gil, M. Pilar
Ploquin, Mickael J. Y.
Watford, Wendy T.
Lee, Seung-Hwan
Kim, Kwangsin
Wang, Xin
Kanno, Yuka
O'Shea, John J.
Biron, Christine A.
TI Regulating type 1 IFN effects in CD8 T cells during viral infections:
changing STAT4 and STAT1 expression for function
SO BLOOD
LA English
DT Article
ID INTERFERON-GAMMA PRODUCTION; NATURAL-KILLER-CELLS; FLOW-CYTOMETRY; I
INTERFERONS; RESPONSES; ALPHA/BETA; ACTIVATION; PATHWAYS; LYMPHOCYTES;
CANCER
AB Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 compared with STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation. (Blood. 2012;120(18):3718-3728)
C1 [Gil, M. Pilar; Ploquin, Mickael J. Y.; Lee, Seung-Hwan; Kim, Kwangsin; Wang, Xin; Biron, Christine A.] Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02903 USA.
[Watford, Wendy T.; Kanno, Yuka; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
RP Biron, CA (reprint author), Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Box G-B6,171 Meeting St, Providence, RI 02903 USA.
EM christine_biron@brown.edu
RI Kanno, Yuka/B-5802-2013;
OI Kanno, Yuka/0000-0001-5668-9319
FU National Institutes of Health (NIH) [AI55677]; Canadian Institute of
Health Research; NIH National Center for Research Resources Shared
Instrumentation Grant [1S10RR021051-01]
FX The work was supported by the National Institutes of Health (NIH; grant
AI55677) and a fellowship from the Canadian Institute of Health
Research. Purchase and operation of FACSAria was supported by the NIH
National Center for Research Resources Shared Instrumentation Grant
(grant 1S10RR021051-01).
NR 45
TC 31
Z9 31
U1 1
U2 9
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2012
VL 120
IS 18
BP 3718
EP 3728
DI 10.1182/blood-2012-05-428672
PG 11
WC Hematology
SC Hematology
GA 044MW
UT WOS:000311624800015
PM 22968462
ER
PT J
AU Ranuncolo, SM
Pittaluga, S
Evbuomwan, MO
Jaffe, ES
Lewis, BA
AF Ranuncolo, Stella M.
Pittaluga, Stefania
Evbuomwan, Moses O.
Jaffe, Elaine S.
Lewis, Brian A.
TI Hodgkin lymphoma requires stabilized NIK and constitutive RelB
expression for survival
SO BLOOD
LA English
DT Article
ID NF-KAPPA-B; REED-STERNBERG CELLS; MULTIPLE-MYELOMA; ALPHA-GENE;
MUTATIONS; RECEPTOR; KINASE; PATHOGENESIS; PATHWAY; DISEASE
AB We have analyzed the role of the REL family members in Hodgkin lymphoma (HL). shRNA targeting of each REL member showed that HL was uniquely dependent on relB, in contrast to several other B-cell lymphomas. In addition, relA and c-rel shRNA expression also decreased HL cell viability. In exploring relB activation further, we found stable NF-kappa B inducing kinase (NIK) protein in several HL cell lines and that NIK shRNA also affected HL cell line viability. More importantly, 49 of 50 HL patient biopsies showed stable NIK protein, indicating that NIK and the noncanonical pathway are very prevalent in HL. Lastly, we have used a NIK inhibitor that reduced HL but not other B-cell lymphoma cell viability. These data show that HL is uniquely dependent on relB and that the noncanonical pathway can be a therapeutic target for HL. Furthermore, these results show that multiple REL family members participate in the maintenance of a HL phenotype. (Blood.2012;120(18):3756-3763)
C1 [Ranuncolo, Stella M.; Lewis, Brian A.] NCI, Metab Branch, Ctr Canc Res, Transcript Regulat & Biochem Unit,NIH, Rockville, MD 20852 USA.
[Pittaluga, Stefania; Evbuomwan, Moses O.; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Rockville, MD 20852 USA.
RP Lewis, BA (reprint author), NCI, Metab Branch, Ctr Canc Res, Transcript Regulat & Biochem Unit,NIH, Bldg 10,Rm 6B05,9000 Rockville Pike, Rockville, MD 20852 USA.
EM lewisbri@mail.nih.gov
OI Jaffe, Elaine/0000-0003-4632-0301
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 46
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Z9 28
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD NOV 1
PY 2012
VL 120
IS 18
BP 3756
EP 3763
DI 10.1182/blood-2012-01-405951
PG 8
WC Hematology
SC Hematology
GA 044MW
UT WOS:000311624800019
PM 22968463
ER
PT J
AU Helmich, RC
Hallett, M
Deuschl, G
Toni, I
Bloem, BR
AF Helmich, Rick C.
Hallett, Mark
Deuschl, Guenther
Toni, Ivan
Bloem, Bastiaan R.
TI Cerebral causes and consequences of parkinsonian resting tremor: a tale
of two circuits?
SO BRAIN
LA English
DT Review
DE Parkinson's disease; tremor; basal ganglia; cerebellum; thalamus
ID DEEP BRAIN-STIMULATION; MPTP-TREATED MONKEYS; SINGLE-UNIT ANALYSIS;
PRIMARY MOTOR CORTEX; POSITRON-EMISSION-TOMOGRAPHY; THALAMIC NUCLEAR
GROUP; CAUDAL ZONA INCERTA; RE-EMERGENT TREMOR; 5-YEAR FOLLOW-UP;
SUBTHALAMIC NUCLEUS
AB Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed 'dimmer-switch model' that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression.
C1 [Helmich, Rick C.; Toni, Ivan] Radboud Univ Nijmegen, Ctr Cognit Neuroimaging, Donders Inst Brain Cognit & Behav, NL-6500 HB Nijmegen, Netherlands.
[Helmich, Rick C.; Bloem, Bastiaan R.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Neurol, NL-6500 HB Nijmegen, Netherlands.
[Helmich, Rick C.; Bloem, Bastiaan R.] Parkinson Ctr Nijmegen ParC, NL-6500 HB Nijmegen, Netherlands.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Deuschl, Guenther] Univ Kiel, Dept Neurol, D-24118 Kiel, Germany.
RP Helmich, RC (reprint author), Radboud Univ Nijmegen, Med Ctr, Neurol Dept HP 935, POB 9101, NL-6500 HB Nijmegen, Netherlands.
EM r.helmich@neuro.umcn.nl
RI Helmich, Rick/A-3058-2013; Bloem, Bastiaan/E-3812-2010; Deuschl,
Gunther/A-7986-2010; Bloem, B.R./H-8013-2014; Helmich, Rick/R-6333-2016;
OI Helmich, Rick/0000-0003-4035-6573; Toni, Ivan/0000-0003-0936-3601
FU Alkemade-Keuls Foundation; Netherlands Organisation for Scientific
Research (NWO) [016.076.352, 452-03-339, 433-09-248]; German Research
Council [SFB 855]; NIH Intramural Program
FX The Alkemade-Keuls Foundation (to B.R.B.); the Netherlands Organisation
for Scientific Research (NWO; VIDI grant No. 016.076.352 to B.R.B.; VIDI
grant No. 452-03-339 to I.T.; Brain & Cognition grant No. 433-09-248 to
I.T.); the German Research Council (SFB 855 to G.D.) and the NIH
Intramural Program (to M.H.).
NR 187
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U1 2
U2 32
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD NOV
PY 2012
VL 135
BP 3206
EP 3226
DI 10.1093/brain/aws023
PN 11
PG 21
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 044SV
UT WOS:000311644800010
PM 22382359
ER
PT J
AU Moeller, SJ
Hajcak, G
Parvaz, MA
Dunning, JP
Volkow, ND
Goldstein, RZ
AF Moeller, Scott J.
Hajcak, Greg
Parvaz, Muhammad A.
Dunning, Jonathan P.
Volkow, Nora D.
Goldstein, Rita Z.
TI Psychophysiological prediction of choice: relevance to insight and drug
addiction
SO BRAIN
LA English
DT Article
DE cocaine addiction; insight; choice behaviour; event-related potentials;
late positive potential; unconscious motivation
ID CURRENT COCAINE USERS; ATTENTIONAL BIAS; MOTIVATED ATTENTION; EMOTION
REGULATION; HEROIN DEPENDENCE; NEURAL RESPONSES; MONETARY REWARD; CUES;
BRAIN; ASSOCIATIONS
AB An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400-1000 ms) and late (1000-2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice-and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)-when insight (and self-report) is compromised.
C1 [Moeller, Scott J.; Parvaz, Muhammad A.; Goldstein, Rita Z.] Brookhaven Natl Lab, Upton, NY 11973 USA.
[Hajcak, Greg] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA.
[Dunning, Jonathan P.] Nevada State Coll, Dept Social Sci, Henderson, NV 89002 USA.
[Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA.
[Volkow, Nora D.] NIAAA, Bethesda, MD 20892 USA.
RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, 30 Bell Ave,Bldg 490, Upton, NY 11973 USA.
EM rgoldstein@bnl.gov
RI Moeller, Scott/L-5549-2016;
OI Moeller, Scott/0000-0002-4449-0844; Parvaz, Muhammad/0000-0002-2671-2327
FU U.S. Department of Energy [DE-AC02-98CHI-886]; National Institute on
Drug Abuse [1R01DA023579, 1F32DA030017-01]
FX The authors gratefully acknowledge the contributions of Thomas Maloney,
Patricia A. Woicik, Nelly Alia-Klein, Frank Telang, Gene-Jack Wang and
Nicasia Beebe-Wang. This article has been authored by Brookhaven Science
Associates, LLC under Contract No. DE-AC02-98CHI-886 with the U.S.
Department of Energy. The United States Government retains, and the
publisher, by accepting the article for publication, acknowledges, a
world-wide license to publish or reproduce the published form of this
manuscript, or allow others to do so, for the United States Government
purposes.; This study was supported by grants from the National
Institute on Drug Abuse (to R.Z.G.: 1R01DA023579; to S.J.M.:
1F32DA030017-01).
NR 59
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U1 3
U2 23
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
J9 BRAIN
JI Brain
PD NOV
PY 2012
VL 135
BP 3481
EP 3494
DI 10.1093/brain/aws252
PN 11
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 044SV
UT WOS:000311644800031
PM 23148349
ER
PT J
AU Wegner, JK
Sterling, A
Guha, R
Bender, A
Faulon, JL
Hastings, J
O'Boyle, N
Overington, J
Van Vlijmen, H
Willighagen, E
AF Wegner, Joerg Kurt
Sterling, Aaron
Guha, Rajarshi
Bender, Andreas
Faulon, Jean-Loup
Hastings, Janna
O'Boyle, Noel
Overington, John
Van Vlijmen, Herman
Willighagen, Egon
TI Cheminformatics
SO COMMUNICATIONS OF THE ACM
LA English
DT Article
ID ELECTRONIC LABORATORY NOTEBOOKS; CHEMICAL-STRUCTURES; CHEMISTRY;
INFORMATION; MOLECULES; COMPUTER; LANGUAGE; BIOLOGY; DESIGN; SYSTEM
C1 [Wegner, Joerg Kurt] Johnson & Johnson, Janssen Pharmaceut Co, Integrat Syst Biol Dept, Beerse, Belgium.
[Sterling, Aaron] Iowa State Univ, Dept Comp Sci, Ames, IA USA.
[Guha, Rajarshi] NIH, Bethesda, MD 20892 USA.
[Bender, Andreas] Univ Cambridge, Unilever Ctr Mol Informat, Cambridge, England.
[Faulon, Jean-Loup] UniverSud Paris, Evry Univ, Dept Biol, Paris, France.
[Faulon, Jean-Loup] French Natl Ctr Sci Res, Inst Syst & Synthet Biol, Paris, France.
[O'Boyle, Noel] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Cork, Ireland.
[Overington, John] European Bioinformat Inst, Hinxton, South Cambs, England.
[Overington, John] European Mol Biol Lab, Heidelberg, Germany.
[Van Vlijmen, Herman] Leiden Univ, NL-2300 RA Leiden, Netherlands.
[Van Vlijmen, Herman] Johnson & Johnson, Janssen Pharmaceut Co, Dept Mol Sci, Beerse, Belgium.
[Willighagen, Egon] Maastricht Univ, Dept Bioinformat, Maastricht, Netherlands.
RP Wegner, JK (reprint author), Johnson & Johnson, Janssen Pharmaceut Co, Integrat Syst Biol Dept, Beerse, Belgium.
EM jwegner@its.jnj.com; sterling@iastate.edu; guhar@mail.nih.gov;
andreas.bender@cantab.net; Jean-Loup.Faulon@univ-evry.fr;
hastings@ebi.ac.uk; baoilleach@gmail.com; jpo@ebi.ac.uk;
hvvlijme@its.jnj.com; egon.willighagen@maastrichtuniversity.nl
RI Willighagen, Egon/C-6136-2008; Bender, Andreas/C-6942-2009; Overington,
John/G-8607-2015;
OI Willighagen, Egon/0000-0001-7542-0286; Bender,
Andreas/0000-0002-6683-7546; Overington, John/0000-0002-5859-1064;
Hastings, Janna/0000-0002-3469-4923; O'Boyle, Noel/0000-0003-4879-2003
FU National Science Foundation [CCF-1049899]; Unilever; European Union
project EU-OPEN-SCREEN
FX We would like to thank Danny Verbinnen of Janssen Pharmaceutical
Companies for sharing his insight into ELNs and John Van Drie of Van
Drie Consulting for his insight into cheminformatics. This article was
written while Aaron Sterling was visiting the Department of Electrical
Engineering and Computer Science at Northwestern University where he was
supported in part by National Science Foundation grant CCF-1049899.
Andreas Bender thanks Unilever for funding. Janna Hastings thanks the
European Union project EU-OPEN-SCREEN for funding.
NR 40
TC 8
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U1 0
U2 16
PU ASSOC COMPUTING MACHINERY
PI NEW YORK
PA 2 PENN PLAZA, STE 701, NEW YORK, NY 10121-0701 USA
SN 0001-0782
J9 COMMUN ACM
JI Commun. ACM
PD NOV
PY 2012
VL 55
IS 11
BP 65
EP 75
DI 10.1145/2366316.2366334
PG 11
WC Computer Science, Hardware & Architecture; Computer Science, Software
Engineering; Computer Science, Theory & Methods
SC Computer Science
GA 040BE
UT WOS:000311293300026
ER
PT J
AU Lester, BM
Lin, H
DeGarmo, DS
Fisher, PA
LaGasse, LL
Levine, TP
Shankaran, S
Bada, HS
Bauer, CR
Hammond, JA
Whitaker, TM
Higgins, RD
AF Lester, Barry M.
Lin, Hai
DeGarmo, David S.
Fisher, Philip A.
LaGasse, Linda L.
Levine, Todd P.
Shankaran, Seetha
Bada, Henrietta S.
Bauer, Charles R.
Hammond, Jane A.
Whitaker, Toni M.
Higgins, Rosemary D.
TI Neurobehavioral disinhibition predicts initiation of substance use in
children with prenatal cocaine exposure
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Neurodevelopmental disinhibition; Substance use initiation; Prenatal
cocaine exposure
ID COMMUNITY VIOLENCE PROJECT; MATERNAL LIFE-STYLE; USE DISORDER; EARLY
ADOLESCENCE; DRUG-USE; BEHAVIORAL DISINHIBITION; EXTERNALIZING SPECTRUM;
ADULT PSYCHOPATHOLOGY; CONDUCT PROBLEMS; EARLY AGE
AB Background: In previous work we (Fisher et al., 2011) examined the emergence of neurobehavioral disinhibition (ND) in adolescents with prenatal substance exposure. We computed ND factor scores at three age points (8/9, 11 and 13/14 years) and found that both prenatal substance exposure and early adversity predicted ND. The purpose of the current study was to determine the association between these ND scores and initiation of substance use between ages Sand 16 in this cohort as early initiation of substance use has been related to later substance use disorders. Our hypothesis was that prenatal cocaine exposure predisposes the child to ND, which, in turn, is associated with initiation of substance use by age 16. Methods: We studied 386 cocaine exposed and 517 unexposed children followed since birth in a longitudinal study. Five dichotomous variables were computed based on the subject's report of substance use: alcohol only; tobacco only; marijuana only; illicit substances and any substance.
Results: Cox proportional hazard regression showed that the 8/9 year ND score was related to initiation of alcohol, tobacco, illicit and any substance use but not marijuana use. The trajectory of ND across the three age periods was related to substance use initiation in all five substance use categories. Prenatal cocaine exposure, although initially related to tobacco, marijuana and illicit substance initiation, was no longer significant with ND scores in the models.
Conclusion: Prenatal drug exposure appears to be a risk pathway to ND, which by 8/9 years portends substance use initiation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Lester, Barry M.] Brown Univ, Women & Infants Hosp Rhode Isl, Warren Alpert Med Sch, Brown Ctr Study Children Risk,Dept Pediat, Providence, RI 02905 USA.
[Lester, Barry M.; Lin, Hai; Levine, Todd P.] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02905 USA.
[Lester, Barry M.; Lin, Hai; LaGasse, Linda L.; Levine, Todd P.] Brown Univ, Dept Psychiat & Human Behav, Warren Alpert Med Sch, Providence, RI 02905 USA.
[DeGarmo, David S.; Fisher, Philip A.] Oregon Social Learning Ctr, Eugene, OR 97401 USA.
[Fisher, Philip A.] Univ Oregon, Dept Pediat, Eugene, OR 97403 USA.
[Shankaran, Seetha] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Bada, Henrietta S.] Univ Kentucky, Coll Med, Dept Pediat, Lexington, KY USA.
[Bauer, Charles R.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Hammond, Jane A.] Res Triangle Inst, Stat & Epidemiol Unit, Res Triangle Pk, NC 27709 USA.
[Whitaker, Toni M.] Univ Tennessee, Dept Pediat, Memphis, TN USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Lester, BM (reprint author), Brown Univ, Women & Infants Hosp Rhode Isl, Warren Alpert Med Sch, Brown Ctr Study Children Risk,Dept Pediat, 101 Dudley St, Providence, RI 02905 USA.
EM Barry_Lester@Brown.edu
FU NIH; National Institute of Child Health and Human Development (NICHD)
Neonatal Research Network; National Institute on Drug Abuse (NIDA)
[U10-DA-024117-01, U10-HD-21385, U10-DA-024128-06, U10-HD-2786,
U10-DA-024119-01, U10-HD-27904, U10-DA-024118-01, U10-HD-21397]; NICHD
[N01-HD-2-3159]
FX This work was supported by NIH grants: Supported by the National
Institute of Child Health and Human Development (NICHD) Neonatal
Research Network and an interinstitute agreement with the National
Institute on Drug Abuse (NIDA) through cooperative agreements:
U10-DA-024117-01, U10-HD-21385 (to SS), U10-DA-024128-06, U10-HD-2786
(to HSB), U10-DA-024119-01, U10-HD-27904 (to BML), and U10-DA-024118-01,
U10-HD-21397 (to CRB); NICHD contract N01-HD-2-3159 (to BML).
NR 58
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Z9 20
U1 6
U2 12
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD NOV 1
PY 2012
VL 126
IS 1-2
BP 80
EP 86
DI 10.1016/j.drugalcdep.2012.04.014
PG 7
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA 045PA
UT WOS:000311708100012
PM 22608010
ER
PT J
AU Jalah, R
Patel, V
Kulkarni, V
Rosati, M
Alicea, C
Ganneru, B
von Gegerfelt, A
Huang, WS
Guan, YJ
Broderick, KE
Sardesai, NY
LaBranche, C
Montefiori, DC
Pavlakis, GN
Felber, BK
AF Jalah, Rashmi
Patel, Vainav
Kulkarni, Viraj
Rosati, Margherita
Alicea, Candido
Ganneru, Brunda
von Gegerfelt, Agneta
Huang, Wensheng
Guan, Yongjun
Broderick, Kate E.
Sardesai, Niranjan Y.
LaBranche, Celia
Montefiori, David C.
Pavlakis, George N.
Felber, Barbara K.
TI IL-12 DNA as molecular vaccine adjuvant increases the cytotoxic T cell
responses and breadth of humoral immune responses in SIV DNA vaccinated
macaques
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article; Proceedings Paper
CT DNA Vaccines Meeting
CY JUL 12-14, 2011
CL San Diego, CA
DE in vivo electroporation; HIV; SIVsmE660; SIVmac239; antibody;
neutralizing antibody; avidity; central memory; transitional memory;
effector memory
ID RHESUS MACAQUES; IN-VIVO; IFN-GAMMA; THERAPEUTIC VACCINATION;
INTERLEUKIN-12 IL-12; SHIV89.6P CHALLENGE; SIVMAC251 CHALLENGE;
COMPARATIVE ABILITY; INFECTED MACAQUES; MEMORY RESPONSE
AB Intramuscular injection of macaques with an IL-12 expression plasmid (0.1 or 0.4 mg DNA/animal) optimized for high level of expression and delivered using in vivo electroporation, resulted in the detection of systemic IL-12 cytokine in the plasma. Peak levels obtained by day 4-5 post injection were paralleled by a rapid increase of IFN-gamma, indicating bioactivity of the IL-12 cytokine. Both plasma IL-12 and IFN-gamma levels were reduced to basal levels by day 14, indicating a short presence of elevated levels of the bioactive IL-12. The effect of IL-12 as adjuvant together with an SIVmac239 DNA vaccine was further examined comparing two groups of rhesus macaques vaccinated in the presence or absence of IL-12 DNA. The IL-12 DNA-adjuvanted group developed significantly higher SIV-specific cellular immune responses, including IFN-gamma(+) Granzyme B+ T cells, demonstrating increased levels of vaccine-induced T cells with cytotoxic potential, and this difference persisted for 6 mo after the last vaccination. Coinjection of IL-12 DNA led to increases in Gag-specific CD4(+) and CD4(+)CD8(+) double-positive memory T cell subsets, whereas the Env-specific increases were mainly mediated by the CD8(+) and CD4(+) CD8(+) double-positive memory T cell subsets. The IL-12 DNA-adjuvanted vaccine group developed higher binding antibody titers to Gag and mac251 Env, and showed higher and more durable neutralizing antibodies to heterologous SIVsmE660. Therefore, co-delivery of IL-12 DNA with the SIV DNA vaccine enhanced the magnitude and breadth of immune responses in immunized rhesus macaques, and supports the inclusion of IL-12 DNA as vaccine adjuvant.
C1 [Jalah, Rashmi; Patel, Vainav; Kulkarni, Viraj; Rosati, Margherita; Alicea, Candido; Ganneru, Brunda; von Gegerfelt, Agneta; Pavlakis, George N.; Felber, Barbara K.] Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, CCR, Frederick, MD USA.
[Huang, Wensheng; Guan, Yongjun] Univ Maryland, Sch Med, Inst Human Virol, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Broderick, Kate E.; Sardesai, Niranjan Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[LaBranche, Celia; Montefiori, David C.] Duke Univ, Med Ctr, Dept Surg, Lab AIDS Vaccine Res & Dev, Durham, NC 27710 USA.
RP Pavlakis, GN (reprint author), Frederick Natl Lab Canc Res, Human Retrovirus Sect, Vaccine Branch, CCR, Frederick, MD USA.
EM pavlakig@mail.nih.gov; felberb@mail.nih.gov
RI bebarta, vikhyat/K-3476-2015
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health (NCI/NIH); NIH HHSN [27201100016C]
FX We are grateful to D. Weiss, J. Treece, I. Kalisz, V. Kalyanaraman, P.
Markham and staff at Advanced BioScience Laboratories, Inc., Rockville,
for their expert help. We thank A. Valentin for discussions, J. Bear and
B. Chowdhury for technical assistance, and T. Jones for editorial
assistance. This work was supported by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health
(NCI/NIH) and by NIH HHSN 27201100016C.
NR 65
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U1 0
U2 8
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD NOV
PY 2012
VL 8
IS 11
SI SI
BP 1620
EP 1629
DI 10.4161/hv.21407
PG 10
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA 048GD
UT WOS:000311897900016
PM 22894956
ER
PT J
AU Ferreira, VP
Saggu, G
Pereira, MH
Araujo, RN
Vale, VF
Lima-Ill, KF
Pangburn, MK
Ribeiro, JMC
Gontijo, NF
Collin, N
Valenzuela, JG
AF Ferreira, Viviana P.
Saggu, Gurpanna
Pereira, Marcos H.
Araujo, Ricardo N.
Vale, Vladimir F.
Lima-Ill, Kolyvan F.
Pangburn, Michael K.
Ribeiro, Jose M. C.
Gontijo, Nelder F.
Collin, Nicolas
Valenzuela, Jesus G.
TI LJM19, a salivary protein from the sand fly vector that transmits
leishmaniasis, is a novel inhibitor of the classical pathway of
complement
SO IMMUNOBIOLOGY
LA English
DT Meeting Abstract
C1 [Ferreira, Viviana P.; Saggu, Gurpanna] Univ Toledo, Dept Med Microbiol & Immunol, Coll Med & Hlth Sci, Toledo, OH 43606 USA.
[Pereira, Marcos H.; Araujo, Ricardo N.; Vale, Vladimir F.; Lima-Ill, Kolyvan F.; Gontijo, Nelder F.] Univ Fed Minas Gerais, Dept Parasitol, Lab Physiol Hematophagous Insects, Belo Horizonte, MG, Brazil.
[Pangburn, Michael K.] Univ Texas Hlth Ctr Tyler, Dept Biochem, Tyler, TX 75710 USA.
[Ribeiro, Jose M. C.] NIAID, Vector Biol Sect, LMVR, NIH, Rockville, MD USA.
[Collin, Nicolas] Univ Lausanne, Dept Biochem, Fac Biol & Med, Lausanne, Switzerland.
[Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, LMVR, NIH, Rockville, MD USA.
RI Pereira, Marcos/A-3774-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER GMBH, URBAN & FISCHER VERLAG
PI JENA
PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY
SN 0171-2985
J9 IMMUNOBIOLOGY
JI Immunobiology
PD NOV
PY 2012
VL 217
IS 11
MA 151
BP 1182
EP 1182
DI 10.1016/j.imbio.2012.08.153
PG 1
WC Immunology
SC Immunology
GA 038PY
UT WOS:000311187800165
ER
PT J
AU Gomez-Lopez, N
Laresgoiti-Servitje, E
AF Gomez-Lopez, Nardhy
Laresgoiti-Servitje, Estibalitz
TI T regulatory cells: regulating both term and preterm labor?
SO IMMUNOLOGY AND CELL BIOLOGY
LA English
DT Editorial Material
ID DISTINCT SUBSETS; PREGNANCY; TREGS
C1 [Gomez-Lopez, Nardhy] Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Perinatol Res Branch,NICHD,NIH, Detroit, MI 48202 USA.
[Laresgoiti-Servitje, Estibalitz] Univ Panamer, Dept Immunol, Amer British Cowdray Med Ctr, Mexico City, DF, Mexico.
RP Gomez-Lopez, N (reprint author), Wayne State Univ, Dept Obstet & Gynecol, CS Mott Ctr Human Growth & Dev, Perinatol Res Branch,NICHD,NIH, Detroit, MI 48202 USA.
EM ngomezlo@med.wayne.edu
RI Gomez-Lopez, Nardhy/R-7664-2016; Laresgoiti-Servitje,
Estibalitz/B-7658-2014
OI Gomez-Lopez, Nardhy/0000-0002-3406-5262; Laresgoiti-Servitje,
Estibalitz/0000-0002-3271-9955
NR 13
TC 6
Z9 6
U1 1
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0818-9641
J9 IMMUNOL CELL BIOL
JI Immunol. Cell Biol.
PD NOV-DEC
PY 2012
VL 90
IS 10
BP 919
EP 920
DI 10.1038/icb.2012.48
PG 2
WC Cell Biology; Immunology
SC Cell Biology; Immunology
GA 047IL
UT WOS:000311833200002
PM 23032368
ER
PT J
AU Roschewski, M
Dunleavy, K
Wilson, WH
AF Roschewski, Mark
Dunleavy, Kieron
Wilson, Wyndham H.
TI Diffuse large B cell lymphoma: molecular targeted therapy
SO INTERNATIONAL JOURNAL OF HEMATOLOGY
LA English
DT Article
DE Diffuse large B cell lymphoma; DLBCL; NF-kappa B; STAT3; BCR signaling
ID NON-HODGKINS-LYMPHOMA; PROTEASOME INHIBITOR BORTEZOMIB; RITUXIMAB PLUS
CYCLOPHOSPHAMIDE; TYROSINE KINASE INHIBITOR; CHOP-LIKE CHEMOTHERAPY;
DOSE-ADJUSTED EPOCH; TRIAL MINT GROUP; NF-KAPPA-B; GERMINAL-CENTER;
PHASE-II
AB Diffuse large B cell lymphoma (DLBCL) is a biologically heterogeneous disease and the most common subtype of B cell non-Hodgkin's lymphoma in the USA. Even though it is a curable lymphoma in advanced stages, up to 40 % of patients eventually relapse or fail to achieve remission. Improved understanding of the biologic complexity of DLBCL reveals a diverse range of oncogenic driver mutations and signaling pathways that are essential for growth and survival of malignant cells. Since many of these signaling pathways can be targeted by small-molecule inhibitors, the therapy for DLBCL is currently undergoing a paradigm shift away from conventional chemotherapy and toward targeted agents that capitalize on an improved biologic understanding of the subsets with the highest risk of treatment failure. Participation in well-conducted and rationally designed clinical trials will be essential to realize the potential of these targeted agents and realize the goal of improving overall outcomes in the most common B cell lymphoma in the world.
C1 [Roschewski, Mark; Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Metab Branch, NIH, Bethesda, MD 20892 USA.
RP Roschewski, M (reprint author), NCI, Lymphoma Therapeut Sect, Metab Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM roschewskimj@mail.nih.gov; dunleavk@mail.nih.gov; wilsonw@mail.nih.gov
OI Roschewski, Mark/0000-0003-0278-2635
FU NIH
FX All research support came from the Intramural Research Program of the
NIH.
NR 95
TC 12
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U1 0
U2 6
PU SPRINGER JAPAN KK
PI TOKYO
PA CHIYODA FIRST BLDG EAST, 3-8-1 NISHI-KANDA, CHIYODA-KU, TOKYO, 101-0065,
JAPAN
SN 0925-5710
J9 INT J HEMATOL
JI Int. J. Hematol.
PD NOV
PY 2012
VL 96
IS 5
BP 552
EP 561
DI 10.1007/s12185-012-1198-3
PG 10
WC Hematology
SC Hematology
GA 043BQ
UT WOS:000311518300006
PM 23086603
ER
PT J
AU Abbineni, G
Bisht, K
Roth, H
Hergenrother, P
Haglund, K
AF Abbineni, G.
Bisht, K.
Roth, H.
Hergenrother, P.
Haglund, K.
TI S-PAC-1, a Small Molecule Activator of Procaspase 3, Sensitizes Human
Breast Cancer and Other Cell Lines to Ionizing Radiation
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Abbineni, G.; Bisht, K.; Haglund, K.] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Roth, H.; Hergenrother, P.] Univ Illinois, Dept Chem, Urbana, IL USA.
NR 0
TC 1
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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 NOV 1
PY 2012
VL 84
IS 3
SU S
BP S698
EP S698
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902274
ER
PT J
AU Chen, Y
Calkins, G
Hornicek, F
Harmon, D
Giraud, C
Nielsen, G
Meltzer, P
Suit, H
Michaelson, J
DeLaney, T
AF Chen, Y.
Calkins, G.
Hornicek, F.
Harmon, D.
Giraud, C.
Nielsen, G.
Meltzer, P.
Suit, H.
Michaelson, J.
DeLaney, T.
TI Prognosis of Radiation Associated Bone and Soft-tissue Sarcomas
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Chen, Y.; Calkins, G.; Hornicek, F.; Harmon, D.; Giraud, C.; Nielsen, G.; Suit, H.; Michaelson, J.; DeLaney, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Meltzer, P.] NCI, NIH, Bethesda, MD 20892 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S138
EP S138
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542900342
ER
PT J
AU Citrin, DE
Horton, J
White, A
Hudak, K
Scroggins, B
Chung, E
AF Citrin, D. E.
Horton, J.
White, A.
Hudak, K.
Scroggins, B.
Chung, E.
TI Bone Marrow Mesenchymal Stromal Cell Infusion Improves Radiation-induced
Cutaneous Fibrosis in a Murine Model
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Citrin, D. E.; Horton, J.; White, A.; Hudak, K.; Scroggins, B.; Chung, E.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
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 NOV 1
PY 2012
VL 84
IS 3
SU S
BP S105
EP S106
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542900262
ER
PT J
AU Greer, LL
Ning, H
Zhuge, Y
Erickson, D
Kaushal, A
Kamrava, M
Kramer, K
Kiteley, R
Belard, A
O'Connell, JJ
AF Greer, L. L.
Ning, H.
Zhuge, Y.
Erickson, D.
Kaushal, A.
Kamrava, M.
Kramer, K.
Kiteley, R.
Belard, A.
O'Connell, J. J.
TI Dosimetric Comparison of Photon Stereotactic Ablative Radiation Therapy
(SABR) and Proton SABR in the treatment of Prostate Cancer Patients
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Greer, L. L.; Erickson, D.; Kiteley, R.; O'Connell, J. J.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Ning, H.; Zhuge, Y.; Kaushal, A.] NIH, Bethesda, MD 20892 USA.
[Kamrava, M.] UCLA Dept Radiat Oncol, Los Angeles, CA USA.
[Kramer, K.; Belard, A.] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S411
EP S411
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901229
ER
PT J
AU Ho, J
Edgerly, M
Alimchandani, M
Quezado, M
Camphausen, K
Fojo, T
Kaushal, A
AF Ho, J.
Edgerly, M.
Alimchandani, M.
Quezado, M.
Camphausen, K.
Fojo, T.
Kaushal, A.
TI The Role of Radiation Therapy in Adrenocortical Carcinoma
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Ho, J.; Edgerly, M.; Alimchandani, M.; Quezado, M.; Camphausen, K.; Fojo, T.; Kaushal, A.] NIH, Bethesda, MD 20892 USA.
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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S422
EP S422
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901257
ER
PT J
AU Jones, G
Camphausen, K
Wyndham, W
Smart, D
AF Jones, G.
Camphausen, K.
Wyndham, W.
Smart, D.
TI Characterization of Unconventional Response of Gray Zone Lymphoma to
Conventional Radiation Treatment
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Jones, G.; Camphausen, K.; Wyndham, W.; Smart, D.] NCI, Bethesda, MD 20892 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S622
EP S623
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902076
ER
PT J
AU Kahn, J
Hayman, TJ
Camphausen, K
Tofilon, PJ
AF Kahn, J.
Hayman, T. J.
Camphausen, K.
Tofilon, P. J.
TI The mTORC1/mTORC2 Inhibitor AZD2014 Enhances the Radiosensitivity of
Glioblastoma Stem-like Cells
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Kahn, J.; Hayman, T. J.; Camphausen, K.; Tofilon, P. J.] NCI, Bethesda, MD 20892 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S697
EP S697
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902272
ER
PT J
AU Kahn, J
Gillespie, A
Ondos, J
Dombi, E
Camphausen, K
Widemann, B
Kaushal, A
AF Kahn, J.
Gillespie, A.
Ondos, J.
Dombi, E.
Camphausen, K.
Widemann, B.
Kaushal, A.
TI Radiation Therapy in Management of Sporadic and Neurofibromatosis Type 1
(NF1) Associated Malignant Peripheral Nerve Sheath Tumors (MPNST)
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Kahn, J.; Gillespie, A.; Ondos, J.; Dombi, E.; Camphausen, K.; Widemann, B.; Kaushal, A.] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
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 NOV 1
PY 2012
VL 84
IS 3
SU S
BP S638
EP S638
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902116
ER
PT J
AU Kesarwala, AH
Lu, DJ
Xanthopoulos, E
Apisarnthanarax, S
Evans, T
Aggarwal, C
Cohen, RB
Langer, CJ
Rengan, R
Simone, CB
AF Kesarwala, A. H.
Lu, D. J.
Xanthopoulos, E.
Apisarnthanarax, S.
Evans, T.
Aggarwal, C.
Cohen, R. B.
Langer, C. J.
Rengan, R.
Simone, C. B.
TI The Role of Advanced Imaging in Assessing Response to Definitive
Chemoradiation Prior to Prophylactic Cranial Irradiation in
Limited-Stage Small Cell Lung Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Kesarwala, A. H.] NCI, Bethesda, MD 20892 USA.
[Lu, D. J.; Xanthopoulos, E.; Apisarnthanarax, S.; Evans, T.; Aggarwal, C.; Cohen, R. B.; Langer, C. J.; Rengan, R.; Simone, C. B.] Univ Penn, Philadelphia, PA 19104 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S581
EP S581
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901676
ER
PT J
AU Kesarwala, AH
Ko, C
O'Meara, WP
Ning, H
Haglund, KE
Xanthopoulos, E
Rengan, R
AF Kesarwala, A. H.
Ko, C.
O'Meara, W. P.
Ning, H.
Haglund, K. E.
Xanthopoulos, E.
Rengan, R.
TI Feasibility of Proton Therapy for Elective Nodal Irradiation in Patients
With Locally Advanced Non-small Cell Lung Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Kesarwala, A. H.; Ning, H.; Haglund, K. E.] NCI, Bethesda, MD 20892 USA.
[Ko, C.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[O'Meara, W. P.] Lahey Clin Fdn, Burlington, MA USA.
[Xanthopoulos, E.; Rengan, R.] Univ Penn, Philadelphia, PA 19104 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S577
EP S578
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901667
ER
PT J
AU Kesarwala, AH
Pfalzer, LA
Stout, NL
O'Meara, WP
AF Kesarwala, A. H.
Pfalzer, L. A.
Stout, N. L.
O'Meara, W. P.
TI Symptoms, Physical Impairments, and Function in Breast Cancer Patients
with 1-3 Positive Axillary Lymph Nodes
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Kesarwala, A. H.] NCI, Bethesda, MD 20892 USA.
[Pfalzer, L. A.] Univ Michigan, Flint, MI 48503 USA.
[Stout, N. L.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[O'Meara, W. P.] Lahey Clin Fdn, Burlington, MA USA.
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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S114
EP S115
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542900286
ER
PT J
AU Lawrence, Y
Vikram, B
Dignam, JJ
Chakravarti, A
Freidlin, B
Curran, W
Bentzen, SM
Okunieff, P
Coleman, CN
AF Lawrence, Y.
Vikram, B.
Dignam, J. J.
Chakravarti, A.
Freidlin, B.
Curran, W.
Bentzen, S. M.
Okunieff, P.
Coleman, C. N.
TI NCI-RTOG Translational-Program Strategic Guidelines for the Early Stage
Development of Radiosensitizers
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Lawrence, Y.] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
[Lawrence, Y.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA.
[Vikram, B.] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Dignam, J. J.] Univ Chicago, Chicago, IL 60637 USA.
[Chakravarti, A.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Freidlin, B.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
[Curran, W.] Emory Univ, Atlanta, GA 30322 USA.
[Bentzen, S. M.] Univ Wisconsin, Madison, WI USA.
[Okunieff, P.] Univ Florida, Gainesville, FL USA.
[Coleman, C. N.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RI Bentzen, Soren/E-3997-2012
OI Bentzen, Soren/0000-0002-7444-7564
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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S708
EP S708
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902302
ER
PT J
AU Matsuo, M
Matsumoto, S
Saito, K
Takakusagi, Y
Morris, D
Munasinghe, J
Devasahayam, N
Subramanian, S
Mitchell, J
Krishna, M
AF Matsuo, M.
Matsumoto, S.
Saito, K.
Takakusagi, Y.
Morris, D.
Munasinghe, J.
Devasahayam, N.
Subramanian, S.
Mitchell, J.
Krishna, M.
TI Chronic and Cyclic Hypoxia in Fractionated Radiation Therapy
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Matsuo, M.; Matsumoto, S.; Saito, K.; Takakusagi, Y.; Morris, D.; Munasinghe, J.; Devasahayam, N.; Subramanian, S.; Mitchell, J.; Krishna, M.] NIH, Bethesda, MD 20892 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S687
EP S687
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902244
ER
PT J
AU Mirabeau-Beale, KL
Chen, M
Sun, L
D'Amico, AV
AF Mirabeau-Beale, K. L.
Chen, M.
Sun, L.
D'Amico, A. V.
TI Metachronous Cancer Diagnosis in Men With Prostate Cancer and the Risk
of Prostate Cancer-specific Mortality: A Competing Risks Analysis
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Mirabeau-Beale, K. L.] Harvard Radiat Oncol Program, Boston, MA USA.
[Chen, M.] Univ Connecticut, Storrs, CT USA.
[Sun, L.] NCI, DCCPS, Bethesda, MD 20892 USA.
[D'Amico, A. V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[D'Amico, A. V.] Dana Farber Canc Inst, Boston, MA 02115 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S540
EP S540
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901569
ER
PT J
AU Russo, AL
Chen, M
Sun, L
Aizer, A
Hattangadi, J
D'Amico, AV
AF Russo, A. L.
Chen, M.
Sun, L.
Aizer, A.
Hattangadi, J.
D'Amico, A. V.
TI Advancing Age Within Established Gleason Score Categories and the Risk
of Prostate Cancer-specific Mortality
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Russo, A. L.; Aizer, A.; Hattangadi, J.] Harvard Radiat Oncol Program, Boston, MA USA.
[Chen, M.] Univ Connecticut, Storrs, CT USA.
[Sun, L.] NCI, Bethesda, MD 20892 USA.
[D'Amico, A. V.] Brigham & Womens Hosp, Boston, MA 02115 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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S535
EP S535
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901557
ER
PT J
AU Simone, CB
Sibley, C
Dan, TD
Boyce, DM
Smith, S
Lippman, M
Glatstein, E
Bluemke, DA
Camphausen, K
Simone, NL
AF Simone, C. B.
Sibley, C.
Dan, T. D.
Boyce, D. M.
Smith, S.
Lippman, M.
Glatstein, E.
Bluemke, D. A.
Camphausen, K.
Simone, N. L.
TI Cardiac Toxicity is Not Increased 25 Years After Treatment of
Early-stage Breast Carcinoma With Mastectomy or Breast Conservation
Therapy From the National Cancer Institute Randomized Trial
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Simone, C. B.; Glatstein, E.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Sibley, C.; Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Dan, T. D.; Smith, S.; Camphausen, K.] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA.
[Boyce, D. M.] Johns Hopkins Univ, Sch Med Pulm & Crit Care Med, Baltimore, MD USA.
[Lippman, M.] Univ Miami Hlth Syst, Dept Med, Div Hematol Oncol, Miami, FL USA.
[Simone, N. L.] Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA.
RI Sibley, Christopher/C-9900-2013
NR 0
TC 0
Z9 0
U1 0
U2 2
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 NOV 1
PY 2012
VL 84
IS 3
SU S
BP S35
EP S36
PG 2
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542900091
ER
PT J
AU Vogel, J
Sia-Atanacio, A
Adams, K
Martucci, V
Prodanov, T
Camphausen, K
Fojo, A
Pacak, K
Kaushal, A
AF Vogel, J.
Sia-Atanacio, A.
Adams, K.
Martucci, V.
Prodanov, T.
Camphausen, K.
Fojo, A.
Pacak, K.
Kaushal, A.
TI Radiation Therapy in Management of Malignant Pheochromocytoma
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Vogel, J.; Sia-Atanacio, A.; Adams, K.; Martucci, V.; Prodanov, T.; Camphausen, K.; Fojo, A.; Pacak, K.; Kaushal, A.] NIH, Bethesda, MD 20892 USA.
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 0360-3016
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2012
VL 84
IS 3
SU S
BP S421
EP S421
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542901256
ER
PT J
AU Zheng, S
Acerbi, I
Kuhn, NZ
Au, A
Park, CC
Weaver, VM
AF Zheng, S.
Acerbi, I.
Kuhn, N. Z.
Au, A.
Park, C. C.
Weaver, V. M.
TI Ionizing Radiation Modifies Tissue Tension, Mechanosignaling, and
Apoptosis in Human Breast
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology
(ASTRO)
CY OCT 28-31, 2012
CL Boston, MA
SP Amer Soc Radiat Oncol (ASTRO)
C1 [Zheng, S.; Acerbi, I.; Weaver, V. M.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Zheng, S.; Acerbi, I.; Weaver, V. M.] Univ Calif San Francisco, Ctr Bioengn & Tissue Regenerat, San Francisco, CA 94143 USA.
[Kuhn, N. Z.] NCI, Off Phys Sci Oncol, Ctr Strateg Sci Initiat, Off Director,NIH, Bethesda, MD 20892 USA.
[Au, A.] UCSF Carol Franc Buck Breast Care Ctr, San Francisco, CA USA.
[Park, C. C.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA.
[Weaver, V. M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
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 NOV 1
PY 2012
VL 84
IS 3
SU S
BP S669
EP S669
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 030BP
UT WOS:000310542902197
ER
PT J
AU Hasumi, H
Baba, M
Hasumi, Y
Huang, Y
Oh, H
Hughes, RM
Klein, ME
Takikita, S
Nagashima, K
Schmidt, LS
Linehan, WM
AF Hasumi, Hisashi
Baba, Masaya
Hasumi, Yukiko
Huang, Ying
Oh, Hyoungbin
Hughes, Robert M.
Klein, Mara E.
Takikita, Shoichi
Nagashima, Kunio
Schmidt, Laura S.
Linehan, W. Marston
TI Regulation of Mitochondrial Oxidative Metabolism by Tumor Suppressor
FLCN
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; TUBEROUS SCLEROSIS COMPLEX;
RENAL-CELL CARCINOMA; HOGG-DUBE-SYNDROME; SKELETAL-MUSCLE;
GENE-EXPRESSION; MTOR ACTIVATION; KIDNEY TUMORS; PROTEIN; CANCER
AB Background Birt-Hogg-Dub (BHD) syndrome is a hereditary hamartoma syndrome that predisposes patients to develop hair follicle tumors, lung cysts, and kidney cancer. Genetic studies of BHD patients have uncovered the causative gene, FLCN, but its function is incompletely understood.
Methods Mice with conditional alleles of FLCN and/or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A), a transcriptional coactivator that regulates mitochondrial biogenesis, were crossbred with mice harboring either muscle creatine kinase (CKM) Cre or myogenin (MYOG) Cre transgenes to knock out FLCN and/or PPARGC1A in muscle, or cadherin 16 (CDH16)Cre transgenes to knock out FLCN and/or PPARGC1A in kidney. Real-time polymerase chain reaction, immunoblotting, electron microscopy, and metabolic profiling assay were performed to evaluate mitochondrial biogenesis and function in muscle. Immunoblotting, electron microscopy, and histological analysis were used to investigate expression and the pathological role of PPARGC1A in FLCN-deficient kidney. Real-time polymerase chain reaction, oxygen consumption measurement, and flow cytometry were carried out using a FLCN-null kidney cancer cell line. All statistical analyses were two-sided.
Results Muscle-targeted FLCN knockout mice underwent a pronounced metabolic shift toward oxidative phosphorylation, including increased mitochondrial biogenesis (FLCNf/f vs FLCNf/f/CKMCre: % mitochondrial area mean 7.8% vs 17.8%; difference 10.0%; 95% confidence interval 5.7% to 14.3%; P < .001), and the observed increase in mitochondrial biogenesis was PPARGC1A dependent. Reconstitution of FLCN-null kidney cancer cells with wild-type FLCN suppressed mitochondrial metabolism and PPARGC1A expression. Kidney-targeted PPARGC1A inactivation partially rescued the enlarged kidney phenotype and abrogated the hyperplastic cells observed in the FLCN-deficient kidney.
Conclusion FLCN deficiency and subsequent increased PPARGC1A expression result in increased mitochondrial function and oxidative metabolism as the source of cellular energy, which may give FLCN-null kidney cells a growth advantage and drive hyperplastic transformation.
C1 [Hasumi, Hisashi; Baba, Masaya; Hasumi, Yukiko; Huang, Ying; Oh, Hyoungbin; Hughes, Robert M.; Klein, Mara E.; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Takikita, Shoichi] NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA.
[Nagashima, Kunio] SAIC Frederick Inc, Image Anal Lab, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Schmidt, Laura S.] SAIC Frederick Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, 10 Ctr Dr,MSC 1107,CRC Rm 1-5940W, Bethesda, MD 20892 USA.
EM wml@nih.gov
RI Baba, Masaya/L-7490-2013
OI Baba, Masaya/0000-0002-5308-6683
FU National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research; Frederick National Laboratory for Cancer Research,
NIH [HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. This project was funded in part with federal funds
from the Frederick National Laboratory for Cancer Research, NIH, under
contract HHSN261200800001E.
NR 59
TC 25
Z9 25
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD NOV
PY 2012
VL 104
IS 22
BP 1750
EP 1764
DI 10.1093/jnci/djs418
PG 15
WC Oncology
SC Oncology
GA 045BK
UT WOS:000311669100010
PM 23150719
ER
PT J
AU Robert, MA
Legros, M
Facchinelli, L
Valerio, L
Ramsey, JM
Scott, TW
Gould, F
Lloyd, AL
AF Robert, Michael A.
Legros, Mathieu
Facchinelli, Luca
Valerio, Laura
Ramsey, Janine M.
Scott, Thomas W.
Gould, Fred
Lloyd, Alun L.
TI Mathematical Models as Aids for Design and Development of Experiments:
The Case of Transgenic Mosquitoes
SO JOURNAL OF MEDICAL ENTOMOLOGY
LA English
DT Article
DE Aedes aegypti; transgenic female-killing; field cage experiment;
experimental design; mathematical model
ID AEDES-AEGYPTI DIPTERA; GENETIC-CONTROL SYSTEMS; STERILE MALES; BORNE
DISEASES; INSECT PESTS; HUMAN BLOOD; CULICIDAE; DENGUE; POPULATION;
RELEASE
AB We demonstrate the utility of models as aids in the design and development of experiments aimed at measuring the effects of proposed vector population control strategies. We describe the exploration of a stochastic, age-structured model that simulates field cage experiments that test the ability of a female-killing strain of the mosquito Aedes aegypti (L.) to suppress a wild-type population. Model output predicts that choices of release ratio and population size can impact mean extinction time and variability in extinction time among experiments. We find that unless fitness costs are >80% they will not be detectable in experiments with high release ratios. At lower release ratios, the predicted length of the experiment increases significantly for fitness costs >20%. Experiments with small populations may more accurately reflect field conditions, but extinction can occur even in the absence of a functional female-killing construct because of stochastic effects. We illustrate how the model can be used to explore experimental designs that aim to study the impact of density dependence and immigration; predictions indicate that cage population eradication may not always be obtainable in an operationally realistic time frame. We propose a method to predict the extinction time of a cage population based on the rate of population reduction with the goal of shortening the duration of the experiment. We discuss the model as a tool for exploring and assessing the utility of a wider range of scenarios than would be feasible to test experimentally because of financial and temporal restraints.
C1 [Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Dept Math, Raleigh, NC 27695 USA.
[Robert, Michael A.; Lloyd, Alun L.] N Carolina State Univ, Biomath Grad Progarm, Raleigh, NC 27695 USA.
[Legros, Mathieu; Gould, Fred] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA.
[Legros, Mathieu; Facchinelli, Luca; Valerio, Laura; Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Valerio, Laura] Univ Roma La Sapienza, Cenci Bolognetti Fdn, Inst Pasteur, Rome, Italy.
[Ramsey, Janine M.] Ctr Reg Invest Salud Publ, Inst Nacl Salud Publ, Tapachula, Chiapas, Mexico.
[Scott, Thomas W.; Gould, Fred; Lloyd, Alun L.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Robert, MA (reprint author), N Carolina State Univ, Dept Math, Box 8203, Raleigh, NC 27695 USA.
EM marober5@ncsu.edu
RI Legros, Mathieu/E-6767-2011; Lloyd, Alun/H-4944-2012;
OI Legros, Mathieu/0000-0003-3807-8594; Facchinelli,
Luca/0000-0002-8987-1472
FU National Institutes of Health (NIH) [R01AI091980-01A1]; Foundation for
the NIH through the Grand Challenges in Global Health initiative; North
Carolina State University Mathematics Research Experience for Graduate
Students (NSF) [DMS-EMSW21-MCTP-0943855]; Pasteur Institute-Cenci
Bolognetti Foundation
FX This work is funded by National Institutes of Health (NIH) grant
R01AI091980-01A1, a grant to the Regents of the University of California
from the Foundation for the NIH through the Grand Challenges in Global
Health initiative. Our analysis was improved by discussions fostered by
the Research and Policy for Infectious Disease Dynamics (RAPIDD) program
of the Science and Technology Directory, Department of Homeland
Security, and Fogarty International Center, NIH. M. A. Robert was
supported in part by the North Carolina State University Mathematics
Research Experience for Graduate Students (NSF grant
DMS-EMSW21-MCTP-0943855). L. V. was supported by a Pasteur
Institute-Cenci Bolognetti Foundation grant. We extend our gratitude to
two anonymous reviewers and Steven Juliano for comments that improved
the content of this article.
NR 49
TC 3
Z9 3
U1 3
U2 26
PU ENTOMOLOGICAL SOC AMER
PI LANHAM
PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA
SN 0022-2585
J9 J MED ENTOMOL
JI J. Med. Entomol.
PD NOV
PY 2012
VL 49
IS 6
BP 1177
EP 1188
DI 10.1603/ME11205
PG 12
WC Entomology; Veterinary Sciences
SC Entomology; Veterinary Sciences
GA 040EC
UT WOS:000311303200002
PM 23270145
ER
PT J
AU Kohlmeier, KA
Ishibashi, M
Wess, J
Bickford, ME
Leonard, CS
AF Kohlmeier, Kristi A.
Ishibashi, Masaru
Wess, Juergen
Bickford, Martha E.
Leonard, Christopher S.
TI Knockouts reveal overlapping functions of M-2 and M-4 muscarinic
receptors and evidence for a local glutamatergic circuit within the
laterodorsal tegmental nucleus
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE muscarinic receptors; GIRK channels; R-type Ca2+ channels; cholinergic
neural pathways; brain slice; sleep; arousal; motivation; ascending
arousal system
ID PONTINE RETICULAR-FORMATION; MESOPONTINE CHOLINERGIC NEURONS; EVOKED
CALCIUM TRANSIENTS; EYE-MOVEMENT SLEEP; BRAIN-STEM CORE;
ACETYLCHOLINE-RECEPTORS; RAT-BRAIN; PONTOMESENCEPHALIC TEGMENTUM; BASAL
FOREBRAIN; C57BL/6J MOUSE
AB Kohlmeier KA, Ishibashi M, Wess J, Bickford ME, Leonard CS. Knockouts reveal overlapping functions of M-2 and M-4 muscarinic receptors and evidence for a local glutamatergic circuit within the laterodorsal tegmental nucleus. J Neurophysiol 108: 2751-2766, 2012. First published September 5, 2012; doi:10.1152/jn.01120.2011.-Cholinergic neurons in the laterodorsal tegmental (LDT) and peduncolopontine tegmental (PPT) nuclei regulate reward, arousal, and sensory gating via major projections to midbrain dopamine regions, the thalamus, and pontine targets. Muscarinic acetylcholine receptors (mAChRs) on LDT neurons produce a membrane hyperpolarization and inhibit spike-evoked Ca2+ transients. Pharmacological studies suggest M-2 mAChRs are involved, but the role of these and other localized mAChRs (M1--M-4) has not been definitively tested. To identify the underlying receptors and to circumvent the limited receptor selectivity of available mAChR ligands, we used light- and electron-immunomicroscopy and whole cell recording with Ca2+ imaging in brain slices from knockout mice constitutively lacking either M-2, M-4, or both mAChRs. Immunomicroscopy findings support a role for M-2 mAChRs, since cholinergic and noncholinergic LDT and pedunculopontine tegmental neurons contain M-2-specific immunoreactivity. However, whole cell recording revealed that the presence of either M-2 or M-4 mAChRs was sufficient, and that the presence of at least one of these receptors was required for these carbachol actions. Moreover, in the absence of M-2 and M-4 mAChRs, carbachol elicited both direct excitation and barrages of spontaneous excitatory postsynaptic potentials (sEPSPs) in cholinergic LDT neurons mediated by M-1 and/or M-3 mAChRs. Focal carbachol application to surgically reduced slices suggest that local glutamatergic neurons are a source of these sEPSPs. Finally, neither direct nor indirect excitation were knockout artifacts, since each was detected in wild-type slices, although sEPSP barrages were delayed, suggesting M 2 and M 4 receptors normally delay excitation of glutamatergic inputs. Collectively, our findings indicate that multiple mAChRs coordinate cholinergic outflow from the LDT in an unexpectedly complex manner. An intriguing possibility is that a local circuit transforms LDT muscarinic inputs from a negative feedback signal for transient inputs into positive feedback for persistent inputs to facilitate different firing patterns across behavioral states.
C1 [Ishibashi, Masaru; Leonard, Christopher S.] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
[Kohlmeier, Kristi A.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Copenhagen, Denmark.
[Wess, Juergen] NIDDK, Bethesda, MD USA.
[Bickford, Martha E.] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
RP Leonard, CS (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA.
EM chris_leonard@nymc.edu
FU National Institutes of Health [NS27881, HL64150, NS35377]
FX Research was supported by National Institutes of Health grants NS27881
(C. S. Leonard), HL64150 (C. S. Leonard), and NS35377 (M. E. Bickford).
NR 77
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Z9 10
U1 2
U2 4
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2012
VL 108
IS 10
BP 2751
EP 2766
DI 10.1152/jn.01120.2011
PG 16
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 039EK
UT WOS:000311226600010
PM 22956788
ER
PT J
AU Kurdziel, KA
AF Kurdziel, Karen A.
TI Radiation Exposure Should Not Limit Bone Scintigraphy with F-18-NaF
REPLY
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Letter
C1 NCI, NIH, Bethesda, MD 20892 USA.
RP Kurdziel, KA (reprint author), NCI, NIH, 10 Ctr Dr,Room B3B403, Bethesda, MD 20892 USA.
EM kurdziek@mail.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD NOV
PY 2012
VL 53
IS 11
BP 1818
EP 1819
DI 10.2967/jnumed.112.111484
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 037TC
UT WOS:000311128400031
ER
PT J
AU Volkin, D
Yerram, N
Ahmed, F
Lankford, D
Baccala, A
Gupta, GN
Hoang, A
Nix, J
Metwalli, AR
Lang, DM
Bratslavsky, G
Linehan, WM
Pinto, PA
AF Volkin, Dmitry
Yerram, Nitin
Ahmed, Faisal
Lankford, Dawud
Baccala, Angelo
Gupta, Gopal N.
Hoang, Anthony
Nix, Jeffrey
Metwalli, Adam R.
Lang, David M.
Bratslavsky, Gennady
Linehan, W. Marston
Pinto, Peter A.
TI Partial adrenalectomy minimizes the need for long-term hormone
replacement in pediatric patients with pheochromocytoma and von
Hippel-Lindau syndrome
SO JOURNAL OF PEDIATRIC SURGERY
LA English
DT Article
DE Adrenalectomy; Partial adrenalectomy; Pediatric VHL; Pheochromocytoma
ID LAPAROSCOPIC PARTIAL ADRENALECTOMY; QUALITY-OF-LIFE; HEREDITARY
PHEOCHROMOCYTOMA; BILATERAL ADRENALECTOMY; SURGERY; DISEASE;
INSUFFICIENCY; EXPERIENCE; MANAGEMENT; NEOPLASIA
AB Purpose: Children with von Hippel-Lindau syndrome (VHL) are at an increased risk for developing bilateral pheochromocytomas. In an effort to illustrate the advantage of partial adrenalectomy (PA) over total adrenalectomy in children with VHL, we report the largest single series on PA for pediatric patients with VHL, demonstrating a balance between tumor removal and preservation of adrenocortical function.
Methods: From 1994 to 2011, a prospectively maintained database was reviewed to evaluate 10 pediatric patients with hereditary pheochromocytoma for PA. Surgery was performed if there was clinical evidence of pheochromocytoma and if normal adrenocortical tissue was evident on preoperative imaging and/or intraoperative ultrasonography. Perioperative data were collected, and patients were observed for postoperative steroid use and tumor recurrence.
Results: Ten pediatric patients with a diagnosis of VHL underwent 18 successful partial adrenalectomies (4 open, 14 laparoscopic). The median tumor size removed was 2.6 cm (range, 1.2-6.5 cm). Over a median follow-up of 7.2 years (range, 2.6-15.8 years), additional tumors in the ipsilateral adrenal gland were found in 2 patients. One patient underwent completion adrenalectomy, and 1 underwent a salvage PA with resection of the ipsilateral lesion. One patient required short-term steroid replacement therapy. At last follow-up, 7 patients had no radiographic or laboratory evidence of pheochromocytoma.
Conclusion: At our institution, PA is the preferred form of management for pheochromocytoma in the (VHL) pediatric population. This surgical approach allows for removal of tumor while preserving adrenocortical function and minimizing the adverse effects of long-term steroid replacement on puberty and quality of life. (c) 2012 Published by Elsevier Inc.
C1 [Pinto, Peter A.] NCI, Fellowship Program, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Fellowship Program, Urol Oncol Branch, Ctr Canc Res, 10 Ctr Dr,MSC 1210, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX This research was supported, in part, by the Intramural Research Program
of the National Cancer Institute, National Institutes of Health.
NR 30
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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 0022-3468
J9 J PEDIATR SURG
JI J. Pediatr. Surg.
PD NOV
PY 2012
VL 47
IS 11
BP 2077
EP 2082
DI 10.1016/j.jpedsurg.2012.07.003
PG 6
WC Pediatrics; Surgery
SC Pediatrics; Surgery
GA 039DG
UT WOS:000311222500031
PM 23164001
ER
PT J
AU Chen, AP
Setser, A
Anadkat, MJ
Cotliar, J
Olsen, EA
Garden, BC
Lacouture, ME
AF Chen, Alice P.
Setser, Ann
Anadkat, Milan J.
Cotliar, Jonathan
Olsen, Elise A.
Garden, Benjamin C.
Lacouture, Mario E.
TI Grading dermatologic adverse events of cancer treatments: The Common
Terminology Criteria for Adverse Events Version 4.0
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE adverse events; cancer treatment; Common Terminology Criteria for
Adverse Events; drug reactions; grading system; side effects
ID HAND-FOOT SYNDROME; INDUCED SKIN RASH; CUTANEOUS REACTIONS; CELL
CARCINOMA; MANAGEMENT; TOXICITY; CHEMOTHERAPY; CETUXIMAB; RADIOTHERAPY;
INHIBITORS
AB Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. (J Am Acad Dermatol 2012;67:1025-39.)
C1 [Garden, Benjamin C.; Lacouture, Mario E.] Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, New York, NY 10022 USA.
[Chen, Alice P.] NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Setser, Ann] NCI, Invest Drug Branch, NIH, Canc Therapy Evaluat Program, Rockville, MD USA.
[Anadkat, Milan J.] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA.
[Cotliar, Jonathan] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA.
[Olsen, Elise A.] Duke Univ, Med Ctr, Dept Med, Div Dermatol, Durham, NC 27710 USA.
[Olsen, Elise A.] Duke Univ, Med Ctr, Dept Med, Div Oncol, Durham, NC 27710 USA.
RP Lacouture, ME (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Dermatol Serv, Suite 228,160 E 53 St, New York, NY 10022 USA.
EM lacoutum@mskcc.org
FU US National Institutes of Health; Zell Scholarship from the Robert H.
Lurie Comprehensive Cancer Center of Northwestern University;
Dermatology Foundation Career Development Award
FX Supported by US National Institutes of Health; Dr Lacouture receives
funding from a Zell Scholarship from the Robert H. Lurie Comprehensive
Cancer Center of Northwestern University and a Dermatology Foundation
Career Development Award.
NR 34
TC 44
Z9 52
U1 1
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD NOV
PY 2012
VL 67
IS 5
BP 1025
EP 1039
DI 10.1016/j.jaad.2012.02.010
PG 15
WC Dermatology
SC Dermatology
GA 033EI
UT WOS:000310776600064
PM 22502948
ER
PT J
AU Sahasrabuddhe, VV
Sherman, ME
AF Sahasrabuddhe, Vikrant V.
Sherman, Mark E.
TI Human Papillomavirus Vaccines for Cervical Cancer Prevention:
Translating Possibility Into Reality
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID EFFICACY
C1 [Sahasrabuddhe, Vikrant V.; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Sahasrabuddhe, VV (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 5032, Rockville, MD 20852 USA.
EM vikrant.sahasrabuddhe@nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 11
TC 2
Z9 2
U1 0
U2 3
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 NOV
PY 2012
VL 104
IS 22
BP 1698
EP 1701
DI 10.1093/jnci/djs453
PG 4
WC Oncology
SC Oncology
GA 045BK
UT WOS:000311669100005
PM 23104325
ER
PT J
AU Wentzensen, N
Sun, C
Ghosh, A
Kinney, W
Mirabello, L
Wacholder, S
Shaber, R
LaMere, B
Clarke, M
Lorincz, AT
Castle, PE
Schiffman, M
Burk, RD
AF Wentzensen, Nicolas
Sun, Chang
Ghosh, Arpita
Kinney, Walter
Mirabello, Lisa
Wacholder, Sholom
Shaber, Ruth
LaMere, Brandon
Clarke, Megan
Lorincz, Attila T.
Castle, Philip E.
Schiffman, Mark
Burk, Robert D.
TI Methylation of HPV18, HPV31, and HPV45 Genomes and Cervical
Intraepithelial Neoplasia Grade 3
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS DNA; CANCER; PROGRESSION; PRECANCER; BIOMARKER;
TESTS; WOMEN; RISK; GENE
AB Background Persistent infections with carcinogenic human papillomavirus (HPV) types are the necessary cause of cervical cancer. We recently demonstrated that the HPV16 genome is strongly methylated in cervical precancer compared with transient infections. However, the extent of methylation in other HPV types and its role in progression to cancer is poorly understood.
Methods We analyzed whole-genome methylation patterns of the three next most carcinogenic HPV genotypes: HPV31 (closely related to HPV16), and two other closely related types, HPV18 and HPV45. DNA was extracted from cervical cytology specimens from 92 women with precancer and 96 women infected with HPV31, HPV18, or HPV45, but who had no cytological or histological abnormalities. After bisulfite modification, genome-wide pyrosequencing was performed covering 80106 sites. We calculated differences in median methylation, odds ratios, areas under the curve, and Spearman rank correlation coefficients for methylation levels between different sites. All statistical tests were two-sided.
Results For all three HPV types, we observed strongly elevated methylation levels at multiple CpG sites in the E2, L2, and L1 regions among women with cervical intraepithelial neoplasia grade 3 compared with women with transient infections. We observed high correlation of methylation patterns between phylogenetically related types. The highest areas under the curve were 0.81 for HPV31, 0.85 for HPV18, and 0.98 for HPV45. Differential methylation patterns in cervical intraepithelial neoplasia grade 3 patients with multiple infections suggest that methylation can clarify which of the infections is causal.
Conclusions Carcinogenic HPV DNA methylation indicates transforming HPV infections. Our findings show that methylation of carcinogenic HPV types is a general phenomenon that warrants development of diagnostic assays.
C1 [Wentzensen, Nicolas; Ghosh, Arpita; Mirabello, Lisa; Wacholder, Sholom; Clarke, Megan; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Sun, Chang; Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Sun, Chang] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Minist Educ, Kunming, Peoples R China.
[Sun, Chang] Yunnan Univ, Minist Educ, Key Lab Microbial Div SW China, Kunming, Peoples R China.
[Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
[Shaber, Ruth] Kaiser Permanente, Care Management Inst, Oakland, CA USA.
[LaMere, Brandon] Kaiser Permanente, Div Res, Womens Hlth Res Inst, Oakland, CA USA.
[Lorincz, Attila T.] Univ London, Wolfson Inst Prevent Med, Ctr Canc Prevent, London, England.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5024, Rockville, MD 20852 USA.
EM wentzenn@mail.nih.gov; burk@aecom.yu.edu
RI Sun, Chang/I-6326-2012
FU National Cancer Institute
FX The research was funded by the Intramural Research Program of the
National Cancer Institute. The funding source had no influence on the
design, conduct, and evaluation of the study.
NR 24
TC 46
Z9 48
U1 2
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 NOV
PY 2012
VL 104
IS 22
BP 1738
EP 1749
DI 10.1093/jnci/djs425
PG 12
WC Oncology
SC Oncology
GA 045BK
UT WOS:000311669100009
PM 23093560
ER
PT J
AU Patlolla, AK
Todorov, TI
Tchounwou, PB
van der Voet, G
Centeno, JA
AF Patlolla, Anita K.
Todorov, Todor I.
Tchounwou, Paul B.
van der Voet, Gijsbert
Centeno, Jose A.
TI Arsenic-induced biochemical and genotoxic effects and distribution in
tissues of Sprague-Dawley rats
SO MICROCHEMICAL JOURNAL
LA English
DT Article
DE Arsenic exposure; Tissue distribution; Genotoxicity; Hepatotoxicity;
Rats
ID INDUCED CELL-TRANSFORMATION; HAMSTER EMBRYO CELLS; SODIUM ARSENITE;
HYPERENDEMIC VILLAGES; DRINKING-WATER; IN-VITRO; TRIOXIDE; EXPOSURE;
TOXICITY; MECHANISMS
AB Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 +/- 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15,20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GFT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. in contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. Published by Elsevier B.V.
C1 [Patlolla, Anita K.; Tchounwou, Paul B.] Jackson State Univ, NIH RCMI Ctr Environm Hlth, Jackson, MS USA.
[Todorov, Todor I.] US Geol Survey, Crustal Geophys & Geochem Sci Ctr, Denver, CO 80225 USA.
[Centeno, Jose A.] Joint Pathol Ctr, Biophys Toxicol Lab, Silver Spring, MD 20910 USA.
[van der Voet, Gijsbert] Hlth Council Netherlands, The Hague, Netherlands.
RP Centeno, JA (reprint author), Joint Base Andrews Air Naval Facil Washington, Biophys Toxicol Lab, Joint Pathol Ctr, Malcolm Grow Med Clin, 1057 W Perimeter Rd, Joint Base Andrews, MD 20762 USA.
EM Jose.Centeno@afncr.af.mil
FU National Institutes of Health-RCMI Grant [1G12RR13459]
FX This research was financially supported by the National Institutes of
Health-RCMI Grant No. 1G12RR13459 awarded to PBT.
NR 77
TC 7
Z9 7
U1 1
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0026-265X
J9 MICROCHEM J
JI Microchem J.
PD NOV
PY 2012
VL 105
SI SI
BP 101
EP 107
DI 10.1016/j.microc.2012.08.013
PG 7
WC Chemistry, Analytical
SC Chemistry
GA 039QE
UT WOS:000311260800017
PM 23175155
ER
PT J
AU Fang, F
Chen, HL
Feldman, AL
Kamel, F
Ye, WM
Wirdefeldt, K
AF Fang, Fang
Chen, Honglei
Feldman, Adina L.
Kamel, Freya
Ye, Weimin
Wirdefeldt, Karin
TI Head injury and Parkinson's disease: A population-based study
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson disease; head injury; nested case-control study; odds ratio
ID ENVIRONMENTAL RISK-FACTORS; TRAUMATIC BRAIN-INJURY; HISTORY
AB Background: The epidemiological evidence on head injury and the risk of Parkinson's disease (PD) has been inconsistent.
Methods: We examined the relation between previous hospitalization for head injury and PD using a population-based nested case-control design based on the Swedish National Patient Register from 2001 until 2007, including 18,648 PD cases and 93,240 controls, randomly selected from the general population. Exposure was defined as hospitalization for head injury between 1987 and index date.
Results: Overall, previous hospitalization resulting from head injury was associated with an increased risk of PD; this association appeared to be largely explained by head injuries experienced recently, especially within 1 year before PD ascertainment.
Conclusions: Our results do not provide convincing evidence for a causal relationship between head injury later in life and PD. (C) 2012 Movement Disorder Society
C1 [Fang, Fang; Feldman, Adina L.; Ye, Weimin; Wirdefeldt, Karin] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Chen, Honglei; Kamel, Freya] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
[Wirdefeldt, Karin] Karolinska Inst, Dept Clin Neurosci, SE-17177 Stockholm, Sweden.
RP Wirdefeldt, K (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, SE-17177 Stockholm, Sweden.
EM karin.wirdefeldt@ki.se
RI Feldman, Adina/H-3435-2012;
OI Feldman, Adina/0000-0002-9388-6896; Fang, Fang/0000-0002-3310-6456;
Kamel, Freya/0000-0001-5052-6615; Chen, Honglei/0000-0003-3446-7779
FU Swedish Research Council (SIMSAM) [80748301]; Swedish Parkinson
Foundation; Swedish Medical Society; Swedish Society for Medical
Research; Swedish Brain Foundation; National Institutes of Health, the
National Institute of Environmental Health Sciences [Z01-ES-101986]
FX The study was supported by the Swedish Research Council (SIMSAM grant
no. 80748301), the Swedish Parkinson Foundation, the Swedish Medical
Society, the Swedish Society for Medical Research, the Swedish Brain
Foundation, and the intramural research program of the National
Institutes of Health, the National Institute of Environmental Health
Sciences (Z01-ES-101986 and unmet need funding). The funding sources had
no role in the design of the study or the decision to submit the
manuscript for publication.
NR 22
TC 10
Z9 10
U1 0
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV
PY 2012
VL 27
IS 13
BP 1632
EP 1635
DI 10.1002/mds.25143
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 045KU
UT WOS:000311695500013
PM 23143933
ER
PT J
AU Goldman, SM
Kamel, F
Ross, GW
Bhudhikanok, GS
Hoppin, JA
Korell, M
Marras, C
Meng, C
Umbach, DM
Kasten, M
Chade, AR
Comyns, K
Richards, MB
Sandler, DP
Blair, A
Langston, JW
Tanner, CM
AF Goldman, Samuel M.
Kamel, Freya
Ross, G. Webster
Bhudhikanok, Grace S.
Hoppin, Jane A.
Korell, Monica
Marras, Connie
Meng, Cheryl
Umbach, David M.
Kasten, Meike
Chade, Anabel R.
Comyns, Kathleen
Richards, Marie B.
Sandler, Dale P.
Blair, Aaron
Langston, J. William
Tanner, Caroline M.
TI Genetic modification of the association of paraquat and Parkinson's
disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; paraquat; glutathione transferase; pesticide;
gene-environment interaction
ID GLUTATHIONE-S-TRANSFERASE; ENVIRONMENTAL RISK-FACTORS; PESTICIDE
EXPOSURE; OXIDATIVE STRESS; AGRICULTURAL HEALTH; P1 POLYMORPHISMS;
NEURON LOSS; O-QUINONES; POPULATION; MECHANISM
AB Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson's disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity. We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S-transferase M1 (GSTM1) or T1 (GSTT1). Eighty-seven PD subjects and 343 matched controls were recruited from the Agricultural Health Study, a study of licensed pesticide applicators and spouses in Iowa and North Carolina. PD was confirmed by in-person examination. Paraquat use and covariates were determined by interview. We genotyped subjects for homozygous deletions of GSTM1 (GSTM1*0) and GSTT1 (GSTT1*0) and tested interaction between paraquat use and genotype using logistic regression. Two hundred and twenty-three (52%) subjects had GSTM1*0, 95 (22%) had GSTT1*0, and 73 (17%; all men) used paraquat. After adjustment for potential confounders, there was no interaction with GSTM1. In contrast, GSTT1 genotype significantly modified the association between paraquat and PD. In men with functional GSTT1, the odds ratio (OR) for association of PD with paraquat use was 1.5 (95% confidence interval [CI]: 0.63.6); in men with GSTT1*0, the OR was 11.1 (95% CI: 3.044.6; P interaction: 0.027). Although replication is needed, our results suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat. (C) 2012 Movement Disorder Society
C1 [Goldman, Samuel M.; Bhudhikanok, Grace S.; Korell, Monica; Meng, Cheryl; Comyns, Kathleen; Langston, J. William; Tanner, Caroline M.] Parkinsons Inst, Sunnyvale, CA 94085 USA.
[Kamel, Freya; Hoppin, Jane A.; Sandler, Dale P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Marras, Connie] Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada.
[Umbach, David M.] NIEHS, Biostat Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Kasten, Meike] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
[Kasten, Meike] Med Univ Lubeck, Dept Clin & Mol Neurogenet, D-23538 Lubeck, Germany.
[Chade, Anabel R.] Favaloro Univ, Inst Neurosci, Inst Cognit Neurol, Buenos Aires, DF, Argentina.
[Richards, Marie B.] Westat Corp, Durham, NC USA.
[Blair, Aaron] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
RP Goldman, SM (reprint author), Parkinsons Inst, 675 Almanor Ave, Sunnyvale, CA 94085 USA.
EM sgoldman@thepi.org
RI Goldman, Samuel/A-2225-2014;
OI Goldman, Samuel/0000-0002-3039-9927; Kamel, Freya/0000-0001-5052-6615;
Sandler, Dale/0000-0002-6776-0018
FU National Institutes of Health, National Institute of Environmental
Health Sciences (NIEHS) [Z01-ES044007, Z01-ES049030]; National Cancer
Institute [Z01-CP010119]; NIEHS [R01-ES10803, U54 ES012077]; Michael J.
Fox Foundation
FX This research was supported, in part, by the Intramural Research Program
of the National Institutes of Health, National Institute of
Environmental Health Sciences (NIEHS) grants (Z01-ES044007 and
Z01-ES049030), a National Cancer Institute grant (Z01-CP010119), NIEHS
grants R01-ES10803 and U54 ES012077, the Michael J. Fox Foundation, and
James and Sharron Clark.
NR 74
TC 25
Z9 25
U1 1
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV
PY 2012
VL 27
IS 13
BP 1652
EP 1658
DI 10.1002/mds.25216
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 045KU
UT WOS:000311695500016
PM 23045187
ER
PT J
AU Hua, P
Liu, WG
Kuo, SH
Zhao, YY
Chen, L
Zhang, N
Wang, C
Guo, SW
Wang, L
Xiao, H
Kwan, JY
Wu, TX
AF Hua, Ping
Liu, Weiguo
Kuo, Sheng-Han
Zhao, Yanyan
Chen, Ling
Zhang, Ning
Wang, Chun
Guo, Suwan
Wang, Li
Xiao, Hong
Kwan, Justin Y.
Wu, Tianxia
TI Association of Tef polymorphism with depression in Parkinson disease
SO MOVEMENT DISORDERS
LA English
DT Article
DE Parkinson's disease; depression; Tef; circadian genes
ID SEROTONIN TRANSPORTER GENE; MINI-MENTAL-STATE; ALLELIC VARIATION; MAJOR
DEPRESSION; MOOD DISORDERS; CLOCK; NUCLEOTIDE; EXPRESSION; THERAPY;
IMPACT
AB Background: Circadian rhythm disturbance has been implicated in depression, and polymorphisms of circadian genes Cry1, Cry2, and Tef are associated with depression. However, the relationship between these genes and depression symptoms in Parkinson's disease (PD) has not been established. Methods: Four hundred eight subjects with PD participated in this study. Demographics, UPDRS, MiniMental Status Examination (MMSE), and Hamilton Rating Scale for Depression (HAMD) were obtained in all subjects. Frequency of polymorphisms of Cry1 rs2287161, Cry2 rs10838524, and Tef rs738499 was determined, and the association between genetic polymorphisms of circadian genes and HAMD scores in patients with PD was examined. Results: Tef, but not Cry1 or Cry2, is associated with HAMD scores in patients with PD in a linear regression model after adjusting for clinical variables (P = 0.004). Conclusions: The polymorphism of Tef rs738499 is associated with depression symptoms in PD. (C) 2012 Movement Disorder Society
C1 [Hua, Ping; Liu, Weiguo; Zhao, Yanyan] Nanjing Med Univ, Affiliated Brain Hosp, Dept Neurol, Nanjing 210029, Jiangsu, Peoples R China.
[Kuo, Sheng-Han] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA.
[Wang, Li] Nanjing Med Univ, Affiliated Brain Hosp, Clin Lab, Nanjing 210029, Jiangsu, Peoples R China.
[Xiao, Hong] Nanjing Med Univ, Affiliated Brain Hosp, Inst Sci Res, Nanjing 210029, Jiangsu, Peoples R China.
[Kwan, Justin Y.] Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA.
[Wu, Tianxia] NINDS, NIH, Bethesda, MD 20892 USA.
RP Liu, WG (reprint author), Nanjing Med Univ, Nanjing Brain Hosp, Dept Neurol, Nanjing 210029, Jiangsu, Peoples R China.
EM liuweiguo1111@sina.com
FU National Natural Science [81170309]; Medical Science and Technology
Foundation Project of Chinese Traditional Medicine from Jiangsu Province
[LB09088]; Key Project of Medical Science and Technology Development
Foundation from the Nanjing Department of Health [200905016]; American
Academy of Neurology Research Fellowship; Parkinson Disease Foundation
FX The study was supported by the National Natural Science (81170309),
Medical Science and Technology Foundation Project of Chinese Traditional
Medicine from Jiangsu Province (LB09088), and Key Project of Medical
Science and Technology Development Foundation from the Nanjing
Department of Health (200905016), an American Academy of Neurology
Research Fellowship, and the Parkinson Disease Foundation.
NR 35
TC 9
Z9 10
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
J9 MOVEMENT DISORD
JI Mov. Disord.
PD NOV
PY 2012
VL 27
IS 13
BP 1694
EP 1697
DI 10.1002/mds.25195
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 045KU
UT WOS:000311695500024
PM 23138696
ER
PT J
AU Raphaelson, M
Inati, SK
AF Raphaelson, Marc
Inati, Sara K.
TI Treating Sleep Disorders in Neurology Practice
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Sleep disorders; Neurology; Practice; Diagnosis; Treatment; Integrate
ID POSTTRAUMATIC-STRESS-DISORDER; POSITIVE AIRWAY PRESSURE; RESTLESS LEGS
SYNDROME; EXCESSIVE DAYTIME SLEEPINESS; AMYOTROPHIC-LATERAL-SCLEROSIS;
SEXUAL-ASSAULT SURVIVORS; MULTIPLE SYSTEM ATROPHY; ACUTE
ISCHEMIC-STROKE; MARIE-TOOTH-DISEASE; QUALITY-OF-LIFE
AB Neurologists treat many people with unrecognized sleep disorders. This review recommends that new and established patients routinely complete standard sleep questionnaires as an aid to clinical history. Because there is high prevalence of treatable primary sleep disorders among neurologic patients, routine diagnostic sleep testing is indicated for patients with stroke, neuromuscular disease, dementia, REM behavioral disorder, atypical or treatment-refractory insomnia, and chronic and unexplained fatigue or sleepiness. As local and national regulatory momentum favors increasing care coordination and integration, neurologists should develop a clinical pathway to diagnose and treat sleep disorders within the practice or through a collegial expert network.
C1 [Inati, Sara K.] NINDS, EEG Sect, NIH, Bethesda, MD 20894 USA.
RP Raphaelson, M (reprint author), 224D Cornwall St,Suite 101B, Leesburg, VA 20176 USA.
EM raphaels4@aol.com
FU Intramural Research Program on the NIH, NINDS
FX This research was supported in part by the Intramural Research Program
on the NIH, NINDS.
NR 124
TC 0
Z9 0
U1 3
U2 9
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 NOV
PY 2012
VL 30
IS 4
BP 1007
EP +
DI 10.1016/j.ncl.2012.08.015
PG 20
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 047XI
UT WOS:000311874400004
PM 23099127
ER
PT J
AU Aziz, NM
Miller, JL
Curtis, JR
AF Aziz, Noreen M.
Miller, Jeri L.
Curtis, J. Randall
TI Palliative and end-of-life care research: Embracing new opportunities
SO NURSING OUTLOOK
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ADVANCE DIRECTIVES; ADVANCED CANCER;
COMMUNICATION; OUTCOMES; HEALTH; ASSOCIATIONS; ONCOLOGISTS; PREFERENCES;
DISCUSSIONS
AB The past two decades have witnessed dramatic advances in palliative and end-of-life care research with increased understanding of the burden of life-limiting diseases on patients, families, clinicians, and our healthcare system; and researchers have documented palliative care interventions that improve patient and family outcomes and reduce the costs of care (Detering, Hancock, Reade, & Silvester, 2010). These advances have led to a new era of palliative and end-of-life care research and practice with widespread recognition of its accomplishments and successes. Consequently, we now have an important opportunity to reassess our recent successes and challenges and to identify the goals and benchmarks that will ensure ongoing robust advances in this now-recognized and critical scientific area. High-quality palliative and end-of-life care will be best informed by methodologically strong research efforts that generate a body of evidence with the capacity to support and direct care and effect changes in practice. It is in this context that the National Institute of Nursing Research conceptualized and led a Summit titled The Science of Compassion: Future Directions in End-of-Life and Palliative Care Research in August, 2011. In this summary article, we present brief overviews of the six articles chosen for this Special Issue of Nursing Outlook, examine their key conclusions, articulate gaps and needs, and discuss next steps in palliative and end-of-life care research through the lens of these six topics. Cite this article: Aziz, N. M., Miller, J. L., & Curtis, J. R. (2012, DECEMBER). Palliative and end-of-life care research: Embracing new opportunities. Nursing Outlook, 60(6), 384-390. http://dx.doi.or/10.1016/j.outlook.2012.08.006.
C1 [Aziz, Noreen M.; Miller, Jeri L.] NINR, NIH, Off Extramural Programs, Div Extramural Act, Bethesda, MD 20892 USA.
[Curtis, J. Randall] Univ Washington, Sch Med, Seattle, WA USA.
[Curtis, J. Randall] Univ Washington, Sch Nursing, Seattle, WA 98195 USA.
RP Aziz, NM (reprint author), NINR, NIH, Off Extramural Programs, Div Extramural Act, 6701 Democracy Blvd,Suite 710,1 Democracy Plaza, Bethesda, MD 20892 USA.
EM azizn@mail.nih.gov
FU Intramural NIH HHS [Z99 NR999999]
NR 50
TC 12
Z9 12
U1 6
U2 19
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
J9 NURS OUTLOOK
JI Nurs. Outlook
PD NOV-DEC
PY 2012
VL 60
IS 6
BP 384
EP 390
DI 10.1016/j.outlook.2012.08.006
PG 7
WC Nursing
SC Nursing
GA 043EU
UT WOS:000311526500010
PM 23141198
ER
PT J
AU Li, Y
Deng, C
Hu, X
Patel, B
Fu, X
Qiu, Y
Brand, M
Zhao, K
Huang, S
AF Li, Y.
Deng, C.
Hu, X.
Patel, B.
Fu, X.
Qiu, Y.
Brand, M.
Zhao, K.
Huang, S.
TI Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1
function in hematopoiesis and leukemogenesis
SO ONCOGENE
LA English
DT Article
DE TAL1/SCL; LSD1; H3K4 demethylation; serine phosphorylation; epigenetic
regulation; leukemogenesis
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; TRANSCRIPTION FACTOR
TAL1/SCL; BETA-GLOBIN LOCUS; STEM-CELLS; CHROMOSOME-TRANSLOCATION;
ERYTHROID-CELLS; GENE-EXPRESSION; TRANSGENIC MICE; SCL GENE
AB TAL1/SCL is a hematopoietic-specific oncogene and its activity is regulated by associated transcriptional co-activators and corepressors. Dysregulation of TAL1 activity has been associated with T-cell leukemogenesis. However, it remains unclear how the interactions between TAL1 and corepressors versus co-activators are properly regulated. Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis. Knockdown of TAL1 or LSD1 led to a derepression of the TAL1 target genes in T-cell acute lymphoblast leukemia (T-ALL) Jurkat cells, which is accompanied by elevating promoter H3K4 methylation. Similarly, treatment of PKA activator forskolin resulted in derepression of target genes by reducing its interaction with LSD1 while PKA inhibitor H89 represses them by suppressing H3K4 methylation levels. Consistent with the dual roles of TAL1 in transcription, TAL1-associated LSD1 is decreased while recruitment of hSET1 is increased at the TAL1 targets during erythroid differentiation. This process is accompanied by a dramatic increase in H3K4 methylation. Thus, our data revealed a novel interplay between PKA phosphorylation and TAL1-mediated epigenetic regulation that regulates hematopoietic transcription and differentiation programs during hematopoiesis and leukemogenesis. Oncogene (2012) 31, 5007-5018; doi:10.1038/onc.2012.8; published online 6 February 2012
C1 [Li, Y.; Hu, X.; Fu, X.] Jilin Univ, Coll Life Sci, Changchun 130023, Peoples R China.
[Qiu, Y.] Univ Florida, Coll Med, Dept Anat & Cell Biol, Gainesville, FL 32610 USA.
[Qiu, Y.; Huang, S.] Univ Florida, Coll Med, Shands Canc Ctr, Gainesville, FL 32610 USA.
[Brand, M.] Ottawa Hosp, Sprott Ctr Stem Cell Res, Res Inst, Ottawa, ON, Canada.
[Zhao, K.] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Li, Y.; Deng, C.; Hu, X.; Patel, B.; Huang, S.] Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
RP Huang, S (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA.
EM sumingh@ufl.edu
FU National Institute of Health [R01HL090589, R01HL091929,
R01HL091929-01A1S1, R01HL095674]; NIH [5T32-CA9126-34]; Intramural
Research programs, National Heart Lung Blood Institute and National
Institute of Health
FX We are grateful to members of the Huang laboratory for their suggestions
and comments. This work was supported by grants from the National
Institute of Health (SH, R01HL090589, R01HL091929 and
R01HL091929-01A1S1-the ARRA Administrative supplement; YQ, R01HL095674).
BP is supported by NIH T32 training grant (5T32-CA9126-34). KZ is
supported by the Intramural Research programs, National Heart Lung Blood
Institute and National Institute of Health.
NR 59
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 0950-9232
J9 ONCOGENE
JI Oncogene
PD NOV
PY 2012
VL 31
IS 48
BP 5007
EP 5018
DI 10.1038/onc.2012.8
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 048CU
UT WOS:000311888600005
PM 22310283
ER
PT J
AU Moore, SC
Patel, AV
Matthews, CE
de Gonzalez, AB
Park, Y
Katki, HA
Linet, MS
Weiderpass, E
Visvanathan, K
Helzlsouer, KJ
Thun, M
Gapstur, SM
Hartge, P
Lee, IM
AF Moore, Steven C.
Patel, Alpa V.
Matthews, Charles E.
de Gonzalez, Amy Berrington
Park, Yikyung
Katki, Hormuzd A.
Linet, Martha S.
Weiderpass, Elisabete
Visvanathan, Kala
Helzlsouer, Kathy J.
Thun, Michael
Gapstur, Susan M.
Hartge, Patricia
Lee, I-Min
TI Leisure Time Physical Activity of Moderate to Vigorous Intensity and
Mortality: A Large Pooled Cohort Analysis
SO PLOS MEDICINE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE MORTALITY; RANDOMIZED CONTROLLED-TRIAL; LOW-DOSE
ASPIRIN; LIFE EXPECTANCY; PRIMARY PREVENTION; ALL-CAUSE; POSTMENOPAUSAL
WOMEN; REGRESSION-MODELS; MEASUREMENT ERROR; BREAST-CANCER
AB Background: Leisure time physical activity reduces the risk of premature mortality, but the years of life expectancy gained at different levels remains unclear. Our objective was to determine the years of life gained after age 40 associated with various levels of physical activity, both overall and according to body mass index (BMI) groups, in a large pooled analysis.
Methods and Findings: We examined the association of leisure time physical activity with mortality during follow-up in pooled data from six prospective cohort studies in the National Cancer Institute Cohort Consortium, comprising 654,827 individuals, 21-90 y of age. Physical activity was categorized by metabolic equivalent hours per week (MET-h/wk). Life expectancies and years of life gained/lost were calculated using direct adjusted survival curves (for participants 40+ years of age), with 95% confidence intervals (CIs) derived by bootstrap. The study includes a median 10 y of follow-up and 82,465 deaths. A physical activity level of 0.1-3.74 MET-h/wk, equivalent to brisk walking for up to 75 min/wk, was associated with a gain of 1.8 (95% CI: 1.6-2.0) y in life expectancy relative to no leisure time activity (0 MET-h/wk). Higher levels of physical activity were associated with greater gains in life expectancy, with a gain of 4.5 (95% CI: 4.3-4.7) y at the highest level (22.5+ MET-h/wk, equivalent to brisk walking for 450+ min/wk). Substantial gains were also observed in each BMI group. In joint analyses, being active (7.5+ MET-h/wk) and normal weight (BMI 18.5-24.9) was associated with a gain of 7.2 (95% CI: 6.5-7.9) y of life compared to being inactive (0 MET-h/wk) and obese (BMI 35.0+). A limitation was that physical activity and BMI were ascertained by self report.
Conclusions: More leisure time physical activity was associated with longer life expectancy across a range of activity levels and BMI groups.
C1 [Moore, Steven C.; Matthews, Charles E.; de Gonzalez, Amy Berrington; Park, Yikyung; Katki, Hormuzd A.; Linet, Martha S.; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Patel, Alpa V.; Thun, Michael; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Dept Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Samfundet Folkhalsan, Helsinki, Finland.
[Visvanathan, Kala; Helzlsouer, Kathy J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Lee, I-Min] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
RP Moore, SC (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM moorest@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; matthews, Charles/E-8073-2015; Weiderpass,
Elisabete/M-4029-2016; Moore, Steven/D-8760-2016;
OI matthews, Charles/0000-0001-8037-3103; Weiderpass,
Elisabete/0000-0003-2237-0128; Moore, Steven/0000-0002-8169-1661; Park,
Yikyung/0000-0002-6281-489X
FU Intramural Research Program of the US National Institutes of Health
(NIH); Division of Cancer Control and Population Sciences, National
Cancer Institute (NCI), NIH; Intramural Research Program of the NCI;
National Institute of Aging [U01 AG18033]; NCI [CA105069]; Swedish
Research Council; Swedish Cancer Society; [CA047988]; [HL043851];
[HL080467]
FX Supported by the Intramural Research Program of the US National
Institutes of Health (NIH) and the Division of Cancer Control and
Population Sciences, National Cancer Institute (NCI), NIH. The NIH-AARP
Diet and Health study was supported by the Intramural Research Program
of the NCI. CLUE was supported by the National Institute of Aging, grant
number: U01 AG18033 and NCI, grant number: CA105069. The US Radiologic
Technologists study was supported by the Intramural Research Program of
the NCI. The Women's Health Study was supported by grant numbers
CA047988, HL043851, and HL080467. The Swedish Women's Lifestyle and
Health study is supported by grants from the Swedish Research Council
and Swedish Cancer Society. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 43
TC 110
Z9 112
U1 4
U2 34
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD NOV
PY 2012
VL 9
IS 11
AR e1001335
DI 10.1371/journal.pmed.1001335
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA 048CW
UT WOS:000311888800001
PM 23139642
ER
PT J
AU Forsythe, LP
Romano, JM
Jensen, MP
Thorn, BE
AF Forsythe, Laura P.
Romano, Joan M.
Jensen, Mark P.
Thorn, Beverly E.
TI Attachment Style Is Associated With Perceived Spouse Responses and
Pain-Related Outcomes
SO REHABILITATION PSYCHOLOGY
LA English
DT Article
DE chronic pain; attachment; spouse responses; pain behavior; depression
ID STUDIES DEPRESSION SCALE; ADULT ATTACHMENT; BEHAVIORAL INTERACTIONS;
MARITAL SATISFACTION; SOCIAL SUPPORT; SELF; DISABILITY; INVENTORY;
COUPLES; MODELS
AB Purpose/Objective: Attachment theory can provide a heuristic model for examining factors that may influence the relationship of social context to adjustment in chronic pain. This study examined the associations of attachment style with self-reported pain behavior, pain intensity, disability, depression, and perceived spouse responses to pain behavior. We also examined whether attachment style moderates associations between perceived spouse responses and self-reported pain behavior and depressive symptoms, as well as perceived spouse responses as a mediator of these associations. Method: Individuals with chronic pain (N = 182) completed measures of self-reported attachment style, perceived spouse responses, and pain-related criterion variables. Results: Secure attachment was inversely associated with self-reported pain behaviors, pain intensity, disability, depressive symptoms, and perceived negative spouse responses; preoccupied and fearful attachment scores were positively associated with these variables. In multivariable regression models, both attachment style and perceived spouse responses were uniquely associated with self-reported pain behavior and depressive symptoms. Attachment style did not moderate associations between perceived spouse responses to self-reported pain behavior and pain criterion variables, but negative spouse responses partially mediated some relationships between attachment styles and pain outcomes. Conclusions/Implications: Findings suggest that attachment style is associated with pain-related outcomes and perceptions of spouse responses. The hypothesized moderation effects for attachment were not found; however, mediation analyses showed that perceived spouse responses may partially explain associations between attachment and adjustment to pain. Future research is needed to clarify how attachment style and the social environment affect the pain experience.
C1 [Forsythe, Laura P.; Thorn, Beverly E.] Univ Alabama, Dept Psychol, Tuscaloosa, AL 35487 USA.
[Romano, Joan M.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Jensen, Mark P.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA.
RP Forsythe, LP (reprint author), NCI, Off Canc Survivorship, 6116 Execut Blvd,Suite 404,MSC 8336, Bethesda, MD 20892 USA.
EM laura.forsythe@nih.gov
FU NICHD NIH HHS [P01 HD033988, P01 HD33988]
NR 55
TC 8
Z9 9
U1 1
U2 21
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0090-5550
EI 1939-1544
J9 REHABIL PSYCHOL
JI Rehabil. Psychol.
PD NOV
PY 2012
VL 57
IS 4
BP 290
EP 300
DI 10.1037/a0030083
PG 11
WC Psychology, Clinical; Rehabilitation
SC Psychology; Rehabilitation
GA 047EG
UT WOS:000311819900003
PM 23148713
ER
PT J
AU Leopold, A
Krueger, F
dal Monte, O
Pardini, M
Pulaski, SJ
Solomon, J
Grafman, J
AF Leopold, Anne
Krueger, Frank
dal Monte, Olga
Pardini, Matteo
Pulaski, Sarah J.
Solomon, Jeffrey
Grafman, Jordan
TI Damage to the left ventromedial prefrontal cortex impacts affective
theory of mind
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE affective theory of mind; ventromedial prefrontal cortex; traumatic
brain injury; emotional intelligence; empathy
ID EMOTIONAL INTELLIGENCE; BRAIN-LESIONS; RHESUS-MONKEY; FALSE BELIEF;
HEAD-INJURY; DISSOCIATION; IMPAIRMENTS; EMPATHY; DEPRESSION; AUTISM
AB Studies investigating theory of mind (ToM) abilities (i.e. ability to understand and predict others' mental states) have revealed that affective and cognitive functions play a significant role and that each of those functions are associated with distinct neural networks. Cognitive facets of ToM have implicated the medial prefrontal cortex, temporo-parietal junction and the anterior paracingulate cortex, whereas affective facets have implicated the ventromedial prefrontal cortex (vmPFC). Although the vmPFC has repeatedly shown to be critical for affective functions, knowledge regarding the exact role of the left and right vmPFC in affective ToM is still obscure. Here, we compared performances of 30 patients with left, right and bilateral vmPFC lesions to two comparison groups (one without and one with brain injuries) on the Faux Pas Recognition task measuring the facets of ToM. We also investigated whether any deficits may be associated with other emotional measures, namely emotional empathy and emotional intelligence. Our results extend earlier findings by showing that the vmPFC is associated with abilities in affective ToM. More importantly, our results revealed that the left, and not the right vmPFC as indicated previously, is involved in affective ToM and that this deficit is associated with emotional intelligence.
C1 [Krueger, Frank] George Mason Univ, Dept Mol Neurosci, Fairfax, VA 22030 USA.
[Grafman, Jordan] Kessler Fdn Res Ctr, Traumat Brain Injury Res Lab, W Orange, NJ 07052 USA.
[Krueger, Frank] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[dal Monte, Olga] Univ Turin, Dept Neuropsychol, Turin, Italy.
[dal Monte, Olga] Henry M Jackson Fdn, Rockville, MD USA.
[Pardini, Matteo] Univ Genoa, Dept Neurosci Ophthalmol & Genet, Genoa, Italy.
[Solomon, Jeffrey] Med Numer, Germantown, MD USA.
[Leopold, Anne; dal Monte, Olga; Pulaski, Sarah J.] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Leopold, Anne] Univ Utrecht, Dept Social & Hlth Psychol, Utrecht, Netherlands.
RP Krueger, F (reprint author), George Mason Univ, Dept Mol Neurosci, 4400 Univ Dr,Mail Stop 2A1, Fairfax, VA 22030 USA.
EM FKrueger@gmu.edu; jgrafman@kesslerfoundation.org
RI Pardini, Matteo/F-8414-2010;
OI Pardini, Matteo/0000-0002-4740-1982; Grafman, Jordan
H./0000-0001-8645-4457; dal monte, olga/0000-0002-7823-4769
FU National Naval Medical Center; U.S. National Institute of Neurological
Disorders and Stroke; U.S. Army Medical Research and Material Command
[DAMD17-01-1-0675]
FX The views expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the Department of
the Navy, the Department of Defense, or the U. S. Government. The
authors are grateful to all the Vietnam veterans who participated in
this study. Without their long-term commitment to improving the health
care of veterans, this study could not have been completed. We thank the
National Naval Medical Center for their support and provision of their
facilities. We are grateful to S. Bonifant, B. Cheon, C. Ngo, A.
Greathouse, K. Reding and G. Tasick for their invaluable help with the
testing of participants and organization of this study. The work was
supported by the U.S. National Institute of Neurological Disorders and
Stroke intramural research program and a project grant from the U.S.
Army Medical Research and Material Command administrated by the Henry M.
Jackson Foundation (Vietnam Head Injury Study Phase III: a 30-year
post-injury follow-up study), grant number: DAMD17-01-1-0675.
NR 72
TC 32
Z9 33
U1 7
U2 47
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD NOV
PY 2012
VL 7
IS 8
BP 871
EP 880
DI 10.1093/scan/nsr071
PG 10
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 045BZ
UT WOS:000311671100001
PM 22021651
ER
PT J
AU Chen, KG
Mallon, BS
Hamilton, RS
Kozhich, OA
Park, K
Hoeppner, DJ
Robey, PG
McKay, RDG
AF Chen, Kevin G.
Mallon, Barbara S.
Hamilton, Rebecca S.
Kozhich, Olga A.
Park, Kyeyoon
Hoeppner, Daniel J.
Robey, Pamela G.
McKay, Ronald D. G.
TI Non-colony type monolayer culture of human embryonic stem cells
SO STEM CELL RESEARCH
LA English
DT Article
ID TERM SELF-RENEWAL; ROCK INHIBITOR; IN-VIVO; SURVIVAL; GROWTH;
DISSOCIATION; EXPRESSION; SUPPORTS; LINES; ESCS
AB Regenerative medicine, relying on human embryonic stem cell (hESC) technology, opens promising new avenues for therapy of many severe diseases. However, this approach is restricted by limited production of the desired cells due to the refractory properties of hESC growth in vitro. It is further hindered by insufficient control of cellular stress, growth rates, and heterogeneous cellular states under current culture conditions. In this study, we report a novel cell culture method based on a non-colony type monotayer (NCM) growth. Human ESCs under NCM remain pluripotent as determined by teratoma assays and sustain the potential to differentiate into three germ layers. This NCM culture has been shown to homogenize cellular states, precisely control growth rates, significantly increase cell production, and enhance hESC recovery from cryopreservation without compromising chromosomal integrity. This culture system is simple, robust, scalable, and suitable for high-throughput screening and drug discovery. Published by Elsevier B.V.
C1 [Chen, Kevin G.; Mallon, Barbara S.; Hamilton, Rebecca S.; Park, Kyeyoon; Robey, Pamela G.; McKay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, NIH, Stem Cell Unit, Bethesda, MD 20892 USA.
[Kozhich, Olga A.; Hoeppner, Daniel J.; McKay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Chen, KG (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Stem Cell Unit, 37 Convent Dr,Room 1000, Bethesda, MD 20892 USA.
EM cheng@mail.nih.gov; ronald.mckay@libd.org
RI Robey, Pamela/H-1429-2011; Chen, Kevin/D-6769-2011
OI Robey, Pamela/0000-0002-5316-5576; Chen, Kevin/0000-0003-2983-6330
FU NIH
FX The NIH Stem Cell Unit is supported by NIH funds. We thank Dr. Joshua
Chenoweth for the discussion, Dr. Peter Andrews for providing antibodies
described in Supplemental information, Dr. Guokai Chen for the BC1 line,
and Dr. Tianmin Ivy Zhang and Dr. Qi Zheng (Applied StemCell Inc.) for
conducting the teratoma assays.
NR 42
TC 14
Z9 14
U1 0
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
J9 STEM CELL RES
JI Stem Cell Res.
PD NOV
PY 2012
VL 9
IS 3
BP 237
EP 248
DI 10.1016/j.scr.2012.06.003
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 044XP
UT WOS:000311658800008
PM 22910561
ER
PT J
AU Jaiswal, KR
Xin, HW
Anderson, A
Wiegand, G
Kim, B
Miller, T
Hari, D
Ray, S
Koizumi, T
Rudloff, U
Thorgeirsson, SS
Avital, I
AF Jaiswal, Kshama R.
Xin, Hong-Wu
Anderson, Andrew
Wiegand, Gordon
Kim, Bo
Miller, Tyler
Hari, Danielle
Ray, Satyajit
Koizumi, Tomotake
Rudloff, Udo
Thorgeirsson, Snorri S.
Avital, Itzhak
TI Comparative testing of various pancreatic cancer stem cells results in a
novel class of pancreatic-cancer-initiating cells
SO STEM CELL RESEARCH
LA English
DT Article
ID SIDE POPULATION CELLS; LINES; HYPOXIA
AB No systemic therapy is effective against pancreatic cancer (PC). Pancreatic cancer stem cells (PCSC) are hypothesized to account for therapeutic resistance. Several PCSC subpopulations were reported, each characterized by different markers. To be able to target PCSC, we sought to better define this putative heterogeneity. Therefore, we tested most of the known putative PCSC markers in established and fresh tumor cell lines. CD20, CD24, CD44, CD133, CD184 (CXCR4), CD326 (EpCam, ESA), Sox-2, OCT 3/4, and the side-population (SP) were tested in five PC cell lines, and the effects of confluency, hypoxia, radiation, and gemcitabine on the SP. The testing phase suggested several putative PCSC populations that were further tested and validated for their tumor-initiating capacity against known PCSC in 3 established and 1 fresh PC cell lines. Cell surface and intracellular markers showed significant variability among cell lines. SP was the only common marker in all cell lines and consistently less than 1%. SP response to confluence, hypoxia, radiation, and gemcitabine was inconsistent between cell lines. The initial testing phase suggested that SP/CD44-CD24-CD326+ cells might be a novel PCSC subpopulation. Tumor initiation capacity tests in nude mice confirmed their increased tumorigenicity over previously reported PCSC. Our data better define the heterogeneity of reported PCSC in cell lines tested in this study. We propose that prior to targeting PC via PCSC, one will need to gain more insight into this heterogeneity. Finally, we show that SP/CD44-CD24-CD326+ cells are a novel subpopulation of pancreatic cancer tumor initiating cells. Further mechanistic studies may lead to better targeting of PC via targeting this novel PCSC. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Thorgeirsson, Snorri S.] NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Jaiswal, Kshama R.; Xin, Hong-Wu; Anderson, Andrew; Wiegand, Gordon; Kim, Bo; Miller, Tyler; Hari, Danielle; Ray, Satyajit; Koizumi, Tomotake; Rudloff, Udo; Avital, Itzhak] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jaiswal, Kshama R.] Univ Colorado, Denver Hlth Med Ctr, Denver, CO 80204 USA.
RP Thorgeirsson, SS (reprint author), NCI, Ctr Excellence Integrat Canc Biol & Genom, Expt Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov; itzhak.avital@gmail.com
FU NIH/National Cancer Institute; National Cancer Institute
FX Douglas Burka and Chenwi Ambe have contributed to this work. This study
was supported by the intramural grant provided by the NIH/National
Cancer Institute.; Research was supported by intramural funding from the
National Cancer Institute.
NR 29
TC 9
Z9 9
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
J9 STEM CELL RES
JI Stem Cell Res.
PD NOV
PY 2012
VL 9
IS 3
BP 249
EP 260
DI 10.1016/j.scr.2012.08.001
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 044XP
UT WOS:000311658800009
PM 22963768
ER
PT J
AU Sinert, R
Brandler, E
Subramanian, RA
Miller, AC
AF Sinert, Richard
Brandler, Ethan
Subramanian, Ramanand Arun
Miller, Andrew C.
TI Does the Current Definition of Contrast-induced Acute Kidney Injury
Reflect a True Clinical Entity?
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID ACUTE-RENAL-FAILURE; PERCUTANEOUS CORONARY INTERVENTION; ENHANCED
COMPUTED-TOMOGRAPHY; SERUM CREATININE CHANGES; LENGTH-OF-STAY; INDUCED
NEPHROPATHY; RISK-FACTORS; HOSPITALIZED-PATIENTS; MORTALITY;
NEPHROTOXICITY
AB Objectives Contrast-induced acute kidney injury (CI-AKI) is defined as either a 25% increase in or an absolute elevation in serum creatinine (SCr) of 0.5 mg/dL, 48 to 72 hours after parenteral contrast exposure. The objective of this study was to compare the incidence and complications of AKI between patients exposed and those unexposed to intravenous (IV) contrast. Methods This was a retrospective cohort study using the electronic medical record of adult patients (>18 years) with and without contrast-enhanced abdominal or chest computed tomography (CT) between May 2008 and April 2009. Inclusion criteria were emergency department (ED) patients with normal renal function who received either a contrast-enhanced abdominal or a contrast-enhanced chest CT, compared to those unexposed to IV contrast, with a repeat SCr within 48 to 72 hours. Exclusion criteria were contrast exposure within 7 days before the index visit. CI-AKI in the contrast-exposed group and AKI in the contrast-unexposed group were defined by the same changes in SCr 48 to 72 hours after contrast or ED admission. Data were described by proportions or medians with 95% confidence intervals (CIs) or interquartile ranges (IQR; 25% to 75%). Group comparisons were by Mann-Whitney U or Fisher's exact test (a = 0.05, two tails). Results The contrast-exposed (n = 773) and contrast-unexposed (n = 2,956) patients were evenly matched for initial demographic, renal, and metabolic parameters. The incidence of CI-AKI/AKI was significantly higher for the patients unexposed versus exposed to contrast (8.96% vs. 5.69%, p = 0.003). There was no significant difference in mortality rates between contrast-exposed and unexposed patients (9.09% vs. 6.79%, p = 0.533). Conclusions The definition of CI-AKI for ED patients with normal renal function may not represent a true clinical entity and the definition warrants revision.
C1 [Sinert, Richard; Brandler, Ethan] Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA.
[Subramanian, Ramanand Arun] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Falls Church, VA USA.
[Miller, Andrew C.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Miller, Andrew C.] Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA.
RP Sinert, R (reprint author), Suny Downstate Med Ctr, Dept Emergency Med, Brooklyn, NY 11203 USA.
EM Richard.Sinert@Downstate.edu
OI Brandler, Ethan/0000-0003-4647-8483; Miller, Andrew/0000-0001-8474-5090
NR 35
TC 16
Z9 16
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD NOV
PY 2012
VL 19
IS 11
BP 1261
EP 1267
DI 10.1111/acem.12011
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA 041DQ
UT WOS:000311377300007
PM 23167857
ER
PT J
AU Whitehead, NS
Hammond, JA
Williams, MA
Huggins, W
Hoover, S
Hamilton, CM
Ramos, EM
Junkins, HA
Harlan, WR
Hogue, CJ
AF Whitehead, Nedra S.
Hammond, Jane A.
Williams, Michelle A.
Huggins, Wayne
Hoover, Sonja
Hamilton, Carol M.
Ramos, Erin M.
Junkins, Heather A.
Harlan, William R.
Hogue, Carol J.
CA Phenx Reprod Hlth Working Grp
TI The PhenX Toolkit pregnancy and birth collections
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE Pregnancy; Birth; Risk factors; Pregnancy outcomes
ID GENOME-WIDE ASSOCIATION; GESTATIONAL DIABETES-MELLITUS; PRETERM BIRTH;
INSIGHTS; GENETICS; CONSEQUENCES; QUALITY; WOMEN
AB Purpose: Pregnancy and childbirth are normal conditions, but complications and adverse outcomes are common. Both genetic and environmental factors influence the course of pregnancy. Genetic epidemiologic research into pregnancy outcomes could be strengthened by the use of common measures, which would allow data from different studies to be combined or compared. Here, we introduce perinatal researchers to the PhenX Toolkit and the Collections related to pregnancy and childbirth.
Methods: The Pregnancy and Birth Collections were drawn from measures in the PhenX Tooklit. The lead author selected a list of measures for each Collection, which was reviewed by the remaining authors and revised on the basis of their comments. We chose the measures we thought were most relevant for perinatal research and had been linked most strongly to perinatal outcomes.
Results: The Pregnancy and Birth Health Conditions Collection includes 24 measures related to pregnancy and fertility history, maternal complications, and infant complications. The Pregnancy and Birth Outcome Risk Factors Collection includes 43 measures of chemical, medical, psychosocial, and personal factors associated with pregnancy outcomes.
Conclusions: The biological complexity of pregnancy and its sensitivity to environmental and genomic influences suggest that multidisciplinary approaches are needed to generate new insights or practical interventions. To fully exploit new research methods and resources, we encourage the biomedical research community to adopt standard measures to facilitate pooled or meta-analyses. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Whitehead, Nedra S.; Hammond, Jane A.; Huggins, Wayne; Hoover, Sonja; Hamilton, Carol M.] RTI Int, San Francisco, CA USA.
[Williams, Michelle A.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Ramos, Erin M.; Junkins, Heather A.] NIH, Natl Human Genet Res Inst, Bethesda, MD 20892 USA.
[Hamilton, Carol M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Whitehead, NS (reprint author), RTI Int, 2951 Flowers Rd,Suite 119, Atlanta, GA 30341 USA.
EM nwhitehead@rti.org
RI Haines, Jonathan/C-3374-2012; Hogue, Carol/H-5442-2012
FU NHGRI NIH HHS [U01 HG004597, U01 HG004597-01]
NR 30
TC 1
Z9 1
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD NOV
PY 2012
VL 22
IS 11
BP 753
EP 758
DI 10.1016/j.annepidem.2012.08.004
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 036YI
UT WOS:000311067800001
PM 22954959
ER
PT J
AU Zadeh, S
Wiener, L
Pao, M
AF Zadeh, Sima
Wiener, Lori
Pao, Maryland
TI MY CHOICE, MY VOICE: END OF LIFE PLANNING WITH ADOLESCENTS AND YOUNG
ADULTS
SO ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Meeting Abstract
ID PALLIATIVE CARE; CHILDREN
C1 [Zadeh, Sima; Wiener, Lori] NCI, Bethesda, MD 20892 USA.
[Pao, Maryland] NIMH, Bethesda, MD 20892 USA.
NR 8
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1743-7555
J9 ASIA-PAC J CLIN ONCO
JI Asia-Pac. J. Clin. Oncol.
PD NOV
PY 2012
VL 8
SU 3
SI SI
MA 520
BP 258
EP 258
PG 1
WC Oncology
SC Oncology
GA 030CB
UT WOS:000310544400118
ER
PT J
AU Kim, TH
Jiang, HH
Lim, SM
Youn, YS
Choi, KY
Lee, S
Chen, XY
Byun, Y
Lee, KC
AF Kim, Tae Hyung
Jiang, Hai Hua
Lim, Sung Mook
Youn, Yu Seok
Choi, Ki Young
Lee, Seulki
Chen, Xiaoyuan
Byun, Youngro
Lee, Kang Choon
TI Site-Specific PEGylated Exendin-4 Modified with a High Molecular Weight
Trimeric PEG Reduces Steric Hindrance and Increases Type 2 Antidiabetic
Therapeutic Effects
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID GLUCAGON-LIKE PEPTIDE-1; APOPTOSIS-INDUCING LIGAND; POLYETHYLENE-GLYCOL;
SYNTHETIC EXENDIN-4; CONJUGATION; PROTEINS; DESIGN; POTENT
AB The purpose of this study was to optimize an Exendin-4 (Ex4-Cys) site-specific PEGylation method with a high-molecular-weight trimeric PEG. Here, we describe the preparation of C-terminal specific PEGylated Ex4-Cys (C40-tPEG-Ex4-Cys), which was performed using cysteine and amine residue specific coupling reactions between Ex4-Cys and activated trimeric PEG. The C40-PEG-Ex4-Cys was obtained at high yields (similar to 83%) and characterized by MALDI-TOF mass spectrometry. The receptor binding affinity of C40-PEG(5K)-Ex4-Cys was 3.5-fold higher than that of N-terminal PEGylated Ex4-Cys (N-ter-PEG(5K)-Ex4-Cy5), and receptor binding by the trimeric PEG (tPEG; 23, 50 kDa) adduct was much higher than that of branched PEG (20 kDa). Furthermore, C40-tPEG(50K)-Ex4-Cys was found to have greater blood circulating t(1/2) and AUC(inf) values than native Ex4-Cys by 7.53- and 45.61-fold, respectively. Accordingly; its hypoglycemic duration was much greater at 59.2 h than that of native Ex4-Cys at 7.3 h, with a dose of 25 nM/kg. The results of this study; show that C-terminal specific PEGylation using trimeric PEG is effective when applied to Ex4-Cys and suggest that C40-tPEG(50K)-Ex4-Cys has considerable potential as a type 2 antidiabetic agent.
C1 [Kim, Tae Hyung; Jiang, Hai Hua; Lim, Sung Mook; Youn, Yu Seok; Lee, Kang Choon] Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea.
[Choi, Ki Young; Lee, Seulki; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Byun, Youngro] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea.
RP Lee, KC (reprint author), Sungkyunkwan Univ, Coll Pharm, 300 Chonchon Dong, Suwon 440746, South Korea.
EM kcleep@skku.edu
RI BYUN, YOUNG RO/D-5735-2013; CHOI, KI YOUNG/Q-7177-2016
FU Converging Research Center Program through the National Research
Foundation of Korea (NRF); Ministry of Education, Science, and
Technology [2011-K000796]
FX This work was supported in part by the Converging Research Center
Program through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science, and Technology (2011-K000796).
NR 25
TC 14
Z9 15
U1 3
U2 39
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 NOV
PY 2012
VL 23
IS 11
BP 2214
EP 2220
DI 10.1021/bc300265n
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 040LV
UT WOS:000311325000008
PM 23116483
ER
PT J
AU Lim, J
Turkbey, B
Bernardo, M
Bryant, LH
Garzoni, M
Pavan, GM
Nakajima, T
Choyke, PL
Simanek, EE
Kobayashi, H
AF Lim, Jongdoo
Turkbey, Baris
Bernardo, Marcelino
Bryant, L. Henry, Jr.
Garzoni, Matteo
Pavan, Giovanni M.
Nakajima, Takahito
Choyke, Peter L.
Simanek, Eric E.
Kobayashi, Hisataka
TI Gadolinium MRI Contrast Agents Based on Triazine Dendrimers: Relaxivity
and In Vivo Pharmacokinetics
SO BIOCONJUGATE CHEMISTRY
LA English
DT Article
ID NEPHROGENIC SYSTEMIC FIBROSIS; MAGNETIC RESONANCE LYMPHANGIOGRAPHY;
DRUG-DELIVERY; CAPILLARY-ELECTROPHORESIS; EFFICIENT GENERATION;
MOLECULAR-DYNAMICS; AM1-BCC MODEL; FORCE-FIELD; MICE; SIZE
AB Four gadolinium (Gd)-based macromolecular contrast agents, G3-(Gd-DOTA)(24), GS-(Gd-DOTA)(96), G3-(Gd-DTPA)(24), and G5-(Gd-DTPA)(96), were prepared that varied in the size of dendrimer (generation three and five), the type of chelate group (DTPA or DOTA), and the theoretical number of metalated chelates (24 and 96). Synthesis relied on a dichlorotriazine derivatized with a DOTA or DTPA. ligand that was incorporated into the dendrimer and ultimately metalated with Gd ions. Paramagnetic characteristics and in vivo pharmacokinetics of all four contrast agents were investigated. The DOTA-containing agents, G3-(Gd-DOTA)(24) and GS-(Gd-DOTA)(96), demonstrated exceptionally high r1 relaxivity values at off-peak magnetic fields. Additionally, G5-(Gd-DOTA)(96) showed increased r1 relaxivity in serum compared to that in PBS, which was consistent with in vivo images. While G3-(Gd-DOTA)(24) and G3-(Gd-DTPA)(24) were rapidly excreted into the urine, GS-(Gd-DOTA)(96) and GS-(Gd-DTPA)(96) did not clear as quickly through the kidneys. Molecular simulation of the DOTA-containing dendrimers suggests that a majority of the metalated ligands are accessible to water. These triazine dendrimer-based MRI contrast agents exhibit several promising features such as high in vivo r1 relaxivity, desirable pharmacokinetics, and well-defined structure.
C1 [Turkbey, Baris; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lim, Jongdoo; Simanek, Eric E.] Texas Christian Univ, Dept Chem, Ft Worth, TX 76129 USA.
[Bernardo, Marcelino] NCI, SAIC Frederick Inc, NIH, Frederick, MD 21702 USA.
[Bryant, L. Henry, Jr.] NIH, Lab Diagnost Radiol Res Radiol & Imaging Sci, Warren Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Garzoni, Matteo; Pavan, Giovanni M.] Univ Appl Sci So Switzerland, Dept Innovat Technol, CH-6928 Galleria 2, Manno, Switzerland.
RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kobayash@mail.nih.gov
RI Pavan, Giovanni M./E-7474-2011
OI Pavan, Giovanni M./0000-0002-3473-8471
FU National Institutes of Health [GM 65460]; Robert A. Welch Foundation
[A-0008]; Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the National Institutes of Health (GM 65460 to EES)
and the Robert A. Welch Foundation (EES, A-0008).
NR 40
TC 22
Z9 23
U1 6
U2 57
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 NOV
PY 2012
VL 23
IS 11
BP 2291
EP 2299
DI 10.1021/bc300461r
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA 040LV
UT WOS:000311325000016
PM 23035964
ER
PT J
AU Palmer, JM
Lee, SJ
Chai, XY
Storer, BE
Flowers, MED
Schultz, KR
Inamoto, Y
Cutler, C
Pidala, J
Arora, M
Jacobsohn, DA
Carpenter, PA
Pavletic, SZ
Martin, PJ
AF Palmer, Jeanne M.
Lee, Stephanie J.
Chai, Xiaoyu
Storer, Barry E.
Flowers, Mary E. D.
Schultz, Kirk R.
Inamoto, Yoshihiro
Cutler, Corey
Pidala, Joseph
Arora, Mukta
Jacobsohn, David A.
Carpenter, Paul A.
Pavletic, Steven Z.
Martin, Paul J.
TI Poor Agreement between Clinician Response Ratings and Calculated
Response Measures in Patients with Chronic Graft-versus-Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host
disease; Response assessment
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; THERAPEUTIC
RESPONSE; CHRONIC GVHD; PHASE-II; CRITERIA; RELIABILITY; TRIALS
AB In 2005, a National Institutes of Health consensus conference was held to refine methods for research in patients with chronic graft-versus-host disease, including proposed objective response measures and a provisional algorithm for calculating organ-specific and overall response. In this study, we used weighted kappa statistics to evaluate the level of agreement between clinician response ratings and calculated response categories in patients with chronic graft-versus-host disease. The study included 290 patients who had paired enrollment and follow-up visits. Based on a set of objective measures, 37% of the patients had an overall complete or partial response, whereas clinicians reported an overall complete or partial response rate of 71% (slight to fair agreement, weighted kappa 0.20). Agreement rates between calculated organ-specific responses and clinician-reported changes in skin, mouth, and eyes were fair to moderate (weighted kappa, 0.28-0.54). We conclude that for both overall and organ-specific comparisons, clinician response ratings did not agree well with calculated response categories. Possible reasons for this discrepancy include a high clinical sensitivity for detecting response, a clinical predisposition to recognize selective improvements as overall response, the large change in objective measures proposed to define response, and the high incidence of progressive disease based on new manifestations. Conclusions from prior literature reporting high overall response rates based on clinician judgment would not be supported if the provisional algorithm had been applied to calculate response. Our analysis also highlights the need to define an overall response measure that incorporates both patient-reported and objective measures and accurately reflects the outcome in patients with a mixed response in which one organ or site improves, whereas another shows new involvement. Biol Blood Marrow Transplant 18: 1649-1655 (2012) (C) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
C1 [Palmer, Jeanne M.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
[Lee, Stephanie J.; Chai, Xiaoyu; Storer, Barry E.; Flowers, Mary E. D.; Inamoto, Yoshihiro; Carpenter, Paul A.; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Schultz, Kirk R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Arora, Mukta] Univ Minnesota, Minneapolis, MN USA.
[Jacobsohn, David A.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA.
RP Palmer, JM (reprint author), Med Coll Wisconsin, Div Hematol & Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA.
EM sjlee@fhcrc.org
FU NIH/NCI [CA 118953]
FX This work was supported by grant CA 118953 (PI: Lee, SJ) NIH/NCI.
NR 21
TC 15
Z9 15
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 NOV
PY 2012
VL 18
IS 11
BP 1649
EP 1655
DI 10.1016/j.bbmt.2012.05.005
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 029KF
UT WOS:000310493700006
PM 22691695
ER
PT J
AU Ribeiro, LA
Roessler, E
Hu, P
Pineda-Alvarez, DE
Zhou, N
Jones, M
Chandrasekharappa, S
Richieri-Costa, A
Muenke, M
AF Ribeiro, Lucilene A.
Roessler, Erich
Hu, Ping
Pineda-Alvarez, Daniel E.
Zhou, Nan
Jones, MaryPat
Chandrasekharappa, Settara
Richieri-Costa, Antonio
Muenke, Maximilian
TI Comparison of mutation findings in ZIC2 between microform and classical
holoprosencephaly in a Brazilian cohort
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE ZIC2; mutation; alanine tract expansion or contraction; poly-histidine
tract expansion; holoprosencephaly; polymorphism
ID NEURAL-TUBE DEFECTS; LOSS-OF-FUNCTION; POLYHISTIDINE TRACT POLYMORPHISM;
MOLECULAR EVALUATION; GENE; PHENOTYPE; TGIF; SIX3; ASSOCIATION; DISEASE
AB BACKGROUND Holoprosencephaly is the most frequent congenital malformation of the forebrain in humans. It is anatomically classified by the relative degree of abnormal formation and separation of the developing central nervous system. Mutations of ZIC2 are the second most common heterozygous variations detected in holoprosencephaly (HPE) patients. Mutations in most known HPE genes typically result in variable phenotypes that rage from classic alobar HPE to microforms represented by hypotelorism, solitary central maxillary incisor (SCMI), and cleft lip/palate, among others. Patients with HPE owing to ZIC2 mutations have recently been described by a distinct phenotype compared with mutations in other HPE causative genes. METHODS We report the comparison of ZIC2 molecular findings by Sanger bidirectional DNA sequencing and ad hoc genotyping in a cohort of 105 Brazilian patients within the clinical spectrum of HPE, including classic and microform groups. RESULTS We detected a total of five variants in the ZIC2 gene: a common histidine tract expansion c.716_718dup (p.His239dup), a rare c.1377_1391del_homozygous (p.Ala466_470del, or Ala 15 to 10 contraction), a novel intronic c.1239+18G>A variant, a novel frameshift c.1215dupC (p.Ser406Glnfs*11), and a c.1401_1406dup (p.Ala469_470dup, or alanine tract expansion to 17 residues). CONCLUSIONS From these patients, only the latter two mutations found in classic HPE are likely to be medically significant. In contrast, variants detected in the microform group are not likely to be pathogenic. We show conclusively that the histidine tract expansion is a polymorphic alteration that demonstrates considerable differences in allele frequencies across different ethnic groups. Therefore, careful population studies of rare variants can improve genotype-phenotype correlations. Birth Defects Research (Part A) 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Roessler, Erich; Hu, Ping; Pineda-Alvarez, Daniel E.; Zhou, Nan; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Ribeiro, Lucilene A.; Richieri-Costa, Antonio] Univ Sao Paolo, Hosp Rehabil & Craniofacial Anomalies, Mol Genet Lab, Bauru, Sao Paolo, Brazil.
[Ribeiro, Lucilene A.; Richieri-Costa, Antonio] Univ Sao Paolo, Hosp Rehabil & Craniofacial Anomalies, Clin Genet Serv, Bauru, Sao Paolo, Brazil.
[Jones, MaryPat; Chandrasekharappa, Settara] NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,Bldg 35,Room 1B403, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
RI Richieri-Costa, Antonio/B-2514-2013; Ribeiro-Bicudo,
Lucilene/G-9528-2013
FU Division of Intramural Research, National Human Genome Research, the
National Institutes of Health
FX Supported by funds from the Division of Intramural Research, National
Human Genome Research, the National Institutes of Health.
NR 46
TC 3
Z9 3
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD NOV
PY 2012
VL 94
IS 11
BP 912
EP 917
DI 10.1002/bdra.23047
PG 6
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 039HD
UT WOS:000311234400008
PM 22847929
ER
PT J
AU Zibly, Z
Schlaff, CD
Gordon, I
Munasinghe, J
Camphausen, KA
AF Zibly, Zion
Schlaff, Cody D.
Gordon, Ira
Munasinghe, Jeeva
Camphausen, Kevin A.
TI A novel rodent model of spinal metastasis and spinal cord compression
SO BMC NEUROSCIENCE
LA English
DT Article
DE Spinal metastasis; Spinal cord compression; Animal model; Rat
ID BONE; NEOPLASMS; CANCER
AB Background: Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. A major obstacle in the research of spinal metastatic disease is the lack of a simple reproducible animal model that mimics the natural course of the disease. In this study, we present a highly reproducible rodent model that can be used for different types of cancers while mimicking the natural course of human metastatic spinal cord compression syndrome.
Results: All sixteen Fisher 344 rats survived the dorsal approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats survived the sham control surgery. By Day 13 functional analysis via the modified Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease in motor function; median functional score was 3 for the tumor group (p = 0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging illustrated repeated and consistent tumor formation, furthermore, onset of neurological sequale was the result of tumor formation and cord compression as confirmed by histological examination.
Conclusions: Analysis of these findings demonstrates a repeatable and consistent tumor growth model for cancer spinal metastases in rats. This novel rat model requires a less intricate surgical procedure, and as a result minimizes procedure time while subsequently increasing consistency. Therefore, this model allows for the preclinical evaluation of therapeutics for spinal metastases that more closely replicates physiological findings.
C1 [Zibly, Zion; Schlaff, Cody D.; Gordon, Ira; Camphausen, Kevin A.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Zibly, Zion] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva] Natl Inst Neurol Disorders & Stroke, Cell & Canc Biol Branch, NCI, NIH, Bethesda, MD 20892 USA.
RP Zibly, Z (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM zzibly@yahoo.com
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX Financial support: This research was supported in part by the Intramural
Research Program of the National Institutes of Health, National Cancer
Institute.
NR 10
TC 2
Z9 4
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2202
J9 BMC NEUROSCI
JI BMC Neurosci.
PD NOV 1
PY 2012
VL 13
AR 137
DI 10.1186/1471-2202-13-137
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 045GB
UT WOS:000311682300001
PM 23116234
ER
PT J
AU Turkbey, EB
Nacif, MS
Noureldin, RA
Sibley, CT
Liu, S
Lima, JAC
Bluemke, DA
AF Turkbey, E. B.
Nacif, M. S.
Noureldin, R. A.
Sibley, C. T.
Liu, S.
Lima, J. A. C.
Bluemke, D. A.
TI Differentiation of myocardial scar from potential pitfalls and artefacts
in delayed enhancement MRI
SO BRITISH JOURNAL OF RADIOLOGY
LA English
DT Article
ID SENSITIVE INVERSION-RECOVERY; STATE FREE PRECESSION; INFARCTION;
VIABILITY; 3D
AB Delayed enhancement cardiac magnetic resonance (DE-CMR) imaging is used increasingly to identify and quantify focal myocardial scar. Our objective is to describe factors used in the interpretation of DE-CMR images and to highlight potential pitfalls and artefacts that mimic myocardial scar. Inversion recovery gradient recalled echo sequence is commonly accepted as the standard of reference for DE-CMR. There are also alternative sequences that can be performed in a single breath-hold or with free breathing. Radiologists need to be aware of factors affecting image quality, and potential pitfalls and artefacts that may generate focal hyperintense areas that mimic myocardial scar.
C1 [Turkbey, E. B.; Nacif, M. S.; Noureldin, R. A.; Sibley, C. T.; Liu, S.; Bluemke, D. A.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Turkbey, E. B.; Nacif, M. S.; Lima, J. A. C.] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA.
[Nacif, M. S.; Lima, J. A. C.] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
[Sibley, C. T.; Liu, S.; Bluemke, D. A.] Natl Inst Biomed Imaging & Bioengn, NIH Clin Ctr, Bethesda, MD USA.
RP Bluemke, DA (reprint author), NIH, Ctr Clin, 9000 Rockville Pike,Bldg 10,Room 1C355, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI Sibley, Christopher/C-9900-2013;
OI Bluemke, David/0000-0002-8323-8086
NR 20
TC 3
Z9 3
U1 0
U2 4
PU BRITISH INST RADIOLOGY
PI LONDON
PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND
SN 0007-1285
J9 BRIT J RADIOL
JI Br. J. Radiol.
PD NOV
PY 2012
VL 85
IS 1019
BP E1145
EP E1154
DI 10.1259/bjr/25893477
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 044EY
UT WOS:000311603400025
PM 23091294
ER
PT J
AU Gong, J
Hutter, C
Baron, JA
Berndt, S
Caan, B
Campbell, PT
Casey, G
Chan, AT
Cotterchio, M
Fuchs, CS
Gallinger, S
Giovannucci, E
Harrison, T
Hayes, R
Hsu, L
Jiao, S
Lin, Y
Lindor, NM
Newcomb, P
Pflugeisen, B
Phipps, AI
Rohan, T
Schoen, R
Seminara, D
Slattery, ML
Stelling, D
Thomas, F
Warnick, G
White, E
Potter, J
Peters, U
AF Gong, Jian
Hutter, Carolyn
Baron, John A.
Berndt, Sonja
Caan, Bette
Campbell, Peter T.
Casey, Graham
Chan, Andrew T.
Cotterchio, Michelle
Fuchs, Charles S.
Gallinger, Steven
Giovannucci, Edward
Harrison, Tabitha
Hayes, Richard
Hsu, Li
Jiao, Shuo
Lin, Yi
Lindor, Noralane M.
Newcomb, Polly
Pflugeisen, Bethann
Phipps, Amanda I.
Rohan, Thomas
Schoen, Robert
Seminara, Daniela
Slattery, Martha L.
Stelling, Deanna
Thomas, Fridtjof
Warnick, Greg
White, Emily
Potter, John
Peters, Ulrike
TI A Pooled Analysis of Smoking and Colorectal Cancer: Timing of Exposure
and Interactions with Environmental Factors
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CIGARETTE-SMOKING; COLON-CANCER; UNITED-STATES; TOBACCO USE; RESPONSE
RELATIONSHIPS; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; LUNG-CANCER;
FOLLOW-UP; RISK
AB Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association.
Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors.
Results: Current smokers [OR, 1.26; 95% confidence interval (Cl), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04).
Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking.
Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev; 21(11); 1974-85. (C)2012 AACR.
C1 [Gong, Jian; Hutter, Carolyn; Harrison, Tabitha; Hsu, Li; Jiao, Shuo; Lin, Yi; Newcomb, Polly; Pflugeisen, Bethann; Phipps, Amanda I.; Stelling, Deanna; Warnick, Greg; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Hutter, Carolyn; Newcomb, Polly; Phipps, Amanda I.; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98109 USA.
[Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98109 USA.
[Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA.
[Caan, Bette] Kaiser Permanente, Div Res, Med Care Program, Oakland, CA USA.
[Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Cotterchio, Michelle] Canc Care Ontario, Populat Studies & Surveillance, Toronto, ON, Canada.
[Gallinger, Steven] Toronto Gen Hosp, Div Gen Surg, Univ Hlth Network, Toronto, ON, Canada.
[Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA.
[Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA.
[Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA.
[Hayes, Richard] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA.
[Schoen, Robert] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA.
[Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA.
[Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Potter, John] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA.
RP Peters, U (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA.
EM upeters@fhcrc.org
RI Gallinger, Steven/E-4575-2013;
OI Potter, John/0000-0001-5439-1500
FU National Cancer Institute, NIH under RFA [CA-95-011]; Australasian
Colorectal Cancer Family Registry [U01 CA097735]; Mayo Clinic
Cooperative Family Registry for Colon Cancer Studies [U01 CA074800];
Seattle Colorectal Cancer Family Registry [U01 CA074794]; Ontario
Registry for Studies of Familial Colorectal Cancer [U01 CA074783];
Ontario Research Fund; Canadian Institutes of Health Research; Cancer
Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society
Research Institute; NIH [P01 CA 055075, R01 137178, P50 CA 127003];
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Division of Cancer Prevention, National Cancer Institute, U.S.
Department of Health and Human Services; Intramural Research Program of
the National Cancer Institute; NIH from the National Cancer Institute
and Office of Dietary Supplements [K05 CA154337]; National Heart, Lung,
and Blood Institute, NIH, U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
FX CCFR was supported by the National Cancer Institute, NIH under RFA #
CA-95-011 and through cooperative agreements with members of the Colon
Cancer Family Registry and P.I.s.; The following Colon CFR centers
contributed data to the manuscript and were supported by the following
sources: Australasian Colorectal Cancer Family Registry (U01 CA097735),
Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01
CA074800), Seattle Colorectal Cancer Family Registry (U01 CA074794), and
the Ontario Registry for Studies of Familial Colorectal Cancer (U01
CA074783). The OFCCR was also supported by a GL2 grant from the Ontario
Research Fund, the Canadian Institutes of Health Research, and the
Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer
Society Research Institute.; HPFS is supported by the NIH (P01 CA
055075, R01 137178, and P50 CA 127003).; PLCO is supported by the
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics and supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, U.S. Department of Health and
Human Services. Control samples were derived from the PLCO Screening
Trial, which was supported by the Intramural Research Program of the
National Cancer Institute.; VITAL is supported in part by the NIH (K05
CA154337) from the National Cancer Institute and Office of Dietary
Supplements.; The WHI program is funded by the National Heart, Lung, and
Blood Institute, NIH, U.S. Department of Health and Human Services
through contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and
HHSN271201100004C.
NR 61
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U1 0
U2 7
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 NOV
PY 2012
VL 21
IS 11
BP 1974
EP 1985
DI 10.1158/1055-9965.EPI-12-0692
PG 12
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 035GP
UT WOS:000310931700010
PM 23001243
ER
PT J
AU Wu, LC
Kleinerman, RA
Curtis, RE
Savage, SA
de Gonzalez, AB
AF Wu, Lindsey C.
Kleinerman, Ruth A.
Curtis, Rochelle E.
Savage, Sharon A.
de Gonzalez, Amy Berrington
TI Patterns of Bone Sarcomas as a Second Malignancy in Relation to
Radiotherapy in Adulthood and Histologic Type
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; CHILDHOOD-CANCER; SOFT-TISSUE; OSTEOSARCOMA;
COHORT; RISK; AGE; CHEMOTHERAPY; NEOPLASMS; EXPOSURE
AB Background: Radiotherapy decreases cancer mortality, but is associated with an increased incidence of second primary cancers, including osteosarcomas, especially after exposure in childhood. It remains uncertain whether radiation is related to other histologic types of bone sarcomas such as chondrosarcomas that are more common in adulthood.
Methods: Using data from 1973 to 2008 Surveillance Epidemiology and End Results registries, we evaluated long-term risk of bone cancer in 1,284,537 adult 5-year cancer survivors. We used standardized incidence ratios (SIR) to compare second bone sarcoma rates to the general population for each histologic type. We also used multivariate Poisson regression to estimate the relative risk (RR) associated with radiotherapy for the most common subtypes, osteosarcoma and chondrosarcoma.
Results: By the end of 2008, 159 second bone sarcomas were reported. Compared with the general population, the risk of developing any bone sarcoma was increased by 25% in patients with no history of radiotherapy [Observed (0) = 89, SIR = 1.25(1.00-1.54)] and by 257% in patients with a history of radiotherapy [O = 70, SIR = 3.57 (2.78-4.50)]. For each histologic subtype, SIRs were higher among patients who had previously received radiotherapy than among those who had not. The RR for radiotherapy for osteosarcorna (n = 63) was 5.08 (3.05-8.59) and for chondrosarcoma = 69) was 1.54 (0.88-2.59), and these risks were even greater for second sarcomas that arose in the radiotherapy field used to treat the first cancer [osteosarcoma, RR = 10.35 (4.96-23.66); chondrosarcoma RR = 8.21 (2.09-39.89)].
Conclusions: Our findings provide the first evidence of a likely association between radiation exposure and chondrosarcoma.
Impact: These results further our understanding of radiotherapy-related cancer risks and will potentially direct practices in long-term surveillance of cancer survivors. Cancer Epidemiol Biomarkers Prev; 21(11); 1993-9. (C)2012 AACR.
C1 [Wu, Lindsey C.] NCI, NIH, HHMI, Rockville, MD 20852 USA.
[Wu, Lindsey C.; Kleinerman, Ruth A.; Curtis, Rochelle E.; de Gonzalez, Amy Berrington] NCI, Radiat Epidemiol Branch, NIH, Rockville, MD 20852 USA.
[Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Wu, Lindsey C.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Wu, LC (reprint author), NCI, NIH, HHMI, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM lindsey.c.wu@gmail.com
RI Savage, Sharon/B-9747-2015;
OI Savage, Sharon/0000-0001-6006-0740; Kleinerman, Ruth/0000-0001-7415-2478
FU Howard Hughes Medical Institute Research Scholar Program; intramural
research program of the NIH
FX This work was supported by Howard Hughes Medical Institute Research
Scholar Program (to L. Wu). This research was also supported in part by
the intramural research program of the NIH (R. Kleinerman, R. Curtis, S.
Savage, and A. Berrington).
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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 NOV
PY 2012
VL 21
IS 11
BP 1993
EP 1999
DI 10.1158/1055-9965.EPI-12-0810
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 035GP
UT WOS:000310931700012
PM 22964827
ER
PT J
AU Huang, WY
Su, LJ
Hayes, RB
Moore, LE
Katki, HA
Berndt, SI
Weissfeld, JL
Yegnasubramanian, S
Purdue, MP
AF Huang, Wen-Yi
Su, L. Joseph
Hayes, Richard B.
Moore, Lee E.
Katki, Hormuzd A.
Berndt, Sonja I.
Weissfeld, Joel L.
Yegnasubramanian, Srinivasan
Purdue, Mark P.
TI Prospective Study of Genomic Hypomethylation of Leukocyte DNA and
Colorectal Cancer Risk
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID FOLIC-ACID; LINE-1 HYPOMETHYLATION; MICROSATELLITE INSTABILITY; FOLATE
INTAKE; METHYLATION; ADENOMA; TRIAL; DEFICIENCY; PREVENTION; BIOMARKER
AB Background: Systematic genome-wide reductions of methylated cytosine (5-mC) levels have been observed in colorectal cancer tissue and are suspected to play a role in carcinogenesis, possibly as a consequence of inadequate folate intake. Reduced 5-mC levels in peripheral blood leukocytes have been associated with increased risk of colorectal cancer and adenoma in cross-sectional studies.
Methods: To minimize disease- and/or treatment-related effects, we studied leukocyte 5-mC levels in prospectively collected blood specimens of 370 cases and 493 controls who were cancer-free at blood collection from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Leukocyte 5-mC level was determined by a high-pressure liquid chromatography (HPLC)/tandem mass spectrometry method and expressed as the relative amount of methyl to total cytosine residues, or %5-mC. We estimated the association between colorectal cancer risk and %5-mC categories by computing ORs and 95% confidence intervals (CI) through logistic regression modeling.
Results: We observed no dose-dependent association between colorectal cancer and%5-mC categories (lowest vs. highest tertile: OR, 1.14; 95% CI, 0.80-1.63; P-trend = 0.51). However, among subjects whose 5-mC levels were at the highest tertile, we observed an inverse association between natural folate intake and colorectal cancer (highest tertile of natural folate vs. lowest: OR, 0.35; 95% CI, 0.17-0.71; P-trend = 0.003; P-interaction = 0.003).
Conclusions: This prospective investigation show no clear association between leukocyte 5-mC level and subsequent colorectal cancer risk but a suggestive risk modification between 5-mC level and natural folate intake. Impact: Adequate folate status may protect against colorectal carcinogenesis through mechanisms involving adequate DNA methylation in the genome. Cancer Epidemiol Biomarkers Prev; 21(11); 2014-21. (C)2012 AACR.
C1 [Huang, Wen-Yi; Moore, Lee E.; Katki, Hormuzd A.; Berndt, Sonja I.; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Su, L. Joseph] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA.
[Weissfeld, Joel L.] Univ Pittsburgh, Dept Epidemiol, Inst Canc, Pittsburgh, PA 15261 USA.
[Yegnasubramanian, Srinivasan] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Huang, WY (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8110,MSC 7240, Bethesda, MD 20892 USA.
EM huangw@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; Purdue, Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; Hayes, Richard/0000-0002-0918-661X
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Division of Cancer Prevention, National Cancer Institute, NIH,
Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics and contracts from the
Division of Cancer Prevention, National Cancer Institute, NIH,
Department of Health and Human Services.
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U2 8
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 NOV
PY 2012
VL 21
IS 11
BP 2014
EP 2021
DI 10.1158/1055-9965.EPI-12-0700-T
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 035GP
UT WOS:000310931700015
PM 23001241
ER
PT J
AU Cook, MB
Kamangar, F
Weinstein, SJ
Albanes, D
Virtamo, J
Taylor, PR
Abnet, CC
Wood, RJ
Petty, G
Cross, AJ
Dawsey, SM
AF Cook, Michael B.
Kamangar, Farin
Weinstein, Stephanie J.
Albanes, Demetrius
Virtamo, Jarmo
Taylor, Philip R.
Abnet, Christian C.
Wood, Richard J.
Petty, Gayle
Cross, Amanda J.
Dawsey, Sanford M.
TI Iron in Relation to Gastric Cancer in the Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HELICOBACTER-PYLORI; SERUM FERRITIN; STOMACH-CANCER; CARDIA CANCER;
RISK; ADENOCARCINOMAS; DEFICIENCY; JAPANESE; STORES; CARCINOGENESIS
AB Background: Iron is an essential micronutrient that can have carcinogenic effects when at high or low concentrations. Previous studies of iron in relation to gastric cancer have not assessed subtype-specific relationships. We used the prospective Alpha-Tocopherol, Beta-Carotene (ATBC) Cancer Prevention Study to assess whether iron metrics were associated with gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC).
Methods: We selected 341 incident gastric cancer cases (86 cardia, 172 noncardia, and 83 nonspecified), accrued during 22 years of follow-up, and 341 individually matched controls. We measured prediagnostic serum iron, ferritin, unsaturated iron binding capacity, and C-reactive protein. Total iron-binding capacity (TIBC) and transferrin saturation were estimated from these metrics. Dietary iron exposures were estimated from a food frequency questionnaire. Multivariable logistic regression was used for analysis.
Results: Serum iron metrics were not associated with GCC, except for a potential "n"-shaped relationship with TIBC (global P = 0.038). GNCC was inversely associated with serum ferritin (global P = 0.024), serum iron (global P = 0.060) and, possibly, transferrin saturation. TIBC appeared to share a "u"-shaped relationship with GNCC (global P = 0.033). Dietary iron exposures were not associated with either subsite. Adjustment for Helicobacter pylori and gastric atrophy had little effect on observed associations.
Conclusions: We found little evidence for the involvement of iron exposure in the pathogenesis of GCC. GNCC was associated with an iron profile similar to that of iron deficiency.
Impact: Our findings indicate that inverse associations between iron metrics and gastric cancer are driven by associations with GNCC. Further elucidation of potential mechanisms is warranted. Cancer Epidemiol Biomarkers Prev; 21(11); 2033-42. (C)2012 AACR.
C1 [Cook, Michael B.; Kamangar, Farin; Weinstein, Stephanie J.; Albanes, Demetrius; Taylor, Philip R.; Abnet, Christian C.; Cross, Amanda J.; Dawsey, Sanford M.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA.
[Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21239 USA.
[Wood, Richard J.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Boston, MA 02125 USA.
[Wood, Richard J.; Petty, Gayle] Tufts Univ, Nutr Evaluat Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Cook, MB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Suite 550,Room 5014, Rockville, MD 20852 USA.
EM michael.cook@nih.gov
RI Cook, Michael/A-5641-2009; Albanes, Demetrius/B-9749-2015; Abnet,
Christian/C-4111-2015
OI Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH, Department of Health and Human
Services
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics, National Cancer Institute, NIH, Department of Health and Human
Services.
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U1 0
U2 5
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 NOV
PY 2012
VL 21
IS 11
BP 2033
EP 2042
DI 10.1158/1055-9965.EPI-12-0799
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 035GP
UT WOS:000310931700017
PM 23001240
ER
PT J
AU Weaver, KE
Forsythe, LP
Reeve, BB
Alfano, CM
Rodriguez, JL
Sabatino, SA
Hawkins, NA
Rowland, JH
AF Weaver, Kathryn E.
Forsythe, Laura P.
Reeve, Bryce B.
Alfano, Catherine M.
Rodriguez, Juan L.
Sabatino, Susan A.
Hawkins, Nikki A.
Rowland, Julia H.
TI Mental and Physical Health-Related Quality of Life among US Cancer
Survivors: Population Estimates from the 2010 National Health Interview
Survey
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID BREAST-CANCER; PSYCHOLOGICAL DISTRESS; IMPACT; INTERVENTIONS;
METAANALYSIS; DISPARITIES; BEHAVIORS; OUTCOMES; SCORES; ADULTS
AB Background: Despite extensive data on health-related quality of life (HRQOL) among cancer survivors, we do not yet have an estimate of the percentage of survivors with poor mental and physical HRQOL compared with population norms. HRQOL population means for adult-onset cancer survivors of all ages and across the survivorship trajectory also have not been published.
Methods: Survivors (N = 1,822) and adults with no cancer history (N = 24,804) were identified from the 2010 National Health Interview Survey. The PROMIS (R) Global Health Scale was used to assess HRQOL. Poor HRQOL was defined as 1 SD or more below the PROMIS (R) population norm.
Results: Poor physical and mental HRQOL were reported by 24.5% and 10.1% of survivors, respectively, compared with 10.2% and 5.9% of adults without cancer (both P < 0.0001). This represents a population of approximately 3.3 million and 1.4 million U.S. survivors with poor physical and mental HRQOL. Adjusted mean mental and physical HRQOL scores were similar for breast, prostate, and melanoma survivors compared with adults without cancer. Survivors of cervical, colorectal, hematologic, short-survival, and other cancers had worse physical HRQOL; cervical and short-survival cancer survivors reported worse mental HROOL.
Conclusion: These data elucidate the burden of cancer diagnosis and treatment among U.S. survivors and can be used to monitor the impact of national efforts to improve survivorship care and outcomes.
Impact: We present novel data on the number of U.S. survivors with poor HRQOL. Interventions for high-risk groups that can be easily implemented are needed to improve survivor health at a population level. Cancer Epidemiol Biomarkers Prev; 21(11); 2108-17. (C) 2012 AACR.
C1 [Weaver, Kathryn E.] Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27157 USA.
[Forsythe, Laura P.; Alfano, Catherine M.; Rowland, Julia H.] NCI, Off Canc Survivorship, NIH, DHHS, Bethesda, MD 20892 USA.
[Forsythe, Laura P.] NCI, Ctr Canc Training, NIH, DHHS, Bethesda, MD 20892 USA.
[Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC USA.
[Rodriguez, Juan L.; Sabatino, Susan A.; Hawkins, Nikki A.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA.
RP Weaver, KE (reprint author), Wake Forest Sch Med, Dept Social Sci & Hlth Policy, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM keweaver@wakehealth.edu
FU National Cancer Institute at the NIH [HHSN 261201100189P]
FX This work was supported by the National Cancer Institute at the NIH.
Contract no. HHSN 261201100189P.
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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 NOV
PY 2012
VL 21
IS 11
BP 2108
EP 2117
DI 10.1158/1055-9965.EPI-12-0740
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 035GP
UT WOS:000310931700026
PM 23112268
ER
PT J
AU Benicky, J
Hafko, R
Sanchez-Lemus, E
Aguilera, G
Saavedra, JM
AF Benicky, Julius
Hafko, Roman
Sanchez-Lemus, Enrique
Aguilera, Greti
Saavedra, Juan M.
TI Six Commercially Available Angiotensin II AT(1) Receptor Antibodies are
Non-specific
SO CELLULAR AND MOLECULAR NEUROBIOLOGY
LA English
DT Article
DE GPCR receptor antibodies; Antibody characterization; Angiotensin II
receptors; Renin-angiotensin System; AT(1) receptor immunocytochemistry;
AT(1) receptor antibodies; AT(1A) receptor knock-out
ID BLOOD-PRESSURE REGULATION; HYPOTHALAMIC CELL-LINE; ADRENERGIC-RECEPTORS;
DEFICIENT MICE; RAT-BRAIN; EXPRESSION; SPECIFICITY; SUBTYPES; MOUSE;
GENE
AB Commercially available Angiotensin II AT(1) receptor antibodies are widely employed for receptor localization and quantification, but they have not been adequately validated. In this study, six commercially available AT(1) receptor antibodies were characterized by established criteria: sc-1173 and sc-579 from Santa Cruz Biotechnology, Inc., AAR-011 from Alomone Labs, Ltd., AB15552 from Millipore, and ab18801 and ab9391 from Abcam. The immunostaining patterns observed were different for every antibody tested, and were unrelated to the presence or absence of AT(1) receptors. The antibodies detected a 43 kDa band in western blots, corresponding to the predicted size of the native AT(1) receptor. However, identical bands were observed in wild-type mice and in AT(1A) knock-out mice not expressing the target protein. Moreover, immunoreactivity detected in rat hypothalamic 4B cells not expressing AT(1) receptors or transfected with AT(1A) receptor construct was identical, as revealed by western blotting and immunocytochemistry in cultured 4B cells. Additional prominent immunoreactive bands above and below 43 kDa were observed by western blotting in extracts from tissues of AT(1A) knock-out and wild-type mice and in 4B cells with or without AT(1) receptor expression. In all cases, the patterns of immunoreactivity were independent of the AT(1) receptor expression and different for each antibody studied. We conclude that, in our experimental setup, none of the commercially available AT(1) receptor antibodies tested met the criteria for specificity and that competitive radioligand binding remains the only reliable approach to study AT(1) receptor physiology in the absence of full antibody characterization.
C1 [Benicky, Julius; Hafko, Roman; Sanchez-Lemus, Enrique; Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH, Bethesda, MD 20892 USA.
[Aguilera, Greti] NICHD, Sect Endocrine Physiol, PDEGEN, NIH,CRC, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, DIRP, NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 39
TC 33
Z9 33
U1 0
U2 7
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0272-4340
J9 CELL MOL NEUROBIOL
JI Cell. Mol. Neurobiol.
PD NOV
PY 2012
VL 32
IS 8
BP 1353
EP 1365
DI 10.1007/s10571-012-9862-y
PG 13
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA 045AR
UT WOS:000311666900013
PM 22843099
ER
PT J
AU Zakharov, AV
Lagunin, AA
Filimonov, DA
Poroikov, VV
AF Zakharov, Alexey V.
Lagunin, Alexey A.
Filimonov, Dmitry A.
Poroikov, Vladimir V.
TI Quantitative Prediction of Antitarget Interaction Profiles for Chemical
Compounds
SO CHEMICAL RESEARCH IN TOXICOLOGY
LA English
DT Article
ID ACUTE TOXICITY; MODELS; TARGETS
AB The evaluation of possible interactions between chemical compounds and antitarget proteins is an important task of the research and development process. Here, we describe the development and validation of QSAR models for the prediction of antitarget end-points, created on the basis of multilevel and quantitative neighborhoods of atom descriptors and self-consistent regression. Data on 4000 chemical compounds interacting with 18 antitarget proteins (13 receptors, 2 enzymes, and 3 transporters) were used to model 32 sets of end-points (IC50, K-i, and K-act). Each set was randomly divided into training and test sets in a ratio of 80% to 20%, respectively. The test sets were used for external validation of QSAR models created on the basis of the training sets. The coverage of prediction for all test sets exceeded 95%, and for half of the test sets, it was 100%. The accuracy of prediction for 29 of the end-points, based on the external test sets, was typically in the range of R-test(2) = 0.6-0.9; three tests sets had lower R-test(2) values, specifically 0.55-0.6. The proposed approach showed a reasonable accuracy of prediction for 91% of the antitarget end-points and high coverage for all external test sets. On the basis of the created models, we have developed a freely available online service for in silica prediction of 32 antitarget end-points: http://www.pharmaexpert.ru/GUSAR/antitargets.html.
C1 [Zakharov, Alexey V.] NCI, NIH, Frederick, MD 21702 USA.
[Zakharov, Alexey V.; Lagunin, Alexey A.; Filimonov, Dmitry A.; Poroikov, Vladimir V.] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119121, Russia.
RP Zakharov, AV (reprint author), NCI, NIH, 376 Boyles St, Frederick, MD 21702 USA.
EM alexey.zakharov@nih.gov
RI Poroikov, Vladimir/O-2769-2013; Lagunin, Alexey/G-3745-2010
OI Poroikov, Vladimir/0000-0001-7937-2621; Lagunin,
Alexey/0000-0003-1757-8004
FU RFBR [12-07-00597]; RFBR/NIH [12-04-91445/RUBI-31081-MO-12]
FX This work is partially supported by RFBR grant number 12-07-00597 (to
D.A.F. and A.A.L.) and RFBR/NIH grant number
12-04-91445/RUBI-31081-MO-12 (to V.V.P.).
NR 26
TC 21
Z9 23
U1 0
U2 5
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0893-228X
J9 CHEM RES TOXICOL
JI Chem. Res. Toxicol.
PD NOV
PY 2012
VL 25
IS 11
BP 2378
EP 2385
DI 10.1021/tx300247r
PG 8
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology
SC Pharmacology & Pharmacy; Chemistry; Toxicology
GA 038KO
UT WOS:000311173800010
PM 23078046
ER
PT J
AU Wang, L
Song, YQ
Manson, JE
Pilz, S
Marz, W
Michaelsson, K
Lundqvist, A
Jassal, SK
Barrett-Connor, E
Zhang, CL
Eaton, CB
May, HT
Anderson, JL
Sesso, HD
AF Wang, Lu
Song, Yiqing
Manson, JoAnn E.
Pilz, Stefan
Maerz, Winfried
Michaelsson, Karl
Lundqvist, Annamari
Jassal, Simerjot K.
Barrett-Connor, Elizabeth
Zhang, Cuilin
Eaton, Charles B.
May, Heidi T.
Anderson, Jeffrey L.
Sesso, Howard D.
TI Circulating 25-Hydroxy-Vitamin D and Risk of Cardiovascular Disease A
Meta-Analysis of Prospective Studies
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE 25-hydroxy-vitamin D; cardiovascular disease; meta-analysis; prospective
study
ID VITAMIN-D DEFICIENCY; SERUM 25-HYDROXYVITAMIN D; RENIN-ANGIOTENSIN
SYSTEM; SUDDEN CARDIAC DEATH; ALL-CAUSE MORTALITY; DOSE-RESPONSE DATA;
PARATHYROID-HORMONE; MYOCARDIAL-INFARCTION; CORONARY-ANGIOGRAPHY;
GENERAL-POPULATION
AB Background-Vitamin D status has been linked to the risk of cardiovascular disease (CVD). However, the optimal 25-hydroxy-vitamin D (25[OH]-vitamin D) levels for potential cardiovascular health benefits remain unclear.
Methods and Results-We searched MEDLINE and EMBASE from 1966 through February 2012 for prospective studies that assessed the association of 25(OH)-vitamin D concentrations with CVD risk. A total of 24 articles met our inclusion criteria, from which 19 independent studies with 6123 CVD cases in 65 994 participants were included for a meta-analysis. In a comparison of the lowest with the highest 25(OH)-vitamin D categories, the pooled relative risk was 1.52 (95% confidence interval, 1.30-1.77) for total CVD, 1.42 (95% confidence interval, 1.19-1.71) for CVD mortality, 1.38 (95% confidence interval, 1.21-1.57) for coronary heart disease, and 1.64 (95% confidence interval, 1.27-2.10) for stroke. These associations remained strong and significant when analyses were limited to studies that excluded participants with baseline CVD and were better controlled for season and confounding. We used a fractional polynomial spline regression analysis to assess the linearity of dose-response association between continuous 25(OH)-vitamin D and CVD risk. The CVD risk increased monotonically across decreasing 25(OH)-vitamin D below approximate to 60 nmol/L, with a relative risk of 1.03 (95% confidence interval, 1.00-1.06) per 25-nmol/L decrement in 25(OH)-vitamin D.
Conclusions-This meta-analysis demonstrated a generally linear, inverse association between circulating 25(OH)-vitamin D ranging from 20 to 60 nmol/L and risk of CVD. Further research is needed to clarify the association of 25(OH)-vitamin D higher than 60 nmol/L with CVD risk and assess causality of the observed associations. (Circ Cardiovasc Qual Outcomes. 2012;5:819-829.)
C1 [Wang, Lu; Song, Yiqing; Manson, JoAnn E.; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA.
[Manson, JoAnn E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Pilz, Stefan] Med Univ Graz, Dept Internal Med, Div Endocrinol & Metab, Graz, Austria.
[Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Maerz, Winfried] Synlab Serv LLC, Synlab Acad, Mannheim, Germany.
[Maerz, Winfried] Univ Mannheim, Mannheim Inst Publ Hlth, Mannheim, Germany.
[Michaelsson, Karl] Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.
[Lundqvist, Annamari] Natl Inst Hlth & Welfare, Helsinki, Finland.
[Jassal, Simerjot K.] Univ Calif, Dept Med, Div Gen Internal Med & Geriatr, La Jolla, CA USA.
[Jassal, Simerjot K.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Barrett-Connor, Elizabeth] Univ Calif, Div Epidemiol, Dept Family & Prevent Med, La Jolla, CA USA.
[Zhang, Cuilin] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA.
[Eaton, Charles B.] Brown Univ, Alpert Med Sch, Ctr Primary Care & Prevent, Pawtucket, RI USA.
[May, Heidi T.] Intermt Med Ctr, Cardiovasc Dept, Murray, KY USA.
[Anderson, Jeffrey L.] Univ Utah, Sch Med, Div Cardiol, Salt Lake City, UT USA.
RP Wang, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
EM luwang@rics.bwh.harvard.edu
OI May, Heidi/0000-0002-7524-5905
FU National Institutes of Health (NIH)/National Heart, Lung, and Blood
Institute (NHLBI), Bethesda, MD [R00-HL095649]; NIH/National Institute
of Diabetes and Digestive and Kidney Disease (NIDDK) [R01-DK088078]; NIH
[HL34594, CA138962]; Intramural Research Program of the Eunice Kennedy
Shriver NIH/National Institute of Child Health & Human Development
(NICHD); NIH/National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS)/National Institute on Aging (NIA)/National Center
for Research Resources (NCRR); NIH Roadmap for Medical Research [U01
AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01
AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]
FX Dr Wang is supported by grant R00-HL095649 from the National Institutes
of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI),
Bethesda, MD. Dr Song is funded by grant R01-DK088078 from the
NIH/National Institute of Diabetes and Digestive and Kidney Disease
(NIDDK). Dr JoAnn Manson is funded by grants HL34594 and CA138962 from
the NIH. Dr Zhang is supported by the Intramural Research Program of the
Eunice Kennedy Shriver NIH/National Institute of Child Health & Human
Development (NICHD). The Osteoporotic Fractures in Men (MrOS) Study is
supported by the NIH/National Institute of Arthritis and Musculoskeletal
and Skin Diseases (NIAMS)/National Institute on Aging (NIA)/National
Center for Research Resources (NCRR) and NIH Roadmap for Medical
Research under the following grant numbers: U01 AR45580, U01 AR45614,
U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197,
U01-AG027810, and UL1 RR024140. These funding sources had no role in the
design and conduct of the study; collection, management, analysis, and
interpretation of the data; and preparation, review, or approval of the
article.
NR 49
TC 190
Z9 200
U1 2
U2 32
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-7705
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD NOV
PY 2012
VL 5
IS 6
BP 819
EP 829
DI 10.1161/CIRCOUTCOMES.112.967604
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 041NZ
UT WOS:000311409800018
PM 23149428
ER
PT J
AU Lamprea-Montealegre, JA
Astor, BC
McClelland, RL
de Boer, IH
Burke, GL
Sibley, CT
O'Leary, D
Sharrett, AR
Szklo, M
AF Lamprea-Montealegre, Julio A.
Astor, Brad C.
McClelland, Robin L.
de Boer, Ian H.
Burke, Gregory L.
Sibley, Christopher T.
O'Leary, Daniel
Sharrett, A. Richey
Szklo, Moyses
TI CKD, Plasma Lipids, and Common Carotid Intima-Media Thickness: Results
from the Multi-Ethnic Study of Atherosclerosis
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; CORONARY-HEART-DISEASE; NONTRADITIONAL
RISK-FACTORS; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR EVENTS;
MYOCARDIAL-INFARCTION; DIALYSIS PATIENTS; TOTAL CHOLESTEROL; LIPOPROTEIN
ABNORMALITIES; MALNUTRITION
AB Background and objectives Altered levels of atherogenic lipoproteins have been shown to be common in mild kidney dysfunction. This study sought to determine the associations between plasma lipids (including LDL particle distribution) and subclinical atherosclerosis measured by the common carotid intima-media thickness (TMT) across levels of estimated GFR (eGFR) and to assess whether inflammation modifies these associations.
Design, setting, participants, & measurements Cross-sectional analyses of 6572 participants in the Multi-Ethnic Study of Atherosclerosis enrolled from 2000 to 2002 were performed.
Results CKD, defined as eGFR <60 ml/min per 1.73 m(2), was present in 853 individuals (13.0%). Associations of total cholesterol and LDL cholesterol (LDL-C) with IMT were J shaped, particularly among participants with CKD (P value for interaction, P=0.01). HDL cholesterol (HDL-C) and small-dense LDL-C were consistently and linearly associated with IMT across levels of eGFR. The results showed differences in IMT of -21.41 (95% confidence interval, -41.00, -1.57) in eGFR >= 60 and -58.49 (-126.61, 9.63) in eGFR <60 per unit difference in log-transformed HDL-C, and 4.83 (3.16, 6.50) in eGFR >= 60 and 7.48 (1.45, 13.50) in eGFR <60 per 100 nmol/L difference in small-dense LDL. Among participants with CKD, inflammation significantly modified the associations of total cholesterol and LDL-C with IMT (P values for interaction, P<0.01 and P<0.001, respectively).
Conclusions Compared with total cholesterol and LDL-C, abnormalities in HDL-C and small-dense LDL-C are more strongly and consistently associated with subclinical atherosclerosis in CKD. Inflammation modifies the association between total cholesterol and LDL-C with IMT. Clin J Am Soc Nephrol 7: 1777-1785, 2012. doi: 10.2215/CJN.02090212
C1 [Lamprea-Montealegre, Julio A.; Sharrett, A. Richey; Szklo, Moyses] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Lamprea-Montealegre, Julio A.; Sharrett, A. Richey; Szklo, Moyses] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Astor, Brad C.] Univ Wisconsin, Dept Med & Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA.
[McClelland, Robin L.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[de Boer, Ian H.] Univ Washington, Dept Med, Seattle, WA USA.
[Burke, Gregory L.] Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Sibley, Christopher T.] NIH, Bethesda, MD 20892 USA.
[O'Leary, Daniel] Tufts Med Ctr, Dept Radiol, Boston, MA USA.
RP Szklo, M (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA.
EM mszklo@jhsph.edu
RI Sibley, Christopher/C-9900-2013
NR 39
TC 14
Z9 15
U1 0
U2 3
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD NOV
PY 2012
VL 7
IS 11
BP 1777
EP 1785
DI 10.2215/CJN.02090212
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA 033CO
UT WOS:000310770600007
PM 22879436
ER
PT J
AU Bahta, M
Burke, TR
AF Bahta, M.
Burke, T. R.
TI Yersinia pestis and Approaches to Targeting its Outer Protein H
Protein-Tyrosine Phosphatase (YopH)
SO CURRENT MEDICINAL CHEMISTRY
LA English
DT Review
DE Inhibitors; plague; protein-tyrosine phosphatase (PTP); Yersinia pestis;
YopH; TTSS; P-loop; WPD-loop; EGFR; F(2)Pmp
ID SIGNAL-TRANSDUCTION INHIBITORS; ALPHA-KETOCARBOXYLIC ACIDS;
SMALL-MOLECULE INHIBITORS; CRYSTAL-STRUCTURE; CLICK CHEMISTRY; DRUG
DISCOVERY; PHOSPHOTYROSYL MIMETICS; VIRULENCE DETERMINANT; BIDENTATE
INHIBITORS; POTENT INHIBITION
AB Plague is an infectious disease with a high mortality rate that has repeatedly impacted human society. It remains a threat in many parts of the world today. Plague is caused by the bacterium, Yersinia pestis (Y. pestis), which has as one of its required virulence factors, the protein-tyrosine phosphatase, YopH. Therefore, YopH represents a potential target for the treatment of Y. pestis infection. Recent recognition of Y. pestis as a possible bioterrorism agent and the fact that it is still the cause of endemic disease around the world make it an important object of study and heighten the need for new anti-plague agents. The current review covers aspects of plague and its historical occurrence and summarizes approaches to developing YopH inhibitors.
C1 [Bahta, M.; Burke, T. R.] NCI, Biol Chem Lab, Frederick Natl Lab Canc Res, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), 1050 Boyles St Room 217, Frederick, MD 21702 USA.
EM burkete@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU NIH, Frederick National Laboratory for Cancer Research, National Cancer
Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the NIH, Frederick National Laboratory for Cancer Research, National
Cancer Institute, National Institutes of Health. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government.
NR 92
TC 9
Z9 9
U1 1
U2 12
PU BENTHAM SCIENCE PUBL LTD
PI SHARJAH
PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB
EMIRATES
SN 0929-8673
J9 CURR MED CHEM
JI Curr. Med. Chem.
PD NOV
PY 2012
VL 19
IS 33
BP 5726
EP 5734
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology &
Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA 038CL
UT WOS:000311152700014
PM 22934808
ER
PT J
AU Biancotto, A
Feng, XM
Langweiler, M
Young, NS
McCoy, JP
AF Biancotto, Angelique
Feng, Xingmin
Langweiler, Marc
Young, Neal S.
McCoy, J. Philip
TI Effect of anticoagulants on multiplexed measurement of
cytokine/chemokines in healthy subjects
SO CYTOKINE
LA English
DT Article
DE Cytokines/chemokines; Plasma; Serum; Anticoagulants
ID SOLUBLE CD40 LIGAND; STORAGE-CONDITIONS; CYTOKINE LEVELS; PLASMA
SAMPLES; SERUM; ELISA; IMMUNOASSAY; ASSAYS; BLOOD
AB Introduction: Cytokines are humoral regulatory molecules that act together in immunologic pathways. Monitoring cytokines and their variations within physiologic ranges is critical for biomarker discovery. Therefore, we evaluated the performance characteristics of 72 analytes measured by multiplex cytokine immunoassay, with an emphasis on the differences of analytes measured in serum compared to plasma, and, in plasma, on the impact of anticoagulants on the cytokine measurement.
Methods: We used fluorescent bead-based (Luminex) immunoassay kits to simultaneously measure 72 analytes. We tested serum and plasma samples from 11 matched donors. Plasma samples were anticoagulated with sodium heparin, sodium citrate dextrose and ethylene diamine tetra-acetic acid (EDTA), respectively.
Results: Of the 72 cytokines, 12 were undetectable in all types of specimen samples. Nineteen analytes, including PDGF-bb, IL-4, IL-8, IL-9, FGF-b, PAI-1, CXCL-5, CCL-5, CD40L, EGF, VEGF, IL-2ra, IL-3, SDF-1a, PCT, MCP-3, GIP, IL-16 and fibrinogen, showed significant differences between measurements in serum and all types of plasma, regardless of anticoagulant. Among plasma samples, 10 analytes (eotaxin, SCGF-b, MCP-1, SCF, MIP-1b, VEGF, RANTES, PDGF-b, PAI-1 and ITAC) showed significantly higher concentrations in heparinized plasma compared to citrated and EDTA plasma. IP-10, and CTAK were the only 2 cytokines that presented different concentrations in citrate and EDTA plasma.
Conclusions: With their small volume, low cost per test, and multiplex capacity, Luminex-based cytokine assays have enormous potential utility for screening in epidemiologic studies. In our study, we showed that many cytokines' concentrations differed between serum and plasma samples, and that different anticoagulants used in preparation of plasma samples also affected the measurement of some cytokines. There was no optimal sample preparation that was clearly superior for the measurement of all analytes measured. Ultimately, the utility of cytokine measurement, as biomarker or to monitor the immune system, will depend on attention to detail in the collection and processing of samples in addition to assay precision. Published by Elsevier Ltd.
C1 [Biancotto, Angelique; Langweiler, Marc; Young, Neal S.; McCoy, J. Philip] NIH, Ctr Human Immunol Autoimmun & Inflammat, Bethesda, MD 28092 USA.
[Feng, Xingmin; Young, Neal S.; McCoy, J. Philip] NHLBI, Hematol Branch, NIH, Bethesda, MD 28092 USA.
RP McCoy, JP (reprint author), NIH, 10 Ctr Dr,MSC 1357,Bldg 10,Rm 8C103D, Bethesda, MD 20892 USA.
EM mccoyjp@mail.nih.gov
FU Intramural NIH HHS [Z99 HL999999, ZIC HL005905-04]
NR 20
TC 30
Z9 30
U1 2
U2 15
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2012
VL 60
IS 2
BP 438
EP 446
DI 10.1016/j.cyto.2012.05.019
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 029KL
UT WOS:000310494300018
PM 22705152
ER
PT J
AU Morley, K
Seth, D
Monteleone, P
Duly, A
Haber, P
Addolorato, G
Leggio, L
AF Morley, Kirsten
Seth, Devanshi
Monteleone, Palmiero
Duly, Alastair
Haber, Paul
Addolorato, Giovanni
Leggio, Lorenzo
TI GHRELIN GENE POLYMORPHISMS IN ALCOHOL DEPENDENCE
SO DRUG AND ALCOHOL REVIEW
LA English
DT Meeting Abstract
C1 [Morley, Kirsten; Haber, Paul] Univ Sydney, Sydney Med Sch, Discipline Addict Med, Sydney, NSW 2006, Australia.
[Seth, Devanshi; Duly, Alastair] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW 2006, Australia.
[Monteleone, Palmiero] Univ Naples SUN, Dept Psychiat, Naples, Italy.
[Haber, Paul] Royal Prince Alfred Hosp, Drug Hlth Serv, Sydney, NSW, Australia.
[Addolorato, Giovanni] Univ Cattolica Sacro Cuore, Inst Internal Med, Rome, Italy.
[Leggio, Lorenzo] NIAAA, Bethesda, MD 90034 USA.
EM kirsten.morley@sydney.edu.au
RI Leggio, Lorenzo/M-2972-2016
NR 1
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0959-5236
J9 DRUG ALCOHOL REV
JI Drug Alcohol Rev.
PD NOV
PY 2012
VL 31
SU 1
SI SI
BP 52
EP 53
PG 2
WC Substance Abuse
SC Substance Abuse
GA 039HX
UT WOS:000311236700162
ER
PT J
AU Reid, BC
Ghazarian, AA
DeMarini, DM
Sapkota, A
Jack, D
Lan, Q
Winn, DM
Birnbaum, LS
AF Reid, Britt C.
Ghazarian, Armen A.
DeMarini, David M.
Sapkota, Amir
Jack, Darby
Lan, Qing
Winn, Deborah M.
Birnbaum, Linda S.
TI Research Opportunities for Cancer Associated with Indoor Air Pollution
from Solid-Fuel Combustion
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE cancer; environmental exposures; environmental health risks;
epidemiology; household air pollution; indoor air pollution; public
health; solid-fuel combustion
ID POLYCYCLIC AROMATIC-HYDROCARBONS; HOUSEHOLD STOVE IMPROVEMENT;
LUNG-CANCER; RISK-FACTORS; WOOD SMOKE; SUSCEPTIBILITY LOCUS; CERVICAL
NEOPLASIA; NORTHEAST CHINA; TOBACCO-SMOKE; XUAN WEI
AB BACKGROUND: Indoor air pollution (LAP) derived largely from the use of solid fuels for cooking and heating affects about 3 billion people worldwide, resulting in substantial adverse health outcomes, including cancer. Women and children from developing countries are the most exposed populations. A workshop was held in Arlington, Virginia, 9-11 May 2011, to better understand women's and children's potential health effects from LAP in developing countries. Workshop participants included international scientists, manufacturers, policy and regulatory officials, community leaders, and advocates who held extensive discussions to help identify future research needs.
OBJECTIVES: Our objective was to identify research opportunities regarding IAP and cancer, including research questions that could be incorporated into studies of interventions to reduce LAP exposure. In this commentary, we describe the state of the science in understanding LAP and its associations with cancer and suggest research opportunities for improving our understanding of the issues.
DISCUSSION: Opportunities for research on LAP and cancer include studies of the effect of LAP on cancers other than lung cancer; studies of genetic factors that modify susceptibility; studies to determine whether the effects of TAP are mediated via germline, somatic, and/or epigenetic changes; and studies of the effects of TAP exposure via dermal and/or oral routes.
CONCLUSIONS: LAP from indoor coal use increases the risk of lung cancer. Installing chimneys can reduce risk, and some genotypes, including GSTM1-null, can increase risk. Additional research is needed regarding the effects of IAP on other cancers and the effects of different types of solid fuels, oral and dermal routes of LAP exposure, genetic and epigenetic mechanisms, and genetic susceptibility.
C1 [Reid, Britt C.] NCI, Modifiable Risk Factors Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH,DHHS, Bethesda, MD 20892 USA.
[DeMarini, David M.] US EPA, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA.
[Sapkota, Amir] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA.
[Jack, Darby] Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY USA.
[Lan, Qing] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Birnbaum, Linda S.] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NCI, NIH, DHHS, Res Triangle Pk, NC USA.
RP Reid, BC (reprint author), NCI, Modifiable Risk Factors Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH,DHHS, 6130 Execut Blvd,Room 5134, Bethesda, MD 20892 USA.
EM reidbr@mail.nih.gov
RI Sapkota, Amir/A-5968-2011
FU NICHD NIH HHS [R24 HD041041]
NR 53
TC 11
Z9 13
U1 6
U2 46
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1495
EP 1498
DI 10.1289/ehp.1204962
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000015
PM 22846419
ER
PT J
AU Cote, I
Anastas, PT
Birnbaum, LS
Clark, RM
Dix, DJ
Edwards, SW
Preuss, PW
AF Cote, Ila
Anastas, Paul T.
Birnbaum, Linda S.
Clark, Rebecca M.
Dix, David J.
Edwards, Stephen W.
Preuss, Peter W.
TI Advancing the Next Generation of Health Risk Assessment
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE bioinformatics; molecular biology; NexGen; "omics"; risk assessment;
systems biology
ID NATIONAL TOXICOLOGY PROGRAM; ENVIRONMENTAL CHEMICALS; EXPOSURE
AB BACKGROUND: Over the past 20 years, knowledge of the genome and its function has increased dramatically, but risk assessment methodologies using such knowledge have not advanced accordingly.
OBJECTIVE: This commentary describes a collaborative effort among several federal and state agencies to advance the next generation of risk assessment. The objective of the NexGen program is to begin to incorporate recent progress in molecular and systems biology into risk assessment practice. The ultimate success of this program will be based on the incorporation of new practices that facilitate faster, cheaper, and/or more accurate assessments of public health risks.
METHODS: We are developing prototype risk assessments that compare the results of traditional, data-rich risk assessments with insights gained from new types of molecular and systems biology data. In this manner, new approaches can be validated, traditional approaches improved, and the value of different types of new scientific information better understood.
DISCUSSION AND CONCLUSIONS: We anticipate that these new approaches will have a variety of applications, such as assessment of new and existing chemicals in commerce and the design of chemical products and processes that reduce or eliminate the use or generation of hazardous substances. Additionally, results of the effort are likely to spur further research and test methods development. Full implementation of new approaches is likely to take 10-20 years.
C1 [Cote, Ila; Clark, Rebecca M.; Preuss, Peter W.] US EPA, Washington, DC 20460 USA.
[Cote, Ila; Dix, David J.; Edwards, Stephen W.] US EPA, Res Triangle Pk, NC 27711 USA.
[Anastas, Paul T.] Yale Univ, New Haven, CT USA.
[Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cote, I (reprint author), US EPA, 1200 Penn Ave NW,MD 8601P, Washington, DC 20460 USA.
EM cote.ila@epa.gov
RI Anastas, Paul/L-3258-2013
OI Anastas, Paul/0000-0003-4777-5172
NR 33
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U1 1
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PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1499
EP 1502
DI 10.1289/ehp.1104870
PG 4
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000016
PM 22875311
ER
PT J
AU Little, MP
Azizova, TV
Bazyka, D
Bouffler, SD
Cardis, E
Chekin, S
Chumak, VV
Cucinotta, FA
de Vathaire, F
Hall, P
Harrison, JD
Hildebrandt, G
Ivanov, V
Kashcheev, VV
Klymenko, SV
Kreuzer, M
Laurent, O
Ozasa, K
Schneider, T
Tapio, S
Taylor, AM
Tzoulaki, I
Vandoolaeghe, WL
Wakeford, R
Zablotska, LB
Zhang, W
Lipshultz, SE
AF Little, Mark P.
Azizova, Tamara V.
Bazyka, Dimitry
Bouffler, Simon D.
Cardis, Elisabeth
Chekin, Sergey
Chumak, Vadim V.
Cucinotta, Francis A.
de Vathaire, Florent
Hall, Per
Harrison, John D.
Hildebrandt, Guido
Ivanov, Victor
Kashcheev, Valeriy V.
Klymenko, Sergiy V.
Kreuzer, Michaela
Laurent, Olivier
Ozasa, Kotaro
Schneider, Thierry
Tapio, Soile
Taylor, Andrew M.
Tzoulaki, Ioanna
Vandoolaeghe, Wendy L.
Wakeford, Richard
Zablotska, Lydia B.
Zhang, Wei
Lipshultz, Steven E.
TI Systematic Review and Meta-analysis of Circulatory Disease from Exposure
to Low-Level Ionizing Radiation and Estimates of Potential Population
Mortality Risks
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
DE cancer; circulatory disease; heart disease; radiation; stroke
ID ATOMIC-BOMB SURVIVORS; CORONARY-HEART-DISEASE; POWER INDUSTRY WORKERS;
NUCLEAR-FUELS PLC; LOW-DOSE EXPOSURE; CARDIOVASCULAR-DISEASE;
EPIDEMIOLOGIC EVIDENCE; MAYAK PA; CANCER; COHORT
AB BACKGROUND: Although high doses of ionizing radiation have long been linked to circulatory disease, evidence for an association at lower exposures remains controversial. However, recent analyses suggest excess relative risks at occupational exposure levels.
OBJECTIVES: We performed a systematic review and meta-analysis to summarize information on circulatory disease risks associated with moderate- and low-level whole-body ionizing radiation exposures.
METHODS: We conducted PubMed/ISI Thomson searches of peer-reviewed papers published since 1990 using the terms "radiation" AND "heart" AND "disease," OR "radiation" AND "stroke," OR "radiation" AND "circulatory" AND "disease." Radiation exposures had to be whole-body, with a cumulative mean dose of < 0.5 Sv, or at a low dose rate (< 10 mSv/day). We estimated population risks of circulatory disease from low-level radiation exposure using excess relative risk estimates from this meta-analysis and current mortality rates for nine major developed countries.
RESULTS: Estimated excess population risks for all circulatory diseases combined ranged from 2.5%/Sv [95% confidence interval (Cl): 0.8, 4.2] for France to 8.5%/Sv (95% CI: 4.0, 13.0) for Russia.
CONCLUSIONS: Our review supports an association between circulatory disease mortality and low and moderate doses of ionizing radiation. Our analysis was limited by heterogeneity among studies (particularly for noncardiac end points), the possibility of uncontrolled confounding in some occupational groups by lifestyle factors, and higher dose groups (> 0.5 Sv) generally driving the observed trends. If confirmed, our findings suggest that overall radiation-related mortality is about twice that currently estimated based on estimates for cancer end points alone (which range from 4.2% to 5.6%/Sv for these populations).
C1 [Little, Mark P.] NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA.
[Azizova, Tamara V.] So Urals Biophys Inst, Ozyorsk, Russia.
[Bazyka, Dimitry; Chumak, Vadim V.] Res Ctr Radiat Med, Kiev, Ukraine.
[Bouffler, Simon D.; Harrison, John D.; Zhang, Wei] Hlth Protect Agcy, Ctr Radiat Chem & Environm Hazards, Chilton, England.
[Cardis, Elisabeth] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Chekin, Sergey; Ivanov, Victor; Kashcheev, Valeriy V.] Russian Acad Med Sci, Med Radiol Res Ctr, Obninsk, Russia.
[Cucinotta, Francis A.] NASA, Lyndon B Johnson Space Ctr, Space Radiat Program, Houston, TX 77058 USA.
[de Vathaire, Florent] Inst Gustave Roussy, INSERM, Radiat Epidemiol Grp, Unite U1018, F-94805 Villejuif, France.
[Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hildebrandt, Guido] Univ Leipzig, Dept Radiotherapy & Radiat Oncol, Leipzig, Germany.
[Hildebrandt, Guido] Univ Rostock, Dept Radiotherapy & Radiat Oncol, Rostock, Germany.
[Kreuzer, Michaela] Fed Off Radiat Protect, Dept Radiat Protect & Hlth, Oberschleissheim, Germany.
[Laurent, Olivier] Inst Radioprotect & Surete Nucl, Lab Epidemiol, Fontenay Aux Roses, France.
[Ozasa, Kotaro] Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan.
[Schneider, Thierry] CEPN Nucl Evaluat Protect Ctr, Fontenay Aux Roses, France.
[Tapio, Soile] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Radiat Biol ISB, Oberschleissheim, Germany.
[Taylor, Andrew M.] UCL, Inst Cardiovasc Sci, London, England.
[Taylor, Andrew M.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Tzoulaki, Ioanna; Vandoolaeghe, Wendy L.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Epidemiol & Biostat, London, England.
[Wakeford, Richard] Univ Manchester, Dalton Nucl Inst, Manchester, Lancs, England.
[Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Lipshultz, Steven E.] Univ Miami, Dept Pediat, Leonard M Miller Sch Med, Miami, FL 33152 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, NIH, Dept Hlth & Human Serv, Execut Plaza S,6120 Execut Blvd,MSC 7238, Rockville, MD 20852 USA.
EM mark.little@nih.gov
RI Taylor, Andrew/C-4311-2008; Tapio, Soile/M-7358-2014; Kashcheev,
Valeriy/L-7794-2015; Chumak, Vadim/N-6960-2015; de Vathaire,
Florent/L-2983-2016; Ivanov, Victor/R-9385-2016; Cardis,
Elisabeth/C-3904-2017;
OI Little, Mark/0000-0003-0980-7567; Klymenko, Sergiy/0000-0002-9758-7316;
Tapio, Soile/0000-0001-9860-3683; Wakeford, Richard/0000-0002-2934-0987;
Kashcheev, Valeriy/0000-0003-4108-9761; Chumak,
Vadim/0000-0001-6045-9356; Ivanov, Victor/0000-0003-1372-0018; Bazyka,
Dimitry/0000-0001-9982-5990
FU European Commission (EC) [FP6-036465]; Intramural Research Program of
the National Institutes of Health (NIH); National Cancer Institute;
Japanese Ministry of Health, Labour and Welfare; U.S. Department of
Energy through the National Academy of Sciences
FX This work was funded partially by the European Commission (EC) under
contract FP6-036465 [NOn-Targeted Effects of ionising radiation (NOTE)
integrated project]. This research was also supported by the Intramural
Research Program of the National Institutes of Health (NIH) and the
National Cancer Institute. This report makes use of data obtained from
the Radiation Effects Research Foundation (RERF), Hiroshima and
Nagasaki, Japan. RERF is a private, nonprofit foundation funded by the
Japanese Ministry of Health, Labour and Welfare and the U.S. Department
of Energy, the latter through the National Academy of Sciences.
NR 59
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U2 27
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1503
EP 1511
DI 10.1289/ehp.1204982
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000017
PM 22728254
ER
PT J
AU Cupul-Uicab, LA
Skjaerven, R
Haug, K
Travlos, GS
Wilson, RE
Eggesbo, M
Hoppin, JA
Whitworth, KW
Longnecker, MP
AF Cupul-Uicab, Lea A.
Skjaerven, Rolv
Haug, Kjell
Travlos, Gregory S.
Wilson, Ralph E.
Eggesbo, Merete
Hoppin, Jane A.
Whitworth, Kristina W.
Longnecker, Matthew P.
TI Exposure to Tobacco Smoke in Utero and Subsequent Plasma Lipids, ApoB,
and CRP among Adult Women in the MoBa Cohort
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE clinical chemistry; C-reactive protein; metabolic syndrome; plasma
lipids; prenatal exposure delayed effects; smoking; women
ID MATERNAL-SMOKING; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; NORWEGIAN
MOTHER; CHILD COHORT; PARENTAL SMOKING; BIRTH-WEIGHT; RISK-FACTORS;
PREGNANCY; HYPERTENSION
AB BACKGROUND: Recent findings suggest that maternal smoking during pregnancy may play a role in the development of metabolic alterations in offspring during childhood. However, whether such exposure increases the risk of developing similar metabolic alterations during adulthood is uncertain.
OBJECTIVE: We evaluated the association of in utero exposure to maternal tobacco smoke with plasma lipids, apolipoprotein B (apoB), and C-reactive protein (CRP) in adulthood.
METHODS: The study was based on a subsample of the Norwegian Mother and Child Cohort Study (MoBa) and included 479 pregnant women with plasma lipids, apoB, and CRP measurements. Information on in utero exposure to tobacco smoke, personal smoking, and other factors were obtained from the women by a self-completed questionnaire at enrollment, at approximately 17 weeks of gestation.
RESULTS: Women exposed to tobacco smoke in utero had higher triglycerides [10.7% higher; 95% confidence interval (CI): 3.9, 17.9] and lower high-density lipoprotein cholesterol (HDL) (-1.9 mg/dL; 95% CI: -4.3, 0.5) compared with unexposed women, after adjusting for age, physical activity, education, personal smoking, and current body mass index (BMI). Exposed women were also more likely to have triglycerides >= 200 mg/dL., [adjusted odds ratio (aOR) = 2.5; 95% CI: 1.3, 5.1] and HDL < 50 mg/dL (aOR = 2.3; 95% CI: 1.1, 5.0). Low-density lipoprotein cholesterol, total cholesterol, and apoB were not associated with the exposure. CRP was increased among exposed women; however, after adjustment for BMI, the association was completely attenuated.
CONCLUSIONS: In this population, in utero exposure to tobacco smoke was associated with high triglycerides and low HDL in adulthood, 18-44 years after exposure.
C1 [Cupul-Uicab, Lea A.; Hoppin, Jane A.; Whitworth, Kristina W.; Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Skjaerven, Rolv; Haug, Kjell] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway.
[Skjaerven, Rolv] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway.
[Travlos, Gregory S.; Wilson, Ralph E.] NIEHS, Cellular & Mol Pathol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Eggesbo, Merete] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, Oslo, Norway.
RP Cupul-Uicab, LA (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM cupuluicabl@niehs.nih.gov
RI CUPUL UICAB, LEA/C-8699-2014;
OI CUPUL UICAB, LEA/0000-0001-6190-4474; Longnecker,
Matthew/0000-0001-6073-5322; Eggesbo, Merete/0000-0002-0006-5336
FU Intramural Research Program of the National Institutes of Health (NIH),
National Institute of Environmental Health Sciences (NIEHS); Norwegian
Ministry of Health [N01-ES-75558]; NIH/NIEHS, NIH/National Institute of
Neurological Disorders and Stroke [1 UO1 NS 047537-01]; Norwegian
Research Council/FUGE [151918/S10]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute of
Environmental Health Sciences (NIEHS). The Norwegian Mother and Child
Cohort Study is supported by the Norwegian Ministry of Health, contract
N01-ES-75558 with the NIH/NIEHS, NIH/National Institute of Neurological
Disorders and Stroke (grant 1 UO1 NS 047537-01), and the Norwegian
Research Council/FUGE (grant 151918/S10).
NR 38
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PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1532
EP 1537
DI 10.1289/ehp.1104563
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000021
PM 22814200
ER
PT J
AU Chulada, PC
Kennedy, S
Mvula, MM
Jaffee, K
Wildfire, J
Thornton, E
Cohn, RD
Grimsley, LF
Mitchell, H
El-Dahr, J
Sterling, Y
Martin, WJ
White, L
Stephens, KU
Lichtveld, M
AF Chulada, Patricia C.
Kennedy, Suzanne
Mvula, Mosanda M.
Jaffee, Katy
Wildfire, Jeremy
Thornton, Eleanor
Cohn, Richard D.
Grimsley, L. Faye
Mitchell, Herman
El-Dahr, Jane
Sterling, Yvonne
Martin, William J.
White, LuAnn
Stephens, Kevin U.
Lichtveld, Maureen
TI The Head-off Environmental Asthma in Louisiana (HEAL) Study-Methods and
Study Population
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE asthma; asthma case management; asthma counselor; environmental
intervention; Hurricane Katrina; indoor allergens; mold
ID INNER-CITY ASTHMA; KATRINA NEW-ORLEANS; HURRICANE-KATRINA; URBAN
COMMUNITIES; CHILDREN; HOMES; INTERVENTION; MANAGEMENT; MORBIDITY;
EXPOSURES
AB BACKGROUND: In the city of New Orleans, Louisiana, and surrounding parishes (NOLA), children with asthma were perilously impacted by Hurricane Katrina as a result of disrupted health care, high home mold and allergen levels, and high stress.
OBJECTIVES: The Head-off Environmental Asthma in Louisiana (HEAL) study was conducted to examine relationships between the post-Katrina environment and childhood asthma in NOLA and assess a novel asthma counselor intervention that provided case management and guidance for reducing home mold and allergen levels.
METHODS: Children (4-12 years old) with moderate-to-severe asthma were recruited from NOLA schools. Over 1 year, they received two clinical evaluations, three home environmental evaluations, and the asthma intervention. Quarterly end points included symptom days, medication use, and unscheduled emergency department or clinic visits. A community advisory group was assembled and informed HEAL at all phases.
RESULTS: Of the children (n = 182) enrolled in HEAL, 67% were African American, and 25% came from households with annual incomes < $15,000: HEAL children were symptomatic, averaging 6.6 symptom days in the 2 weeks before baseline, and had frequent unscheduled visits to clinics or emergency departments (76% had at least one unscheduled visit in the preceding 3 months). In this report, we describe study design and baseline characteristics of HEAL children.
CONCLUSIONS: Despite numerous challenges faced by investigators, study staff, and participants, including destroyed infrastructure, disrupted lives, and lost jobs, HEAL was successful in terms of recruitment and retention, the high quality of data collected that will provide insight into asthma-allergen relationships, and the asthma intervention. This success was attributable to using an adaptive approach and refining processes as needed.
C1 [Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kennedy, Suzanne; Jaffee, Katy; Wildfire, Jeremy; Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Mvula, Mosanda M.; Stephens, Kevin U.] New Orleans Hlth Dept, New Orleans, LA USA.
[Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA.
[Cohn, Richard D.] SRA Int Inc, Durham, NC USA.
[Grimsley, L. Faye; White, LuAnn; Lichtveld, Maureen] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[El-Dahr, Jane] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Sterling, Yvonne] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
[Martin, William J.] NICHD, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
RP Chulada, PC (reprint author), Westat Corp, 1009 Slater Rd,Suite 110, Durham, NC 27703 USA.
EM patriciachulada@westat.com
FU National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma
Network; National Center on Minority Health and Health Disparities under
Foundation for the NIH; 501(c)(3) charitable organization; Louisiana
Board of Regents RC/EEP
FX This project has been funded, in whole or in part, with federal funds
from the National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH), under contract NO1-ES-55553..
Additional funding support was provided by the Merck Childhood Asthma
Network and the National Center on Minority Health and Health
Disparities under the auspices of the Foundation for the NIH, a
nonprofit, 501(c)(3) charitable organization that raises private-sector
funds for a broad portfolio of unique programs that complement and
enhance the NIH priorities and activities. Other organizations that
contributed include the National Toxicology Program (NIEHS), the U.S.
Environmental Protection Agency (Cincinnati, OH), and the de Laski
Family Foundation. The Clinical and Translational Research Center of
Tulane and Louisiana State Universities Schools of Medicine was
supported in whole or in part by funds provided through the Louisiana
Board of Regents RC/EEP. H.M., J.W., KJ., and S.K. are employed by Rho
Federal Systems Division, Inc., R.D.C. is employed by SEA International,
Inc., ET. is employed by Visionary Consulting Partners, LLC, Rho Federal
Systems Division, Inc.
NR 31
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U1 1
U2 14
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1592
EP 1599
DI 10.1289/ehp.1104239
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000030
PM 22895349
ER
PT J
AU Grimsley, LF
Chulada, PC
Kennedy, S
White, L
Wildfire, J
Cohn, RD
Mitchell, H
Thornton, E
El-Dahr, J
Mvula, MM
Sterling, Y
Martin, WJ
Stephens, KU
Lichtveld, M
AF Grimsley, L. Faye
Chulada, Patricia C.
Kennedy, Suzanne
White, LuAnn
Wildfire, Jeremy
Cohn, Richard D.
Mitchell, Herman
Thornton, Eleanor
El-Dahr, Jane
Mvula, Mosanda M.
Sterling, Yvonne
Martin, William J.
Stephens, Kevin U.
Lichtveld, Maureen
TI Indoor Environmental Exposures for Children with Asthma Enrolled in the
HEAL Study, Post-Katrina New Orleans
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE allergens; asthma; endotoxin; environmental remediation; glucan;
Hurricane Katrina; mold
ID INNER-CITY CHILDREN; RELATIVE MOLDINESS INDEX; DUST-MITE ALLERGENS;
ALTERNARIA-ALTERNATA; HURRICANE-KATRINA; ENDOTOXIN EXPOSURE; US HOMES;
MOLD; ATOPY; CHILDHOOD
AB BACKGROUND: Rain and flooding from Hurricane Katrina resulted in widespread growth of mold and bacteria and production of allergens in New Orleans, Louisiana, which may have led to increased exposures and morbidity in children with asthma.
OBJECTIVES: The goal of the Head-off Environmental Asthma in Louisiana (HEAL) study was to characterize post-Katrina exposures to mold and allergens in children with asthma.
METHODS: The homes of 182 children with asthma in New Orleans and surrounding parishes were evaluated by visual inspection, temperature and moisture measurements, and air and dust sampling. Air was collected using vacuum-pump spore traps and analyzed for > 30 mold taxa using bright field microscopy. Dust was collected from the children's beds and bedroom floors and analyzed for mouse (Mus m 1), dust mite (Der p 1), cockroach (Bla g 1), and mold (Alternaria mix) allergens using ELISA.
RESULTS: More than half (62%) of the children were living in homes that had been damaged by rain, flooding, or both. Geometric mean indoor and outdoor airborne mold levels were 501 and 3,958 spores/m(3), respectively. Alternaria antigen was detected in dust from 98% of homes, with 58% having concentrations > 10 mu g/g. Mus m 1, Der p 1, and Bla g 1 were detected in 60%, 35%, and 20% of homes, respectively, at low mean concentrations.
CONCLUSIONS: Except for Alternaria antigen in dust, concentrations of airborne mold (ratio of indoor to outdoor mold) and dust allergens in the homes of HEAL children were lower than measurements found in other studies, possibly because of extensive post-Katrina mold remediation and renovations, or because children moved into cleaner homes upon returning to New Orleans.
C1 [Grimsley, L. Faye; White, LuAnn; Lichtveld, Maureen] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Kennedy, Suzanne; Wildfire, Jeremy; Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Cohn, Richard D.] SRA Int Inc, Durham, NC USA.
[Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA.
[El-Dahr, Jane] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Mvula, Mosanda M.; Stephens, Kevin U.] New Orleans Hlth Dept, New Orleans, LA USA.
[Sterling, Yvonne] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
[Martin, William J.] NICHD, NIH, US Dept HHS, Bethesda, MD USA.
RP Grimsley, LF (reprint author), 1440 Canal St,Suite 2100,SL-29, New Orleans, LA 70112 USA.
EM Grimsley@tulane.edu
FU National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma
Network; National Center on Minority Health and Health Disparities under
the auspices of the Foundation for the NIH; 501(c)(3) charitable
organization; Louisiana Board of Regents RC/EEP
FX This project has been funded, in whole or in part, with federal funds
from the National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH), under contract NO1-ES-55553.
Additional funding support was provided by the Merck Childhood Asthma
Network and the National Center on Minority Health and Health
Disparities under the auspices of the Foundation for the NIH, a
nonprofit, 501(c)(3) charitable organization that raises private-sector
funds for a broad portfolio of unique programs that complement and
enhance the NIH priorities and activities. Other organizations that
contributed include the National Toxicology Program (NIEHS), the U.S.
Environmental Protection Agency (Cincinnati, OH), and the de Laski
Family Foundation. The Clinical and Translational Research Center of
Tulane and Louisiana State Universities, Schools of Medicine was
supported in whole or in part by funds provided through the Louisiana
Board of Regents RC/EEP. H.M., J.W., and S.K. are employed by Rho
Federal Systems Division, Inc. R.D.C. is employed by SRA International,
Inc. E.T. is employed by Visionary Consulting Partners, LLC.
NR 48
TC 10
Z9 10
U1 2
U2 27
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1600
EP 1606
DI 10.1289/ehp.1104840
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000031
PM 22894816
ER
PT J
AU Mitchell, H
Cohn, RD
Wildfire, J
Thornton, E
Kennedy, S
El-Dahr, JM
Chulada, PC
Mvula, MM
Grimsley, LF
Lichtveld, MY
White, LE
Sterling, YM
Stephens, KU
Martin, WJ
AF Mitchell, Herman
Cohn, Richard D.
Wildfire, Jeremy
Thornton, Eleanor
Kennedy, Suzanne
El-Dahr, Jane M.
Chulada, Patricia C.
Mvula, Mosanda M.
Grimsley, L. Faye
Lichtveld, Maureen Y.
White, LuAnn E.
Sterling, Yvonne M.
Stephens, Kevin U., Sr.
Martin, William J., II
TI Implementation of Evidence-based Asthma Interventions in Post-Katrina
New Orleans: The Head-off Environmental Asthma in Louisiana (HEAL) Study
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
DE asthma case management; asthma counselor; asthma morbidity;
environmental intervention; Hurricane Katrina; indoor allergens; mold
ID INNER-CITY ASTHMA; CHILDREN; MORBIDITY; SYMPTOMS; CARE; HOME
AB BACKGROUND: Childhood asthma morbidity and mortality in New Orleans, Louisiana, is among the highest in the nation. In August 2005, Hurricane Katrina created an environmental disaster that led to high levels of mold and other allergens and disrupted health care for children with asthma.
OBJECTIVES: We implemented a unique hybrid asthma counselor and environmental intervention based on successful National Institutes of Health asthma interventions from the National Cooperative Inner City Asthma (NCICAS) and Inner-City Asthma (ICAS) Studies with the goal of reducing asthma symptoms in New Orleans children after Hurricane Katrina.
METHODS: Children (4-12 years old) with moderate-to-severe asthma (fl = 182) received asthma counseling and environmental intervention for approximately 1 year. HEAL was evaluated employing several analytical approaches including a pre post evaluation of symptom changes over the entire year, an analysis of symptoms according to the timing of asthma counselor contact, and a comparison to previous evidence-based interventions.
RESULTS: Asthma symptoms during the previous 2 weeks decreased from 6.5 days at enrollment to 3.6 days at the 12-month symptom assessment (a 45% reduction, p < 0.001), consistent with changes observed after NCICAS and ICAS interventions.(35% and 62% reductions in symptom days, respectively). Children whose families had contact with a HEAL asthma counselor by 6 months showed a 4.09-day decrease [95% confidence interval (CI): 3.25 to 4.94-day decrease] in symptom days, compared with a 1.79-day decrease (95% Cl: 0.90, 2.67) among those who had not yet seen an asthma counselor (p < 0.001).
CONCLUSIONS: The novel combination of evidence-based asthma interventions was associated with improved asthma symptoms among children in post-Katrina New Orleans. Post-intervention changes in symptoms were consistent with previous randomized trials of NCICAS and ICAS interventions.
C1 [Mitchell, Herman; Wildfire, Jeremy; Kennedy, Suzanne] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA.
[Cohn, Richard D.] SRA Int Inc, Durham, NC USA.
[Thornton, Eleanor] Visionary Consulting Partners LLC, Fairfax Stn, VA USA.
[El-Dahr, Jane M.] Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA.
[Chulada, Patricia C.] NIEHS, Clin Res Program, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Mvula, Mosanda M.; Stephens, Kevin U., Sr.] New Orleans Hlth Dept, New Orleans, LA USA.
[Grimsley, L. Faye; Lichtveld, Maureen Y.; White, LuAnn E.] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA.
[Sterling, Yvonne M.] Louisiana State Univ, Sch Nursing, Hlth Sci Ctr, New Orleans, LA USA.
[Martin, William J., II] NICHD, NIH, US Dept HHS, Bethesda, MD USA.
RP Mitchell, H (reprint author), Rho Fed Syst Div Inc, 6330 Quadrangle Dr, Chapel Hill, NC 27517 USA.
EM herman_mitchell@rhoworld.com
FU National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH) [NO1-ES-55553]; Merck Childhood Asthma
Network; National Center on Minority Health and Health Disparities under
Foundation for the NIH; 501(c)(3) charitable organization; Louisiana
Board of Regents RC/EEP
FX This project has been funded, in whole or in part, with federal funds
from the National Institute of Environmental Health Sciences (NIEHS),
National Institutes of Health (NIH), under contract NO1-ES-55553.
Additional funding support was provided by the Merck Childhood Asthma
Network and the National Center on Minority Health and Health
Disparities under the auspices of the Foundation for the NIH, a
nonprofit, 501(c)(3) charitable organization that raises private-sector
funds for a broad portfolio of unique programs that complement and
enhance the NIH priorities and activities. Other organizations that
contributed include the National Toxicology Program (NIEHS), the U.S.
Environmental Protection Agency (Cincinnati, OH), and the de Laski
Family Foundation. The Clinical and Translational Research Center of
Tulane and Louisiana State Universities Schools of Medicine was
supported in whole or in part by funds provided through the Louisiana
Board of Regents RC/EEP. H.M., J.W., and S.K. are employed by Rho
Federal Systems Division, Inc. R.D.C. is employed by SRA International,
Inc. E.T. is employed by Visionary Consulting Partners, LLC.
NR 21
TC 7
Z9 7
U1 0
U2 6
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV
PY 2012
VL 120
IS 11
BP 1607
EP 1612
DI 10.1289/ehp.1104242
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 036ZE
UT WOS:000311070000032
PM 22894795
ER
PT J
AU Karp, JE
Garrett-Mayer, E
Estey, EH
Rudek, MA
Smith, BD
Greer, JM
Drye, DM
Mackey, K
Dorcy, KS
Gore, SD
Levis, MJ
McDevitt, MA
Carraway, HE
Pratz, KW
Gladstone, DE
Showel, MM
Othus, M
Doyle, LA
Wright, JJ
Pagel, JM
AF Karp, Judith E.
Garrett-Mayer, Elizabeth
Estey, Elihu H.
Rudek, Michelle A.
Smith, B. Douglas
Greer, Jacqueline M.
Drye, D. Michelle
Mackey, Karen
Dorcy, Kathleen Shannon
Gore, Steven D.
Levis, Mark J.
McDevitt, Michael A.
Carraway, Hetty E.
Pratz, Keith W.
Gladstone, Douglas E.
Showel, Margaret M.
Othus, Megan
Doyle, L. Austin
Wright, John J.
Pagel, John M.
TI Randomized phase II study of two schedules of flavopiridol given as
timed sequential therapy with cytosine arabinoside and mitoxantrone for
adults with newly diagnosed, poor-risk acute myelogenous leukemia
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Article
DE acute myelogenous leukemia; poor risk; flavopiridol; ara-C; mitoxantrone
ID ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; 72-HOUR
CONTINUOUS-INFUSION; BREAST-CARCINOMA CELLS; GROUP-B; TRANSCRIPTIONAL
REPRESSION; CYTOTOXIC SYNERGY; CLINICAL-TRIALS; DOWN-REGULATION; OLDER
PATIENTS
AB Background
Flavopiridol is a protein-bound, cytotoxic, cyclin dependent kinase inhibitor. A phase II trial of flavopiridol followed by ara-C and mitoxantrone with flavopiridol given by 1-h bolus for adults with newly-diagnosed, poor-risk acute myelogenous leukemia yielded 67% complete remission with median disease-free survival of 13.6 months.
Design and Methods
We compared bolus flavopiridol (50 mg/m(2)/day, Arm A) versus 'hybrid' flavopiridol (30 mg/m(2) over 30 min followed by 40 mg/m(2) over 4 h, Arm B) followed by ara-C and mitoxantrone in 78 patients (39 per arm) with newly diagnosed, poor-risk acute myelogenous leukemia. To mitigate imbalance, patients were stratified by presence or absence of secondary leukemia and therapy for antecedent disorder.
Results
Death at or before Day 60 occurred in 8% of patients per arm. Complete remission plus complete remission with incomplete recovery was 68% (Arm A, 62%; Arm B, 74%) overall, and 65% or over in both arms for patients with secondary leukemia and leukemia with adverse genetics. In Arm A 91% and in Arm B 86% of patients received chemotherapy and/or allogeneic transplantation in complete remission. Median overall survival for all remission patients has not been reached for either arm, with median disease free survival of 13.6 months for Arm A and of 12.0 months for Arm B.
Conclusions
Both flavopiridol schedules produce comparably encouraging results in adults with poor-risk acute myelogenous leukemia. Given the greater ease of bolus administration, we are conducting a randomized phase II study of bolus flavopiridol followed by ara-c and mitoxantrone versus conventional induction therapy for patients aged 70 years and under with intermediate or poor-risk acute myelogenous leukemia. This study is registered at www.clinicaltrials.gov as #NCT 00407966.
C1 [Karp, Judith E.; Smith, B. Douglas; Greer, Jacqueline M.; Drye, D. Michelle; Mackey, Karen; Gore, Steven D.; Levis, Mark J.; McDevitt, Michael A.; Carraway, Hetty E.; Pratz, Keith W.; Gladstone, Douglas E.; Showel, Margaret M.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, Baltimore, MD 21231 USA.
[Garrett-Mayer, Elizabeth] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Seattle Canc Care Alliance, Seattle, WA USA.
[Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Estey, Elihu H.; Dorcy, Kathleen Shannon; Othus, Megan; Pagel, John M.] Univ Washington, Seattle, WA 98195 USA.
[Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Chem Therapeut, Baltimore, MD 21231 USA.
[Doyle, L. Austin; Wright, John J.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Karp, JE (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Div Hematol Malignancies, 1650 Orleans St,CRB 1,Room 2M44, Baltimore, MD 21231 USA.
EM jkarp2@jhmi.edu
FU NCI Cooperative Agreement [U01 CA70095]; NCI Cancer Center Support Grant
[2P30 CA06973-46]; National Center for Research Resources Grant [UL1
RR025005]
FX this work was supported in part by NCI Cooperative Agreement U01 CA70095
(JEK and MAR), NCI Cancer Center Support Grant 2P30 CA06973-46, National
Center for Research Resources Grant UL1 RR025005 (a component of the
National Institutes of Health Roadmap for Medical Research), and
philanthropic funds from Dr. Robert E. Fischell in memory of his late
wife Marian (JEK). The contents of the project are solely the
responsibility of the authors and do not necessarily represent the
official view of NCI, NCRR, or NIH.
NR 38
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U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD NOV
PY 2012
VL 97
IS 11
BP 1736
EP 1742
DI 10.3324/haematol.2012.062539
PG 7
WC Hematology
SC Hematology
GA 043WL
UT WOS:000311581300023
PM 22733022
ER
PT J
AU Bereal-Williams, C
Machado, RF
McGowan, V
Chi, A
Hunter, CJ
Kato, GJ
AF Bereal-Williams, Candice
Machado, Roberto F.
McGowan, Vicki, II
Chi, Amy
Hunter, Christian J.
Kato, Gregory J.
TI Atorvastatin reduces serum cholesterol and triglycerides with limited
improvement in vascular function in adults with sickle cell anemia
SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
LA English
DT Letter
DE atorvastatin; sickle cell anemia; nitric oxide resistance; vascular
fuction
ID PULMONARY-HYPERTENSION; MEDIATED VASODILATION; DISEASE; DYSFUNCTION;
SIMVASTATIN; ADHESION; MOUSE; MEN
C1 [Bereal-Williams, Candice; McGowan, Vicki, II; Chi, Amy; Hunter, Christian J.; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Machado, Roberto F.] Univ Illinois, Coll Med, Div Pulm Crit Care Sleep & Allergy, Chicago, IL USA.
RP Kato, GJ (reprint author), 9000 Rockville Pike,MSC 1476,Bldg 10CRC,Room 5-51, Bethesda, MD 20892 USA.
EM gkato@mail.nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [Z01 CL008052-05]; NHLBI NIH HHS [ZIA HL006023]; PHS
HHS [1 ZIAHL006023-03]
NR 12
TC 6
Z9 6
U1 0
U2 0
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOL-HEMATOL J
JI Haematol-Hematol. J.
PD NOV
PY 2012
VL 97
IS 11
BP 1768
EP 1770
DI 10.3324/haematol.2011.054957
PG 3
WC Hematology
SC Hematology
GA 043WL
UT WOS:000311581300028
PM 22773602
ER
PT J
AU Marton, A
Vizler, C
Kusz, E
Temesfoi, V
Szathmary, Z
Nagy, K
Szegletes, Z
Varo, G
Siklos, L
Katona, RL
Tubak, V
Howard, OMZ
Duda, E
Minarovits, J
Nagy, K
Buzas, K
AF Marton, Annamaria
Vizler, Csaba
Kusz, Erzsebet
Temesfoi, Viktoria
Szathmary, Zsuzsa
Nagy, Krisztina
Szegletes, Zsolt
Varo, Gyorgy
Siklos, Laszlo
Katona, Robert L.
Tubak, Vilmos
Howard, O. M. Zack
Duda, Erno
Minarovits, Janos
Nagy, Katalin
Buzas, Krisztina
TI Melanoma cell-derived exosomes alter macrophage and dendritic cell
functions in vitro
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE Melanoma; Tumor immunity; Exosomes; Cytokine profile
ID NF-KAPPA-B; PROGRESSION; INHIBITOR; TUMORS
AB To clarify controversies in the literature of the field, we have purified and characterized B16F1 melanoma cell derived exosomes (mcd-exosomes) then we attempted to dissect their immunological activities. We tested how mcd-exosomes influence CD4+T cell proliferation induced by bone marrow derived dendritic cells; we quantified NF-kappa B activation in mature macrophages stimulated with mcd-exosomes, and we compared the cytokine profile of LPS-stimulated, IL-4 induced, and mcd-exosome treated macrophages. We observed that mcd-exosomes helped the maturation of dendritic cells, enhancing T cell proliferation induced by the treated dendritic cells. The exosomes also activated macrophages, as measured by NF-kappa B activation. The cytokine and chemokine profile of macrophages treated with tumor cell derived exosomes showed marked differences from those induced by either LPS or IL-4, and it suggested that exosomes may play a role in the tumor progression and metastasis formation through supporting tumor immune escape mechanisms. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Marton, Annamaria; Vizler, Csaba; Kusz, Erzsebet; Temesfoi, Viktoria; Tubak, Vilmos; Duda, Erno; Buzas, Krisztina] Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary.
[Szathmary, Zsuzsa] Galenbio Kft, Mosonmagyarovar, Hungary.
[Nagy, Krisztina; Szegletes, Zsolt; Varo, Gyorgy; Siklos, Laszlo] Hungarian Acad Sci, Biol Res Ctr, Inst Biophys, H-6701 Szeged, Hungary.
[Katona, Robert L.] Hungarian Acad Sci, Biol Res Ctr, Inst Genet, H-6701 Szeged, Hungary.
[Howard, O. M. Zack] NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA.
[Minarovits, Janos] Natl Ctr Epidemiol, Microbiol Res Grp, Budapest, Hungary.
[Nagy, Katalin; Buzas, Krisztina] Univ Szeged, Fac Dent, Szeged, Hungary.
RP Buzas, K (reprint author), Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6701 Szeged, Hungary.
EM kr.buzas@gmail.com
RI Howard, O M Zack/B-6117-2012;
OI Howard, O M Zack/0000-0002-0505-7052; Duda, Erno/0000-0002-0964-1627
FU National Science Fund of Hungary OTKA [PD 84064, OTKA K 81180,
GOP-1.1.1-11-2011-0003, TAMOP-4.2.2/B-10/1-2010-0012]; Hungarian Academy
of Sciences
FX This work was supported by the National Science Fund of Hungary OTKA PD
84064, OTKA K 81180 and GOP-1.1.1-11-2011-0003 and
TAMOP-4.2.2/B-10/1-2010-0012. C. Vizier was the recipient of a Bolyai
fellowship of the Hungarian Academy of Sciences.
NR 18
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U1 4
U2 20
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
J9 IMMUNOL LETT
JI Immunol. Lett.
PD NOV-DEC
PY 2012
VL 148
IS 1
BP 34
EP 38
DI 10.1016/j.imlet.2012.07.006
PG 5
WC Immunology
SC Immunology
GA 042IH
UT WOS:000311464400004
PM 22898052
ER
PT J
AU Biesecker, LG
AF Biesecker, Leslie G.
TI The New World of Clinical Genomics
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Editorial Material
C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Biesecker, LG (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,Room 4A56, Bethesda, MD 20892 USA.
EM lesb@helix.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP 3912
EP 3914
DI 10.1210/jc.2012-3288
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500036
PM 23129594
ER
PT J
AU Havens, PL
Mulligan, K
Hazra, R
Flynn, P
Rutledge, B
Van Loan, MD
Lujan-Zilbermann, J
Kapogiannis, BG
Wilson, CM
Stephensen, CB
AF Havens, Peter L.
Mulligan, Kathleen
Hazra, Rohan
Flynn, Patricia
Rutledge, Brandy
Van Loan, Marta D.
Lujan-Zilbermann, Jorge
Kapogiannis, Bill G.
Wilson, Craig M.
Stephensen, Charles B.
CA HIV AIDS Interventions ATN 063
TI Serum 25-Hydroxyvitamin D Response to Vitamin D-3 Supplementation 50,000
IU Monthly in Youth with HIV-1 Infection
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID BONE-MINERAL DENSITY; D-DEFICIENCY RICKETS; ERGOCALCIFEROL VITAMIN-D-2;
ANTIRETROVIRAL THERAPY; ABACAVIR-LAMIVUDINE; CONTROLLED-TRIAL; D
INSUFFICIENCY; CHOLECALCIFEROL; TENOFOVIR; ADOLESCENTS
AB Context: Vitamin D deficiency and insufficiency occur frequently in youth with HIV infection, particularly among those receiving the antiretroviral drug efavirenz. Optimal vitamin D dosing for treatment is unclear.
Objective: Our objective was to evaluate safety and measure change in 25-hydroxyvitamin D (25-OHD) concentration from baseline to study wk 4 and 12 during treatment with vitamin D-3, 50,000 IU monthly.
Design, Setting, and Participants: We conducted a randomized double-blind, placebo-controlled multicenter trial of HIV-infected youth ages 18-24 yr, with viral load below 5000 copies/ml, on stable antiretroviral therapy.
Intervention: Intervention included vitamin D-3, 50,000 IU (n = 102), or matching placebo (n = 101) administered in three directly observed oral doses at monthly intervals.
Results: At baseline, mean (SD) age was 20.9 (2.0) yr; 37% were female and 52% African-American, and 54% were vitamin D deficient/insufficient (25-OHD < 20 ng/ml), with no randomized group differences. Of evaluable participants vitamin D deficient/insufficient at baseline who were administered vitamin D, 43 of 46 (93%) had sufficient 25-OHD by wk 12. Vitamin D supplementation increased 25-OHD serum concentration from a baseline of 21.9 (13.3) to 35.9 (19.1) ng/ml at wk 12 (P < 0.001) with no change for placebo. Although use of the antiretroviral efavirenz was associated with lower baseline 25-OHD concentration, efavirenz did not diminish the response to vitamin D supplementation. There was no treatment-related toxicity.
Conclusions: Supplementation with vitamin D-3 50,000 IU monthly for three doses was safe. Increases in 25-OHD occurred in treated participants regardless of antiretroviral regimen. (J Clin Endocrinol Metab 97: 4004-4013, 2012)
C1 [Havens, Peter L.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53201 USA.
[Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94110 USA.
[Hazra, Rohan; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Flynn, Patricia] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Rutledge, Brandy] WESTAT Corp, Rockville, MD 20850 USA.
[Van Loan, Marta D.; Stephensen, Charles B.] ARS, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA.
[Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL 33606 USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL 35294 USA.
RP Havens, PL (reprint author), Suite C450,POB 1997, Milwaukee, WI 53201 USA.
EM phavens@mcw.edu
FU National Institutes of Health (NIH) through the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) [U01 HD
040533, U01 HD 040474]; National Institutes on Drug Abuse and Mental
Health; National Institute of Allergy and Infectious Diseases; NICHD;
National Institute of Mental Health [U01 A1068632]; General Clinical
Research Center Program of the National Center for Research Resources;
NIH; Department of Health and Human Services; Children's National
Medical Center [M01RR020359]; University of Pennsylvania/Children's
Hospital of Philadelphia [NCRRUL1-RR-024134]; University of California
at San Francisco [UL1 RR024131]; Seattle Children's Hospital
[UL1-RR025014]; Texas Children's Hospital and Baylor College of Medicine
[M01-RR00188]; Boston University Medical Center [UL1-RR02517]; SUNY
Stony Brook [M01RR10710]; Louisiana Board of Regents RC/EEP [RC/EEP-06]
FX This work was supported by the ATN from the National Institutes of
Health (NIH) (U01 HD 040533 and U01 HD 040474) through the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) (to B.G.K.), with supplemental funding from the National
Institutes on Drug Abuse (N. Borek) and Mental Health (P. Brouwers and
S. Allison). The protocol was co-endorsed by the IMPAACT Group. Support
for the IMPAACT Group was provided by the National Institute of Allergy
and Infectious Diseases, the NICHD, and the National Institute of Mental
Health (U01 A1068632). The study was scientifically reviewed by the
ATN's Therapeutic Leadership Group. Network, scientific, and logistical
support was provided by the ATN Coordinating Center (C.W. and C.
Partlow) at The University of Alabama at Birmingham. Network operations
and analytic support was provided by the ATN Data and Operations Center
at Westat, Inc. (J. Korelitz and B. Driver).; Eight of the participating
sites used their General Clinical Research Center/Pediatric Clinical
Research Center for the study; the centers were supported by grants from
the General Clinical Research Center Program of the National Center for
Research Resources, NIH, Department of Health and Human Services as
follows: Children's National Medical Center, M01RR020359; University of
Pennsylvania/Children's Hospital of Philadelphia, NCRRUL1-RR-024134;
University of California at San Francisco, UL1 RR024131; Seattle
Children's Hospital, UL1-RR025014; Texas Children's Hospital and Baylor
College of Medicine, M01-RR00188; Boston University Medical Center,
UL1-RR02517; and SUNY Stony Brook, M01RR10710. The Tulane University
Health Sciences Center used its Clinical and Translational Research
Center for the study; the center was supported in whole or in part by
funds provided through the Louisiana Board of Regents RC/EEP
(RC/EEP-06).
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SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP 4004
EP 4013
DI 10.1210/jc.2012-2600
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500049
PM 22933542
ER
PT J
AU Kritchevsky, SB
Tooze, JA
Neiberg, RH
Schwartz, GG
Hausman, DB
Johnson, MA
Bauer, DC
Cauley, JA
Shea, MK
Cawthon, PM
Harris, TB
Rubin, SM
Tylavsky, FA
Houston, DK
AF Kritchevsky, Stephen B.
Tooze, Janet A.
Neiberg, Rebecca H.
Schwartz, Gary G.
Hausman, Dorothy B.
Johnson, Mary Ann
Bauer, Douglas C.
Cauley, Jane A.
Shea, M. Kyla
Cawthon, Peggy M.
Harris, Tamara B.
Rubin, Susan M.
Tylavsky, Francis A.
Houston, Denise K.
CA Hlth ABC Study
TI 25-Hydroxyvitamin D, Parathyroid Hormone, and Mortality in Black and
White Older Adults: The Health ABC Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE MORTALITY; RANDOMIZED
CONTROLLED-TRIALS; VITAMIN-D DEFICIENCY; SERUM CONCENTRATIONS; RISK;
COMMUNITY; ASSOCIATION; POPULATION; WOMEN
AB Context: Previous 25-hydroxyvitamin D [25(OH)D] and mortality studies have included mostly individuals of European descent. Whether the relationship is similar in Blacks and to what extent differences in 25(OH)D explain racial disparities in mortality is unclear.
Objective: The objective of the study was to examine the relationship between 25(OH)D, PTH, and mortality in Black and white community-dwelling older adults over 8.5 yr of follow-up.
Design and Setting: Health ABC is a prospective cohort study conducted in Memphis, TN, and Pittsburgh, PA.
Participants: Well-functioning Blacks and whites aged 71-80 yr with measured 25(OH)D and PTH (n = 2638; 49% male, 39% Black) were included in the study.
Main Outcome Measure: Multivariate-adjusted proportional hazards models estimated the hazard ratios (HR) for all-cause, cardiovascular, cancer, and noncancer, noncardiovascular mortality (n = 691 deaths).
Results: Mean 25(OH)D concentrations were higher in whites than in Blacks [mean (SD): 29.0 (9.9) and 20.8 (8.7) ng/ml, respectively; P < 0.001]. Serum 25(OH)D by race interactions were not significant, however. Lower 25(OH)D concentrations were associated with higher mortality in Blacks and whites combined [HR (95% confidence interval [CI] 2.27 (1.59-3.24), 1.48 (1.20-1.84), and 1.25 (1.02-1.52) for <10, 10 to <20, and 20 to <30 vs. >= 30 ng/ml]. In the multivariate model without 25(OH)D, Blacks had 22% higher mortality than whites [HR (95% CI) 1.22 (1.01, 1.48)]; after including 25(OH)D in the model, the association was attenuated [1.09 (0.90-1.33)]. The mortality population attributable risks (95% CI) for 25(OH)D concentrations less than 20 ng/ml and less than 30 ng/ml in Blacks were 16.4% (3.1-26.6%) and 37.7% (11.6-55.1%) and in whites were 8.9% (3.9-12.7%) and 11.1% (-2.7 to 22.0%), respectively. PTH was also associated with mortality [HR (95% CI) 1.80 (1.33-2.43) for >= 70 vs. <23 pg/ml].
Conclusions: Low 25(OH)D and high PTH concentrations were associated with increased mortality in Black and white community-dwelling older adults. Because 25(OH)D concentrations were much lower in Blacks, the potential impact of remediating low 25(OH)D concentrations was greater in Blacks than whites. (J Clin Endocrinol Metab 97: 4156-4165, 2012)
C1 [Kritchevsky, Stephen B.] Wake Forest Sch Med, Dept Internal Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Winston Salem, NC 27157 USA.
[Tooze, Janet A.; Neiberg, Rebecca H.] Wake Forest Sch Med, Dept Biostat, Winston Salem, NC 27157 USA.
[Schwartz, Gary G.] Wake Forest Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA.
[Hausman, Dorothy B.; Johnson, Mary Ann] Univ Georgia, Dept Food & Nutr, Athens, GA 30602 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Rubin, Susan M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94120 USA.
[Harris, Tamara B.] NIA, Lab Epidemiol & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Tylavsky, Francis A.] Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38163 USA.
RP Kritchevsky, SB (reprint author), Wake Forest Sch Med, Dept Internal Med, Sticht Ctr Aging, Sect Gerontol & Geriatr Med, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM skritche@wakehealth.edu
OI Kritchevsky, Stephen/0000-0003-3336-6781; Cauley, Jane
A/0000-0003-0752-4408
FU National Institutes of Health, National Institute on Aging; National
Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01
AG029364, R01 AG028050]; National Institute of Nursing Research [R01
NR012459]; Wake Forest University Claude D. Pepper Older Americans
Independence Center [P30 AG021332]
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute on Aging, and National
Institute on Aging Contracts N01-AG-6-2101, N01-AG-6-2103, and
N01-AG-6-2106; National Institute on Aging Grants R01 AG029364 and R01
AG028050; National Institute of Nursing Research Grant R01 NR012459; and
the Wake Forest University Claude D. Pepper Older Americans Independence
Center Grant P30 AG021332.
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP 4156
EP 4165
DI 10.1210/jc.2012-1551
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500066
PM 22942386
ER
PT J
AU Crocker, MK
Barak, S
Millo, CM
Beall, SA
Niyyati, M
Chang, R
Avila, NA
Van Ryzin, C
Segars, J
Quezado, M
Merke, DP
AF Crocker, Melissa K.
Barak, Stephanie
Millo, Corina M.
Beall, Stephanie A.
Niyyati, Mahtab
Chang, Richard
Avila, Nilo A.
Van Ryzin, Carol
Segars, James
Quezado, Martha
Merke, Deborah P.
TI Use of PET/CT with Cosyntropin Stimulation to Identify and Localize
Adrenal Rest Tissue following Adrenalectomy in a Woman with Congenital
Adrenal Hyperplasia
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID 21-HYDROXYLASE DEFICIENCY; ADRENOCORTICOTROPIN HYPERSECRETION; BILATERAL
ADRENALECTOMY; TUMORS; PATIENT; PREVALENCE; MALES
AB Context: Adrenalectomy is an experimental treatment option for select patients with congenital adrenal hyperplasia who have failed medical therapy. After adrenalectomy, adrenal rest tissue can remain in extraadrenal locations, cause recurrent hyperandrogenism, and be difficult to localize.
Objective: The aim of the study was to investigate the usefulness of positron emission tomography/computerized tomography (PET/CT) in identifying adrenal rest tissue.
Subject: A female with salt-wasting 21-hydroxylase deficiency who had bilateral adrenalectomy at age 17 yr presented with hyperandrogenism at age 32 yr. Pelvic magnetic resonance imaging and ultrasound imaging were nondiagnostic for the source of androgen production.
Methods and Results: A baseline F-18 labeled fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scan showed no active uptake; however, a second scan preceded by a 250-mu g cosyntropin injection identified three areas of active uptake near both ovaries. Subsequent ovarian venous sampling showed elevations in 17-hydroxyprogesterone, androstenedione, and 21-deoxycortisol in both ovarian veins compared to a peripheral vein at baseline and more so after cosyntropin administration. At laparoscopy, three well-circumscribed nodules (2.4 x 0.9 x 1.3 cm, 1.2 x 1.5 x 1.5 cm, and 2 x 1.5 x 1 cm) lying lateral to the fallopian tubes adjacent to the broad ligaments were removed. The paraovarian nodules and previously removed adrenal glands had similar histology and immunohistochemistry. Postoperatively, androgen concentrations were undetectable, with no response to cosyntropin stimulation.
Conclusions: Patients with CAH after an adrenalectomy may experience recurrent hyperandrogenism due to adrenal rest tissue. 18F-FDG PET/CT with cosyntropin stimulation accurately identified adrenal rest tissue not visualized with conventional imaging, allowing for successful surgical resection. (J Clin Endocrinol Metab 97: E2084-E2089, 2012)
C1 [Crocker, Melissa K.; Segars, James; Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Crocker, Melissa K.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Barak, Stephanie; Quezado, Martha] NCI, NIH, Bethesda, MD 20892 USA.
[Millo, Corina M.; Beall, Stephanie A.; Chang, Richard; Van Ryzin, Carol; Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Niyyati, Mahtab] NIDDK, NIH, Bethesda, MD 20892 USA.
[Avila, Nilo A.] Vet Affairs Med Ctr, Serv Radiol, Washington, DC 20422 USA.
[Avila, Nilo A.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Crocker, MK (reprint author), 330 Longwood Ave, Boston, MA 02115 USA.
EM melissa.crocker@childrens.harvard.edu
FU The Intramural Research Programs of The Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institutes of Health Clinical Center
FX This work was funded by The Intramural Research Programs of The Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) and the National Institutes of Health Clinical Center.
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U2 4
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP E2084
EP E2089
DI 10.1210/jc.2012-2298
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500007
PM 22904181
ER
PT J
AU Dauber, A
LaFranchi, SH
Maliga, Z
Lui, JC
Moon, JE
McDeed, C
Henke, K
Zonana, J
Kingman, GA
Pers, TH
Baron, J
Rosenfeld, RG
Hirschhorn, JN
Harris, MP
Hwa, V
AF Dauber, Andrew
LaFranchi, Stephen H.
Maliga, Zoltan
Lui, Julian C.
Moon, Jennifer E.
McDeed, Cailin
Henke, Katrin
Zonana, Jonathan
Kingman, Garrett A.
Pers, Tune H.
Baron, Jeffrey
Rosenfeld, Ron G.
Hirschhorn, Joel N.
Harris, Matthew P.
Hwa, Vivian
TI Novel Microcephalic Primordial Dwarfism Disorder Associated with
Variants in the Centrosomal Protein Ninein
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID GROWTH-FACTOR-I; MEIER-GORLIN-SYNDROME; DNA-SEQUENCING DATA;
SECKEL-SYNDROME; MOLECULAR CHARACTERIZATION; POSTNATAL-GROWTH; GENE;
MUTATIONS; ORGANIZATION; DUPLICATION
AB Context: Microcephalic primordial dwarfism (MPD) is a rare, severe form of human growth failure in which growth restriction is evident in utero and continues into postnatal life. Single causative gene defects have been identified in a number of patients with MPD, and all involve genes fundamental to cellular processes including centrosome functions.
Objective: The objective of the study was to find the genetic etiology of a novel presentation of MPD.
Design: The design of the study was whole-exome sequencing performed on two affected sisters in a single family. Molecular and functional studies of a candidate gene were performed using patient-derived primary fibroblasts and a zebrafish morpholino oligonucleotides knockdown model.
Patients: Two sisters presented with a novel subtype of MPD, including severe intellectual disabilities.
Main Outcome Measures: NIN, encoding Ninein, a centrosomal protein critically involved in asymmetric cell division, was identified as a candidate gene, and functional impacts in fibroblasts and zebrafish were studied.
Results: From 34,606 genomic variants, two very rare missense variants in NIN were identified. Both pro-bands were compound heterozygotes. In the zebrafish, ninein knock down led to specific and novel defects in the specification and morphogenesis of the anterior neuroectoderm, resulting in a deformity of the developing cranium with a small, squared skull highly reminiscent of the human phenotype.
Conclusion: We identified a novel clinical subtype of MPD in two sisters who have rare variants in NIN. We show, for the first time, that reduction of ninein function in the developing zebrafish leads to specific deficiencies of brain and skull development, offering a developmental basis for the myriad phenotypes in our patients. (J Clin Endocrinol Metab 97: E2140-E2151, 2012)
C1 [Dauber, Andrew; Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Moon, Jennifer E.; Pers, Tune H.; Hirschhorn, Joel N.] Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
[McDeed, Cailin; Henke, Katrin; Harris, Matthew P.] Childrens Hosp, Dept Orthopaed Res, Boston, MA 02115 USA.
[Kingman, Garrett A.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Dauber, Andrew; Moon, Jennifer E.; Pers, Tune H.; Hirschhorn, Joel N.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[LaFranchi, Stephen H.; Rosenfeld, Ron G.; Hwa, Vivian] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA.
[Zonana, Jonathan] Oregon Hlth & Sci Univ, Dept Mol & Med Genet & Pediat, Portland, OR 97239 USA.
[Maliga, Zoltan] Max Planck Inst Cell Biol & Genet, D-01307 Dresden, Germany.
[Lui, Julian C.; Baron, Jeffrey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[McDeed, Cailin; Henke, Katrin; Hirschhorn, Joel N.; Harris, Matthew P.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
[Kingman, Garrett A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Pers, Tune H.] Tech Univ Denmark, Ctr Biol Sequence, DK-5617 BA Eindhoven, Denmark.
RP Dauber, A (reprint author), Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.
EM andrew.dauber@childrens.harvard.edu
RI Lui, Chun Kin Julian/E-2253-2012
FU National Institutes of Health [5K12HD052896]; March of Dimes Grant
[6-FY09-507]; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health; Nikon Imaging Center at Harvard Medical School;
Danish Council for Independent Research Medical Sciences
FX This work was supported by National Institutes of Health Grant
5K12HD052896 (to A.D.), March of Dimes Grant 6-FY09-507 (to J.N.H.), The
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health (to J.C.L. and J.B.) as well as The Nikon Imaging Center at
Harvard Medical School. T.H.P. is supported by The Danish Council for
Independent Research Medical Sciences (FSS).
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U2 6
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PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP E2140
EP E2151
DI 10.1210/jc.2012-2150
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500017
PM 22933543
ER
PT J
AU Vezzosi, D
Libe, R
Baudry, C
Rizk-Rabin, M
Horvath, A
Levy, I
Rene-Corail, F
Ragazzon, B
Stratakis, CA
Vandecasteele, G
Bertherat, J
AF Vezzosi, Delphine
Libe, Rossella
Baudry, Camille
Rizk-Rabin, Marthe
Horvath, Anelia
Levy, Isaac
Rene-Corail, Fernande
Ragazzon, Bruno
Stratakis, Constantine A.
Vandecasteele, Gregoire
Bertherat, Jerome
TI Phosphodiesterase 11A (PDE11A) Gene Defects in Patients with
ACTH-Independent Macronodular Adrenal Hyperplasia (AIMAH): Functional
Variants May Contribute to Genetic Susceptibility of Bilateral Adrenal
Tumors
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID NODULAR ADRENOCORTICAL DISEASE; CUSHINGS-SYNDROME; REGULATORY SUBUNIT;
CARNEY COMPLEX; I-ALPHA; MUTATIONS; PROTEIN; EXPRESSION; RECEPTORS;
FREQUENT
AB Context: Phosphodiesterases (PDEs) are key regulatory enzymes of intracellular cAMP levels. PDE11A function has been linked to predisposition to adrenocortical tumors.
Objective: The aim of the study was to study the PDE11A gene in a large cohort of patients with ACTH-independent macronodular adrenal hyperplasia (AIMAH) and in control subjects.
Design: The PDE11A entire coding region was sequenced in 46 patients with AIMAH and 192 controls. Two variants found in AIMAH patients were transiently expressed in HEK 293 and adrenocortical H295R cells for further functional studies.
Results: The frequency of all PDE11A variants was significantly higher among patients with AIMAH (28%) compared to controls (7.2%) (P = 5 x 10(-5)). Transfection of the two PDE11A variants found in AIMAH patients only (D609N or M878V) showed that cAMP levels were higher, after forskolin stimulation, in cells transfected with the PDE11A mutants, compared to cells transfected with the wild-type PDE11A in HEK 293 cells (P < 0.05). Moreover, transfection with mutants PDE11A increased transcriptional activity of a cAMP-response element reporter construct compared to wild-type PDE11A in HEK 293 cells (P < 0.0004 for D609N and P < 0.003 for M878V) and in the adrenocortical H295R cells (P < 0.05 for D609N and M878V). In addition, analysis of cAMP levels in intact living culture cells by fluorescence resonance energy transfer probes showed increased cAMP in forskolin-treated cells transfected with PDE11A variants compared with wild-type PDE11A (P < 0.05).
Conclusion: We conclude that PDE11A genetic variants may increase predisposition to AIMAH. (J Clin Endocrinol Metab 97: E2063-E2069, 2012)
C1 [Vezzosi, Delphine; Libe, Rossella; Baudry, Camille; Rizk-Rabin, Marthe; Rene-Corail, Fernande; Ragazzon, Bruno; Bertherat, Jerome] INSERM, Unite 1016, CNRS, UMR 8104,Inst Cochin, F-75014 Paris, France.
[Vezzosi, Delphine; Libe, Rossella; Baudry, Camille; Rizk-Rabin, Marthe; Ragazzon, Bruno; Bertherat, Jerome] Univ Paris 05, Fac Med Paris 5, F-75005 Paris, France.
[Vezzosi, Delphine] Hop Larrey, Dept Endocrinol, F-31480 Toulouse, France.
[Libe, Rossella; Baudry, Camille; Bertherat, Jerome] Hop Cochin, Reference Ctr Rare Adrenal Dis, AP HP, Dept Endocrinol, F-75014 Paris, France.
[Horvath, Anelia; Levy, Isaac; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol Genet, NIH, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA.
[Vandecasteele, Gregoire] INSERM, UMR S 769, Labex Lab Excellence Res Medicat & Innovat Therap, F-92296 Chatenay Malabry, France.
[Vandecasteele, Gregoire] Univ Paris Sud, Inst Federatif Rech 141, F-92296 Chatenay Malabry, France.
RP Bertherat, J (reprint author), Hop Cochin 27, Serv Endocrinol, Rue Faubourg St Jacques, F-75014 Paris, France.
EM jerome.bertherat@cch.aphp.fr
RI Ragazzon, Bruno/E-6541-2017
OI Ragazzon, Bruno/0000-0001-9476-4973
FU Intramural Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development, National Institutes of Health;
Agence Nationale de la Recherche [ANR08-GENOPAT-002, ANR-10-Blan-1136];
Institut National du Cancer
FX This work was supported by the Intramural Program (to A.H., I.L., C.S.)
of the Eunice Kennedy Shriver National Institute of Child Health and
Human Development, National Institutes of Health; and by the Agence
Nationale de la Recherche (ANR08-GENOPAT-002; and ANR-10-Blan-1136).
D.V. is the recipient of a fellowship from the Institut National du
Cancer.
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U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2012
VL 97
IS 11
BP E2063
EP E2069
DI 10.1210/jc.2012-2275
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 032IT
UT WOS:000310710500004
PM 22996146
ER
PT J
AU Magnani, JW
Newton-Cheh, C
O'Donnell, CJ
Levy, D
AF Magnani, Jared W.
Newton-Cheh, Christopher
O'Donnell, Christopher J.
Levy, Daniel
TI Development and application of a longitudinal electrocardiogram
repository: the Framingham Heart Study
SO JOURNAL OF ELECTROCARDIOLOGY
LA English
DT Article
DE Electrocardiography; Epidemiology; Repository; Framingham
ID CHRONIC ATRIAL-FIBRILLATION
AB The electrocardiogram (ECG) has widespread use in clinical care and research. Despite its extensive use and study, important gaps remain in examining prospective, repeated longitudinal ECG measures, and their association with cardiovascular outcomes. The Framingham Heart Study (FRS) is a community-based study designed to examine risk factors and outcomes associated with cardiovascular disease. Here, we describe a novel effort in the FHS to develop a unique resource: serial ECGs conducted on 3 generations of study participants spanning multiple decades (1986 to the present). We describe the FHS and the role the ECG has had in conducting cardiovascular epidemiology in the FHS. We then describe potential applications for a longitudinal ECG repository. We expect the Framingham ECG repository to enhance cardiovascular research and epidemiologic study. Such a resource will complement the phenotypic and genotypic characterization of FHS, facilitating novel investigations of cardiovascular epidemiology. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA.
[Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Newton-Cheh, Christopher; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham, MA USA.
[O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA.
EM jmagnani@bu.edu
FU National Institutes of Health (NIH) [R21HL106092]; American Heart
Association [09FTF219028]; NIH [6R01-NS17950, N01-HC25195]
FX Dr Magnani is supported by grants from the National Institutes of Health
(NIH) (R21HL106092) and the American Heart Association (09FTF219028).
This work was supported by NIH grants 6R01-NS17950, N01-HC25195.
NR 13
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U1 0
U2 6
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0022-0736
J9 J ELECTROCARDIOL
JI J. Electrocardiol.
PD NOV-DEC
PY 2012
VL 45
IS 6
BP 673
EP 676
DI 10.1016/j.jelectrocard.2012.06.016
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 032ZZ
UT WOS:000310763300026
PM 22832152
ER
PT J
AU Eberlein, M
Reed, RM
Permutt, S
Chahla, MF
Bolukbas, S
Nathan, SD
Iacono, A
Pearse, DB
Fessler, HE
Shah, AS
Orens, JB
Brower, RG
AF Eberlein, Michael
Reed, Robert M.
Permutt, Solbert
Chahla, Mayy F.
Bolukbas, Servet
Nathan, Steven D.
Iacono, Aldo
Pearse, David B.
Fessler, Henry E.
Shah, Ashish S.
Orens, Jonathan B.
Brower, Roy G.
TI Parameters of donor-recipient size mismatch and survival after bilateral
lung transplantation
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE lung transplantation; lung size mismatch; gender mismatch
ID BRONCHIOLITIS OBLITERANS SYNDROME; MAXIMAL EXPIRATORY FLOW;
INTERNATIONAL-SOCIETY; PULMONARY-FIBROSIS; RECOIL PRESSURE;
SURFACE-TENSION; HEART; MECHANICS; CAPACITY; REGISTRY
AB BACKGROUND: The purpose of this study was to investigate the relationship between donor recipient height, gender and predicted estimates of total lung capacity (pTLC) mismatches and post-transplant survival.
METHODS: The lung transplant databases at three programs were reviewed. The pTLC ratios (donor pTLC/recipient pTLC) and height ratios (donor height/recipient height) were calculated retrospectively. Patients were grouped according to pTLC ratio <= 1.0 or >1.0 and height ratio <= 1.0 or >1.0, and according to gender (mis-)matching. A time-to-event analysis was performed for risk of death after transplantation conditional on 30-day survival using Kaplan-Meier survival and Cox proportional hazard models.
RESULTS: There were 211 adult bilateral lung transplant recipients who qualified for the analysis. Mean follow-up was comparable for all cohorts (range 2.21 to 3.85 years). In the univariate Cox proportional hazard models, a pTLC ratio >1.0 (HR 0.43, p = 0.002) and a height ratio >1.0 (HR 0.61, p = 0.03) were associated with better survival, and a female-donor-to-male-recipient gender mismatch (F-to-M) was associated with worse survival (HR 2.35, p = 0.01). In the multivariate Cox proportional hazard model accounting for F-to-M gender mismatch and height ratio >1.0, a pTLC ratio >1.0 remained associated with survival (HR 0.38, p = 0.015). However, accounting for a pTLC ratio >1.0, a height ratio of >1.0 and F-to-M mismatch were not associated with survival.
CONCLUSIONS: A pTLC ratio >1.0 is associated with improved survival after bilateral lung transplantation. The pTLC ratio might better reflect allograft thorax mismatch than the height ratio, as it also accounts for effects of gender on lung and thoracic volumes. J Heart Lung Transplant 2012;31:1207-13 (C) 2012 International Society for Heart and Lung Transplantation. All rights reserved.
C1 [Eberlein, Michael; Permutt, Solbert; Pearse, David B.; Fessler, Henry E.; Orens, Jonathan B.; Brower, Roy G.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21205 USA.
[Chahla, Mayy F.] Johns Hopkins Univ, Sch Med, Dept Med, Div Hosp Med, Baltimore, MD 21205 USA.
[Eberlein, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Reed, Robert M.; Iacono, Aldo] Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA.
[Bolukbas, Servet] Dr Horst Schmidt Klin, Dept Thorac Surg, Wiesbaden, Germany.
[Nathan, Steven D.] Inova Fairfax Hosp, Adv Lung Dis Program, Falls Church, VA USA.
[Shah, Ashish S.] Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA.
RP Eberlein, M (reprint author), Univ Iowa, Carver Coll Med, Div Pulm Crit Care & Occupat Med, 200 Hawkins Dr,C326, Iowa City, IA 52242 USA.
EM michael-eberlein@uiowa.edu
OI Shah, Ashish/0000-0002-1821-9110
NR 24
TC 27
Z9 27
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD NOV
PY 2012
VL 31
IS 11
BP 1207
EP 1213
DI 10.1016/j.healun.2011.07.015
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA 028II
UT WOS:000310415600010
PM 22036314
ER
PT J
AU Jones, TH
Adams, RMM
Spande, TF
Garraffo, HM
Kaneko, T
Schultz, TR
AF Jones, Tappey H.
Adams, Rachelle M. M.
Spande, Thomas F.
Garraffo, H. Martin
Kaneko, Tetsuo
Schultz, Ted R.
TI Histrionicotoxin Alkaloids Finally Detected in an Ant
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID DENDROBATID POISON FROGS; ARTHROPOD SOURCE; SKIN ALKALOIDS; DIETARY
SOURCE; C-13 NMR; DECAHYDROQUINOLINES; PUMILIOTOXINS; MADAGASCAR;
CHEMISTRY; COMMON
AB Workers of the ant Carebarella bicolor collected in Panama were found to have two major poison-frog alkaloids, cis- and trans-fused decahydroquinolines (DHQs) of the 269AB type, four minor 269AB isomers, two minor 269B isomers, and three isomers of DHQ 271D. For the first time in an ant, however, the DHQs were accompanied by six histrionicotoxins (HIXs), viz, 283A, 285A, 285B, 285C, 287A, and 287D. This co-occurrence of the HTX and DHQ alkaloids is the usual pattern seen in dendrobatid frogs. This finding contrasts with our earlier study, where workers of a Brazilian ant, Solenopsis (Diplorhoptrum) sp., were found to have a very similar DHQ complex but failed to show HTXs. Several new DHQ alkaloids of MW 271 (named in the frog as 271G) are reported from the above ants that have both m/z 202 and 204 as major fragment ions, unlike the spectrum seen for the poison-frog alkaloid 271D, which has only an m/z 204 base peak. Found also for the first time in skin extracts from the comparison frog Oophaga granulifera of Costa Rica is a trace DHQ of MW 273. It is coded as 273F in the frog; a different isomer is found in the ant.
C1 [Jones, Tappey H.] Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA.
[Adams, Rachelle M. M.] Univ Copenhagen, Ctr Social Evolut, Dept Biol, DK-2100 Copenhagen, Denmark.
[Spande, Thomas F.; Garraffo, H. Martin; Kaneko, Tetsuo] NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Schultz, Ted R.] Smithsonian Inst, Dept Entomol, NHB, Washington, DC 20013 USA.
RP Jones, TH (reprint author), Virginia Mil Inst, Dept Chem, Lexington, VA 24450 USA.
EM jonesth@vmi.edu
RI Adams, Rachelle/J-8846-2013
OI Adams, Rachelle/0000-0002-0918-9861
NR 24
TC 5
Z9 5
U1 3
U2 24
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
J9 J NAT PROD
JI J. Nat. Prod.
PD NOV
PY 2012
VL 75
IS 11
BP 1930
EP 1936
DI 10.1021/np300485v
PG 7
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA 042HC
UT WOS:000311461300009
PM 23088730
ER
PT J
AU Mozer, BA
Sandstrom, DJ
AF Mozer, Brian A.
Sandstrom, David J.
TI Drosophila neuroligin 1 regulates synaptic growth and function in
response to activity and phosphoinositide-3-kinase
SO MOLECULAR AND CELLULAR NEUROSCIENCE
LA English
DT Article
DE Drosophila; Neuroligin; Neurexin; Synapse; Activity;
Phosphoinositide-3-kinase
ID FRAGILE-X-SYNDROME; NEUROMUSCULAR-JUNCTION; GLUTAMATERGIC SYNAPSES;
INHIBITORY SYNAPSES; TRANSMITTER RELEASE; HIPPOCAMPAL-NEURONS; GENETIC
DISSECTION; AMPA RECEPTORS; PLASTICITY; NEUREXINS
AB Neuroligins are postsynaptic neural cell adhesion molecules that mediate synaptic maturation and function in vertebrates and invertebrates, but their mechanisms of action and regulation are not well understood. At the Drosophila larval neuromuscular junction (NMJ), previous analysis demonstrated a requirement for Drosophila neuroligin 1 (dnlg1) in synaptic growth and maturation. The goal of the present study was to better understand the effects and mechanisms of loss-of-function and overexpression of dnlg1 on synapse size and function, and to identify signaling pathways that control dnlg1 expression. Consistent with reduced synapse size, evoked excitatory junctional currents (EJCs) were diminished in dnlg1 mutants but displayed normal Ca2+ sensitivity and short-term plasticity. However, postsynaptic function was also perturbed, in that glutamate receptor staining and the distribution of amplitudes of miniature excitatory junctional currents (mEJCs) were abnormal in mutants. All the above phenotypes were rescued by a genomic transgene. Overexpression of dnlg1 in muscle resulted in synaptic overgrowth, but reduced the amplitudes of EJCs and mEJCs. Overgrowth and reduced EJC amplitude required Drosophila neurexin 1 (dnrx1) function, suggesting that increased DNlg1/DNrx1 signaling attenuates synaptic transmission and regulates growth through a retrograde mechanism. In contrast, reduced mEJC amplitude was independent of dnrx1. Synaptic overgrowth, triggered by neuronal hyperactivity, absence of the E3 ubiquitin ligase highwire, and increased phosphoinositide-3-kinase (PI3K) signaling in motor neurons reduced synaptic DNlg1 levels. Likewise, postsynaptic attenuation of PI3K, which increases synaptic strength, was associated with reduced DNlg1 levels. These observations suggest that activity and PI3K signaling pathways modulate growth and synaptic transmission through dnlg1-dependent mechanisms. Published by Elsevier Inc.
C1 [Mozer, Brian A.] NHLBI, Ctr Dev Biol, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
[Sandstrom, David J.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Mozer, BA (reprint author), NHLBI, Ctr Dev Biol, Lab Biochem Genet, NIH, Bldg 10,Rm 7N317,10 Ctr Dr, Bethesda, MD 20892 USA.
EM mozerb@nhlbi.nih.gov
FU National Institute of Heart, Lung and Blood; National Institute of
Mental Health
FX The work was supported by the intramural research program of the
National Institute of Heart, Lung and Blood (B.A.M.) and the National
Institute of Mental Health (D.J.S.). We thank Marshall Nirenberg for his
early support of this work, Shu-Hwa Yu for assistance with
immuno-staining experiments, Devera Schoenberg (DIR, NINDS) for
proofreading of the manuscript, the NHLBI Intramural Light Microscope
Core Facility, and Jun Zhu and Ting Ni for help with qPCR. We thank
Howard Nash, NIMH, for support and critical reading of the manuscript,
Benjamin White, NIMH, for critical reading of the manuscript and the use
of equipment, and our colleagues at the NIH and elsewhere that provided
equipment, reagents and fly strains.
NR 78
TC 7
Z9 7
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1044-7431
J9 MOL CELL NEUROSCI
JI Mol. Cell. Neurosci.
PD NOV
PY 2012
VL 51
IS 3-4
BP 89
EP 100
DI 10.1016/j.mcn.2012.08.010
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 044DL
UT WOS:000311599500004
PM 22954894
ER
PT J
AU Miao, YL
Williams, CJ
AF Miao, Yi-Liang
Williams, Carmen J.
TI Calcium signaling in mammalian egg activation and embryo development:
The influence of subcellular localization
SO MOLECULAR REPRODUCTION AND DEVELOPMENT
LA English
DT Review
DE fertilization; oocyte; calcium influx; SOCE; CaMKII
ID PROTEIN-KINASE-C; GREEN-FLUORESCENT PROTEIN; FERTILIZED MOUSE EGGS;
OPERATED CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; STROMAL
INTERACTION MOLECULE; DOMAIN-MEDIATED ACTIVATION; GERMINAL VESICLE
BREAKDOWN; SRC FAMILY KINASE; PHOSPHOLIPASE-C
AB Calcium (Ca2+) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca2+ signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca2+ sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca2+ in many cell types and of the impact of cellular localization on Ca2+ signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca2+ is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca2+ release and effectors of Ca2+ signals. We then summarize studies exploring how Ca2+ directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca2+ signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe for future research. Mol. Reprod. Dev. 79: 742756, 2012. Published 2012. This article is a US government work and, as such, is in the public domain in the United States of America.
C1 [Miao, Yi-Liang; Williams, Carmen J.] NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,DHHS, Res Triangle Pk, NC 27709 USA.
RP Williams, CJ (reprint author), NIEHS, Reprod Med Grp, Lab Reprod & Dev Toxicol, NIH,DHHS, POB 12233,MD E4-05, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
FU Intramural Research Program of the NIH; National Institutes of
Environmental Health Sciences [Z01ES102985]
FX Grant sponsor: Intramural Research Program of the NIH; Grant sponsor:
National Institutes of Environmental Health Sciences; Grant number:
Z01ES102985
NR 139
TC 26
Z9 27
U1 3
U2 19
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1040-452X
J9 MOL REPROD DEV
JI Mol. Reprod. Dev.
PD NOV
PY 2012
VL 79
IS 11
BP 742
EP 756
DI 10.1002/mrd.22078
PG 15
WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology;
Reproductive Biology
SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology;
Reproductive Biology
GA 040CL
UT WOS:000311297000001
PM 22888043
ER
PT J
AU Chang, S
Sharan, SK
AF Chang, Suhwan
Sharan, Shyam K.
TI BRCA1 and MicroRNAs: Emerging networks and potential therapeutic targets
SO MOLECULES AND CELLS
LA English
DT Review
DE antagomir; breast cancer; BRCA1; microRNA mimic; microRNAs
ID BREAST-CANCER RISK; POLYMERASE-II HOLOENZYME; OVARIAN-CANCER; MUTATION
CARRIERS; DOWN-REGULATION; CELL-PROLIFERATION; EZH2 EXPRESSION; IN-VIVO;
GENE; GROWTH
AB BRCA1 is a well-known tumor suppressor implicated in familial breast and ovarian cancer. Since its cloning in 1994, numerous studies have established BRCA1's role in diverse cellular and biochemical processes, such as DNA damage repair, cell cycle control, and transcriptional regulation as well as ubiquitination. In addition, a number of recent studies have functionally linked this tumor suppressor to another important cellular regulator, microRNAs, which are short (19-22 nt) RNAs that were discovered in the nematode in 1993. Soon their presence and function were validated in mammals, and since then, the role of microRNAs has been actively investigated in almost all biological processes, including cancer. In this review, we will describe recent progress in the understanding of the BRCA1 function through microRNAs and the role of microRNAs in regulating BRCA1, with emphasis on the implication of these processes on the development and progression of cancer. We will also discuss the therapeutic potential of microRNA mimics or inhibitors of microRNAs to affect BRCA1 function.
C1 [Chang, Suhwan; Sharan, Shyam K.] Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
RP Sharan, SK (reprint author), Frederick Natl Lab Canc Res, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
EM sharans@mail.nih.gov
FU Center for Cancer Research Intramural Program, National Cancer
Institute, National Institutes of Health, U.S. Department of Health and
Human Services
FX This work is supported by the Center for Cancer Research Intramural
Program, National Cancer Institute, National Institutes of Health, a
part of the U.S. Department of Health and Human Services.
NR 80
TC 12
Z9 12
U1 0
U2 5
PU KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
PI SEOUL
PA 635-4, YUCKSAM-DONG, GANGNAM-GU, SEOUL 135-703, SOUTH KOREA
SN 1016-8478
J9 MOL CELLS
JI Mol. Cells
PD NOV
PY 2012
VL 34
IS 5
BP 425
EP 432
DI 10.1007/s10059-012-0118-y
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 043AZ
UT WOS:000311516400002
PM 22936386
ER
PT J
AU Gargis, AS
Kalman, L
Berry, MW
Bick, DP
Dimmock, DP
Hambuch, T
Lu, F
Lyon, E
Voelkerding, KV
Zehnbauer, BA
Agarwala, R
Bennett, SF
Chen, B
Chin, ELH
Compton, JG
Das, S
Farkas, DH
Ferber, MJ
Funke, BH
Furtado, MR
Ganova-Raeva, LM
Geigenmuller, U
Gunselman, SJ
Hegde, MR
Johnson, PLF
Kasarskis, A
Kulkarni, S
Lenk, T
Liu, CSJ
Manion, M
Manolio, TA
Mardis, ER
Merker, JD
Rajeevan, MS
Reese, MG
Rehm, HL
Simen, BB
Yeakley, JM
Zook, JM
Lubin, IM
AF Gargis, Amy S.
Kalman, Lisa
Berry, Meredith W.
Bick, David P.
Dimmock, David P.
Hambuch, Tina
Lu, Fei
Lyon, Elaine
Voelkerding, Karl V.
Zehnbauer, Barbara A.
Agarwala, Richa
Bennett, Sarah F.
Chen, Bin
Chin, Ephrem L. H.
Compton, John G.
Das, Soma
Farkas, Daniel H.
Ferber, Matthew J.
Funke, Birgit H.
Furtado, Manohar R.
Ganova-Raeva, Lilia M.
Geigenmueller, Ute
Gunselman, Sandra J.
Hegde, Madhuri R.
Johnson, Philip L. F.
Kasarskis, Andrew
Kulkarni, Shashikant
Lenk, Thomas
Liu, C. S. Jonathan
Manion, Megan
Manolio, Teri A.
Mardis, Elaine R.
Merker, Jason D.
Rajeevan, Mangalathu S.
Reese, Martin G.
Rehm, Heidi L.
Simen, Birgitte B.
Yeakley, Joanne M.
Zook, Justin M.
Lubin, Ira M.
TI Assuring the quality of next-generation sequencing in clinical
laboratory practice
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
C1 [Gargis, Amy S.; Kalman, Lisa; Zehnbauer, Barbara A.; Chen, Bin; Lubin, Ira M.] Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA 30333 USA.
[Berry, Meredith W.; Lu, Fei] SeqWright Inc, Houston, TX USA.
[Bick, David P.; Dimmock, David P.] Med Coll Wisconsin, Dept Pediat, Div Genet, Milwaukee, WI 53226 USA.
[Hambuch, Tina] Illumina Clin Serv, San Diego, CA USA.
[Lyon, Elaine; Voelkerding, Karl V.] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Lyon, Elaine; Voelkerding, Karl V.] ARUP Labs, Inst Clin & Expt Pathol, Salt Lake City, UT USA.
[Agarwala, Richa] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Bennett, Sarah F.] Ctr Medicare & Medicaid Serv, Div Lab Serv, Baltimore, MD USA.
[Chin, Ephrem L. H.; Hegde, Madhuri R.] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Compton, John G.] GeneDx Inc, Gaithersburg, MD USA.
[Das, Soma] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Farkas, Daniel H.] Sequenom Ctr Mol Med Inc, Grand Rapids, MI USA.
[Ferber, Matthew J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Funke, Birgit H.; Rehm, Heidi L.] Partners Healthcare Ctr Personalized Genet Med, Mol Med Lab, Cambridge, MA USA.
[Funke, Birgit H.; Rehm, Heidi L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[Furtado, Manohar R.] Life Technol, Foster City, CA USA.
[Ganova-Raeva, Lilia M.] Ctr Dis Control & Prevent, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA USA.
[Geigenmueller, Ute] Correlagen Diagnost Inc, Waltham, MA USA.
[Gunselman, Sandra J.] Kailos Genet Inc, Huntsville, AL USA.
[Johnson, Philip L. F.] Emory Univ, Dept Biol, Atlanta, GA 30322 USA.
[Kasarskis, Andrew] Pacific Biosci, Menlo Pk, CA USA.
[Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.
[Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Lenk, Thomas] Celera Corp, Alameda, CA USA.
[Liu, C. S. Jonathan; Manion, Megan] Softgenet LLC, State Coll, PA USA.
[Manolio, Teri A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Mardis, Elaine R.] Washington Univ, Genome Ctr, St Louis, MO USA.
[Mardis, Elaine R.] Washington Univ, Dept Genet & Mol Microbiol, St Louis, MO USA.
[Merker, Jason D.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA.
[Rajeevan, Mangalathu S.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
[Reese, Martin G.] Omica Inc, Emeryville, CA USA.
[Simen, Birgitte B.] A Roche Co, Life Sci 454, Branford, CT USA.
[Yeakley, Joanne M.] Illumina Inc, San Diego, CA USA.
[Zook, Justin M.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA.
RP Gargis, AS (reprint author), Ctr Dis Control & Prevent, Div Lab Sci & Stand, Atlanta, GA 30333 USA.
EM ILubin@cdc.gov
RI Zook, Justin/B-7000-2008; Dimmock, David/I-7913-2015
OI Zook, Justin/0000-0003-2309-8402; Dimmock, David/0000-0001-6690-2523
FU NHGRI NIH HHS [R44 HG006579]
NR 4
TC 180
Z9 183
U1 0
U2 30
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD NOV
PY 2012
VL 30
IS 11
BP 1033
EP 1036
DI 10.1038/nbt.2403
PG 4
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 037FL
UT WOS:000311087500014
PM 23138292
ER
PT J
AU Bilke, S
Gindin, Y
AF Bilke, Sven
Gindin, Yevgeniy
TI Analyzing the association of SCNA boundaries with replication timing
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
C1 [Bilke, Sven; Gindin, Yevgeniy] NCI, Bethesda, MD 20892 USA.
RP Bilke, S (reprint author), NCI, Bethesda, MD 20892 USA.
EM bilkes@mail.nih.gov
NR 4
TC 2
Z9 2
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD NOV
PY 2012
VL 30
IS 11
BP 1043
EP 1045
DI 10.1038/nbt.2415
PG 4
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 037FL
UT WOS:000311087500017
PM 23138295
ER
PT J
AU Tan, IL
McArthur, JC
Venkatesan, A
Nath, A
AF Tan, Ik L.
McArthur, Justin C.
Venkatesan, Arun
Nath, Avindra
TI Atypical manifestations and poor outcome of herpes simplex encephalitis
in the immunocompromised
SO NEUROLOGY
LA English
DT Article
ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; POLYMERASE-CHAIN-REACTION; CLINICAL
PRESENTATIONS; MULTIPLE-SCLEROSIS; VIRUS ENCEPHALITIS; 1 INFECTION;
MULTICENTER; DEFICIENCY; EXPERIENCE; THERAPY
AB Objective: To characterize clinical features, neuroimaging, and outcomes of herpes simplex encephalitis (HSE) in immunocompromised individuals.
Methods: We performed a retrospective case control review of patients diagnosed with HSE. Adult patients were dichotomized into immunocompromised (n=14) and immunocompetent groups (n=15).
Results: Fewer immunocompromised patients presented with prodromal symptoms and focal deficits. While the majority of CSF profiles in the immunocompromised patients were mononuclear cells predominant, 3 had polymorphonuclear predominance and another 3 had normal profiles. MRI showed widespread cortical involvement, with brainstem or cerebellar involvement in some. Two immunocompromised patients had recurrent HSE. The immunosuppressed state was associated with a decrease in Karnofsky Performance Status Scale (KPSS) score of 23.1 (p=0.018). Every 1-day delay in initiation of acyclovir was associated with a decrease in KPSS of 10.2 (p=0.002), and every 10 cell/mm(3) increase of CSF leukocytosis was associated with an increase in KPSS of 0.7 (p=0.009). Mortality rate was 6 times higher in the immunocompromised patients.
Conclusions: Immunocompromised states may predispose to HSE with atypical clinical and neuro-radiologic features. Immunocompromised individuals with HSE have significantly worse outcomes and mortality. Early diagnosis and treatment is associated with improved outcome. The findings are particularly important in light of the increasing use of potent immunosuppressive and immunomodulatory therapies. Neurology (R) 2012; 79: 2125-2132
C1 [Tan, Ik L.; McArthur, Justin C.; Venkatesan, Arun] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
[Nath, Avindra] Natl Inst Neurol Disorders & Stroke, Sect Infect Nervous Syst, NIH, Bethesda, MD USA.
RP Nath, A (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Infect Nervous Syst, NIH, Bethesda, MD USA.
EM natha@ninds.nih.gov
FU NIH [1P30MH075673, UL1RR025005, R01NS056884, NS44807]; National
Institute of Neurological Disorders and Stroke; Steg family; Biogen-Idec
FX Supported in part by NIH grants 1P30MH075673, UL1RR025005, R01NS056884,
1P30MH075673, and NS44807 (J.C.M.), National Institute of Neurological
Disorders and Stroke intramural funds, and the Steg family.; I.L. Tan
reports no disclosures. J.C. McArthur has received grants from NIH and
Biogen-Idec and stock options from Gliamed. A. Venkatesan and A. Nath
report no disclosures. Go to Neurology.org for full disclosures.
NR 34
TC 27
Z9 27
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD NOV
PY 2012
VL 79
IS 21
BP 2125
EP 2132
DI 10.1212/WNL.0b013e3182752ceb
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 039YK
UT WOS:000311284300011
PM 23136265
ER
PT J
AU Chuang, JY
Wang, SA
Yang, WB
Yang, HC
Hung, CY
Su, TP
Chang, WC
Hung, JJ
AF Chuang, J-Y
Wang, S-A
Yang, W-B
Yang, H-C
Hung, C-Y
Su, T-P
Chang, W-C
Hung, J-J
TI Sp1 phosphorylation by cyclin-dependent kinase 1/cyclin B1 represses its
DNA-binding activity during mitosis in cancer cells
SO ONCOGENE
LA English
DT Article
DE Sp1; CDK1; PP2A; myosin; mitosis
ID TRANSCRIPTION FACTOR SP1; GENE-TRANSCRIPTION; HEAT-SHOCK; PROTEIN;
EXPRESSION; PROMOTER; OVEREXPRESSION; ACTIVATION; STABILITY; FACTOR-1
AB Sp1 is important for the transcription of many genes. Our previous studies have shown that Sp1 is degraded in normal cell, but it is preserved in cancer cells during mitosis and exists a priori in the daughter cells, ready to engage in gene transcription and thereby contributes to the proliferation and survival of cancer cells. The mechanism by which Sp1 is preserved in cancer cells during mitosis remains unknown. In this study, we observed that Sp1 strongly colocalized with cyclin-dependent kinase 1 (CDK1)/cyclin B1 during mitosis. Moreover, we showed that Sp1 is a novel mitotic substrate of CDK1/cyclin B1 and is phosphorylated by it at Thr 739 before the onset of mitosis. Phospho-Sp1 reduced its DNA-binding ability and facilitated the chromatin condensation process during mitosis. Mutation of Thr739 to alanine resulted in Sp1 remaining in the chromosomes, delayed cell-cycle progression, and eventually led to apoptosis. Screening of Sp1-associated proteins during mitosis by using liquid chromatography/mass spectrometry indicated the tethering of Sp1 to myosin/F-actin. Furthermore, phospho-Sp1 and myosin/F-actin appeared to exist as a congregated ring at the periphery of the chromosome. However, at the end of mitosis and the beginning of interphase, Sp1 was dephosphorylated by PP2A and returned to the chromatin. These results indicate that cancer cells use CDK1 and PP2A to regulate the movement of Sp1 in and out of the chromosomes during cell-cycle progression, which may benefit cancer-cell proliferation. Oncogene (2012) 31, 4946-4959; doi:10.1038/onc.2011.649; published online 23 January 2012
C1 [Chuang, J-Y; Wang, S-A; Yang, W-B; Yang, H-C; Hung, J-J] Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 701, Taiwan.
[Hung, C-Y; Chang, W-C; Hung, J-J] Natl Cheng Kung Univ, Coll Med, Inst Med, Tainan 70101, Taiwan.
[Su, T-P] Natl Inst Drug Abuse, NIH, Baltimore, MD USA.
[Chang, W-C; Hung, J-J] Dept Pharmacol, Tainan, Taiwan.
[Chang, W-C; Hung, J-J] Natl Cheng Kung Univ, Ctr Infect Dis & Signal Transduct, Tainan 701, Taiwan.
[Chang, W-C] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei, Taiwan.
RP Hung, JJ (reprint author), Natl Cheng Kung Univ, Inst Bioinformat & Biosignal Transduct, Coll Biosci & Biotechnol, Tainan 701, Taiwan.
EM petehung@mail.ncku.edu.tw
OI Yang, Wen-Bin/0000-0002-6497-4176
FU National Cheng Kung University project of the Program for Promoting
Academic Excellence and Developing World Class Research Centers;
National Science Council, Taiwan [NSC 97-2320-B-006-016-MY3, NSC
97-2311-B-006-002-MY3]
FX This work was supported by the National Cheng Kung University project of
the Program for Promoting Academic Excellence and Developing World Class
Research Centers, together with grants NSC 97-2320-B-006-016-MY3 and NSC
97-2311-B-006-002-MY3 obtained from the National Science Council,
Taiwan.
NR 31
TC 5
Z9 5
U1 1
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD NOV
PY 2012
VL 31
IS 47
BP 4946
EP 4959
DI 10.1038/onc.2011.649
PG 14
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 041VU
UT WOS:000311430200006
PM 22266860
ER
PT J
AU Zhao, BY
Pisitkun, T
Hoffert, JD
Knepper, MA
Saeed, F
AF Zhao, Boyang
Pisitkun, Trairak
Hoffert, Jason D.
Knepper, Mark A.
Saeed, Fahad
TI CPhos: A program to calculate and visualize evolutionarily conserved
functional phosphorylation sites
SO PROTEOMICS
LA English
DT Article
DE Bioinformatics; Conservation; Functional significance; Information
theory; Phosphorylation sites
ID PROTEIN-PHOSPHORYLATION; MATHEMATICAL-THEORY; SEQUENCE ALIGNMENT;
PREDICTION; COMMUNICATION
AB Profiling using high-throughput MS has discovered an overwhelming number of novel protein phosphorylation sites (phosphosites). However, the functional relevance of these sites is not always clear. In light of recent studies on the evolutionary mechanism of phosphorylation, we have developed CPhos, a Java program that can assess the conservation of phosphosites among species using an information theory-based approach. The degree of conservation established using CPhos can be used to assess the functional significance of phosphosites. CPhos has a user friendly graphical user interface and is available both as a web service and as a standalone Java application to assist phosphoproteomic researchers in analyzing and prioritizing lists of phosphosites for further experimental validation. CPhos can be accessed or downloaded at http://helixweb.nih.gov/CPhos/.
C1 [Zhao, Boyang; Pisitkun, Trairak; Hoffert, Jason D.; Knepper, Mark A.; Saeed, Fahad] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Saeed, F (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Room 6N312,MSC 1603, Bethesda, MD 20892 USA.
EM fahad.saeed@nih.gov
OI Pisitkun, Trairak/0000-0001-6677-2271
FU NHLBI [Z01-HL-001285]; National Institute of Biomedical Imaging and
Bioengineering
FX We thank members of the Knepper lab and Kelly Brock for discussions and
suggestions. This work was supported by the Intramural Budget of the
NHLBI (NHLBI Project no. Z01-HL-001285). Boyang Zhao was a student
intern from the University of Michigan in the National Institutes of
Health Biomedical Engineering Summer Internship Program, funded by the
National Institute of Biomedical Imaging and Bioengineering.
NR 29
TC 15
Z9 15
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD NOV
PY 2012
VL 12
IS 22
BP 3299
EP 3303
DI 10.1002/pmic.201200189
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 044JR
UT WOS:000311616000004
PM 23001821
ER
PT J
AU Cornblatt, BA
Carrion, RE
Addington, J
Seidman, L
Walker, EF
Cannon, TD
Cadenhead, KS
McGlashan, TH
Perkins, DO
Tsuang, MT
Woods, SW
Heinssen, R
Lencz, T
AF Cornblatt, Barbara A.
Carrion, Ricardo E.
Addington, Jean
Seidman, Larry
Walker, Elaine F.
Cannon, Tyronne D.
Cadenhead, Kristin S.
McGlashan, Thomas H.
Perkins, Diana O.
Tsuang, Ming T.
Woods, Scott W.
Heinssen, Robert
Lencz, Todd
TI Risk Factors for Psychosis: Impaired Social and Role Functioning
SO SCHIZOPHRENIA BULLETIN
LA English
DT Article
DE clinical high risk; functional deficits; prodromal; social risk factors;
functional outcome; attenuated positive symptoms
ID CLINICAL HIGH-RISK; 2ND-GENERATION ANTIPSYCHOTICS; NEUROCOGNITIVE
DEFICITS; SCHIZOPHRENIA PRODROME; NEGATIVE SYMPTOMS; ADOLESCENTS;
INDIVIDUALS; PERFORMANCE; REHABILITATION; COMPETENCE
AB Objectives: Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Methods: Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. Results: At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Conclusions: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.
C1 [Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA.
[Cornblatt, Barbara A.; Lencz, Todd] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA.
[Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA.
[Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
[Seidman, Larry] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div,Beth Israel Deaco, Boston, MA 02115 USA.
[Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Cannon, Tyronne D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA.
[Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA.
[Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA USA.
[Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
RP Cornblatt, BA (reprint author), N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA.
EM Cornblat@lij.edu
RI Lencz, Todd/J-3418-2014;
OI Lencz, Todd/0000-0001-8586-338X; Carrion, Ricardo/0000-0002-6393-392X
FU National Institute of Mental Health [R01 MH061523, U01 MH081857, R18
MH43518, U01 MH081928, P50 MH080272, R01 MH65079, RO1 MH062066, 5U01
MH081988, R01 MH60720, K24 MH76191, K05 MH01654, U01 MH066069, P50
MH064065, U01 MH74356, U01 MH082022, R41 MH083436, U01 MH066134]; Eli
Lilly; Merck; Clinical Data Inc.; GoldenHelix, Inc.; Guidepoint Global;
Cowen Co; Janssen Pharmaceuticals; Dainippon Sumitomo Pharma;
AstraZeneca Pharmaceuticals; Bristol-Myers Squibb; Otsuka Pharmaceutical
Co Ltd; Eli Lilly and Company; Pfizer; GlaxoSmithKline; Forest Labs;
Shire; UCB Pharma; Bristol- Myers Squibb
FX National Institute of Mental Health (R01 MH061523, U01 MH081857 to Dr
B.A.C.; R18 MH43518, U01 MH081928, P50 MH080272 to Dr L.S.; R01 MH65079
to Dr T.D.C.; RO1 MH062066, 5U01 MH081988 to Dr E.F.W.; R01 MH60720, K24
MH76191 to Dr K.S.C.; K05 MH01654 to Dr T.H.M.; U01 MH066069, P50
MH064065 to Dr D.O.P.; R18 MH43518 to Dr M.T.; U01 MH74356, U01
MH082022, R41 MH083436 to Dr S.W.W.; and U01 MH066134 to Dr J.A.).; We
thank the study participants for their time and effort. We also thank
Jennifer Johnson, PhD (UCLA), Diane Kirsopp, BA (University of Toronto),
and Roy Money, MS (Yale University) for their contributions to the NAPLS
I database described in this article. The authors also thank Andrea
Auther, PhD, Lauren Baskir, PhD, and Ruth Olsen, BS. Conflict of
interest: Dr. Cornblatt was the original developer of the CPT-IP and has
been an advisor for Bristol-Myers Squibb and Merck. Dr. Lencz has
received consulting fees and/or honoraria from Eli Lilly, Merck,
Clinical Data Inc., GoldenHelix, Inc., Guidepoint Global, and Cowen &
Co. Dr. Carrion has not received funding from for-profit entities. Dr.
Seidman has not received funding from for-profit entities in the past 12
months. In the past he received unrestricted educational support from
Janssen Pharmaceuticals and has served as a consultant for Shire. Dr.
Walker has not received funding from for-profit entities. Dr. Cannon has
served as a consultant for Janssen Pharmaceuticals and Eli Lilly and
Company. Dr. Cadenhead has not received funding from for-profit
entities. Dr. McGlashan has served as a consultant for Eli Lilly and
Company, Pfizer, Solvay/Wyeth, and Roche Pharmaceuticals. Dr. Perkins
has received research funding from Janssen Pharmaceuticals and Dainippon
Sumitomo Pharma in the past 12 months. In the past Dr. Perkins received
research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb,
Otsuka Pharmaceutical Co Ltd, Eli Lilly and Company, Janssen
Pharmaceuticals, and Pfizer and consulting and educational fees from
AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and
Company, Janssen Pharmaceuticals, GlaxoSmithKline, Forest Labs, Pfizer,
and Shire. Dr. Tsuang has received research grants from Janssen
Pharmaceuticals. Dr. Woods has received research funding support from
multiple for-profit entities including UCB Pharma and Bristol- Myers
Squibb and has consulted for Otsuka and Schering-Plough. Dr Woods has
not served on speaker's bureaus. Dr. Heinssen is an employee of the
nonprofit National Institutes of Health and has had no financial
relationships with for-profit entities. Dr. Addington has served as a
consultant for Pfizer, AstraZeneca Pharmaceuticals, and Janssen
Pharmaceuticals.
NR 44
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U1 7
U2 30
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0586-7614
J9 SCHIZOPHRENIA BULL
JI Schizophr. Bull.
PD NOV
PY 2012
VL 38
IS 6
BP 1247
EP 1257
DI 10.1093/schbul/sbr136
PG 11
WC Psychiatry
SC Psychiatry
GA 035KD
UT WOS:000310944500020
PM 22080497
ER
PT J
AU Foroud, T
Koller, DL
Lai, DB
Sauerbeck, L
Anderson, C
Ko, N
Deka, R
Mosley, TH
Fornage, M
Woo, D
Moomaw, CJ
Hornung, R
Huston, J
Meissner, I
Bailey-Wilson, JE
Langefeld, C
Rouleau, G
Connolly, ES
Worrall, BB
Kleindorfer, D
Flaherty, ML
Martini, S
Mackey, J
La Rosa, FD
Brown, RD
Broderick, JP
AF Foroud, Tatiana
Koller, Daniel L.
Lai, Dongbing
Sauerbeck, Laura
Anderson, Craig
Ko, Nerissa
Deka, Ranjan
Mosley, Thomas H.
Fornage, Myriam
Woo, Daniel
Moomaw, Charles J.
Hornung, Richard
Huston, John
Meissner, Irene
Bailey-Wilson, Joan E.
Langefeld, Carl
Rouleau, Guy
Connolly, E. Sander
Worrall, Bradford B.
Kleindorfer, Dawn
Flaherty, Matthew L.
Martini, Sharyl
Mackey, Jason
La Rosa, Felipe De Los Rios
Brown, Robert D., Jr.
Broderick, Joseph P.
CA FIA Study Investigators
TI Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of
Anril and SOX17 in Disease Risk
SO STROKE
LA English
DT Article
DE genome-wide association study; intracranial aneurysm
ID ABDOMINAL AORTIC-ANEURYSM; SUBARACHNOID HEMORRHAGE; CHROMOSOME 9P21;
SMOKING; POPULATIONS; ALCOHOL; VARIANT; STROKE; LOCI
AB Background-Genome-wide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA.
Method-We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a meta-analysis.
Results-There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach-genome-wide significance. However, the-meta-analysis yielded-genome-wide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P = 3.6x10(-8)) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P = 8.7x10(-5)). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype.
Conclusion-In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA). (Stroke. 2012; 43: 2846-2852.)
C1 [Foroud, Tatiana; Koller, Daniel L.; Lai, Dongbing; Mackey, Jason] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Sauerbeck, Laura; Deka, Ranjan; Woo, Daniel; Moomaw, Charles J.; Hornung, Richard; Kleindorfer, Dawn; Flaherty, Matthew L.; Martini, Sharyl; La Rosa, Felipe De Los Rios; Broderick, Joseph P.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Anderson, Craig] Royal Prince Alfred Hosp, George Inst Global Hlth, Sydney, NSW, Australia.
[Anderson, Craig] Univ Sydney, Sydney, NSW 2006, Australia.
[Ko, Nerissa] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr, Houston, TX USA.
[Huston, John; Meissner, Irene; Brown, Robert D., Jr.] Mayo Clin, Rochester, MN USA.
[Bailey-Wilson, Joan E.] Natl Human Genome Res Inst, Baltimore, MD USA.
[Langefeld, Carl] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Rouleau, Guy] Univ Montreal, Montreal, PQ, Canada.
[Connolly, E. Sander] Columbia Univ, Sch Med, New York, NY USA.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
RP Foroud, T (reprint author), Indiana Univ Sch Med, 410 W 10th St, Indianapolis, IN 46202 USA.
EM tforoud@iupui.edu
RI Mackey, Jason/I-6445-2013
OI Mackey, Jason/0000-0002-6867-8630
FU Intramural Research Program of NGHRI (NIH); National Health and Medical
Research Council of Australia; Health Research Council of New Zealand;
[R01NS39512]; [R01NS36695]; [K02NS060892]; [HHMI P0012375];
[HHSN268201100005C]; [HHSN268201100006C]; [HHSN268201100007C];
[HHSN268201100008C]; [HHSN268201100009C]; [HHSN268201100010C];
[HHSN268201100011C]; [HHSN268201100012C]; [R01HL087641]
FX This project was supported by R01NS39512, R01NS36695, K02NS060892, HHMI
P0012375, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367
R01HL086694, U01HG004402, HHSN268200625226C N01HC55015, N01HC55016,
N01HC55018, N01HC55019, N01HC55020, N01HC55021, N01HC55022, R01HL087641,
UL1RR025005, U01 HL096917, and R01HL093029, and the Intramural Research
Program of NGHRI (NIH). Addition funding was provided by the National
Health and Medical Research Council of Australia and the Health Research
Council of New Zealand.
NR 27
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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 NOV
PY 2012
VL 43
IS 11
BP 2846
EP U134
DI 10.1161/STROKEAHA.112.656397
PG 23
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 028OV
UT WOS:000310432800265
PM 22961961
ER
PT J
AU Cheng, B
Ebinger, M
Kufner, A
Koehrmann, M
Wu, O
Kang, DW
Liebeskind, D
Tourdias, T
Singer, OC
Christensen, S
Warach, S
Luby, M
Fiebach, JB
Fiehler, J
Gerloff, C
Thomalla, G
AF Cheng, Bastian
Ebinger, Martin
Kufner, Anna
Koehrmann, Martin
Wu, Ona
Kang, Dong-Wha
Liebeskind, David
Tourdias, Thomas
Singer, Oliver C.
Christensen, Soren
Warach, Steve
Luby, Marie
Fiebach, Jochen B.
Fiehler, Jens
Gerloff, Christian
Thomalla, Goetz
CA Stroke Imaging Repository STIR
TI Hyperintense Vessels on Acute Stroke Fluid-Attenuated Inversion Recovery
Imaging Associations With Clinical and Other MRI Findings
SO STROKE
LA English
DT Article
DE acute stroke; diffusion-weighted; fluid-attenuated inversion recovery;
magnetic resonance imaging; stroke
ID FLAIR MRI; ABNORMALITIES; TRIAL
AB Background and Purpose-Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV.
Methods-We analyzed data of 516 patients from the previously published PRE-FLAIR study (PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients <= 3 and <= 4.5 hours of symptom onset-a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings.
Results-Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9 mL; P<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6; P<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6-49.9; P<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80-0.90) and sensitivity of 0.76 (95% CI, 0.69-0.83).
Conclusions-HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy. (Stroke. 2012;43:2957-2961.)
C1 [Cheng, Bastian; Gerloff, Christian; Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, D-20246 Hamburg, Germany.
[Ebinger, Martin; Kufner, Anna; Fiebach, Jochen B.] Charite, Centrum Schlaganfallforsch, D-13353 Berlin, Germany.
[Koehrmann, Martin] Univ Erlangen Nurnberg, Neurol Klin, Erlangen, Germany.
[Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Boston, MA USA.
[Kang, Dong-Wha] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea.
[Liebeskind, David] Univ Calif, Dept Neurol, Oakland, CA USA.
[Tourdias, Thomas] Univ Bordeaux, Serv NeuroImagerie Diagnost Therapeut, Bordeaux, France.
[Singer, Oliver C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neuroradiol, Erlangen, Germany.
[Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia.
[Warach, Steve; Luby, Marie] NINDS, Bethesda, MD 20892 USA.
Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neuroradiol Diagnost & Intervent, D-20246 Hamburg, Germany.
RP Cheng, B (reprint author), Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, Martinistr 52, D-20246 Hamburg, Germany.
EM b.cheng@uke.uni-hamburg.de
OI Fiebach, Jochen B./0000-0002-7936-6958
FU Boehringer Ingelheim; Lundbeck; Siemens; Syngis; Synarc; Bayer Vital;
EBS Technologies; Glaxo Smith Kline; Pfizer; Sanofi Aventis; Silk Road
Medical; UCB; CoAxia; Concentric Medical, Inc.; Else
Kro-ner-Fresenius-Stiftung; French Government (PHRC); National
Institutes of Health [R01NS059775, R01NS063925, P50NS051343]; GE; Olea;
Imaging Biometrics; National Institute of Neurological Disorders and
Stroke (NINDS); Else-Kroner-Fresenius-Stiftung [2009_A36]; Federal
Ministry of Education and Research via the grant Center for Stroke
Research Berlin [01 EO 0801]; European Union [202213, 223153];
Volkswagen Foundation; Deutsche Forschungsgemeinschaft; National Health
and Medical Research Council (Australia); National Stroke Foundation
(Australia); Heart Foundation of Australia; French national grant "Le
programme hospitalier de recherche Clinique" (PHRC)
FX J.B.F. has received fees as a board member, consultant, or lecturer from
Boehringer Ingelheim, Lundbeck, Siemens, Syngis, and Synarc. C.G. has
received fees as a consultant or lecture fees from Bayer Vital,
Boehringer Ingelheim, EBS Technologies, Glaxo Smith Kline, Lundbeck,
Pfizer, Sanofi Aventis, Silk Road Medical, and UCB. D.L. has received
fees as a consultant for CoAxia and Concentric Medical, Inc. G.T. has
received a research grant from the Else Kro-ner-Fresenius-Stiftung. T.T.
has received a national grant from the French Government (PHRC). O.W.
was supported in part by grants from the National Institutes of Health
(R01NS059775, R01NS063925, P50NS051343) and received royalties and
licensing fees from GE, Olea, and Imaging Biometrics.; This work was
supported by the National Institute of Neurological Disorders and Stroke
(NINDS). The PREdictive value of FLAIR and DWI for the identification of
acute ischemic stroke patients <= 3 and <= 4.5 h of symptom onset-a
multicenter study (PRE-FLAIR) has received funding from the
Else-Kroner-Fresenius-Stiftung (2009_A36). In Berlin, data were
collected within the 1000+ study, which has received funding from the
Federal Ministry of Education and Research via the grant Center for
Stroke Research Berlin (01 EO 0801). This work was further supported by
the European Union's Seventh Framework Programme grant agreement No.
202213 and No 223153 (European Stroke Network), the Volkswagen
Foundation, and the Deutsche Forschungsgemeinschaft. Echoplanar Imaging
Thrombolysis Evaluation Trial (EPITHET) was a Phase II prospective,
randomized, double-blinded, placebo-controlled, multinational trial
funded by the National Health and Medical Research Council (Australia),
the National Stroke Foundation (Australia), and the Heart Foundation of
Australia. Valeur predictive des parametres IRM a la phase aigue de
l'accident vasculaire cerebral: application a la gestion des
essaistherapeutiques (VIRAGE) is a national multicentre study supported
by French national grant "Le programme hospitalier de recherche
Clinique" (PHRC).
NR 17
TC 16
Z9 23
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD NOV
PY 2012
VL 43
IS 11
BP 2957
EP 2961
DI 10.1161/STROKEAHA.112.658906
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 028OV
UT WOS:000310432800282
PM 22933582
ER
PT J
AU Dani, KA
An, L
Henning, EC
Shen, J
Warach, S
AF Dani, Krishna A.
An, Li
Henning, Erica C.
Shen, Jun
Warach, Steven
CA Natl Inst Neurological Disorders S
TI Multivoxel MR Spectroscopy in Acute Ischemic Stroke Comparison to the
Stroke Protocol MRI
SO STROKE
LA English
DT Article
DE magnetic resonance spectroscopy; spectroscopy; stroke
ID MAGNETIC-RESONANCE-SPECTROSCOPY; FOCAL ISCHEMIA; BRAIN; HYPERGLYCEMIA;
INFARCTION; DIFFUSION; PENUMBRA; LACTATE; TIME
AB Background and Purpose-Few patients with stroke have been imaged with MR spectroscopy (MRS) within the first few hours after onset. We compared data from current MRI protocols to MRS in subjects with ischemic stroke.
Methods-MRS was incorporated into the standard clinical MRI stroke protocol for subjects <24 hours after onset. MRI and clinical correlates for the metabolic data from MRS were sought.
Results-One hundred thirty-six MRS voxels from 32 subjects were analyzed. Lactate preceded the appearance of the lesion on diffusion-weighted imaging in some voxels but in others lagged behind it. Current protocols may predict up to 41% of the variance of MRS metabolites. Serum glucose concentration and time to maximum partially predicted the concentration of all major metabolites.
Conclusion-MRS may be helpful in acute stroke, especially for lactate detection when perfusion-weighted imaging is unavailable. Current MRI protocols do provide surrogate markers for some indices of metabolic activity. (Stroke. 2012;43:2962-2967.)
C1 [Dani, Krishna A.; An, Li; Henning, Erica C.; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Shen, Jun] NIMH, NIH, Bethesda, MD 20892 USA.
RP Warach, S (reprint author), UT SW Med Ctr, Dept Neurol & Neurotherapeut, Seton UT SW Clin Res Inst, 1400 N IH 35,Suite 2-240, Austin, TX 78701 USA.
EM swarach@seton.org
FU Division of Intramural Research of the National Institutes of Health,
National Institute of Neurological Disorders and Stroke; Patrick
Berthoud Charitable Trust
FX This research was supported by the Division of Intramural Research of
the National Institutes of Health, National Institute of Neurological
Disorders and Stroke. Dr Dani was supported by the Patrick Berthoud
Charitable Trust.
NR 17
TC 7
Z9 8
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD NOV
PY 2012
VL 43
IS 11
BP 2962
EP 2967
DI 10.1161/STROKEAHA.112.656058
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 028OV
UT WOS:000310432800283
PM 23091121
ER
PT J
AU Romero, JR
Preis, SR
Beiser, AS
DeCarli, C
Lee, DY
Viswanathan, A
Benjamin, EJ
Fontes, J
Au, R
Pikula, A
Wang, J
Kase, CS
Wolf, PA
Irrizary, MC
Seshadri, S
AF Romero, Jose Rafael
Preis, Sarah R.
Beiser, Alexa S.
DeCarli, Charles
Lee, Dong Young
Viswanathan, Anand
Benjamin, Emelia J.
Fontes, Joao
Au, Rhoda
Pikula, Aleksandra
Wang, Jimmy
Kase, Carlos S.
Wolf, Philip A.
Irrizary, Michael C.
Seshadri, Sudha
TI Lipoprotein Phospholipase A2 and Cerebral Microbleeds in the Framingham
Heart Study
SO STROKE
LA English
DT Article
DE cerebral microbleed; intracranial hemorrhage; inflammation; lipids and
lipoprotein; magnetic; resonance; microcirculation
ID APOLIPOPROTEIN-E POLYMORPHISM; INTRACEREBRAL HEMORRHAGE; RISK-FACTORS;
ISCHEMIC-STROKE; ROTTERDAM SCAN; A(2); PREVALENCE; DISEASE; PLASMA;
ASSOCIATION
AB Background and Purpose-Cerebral microbleeds (CMB) attributable to cerebral amyloid angiopathy generally occur in lobar regions, whereas those attributable to hypertensive vasculopathy are deep. Inflammation may be an underlying mechanism for CMB, with varying associations according to CMB location. Lipoprotein phospholipase-A2 (Lp-PLA2) is a circulating enzyme marker of vascular inflammation associated with risk of ischemic stroke and dementia. We hypothesized that higher Lp-PLA2 levels would be related to higher prevalence of CMB, with possible regional specificity.
Methods-Framingham Offspring participants aged 65 years or older with available Lp-PLA2 measures and brain magnetic resonance imaging were included. Logistic regression models were used to relate Lp-PLA2 activity and mass to presence of CMB, adjusted for age, sex, medication use (aspirin, anticoagulants, and statins), systolic blood pressure, APOE, current smoking, and diabetes.
Results-Eight--hundred nineteen participants (mean age, 73 years; 53% women) were included; 106 (13%) had CMB, 82 (10%) were lobar, and 27 (3%) were deep. We did not observe significant associations of CMB and LpPLA2 measures in multivariable adjusted analyses. However, there was a significant interaction between APOE genotype and Lp-PLA2 activity in their relation to presence of deep CMB (P interaction=0.01). Among persons with APOE e3/ e3, the odds ratio for deep CMB was 0.95 (confidence interval, 0.59-1.53; P=0.83), whereas among those with at least 1 e2 or e4 allele, odds ratio was 3.46 (confidence interval, 1.43-8.36; P=0.006).
Conclusions-In our -community--based sample of older adults, there was no significant association of Lp-PLA2 with total or lobar CMB. The association of higher levels of Lp-PLA2 activity with deep CMB among those with at least 1 APOE e2 or e4 allele merits replication. (Stroke. 2012; 43: 3091-3094.)
C1 [Romero, Jose Rafael; Beiser, Alexa S.; Au, Rhoda; Pikula, Aleksandra; Kase, Carlos S.; Wolf, Philip A.; Seshadri, Sudha] Boston Univ, Dept Neurol, Sch Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.] Boston Univ, Dept Neurol, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Fontes, Joao] Boston Univ, Dept Neurol, Cardiol Sect, Boston, MA 02118 USA.
[Wang, Jimmy] Boston Univ, Dept Neurol, Dept Radiol, Boston, MA 02118 USA.
[Preis, Sarah R.; Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
[Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Irrizary, Michael C.] GlaxoSmithKline, WW Epidemiol Res & Dev Neurosci Sect, Res Triangle Pk, NC USA.
[Romero, Jose Rafael; Preis, Sarah R.; Beiser, Alexa S.; Benjamin, Emelia J.; Fontes, Joao; Au, Rhoda; Pikula, Aleksandra; Kase, Carlos S.; Wolf, Philip A.; Seshadri, Sudha] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Romero, JR (reprint author), Boston Univ, Dept Neurol, Sch Med, 715 Albany St,B-608, Boston, MA 02118 USA.
EM joromero@bmc.org
RI Lee, Dong Young/J-5575-2012;
OI Preis, Sarah/0000-0002-9360-4166; Seshadri, Sudha/0000-0001-6135-2622;
Pikula, Aleksandra/0000-0002-8378-5522; Au, Rhoda/0000-0001-7742-4491;
Benjamin, Emelia/0000-0003-4076-2336; Beiser, Alexa/0000-0001-8551-7778
FU Framingham Heart Study's National Heart, Lung, and Blood Institute
[N01-HC-25195]; National Institute of Neurological Disorders and Stroke
[R01 NS17950]; National Institute on Aging [R01 AG16495, AG08122,
AG033193, AG031287, K23AG038444]; National Institutes of Health [1RO1
HL64753, R01 HL076784, 1 R01 AG028321]
FX This work (design and conduct of the study, collection, and management
of the data) was supported by the Framingham Heart Study's National
Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants
from the National Institute of Neurological Disorders and Stroke (R01
NS17950), the National Institute on Aging (R01 AG16495; AG08122;
AG033193; AG031287; K23AG038444), and National Institutes of Health
grants (1RO1 HL64753; R01 HL076784; 1 R01 AG028321).
NR 35
TC 13
Z9 14
U1 4
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD NOV
PY 2012
VL 43
IS 11
BP 3091
EP U525
DI 10.1161/STROKEAHA.112.656744
PG 13
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 028OV
UT WOS:000310432800305
PM 22961963
ER
PT J
AU Lee, HJ
Chung, JY
Hewitt, SM
Yu, E
Hong, SM
AF Lee, Hee Jin
Chung, Joon-Yong
Hewitt, Stephen M.
Yu, Eunsil
Hong, Seung-Mo
TI HER3 overexpression is a prognostic indicator of extrahepatic
cholangiocarcinoma
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Extrahepatic; Bile duct; Cholangiocarcinoma; HER2; HER3;
Immunohistochemistry; Prognosis
ID EPIDERMAL-GROWTH-FACTOR; C-ERBB-3 PROTEIN EXPRESSION; TYROSINE
KINASE-ACTIVITY; IN-SITU HYBRIDIZATION; BILIARY-TRACT; FACTOR-RECEPTOR;
GASTRIC-CANCER; LUNG-CANCER; INTRAHEPATIC CHOLANGIOCARCINOMA;
PANCREATIC-CANCER
AB Members of the HER (ERBB) receptor protein tyrosine kinase family play an important role in regulating cellular division, proliferation, differentiation, and migration and have prognostic significance in a number of cancers. Here, we sought to define their role in extrahepatic cholangiocarcinoma (EHCC). HER2 and HER3 protein expression was studied in 230 EHCC cases using a tissue microarray and compared with clinicopathological variables, including the survival of EHCC patients. HER3 was predominantly localized to the cytoplasm, whereas HER2 exhibited a membranous expression pattern. Overexpression of HER2 and HER3 was observed in 6 % (13/224) and 39 % (90/230) of EHCCs, respectively. Membranous HER2 overexpression occurred more frequently in intraductal papillary neoplasms with an associated invasive carcinoma than in tubular adenocarcinomas (P = 0.02). HER3 protein was more commonly overexpressed in nodular and infiltrative than in papillary tumors (P = 0.03). HER3 overexpression was associated with decreased survival in both univariate (P = 0.01) and multivariate (P = 0.008) analyses, whereas HER2 overexpression was not associated with survival. HER2 and HER3 are overexpressed in subsets of EHCC patients. Notably, HER3 overexpression is correlated with decreased patient survival, suggesting that HER3 constitutes a prognostic factor as well as a potential candidate for targeted therapy.
C1 [Lee, Hee Jin; Yu, Eunsil; Hong, Seung-Mo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul 138736, South Korea.
[Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Hong, SM (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, 388-1 Pungnap Dong, Seoul 138736, South Korea.
EM smhong28@gmail.com
OI Hewitt, Stephen/0000-0001-8283-1788; Hong, Seung-Mo/0000-0002-8888-6007;
Chung, Joon-Yong/0000-0001-5041-5982
NR 62
TC 5
Z9 5
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD NOV
PY 2012
VL 461
IS 5
BP 521
EP 530
DI 10.1007/s00428-012-1321-0
PG 10
WC Pathology
SC Pathology
GA 029ZK
UT WOS:000310537200006
PM 23052372
ER
PT J
AU Engelhardt, K
Gertz, E
Keles, S
Schaffer, A
Ceja, R
Sassi, A
Graham, L
Massaad, M
Mellouli, F
Benmustapha, I
Khemiri, M
Kilic, S
Etzioni, A
Freeman, A
Thiel, J
Schulze, I
Al-Herz, W
Metin, A
Sanal, O
Yeganeh, M
Niehues, T
Siepermann, K
Weinspach, S
Unal, E
Patiroglu, T
Dasouki, M
Yilmaz, M
Genel, F
Aytekin, C
Kutukculer, N
Somer, A
Kilic, M
Reisli, I
Camcioglu, Y
Gennery, A
Cant, A
Jones, A
Gaspar, H
Pietrogrande, M
Baz, Z
Al-Tamemi, S
Lougaris, V
Lefranc, G
Megarbane, A
Boutros, J
Galal, N
Bejaoui, M
Barbouche, M
Geha, R
Chatila, T
Grimbacher, B
AF Engelhardt, K.
Gertz, E.
Keles, S.
Schaeffer, A.
Ceja, R.
Sassi, A.
Graham, L.
Massaad, M.
Mellouli, F.
Benmustapha, I
Khemiri, M.
Kilic, S.
Etzioni, A.
Freeman, A.
Thiel, J.
Schulze, I
Al-Herz, W.
Metin, A.
Sanal, O.
Yeganeh, M.
Niehues, T.
Siepermann, K.
Weinspach, S.
Unal, E.
Patiroglu, T.
Dasouki, M.
Yilmaz, M.
Genel, F.
Aytekin, C.
Kutukculer, N.
Somer, A.
Kilic, M.
Reisli, I
Camcioglu, Y.
Gennery, A.
Cant, A.
Jones, A.
Gaspar, H.
Pietrogrande, M.
Baz, Z.
Al-Tamemi, S.
Lougaris, V
Lefranc, G.
Megarbane, A.
Boutros, J.
Galal, N.
Bejaoui, M.
Barbouche, M.
Geha, R.
Chatila, T.
Grimbacher, B.
TI DOCK8 deficiency and diagnostic guidelines for hyper-IgE syndromes
SO ALLERGY
LA English
DT Meeting Abstract
CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology
(EAACI)
CY JUN 16-20, 2012
CL Geneva, SWITZERLAND
SP European Acad Allergy & Clin Immunol (EAACI)
C1 [Engelhardt, K.; Graham, L.] UCL, Dept Immunol & Mol Pathol, London, England.
[Gertz, E.; Schaeffer, A.] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Keles, S.; Ceja, R.; Chatila, T.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Immunol Allergy & Rheumatol, Los Angeles, CA 90095 USA.
[Sassi, A.; Benmustapha, I; Barbouche, M.] Inst Pasteur, Dept Immunol, Tunis, Tunisia.
[Massaad, M.; Geha, R.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Mellouli, F.; Bejaoui, M.] Bone Marrow Transplantat Ctr, Dept Pediat, Tunis, Tunisia.
[Khemiri, M.] Childrens Hosp, Dept Pediat, Tunis, Tunisia.
[Kilic, S.] Uludag Univ, Fac Med, Dept Pediat Immunol, Bursa, Turkey.
[Etzioni, A.] Technion Israel Inst Technol, Rappaport Fac Med, Meyers Children Hosp, Haifa, Israel.
[Freeman, A.] NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Thiel, J.; Schulze, I; Grimbacher, B.] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany.
[Al-Herz, W.] Al Sabah Hosp, Dept Pediat, Kuwait, Kuwait.
[Metin, A.] SB Ankara Diskapi Childrens Hosp, Pediat Immunol Unit, Ankara, Turkey.
[Sanal, O.] Hacettepe Univ, Childrens Hosp, Div Immunol, Ankara, Turkey.
[Yeganeh, M.] Univ Tehran Med Sci, Children Med Ctr, Immunol Asthma & Allergy Res Inst, Tehran, Iran.
[Niehues, T.; Siepermann, K.] HELIOS Klinikum Krefeld, Zentrum Kinder & Jugendmed, Krefeld, Germany.
[Weinspach, S.] Univ Dusseldorf, Dept Pediat Oncol Hematol & Clin Immunol 18, Ctr Child & Adolescent Med, Dusseldorf, Germany.
[Unal, E.; Patiroglu, T.] Erciyes Univ, Fac Med, Dept Pediat, Div Pediat Immunol, Kayseri, Turkey.
[Dasouki, M.] Univ Kansas, Med Ctr, Dept Pediat, Kansas City, KS 66103 USA.
[Yilmaz, M.] Cukurova Univ, Adana, Turkey.
[Genel, F.] Behcet Uz State Hosp, Div Pediat Immunol, Izmir, Turkey.
[Aytekin, C.] Dr Sami Ulus State Hosp, Ankara, Turkey.
[Kutukculer, N.] Ege Univ, Fac Med, Dept Pediat, Izmir, Turkey.
[Somer, A.] Istanbul Univ, Istanbul Fac Med, Div Infect Dis & Immunol, Istanbul, Turkey.
[Kilic, M.] Firat Univ, TR-23169 Elazig, Turkey.
[Reisli, I] Selcuk Univ, Div Pediat Allergy & Immunol, Konya, Turkey.
[Camcioglu, Y.] Istanbul Univ, Cerrahpasa Med Fac, Div Pediat Allergy Immunol & Infect Dis, Istanbul, Turkey.
[Gennery, A.; Cant, A.] Newcastle Univ, Childrens Bone Marrow Transplant Unit, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Jones, A.; Gaspar, H.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Pietrogrande, M.] Univ Milan, Dept Maternal & Pediat Sci, Fdn IRCCS Policlin Milano, Milan, Italy.
[Baz, Z.] St George Hosp Univ, Med Ctr, Dept Pediat, Beirut, Lebanon.
[Al-Tamemi, S.] Sultan Qaboos Univ, Dept Pediat, Muscat, Oman.
[Lougaris, V] Univ Brescia, Dept Pediat, Brescia, Italy.
[Lougaris, V] Univ Brescia, Inst Mol Med, Brescia, Italy.
[Lefranc, G.] Univ Montpellier 2, Montpellier, France.
[Lefranc, G.] CNRS, Inst Human Genet, Montpellier, France.
[Megarbane, A.] St Joseph Univ, Med Genet Unit, Beirut, Lebanon.
[Boutros, J.; Galal, N.] Cairo Univ, Primary Immunodeficiency Clin, Specialized Pediat Hosp, Cairo, Egypt.
[Etzioni, A.] Rambam Hlth Care Campus, Haifa, Israel.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD NOV
PY 2012
VL 67
SU 96
SI SI
MA 387
BP 163
EP 164
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 026CA
UT WOS:000310247700373
ER
PT J
AU Carter, M
Clayton, S
Wilson, T
Scott, L
Maric, I
Simakova, O
Jung, M
Metcalfe, D
AF Carter, M.
Clayton, S.
Wilson, T.
Scott, L.
Maric, I
Simakova, O.
Jung, M.
Metcalfe, D.
TI Idiopathic anaphylaxis and the occurrence of clonal mast cell disease
SO ALLERGY
LA English
DT Meeting Abstract
CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology
(EAACI)
CY JUN 16-20, 2012
CL Geneva, SWITZERLAND
SP European Acad Allergy & Clin Immunol (EAACI)
C1 [Carter, M.; Clayton, S.; Wilson, T.; Scott, L.; Jung, M.; Metcalfe, D.] NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
J9 ALLERGY
JI Allergy
PD NOV
PY 2012
VL 67
SU 96
SI SI
MA 760
BP 297
EP 297
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA 026CA
UT WOS:000310247701363
ER
PT J
AU Albanese, E
Hardy, R
Wills, A
Kuh, D
Guralnik, J
Richards, M
AF Albanese, Emiliano
Hardy, Rebecca
Wills, Andrew
Kuh, Diana
Guralnik, Jack
Richards, Marcus
TI No association between gain in body mass index across the life course
and midlife cognitive function and cognitive reserve-The 1946 British
birth cohort study
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Epidemiology; Cognitive function; Body size; Adiposity; Vascular risk
factors
ID ALZHEIMER-DISEASE; CENTRAL OBESITY; METABOLIC SYNDROME; ADULT LIFE;
DEMENTIA; RISK; ADIPOSITY; DECLINE; WEIGHT; WOMEN
AB Background: The association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied.
Methods: In more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors.
Results: Independent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (beta per SD increase in BMI in men = -0.11; 95% confidence interval [CI]: -0.19, -0.02), verbal fluency (beta in women = -0.11; 95% CI: -0.20, -0.02), and lower National Adult Reading Test score (beta in women = -0.08; 95% CI: -0.15, -0.01), but not with speed/concentration (beta in men = 0.02; 95% CI: -0.11, 0.07). Associations were largely explained by educational attainment and SEP (P >= .10). However, BMI gain at 53 years in men was independently associated with better memory (beta = 0.12; 95% CI: 0.03, 0.22), and both underweight (beta = -1.54; 95% CI: -2.52, -0.57) and obese (beta = -0.30; 95% CI: -2.52, -0.57) women at 53 years had significantly lower memory scores.
Conclusion: The adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation. (C) 2012 The Alzheimer's Association. All rights reserved.
C1 [Albanese, Emiliano; Hardy, Rebecca; Wills, Andrew; Kuh, Diana; Richards, Marcus] Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
[Albanese, Emiliano; Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Albanese, E (reprint author), Royal Free & Univ Coll Med Sch, Dept Epidemiol & Publ Hlth, MRC Unit Lifelong Hlth & Ageing, London WC1E 6BT, England.
EM emiliano.albanese@nih.gov
FU MRC Unit for Lifelong Health and Ageing, United Kingdom; Intramural
Research Program of the National Institute on Aging, National Institutes
of Health
FX This study was funded by the MRC Unit for Lifelong Health and Ageing,
United Kingdom, and is supported in part by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health.
NR 47
TC 2
Z9 2
U1 3
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD NOV
PY 2012
VL 8
IS 6
BP 470
EP 482
DI 10.1016/j.jalz.2011.09.228
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 038KW
UT WOS:000311174600002
PM 22858531
ER
PT J
AU Guttmacher, AE
AF Guttmacher, Alan E.
TI Every birth a healthy birth
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
ID SYSTEMATIC ANALYSIS; TRENDS
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Guttmacher, AE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
NR 4
TC 1
Z9 1
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
BP 343
EP 344
DI 10.1016/j.ajog.2012.09.015
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000010
PM 23107077
ER
PT J
AU Caritis, SN
Sharma, S
Venkataramanan, R
Hankins, GD
Miodovnik, M
Hebert, MF
Umans, JG
Benedetti, T
Mattison, D
Zajicek, A
Fischer, D
Jackson, A
AF Caritis, Steve N.
Sharma, Shringi
Venkataramanan, Raman
Hankins, Gary D.
Miodovnik, Menachem
Hebert, Mary F.
Umans, Jason G.
Benedetti, Thomas
Mattison, Donald
Zajicek, Anne
Fischer, Dawn
Jackson, Aimee
CA Eunice Kennedy Shriver Natl Inst C
TI Pharmacology and placental transport of 17-hydroxyprogesterone caproate
in singleton gestation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cord blood; pharmacokinetics; placenta; preterm birth
ID RANDOMIZED CONTROLLED-TRIAL; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE;
PRETERM BIRTH; HYDROXYPROGESTERONE CAPROATE; PREVENTION; METABOLISM;
PROGESTERONE; PREGNANCY; AGENT
AB OBJECTIVE: The purpose of this study was to estimate pharmacokinetic parameters and to evaluate placental transport of 17-hydroxyprogesterone caproate (17-OHPC) in singleton gestation.
STUDY DESIGN: Sixty-one women who received weekly injections of 17-OHPC underwent 2 pharmacokinetic studies at 20 + 0 to 24 + 6 weeks' gestation (study 1) and 31 + 0 to 34 + 6 weeks' gestation (study 2); daily blood samples were obtained between injections. In 18 women, blood samples were obtained over a 28-day period beyond the last injection (extended study). Maternal and/or cord blood were obtained at delivery.
RESULTS: The half-life (median +/- SD) of 17-OHPC was 16.2 +/- 6 days. Concentrations of 17-OHPC were higher during study 2 than during study 1. Body mass index affected maternal 17-OHPC concentrations. Cord: maternal 17-OHPC concentration ratios averaged 0.2; 17-OHPC was detectible in cord plasma 44 days after the last maternal injection.
CONCLUSION: The apparent half-life of 17-OHPC is long, and pharmacokinetic parameters vary widely between subjects and are affected by maternal body mass index. The drug crosses the placental barrier.
C1 [Caritis, Steve N.; Fischer, Dawn] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
[Sharma, Shringi; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Hankins, Gary D.; Jackson, Aimee] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA.
[Miodovnik, Menachem; Umans, Jason G.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Miodovnik, Menachem; Umans, Jason G.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Umans, Jason G.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC USA.
[Hebert, Mary F.] Univ Washington, Dept Pharm, Sch Med, Seattle, WA USA.
[Benedetti, Thomas] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Mattison, Donald; Zajicek, Anne] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
RI Mattison, Donald/L-4661-2013;
OI Mattison, Donald/0000-0001-5623-0874; caritis, steve/0000-0002-2169-0712
FU Obstetric Fetal Pharmacology Research Units Network of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
[U10HD047905, U10HD047892]; [1 UL1RR031975]
FX Supported by the Obstetric Fetal Pharmacology Research Units Network of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development through cooperative agreements U10HD047905, U10HD047892,
U10HD047892, and U10HD047892 with additional support by 1 UL1RR031975.
NR 21
TC 0
Z9 0
U1 0
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
AR 398.e1
DI 10.1016/j.ajog.2012.08.015
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000024
PM 22967833
ER
PT J
AU Caritis, SN
Simhan, HN
Zhao, Y
Rouse, DJ
Peaceman, AM
Sciscione, A
Spong, CY
Varner, MW
Malone, FD
Iams, JD
Mercer, BM
Thorp, JM
Sorokin, Y
Carpenter, M
Lo, J
Ramin, SM
Harper, M
AF Caritis, Steve N.
Simhan, Hyagriv N.
Zhao, Yuan
Rouse, Dwight J.
Peaceman, Alan M.
Sciscione, Anthony
Spong, Catherine Y.
Varner, Michael W.
Malone, Fergal D.
Iams, Jay D.
Mercer, Brian M.
Thorp, John M., Jr.
Sorokin, Yoram
Carpenter, Marshall
Lo, Julie
Ramin, Susan M.
Harper, Margaret
CA Eunice Kennedy Shriver Natl Inst C
TI Relationship between 17-hydroxyprogesterone caproate concentrations and
gestational age at delivery in twin gestation
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE 17-hydroxyprogesterone caproate; pharmacodynamics; twin gestation
ID 17-ALPHA-HYDROXYPROGESTERONE CAPROATE; PREMATURITY; PREVENTION;
PREGNANCY
AB OBJECTIVE: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action.
STUDY DESIGN: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed.
RESULTS: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group.
CONCLUSION: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation.
C1 [Caritis, Steve N.; Simhan, Hyagriv N.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Dept Obstet, Med Sch Birmingham, Birmingham, AL USA.
[Rouse, Dwight J.] Univ Alabama Birmingham, Dept Gynecol, Med Sch Birmingham, Birmingham, AL USA.
[Peaceman, Alan M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Sciscione, Anthony] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Malone, Fergal D.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Iams, Jay D.] Ohio State Univ, Ohio State Coll Med, Cleveland, OH USA.
[Mercer, Brian M.] Case Western Reserve Univ, Sch Med, Metrohlth Med Ctr, Cleveland, OH USA.
[Thorp, John M., Jr.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Sorokin, Yoram] Wayne State Univ, Sch Med, Detroit, MI USA.
[Carpenter, Marshall] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Lo, Julie] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Zhao, Yuan] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Caritis, SN (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27869, HD21410, HD40512, HD34136, HD34208,
HD40485, HD27915, HD40544, HD40560, HD27917, HD40500, HD34116, HD40545,
HD27860, HD3680]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD27869, HD21410, HD40512, HD34136, HD34208, HD40485, HD27915, HD40544,
HD40560, HD27917, HD40500, HD34116, HD40545, HD27860, HD3680) and does
not necessarily represent the official views of the NICHD or the
National Institutes of Health.
NR 14
TC 0
Z9 1
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
AR 396.e1
DI 10.1016/j.ajog.2012.08.001
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000023
PM 22959763
ER
PT J
AU Grobman, WA
Thom, EA
Spong, CY
Iams, JD
Saade, GR
Mercer, BM
Tita, ATN
Rouse, DJ
Sorokin, Y
Wapner, RJ
Leveno, KJ
Blackwell, S
Esplin, MS
Tolosa, JE
Thorp, JM
Caritis, SN
Van Dorsten, JP
AF Grobman, William A.
Thom, Elizabeth A.
Spong, Catherine Y.
Iams, Jay D.
Saade, George R.
Mercer, Brian M.
Tita, Alan T. N.
Rouse, Dwight J.
Sorokin, Yoram
Wapner, Ronald J.
Leveno, Kenneth J.
Blackwell, Sean
Esplin, M. Sean
Tolosa, Jorge E.
Thorp, John M., Jr.
Caritis, Steve N.
Van Dorsten, J. Peter
CA Eunice Kennedy Shriver Natl Inst C
TI 17 alpha-hydroxyprogesterone caproate to prevent prematurity in
nulliparas with cervical length less than 30 mm
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE nulliparous; progesterone; progestogen; short cervix
ID SPONTANEOUS PRETERM BIRTH; 17-ALPHA-HYDROXYPROGESTERONE CAPROATE;
DOUBLE-BLIND; CLINICAL-TRIALS; WEEKS GESTATION; RISK; DELIVERY;
PROGESTERONE; WOMEN; PREDICTION
AB OBJECTIVE: We sought to evaluate whether 17 alpha-hydroxyprogesterone caproate (17-OHP) reduces preterm birth (PTB) in nulliparous women with a midtrimester cervical length (CL) <30 mm.
STUDY DESIGN: In this multicenter randomized controlled trial, nulliparous women with a singleton gestation between 16 and 22 3/7 weeks with an endovaginal CL <30 mm (<10th percentile in this population) were randomized to weekly intramuscular 17-OHP (250 mg) or placebo through 36 weeks. The primary outcome was PTB <37 weeks.
RESULTS: The frequency of PTB did not differ between the 17-OHP (n = 327) and placebo (n = 330) groups (25.1% vs 24.2%; relative risk, 1.03; 95% confidence interval, 0.79-1.35). There also was no difference in the composite adverse neonatal outcome (7.0% vs 9.1%; relative risk, 0.77; 95% confidence interval, 0.46-1.30).
CONCLUSION: Weekly 17-OHP does not reduce the frequency of PTB in nulliparous women with a midtrimester CL <30 mm.
C1 [Grobman, William A.] Northwestern Univ, Chicago, IL 60611 USA.
[Thom, Elizabeth A.] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Iams, Jay D.] Ohio State Univ, Columbus, OH 43210 USA.
[Saade, George R.] Univ Texas Med Branch, Galveston, TX USA.
[Mercer, Brian M.] Case Western Reserve Univ, Metrohlth Med Ctr, Cleveland, OH USA.
[Tita, Alan T. N.] Univ Alabama Birmingham, Birmingham, AL USA.
[Rouse, Dwight J.] Brown Univ, Providence, RI 02912 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Wapner, Ronald J.] Columbia Univ, New York, NY USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Blackwell, Sean] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Esplin, M. Sean] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Thorp, John M., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Van Dorsten, J. Peter] Med Univ S Carolina, Charleston, SC 29425 USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Grobman, WA (reprint author), Northwestern Univ, Chicago, IL 60611 USA.
OI caritis, steve/0000-0002-2169-0712
FU National Center for Research Resources [NCRR] from NICHD [HD21410, UL1
RR024153, UL1 TR000005, HD27869, HD27915, HD27917, HD34116, HD34208,
5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1
RR024989]; NICHD [HD40545, HD40560, HD40485, HD53097, HD53118]
FX The project described was supported by grant numbers HD21410, UL1
RR024153, UL1 TR000005, HD27869, HD27915, HD27917, HD34116, HD34208,
5UL1RR025764, HD36801, HD40500, HD40512, HD40544, M01 RR00080, UL1
RR024989 (National Center for Research Resources [NCRR]), HD40545,
HD40560, HD40485, HD53097, and HD53118 from the NICHD.
NR 23
TC 1
Z9 2
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
AR 390.e1
DI 10.1016/j.ajog.2012.09.013
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000021
PM 23010094
ER
PT J
AU McElrath, TF
Lim, KH
Pare, E
Rich-Edwards, J
Pucci, D
Troisi, R
Parry, S
AF McElrath, Thomas F.
Lim, Kee-Hak
Pare, Emmanuelle
Rich-Edwards, Janet
Pucci, Dominick
Troisi, Rebecca
Parry, Samuel
TI Longitudinal evaluation of predictive value for preeclampsia of
circulating angiogenic factors through pregnancy
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE angiogenic factor; PlGF; preeclampsia; sFlt-1
ID PLACENTAL GROWTH-FACTOR; FOR-GESTATIONAL-AGE; TYROSINE KINASE-1;
MATERNAL PLASMA; 1ST-TRIMESTER; RISK; 2ND-TRIMESTER; PATHOGENESIS;
ENDOGLIN; MARKERS
AB OBJECTIVE: The purpose of this study was to examine whether longitudinally sampled maternal angiogenic concentrations predict preeclampsia.
STUDY DESIGN: Plasma sFlt-1 and placental growth factor (PlGF) concentrations in healthy pregnant women were quantified at 10, 17, 25, and 35 weeks' gestation. Preeclampsia was diagnosed with criteria from the American College of Obstetricians and Gynecologists.
RESULTS: In the first trimester, sensitivity/specificity for PlGF and sFlt-1 were 55/43% and 57/40%, respectively, and did not improve appreciably as the pregnancy progressed. Among pregnancies that later experienced preeclampsia, median PlGF was lower beginning in the second trimester, but sFlt-1 was not higher until the third trimester. Analyte positive predictive values approached 10% in the third trimester. Negative predictive values were >90% for the entire pregnancy.
CONCLUSION: Prediction of preeclampsia in early pregnancy was not possible with the use of maternal angiogenic protein concentrations. Even in late pregnancy, positive predictive values were not useful clinically. Negative predictive values are similarly unlikely to prove useful as a tool with which to a rule out suspected disease.
C1 [McElrath, Thomas F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA.
[Lim, Kee-Hak] Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Maternal Fetal Med, Boston, MA USA.
[Pare, Emmanuelle; Parry, Samuel] Hosp Univ Penn, Div Maternal Fetal Med, Philadelphia, PA 19104 USA.
[Pucci, Dominick] Abbott Diagnost Div, Abbott Pk, IL USA.
[Troisi, Rebecca] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP McElrath, TF (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Maternal Fetal Med, Boston, MA 02115 USA.
FU Abbott Diagnostics Division [9MZ-04-06N03]
FX Supported by an unrestricted grant from Abbott Diagnostics Division
(9MZ-04-06N03).
NR 36
TC 16
Z9 17
U1 1
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
AR 407.e1
DI 10.1016/j.ajog.2012.08.010
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000028
PM 22981320
ER
PT J
AU Zyczynski, HM
Rickey, L
Dyer, KY
Wilson, T
Stoddard, AM
Gormley, EA
Hsu, Y
Kusek, JW
Brubaker, L
AF Zyczynski, Halina M.
Rickey, Leslie
Dyer, Keisha Y.
Wilson, Tracey
Stoddard, Anne M.
Gormley, E. Ann
Hsu, Yvonne
Kusek, John W.
Brubaker, Linda
CA Urinary Incontinence Treatment
TI Sexual activity and function in women more than 2 years after
midurethral sling placement
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE mesh; midurethral sling; sexual function; surgery; urinary incontinence
ID STRESS URINARY-INCONTINENCE; SURGERY
AB OBJECTIVE: The purpose of this study was to assess prospectively the effects of midurethral sling surgery on sexual function and activity.
STUDY DESIGN: Sexual activity and function was assessed in 597 women with stress urinary incontinence who were enrolled in a randomized equivalence trial of retropubic compared with transobturator midurethral slings. Repeated measures analysis of variance was used to assess changes in Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores over a 2-year period.
RESULTS: Significant, similar improvements in sexual function were seen in both midurethral sling groups. Mean Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire scores increased from 32.8 at baseline to 37.6 at 6 months and 37.3 at 24 months (P < .0001). Dyspareunia, incontinence during sex, and fear of incontinence during sex each significantly improved after surgery. Preoperative urge incontinence was associated with abstinence after surgery (P = .02); postoperative urge incontinence negatively impacted sexual function (P = .047).
CONCLUSION: Midurethral sling surgery for stress urinary incontinence significantly improves sexual function, although coexistent urge incontinence has a negative impact.
C1 [Zyczynski, Halina M.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
[Rickey, Leslie] Univ Maryland, Sch Med, Dept Urol, Baltimore, MD 21201 USA.
[Kusek, John W.] NIDDKD, Bethesda, MD USA.
[Dyer, Keisha Y.] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA.
[Wilson, Tracey] Univ Alabama Birmingham, Div Urol, Birmingham, AL USA.
[Stoddard, Anne M.] New England Res Inst, Watertown, MA 02172 USA.
[Gormley, E. Ann] Dartmouth Hitchcock Med Ctr, Div Urol, Lebanon, NH 03766 USA.
[Hsu, Yvonne] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Obstet & Gynecol, Maywood, IL USA.
[Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Dept Urol, Maywood, IL USA.
RP Zyczynski, HM (reprint author), Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
FU National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK58225, U01 DK58229, U01 DK58234, U01 DK58231, U01 DK60379, U01
DK60380, U01DK60393, U01 DK60395, U01 DK60397, U01DK 60401]; National
Institute of Child Health and Human Development and Office of Research
in Women's Health, National Institutes of Health; Pfizer
FX Supported by cooperative agreements from the National Institute of
Diabetes and Digestive and Kidney Diseases (U01 DK58225, U01 DK58229,
U01 DK58234, U01 DK58231, U01 DK60379, U01 DK60380, U01DK60393, U01
DK60395, U01 DK60397, and U01DK 60401) and by the National Institute of
Child Health and Human Development and Office of Research in Women's
Health, National Institutes of Health.; H.M.Z. is a consultant for
Johnson & Johnson Inc. L. R. holds a research grant from Pfizer. The
remaining authors report no potential conflict of interest.
NR 18
TC 5
Z9 5
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2012
VL 207
IS 5
AR 421.e1
DI 10.1016/j.ajog.2012.06.053
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 030JM
UT WOS:000310567000035
PM 22840975
ER
PT J
AU Bolger, SJ
Hurtado, PAG
Hoffert, JD
Saeed, F
Pisitkun, T
Knepper, MA
AF Bolger, Steven J.
Hurtado, Patricia A. Gonzales
Hoffert, Jason D.
Saeed, Fahad
Pisitkun, Trairak
Knepper, Mark A.
TI Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal
collecting duct cells
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE beta-catenin; c-Jun; mpkCCD cells; systems biology; transcription
ID EPITHELIAL SODIUM-CHANNEL; LIGHT-CHAIN KINASE; LONG-TERM REGULATION;
TANDEM MASS-SPECTRA; BETA-CATENIN; PROTEIN-KINASE; C-JUN; WATER CHANNEL;
RAT-KIDNEY; MODIFIED PEPTIDES
AB Bolger SJ, Gonzales Hurtado PA, Hoffert JD, Saeed F, Pisitkun T, Knepper MA. Quantitative phosphoproteomics in nuclei of vasopressin-sensitive renal collecting duct cells. Am J Physiol Cell Physiol 303: C1006-C1020, 2012. First published September 19, 2012; doi:10.1152/ajpcell.00260.2012.-Vasopressin regulates transport across the collecting duct epithelium in part via effects on gene transcription. Transcriptional regulation occurs partially via changes in phosphorylation of transcription factors, transcriptional coactivators, and protein kinases in the nucleus. To test whether vasopressin alters the nuclear phosphoproteome of vasopressin-sensitive cultured mouse mpkCCD cells, we used stable isotope labeling and mass spectrometry to quantify thousands of phosphorylation sites in nuclear extracts and nuclear pellet fractions. Measurements were made in the presence and absence of the vasopressin analog dDAVP. Of the 1,251 sites quantified, 39 changed significantly in response to dDAVP. Network analysis of the regulated proteins revealed two major clusters ("cell-cell adhesion" and "transcriptional regulation") that were connected to known elements of the vasopressin signaling pathway. The hub proteins for these two clusters were the transcriptional coactivator beta-catenin and the transcription factor c-Jun. Phosphorylation of beta-catenin at Ser552 was increased by dDAVP [log(2)(dDAVP/vehicle) = 1.79], and phosphorylation of c-Jun at Ser73 was decreased [log2(dDAVP/vehicle) = -0.53]. The beta-catenin site is known to be targeted by either protein kinase A or Akt, both of which are activated in response to vasopressin. The c-Jun site is a canonical target for the MAP kinase Jnk2, which is downregulated in response to vasopressin in the collecting duct. The data support the idea that vasopressin-mediated control of transcription in collecting duct cells involves selective changes in the nuclear phosphoproteome. All data are available to users at http://helixweb.nih.gov/ESBL/Database/mNPPD/.
C1 [Bolger, Steven J.; Hurtado, Patricia A. Gonzales; Hoffert, Jason D.; Saeed, Fahad; Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NHLBI, Epithelial Syst Biol Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
RI Saeed, Fahad/D-1545-2013;
OI Pisitkun, Trairak/0000-0001-6677-2271
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute [Z01-HL001285]
FX This work was funded by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute (Project Z01-HL001285 to M. A.
Knepper).
NR 67
TC 14
Z9 14
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD NOV
PY 2012
VL 303
IS 10
BP C1006
EP C1020
DI 10.1152/ajpcell.00260.2012
PG 15
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 038YB
UT WOS:000311208900003
PM 22992673
ER
PT J
AU Izumi, Y
Li, JX
Villers, C
Hashimoto, K
Burg, MB
Ferraris, JD
AF Izumi, Yuichiro
Li, Jinxi
Villers, Courtney
Hashimoto, Kosuke
Burg, Maurice B.
Ferraris, Joan D.
TI Mutations that reduce its specific DNA binding inhibit high NaCl-induced
nuclear localization of the osmoprotective transcription factor NFAT5
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE high NaCl; NUP88; leptomycin B; XPO1
ID OSMOTIC RESPONSE ELEMENT; DAMAGE-INDUCIBLE KINASE; FACTOR TONEBP/OREBP;
NUCLEOCYTOPLASMIC TRAFFICKING; GENE-EXPRESSION; PROTEIN; TONICITY;
STRESS; PHOSPHORYLATION; CONTRIBUTES
AB Izumi Y, Li J, Villers C, Hashimoto K, Burg MB, Ferraris JD. Mutations that reduce its specific DNA binding inhibit high NaCl-induced nuclear localization of the osmoprotective transcription factor NFAT5. Am J Physiol Cell Physiol 303: C1061-C1069, 2012. First published September 19, 2012; doi:10.1152/ajpcell.00265.2012.The transcription factor nuclear factor of activated T cell 5 (NFAT5) is activated by the stress of hypertonicity (e.g., high NaCl). Increased expression of NFAT5 target genes causes accumulation of protective organic osmolytes and heat shock proteins. Under normotonic conditions (similar to 300 mosmol/kgH(2)O), NFAT5 is distributed between the nucleus and cytoplasm, hypertonicity causes it to translocate into the nucleus, and hypotonicity causes it to translocate into the cytoplasm. The mechanism of translocation is complex and not completely understood. NFAT5-T298 is a known contact site of NFAT5 with its specific DNA element [ osmotic response element (ORE)]. In the present study, we find that mutation of NFAT5-T298 to alanine or aspartic acid not only reduces binding of NFAT5 to OREs (EMSA) but also proportionately reduces high NaCl-induced nuclear translocation of NFAT5. Combined mutation of other NFAT5 DNA contact sites (R293A/E299A/R302A) also greatly reduces both specific DNA binding and nuclear localization of NFAT5. NFAT5-T298 is a potential phosphorylation site, but, using protein mass spectrometry, we do not find phosphorylation at NFAT5-T298. Further, decreased high NaCl-induced nuclear localization of NFAT5 mutated at T298 does not involve previously known regulatory mechanisms, including hypotonicity-induced export of NFAT5, regulated by phosphorylation of NFAT5-S155, XPO1 (CRM1/exportin1)-mediated export of NFAT5 from the nucleus, or hypertonicity-induced elevation of NUP88, which enhances nuclear localization of NFAT5. We conclude that specific DNA binding of NFAT5 contributes to its nuclear localization, by mechanisms, as yet undetermined, but independent of ones previously described to regulate NFAT5 distribution.
C1 [Izumi, Yuichiro; Li, Jinxi; Villers, Courtney; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Hashimoto, Kosuke] Natl Lib Med, Computat Biol Branch, NIH, Bethesda, MD USA.
RP Ferraris, JD (reprint author), 10 Ctr Dr, Bethesda, MD USA.
EM ferraris@nhlbi.nih.gov
FU Intramural Research Program of the National Heart, Lung, and Blood
Institute
FX This research was supported by the Intramural Research Program of the
National Heart, Lung, and Blood Institute.
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD NOV
PY 2012
VL 303
IS 10
BP C1061
EP C1069
DI 10.1152/ajpcell.00265.2012
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA 038YB
UT WOS:000311208900008
PM 22992674
ER
PT J
AU Patterson, K
Catalan, MA
Melvin, JE
Yule, DI
Crampin, EJ
Sneyd, J
AF Patterson, Kate
Catalan, Marcelo A.
Melvin, James E.
Yule, David I.
Crampin, Edmund J.
Sneyd, James
TI A quantitative analysis of electrolyte exchange in the salivary duct
SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
LA English
DT Article
DE salivary glands; tubular transport; membrane transport
ID TRANSMEMBRANE CONDUCTANCE REGULATOR; RAT SUBMANDIBULAR-GLAND;
CYSTIC-FIBROSIS; MATHEMATICAL-MODEL; TRANSDUCTAL FLUXES; FLUID
SECRETION; HCO3-SECRETION; CFTR ACTIVITY; MAIN DUCT; MOUSE
AB Patterson K, Catalan MA, Melvin JE, Yule DI, Crampin EJ, Sneyd J. A quantitative analysis of electrolyte exchange in the salivary duct. Am J Physiol Gastrointest Liver Physiol 303: G1153-G1163, 2012. First published August 16, 2012; doi:10.1152/ajpgi.00364.2011.-A healthy salivary gland secretes saliva in two stages. First, acinar cells generate primary saliva, a plasma-like, isotonic fluid high in Na+ and Cl-. In the second stage, the ducts exchange Na+ and Cl- for K+ and HCO3-, producing a hypotonic final saliva with no apparent loss in volume. We have developed a tool that aims to understand how the ducts achieve this electrolyte exchange while maintaining the same volume. This tool is part of a larger multi-scale model of the salivary gland and can be used at the duct or gland level to investigate the effects of genetic and chemical alterations. In this study, we construct a radially symmetric mathematical model of the mouse salivary gland duct, representing the lumen, the cell, and the interstitium. For a given flow and primary saliva composition, we predict the potential differences and the luminal and cytosolic concentrations along a duct. Our model accounts well for experimental data obtained in wild-type animals as well as knockouts and chemical inhibitors. Additionally, the luminal membrane potential of the duct cells is predicted to be very depolarized compared with acinar cells. We investigate the effects of an electrogenic vs. electroneutral anion exchanger in the luminal membrane on concentration and the potential difference across the luminal membrane as well as how impairing the cystic fibrosis transmembrane conductance regulator channel affects other ion transporting mechanisms. Our model suggests the electrogenicity of the anion exchanger has little effect in the submandibular duct.
C1 [Patterson, Kate; Sneyd, James] Univ Auckland, Dept Math, Auckland 1142, New Zealand.
[Catalan, Marcelo A.; Melvin, James E.] Natl Inst Dent & Craniofacial Res, Secretory Mech & Dysfunct Sect, Div Intramural Res, NIH, Bethesda, MD USA.
[Yule, David I.] Univ Rochester, Med Ctr, Dept Pharmacol & Physiol, Rochester, NY 14642 USA.
[Yule, David I.] Univ Rochester, Med Ctr, Ctr Oral Biol, Rochester, NY 14642 USA.
[Crampin, Edmund J.] Univ Auckland, Auckland Bioengn Inst, Auckland 1142, New Zealand.
[Crampin, Edmund J.] Univ Auckland, Dept Engn Sci, Auckland 1142, New Zealand.
RP Patterson, K (reprint author), Univ Auckland, Dept Math, Private Bag 92019, Auckland 1142, New Zealand.
EM k.patterson@math.auckland.ac.nz
RI Sneyd, James/C-8995-2009;
OI Sneyd, James/0000-0001-7305-2862; Catalan, Marcelo/0000-0003-3544-2821
FU National Institute of Dental Research Grant [R01-DE-19245]
FX This work was supported by the National Institute of Dental Research
Grant R01-DE-19245.
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PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1857
J9 AM J PHYSIOL-GASTR L
JI Am. J. Physiol.-Gastroint. Liver Physiol.
PD NOV
PY 2012
VL 303
IS 10
BP G1153
EP G1163
DI 10.1152/ajpgi.00364.2011
PG 11
WC Gastroenterology & Hepatology; Physiology
SC Gastroenterology & Hepatology; Physiology
GA 039DH
UT WOS:000311222700009
PM 22899825
ER
PT J
AU McMurray, B
AF McMurray, Bob
TI Bob McMurray Award for Distinguished Scientific Early Career
Contributions to Psychology
SO AMERICAN PSYCHOLOGIST
LA English
DT Biographical-Item
C1 [McMurray, Bob] Natl Inst Environm Hlth Sci, Chris Portiers Lab, Res Triangle Pk, NC 27709 USA.
[McMurray, Bob] Univ Rochester, Rochester, NY 14627 USA.
[McMurray, Bob] Cornell, Dept Psychol, Ithaca, NY USA.
[McMurray, Bob] Delta Ctr, Iowa City, IA USA.
[McMurray, Bob] Univ Illinois, Chicago, IL 60680 USA.
[McMurray, Bob] Univ Kansas, Lawrence, KS 66045 USA.
RP McMurray, B (reprint author), Natl Inst Environm Hlth Sci, Chris Portiers Lab, Res Triangle Pk, NC 27709 USA.
NR 1
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U2 4
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
J9 AM PSYCHOL
JI Am. Psychol.
PD NOV
PY 2012
VL 67
IS 8
BP 635
EP 637
DI 10.1037/a0030052
PG 3
WC Psychology, Multidisciplinary
SC Psychology
GA 036EC
UT WOS:000311008200010
ER
PT J
AU Watson, DLB
Sanoff, R
Mackintosh, JE
Saver, JL
Ford, GA
Price, C
Starkman, S
Eckstein, M
Conwit, R
Grace, A
Murtagh, MJ
AF Watson, Duika L. Burges
Sanoff, Randy
Mackintosh, Joan E.
Saver, Jeffrey L.
Ford, Gary A.
Price, Christopher
Starkman, Sidney
Eckstein, Marc
Conwit, Robin
Grace, Anna
Murtagh, Madeleine J.
TI Evidence From the Scene: Paramedic Perspectives on Involvement in
Out-of-Hospital Research
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID EMERGENCY MEDICAL-SERVICES; RANDOMIZED CONTROLLED-TRIALS; EXPLICIT
INFORMED-CONSENT; CLINICAL-RESEARCH; HEALTH-CARE; STROKE; THROMBOLYSIS;
PARTICIPATION; SYSTEMS; ELICITATION
AB Study objective: In the context of calls to develop better systems for out-of-hospital clinical research, we seek to understand paramedics' perceptions of involvement in research and the barriers and facilitators to that involvement.
Methods: This was a qualitative study using semistructured focus groups with 58 United Kingdom paramedics and interviews with 30 US firefighter-paramedics. The study focused on out-of-hospital research (trials of out-of-hospital treatment for stroke), whereby paramedics identified potential study subjects or obtained consent and administered study treatment in the field. Data were analyzed with a thematic and discourse approach.
Results: Three key themes emerged as significant facilitators and barriers to paramedic involvement in research: patient benefit, professional identity and responsibility, and time. Paramedics showed willingness and capacity to engage in research but also some reticence because of the perceived sacrifice of autonomy and challenge to their identity. Paramedics work in a time-sensitive environment and were concerned that research would increase time taken in the field.
Conclusion: Awareness of these perspectives will help with development of out-of-hospital research protocols and potentially facilitate greater participation. [Ann Emerg Med. 2012;60:641-650.]
C1 [Murtagh, Madeleine J.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
[Watson, Duika L. Burges; Mackintosh, Joan E.; Murtagh, Madeleine J.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Watson, Duika L. Burges] Univ Durham, Sch Med & Hlth, Durham DH1 3HP, England.
[Sanoff, Randy; Saver, Jeffrey L.; Starkman, Sidney; Grace, Anna] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Price, Christopher] Northumbria Healthcare NHS Fdn Trust, Stroke Res Grp, Northumbria, Northd, England.
[Ford, Gary A.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Eckstein, Marc] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Eckstein, Marc] Los Angeles City Fire Dept, Los Angeles, CA USA.
[Conwit, Robin] NINDS, Bethesda, MD 20892 USA.
RP Murtagh, MJ (reprint author), Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.
EM mm399@le.ac.uk
OI Burges Watson, Duika/0000-0002-5791-9670; Saver,
Jeffrey/0000-0001-9141-2251
FU United Kingdom-based National Institute for Health Research (NIHR);
US-based National Institutes of Health (NIH); NIHR [RP-PG-0606-1241];
NIH-NINDS [U01 NS 44364]
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). This interview study forms part of an integrated
program of research, the Developing and Assessing Services for
Hyper-acute Stroke (DASH) trial, conducted in England. This incorporates
an international comparative component involving the Field
Administration of Stroke Therapy-Magnesium (FAST-MAG) phase 3 trial.
DASH is funded by the United Kingdom-based National Institute for Health
Research (NIHR). FAST-MAG is funded by the US-based National Institutes
of Health (NIH). This article presents independent research commissioned
by the NIHR under its Programme Grants for Applied Research
(RP-PG-0606-1241). Professor Ford is supported by an NIHR Senior
Investigator Award. Supported in part by NIH-NINDS Award U01 NS 44364.
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PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD NOV
PY 2012
VL 60
IS 5
BP 641
EP 650
DI 10.1016/j.annemergmed.2011.12.002
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA 035FN
UT WOS:000310928800019
ER
PT J
AU Grady, PA
AF Grady, Patricia A.
TI "The National Institute of Nursing Research: Delivering on the promise"
SO APPLIED NURSING RESEARCH
LA English
DT Editorial Material
C1 NINR, NIH, Bethesda, MD 20892 USA.
RP Grady, PA (reprint author), NINR, NIH, Bethesda, MD 20892 USA.
EM info@ninr.nih.gov
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0897-1897
J9 APPL NURS RES
JI Appl. Nurs. Res.
PD NOV
PY 2012
VL 25
IS 4
BP 229
EP 230
DI 10.1016/j.apnr.2012.06.002
PG 2
WC Nursing
SC Nursing
GA 035FJ
UT WOS:000310928400001
PM 23102109
ER
PT J
AU Shankaran, S
Barnes, PD
Hintz, SR
Laptook, AR
Zaterka-Baxter, KM
McDonald, SA
Ehrenkranz, RA
Walsh, MC
Tyson, JE
Donovan, EF
Goldberg, RN
Bara, R
Das, A
Finer, NN
Sanchez, PJ
Poindexter, BB
Van Meurs, KP
Carlo, WA
Stoll, BJ
Duara, S
Guillet, R
Higgins, RD
AF Shankaran, Seetha
Barnes, Patrick D.
Hintz, Susan R.
Laptook, Abbott R.
Zaterka-Baxter, Kristin M.
McDonald, Scott A.
Ehrenkranz, Richard A.
Walsh, Michele C.
Tyson, Jon E.
Donovan, Edward F.
Goldberg, Ronald N.
Bara, Rebecca
Das, Abhik
Finer, Neil N.
Sanchez, Pablo J.
Poindexter, Brenda B.
Van Meurs, Krisa P.
Carlo, Waldemar A.
Stoll, Barbara J.
Duara, Shahnaz
Guillet, Ronnie
Higgins, Rosemary D.
CA Eunice Kennedy Shriver Natl Inst C
TI Brain injury following trial of hypothermia for neonatal
hypoxic-ischaemic encephalopathy
SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
LA English
DT Article
ID WHOLE-BODY HYPOTHERMIA; SYSTEMIC HYPOTHERMIA; RANDOMIZED-TRIAL; TERM
NEWBORNS; MRI; ASPHYXIA; PATTERNS; INFANTS; AGE
AB Objective The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic-ischaemic encephalopathy treated with hypothermia.
Design and patients Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18-22 months of age.
Results Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability.
Conclusions Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18-22 months following hypothermia for neonatal encephalopathy.
C1 [Shankaran, Seetha] Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Neonatol, Detroit, MI 48201 USA.
[Barnes, Patrick D.] Stanford Univ, Sch Med, Dept Radiol & Pediat, Palo Alto, CA 94304 USA.
[Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
[Laptook, Abbott R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Zaterka-Baxter, Kristin M.] RTI Int, Dept Stat & Epidemiol, Research Pk, NC USA.
[McDonald, Scott A.; Das, Abhik] RTI Int, Stat & Epidemiol, Research Pk, NC USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Walsh, Michele C.] Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA.
[Tyson, Jon E.] Univ Texas Houston, Med Sch Houston, Ctr Clin Res & Evidence Based Med, Houston, TX USA.
[Donovan, Edward F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA.
[Goldberg, Ronald N.] Duke Univ, Dept Pediat, Durham, NC 27706 USA.
[Bara, Rebecca] Wayne State Univ, Sch Med, Dept Pediat, Detroit, MI 48201 USA.
[Finer, Neil N.] Univ Calif San Diego, Med Ctr, Dept Paediat Neonatol, La Jolla, CA 92093 USA.
[Sanchez, Pablo J.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Poindexter, Brenda B.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN USA.
[Van Meurs, Krisa P.] Lucile Packard Childrens Hosp, Div Neonatol, Palo Alto, CA USA.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Stoll, Barbara J.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Duara, Shahnaz] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA.
[Guillet, Ronnie] Univ Rochester, Sch Med & Dent, Rochester, NY USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Shankaran, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Dept Pediat Neonatol, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM sshankar@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); Pfizer; Environmental
Protection Agency; Gerber Foundation
FX The National Institutes of Health and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD)
provided grant support for the Neonatal Research Network's whole-body
hypothermia and follow-up studies.; Dr Cotten reports having served on
the data and safety monitoring board for the Inhibitex phase 3 study of
Vernonate for the prevention of infections in preterm infants. Dr
Donovan reports having received support from the Environmental
Protection Agency (Lanphear) and the Gerber Foundation. Dr Carlo reports
holding stock options at the Pediatrix Medical Group. Dr Stevenson
reports having received research support from Pfizer.
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PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1359-2998
J9 ARCH DIS CHILD-FETAL
JI Arch. Dis. Child.-Fetal Neonatal Ed.
PD NOV
PY 2012
VL 97
IS 6
BP F398
EP F404
DI 10.1136/archdischild-2011-301524
PG 7
WC Pediatrics
SC Pediatrics
GA 036JS
UT WOS:000311022800003
PM 23080477
ER
PT J
AU Mortimer, K
Gordon, SB
Jindal, SK
Accinelli, RA
Balmes, J
Martin, WJ
AF Mortimer, Kevin
Gordon, Stephen B.
Jindal, Surinder K.
Accinelli, Roberto A.
Balmes, John
Martin, William J., II
TI Household Air Pollution Is a Major Avoidable Risk Factor for
Cardiorespiratory Disease
SO CHEST
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; WOOD SMOKE EXPOSURE; SOLID-FUEL USE;
CHRONIC-BRONCHITIS; BIOMASS FUEL; LUNG-CANCER; RESPIRATORY SYMPTOMS;
CHILDHOOD PNEUMONIA; CARBON-MONOXIDE; BIRTH-WEIGHT
AB Household air pollution (HAP) from biomass fuels, coal, and kerosene burned in open fires, primitive stoves, and lamps causes at least 2 million deaths per year. Many of these deaths occur in children <5 years of age with pneumonia and in women with COPD, lung cancer, and cardiovascular disease. HAP is inextricably linked to poverty, with activities to obtain fuel consuming a large proportion of the time and financial resources of poor households. Thus, fewer resources used in this way means less is available for basic needs like food, education, and health care. The burden of work and the exposure to smoke, particularly during cooking, are predominantly borne by women and children. Although historically HAP has not received sufficient attention from the scientific, medical, public health, development, and policy-making communities, the tide has clearly changed with the broad-based support and launch of the Global Alliance for Clean Cookstoves in 2010. There is now considerable reason for optimism that this substantial cause of cardiorespiratory morbidity and mortality will be addressed comprehensively and definitively. Drawing on our experience from four continents, we provide background information on the problem of HAP, health impacts of HAP, opportunities for research, and the current best solutions. CHEST 2012; 142(5):1308-1315
C1 [Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Mortimer, Kevin; Gordon, Stephen B.] Univ Liverpool, Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England.
[Jindal, Surinder K.] Postgrad Inst Med Educ & Res, Dept Pulm Med, Chandigarh 160012, India.
[Accinelli, Roberto A.] Univ Peruana Cayetano Heredia, Inst Invest Altura, Lima, Peru.
[Balmes, John] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Balmes, John] Univ Calif San Francisco, Berkeley, CA USA.
RP Martin, WJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, US Natl Inst Hlth, 31 Ctr Dr, Bethesda, MD 20892 USA.
EM wjmartin@mail.nih.gov
OI Gordon, Stephen/0000-0001-6576-1116; Mortimer, Kevin/0000-0002-8118-8871
FU Medical Research Council [MR/K006533/1]
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PU AMER COLL CHEST PHYSICIANS
PI NORTHBROOK
PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA
SN 0012-3692
J9 CHEST
JI Chest
PD NOV
PY 2012
VL 142
IS 5
BP 1308
EP 1315
DI 10.1378/chest.12-1596
PG 8
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 036EV
UT WOS:000311010100036
PM 23131939
ER
PT J
AU Saavedra, JM
AF Saavedra, Juan M.
TI Angiotensin II AT(1) receptor blockers as treatments for inflammatory
brain disorders
SO CLINICAL SCIENCE
LA English
DT Review
DE angiotensin II type I receptor blocker (ARB); brain; inflammation;
neuronal injury; renin-angiotensin system
ID SPONTANEOUSLY HYPERTENSIVE-RATS; CEREBRAL-BLOOD-FLOW;
CENTRAL-NERVOUS-SYSTEM; QUALITY-OF-LIFE; INNATE IMMUNE-RESPONSE;
FACTOR-KAPPA-B; CONVERTING ENZYME-INHIBITORS; RENIN-ANGIOTENSIN;
PPAR-GAMMA; ALZHEIMERS-DISEASE
AB The effects of brain AngII (angiotensin II) depend on AT(1) receptor (AngII type I receptor) stimulation and include regulation of cerebrovascular flow, autonomic and hormonal systems, stress, innate immune response and behaviour. Excessive brain AT(1) receptor activity associates with hypertension and heart failure, brain ischaemia, abnormal stress responses, blood brain barrier breakdown and inflammation. These are risk factors leading to neuronal injury, the incidence and progression of neurodegerative, mood and traumatic brain disorders, and cognitive decline. In rodents, ARBs (AT(1) receptor blockers) ameliorate stress-induced disorders, anxiety and depression, protect cerebral blood flow during stroke, decrease brain inflammation and amyloid-beta neurotoxicity and reduce traumatic brain injury. Direct anti-inflammatory protective effects, demonstrated in cultured microglia, cerebrovascular endothelial cells, neurons and human circulating monocytes, may result not only in AT(1) receptor blockade, but also from PPAR gamma (peroxisome-proliferator-activated receptor gamma) stimulation. Controlled clinical studies indicate that ARBs protect cognition after stroke and during aging, and cohort analyses reveal that these compounds significantly reduce the incidence and progression of Alzheimer's disease. ARBs are commonly used for the therapy of hypertension, diabetes and stroke, but have not been studied in the context of neurodegenerative, mood or traumatic brain disorders, conditions lacking effective therapy. These compounds are well-tolerated pleiotropic neuroprotective agents with additional beneficial cardiovascular and metabolic profiles, and their use in central nervous system disorders offers a novel therapeutic approach of immediate translational value. ARBs should be tested for the prevention and therapy of neurodegenerative disorders, in particular Alzheimer's disease, affective disorders, such as co-morbid cardiovascular disease and depression, and traumatic brain injury.
C1 NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Div Intramural Res Programs, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM Saavedrj@mail.nih.gov
FU Division of Intramural Research Programs, National Institute of Mental
Health, Department of Health and Human Services, U.S.A
FX My own work is supported by the Division of Intramural Research
Programs, National Institute of Mental Health, Department of Health and
Human Services, U.S.A.
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PI LONDON
PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
SN 0143-5221
J9 CLIN SCI
JI Clin. Sci.
PD NOV
PY 2012
VL 123
IS 9-10
BP 567
EP 590
DI 10.1042/CS20120018
PG 24
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 035FC
UT WOS:000310927600005
PM 22827472
ER
PT J
AU Casagrande, SS
Cowie, CC
AF Casagrande, Sarah Stark
Cowie, Catherine C.
TI Health Insurance Coverage Among People With and Without Diabetes in the
U.S. Adult Population
SO DIABETES CARE
LA English
DT Article
ID PREVENTIVE CARE; RISK; COMPLICATIONS; RECEIPT; DISEASE; ACCESS
AB OBJECTIVE-To compare health insurance coverage and type of coverage for adults with and without diabetes.
RESEARCH DESIGN AND METHODS-The data used were from 2,704 adults who self-reported diabetes and 25,008 adults without reported diabetes in the 2009 National Health Interview Survey. Participants reported on their current type of health insurance coverage, demographic information, diabetes-related factors, and comorbidities. If uninsured, participants reported reasons for not having health insurance.
RESULTS-Among all adults with diabetes, 90% had some form of health insurance coverage, including 85% of people 18-64 years of age and similar to 100% of people >= 65 years of age; 81% of people without diabetes had some type of coverage (vs. diabetes, P < 0.0001), including 78% of people 18-64 years of age and 99% of people >= 65 years of age. More adults 18-64 years of age with diabetes had Medicare coverage (14% vs. no diabetes, 3%; P < 0.0001); fewer people with diabetes had private insurance (58% vs. no diabetes, 66%; P < 0.0001). People 18-64 years of age with diabetes more often had two health insurance sources compared with people without diabetes (13 vs. 5%, P < 0.0001). The most common private plan was a preferred provider organization (PPO) followed by a health maintenance organization/independent practice organization (HMO/IPA) plan regardless of diabetes status. For participants 18-64 years of age, high health insurance cost was the most common reason for not having coverage.
CONCLUSIONS-Two million adults,65 years of age with diabetes had no health insurance coverage, which has considerable public health and economic impact. Health care reform should work toward ensuring that people with diabetes have coverage for routine care. Diabetes Care 35: 2243-2249, 2012
C1 [Casagrande, Sarah Stark] Social & Sci Syst Inc, Silver Spring, MD USA.
[Cowie, Catherine C.] NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA.
RP Casagrande, SS (reprint author), Social & Sci Syst Inc, Silver Spring, MD USA.
EM scasagrande@s-3.com
FU National Institute of Diabetes and Digestive and Kidney Diseases
[HH-SN-267200700001G]
FX This work was financially supported by the National Institute of
Diabetes and Digestive and Kidney Diseases (HH-SN-267200700001G).
NR 21
TC 4
Z9 4
U1 3
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD NOV
PY 2012
VL 35
IS 11
BP 2243
EP 2249
DI 10.2337/dc12-0257
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 041TM
UT WOS:000311424100026
ER
PT J
AU Steinert, EM
Schwartz, RH
Singh, NJ
AF Steinert, Elizabeth M.
Schwartz, Ronald H.
Singh, Nevil J.
TI At low precursor frequencies, the T-cell response to chronic
self-antigen results in anergy without deletion
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Clonal anergy; Clonal deletion; Immunological tolerance; Precursor
frequency; T cells
ID IN-VIVO; ADAPTIVE TOLERANCE; NAIVE; COMPETITION; PROLIFERATION;
DIFFERENTIATION; EXPOSURE
AB The behavior of self-reactive T cells in the peripheral immune system has often been studied by following the fate of adoptively transferred antigen-specific T cells in antigen expressing mice. In most cases, after a period of expansion, such cells undergo a slow clonal deletion, accompanied by the onset of anergy and/or suppression in the remaining cells. Here, we demonstrate that at initial frequencies approaching those found in normal repertoires, it is possible to completely avoid deletion and still maintain peripheral tolerance. At starting numbers of <1000 T cells, stimulation by chronic self-antigens resulted in a period of robust clonal expansion, followed by a steady plateau phase extending beyond 4 months. Despite their stable persistence, the self-reactive T cells did not convert to a Foxp3+ fate. However, they displayed a considerable block in their ability to make IL-2, consistent with the onset of anergy in a precursor frequency or deletion independent fashion.
C1 [Singh, Nevil J.] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Steinert, Elizabeth M.] Univ Minnesota, Sch Med, Dept Microbiol, Ctr Immunol, Minneapolis, MN 55455 USA.
RP Singh, NJ (reprint author), NIAID, Lab Cellular & Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nsingh@niaid.nih.gov
FU NIH, NIAID
FX We thank Eleanore Chuang for assistance with experiments, and Pascal
Chappert for discussions. This research was supported by the Intramural
Research Program of the NIH, NIAID.
NR 21
TC 6
Z9 6
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD NOV
PY 2012
VL 42
IS 11
BP 2875
EP 2880
DI 10.1002/eji.201242518
PG 6
WC Immunology
SC Immunology
GA 030BY
UT WOS:000310544000007
PM 22806568
ER
PT J
AU Baig, S
Garcia, F
Fricano, K
Deng, J
Mao, M
Christman, J
Chatterjee, S
Block, M
Minshall, R
Ye, R
Gantner, B
Bonini, MG
AF Baig, Saqib
Garcia, Farnaz
Fricano, Kristine
Deng, Jing
Mao, Mao
Christman, John
Chatterjee, Saurabh
Block, Michelle
Minshall, Richard
Ye, Richard
Gantner, Benjamin
Bonini, Marcelo G.
TI Ablation of NNOS/NOS1 Leads to the Suppression of the Systemic
Inflammatory Response via Suppressor of Cytokine Signaling (SOCS-1)
Upregulation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Baig, Saqib; Garcia, Farnaz; Fricano, Kristine; Deng, Jing; Mao, Mao; Christman, John; Minshall, Richard; Ye, Richard; Gantner, Benjamin; Bonini, Marcelo G.] Univ Illinois, Chicago, IL 60680 USA.
[Chatterjee, Saurabh] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Block, Michelle] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
RI Mao, Mao/E-3783-2013
OI Mao, Mao/0000-0003-1524-8853
NR 0
TC 0
Z9 0
U1 0
U2 2
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 NOV 1
PY 2012
VL 53
SU 2
BP S74
EP S74
DI 10.1016/j.freeradbiomed.2012.10.221
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600188
ER
PT J
AU Bellavia, L
Solomon, SB
Sweeney, D
Piknova, B
Perlegas, A
Helms, CC
King, SB
Raat, NJH
Kern, SJ
Sun, JF
Mcphail, LC
Schechter, AN
Natanson, C
Gladwin, MT
Kim-Shapiro, DB
AF Bellavia, Landon
Solomon, Steven B.
Sweeney, Daniel
Piknova, Barbora
Perlegas, Andreas
Helms, Christine C.
King, S. Bruce
Raat, Nicolaas J. H.
Kern, Steven J.
Sun, Junfeng
Mcphail, Linda C.
Schechter, Alan N.
Natanson, Charles
Gladwin, Mark T.
Kim-Shapiro, Daniel B.
TI Angeli's Salt Counteracts the Vasoactive Effects of Elevated Plasma
Hemoglobin
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Mcphail, Linda C.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Solomon, Steven B.; Sweeney, Daniel; Piknova, Barbora; Kern, Steven J.; Sun, Junfeng; Schechter, Alan N.; Natanson, Charles] NIH, Bethesda, MD USA.
[Gladwin, Mark T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
RI McPhail, Linda/D-9505-2013
OI McPhail, Linda/0000-0002-8670-306X
NR 0
TC 0
Z9 0
U1 0
U2 3
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 NOV 1
PY 2012
VL 53
SU 2
BP S178
EP S178
DI 10.1016/j.freeradbiomed.2012.10.489
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600469
ER
PT J
AU Bhattacharjee, S
Jiang, JJ
Chatterjee, S
Deterding, L
Sinha, B
Mason, R
AF Bhattacharjee, Suchandra
Jiang, Jinjie
Chatterjee, Saurabh
Deterding, Leesa
Sinha, Birandra
Mason, Ron
TI Site-Specific Detection and Imaging of Free Radicals in DNA Induced by
Cu(11)-H2O2 Oxidizing System and Its Repair Using ESR, Immuno-Spin
Trapping, Confocal Microscopy, LC-MS and MS/MS
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Bhattacharjee, Suchandra; Jiang, Jinjie; Deterding, Leesa; Sinha, Birandra; Mason, Ron] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 10
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 NOV 1
PY 2012
VL 53
SU 2
BP S133
EP S133
DI 10.1016/j.freeradbiomed.2012.10.361
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600346
ER
PT J
AU Ehrenshaft, M
Roberts, JE
Mason, RP
AF Ehrenshaft, Marilyn
Roberts, Joan E.
Mason, Ronald P.
TI Hypericin Photosensitization of alpha-Crystallin in Human Lens
Epithelial Cells
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA.
[Roberts, Joan E.] Fordham Univ, Bronx, NY 10458 USA.
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 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S134
EP S134
DI 10.1016/j.freeradbiomed.2012.10.365
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600350
ER
PT J
AU Esworthy, RS
Kim, BW
Doroshow, JH
Leto, TL
Chu, FF
AF Esworthy, Robert Steven
Kim, Byung-Wook
Doroshow, James H.
Leto, Thomas L.
Chu, Fong-Fong
TI Glutathione Peroxidase-1 and-2 Protect Mice from Salmonella-Induced
Colitis
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Esworthy, Robert Steven; Kim, Byung-Wook; Chu, Fong-Fong] Beckman Res Inst City Hope, Duarte, CA USA.
[Doroshow, James H.] NCI, Bethesda, MD 20892 USA.
[Leto, Thomas L.] NIAID, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S75
EP S75
DI 10.1016/j.freeradbiomed.2012.10.224
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600191
ER
PT J
AU Ganini, D
Mason, RP
AF Ganini, Douglas
Mason, Ronald P.
TI Lipoperoxidation with Consequent Protein Radical Formation During LDL
Oxidation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Ganini, Douglas; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
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 NOV 1
PY 2012
VL 53
SU 2
BP S135
EP S135
DI 10.1016/j.freeradbiomed.2012.10.366
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600351
ER
PT J
AU Helms, CC
Marvel, M
Stahle, M
Hantgan, RR
Kato, GJ
Lee, JS
Gladwin, M
Kim-Shapiro, DB
AF Helms, Christine Carlisle
Marvel, Madison
Stahle, Mary
Hantgan, Roy R.
Kato, Gregory J.
Lee, Janet S.
Gladwin, Mark
Kim-Shapiro, Daniel B.
TI The Role of Free Radicals in Hemolysis Associated Platelet Activation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Helms, Christine Carlisle; Marvel, Madison; Stahle, Mary; Hantgan, Roy R.; Kim-Shapiro, Daniel B.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Kato, Gregory J.] NHLBI, NIH, Bethesda, MD USA.
[Lee, Janet S.; Gladwin, Mark] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
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 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S162
EP S163
DI 10.1016/j.freeradbiomed.2012.10.444
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600426
ER
PT J
AU Horinouchi, Y
Summers, FA
Ehrenshaft, M
Mason, RP
AF Horinouchi, Yuya
Summers, Fiona A.
Ehrenshaft, Marilyn
Mason, Ronald P.
TI An Aromatic Nitroso Compound, N,N-Dimethyl-4-Nitrosoaniline, Generates
Free Radicals in Hepatocytes as Detected Via Immuno-Spin Trapping
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Horinouchi, Yuya; Summers, Fiona A.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
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 NOV 1
PY 2012
VL 53
SU 2
BP S22
EP S23
DI 10.1016/j.freeradbiomed.2012.10.053
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600049
ER
PT J
AU Jang, S
Gao, Y
Abdelmegeed, MA
Banerjee, A
Yu, LR
Song, BJ
AF Jang, Sehwan
Gao, Yuan
Abdelmegeed, Mohamed A.
Banerjee, Atrayee
Yu, Li-Rong
Song, B. J.
TI Role of JNK-Mediated Phosphorylation in Mitochondrial Dysfunction and
Liver Injury
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Jang, Sehwan; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, B. J.] NIAAA, NIH, Bethesda, MD USA.
[Gao, Yuan; Yu, Li-Rong] US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV 1
PY 2012
VL 53
SU 2
BP S143
EP S144
DI 10.1016/j.freeradbiomed.2012.10.389
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600373
ER
PT J
AU Kumar, A
Ganini-Da Silva, D
Deterding, LJ
Ehrenshaft, M
Mason, RP
AF Kumar, Ashutosh
Ganini-Da Silva, Douglas
Deterding, Leesa J.
Ehrenshaft, Marilyn
Mason, Ronald P.
TI Immuno-Spin Trapping of Heme-Induced Protein Radicals; Implications for
Heme Oxygenase-1 Induction and Heme Degradation
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Kumar, Ashutosh; Ganini-Da Silva, Douglas; Deterding, Leesa J.; Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV 1
PY 2012
VL 53
SU 2
BP S135
EP S136
DI 10.1016/j.freeradbiomed.2012.10.369
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600354
ER
PT J
AU Mukhopadhyay, P
Horvath, B
Zsengeller, Z
Batkai, S
Cao, ZX
Kechrid, M
Erdelyi, K
Tanchian, G
Liaudet, L
Stillman, IE
Joseph, J
Kalyanaraman, B
Pacher, P
AF Mukhopadhyay, Partha
Horvath, Bela
Zsengeller, Zsuzsanna
Batkai, Sandor
Cao, Zongxian
Kechrid, Malek
Erdelyi, Katalin
Tanchian, Galin
Liaudet, Lucas
Stillman, Isaac E.
Joseph, Joy
Kalyanaraman, Balaraman
Pacher, Pal
TI Mitochondrially Targeted Antioxidants Ameliorate Inflammatory Response
and Tissue Injury Associated with Hepatic Ischemia-Reperfusion in Mice
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Mukhopadhyay, Partha; Horvath, Bela; Batkai, Sandor; Cao, Zongxian; Kechrid, Malek; Erdelyi, Katalin; Tanchian, Galin; Pacher, Pal] NIH, Bethesda, MD USA.
[Zsengeller, Zsuzsanna; Stillman, Isaac E.] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Zsengeller, Zsuzsanna; Stillman, Isaac E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RI Horvath, Bela/A-7368-2009; Pacher, Pal/B-6378-2008; Batkai,
Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
NR 0
TC 0
Z9 0
U1 0
U2 5
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 NOV 1
PY 2012
VL 53
SU 2
BP S113
EP S113
DI 10.1016/j.freeradbiomed.2012.10.276
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600293
ER
PT J
AU Nagababu, E
Hesdorffer, CS
Rifkind, JM
AF Nagababu, Enika
Hesdorffer, Charles S.
Rifkind, Joseph M.
TI Increased Oxidative Stress in Humans Under Pathological Conditions
Measured by Fluorescent Heme Degradation Product in Red Blood Cells and
Whole Blood
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Nagababu, Enika; Hesdorffer, Charles S.; Rifkind, Joseph M.] NIA, Bethesda, MD 20892 USA.
NR 0
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 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S127
EP S127
DI 10.1016/j.freeradbiomed.2012.10.315
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600331
ER
PT J
AU Nam, Y
Dang, DK
Tu, THT
Bach, JH
Shin, EJ
Bing, G
Hong, JS
Kim, HC
AF Nam, Yunsung
Dang, Duy-Khanh
Thu-Hien Thi Tu
Bach, Jae-Hyung
Shin, Eun-Joo
Bing, Guoying
Hong, Jau-Shyong
Kim, Hyoung-Chun
TI Dynorphin Provides Neuroprotection Against Methamphetamine-Induced
Neurotoxicity via Activating Glutathione-Dependent Antioxidant Enzymes,
but not via Modulating Classical kappa-Opioid Receptors
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Nam, Yunsung; Dang, Duy-Khanh; Thu-Hien Thi Tu; Bach, Jae-Hyung; Shin, Eun-Joo; Kim, Hyoung-Chun] Kangwon Natl Univ, Kangwon Do, South Korea.
[Nam, Yunsung] Chung Ang Univ, Seoul, South Korea.
[Bing, Guoying] Univ Kentucky, Med Ctr, Lexington, KY 40506 USA.
[Hong, Jau-Shyong] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 NOV 1
PY 2012
VL 53
SU 2
BP S69
EP S69
DI 10.1016/j.freeradbiomed.2012.10.208
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600176
ER
PT J
AU Park, JW
Piknova, B
Schechter, AN
AF Park, Ji-Won
Piknova, Barbora
Schechter, Alan N.
TI Effect of Blood Nitrite and Nitrate Levels on Platelet Function in Mice
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Park, Ji-Won; Piknova, Barbora; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA.
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 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S184
EP S185
DI 10.1016/j.freeradbiomed.2012.10.509
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600489
ER
PT J
AU Piknova, B
Silva, AC
Schechter, AN
AF Piknova, Barbora
Silva, Afonso C.
Schechter, Alan N.
TI NO Production in Rat Brain - Possible Non-enzymatic Pathways
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Piknova, Barbora; Schechter, Alan N.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Silva, Afonso C.] NINDS, NIH, Bethesda, MD USA.
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 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S185
EP S185
DI 10.1016/j.freeradbiomed.2012.10.510
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600490
ER
PT J
AU Summers, FA
Mason, RP
Ehrenshaft, M
AF Summers, Fiona A.
Mason, Ronald P.
Ehrenshaft, Marilyn
TI Development of Immunoblotting Techniques for DNA Radical Detection
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Summers, Fiona A.; Mason, Ronald P.; Ehrenshaft, Marilyn] NIEHS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD NOV 1
PY 2012
VL 53
SU 2
BP S139
EP S139
DI 10.1016/j.freeradbiomed.2012.10.379
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600364
ER
PT J
AU Takakusagi, Y
Matsumoto, S
Saito, K
Matsuo, M
DeGraff, W
Choudhuri, R
Devasahayam, N
Subramanian, S
Munasinghe, JP
Hart, CP
Krishna, MC
Mitchell, JB
AF Takakusagi, Yoichi
Matsumoto, Shingo
Saito, Keita
Matsuo, Masayuki
DeGraff, William
Choudhuri, Rajani
Devasahayam, Nallathamby
Subramanian, Sankaran
Munasinghe, Jeeva P.
Hart, Charles P.
Krishna, Murali C.
Mitchell, James B.
TI Enhancement of the Efficacy of Hypoxia Dependent Cytotoxicity of the
Bioreductively Activated Hypoxia-Activated Prodrug TH-302
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Meeting Abstract
CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine
(SFRBM)
CY NOV 14-18, 2012
CL San Diego, CA
SP Soc Free Rad Biol & Med (SFRBM)
C1 [Takakusagi, Yoichi; Matsumoto, Shingo; Saito, Keita; Matsuo, Masayuki; DeGraff, William; Choudhuri, Rajani; Devasahayam, Nallathamby; Subramanian, Sankaran; Krishna, Murali C.; Mitchell, James B.] Natl Canc Inst, Bethesda, MD USA.
[Munasinghe, Jeeva P.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 6
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 NOV 1
PY 2012
VL 53
SU 2
BP S119
EP S119
DI 10.1016/j.freeradbiomed.2012.10.294
PG 1
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 031RS
UT WOS:000310660600311
ER
PT J
AU Sokolov, MV
Panyutin, IG
Neumann, RD
AF Sokolov, Mykyta V.
Panyutin, Igor G.
Neumann, Ronald D.
TI Whole-genome gene expression profiling reveals the major role of nitric
oxide in mediating the cellular transcriptional response to ionizing
radiation in normal human fibroblasts
SO GENOMICS
LA English
DT Article
DE Nitric oxide; Normal human fibroblast; Ionizing radiation; DNA
microarray
ID TARGETED CYTOPLASMIC IRRADIATION; HUMAN-CELLS; RADIOADAPTIVE RESPONSE;
GLIOMA-CELLS; RADIORESISTANCE; PARTICLES; INDUCTION; APOPTOSIS;
SURVIVAL; ARREST
AB The indirect biological effects of ionizing radiation (IR) are thought to be mediated largely by reactive oxygen and nitrogen species (ROS and RNS). However, no data are available on how nitric oxide (NO) modulates the response of normal human cells to IR exposures at the level of the whole transcriptome. Here, we examined the effects of NO and ROS scavengers, carboxy-PTIO and DMSO, on changes in global gene expression in cultured normal human fibroblasts after exposures to gamma-rays, aiming to elucidate the involvement of ROS and RNS in transcriptional response to IR. We found that NO depletion dramatically affects the gene expression in normal human cells following irradiation with gamma-rays. We observed striking (more than seven-fold) reduction of the number of upregulated genes upon NO scavenging compared to reference irradiated cell cultures. NO scavenging in irradiated IMR-90 cells results in induction of p53 signaling, DNA damage and DNA repair pathways. Published by Elsevier Inc.
C1 [Sokolov, Mykyta V.; Panyutin, Igor G.; Neumann, Ronald D.] NIH, Div Nucl Med, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
RP Sokolov, MV (reprint author), 9000 Rockville Pike,Bldg 10,Room 4049, Bethesda, MD 20892 USA.
EM sokolovm@mail.nih.gov; ipanyuting@mail.nih.gov; rneumann@mail.nih.gov
FU National Institutes of Health, Clinical Center
FX We wish to thank W. DeGraff for his invaluable help with cell culture
irradiation. This work was supported by the Intramural Research Program
of the National Institutes of Health, Clinical Center.
NR 34
TC 1
Z9 1
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0888-7543
J9 GENOMICS
JI Genomics
PD NOV
PY 2012
VL 100
IS 5
BP 277
EP 281
DI 10.1016/j.ygeno.2012.07.007
PG 5
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA 035GJ
UT WOS:000310931100003
PM 22814268
ER
PT J
AU Soto-Pantoja, D
Miller, T
Pendrak, M
DeGraff, W
Sullivan, C
Ridnour, L
Abu-Asab, M
Wink, D
Tsokos, M
Roberts, D
AF Soto-Pantoja, David
Miller, Thomas
Pendrak, Michael
DeGraff, William
Sullivan, Camille
Ridnour, Lisa
Abu-Asab, Mones
Wink, David
Tsokos, Maria
Roberts, David
TI Thrombospondin-1 signaling through CD47 regulates cell and tissue
radiosensitivity via autophagy
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Soto-Pantoja, David; Miller, Thomas; Pendrak, Michael; Sullivan, Camille; Abu-Asab, Mones; Tsokos, Maria; Roberts, David] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[DeGraff, William; Ridnour, Lisa; Wink, David] NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA.
RI Miller, Thomas/G-1215-2011
OI Miller, Thomas/0000-0001-8645-2785
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1519
EP 1520
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700016
ER
PT J
AU Tran, D
Lim, JM
Liu, M
Stalnaker, S
Wells, L
Ten Hagen, K
David, L
AF Tran, Duy
Lim, Jae-Min
Liu, Mian
Stalnaker, Stephanie
Wells, Lance
Ten Hagen, Kelly
David, Live
TI alpha-Dystroglycan O-mannosylation influences the subsequent addition of
GalNAc by UDP-GalNAc polypeptide N-acetylgalactosaminyltransferases
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Tran, Duy; Ten Hagen, Kelly] NIDCR, NIH, Bethesda, MD USA.
[Lim, Jae-Min; Liu, Mian; Stalnaker, Stephanie; Wells, Lance; David, Live] Univ Georgia, CCRC, Athens, GA 30602 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1546
EP 1546
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700087
ER
PT J
AU Bond, M
Ghosh, S
Krause, M
Hanover, J
AF Bond, Michelle
Ghosh, Salil
Krause, Michael
Hanover, John
TI The Caenorhabditis elegans innate immune response to S-aureus is
modulated by O-GlcNAc transferase
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Bond, Michelle; Krause, Michael; Hanover, John] NIDDK, NIH, Bethesda, MD 20892 USA.
[Ghosh, Salil] US FDA, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1551
EP 1552
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700105
ER
PT J
AU Petrie, R
Yamada, K
AF Petrie, Ryan
Yamada, Kenneth
TI Actomyosin cytoskeletal organization distinguishes lobopodia from
lamellipodia
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Petrie, Ryan; Yamada, Kenneth] NIDCR, Lab Cell & Dev Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1583
EP 1583
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700194
ER
PT J
AU Tian, E
Hoffman, M
Ten Hagen, K
AF Tian, E.
Hoffman, Matthew
Ten Hagen, Kelly
TI O-glycosylation modulates integrin and FGF signaling by influencing the
secretion of basement membrane
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Tian, E.; Hoffman, Matthew; Ten Hagen, Kelly] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1621
EP 1621
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700309
ER
PT J
AU Tsutsui, Y
Ramakrishnan, B
Qasba, P
AF Tsutsui, Yuko
Ramakrishnan, Boopathy
Qasba, Pradman
TI A Crystal Structure of Human beta-1,4-Galactosyltransferase 7
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 Frederick Natl Lab Canc Res, Frederick, MD USA.
SAIC Frederick Inc, SGS, CCR NP, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1641
EP 1641
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700367
ER
PT J
AU Wang, LL
Campbell, C
Cummings, R
Gerlach, JQ
Gildersleeve, JC
Huflejt, M
Joshi, L
Kane, M
Pieters, R
Reichardt, N
Smith, D
Mahal, LK
AF Wang, Linlin
Campbell, Christopher
Cummings, Richard
Gerlach, Jared Q.
Gildersleeve, Jeffrey C.
Huflejt, Margaret
Joshi, Lokesh
Kane, Marian
Pieters, Roland
Reichardt, Neils
Smith, David
Mahal, Lara K.
TI Cross-platform comparison of carbohydrate microarrays: Six groups and
five lectins
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Joint Meeting of the Society-for-Glycobiology and
American-Society-for-Matrix-Biology
CY NOV 11-14, 2012
CL San Diego, CA
SP Soc Glycobiol, Amer Soc Matrix Biol
C1 [Huflejt, Margaret] NYU, Langone Med Ctr, New York, NY 10003 USA.
[Campbell, Christopher] NCI, Bethesda, MD 20892 USA.
[Cummings, Richard; Smith, David] Emory Univ, Atlanta, GA 30322 USA.
[Gerlach, Jared Q.; Joshi, Lokesh; Kane, Marian] NUI Galway, Natl Diagnost Ctr, Galway, Ireland.
[Pieters, Roland] Univ Utrecht, NL-3508 TC Utrecht, Netherlands.
RI Gildersleeve, Jeffrey/N-3392-2014
NR 0
TC 0
Z9 0
U1 0
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2012
VL 22
IS 11
BP 1647
EP 1647
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 027QS
UT WOS:000310368700383
ER
PT J
AU Heroux, M
Iannotti, RJ
Currie, D
Pickett, W
Janssen, I
AF Heroux, Mariane
Iannotti, Ronald J.
Currie, Dorothy
Pickett, William
Janssen, Ian
TI The food retail environment in school neighborhoods and its relation to
lunchtime eating behaviors in youth from three countries
SO HEALTH & PLACE
LA English
DT Article
DE Food retail environment; Lunchtime eating behavior; Obesity; School;
Youth
ID US PUBLIC-SCHOOLS; PHYSICAL-ACTIVITY; OBESITY; OVERWEIGHT; ADOLESCENTS;
CONSUMPTION; CHILDHOOD; PATTERNS; ASSOCIATIONS; RESTAURANTS
AB This study examined the relation between the chain food retail environment surrounding schools, youths' lunchtime eating behavior, and youths' obesity levels across three countries. Participants consisted of 26,778 students 13-15 years old from 687 schools across Canada, Scotland and the US. The density of convenience stores, chain fast food restaurants, and chain cafes within 1 km of each school was measured. Lunchtime eating behaviors, weight, and height were self-reported. Although the density of chain food retailers was highest in the US, fewer American students (2.6%) routinely ate their lunch at a food retailer during the school week than did Canadian (7.7%) and Scottish (43.7%) students. The density of chain food retailers was associated with eating lunch at a food retailer in Canada only whereby students attending schools with 1-2, 3-4, and 5+ chain food retailers within 1 km from their schools were 1.39 (95% CI: 0.84-2.29), 1.87 (95% CI: 1.10-3.20), and 2.50 (95% CI: 1.56-4.01) times more likely to eat at a chain food retailer compared to students attending schools with no nearby chain food retailers. No associations were found between chain food retailer density and obesity. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Heroux, Mariane; Janssen, Ian] Queens Univ, Sch Kinesiol & Hlth Studies, Kingston, ON K7L 3N6, Canada.
[Iannotti, Ronald J.] Eunice Kennedy Shriver Natl Inst Chil Hlth & Huma, Prevent Res Branch, Bethesda, MD 20892 USA.
[Currie, Dorothy] Univ St Andrews, Child & Adolescent Hlth Res Unit, St Andrews KY16 9TF, Fife, Scotland.
[Pickett, William; Janssen, Ian] Queens Univ, Dept Epidemiol & Community Hlth, Kingston, ON K7L 3N6, Canada.
[Pickett, William] Kingston Gen Hosp, Dept Emergency Med, Kingston, ON K7L 3N6, Canada.
RP Janssen, I (reprint author), Queens Univ, Sch Kinesiol & Hlth Studies, 28 Div St, Kingston, ON K7L 3N6, Canada.
EM ian.janssen@queensu.ca
RI Janssen, Ian/B-7700-2009
FU Public Health Agency of Canada, Health Canada; Canadian Institutes of
Health Research [MOP 97962]; Heart and Stroke Foundation of Canada [PCR
101415]; NHS Health Scotland; Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; Maternal and Child Health Bureau of the Health Resources
and Services Administration; Canadian Institutes of Health Research
doctoral award; Canada Research Chair award
FX The HBSC is a WHO/Euro collaborative study; International Coordinator of
the 2009-2010 study is Candace Currie, St. Andrews University, Scotland;
Data Bank Manager is Oddrun Samdal, University of Bergen, Norway. This
Canadian HBSC (PI: John Freeman, William Pickett) was funded by the
Public Health Agency of Canada, Health Canada, the Canadian Institutes
of Health Research (MOP 97962), and the Heart and Stroke Foundation of
Canada (PCR 101415). The Scottish HBSC (PI: Candace Currie) was
supported by NHS Health Scotland. The US HBSC (PI: Ronald J Iannotti)
was partially supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the Maternal and Child Health Bureau of the Health Resources and
Services Administration. M Heroux was supported by a Canadian Institutes
of Health Research doctoral award and I Janssen was supported by a
Canada Research Chair award.
NR 53
TC 14
Z9 14
U1 2
U2 19
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8292
J9 HEALTH PLACE
JI Health Place
PD NOV
PY 2012
VL 18
IS 6
BP 1240
EP 1247
DI 10.1016/j.healthplace.2012.09.004
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 037XW
UT WOS:000311140800005
PM 23041489
ER
PT J
AU Ferrer, RA
Klein, WMP
Zajac, LE
Sutton-Tyrrell, K
Muldoon, MF
Kamarck, TW
AF Ferrer, Rebecca A.
Klein, William M. P.
Zajac, Laura E.
Sutton-Tyrrell, Kim
Muldoon, Matthew F.
Kamarck, Thomas W.
TI Unrealistic Optimism Is Associated With Subclinical Atherosclerosis
SO HEALTH PSYCHOLOGY
LA English
DT Article
DE unrealistic optimism; risk perceptions; cardiovascular disease;
subclinical atherosclerosis
ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; RISK PERCEPTIONS;
SELF-AFFIRMATION; PERSONAL RISK; ATTACK RISK; HEALTH; SMOKING;
PREDICTION; FUTURE
AB Objective: Unrealistic-optimism typically conceptualized as underestimation of comparative risk-has been previously associated with poorer health behaviors and outcomes, but no research to date has examined the association between unrealistic optimism and subclinical or clinical disease endpoints. Here, cross-sectional data from one time point in the Pittsburgh Healthy Heart study are used to examine whether unrealistic optimism about risk of heart disease is associated with carotid artery intima-media thickness (IMT), a subclinical marker of atherosclerosis. Methods: Participants were 148 adults aged 57-77. Objective risk score was calculated using the Framingham calculator, and IMT was regressed on risk score and perceived risk. Controlling for the Framingham risk score effectively equated risk across the sample, meaning that lower risk perceptions represented unrealistic optimism. Results: When controlling for the risk score, risk perceptions were negatively associated with IMT (beta = -.21, p < .01, t = -2.79, d = .46), a finding that was not moderated by gender. The risk score was also associated with IMT (beta = .42, p < .001, t = 5.55, d = .91). Conclusions: Unrealistic optimism was associated with subclinical atherosclerosis. Future longitudinal research is necessary to evaluate the temporal sequence as well as to examine putative explanatory mechanisms.
C1 [Ferrer, Rebecca A.] NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA.
[Klein, William M. P.; Zajac, Laura E.; Kamarck, Thomas W.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Sutton-Tyrrell, Kim] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Muldoon, Matthew F.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA.
RP Ferrer, RA (reprint author), NCI, Basic Biobehav & Psychol Sci Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,Room 4056, Rockville, MD 20852 USA.
EM ferrerra@mail.nih.gov
FU Heart, Lung, and Blood Institute [HL56346]
FX This study was supported by Heart, Lung, and Blood Institute (HL56346).
NR 38
TC 5
Z9 5
U1 2
U2 7
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0278-6133
J9 HEALTH PSYCHOL
JI Health Psychol.
PD NOV
PY 2012
VL 31
IS 6
BP 815
EP 820
DI 10.1037/a0027675
PG 6
WC Psychology, Clinical; Psychology
SC Psychology
GA 036IA
UT WOS:000311018400017
PM 22429124
ER
PT J
AU Tarantal, AF
Skarlatos, SI
AF Tarantal, Alice F.
Skarlatos, Sonia I.
TI Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood
Diseases: An NHLBI Resource for the Gene Therapy Community
SO HUMAN GENE THERAPY
LA English
DT Review
ID MESENCHYMAL STEM-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; HIV-1-DERIVED
LENTIVIRAL VECTORS; CHRONIC GRANULOMATOUS-DISEASE; LEBER CONGENITAL
AMAUROSIS; RHESUS-MONKEYS; MACACA-MULATTA; IN-VIVO; NONHUMAN-PRIMATES;
RETROVIRAL VECTORS
AB The goals of the National Heart, Lung, and Blood Institute (NHLBI) Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases are to conduct gene transfer studies in monkeys to evaluate safety and efficiency; and to provide NHLBI-supported investigators with expertise, resources, and services to actively pursue gene transfer approaches in monkeys in their research programs. NHLBI-supported projects span investigators throughout the United States and have addressed novel approaches to gene delivery; "proof-of-principle"; assessed whether findings in small-animal models could be demonstrated in a primate species; or were conducted to enable new grant or IND submissions. The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood Diseases successfully aids the gene therapy community in addressing regulatory barriers, and serves as an effective vehicle for advancing the field.
C1 [Tarantal, Alice F.] Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Fetal Monkey Gene Transfer Heart Lung & Blood, Davis, CA 95616 USA.
[Tarantal, Alice F.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA.
[Tarantal, Alice F.] Univ Calif Davis, Dept Cell Biol & Human Anat, Davis, CA 95616 USA.
[Skarlatos, Sonia I.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Tarantal, AF (reprint author), Univ Calif Davis, Calif Natl Primate Res Ctr, Ctr Fetal Monkey Gene Transfer Heart Lung & Blood, Pedrick & Hutchison Rd, Davis, CA 95616 USA.
EM aftarantal@primate.ucdavis.edu
FU NIH [HL069748, HL085794]; California National Primate Research Center
base operating grant (NIH) [RR00169, OD011107]
FX The Center for Fetal Monkey Gene Transfer for Heart, Lung, and Blood
Diseases is supported by NIH grants (HL069748 and HL085794) and by the
California National Primate Research Center base operating grant (NIH
grant RR00169 and OD011107).
NR 62
TC 6
Z9 6
U1 0
U2 23
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD NOV
PY 2012
VL 23
IS 11
BP 1130
EP 1135
DI 10.1089/hum.2012.178
PG 6
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 037BV
UT WOS:000311076900002
PM 22974119
ER
PT J
AU Klebanoff, CA
Gattinoni, L
Restifo, NP
AF Klebanoff, Christopher A.
Gattinoni, Luca
Restifo, Nicholas P.
TI Sorting Through Subsets: Which T-Cell Populations Mediate Highly
Effective Adoptive Immunotherapy?
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Review
DE adoptive cell transfer; CD8(+) T cell; naive CD8(+) T cell; central
memory CD8(+) T cell; effector CD8(+) T cell; memory lymphocyte; T-cell
subsets; gene engineering; chimeric antigen receptor; clinical trials
ID TUMOR-INFILTRATING LYMPHOCYTES; SUPERIOR ANTITUMOR IMMUNITY; HLA-PEPTIDE
TETRAMERS; IN-VIVO PERSISTENCE; IFN-GAMMA SECRETION; MEMORY STEM-CELLS;
METASTATIC MELANOMA; PERIPHERAL-BLOOD; TRANSFER THERAPY; GENE-EXPRESSION
AB CD8(+) T cells have been described as being naive or one of 4 antigen (Ag)-experienced subtypes representing a continuum of differentiation and maturation: T memory stem cell, central memory T cell, effector memory T cell, and terminally differentiated effector T cells. In mice, adoptive cell transfer of less-differentiated naive T cells, T memory stem cell, and central memory T cell subsets have consistently demonstrated superior in vivo expansion, persistence, and antitumor capacities relative to the more differentiated effector memory T cell and effector T cell subsets. Retrospective analyses from human adoptive cell transfer trials have confirmed that transfer of less-differentiated T-cell subsets is highly correlated with objective clinical responses. These findings, combined with the recent ability to convey de novo Ag reactivity with high efficiency through genetic engineering of exogenous T-cell or chimeric Ag receptors, now challenge the field with 3 important questions: (1) how should less-differentiated T-cell subsets be isolated for human clinical trials?; (2) what is the best means of expanding T cells ex vivo in such a way as to not corrupt the beneficial traits of the younger subsets?; and (3) is it necessary to physically separate younger subsets from their more differentiated counterparts? Answering these questions will allow for the rational development of the next generation of highly effective and potentially curative T-cell therapies for the treatment of cancer.
C1 [Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gattinoni, Luca] NCI, Expt Transplant & Immunol Branch, Bethesda, MD 20892 USA.
[Restifo, Nicholas P.] NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10-CRC,Room 3-5762, Bethesda, MD 20892 USA.
EM restifo@nih.gov
RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008;
OI Gattinoni, Luca/0000-0003-2239-3282; Restifo, Nicholas
P./0000-0003-4229-4580
FU Intramural NIH HHS [ZIA BC010763-07]
NR 125
TC 75
Z9 80
U1 1
U2 41
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 651
EP 660
PG 10
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100001
PM 23090074
ER
PT J
AU Zhu, SG
Van den Eynde, BJ
Coulie, PG
Li, YF
El-Gamil, M
Rosenberg, SA
Robbins, PF
AF Zhu, Shigui
Van den Eynde, Benoit J.
Coulie, Pierre G.
Li, Yong F.
El-Gamil, Mona
Rosenberg, Steven A.
Robbins, Paul F.
TI Characterization of T-cell Receptors Directed Against
HLA-A*01-restricted and C*07-restricted Epitopes of MAGE-A3 and MAGE-A12
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Article
DE T-cell receptors; cancer/germline antigens; T-cell epitopes; cancer
immunotherapy
ID TUMOR-INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; ENGINEERED
LYMPHOCYTES; MONOCLONAL-ANTIBODY; CANCER REGRESSION; GENE-THERAPY;
PHASE-II; ANTIGEN; EXPRESSION; TCR
AB The ability of T cells that have been genetically engineered to express T-cell receptors (TCRs) directed against tumor antigens to mediate tumor regression has been demonstrated in several clinical trials. These TCRs have primarily targeted HLAA*0201-restricted TCRs, as approximately 50% of whites, who represent the predominant population of patients who develop melanomas, expresses this HLA class I allele. These therapies could be extended to additional patients through the use of TCRs that target epitopes that are presented by additional class I alleles that are prevalent in this population such as HLA-C*07 and HLAA* 01, which are expressed by approximately 50% and 30% of the patient population respectively. Therefore, 2 TCRs that recognize an epitope of MAGE-A12 in the context of HLA-C*07 and 2 TCRs that recognize an epitope of MAGE-A3 in the context of HLA-A*01 were isolated from tumor-reactive T-cell clones and cloned in a recombinant retroviral expression vector. Comparative studies indicated that one of the 2 MAGE-A3-reactive TCRs and one of the 2 MAGE-A12-reactive TCRs were superior to the additional TCRs in conferring transduced peripheral blood mononuclear cells with the capacity to recognize a broad array of antigen and MHC-positive target cells. These results provide support for the use of these TCRs in cancer adoptive immunotherapy trials.
C1 [Zhu, Shigui; Li, Yong F.; El-Gamil, Mona; Rosenberg, Steven A.; Robbins, Paul F.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Van den Eynde, Benoit J.] de Duve Inst, Ludwig Inst Canc Res, Brussels, Belgium.
[Coulie, Pierre G.] Catholic Univ Louvain, de Duve Inst, B-1200 Brussels, Belgium.
RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, CRC 3-5744,10 Ctr Dr, Bethesda, MD 20892 USA.
EM paul_robbins@nih.gov
FU Intramural NIH HHS [ZIC BC010948-02]
NR 40
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 680
EP 688
PG 9
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100004
PM 23090077
ER
PT J
AU Gros, A
Turcotte, S
Tran, E
Hanada, K
Wunderlich, JR
Rosenberg, S
AF Gros, Alena
Turcotte, Simon
Tran, Eric
Hanada, Ken-ichi
Wunderlich, John R.
Rosenberg, Steven
TI Selection of PD-1, LAG-3, TIM-3 and 41BB Positive CD8 T Cells in the
Fresh Tumor Digest Enriches for Melanoma-Reactive Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Melanoma immunotherapy; Adoptive immunotherapy; Tumor infiltration
lymphocytes
C1 [Gros, Alena; Turcotte, Simon; Tran, Eric; Hanada, Ken-ichi; Wunderlich, John R.; Rosenberg, Steven] NCI, Surg Branch, Bethesda, MD 20892 USA.
RI Hanada, Ken-ichi/L-2481-2013
OI Hanada, Ken-ichi/0000-0003-2959-1257
NR 0
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 722
EP 723
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100014
ER
PT J
AU Haso, W
Lee, DW
Pastan, IH
Dimitrov, DS
Fitzgerald, D
Mackall, CL
Orentas, RJ
AF Haso, Waleed
Lee, Daniel W.
Pastan, Ira H.
Dimitrov, Dimiter S.
Fitzgerald, David
Mackall, Crystal L.
Orentas, Rimas J.
TI Targeting CD22 Expressing B Cell Leukemia With Chimeric Antigen
Receptors (CAR): Engineering Membrane Proximity and Second Signaling
Motifs for Optimal Activity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Adoptive immunotherapy; B-ALL; Chimeric receptors
C1 [Haso, Waleed; Lee, Daniel W.; Mackall, Crystal L.; Orentas, Rimas J.] NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA.
[Pastan, Ira H.; Fitzgerald, David] NCI, Mol Biol Lab, CCR, NIH, Frederick, MD 21701 USA.
[Dimitrov, Dimiter S.] NCI, Prot Interact Grp, CCRNP, 2BRP,SAIC Frederick Inc,NIH, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 723
EP 723
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100016
ER
PT J
AU Ji, Y
Escobar, T
Klebanoff, C
Yu, ZY
Sukumar, M
Franco, Z
Palmer, D
Roychoudhuri, R
Leonardi, A
Muljo, S
Restifo, N
Gattinoni, L
AF Ji, Yun
Escobar, Thelma
Klebanoff, Christopher
Yu, Zhiya
Sukumar, Madhusudhanan
Franco, Zulmarie
Palmer, Douglas
Roychoudhuri, Rahul
Leonardi, Anthony
Muljo, Stefan
Restifo, Nicholas
Gattinoni, Luca
TI MIR155 Augments the Anti-Tumor Activity of CD8+T Cells by Enhancing
Responsiveness to Homeostatic Cytokines in the Absence of
Lymphodepletion
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Engineering; Adoptive immunotherapy; CD8+T cells
C1 [Ji, Yun; Klebanoff, Christopher; Yu, Zhiya; Sukumar, Madhusudhanan; Franco, Zulmarie; Palmer, Douglas; Roychoudhuri, Rahul; Leonardi, Anthony; Restifo, Nicholas; Gattinoni, Luca] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Escobar, Thelma; Muljo, Stefan] NIAID, Immunol Lab, Bethesda, MD 20892 USA.
RI Muljo, Stefan/F-5671-2015
OI Muljo, Stefan/0000-0003-1013-446X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 724
EP 724
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100020
ER
PT J
AU Long, AH
Haso, W
Lee, D
Highfill, S
Orentas, R
Mackall, C
AF Long, Adrienne H.
Haso, Waleed
Lee, Daniel
Highfill, Steven
Orentas, Rimas
Mackall, Crystal
TI Evaluating the Susceptibility of Solid Tumors to Chimeric Antigen
Receptor Modified T Cell Therapies
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Cancer immunotherapy; Adoptive immunotherapy; Chimeric receptors
C1 [Long, Adrienne H.; Haso, Waleed; Lee, Daniel; Highfill, Steven; Orentas, Rimas; Mackall, Crystal] NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Long, Adrienne H.] Northwestern Univ, Dept Microbiol Immunol, Feinberg Sch Med, Chicago, IL 60611 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 726
EP 726
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100024
ER
PT J
AU Bergamaschi, C
Valentin, A
Kulkarni, V
Bear, J
Rosati, M
Alicea, C
Sowder, R
Chertova, E
Felber, BK
Pavlakis, GN
AF Bergamaschi, Cristina
Valentin, Antonio
Kulkarni, Viraj
Bear, Jenifer
Rosati, Margherita
Alicea, Candido
Sowder, Raymond
Chertova, Elena
Felber, Barbara K.
Pavlakis, George N.
TI Pharmacokinetics and Immunological Effects of Human IL-15/IL-15RA
Heterodimeric Complexes in Mice and Macaques
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Cancer immunotherapy; Interleukin-15; CD8+T cells
C1 [Bergamaschi, Cristina; Valentin, Antonio; Kulkarni, Viraj; Bear, Jenifer; Rosati, Margherita; Alicea, Candido; Felber, Barbara K.; Pavlakis, George N.] Frederick Natl Lab Canc Res, Vaccine Branch, Ctr Canc Res, Frederick, MD USA.
[Sowder, Raymond; Chertova, Elena] SAIC Frederick Inc, Retroviral Prot Chem Core, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 728
EP 729
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100032
ER
PT J
AU Hollevoet, K
Antignani, A
Fitzgerald, D
Pastan, I
AF Hollevoet, Kevin
Antignani, Antonella
Fitzgerald, David
Pastan, Ira
TI Combining the Recombinant Immunotoxin SS1P With the BH3-MIMETIC ABT-737
Induces Cell Death in Pancreatic Cancer Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Cancer immunotherapy; Apoptosis; Targeted therapeutics
C1 [Hollevoet, Kevin; Pastan, Ira] NCI, Moleculary Biol Sect, Mol Biol Lab, Bethesda, MD 20892 USA.
[Antignani, Antonella; Fitzgerald, David] NCI, Biotherapy Sect, Mol Biol Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 729
EP 730
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100035
ER
PT J
AU Wolfl, M
Schwinn, S
Yoo, YE
Ress, ML
Chopra, M
Schreiber, SC
Ayala, VI
Ohlen, C
Eyrich, M
Beilhack, A
Schlegel, PG
AF Woelfl, Matthias
Schwinn, Stefanie
Yoo, Young-Eun
Ress, Marie L.
Chopra, Martin
Schreiber, Susanne C.
Ayala, Victor I.
Ohlen, Claes
Eyrich, Matthias
Beilhack, Andreas
Schlegel, Paul G.
TI Dasatinib Primes Human Cells of Myeloid Origin to TLR-induced IL12
Synthesis
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Combination immunotherapy; Dendritic cell; Targeted therapeutics
C1 [Woelfl, Matthias; Schwinn, Stefanie; Yoo, Young-Eun; Ress, Marie L.; Schreiber, Susanne C.; Eyrich, Matthias; Schlegel, Paul G.] Univ Wurzburg, Childrens Hosp, Wurzburg, Germany.
[Chopra, Martin; Beilhack, Andreas] Univ Wurzburg, Dept Med 2, Wurzburg, Germany.
[Ayala, Victor I.; Ohlen, Claes] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
RI Woelfl, Matthias/J-9946-2012
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 736
EP 736
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100053
ER
PT J
AU Castiello, L
Stroncek, DF
Terabe, M
Khuu, H
Wood, LV
Berzofsky, JA
Sabatino, M
AF Castiello, Luciano
Stroncek, David F.
Terabe, Masaki
Khuu, Hanh
Wood, Lauren V.
Berzofsky, Jay A.
Sabatino, Marianna
TI Transcriptional Signatures in Dendritic Cells: Correlation of Patient
Variability With Clinical Outcome
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE DC-based vaccine; Biomarker; Prostate cancer
C1 [Castiello, Luciano; Stroncek, David F.; Khuu, Hanh; Sabatino, Marianna] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Terabe, Masaki; Wood, Lauren V.; Berzofsky, Jay A.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RI Castiello, Luciano/K-8616-2016
OI Castiello, Luciano/0000-0001-7146-3158
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 739
EP 739
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100060
ER
PT J
AU Ascierto, ML
Schechterly, C
Bedognetti, D
De Giorgi, V
Reinboth, J
Tomei, S
Uccelini, L
Liu, QZ
Wang, EN
Alter, H
De Maria, A
Marincola, F
AF Ascierto, Maria Libera
Schechterly, Cathy
Bedognetti, Davide
De Giorgi, Valeria
Reinboth, Jenny
Tomei, Sara
Uccelini, Lorenzo
Liu, Quizhen
Wang, Ena
Alter, Harvey
De Maria, Andrea
Marincola, Francesco
TI Effect of HCV Viraemia on NK Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE HAV/HBV/HCV infections; Immune escape; Innate immunity
C1 [Ascierto, Maria Libera; Schechterly, Cathy; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jenny; Tomei, Sara; Uccelini, Lorenzo; Liu, Quizhen; Wang, Ena; Alter, Harvey; Marincola, Francesco] NIH, Bethesda, MD 20892 USA.
[Ascierto, Maria Libera; De Maria, Andrea] Univ Genoa, Genoa, Italy.
RI De Giorgi, Valeria/D-4582-2017
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 748
EP 748
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100087
ER
PT J
AU Reinboth, J
Ascierto, ML
Chen, NG
Zhang, Q
Yu, YA
Aguilar, RJ
Worschech, A
Zhao, YD
Wang, E
Marincola, FM
Szalay, AA
AF Reinboth, Jennifer
Ascierto, Maria L.
Chen, Nanhai G.
Zhang, Qian
Yu, Yong A.
Aguilar, Richard J.
Worschech, Andrea
Zhao, Yingdong
Wang, Ena
Marincola, Francesco M.
Szalay, Aladar A.
TI Correlation Between Human and Oncolytic Vaccinia Virus Transcriptional
Profile
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Engineering; Therapeutic vaccine; Melanoma
C1 [Reinboth, Jennifer; Chen, Nanhai G.; Zhang, Qian; Yu, Yong A.; Aguilar, Richard J.; Szalay, Aladar A.] Genelux Corp, San Diego Sci Ctr, San Diego, CA USA.
[Reinboth, Jennifer; Ascierto, Maria L.; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, CC & Trans NIH Ctr Human Immunol, Bethesda, MD 20892 USA.
[Reinboth, Jennifer; Szalay, Aladar A.] Univ Wurzburg, Dept Biochem, Wurzburg, Germany.
[Ascierto, Maria L.] Univ Genoa, Dept Hlth Sci, Genoa, Italy.
[Ascierto, Maria L.] Univ Genoa, Ctr Excellence Biomed Res, Genoa, Italy.
[Chen, Nanhai G.; Zhang, Qian; Yu, Yong A.; Szalay, Aladar A.] Univ Calif San Diego, Dept Radiat Oncol, Rebecca & John Moores Comprehens Canc Ctr, San Diego, CA 92103 USA.
[Worschech, Andrea] Univ Wurzburg, Dept Internal Med 2, Wurzburg, Germany.
[Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 748
EP 748
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100089
ER
PT J
AU Bedognetti, D
Zoppoli, G
Sertoli, MR
Ascierto, ML
Marincola, F
Ansaldi, F
De Maria, A
AF Bedognetti, Davide
Zoppoli, Gabriele
Sertoli, Mario Roberto
Ascierto, Maria Libera
Marincola, Francesco
Ansaldi, Filippo
De Maria, Andrea
TI Attenuated Humoral Response to Seasonal and Pandemic (A/H1N1 2009)
Virosomal and MF-59 Adjuvated Influenza Vaccines in Complete Remission
Non-hodgkin Lymphoma Patients Previously Treated With Rituximab
Containing Regimens
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE B cell; Lymphoma; Immunotherapy
C1 [Bedognetti, Davide; Ascierto, Maria Libera; Marincola, Francesco] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Zoppoli, Gabriele; Sertoli, Mario Roberto; Ansaldi, Filippo; De Maria, Andrea] IRCCS San Martino IST, Genoa, Italy.
RI de maria, andrea/F-7116-2016
OI de maria, andrea/0000-0001-5782-333X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 749
EP 749
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100091
ER
PT J
AU Bouchlaka, MN
Sckisel, GD
Chen, MY
Mirsoian, A
Zamora, AE
Maverakis, E
Hsiao, HH
Monjazeb, AM
Murphy, WJ
Taub, D
AF Bouchlaka, Myriam N.
Sckisel, Gail D.
Chen, Mingyi
Mirsoian, Annie
Zamora, Anthony E.
Maverakis, Emanual
Hsiao, Hui-Hua
Monjazeb, Arta M.
Murphy, William J.
Taub, Dennis
TI Aging Results in Acute TNF-alpha-dependent Lethality Following Systemic
Immunotherapy: Impact of Body Fat Content
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Toxicity; Combination immunotherapy; Macrophages
C1 [Bouchlaka, Myriam N.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Hsiao, Hui-Hua; Monjazeb, Arta M.; Murphy, William J.] Univ Calif Davis, Sacramento, CA USA.
[Taub, Dennis] NIA, IRP, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA.
RI Maverakis, Emanual/E-1185-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 751
EP 751
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100096
ER
PT J
AU Salerno, EP
Wang, E
Marincola, F
Slingluff, CL
AF Salerno, Elise P.
Wang, Ena
Marincola, Franco
Slingluff, Craig L.
TI Topical Imiquimod Induces Immune Activation and Regressions of Cutaneous
Melanoma Metastases
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Advanced cancer immune response; Combination immunotherapy; Tumor
microenvironment
C1 [Salerno, Elise P.; Slingluff, Craig L.] Univ Virginia, Dept Surg, Div Surg Oncol, Charlottesville, VA USA.
[Wang, Ena; Marincola, Franco] NIH, Infect Dis & Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Franco] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 751
EP 752
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100098
ER
PT J
AU Subleski, J
Back, T
Scarzello, A
Weiss, J
Robert, WH
AF Subleski, Jeff
Back, Tim
Scarzello, Anthony
Weiss, Jonathan
Robert, Wiltrout H.
TI Blocking IL-18 During IL-12+IL-15 Therapy Ameliorates Toxicity and
Eradicates Malignancy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE IL-12; Interleukin-15; Toxicity
C1 [Subleski, Jeff; Back, Tim; Scarzello, Anthony; Weiss, Jonathan; Robert, Wiltrout H.] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 752
EP 752
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100099
ER
PT J
AU Weiss, JM
Subleski, JJ
Back, T
Chen, X
Watkins, SK
Yagita, H
Sayers, TJ
Murphy, WJ
Wiltrout, RH
AF Weiss, Jonathan M.
Subleski, Jeff J.
Back, Tim
Chen, Xin
Watkins, Stephanie K.
Yagita, Hideo
Sayers, Thomas J.
Murphy, William J.
Wiltrout, Robert H.
TI Regulatory T Cells and Myeloid-derived Suppressor Cells in the Tumor
Microenvironment Undergo FAS-dependent Cell Death During IL-2/ACD40
Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Combination immunotherapy; Treg cells; Tumor microenvironment
C1 [Weiss, Jonathan M.; Subleski, Jeff J.; Back, Tim; Watkins, Stephanie K.; Wiltrout, Robert H.] Frederick Natl Lab Canc Res, Canc & Inflammat Program, Frederick, MD USA.
[Chen, Xin; Sayers, Thomas J.] SAIC Frederick, Basic Sci Program, Frederick, MD USA.
[Yagita, Hideo] Juntendo Univ, Sch Med, Tokyo 113, Japan.
[Murphy, William J.] Univ Calif Davis, Davis, CA 95616 USA.
RI Sayers, Thomas/G-4859-2015; Chen, Xin/I-6601-2015
OI Chen, Xin/0000-0002-2628-4027
NR 0
TC 0
Z9 0
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 753
EP 753
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100102
ER
PT J
AU Ascierto, ML
Idowu, MO
Zhao, YD
Bedognetti, D
Tomei, S
Ascierto, PA
Wang, E
Marincola, F
De Maria, A
Manjili, M
AF Ascierto, Maria Libera
Idowu, Michael O.
Zhao, Yingdong
Bedognetti, Davide
Tomei, Sara
Ascierto, Paolo A.
Wang, Ena
Marincola, Francesco
De Maria, Andrea
Manjili, Masoud
TI NK Cell Molecular Signatures are Predictive of Relapse Free Survival of
Favorable Prognosis of Breast Cancer Patients
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Micrenvironment; Tumor immunity; Innate immunity
C1 [Ascierto, Maria Libera; Zhao, Yingdong; Bedognetti, Davide; Tomei, Sara; Wang, Ena; Marincola, Francesco] NIH, Bethesda, MD 20892 USA.
[Ascierto, Paolo A.] Ist Tumori Fdn G Pascale, Naples, Italy.
[Idowu, Michael O.; De Maria, Andrea; Manjili, Masoud] Virginia Commonwealth Univ, Richmond, VA USA.
RI de maria, andrea/F-7116-2016
OI de maria, andrea/0000-0001-5782-333X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 754
EP 755
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100106
ER
PT J
AU De Giorgi, V
Tomei, S
Liu, QZ
Wunderlich, J
Uccellini, L
Ascierto, ML
Bedognetti, D
Wang, E
Marincola, FM
AF De Giorgi, Valeria
Tomei, Sara
Liu, Qiuzhen
Wunderlich, John
Uccellini, Lorenzo
Ascierto, Maria L.
Bedognetti, Davide
Wang, Ena
Marincola, Franco M.
TI Genomic Characterization of Melanoma Cell Lines
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Tumor immunity; Immunomodulation; Melanoma
C1 [De Giorgi, Valeria; Tomei, Sara; Liu, Qiuzhen; Uccellini, Lorenzo; Ascierto, Maria L.; Bedognetti, Davide; Wang, Ena; Marincola, Franco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Bethesda, MD 20892 USA.
[Wunderlich, John] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RI De Giorgi, Valeria/D-4582-2017
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 755
EP 756
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100109
ER
PT J
AU Wennerberg, E
Kremer, V
Childs, R
Lundqvist, A
AF Wennerberg, Erik
Kremer, Veronika
Childs, Richard
Lundqvist, Andreas
TI IFN-GAMMA-inducible Protein-10 Stimulates Migration of Activated Natural
Killer Cells Toward Melanoma Tumors
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Adoptive immunotherapy; Chemokines; NK cells
C1 [Wennerberg, Erik; Kremer, Veronika; Lundqvist, Andreas] Karolinska Inst, Stockholm, Sweden.
[Childs, Richard; Lundqvist, Andreas] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 757
EP 757
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100114
ER
PT J
AU Riccobon, A
Ancarani, V
Pancisi, E
Petrini, M
Fiammenghi, L
Granato, AM
Soldati, V
Ridolfi, L
de Rosa, F
Valmorri, L
Gentili, G
Nanni, O
Migliori, G
Amadori, D
Marincola, FM
Ridolfi, R
Guidoboni, M
AF Riccobon, Angela
Ancarani, Valentina
Pancisi, Elena
Petrini, Massimiliano
Fiammenghi, Laura
Granato, Anna Maria
Soldati, Valentina
Ridolfi, Laura
de Rosa, Francesco
Valmorri, Linda
Gentili, Giorgia
Nanni, Oriana
Migliori, Giuseppe
Amadori, Dino
Marincola, Francesco M.
Ridolfi, Ruggero
Guidoboni, Massimo
TI DC Vaccine Potency Correlates With Efficient Induction of Tumor-specific
Immune Responses After Vaccination of Advanced Melanoma Patients:
Preliminary Data With an in vitro Functional Assay
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE DC-based vaccine; Immunotherapy
C1 [Valmorri, Linda; Gentili, Giorgia; Nanni, Oriana] IRCCS IRST, Biostat & Clin Trial Unit, Meldola, FC, Italy.
[Migliori, Giuseppe] Morgagni Pierantoni Hosp, Blood Transfus Unit, Forli, FC, Italy.
[Marincola, Francesco M.; Guidoboni, Massimo] NIH, IDIS DTM, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 762
EP 763
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100129
ER
PT J
AU Klebanoff, CA
Scott, CD
Leonardi, AJ
Ji, Y
Roychoudhuri, R
Wang, E
Yu, ZY
Marincola, FM
Gattinoni, L
Restifo, NP
AF Klebanoff, Christopher A.
Scott, Christopher D.
Leonardi, Anthony J.
Ji, Yun
Roychoudhuri, Rahul
Wang, Ena
Yu, Zhiya
Marincola, Francesco M.
Gattinoni, Luca
Restifo, Nicholas P.
TI Memory CD8(+) T Cells Induce Precocious Effector Differentiation of
NAiVE CD8(+) T Cells in a FASL-FAS Dependent Manner: A New Mode of T-T
Lymphocyte Interaction and Cross Talk
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Melanoma immunotherapy; Adoptive immunotherapy; Memory CD8+T cells
C1 [Klebanoff, Christopher A.; Scott, Christopher D.; Leonardi, Anthony J.; Ji, Yun; Roychoudhuri, Rahul; Yu, Zhiya; Gattinoni, Luca; Restifo, Nicholas P.] NCI, CCR, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NCI, CC, Bethesda, MD 20892 USA.
RI Restifo, Nicholas/A-5713-2008
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 765
EP 765
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100136
ER
PT J
AU Sukumar, M
Liu, J
Ji, Y
Roychoudhuri, R
Yu, ZY
Klebanoff, C
Finkel, T
Restifo, N
Gattinoni, L
AF Sukumar, Madhusudhanan
Liu, Jie
Ji, Yun
Roychoudhuri, Rahul
Yu, Zhiya
Klebanoff, Christopher
Finkel, Toren
Restifo, Nicholas
Gattinoni, Luca
TI Inhibition of Glycolytic Flux Enhances CD8+T Cell Memory, Stemness and
Anti-tumor Function
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Adoptive immunotherapy; Memory CD8+T cells; Immune-mediated tumor
rejection
C1 [Sukumar, Madhusudhanan; Ji, Yun; Roychoudhuri, Rahul; Yu, Zhiya; Klebanoff, Christopher; Restifo, Nicholas; Gattinoni, Luca] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Liu, Jie; Finkel, Toren] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 766
EP 766
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100139
ER
PT J
AU Highfill, SL
Mackall, CL
AF Highfill, Steven L.
Mackall, Crystal L.
TI Overcoming Tumor-induced Negative Regulatory Pathways in Murine Models
of Rhabdomyosarcoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE MDSC; PD-1
C1 [Highfill, Steven L.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 776
EP 777
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100168
ER
PT J
AU Liu, QZ
Tomei, S
Ascierto, ML
Giorgi, VD
Dai, CL
Uccellini, L
Spivey, T
Pos, Z
Thomas, J
Reinboth, J
Murtas, D
Bedognetti, D
Wang, E
Marincola, FM
AF Liu, Qiuzhen
Tomei, Sara
Ascierto, Maria L.
Giorgi, Valeria D.
Dai, Cuilian
Uccellini, Lorenzo
Spivey, Tara
Pos, Zoltan
Thomas, Jaime
Reinboth, Jennifer
Murtas, Daniela
Bedognetti, Davide
Wang, Ena
Marincola, Francesco M.
TI NOS1 Overexpression by Melanoma Cells Contributes to Type I IFN alpha
Signal Dysfunction in Immune Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Immunosuppression; IFNalpha; Melanoma
C1 [Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria L.; Giorgi, Valeria D.; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Infect Dis & Immunogenet Sect IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Liu, Qiuzhen; Tomei, Sara; Ascierto, Maria L.; Giorgi, Valeria D.; Uccellini, Lorenzo; Spivey, Tara; Pos, Zoltan; Thomas, Jaime; Reinboth, Jennifer; Murtas, Daniela; Bedognetti, Davide; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Liu, Qiuzhen] So Med Univ, Canc Res Inst, Guangzhou, Guangdong, Peoples R China.
[Dai, Cuilian] Zunyi Med Coll, Affiliated Hosp, Dept Cardiol, Zunyi, Peoples R China.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 777
EP 778
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100171
ER
PT J
AU Ma, C
Kapanadze, T
Gamrekelashvili, J
Manns, MP
Korangy, F
Greten, TF
AF Ma, Chi
Kapanadze, Tamar
Gamrekelashvili, Jaba
Manns, Michael P.
Korangy, Firouzeh
Greten, Tim F.
TI Anti-GR-1 Antibody Depletion Fails to Eliminate Hepatic Myeloid Derived
Suppressor Cells in Tumor Bearing Mice
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Myeloid derived suppressor cell
C1 [Ma, Chi; Kapanadze, Tamar; Gamrekelashvili, Jaba; Korangy, Firouzeh; Greten, Tim F.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kapanadze, Tamar; Gamrekelashvili, Jaba; Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany.
RI Greten, Tim/B-3127-2015
OI Greten, Tim/0000-0002-0806-2535
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 778
EP 778
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100172
ER
PT J
AU Maccalli, C
Volonte, A
Wang, E
Sanvito, F
Albarello, L
Doglioni, C
Marincola, FM
Parmiani, G
AF Maccalli, Cristina
Volonte, Andrea
Wang, Ena
Sanvito, Francesca
Albarello, Luca
Doglioni, Claudio
Marincola, Francesco M.
Parmiani, Giorgio
TI Cancer Stem Cells Isolated From Solid Tumors can Display
Immunomodulatory Activity for T Cell Responses
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Tumor immunity; Indoleamine 2,3-dioxygenase 1; Immunomodulation
C1 [Sanvito, Francesca; Albarello, Luca; Doglioni, Claudio] Ist Sci San Raffaele, Unit Pathol, I-20132 Milan, Italy.
[Wang, Ena; Marincola, Francesco M.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Wang, Ena; Marincola, Francesco M.] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 778
EP 778
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100173
ER
PT J
AU Fujisawa, T
Rubin, B
Suzuki, A
Patel, PS
Gahl, WA
Joshi, BH
Puri, RK
AF Fujisawa, Toshio
Rubin, Benjamin
Suzuki, Akiko
Patel, Prabhudas S.
Gahl, Wiiliam A.
Joshi, Bharat H.
Puri, Raj K.
TI Cysteamine Inhibits Invasion, Metastasis and Extends Survival by
Down-regulating Matrix Metalloproteinases in vivo Mouse Model of Human
Pancreatic Cancer
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Metastases; Animal model; Tumor microenvironment
C1 [Fujisawa, Toshio; Suzuki, Akiko; Patel, Prabhudas S.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA.
[Fujisawa, Toshio] NTT Med Ctr Tokyo, Dept Gastroenterol, Tokyo, Japan.
[Rubin, Benjamin] Suburban Hosp, Johns Hopkins Sch Med, Dept Ophthalmol, Bethesda, MD USA.
[Gahl, Wiiliam A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 785
EP 785
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100194
ER
PT J
AU Izhak, L
Ambrosino, E
O'Konek, JJ
Parish, ST
Xia, Z
Venzon, D
Berzofsky, JA
Terabe, M
AF Izhak, Liat
Ambrosino, Elena
O'Konek, Jessica J.
Parish, Stanley T.
Xia, Zheng
Venzon, David
Berzofsky, Jay A.
Terabe, Masaki
TI Delicate Balance Among Three Types of T Cells in Concurrent Regulation
of Tumor Immunity
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Immunosuppression; Tumor immunity; Regulatory T cells
C1 [Izhak, Liat; Ambrosino, Elena; O'Konek, Jessica J.; Parish, Stanley T.; Xia, Zheng; Berzofsky, Jay A.; Terabe, Masaki] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA.
[Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 786
EP 786
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100198
ER
PT J
AU Jin, P
Civini, S
Wang, HD
Ren, JQ
Sabatino, M
Wang, E
Marincola, F
Stroncek, D
AF Jin, Ping
Civini, Sara
Wang, Heidi
Ren, Jiaqiang
Sabatino, Marianna
Wang, Ena
Marincola, Francesco
Stroncek, David
TI Bone Marrow-derived Stromal Cells (BMSC) Show Both Pro-inflammatory and
Immunosuppressive Characteristics in Melanoma Microenvironment: An in
vitro Study by Co-culture of BMSC, TIL and Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Immunomodulation; Tumor microenvironment; Tumor stromal cells
C1 [Jin, Ping; Civini, Sara; Wang, Heidi; Ren, Jiaqiang; Sabatino, Marianna; Wang, Ena; Marincola, Francesco; Stroncek, David] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 787
EP 787
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100200
ER
PT J
AU Kotlan, B
Liszkay, G
Naszados, G
Godeny, M
Toth, L
Gobor, L
Szollar, A
Plotar, V
Toth, E
Kasler, M
Marincola, FM
AF Kotlan, Beatrix
Liszkay, Gabriella
Naszados, Gyorgy
Godeny, Maria
Toth, Laszlo
Gobor, Laszlo
Szollar, Andras
Plotar, Vanda
Toth, Erika
Kasler, Miklos
Marincola, Francesco M.
TI Tracking Tumor Infiltrating B Cells Revealed Cancer Initiating Cells
That Coexpress Unique GD3 Sialilated Glycosphingolipides and CD20 in
Metastatic Malignant Melanomas
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Metastases; B cell; Melanoma
C1 [Plotar, Vanda; Toth, Erika] Natl Inst Oncol, Ctr Surg & Mol Tumorpathol, Budapest, Hungary.
[Kasler, Miklos] Natl Inst Oncol, Board Directors, Budapest, Hungary.
[Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 787
EP 787
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100201
ER
PT J
AU Scarzello, A
Stauffer, J
Subleski, J
Weiss, J
Ortaldo, J
Wiltrout, R
AF Scarzello, Anthony
Stauffer, Jim
Subleski, Jeff
Weiss, Jon
Ortaldo, John
Wiltrout, Robert
TI AKT plus beta-CAT Liver Tumor Development is Dependent on B Cells
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE B cell; Tumor microenvironment
C1 [Scarzello, Anthony; Stauffer, Jim; Subleski, Jeff; Weiss, Jon; Ortaldo, John; Wiltrout, Robert] NCI, Canc & Inflammat Program, LEI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 788
EP 788
PG 1
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100203
ER
PT J
AU Tomei, S
Civini, S
Bedognetti, D
De Giorgi, V
Reinboth, J
Ascierto, ML
Liu, QZ
Uccellini, L
Wang, E
Marincola, FM
AF Tomei, Sara
Civini, Sara
Bedognetti, Davide
De Giorgi, Valeria
Reinboth, Jennifer
Ascierto, Maria Libera
Liu, Qiuzhen
Uccellini, Lorenzo
Wang, Ena
Marincola, Francesco M.
TI The Immune-related Role of BRAF Mutation in Melanoma
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Meeting Abstract
CT 27th Annual Scientific Meeting of the
Society-for-Immunotherapy-of-Cancer (SITC)
CY OCT 24-28, 2012
CL North Bethesda, MD
SP Soc Immunotherapy Canc (SITC)
DE Melanoma
C1 [Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, IDIS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Tomei, Sara; Bedognetti, Davide; De Giorgi, Valeria; Reinboth, Jennifer; Ascierto, Maria Libera; Liu, Qiuzhen; Uccellini, Lorenzo; Wang, Ena; Marincola, Francesco M.] NIH, Trans NIH Ctr Human Immunol CHI, Bethesda, MD 20892 USA.
[Civini, Sara] NIH, CPS, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RI De Giorgi, Valeria/D-4582-2017
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2012
VL 35
IS 9
BP 788
EP 789
PG 2
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 028OF
UT WOS:000310431100205
ER
PT J
AU Stijleman, IJ
Swaner, K
Nilson, D
Jensen, T
Lubet, RA
Cessna, MH
Davis, CA
Bernard, PS
AF Stijleman, I. J.
Swaner, K.
Nilson, D.
Jensen, T.
Lubet, R. A.
Cessna, M. H.
Davis, C. A.
Bernard, P. S.
TI Analysis of Biomarkers for Colon Cancer Progression and Chemoprevention
Using RT-qPCR in Formalin Fixed Paraffin Embedded Colon Tissues
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY OCT 25-27, 2012
CL Long Beach, CA
SP Assoc Mol Pathol
C1 [Stijleman, I. J.; Davis, C. A.; Bernard, P. S.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Swaner, K.; Nilson, D.; Jensen, T.; Cessna, M. H.] Intermt Hlth Care, Salt Lake City, UT USA.
[Lubet, R. A.] NCI, Bethesda, MD 20892 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 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2012
VL 14
IS 6
BP 709
EP 709
PG 1
WC Pathology
SC Pathology
GA 025HG
UT WOS:000310178600304
ER
PT J
AU Xi, L
Navarro, W
Quezado, MM
Oberholtzer, CJ
Fine, HA
Raffeld, M
AF Xi, L.
Navarro, W.
Quezado, M. M.
Oberholtzer, C. J.
Fine, H. A.
Raffeld, M.
TI Quantitative MGMT Promoter Methylation Analysis Using Bisulfite
Pyrosequencing for Molecular Diagnostic Testing in Glioblastoma
Multiforme
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY OCT 25-27, 2012
CL Long Beach, CA
SP Assoc Mol Pathol
C1 [Xi, L.; Navarro, W.; Quezado, M. M.; Oberholtzer, C. J.; Fine, H. A.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 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 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2012
VL 14
IS 6
BP 713
EP 713
PG 1
WC Pathology
SC Pathology
GA 025HG
UT WOS:000310178600319
ER
PT J
AU Tangrea, MA
Hipp, JD
Armani, MD
Hanson, JC
Rodriguez-Canales, J
Blackler, AR
Chowdhuri, SR
Xi, L
Raffeld, M
O'Flaherty, N
Markey, SP
Filie, AC
Cheng, J
Morgan, NY
Pohida, TJ
Bonner, RF
Balis, U
Emmert-Buck, MR
AF Tangrea, M. A.
Hipp, J. D.
Armani, M. D.
Hanson, J. C.
Rodriguez-Canales, J.
Blacklert, A. R.
Chowdhuri, S. Roy
Xi, L.
Raffeld, M.
O'Flaherty, N.
Markey, S. P.
Filie, A. C.
Cheng, J.
Morgan, N. Y.
Pohida, T. J.
Bonner, R. F.
Balis, U.
Emmert-Buck, M. R.
TI Advanced Microdissection Technologies with Potential Clinical
Applications
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY OCT 25-27, 2012
CL Long Beach, CA
SP Assoc Mol Pathol
C1 [Tangrea, M. A.; Armani, M. D.; Hanson, J. C.; Rodriguez-Canales, J.; Blacklert, A. R.; Xi, L.; Raffeld, M.; O'Flaherty, N.; Filie, A. C.; Emmert-Buck, M. R.] NCI, Bethesda, MD 20892 USA.
[Hipp, J. D.; Cheng, J.; Balis, U.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Chowdhuri, S. Roy] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Markey, S. P.] NIMH, Bethesda, MD 20892 USA.
[Morgan, N. Y.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Pohida, T. J.] NIH, Bethesda, MD 20892 USA.
[Bonner, R. F.] NICHHD, Bethesda, MD 20892 USA.
RI Bonner, Robert/C-6783-2015
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2012
VL 14
IS 6
BP 739
EP 739
PG 1
WC Pathology
SC Pathology
GA 025HG
UT WOS:000310178600422
ER
PT J
AU Xi, L
Evbuomwan, MO
Raffeld, M
AF Xi, L.
Evbuomwan, M. O.
Raffeld, M.
TI Evaluation of the Ion Torrent AmpliSeq 1.0 Cancer Panel for Molecular
Profiling in Thoracic Malignancies
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology
CY OCT 25-27, 2012
CL Long Beach, CA
SP Assoc Mol Pathol
C1 [Xi, L.; Evbuomwan, M. O.; Raffeld, M.] NCI, NIH, Bethesda, MD 20892 USA.
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 1525-1578
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2012
VL 14
IS 6
BP 743
EP 743
PG 1
WC Pathology
SC Pathology
GA 025HG
UT WOS:000310178600438
ER
PT J
AU Baratz, R
Rubovitch, V
Tweedie, D
Greig, NH
Pick, CG
AF Baratz, R.
Rubovitch, V
Tweedie, D.
Greig, N. H.
Pick, C. G.
TI Thalidomide analog, 3 ' 6,dithiothalidomide, administration post minimal
traumatic brain injury reduce TNF-alpha and improve cognitive
performance in mice
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Baratz, R.; Rubovitch, V; Pick, C. G.] Tel Aviv Univ, Sackler Sch Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel.
[Tweedie, D.; Greig, N. H.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RI Pick, Chaim/D-4789-2009
NR 0
TC 0
Z9 0
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S91
EP S92
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600235
ER
PT J
AU Eiden, LE
Stroth, N
Holighaus, Y
Ait-Ali, D
Mustafa, T
AF Eiden, Lee E.
Stroth, Nikolas
Holighaus, Yvonne
Ait-Ali, Djida
Mustafa, Tomris
TI PACAP's dual role as a stress transducer and neuroprotectant in the
brain
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 [Eiden, Lee E.; Stroth, Nikolas; Holighaus, Yvonne; Ait-Ali, Djida; Mustafa, Tomris] NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, IRP, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S195
EP S195
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600445
ER
PT J
AU Gal, R
Kaiser, M
Haspel, G
Libersat, F
AF Gal, R.
Kaiser, M.
Haspel, G.
Libersat, F.
TI Stereotaxis in the wild: how a parasitoid wasp finds its host's brain
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Gal, R.; Kaiser, M.; Libersat, F.] Ben Gurion Univ Negev, Dept Life Sci, IL-84105 Beer Sheva, Israel.
[Haspel, G.] NINDS, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S38
EP S38
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600091
ER
PT J
AU Harel, A
Kravitz, DJ
Baker, CI
AF Harel, A.
Kravitz, D. J.
Baker, C., I
TI Deconstructing visual scenes in cortex: gradients of object and spatial
layout information
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Harel, A.; Kravitz, D. J.; Baker, C., I] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S50
EP S50
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600126
ER
PT J
AU Jensen, RT
Moody, TW
Coy, DH
AF Jensen, R. T.
Moody, T. W.
Coy, D. H.
TI GPCR peptide receptor mediated imaging/cytotoxicity
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 NIH, Bethesda, MD 20892 USA.
Tulane Univ, New Orleans, LA 70118 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S192
EP S193
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600441
ER
PT J
AU Levi, YF
Vedin, I
Cederholm, T
Basun, H
Irving, GF
Jonhagen, ME
Vessby, B
Wahlund, LO
Salem, N
Palmblad, J
AF Levi, Freund Y.
Vedin, I
Cederholm, T.
Basun, H.
Irving, Faxen G.
Jonhagen, Eriksdotter M.
Vessby, B.
Wahlund, L. O.
Salem, N., Jr.
Palmblad, J.
TI Effects of a DHA rich omega-3 fatty acid supplementation for Alzheimer
disease patients on fatty acid composition in cerebrospinal fluid,
disease biomarkers and cognition: The OmegAD study
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Levi, Freund Y.; Irving, Faxen G.; Jonhagen, Eriksdotter M.; Wahlund, L. O.] Karolinska Inst, Dept Neurobiol Caring Sci & Soc, Karoli Stockholm, Sweden.
[Levi, Freund Y.; Vedin, I; Palmblad, J.] Karolinska Inst, Dept Med, Karoli Stockholm, Sweden.
[Cederholm, T.; Vessby, B.] Univ Uppsala Hosp, Div Clin Nutr, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Cederholm, T.; Vessby, B.] Univ Uppsala Hosp, Div Metab Res, Uppsala, Sweden.
[Basun, H.] Univ Uppsala Hosp, Div Geriatr, Dept Publ Hlth & Caring Sci, Uppsala, Sweden.
[Salem, N., Jr.] NIAAA, NIH, Rockville, MD 20852 USA.
RI Eriksdotter, Maria/I-5427-2015
OI Eriksdotter, Maria/0000-0003-2498-4000
NR 0
TC 0
Z9 0
U1 0
U2 7
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S36
EP S36
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600086
ER
PT J
AU Loh, YP
AF Loh, Y. Peng
TI Serpinins promote granule biogenesis and neuroprotection
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 [Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Hisatsugu Koshimizu & Niamh X Cawley Sect Cellula, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S189
EP S189
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600435
ER
PT J
AU Moody, TW
Osefo, N
Mantey, SA
Jensen, RT
AF Moody, Terry W.
Osefo, Nauramy
Mantey, Samuel A.
Jensen, Robert T.
TI Peptide transactivation of epidermal growth factor receptors
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 NCI Off Director, DHHS, NIH, CCR, Bethesda, MD USA.
NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S194
EP S194
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600444
ER
PT J
AU Moody, TW
Leyton, J
Osefo, N
Jensen, RT
AF Moody, Terry W.
Leyton, Julius
Osefo, Nauramy
Jensen, Robert T.
TI PACAP causes tyrosine phosphorylation of focal adhesion kinase, paxillin
and epidermal growth factor receptors in lung cancer cells
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 10th International Symposium on VIP-PACAP and Related Peptides
CY DEC 13-16, 2011
CL Eilat, ISRAEL
C1 NCI, DHHS, NIH, Off Director,CCR, Bethesda, MD USA.
NIDDK, Digest Dis Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S145
EP S145
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600363
ER
PT J
AU Pick, CG
Rachmany, L
Rubovitch, V
Tweedie, D
Hoffer, BJ
Greig, NH
AF Pick, C. G.
Rachmany, L.
Rubovitch, V
Tweedie, D.
Hoffer, B. J.
Greig, N. H.
TI Exendin-4 reverses behavioral impairments induced by traumatic brain
injury in mice
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 [Pick, C. G.; Rachmany, L.; Rubovitch, V] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, Tel Aviv, Israel.
[Tweedie, D.; Greig, N. H.] NIA, Drug Design & Dev Sect, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Hoffer, B. J.] Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
RI Pick, Chaim/D-4789-2009
NR 0
TC 0
Z9 0
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S184
EP S184
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600428
ER
PT J
AU Rachmany, L
Rubovitch, V
Tweedie, D
Greig, NH
Schreiber, S
Pick, CG
AF Rachmany, L.
Rubovitch, V
Tweedie, D.
Greig, N. H.
Schreiber, S.
Pick, C. G.
TI Cognitive amelioration as a result of Exendin-4 (GLP-1R agonist)
administration after inducing minimal traumatic brain injury from blast
in mice
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Rachmany, L.; Rubovitch, V; Pick, C. G.] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel.
[Tweedie, D.; Greig, N. H.] NIA, Drug Design & Dev Sect, IRP, NIH, Baltimore, MD 21224 USA.
[Schreiber, S.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel.
RI Schreiber, Shaul/E-5821-2010; Pick, Chaim/D-4789-2009
OI Schreiber, Shaul/0000-0002-2189-0693;
NR 0
TC 0
Z9 0
U1 0
U2 4
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S94
EP S94
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600242
ER
PT J
AU Rapoport, S
Lavzin, M
Polsky, A
Garion, L
Schiller, J
AF Rapoport, S.
Lavzin, M.
Polsky, A.
Garion, L.
Schiller, J.
TI Active dendritic processing in layer-4 neurons of the rat barrel cortex
in-vivo
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT 20th Annual Meeting of the Israel-Society-for-Neuroscience
CY DEC 11-13, 2011
CL Eilat, ISRAEL
SP Israel Soc Neurosci
C1 [Rapoport, S.; Lavzin, M.; Garion, L.; Schiller, J.] Technion Israel Inst Technol, Dept Physiol, Rappaport Fac Med, IL-31096 Haifa, Israel.
[Rapoport, S.; Lavzin, M.; Garion, L.; Schiller, J.] Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel.
[Polsky, A.] Natl Inst Neurol Disorders & Stroke, Synapt Physiol Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S65
EP S65
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600165
ER
PT J
AU Reitman, M
AF Reitman, Marc
TI BRS-3 (Bombesin Receptor Subtype-3) agonists for the treatment of
obesity
SO JOURNAL OF MOLECULAR NEUROSCIENCE
LA English
DT Meeting Abstract
CT Summer Neuropeptide Conference / Meeting of the
European-Neuropeptide-Club (ENC)
CY MAY 22-25, 2011
CL Boston, MA
SP European Neuropeptide Club (ENC)
C1 [Reitman, Marc] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 0895-8696
J9 J MOL NEUROSCI
JI J. Mol. Neurosci.
PD NOV
PY 2012
VL 48
SU 1
BP S179
EP S179
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 030BC
UT WOS:000310541600420
ER
PT J
AU Shneider, BL
Abel, B
Haber, B
Karpen, SJ
Magee, JC
Romero, R
Schwarz, K
Bass, LM
Kerkar, N
Miethke, AG
Rosenthal, P
Turmelle, Y
Robuck, PR
Sokol, RJ
AF Shneider, Benjamin L.
Abel, Bob
Haber, Barbara
Karpen, Saul J.
Magee, John C.
Romero, Rene
Schwarz, Kathleen
Bass, Lee M.
Kerkar, Nanda
Miethke, Alexander G.
Rosenthal, Philip
Turmelle, Yumirle
Robuck, Patricia R.
Sokol, Ronald J.
CA Childhood Liver Dis Res Educ
TI Portal Hypertension in Children and Young Adults With Biliary Atresia
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Article
DE ascites; hepatopulmonary syndrome; hypersplenism; pediatric; varices
ID EXPERT PEDIATRIC OPINION; PLATELET RATIO INDEX; KASAI OPERATION;
VARICEAL HEMORRHAGE; CONSENSUS WORKSHOP; ESOPHAGEAL-VARICES; PROGNOSTIC
VALUE; HEPATITIS-C; EXPERIENCE; LIVER
AB Objective: Biliary atresia (BA) frequently results in portal hypertension (PHT), complications of which lead to significant morbidity and mortality. The Childhood Liver Disease Research and Education Network was used to perform a cross-sectional multicentered analysis of PHT in children with BA.
Methods: Subjects with BA receiving medical management at a Childhood Liver Disease Research and Education Network site were enrolled. A priori, clinically evident PHT was defined as "definite'' when there was either history of a complication of PHT or clinical findings consistent with PHT (both splenomegaly and thrombocytopenia). PHT was denoted as "possible'' if one of the findings was present in the absence of a complication, whereas PHT was "absent'' if none of the criteria were met.
Results: A total of 163 subjects were enrolled between May 2006 and December 2009. At baseline, definite PHT was present in 49%, possible in 17%, and absent in 34% of subjects. Demographics, growth, and anthropometrics were similar amongst the 3 PHT categories. Alanine aminotransferase, gamma-glutamyl transpeptidase, and sodium levels were similar, whereas there were significant differences in aspartate aminotransferase (AST), AST/alanine aminotransferase, albumin, total bilirubin, prothrombin time, white blood cell count, platelet count, and AST/platelet count between definite and absent PHT. Thirty-four percent of those with definite PHT had either prothrombin time >15 seconds or albumin <3 g/dL.
Conclusions: Clinically definable PHT is present in two-thirds of North American long-term BA survivors with their native livers. The presence of PHT is associated with measures of hepatic injury and dysfunction, although in this selected cohort, the degree of hepatic dysfunction is relatively mild and growth is preserved.
C1 [Shneider, Benjamin L.] UPMC, Childrens Hosp Pittsburgh, Div Pediat Gastoenterol Hepatol & Nutr, Pittsburgh, PA 15224 USA.
[Abel, Bob; Magee, John C.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Haber, Barbara] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Karpen, Saul J.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Romero, Rene] Emory Univ, Atlanta, GA USA.
[Schwarz, Kathleen] Johns Hopkins Univ, Baltimore, MD USA.
[Bass, Lee M.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Kerkar, Nanda] Mt Sinai Sch Med, New York, NY USA.
[Miethke, Alexander G.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Turmelle, Yumirle] Washington Univ, St Louis, MO USA.
[Robuck, Patricia R.] NIDDKD, NIH, Bethesda, MD 20892 USA.
[Sokol, Ronald J.] Univ Colorado, Aurora, CO USA.
[Sokol, Ronald J.] Childrens Hosp Colorado, Aurora, CO USA.
RP Shneider, BL (reprint author), UPMC, Childrens Hosp Pittsburgh, Div Pediat Gastoenterol Hepatol & Nutr, 4401 Penn Ave, Pittsburgh, PA 15224 USA.
EM Benjamin.Shneider@chp.edu
FU National Center for Research Resources [5M01 RR00069, UL1RR025780,
UL1RR024153, UL1RR024134, UL1RR024131, UL1RR025005, UL1RR025741,
UL1RR029877]; National Institute of Diabetes, Digestive and Kidney
Diseases [DK 62453, DK 62497, DK 62481, DK 62470, DK 62500, DK 62530, DK
62445, DK 62466, DK 62456, DK 62452, DK 62436, DK 84585]
FX This work was financially supported by the National Center for Research
Resources (5M01 RR00069 [R.J.S.], UL1RR025780 [Colorado], UL1RR024153
[Pittsburgh], UL1RR024134 [Philadelphia], UL1RR024131 [San Francisco],
UL1RR025005 [Baltimore], UL1RR025741 [Chicago]), UL1RR029877 [New York]
and the National Institute of Diabetes, Digestive and Kidney Diseases
(DK 62453 [R.J.S.], DK 62497 [A.G.M.], DK 62481 [B.A.H.], DK 62470
[S.J.K.], DK 62500 [P.R.], DK 62530 [K.S.], DK 62445 [N.K.], DK 62466
[B.L.S.], DK 62456 [J.C.M.], DK 62452 [Y.T.], DK 62436 [L.B.], DK 84585
[R.R.].
NR 29
TC 16
Z9 17
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD NOV
PY 2012
VL 55
IS 5
BP 567
EP 573
DI 10.1097/MPG.0b013e31826eb0cf
PG 7
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 030LH
UT WOS:000310571700024
PM 22903006
ER
PT J
AU Briassoulis, G
Kuburovic, V
Xekouki, P
Patronas, N
Keil, MF
Lyssikatos, C
Stajevic, M
Kovacevic, G
Stratakis, CA
AF Briassoulis, George
Kuburovic, Vladimir
Xekouki, Paraskevi
Patronas, Nicholas
Keil, Meg F.
Lyssikatos, Charalampos
Stajevic, Mila
Kovacevic, Gordana
Stratakis, Constantine A.
TI Recurrent Left Atrial Myxomas in Carney Complex: A Genetic Cause of
Multiple Strokes that can be Prevented
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Carney complex; embolic; myxomas; regulatory subunit of the protein
kinase gene; stroke
ID CARDIAC MYXOMAS; REGULATORY SUBUNIT; MUTATIONS; PATIENT; ANEURYSMS;
PRKAR1A
AB Background: Intracardiac myxomas in Carney complex are significant causes of cardiovascular morbidity and mortality through embolic stroke and heart failure. The genetic, clinical, and laboratory characteristics of Carney complex-related strokes from atrial myxomas have not been described. The regulatory subunit (R1A) of the protein kinase gene (PRKAR1A) is mutated in >60% of patients with Carney complex. Methods: We studied patients with strokes and cardiac myxomas that were hospitalized in our institution and elsewhere; a total of 7 patients with 16 recurrent atrial myxomas and >14 episodes of strokes were identified. Results: Neurologic deficits were reported; in 1 patient, an aneurysm developed at the site of a previous stroke. All patients were females, were also diagnosed with Cushing syndrome, and all had additional tumors or other Carney complex manifestations. Other than gender, although there was a trend for patients being overweight and hypertensive, no other risk factors were identified. A total of 5 patients (71%) had a PRKAR1A mutation; all mutations (c418_419delCA, c.340delG/p.Val113fsX15, c.353_365del13/p.Ile118fsX6, c.491_492delTG/p.Val164fsX4, and c.17711G.A) were located in exons 3 to 5 and introns 2 to 3, and all led to a non-sense PRKAR1A mRNA. Conclusions: Female patients with Carney complex appear to be at a high risk for recurrent atrial myxomas that lead to multiple strokes. Early identification of a female patient with Carney complex is of paramount importance for the early diagnosis of atrial myxomas and the prevention of strokes.
C1 [Briassoulis, George; Xekouki, Paraskevi; Keil, Meg F.; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Kuburovic, Vladimir] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Cardiol, Belgrade, Serbia.
[Stajevic, Mila] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Cardiac Surg, Belgrade, Serbia.
[Kovacevic, Gordana] Mother & Child Hlth Care Inst Serbia Dr Vukan Cup, Dept Pediat Neurol, Belgrade, Serbia.
[Patronas, Nicholas] NIH, Clin Res Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH)
[Z01-HD-000642-04]; Intensive Care Unit, Department of Pediatrics,
Regional University Hospital, University of Crete, Heraklion, Greece
FX Supported in part by the Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD), intramural National
Institutes of Health (NIH) project Z01-HD-000642-04 to Dr. Stratakis,
and by the Intensive Care Unit, Department of Pediatrics, Regional
University Hospital, University of Crete, Heraklion, Greece (Dr.
Briassoulis).
NR 17
TC 3
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD NOV
PY 2012
VL 21
IS 8
AR 914.e1
DI 10.1016/j.jstrokecerebrovasdis.2012.01.006
PG 8
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 031LM
UT WOS:000310641900079
PM 22341669
ER
PT J
AU Nansel, TR
Haynie, DL
Lipsky, LM
Laffel, LMB
Mehta, SN
AF Nansel, Tonja R.
Haynie, Denise L.
Lipsky, Leah M.
Laffel, Lori M. B.
Mehta, Sanjeev N.
TI Multiple Indicators of Poor Diet Quality in Children and Adolescents
with Type 1 Diabetes Are Associated with Higher Body Mass Index
Percentile but not Glycemic Control
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Diabetes mellitus, type 1; Diet; Disease management; Body weight
ID NUTRIENT-RICH FOODS; BLOOD-GLUCOSE CONTROL; WEIGHT-GAIN; COMPLICATIONS
TRIAL; INSULIN THERAPY; RISK-FACTORS; US CHILDREN; YOUTH; PREVALENCE;
NUTRITION
AB Background Diet is a cornerstone of type 1 diabetes treatment, and poor diet quality may affect glycemic control and other health outcomes. Yet diet quality in children and adolescents with type 1 diabetes remains understudied.
Objective To evaluate multiple indicators of diet quality in children and adolescents with type I diabetes and their associations with hemoglobin A1c and body mass index percentile.
Design In this cross-sectional study, participants completed 3-day diet records, and data were abstracted from participants' medical records. Diet quality indicators included servings of fruit, vegetables, and whole grains; Healthy Eating Index-2005 (HEI-2005) score; Nutrient Rich Foods 9.3 score (NRF 9.3); and glycemic index.
Participants/setting Children and adolescents with type >= 1 diabetes year, aged 8 to 18 years, were recruited at routine clinic visits. Of 291 families enrolled, 252 provided diet data.
Statistical analyses Associations of diet quality indicators to HbA1c and body mass index percentile were examined using analysis of covariance and multiple linear regression.
Results Participants demonstrated low adherence to dietary guidelines; mean HEI-2005 score was 53.4 +/- 11.0 (range=26.7 to 81.2). Intake of fruit, vegetables, and whole grains was less than half the recommended amount. Almost half of the participants' daily energy intake was derived from refined-grain products, desserts, chips, and sweetened beverages. Higher fruit (P=0.04) and whole-grain (P=0.03) intake were associated with lower HbA1c in unadjusted, but not adjusted analyses; vegetable intake, HEI-2005 score, NRF 9.3 score, and glycemic index were not associated with HbA1c. Higher fruit (P=0.01) and whole-grain (P=0.04) intake and NRF 9.3 score (P=0.02), but not other diet quality indicators, were associated with lower body mass index percentile in adjusted analyses.
Conclusions Data demonstrate poor diet quality in youth with type 1 diabetes and provide support for the importance of diet quality for weight management. Future research on determinants of dietary intake and methods to promote improved diet quality would be useful to inform clinical care. J Acad Nutr Diet. 2012;112:1728-1735.
C1 [Nansel, Tonja R.; Haynie, Denise L.; Lipsky, Leah M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Laffel, Lori M. B.] Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Boston, MA USA.
[Laffel, Lori M. B.; Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA.
RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, 6100 Execut Blvd,Room 7B13R,MSC 7510, Bethesda, MD 20892 USA.
EM nanselt@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079;
Lipsky, Leah/0000-0003-2645-4388
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200703434C]
FX This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development (contract no. HHSN267200703434C).
NR 54
TC 19
Z9 21
U1 0
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD NOV
PY 2012
VL 112
IS 11
BP 1728
EP 1735
DI 10.1016/j.jand.2012.08.029
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 033RT
UT WOS:000310819200005
PM 23102173
ER
PT J
AU Tse, J
Nansel, TR
Haynie, DL
Mehta, SN
Laffel, LMB
AF Tse, Julia
Nansel, Tonja R.
Haynie, Denise L.
Mehta, Sanjeev N.
Laffel, Lori M. B.
TI Disordered Eating Behaviors Are Associated with Poorer Diet Quality in
Adolescents with Type 1 Diabetes
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Type 1 diabetes; Disordered eating; Dietary quality; Diabetes
management; Diabetes Eating Problem Survey
ID COMPLICATIONS TRIAL; BODY-WEIGHT; OVERWEIGHT; CHILDREN; MELLITUS;
BARRIERS; FEMALES; OBESITY; ADULTS; GIRLS
AB Disordered eating behaviors may pose a risk for poor long-term health outcomes in patients with type 1 diabetes. This cross-sectional study examined associations of disordered eating behaviors with diet quality, diet-related attitudes, and diabetes management in adolescents with type 1 diabetes (N=151, 48% female). Participants, recruited July 2008 through February 2009, completed 3-day diet records and survey measures, including the Diabetes Eating Problem Survey (DEPS) and measures of eating-related attitudes. Biomedical data were obtained from medical records. Participants scoring more than 1 standard deviation above the mean DEPS were classified as at risk for disordered eating. The Healthy Eating Index-2005 was calculated to assess diet quality. Analysis of covariance was used to test for differences between risk groups in diet quality, eating attitudes, and diabetes management controlling forage, sex, and body mass index (BMI) percentile. Youth at risk for disordered eating were more likely to be overweight/obese than those at low risk (59.1% vs 31.8%, P=0.01). The at-risk group had poorer diet quality (P=0.003) as well as higher intake of total fat (P=0.01) and saturated fat (P=0.007) compared with the low-risk group. The at-risk group reported lower self-efficacy (P=0.005), greater barriers (P<0.001), and more negative outcome expectations (P<0.001) for healthful eating, as well as worse dietary satisfaction (P=0.004). The at-risk group had lower diabetes adherence (P<0.01), less-frequent blood glucose monitoring (P<0.002), and higher hemoglobin A1c (P<0.001). The constellation of excess weight, poorer dietary intake, and poorer diabetes management associated with youth at risk for disordered eating suggests potential risk of future poor health outcomes. Attention should be given to healthful weight management, especially among overweight youth with type 1 diabetes. J Acad Nutr Diet 2012;112:1810-1814.
C1 [Tse, Julia; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA.
[Laffel, Lori M. B.] Harvard Univ, Sch Med, Adolescent & Young Adult Sect, Boston, MA 02115 USA.
RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bldg 6100,Room 7805,MSC 7510, Bethesda, MD 20892 USA.
EM nanselt@mail.nih.gov
OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development [HHSN267200703434C]
FX This research was supported by the intramural research program of the
National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health and Human Development, contract number
HHSN267200703434C.
NR 28
TC 11
Z9 11
U1 1
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD NOV
PY 2012
VL 112
IS 11
BP 1810
EP 1814
DI 10.1016/j.jand.2012.06.359
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 033RT
UT WOS:000310819200014
PM 23102180
ER
PT J
AU Shaw, P
AF Shaw, Philip
TI Attention-Deficit/Hyperactivity Disorder and the Battle for Control of
Attention
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
ID DEFICIT HYPERACTIVITY DISORDER; WORKING-MEMORY; PLASTICITY; BRAIN
C1 NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI, Bethesda, MD 20892 USA.
RP Shaw, P (reprint author), NIMH, Sect Neurobehav Clin Res, Social & Behav Res Branch, NHGRI, Bldg 13,Room B1B36, Bethesda, MD 20892 USA.
EM shawp@mail.nih.gov
FU Intramural NIH HHS
NR 13
TC 3
Z9 3
U1 3
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2012
VL 51
IS 11
BP 1116
EP 1118
DI 10.1016/j.jaac.2012.06.016
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 035IF
UT WOS:000310939300004
PM 23101738
ER
PT J
AU Smith, L
Brinton, LA
Freedman, ND
Gierach, GL
AF Smith, Llewellyn
Brinton, Louise A.
Freedman, Neal D.
Gierach, Gretchen L.
TI Re: Body Mass Index and Risk of Lung Cancer Among Never, Former, and
Current Smokers Response
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Letter
C1 [Smith, Llewellyn; Brinton, Louise A.; Gierach, Gretchen L.] NCI, Hormonal & Reprod Epidemiol Branch, NIH, Rockville, MD USA.
[Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Gierach, GL (reprint author), 6120 Execut Blvd,Ste 550,Rm 5016, Rockville, MD 20852 USA.
EM gierachg@mail.nih.gov
RI Brinton, Louise/G-7486-2015; Freedman, Neal/B-9741-2015; Gierach,
Gretchen/E-1817-2016
OI Brinton, Louise/0000-0003-3853-8562; Freedman, Neal/0000-0003-0074-1098;
Gierach, Gretchen/0000-0002-0165-5522
NR 2
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD NOV
PY 2012
VL 104
IS 21
BP 1681
EP 1681
DI 10.1093/jnci/djs382
PG 1
WC Oncology
SC Oncology
GA 035SS
UT WOS:000310969600012
ER
PT J
AU Guise, JM
Nagel, JD
Regensteiner, JG
AF Guise, Jeanne-Marie
Nagel, Joan D.
Regensteiner, Judith G.
CA Bldg Interdisciplinary Res Careers
TI Best Practices and Pearls in Interdisciplinary Mentoring from Building
Interdisciplinary Research Careers in Women's Health Directors
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID ACADEMIC MEDICINE; SCIENCE; OPPORTUNITIES; CHALLENGES; FACULTY; PROGRAM
AB Background: Increasingly, national programs and leaders are looking at interdisciplinary collaborations as essential to future research. Twelve years ago, the National Institutes of Health (NIH) Office of Research on Women's Health (ORWH) developed and implemented the Building Interdisciplinary Research Careers in Women's Health (BIRCWH) K12 program to focus on interdisciplinary mentored career development for junior faculty in women's health research.
Methods: We applied a mixed-methods approach using an electronic survey and in-person presentations and discussions to understand best practices and lessons learned for interdisciplinary mentoring across BIRCWH K12 program leaders.
Results and Conclusions: We received responses from all 29 active BIRCWH programs. Factors associated with success included ensuring sufficient protected time for regular (weekly or biweekly) mentoring; mentors promoting the research independence of the Scholar; a team mentoring approach, including career as well as content mentors; and explicit and clear expectations outlined between the Scholar and mentor. The majority of programs conduct formal evaluations of mentorship, and 79% of programs offer training in mentorship for either Scholars, mentors, or both. This article presents program leaders' best practices, challenges, and lessons learned from mentoring junior faculty who are conducting women's health research, whether basic, clinical, behavioral, translational, or health services research, using an interdisciplinary mentoring approach.
C1 [Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Portland, OR 97239 USA.
[Nagel, Joan D.] NIH, Off Res Womens Hlth, Washington, DC USA.
[Regensteiner, Judith G.] Univ Colorado, Sch Med, Dept Med, Ctr Womens Hlth Res, Denver, CO USA.
[Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.
[Guise, Jeanne-Marie] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97239 USA.
RP Guise, JM (reprint author), Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Div Maternal Fetal Med, Mail Code L466,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM guisej@ohsu.edu
OI Sherman, Bonnie/0000-0002-6322-8366
FU NICHD NIH HHS [K12 HD043488, K12 HD051953, K12 HD055884]; NIDA NIH HHS
[P50 DA005312]
NR 12
TC 3
Z9 3
U1 0
U2 14
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
J9 J WOMENS HEALTH
JI J. Womens Health
PD NOV
PY 2012
VL 21
IS 11
BP 1114
EP 1127
DI 10.1089/jwh.2012.3788
PG 14
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA 034BI
UT WOS:000310844700002
PM 22994986
ER
PT J
AU Breman, JG
AF Breman, Joel G.
TI Resistance to artemisinin-based combination therapy
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID ARTEMETHER-LUMEFANTRINE; FALCIPARUM-MALARIA; SELECTION; AFRICA
C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM jbreman@nih.gov
NR 8
TC 22
Z9 24
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD NOV
PY 2012
VL 12
IS 11
BP 820
EP 822
DI 10.1016/S1473-3099(12)70226-8
PG 3
WC Infectious Diseases
SC Infectious Diseases
GA 029JT
UT WOS:000310492300004
PM 22940026
ER
PT J
AU Amaratunga, C
Sreng, S
Suon, S
Phelps, ES
Stepniewska, K
Lim, P
Zhou, CJ
Mao, S
Anderson, JM
Lindegardh, N
Jiang, HY
Song, JP
Su, XZ
White, NJ
Dondorp, AM
Anderson, TJC
Fay, MP
Mu, JB
Duong, S
Fairhurst, RM
AF Amaratunga, Chanaki
Sreng, Sokunthea
Suon, Seila
Phelps, Erika S.
Stepniewska, Kasia
Lim, Pharath
Zhou, Chongjun
Mao, Sivanna
Anderson, Jennifer M.
Lindegardh, Niklas
Jiang, Hongying
Song, Jianping
Su, Xin-zhuan
White, Nicholas J.
Dondorp, Arjen M.
Anderson, Tim J. C.
Fay, Michael P.
Mu, Jianbing
Duong, Socheat
Fairhurst, Rick M.
TI Artemisinin-resistant Plasmodium falciparum in Pursat province, western
Cambodia: a parasite clearance rate study
SO LANCET INFECTIOUS DISEASES
LA English
DT Article
ID POPULATION-STRUCTURE; G6PD VIANGCHAN; HEMOGLOBIN-E; MALARIA; ARTESUNATE;
SUSCEPTIBILITY; HERITABILITY; THALASSEMIA; MECHANISM; VARIANT
AB Background Artemisinin-resistant Plasmodium falciparum has been reported in Pailin, western Cambodia, detected as a slow parasite clearance rate in vivo. Emergence of this phenotype in western Thailand and possibly elsewhere threatens to compromise the effectiveness of all artemisinin-based combination therapies. Parasite genetics is associated with parasite clearance rate but does not account for all variation. We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia.
Methods Between June 19 and Nov 28,2009, and June 26 and Dec 6,2010, we enrolled patients aged 10 years or older with uncomplicated falciparum malaria, a density of asexual parasites of at least 10000 per mu L of whole blood, no symptoms or signs of severe malaria, no other cause of febrile illness, and no chronic illness. We gave participants 4 mg/kg artesunate at 0,24, and 48 h, 15 mg/kg mefloquine at 72 h, and 10 mg/kg mefloquine at 96 h. We assessed parasite density on thick blood films every 6 h until undetectable. The parasite clearance half-life was calculated from the parasite clearance curve. We genotyped parasites with 18 microsatellite markers and patients for haemoglobin E, alpha-thalassaeinia, and a mutation of GOD, which encodes glucose-6-phosphate dehydrogenase. To account for the possible effects of acquired immunity on half-life, we used three surrogates for increased likelihood of exposure to P falciparum: age, sex, and place of residence. This study is registered with ClinicalTrials.gov, number NCT00341003.
Findings We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. We enrolled 168 patients with falciparum malaria who met inclusion criteria. The geometric mean half-life was 5.85 h (95% CI 5.54-6.18) in Pursat, similar to that reported in Pailin (p=0.109). We identified two genetically different parasite clone groups: parasite group 1 (PG1) and parasite group 2 (PG2). Non-significant increases in parasite clearance half-life were seen in patients with haemoglobin E (0.55 h; p=0.078), those of male sex (0.96 h; p=0.064), and in 2010 (0.68 h; p=0.068); PG1 was associated with a significant increase (0.79 h; p=0.033). The mean parasite heritability of half-life was 0.40 (SD 0.17).
Interpretation Heritable artemisinin resistance is established in a second Cambodian province. To accurately identify parasites that are intrinsically susceptible or resistant to artemisinins, future studies should explore the effect of erythrocyte polymorphisms and specific immune responses on half-life variation.
C1 [Amaratunga, Chanaki; Phelps, Erika S.; Lim, Pharath; Anderson, Jennifer M.; Jiang, Hongying; Su, Xin-zhuan; Mu, Jianbing; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Fay, Michael P.] NIAID, Biostat Res Brand, NIH, Rockville, MD 20852 USA.
[Sreng, Sokunthea; Suon, Seila; Lim, Pharath; Duong, Socheat] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
[Stepniewska, Kasia] Univ Oxford, Nuffield Dept Clin Med, Worldwide Antimalarial Resistance Network, Oxford, England.
[Stepniewska, Kasia] Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med, Oxford, England.
[Zhou, Chongjun; Song, Jianping] Guangzhou Univ Tradit Chinese Med, Res Ctr Qinghao, Guangzhou, Guangdong, Peoples R China.
[Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia.
[Lindegardh, Niklas; White, Nicholas J.; Dondorp, Arjen M.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok 10700, Thailand.
[Anderson, Tim J. C.] Texas Biomed Res Inst, San Antonio, TX USA.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM rfairhurst@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625; Su, Xinzhuan/0000-0003-3246-3248
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Funding Division of Intramural Research, National Institute of Allergy
and Infectious Diseases, National Institutes of Health.
NR 36
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U1 4
U2 25
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1473-3099
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD NOV
PY 2012
VL 12
IS 11
BP 851
EP 858
DI 10.1016/S1473-3099(12)70181-0
PG 8
WC Infectious Diseases
SC Infectious Diseases
GA 029JT
UT WOS:000310492300024
PM 22940027
ER
PT J
AU Kikuchi, J
Takashina, T
Kinoshita, I
Kikuchi, E
Shimizu, Y
Sakakibara-Konishi, J
Oizumi, S
Marquez, VE
Nishimura, M
Dosaka-Akita, H
AF Kikuchi, Junko
Takashina, Taichi
Kinoshita, Ichiro
Kikuchi, Eiki
Shimizu, Yasushi
Sakakibara-Konishi, Jun
Oizumi, Satoshi
Marquez, Victor E.
Nishimura, Masaharu
Dosaka-Akita, Hirotoshi
TI Epigenetic therapy with 3-deazaneplanocin A, an inhibitor of the histone
methyltransferase EZH2, inhibits growth of non-small cell lung cancer
cells
SO LUNG CANCER
LA English
DT Article
DE 3-Deazaneplanocin A (DZNep); Polycomb-group protein; EZH2; Non-small
cell lung cancer; Epigenetics; Proliferation; Apoptosis
ID ZESTE HOMOLOG 2; S-ADENOSYLHOMOCYSTEINE HYDROLASE; BRONCHIAL
EPITHELIAL-CELLS; PROSTATE-CANCER; CYCLIN-A; PHARMACOLOGICAL DISRUPTION;
GROUP PROTEINS; EXPRESSION; POLYCOMB; ENHANCER
AB EZH2 (enhancer of zeste homolog 2) is the catalytic subunit of PRC2 (polycomb repressive complex 2), which mediates histone methyltransferase activity and functions as transcriptional repressor involved in gene silencing. EZH2 is involved in malignant transformation and biological aggressiveness of several human malignancies. We previously demonstrated that non-small cell lung cancers (NSCLCs) also overexpress EZH2 and that high expression of EZH2 correlates with poor prognosis. Growing evidence indicates that EZH2 may be an appropriate therapeutic target in malignancies, including NSCLCs. Recently, an S-adenosyl-L-homocysteine hydrolase inhibitor, 3-Deazaneplanocin A (DZNep), has been shown to deplete and inhibit EZH2. The aim of this study was to determine the effect of DZNep in NSCLC cells. Knockdown of EZH2 by small-interfering RNA (siRNA) resulted in decreased growth of four NSCLC cell lines. MTT assays demonstrated that DZNep treatment resulted in dose-dependent inhibition of proliferation in the NSCLC cell lines with a half maximal inhibitory concentration (IC50) ranging from 0.08 to 0.24 mu M. Immortalized but non-cancerous bronchial epithelial and fibroblast cell lines were less sensitive to DZNep than the NSCLC cell lines. Soft agarose assays demonstrated that anchorage-independent growth was also reduced in all three NSCLC cell lines that were evaluated using this assay. Flow cytometry analysis demonstrated that DZNep induced apoptosis and G1 cell cycle arrest in NSCLC cells, which was partially associated with cyclin A decrease and p27(Kip1) accumulation. DZNep depleted cellular levels of EZH2 and inhibited the associated histone H3 lysine 27 trimethylation. These results indicated that an epigenetic therapy that pharmacologically targets EZH2 via DZNep may constitute a novel approach to treatment of NSCLCs. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
C1 [Kinoshita, Ichiro] Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, Sapporo, Hokkaido 0608638, Japan.
[Kikuchi, Junko; Takashina, Taichi; Kikuchi, Eiki; Sakakibara-Konishi, Jun; Oizumi, Satoshi; Nishimura, Masaharu] Hokkaido Univ, Sch Med, Dept Med 1, Sapporo, Hokkaido 0608638, Japan.
[Marquez, Victor E.] NCI, Biol Chem Lab, FNLCR, NIH, Frederick, MD 21702 USA.
RP Kinoshita, I (reprint author), Hokkaido Univ, Grad Sch Med, Dept Med Oncol, Kita Ku, North 15,West 7, Sapporo, Hokkaido 0608638, Japan.
EM kinoshii@med.hokudai.ac.jp
RI Kikuchi, Eiki/M-9688-2014; Nishimura, Masaharu/A-4062-2012
FU Japan Society for the Promotion of Science; Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research
FX This study was supported in part by a Grant-in-Aid for Scientific
Research (C) from the Japan Society for the Promotion of Science. This
research was also supported in part by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research. The
authors thank Namiko Sawada for technical assistance.
NR 40
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U1 1
U2 17
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
J9 LUNG CANCER
JI Lung Cancer
PD NOV
PY 2012
VL 78
IS 2
BP 138
EP 143
DI 10.1016/j.lungcan.2012.08.003
PG 6
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 035JZ
UT WOS:000310944000003
PM 22925699
ER
PT J
AU Kang, C
Drayna, D
AF Kang, Changsoo
Drayna, Dennis
TI A role for inherited metabolic deficits in persistent developmental
stuttering
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Review
DE Stuttering; Linkage; Lysosomal targeting pathway; GNPTAB; NAGPA
ID 6-PHOSPHATE UNCOVERING ENZYME; PSEUDO-HURLER POLYDYSTROPHY;
MUCOLIPIDOSIS-II; ULTRASONIC VOCALIZATION; ALPHA/BETA-SUBUNITS; MICE;
MUTATIONS; LINKAGE; GENE; TWIN
AB Stuttering is a common but poorly understood speech disorder. Consistent evidence for the involvement of genetic factors in stuttering has motivated studies aimed at identifying causative genetic variants that could shed light on the underlying molecular and cellular deficits in this disorder. Such studies have begun to identify causative genes. The purpose of this review is to summarize the gene discoveries to date, and to cover the subsequent functional studies that are beginning to provide insights into how these gene mutations might cause stuttering. Surprisingly, the first variant genes to be associated with stuttering are those encoding the lysosomal targeting system, GNPTAB, GNPTG, and NAGPA. Although mutations in NAGPA have not been associated with a disorder in humans, mutations in GNPTAB and GNPTG cause mucolipidosis types II and III, which are rare autosomal recessive lysosomal storage disorders, associated with pathology of bone, connective tissue, liver, spleen, and brain. Analysis of mutations in these genes has so far identified predominantly missense mutations in stuttering, in contrast to the truncating and other mutations that result in very low GNPTAB/G enzyme activity and are historically associated with mucolipidosis. Genetic evidence for the role of lysosomal targeting mutations in stuttering has now been buttressed by biochemical studies of the mutant enzymes found in this disorder. While data on the GlcNAc-phosphotransferase encoded by GNPTAB/G remains limited and only suggestive, a study of the enzyme encoded by NAGPA has shown that the mutations found in stuttering reduce the overall cellular activity of this enzyme by about half, and that they result in deficits in intracellular processing and trafficking that lead to a reduced cellular half life. How these deficits result in the presumed speech-specific neuropathology associated with stuttering is not yet known. However these findings have opened several new lines of inquiry, including studies in mice carrying human stuttering mutations, that represent promising approaches to this disorder. Published by Elsevier Inc.
C1 [Kang, Changsoo; Drayna, Dennis] NIDCD, NIH, Rockville, MD 20850 USA.
RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court,Room 2B-46, Rockville, MD 20850 USA.
EM drayna@nidcd.nih.gov
FU NIH/NIDCD [Z01-000046-12]; Stuttering Foundation of America
FX We thank Stuart Kornfeld, Thomas Friedman, and Allen Braun for valuable
comments on the manuscript. This work was supported by the NIH/NIDCD
intramural grant Z01-000046-12 and by the Stuttering Foundation of
America.
NR 47
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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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2012
VL 107
IS 3
BP 276
EP 280
DI 10.1016/j.ymgme.2012.07.020
PG 5
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 032LM
UT WOS:000310720200006
PM 22884963
ER
PT J
AU Punwani, D
Gonzalez-Espinosa, D
Comeau, AM
Dutra, A
Pak, E
Puck, J
AF Punwani, Divya
Gonzalez-Espinosa, Diana
Comeau, Anne Marie
Dutra, Amalia
Pak, Evgenia
Puck, Jennifer
TI Cellular calibrators to quantitate T-cell receptor excision circles
(TRECs) in clinical samples
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE TREC; SCID; newborn screening; Calibrator; Test standardization; Primary
immunodeficiency
ID SEVERE COMBINED IMMUNODEFICIENCY; RECENT THYMIC EMIGRANTS;
TRANSPLANTATION; GENE; THERAPY; DISEASE; OUTPUT; PCR
AB T-cell receptor excision circles (TRECs) are circular DNA molecules formed during rearrangement of the T-cell receptor (TCR) genes during lymphocyte development. Copy number of the junctional portion of the delta Rec-psi J alpha TREC, assessed by quantitative PCR (qPCR) using DNA from dried blood spots (DBS), is a biomarker for newly formed T cells and absent or low numbers of TRECs indicate SCID (severe combined immunodeficiency) or T lymphocytopenia. No quantitation standard for TRECs exists. To permit comparison of TREC qPCR results with a reliable method for counting TRECs across different laboratories, we sought to construct a stable cell line containing a normal human chromosomal constitution and a single copy of the TREC junction sequence. A human EBV (Epstein Barr virus)-transformed B-cell line was transduced with a lentivirus encoding mCherry fluorescence, puromycin resistance and the delta Rec-psi J alpha. TREC sequence. A TREC-EBV cell line, with each cell carrying a single lentiviral insertion was established, expanded and shown to have one TREC copy per diploid genome. Graded numbers of TREC-EBV cells added to aliquots of T lymphocyte depleted blood showed TREC copy number proportional to TREC-EBV cell number. TREC-EBV cells, therefore, constitute a reproducible cellular calibrator for TREC assays, useful for both population-based screening for severe combined immunodeficiency and evaluation of naive T-cell production in clinical settings. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Punwani, Divya; Gonzalez-Espinosa, Diana; Puck, Jennifer] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Comeau, Anne Marie] Univ Massachusetts, Sch Med, Dept Pediat, New England Newborn Screening Program, Worcester, MA 01610 USA.
[Dutra, Amalia; Pak, Evgenia] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Puck, J (reprint author), UCSF Dept Pediat, Box 0519,513 Parnassus Ave,HSE 301A, San Francisco, CA 94143 USA.
EM puckj@peds.ucsf.edu
FU UMMS [DHHS/CDC U01EH000362]; NIH NHGRI Intramural Research Program; NIH
[RO3 HD060311]; Jeffrey Modell Foundation
FX The authors thank Robert Vogt, CDC, Atlanta, for helpful discussions and
Michael McManus, UCSF, who provided the MP-283 lentiviral vector. This
study was supported by DHHS/CDC U01EH000362 subcontract from UMMS, the
NIH NHGRI Intramural Research Program (AD and EP) and by NIH RO3
HD060311 and the Jeffrey Modell Foundation (JMP). The authors declare no
competing financial interests.
NR 32
TC 4
Z9 5
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2012
VL 107
IS 3
BP 586
EP 591
DI 10.1016/j.ymgme.2012.09.018
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 032LM
UT WOS:000310720200049
PM 23062576
ER
PT J
AU Chandler, RJ
Venditti, CP
AF Chandler, Randy J.
Venditti, Charles P.
TI Pre-clinical efficacy and dosing of an AAV8 vector expressing human
methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia
(MMA)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Methylmalonic acidemia; MMA; Gene therapy; Adeno-associated virus; AAV;
Organic acidemia
ID GENE DELIVERY RESCUES; MUT(0)
AB We demonstrate that human methylmalonyl-CoA mutase (MUT), delivered using an AAV serotype 8 vector, rescues the lethal phenotype displayed by mice with MMA and provides long-term phenotypic correction. In addition to defining a lower limit of effective dosing, our studies establish that neither a species barrier to mitochondrial processing nor an apparent immune response to MUT limits the murine model as an experimental platform to test the efficacy of human gene therapy vectors for MMA. Published by Elsevier Inc.
C1 [Chandler, Randy J.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA.
RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, NIH, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
FU Intramural NIH HHS [Z99 HG999999, ZIA HG200318-09]
NR 11
TC 5
Z9 5
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 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2012
VL 107
IS 3
BP 617
EP 619
DI 10.1016/j.ymgme.2012.09.019
PG 3
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 032LM
UT WOS:000310720200056
PM 23046887
ER
PT J
AU Zhao, JF
Stagno, JR
Varticovski, L
Nimako, E
Rishi, V
McKinnon, K
Akee, R
Shoemaker, RH
Ji, XH
Vinson, C
AF Zhao, Jianfei
Stagno, Jason R.
Varticovski, Lyuba
Nimako, Eric
Rishi, Vikas
McKinnon, Kathy
Akee, Rhone
Shoemaker, Robert H.
Ji, Xinhua
Vinson, Charles
TI P6981, An Arylstibonic Acid, Is a Novel Low Nanomolar Inhibitor of cAMP
Response Element-Binding Protein Binding to DNA
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID CLEAR-CELL SARCOMA; HELIX-LOOP-HELIX; GCN4 LEUCINE-ZIPPER; COILED-COIL;
TRANSCRIPTION FACTORS; DIMERIZATION SPECIFICITY; MALIGNANT-MELANOMA;
MYELOID-LEUKEMIA; SOFT PARTS; CREB
AB Several basic leucine zipper (B-ZIP) transcription factors have been implicated in cancer, substance abuse, and other pathological conditions. We previously identified arylstibonic acids that bind to B-ZIP proteins and inhibit their interaction with DNA. In this study, we used electrophoretic mobility shift assay to analyze 46 arylstibonic acids for their activity to disrupt the DNA binding of three B-ZIP [CCAAT/enhancer-binding protein alpha, cyclic AMP-response element-binding protein (CREB), and vitellogenin gene-binding protein (VBP)] and two basic helix-loop-helix leucine zipper (B-HLH-ZIP) [USF (upstream stimulating factor) and Mitf] proteins. Twenty-five arylstibonic acids showed activity at micromolar concentrations. The most active compound, P6981 [2-(3-stibonophenyl)malonic acid], had half-maximal inhibition at similar to 5 nM for CREB. Circular dichroism thermal denaturation studies indicated that P6981 binds both the B-ZIP domain and the leucine zipper. The crystal structure of an arylstibonic acid, NSC13778, bound to the VBP leucine zipper identified electrostatic interactions between both the stibonic and carboxylic acid groups of NSC13778 [(E)-3-(3-stibonophenyl)acrylic acid] and arginine side chains of VBP, which is also involved in interhelical salt bridges in the leucine zipper. P6981 induced GFP-B-ZIP chimeric proteins to partially localize to the cytoplasm, demonstrating that it is active in cells. P6981 inhibited the growth of a patient-derived clear cell sarcoma cell line whose oncogenic potential is driven by a chimeric protein EWS-ATF1 (Ewing's sarcoma protein-activating transcription factor 1), which contains the DNA binding domain of ATF1, a B-ZIP protein. NSC13778 inhibited the growth of xenografted clear cell sarcoma, and no toxicity was observed. These experiments suggest that antimony containing arylstibonic acids are promising leads for suppression of DNA binding activities of B-ZIP and B-HLH-ZIP transcription factors.
C1 [Vinson, Charles] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Stagno, Jason R.; Ji, Xinhua] Natl Canc Inst, Macromol Crystallog Lab, Frederick, MD USA.
[Varticovski, Lyuba; McKinnon, Kathy] NCI, Lab Receptor Biol & Gene Express, Vaccine Branch, Bethesda, MD 20892 USA.
[Akee, Rhone] SAIC Frederick, Nat Prod Support Grp, Frederick, MD USA.
[Shoemaker, Robert H.] Frederick Natl Lab Canc Res, Dev Therapeut Program, Frederick, MD USA.
RP Vinson, C (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3128,37 Convent Dr, Bethesda, MD 20892 USA.
EM vinsonc@mail.nih.gov
FU Center for Cancer Research, National Institutes of Health National
Cancer Institute
FX This work was supported by the Intramural Research Program of the Center
for Cancer Research, National Institutes of Health National Cancer
Institute.
NR 51
TC 5
Z9 5
U1 1
U2 10
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD NOV
PY 2012
VL 82
IS 5
BP 814
EP 823
DI 10.1124/mol.112.080820
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 037WS
UT WOS:000311137800005
PM 22851716
ER
PT J
AU Amalou, H
Wood, BJ
AF Amalou, Hayet
Wood, Bradford J.
TI Biopsy and personalized medicine
SO NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
LA English
DT Letter
ID OVARIAN-CANCER; FUSION; NAVIGATION; ABLATION; GUIDANCE
C1 [Amalou, Hayet; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Bethesda, MD 20892 USA.
RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, MSC 1182, Bethesda, MD 20892 USA.
EM bwood@nih.gov
FU Intramural NIH HHS [ZID BC011242-04, ZIA CL040011-05, ZIA CL040015-04]
NR 10
TC 1
Z9 1
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5045
J9 NAT REV GASTRO HEPAT
JI Nat. Rev. Gastroenterol. Hepatol.
PD NOV
PY 2012
VL 9
IS 11
BP 683
EP 683
DI 10.1038/nrgastro.2012.100-c1
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 033FQ
UT WOS:000310780000010
PM 23026901
ER
PT J
AU Csiszovszki, Z
Lewis, DEA
Le, P
Sneppen, K
Semsey, S
AF Csiszovszki, Zsolt
Lewis, Dale E. A.
Le, Phuoc
Sneppen, Kim
Semsey, Szabolcs
TI Specific contacts of the -35 region of the galP1 promoter by RNA
polymerase inhibit GalR-mediated DNA looping repression
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ESCHERICHIA-COLI; TRANSCRIPTION INITIATION; COMPLEX-FORMATION;
ALPHA-SUBUNIT; REPRESSOSOME; BINDING; PROTEIN; SEQUENCES; OPERON; GENE
AB The P1 promoter of the galactose operon in Escherichia coli is one of the best studied examples of 'extended -10' promoters. Recognition of the P1 promoter does not require specific contacts between RNA polymerase and its poor -35 element. To investigate whether specific recognition of the -35 element would affect the regulation of P1 by GalR, we mutagenized the -35 element of P1, isolated variants of the -35 element and studied the regulation of the mutant promoters by in vitro transcription assays and by mathematical modeling. The results show that the GalR-mediated DNA loop is less efficient in repressing P1 transcription when RNA polymerase binds to the -10 and -35 elements concomitantly. Our results suggest that promoters that lack specific -35 element recognition allow decoupling of local chromosome structure from transcription initiation.
C1 [Sneppen, Kim; Semsey, Szabolcs] Univ Copenhagen, Niels Bohr Inst, CMOL, DK-2100 Copenhagen, Denmark.
[Csiszovszki, Zsolt; Lewis, Dale E. A.; Le, Phuoc] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Semsey, S (reprint author), Univ Copenhagen, Niels Bohr Inst, CMOL, Blegdamsvej 17, DK-2100 Copenhagen, Denmark.
EM semsey@nbi.dk
RI Semsey, Szabolcs/L-6329-2013;
OI Semsey, Szabolcs/0000-0002-4522-5495; Sneppen, Kim/0000-0001-9820-3567
FU Danish Council for Independent Research, Natural Sciences; Intramural
Research Program of the National Institutes of Health, National Cancer
Institute, Center for Cancer Research; Danish National Research
Foundation
FX Danish Council for Independent Research, Natural Sciences, the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research and the Danish
National Research Foundation. Funding for open access charge: Danish
National Research Foundation.
NR 43
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2012
VL 40
IS 20
BP 10064
EP 10072
DI 10.1093/nar/gks796
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 035TC
UT WOS:000310970700017
PM 22941635
ER
PT J
AU Dickey, JS
Baird, BJ
Redon, CE
Avdoshina, V
Palchik, G
Wu, JF
Kondratyev, A
Bonner, WM
Martin, OA
AF Dickey, Jennifer S.
Baird, Brandon J.
Redon, Christophe E.
Avdoshina, Valeriya
Palchik, Guillermo
Wu, Junfang
Kondratyev, Alexei
Bonner, William M.
Martin, Olga A.
TI Susceptibility to bystander DNA damage is influenced by replication and
transcriptional activity
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; PRIMARY HUMAN FIBROBLASTS; IRRADIATED
GLIOMA-CELLS; TOPOISOMERASE-I; NITRIC-OXIDE; INTERCELLULAR
COMMUNICATION; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; EXCISION-REPAIR;
HISTONE H2A.X
AB Direct cellular DNA damage may lead to genome destabilization in unexposed, bystander, cells sharing the same milieu with directly damaged cells by means of the bystander effect. One proposed mechanism involves double strand break (DSB) formation in S phase cells at sites of single strand lesions in the DNA of replication complexes, which has a more open structure compared with neighboring DNA. The DNA in transcription complexes also has a more open structure, and hence may be susceptible to bystander DSB formation from single strand lesions. To examine whether transcription predisposes non-replicating cells to bystander effect-induced DNA DSBs, we examined two types of primary cells that exhibit high levels of transcription in the absence of replication, rat neurons and human lymphocytes. We found that non-replicating bystander cells with high transcription rates exhibited substantial levels of DNA DSBs, as monitored by gamma-H2AX foci formation. Additionally, as reported in proliferating cells, TGF-beta and NO were found to mimic bystander effects in cell populations lacking DNA synthesis. These results indicate that cell vulnerability to bystander DSB damage may result from transcription as well as replication. The findings offer insights into which tissues may be vulnerable to bystander genomic destabilization in vivo.
C1 [Dickey, Jennifer S.; Baird, Brandon J.; Redon, Christophe E.; Bonner, William M.; Martin, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20952 USA.
[Avdoshina, Valeriya; Wu, Junfang] Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA.
[Palchik, Guillermo; Kondratyev, Alexei] Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20057 USA.
[Kondratyev, Alexei] Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20057 USA.
RP Dickey, JS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Vitro Diagnost, Silver Spring, MD 20993 USA.
EM Jennifer.Dickey@fda.hhs.gov; Olga.Martin@petermac.org
OI Palchik, Guillermo/0000-0003-2161-3976
FU National Cancer Institute, National Institutes of Health, USA; National
Institute for Allergies and Infectious Disease (NIAID) Trans-NIH
Biodefense Program; National Institute of Neuorlogical Disorders and
Stroke [NS056057]
FX The Intramural Funding Program of the National Cancer Institute,
National Institutes of Health, USA, and the National Institute for
Allergies and Infectious Disease (NIAID) Trans-NIH Biodefense Program;
National Institute of Neuorlogical Disorders and Stroke [NS056057 to A.
K., in part]. Funding for open access charge: Intramural funding program
of the National Cancer Institute, National Institutes of Health, USA.
NR 59
TC 18
Z9 18
U1 0
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2012
VL 40
IS 20
BP 10274
EP 10286
DI 10.1093/nar/gks795
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 035TC
UT WOS:000310970700035
PM 22941641
ER
PT J
AU Zheng, XH
Mueller, GA
DeRose, EF
London, RE
AF Zheng, Xunhai
Mueller, Geoffrey A.
DeRose, Eugene F.
London, Robert E.
TI Metal and ligand binding to the HIV-RNase H active site are remotely
monitored by Ile556
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID VIRUS REVERSE-TRANSCRIPTASE; CARBON-13 MAGNETIC RESONANCE;
RIBONUCLEASE-H; ESCHERICHIA-COLI; RNA/DNA HYBRID; METHYL-GROUPS;
CATALYTIC MECHANISM; BACKBONE DYNAMICS; CRYSTAL-STRUCTURE; STRUCTURAL
BASIS
AB HIV-1 reverse transcriptase (RT) contains a C-terminal ribonuclease H (RH) domain on its p66 subunit that can be expressed as a stable, although inactive protein. Recent studies of several RH enzymes demonstrate that substrate binding plays a major role in the creation of the active site. In the absence of substrate, the C-terminal helix E of the RT RNase H domain is dynamic, characterized by severe exchange broadening of its backbone amide resonances, so that the solution characterization of this region of the protein has been limited. Nuclear magnetic resonance studies of C-13-labeled RH as a function of experimental conditions reveal that the delta 1 methyl resonance of Ile556, located in a short, random coil segment following helix E, experiences a large C-13 shift corresponding to a conformational change of Ile556 that results from packing of helix E against the central beta-sheet. This shift provides a useful basis for monitoring the effects of various ligands on active site formation. Additionally, we report that the RNase H complexes formed with one or both divalent ions can be individually observed and characterized using diamagnetic Zn2+ as a substitute for Mg2+. Ordering of helix E results specifically from the interaction with the lower affinity binding to the A divalent ion site.
C1 [Zheng, Xunhai; Mueller, Geoffrey A.; DeRose, Eugene F.; London, Robert E.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM london@niehs.nih.gov
RI Zheng, Xunhai/G-1187-2015
OI Zheng, Xunhai/0000-0003-0390-2491
FU Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health [Z01-ES050147]; National
Institutes of Health, NIEHS [HHSN273200700046U]; National Institute of
Environmental Health Sciences, National Institutes of Health, U.S.
Department of Health and Human Services [HHSN273201100001C]
FX Research Project Number Z01-ES050147 to R. E. L. in the Intramural
Research Program of the National Institute of Environmental Health
Sciences, National Institutes of Health. E. F. D. is supported by
National Institutes of Health, NIEHS, under Delivery Order
HHSN273200700046U. Chemical synthesis of
2-hydroxyisoquinoline-1,3(2H,4H)-dione was performed for the National
Institute of Environmental Health Sciences, National Institutes of
Health, U.S. Department of Health and Human Services, under contract No.
HHSN273201100001C. Funding for open access charge: Research Project
Number Z01-ES050147 to R. E. L. in the Intramural Research Program of
the National Institute of Environmental Health Sciences, National
Institutes of Health.
NR 50
TC 6
Z9 6
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2012
VL 40
IS 20
BP 10543
EP 10553
DI 10.1093/nar/gks791
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 035TC
UT WOS:000310970700057
PM 22941642
ER
PT J
AU Richards, JM
Plate, RC
Ernst, M
AF Richards, Jessica M.
Plate, Rista C.
Ernst, Monique
TI Neural systems underlying motivated behavior in adolescence:
Implications for preventive medicine
SO PREVENTIVE MEDICINE
LA English
DT Review
DE Triadic Model; Risk-taking; Neuroimaging; Striatum; Amygdala; Prefrontal
cortex; Development; Prevention
ID ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; PREFRONTAL CORTEX;
DEVELOPMENTAL DIFFERENCES; ORBITOFRONTAL CORTEX; ACTIVATION TREATMENT;
DEPRESSIVE SYMPTOMS; FACIAL EXPRESSIONS; BRAIN-DEVELOPMENT; CHOICE
SELECTION
AB Objective: Although a time of increased independence and autonomy, adolescence is also a time of vulnerabilities, through increased risk-taking and the emergence of psychopathology. Neurodevelopmental changes during this period may provide a neurobiological basis for this normative rise in deleterious behaviors. Thus, the objective of this review was to identify neurodevelopmental processes underlying the emergence of risk-taking and psychopathology in adolescence, and discuss implications of these findings for prevention.
Method: This article reviews literature examining developmental and contextual factors influencing neural functioning in systems mediating threat, reward, and cognitive control. This literature is discussed from the perspective of the Triadic Neural Systems Model of motivated behavior.
Results: Neuroimaging research suggests that neurodevelopmental and contextual factors both contribute to a shift in the functional equilibrium among the Triadic nodes. This equilibrium shift may contribute to negative outcomes of adolescent risk behavior. Most importantly, the balance of this equilibrium and its sensitivity to social and appetitive contexts may be exploited to facilitate prevention of deleterious outcomes.
Conclusion: Understanding developmental and contextual factors that influence functioning in motivational neural circuits can inform research on adolescent risk-taking, and may provide targets for novel preventions, for example through the use of incentives to reduce deleterious outcomes. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Plate, Rista C.; Ernst, Monique] Natl Inst Mental Hlth, Bethesda, MD 20817 USA.
[Richards, Jessica M.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
RP Ernst, M (reprint author), Natl Inst Mental Hlth, NIMH Bldg 15-K,Room 110,MSC-2670, Bethesda, MD 20817 USA.
EM jessic1@umd.edu; rista.plate@nih.gov; ernstm@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 64
TC 8
Z9 8
U1 2
U2 16
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 NOV 1
PY 2012
VL 55
SU 1
BP S7
EP S16
DI 10.1016/j.ypmed.2011.11.016
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 036VV
UT WOS:000311061300003
PM 22198622
ER
PT J
AU Babu, S
Nutman, TB
AF Babu, Subash
Nutman, Thomas B.
TI Immunopathogenesis of lymphatic filarial disease
SO SEMINARS IN IMMUNOPATHOLOGY
LA English
DT Review
DE Filariasis; Pathology; Lymphedema; Hydrocele; Cytokines; Immunity
ID WUCHERERIA-BANCROFTI INFECTION; TUMOR-NECROSIS-FACTOR; ENDOSYMBIOTIC
WOLBACHIA BACTERIA; TROPICAL PULMONARY EOSINOPHILIA; ANTIGEN-PRESENTING
CELLS; PARASITE-SPECIFIC ANERGY; SELECTIVE UP-REGULATION; NEMATODE
BRUGIA-MALAYI; HUMAN DENDRITIC CELLS; REGULATORY T-CELLS
AB Although two thirds of the 120 million people infected with lymph-dwelling filarial parasites have subclinical infections, similar to 40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process-the first initiated by the parasite and host innate immune system and the second propagated mainly by the host's adaptive immune system and by other factors (including secondary infections).
C1 [Babu, Subash] Natl Inst Res TB, Chennai 600031, Tamil Nadu, India.
[Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Babu, Subash] NIRT, Chennai, Tamil Nadu, India.
RP Babu, S (reprint author), Natl Inst Res TB, 1 Mayor Sathiyamurthy Rd, Chennai 600031, Tamil Nadu, India.
EM sbabu@mail.nih.gov
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 141
TC 32
Z9 32
U1 0
U2 21
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2297
J9 SEMIN IMMUNOPATHOL
JI Semin. Immunopathol.
PD NOV
PY 2012
VL 34
IS 6
BP 847
EP 861
DI 10.1007/s00281-012-0346-4
PG 15
WC Immunology; Pathology
SC Immunology; Pathology
GA 035XX
UT WOS:000310988000009
PM 23053393
ER
PT J
AU Skolnick, P
AF Skolnick, Phil
TI Anxioselective anxiolytics: on a quest for the Holy Grail
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID GENERALIZED ANXIETY DISORDER; GABA(A) RECEPTOR SUBTYPE; AMINOBUTYRIC
ACID(A) RECEPTORS; SELECTIVE PARTIAL AGONIST; BENZODIAZEPINE-RECEPTORS;
A RECEPTORS; BETA-CARBOLINE; PHARMACOLOGICAL PROFILE; PSYCHOMOTOR
PERFORMANCE; ALPHA-SUBUNIT
AB The discovery of benzodiazepine receptors provided the impetus to discover and develop anxioselective anxiolytics (Valium without the side effects'). The market potential for an anxioselective based on the gamma-aminobutyric acid A (GABA(A)) receptor resulted in clinical trials of multiple compounds. In contrast to the anxioselective profile displayed in preclinical models, compounds such as bretazenil, TPA023, and MRK 409 produced benzodiazepine-like side effects (sedation, dizziness) in Phase I studies, whereas alpidem and ocinaplon exhibited many of the characteristics of an anxioselective in the clinic. Alpidem was briefly marketed for the treatment of anxiety, but was withdrawn because of liver toxicity. Reversible elevations in liver enzymes halted development of ocinaplon in Phase III. The clinical profiles of these two molecules demonstrate that it is possible to develop GABA(A) receptor-based anxioselectives. However, despite the formidable molecular toolbox at our disposal, we are no better informed about the GABA(A) receptors responsible for an anxioselective profile in the clinic. Here, I discuss the evolution of a quest, spanning four decades, for molecules that retain the rapid and robust anti-anxiety actions of benzodiazepines without the side effects that limit their usefulness.
C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA.
RP Skolnick, P (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Suite 4123, Bethesda, MD 20892 USA.
EM phil.skolnick@nih.gov
FU Intramural NIH HHS [Z99 DA999999]
NR 73
TC 27
Z9 29
U1 0
U2 12
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD NOV
PY 2012
VL 33
IS 11
BP 611
EP 620
DI 10.1016/j.tips.2012.08.003
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 038LT
UT WOS:000311176900008
PM 22981367
ER
PT J
AU Robertson, BD
Altmann, D
Barry, C
Bishai, B
Cole, S
Dick, T
Duncan, K
Dye, C
Ehrt, S
Esmail, H
Flynn, J
Hafner, R
Handley, G
Hanekom, W
van Helden, P
Kaplan, G
Kaufmann, SHE
Kim, P
Lienhardt, C
Mizrahi, V
Rubin, E
Schnappinger, D
Sherman, D
Thole, J
Vandal, O
Walzl, G
Warner, D
Wilkinson, R
Young, D
AF Robertson, Brian D.
Altmann, Danny
Barry, Clif
Bishai, Bill
Cole, Stewart
Dick, Thomas
Duncan, Ken
Dye, Chris
Ehrt, Sabine
Esmail, Hanif
Flynn, JoAnne
Hafner, Richard
Handley, Gray
Hanekom, Willem
van Helden, Paul
Kaplan, Gilla
Kaufmann, Stefan H. E.
Kim, Peter
Lienhardt, Christian
Mizrahi, Valerie
Rubin, Eric
Schnappinger, Dirk
Sherman, David
Thole, Jelle
Vandal, Omar
Walzl, Gerhard
Warner, Digby
Wilkinson, Robert
Young, Douglas
TI Detection and treatment of subclinical tuberculosis
SO TUBERCULOSIS
LA English
DT Editorial Material
DE Detection; Treatment; Subclinical; Tuberculosis
ID NONREPLICATING MYCOBACTERIUM-TUBERCULOSIS; RANDOMIZED-TRIAL; SYSTEMS
BIOLOGY; STRATEGIES; VACCINE; TB; PREVALENCE; INFECTION; THERAPY
AB Reduction of active disease by preventive therapy has the potential to make an important contribution towards the goal of tuberculosis (TB) elimination. This report summarises discussions amongst a Working Group convened to consider areas of research that will be important in optimising the design and delivery of preventative therapies. The Working Group met in Cape Town on 26th February 2012, following presentation of results from the GC11 Grand Challenges in Global Health project to discover drugs for latent TB. (C) 2012 Elsevier Ltd. All rights reserved.
C1 [Robertson, Brian D.] Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, London SW7 2AZ, England.
[Altmann, Danny] Wellcome Trust Res Labs, London, England.
[Barry, Clif] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA.
[Bishai, Bill] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa.
[Cole, Stewart] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland.
[Dick, Thomas] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
[Duncan, Ken; Vandal, Omar] Bill & Melinda Gates Fdn, Seattle, WA USA.
[Dye, Chris; Lienhardt, Christian] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland.
[Ehrt, Sabine; Schnappinger, Dirk] Weill Cornell Med Coll, New York, NY USA.
[Flynn, JoAnne] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Hanekom, Willem; Mizrahi, Valerie; Warner, Digby; Wilkinson, Robert] Univ Cape Town, ZA-7700 Rondebosch, South Africa.
[van Helden, Paul; Walzl, Gerhard] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa.
[Kaplan, Gilla] Publ Hlth Res Inst Ctr, Newark, NJ USA.
[Kaufmann, Stefan H. E.] Max Planck Inst Infect Biol, Berlin, Germany.
[Rubin, Eric] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Sherman, David] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Thole, Jelle] TB Vaccine Initiat, Lelystad, Netherlands.
[Wilkinson, Robert; Young, Douglas] Univ London Imperial Coll Sci Technol & Med, MRC Natl Inst Med Res, London SW7 2AZ, England.
RP Robertson, BD (reprint author), Univ London Imperial Coll Sci Technol & Med, MRC Ctr Mol Bacteriol & Infect, Flowers Bldg,S Kensington Campus, London SW7 2AZ, England.
EM b.robertson@imperial.ac.uk
RI Barry, III, Clifton/H-3839-2012; Kaufmann, Stefan HE/I-5454-2014;
OI Dye, Christopher/0000-0002-2957-1793; Esmail, Hanif/0000-0002-4278-9316;
Walzl, Gerhard/0000-0003-2487-125X; Robertson, Brian
D./0000-0001-5785-5307; Kaufmann, Stefan HE/0000-0001-9866-8268;
Altmann, Daniel/0000-0002-2436-6192; Rubin, Eric/0000-0001-5120-962X;
Wilkinson, Robert/0000-0002-2753-1800
FU Medical Research Council [MC_U117588499]; Wellcome Trust [077381]
NR 41
TC 16
Z9 16
U1 0
U2 19
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD NOV
PY 2012
VL 92
IS 6
BP 447
EP 452
DI 10.1016/j.tube.2012.06.004
PG 6
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA 039PQ
UT WOS:000311259400001
PM 22819716
ER
PT J
AU Ginther, DK
Haak, LL
Schaffer, WT
Kington, R
AF Ginther, Donna K.
Haak, Laurel L.
Schaffer, Walter T.
Kington, Raynard
TI Are Race, Ethnicity, and Medical School Affiliation Associated With NIH
R01 Type 1 Award Probability for Physician Investigators?
SO ACADEMIC MEDICINE
LA English
DT Article
ID SCIENCE
AB Purpose
To analyze the relationship among National Institutes of Health (NIH) R01 Type 1 applicant degree, institution type, and race/ethnicity, and application award probability.
Method
The authors used 2000-2006 data from the NIH IMPAC II grants database and other sources to determine which individual and institutional characteristics of applicants may affect the probability of applications being awarded funding. They used descriptive statistics and probit models to estimate correlations between race/ethnicity, degree (MD or PhD), and institution type (medical school or other institution), and application award probability, controlling for a large set of observable characteristics.
Results
Applications from medical schools were significantly more likely than those from other institutions to receive funding, as were applications from MDs versus PhDs. Overall, applications from blacks and Asians were less likely than those from whites to be awarded funding; however, among applications from MDs at medical schools, there was no difference in funding probability between whites and Asians, and the difference between blacks and whites decreased to 7.8%. The inclusion of human subjects significantly decreased the likelihood of receiving funding.
Conclusions
Compared with applications from whites, applications from blacks have a lower probability of being awarded R01 Type 1 funding, regardless of the investigator's degree. However, funding probability is increased for applications with MD investigators and for those from medical schools. To some degree, these advantages combine so that applications from black MDs at medical schools have the smallest difference in funding probability compared with those from whites.
C1 [Ginther, Donna K.] Univ Kansas, Dept Econ, Lawrence, KS 66045 USA.
[Ginther, Donna K.] Univ Kansas, Ctr Sci Technol & Econ Policy, Lawrence, KS 66045 USA.
[Haak, Laurel L.] Thomson Reuters, Discovery Log, Rockville, MD USA.
[Schaffer, Walter T.; Kington, Raynard] NIH, Bethesda, MD 20892 USA.
[Kington, Raynard] Grinnell Coll, Grinnell, IA 50112 USA.
RP Ginther, DK (reprint author), Univ Kansas, Dept Econ, 1460 Jayhawk Blvd, Lawrence, KS 66045 USA.
EM dginther@ku.edu
RI Haak, Laurel/C-4986-2008; Ginther, Donna/F-7317-2016;
OI Haak, Laurel/0000-0001-5109-3700; Ginther, Donna/0000-0002-0881-7969;
Schaffer, Walter/0000-0002-2276-4656
FU NIH [1R01AG36820-01, HHSN276200800458U, HHSN276200900100U, 07-6008 OD
OER]
FX Dr. Ginther acknowledges financial support from NIH grant
1R01AG36820-01. Dr. Schaffer is an employee of the NIH, and, as a
result, the NIH supported this work. Dr. Haak of Discovery Logic, a
Thomson Reuters company, acknowledges support from NIH contracts
HHSN276200800458U and HHSN276200900100U, made possible through an NIH
Evaluation Set-Aside Award to W. T. S. (07-6008 OD OER).
NR 22
TC 15
Z9 15
U1 3
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD NOV
PY 2012
VL 87
IS 11
BP 1516
EP 1524
DI 10.1097/ACM.0b013e31826d726b
PG 9
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 030OI
UT WOS:000310579600035
PM 23018334
ER
PT J
AU Klot, JF
Auerbach, JD
Veronese, F
Brown, G
Pei, A
Wira, CR
Hope, TJ
M'boup, S
AF Klot, Jennifer F.
Auerbach, Judith D.
Veronese, Fulvia
Brown, Gina
Pei, April
Wira, Charles R.
Hope, Thomas J.
M'boup, Souleymane
CA Greentree Meeting Sexual Violence
TI Greentree White Paper: Sexual Violence, Genitoanal Injury, and HIV:
Priorities for Research, Policy, and Practice
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID INTIMATE PARTNER VIOLENCE; GENDER-BASED VIOLENCE; HEALTHY-YOUNG WOMEN;
SOUTH-AFRICA; ANAL INTERCOURSE; ANOGENITAL INJURY; EPITHELIAL-CELLS;
GENITAL INJURY; KENYAN WOMEN; RISK-FACTOR
AB The links between sexual violence, genitoanal injury, and HIV are understudied but potentially significant for understanding the epidemic's disproportionate impacts on young women and girls, particularly in sub-Saharan Africa, other hyperendemic areas, and conflict-affected regions. A Scientific Research Planning Meeting was convened by the Social Science Research Council at the Greentree Foundation in New York, March 19-20, 2012, bringing together an interdisciplinary group of researchers, clinicians, and policy makers to identify knowledge needs and gaps in three key areas: (1) the role of genitoanal injury on HIV transmission, acquisition, and pathogenesis; (2) the influence of sex and age-related anatomic characteristics on HIV transmission, acquisition, and pathogenesis; and (3) the role of heterosexual anal intercourse in HIV transmission. This article reflects the consensus that emerged from the Greentree Meeting regarding priority scientific research questions in these three areas, associated data collection and measurement challenges and opportunities, and implications for policy and practice.
C1 [Klot, Jennifer F.; Pei, April] Social Sci Res Council, Brooklyn, NY 11201 USA.
[Veronese, Fulvia; Brown, Gina] NIH, Bethesda, MD 20892 USA.
[Wira, Charles R.] Dartmouth Med Sch, Lebanon, NH USA.
[Hope, Thomas J.] Northwestern Univ, Feinberg Sch Med, Evanston, IL USA.
[M'boup, Souleymane] Univ Cheikh Anta Diop, Hop Le Dantec, Dakar, Senegal.
RP Klot, JF (reprint author), Social Sci Res Council, 15 Pierrepont Plaza, Brooklyn, NY 11201 USA.
EM klot@ssrc.org
RI Hossain, Mazeda/G-1953-2014; Shacklett, Barbara/A-7288-2009;
OI Shacklett, Barbara/0000-0002-7067-732X; Hossain,
Mazeda/0000-0002-1878-8145; Klot, Jennifer/0000-0002-0593-4326
FU National Institutes of Health; Office of AIDS Research; UNAIDS; UN
Action Against Sexual Violence in Armed Conflict; Greentree Foundation
FX Funding for this meeting was provided by the National Institutes of
Health, Office of AIDS Research; UNAIDS, UN Action Against Sexual
Violence in Armed Conflict and the Greentree Foundation. The authors
wish to thank SSRC research assistants and meeting organizers, Miranda
Berry, Patience Mungwari, and April Pei.
NR 90
TC 9
Z9 9
U1 3
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV
PY 2012
VL 28
IS 11
BP 1379
EP 1388
DI 10.1089/aid.2012.0273
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 032XP
UT WOS:000310754100002
PM 22953712
ER
PT J
AU Karasavvas, N
Billings, E
Rao, M
Williams, C
Zolla-Pazner, S
Bailer, RT
Koup, RA
Madnote, S
Arworn, D
Shen, XY
Tomaras, GD
Currier, JR
Jiang, M
Magaret, C
Andrews, C
Gottardo, R
Gilbert, P
Cardozo, TJ
Rerks-Ngarm, S
Nitayaphan, S
Pitisuttithum, P
Kaewkungwal, J
Paris, R
Greene, K
Gao, HM
Gurunathan, S
Tartaglia, J
Sinangil, F
Korber, BT
Montefiori, DC
Mascola, JR
Robb, ML
Haynes, BF
Ngauy, V
Michael, NL
Kim, JH
de Souza, MS
AF Karasavvas, Nicos
Billings, Erik
Rao, Mangala
Williams, Constance
Zolla-Pazner, Susan
Bailer, Robert T.
Koup, Richard A.
Madnote, Sirinan
Arworn, Duangnapa
Shen, Xiaoying
Tomaras, Georgia D.
Currier, Jeffrey R.
Jiang, Mike
Magaret, Craig
Andrews, Charla
Gottardo, Raphael
Gilbert, Peter
Cardozo, Timothy J.
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Paris, Robert
Greene, Kelli
Gao, Hongmei
Gurunathan, Sanjay
Tartaglia, Jim
Sinangil, Faruk
Korber, Bette T.
Montefiori, David C.
Mascola, John R.
Robb, Merlin L.
Haynes, Barton F.
Ngauy, Viseth
Michael, Nelson L.
Kim, Jerome H.
de Souza, Mark S.
CA MOPH TAVEG Collaboration
TI The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces
Antibodies That Target Conserved Regions Within the V2 Loop of gp120
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; RECOMBINANT GLYCOPROTEIN-120 VACCINE;
QUATERNARY NEUTRALIZING EPITOPE; HIV-1/SIV CHIMERIC VIRUS; ENVELOPE
GLYCOPROTEIN; EFFICACY TRIAL; HETEROSEXUAL TRANSMISSION; INTEGRIN
ALPHA(4)BETA(7); MONOCLONAL-ANTIBODIES; CANARYPOX VACCINE
AB The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p = 0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition.
C1 [Karasavvas, Nicos; Madnote, Sirinan; Arworn, Duangnapa; Ngauy, Viseth; de Souza, Mark S.] Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, Bangkok 10400, Thailand.
[Billings, Erik; Currier, Jeffrey R.; Andrews, Charla; Robb, Merlin L.] Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program MHRP, Rockville, MD USA.
[Rao, Mangala; Paris, Robert; Michael, Nelson L.; Kim, Jerome H.] Walter Reed Army Inst Res, USMHRP, Silver Spring, MD USA.
[Williams, Constance; Zolla-Pazner, Susan; Cardozo, Timothy J.] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Williams, Constance; Zolla-Pazner, Susan; Cardozo, Timothy J.] NYU, Sch Med, Dept Pharmacol, New York, NY USA.
[Zolla-Pazner, Susan] Vet Affairs Harbor Healthcare Syst, New York, NY USA.
[Bailer, Robert T.; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Shen, Xiaoying; Tomaras, Georgia D.; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA.
[Jiang, Mike; Magaret, Craig; Gottardo, Raphael; Gilbert, Peter] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi, Thailand.
[Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Royal Thai Army Component, Bangkok 10400, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Vaccine Trial Ctr, Bangkok, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Dept Clin Trop Med, Bangkok, Thailand.
[Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat BIOPHI, Bangkok, Thailand.
[Paris, Robert] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
[Greene, Kelli; Gao, Hongmei; Montefiori, David C.; Mascola, John R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.
[Gurunathan, Sanjay; Tartaglia, Jim] Sanofi Pasteur, Swiftwater, PA USA.
[Sinangil, Faruk] Global Solut Infect Dis, San Francisco, CA USA.
[Korber, Bette T.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA.
RP Karasavvas, N (reprint author), Armed Forces Res Inst Med Sci, US Army Med Component, Dept Retrovirol, 315-6 Rajvithi Rd, Bangkok 10400, Thailand.
EM karasavvan@afrims.org
RI Tomaras, Georgia/J-5041-2016;
OI Korber, Bette/0000-0002-2026-5757
FU U.S. Army Medical Research and Materiel Command (USAMRMC)
[Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases;
Henry M. Jackson Foundation for the Advancement of Military Medicine
[W81XWH-07-2-0067]; U.S. Department of Defense [W81XWH-07-2-0067]; U.S.
National Institute of Allergy and Infectious Diseases; Bill and Melinda
Gates Foundation [OPP38744]; NIH Vaccine Research Center; NIH [HL59725,
AI084119]; Department of Veterans Affairs; Bill and Melinda Gates
Foundation Collaboration for AIDS Vaccine Discovery
FX The authors thank SCHARP for assisting with the microarray analysis,
James Swetnam for providing the biotinylated subtype B linear peptides,
Kelly Soderberg for coordination of sample shipment and project
management, Rob O'Connell for constructive reading of the manuscript,
Robert Parks, Ryan Meyerhoff, and Krissey Lloyd for ELISA technical
assistance, and Ellen Turk for performing the peptide microarray
analysis. These studies were supported in part by an Interagency
Agreement Y1-AI-2642-12 between U.S. Army Medical Research and Materiel
Command (USAMRMC) and the National Institutes of Allergy and Infectious
Diseases. In addition, this work was supported by a cooperative
agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for
the Advancement of Military Medicine and the U.S. Department of Defense.
This research was funded, in part, by the U.S. National Institute of
Allergy and Infectious Diseases. Peptide microarray work was funded by
the Bill and Melinda Gates Foundation's Collaboration for AIDS Vaccine
Discovery (OPP38744) and the NIH Vaccine Research Center. S.Z.P. and
T.J.C. receive funding from NIH Grants HL59725 (S.Z.P.) and AI084119
(T.J.C.) and the Department of Veterans Affairs. Supported in part by
grants from the Bill and Melinda Gates Foundation Collaboration for AIDS
Vaccine Discovery to Dr. Haynes.
NR 69
TC 82
Z9 82
U1 4
U2 16
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV
PY 2012
VL 28
IS 11
BP 1444
EP 1457
DI 10.1089/aid.2012.0103
PG 14
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 032XP
UT WOS:000310754100009
PM 23035746
ER
PT J
AU Solomon, BD
Muenke, M
AF Solomon, Benjamin D.
Muenke, Maximilian
TI When to Suspect a Genetic Syndrome
SO AMERICAN FAMILY PHYSICIAN
LA English
DT Article
ID FAMILY-HISTORY; DISORDERS; DISEASE; CARE; MALFORMATIONS; DIAGNOSIS
AB Family physicians should be able to recognize findings on physical examination and history that suggest the presence of a genetic syndrome to aid in the diagnosis and treatment of potentially affected patients, as well as subspecialty referral. General themes that can alert family physicians to the presence of genetic conditions include dysmorphic features that are evident on physical examination; multiple anomalies in one patient; unexplained neurocognitive impairment; and a family history that is suggestive of a hereditary disease. The presence of one obvious malformation should not limit the full evaluation, because additional, subtler findings will often be important in the differential diagnosis. Taking an accurate three-generation family history is invaluable when considering a genetic syndrome. Important elements include the age and sex of family members; when family members were affected by disease or when they died; the ethnic background; and if there is consanguinity. Genetic subspecialists can assist family physicians in diagnosis, suggest additional testing and referrals if warranted, help direct medical care, and provide counseling for affected patients and their families. (Am Fam Physician. 2012;86(9):826-833. Copyright (C) 2012 American Academy of Family Physicians.)
C1 [Solomon, Benjamin D.; Muenke, Maximilian] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Muenke, Maximilian] NHGRI, Med Genet Residency Training Program, Bethesda, MD 20892 USA.
RP Muenke, M (reprint author), NHGRI, Med Genet Branch, 35 Convent Dr,Room 1B203,MSC 3717, Bethesda, MD 20892 USA.
EM mamuenke@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute, National Institutes of Health, Bethesda, Md
FX This work was supported by the Intramural Research Program of the
National Human Genome Research Institute, National Institutes of Health,
Bethesda, Md.
NR 33
TC 1
Z9 1
U1 0
U2 1
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 NOV 1
PY 2012
VL 86
IS 9
BP 826
EP 833
PG 8
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA 033TO
UT WOS:000310824200008
PM 23113462
ER
PT J
AU Bilous, RW
Gonzalez-Campoy, JM
Fradkin, JE
Mauer, M
Molitch, ME
Narva, AS
Nelson, RG
Sharma, K
Tuttle, KR
Rocco, MV
Berns, JS
Wilt, TJ
Ishani, A
Rector, TS
Slinin, Y
Fitzgerald, P
Carlyle, M
AF Bilous, Rudolf W.
Gonzalez-Campoy, J. Michael
Fradkin, Judith E.
Mauer, Michael
Molitch, Mark E.
Narva, Andrew S.
Nelson, Robert G.
Sharma, Kumar
Tuttle, Katherine R.
Rocco, Michael V.
Berns, Jeffrey S.
Wilt, Timothy J.
Ishani, Areef
Rector, Thomas S.
Slinin, Yelena
Fitzgerald, Patrick
Carlyle, Maureen
TI KDOQI CLINICAL PRACTICE GUIDELINE FOR DIABETES AND CKD: 2012 UPDATE
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Albuminuria; chronic kidney disease; Clinical Practice Guideline;
diabetes; dyslipidemia; evidence-based recommendation; KDOQI
ID CHRONIC KIDNEY-DISEASE; BLOOD-GLUCOSE CONTROL; PLACEBO-CONTROLLED TRIAL;
IMPAIRED RENAL-FUNCTION; CONVERTING ENZYME-INHIBITION; RANDOMIZED
CONTROLLED-TRIAL; IMPROVING GLOBAL OUTCOMES; ALBUMIN EXCRETION RATE;
GLYCEMIC CONTROL; SEVERE HYPOGLYCEMIA
AB The 2012 update of the Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guideline for Diabetes and Chronic Kidney Disease (CKD) is intended to assist the practitioner caring for patients with diabetes and CKD. Substantial high-quality new evidence has emerged since the original 2007 KDOQI guideline that could significantly change recommendations for clinical practice. As such, revisions of prior guidelines are offered that specifically address hemoglobin A(1c) (HbA(1c)) targets, treatments to lower low-density lipoprotein cholesterol (LDL-C) levels, and use of angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin receptor blocker (ARB) treatment in diabetic patients with and without albuminuria. Treatment approaches are addressed in each section and the stated guideline recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.
C1 [Bilous, Rudolf W.] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Bilous, Rudolf W.] James Cook Univ Hosp, Middlesbrough, Cleveland, England.
[Bilous, Rudolf W.] NIH, Metab Med Unit, Bethesda, MD 20892 USA.
[Bilous, Rudolf W.] Univ Minnesota, JDRF, Minneapolis, MN 55455 USA.
[Gonzalez-Campoy, J. Michael; Mauer, Michael] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Gonzalez-Campoy, J. Michael] NIDDK, Div Diabet Endocrinol & Metab Dis DEMD, NIH, Bethesda, MD 20892 USA.
[Fradkin, Judith E.] Yale Univ, New Haven, CT 06520 USA.
[Fradkin, Judith E.] Ctr Dis Control & Prevent, Natl Diabet Educ Program, Atlanta, GA USA.
[Fradkin, Judith E.] Natl Naval Med Ctr, Bethesda, MD USA.
[Molitch, Mark E.] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Evanston, IL 60208 USA.
[Molitch, Mark E.] Univ Calif Los Angeles, Harbor Gen Hosp, Los Angeles, CA 90024 USA.
[Narva, Andrew S.] NIDDK, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA.
[Nelson, Robert G.] NIDDK, Phoenix, AZ USA.
[Sharma, Kumar] Univ Calif San Diego, Ctr Renal Translat Med, San Diego, CA 92103 USA.
[Tuttle, Katherine R.] Providence Sacred Heart Med Ctr, Spokane, WA USA.
[Tuttle, Katherine R.] Natl Diabet Educ Program NIH & CDC, Healthcare Profess Work Grp, Bethesda, MD 20892 USA.
[Tuttle, Katherine R.] Inst Review Board, Spokane, WA USA.
[Tuttle, Katherine R.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
[Tuttle, Katherine R.] Washington State Univ, Pullman, WA 99164 USA.
[Rocco, Michael V.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Berns, Jeffrey S.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Berns, Jeffrey S.] Univ Penn, Sch Med, Penn Presbyterian Med Ctr Philadelphia, Philadelphia, PA 19104 USA.
[Wilt, Timothy J.; Rector, Thomas S.] Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Ishani, Areef] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA.
[Fitzgerald, Patrick] CCDOR, Minneapolis, MN USA.
[Carlyle, Maureen] Minneapolis VA Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Carlyle, Maureen] Univ Minnesota, Minnesota Evidence Based Practice Ctr, Minneapolis, MN 55455 USA.
NR 115
TC 0
Z9 0
U1 0
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD NOV
PY 2012
VL 60
IS 5
BP 858
EP +
PG 30
WC Urology & Nephrology
SC Urology & Nephrology
GA 029PO
UT WOS:000310508100041
ER
PT J
AU Heselmeyer-Haddad, K
Garcia, LYB
Bradley, A
Ortiz-Melendez, C
Lee, WJ
Christensen, R
Prindiville, SA
Calzone, KA
Soballe, PW
Hu, Y
Chowdhury, SA
Schwartz, R
Schaffer, AA
Ried, T
AF Heselmeyer-Haddad, Kerstin
Garcia, Lissa Y. Berroa
Bradley, Amanda
Ortiz-Melendez, Clarymar
Lee, Woei-Jyh
Christensen, Rebecca
Prindiville, Sheila A.
Calzone, Kathleen A.
Soballe, Peter W.
Hu, Yue
Chowdhury, Salim A.
Schwartz, Russell
Schaeffer, Alejandro A.
Ried, Thomas
TI Single-Cell Genetic Analysis of Ductal Carcinoma in Situ and Invasive
Breast Cancer Reveals Enormous Tumor Heterogeneity yet Conserved Genomic
Imbalances and Gain of MYC during Progression
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID COPY-NUMBER ALTERATION; EXPRESSION PROFILES; SERIAL ANALYSIS; HER2
STATUS; HYBRIDIZATION; AMPLIFICATION; METASTASIS; EVOLUTION; ADJACENT;
INSTABILITY
AB Ductal carcinoma in situ (DCIS) is a precursor lesion of invasive ductal carcinoma (IDC) of the breast. To understand the dynamics of genomic alterations in this progression, we used four multicolor fluorescence in situ hybridization probe panels consisting of the oncogenes COX2, MYC, HER2, CCND1, and ZNF217 and the tumor suppressor genes DBC2, CDH1, and TP53 to visualize copy number changes in 13 cases of synchronous DCIS and IDC based on single-cell analyses. The DCIS had a lower degree of chromosomal instability than the IDC. Despite enormous intercellular heterogeneity in DCIS and IDC, we observed signal patterns consistent with a nonrandom distribution of genomic imbalances. CDH1 was most commonly lost, and gain of MYC emerged during progression from DCIS to IDC. Four of 13 DCISs showed identical clonal imbalances in the IDCs. Six cases revealed a switch, and in four of those, the IDC had acquired a gain of MYC. In one case, the major clone in the MC was one of several clones in the DCIS, and in another case, the major clone in the DCIS became one of the two major clones in the IDC. Despite considerable chromosomal instability, in most cases the evolution from DCIS to IDC is determined by recurrent patterns of genomic imbalances, consistent with a biological continuum. (Am J Pathol 2012, 181: 1807-1822; http://dx.doi.org/10.1016/j.ajpath.2012.07.012)
C1 [Heselmeyer-Haddad, Kerstin; Garcia, Lissa Y. Berroa; Bradley, Amanda; Ortiz-Melendez, Clarymar; Calzone, Kathleen A.; Hu, Yue; Ried, Thomas] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Woei-Jyh; Schaeffer, Alejandro A.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Christensen, Rebecca; Soballe, Peter W.] Natl Naval Med Ctr, Bethesda, MD USA.
[Prindiville, Sheila A.] NCI, Coordinating Ctr Clin Trials, Rockville, MD USA.
[Chowdhury, Salim A.] Carnegie Mellon Univ, Joint Carnegie Mellon Univ Pittsburgh PhD Program, Pittsburgh, PA 15213 USA.
[Chowdhury, Salim A.; Schwartz, Russell] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA.
[Schwartz, Russell] Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA.
RP Heselmeyer-Haddad, K (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 50,Room 1408,50 South Dr, Bethesda, MD 20892 USA.
EM heselmek@mail.nih.gov
RI Schwartz, Russell/A-1998-2016
OI Schwartz, Russell/0000-0002-4970-2252
FU NIH, National Cancer Institute; National Library of Medicine; NIH
[1R01CA140214, 1R01AI076318]
FX Supported in part by the Intramural Research Program of the NIH,
National Cancer Institute, and National Library of Medicine and by NIH
grants 1R01CA140214 (R.S. and S.A.C.) and 1R01AI076318 (R.S.).
NR 63
TC 36
Z9 37
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2012
VL 181
IS 5
BP 1807
EP 1822
DI 10.1016/j.ajpath.2012.07.012
PG 16
WC Pathology
SC Pathology
GA 031QK
UT WOS:000310656800030
PM 23062488
ER
PT J
AU Brown, KS
Ebihara, H
Feldmann, H
AF Brown, Kyle S.
Ebihara, Hideki
Feldmann, Heinz
TI Development of a minigenome system for Andes virus, a New World
hantavirus
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID HEMORRHAGIC-FEVER VIRUS; REVERSE GENETICS; L-PROTEIN; PULMONARY
SYNDROME; TULA-HANTAVIRUS; L-POLYMERASE; RNA; TRANSCRIPTION; EXPRESSION;
RESCUE
AB The development of reverse genetics systems for negative-stranded RNA viruses is a rapidly evolving field that has greatly advanced the study of the many different aspects of the viral life cycle. Andes virus (ANDV) is a highly pathogenic hantavirus found in South America that causes hantavirus pulmonary syndrome but to date remains poorly characterized due to the lack of a reverse genetics system for genetic manipulation. Here, we describe the first successful minigenome system for a New World hantavirus, as well as many of the obstacles that still exist in the development of such a system.
C1 [Ebihara, Hideki; Feldmann, Heinz] NIAID, Div Intramural Res, Virol Lab, NIH,Rocky Mt Labs, Hamilton, MT USA.
[Brown, Kyle S.; Feldmann, Heinz] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada.
[Brown, Kyle S.; Feldmann, Heinz] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
RP Feldmann, H (reprint author), NIAID, Div Intramural Res, Virol Lab, NIH,Rocky Mt Labs, Hamilton, MT USA.
EM feldmannh@niaid.nih.gov
FU National Microbiology Laboratory of the Public Health Agency of Canada
FX This work funded by the National Microbiology Laboratory of the Public
Health Agency of Canada. The work was part of the Ph.D. thesis of KSB.
Thank you to Dr. Connie Schmaljohn, U.S Army Medical Research Institute
of Infectious Diseases, Ft. Detrick, MD for providing the Andes virus,
strain Chile 9717869.
NR 29
TC 7
Z9 7
U1 1
U2 5
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 NOV
PY 2012
VL 157
IS 11
BP 2227
EP 2233
DI 10.1007/s00705-012-1401-0
PG 7
WC Virology
SC Virology
GA 031AK
UT WOS:000310611100021
PM 22821183
ER
PT J
AU Soto-Pantoja, DR
Miller, TW
Pendrak, ML
DeGraff, WG
Sullivan, C
Ridnour, LA
Abu-Asab, M
Wink, DA
Tsokos, M
Roberts, DD
AF Soto-Pantoja, David R.
Miller, Thomas W.
Pendrak, Michael L.
DeGraff, William G.
Sullivan, Camille
Ridnour, Lisa A.
Abu-Asab, Mones
Wink, David A.
Tsokos, Maria
Roberts, David D.
TI CD47 deficiency confers cell and tissue radioprotection by activation of
autophagy
SO AUTOPHAGY
LA English
DT Article
DE CD47; autophagosome; ionizing radiation; MAP1A/1BLC3; ATG5; ATG7; p62;
BECN1
ID INTEGRATED STRESS-RESPONSE; ISCHEMIA-REPERFUSION INJURY; RIBOSOME ENTRY
SITE; BREAST-TUMOR CELLS; MESSENGER-RNA; CANCER-CELLS; THROMBOSPONDIN-1;
RADIATION; APOPTOSIS; DEATH
AB Accidental or therapeutic exposure to ionizing radiation has severe physiological consequences and can result in cell death. We previously demonstrated that deficiency or blockade of the ubiquitously expressed receptor CD47 results in remarkable cell and tissue protection against ischemic and radiation stress. Antagonists of CD47 or its ligand THBS1/thrombospondin 1 enhance cell survival and preserve their proliferative capacity. However the signaling pathways that mediate this cell-autonomous radioprotection are unclear. We now report a marked increase in autophagy in irradiated T-cells and endothelial cells lacking CD47. Irradiated T cells lacking CD47 exhibit significant increases in formation of autophagosomes comprising double-membrane vesicles visualized by electron microscopy and numbers of MAP1LC3A/B+ puncta. Moreover, we observed significant increases in BECN1, ATG5, ATG7 and a reduction in SQSTM1/p62 expression relative to irradiated wild-type T cells. We observed similar increases in autophagy gene expression in mice resulting from blockade of CD47 in combination with total body radiation. Pharmacological or siRNA-mediated inhibition of autophagy selectively sensitized CD47-deficient cells to radiation, indicating that enhanced autophagy is necessary for the prosurvival response to CD47 blockade. Moreover, re-expression of CD47 in CD47-deficient T cells sensitized these cells to death by ionizing radiation and reversed the increase in autophagic flux associated with survival. This study indicates that CD47 deficiency confers cell survival through the activation of autophagic flux and identifies CD47 blockade as a pharmacological route to modulate autophagy for protecting tissue from radiation injury.
C1 [Soto-Pantoja, David R.; Miller, Thomas W.; Pendrak, Michael L.; Sullivan, Camille; Abu-Asab, Mones; Tsokos, Maria; Roberts, David D.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[DeGraff, William G.; Ridnour, Lisa A.; Wink, David A.] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Abu-Asab, Mones] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Roberts, DD (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, 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;
Abu-Asab, Mones/0000-0002-4047-1232
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research; NCI
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research (D.D.R., D.A.W., M.T.) and an NCI Director's Career
Development Innovation Award (D.R.S.-P.).
NR 53
TC 29
Z9 30
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
J9 AUTOPHAGY
JI Autophagy
PD NOV
PY 2012
VL 8
IS 11
BP 1628
EP 1642
DI 10.4161/auto.21562
PG 15
WC Cell Biology
SC Cell Biology
GA 033WC
UT WOS:000310831100006
PM 22874555
ER
PT J
AU Hsu, S
Kim, M
Hernandez, L
Grajales, V
Noonan, A
Anver, M
Davidson, B
Annunziata, CM
AF Hsu, Sarah
Kim, Marianne
Hernandez, Lidia
Grajales, Valentina
Noonan, Anne
Anver, Miriam
Davidson, Ben
Annunziata, Christina M.
TI IKK-epsilon Coordinates Invasion and Metastasis of Ovarian Cancer
SO CANCER RESEARCH
LA English
DT Article
ID NICOTINAMIDE N-METHYLTRANSFERASE; BREAST-CANCER; IN-VITRO; KAPPA-B;
EXPRESSION; CARCINOMA; INHIBITOR; MIGRATION; ONCOGENE; IKBKE
AB Inhibitor of I kappa B kinases (IKK) are key regulators of NF-kappa B signaling. Three IKK isoforms-alpha, beta, and epsilon-have been linked to oncogenesis, yet the precise components of NF-kappa B signaling in ovarian cancer have not yet been dissected. We surveyed 120 ovarian cancer specimens for IKK-epsilon expression. Notably, cytoplasmic expression was elevated in metastatic lesions relative to primary tumors (P=0.03). Therefore, we hypothesized that IKK-epsilon drives ovarian cancer metastasis. IKK-epsilon was identified previously as a breast cancer oncogene and was associated with poor clinical outcome in ovarian cancer. We now define an ovarian cancer-specific IKK-epsilon-regulated gene expression signature using stably expressed short hairpin RNA targeting IKK-epsilon. Pathway analysis of the signature indicated that IKK-epsilon regulates expression of genes involved in cell motility and inflammation. We further showed that IKK-epsilon depletion in metastatic ovarian cancer cell lines decreased growth, adhesion, and invasion. Consistently, human xenografts depleted of IKK-epsilon in mice showed decreased aggressiveness, whereas overexpression of IKK-epsilon in a less invasive ovarian cancer cell line increased metastasis in vivo. Taken together, these data provide evidence that IKK-epsilon is a key coordinator of invasion and metastasis programs in ovarian cancer. Inhibition of IKK-epsilon signaling thus emerges as a viable therapeutic strategy in women whose ovarian cancer shows aberrant activation of this pathway. Cancer Res; 72(21); 5494-504. (C)2012 AACR.
C1 [Annunziata, Christina M.] NCI, NIH, Med Oncol Branch, Bethesda, MD USA.
[Anver, Miriam] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Vet Pathol Sect, Frederick, MD USA.
[Davidson, Ben] Oslo Univ Hosp, Div Pathol, Oslo, Norway.
RP Annunziata, CM (reprint author), NCI, NIH, Med Oncol Branch, 10 Ctr Dr,Room 12N226, Bethesda, MD USA.
EM annunzic@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU Intramural Research Program, CCR, NCI; NIH [K99CA151746]; Norwegian
Cancer Society and Health Region of South-Eastern Norway; NCI, NIH
[HSN261200800001E]
FX This work was supported by the Intramural Research Program, CCR, NCI (C.
M. Annunziata), NIH Grant K99CA151746 (C. M. Annunziata), and the
Norwegian Cancer Society and Health Region of South-Eastern Norway (to
B. Davidson), and with Federal funds from the NCI, NIH, under contract
number HSN261200800001E.
NR 25
TC 15
Z9 16
U1 0
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 NOV 1
PY 2012
VL 72
IS 21
BP 5494
EP 5504
DI 10.1158/0008-5472.CAN-11-3993
PG 11
WC Oncology
SC Oncology
GA 030PG
UT WOS:000310582000008
PM 22942254
ER
PT J
AU Manzoor, AA
Lindner, LH
Landon, CD
Park, JY
Simnick, AJ
Dreher, MR
Das, S
Hanna, G
Park, W
Chilkoti, A
Koning, GA
ten Hagen, TLM
Needham, D
Dewhirst, MW
AF Manzoor, Ashley A.
Lindner, Lars H.
Landon, Chelsea D.
Park, Ji-Young
Simnick, Andrew J.
Dreher, Matthew R.
Das, Shiva
Hanna, Gabi
Park, Won
Chilkoti, Ashutosh
Koning, Gerben A.
ten Hagen, Timo L. M.
Needham, David
Dewhirst, Mark W.
TI Overcoming Limitations in Nanoparticle Drug Delivery: Triggered,
Intravascular Release to Improve Drug Penetration into Tumors
SO CANCER RESEARCH
LA English
DT Article
ID TEMPERATURE-SENSITIVE LIPOSOMES; SOLID TUMORS; THERMOSENSITIVE
LIPOSOMES; LOCAL HYPERTHERMIA; SELECTIVE DELIVERY; MILD HYPERTHERMIA;
XENOGRAFT MODEL; BLOOD-VESSELS; MURINE TUMORS; IN-VITRO
AB Traditionally, the goal of nanoparticle-based chemotherapy has been to decrease normal tissue toxicity by improving drug specificity to tumors. The enhanced permeability and retention effect can permit passive accumulation into tumor interstitium. However, suboptimal delivery is achieved with most nanoparticles because of heterogeneities of vascular permeability, which limits nanoparticle penetration. Furthermore, slow drug release limits bioavailability. We developed a fast drug-releasing liposome triggered by local heat that has already shown substantial antitumor efficacy and is in human trials. Here, we show that thermally sensitive liposomes (Dox-TSL) release doxorubicin inside the tumor vasculature. Real-time confocal imaging of doxorubicin delivery to murine tumors in window chambers and histologic analysis of flank tumors illustrates that intravascular drug release increases free drug in the interstitial space. This increases both the time that tumor cells are exposed to maximum drug levels and the drug penetration distance, compared with free drug or traditional pegylated liposomes. These improvements in drug bioavailability establish a new paradigm in drug delivery: rapidly triggered drug release in the tumor bloodstream. Cancer Res; 72(21); 5566-75. (C)2012 AACR.
C1 [Manzoor, Ashley A.; Landon, Chelsea D.; Park, Ji-Young; Das, Shiva; Hanna, Gabi; Park, Won; Dewhirst, Mark W.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA.
[Manzoor, Ashley A.; Das, Shiva; Dewhirst, Mark W.] Duke Univ, Med Phys Program, Durham, NC USA.
[Simnick, Andrew J.; Chilkoti, Ashutosh; Needham, David; Dewhirst, Mark W.] Duke Univ, Dept Biomed Engn, Durham, NC USA.
[Lindner, Lars H.; Koning, Gerben A.; ten Hagen, Timo L. M.] Erasmus MC, Dept Surg, Sect Surg Oncol, Lab Expt Surg Oncol, Rotterdam, Netherlands.
[Lindner, Lars H.] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, Munich, Germany.
[Lindner, Lars H.] German Res Ctr Environm Hlth, CCG Hyperthermia, Helmholtz Zentrum Munchen, Munich, Germany.
[Dreher, Matthew R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Dewhirst, MW (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3455,Med Sci Res Bldg,Rm 201, Durham, NC 27710 USA.
EM mark.dewhirst@duke.edu
RI Koning, Gerben/K-2326-2012;
OI Koning, Gerben/0000-0003-3090-2403; Lindner, Lars/0000-0003-3708-8264
FU NIH/National Cancer Institute [CA42745-21, CA42745-22, CA42745-23];
NIH/National Center for Complementary and Alternative Medicine
[1F31ATT006644-01]; Department of Defense [W81XWH-09-1-0115]; Center for
Interventional Radiology, the intramural research program of the NIH;
Dr. Mildred Scheel Stiftung fuer Krebsforschung (Deutsche Krebshilfe
e.V.)
FX This work was supported by funding provided by grants from the
NIH/National Cancer Institute CA42745-21, 22, 23, NIH/National Center
for Complementary and Alternative Medicine 1F31ATT006644-01, and
Department of Defense W81XWH-09-1-0115. Financial support was also
provided by the Center for Interventional Radiology, the intramural
research program of the NIH, and by a research grant from the "Dr.
Mildred Scheel Stiftung fuer Krebsforschung (Deutsche Krebshilfe e.V.)."
NR 49
TC 136
Z9 138
U1 14
U2 134
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 NOV 1
PY 2012
VL 72
IS 21
BP 5566
EP 5575
DI 10.1158/0008-5472.CAN-12-1683
PG 10
WC Oncology
SC Oncology
GA 030PG
UT WOS:000310582000015
PM 22952218
ER
PT J
AU Murai, J
Huang, SYN
Das, BB
Renaud, A
Zhang, YP
Doroshow, JH
Ji, JP
Takeda, S
Pommier, Y
AF Murai, Junko
Huang, Shar-yin N.
Das, Benu Brata
Renaud, Amelie
Zhang, Yiping
Doroshow, James H.
Ji, Jiuping
Takeda, Shunichi
Pommier, Yves
TI Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors
SO CANCER RESEARCH
LA English
DT Article
ID DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; DNA-DAMAGE;
HOMOLOGOUS RECOMBINATION; EXCISION-REPAIR; CANCER-CELLS; STABILITY;
PATHWAYS; TUMORS; XRCC1
AB Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARP inhibitors with regard to their effects in cancer cells is not fully understood. In this study, we show that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA. Trapped PARP-DNA complexes were more cytotoxic than unrepaired SSBs caused by PARP inactivation, arguing that PARP inhibitors act in part as poisons that trap PARP enzyme on DNA. Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug. We also analyzed repair pathways for PARP-DNA complexes using 30 genetically altered avian DT40 cell lines with preestablished deletions in specific DNA repair genes. This analysis revealed that, in addition to homologous recombination, postreplication repair, the Fanconi anemia pathway, polymerase beta, and FEN1 are critical for repairing trapped PARP-DNA complexes. In summary, our study provides a new mechanistic foundation for the rational application of PARP inhibitors in cancer therapy. Cancer Res; 72(21); 5588-99. (C)2012 AACR.
C1 [Murai, Junko; Huang, Shar-yin N.; Das, Benu Brata; Renaud, Amelie; Doroshow, James H.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Zhang, Yiping; Ji, Jiuping] NCI, Natl Clin Target Validat Lab, NIH, Bethesda, MD 20892 USA.
[Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Murai, Junko; Takeda, Shunichi] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto, Japan.
RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Room 5068, Bethesda, MD 20892 USA.
EM pommier@nih.gov
FU Japan Society for the Promotion of Science (JSPS); Intramural Program of
the National Cancer Institute, Center for Cancer Research; JSPS
Core-to-Core Program
FX J. Murai is a recipient of a fellowship from the Japan Society for the
Promotion of Science (JSPS). This work was supported by the Intramural
Program of the National Cancer Institute, Center for Cancer Research,
and by the JSPS Core-to-Core Program.
NR 50
TC 290
Z9 293
U1 11
U2 51
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 NOV 1
PY 2012
VL 72
IS 21
BP 5588
EP 5599
DI 10.1158/0008-5472.CAN-12-2753
PG 12
WC Oncology
SC Oncology
GA 030PG
UT WOS:000310582000017
PM 23118055
ER
PT J
AU Stabile, LP
Rothstein, ME
Cunningham, DE
Land, SR
Dacic, S
Keohavong, P
Siegfried, JM
AF Stabile, Laura P.
Rothstein, Mary E.
Cunningham, Diana E.
Land, Stephanie R.
Dacic, Sanja
Keohavong, Phouthone
Siegfried, Jill M.
TI Prevention of tobacco carcinogen-induced lung cancer in female mice
using antiestrogens
SO CARCINOGENESIS
LA English
DT Article
ID ESTROGEN-RECEPTOR-ALPHA; HORMONE REPLACEMENT THERAPY; HEPATOCYTE
GROWTH-FACTOR; BREAST-CANCER; AROMATASE INHIBITORS; POSTMENOPAUSAL
WOMEN; GENE-EXPRESSION; MACROPHAGES; SURVIVAL; BETA
AB Increasing evidence shows that estrogens are involved in lung cancer proliferation and progression, and most human lung tumors express estrogen receptor beta (ER beta) as well as aromatase. To determine if the aromatase inhibitor anastrozole prevents development of lung tumors induced by a tobacco carcinogen, alone or in combination with the ER antagonist fulvestrant, ovariectomized female mice received treatments with the tobacco carcinogen 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK) along with daily supplements of androstenedione, the substrate for aromatase. Placebo, anastrozole and/or fulvestrant were administered in both an initiation and a promotion protocol of lung tumorigenesis. The combination of fulvestrant and anastrozole given during NNK exposure resulted in significantly fewer NNK-induced lung tumors (mean = 0.5) compared with placebo (mean = 4.6, P < 0.001), fulvestrant alone (mean = 3.4, P < 0.001) or anastrozole alone (mean = 2.8, P = 0.002). A significantly lower Ki67 cell proliferation index was also observed compared with single agent and control treatment groups. Beginning antiestrogen treatment after NNK exposure, when preneoplastic lesions had already formed, also yielded maximum antitumor effects with the combination. Aromatase expression was found mainly in macrophages infiltrating preneoplastic and tumorous areas of the lungs, whereas ER beta was found in both macrophages and tumor cells. Antiestrogens, especially in combination, effectively inhibited tobacco carcinogen-induced murine lung tumorigenesis and may have application for lung cancer prevention. An important source of estrogen synthesis may be inflammatory cells that infiltrate the lungs in response to carcinogens, beginning early in the carcinogenesis process. ER beta expressed by inflammatory and neoplastic epithelial cells in the lung may signal in response to local estrogen production.
C1 [Stabile, Laura P.; Rothstein, Mary E.; Siegfried, Jill M.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Cunningham, Diana E.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA.
[Dacic, Sanja] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA.
[Keohavong, Phouthone] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA.
Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA.
[Land, Stephanie R.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Stabile, LP (reprint author), Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
EM las22@pitt.edu
OI Keohavong, Phouthone/0000-0001-7812-4925
FU SPORE in Lung Cancer [P50 CA090440]; Comprehensive Cancer Center award
[P30CA047904]; [R21 CA129260]
FX Supported by P50 CA090440, SPORE in Lung Cancer, to J.M.S. and R21
CA129260 to P.K.. This project used the UPCI Animal Facility and Tissue
and Research Pathology Services Facility and was supported in part by
the Comprehensive Cancer Center award P30CA047904.
NR 49
TC 13
Z9 14
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD NOV
PY 2012
VL 33
IS 11
BP 2181
EP 2189
DI 10.1093/carcin/bgs260
PG 9
WC Oncology
SC Oncology
GA 031FL
UT WOS:000310624400020
PM 22859269
ER
PT J
AU John, K
Pratt, M
Beland, FA
Churchwell, MI
McMullen, G
Olivero, OA
Pogribny, IP
Poirier, MC
AF John, Kaarthik
Pratt, M. Margaret
Beland, Frederick A.
Churchwell, Mona I.
McMullen, Gail
Olivero, Ofelia A.
Pogribny, Igor P.
Poirier, Miriam C.
TI Benzo[a]pyrene (BP) DNA adduct formation in DNA repair-deficient p53
haploinsufficient [Xpa(-/-)p53(+/-)] and wild-type mice fed BP and BP
plus chlorophyllin for 28 days
SO CARCINOGENESIS
LA English
DT Article
ID POLYCYCLIC AROMATIC-HYDROCARBONS; NUCLEOTIDE EXCISION-REPAIR;
PIGMENTOSUM GROUP-A; METABOLIZING-ENZYMES; MASS-SPECTROMETRY;
TUMOR-DEVELOPMENT; ULTRAVIOLET-B; MOUSE MODELS; XPA MICE; GENE XPA
AB We have evaluated DNA damage (DNA adduct formation) after feeding benzo[a] pyrene (BP) to wild-type (WT) and cancer-susceptible Xpa(-/-)p53(+/-) mice deficient in nucleotide excision repair and haploinsufficient for the tumor suppressor p53. DNA damage was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ES-MS/MS), which measures r7,t8,t9-trihydroxy-c-10-(N-2-deoxyguanosyl)-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG), and a chemiluminescence immunoassay (CIA), using anti-r7,t8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA antiserum, which measures both BPdG and the other stable BP-DNA adducts. When mice were fed 100 ppm BP for 28 days, BP-induced DNA damage measured in esophagus, liver and lung was typically higher in Xpa(-/-) p53(+/-) mice, compared with WT mice. This result is consistent with the previously observed tumor susceptibility of Xpa(-/-) p53(+/-) mice. BPdG, the major DNA adduct associated with tumorigenicity, was the primary DNA adduct formed in esophagus (a target tissue in the mouse), whereas total BP-DNA adducts predominated in higher levels in the liver (a non-target tissue in the mouse). In an attempt to lower BP-induced DNA damage, we fed the WT and Xpa(-/-) p53(+/-) mice 0.3% chlorophyllin (CHL) in the BP-containing diet for 28 days. The addition of CHL resulted in an increase of BP-DNA adducts in esophagus, liver and lung of WT mice, a lowering of BPdG in esophagi of WT mice and livers of Xpa(-/-) p53(+/-) mice and an increase of BPdG in livers of WT mice. Therefore, the addition of CHL to a BP-containing diet showed a lack of consistent chemoprotective effect, indicating that oral CHL administration may not reduce PAH-DNA adduct levels consistently in human organs.
C1 [John, Kaarthik; Pratt, M. Margaret; Olivero, Ofelia A.; Poirier, Miriam C.] NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA.
US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA.
[Beland, Frederick A.; Churchwell, Mona I.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[McMullen, Gail] NCI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, LCBG, CCR,NIH, Bethesda, MD 20892 USA.
EM poirierm@exchange.nih.gov
FU Intramural Program of the Center for Cancer Research, National Cancer
Institute, National Institutes of Health, Bethesda, MD
FX This study was funded by the Intramural Program of the Center for Cancer
Research, National Cancer Institute, National Institutes of Health,
Bethesda, MD.
NR 45
TC 2
Z9 4
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD NOV
PY 2012
VL 33
IS 11
BP 2236
EP 2241
DI 10.1093/carcin/bgs247
PG 6
WC Oncology
SC Oncology
GA 031FL
UT WOS:000310624400026
PM 22828138
ER
PT J
AU Lao, HC
Akunda, JK
Chun, KS
Flake, GP
Yuspa, SH
Langenbach, R
AF Lao, Huei-Chen
Akunda, Jacqueline K.
Chun, Kyung-Soo
Flake, Gordon P.
Yuspa, Stuart H.
Langenbach, Robert
TI Genetic ablation of cyclooxygenase-2 in keratinocytes produces a
cell-autonomous defect in tumor formation
SO CARCINOGENESIS
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; INDUCED SKIN CARCINOGENESIS; EPITHELIAL-CELLS;
MOUSE SKIN; CANCER; INHIBITION; CHEMOPREVENTION; ANGIOGENESIS;
EXPRESSION; CARCINOMA
AB Using a mouse skin tumor model, we reported previously that cyclooxygenase-2 (COX-2) deficiency reduced papilloma formation. However, this model did not differentiate between the effects of systemic COX-2-deficiency and keratinocyte-specific COX-2 deficiency on tumor formation. To determine whether keratinocyte-specific COX-2 deficiency reduced papilloma formation, v-H-ras-transformed COX-2+/+ and COX-2-/- keratinocytes were grafted onto nude mice and tumor development was compared. Transformed COX-2+/+ and COX-2-/- keratinocytes expressed similar levels of H-ras, epidermal growth factor receptor and phospho-extracellular signal-regulated kinase1/2 in vitro; and COX-2-deficiency did not reduce uninfected or v-H-ras infected keratinocyte replication. In contrast, tumors arising from grafted transformed COX-2+/+ and COX-2-/- keratinocytes expressed similar levels of H-ras, but COX-2 deficiency reduced phospho-extracellular signal-regulated kinase 1/2 and epidermal growth factor receptor levels 50-60% and tumor volume by 80% at 3 weeks. Two factors appeared to account for the reduced papilloma size. First, papillomas derived from COX-2-/- keratinocytes showed about 70% decreased proliferation, as measured by bromodeoxyuridine incorporation, compared with papillomas derived from COX-2+/+ keratinocytes. Second, keratin 1 immunostaining of papillomas indicated that COX-2-/- keratinocytes prematurely initiated terminal differentiation. Differences in the levels of apoptosis and vascularization did not appear to be contributing factors as their levels were similar in tumors derived from COX-2-/- and COX-2+/+ keratinocytes. Overall, the data are in agreement with our previous observations that decreased papilloma number and size on COX-2-/- mice resulted from reduced keratinocyte proliferation and accelerated keratinocyte differentiation. Furthermore, the data indicate that deficiency/inhibition of COX-2 in the initiated keratinocyte is an important determinant of papilloma forming ability.
C1 [Lao, Huei-Chen; Langenbach, Robert] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
[Akunda, Jacqueline K.] Eli Lilly & Co, Dept Oncol, Indianapolis, IN 46285 USA.
[Chun, Kyung-Soo] Keimyung Univ, Coll Pharm, Taegu 704701, South Korea.
[Flake, Gordon P.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Langenbach, R (reprint author), NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
EM langenb1@niehs.nih.gov
FU National Institute of Environmental Health Sciences, National Institute
of Health, Intramural Program
FX This work was supported by the National Institute of Environmental
Health Sciences, National Institute of Health, Intramural Program.
NR 48
TC 5
Z9 6
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
J9 CARCINOGENESIS
JI Carcinogenesis
PD NOV
PY 2012
VL 33
IS 11
BP 2293
EP 2300
DI 10.1093/carcin/bgs267
PG 8
WC Oncology
SC Oncology
GA 031FL
UT WOS:000310624400033
PM 22902545
ER
PT J
AU Johnson, RA
Uddin, T
Aktar, A
Mohasin, M
Alam, MM
Chowdhury, F
Harris, JB
LaRocque, RC
Bufano, MK
Yu, YA
Wu-Freeman, Y
Leung, DT
Sarracino, D
Krastins, B
Charles, RC
Xu, P
Kovac, P
Calderwood, SB
Qadri, F
Ryan, ET
AF Johnson, Russell A.
Uddin, Taher
Aktar, Amena
Mohasin, M.
Alam, Mohammad Murshid
Chowdhury, Fahima
Harris, Jason B.
LaRocque, Regina C.
Bufano, Meagan Kelly
Yu, Yanan
Wu-Freeman, Ying
Leung, Daniel T.
Sarracino, David
Krastins, Bryan
Charles, Richelle C.
Xu, Peng
Kovac, Pavol
Calderwood, Stephen B.
Qadri, Firdausi
Ryan, Edward T.
TI Comparison of Immune Responses to the O-Specific Polysaccharide and
Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients
with Cholera
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID B-CELL RESPONSES; INFECTION-DERIVED IMMUNITY; CONJUGATE VACCINES;
STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; SEROTYPE INABA; CORE REGION;
ANTIBODY; TOXIN; PROTECTION
AB Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses to V. cholerae OSP have not previously been characterized. We assessed immune responses against V. cholerae OSP in adults with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P < 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66, respectively; P < 0.001). Addition of either OSPc: BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targeting V. cholerae LPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targeting V. cholerae OSP.
C1 [Harris, Jason B.; LaRocque, Regina C.; Bufano, Meagan Kelly; Yu, Yanan; Wu-Freeman, Ying; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Johnson, Russell A.; Uddin, Taher; Aktar, Amena; Mohasin, M.; Alam, Mohammad Murshid; Chowdhury, Fahima; Leung, Daniel T.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh.
[LaRocque, Regina C.; Yu, Yanan; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Sarracino, David; Krastins, Bryan] Thermo Fisher Sci, Cambridge, MA USA.
[Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA.
[Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
EM etryan@partners.org
RI Xu, Peng/K-7036-2012; Kovac, Pavol/B-8813-2008;
OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801
FU ICDDR,B; Intramural Research Program of the National Institutes of
Health, NIDDK; National Institutes of Health, National Institute of
Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01
AI077883, K08 AI100923, K08 AI089721]; Fogarty International Center,
Training Grant in Vaccine Development and Public Health [TW005572];
American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in
Global Infectious Diseases [TW05572]; Career Development Awards [K01
TW07409, TW07144]; Fogarty International Clinical Research Scholars
Award [R24 TW007988]; Swedish International Development Cooperation
Agency; Howard Hughes Medical Institute; American Society for Tropical
Medicine & Hygiene-Burroughs Wellcome Fund; Harvard Institute for Global
Health Postdoctoral Fellowship in Global Infectious Diseases
FX This research was supported by the ICDDR,B and by the Intramural
Research Program of the National Institutes of Health, NIDDK, and
extramural grants from the National Institutes of Health, including the
National Institute of Allergy and Infectious Diseases (U01 AI058935 [S.
B. C. and E. T. R.], R03 AI063079 [F. Q.], U01 AI077883 [E. T. R.], K08
AI100923 and K08 AI089721 [R. C. C.]), the Fogarty International Center,
Training Grant in Vaccine Development and Public Health (TW005572 [T.
U., M. M. A., and F. Q.]), an American Recovery and Reinvestment Act
(ARRA) Postdoctoral Fellowship in Global Infectious Diseases (TW05572
[D. T. L.]), Career Development Awards (K01 TW07409 [J.B.H.] and TW07144
[R. C. L.]), and a Fogarty International Clinical Research Scholars
Award (R24 TW007988 [R.A.J. and T. U.]), as well as by the Swedish
International Development Cooperation Agency (F. Q.), a Physician
Scientist Early Career Award from the Howard Hughes Medical Institute
(R. C. L.), a Postdoctoral Fellowship in Tropical Infectious Diseases
from the American Society for Tropical Medicine & Hygiene-Burroughs
Wellcome Fund (D. T. L.), and the Harvard Institute for Global Health
Postdoctoral Fellowship in Global Infectious Diseases (D.T.L).
NR 53
TC 19
Z9 19
U1 1
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 1556-6811
J9 CLIN VACCINE IMMUNOL
JI Clin. Vaccine Immunol.
PD NOV
PY 2012
VL 19
IS 11
BP 1712
EP 1721
DI 10.1128/CVI.00321-12
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 030IF
UT WOS:000310563700002
PM 22993410
ER
PT J
AU Ledgerwood, JE
Hu, Z
Gordon, IJ
Yamshchikov, G
Enama, ME
Plummer, S
Bailer, R
Pearce, MB
Tumpey, TM
Koup, RA
Mascola, JR
Nabel, GJ
Graham, BS
AF Ledgerwood, J. E.
Hu, Z.
Gordon, I. J.
Yamshchikov, G.
Enama, M. E.
Plummer, S.
Bailer, R.
Pearce, M. B.
Tumpey, T. M.
Koup, R. A.
Mascola, J. R.
Nabel, G. J.
Graham, B. S.
CA VRC 304 Study Team
VRC 305 Study Team
TI Influenza Virus H5 DNA Vaccination Is Immunogenic by Intramuscular and
Intradermal Routes in Humans
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID I CLINICAL-TRIAL; HEALTHY-ADULTS; NEUTRALIZING ANTIBODY; CANDIDATE
VACCINE; IMMUNE-RESPONSES; OPEN-LABEL; SAFETY; ANTIGENS
AB Avian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n = 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n = 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens.
C1 [Ledgerwood, J. E.; Gordon, I. J.; Yamshchikov, G.; Enama, M. E.; Plummer, S.; Bailer, R.; Koup, R. A.; Mascola, J. R.; Nabel, G. J.; Graham, B. S.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Hu, Z.] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Pearce, M. B.; Tumpey, T. M.] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
RP Ledgerwood, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ledgerwood@mail.nih.gov
FU NIAID
FX This clinical trial was funded by the NIAID Intramural program.
NR 22
TC 26
Z9 26
U1 0
U2 5
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 NOV
PY 2012
VL 19
IS 11
BP 1792
EP 1797
DI 10.1128/CVI.05663-11
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 030IF
UT WOS:000310563700011
PM 22956656
ER
PT J
AU Southern, T
Bess, L
Harmon, J
Taylor, L
Caldwell, H
AF Southern, Timothy
Bess, Leah
Harmon, Jillian
Taylor, Lacey
Caldwell, Harlan
TI Fluorometric High-Throughput Assay for Measuring Chlamydial Neutralizing
Antibody
SO CLINICAL AND VACCINE IMMUNOLOGY
LA English
DT Article
ID OUTER-MEMBRANE PROTEIN; IN-VITRO NEUTRALIZATION; TRACHOMATIS;
INFECTIONS; DISEASE
AB Chlamydia trachomatis is an obligate intracellular mucosotropic pathogen that causes human infections of global importance. C. trachomatis causes trachoma, the leading cause of preventable blindness worldwide, and is the most common cause of bacterial sexually transmitted disease. Although oculogenital infections are treatable with antibiotics, a vaccine is needed to control C. trachomatis infection. Ideally, a vaccine would provide coverage against most, if not all, naturally occurring antigenically distinct serovariants. The development of a subunit vaccine to prevent oculogenital disease could be advanced by identifying chlamydial antigens that elicit pan-neutralizing antibodies, particularly among infected human populations of known risk factors. There is currently no objective high-throughput in vitro assay to screen human sera for neutralization to aid in identification of these antigens. This report describes an objective, high-throughput in vitro assay that measures C. trachomatis-neutralizing antibodies. Antibody-mediated neutralization of chlamydial infection was performed in a 96-well microtiter format, and neutralization was quantified by immunostaining fixed cells followed by automated fluorometric analysis. This report shows that fluorometric analysis of C. trachomatis infection directly correlates to labor-intensive manual inclusion counts. Furthermore, this report shows that fluorometry can be used to identify C. trachomatis serovar-and serocomplex-specific neutralization. This objective, high-throughput analysis of serum neutralization is amenable to epidemiological studies of human chlamydial infection, human clinical vaccine trials, and preclinical animal model experiments of Chlamydia infection.
C1 [Southern, Timothy; Bess, Leah; Harmon, Jillian; Taylor, Lacey; Caldwell, Harlan] NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
RP Caldwell, H (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
EM hcaldwell@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 19
TC 3
Z9 4
U1 0
U2 7
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 NOV
PY 2012
VL 19
IS 11
BP 1864
EP 1869
DI 10.1128/CVI.00460-12
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 030IF
UT WOS:000310563700022
PM 23015646
ER
PT J
AU Lora, CM
Ricardo, AC
Brecklin, CS
Fischer, MJ
Rosman, RT
Carmona, E
Lopez, A
Balaram, M
Nessel, L
Tao, KX
Xie, DW
Kusek, JW
Go, AS
Lash, JP
AF Lora, Claudia M.
Ricardo, Ana C.
Brecklin, Carolyn S.
Fischer, Michael J.
Rosman, Robert T.
Carmona, Eunice
Lopez, Amada
Balaram, Manjunath
Nessel, Lisa
Tao, Kaixiang (Kelvin)
Xie, Dawei
Kusek, John W.
Go, Alan S.
Lash, James P.
TI Recruitment of Hispanics into an observational study of chronic kidney
disease: The Hispanic Chronic Renal Insufficiency Cohort Study
experience
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Recruitment; Hispanics; CKD
ID BASE-LINE CHARACTERISTICS; UNITED-STATES; TREATMENT TRIALS; POPULATIONS;
STRATEGIES; PREVENTION; MINORITY; RETENTION; BARRIERS; ADULTS
AB Despite the large burden of chronic kidney disease (CKD) in Hispanics, this population has been underrepresented in research studies. We describe the recruitment strategies employed by the Hispanic Chronic Renal Insufficiency Cohort Study, which led to the successful enrollment of a large population of Hispanic adults with CKD into a prospective observational cohort study. Recruitment efforts by bilingual staff focused on community clinics with Hispanic providers in high-density Hispanic neighborhoods in Chicago, academic medical centers, and private nephrology practices. Methods of publicizing the study included church meetings, local Hispanic print media, Spanish television and radio stations, and local health fairs. From October 2005 to July 2008, we recruited 327 Hispanics aged 21-74 years with mild-to-moderate CKD as determined by age-specific estimated glomerular filtration rate (eGFR). Of 716 individuals completing a screening visit, 49% did not meet eGFR inclusion criteria and 46% completed a baseline visit. The mean age at enrollment was 57.1 and 67.1% of participants were male. Approximately 75% of enrolled individuals were Mexican American, 15% Puerto Rican, and 10% had other Latin American ancestry. Eighty two percent of participants were Spanish-speakers. Community-based and academic primary care clinics yielded the highest percentage of participants screened (45.9% and 22.4%) and enrolled (38.2% and 24.5%). However, academic and community-based specialty clinics achieved the highest enrollment yield from individuals screened (61.9% to 71.4%). A strategy focused on primary care and nephrology clinics and the use of bilingual recruiters allowed us to overcome barriers to the recruitment of Hispanics with CKD. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Lora, Claudia M.; Ricardo, Ana C.; Brecklin, Carolyn S.; Fischer, Michael J.; Rosman, Robert T.; Carmona, Eunice; Lopez, Amada; Lash, James P.] Univ Illinois, Chicago, IL USA.
[Lora, Claudia M.; Ricardo, Ana C.; Fischer, Michael J.; Lash, James P.] Jesse Brown VA Med Ctr, Chicago, IL USA.
[Brecklin, Carolyn S.] John H Stroger Hosp, Chicago, IL USA.
[Balaram, Manjunath; Nessel, Lisa; Tao, Kaixiang (Kelvin); Xie, Dawei] Univ Penn, Philadelphia, PA 19104 USA.
[Kusek, John W.] NIDDK, Bethesda, MD USA.
[Go, Alan S.] Kaiser Permanente No Calif, Oakland, CA USA.
RP Lora, CM (reprint author), 820 S Wood St,M-C 793, Chicago, IL 60612 USA.
EM clora1@uic.edu
FU University of Illinois at Chicago Center for Clinical and Translational
Science (CCTS) from the National Center for Research Resources (NCRR)
[UL1RR029879]; VA HSR&D Career Development Award; National Institute of
Diabetes and Digestive and Kidney Disease (NIDDK) [R01 DK072231];
Clinical Translational Science Awards; National Institutes of Health
[M01 RR-013987-06]
FX Dr. Lora's work is supported by the University of Illinois at Chicago
Center for Clinical and Translational Science (CCTS), Award Number
UL1RR029879 from the National Center for Research Resources (NCRR).
Michael J. Fischer was supported by a VA HSR&D Career Development Award.
The HCRIC Study is supported by the National Institute of Diabetes and
Digestive and Kidney Disease (NIDDK) grant, Award Number R01 DK072231.
This work was also supported in part by the Clinical Translational
Science Awards and National Institutes of Health grant for the
University of Illinois at Chicago Clinical Research Center, M01
RR-013987-06. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the NCRR,
NIDDK, National Institutes of Health, or the Department of Veterans
Affairs or the United States government.
NR 30
TC 4
Z9 4
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD NOV
PY 2012
VL 33
IS 6
BP 1238
EP 1244
DI 10.1016/j.cct.2012.07.012
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 033UA
UT WOS:000310825400017
PM 22841929
ER
PT J
AU McDermott, MM
Domanchuk, K
Liu, K
Guralnik, JM
Tian, L
Criqui, MH
Ferrucci, L
Kibbe, M
Jones, DL
Pearce, WH
Zhao, LH
Spring, B
Rejeski, WJ
AF McDermott, Mary M.
Domanchuk, Kathryn
Liu, Kiang
Guralnik, Jack M.
Tian, Lu
Criqui, Michael H.
Ferrucci, Luigi
Kibbe, Melina
Jones, Donald-Lloyd
Pearce, William H.
Zhao, Lihui
Spring, Bonnie
Rejeski, W. Jack
TI The Group Oriented Arterial Leg Study (GOALS) to improve walking
performance in patients with peripheral arterial disease
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Peripheral artery disease; Intermittent claudication; Clinical trial;
Exercise
ID COUNSELING TRIAL ACT; ANKLE BRACHIAL INDEX; PHYSICAL-ACTIVITY;
INTERMITTENT CLAUDICATION; SUPERVISED EXERCISE; FUNCTIONAL DECLINE;
TREADMILL WALKING; LOWER-EXTREMITY; OLDER-ADULTS; DAILY-LIFE
AB People with lower extremity peripheral artery disease (PAD) have greater functional impairment and faster functional decline than those without PAD. We describe methods for the Group Oriented Arterial Leg Study (GOALS), an ongoing randomized controlled clinical trial designed to determine whether a Group-Mediated Cognitive Behavioral (GMCB) intervention improves functional performance in PAD participants, compared to a health education control condition.
In GOALS, PAD participants were randomized to either an intervention or a health education control condition in a parallel design. Both conditions consist of weekly group sessions with other PAD participants. In the intervention, cognitive behavioral techniques are used to assist participants in setting and adhering to home-based walking exercise goals. Participants are encouraged to walk for exercise at home at least 5 days/week. In the control condition, participants receive lectures on health-related topics. After 6 months of on-site weekly sessions, participants are transitioned to telephone follow-up for another 6 months. Participants in the intervention are asked to continue home walking exercise. The primary outcome is change in six-minute walk performance between baseline and six-month follow-up. Secondary outcomes include change in six-minute walk performance at 12-month follow-up, and change in treadmill walking performance, the Walking Impairment Questionnaire, quality of life, and physical activity at six and 12-month follow-up. In conclusion, if our group-mediated cognitive behavioral intervention is associated with improved walking performance in individuals with PAD, results will have major public health implications for the large and growing number of people with PAD. (C) 2012 Elsevier Inc. All rights reserved.
C1 [McDermott, Mary M.; Domanchuk, Kathryn] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Liu, Kiang; Jones, Donald-Lloyd; Zhao, Lihui; Spring, Bonnie] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Hlth Res & Policy, Baltimore, MD 21201 USA.
[Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Criqui, Michael H.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Ferrucci, Luigi] NIA, Bethesda, MD 20892 USA.
[Kibbe, Melina] Jesse Brown Vet Affairs Med Center, Chicago, IL 60612 USA.
[Rejeski, W. Jack] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
RP McDermott, MM (reprint author), Northwestern Univ, Dept Med, Feinberg Sch Med, 750 N Lake Shore Dr,10th Floor, Chicago, IL 60611 USA.
EM mdm608@northwestern.edu
FU National Heart Lung and Blood Institute [R01-HL088589]; National
Institute on Aging
FX This work is supported by the National Heart Lung and Blood Institute
[grant number R01-HL088589] and by the National Institute on Aging.
NR 42
TC 12
Z9 13
U1 3
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD NOV
PY 2012
VL 33
IS 6
BP 1311
EP 1320
DI 10.1016/j.cct.2012.08.001
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 033UA
UT WOS:000310825400025
PM 23158112
ER
PT J
AU Annab, LA
Bortner, CD
Sifre, MI
Collins, JM
Shah, RR
Dixon, D
Kinyamu, HK
Archer, TK
AF Annab, Lois A.
Bortner, Carl D.
Sifre, Marie I.
Collins, Jennifer M.
Shah, Ruchir R.
Dixon, Darlene
Kinyamu, H. Karimi
Archer, Trevor K.
TI Differential responses to retinoic acid and endocrine disruptor
compounds of subpopulations within human embryonic stem cell lines
SO DIFFERENTIATION
LA English
DT Article
DE Human embryonic stem cell; Heterogeneous population; Retinoic acid
differentiation; Endocrine disruptor compounds; Notch signaling;
Chromatin remodeling
ID CHROMATIN-REMODELING COMPLEX; GENE-EXPRESSION; SELF-RENEWAL;
BREAST-CANCER; ES CELLS; PLURIPOTENT; LSD1; CULTURE; COMMITMENT;
RECEPTORS
AB The heterogeneous nature of stem cells is an important issue in both research and therapeutic use in terms of directing cell lineage differentiation pathways, as well as self-renewal properties. Using flow cytometry we have identified two distinct subpopulations by size, large and small, within cultures of human embryonic stem (hES) cell lines. These two cell populations respond differentially to retinoic acid (RA) differentiation and several endocrine disruptor compounds (EDC). The large cell population responds to retinoic acid differentiation with greater than a 50% reduction in cell number and loss of Oct-4 expression, whereas the number of the small cell population does not change and Oct-4 protein expression is maintained. In addition, four estrogenic compounds altered SSEA-3 expression differentially between the two cell subpopulations changing their ratios relative to each other. Both populations express stem cell markers Oct-4, Nanog, Tra-1-60, Tra-1-80 and SSEA-4, but express low levels of differentiation markers common to the three germ layers. Cloning studies indicate that both populations can revive the parental population. Furthermore, whole genome microarray identified approximately 400 genes with significantly different expression between the two populations (p<0.01). We propose the differential response to RA in these populations is due to differential gene expression of Notch signaling members, CoupTF1 and CoupTF2, chromatin remodeling and histone modifying genes that render the small population resistant to RA differentiation. The findings that hES cells exist as heterogeneous populations with distinct responses to differentiation signals and environmental stimuli will be relevant for their use for drug discovery and disease therapy. Published by Elsevier B.V. on behalf of International Society of Differentiation
C1 [Annab, Lois A.; Kinyamu, H. Karimi; Archer, Trevor K.] NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Bortner, Carl D.; Sifre, Marie I.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Collins, Jennifer M.] NIEHS, Microarray Facil, NIH, Res Triangle Pk, NC 27709 USA.
[Shah, Ruchir R.] NIEHS, SRA Int Inc, NIH, Res Triangle Pk, NC 27709 USA.
[Dixon, Darlene] NIEHS, Cellular & Mol Pathol Branch, NTP, NIH, Res Triangle Pk, NC 27709 USA.
RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, MD D4-01,POB 12233, Res Triangle Pk, NC 27709 USA.
EM archer1@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES071006-13, Z99 ES999999, ZIA ES071006-12];
NIEHS NIH HHS [Z01 ES071006, Z01ES071006-10]
NR 69
TC 3
Z9 4
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0301-4681
J9 DIFFERENTIATION
JI Differentiation
PD NOV
PY 2012
VL 84
IS 4
BP 330
EP 343
DI 10.1016/j.diff.2012.07.006
PG 14
WC Cell Biology; Developmental Biology
SC Cell Biology; Developmental Biology
GA 030LR
UT WOS:000310572700006
PM 22906706
ER
PT J
AU Quenet, D
McNally, JG
Dalal, Y
AF Quenet, Delphine
McNally, James G.
Dalal, Yamini
TI Through thick and thin: the conundrum of chromatin fibre folding in vivo
SO EMBO REPORTS
LA English
DT Editorial Material
ID CHROMOSOMES; MODEL; SITU
C1 [Quenet, Delphine; McNally, James G.; Dalal, Yamini] NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
RP Quenet, D (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA.
EM dalaly@mail.nih.gov
OI Dalal, Yamini/0000-0002-7655-6182
FU Intramural NIH HHS [ZIA BC011207-03, ZIA BC011207-04, ZIA BC011207-05,
ZIA BC011207-06, ZIA BC011207-01, ZIA BC011207-02]
NR 12
TC 10
Z9 10
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD NOV
PY 2012
VL 13
IS 11
BP 943
EP 944
DI 10.1038/embor.2012.143
PG 2
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 033DH
UT WOS:000310773300003
PM 23041656
ER
PT J
AU Miguel-Aliaga, I
Oliver, B
Teleman, AA
AF Miguel-Aliaga, Irene
Oliver, Brian
Teleman, Aurelio A.
TI The flies of Icarus: science with wings in Crete
SO EMBO REPORTS
LA English
DT Editorial Material
C1 [Miguel-Aliaga, Irene] Univ Cambridge, Dept Zool, Cambridge, England.
[Oliver, Brian] NIDDKD, Lab Cellular & Dev Biol, Bethesda, MD USA.
[Teleman, Aurelio A.] German Canc Res Ctr, Heidelberg, Germany.
RP Miguel-Aliaga, I (reprint author), Univ Cambridge, Dept Zool, Cambridge, England.
EM im307@cam.ac.uk; briano@helix.nih.gov; a.teleman@dkfz-heidelberg.de
RI Teleman, Aurelio/E-6864-2013
OI Teleman, Aurelio/0000-0002-4237-9368
FU Medical Research Council [MC_UP_1102/3]
NR 0
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 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD NOV
PY 2012
VL 13
IS 11
BP 945
EP 947
DI 10.1038/embor.2012.154
PG 3
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 033DH
UT WOS:000310773300004
PM 23059980
ER
PT J
AU Severson, PL
Tokar, EJ
Vrba, L
Waalkes, MP
Futscher, BW
AF Severson, Paul L.
Tokar, Erik J.
Vrba, Lukas
Waalkes, Michael P.
Futscher, Bernard W.
TI Agglomerates of aberrant DNA methylation are associated with
toxicant-induced malignant transformation
SO EPIGENETICS
LA English
DT Article
DE epigenetics; arsenic; cadmium; DNA methylation; malignant
transformation; long-range epigenetic silencing; agglomerative DNA
methylation; H3K9me3; H3K27me3
ID PROSTATE EPITHELIAL-CELLS; UROTHELIAL CELLS; BREAST-CANCER; BLADDER;
GENE; CARCINOMA; LINES; CARCINOGENESIS; EPIGENETICS; CHROMATIN
AB Epigenetic dysfunction is a known contributor in carcinogenesis, and is emerging as a mechanism involved in toxicant-induced malignant transformation for environmental carcinogens such as arsenicals or cadmium. In addition to aberrant DNA methylation of single genes, another manifestation of epigenetic dysfunction in cancer is agglomerative DNA methylation, which can participate in long-range epigenetic silencing that targets many neighboring genes and has been shown to occur in several types of clinical cancers. Using in vitro model systems of toxicant-induced malignant transformation, we found hundreds of aberrant DNA methylation events that emerge during malignant transformation, some of which occur in an agglomerative fashion. In an arsenite-transformed prostate epithelial cell line, the protocadherin (PCDH), HOXC and HOXD gene family clusters are targeted for agglomerative DNA methylation. The agglomerative DNA methylation changes induced by arsenicals appear to be common and clinically relevant events, since they occur in other human cancer cell lines and models of malignant transformation, as well as clinical cancer specimens. Aberrant DNA methylation in general occurred more often within histone H3 lysine-27 trimethylation stem cell domains. We found a striking association between enrichment of histone H3 lysine-9 trimethylation stem cell domains and toxicant-induced agglomerative DNA methylation, suggesting these epigenetic modifications may become aberrantly linked during malignant transformation. In summary, we found an association between toxicant-induced malignant transformation and agglomerative DNA methylation, which lends further support to the hypothesis that epigenetic dysfunction plays an important role in toxicant-induced malignant transformation.
C1 [Severson, Paul L.; Futscher, Bernard W.] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
[Tokar, Erik J.; Waalkes, Michael P.] Natl Inst Environm Hlth Sci, Natl Toxicol Program Lab, Res Triangle Pk, NC USA.
[Vrba, Lukas] Univ Arizona, Ctr Canc, Tucson, AZ USA.
[Vrba, Lukas] Acad Sci Czech Republic, Inst Plant Mol Biol, Biol Ctr ASCR, CR-37005 Ceske Budejovice, Czech Republic.
RP Futscher, BW (reprint author), Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA.
EM bfutscher@azcc.arizona.edu
RI Vrba, Lukas/J-9268-2015
OI Vrba, Lukas/0000-0003-3042-6275
FU National Institutes of Health [P42 ES04940, ES006694, CA23074,
5T32ES16652-3]
FX This work was supported by the National Institutes of Health (P42
ES04940, ES006694, CA23074, 5T32ES16652-3 to P.S.). We thank the
laboratory of Dr A. Jay Gandolfi for providing the URO-MSC52 and
URO-MSC12+24(-) cell lines. We are grateful to the laboratory of Drs
Donald and Mary Ann Sens for sharing UROtsa, URO-ASSC and URO-CDSC. We
wish to thank Dr Petr Novak for contributing his time and insightful
comments. The costs for publication of this article were deferred by the
Southwest Environmental Health Sciences Center (ES006694). This article
may be the work product of an employee or group of employees of the
National Institute of Environmental Health Sciences (NIEHS), National
Institutes of Health (NIH), however, the statements, opinions or
conclusions contained therein do not necessarily represent the
statements, opinions or conclusions of NIEHS, NIH or the US government.
NR 60
TC 14
Z9 16
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD NOV
PY 2012
VL 7
IS 11
BP 1238
EP 1248
DI 10.4161/epi.22163
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 030PO
UT WOS:000310582800004
PM 22976526
ER
PT J
AU Sturgeon, SR
Balasubramanian, R
Schairer, C
Muss, HB
Ziegler, RG
Arcaro, KF
AF Sturgeon, Susan R.
Balasubramanian, Raji
Schairer, Catherine
Muss, Hyman B.
Ziegler, Regina G.
Arcaro, Kathleen F.
TI Detection of promoter methylation of tumor suppressor genes in serum DNA
of breast cancer cases and benign breast disease controls
SO EPIGENETICS
LA English
DT Article
DE serum DNA; breast cancer; promoter methylation; early marker;
pyrosequencing
ID CELL-FREE DNA; HYPERMETHYLATION; BIOMARKER; PLASMA; CARCINOGENESIS; RISK
AB Tumors are capable of shedding DNA into the blood stream. This shed DNA may be recovered from serum or plasma. The objective of this study was to evaluate whether pyrosequencing promoter DNA in a panel of 12 breast cancer-related genes (APC, BRCA1, CCND2, CDH1, ESR1, GSTP1, HIN1, P16, RAR beta, RASSF1, SFRP1 and TWIST) to measure the degree of methylation would lead to a useful serum-based marker of breast cancer. Serum was obtained from women who were about to undergo a breast biopsy or mastectomy at three hospitals from 1977 to 1987 in Grand Rapids, MI USA. We compared the methylation status of 12 genes in serum DNA obtained from three groups of postmenopausal women (mean age at blood collection: 63.0 y; SD 9.9; range 35-91): breast cancer cases with lymph node-positive disease (n = 241); breast cancer cases with lymph node-negative disease (n = 63); and benign breast disease control subjects (n = 234). Overall, median levels of promoter methylation were low, typically below 5%, for all genes in all study groups. For all genes, median levels of methylation were higher (by 3.3% to 47.6%) in lymph node-positive breast cancer cases than in the controls. Comparing mean methylation level between lymph-node positive cases and controls, the most statistically significant findings, after adjustment of the false-positive rate (q-value), were for TWIST (p = 0.04), SFRP1 (p = 0.16), ESR1 (p = 0.17), P16 (p = 0.19) and APC (p = 0.19). For two of these four genes (TWIST, P16), the median methylation level was also highest in lymph-node positive cases, intermediate in lymph node-negative cases and lowest in the controls. The percent of study subjects with mean methylation scores >= 5% was higher among lymph node-positive cases than controls for ten genes, and significantly higher for HIN1 and TWIST (22.0 vs. 12.2%, p = 0.04 and 37.9 vs. 24.5%, p = 0.004, respectively). Despite relatively consistent variation in methylation patterns among groups, these modest differences did not provide sufficient ability to distinguish between cases and controls in a clinical setting.
C1 [Sturgeon, Susan R.; Balasubramanian, Raji] Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Schairer, Catherine; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Muss, Hyman B.] UNC Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Arcaro, Kathleen F.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA.
RP Sturgeon, SR (reprint author), Univ Massachusetts, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
EM ssturgeon@schoolph.umass.edu
FU Susan G. Komen for the Cure
FX This research was supported by a grant from Susan G. Komen for the Cure.
NR 25
TC 25
Z9 27
U1 0
U2 14
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1559-2294
J9 EPIGENETICS-US
JI Epigenetics
PD NOV
PY 2012
VL 7
IS 11
BP 1258
EP 1267
DI 10.4161/epi.22220
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 030PO
UT WOS:000310582800006
PM 22986510
ER
PT J
AU Yang, CZ
Matro, JC
Huntoon, KM
Ye, DY
Huynh, TT
Fliedner, SMJ
Breza, J
Zhuang, ZP
Pacak, K
AF Yang, Chunzhang
Matro, Joey C.
Huntoon, Kristin M.
Ye, Donald Y.
Huynh, Thanh T.
Fliedner, Stephanie M. J.
Breza, Jan
Zhuang, Zhengping
Pacak, Karel
TI Missense mutations in the human SDHB gene increase protein degradation
without altering intrinsic enzymatic function
SO FASEB JOURNAL
LA English
DT Article
DE pheochromocytoma; paraganglioma; succinate dehydrogenase subunit B;
histone deacetylase inhibitor
ID TUMOR-SUPPRESSOR GENE; SUCCINATE-DEHYDROGENASE; QUALITY-CONTROL;
IN-VIVO; FAMILIAL PHEOCHROMOCYTOMA; HEREDITARY PARAGANGLIOMA; PROLYL
HYDROXYLASE; OXIDATIVE STRESS; LINDAU-DISEASE; GERMLINE SDHB
AB Mutations of succinate dehydrogenase subunit B (SDHB) play a crucial role in the pathogenesis of the most aggressive and metastatic pheochromocytomas (PHEOs) and paragangliomas (PGLs). Although a variety of missense mutations in the coding sequence of the SDHB gene have been found in PHEOs and PGLs, it has been unclear whether these mutations impair mRNA expression, protein stability, subcellular localization, or intrinsic protein function. RT-PCR and Western blot analysis of SDHB mRNA and protein expression from SDHB-related PHEOs and PGLs demonstrated intact mRNA expression but significantly reduced protein expression compared to non-SDHB PHEOs and PGLs. A pulse-chase assay of common SDHB missense mutations in transfected HeLa cell lines demonstrated that the loss of SDHB function was due to a reduction in mutant protein half-life, whereas colocalization of SDHB with mitochondria and immunoprecipitation with SDHA demonstrated intact subcellular localization and complex formation. The half-life of the SDHB protein increased after treatment with histone deacetylase inhibitors (HDACis), implicating the protein quality control machinery in the degradation of mutant SDHB protein. These findings provide the first direct mechanism of functional loss resulting from SDHBmutations and suggest that reducing protein degradation with HDACis may serve as a novel therapeutic paradigm for preventing the development of SDHB-related tumors.-Yang, C., Matro, J. C., Huntoon, K. M., Ye, D. Y., Huynh, T. T., Fliedner, S. M. J., Breza, J., Zhuang, Z., Pacak, K. Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function. FASEB J. 26, 4506-4516 (2012). www.fasebj.org
C1 [Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bethesda, MD 20892 USA.
[Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Breza, Jan] Comenius Univ, Sch Med, Dept Urol, Bratislava, Slovakia.
RP Pacak, K (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, CRC, Bldg 10,Rm 1E-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA.
EM zhuangp@ninds.nih.gov; karel@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Institute of Neurological Disorders and Stroke at
the U. S. National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Neurological Disorders and
Stroke at the U. S. National Institutes of Health.
NR 58
TC 21
Z9 21
U1 1
U2 4
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD NOV
PY 2012
VL 26
IS 11
BP 4506
EP 4516
DI 10.1096/fj.12-210146
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 030MG
UT WOS:000310574200013
PM 22835832
ER
PT J
AU Roudier, E
Forn, P
Perry, ME
Birot, O
AF Roudier, Emilie
Forn, Paul
Perry, Mary Ellen
Birot, Olivier
TI Murine double minute-2 expression is required for capillary maintenance
and exercise-induced angiogenesis in skeletal muscle
SO FASEB JOURNAL
LA English
DT Article
DE VEGF-A; endothelial cell; p53; physiology
ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; GROWTH-FACTOR EXPRESSION; FACTOR
MESSENGER-RNA; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; ISCHEMIC MUSCLE;
CANCER-THERAPY; FACTOR 1-ALPHA; MDM2; P53
AB Exercise-induced angiogenesis is a key determinant of skeletal muscle function. Here, we investigated whether the E3 ubiquitin ligase murine double minute-2 (Mdm2) exerts a proangiogenic function in exercised skeletal muscle. Mdm2 hypomorphic (Mdm2(Puro/Delta 7-9)) mice have a 60% reduction in Mdm2 expression compared with that in wild-type animals. Capillary staining on muscle sections from Mdm2(Puro/Delta 7-9) sedentary mice with a wild-type or knockout background for p53 revealed that deficiency in Mdm2 resulted in 20% capillary regression independently of p53 status. In response to one bout of exercise, protein expression of the proangiogenic vascular endothelial growth factor-A (VEGF-A) was increased by 64% in muscle from wild-type animals, and endothelial cell outgrowth from exercised muscle biopsy samples cultured in a 3-dimensional collagen gel was enhanced by 37%. These proangiogenic responses to exercise were impaired in exercised Mdm2(Puro/Delta 7-9) mice. Prolonged exercise training resulted in increased Mdm2 protein expression (+49%) and capillarization (+24%) in wildtype muscles. However, exercise training-induced angiogenesis was abolished in Mdm2(Puro/Delta 7-9) mice. Finally, exercise training restored Mdm2, VEGF-A, and capillarization levels in skeletal muscles from obese Zucker diabetic fatty rats compared with those in healthy animals. Our results define Mdm2 as a crucial regulator of capillary maintenance and exercise-induced angiogenesis in skeletal muscle.-Roudier, E., Forn, P., Perry, M. E., Birot, O. Murine double minute-2 expression is required for capillary maintenance and exercise-induced angiogenesis in skeletal muscle. FASEB J. 26, 4530-4539 (2012). www.fasebj.org
C1 [Birot, Olivier] York Univ, Fac Hlth, Norman Bethune Coll, Angiogenesis Res Grp, Toronto, ON M3J 1P3, Canada.
[Roudier, Emilie; Birot, Olivier] Univ Montreal, Dept Kinesiol, Montreal, PQ, Canada.
[Perry, Mary Ellen] NCI, Lab Prot Dynam & Signaling, US Natl Inst Hlth, Frederick, MD 21701 USA.
RP Birot, O (reprint author), York Univ, Fac Hlth, Norman Bethune Coll, Angiogenesis Res Grp, Room 353,4700 Keele St, Toronto, ON M3J 1P3, Canada.
EM birot@yorku.ca
FU Natural Sciences and Engineering Research Council of Canada (NSERC)
[341258]; NIH, National Cancer Institute, Center for Cancer Research
FX The authors thank Nicole Morris [National Cancer Institute, U.S.
National Institutes of Health (NIH)] for maintaining the
Mdm2puro/Delta 7-9 mice, and Dr. Raynald Bergeron (University
of Montreal) for his help in the ZDF mouse conditioning. This work was
supported by the Natural Sciences and Engineering Research Council of
Canada (NSERC discovery grant 341258 to O.B.) and by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research (M. E. P.). E. R. and O.B. conceived the study; E. R.,
M. E. P., and O.B. designed experiments; E. R., P. F., and O.B.
performed experiments and analyzed data; M. E. P. supplied
Mdm2puro/Delta 7-9 mice; E. R., M. E. P., and O.B.
participated in the redaction of the manuscript.
NR 54
TC 15
Z9 15
U1 0
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD NOV
PY 2012
VL 26
IS 11
BP 4530
EP 4539
DI 10.1096/fj.12-212720
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 030MG
UT WOS:000310574200015
PM 22835827
ER
PT J
AU Tryndyak, V
de Conti, A
Kobets, T
Kutanzi, K
Koturbash, I
Han, T
Fuscoe, JC
Latendresse, JR
Melnyk, S
Shymonyak, S
Collins, L
Ross, SA
Rusyn, I
Beland, FA
Pogribny, IP
AF Tryndyak, Volodymyr
de Conti, Aline
Kobets, Tetyana
Kutanzi, Kristy
Koturbash, Igor
Han, Tao
Fuscoe, James C.
Latendresse, John R.
Melnyk, Stepan
Shymonyak, Svitlana
Collins, Leonard
Ross, Sharon A.
Rusyn, Ivan
Beland, Frederick A.
Pogribny, Igor P.
TI Interstrain differences in the severity of liver injury induced by a
choline- and folate-deficient diet in mice are associated with
dysregulation of genes involved in lipid metabolism
SO FASEB JOURNAL
LA English
DT Article
DE nonalcoholic fatty liver; interindividual; oxidative stress
ID ELEMENT-BINDING PROTEIN; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE STRESS;
PPAR-ALPHA; HEPATIC STEATOSIS; EXPRESSION; DISEASE; PROGRESSION; CHREBP;
CYTOCHROME-P450
AB Nonalcoholic fatty liver disease (NAFLD) is a major health problem and a leading cause of chronic liver disease in the United States and developed countries. In humans, genetic factors greatly influence individual susceptibility to NAFLD. The goals of this study were to compare the magnitude of interindividual differences in the severity of liver injury induced by methyl-donor deficiency among individual inbred strains of mice and to investigate the underlying mechanisms associated with the variability. Feeding mice a choline-and folate-deficient diet for 12 wk caused liver injury similar to NAFLD. The magnitude of liver injury varied among the strains, with the order of sensitivity being A/J approximate to C57BL/6J approximate to C3H/HeJ < 129S1/SvImJ approximate to CAST/EiJ < PWK/PhJ < WSB/EiJ. The interstrain variability in severity of NAFLD liver damage was associated with dysregulation of genes involved in lipid metabolism, primarily with a down-regulation of the peroxisome proliferator receptor alpha (PPAR alpha)-regulated lipid catabolic pathway genes. Markers of oxidative stress and oxidative stress-induced DNA damage were also elevated in the livers but were not correlated with severity of liver damage. These findings suggest that the PPAR alpha-regulated metabolism network is one of the key mechanisms determining interstrain susceptibility and severity of NAFLD in mice.-Tryndyak, V., de Conti, A., Kobets, T., Kutanzi, K., Koturbash, I., Han, T., Fuscoe, J. C., Latendresse, J. R., Melnyk, S., Shymonyak, S., Collins, L., Ross, S. A., Rusyn, I., Beland, F. A., Pogribny, I. P. Interstrain differences in the severity of liver injury induced by a choline-and folate-deficient diet in mice are associated with dysregulation of genes involved in lipid metabolism. FASEB J. 26, 4592-4602 (2012). www.fasebj.org
C1 [Tryndyak, Volodymyr; Kobets, Tetyana; Kutanzi, Kristy; Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] US FDA, NCTR, Div Biochem Toxicol, Jefferson, AR 72079 USA.
[Han, Tao; Fuscoe, James C.] US FDA, NCTR, Div Syst Biol, Jefferson, AR 72079 USA.
[Latendresse, John R.] US FDA, NCTR, Toxicol Pathol Associates, Jefferson, AR 72079 USA.
[de Conti, Aline] Univ Sao Paulo, Lab Diet Nutr & Canc, Sao Paulo, Brazil.
[Kobets, Tetyana; Shymonyak, Svitlana; Collins, Leonard; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA.
[Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA.
[Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Pogribny, IP (reprint author), US FDA, NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA.
EM igor.pogribny@fda.hhs.gov
RI de Conti, Aline/I-1666-2013; Rusyn, Ivan/S-2426-2016
FU NIEHS NIH HHS [P30 ES010126]
NR 45
TC 15
Z9 15
U1 0
U2 12
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD NOV
PY 2012
VL 26
IS 11
BP 4592
EP 4602
DI 10.1096/fj.12-209569
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 030MG
UT WOS:000310574200021
PM 22872676
ER
PT J
AU Ashkenazi, A
Viard, M
Unger, L
Blumenthal, R
Shai, Y
AF Ashkenazi, Avraham
Viard, Mathias
Unger, Linor
Blumenthal, Robert
Shai, Yechiel
TI Sphingopeptides: dihydrosphingosine-based fusion inhibitors against
wild-type and enfuvirtide-resistant HIV-1
SO FASEB JOURNAL
LA English
DT Article
DE viral envelope protein; sphingolipids
ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MEMBRANE-FUSION; CELL-CELL FUSION;
ENVELOPE GLYCOPROTEIN; MEDIATED FUSION; LIPID RAFTS; COILED-COIL; GP41;
PEPTIDE; CHOLESTEROL
AB Understanding the structural organization of lipids in the cell and viral membranes is essential for elucidating mechanisms of viral fusion that lead to entry of enveloped viruses into their host cells. The HIV lipidome shows a remarkable enrichment in dihydrosphingomyelin, an unusual sphingolipid formed by a dihydrosphingosine backbone. Here we investigated the ability of dihydrosphingosine to incorporate into the site of membrane fusion mediated by the HIV envelope (Env) protein. Dihydrosphingosine as well as cholesterol, fatty acid, and tocopherol was conjugated to highly conserved, short HIV-1 Env-derived peptides with no antiviral activity otherwise. We showed that dihydrosphingosine exclusively endowed nanomolar antiviral activity to the peptides (IC50 as low as 120 nM) in HIV-1 infection on TZM-bl cells and on Jurkat T cells, as well as in the cell-cell fusion assay. These sphingopeptides were active against enfuvirtide-resistant and wild-type CXCR4 and CCR5 tropic HIV strains. The anti-HIV activity was determined by both the peptides and their dihydrosphingosine conjugate. Moreover, their mode of action involved accumulation in the cells and viruses and binding to membranes enriched in sphingomyelin and cholesterol. The data suggest that sphingopeptides are recruited to the HIV membrane fusion site and provide a general concept in developing inhibitors of sphingolipid-mediated biological systems.-Ashkenazi, A., Viard, M., Unger, L., Blumenthal, R., Shai, Y. Sphingopeptides: dihydrosphingosine-based fusion inhibitors against wild-type and enfuvirtide-resistant HIV-1. FASEB J. 26, 4628-4636 (2012). www.fasebj.org
C1 [Ashkenazi, Avraham; Unger, Linor; Shai, Yechiel] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
[Viard, Mathias; Blumenthal, Robert] NCI, Nanobiol Program, Ctr Canc Res, Frederick Natl Lab, Frederick, MD 21701 USA.
[Viard, Mathias] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab, Frederick, MD USA.
RP Shai, Y (reprint author), Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel.
EM yechiel.shai@weizmann.ac.il
FU Israel Science Foundation; Frederick National Laboratory; National
Cancer Institute; U.S. National Institutes of Health [HHSN26120080001E]
FX The authors thank Batya Zarmi for her valuable help with peptide
purification and Winfried Weissenhorn for providing the recent
3-dimensional structure of gp41. This study was supported by the Israel
Science Foundation (to Y. S.) and in part by federal funds (to R. B.)
from the Frederick National Laboratory, National Cancer Institute, U.S.
National Institutes of Health (contract HHSN26120080001E). The content
of this publication does not necessarily reflect the views or policies
of the U. S. Department of Health and Human Services, nor does mention
of trade names, commercial products, or organizations imply endorsement
by the U. S. government. Y. S. is the incumbent of the Harold S. and
Harriet B. Brady Professorial Chair in Cancer Research.
NR 56
TC 14
Z9 14
U1 1
U2 12
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD NOV
PY 2012
VL 26
IS 11
BP 4628
EP 4636
DI 10.1096/fj.12-215111
PG 9
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 030MG
UT WOS:000310574200024
PM 22872679
ER
PT J
AU Linehan, WM
AF Linehan, W. Marston
TI Genetic basis of kidney cancer: Role of genomics for the development of
disease-based therapeutics
SO GENOME RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU-DISEASE; HOGG-DUBE-SYNDROME;
TUMOR-SUPPRESSOR PROTEIN; PARENCHYMAL SPARING SURGERY; TUBEROUS
SCLEROSIS COMPLEX; HEREDITARY LEIOMYOMATOSIS; FUMARATE-HYDRATASE;
CHROMOSOME-TRANSLOCATION; GERMLINE MUTATIONS
AB Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.
C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
EM linehanm@mail.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. The author
thanks Tracey A. Rouault, M. D. for the manuscript review and Georgia
Shaw for editorial and graphics support.
NR 100
TC 38
Z9 43
U1 0
U2 27
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD NOV
PY 2012
VL 22
IS 11
BP 2089
EP 2100
DI 10.1101/gr.131110.111
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 030QE
UT WOS:000310584400001
PM 23038766
ER
PT J
AU Burzynski, GM
Reed, X
Taher, L
Stine, ZE
Matsui, T
Ovcharenko, I
McCallion, AS
AF Burzynski, Grzegorz M.
Reed, Xylena
Taher, Leila
Stine, Zachary E.
Matsui, Takeshi
Ovcharenko, Ivan
McCallion, Andrew S.
TI Systematic elucidation and in vivo validation of sequences enriched in
hindbrain transcriptional control
SO GENOME RESEARCH
LA English
DT Article
ID RECEPTOR-RELATED RECEPTORS; SUPPORT VECTOR MACHINES; CHIP-SEQ;
EMBRYONIC-DEVELOPMENT; HEART ENHANCERS; NERVOUS-SYSTEM; 2008 UPDATE;
ZEBRAFISH; EXPRESSION; GENOME
AB Illuminating the primary sequence encryption of enhancers is central to understanding the regulatory architecture of genomes. We have developed a machine learning approach to decipher motif patterns of hindbrain enhancers and identify 40,000 sequences in the human genome that we predict display regulatory control that includes the hindbrain. Consistent with their roles in hindbrain patterning, MEIS1, NKX6-1, as well as HOX and POU family binding motifs contributed strongly to this enhancer model. Predicted hindbrain enhancers are overrepresented at genes expressed in hindbrain and associated with nervous system development, and primarily reside in the areas of open chromatin. In addition, 77 (0.2%) of these predictions are identified as hindbrain enhancers on the VISTA Enhancer Browser, and 26,000 (60%) overlap enhancer marks (H3K4me1 or H3K27ac). To validate these putative hindbrain enhancers, we selected 55 elements distributed throughout our predictions and six low scoring controls for evaluation in a zebrafish transgenic assay. When assayed in mosaic transgenic embryos, 51/55 elements directed expression in the central nervous system. Furthermore, 30/34 (88%) predicted enhancers analyzed in stable zebrafish transgenic lines directed expression in the larval zebrafish hindbrain. Subsequent analysis of sequence fragments selected based upon motif clustering further confirmed the critical role of the motifs contributing to the classifier. Our results demonstrate the existence of a primary sequence code characteristic to hindbrain enhancers. This code can be accurately extracted using machine-learning approaches and applied successfully for de novo identification of hindbrain enhancers. This study represents a critical step toward the dissection of regulatory control in specific neuronal subtypes.
C1 [Taher, Leila; Ovcharenko, Ivan] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
[Burzynski, Grzegorz M.; Reed, Xylena; Stine, Zachary E.; Matsui, Takeshi; McCallion, Andrew S.] Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD 21205 USA.
[Reed, Xylena] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA.
RP Ovcharenko, I (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA.
EM ovcharen@nig.gov; andy@jhmi.edu
FU National Institute of Neurological Disease and Stroke [NS062972]; NIH,
National Library of Medicine; [GM07814]
FX This work was funded in part by the National Institute of Neurological
Disease and Stroke (NS062972) to A. S. M., the Intramural Research
Program of the NIH, National Library of Medicine to I.O., and a
predoctoral training grant (GM07814) to X.R.
NR 63
TC 7
Z9 7
U1 1
U2 3
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD NOV
PY 2012
VL 22
IS 11
BP 2278
EP 2289
DI 10.1101/gr.139717.112
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 030QE
UT WOS:000310584400020
PM 22759862
ER
PT J
AU Gorkin, DU
Lee, D
Reed, X
Fletez-Brant, C
Bessling, SL
Loftus, SK
Beer, MA
Pavan, WJ
McCallion, AS
AF Gorkin, David U.
Lee, Dongwon
Reed, Xylena
Fletez-Brant, Christopher
Bessling, Seneca L.
Loftus, Stacie K.
Beer, Michael A.
Pavan, William J.
McCallion, Andrew S.
TI Integration of ChIP-seq and machine learning reveals enhancers and a
predictive regulatory sequence vocabulary in melanocytes
SO GENOME RESEARCH
LA English
DT Article
ID STEM-CELL DIFFERENTIATION; NEURAL CREST; GENE-EXPRESSION; HUMAN GENOME;
TRANSCRIPTIONAL ENHANCERS; PROMOTER INTERACTIONS; MOUSE MELANOCYTES;
MOTIF DISCOVERY; OPEN CHROMATIN; MELANOMA
AB We take a comprehensive approach to the study of regulatory control of gene expression in melanocytes that proceeds from large-scale enhancer discovery facilitated by ChIP-seq; to rigorous validation in silico, in vitro, and in vivo; and finally to the use of machine learning to elucidate a regulatory vocabulary with genome-wide predictive power. We identify 2489 putative melanocyte enhancer loci in the mouse genome by ChIP-seq for EP300 and H3K4me1. We demonstrate that these putative enhancers are evolutionarily constrained, enriched for sequence motifs predicted to bind key melanocyte transcription factors, located near genes relevant to melanocyte biology, and capable of driving reporter gene expression in melanocytes in culture (86%; 43/50) and in transgenic zebrafish (70%; 7/10). Next, using the sequences of these putative enhancers as a training set for a supervised machine learning algorithm, we develop a vocabulary of 6-mers predictive of melanocyte enhancer function. Lastly, we demonstrate that this vocabulary has genome-wide predictive power in both the mouse and human genomes. This study provides deep insight into the regulation of gene expression in melanocytes and demonstrates a powerful approach to the investigation of regulatory sequences that can be applied to other cell types.
C1 [Gorkin, David U.; Reed, Xylena; Fletez-Brant, Christopher; Bessling, Seneca L.; Beer, Michael A.; McCallion, Andrew S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
[Gorkin, David U.; Reed, Xylena] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA.
[Lee, Dongwon; Beer, Michael A.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21201 USA.
[Loftus, Stacie K.; Pavan, William J.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
RP Beer, MA (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA.
EM mbeer@jhu.edu; bpavan@nhgri.nih.gov; andy@jhmi.edu
FU National Institute of General Medical Sciences [GM071648]; National
Institute of Neurological Disease and Stroke [NS062972]; National Human
Genome Research Institute's (NHGRI) Intramural Research Program; NSF;
Searle Scholars Program; [GM07814]
FX We thank Barbara Migeon, Kirby Smith, Hongkai Ji, George Wu, Megana
Prasad, Zachary Stine, Samantha Maragh, and Amanda Price for helpful
comments and discussion. This work was funded in part by the National
Institute of General Medical Sciences (GM071648) and the National
Institute of Neurological Disease and Stroke (NS062972) to A. S. M., by
the National Human Genome Research Institute's (NHGRI) Intramural
Research Program (W.J.P., S. K. L.), by an NSF Graduate Research
Fellowship to D. U. G., and by a predoctoral training grant (GM07814) to
X. R. M. A. B. was supported by the Searle Scholars Program and in part
by NS062972.
NR 71
TC 33
Z9 34
U1 1
U2 8
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
J9 GENOME RES
JI Genome Res.
PD NOV
PY 2012
VL 22
IS 11
BP 2290
EP 2301
DI 10.1101/gr.139360.112
PG 12
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 030QE
UT WOS:000310584400021
PM 23019145
ER
PT J
AU Hamasaki-Katagiri, N
Salari, R
Simhadri, VL
Tseng, SC
Needlman, E
Edwards, NC
Sauna, ZE
Grigoryan, V
Komar, AA
Przytycka, TM
Kimchi-Sarfaty, C
AF Hamasaki-Katagiri, N.
Salari, R.
Simhadri, V. L.
Tseng, S. C.
Needlman, E.
Edwards, N. C.
Sauna, Z. E.
Grigoryan, V.
Komar, A. A.
Przytycka, T. M.
Kimchi-Sarfaty, C.
TI Analysis of F9 point mutations and their correlation to severity of
haemophilia B disease
SO HAEMOPHILIA
LA English
DT Article
DE coagulation factor IX; genotype-phenotype association; haemophilia B; in
silico analysis; mRNA free energy; predictive tools
ID FACTOR-IX; PROTEIN; GENE
AB Haemophilia B is an X-linked recessive disorder caused by deficiency of functional coagulation factor IX, which results almost exclusively from mutations in the F9 gene. We sought to determine features, which could distinguish between mutations that cause severe disease symptoms from those that cause non-severe disease symptoms. Towards this objective, we have performed a statistical analysis of reported point mutations in F9. These include: potential local changes in mRNA free energy, codon usage, charge and type of mutated amino acid, location of the mutation with regard to protein secondary structure and functional domain and amino acids' evolutionary conservation scores. Wilcoxon signed-rank tests showed highly significant differences between severe and non-severe disease causing mutations in their effect on free energy of small mRNA fragments and evolutionarily conserved amino acids. Our results suggest that information at the mRNA level as well as conservation of the amino acid correlate well with disease severity. This study demonstrates that computational tools may be used to characterize the severity of haemophilia B associated with point mutations and suggests their utility in predicting the outcome of sequence changes in recombinant proteins.
C1 [Hamasaki-Katagiri, N.; Simhadri, V. L.; Tseng, S. C.; Needlman, E.; Edwards, N. C.; Sauna, Z. E.; Kimchi-Sarfaty, C.] US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Salari, R.; Grigoryan, V.; Przytycka, T. M.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Komar, A. A.] Cleveland State Univ, Dept Biol Geol & Environm Sci, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
RP Kimchi-Sarfaty, C (reprint author), US FDA, Div Hematol, Lab Hemostasis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
EM chava.kimchi-sarfaty@fda.hhs.gov
FU Intramural Research Programme of the National Institutes of Health,
National Library of Medicine
FX The authors thank Ms. Nechama Nelson for her assistance with mfold. This
study was supported in part by the Intramural Research Programme of the
National Institutes of Health, National Library of Medicine. The authors
declare no competing financial interests. The findings and conclusions
in this article have not been formally disseminated by the Food and Drug
Administration and should not be construed to represent any Agency
determination or policy.
NR 19
TC 6
Z9 7
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-8216
J9 HAEMOPHILIA
JI Haemophilia
PD NOV
PY 2012
VL 18
IS 6
BP 933
EP 940
DI 10.1111/j.1365-2516.2012.02848.x
PG 8
WC Hematology
SC Hematology
GA 030EY
UT WOS:000310553600030
PM 22639855
ER
PT J
AU Leiding, JW
Holland, SM
AF Leiding, Jennifer W.
Holland, Steven M.
TI Warts and all: Human papillomavirus in primary immunodeficiencies
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Immunodeficiency; human papillomavirus; warts; squamous; carcinoma;
dysplastic
ID WISKOTT-ALDRICH-SYNDROME; CELL-MEDIATED-IMMUNITY; CERVICAL
INTRAEPITHELIAL NEOPLASIA; ADENOSINE-DEAMINASE DEFICIENCY; LEUKOCYTE
ADHESION DEFICIENCY; BONE-MARROW-TRANSPLANTATION; ACUTE
MYELOID-LEUKEMIA; DOMINANT EPIDERMODYSPLASIA-VERRUCIFORMIS; HPV-16/18
AS04-ADJUVANTED VACCINE; IDIOPATHIC CD4+ LYMPHOCYTOPENIA
AB Infection with human papillomavirus (HPV) is almost universal and eventually asymptomatic, but pathologic infection with HPV is severe, recurrent, and recalcitrant to therapy. It is also an underappreciated manifestation of primary immunodeficiency. Mutations in EVER1, EVER2, GATA2, CXCR4, and dedicator of cytokinesis 8 (DOCK8) are typically associated with extensive HPV infections, whereas several other primary immune defects result in severe HPV much less frequently. We review immunodeficiencies with severe HPV infections and the mechanisms underlying them. (J Allergy Clin Immunol 2012;130:1030-48.)
C1 [Leiding, Jennifer W.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Leiding, JW (reprint author), Univ S Florida, Childrens Reseach Inst, Dept Pediat, Div Allergy Immunol & Rheumatol, 140 7th Ave S Box 9680, St Petersburg, FL 33701 USA.
EM jleiding@health.usf.edu; smh@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.
NR 201
TC 35
Z9 36
U1 0
U2 20
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2012
VL 130
IS 5
BP 1030
EP 1048
DI 10.1016/j.jaci.2012.07.049
PG 19
WC Allergy; Immunology
SC Allergy; Immunology
GA 030LE
UT WOS:000310571400002
PM 23036745
ER
PT J
AU Bousquet, J
Schunemann, HJ
Samolinski, B
Demoly, P
Baena-Cagnani, CE
Bachert, C
Bonini, S
Boulet, LP
Bousquet, PJ
Brozek, JL
Canonica, GW
Casale, TB
Cruz, AA
Fokkens, WJ
Fonseca, JA
van Wijk, RG
Grouse, L
Haahtela, T
Khaltaev, N
Kuna, P
Lockey, RF
Carlsen, KCL
Mullol, J
Naclerio, R
O'Hehir, RE
Ohta, K
Palkonen, S
Papadopoulos, NG
Passalacqua, G
Pawankar, R
Price, D
Ryan, D
Simons, FER
Togias, A
Williams, D
Yorgancioglu, A
Yusuf, OM
Aberer, W
Adachi, M
Agache, I
Ait-Khaled, N
Akdis, CA
Andrianarisoa, A
Annesi-Maesano, I
Ansotegui, IJ
Baiardini, I
Bateman, ED
Bedbrook, A
Beghe, B
Beji, M
Bel, EH
Ben Kheder, A
Bennoor, KS
Bergmann, KC
Berrissoul, F
Bieber, T
Jensen, CB
Blaiss, MS
Boner, AL
Bouchard, J
Braido, F
Brightling, CE
Bush, A
Caballero, F
Calderon, MA
Calvo, MA
Camargos, PAM
Caraballo, LR
Carlsen, KH
Carr, W
Cepeda, AM
Cesario, A
Chavannes, NH
Chen, YZ
Chiriac, AM
Perez, TC
Chkhartishvili, E
Ciprandi, G
Costa, DJ
Cox, L
Custovic, A
Dahl, R
Darsow, U
De Blay, F
Deleanu, D
Denburg, JA
Devillier, P
Didi, T
Dokic, D
Dolen, WK
Douagui, H
Dubakiene, R
Durham, SR
Dykewicz, MS
El-Gamal, Y
El-Meziane, A
Emuzyte, R
Fiocchi, A
Fletcher, M
Fukuda, T
Gamkrelidze, A
Gereda, JE
Diaz, SG
Gotua, M
Guzman, MA
Hellings, PW
Hellquist-Dahl, B
Horak, F
Hourihane, JO
Howarth, P
Humbert, M
Ivancevich, JC
Jackson, C
Just, J
Kalayci, O
Kaliner, MA
Kalyoncu, AF
Keil, T
Keith, PK
Khayat, G
Kim, YY
N'Goran, BK
Koppelman, GH
Kowalski, ML
Kull, I
Kvedariene, V
Larenas-Linnemann, D
Le, LT
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Sanchez-Borges, M.
Scadding, G. K.
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Sheikh, A.
Sisul, J. C.
Sole, D.
Sooronbaev, T.
Spicak, V.
Spranger, O.
Stein, R. T.
Stoloff, S. W.
Sunyer, J.
Szczeklik, A.
Todo-Bom, A.
Toskala, E.
Tremblay, Y.
Valenta, R.
Valero, A. L.
Valeyre, D.
Valiulis, A.
Valovirta, E.
Van Cauwenberge, P.
Vandenplas, O.
van weel, C.
Vichyanond, P.
Viegi, G.
Wang, D. Y.
Wickman, M.
Woehrl, S.
Wright, J.
Yawn, B. P.
Yiallouros, P. K.
Zar, H. J.
Zernotti, M. E.
Zhong, N.
Zidarn, M.
Zuberbier, T.
CA World Hlth Org Collaborating Ctr
TI Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10
years and future needs
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Rhinitis; asthma; Allergic Rhinitis and its Impact on Asthma; allergy;
GRADE
ID QUALITY-OF-LIFE; WORLD-HEALTH-ORGANIZATION; PERSISTENT TYPES;
CONTROLLED-TRIAL; EUROPEAN-UNION; PRIMARY-CARE; 2008 UPDATE; GUIDELINES;
MANAGEMENT; CLASSIFICATION
AB Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified ARas mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIAWorld Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. (J Allergy Clin Immunol 2012;130:1049-62.)
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[Mohammad, Y.] Tishreen Univ, Sch Med, Dept Internal Med, WHO EMRO Collaborating Ctr Training & Res Chron R, Latakia, Syria.
[Morais-Almeida, M.] CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal.
[Muraro, A.] Univ Padua, Dept Pediat, Food Allergy Referral Ctr Veneto Reg, Padua, Italy.
[Nafti, S.] Mustapha Hosp, Algiers, Algeria.
[Namazova-Baranova, L.] Sci Ctr Childrens Hlth RAMS, Moscow, Russia.
[Nekam, K.] Hosp Hospitaller Bros Buda, Budapest, Hungary.
[Neou, A.] Charite, Allergie Ctr Charite ECARF, Dept Dermatol Venerol & Allergy, D-13353 Berlin, Germany.
[Niggemann, B.] German Red Cross Hosp Westend, Berlin, Germany.
[Nizankowska-Mogilnicka, E.] Jagiellonian Univ, Sch Med, Dept Pulmonol, Krakow, Poland.
[Nyembue, T. D.] Kinshasa Univ, ENT Dept, Kinshasa, Zaire.
[Okamoto, Y.] Chiba Univ Hosp, Dept Otorhinolaryngol, Chiba, Japan.
[Okubo, K.] Nippon Med Sch, Dept Otolaryngol, Bunkyo Ku, Tokyo 113, Japan.
[Ouedraogo, S.] Ctr Hosp Univ Pediat Charles de Gaulle, Ouagadougou, Burkina Faso.
[Ozdemir, C.] Marmara Univ, Div Pediat Allergy & Immunol, Istanbul, Turkey.
[Ozdemir, C.] Mem Hlth Grp, Istanbul, Turkey.
[Panzner, P.] Charles Univ Prague, Fac Med Plzen, Dept Immunol & Allergol, Prague, Czech Republic.
[Pali-Schoell, I.] MESSERLI Res Inst, Vienna, Austria.
[Pali-Schoell, I.] Med Univ Vienna, Univ Vet Med Vienna, Vienna, Austria.
[Pali-Schoell, I.] Univ Vienna, Vienna, Austria.
[Park, H. S.] Ajou Univ, Sch Med, Suwon 441749, South Korea.
[Pigearias, B.] NICE, Paris, France.
[Pigearias, B.] Soc Pneumol Langue Francaise, Paris, France.
[Pohl, W.] Krankenhaus Hietzing, Karl Landsteiner Inst Expt & Clin Pneumol, Dept Pulm Med, Vienna, Austria.
[Popov, T. A.] Alexanders Univ Hosp, Clin Allergy & Asthma, Sofia, Bulgaria.
[Postma, D. S.] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Pulmonol, Groningen, Netherlands.
[Potter, P.] Univ Cape Town, Lung Inst, ZA-7925 Cape Town, South Africa.
[Potter, P.] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa.
[Rabe, K. F.] Leiden Univ, Dept Pulmonol, Med Ctr, Leiden, Netherlands.
[Rabe, K. F.] Grosshansdorf Clin, Grosshansdorf, Germany.
[Ratomaharo, J.] Hop Prive Athis Mons, Serv Pneumol, Athis Mons, France.
[Reitamo, S.] Helsinki Univ Hosp, Dept Dermatol, Skin & Allergy Hosp, Helsinki, Finland.
[Ring, J.] Tech Univ Munich, CKCARE, Dept Dermatol Allergy Biederstein, Munich, Germany.
[Roberts, R.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Rogala, B.] Med Univ Silesia, Dept & Clin Internal Dis Allergol & Clin Immunol, Katowice, Poland.
[Romano, A.] Complesso Integrato Columbus, Allergy Unit, Rome, Italy.
[Romano, A.] IRCCS Oasi Maria SS, Troina, Italy.
[Rodriguez, M. Roman] Son Pisa Primary Care Ctr, IB Salut Balear Hlth Serv, Int Primary Care Resp Grp, Palma de Mallorca, Spain.
[Rosado-Pinto, J.] Hosp Luz, Immunoallergy Dept, Lisbon, Portugal.
[Rosenwasser, L.] Univ Missouri, Kansas City Sch Med, Kansas City, MO 64110 USA.
[Rosenwasser, L.] Childrens Mercy Hosp, Kansas City, MO USA.
[Rottem, M.] Emek Med Ctr, Afula, Israel.
[Rottem, M.] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel.
[Sanchez-Borges, M.] Ctr Med Docente La Trinidad, Dept Allergy & Clin Immunol, Caracas, Venezuela.
[Scadding, G. K.] UCL, Royal Natl TNE Hosp, London, England.
[Schmid-Grendelmeier, P.] Univ Zurich Hosp, Dept Dermatol, Allergy Unit, CH-8091 Zurich, Switzerland.
[Sheikh, A.] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, Allergy & Resp Res Grp, Edinburgh, Midlothian, Scotland.
[Sole, D.] Univ Fed Sao Paulo, Dept Pediat, Div Allergy Clin Immunol & Rheumatol, Sao Paulo, Brazil.
[Sooronbaev, T.] Natl Ctr Cardiol & Internal Med, Bishkek, Kyrgyzstan.
[Spicak, V.] Ctr ACI Immunoflow, Czech Initiat Asthma, Prague, Czech Republic.
[Spranger, O.] GAAPP, Vienna, Austria.
[Stein, R. T.; Sunyer, J.] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Stein, R. T.] Pontificia Univ Catolica RGS, Sch Med, Porto Alegre, RS, Brazil.
[Stoloff, S. W.] Univ Nevada, Sch Med, Reno, NV 89557 USA.
[Sunyer, J.] Hosp Mar, Municipal Inst Med Res IMIM, Barcelona, Spain.
[Sunyer, J.] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Sunyer, J.] Univ Pompeu Fabra UPF, Barcelona, Spain.
[Szczeklik, A.] Jagiellonian Univ, Coll Med, Krakow, Poland.
[Todo-Bom, A.] Coimbra Univ Hosp, Immunoallergy Dept, Coimbra, Portugal.
[Toskala, E.] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Toskala, E.] Finnish Inst Occupat Hlth, Helsinki, Finland.
[Tremblay, Y.] Univ Laval, Fac Med, Dept Obstet & Gynecol, Laval, PQ, Canada.
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[Valeyre, D.] Univ Paris 13, Bobigny, France.
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[Valovirta, E.] Univ Turku, Dept Lung Dis & Clin Immunol, Turku, Finland.
[Van Cauwenberge, P.] Univ Ghent, Dept Otorhinolaryngol, B-9000 Ghent, Belgium.
[Vandenplas, O.] Catholic Univ Louvain, Univ Hosp Mt Godinne, Yvoir, Belgium.
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[Vichyanond, P.] Siriraj Hosp, Fac Med, Dept Pediat, Bangkok, Thailand.
[Viegi, G.] CNR, IBIM, Palermo, Italy.
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[Wang, D. Y.] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore.
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[Wickman, M.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Woehrl, S.] Floridsdorf Allergy Ctr FAZ, Vienna, Austria.
[Woehrl, S.] Med Univ Vienna, Dept Dermatol, DIAID, Vienna, Austria.
[Wright, J.] Bradford Teaching Hosp Fdn Trust, Bradford Inst Hlth Res, Bradford, W Yorkshire, England.
[Yawn, B. P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA.
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Guangzhou Med Univ, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.
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[Zuberbier, T.] Charite, Dept Dermatol, Allergy Ctr Charite, D-13353 Berlin, Germany.
[Zuberbier, T.] Charite, Network Excellence, Global Allergy & Asthma European Network GA2LEN, D-13353 Berlin, Germany.
RP Bousquet, J (reprint author), CHU Montpellier, F-34295 Montpellier 05, France.
EM jean.bousquet@inserm.fr
RI Deleanu, Diana/G-3963-2015; Fonseca, Joao/B-7562-2008; Bindslev-Jensen,
Carsten/H-1877-2011; CESARIO, Alfredo/O-4215-2015; Annesi-Maesano,
Isabella/D-9173-2016; van Weel, Chris/D-4375-2009; Custovic,
Adnan/A-2435-2012; Osborne, Nicholas/N-4915-2015; Sunyer, J/G-6909-2014;
Wohrl, Stefan/B-6954-2013; Casale, Thomas/K-4334-2013; Stein,
Renato/G-2975-2012; FMUP, CINTESIS/C-6631-2014; Chavannes,
Niels/F-1148-2011; Wright, John/H-1624-2012; Sheikh, Aziz /D-2818-2009;
Baigenjin, Abay/P-4137-2014; Stein, Renato/K-2568-2014; Kvedariene,
Violeta /D-7730-2011; Namazova-Baranova, Leyla/D-4934-2013; Sole,
Dirceu/D-7789-2013; Dahl, Ronahl/F-8170-2013; jackson,
cathy/H-4869-2013; O'Hehir, Robyn/H-3627-2011;
OI Mazon, Angel/0000-0001-5639-1037; Namazova-Baranova,
Leyla/0000-0002-2209-7531; Terreehorst, Ingrid/0000-0002-3264-2740;
Deleanu, Diana/0000-0002-8431-8352; Bonini, Sergio/0000-0003-0079-3031;
Masjedi, Mohammadreza/0000-0003-4964-3851; Fonseca,
Joao/0000-0002-0887-8796; Bindslev-Jensen, Carsten/0000-0002-8940-038X;
CESARIO, Alfredo/0000-0003-4687-0709; van Weel,
Chris/0000-0003-3653-4701; Custovic, Adnan/0000-0001-5218-7071; Osborne,
Nicholas/0000-0002-6700-2284; Sunyer, J/0000-0002-2602-4110; Wohrl,
Stefan/0000-0002-6324-0007; Papadopoulos, Nikolaos/0000-0002-2508-3872;
Bousquet, Philippe Jean/0000-0002-0217-5483; Casale,
Thomas/0000-0002-3149-7377; FMUP, CINTESIS/0000-0001-7248-2086;
Chavannes, Niels/0000-0002-8607-9199; Wright, John/0000-0001-9572-7293;
Sheikh, Aziz /0000-0001-7022-3056; Baigenjin, Abay/0000-0002-7703-5004;
Romano, Antonino/0000-0001-9742-9898; Price, David/0000-0002-9728-9992;
O'Hehir, Robyn/0000-0002-3489-7595; Fiocchi,
Alessandro/0000-0002-2549-0523; Ryan, Dermot/0000-0002-4115-7376; Park,
Hae-Sim/0000-0003-2614-0303; Popov, Todor/0000-0001-5052-5866; Kull,
Inger/0000-0001-6096-3771; Makela, Mika/0000-0002-2933-3111; Panzner,
Petr/0000-0002-1291-450X
FU Stallergenes; ALK-Abello; European Academy of Allergy and Clinical
Immunology (EAACI); MSD; Novartis; Nycomed/Takeda; PHADIA/Thermo
Fischer; 3M; AstraZeneca; GlaxoSmithKline; Merck Frosst; Altair; Amgen;
Asmacure; Boehringer-Ingelheim; Genentech; Pharmaxis; Schering; Wyeth;
Ache; Brazilian Research Council; Fundacao de Amparo a Pesquisa da
Bahia; Fundacao Ciencia e Tecnologia; Sociedade Portuguesa de
Alergologia e Immunologia Clinica; Abdi Ibrahim; MSD; OrionPharma;
Nasonebs; Merck; McNeal; Chiesi; Nycomed; Air Liquid Healthcare;
Mundipharma; Almirall; Kyorin; Teva; UK National Health Service;
Aerocrine; AKL Ltd; PREDICTA; Swiss National Science Foundation; MeDALL;
Global Allergy and Asthma European Network (GA 2LEN); Christine Kuthe
Center for Allergy Research and Education; Faes Farma; Bial; Johnson
Johnson; Sanofi; HAD treasurer; Innovative Medicine Initiative (EU);
Helse Sor-Ost RHF (Southern and Eastern Norway Regional Health
Authority); MEDA; Alcon; ISTA; Thermo-Fisher; Airsonett; Medical
Research Council; Moulton Charitable Trust; AB Science; Canadian
Institutes for Health Research; AllerGen NCE; Merck/Schering-Plough;
Circassia; University Hospital; Medical School of Universidad Autonoma
de Nuevo Leon, Mexico; Children's Research Foundation (Ireland); Danone;
Food Standards Agency (United Kingdom); European Union (EU); DTG;
Netherlands Asthma Foundation; Merck-Sharp-Dohme, Mexico; Allerquim
Mexico; Abbott; Apotex; HRA; MedImmune; Schering-Plough; Proctor Gamble;
Sunovion (Sepracor); Phadia; Servier; CSC JohnsonJohnson; Oxygen Plus;
New Medics; European Respiratory Society; Societe de Pneumologie de
Langue Francaise Asthma; Ministry of Health, Welfare, and Labor; Altana;
Takeda; UCB; Uriach advisory board; NAPP; Royal College of GPs Clinical
Champion in Allergy; Agency for Healthcare Research and Quality (AHRQ);
AnseII; Bayer Schering; OST; Fujisawa; IHAL; Henkel; Kryolan; Leti; MSO;
Procter and Gamble; Sanofi-Aventis; Scientific Advisory Board for the
German Society for Allergy and Clinical Immunology; German Federal
Ministry of Consumer Protection; European Centre for Allergy Research
Foundation (ECARF)
FX J. Bousquet has received honoraria from Stallergenes, Actelion,
Almirall, AstraZeneca, Chiesi, GlaxoSmithKline, Merck, Novartis, OM
Pharma, Sanofi, Teva, and Uriach. P. Demoly is a speaker for and on the
advisory board of Stallergenes and ALK-Abello; is a consultant for
Therabel and Crucell; is a speaker for Merck/Schering- Plough,
AstraZeneca, and GlaxoSmithKline; has received research support from
Stallergenes and ALK-Abello; and is the Vice President of the European
Academy of Allergy and Clinical Immunology (EAACI). S. Bonini has a
scientific board member and speaker at Symposia sponsored by A.
Menarini, MS&D, Novartis, Nycomed/Takeda, PHADIA/Thermo Fischer, and
Stallergenes and is a member of the LIBRA (Italian Guidelines for
Asthma, Rhinitis, and COPD) executive board. L. P. Boulet is on the
advisory boards for AstraZeneca, GlaxoSmithKline, Merck Frosst, and
Novartis; has received lecture fees from 3M, AstraZeneca,
GlaxoSmithKline, Merck Frosst, and Novartis; has received research
support from Altair, Amgen, Asmacure, AstraZeneca, Boehringer-Ingelheim,
Genentech, GlaxoSmithKline, Pharmaxis, Schering, Wyeth, and Merck
Frosst; is chair for the Canadian Thoracic Society Respiratory
Guidelines Committee and the Global Initiative for Asthma (GINA)
Guidelines and Implementation Committee; is an organizational holder for
the Laval University Chair on Knowledge Transfer, Prevention and
Education in Respiratory and Cardiovascular Health; and is a member of
the Knowledge Translation Canada. T. B. Casale is on the Stallergenes
advisory board, is a consultant for Roche has received research support
from Stallergenes and Roche, and is Executive Vice President for the
American Academy of Allergy, Asthma & Immunology (AAAAI). A. A. Cruz is
an advisor and lecturer for Merck and Mantecorp; is a lecturer for
GlaxoSmithKline, Novartis, Chiesi, and Aventis; has received an
educational grant from Ache; and has received research support from the
Brazilian Research Council, Fundacao de Amparo a Pesquisa da Bahia, and
GlaxoSmithKline. W. J. Fokkens has received research support from
GlaxoSmithKline and provided legal consultation/expert witness testimony
for Stallergenes. J. A. Fonseca has received lecture and consulting fees
from Merck has received research support from the Fundacao Ciencia e
Tecnologia and is Vice President of the Sociedade Portuguesa de
Alergologia e Immunologia Clinica. L. Grouse has received funds from
Novartis for personal services. T. Haahtela has received lecture fees
from Abdi Ibrahim, GlaxoSmithKline, MSD, and OrionPharma and has
received research support from Stallergenes. K. C. Lodrup Carlsen has
received research support from MeDALL EU. R. Naclerio is on the
speaker's bureau for Merck and Sunovion; is a consultant for Teva,
Kalypsys, and Regeneron; and has received research support from
Nasonebs, GlaxoSmithKline, Merck, and McNeal. K. Ohta has received
lecture honoraria from MSD, Novartis, and GlaxoSmithKline. S. Palkonen's
employer received grants from Novartis, GlaxoSmithKline,
Boehringer-Ingelheim, Pfizer, Chiesi, ALK-Abello , Stallergenes,
Nycomed, AstraZeneca, and Air Liquid Healthcare. N. G. Papadopoulos has
received honoraria from Merck, AllergoPharma, Abbott, and Uriach. D.; r
Price has received consultancy fees from Merck, Mundipharma, Novartis,
GlaxoSmithKline, Almirall, Chiesi, Kyorin, and Teva; has received
consultancy fees and grants from Pfizer, AstraZeneca, and
Boehringer-Ingelheim; has received research support from the UK National
Health Service, Aerocrine, and Nycomed; holds shares in AKL Ltd; and is
director of Research in Real Life Ltd. D. Ryan is a consultant for
Uriach and is Allergy Lead for the International Primary Care
Respiratory Group. F. E. R. Simons is on the Rupatadine Medical Advisory
Board. D. Williams's spouse is employed by GlaxoSmithKline. A.
Yorgancioglu has received honoraria from MSD, GlaxoSmithKline, and
Novartis and has received research support from Chiesi. O. M. Yosuf has
received honoraria from and is director and chair of research for the
International Primary Care Respiratory Group. C. A. Akdis has received
research support from Novartis, PREDICTA, Swiss National Science
Foundation, MeDALL, the Global Allergy and Asthma European Network (GA
2LEN), and the Christine Kuthe Center for Allergy Research
and Education; has provided legal consultation/expert witness testimony
on the topics of Actellion Th2-specific receptors, Aventis T-cell and
B-cell regulation, Stallergenes allergen-specific immunotherapy, and
Allergopharma allergen-specific immunotherapy; is a Fellow and interest
group member of the AAAAI; is president of the EAACI; and is a GA
2LEN ex-com memberWPleader. I. J. Ansotegui has received
consulting fees and honoraria from Faes Farma and Bial, has received
consulting fees from Johnson & Johnson and Sanofi, and has received
honoraria from AstraZeneca. E. D. Bateman is a consultant for and on the
advisory board of Almirall; is on the advisory board of Forest,
Novartis, Napp Pharma, and Actelion; has received lecture and
consultancy fees and grants and is on the advisory board for Boehringer
Ingelheim; has received lecture fees and is on the advisory board for
GlaxoSmithKline, Nycomed, and AstraZeneca; is a consultant for
ALK-Abello; and is the GINA chair of board. E. H. Bel has received
research support from GlaxoSmithKline, Novartis, and Innovative Medicine
Initiative (EU). M. S. Blaiss is a speaker for GlaxoSmithKline, Merck,
AstraZeneca, Nycomed, Sunovion, and Genentech; is a consultant for
Alcon, ISTA, Allergan, Proctor & Gamble, and Pfizer; has received
research support from GlaxoSmithKline; and is HAD treasurer. M. A.
Calderon is a speaker for ALK-Abello, Merck, and STG. K. H. Carlsen has
received research support from Helse Sor-Ost RHF (Southern and Eastern
Norway Regional Health Authority). W. Carr is a consultant for and has
received research support from MEDA, Alcon, and ISTA. A. M. Cepeda is a
speaker for MSD, AstraZeneca, and Novartis and has received research
support from Novartis and Universidad Metropolitana. L. Cox is a speaker
for Thermo-Fisher and ISTA and has received research support from
Stallergenes and Teva. A. Custovic has received lecture fees from
GlaxoSmithKline, Thermo-Fisher, MSD, and Airsonett; is on the advisory
board for Novartis; and has received research support from the Medical
Research Council and Moulton Charitable Trust. R. Dahl has received
lecture fees from ALK-Abello and MSD, has received research support from
ALK-Abello and Stallergenes, and is chair of the Danish Respiratory
Society. U. Darsow is a consultant for Benoard. F. De Blay has received
research support from Stallergenes, ALK-Abello, Novartis,
GlaxoSmithKline, AB Science, and Amgen. J. A.; r Denburg has received
research support from the Canadian Institutes for Health Research and
AllerGen NCE. P. Devillier has received consultancy fees and honoraria
from Stallergenes and has received consultancy fees from
Merck/Schering-Plough, GlaxoSmithKline, and AstraZeneca. S. R. Durham is
a consultant and speaker for ALK-Abello and Merck, is a speaker for
GlaxoSmithKline, has received consultancy fees from Boehringer Ingelheim
and Circassia, has received research support from ALK-Abello and
Novartis, has provided legal consultation/expert witness testimony on
the topic of topical corticosteroids and antihistamines in allergic
rhinitis is on the Immune Tolerance Network/National Institute of
Allergy and Infectious Diseases (NIAID) steering committee, and is on
the British Society for Allergy and Clinical Immunology standards of
care committee. M. S. Dykewicz is a consultant for Merck; is on the
AAAAI Board of Directors, Needs Assessment Committee,
Rhinitis/Sinusitis/Ocular Diseases Committee, and Web Site Oversight
Committee; and is on the American College of Allergy, Asthma &
Immunology (ACAAI) Program Directors Advisory Committee (chair), Annual
Program Planning Committee, Publications Committee, Rhinitis-Sinusitis
Committee, Occupational Health Committee, Ocular Allergy Committee. A.
Fiocchi has received research support from Stallergenes. S. Gonzalez
Diaz is a speaker for GlaxoSmithKline, MSD, and Takeda and has received
research support from the University Hospital and Medical School of
Universidad Autonoma de Nuevo Leon, Mexico. M. Gotua has received
honoraria from GlaxoSmithKline and AstraZeneca. J. O'B. Hourihane has
received research support from the Children's Research Foundation
(Ireland), Danone, the Food Standards Agency (United Kingdom), and
Stallergenes; in addition, his employer, University College Cork, holds
a patent on challenge outcome predictor software. M. Humbert has
received consultancy and lecture fees from AstraZeneca, GlaxoSmithKline,
Novartis, Pfizer, Stallergenes, and Teva. J. C. Ivancevich is on the
Faes Farma advisory board, is speaker for Laboratorios Casasco
Argentina, and is Web editor for the World Allergy Organization and
Interasma. O. Kalayci was the Uriach Pharma chairperson at the company
sponsor symposium. M. A. Kaliner is a consultant for Ista and Alcon, has
received research support from multiple allergy and asthma companies,
and has provided legal consultation/expert witness testimony for Alcon.
T. Keil has received research support from the European Union (EU) and
DTG. P. K. Keith is a speaker for and has received research support from
GlaxoSmithKline and Merck. B. Koffi N'Goran is a speaker for AstraZeneca
and GlaxoSmithKline. G. H. Koppelman has received research support from
the Netherlands Asthma Foundation and MeDALL. D. E. Larenas-Linnemann
has received a speaker's fee and travel grant from Merck-Sharp-Dohme,
Mexico; has received a speaker's fee from AstraZeneca; has received
travel grants from Allerquim Mexico, ALK-Abello, and Stallergenes; has
received research support from Allerquim Mexico, ALK-Abello,
Stallergenes, and Greer Laboratories; and is chair of the IT committee
for the AAAAI and Mexican College of Clinical Immunology and Allergy. L.
T. Le has received honoraria from GlaxoSmithKline and AstraZeneca, has
received research support and honoraria from MSD, and is chair of the
Respiratory Society of Ho Chi Minh City, Vietnam. C. Lemiere is on the
AstraZeneca advisory board. P. Lieberman is an advisor for the Allergy
Foundation of America. B.; r Lipworth has provided legal
consultation/expert witness testimony for Nycomed on the topic of nasal
ciclesonide. B. Mahboub is employed by the Dubai Health Authority and
the University of Sharjah. F. D. Martinez is a consultant for MedImmune
and has received lecture honorarium and travel fees from Abbott. E. O.
Meltzer is a consultant and on the advisory board for Alcon,
AstraZeneca, Bausch + Lomb, Dey, Forest, Ista, Johnson & Johnson, Meda,
Merck, ONO Pharma, OptiNose, Proctor& Gamble, Rady Children's Hospital,
Rigel, Sanofi Aventis, Sepracor, Stallergenes, Teva, Alexza, Boehringer
Ingelheim, Kalypsys, and Sunovion; is a speaker for the AAAAI, Alcon,
Allergists for Israel, Dey, Florida Allergy Asthma Immunol Society,
Ista, Sepracor, Teva, Merck, and Sunovion; has received research support
from Amgen, Apotex, HRA, MedImmune, Schering-Plough, Alcon, AstraZeneca,
Boehringer Ingelheim, GlaxoSmithKline, Novartis, Proctor & Gamble,
Sunovion (Sepracor), and Teva; has provided legal consultation/expert
witness testimony for Aventis Pharmaceuticals and Sanofi Aventis in the
USLLC v. Barr Laboratories Fexofenadine Litigation; and is a Fellow of
the AAAAI, ACAAI, and World Allergy Organization (WAO). H. Merk has
received research support from Phadia and has provided legal
consultation/expert witness testimony for Novartis and ALK-Abello. F.
Mihaltan has received consulting fees and honoraria from AstraZeneca,
GlaxoSmithKline, MSD, Novartis, Nycomed, Boehringer Ingelheim, Servier,
Sanofi, Pfizer, CSC Johnson&Johnson, Oxygen Plus, and New Medics. S.
Nafti has received research support from the European Respiratory
Society and the Societe de Pneumologie de Langue Francaise Asthma and
has provided legal consultation/expert witness testimony for
GlaxoSmithKline on the topics of asthma and chronic obstructive
pulmonary disease. Y. Okamoto is a medical advisory for Taibo
Pharmaceutical Co, Ono Pharmaceutical Co, and Meiji Nyugyo Co and has
received research support from the Ministry of Health, Welfare, and
Labor. D. S. Postma has received consultancy fees from Nycomed,
GlaxoSmithKline, AstraZeneca, and Chiesi. K. F. Rabe has received
research support from Altana, Novartis, AstraZeneca, and MSD and has
provided legal consultation/expert witness testimony for AstraZeneca,
Chiesi, Novartis, MSD, and GlaxoSmithKline. J. Ring has received
research support from ALK-Abello, Allergopharma, Almirall-Hermal,
Astellas, Bencard, Biogen-Idec, Gladerma, GlaxoSmithKline, Leo, MSD,
Novartis, Phadia, PLS Design, and Stallergenes. R. Roberts is president
of the World Organization of Family Doctors and the American Academy of
Family Physicians Foundation and is Vice Chair of the Interstate
Postgraduate Medical Association. B. Rogala has received lecture fees
from Takeda, Nycomed, Teva, UCB, and Chiesi and is on the advisory board
for MSD and AstraZeneca. G. K. Scadding has received research support
from and is a speaker for ALK-Abello and GlaxoSmithKline, is on the
Uriach advisory board, and is a speaker for Merck. A. Sheikh has
received consultancy fees from Phadia and NAPP and is a Royal College of
GPs Clinical Champion in Allergy. S. W. Stoloff is a consultant and on
the advisory board for Teva and is a consultant for Aerocrine, Merck,
and Sunovion. B. P. Yawn has received research support from the Agency
for Healthcare Research and Quality (AHRQ) and the National Heart, Lung,
and Blood Institute (NHLBI). T.; r Zuberbier has received consultancy
fees, honoraria, and/or research support from AnseII, Bayer Schering,
OST, Fujisawa, IHAL, Henkel, Kryolan, Leti, MSO, Novartis, Procter and
Gamble, Sanofi-Aventis, Schering-Plough, Stallergenes, and UCB; is on
the Scientific Advisory Board for the German Society for Allergy and
Clinical Immunology; is on the Expert Commission "Novel Food'' of the
German Federal Ministry of Consumer Protection; is Head of the European
Centre for Allergy Research Foundation (ECARF); is a Committee member of
the World Health Organization (WHO) Initiative Allergic Rhinitis and its
Impact on Asthma (ARIA); is a Member or the WAO Communications Council;
and is Secretary General of GA 2 LEN. The rest of the authors declare
that they have no relevant conflicts of interest.
NR 107
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U1 14
U2 160
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2012
VL 130
IS 5
BP 1049
EP 1062
DI 10.1016/j.jaci.2012.07.053
PG 14
WC Allergy; Immunology
SC Allergy; Immunology
GA 030LE
UT WOS:000310571400003
PM 23040884
ER
PT J
AU Wilson, S
Rand, C
Taggart, V
AF Wilson, Sandra
Rand, Cynthia
Taggart, Virginia
TI Guidance is also needed on how to choose from existing asthma-specific
quality-of-life measures Reply
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
C1 [Wilson, Sandra] Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA.
[Rand, Cynthia] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Taggart, Virginia] NHLBI, Div Lung Dis, Bethesda, MD 20892 USA.
RP Wilson, S (reprint author), Palo Alto Med Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA.
EM taggartv@nih.gov
NR 4
TC 0
Z9 0
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2012
VL 130
IS 5
BP 1219
EP 1220
DI 10.1016/j.jaci.2012.08.035
PG 2
WC Allergy; Immunology
SC Allergy; Immunology
GA 030LE
UT WOS:000310571400033
ER
PT J
AU Macvanin, M
Edgar, R
Cui, F
Trostel, A
Zhurkin, V
Adhya, S
AF Macvanin, Mirjana
Edgar, Rotem
Cui, Feng
Trostel, Andrei
Zhurkin, Victor
Adhya, Sankar
TI Noncoding RNAs Binding to the Nucleoid Protein HU in Escherichia coli
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID MICROARRAY ANALYSIS; MESSENGER-RNAS; DNA-BINDING; RIBOSOMAL-RNA;
IDENTIFICATION; TRANSLATION; COMPLEXES; GENOME; ARRAYS; IHF
AB Some unidentified RNA molecules, together with the nucleoid protein HU, were suggested to be involved in the nucleoid structure of Escherichia coli. HU is a conserved protein known for its role in binding to DNA and maintaining negative supercoils in the latter. HU also binds to a few RNAs, but the full spectrum of its binding targets in the cell is not known. To understand any interaction of HU with RNA in the nucleoid structure, we immunoprecipitated potential HU-RNA complexes from cells and examined bound RNAs by hybridization to whole-genome tiling arrays. We identified associations between HU and 10 new intragenic and intergenic noncoding RNAs (ncRNAs), 2 of which are homologous to the annotated bacterial interspersed mosaic elements (BIMEs) and boxC DNA repeat elements. We confirmed direct binding of HU to BIME RNA in vitro. We also studied the nucleoid shape of HU and two of the ncRNA mutants (nc1 and nc5) by transmission electron microscopy and showed that both HU and the two ncRNAs play a role in nucleoid morphology. We propose that at least two of the ncRNA species complex with HU and help the formation or maintenance of the architecture of the E. coli chromosome. We also observed binding of HU with rRNA and tRNA segments, a few small RNAs, and a distinct small set of mRNAs, although the significance, if any, of these associations is not known.
C1 [Macvanin, Mirjana; Edgar, Rotem; Trostel, Andrei; Adhya, Sankar] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cui, Feng; Zhurkin, Victor] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM adhyas@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research.
NR 60
TC 13
Z9 13
U1 1
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2012
VL 194
IS 22
BP 6046
EP 6055
DI 10.1128/JB.00961-12
PG 10
WC Microbiology
SC Microbiology
GA 030SB
UT WOS:000310589300004
PM 22942248
ER
PT J
AU Varga, JJ
Losada, L
Zelazny, AM
Brinkac, L
Harkins, D
Radune, D
Hostetler, J
Sampaio, EP
Ronning, CM
Nierman, WC
Greenberg, DE
Holland, SM
Goldberg, JB
AF Varga, John J.
Losada, Liliana
Zelazny, Adrian M.
Brinkac, Lauren
Harkins, Derek
Radune, Diana
Hostetler, Jessica
Sampaio, Elizabeth P.
Ronning, Catherine M.
Nierman, William C.
Greenberg, David E.
Holland, Steven M.
Goldberg, Joanna B.
TI Draft Genome Sequence Determination for Cystic Fibrosis and Chronic
Granulomatous Disease Burkholderia multivorans Isolates
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID CEPACIA
AB Burkholderia multivorans is a Gram-negative bacterium and a member of the Burkholderia cepacia complex, which is frequently associated with respiratory infections in people with cystic fibrosis (CF) and chronic granulomatous disease (CGD). We are reporting the genome sequences of 4 B. multivorans strains, 2 from CF patients and 2 from CGD patients.
C1 [Varga, John J.; Goldberg, Joanna B.] Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA.
[Varga, John J.; Losada, Liliana; Brinkac, Lauren; Harkins, Derek; Radune, Diana; Hostetler, Jessica; Ronning, Catherine M.; Nierman, William C.] J Craig Venter Inst, Rockville, MD USA.
[Zelazny, Adrian M.] NIAID, Microbiol Serv, Dept Lab Med, Ctr Clin,NIH, Bethesda, MD 20892 USA.
[Zelazny, Adrian M.; Sampaio, Elizabeth P.; Greenberg, David E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Leprosy Lab, Inst Oswaldo Cruz, BR-21045900 Rio De Janeiro, Brazil.
[Nierman, William C.] George Washington Univ, Washington, DC USA.
[Greenberg, David E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
RP Goldberg, JB (reprint author), Univ Virginia Hlth Syst, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA USA.
EM jbg2b@virginia.edu
RI Varga, John/I-8130-2012
OI Varga, John/0000-0002-4868-1971
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200900007C, N01-AI30071]; National Institutes of Health
[5T32AI055432]
FX This project has been funded in whole with federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
contract numbers HHSN272200900007C and N01-AI30071. J.J.V. was supported
by the National Institutes of Health grant 5T32AI055432, awarded to the
University of Virginia.
NR 6
TC 4
Z9 4
U1 0
U2 1
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 NOV
PY 2012
VL 194
IS 22
BP 6356
EP 6357
DI 10.1128/JB.01306-12
PG 2
WC Microbiology
SC Microbiology
GA 030SB
UT WOS:000310589300068
PM 23105085
ER
PT J
AU Hong, P
Chen, K
Huang, BH
Liu, M
Cui, M
Rozenberg, I
Chaqour, B
Pan, XY
Barton, ER
Jiang, XC
Siddiqui, MAQ
AF Hong, Peng
Chen, Kang
Huang, Bihui
Liu, Min
Cui, Miao
Rozenberg, Inna
Chaqour, Brahim
Pan, Xiaoyue
Barton, Elisabeth R.
Jiang, Xian-Cheng
Siddiqui, M. A. Q.
TI HEXIM1 controls satellite cell expansion after injury to regulate
skeletal muscle regeneration
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID RNA-POLYMERASE-II; ELONGATION-FACTOR-B; P-TEFB; STEM-CELLS;
TRANSCRIPTION-ELONGATION; SELF-RENEWAL; MUSCULAR-DYSTROPHY; CLP-1 GENE;
ACTIVATION; PAX7
AB The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetatnide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell-mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases.
C1 [Hong, Peng; Rozenberg, Inna; Chaqour, Brahim; Pan, Xiaoyue; Jiang, Xian-Cheng; Siddiqui, M. A. Q.] Suny Downstate Med Ctr, Dept Cell Biol, New York, NY USA.
[Hong, Peng; Chaqour, Brahim; Pan, Xiaoyue; Jiang, Xian-Cheng; Siddiqui, M. A. Q.] Suny Downstate Med Ctr, Ctr Cardiovasc & Muscle Res, New York, NY USA.
[Chen, Kang] NICHHD, Perinatol Res Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Kang] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Huang, Bihui] Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY USA.
[Liu, Min] Univ Penn, Dept Physiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Cui, Miao] Mt Sinai Med Ctr, Dept Med, Div Clin Immunol, New York, NY 10029 USA.
[Barton, Elisabeth R.] Univ Penn, Sch Dent Med, Dept Anat & Cell Biol, Philadelphia, PA 19104 USA.
RP Siddiqui, MAQ (reprint author), 450 Clarkson Ave,Box 5, Brooklyn, NY 11203 USA.
EM MAQ.Siddiqui@downstate.edu
FU NIH [HL073399, AR052646]; intramural SUNY funds; Wayne State University
School of Medicine
FX We sincerely thank Katherine Hajjar and Gianna Ballon (Weill Cornell
Medical College); Weifeng Xu, Meimei Shan, and Xiaodong Ge (Mount Sinai
Medical Center); and Weijun Jin and Michael Wagner (SUNY Downstate
Medical Center) for comments on experimental design and the article as
well as Zhiqiang Li and Hui Jiang (SUNY Downstate Medical Center) for
technical support. This work was supported in parr by NIH grants
HL073399 (to M.A.Q. Siddiqui) and AR052646 (to E.R. Barton), intramural
SUNY funds (to M.A.Q. Siddiqui), and a research grant from the Wayne
State University School of Medicine (to K. Chen).
NR 58
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Z9 5
U1 0
U2 5
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2012
VL 122
IS 11
BP 3873
EP 3887
DI 10.1172/JCI62818
PG 15
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 031WP
UT WOS:000310673600018
PM 23023707
ER
PT J
AU Helft, J
Manicassamy, B
Guermonprez, P
Hashimoto, D
Silvin, A
Agudo, J
Brown, BD
Schmolke, M
Miller, JC
Leboeuf, M
Murphy, KM
Garcia-Sastre, A
Merad, M
AF Helft, Julie
Manicassamy, Balaji
Guermonprez, Pierre
Hashimoto, Daigo
Silvin, Aymeric
Agudo, Judith
Brown, Brian D.
Schmolke, Mirco
Miller, Jennifer C.
Leboeuf, Marylene
Murphy, Kenneth M.
Garcia-Sastre, Adolfo
Merad, Miriam
TI Cross-presenting CD103(+) dendritic cells are protected from influenza
virus infection
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MHC CLASS-I; T-CELLS; LYMPH-NODE; ANTIGEN; SUBSETS; IMMUNITY; RESPONSES;
VIVO; INNATE; INTERFERENCE
AB CD8(+) cytotoxic T cells are critical for viral clearance from the lungs upon influenza virus infection. The contribution of antigen cross-presentation by DCs to the induction of anti-viral cytotoxic T cells remains controversial. Here, we used a recombinant influenza virus expressing a nonstructural 1-GFP (NS1-GFP) reporter gene to visualize the route of antigen presentation by lung DCs upon viral infection in mice. We found that lung CD103(+) DCs were the only subset of cells that carried intact GFP protein to the draining LNs. Strikingly, lung migratory CD103(+) DCs were not productively infected by influenza virus and thus were able to induce virus-specific CD8(+) T cells through the cross-presentation of antigens from virally infected cells. We also observed that CD103(+) DC resistance to infection correlates with an increased anti-viral state in these cells that is dependent on the expression of type I IFN receptor. These results show that efficient cross-priming by migratory lung DCs is coupled to the acquisition of an anti-viral status, which is dependent on the type I IFN signaling pathway.
C1 [Helft, Julie; Hashimoto, Daigo; Silvin, Aymeric; Miller, Jennifer C.; Leboeuf, Marylene; Merad, Miriam] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA.
[Helft, Julie; Hashimoto, Daigo; Silvin, Aymeric; Agudo, Judith; Brown, Brian D.; Miller, Jennifer C.; Leboeuf, Marylene; Merad, Miriam] Mt Sinai Sch Med, Inst Immunol, New York, NY 10029 USA.
[Manicassamy, Balaji; Schmolke, Mirco; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA.
[Manicassamy, Balaji; Schmolke, Mirco; Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA.
[Guermonprez, Pierre] Kings Coll London, Ctr Mol & Cellular Biol Inflammat, London WC2R 2LS, England.
[Guermonprez, Pierre] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England.
[Agudo, Judith; Brown, Brian D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Murphy, Kenneth M.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Murphy, Kenneth M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
[Garcia-Sastre, Adolfo] Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY 10029 USA.
[Merad, Miriam] NIAID, Mucosal Immunol Studies Team, Portland, OR USA.
RP Merad, M (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1425 Madison Ave, New York, NY USA.
EM Miriam.merad@mssm.edu
RI Hashimoto, Daigo/O-1013-2013
OI Hashimoto, Daigo/0000-0001-9489-9704
FU NIH [U01 AI10008, R01 HL086899, R01AI046954, P01AI058113, U19AI083025,
1K99AI095320-01]; Center for Research on Influenza Pathogenesis (CRIP),
an National Institute of Allergy and Infectious Diseases Centers of
Excellence for Influenza Research and Surveillance network
[HHSN266200700010C]; Fulbright-Generalitat de Catalunya; Beatriu de
Pinos postdoctoral fellowship; [JDRF-17-2010-770]; [DP2DK083052-01]
FX M. Merad is supported by NIH grants U01 AI10008 and R01 HL086899. A.
Garcia-Sastre is supported by NIH grants R01AI046954, P01AI058113, and
U19AI083025, and by Center for Research on Influenza Pathogenesis
(CRIP), an National Institute of Allergy and Infectious Diseases Centers
of Excellence for Influenza Research and Surveillance network supported
CRIP (contract number HHSN266200700010C). K.M. Murphy is an investigator
of the Howard Hughes Medical Institute. B. Manicassamy is supported by
NIH K99 Pathway to Independence award (1K99AI095320-01). B.D. Brown is
supported by JDRF-17-2010-770 and DP2DK083052-01. J. Agudo is supported
by a Fulbright-Generalitat de Catalunya postdoctoral fellowship and a
Beatriu de Pinos postdoctoral fellowship. We thank C. Schindler for
kindly providing the Stat2-/- mice. We thank C. Munoz-Fontela
for providing the PR8-OTI influenza virus.
NR 41
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U1 2
U2 10
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2012
VL 122
IS 11
BP 4037
EP 4047
DI 10.1172/JCI60659
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 031WP
UT WOS:000310673600033
PM 23041628
ER
PT J
AU Noh, KH
Kim, BW
Song, KH
Cho, H
Lee, YH
Kim, JH
Chung, JY
Kim, JH
Hewitt, SM
Seong, SY
Mao, CP
Wu, TC
Kim, TW
AF Noh, Kyung Hee
Kim, Bo Wook
Song, Kwon-Ho
Cho, Hanbyoul
Lee, Young-Ho
Kim, Jin Hee
Chung, Joon-Yong
Kim, Jae-Hoon
Hewitt, Stephen M.
Seong, Seung-Yong
Mao, Chih-Ping
Wu, T. -C.
Kim, Tae Woo
TI Nanog signaling in cancer promotes stem-like phenotype and immune
evasion
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TUMOR-INFILTRATING LYMPHOCYTES; CELL-LIKE PROPERTIES; CERVICAL-CANCER;
ANTITUMOR IMMUNITY; VACCINE POTENCY; SELF-RENEWAL; HIGH NUMBER;
RESISTANCE; PATHWAY; AKT
AB Adaptation of tumor cells to the host is a major cause of cancer progression, failure of therapy, and ultimately death. Immune selection drives this adaptation in human cancer by enriching tumor cells with a cancer stem cell-like (CSC-like) phenotype that makes them resistant to CTL-mediated apoptosis; however, the mechanisms that mediate CSC maintenance and proliferation are largely unknown. Here, we report that CTL-mediated immune selection drives the evolution of tumor cells toward a CSC-like phenotype and that the CSC-like phenotype arises through the Akt signaling pathway via transcriptional induction of Tcl1a by Nanog. Furthermore, we found that hyperactivation of the Nanog/Tcl1a/Akt signaling axis was conserved across multiple types of human cancer. Inhibition of Nanog in a murine model of colon cancer rendered tumor cells susceptible to immune-mediated clearance and led to successful, long-term control of the disease. Our fmdings establish a firm link among immune selection, disease progression, and the development of a stem-like tumor phenotype in human cancer and implicate the Nanog/Tcl1a/Akt pathway as a central molecular target in this process.
C1 [Mao, Chih-Ping; Wu, T. -C.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21231 USA.
[Wu, T. -C.] Johns Hopkins Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21231 USA.
[Wu, T. -C.] Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21231 USA.
[Wu, T. -C.] Johns Hopkins Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21231 USA.
[Noh, Kyung Hee; Song, Kwon-Ho; Lee, Young-Ho; Kim, Jin Hee; Kim, Tae Woo] Korea Univ, Grad Sch Med, Div Infect & Immunol, Seoul 425707, South Korea.
[Kim, Bo Wook; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA.
[Kim, Bo Wook; Chung, Joon-Yong; Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Cho, Hanbyoul; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul, South Korea.
[Seong, Seung-Yong] Seoul Natl Univ, Coll Med, Dept Microbiol & Immunol, Seoul, South Korea.
RP Wu, TC (reprint author), Johns Hopkins Sch Med, Dept Pathol, CRB 2 Room 309,1550 Orleans St, Baltimore, MD 21231 USA.
EM wutc@jhmi.edu; twkim0421@korea.com
RI Seong, Seung Yong /J-2764-2012;
OI Hewitt, Stephen/0000-0001-8283-1788; Chung,
Joon-Yong/0000-0001-5041-5982
FU National Research Foundation of Korea [2012-007527, 2011-0027588,
2011-0002608]; Korea Healthcare Technology RD Project [A062260]; United
States National Cancer Institute [P50 CA098252, RO1 CA114425]
FX This work was supported by funding from the National Research Foundation
of Korea (2012-007527, 2011-0027588, and 2011-0002608), the Korea
Healthcare Technology R&D Project (A062260), and the United States
National Cancer Institute (P50 CA098252 and RO1 CA114425). The authors
thank Katherine Liu for the preparation of the manuscript.
NR 43
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Z9 64
U1 1
U2 14
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2012
VL 122
IS 11
BP 4077
EP 4093
DI 10.1172/JCI64057
PG 17
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 031WP
UT WOS:000310673600036
PM 23093782
ER
PT J
AU Romond, EH
Jeong, JH
Rastogi, P
Swain, SM
Geyer, CE
Ewer, MS
Rathi, V
Fehrenbacher, L
Brufsky, A
Azar, CA
Flynn, PJ
Zapas, JL
Polikoff, J
Gross, HM
Biggs, DD
Atkins, JN
Tan-Chiu, E
Zheng, P
Yothers, G
Mamounas, EP
Wolmark, N
AF Romond, Edward H.
Jeong, Jong-Hyeon
Rastogi, Priya
Swain, Sandra M.
Geyer, Charles E., Jr.
Ewer, Michael S.
Rathi, Vikas
Fehrenbacher, Louis
Brufsky, Adam
Azar, Catherine A.
Flynn, Patrick J.
Zapas, John L.
Polikoff, Jonathan
Gross, Howard M.
Biggs, David D.
Atkins, James N.
Tan-Chiu, Elizabeth
Zheng, Ping
Yothers, Greg
Mamounas, Eleftherios P.
Wolmark, Norman
TI Seven-Year Follow-Up Assessment of Cardiac Function in NSABP B-31, a
Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by
Paclitaxel (ACP) With ACP Plus Trastuzumab As Adjuvant Therapy for
Patients With Node-Positive, Human Epidermal Growth Factor Receptor
2-Positive Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CUMULATIVE INCIDENCE; OLDER WOMEN; CHEMOTHERAPY; ANTHRACYCLINE;
CARDIOTOXICITY; DYSFUNCTION; TESTS; N9831; RISK
AB Purpose
Cardiac dysfunction (CD) is a recognized risk associated with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, especially when the treatment regimen includes anthracyclines. Given the demonstrated efficacy of trastuzumab, ongoing assessment of cardiac safety and identification of risk factors for CD are important for optimal patient care.
Patients and Methods
In National Surgical Adjuvant Breast and Bowel Project B-31, a phase III adjuvant trial, 1,830 patients who met eligibility criteria for initiation of trastuzumab were evaluated for CD. Recovery from CD was also assessed. A statistical model was developed to estimate the risk of severe congestive heart failure (CHF). Baseline patient characteristics associated with anthracycline-related decline in cardiac function were also identified.
Results At 7-year follow-up, 37 (4.0%) of 944 patients who received trastuzumab experienced a cardiac event (CE) versus 10 (1.3%) of 743 patients in the control arm. One cardiac-related death has occurred in each arm of the protocol. A Cardiac Risk Score, calculated using patient age and baseline left ventricular ejection fraction (LVEF) by multiple-gated acquisition scan, statistically correlates with the risk of a CE. After stopping trastuzumab, the majority of patients who experienced CD recovered LVEF in the normal range, although some decline from baseline often persists. Only two CEs occurred more than 2 years after initiation of trastuzumab.
Conclusion
The late development of CHF after the addition of trastuzumab to paclitaxel after doxorubicin/cyclophosphamide chemotherapy is uncommon. The risk versus benefit of trastuzumab as given in this regimen remains strongly in favor of trastuzumab. J Clin Oncol 30:3792-3799. (C) 2012 by American Society of Clinical Oncology
C1 [Romond, Edward H.; Jeong, Jong-Hyeon; Rastogi, Priya; Swain, Sandra M.; Geyer, Charles E., Jr.; Fehrenbacher, Louis; Brufsky, Adam; Azar, Catherine A.; Flynn, Patrick J.; Zapas, John L.; Polikoff, Jonathan; Gross, Howard M.; Biggs, David D.; Atkins, James N.; Zheng, Ping; Yothers, Greg; Mamounas, Eleftherios P.; Wolmark, Norman] Operat & Biostat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA.
[Jeong, Jong-Hyeon; Zheng, Ping; Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Rastogi, Priya; Brufsky, Adam] Univ Pittsburgh, Magee Womens Hosp, Sch Med, UPMC, Pittsburgh, PA 15213 USA.
[Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Romond, Edward H.] Univ Kentucky, Lucille Parker Markey Canc Ctr, Lexington, KY USA.
[Swain, Sandra M.] Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
[Geyer, Charles E., Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Ewer, Michael S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Rathi, Vikas] Bon Secours Hlth Syst, Midlothian, VA USA.
[Fehrenbacher, Louis] Kaiser Permanente No Calif, Vallejo, CA USA.
[Polikoff, Jonathan] Kaiser Permanente, San Diego, CA USA.
[Azar, Catherine A.] Colorado Canc Res Program, CCOP, Denver, CO USA.
[Flynn, Patrick J.] CCOP, St Louis Pk, MN USA.
[Zapas, John L.] Franklin Sq Hosp Ctr, Baltimore, MD USA.
[Gross, Howard M.] CCOP, Dayton, OH USA.
[Mamounas, Eleftherios P.] Aultman Hosp Canc Ctr, Canton, OH USA.
[Biggs, David D.] Christiana Care Hlth Syst, CCOP, Newark, DE USA.
[Atkins, James N.] CCOP SE Canc Control Consortium, Goldsboro, NC USA.
[Tan-Chiu, Elizabeth] Florida Canc Res Inst, Plantation, FL USA.
RP Rastogi, P (reprint author), Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, E Commons Profess Bldg,5th Floor, Pittsburgh, PA 15212 USA.
EM rastogip@upmc.edu
FU National Cancer Institute, Department of Health and Human Services,
Public Health Service; Genentech; [U10-CA-12027]; [U10-CA-69651];
[U10-CA-37377]; [U10-CA-69974]
FX Supported by Grants No. U10-CA-12027, U10-CA-69651, U10-CA-37377, and
U10-CA-69974 from the National Cancer Institute, Department of Health
and Human Services, Public Health Service, and by Genentech.
NR 22
TC 146
Z9 147
U1 0
U2 8
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD NOV 1
PY 2012
VL 30
IS 31
BP 3792
EP 3799
DI 10.1200/JCO.2011.40.0010
PG 8
WC Oncology
SC Oncology
GA 030PT
UT WOS:000310583300014
PM 22987084
ER
PT J
AU Kantarjian, H
Thomas, D
Wayne, AS
O'Brien, S
AF Kantarjian, Hagop
Thomas, Deborah
Wayne, Alan S.
O'Brien, Susan
TI Monoclonal Antibody-Based Therapies: A New Dawn in the Treatment of
Acute Lymphoblastic Leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Review
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHILDRENS ONCOLOGY GROUP; MINIMAL RESIDUAL
DISEASE; B-CELL MALIGNANCIES; INOTUZUMAB OZOGAMICIN; HYPER-CVAD;
HEMATOLOGIC MALIGNANCIES; GEMTUZUMAB OZOGAMICIN; CYTOTOXIC ACTIVITY;
PEDIATRIC-PATIENTS
C1 [Kantarjian, Hagop] Univ Texas MD Anderson Canc Ctr, Leukemia Dept, Houston, TX 77030 USA.
[Wayne, Alan S.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Kantarjian, H (reprint author), Univ Texas MD Anderson Canc Ctr, Leukemia Dept, 1515 Holcombe Blvd,Box 428, Houston, TX 77030 USA.
EM hkantarj@mdanderson.org
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; National
Institutes of Health [CA016672]
FX Supported in part by the Intramural Research Program of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research, and by National Institutes of Health Grant No. CA016672.
NR 69
TC 42
Z9 42
U1 0
U2 5
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD NOV 1
PY 2012
VL 30
IS 31
BP 3876
EP 3883
DI 10.1200/JCO.2012.41.6768
PG 8
WC Oncology
SC Oncology
GA 030PT
UT WOS:000310583300025
PM 22891271
ER
PT J
AU Ehler, M
Filbir, F
Mhaskar, HN
AF Ehler, M.
Filbir, F.
Mhaskar, H. N.
TI Locally Learning Biomedical Data Using Diffusion Frames
SO JOURNAL OF COMPUTATIONAL BIOLOGY
LA English
DT Article
DE graphs and networks; machine learning
ID NONLINEAR DIMENSIONALITY REDUCTION; MACULAR DEGENERATION; GEOMETRIC
DIFFUSIONS; STRUCTURE DEFINITION; HARMONIC-ANALYSIS; LAPLACIAN; SPHERE;
REPRESENTATION; EIGENFUNCTIONS; DIAGNOSIS
AB Diffusion geometry techniques are useful to classify patterns and visualize high-dimensional datasets. Building upon ideas from diffusion geometry, we outline our mathematical foundations for learning a function on high-dimension biomedical data in a local fashion from training data. Our approach is based on a localized summation kernel, and we verify the computational performance by means of exact approximation rates. After these theoretical results, we apply our scheme to learn early disease stages in standard and new biomedical datasets.
C1 [Ehler, M.; Filbir, F.] Helmholtz Zentrum Munchen, Inst Biomath & Biometry, D-85764 Neuherberg, Germany.
[Ehler, M.] NICHD, NIH, Sect Med Biophys, Bethesda, MD USA.
[Mhaskar, H. N.] CALTECH, Dept Math, Pasadena, CA 91125 USA.
[Mhaskar, H. N.] Claremont Grad Univ, Dept Math, Claremont, CA USA.
RP Ehler, M (reprint author), Helmholtz Zentrum Munchen, Inst Biomath & Biometry, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
EM martin.ehler@helmholtz-muenchen.de
FU NIH/DFG Research Career Transition Awards Program [EH 405/1-1/575910];
Deutsche Forschungsgemeinschaft [FI 883/3-1]; National Science
Foundation [DMS-0908037]; U.S. Army Research Office [W911NF-09-1-0465]
FX M.E. was supported by the NIH/DFG Research Career Transition Awards
Program (EH 405/1-1/575910). The research of F.F. was partially funded
by Deutsche Forschungsgemeinschaft grant FI 883/3-1. H.N.M. was
supported, in part, by grant DMS-0908037 from the National Science
Foundation and grant W911NF-09-1-0465 from the U.S. Army Research
Office.
NR 51
TC 4
Z9 4
U1 0
U2 2
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1066-5277
J9 J COMPUT BIOL
JI J. Comput. Biol.
PD NOV
PY 2012
VL 19
IS 11
BP 1251
EP 1264
DI 10.1089/cmb.2012.0187
PG 14
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 033YN
UT WOS:000310837400004
PM 23101786
ER
PT J
AU Hildreth, RL
Bullough, MD
Zhang, AP
Chen, HL
Schwartz, PH
Panchision, DM
Colberg-Poley, AM
AF Hildreth, Richard L.
Bullough, Matthew D.
Zhang, Aiping
Chen, Hui-Ling
Schwartz, Philip H.
Panchision, David M.
Colberg-Poley, Anamaris M.
TI Viral mitochondria-localized inhibitor of apoptosis (UL37 exon 1
protein) does not protect human neural precursor cells from human
cytomegalovirus-induced cell death
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; SUBVENTRICULAR ZONE; NERVOUS-SYSTEM; STEM-CELLS;
NEURONAL DIFFERENTIATION; PROGENITOR CELLS; INFECTION; VIRUS;
ASTROCYTES; BRAIN
AB Congenital human cytomegalovirus (HCMV) infection can cause severe brain abnormalities. Apoptotic HCMV-infected brain cells have been detected in a congenitally infected infant. In biologically relevant human neural precursor cells (hNPCs), cultured in physiological oxygen tensions, HCMV infection (m.o.i. of 1 or 3) induced cell death within 3 days post-infection (p.i.) and increased thereafter. Surprisingly, its known anti-apoptotic genes, including the potent UL37 exon 1 protein (pUL37x1) or viral mitochondria-localized inhibitor of apoptosis (vMIA), which protects infected human fibroblasts (HFFs) from apoptosis and from caspase-independent, mitochondrial serine protease-mediated cell death, were expressed by 2 days p.i. Consistent with this finding, an HCMV UL37x1 mutant, BADsubstitutionUL37x1 (BADsubUL37x1) induced cell death in hNPCs (m.o.i.=1) to level which were indistinguishable from parental virus (BADwild-type)-infected hNPCs. Surprisingly, although BADsubUL37x1 is growth defective in permissive HFFs, it produced infectious progeny in hNPCs with similar kinetics and to levels comparable to BADwild-type-infected hNPCs (m.o.i.=1). While delayed at a lower multiplicity (m.o.i.=0.3), the BADsubUL37x1 mutant reached similar levels to revertant within 12 days, in contrast to its phenotype in HFFs. The inability of pUL37x1/vMIA to protect hNPCs from HCMV-induced cell death did not result from impaired trafficking as pUL37x1/vMIA trafficked efficiently to mitochondria in transfected hNPCs and in HCMV-infected hNPCs. These results establish that pUL37x1/vMIA, although protective in permissive HFFs, does not protect HCMV-infected hNPCs from cell death under physiologically relevant oxygen tensions. They further suggest that pUL37x1/vMIA is not essential for HCMV growth in hNPCs and has different cell type-specific roles.
C1 [Hildreth, Richard L.; Bullough, Matthew D.; Zhang, Aiping; Colberg-Poley, Anamaris M.] Childrens Res Inst, Res Ctr Genet Med, Washington, DC 20010 USA.
[Hildreth, Richard L.; Colberg-Poley, Anamaris M.] George Washington Univ, Mol Med Program, Washington, DC 20052 USA.
[Chen, Hui-Ling] Childrens Res Inst, Ctr Neurosci Res, Washington, DC 20010 USA.
[Chen, Hui-Ling] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Schwartz, Philip H.] Childrens Hosp Orange Cty, Res Inst, Orange, CA 92668 USA.
[Panchision, David M.] NIMH, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA.
[Colberg-Poley, Anamaris M.] George Washington Univ, Dept Biochem & Mol Biol, Washington, DC 20052 USA.
[Colberg-Poley, Anamaris M.] George Washington Univ, Dept Integrat Syst Biol, Washington, DC 20052 USA.
RP Colberg-Poley, AM (reprint author), Childrens Res Inst, Res Ctr Genet Med, Washington, DC 20010 USA.
EM acolberg-poley@cnmcresearch.org
FU NIH [R01 AI057906]; National Center for Research Resources
[UL1RR031988]; Children's Research Institute funds; [1P30HD40677]
FX The authors thank Dr Tom Shenk for the gift of the recombinant HCMV
viruses BADwt, BADrev, BADsubUL37x1 and antibody mAb4B-6B, Dr Bill Britt
for the gift of mAb28-4, mAb28-19 and mAb65-8. We are grateful to Drs
Lina Chakrabarti and Chad Williamson for help in analysing the flow
cytometry and quantifying the MetaMorph co-localization signals,
respectively. The studies were supported by NIH R01 AI057906, National
Center for Research Resources UL1RR031988 and Children's Research
Institute funds to A.C.P. Confocal microscopy imaging was performed in
the Cellular Imaging & Analysis Core at Children's Research Institute
and was supported by a core grant to the Children's Intellectual and
Developmental Disabilities Research Center (1P30HD40677). Its contents
are solely the responsibility of the authors and do not necessarily
represent the official views of the National Center for Research
Resources or the National Institutes of Health. These studies were
performed by R.L.H. in partial fulfilment of his doctoral studies in the
Molecular Medicine Program at George Washington University Institute of
Biomedical Sciences.
NR 56
TC 2
Z9 2
U1 1
U2 8
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD NOV
PY 2012
VL 93
BP 2436
EP 2446
DI 10.1099/vir.0.044784-0
PN 11
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 033RW
UT WOS:000310819600015
PM 22875256
ER
PT J
AU Yewdell, JW
David, A
AF Yewdell, Jonathan W.
David, Alexandre
TI Editorial: Proteostenosis: cancer's Achilles heel?
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
DE defective ribosomal products; multiple myeloma; proteasome;
proteostasis; protein synthesis; rapidly degraded polypeptides;
ubiquitin
ID PROTEIN-SYNTHESIS; OXIDATIVE-STRESS; MAMMALIAN-CELLS; LIVED PROTEINS;
DEGRADATION; PROTEASOME; IMMUNOPROTEASOME
C1 [Yewdell, Jonathan W.; David, Alexandre] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 33, Bethesda, MD 20892 USA.
EM jyewdell@niaid.nih.gov
OI David, Alexandre/0000-0003-3365-1339
FU Intramural NIH HHS
NR 20
TC 1
Z9 1
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD NOV
PY 2012
VL 92
IS 5
BP 913
EP 915
DI 10.1189/jlb.0612272
PG 3
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 030QF
UT WOS:000310584500001
PM 23118441
ER
PT J
AU Shen, J
AF Shen, Jun
TI Preserving the excitation profile of small flip angle RF pulses in the
presence of rapid transverse relaxation
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE RF pulse design; Linear response theory; Relaxation effects
ID SELECTIVE EXCITATION; ACCOMMODATE RELAXATION; DESIGN
AB Degradation of excitation profile of selective RF pulses by rapid transverse relaxation has been a long-standing concern. In this report we demonstrate that transverse relaxation can be incorporated into small flip angle RF pulse design based on the linear response theory. Small flip angle pulses that were designed without considering transverse relaxation effects can be transformed for a predefined pulse duration/T-2 ratio. The transformed pulses, within the realm of the linear response theory, produce the same transverse frequency response as if there were no relaxation. Published by Elsevier Inc.
C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA.
RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM shenj@intra.nimh.nih.gov
FU Intramural Research Program of the NIH, NIMH
FX The author thanks the reviewers and the editor for their helpful
comments. This work is supported by the Intramural Research Program of
the NIH, NIMH.
NR 20
TC 2
Z9 2
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
J9 J MAGN RESON
JI J. Magn. Reson.
PD NOV
PY 2012
VL 224
BP 8
EP 12
DI 10.1016/j.jmr.2012.08.012
PG 5
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA 033AP
UT WOS:000310765000002
PM 23000975
ER
PT J
AU Fujimura, KE
Rauch, M
Matsui, E
Iwai, S
Calatroni, A
Lynn, H
Mitchell, H
Johnson, CC
Gern, JE
Togias, A
Boushey, HA
Kennedy, S
Lynch, SV
AF Fujimura, Kei E.
Rauch, Marcus
Matsui, Elizabeth
Iwai, Shoko
Calatroni, Agustin
Lynn, Henry
Mitchell, Herman
Johnson, Christine C.
Gern, James E.
Togias, Alkis
Boushey, Homer A.
Kennedy, Suzanne
Lynch, Susan V.
TI Development of a standardized approach for environmental microbiota
investigations related to asthma development in children
SO JOURNAL OF MICROBIOLOGICAL METHODS
LA English
DT Article
DE Dust microbiome; Standardized sampling; Phylogenetic microarray;
454-Pyrosequencing
ID 16S RIBOSOMAL-RNA; GUT MICROBIOME; DIVERSITY; BACTERIA; ALLERGY
AB Standardized studies examining environmental microbial exposure in populations at risk for asthma are necessary to improve our understanding of the role this factor plays in disease development. Here we describe studies aimed at developing guidelines for high-resolution culture-independent microbiome profiling, using a phylogenetic microarray (PhyloChip), of house dust samples in a cohort collected as part of the NIH-funded Inner City Asthma Consortium (ICAC). We demonstrate that though extracted DNA concentrations varied across dust samples, the majority produced sufficient 16S rRNA to be profiled by the array. Comparison of array and 454-pyrosequencing performed in parallel on a subset of samples, illustrated that increasingly deeper sequencing efforts validated greater numbers of array-detected taxa. Community composition agreement across samples exhibited a hierarchy in concordance, with the highest level of agreement in replicate array profiles followed by samples collected from adjacent 1 x 1 m(2) sites in the same room, adjacent sites with different sized sampling quadrants (1 x 1 and 2 x 2 m(2)), different sites within homes (living and bedroom) to lowest in living room samples collected from different homes. The guidelines for sample collection and processing in this pilot study extend beyond PhyloChip based studies of house-associated microbiota, and bear relevance for other microbiome profiling approaches such as next-generation sequencing. (C) 2012 Elsevier B.V. All rights reserved.
C1 [Fujimura, Kei E.; Rauch, Marcus; Iwai, Shoko; Lynch, Susan V.] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Matsui, Elizabeth] Johns Hopkins Univ, Sch Med, Div Pediat Allergy & Immunol, Baltimore, MD 21287 USA.
[Calatroni, Agustin; Lynn, Henry; Mitchell, Herman; Kennedy, Suzanne] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA.
[Johnson, Christine C.] Henry Ford Hlth Syst, Div Allergy & Immunol, Dept Publ Hlth Sci, Dept Internal Med, Detroit, MI 48202 USA.
[Gern, James E.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat & Med, Madison, WI 53792 USA.
[Togias, Alkis] NIAID, Bethesda, MD 20814 USA.
[Boushey, Homer A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
RP Lynch, SV (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM susan.lynch@ucsf.edu
OI Johnson, Christine Cole/0000-0002-6864-6604
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-AI-25482, HHSN272200900052C,
HHSN2722010000521]; National Center for Research Resources, National
Institutes of Health [RR00052, M01RR00533, 1UL1RR025771, M01RR00071,
1UL1RR024156, 5UL1RR024992-02]
FX This project has been funded in whole or in part with federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, under contract numbers NO1-AI-25496, NO1-AI-25482,
HHSN272200900052C and HHSN2722010000521. Additional support was provided
by the National Center for Research Resources, National Institutes of
Health, under grants RR00052, M01RR00533, 1UL1RR025771, M01RR00071,
1UL1RR024156, and 5UL1RR024992-02.
NR 32
TC 4
Z9 4
U1 1
U2 19
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-7012
J9 J MICROBIOL METH
JI J. Microbiol. Methods
PD NOV
PY 2012
VL 91
IS 2
BP 231
EP 239
DI 10.1016/j.mimet.2012.08.016
PG 9
WC Biochemical Research Methods; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 034HP
UT WOS:000310863800003
PM 22975469
ER
PT J
AU Brown, P
Gipson, C
AF Brown, Patricia
Gipson, Chester
TI A word from OLAW and USDA
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
RP Brown, P (reprint author), NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
J9 LAB ANIMAL
JI Lab Anim.
PD NOV
PY 2012
VL 41
IS 11
BP 308
EP 308
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 031PG
UT WOS:000310653800015
PM 23079911
ER
PT J
AU Peickert, S
Waurig, J
Dittfeld, C
Dietrich, A
Garbe, Y
Kabus, L
Baumann, M
Grade, M
Ried, T
Kunz-Schughart, LA
AF Peickert, Susann
Waurig, Julia
Dittfeld, Claudia
Dietrich, Antje
Garbe, Yvette
Kabus, Lydia
Baumann, Michael
Grade, Marian
Ried, Thomas
Kunz-Schughart, Leoni A.
TI Rapid re-expression of CD133 protein in colorectal cancer cell lines in
vitro and in vivo
SO LABORATORY INVESTIGATION
LA English
DT Article
DE cancer stem cell hypothesis; CD133 protein; colorectal cancer cell line;
2-D culture; 3-D culture; radio-/chemotherapy; xenograft
ID TUMOR-INITIATING CELLS; PLASMA-MEMBRANE PROTRUSIONS; HUMAN COLON-CANCER;
STEM-CELLS; RECTAL-CANCER; PREOPERATIVE CHEMORADIOTHERAPY;
GENE-EXPRESSION; MARKER CD133; SOLID TUMORS; HUMAN GLIOMA
AB Studies related to the cancer stem cell hypothesis are challenging because of the imperfect tools to identify cell populations of interest and controversy on the usefulness of established cancer cell lines. We previously found CD133 to not be selective for a tumor-propagating or radioresistant population in a near-diploid, microsatellite-instable colorectal carcinoma (CRC) cell line. Because of discrepant literature data, we herein systematically analyzed the behavior of microsatellite-stable cell line subpopulations reflecting the more frequent carcinogenesis pathway in spontaneous CRC. CD133(+) and CD133(-/low) populations were isolated by fluorescence-activated cell sorting and further processed. HT29 and SW620 cells were studied in detail in monolayer and/or spheroid culture assays and upon subcutaneous injection in NMRI (nu/nu) mice using a limiting dilution approach. CD133(-/low) HT29 cells showed a significantly lower clonogenic survival and reduced spheroid formation capacity than their CD133+ counterparts. However, the cell populations neither differed in growth kinetics and response to treatment in vitro nor in tumor formation capacity when injecting as low as 10 cells. CD 133(-/low) HT29 cells rapidly re-expressed CD 133 protein in vitro and in vivo as shown by flow cytometry and/or western blot analyses, and they also showed a particular survival benefit under tissue normoxic conditions. In contrast, CD133 protein in the CD133(+) population was quite stable throughout culturing. The observation of CD133 re-expression and lack of difference in tumor take rate of subpopulations was confirmed in SW620 cells. Here, we found cell density to affect CD133 re-expression in the CD133(-)-sorted population. And even SW480 cells, classified as a CD133(-) cell line, presented some CD133 protein on their surface upon in vivo engraftment. We conclude that (i) CD133 protein expression shows high plasticity in CRC cell lines, and (ii) in vitro CD133 status on the cell surface neither determines tumorigenic potential nor CD133 profile in vivo. Laboratory Investigation (2012) 92, 1607-1622; doi:10.1038/labinvest.2012.124; published online 10 September 2012
C1 [Peickert, Susann; Waurig, Julia; Dittfeld, Claudia; Dietrich, Antje; Garbe, Yvette; Kabus, Lydia; Baumann, Michael; Kunz-Schughart, Leoni A.] Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany.
[Baumann, Michael] Tech Univ Dresden, Dept Radiat Oncol, Fac Med, D-01307 Dresden, Germany.
[Baumann, Michael] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, D-01307 Dresden, Germany.
[Grade, Marian] Univ Med Gottingen, Dept Gen & Visceral Surg, Gottingen, Germany.
[Ried, Thomas] NCI, NIH, Bethesda, MD 20892 USA.
RP Kunz-Schughart, LA (reprint author), Tech Univ Dresden, OncoRay Natl Ctr Radiat Res Oncol, Med Fac Carl Gustav Carus, Fetscherstr 74,PF 86, D-01307 Dresden, Germany.
EM leoni.kunz-schughart@oncoray.de
FU German Research Foundation (DFG) [KU 971/7-1, GR 3376/2-1, KFO179]; BMBF
in the program 'Center for Innovation Competence'
FX We thank Mrs Marit Wondrak and Mrs Melanie Huether for excellent
technical assistance. This work was supported by the German Research
Foundation (DFG) through grants KU 971/7-1 and GR 3376/2-1, and the
KFO179. OncoRay is funded by the BMBF in the program 'Center for
Innovation Competence'. Disclaimer: The authors alone are responsible
for the content and writing of the paper.
NR 65
TC 12
Z9 12
U1 1
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
J9 LAB INVEST
JI Lab. Invest.
PD NOV
PY 2012
VL 92
IS 11
BP 1607
EP 1622
DI 10.1038/labinvest.2012.124
PG 16
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA 032ZL
UT WOS:000310761800009
PM 22964855
ER
PT J
AU Beral, V
Bull, D
Pirie, K
Reeves, G
Peto, R
Skegg, D
LaVecchia, C
Magnusson, C
Pike, MC
Thomas, D
Hamajima, N
Hirose, K
Tajima, K
Rohan, T
Friedenreich, CM
Calle, EE
Gapstur, SM
Patel, AV
Coates, RJ
Liff, JM
Talamini, R
Chantarakul, N
Koetsawang, S
Rachawat, D
Marcou, Y
Kakouri, E
Duffy, SW
Morabia, A
Schuman, L
Stewart, W
Szklo, M
Coogan, PF
Palmer, JR
Rosenberg, L
Band, P
Coldman, AJ
Gallagher, RP
Hislop, TG
Yang, P
Cummings, SR
Canfell, K
Sitas, F
Chao, P
Lissowska, J
Horn-Ross, PL
John, EM
Kolonel, LM
Nomura, AMY
Ghiasvand, R
Hu, J
Johnson, KC
Mao, Y
Callaghan, K
Crossley, B
Goodill, A
Green, J
Hermon, C
Key, T
Lindgard, I
Liu, B
Pirie, K
Reeves, G
Collins, R
Doll, R
Peto, R
Bishop, T
Fentiman, IS
De Sanjose, S
Gonzaler, CA
Lee, N
Marchbanks, P
Ory, HW
Peterson, HB
Wingo, P
Ebeling, K
Kunde, D
Nishan, P
Hopper, JL
Eliassen, H
Gajalakshmi, V
Martin, N
Pardthaisong, T
Silpisornkosol, S
Theetranont, C
Boosiri, B
Chutivongse, S
Jimakorn, P
Virutamasen, P
Wongsrichanalai, C
Neugut, A
Santella, R
Baines, CJ
Kreiger, N
Miller, AB
Wall, C
Tjonneland, A
Jorgensen, T
Stahlberg, C
Pedersen, AT
Flesch-Janys, D
Hakansson, N
Cauley, J
Heuch, I
Adami, HO
Persson, I
Weiderpass, E
Magnusson, C
Chang-Claude, J
Kaaks, R
McCredie, M
Paul, C
Skegg, DCG
Spears, GFS
Iwasaki, M
Tsugane, S
Anderson, G
Daling, JR
Hampton, J
Hutchinson, WB
Li, CI
Malone, K
Mandelson, M
Newcomb, P
Noonan, EA
Ray, RM
Stanford, JL
Tang, MTC
Thomas, DB
Weiss, NS
White, E
Izquierdo, A
Viladiu, P
Fourkala, EO
Jacobs, I
Menon, U
Ryan, A
Cuevas, HR
Ontiveros, P
Palet, A
Salazar, SB
Aristizabal, N
Cuadros, A
Tryggvadottir, L
Tulinius, H
Riboli, E
Andrieu, N
Bachelot, A
Le, MG
Bremond, A
Gairard, B
Lansac, J
Piana, L
Renaud, R
Clavel-Chapelon, F
Fournier, A
Touillaud, M
Mesrine, S
Chabbert-Buffet, N
Boutron-Ruault, MC
Wolk, A
Torres-Mejia, G
Franceschi, S
Romieu, I
Boyle, P
Lubin, F
Modan, B
Ron, E
Wax, Y
Friedman, GD
Hiatt, RA
Levi, F
Kosmelj, K
Primic-Zakelj, M
Ravnihar, B
Stare, J
Ekbom, A
Erlandsson, G
Persson, I
Beeson, WL
Fraser, G
Peto, J
Hanson, RL
Leske, MC
Mahoney, MC
Nasca, PC
Varma, AO
Weinstein, AL
Hartman, ML
Olsson, H
Goldbohm, RA
van den Brandt, PA
Palli, D
Teitelbaum, S
Apelo, RA
Baens, J
de la Cruz, JR
Javier, B
Lacaya, LB
Ngelangel, CA
La Vecchia, C
Negri, E
Marubini, E
Ferraroni, M
Pike, MC
Gerber, M
Richardson, S
Segala, C
Gatei, D
Kenya, P
Kungu, A
Mati, JG
Brinton, LA
Freedman, M
Hoover, R
Schairer, C
Ziegler, R
Banks, E
Spirtas, R
Lee, HP
Rookus, MA
van Leeuwen, FE
Schoenberg, JA
Graff-Iversen, S
Selmer, R
Jones, L
McPherson, K
Neil, A
Vessey, M
Yeates, D
Mabuchi, K
Preston, D
Hannaford, P
Kay, C
McCann, SE
Rosero-Bixby, L
Gao, YT
Jin, F
Yuan, JM
Wei, HY
Yun, T
Zhiheng, C
Berry, G
Booth, JC
Jelihovsky, T
MacLennan, R
Shearman, R
Hadjisavvas, A
Kyriacou, K
Loisidou, M
Zhou, X
Wang, QS
Kawai, M
Minami, Y
Tsuji, I
Lund, E
Kumle, M
Stalsberg, H
Shu, XO
Zheng, W
Monninkhof, EM
Onland-Moret, NC
Peeters, PHM
Katsouyanni, K
Trichopoulou, A
Trichopoulos, D
Tzonou, A
Baltzell, KA
Dabancens, A
Martinez, L
Molina, R
Salas, O
Alexander, FE
Anderson, K
Folsom, AR
Gammon, MD
Hulka, BS
Millikan, R
Chilvers, CED
Lumachi, F
Bain, C
Schofield, F
Siskind, V
Rebbeck, TR
Bernstein, LR
Enger, S
Haile, RW
Paganini-Hill, A
Ross, RK
Ursin, G
Wu, AH
Yu, MC
Ewertz, DM
Clarke, EA
Bergkvist, L
Anderson, GL
Gass, M
O'Sullivan, MJ
Kalache, A
Farley, TMM
Holck, S
Meirik, O
Fukao, A
AF Beral, V.
Bull, D.
Pirie, K.
Reeves, G.
Peto, R.
Skegg, D.
LaVecchia, C.
Magnusson, C.
Pike, M. C.
Thomas, D.
Hamajima, N.
Hirose, K.
Tajima, K.
Rohan, T.
Friedenreich, C. M.
Calle, E. E.
Gapstur, S. M.
Patel, A. V.
Coates, R. J.
Liff, J. M.
Talamini, R.
Chantarakul, N.
Koetsawang, S.
Rachawat, D.
Marcou, Y.
Kakouri, E.
Duffy, S. W.
Morabia, A.
Schuman, L.
Stewart, W.
Szklo, M.
Coogan, P. F.
Palmer, J. R.
Rosenberg, L.
Band, P.
Coldman, A. J.
Gallagher, R. P.
Hislop, T. G.
Yang, P.
Cummings, S. R.
Canfell, K.
Sitas, F.
Chao, P.
Lissowska, J.
Horn-Ross, P. L.
John, E. M.
Kolonel, L. M.
Nomura, A. M. Y.
Ghiasvand, R.
Hu, J.
Johnson, K. C.
Mao, Y.
Callaghan, K.
Crossley, B.
Goodill, A.
Green, J.
Hermon, C.
Key, T.
Lindgard, I.
Liu, B.
Pirie, K.
Reeves, G.
Collins, R.
Doll, R.
Peto, R.
Bishop, T.
Fentiman, I. S.
De Sanjose, S.
Gonzaler, C. A.
Lee, N.
Marchbanks, P.
Ory, H. W.
Peterson, H. B.
Wingo, P.
Ebeling, K.
Kunde, D.
Nishan, P.
Hopper, J. L.
Eliassen, H.
Gajalakshmi, V.
Martin, N.
Pardthaisong, T.
Silpisornkosol, S.
Theetranont, C.
Boosiri, B.
Chutivongse, S.
Jimakorn, P.
Virutamasen, P.
Wongsrichanalai, C.
Neugut, A.
Santella, R.
Baines, C. J.
Kreiger, N.
Miller, A. B.
Wall, C.
Tjonneland, A.
Jorgensen, T.
Stahlberg, C.
Pedersen, A. Tonnes
Flesch-Janys, D.
Hakansson, N.
Cauley, J.
Heuch, I.
Adami, H. O.
Persson, I.
Weiderpass, E.
Magnusson, C.
Chang-Claude, J.
Kaaks, R.
McCredie, M.
Paul, C.
Skegg, D. C. G.
Spears, G. F. S.
Iwasaki, M.
Tsugane, S.
Anderson, G.
Daling, J. R.
Hampton, J.
Hutchinson, W. B.
Li, C. I.
Malone, K.
Mandelson, M.
Newcomb, P.
Noonan, E. A.
Ray, R. M.
Stanford, J. L.
Tang, M. T. C.
Thomas, D. B.
Weiss, N. S.
White, E.
Izquierdo, A.
Viladiu, P.
Fourkala, E. O.
Jacobs, I.
Menon, U.
Ryan, A.
Cuevas, H. R.
Ontiveros, P.
Palet, A.
Salazar, S. B.
Aristizabal, N.
Cuadros, A.
Tryggvadottir, L.
Tulinius, H.
Riboli, E.
Andrieu, N.
Bachelot, A.
Le, M. G.
Bremond, A.
Gairard, B.
Lansac, J.
Piana, L.
Renaud, R.
Clavel-Chapelon, F.
Fournier, A.
Touillaud, M.
Mesrine, S.
Chabbert-Buffet, N.
Boutron-Ruault, M. C.
Wolk, A.
Torres-Mejia, G.
Franceschi, S.
Romieu, I.
Boyle, P.
Lubin, F.
Modan, B.
Ron, E.
Wax, Y.
Friedman, G. D.
Hiatt, R. A.
Levi, F.
Kosmelj, K.
Primic-Zakelj, M.
Ravnihar, B.
Stare, J.
Ekbom, A.
Erlandsson, G.
Persson, I.
Beeson, W. L.
Fraser, G.
Peto, J.
Hanson, R. L.
Leske, M. C.
Mahoney, M. C.
Nasca, P. C.
Varma, A. O.
Weinstein, A. L.
Hartman, M. L.
Olsson, H.
Goldbohm, R. A.
van den Brandt, P. A.
Palli, D.
Teitelbaum, S.
Apelo, R. A.
Baens, J.
de la Cruz, J. R.
Javier, B.
Lacaya, L. B.
Ngelangel, C. A.
La Vecchia, C.
Negri, E.
Marubini, E.
Ferraroni, M.
Pike, M. C.
Gerber, M.
Richardson, S.
Segala, C.
Gatei, D.
Kenya, P.
Kungu, A.
Mati, J. G.
Brinton, L. A.
Freedman, M.
Hoover, R.
Schairer, C.
Ziegler, R.
Banks, E.
Spirtas, R.
Lee, H. P.
Rookus, M. A.
van Leeuwen, F. E.
Schoenberg, J. A.
Graff-Iversen, S.
Selmer, R.
Jones, L.
McPherson, K.
Neil, A.
Vessey, M.
Yeates, D.
Mabuchi, K.
Preston, D.
Hannaford, P.
Kay, C.
McCann, S. E.
Rosero-Bixby, L.
Gao, Y. T.
Jin, F.
Yuan, J-M
Wei, H. Y.
Yun, T.
Zhiheng, C.
Berry, G.
Booth, J. Cooper
Jelihovsky, T.
MacLennan, R.
Shearman, R.
Hadjisavvas, A.
Kyriacou, K.
Loisidou, M.
Zhou, X.
Wang, Q-S
Kawai, M.
Minami, Y.
Tsuji, I.
Lund, E.
Kumle, M.
Stalsberg, H.
Shu, X. O.
Zheng, W.
Monninkhof, E. M.
Onland-Moret, N. C.
Peeters, P. H. M.
Katsouyanni, K.
Trichopoulou, A.
Trichopoulos, D.
Tzonou, A.
Baltzell, K. A.
Dabancens, A.
Martinez, L.
Molina, R.
Salas, O.
Alexander, F. E.
Anderson, K.
Folsom, A. R.
Gammon, M. D.
Hulka, B. S.
Millikan, R.
Chilvers, C. E. D.
Lumachi, F.
Bain, C.
Schofield, F.
Siskind, V.
Rebbeck, T. R.
Bernstein, L. R.
Enger, S.
Haile, R. W.
Paganini-Hill, A.
Ross, R. K.
Ursin, G.
Wu, A. H.
Yu, M. C.
Ewertz, Denmark M.
Clarke, E. A.
Bergkvist, L.
Anderson, G. L.
Gass, M.
O'Sullivan, M. J.
Kalache, A.
Farley, T. M. M.
Holck, S.
Meirik, O.
Fukao, A.
CA Collaborative Grp Hormonal Factors
Collaborative Grp Hormonal Factors
S Hankinson Nurses Hlth Study I II Res Grp
TI Menarche, menopause, and breast cancer risk: individual participant
meta-analysis, including 118 964 women with breast cancer from 117
epidemiological studies
SO LANCET ONCOLOGY
LA English
DT Article
ID REQUIRING PROLONGED OBSERVATION; COLLABORATIVE REANALYSIS;
POSTMENOPAUSAL WOMEN; SEX-HORMONES; AGE; THERAPY; PATIENT; TRIALS;
RECALL; REPRODUCIBILITY
AB Background Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.
Methods Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.
Findings Breast cancer risk increased by a factor of 1.050 (95% CI 1.044-1.057; p < 0.0001) for every year younger at menarche, and independently by a smaller amount (1.029, 1.025-1.032; p < 0.0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1.43, 1.33-1.52, p < 0.001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p < 0.006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p < 0.01 for both comparisons).
Interpretation The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.
Funding Cancer Research UK.
C1 [Beral, V.; Bull, D.; Pirie, K.; Reeves, G.] Univ Oxford, Canc Epidemiol Unit, Oxford OX3 7LF, England.
[Peto, R.] Univ Oxford, CRUK MRC BHF Clin Trial Serv Unit, Oxford OX3 7LF, England.
[Peto, R.] Univ Oxford, Epidemiol Studies Unit, Oxford OX3 7LF, England.
[Skegg, D.] Univ Otago, Dunedin, New Zealand.
[LaVecchia, C.] Ist Mario Negri, Milan, Italy.
[LaVecchia, C.] Univ Milan, Milan, Italy.
[Magnusson, C.] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
[Pike, M. C.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Thomas, D.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Hamajima, N.; Hirose, K.; Tajima, K.] Aichi Canc Res Inst, Nagoya, Aichi, Japan.
[Rohan, T.] Albert Einstein Coll Med, New York, NY USA.
[Friedenreich, C. M.] Alberta Hlth Serv, Calgary, AB, Canada.
[Calle, E. E.; Gapstur, S. M.; Patel, A. V.] Amer Canc Soc, Atlanta, GA USA.
[Coates, R. J.; Liff, J. M.] Emory Univ, Atlanta, GA USA.
[Talamini, R.] Aviano Canc Ctr, Pordenone, Italy.
[Chantarakul, N.; Koetsawang, S.; Rachawat, D.] Mahidol Univ, Bangkok, Thailand.
[Marcou, Y.; Kakouri, E.] Bank Cyprus Oncol Ctr, Nicosia, Cyprus.
[Duffy, S. W.] Barts & London Queen Marys Sch Med & Dent, London, England.
[Morabia, A.; Schuman, L.; Stewart, W.; Szklo, M.] Johns Hopkins Univ, Breast Tumor Collaborat Study, Baltimore, MD USA.
[Coogan, P. F.; Palmer, J. R.; Rosenberg, L.] Boston Univ, Sloane Epidemiol Ctr, Boston, MA USA.
[Band, P.; Coldman, A. J.; Gallagher, R. P.; Hislop, T. G.; Yang, P.] British Columbia Canc Agcy, Vancouver, BC, Canada.
[Cummings, S. R.] Calif Pacific Med Ctr, San Francisco, CA USA.
[Canfell, K.; Sitas, F.] Canc Council NSW, Sydney, NSW, Australia.
[Chao, P.; Lissowska, J.] Canc Ctr & M Sklodowska Curie Inst Oncol, Warsaw, Poland.
[Horn-Ross, P. L.; John, E. M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Kolonel, L. M.; Nomura, A. M. Y.] Univ Hawaii, Canc Res Ctr, Honolulu, HI USA.
[Ghiasvand, R.] Univ Tehran, Inst Canc, Canc Res Ctr, Tehran, Iran.
[Hu, J.; Johnson, K. C.; Mao, Y.] Canadian Canc Registries Epidemiol Res Grp, Ottawa, ON, Canada.
[Beral, V.; Bull, D.; Callaghan, K.; Crossley, B.; Goodill, A.; Green, J.; Hermon, C.; Key, T.; Lindgard, I.; Liu, B.; Pirie, K.; Reeves, G.] Canc Res UK Epidemiol Unit, Oxford, England.
[Collins, R.; Doll, R.; Peto, R.] Canc Res UK MRC BHF, Clin Trial Serv, Oxford, England.
[Collins, R.; Doll, R.; Peto, R.] Canc Res UK MRC BHF, Epidemiol Studies Unit, Oxford, England.
[Bishop, T.] Canc Res UK Genet Epidemiol Lab, Leeds, W Yorkshire, England.
[Fentiman, I. S.] Canc Res UK, London, England.
[De Sanjose, S.; Gonzaler, C. A.] Catalan Inst Oncol, Barcelona, Spain.
[Lee, N.; Marchbanks, P.; Ory, H. W.; Peterson, H. B.; Wingo, P.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Ebeling, K.; Kunde, D.; Nishan, P.] Cent Inst Canc Res, Berlin, Germany.
[Hopper, J. L.] Univ Melbourne, Ctr Genet Epidemiol, Melbourne, Vic, Australia.
[Eliassen, H.; S Hankinson Nurses Hlth Study I II Res Grp] Harvard Med Sch, Brigham & Womens Hosp, Channing Lab, Boston, MA USA.
[Gajalakshmi, V.] Chennai Canc Inst, Madras, Tamil Nadu, India.
[Martin, N.; Pardthaisong, T.; Silpisornkosol, S.; Theetranont, C.] Chiang Mai Univ, Chiang Mai, Thailand.
[Boosiri, B.; Chutivongse, S.; Jimakorn, P.; Virutamasen, P.; Wongsrichanalai, C.] Chulalongkorn Univ, Bangkok, Thailand.
[Neugut, A.; Santella, R.] Columbia Univ, New York, NY 10027 USA.
[Baines, C. J.; Kreiger, N.; Miller, A. B.; Wall, C.] Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Tjonneland, A.] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Jorgensen, T.; Stahlberg, C.; Pedersen, A. Tonnes] Res Ctr Prevent & Hlth, Danish Nurse Cohort Study, Capital Reg, Denmark.
[Flesch-Janys, D.] Univ Canc Ctr Hamburg, Dept Canc Epidemiol Clin Canc Registry, Hamburg, Germany.
[Hakansson, N.] Karolinska Inst, Dept Environm Med, Stockholm, Sweden.
[Cauley, J.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Heuch, I.] Univ Bergen, Dept Math, N-5007 Bergen, Norway.
[Adami, H. O.; Persson, I.; Weiderpass, E.] Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden.
[Magnusson, C.] Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.
[Chang-Claude, J.; Kaaks, R.] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[McCredie, M.; Paul, C.; Skegg, D. C. G.; Spears, G. F. S.] Univ Otago, Dunedin, New Zealand.
[Iwasaki, M.; Tsugane, S.] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan.
[Anderson, G.; Daling, J. R.; Hampton, J.; Hutchinson, W. B.; Li, C. I.; Malone, K.; Mandelson, M.; Newcomb, P.; Noonan, E. A.; Ray, R. M.; Stanford, J. L.; Tang, M. T. C.; Thomas, D. B.; Weiss, N. S.; White, E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Izquierdo, A.; Viladiu, P.] Girona Canc Registry, Girona, Spain.
[Fourkala, E. O.; Jacobs, I.; Menon, U.; Ryan, A.] UCL, Dept Womens Canc, Inst Womens Hlth, Gynaecol Canc Res Ctr, London, England.
[Cuevas, H. R.; Ontiveros, P.; Palet, A.; Salazar, S. B.] Hosp Gen Mexico City, Mexico City, DF, Mexico.
[Aristizabal, N.; Cuadros, A.] Univ Hosp, Cali, Colombia.
[Tryggvadottir, L.; Tulinius, H.] Iceland Canc Soc, Reykjavik, Iceland.
[Riboli, E.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Andrieu, N.; Bachelot, A.; Le, M. G.; Bremond, A.; Gairard, B.; Lansac, J.; Piana, L.; Renaud, R.] Inst Gustave Roussy, Villejuif, France.
[Clavel-Chapelon, F.; Fournier, A.; Touillaud, M.; Mesrine, S.; Chabbert-Buffet, N.; Boutron-Ruault, M. C.] Paris S Univ, INSERM, Inst Gustave Roussy, EPIC Grp E3N, Villejuif, France.
[Wolk, A.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Torres-Mejia, G.] Inst Nacl Salud Publ, Morelos, Mexico.
[Franceschi, S.; Romieu, I.] Int Agcy Res Canc, F-69372 Lyon, France.
[Boyle, P.] Int Prevent Res Inst, Lyon, France.
[Lubin, F.; Modan, B.; Ron, E.; Wax, Y.] Israel Chaim Sheba Med Ctr, Tel Hashomer, Israel.
[Friedman, G. D.; Hiatt, R. A.] Kaiser Permanente, Oakland, CA USA.
[Levi, F.] Inst Univ Med Sociale & Prevent, Lausanne, Switzerland.
[Kosmelj, K.; Primic-Zakelj, M.; Ravnihar, B.; Stare, J.] Inst Oncol, Ljubljana, Slovenia.
[Ekbom, A.; Erlandsson, G.; Persson, I.] Karolinska Inst, Stockholm, Sweden.
[Beeson, W. L.; Fraser, G.] Loma Linda Univ, Loma Linda, CA 92350 USA.
[Peto, J.] Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England.
[Hanson, R. L.; Leske, M. C.; Mahoney, M. C.; Nasca, P. C.; Varma, A. O.; Weinstein, A. L.] Long Isl Breast Canc Study, Long Isl City, NY USA.
[Hartman, M. L.; Olsson, H.] Univ Hosp, Lund, Sweden.
[Goldbohm, R. A.; van den Brandt, P. A.] Maastricht Univ, Maastricht, Netherlands.
[Palli, D.] ISPO, Mol & Nutrit Epidemiol Unit, Florence, Italy.
[Teitelbaum, S.] Mt Sinai Sch Med, New York, NY 10029 USA.
[Apelo, R. A.; Baens, J.; de la Cruz, J. R.; Javier, B.; Lacaya, L. B.; Ngelangel, C. A.] Univ Philippines, Manila, Philippines.
[La Vecchia, C.; Negri, E.] Ist Mario Negri, Milan, Italy.
[La Vecchia, C.; Negri, E.] Univ Milan, I-20122 Milan, Italy.
[Marubini, E.] Ist Nazl Tumori, Div Stat Med & Biometria, Milan, Italy.
[Ferraroni, M.] Ist Stat Med & Biometria, Milan, Italy.
[Pike, M. C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Gerber, M.; Richardson, S.; Segala, C.] Montpellier Canc Ctr, Montpellier, France.
[Gerber, M.; Richardson, S.; Segala, C.] INSERM, Montpellier, France.
[Gatei, D.; Kenya, P.; Kungu, A.; Mati, J. G.] Nairobi Ctr Res Reprod, Nairobi, Kenya.
[Brinton, L. A.; Freedman, M.; Hoover, R.; Schairer, C.; Ziegler, R.] NCI, Bethesda, MD 20892 USA.
[Banks, E.] Australian Natl Univ, Natl Ctr Epidemiol & Populat Hlth, Canberra, ACT, Australia.
[Spirtas, R.] NICHHD, Bethesda, MD 20892 USA.
[Lee, H. P.] Natl Univ Singapore, Singapore 117548, Singapore.
[Rookus, M. A.; van Leeuwen, F. E.] Netherlands Canc Inst, Amsterdam, Netherlands.
[Schoenberg, J. A.] New Jersey State Dept Hlth, Trenton, NJ 08625 USA.
[Graff-Iversen, S.; Selmer, R.] Norwegian Inst Publ Hlth, Oslo, Norway.
[Jones, L.; McPherson, K.; Neil, A.; Vessey, M.; Yeates, D.] Dept Publ Hlth, Oxford, England.
[Mabuchi, K.; Preston, D.] Radiat Effects Res Fdn, Hiroshima, Japan.
[Hannaford, P.; Kay, C.] Royal Coll Gen Practitioners Oral Contracept Study, London, England.
[McCann, S. E.] Roswell Pk Canc Inst, New York, NY USA.
[Rosero-Bixby, L.] Univ Costa Rica, San Jose, Costa Rica.
[Gao, Y. T.; Jin, F.; Yuan, J-M] Shanghai Canc Inst, Shanghai, Peoples R China.
[Wei, H. Y.; Yun, T.; Zhiheng, C.] Shanghai Inst Planned Parenthood Res, Shanghai, Peoples R China.
[Berry, G.; Booth, J. Cooper; Jelihovsky, T.; MacLennan, R.; Shearman, R.] Univ Sydney, Dept Publ Hlth, Sydney, NSW 2006, Australia.
[Hadjisavvas, A.; Kyriacou, K.; Loisidou, M.] Cyprus Inst Neurol & Genet, Nicosia, Cyprus.
[Zhou, X.] Wuhan Univ, Zhongman Hosp, Wuhan 430072, Peoples R China.
[Wang, Q-S] Tianjin Canc Inst, Tianjin, Peoples R China.
[Kawai, M.; Minami, Y.; Tsuji, I.] Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan.
[Lund, E.; Kumle, M.; Stalsberg, H.] Univ Tromso, Tromso, Norway.
[Shu, X. O.; Zheng, W.] Vanderbilt Univ, Nashville, TN USA.
[Monninkhof, E. M.; Onland-Moret, N. C.; Peeters, P. H. M.] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Katsouyanni, K.; Trichopoulou, A.; Trichopoulos, D.; Tzonou, A.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Baltzell, K. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Dabancens, A.; Martinez, L.; Molina, R.; Salas, O.] Univ Chile, Santiago, Chile.
[Alexander, F. E.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Anderson, K.; Folsom, A. R.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Gammon, M. D.; Hulka, B. S.; Millikan, R.] Univ N Carolina Chapel Hill, Sch Publ Hlth, Chapel Hill, NC USA.
[Chilvers, C. E. D.] Univ Nottingham, Nottingham NG7 2RD, England.
[Lumachi, F.] Univ Padua, Sch Med, Padua, Italy.
[Bain, C.; Schofield, F.; Siskind, V.] Univ Queensland, Brisbane, Qld, Australia.
[Rebbeck, T. R.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Bernstein, L. R.; Enger, S.; Haile, R. W.; Paganini-Hill, A.; Ross, R. K.; Ursin, G.; Wu, A. H.; Yu, M. C.] Univ So Calif, Los Angeles, CA USA.
[Ewertz, Denmark M.] Univ So Denmark, Odense Univ Hosp, Dept Oncol, Odense, Denmark.
[Clarke, E. A.] Univ Toronto, Toronto, ON, Canada.
[Kalache, A.; Farley, T. M. M.; Holck, S.; Meirik, O.] World Hlth Org, World Bank Special Programme Res, UNDP, UNFPA, Geneva, Switzerland.
[Fukao, A.] Yamagata Univ, Grad Sch Med, Yamagata 990, Japan.
RP Beral, V (reprint author), Univ Oxford, Canc Epidemiol Unit, Richard Doll Bldg, Oxford OX3 7LF, England.
RI Tsugane, Shocichiro/A-2424-2015; Heuch, Ivar/A-4510-2008; Negri,
Eva/B-7244-2013; KAWAI, MASAAKI/B-3461-2008; Jacobs, Ian/F-1743-2013;
Boutron Ruault, Marie-Christine/G-3705-2013; Boutron,
Marie-Christine/K-8168-2013; Loizidou, Maria/C-6607-2009; Hakansson,
Niclas/L-7913-2013; Clavel-Chapelon, Francoise/G-6733-2014; ANDRIEU,
Nadine/H-4255-2014; de Sanjose Llongueras, Silvia/H-6339-2014; Hartman,
Mikael/B-4324-2011; Boutron-Ruault, Marie-Christine/H-3936-2014;
Brinton, Louise/G-7486-2015; Onland-Moret, N. Charlotte/G-9185-2011;
Lumachi, Franco/K-9501-2015; Hamajima, Nobuyuki/I-7237-2014; IBIS,
GENICA/O-1906-2015; Richardson, Sylvia/G-4691-2015; Weiderpass,
Elisabete/M-4029-2016; Ferraroni, Monica/D-6548-2017;
OI Heuch, Ivar/0000-0003-3386-9688; Negri, Eva/0000-0001-9712-8526; KAWAI,
MASAAKI/0000-0003-1383-0487; Jacobs, Ian/0000-0002-8112-4624; Hakansson,
Niclas/0000-0001-7673-5554; Lissowska, Jolanta/0000-0003-2695-5799;
Sitas, Freddy/0000-0001-9679-1481; La Vecchia,
Carlo/0000-0003-1441-897X; Yuan, Jian-Min/0000-0002-4620-3108; Bishop,
Tim/0000-0002-8752-8785; PALLI, Domenico/0000-0002-5558-2437; Cauley,
Jane A/0000-0003-0752-4408; Brinton, Louise/0000-0003-3853-8562;
Lumachi, Franco/0000-0001-8349-631X; Richardson,
Sylvia/0000-0003-1998-492X; Weiderpass, Elisabete/0000-0003-2237-0128;
Ferraroni, Monica/0000-0002-4542-4996; Magnusson,
Cecilia/0000-0002-8567-6725
FU Cancer Research UK
FX Funding for this collaborative reanalysis of original data was provided
by Cancer Research UK. Funding for the contributing studies is described
in the publications of those studies.
NR 25
TC 100
Z9 101
U1 2
U2 59
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
J9 LANCET ONCOL
JI Lancet Oncol.
PD NOV
PY 2012
VL 13
IS 11
BP 1141
EP 1151
DI 10.1016/S1470-2045(12)70425-4
PG 11
WC Oncology
SC Oncology
GA 030KZ
UT WOS:000310570900045
ER
PT J
AU Comenzo, RL
Reece, D
Palladini, G
Seldin, D
Sanchorawala, V
Landau, H
Falk, R
Wells, K
Solomon, A
Wechalekar, A
Zonder, J
Dispenzieri, A
Gertz, M
Streicher, H
Skinner, M
Kyle, RA
Merlini, G
AF Comenzo, R. L.
Reece, D.
Palladini, G.
Seldin, D.
Sanchorawala, V.
Landau, H.
Falk, R.
Wells, K.
Solomon, A.
Wechalekar, A.
Zonder, J.
Dispenzieri, A.
Gertz, M.
Streicher, H.
Skinner, M.
Kyle, R. A.
Merlini, G.
TI Consensus guidelines for the conduct and reporting of clinical trials in
systemic light-chain amyloidosis
SO LEUKEMIA
LA English
DT Review
DE amyloidosis; free light chains; clinical trials; clinical research
ID STEM-CELL TRANSPLANTATION; BRAIN NATRIURETIC PEPTIDE; HIGH-DOSE
MELPHALAN; SERUM CARDIAC TROPONINS; TWICE-WEEKLY BORTEZOMIB; AL
AMYLOIDOSIS; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHIES;
INTRAVENOUS MELPHALAN; MOLECULAR-MECHANISMS
AB This manuscript summarizes the recommendations that emerged from the first Roundtable on Clinical Research in Immunoglobulin Light-chain Amyloidosis (AL), a meeting sponsored by the Amyloidosis Foundation (Clarkston, MI, USA) to develop a consensus of experts on a modern framework for clinical trial design and drug development in AL. Recent diagnostic and technical advances in AL, and updated consensus guidelines for assessing hematologic and organ responses, enable us to define study populations, appropriate end points, and other criteria for all phases of clinical research. This manuscript provides a framework for the design and conduct of systematic collaborative clinical research in AL to encourage more rapid testing of therapies and to expedite new drug development and approval.
C1 [Comenzo, R. L.] Tufts Med Ctr, Blood Bank, Div Hematol Oncol, Boston, MA 02111 USA.
[Reece, D.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Palladini, G.; Merlini, G.] Univ Pavia, Fdn IRCCS Policlin San Matteo, I-27100 Pavia, Italy.
[Seldin, D.; Sanchorawala, V.; Skinner, M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Landau, H.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Falk, R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wells, K.; Solomon, A.] Univ Tennessee, Grad Sch Med, Knoxville, TN USA.
[Wechalekar, A.] UCL, London, England.
[Zonder, J.] Barbara Ann Karmanos Canc Inst, Detroit, MI USA.
[Dispenzieri, A.; Gertz, M.; Kyle, R. A.] Mayo Clin, Rochester, MN USA.
[Streicher, H.] NCI, Washington, DC USA.
RP Comenzo, RL (reprint author), Tufts Med Ctr, Blood Bank, Div Hematol Oncol, 800 Washington St, Boston, MA 02111 USA.
EM rcomenzo@tuftsmedicalcenter.org
RI Palladini, Giovanni/G-1763-2010;
OI Palladini, Giovanni/0000-0001-5994-5138; Merlini,
Giampaolo/0000-0001-7680-3254; Dispenzieri, Angela/0000-0001-8780-9512
NR 53
TC 59
Z9 64
U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD NOV
PY 2012
VL 26
IS 11
BP 2317
EP 2325
DI 10.1038/leu.2012.100
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 033JL
UT WOS:000310791300003
PM 22475872
ER
PT J
AU O'Connor, FG
Bergeron, MF
Cantrell, J
Connes, P
Harmon, KG
Ivy, E
Kark, J
Klossner, D
Lisman, P
Meyers, BK
O'Brien, K
Ohene-Frempong, K
Thompson, AA
Whitehead, J
Deuster, PA
AF O'Connor, Francis G.
Bergeron, Michael F.
Cantrell, Joyce
Connes, Philippe
Harmon, Kimberly G.
Ivy, Edward
Kark, John
Klossner, Dave
Lisman, Peter
Meyers, Bryce K.
O'Brien, Karen
Ohene-Frempong, Kwaku
Thompson, Alexis A.
Whitehead, James
Deuster, Patricia A.
TI ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for
Warfighters and Athletes
SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
LA English
DT Article
DE ATHLETIC HEALTH; EXERCISE COLLAPSE; HEMOGLOBINOPATHIES; RISK MANAGEMENT
ID SUDDEN-DEATH; ALPHA-THALASSEMIA; BLOOD RHEOLOGY; ADHESION MOLECULES;
ARMED-FORCES; EXERTIONAL RHABDOMYOLYSIS; MALIGNANT HYPERTHERMIA;
EXERCISE PERFORMANCE; ENDURANCE EXERCISE; STRENUOUS EXERCISE
AB O'CONNOR, F. G., M. F. BERGERON, J. CANTRELL, P. CONNES, K. G. HARMON, E. IVY, J. KARK, D. KLOSSNER, P. LISMAN, B. K. MEYERS, K. 0 BRIEN, K. OHENE-FREMPONG, A. A. THOMPSON, J. WHITEHEAD, AND P. A. DEUSTER. ACSM and CHAMP Summit on Sickle Cell Trait: Mitigating Risks for Warfighters and Athletes. Med. Set. Sports Ererc., Vol. 44, No. 11, pp. 2045-2056, 2012. Introduction: An estimated 300 million people worldwide have sickle cell trait (SCT). Although largely benign, SCT has been associated with exertional rhabdomyolysis and exercise-related sudden death in warfighters/athletes (WA). The National Collegiate Athletic Association's policy to confirm a student athlete's SCT status during their preparticipation medical examination prompted reaction from some organizations regarding the rationale and ethical justification of the policy. Methods: On September 26 and 27, 2011, a summit, composed of military and civilian experts in sports medicine and SCT, was convened at the Uniformed Services University in Bethesda, MD. The expert panel was charged with two objectives: 1) to provide specific recommendations to further mitigate the apparent risk with strenuous exercise in WA with SCT and 2) to develop clinical guidelines to identify, treat, and return to duty/play WA suspected to have incurred nonfatal sickle cell collapse. Results: New terminology is introduced, areas of current controversy are explored, consensus recommendations for mitigating risk and managing the WA with SCT are reviewed, and important areas for future research are identified. Conclusion: Further research is needed before conclusions can be drawn regarding the etiology of the increased death rate observed in WA with SCT, and the possibility exists that SCT is a surrogate for as yet another contributing factor for the unexplained deaths.
C1 [O'Connor, Francis G.; Lisman, Peter; Deuster, Patricia A.] Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA.
[Bergeron, Michael F.] Sanford USD Med Ctr, Natl Inst Athlet Hlth & Performance, Sioux Falls, SD USA.
[Cantrell, Joyce] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA.
[Connes, Philippe] Univ Antilles Guyane, INSERM, UMR 665, Pointe A Pitre, Guadeloupe.
[Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA.
[Harmon, Kimberly G.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA.
[Ivy, Edward] NHLBI, Bethesda, MD 20892 USA.
[Kark, John] Howard Univ Hosp, Div Hematol Oncol, Washington, DC USA.
[Klossner, Dave] Natl Collegiate Athlet Assoc, Indianapolis, IN USA.
[Meyers, Bryce K.] Walter Reed Army Inst Res, Div Prevent Med, Silver Spring, MD USA.
[O'Brien, Karen] Madigan Army Med Ctr, Tacoma, WA 98431 USA.
[Ohene-Frempong, Kwaku] Childrens Hosp Philadelphia, Ctr Comprehens Sickle Cell, Philadelphia, PA 19104 USA.
[Thompson, Alexis A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Whitehead, James] Amer Coll Sports Med, Indianapolis, IN USA.
RP O'Connor, FG (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM francis.oconnor@usuhs.edu
RI Deuster, Patricia/G-3838-2015;
OI Deuster, Patricia/0000-0002-7895-0888; Philippe,
Connes/0000-0001-8449-7998
NR 100
TC 21
Z9 21
U1 0
U2 12
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0195-9131
J9 MED SCI SPORT EXER
JI Med. Sci. Sports Exerc.
PD NOV
PY 2012
VL 44
IS 11
BP 2045
EP 2056
DI 10.1249/MSS.0b013e31826851c2
PG 12
WC Sport Sciences
SC Sport Sciences
GA 024QD
UT WOS:000310122800001
PM 22811029
ER
PT J
AU Gorbach, AM
Ackerman, HC
Liu, WM
Meyer, JM
Littel, PL
Seamon, C
Footman, E
Chi, A
Zorca, S
Krajewski, ML
Cuttica, MJ
Machado, RF
Cannon, RO
Kato, GJ
AF Gorbach, Alexander M.
Ackerman, Hans C.
Liu, Wei-Min
Meyer, Joseph M.
Littel, Patricia L.
Seamon, Catherine
Footman, Eleni
Chi, Amy
Zorca, Suzana
Krajewski, Megan L.
Cuttica, Michael J.
Machado, Roberto F.
Cannon, Richard O., III
Kato, Gregory J.
TI Infrared imaging of nitric oxide-mediated blood flow in human sickle
cell disease
SO MICROVASCULAR RESEARCH
LA English
DT Article
ID PULMONARY-HYPERTENSION; ENDOTHELIAL DYSFUNCTION; TRANSCRANIAL DOPPLER;
RISK-FACTORS; ANEMIA; VASODILATION; HEMOGLOBIN; CHILDREN;
CATHETERIZATION; MORTALITY
AB Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1 degrees C, p<0.0001) and SNP (+0.9 degrees C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8 +/- 0.2 degrees C. 6.0 +/- 0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R-2=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD. Published by Elsevier Inc.
C1 [Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Gorbach, Alexander M.; Liu, Wei-Min; Meyer, Joseph M.] Natl Inst Biomed Imaging & Bioengn, Infrared Imaging & Thermometry Unit, NIH, Bethesda, MD USA.
[Littel, Patricia L.; Seamon, Catherine; Footman, Eleni; Chi, Amy; Zorca, Suzana; Krajewski, Megan L.; Cuttica, Michael J.; Machado, Roberto F.; Kato, Gregory J.] NHLBI, Sickle Cell Vasc Dis Sect, Hematol Branch, NIH, Bethesda, MD USA.
[Cannon, Richard O., III] NHLBI, Clin Cardiol Sect, Cardiovasc & Pulm Branch, NIH, Bethesda, MD USA.
[Ackerman, Hans C.; Cuttica, Michael J.; Machado, Roberto F.; Kato, Gregory J.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD USA.
RP Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM hans.ackerman@nih.gov
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Division of Intramural Research, National Heart, Lung and Blood
Institute; National Institute of Biomedical Imaging and Bioengineering
[1ZIAHL006017]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases
FX The authors gratefully acknowledge the expert protocol management by
Mary K. Hall, CIP. We thank Dr. E. Elster, Department of Surgery,
National Naval Medical Center, for encouraging us to use infrared
imaging in this study. This study was funded by the Division of
Intramural Research, National Heart, Lung and Blood Institute and the
National Institute of Biomedical Imaging and Bioengineering
(1ZIAHL006017). HCA is supported by the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases. The authors thank
the staff of the NIH Clinical Center Procedure Unit and the patients
with sickle cell disease who participated in this study.
NR 40
TC 9
Z9 9
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 0026-2862
EI 1095-9319
J9 MICROVASC RES
JI Microvasc. Res.
PD NOV
PY 2012
VL 84
IS 3
BP 262
EP 269
DI 10.1016/j.mvr.2012.06.011
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 034GZ
UT WOS:000310862200005
PM 22784510
ER
PT J
AU Rone, MB
Midzak, AS
Issop, L
Rammouz, G
Jagannathan, S
Fan, JJ
Ye, XY
Blonder, J
Veenstra, T
Papadopoulos, V
AF Rone, Malena B.
Midzak, Andrew S.
Issop, Leeyah
Rammouz, Georges
Jagannathan, Sathvika
Fan, Jinjiang
Ye, Xiaoying
Blonder, Josip
Veenstra, Timothy
Papadopoulos, Vassilios
TI Identification of a Dynamic Mitochondrial Protein Complex Driving
Cholesterol Import, Trafficking, and Metabolism to Steroid Hormones
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID ACUTE REGULATORY PROTEIN; SIDE-CHAIN CLEAVAGE; BENZODIAZEPINE-RECEPTOR;
ENDOPLASMIC-RETICULUM; CELL-DEATH; IN-VITRO; STEROIDOGENESIS; BINDING;
BIOSYNTHESIS; TRANSPORT
AB Steroid hormones are critical for organismal development and health. The rate-limiting step in steroidogenesis is the transport of cholesterol from the outer mitochondrial membrane (OMM) to the cytochrome P450 enzyme CYP11A1 in the inner mitochondrial membrane (IMM). Cholesterol transfer occurs through a complex termed the "transduceosome," in which cytosolic steroidogenic acute regulatory protein interacts with OMM proteins translocator protein and voltage-dependent anion channel (VDAC) to assist with the transfer of cholesterol to OMM. It has been proposed that cholesterol transfer from OMM to IMM occurs at specialized contact sites bridging the two membranes composed of VDAC and IMM adenine nucleotide translocase (ANT). Blue native PAGE of Leydig cell mitochondria identified two protein complexes that were able to bind cholesterol at 66- and 800-kDa. Immunoblot and mass spectrometry analyses revealed that the 800-kDa complex contained the OMM translocator protein (18-kDa) and VDAC along with IMM CYP11A1, ATPase family AAA domain-containing protein 3A (ATAD3A), and optic atrophy type 1 proteins, but not ANT. Knockdown of ATAD3A, but not ANT or optic atrophy type 1, in Leydig cells resulted in a significant decrease in hormone-induced, but not 22R-hydroxycholesterol-supported, steroid production. Using a 22-phenoxazonoxy-5-cholene-3-beta-ol CYP11A1-specific probe, we further demonstrated that the 800-kDa complex offers the microenvironment needed for CYP11A1 activity. Addition of steroidogenic acute regulatory protein to the complex mobilized the cholesterol bound at the 800-kDa complex, leading to increased steroid formation. These results identify a bioactive, multimeric protein complex spanning the OMM and IMM unit that is responsible for the hormone-induced import, segregation, targeting, and metabolism of cholesterol. (Molecular Endocrinology 26: 1868-1882, 2012)
C1 [Papadopoulos, Vassilios] McGill Univ, Ctr Hlth, Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada.
[Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada.
[Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada.
[Rone, Malena B.; Midzak, Andrew S.; Issop, Leeyah; Rammouz, Georges; Jagannathan, Sathvika; Fan, Jinjiang; Papadopoulos, Vassilios] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1A4, Canada.
[Ye, Xiaoying; Blonder, Josip; Veenstra, Timothy] SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Ft Detrick, MD 21702 USA.
RP Papadopoulos, V (reprint author), McGill Univ, Ctr Hlth, Montreal Gen Hosp, 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 Canadian Institutes of Health Research [MOP102647, TGF36110]; Canada
Research Chair in Biochemical Pharmacology; Research Institute of McGill
University Health Center; Le Fonds de la recherche du Quebec-sante
FX This work was supported by a grant from the Canadian Institutes of
Health Research (MOP102647) and a Canada Research Chair in Biochemical
Pharmacology (to V.P.). M.R. was supported in part by a postdoctoral
fellowship from The Research Institute of McGill University Health
Center. A.M. was supported by postdoctoral fellowships from the Canadian
Institutes of Health Research (TGF36110) and Le Fonds de la recherche du
Quebec-sante. The Research Institute of McGill University Health Center
was supported by a Center grant from Le Fonds de la recherche du
Quebec-sante.
NR 38
TC 67
Z9 68
U1 1
U2 21
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD NOV
PY 2012
VL 26
IS 11
BP 1868
EP 1882
DI 10.1210/me.2012-1159
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 030QJ
UT WOS:000310584900008
PM 22973050
ER
PT J
AU Bouladoux, N
Hall, JA
Grainger, JR
dos Santos, LM
Kann, MG
Nagarajan, V
Verthelyi, D
Belkaid, Y
AF Bouladoux, N.
Hall, J. A.
Grainger, J. R.
dos Santos, L. M.
Kann, M. G.
Nagarajan, V.
Verthelyi, D.
Belkaid, Y.
TI Regulatory role of suppressive motifs from commensal DNA
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL IMMUNE-RESPONSES; RETINOIC-ACID;
T-CELLS; TOXOPLASMA-GONDII; IFN-GAMMA; DENDRITIC CELLS; BACTERIAL-DNA;
CPG MOTIFS; OLIGODEOXYNUCLEOTIDES
AB The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T-reg cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes.
C1 [Bouladoux, N.; Hall, J. A.; Grainger, J. R.; dos Santos, L. M.; Belkaid, Y.] NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Hall, J. A.] NYU, Sch Med, Skirball Inst, Kimmel Ctr Biol & Med, New York, NY USA.
[dos Santos, L. M.] Univ Fed Minas Gerais, Lab Gnotobiol & Immunol LAGI, Belo Horizonte, MG, Brazil.
[Kann, M. G.] Univ Maryland, Baltimore, MD 21201 USA.
[Nagarajan, V.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD USA.
[Verthelyi, D.] Ctr Drug Evaluat & Res, Food & Drug Adm, Div Therapeut Proteins, Immunol Lab, Bethesda, MD USA.
RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
EM ybelkaid@niaid.nih.gov
OI Grainger, John/0000-0002-4052-5923
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. We thank C Eigsti and E Stregevsky from the NIAID sorting
facility and K Beacht, V Wang, and T Peterson for technical assistance.
We thank D Chou, M Molloy, S Naik, S Spencer, and E Wohlfert for their
critical reading of the manuscript.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2012
VL 5
IS 6
BP 623
EP 634
DI 10.1038/mi.2012.36
PG 12
WC Immunology
SC Immunology
GA 030LS
UT WOS:000310572800005
PM 22617839
ER
PT J
AU Klatt, NR
Estes, JD
Sun, X
Ortiz, AM
Barber, JS
Harris, LD
Cervasi, B
Yokomizo, LK
Pan, L
Vinton, CL
Tabb, B
Canary, LA
Dang, Q
Hirsch, VM
Alter, G
Belkaid, Y
Lifson, JD
Silvestri, G
Milner, JD
Paiardini, M
Haddad, EK
Brenchley, JM
AF Klatt, N. R.
Estes, J. D.
Sun, X.
Ortiz, A. M.
Barber, J. S.
Harris, L. D.
Cervasi, B.
Yokomizo, L. K.
Pan, L.
Vinton, C. L.
Tabb, B.
Canary, L. A.
Dang, Q.
Hirsch, V. M.
Alter, G.
Belkaid, Y.
Lifson, J. D.
Silvestri, G.
Milner, J. D.
Paiardini, M.
Haddad, E. K.
Brenchley, J. M.
TI Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is
associated with mucosal damage in SIV infection
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS;
RETINOIC-ACID; MICROBIAL TRANSLOCATION; HIV-INFECTION; IMMUNE
ACTIVATION; TH17 CELLS; GENE-EXPRESSION; DENDRITIC CELLS
AB Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of CD103+ DCs and naive T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis.
C1 [Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA.
[Estes, J. D.; Tabb, B.; Lifson, J. D.] Frederick Natl Lab Canc Res, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD USA.
[Sun, X.; Pan, L.; Haddad, E. K.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
[Ortiz, A. M.; Cervasi, B.; Silvestri, G.; Paiardini, M.] Emory Univ, Yerkes Natl Primate Res Ctr, Pathol & Lab Med, Atlanta, GA 30322 USA.
[Ortiz, A. M.] Univ Penn, Sch Med, Cellular & Mol Biol Program, Philadelphia, PA 19104 USA.
[Barber, J. S.; Yokomizo, L. K.; Milner, J. D.] NIAD, Lab Allerg Dis, NIH, Bethesda, MD USA.
[Alter, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst, Boston, MA USA.
[Belkaid, Y.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jbrenchl@mail.nih.gov
FU Intramural National Institute of Allergy and Infectious Diseases, US
National Institutes of Health program; National Cancer Institute,
National Institutes of Health [HHSN261200800001E]; National Institutes
of Health [R01 AI-084836]
FX We would like to acknowledge Heather Cronise, JoAnne Swerczek, Richard
Herbert, and all the veterinary staff at the NIH animal center. We would
like to thank Tracy Meeker and Stephanie Ehnert, and the veterinary
staff at YNPRC. We would like to thank the Cleveland Immunopathogenesis
Consortium (BBC/CLIC) for advice and helpful discussions. We would like
to thank Mark Cameron and Peter Wilkinson from the Genomics core at
VGTI-FL for gene array consultation. Histology support was provided by
the Pathology/Histotechnology Laboratory (PHL) core service located at
the National Cancer Institute-Frederick, Frederick, MD, USA. These
studies were supported by the Intramural National Institute of Allergy
and Infectious Diseases, US National Institutes of Health program, and
in part with federal funds from the National Cancer Institute, National
Institutes of Health, under Contract No. HHSN261200800001E, and National
Institutes of Health R01 AI-084836 under M Paiardini. 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
United States.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2012
VL 5
IS 6
BP 646
EP 657
DI 10.1038/mi.2012.38
PG 12
WC Immunology
SC Immunology
GA 030LS
UT WOS:000310572800007
PM 22643849
ER
PT J
AU Sundaresan, NR
Vasudevan, P
Zhong, L
Kim, G
Samant, S
Parekh, V
Pillai, VB
Ravindra, PV
Gupta, M
Jeevanandam, V
Cunningham, JM
Deng, CX
Lombard, DB
Mostoslavsky, R
Gupta, MP
AF Sundaresan, Nagalingam R.
Vasudevan, Prabhakaran
Zhong, Lei
Kim, Gene
Samant, Sadhana
Parekh, Vishwas
Pillai, Vinodkumar B.
Ravindra, P. V.
Gupta, Madhu
Jeevanandam, Valluvan
Cunningham, John M.
Deng, Chu-Xia
Lombard, David B.
Mostoslavsky, Raul
Gupta, Mahesh P.
TI The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac
hypertrophy by targeting c-Jun
SO NATURE MEDICINE
LA English
DT Article
ID HEAVY-CHAIN EXPRESSION; FOCAL ADHESION KINASE; REGULATES LIFE-SPAN;
CALORIE RESTRICTION; HISTONE DEACETYLASE; GENE-EXPRESSION;
HEART-FAILURE; MICE; ACTIVATION; DISEASE
AB Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy. SIRT6-deficient mouse hearts showed hyperactivation of IGF signaling-related genes and their downstream targets. Mechanistically, SIRT6 binds to and suppresses the promoter of IGF signaling-related genes by interacting with c-Jun and deacetylating histone 3 at Lys9 (H3K9). We also found reduced SIRT6 expression in human failing hearts. These findings disclose a new link between SIRT6 and IGF-Akt signaling and implicate SIRT6 in the development of cardiac hypertrophy and failure.
C1 [Sundaresan, Nagalingam R.; Samant, Sadhana; Pillai, Vinodkumar B.; Ravindra, P. V.; Jeevanandam, Valluvan; Gupta, Mahesh P.] Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, Chicago, IL 60637 USA.
[Vasudevan, Prabhakaran; Parekh, Vishwas; Cunningham, John M.] Univ Chicago, Dept Pediat, Comm Dev Biol, Chicago, IL 60637 USA.
[Zhong, Lei; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA.
[Kim, Gene] Univ Chicago, Cardiol Sect, Dept Med, Chicago, IL 60637 USA.
[Gupta, Madhu] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA.
[Deng, Chu-Xia] NIDDKD, US NIH, Bethesda, MD 20892 USA.
[Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA.
RP Gupta, MP (reprint author), Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM mgupta@surgery.bsd.uchicago.edu
RI Parekh, Vishwas/B-7162-2014; deng, chuxia/N-6713-2016;
OI Parekh, Vishwas/0000-0003-3131-2958; Ravindra, P V/0000-0003-4228-1843
FU US National Institutes of Health [RO1 HL-117041, HL-83423, 111455];
American Heart Association
FX We thank F. Alt, Harvard Medical School, for providing SIRT6 knockout
mice, E. Verdin, University of California, San Francisco, for providing
Flag-SIRT6 wild-type and mutant plasmids, F. VanGool, Institut de
Biologie, Universite Libre de Bruxelles, Gosselies, Belgium, for
providing mouse-SIRT6 expression plasmid and K. Chua, Stanford
University, for providing SIRT6 retroviral vectors and SIRT6 knockout
MEFs. The alpha-MHC promoter vector used to make cardiac-specific SIRT6
transgenic mice was provided by J. Robbins, University of Cincinnati.
This study was supported by US National Institutes of Health grants RO1
HL-117041, HL-83423 and 111455 to M. P. G. N.R.S. was supported by a
postdoctoral fellowship from the American Heart Association.
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2012
VL 18
IS 11
BP 1643
EP +
DI 10.1038/nm.2961
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 033YJ
UT WOS:000310837000024
PM 23086477
ER
PT J
AU Fukazawa, Y
Park, H
Cameron, MJ
Lefebvre, F
Lum, R
Coombes, N
Mahyari, E
Hagen, SI
Bae, JY
Delos Reyes, M
Swanson, T
Legasse, AW
Sylwester, A
Hansen, SG
Smith, AT
Stafova, P
Shoemaker, R
Li, Y
Oswald, K
Axthelm, MK
McDermott, A
Ferrari, G
Montefiori, DC
Edlefsen, PT
Piatak, M
Lifson, JD
Sekaly, RP
Picker, LJ
AF Fukazawa, Yoshinori
Park, Haesun
Cameron, Mark J.
Lefebvre, Francois
Lum, Richard
Coombes, Noel
Mahyari, Eisa
Hagen, Shoko I.
Bae, Jin Young
Delos Reyes, Marcelo, III
Swanson, Tonya
Legasse, Alfred W.
Sylwester, Andrew
Hansen, Scott G.
Smith, Andrew T.
Stafova, Petra
Shoemaker, Rebecca
Li, Yuan
Oswald, Kelli
Axthelm, Michael K.
McDermott, Adrian
Ferrari, Guido
Montefiori, David C.
Edlefsen, Paul T.
Piatak, Michael, Jr.
Lifson, Jeffrey D.
Sekaly, Rafick P.
Picker, Louis J.
TI Lymph node T cell responses predict the efficacy of live attenuated SIV
vaccines
SO NATURE MEDICINE
LA English
DT Article
ID SIMIAN-IMMUNODEFICIENCY-VIRUS; FOLLICULAR HELPER; RHESUS-MONKEYS;
CONTROL REPLICATION; ANTIBODY-RESPONSES; VIRAL LOAD; NEF GENE; MEMORY;
PROTECTION; CHALLENGE
AB Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.
C1 [Fukazawa, Yoshinori; Park, Haesun; Lum, Richard; Coombes, Noel; Mahyari, Eisa; Hagen, Shoko I.; Bae, Jin Young; Delos Reyes, Marcelo, III; Swanson, Tonya; Legasse, Alfred W.; Sylwester, Andrew; Hansen, Scott G.; Axthelm, Michael K.; Picker, Louis J.] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.
[Fukazawa, Yoshinori; Park, Haesun; Lum, Richard; Coombes, Noel; Mahyari, Eisa; Hagen, Shoko I.; Bae, Jin Young; Delos Reyes, Marcelo, III; Swanson, Tonya; Legasse, Alfred W.; Sylwester, Andrew; Hansen, Scott G.; Axthelm, Michael K.; Edlefsen, Paul T.; Picker, Louis J.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA.
[Cameron, Mark J.; Lefebvre, Francois; Smith, Andrew T.; Stafova, Petra; Sekaly, Rafick P.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA.
[Shoemaker, Rebecca; Li, Yuan; Oswald, Kelli; Piatak, Michael, Jr.; Lifson, Jeffrey D.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD USA.
[McDermott, Adrian] US NIAID, Vaccine Res Inst, Bethesda, MD USA.
[Ferrari, Guido; Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC USA.
[Edlefsen, Paul T.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
RP Picker, LJ (reprint author), Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA.
EM pickerl@ohsu.edu
RI Ferrari, Guido/A-6088-2015; mahyari, eisa/L-2002-2016
OI mahyari, eisa/0000-0002-5613-3131
FU Bill and Melinda Gates Foundation [41185]; International AIDS Vaccine
Initiative (IAVI); National Institute of Allergy and Infectious Diseases
FX This work was supported by the Bill and Melinda Gates Foundation (grant
#41185), the International AIDS Vaccine Initiative (IAVI), the National
Institute of Allergy and Infectious Diseases (including the US National
Institutes of Health (NIH) kits (Ambion). The microarray analysis was
conducted using 750 ng of biotinylated complementary RNA hybridized to
HumanHT-12_V4 BeadChips (Illumina) at 58 degrees C for 20 h. The arrays
were scanned using Illumina's iSCAN and quantified using Genome Studio
(Illumina). The analysis of the GenomeStudio output data was conducted
using the R54 and Bioconductor55 software
packages. Quantile normalization was applied, followed by a
log2 transformation. The LIMMA package56 was used
to fit a linear model to each probe and perform (moderated) t tests or F
tests on the groups being compared. To control the expected proportions
of false positives, the FDR for each unadjusted P value was calculated
using the Benjamini and Hochberg method implemented in LIMMA.
Multidimensional scaling was used as a dimensionality reduction method
in R to generate plots for the evaluation of similarities or
dissimilarities between datasets. Ingenuity Pathway Analysis software
(IPA, Ingenuity Systems) was used to annotate genes and rank canonical
pathways. An immune response gene filter, constructed from innate and
adaptive immune response gene queries of Gene Ontology
(http://www.geneontology.org/),T cell activation and complement pathway
genes from IPA and our own IFN- and inflammasomeresponse gene
lists57, was used where noted to reduce datasets for
visualization before FDR estimation. The microarray data are available
through the National Center for Biotechnology Information Gene
Expression Omnibus (GEO superseries GSE40006).
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SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2012
VL 18
IS 11
BP 1673
EP +
DI 10.1038/nm.2934
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 033YJ
UT WOS:000310837000028
PM 22961108
ER
PT J
AU Wilson, RH
Maruoka, S
Whitehead, GS
Foley, JF
Flake, GP
Sever, ML
Zeldin, DC
Kraft, M
Garantziotis, S
Nakano, H
Cook, DN
AF Wilson, Rhonda H.
Maruoka, Shuichiro
Whitehead, Gregory S.
Foley, Julie F.
Flake, Gordon P.
Sever, Michelle L.
Zeldin, Darryl C.
Kraft, Monica
Garantziotis, Stavros
Nakano, Hideki
Cook, Donald N.
TI The Toll-like receptor 5 ligand flagellin promotes asthma by priming
allergic responses to indoor allergens
SO NATURE MEDICINE
LA English
DT Article
ID IMMUNE-RESPONSES; ENDOTOXIN EXPOSURE; AIRWAY HYPERRESPONSIVENESS;
BACTERIAL FLAGELLIN; BIRTH COHORT; CELLS; INNATE; INFLAMMATION;
SALMONELLA; PROTEIN
AB Allergic asthma is a complex disease characterized by eosinophilic pulmonary inflammation, mucus production and reversible airway obstruction(1). Exposure to indoor allergens is a risk factor for asthma, but this disease is also associated with high household levels of total and particularly Gram-negative bacteria(2). The ability of bacterial products to act as adjuvants(3) suggests they might promote asthma by priming allergic sensitization to inhaled allergens. In support of this idea, house dust extracts (HDEs) can activate antigen-presenting dendritic cells (DCs) in vitro and promote allergic sensitization to inhaled innocuous proteins in vivo(4). It is unknown which microbial products provide most of the adjuvant activity in HDEs. A screen for adjuvant activity of microbial products revealed that the bacterial protein flagellin (FLA) stimulated strong allergic airway responses to an innocuous inhaled protein, ovalbumin (OVA). Moreover, Toll-like receptor 5 (TLR5), the mammalian receptor for FLA(5,6), was required for priming strong allergic responses to natural indoor allergens present in HDEs. In addition, individuals with asthma have higher serum levels of FLA-specific antibodies as compared to nonasthmatic individuals. Together, these findings suggest that household FLA promotes the development of allergic asthma by TLR5-dependent priming of allergic responses to indoor allergens.
C1 [Wilson, Rhonda H.; Maruoka, Shuichiro; Whitehead, Gregory S.; Foley, Julie F.; Flake, Gordon P.; Sever, Michelle L.; Zeldin, Darryl C.; Garantziotis, Stavros; Nakano, Hideki; Cook, Donald N.] NIEHS, Biol Res Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Maruoka, Shuichiro] Nihon Univ, Sch Med, Div Resp Med, Tokyo, Japan.
[Kraft, Monica] Duke Univ, Med Ctr, Duke Asthma Allergy & Airway Ctr, Durham, NC USA.
RP Cook, DN (reprint author), NIEHS, Biol Res Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM cookd@niehs.nih.gov
RI Garantziotis, Stavros/A-6903-2009;
OI Garantziotis, Stavros/0000-0003-4007-375X; Sever,
Michelle/0000-0002-2435-1214
FU Intramural Research Program of the US National Institutes of Health
NIEHS
FX This work was supported by the Intramural Research Program of the US
National Institutes of Health NIEHS. We thank the human subjects for
their blood donations and B. Yingling, J. Marshburn and A. Rice of the
NIEHS Clinical Research Unit and D. Beaver of Duke University for
assistance with patient recruitment and serum isolation. J.
Hollingsworth (Duke University) with permission from R. Medzhitov (Yale
University) provided CD11c-Myd88 transgenic mice on a
Myd88-/- background. S. Akira (Osaka University) provided
Tlr2-/-, Tlr4-/- and Myd88-/- mice and
J. Ting (University of North Carolina) provided Nlrc4-/-
mice. D. Wozniak (Ohio State University) provided both strains of P.
aeruginosa, F.-S. Shu (Wayne State University) provided purified FLA
from P. aeruginosa and A. Gewirtz (Emory University) provided FLA from
Escherichia coli. We also thank NIEHS members K. Nakano for genotyping,
L. Perrow for mouse colony management, N. Flagler for histology, J.
Aloor for measuring endotoxin levels in HDEs, M. Sifre and C. Bortner
for help with FACS-based cell sorting, J. Ciencewicki for advice on
airway epithelial cell culture and M. Fessler and S. London for
suggestions on the manuscript.
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PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2012
VL 18
IS 11
BP 1705
EP +
DI 10.1038/nm.2920
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 033YJ
UT WOS:000310837000033
PM 23064463
ER
PT J
AU Gavara, N
Chadwick, RS
AF Gavara, Nuria
Chadwick, Richard S.
TI Determination of the elastic moduli of thin samples and adherent cells
using conical atomic force microscope tips
SO NATURE NANOTECHNOLOGY
LA English
DT Article
ID MECHANICAL-PROPERTIES; CANCER-DETECTION; AFM; APPLICABILITY;
MICRORHEOLOGY
AB The atomic force microscope can detect the mechanical fingerprints of normal and diseased cells at the single-cell level under physiological conditions(1,2). However, atomic force microscopy studies of cell mechanics are limited by the 'bottom effect' artefact that arises from the stiff substrates used to culture cells. Because cells adhered to substrates are very thin(3), this artefact makes cells appear stiffer than they really are(4). Here, we show an analytical correction that accounts for this artefact when conical tips are used for atomic force microscope measurements of thin samples. Our bottom effect cone correction (BECC) corrects the Sneddon's model(5), which is widely used to measure Young's modulus, E. Comparing the performance of BECC and Sneddon's model on thin polyacrylamide gels, we find that although Sneddon's model overestimates E, BECC yields E values that are thickness-independent and similar to those obtained on thick regions of the gel. The application of BECC to measurements on live adherent fibroblasts demonstrates a significant improvement on the estimation of their local mechanical properties.
C1 [Gavara, Nuria; Chadwick, Richard S.] Natl Inst Deafness & Other Commun Disorders, Auditory Mech Sect, NIH, Bethesda, MD 20892 USA.
RP Gavara, N (reprint author), Univ Gottingen, Drittes Phys Inst, Friedrich Hund Pl 1, D-37077 Gottingen, Germany.
EM chadwick@helix.nih.gov
FU US National Institute of Deafness and Other Communication Disorders
FX The authors thank R. Sunyer, V. Luo and K. M. Yamada for critical input.
This work was supported by the Intramural Program of the US National
Institute of Deafness and Other Communication Disorders.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD NOV
PY 2012
VL 7
IS 11
BP 733
EP 736
DI 10.1038/NNANO.2012.163
PG 4
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA 033JQ
UT WOS:000310791900013
PM 23023646
ER
PT J
AU Beers, J
Gulbranson, DR
George, N
Siniscalchi, LI
Jones, J
Thomson, JA
Chen, GK
AF Beers, Jeanette
Gulbranson, Daniel R.
George, Nicole
Siniscalchi, Lauren I.
Jones, Jeffrey
Thomson, James A.
Chen, Guokai
TI Passaging and colony expansion of human pluripotent stem cells by
enzyme-free dissociation in chemically defined culture conditions
SO NATURE PROTOCOLS
LA English
DT Article
ID HUMAN ES CELLS; HUMAN BLASTOCYSTS; SELF-RENEWAL; DIFFERENTIATION; LINES;
DERIVATION; SURVIVAL
AB This protocol describes an EDTA-based passaging procedure to be used with chemically defined E8 medium that serves as a tool for basic and translational research into human pluripotent stem cells (PSCs). In this protocol, passaging one six-well or 10-cm plate of cells takes about 6-7 min. This enzyme-free protocol achieves maximum cell survival without enzyme neutralization, centrifugation or drug treatment. It also allows for higher throughput, requires minimal material and limits contamination. Here we describe how to produce a consistent E8 medium for routine maintenance and reprogramming and how to incorporate the EDTA-based passaging procedure into human induced PSC (iPSC) derivation, colony expansion, cryopreservation and teratoma formation. This protocol has been successful in routine cell expansion, and efficient for expanding large-volume cultures or a large number of cells with preferential dissociation of PSCs. Effective for all culture stages, this procedure provides a consistent and universal approach to passaging human PSCs in E8 medium.
C1 [Beers, Jeanette; Siniscalchi, Lauren I.; Chen, Guokai] NHLBI, Ctr Mol Med, Bethesda, MD 20892 USA.
[Gulbranson, Daniel R.; Thomson, James A.; Chen, Guokai] Morgridge Inst Res, Madison, WI USA.
[Gulbranson, Daniel R.; Thomson, James A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Cell & Regenerat Biol, Madison, WI USA.
[George, Nicole; Jones, Jeffrey] WiCell Inst, Madison, WI USA.
[Jones, Jeffrey] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Thomson, James A.] Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
RP Chen, GK (reprint author), NHLBI, Ctr Mol Med, Bldg 10, Bethesda, MD 20892 USA.
EM guokai.chen@nih.gov
FU NHLBI, NIH Common Fund through the Center for Regenerative Medicine;
Charlotte Geyer Foundation; Morgridge Institute for Research, NIH grant
[UO1ES017166]; NIH [RR-05-19, HHSN309200582085C]; Wisconsin Alumni
Research Foundation
FX This work was supported by NHLBI, NIH Common Fund through the Center for
Regenerative Medicine (to G.C. and J.B.), the Charlotte Geyer
Foundation, the Morgridge Institute for Research, NIH grant UO1ES017166
(to J.A.T.), NIH contract RR-05-19 (to J.A.T.), NIH contract no.
HHSN309200582085C (to J.J.) and private funds from the Wisconsin Alumni
Research Foundation (to J.J.). We thank M. Boehm, T. Finkel and M. Rao
for their suggestions. We thank K. Eastman for editorial assistance.
NR 20
TC 67
Z9 67
U1 3
U2 37
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD NOV
PY 2012
VL 7
IS 11
BP 2029
EP 2040
DI 10.1038/nprot.2012.130
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 030QM
UT WOS:000310585200011
PM 23099485
ER
PT J
AU Fischer, RS
Myers, KA
Gardel, ML
Waterman, CM
AF Fischer, Robert S.
Myers, Kenneth A.
Gardel, Margaret L.
Waterman, Clare M.
TI Stiffness-controlled three-dimensional extracellular matrices for
high-resolution imaging of cell behavior
SO NATURE PROTOCOLS
LA English
DT Article
ID BRANCHING MORPHOGENESIS; FOCAL ADHESIONS; GROWTH CONES; STEM-CELLS;
IN-VITRO; SUBSTRATE; COLLAGEN; MIGRATION; CULTURE; ANGIOGENESIS
AB Regulation of cell functions by the physical properties of the extracellular matrix (ECM) has emerged as a crucial contributor to development and disease. Two specific physical properties of the ECM, stiffness and dimensionality, each influence cell signaling and function. As these ECM physical properties are linked to other properties that also regulate cell behavior, e. g., integrin ligand density, parsing the specific contributions of ECM stiffness and dimensionality has proven difficult. Here we detail a simple protocol, which can be completed in 1-2 d, for combining three-dimensional (3D) ECM engagement with controlled underlying ECM stiffness. In these 'sandwich gels', cells are sandwiched between a 3D fibrillar ECM and an ECM-coupled polyacrylamide gel of defined compliance, allowing the study of the specific effects of ECM compliance on cell function in physiologically relevant 3D ECMs. This type of system enables high-resolution time-lapse imaging and is suitable for a wide range of cell types and molecular perturbations.
C1 [Fischer, Robert S.; Waterman, Clare M.] Natl Heart Lung & Blood Inst NHBLI, Cell Biol & Physiol Ctr, US Natl Inst Hlth NIH, Bethesda, MD USA.
[Myers, Kenneth A.] Univ Sci, Dept Biol Sci, Philadelphia, PA USA.
[Gardel, Margaret L.] Univ Chicago, James Franck Inst, Chicago, IL 60637 USA.
[Gardel, Margaret L.] Inst Biophys Dynam, Chicago, IL USA.
[Gardel, Margaret L.] Univ Chicago, Dept Phys, Chicago, IL 60637 USA.
RP Waterman, CM (reprint author), Natl Heart Lung & Blood Inst NHBLI, Cell Biol & Physiol Ctr, US Natl Inst Hlth NIH, Bethesda, MD USA.
EM fischerr2@nhlbi.nih.gov; watermancm@nhlbi.nih.gov
OI Waterman, Clare/0000-0001-6142-6775
FU NHLBI Intramural Research Program; NIH Director's Pioneer Award
[DP10D00354]
FX R.S.F., K.A.M. and C.M.W. are supported by the NHLBI Intramural Research
Program. M.L.G. is supported by the NIH Director's Pioneer Award
(DP10D00354). We thank Sergey Plotnikov for insightful discussion. We
also acknowledge members of the NIH Electron Microscopy Core Facility
and are grateful for the particularly excellent technical skills of M.
Daniels and P. Connelly.
NR 76
TC 45
Z9 46
U1 5
U2 91
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD NOV
PY 2012
VL 7
IS 11
BP 2056
EP 2066
DI 10.1038/nprot.2012.127
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 030QM
UT WOS:000310585200013
PM 23099487
ER
PT J
AU Chio, A
Calvo, A
Mazzini, L
Cantello, R
Mora, G
Moglia, C
Corrado, L
D'Alfonso, S
Majounie, E
Renton, A
Pisano, F
Ossola, I
Brunetti, M
Traynor, BJ
Restagno, G
AF Chio, Adriano
Calvo, Andrea
Mazzini, Letizia
Cantello, Roberto
Mora, Gabriele
Moglia, Cristina
Corrado, Lucia
D'Alfonso, Sandra
Majounie, Elisa
Renton, Alan
Pisano, Fabrizio
Ossola, Irene
Brunetti, Maura
Traynor, Bryan J.
Restagno, Gabriella
CA PARALS
TI Extensive genetics of ALS A population-based study in Italy
SO NEUROLOGY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSION; CLINICAL
CHARACTERISTICS; SOD1 MUTATIONS; FUS MUTATIONS; ANG GENE; C9ORF72;
TARDBP; EPIDEMIOLOGY; DIAGNOSIS
AB Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases.
Methods: The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have been assessed.
Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset <= 54 years (odds ratio 1.79; p = 0.012).
Conclusions: We have found that similar to 11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease. Neurology (R) 2012;79:1983-1989
C1 [Chio, Adriano; Calvo, Andrea; Moglia, Cristina] Univ Turin, Dept Neurosci, ALS Ctr, Turin, Italy.
AOU San Giovanni Battista Torino, Turin, Italy.
[Mazzini, Letizia; Cantello, Roberto] Amedeo Avogadro Univ, Dept Neurol, ALS Ctr, Novara, Italy.
AOU Maggiore della Carita, Novara, Italy.
[Corrado, Lucia; D'Alfonso, Sandra] A Avogadro Univ, IRCAD, Dept Med Sci, Novara, Italy.
[Mora, Gabriele] Sci Inst Milano, Milan, Italy.
[Majounie, Elisa; Renton, Alan; Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Pisano, Fabrizio] IRCCS, Salvatore Maugeri Fdn, Dept Neurol, Pavia, Italy.
[Pisano, Fabrizio] IRCCS, Salvatore Maugeri Fdn, Dept Neurorehab, Pavia, Italy.
[Pisano, Fabrizio] Sci Inst Veruno, Veruno, Italy.
[Ossola, Irene; Restagno, Gabriella] AO OIRM St Anna, Mol Genet Lab, Turin, Italy.
RP Chio, A (reprint author), Univ Turin, Dept Neurosci, ALS Ctr, Turin, Italy.
EM achio@usa.net
RI Traynor, Bryan/G-5690-2010; D'Alfonso, Sandra/K-7295-2014; Calvo,
Andrea/K-4141-2016; Cantello, Roberto/L-3786-2016; Moglia,
Cristina/K-4142-2016;
OI D'Alfonso, Sandra/0000-0002-3983-9925; Calvo,
Andrea/0000-0002-5122-7243; Cantello, Roberto/0000-0001-6999-5729;
Moglia, Cristina/0000-0001-7377-7222; Chio, Adriano/0000-0001-9579-5341
FU Federazione Italiana Giuoco Calcio; Fondazione Vialli e Mauro per la
Sclerosi Laterale Amiotrofica onlus; Ministero della Salute (Ricerca
Sanitaria Finalizzata); Regione Piemonte (Progetti Finalizzati);
Associazione Amico Canobio; Fondazione Cariplo [2010-0728]; PRIN;
European Community [259867, 278611]; NIH, National Institute on Aging
[Z01-AG000949-02]; Italian Ministry of Health (Ricerca Finalizzata);
Regione Piemonte (Ricerca Finalizzata); University of Torino; Fondazione
Vialli e Mauro onlus; European Commission (Health Seventh Framework
Programme); Compagnia di San Paolo; Fondazione Borgonovo; Fondazione
Cariplo
FX This work was funded in part by Federazione Italiana Giuoco Calcio,
Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus,
Ministero della Salute (Ricerca Sanitaria Finalizzata, 2007), Regione
Piemonte (Progetti Finalizzati 2003 and 2004), Associazione Amico
Canobio, Fondazione Cariplo (no. 2010-0728), and PRIN 2008. The research
leading to these results has received funding from the European
Community's Health Seventh Framework Programme (FP7/2007-2013) (grant
agreements no. 259867 and 278611). This work was supported in part by
the Intramural Research Programs of the NIH, National Institute on Aging
(Z01-AG000949-02).; A. Chio has received research support from Italian
Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca
Finalizzata), University of Torino, Federazione Italiana Giuoco Calcio,
Fondazione Vialli e Mauro onlus, and European Commission (Health Seventh
Framework Programme), and serves on a scientific advisory board for
Biogen Idec and Cytokinetics. A. Calvo has received research support
from Regione Piemonte (Ricerca Finalizzata) and Compagnia di San Paolo.
L. Mazzini has received research support from Fondazione Borgonovo. R.
Cantello reports no disclosures. G. Mora has received research support
from Italian Ministry of Health (Ricerca Finalizzata). C. Moglia and L.
Corrado report no disclosures. S. D'Alfonso has received research
support from Fondazione Cariplo. E. Majunie, A. Renton, F. Pisano, I.
Ossola, M. Brunetti, and B. Traynor report no disclosures. G. Restagno
reports has received research support from Italian Ministry of Health
(Ricerca Finalizzata) and Regione Piemonte (Ricerca Finalizzata). Go to
Neurology.org for full disclosures.
NR 40
TC 64
Z9 66
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 NOV
PY 2012
VL 79
IS 19
BP 1983
EP 1989
DI 10.1212/WNL.0b013e3182735d36
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA 032US
UT WOS:000310745200013
PM 23100398
ER
PT J
AU Ratchford, JN
Costello, K
Reich, DS
Calabresi, PA
AF Ratchford, John N.
Costello, Kathleen
Reich, Daniel S.
Calabresi, Peter A.
TI VARICELLA-ZOSTER VIRUS ENCEPHALITIS AND VASCULOPATHY IN A PATIENT
TREATED WITH FINGOLIMOD
SO NEUROLOGY
LA English
DT Editorial Material
ID RELAPSING MULTIPLE-SCLEROSIS; ORAL FINGOLIMOD
C1 [Ratchford, John N.; Costello, Kathleen; Reich, Daniel S.; Calabresi, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA.
[Reich, Daniel S.] Natl Inst Neurol Disorders & Stroke, Translat Neuroradiol Unit, Neuroimmunol Branch, Bethesda, MD USA.
RP Ratchford, JN (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
EM jratchf1@jhmi.edu
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Intramural NIH HHS
NR 5
TC 39
Z9 39
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD NOV
PY 2012
VL 79
IS 19
BP 2002
EP 2004
DI 10.1212/WNL.0b013e3182735d00
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 032US
UT WOS:000310745200017
PM 23035072
ER
PT J
AU Bao, XF
Lu, SY
Liow, JS
Morse, CL
Anderson, KB
Zoghbi, SS
Innis, RB
Pike, VW
AF Bao, Xiaofeng
Lu, Shuiyu
Liow, Jeih-San
Morse, Cheryl L.
Anderson, Kacey B.
Zoghbi, Sami S.
Innis, Robert B.
Pike, Victor W.
TI [C-11]Rhodamine-123: Synthesis and biodistribution in rodents
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE [C-11]Rhodamine-123; P-gp substrate; Organic cation transporter;
Synthesis; Carbon-11; PET
ID P-GLYCOPROTEIN; IN-VIVO; CYCLOSPORINE-A; FREE-FRACTION; RHODAMINE-123;
BRAIN; RAT; RESISTANCE; PET; INHIBITION
AB Introduction: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t(1/2)=20.4 min) and to study its biodistribution in rodents.
Methods: [C-11]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [C-11]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters: OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30 min after radiotracer administration to wild-type and efflux transporter knockout rodents.
Results: [C-11]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [C-11]carbon dioxide. After intravenous administration of [C-11]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine.
Conclusions: [C-11]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo. Published by Elsevier Inc.
C1 [Bao, Xiaofeng; Lu, Shuiyu; Liow, Jeih-San; Morse, Cheryl L.; Anderson, Kacey B.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Pike, VW (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM pikev@mail.nih.gov
RI Bao, Xiaofeng/K-5278-2013;
OI Lu, Shuiyu/0000-0003-0310-4318
FU National Institutes of Health (NIMH)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIMH). We are grateful to the NIH
Clinical PET Center (Chief: Dr. Peter Herscovitch) for cyclotron
production of carbon-11.
NR 43
TC 6
Z9 7
U1 1
U2 21
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD NOV
PY 2012
VL 39
IS 8
BP 1128
EP 1136
DI 10.1016/j.nucmedbio.2012.06.013
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 031VZ
UT WOS:000310672000005
PM 22898316
ER
PT J
AU Lago, CU
Nowinski, SM
Rundhaug, JE
Pfeiffer, ME
Kiguchi, K
Hirasaka, K
Yang, X
Abramson, EM
Bratton, SB
Rho, O
Colavitti, R
Kenaston, MA
Nikawa, T
Trempus, C
DiGiovanni, J
Fischer, SM
Mills, EM
AF Lago, C. U.
Nowinski, S. M.
Rundhaug, J. E.
Pfeiffer, M. E.
Kiguchi, K.
Hirasaka, K.
Yang, X.
Abramson, E. M.
Bratton, S. B.
Rho, O.
Colavitti, R.
Kenaston, M. A.
Nikawa, T.
Trempus, C.
DiGiovanni, J.
Fischer, S. M.
Mills, E. M.
TI Mitochondrial respiratory uncoupling promotes keratinocyte
differentiation and blocks skin carcinogenesis
SO ONCOGENE
LA English
DT Article
DE mitochondria; uncoupling proteins; skin; carcinogenesis; differentiation
ID STEM-CELLS; HAIR FOLLICLE; SKELETAL-MUSCLE; CANCER-CELLS; MICE;
EXPRESSION; PARAGANGLIOMA; MUTATIONS; PROTEIN-2; METABOLISM
AB Decreased mitochondrial oxidative metabolism is a hallmark bioenergetic characteristic of malignancy that may have an adaptive role in carcinogenesis. By stimulating proton leak, mitochondrial uncoupling proteins (UCP1-3) increase mitochondrial respiration and may thereby oppose cancer development. To test this idea, we generated a mouse model that expresses an epidermal-targeted keratin-5-UCP3 (K5-UCP3) transgene and exhibits significantly increased cutaneous mitochondrial respiration compared with wild type (FVB/N). Remarkably, we observed that mitochondrial uncoupling drove keratinocyte/epidermal differentiation both in vitro and in vivo. This increase in epidermal differentiation corresponded to the loss of markers of the quiescent bulge stem cell population, and an increase in epidermal turnover measured using a bromodeoxyuridine (BrdU)-based transit assay. Interestingly, these changes in K5-UCP3 skin were associated with a nearly complete resistance to chemically-mediated multistage skin carcinogenesis. These data suggest that targeting mitochondrial respiration is a promising novel avenue for cancer prevention and treatment.
C1 [Lago, C. U.; Abramson, E. M.; Bratton, S. B.; Mills, E. M.] Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
[Lago, C. U.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Rundhaug, J. E.; Fischer, S. M.] Univ Texas MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX USA.
[Yang, X.] Fudan Univ, Shanghai 200433, Peoples R China.
[Colavitti, R.] Stanford Univ, Div Radiat & Canc Biol, Stanford, CA 94305 USA.
[Nikawa, T.] Univ Tokushima, Inst Hlth Biosci, Dept Nutr Physiol, Tokushima 770, Japan.
[Trempus, C.] NIEHS, Matrix Biol Grp, Lab Resp Biol, Res Triangle Pk, NC 27709 USA.
RP Mills, EM (reprint author), Univ Texas Austin, Coll Pharm, Div Pharmacol & Toxicol, Inst Cellular & Mol Biol, Austin, TX 78712 USA.
EM ted_mills@mail.utexas.edu
FU National Institutes of Health [DK089224, T32ES07247]
FX EMM was supported by the National Institutes of Health grant # DK089224.
SMN was supported by the National Institutes of Health Toxicology
Training grant T32ES07247.
NR 42
TC 7
Z9 7
U1 0
U2 16
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD NOV
PY 2012
VL 31
IS 44
BP 4725
EP 4731
DI 10.1038/onc.2011.630
PG 7
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA 032MW
UT WOS:000310724400008
PM 22266853
ER
PT J
AU Chew, EY
Clemons, T
SanGiovanni, JP
Danis, R
Domalpally, A
McBee, W
Sperduto, R
Ferris, FL
AF Chew, Emily Y.
Clemons, Traci
SanGiovanni, John Paul
Danis, Ronald
Domalpally, Amitha
McBee, Wendy
Sperduto, Robert
Ferris, Frederick L.
CA AREDS2 Res Grp
TI The Age-related Eye Disease Study 2 (AREDS2) Study Design and Baseline
Characteristics (AREDS2 Report Number 1)
SO OPHTHALMOLOGY
LA English
DT Article
ID HIGH-DOSE SUPPLEMENTATION; FATTY-ACID INTAKE; MACULAR DEGENERATION;
VITAMIN-C; BETA-CAROTENE; UNITED-STATES; ANTIOXIDANT INTAKE; VISUAL
IMPAIRMENT; ALPHA-TOCOPHEROL; FISH CONSUMPTION
AB Purpose: The Age-Related Eye Disease Study (AREDS) demonstrated beneficial effects of oral supplementation with antioxidant vitamins and minerals on the development of advanced age-related macular degeneration (AMD) in persons with at least intermediate AMD (bilateral large drusen with or without pigment changes). Observational data suggest that other oral nutrient supplements might further reduce the risk of progression to advanced AMD. The primary purpose of the Age-Related Eye Disease Study 2 (AREDS2) is to evaluate the efficacy and safety of lutein plus zeaxanthin (L + Z) and/or omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation in reducing the risk of developing advanced AMD. The study also assesses the reduction in zinc and the omission of beta-carotene from original AREDS formulation.
Design: Multicenter, phase III, randomized, controlled clinical trial.
Participants: Persons aged 50 to 85 with bilateral intermediate AMD or advanced AMD in 1 eye.
Methods: All participants were randomly assigned to placebo (n = 1012), L + Z (10 mg/2 mg; n = 1044), omega-3 LCPUFAs (eicosapentaenoic acid + docosahexaenoic acid [650 mg/350 mg]; n = 1069), or the combination of L + Z and omega-3 LCPUFAs (n = 1078). All participants were offered a secondary randomization to 1 of 4 variations of the original AREDS formulation keeping vitamins C (500 mg) and E (400 IU) and copper (2 mg) unchanged while varying zinc and beta-carotene as follows: Zinc remains at the original level (80 mg), lower only zinc to 25 mg, omit beta-carotene only, or lower zinc to 25 mg and omit beta-carotene.
Main Outcome Measures: Progression to advanced AMD determined by centralized grading of annual fundus photographs.
Results: We enrolled 4203 participants at 82 clinical centers located in the United States. Population characteristics at baseline were as follows: Mean age, 74 years; 57% female; 97% white; 7% current smokers; 19% with prior cardiovascular disease; and 44% and 50% taking statin-class cholesterol-lowering drugs and aspirin, respectively. Ocular characteristics include 59% with bilateral large drusen, 32% with advanced AMD in 1 eye and mean visual acuity of 20/32 in eyes without advanced AMD.
Conclusions: This report presents the AREDS2 study design and the participants' baseline demographic and ocular characteristics.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2282-2289 (C) 2012 by the American Academy of Ophthalmology.
C1 [Chew, Emily Y.; SanGiovanni, John Paul; Ferris, Frederick L.] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Clemons, Traci; McBee, Wendy; Sperduto, Robert] EMMES Corp, Rockville, MD USA.
[Danis, Ronald; Domalpally, Amitha] Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA.
RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Applicat, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
RI Domalpally, Amitha/B-2367-2015
FU National Eye Institute/National Institutes of Health (NEI/NIH),
Department of Health and Human Services, Bethesda, MD
[HHS-N-260-2005-00007-C]; ADB Contract [N01-EY-5-0007]; NIH, Office of
Dietary Supplements (ODS); NIH, National Center for Complementary and
Alternative Medicine (NCCAM); NIH, National Institute on Aging (NIA);
NIH, National Heart, Lung and Blood Institute (NHLBI); NIH, National
Institute of Neurological Disorders and Stroke (NINDS)
FX This study is supported by the intramural program funds and contracts
from the National Eye Institute/National Institutes of Health (NEI/NIH),
Department of Health and Human Services, Bethesda, MD, Contract No.
HHS-N-260-2005-00007-C and ADB Contract No. N01-EY-5-0007. Funds were
generously contributed to these contracts by the following NIH
institutes: Office of Dietary Supplements (ODS), National Center for
Complementary and Alternative Medicine (NCCAM), National Institute on
Aging (NIA), National Heart, Lung and Blood Institute (NHLBI), and
National Institute of Neurological Disorders and Stroke (NINDS).
NR 45
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2012
VL 119
IS 11
BP 2282
EP 2289
DI 10.1016/j.ophtha.2012.05.027
PG 8
WC Ophthalmology
SC Ophthalmology
GA 030OH
UT WOS:000310579500014
ER
PT J
AU Elman, MJ
Qin, HJ
Aiello, LP
Beck, RW
Bressler, NM
Ferris, FL
Glassman, AR
Maturi, RK
Melia, M
AF Elman, Michael J.
Qin, Haijing
Aiello, Lloyd Paul
Beck, Roy W.
Bressler, Neil M.
Ferris, Frederick L., III
Glassman, Adam R.
Maturi, Raj K.
Melia, Michele
CA Diabetic Retinopathy Clinical Res
TI Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus
Deferred Laser Treatment Three-Year Randomized Trial Results
SO OPHTHALMOLOGY
LA English
DT Article
ID PLUS PROMPT
AB Objective: To report the 3-year follow-up results within a previously reported randomized trial evaluating prompt versus deferred (for >= 24 weeks) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema (DME).
Design: Multicenter, randomized clinical trial.
Participants: Three hundred sixty-one participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea.
Methods: Ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and random assignment to prompt or deferred (>= 24 weeks) focal/grid laser treatment.
Main Outcome Measures: Best-corrected visual acuity and safety at the 156-week (3-year) visit.
Results: The estimated mean change in visual acuity letter score from baseline through the 3-year visit was 2.9 letters more (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4-5.4 letters; P = 0.02) in the deferral group compared with the prompt laser treatment group. In the prompt laser treatment group and deferral group, respectively, the percentage of eyes with a >= 10-letter gain/loss was 42% and 56% (P = 0.02), whereas the respective percentage of eyes with a >= 10-letter gain/loss was 10% and 5% (P = 0.12). Up to the 3-year visit, the median numbers of injections were 12 and 15 in the prompt and deferral groups, respectively (P = 0.007), including 1 and 2 injections, respectively, from the 2-year up to the 3-year visit. At the 3-year visit, the percentages of eyes with central subfield thickness of 250 mu m or more on time-domain optical coherence tomography were 36% in both groups (P = 0.90). In the deferral group, 54% did not receive laser treatment during the trial. Systemic adverse events seemed to be similar in the 2 groups.
Conclusions: These 3-year results suggest that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better, and possibly worse, for vision outcomes than deferring laser treatment for 24 weeks or more in eyes with DME involving the fovea and with vision impairment. Some of the observed differences in visual acuity at 3 years may be related to fewer cumulative ranibizumab injections during follow-up in the prompt laser treatment group. Follow-up through 5 years continues.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2312-2318 (C) 2012 by the American Academy of Ophthalmology.
C1 [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Melia, Michele] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA.
[Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA.
[Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA.
RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA.
EM drcrstat3@jaeb.org
FU National Eye Institute; National Institute of Diabetes and Digestive and
Kidney Diseases, National Institutes of Health, Bethesda, Maryland
[EY14231, EY14229, EY18817]; Genentech; Office of Research
Administration; Abbott Medical Optics; Allergan; Bausch Lomb;
Bristol-Meyer-Squibb; Carl Zeiss Meditec; EMMES Corporation; ForSight
Labs; LLC Genentech; Genzyme Corporation; Lumenis; Notal Vision;
Novartis; Regeneron
FX Supported through cooperative agreements from the National Eye Institute
and the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health, Bethesda, Maryland (grant nos.:
EY14231, EY14229, and EY18817).; The funding organization (National
Institutes of Health) participated in oversight of the conduct of the
study and review of the manuscript, but not directly in the design or
conduct of the study; nor in the collection, management, analysis, or
interpretation of the data; nor in the preparation of the manuscript.
Genentech provided the ranibizumab for the study. In addition, Genentech
provided funds to DRCR.net to defray the study's clinical site costs. As
described in the Diabetic Retinopathy Clinical Research Network
(DRCR.net) Industry Collaboration Guidelines (available at
www.drcr.net), the DRCR.net had complete control over the design of the
protocol, ownership of the data, and all editorial content of
presentations and publications related to the protocol. A complete list
of all DRCR.net investigator financial disclosures can be found at
www.drcr.net. Writing Committee financial disclosures: Neil M. Bressler:
Grants to investigators at The Johns Hopkins University are negotiated
and administered by the institution (such as the School of Medicine),
which receives the grants, typically through the Office of Research
Administration. Individual investigators who participate in the
sponsored project(s) are not compensated directly by the sponsor, but
may receive salary or other support from the institution to support
their effort on the projects(s). Neil M. Bressler is the principal
investigator of grants at The Johns Hopkins University sponsored by the
following entities (not including the National Institutes of Health):
Abbott Medical Optics, Allergan, Bausch & Lomb, Bristol-Meyer-Squibb,
Carl Zeiss Meditec, EMMES Corporation, ForSight Labs, LLC Genentech,
Genzyme Corporation, Lumenis, Notal Vision, Novartis, and Regeneron. A
complete list of all DRCR. net investigator financial disclosures can be
found at www.drcr.net.
NR 4
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2012
VL 119
IS 11
BP 2312
EP 2318
DI 10.1016/j.ophtha.2012.08.022
PG 7
WC Ophthalmology
SC Ophthalmology
GA 030OH
UT WOS:000310579500018
ER
PT J
AU Daniel, E
Pistilli, M
Pujari, SS
Kacmaz, RO
Nussenblatt, RB
Rosenbaum, JT
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Levy-Clarke, GA
Kempen, JH
AF Daniel, Ebenezer
Pistilli, Maxwell
Pujari, Siddharth S.
Kacmaz, R. Oktay
Nussenblatt, Robert B.
Rosenbaum, James T.
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Levy-Clarke, Grace A.
Kempen, John H.
TI Risk of Hypotony in Noninfectious Uveitis
SO OPHTHALMOLOGY
LA English
DT Article
ID INTRAOCULAR-LENS IMPLANTATION; OCULAR COMPLICATIONS; CYTOMEGALOVIRUS
RETINITIS; ULTRASOUND BIOMICROSCOPY; CYCLODIALYSIS CLEFT;
CATARACT-SURGERY; PHACOEMULSIFICATION; PRESSURE; MACULOPATHY; VITRECTOMY
AB Objective: We sought to describe the risk and risk factors for hypotony in a noninfectious uveitis cohort.
Design: Retrospective cohort study.
Participants: Patients with noninfectious uveitis seen between 1979 and 2007 at 4 academic ocular inflammation specialty clinics.
Methods: Data were collected from medical records by trained, certified, expert reviewers.
Main Outcome Measures: Hypotony (<5 mmHg) and low intraocular pressure (<8 mmHg), each sustained for >= 2 visits spanning >= 30 days.
Results: During follow-up, 126 of 6785 patients (1.86%) developed hypotony at the rate of 0.61% (95% confidence interval [CI], 0.50-0.75%) per eye-year. Cataract surgery was associated with a 7.5-fold risk (adjusted hazard ratio [aHR], 7.51; 95% CI, 3.97-14.23) of incident hypotony. Phacoemulsification, the type of cataract surgery associated with the least hypotony risk still was associated with nearly 5-fold higher hypotony incidence (aHR, 4.87; 95% CI, 2.25-10.55). Increased risk was observed in children (aHR, 2.92; 95% CI, 1.20-7.10) with respect to young adults, and duration of uveitis of >5 years (aHR, 3.08; 95% CI, 1.30-7.31) with respect to uveitis of <6 month duration. Band keratopathy, >= 3+ vitreous cells, exudative retinal detachment, posterior synechia, and a history of pars plana vitrectomy also were associated with greater hypotony incidence. With respect to anterior uveitis, intermediate uveitis (aHR, 0.17; 95% CI, 0.05-0.56) and posterior uveitis (aHR, 0.11; 95% CI, 0.03-0.45) were associated with lower hypotony risk, whereas panuveitis (aHR, 1.25; 95% CI, 0.67-2.35) was similar. Approximately five-sixths (84.1%) of eyes presenting with hypotony had a visual acuity of <20/200 (aOR for visual acuity <20/200, 13.85; 95% CI, 7.23-26.53). Risk factors for prevalent hypotony were similar.
Conclusions: The risk of hypotony is low among eyes with noninfectious uveitis, but is more frequently observed in cases with anterior segment inflammation. Signs of present or past inflammation were associated with greater risk, suggesting excellent inflammatory control may reduce the risk of hypotony. Prior ocular surgery also was associated with higher risk; cataract surgery in particular was associated with much higher risk of hypotony. Lower risk of hypotony with phacoemulsification than with alternative cataract surgery approaches suggests the phacoemulsification approach is preferable.
Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 2377-2385 (C) 2012 by the American Academy of Ophthalmology.
C1 [Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA.
[Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Pujari, Siddharth S.; Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA.
[Pujari, Siddharth S.] Lions Nab Eye Hosp, Miraj, Maharashtra, India.
[Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA USA.
[Nussenblatt, Robert B.; Levy-Clarke, Grace A.] NEI, Immunol Lab, Bethesda, MD 20892 USA.
[Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Daniel, Ebenezer/0000-0002-2027-2316; Pistilli,
Maxwell/0000-0002-4266-4150
FU National Eye Institute [EY014943]; Research to Prevent Blindness (RPB);
Paul and Evanina Mackall Foundation
FX This study was supported primarily by National Eye Institute Grant
EY014943 (J.H.K.). Additional support was provided by Research to
Prevent Blindness (RPB) and the Paul and Evanina Mackall Foundation.
J.H.K. was an RPB James S. Adams Special Scholar Award recipient, J.E.T.
was an RPB Harrington Special Scholar Award recipient, and D.A.J. and
J.T.R. were Research to Prevent Blindness Senior Scientific Investigator
Award recipients during the course of the study. G. A. L.-C. was
previously supported by and R.B.N. continues to be supported by
intramural funds of the National Eye Institute. E. B. S. receives
support from the Department of Veterans' Affairs. 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 25
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2012
VL 119
IS 11
BP 2377
EP 2385
DI 10.1016/j.ophtha.2012.05.032
PG 9
WC Ophthalmology
SC Ophthalmology
GA 030OH
UT WOS:000310579500027
PM 22796306
ER
PT J
AU Nelson, KB
Bingham, P
Edwards, EM
Horbar, JD
Kenny, MJ
Inder, T
Pfister, RH
Raju, T
Soll, RF
AF Nelson, Karin B.
Bingham, Peter
Edwards, Erika M.
Horbar, Jeffrey D.
Kenny, Michael J.
Inder, Terrie
Pfister, Robert H.
Raju, Tonse
Soll, Roger F.
TI Antecedents of Neonatal Encephalopathy in the Vermont Oxford Network
Encephalopathy Registry
SO PEDIATRICS
LA English
DT Article
DE asphyxia; encephalopathy; newborn; perinatal factors; registries
ID CEREBRAL-PALSY; NEWBORN ENCEPHALOPATHY; RISK-FACTORS; TERM INFANTS;
SEIZURE DISORDERS; BIRTH-WEIGHT; BRAIN-INJURY; CHORIOAMNIONITIS; FEVER;
ISCHEMIA
AB BACKGROUND: Neonatal encephalopathy (NE) is a major predictor of death and long-term neurologic disability, but there are few studies of antecedents of NE.
OBJECTIVES: To identify antecedents in a large registry of infants who had NE.
METHODS: This was a maternal and infant record review of 4165 singleton neonates, gestational age of <= 36 weeks, meeting criteria for inclusion in the Vermont Oxford Network Neonatal Encephalopathy Registry.
RESULTS: Clinically recognized seizures were the most prevalent condition (60%); 49% had a 5-minute Apgar score of >= 3 and 18% had a reduced level of consciousness. An abnormal maternal or fetal condition predated labor in 46%; maternal hypertension (16%) or small for gestational age (16%) were the most frequent risk factors. In 8%, birth defects were identified. The most prevalent birth complication was elevated maternal temperature in labor of >= 37.5 degrees C in 27% of mothers with documented temperatures compared with 2% to 3.2% in controls in population-based studies. Clinical chorioamnionitis, prolonged membrane rupture, and maternal hypothyroidism exceeded rates in published controls. Acute asphyxial indicators were reported in 15% (in 35% if fetal bradycardia included) and inflammatory indicators in 24%. Almost one-half had neither asphyxial nor inflammatory indicators. Although most infants with NE were observably ill since the first minutes of life, only 54% of placentas were submitted for examination.
CONCLUSIONS: Clinically recognized asphyxial birth events, indicators of intrauterine exposure to inflammation, fetal growth restriction, and birth defects were each observed in term infants with NE, but much of NE in this large registry remained unexplained. Pediatrics 2012;130:878-886
C1 [Nelson, Karin B.; Pfister, Robert H.; Soll, Roger F.] Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA.
[Nelson, Karin B.] NINDS, Bethesda, MD 20892 USA.
[Bingham, Peter; Edwards, Erika M.; Horbar, Jeffrey D.; Pfister, Robert H.; Soll, Roger F.] Univ Vermont, Dept Pediat, Burlington, VT USA.
[Edwards, Erika M.] Univ Vermont, Dept Math & Stat, Burlington, VT 05405 USA.
[Kenny, Michael J.] Univ Vermont, Dept Med Biostat, Burlington, VT 05405 USA.
[Horbar, Jeffrey D.; Kenny, Michael J.; Pfister, Robert H.; Soll, Roger F.] Vermont Oxford Network, Burlington, VT USA.
[Inder, Terrie] Washington Univ, Dept Pediat, St Louis, MO 63130 USA.
[Raju, Tonse] NICHHD, Bethesda, MD 20892 USA.
RP Nelson, KB (reprint author), 5524 Charles St, Bethesda, MD 20892 USA.
EM nelsonk@ninds.nih.gov
RI Kenny, Michael/N-3244-2013
OI Kenny, Michael/0000-0002-7750-654X
NR 42
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Z9 13
U1 0
U2 6
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2012
VL 130
IS 5
BP 878
EP 886
DI 10.1542/peds.2012-0714
PG 9
WC Pediatrics
SC Pediatrics
GA 029OT
UT WOS:000310505900057
PM 23071210
ER
PT J
AU Wiener, L
Zadeh, S
Battles, H
Baird, K
Ballard, E
Osherow, J
Pao, M
AF Wiener, Lori
Zadeh, Sima
Battles, Haven
Baird, Kristin
Ballard, Elizabeth
Osherow, Janet
Pao, Maryland
TI Allowing Adolescents and Young Adults to Plan Their End-of-Life Care
SO PEDIATRICS
LA English
DT Article
DE adolescents; end-of-life; advance care planning; decision-making; young
adults; cancer; HIV
ID PEDIATRIC PALLIATIVE CARE; DECISION-MAKING; CHILDREN; CANCER; ILLNESS;
PERCEPTIONS; DOCUMENT; PARENTS
AB OBJECTIVE: The objective of this study was to assess and compare the usefulness, helpfulness, and stress associated with reviewing a previously adapted advance care planning guide, My Thoughts, My Wishes, My Voice, in comparison with the widely used adult document Five Wishes by adolescents and young adults (AYAs) living with a serious illness.
METHODS: Fifty-two participants (age 16-28) living with metastatic or recurrent cancer or HIV infection (acquired at birth or early in life) were presented pages randomly from My Thoughts, My Wishes, My Voice and, Five Wishes, and asked to rank 25 items on several factors, including how likely they would be to complete each statement. Participant opinion on suggested changes in content, design, format, and style was obtained and resulted in development of a new document.
RESULTS: AYAs living with a life-threatening illness want to be able to choose and record (1) the kind of medical treatment they want and do not want, (2) how they would liked to be cared for, (3) information for their family and friends to know, and (4) how they would like to be remembered.
CONCLUSIONS: AYA views of what should be included in an advance care planning guide were incorporated into a new document, Voicing My Choices, that provides youth, families and providers an opportunity to reduce the silence around the dying process by allowing an opportunity to share one's voice. We provide guidance on how to incorporate this tool into care. Pediatrics 2012;130:897-905
C1 [Wiener, Lori] NCI, Psychosocial Support & Res Program, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Ballard, Elizabeth] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Ballard, Elizabeth; Pao, Maryland] NIMH, Off Clin Director, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Osherow, Janet] Georgetown Univ, Pediat Infect Dis Dept, Washington, DC USA.
RP Wiener, L (reprint author), NCI, Psychosocial Support & Res Program, Pediat Oncol Branch, Ctr Canc Res,NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural Research Programs of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research; National
Institute of Mental Health; National Institutes of Health (NIH)
FX Supported in part by the Intramural Research Programs of the National
Institutes of Health, National Cancer Institute, Center for Cancer
Research, and the National Institute of Mental Health. Funded by the
National Institutes of Health (NIH).
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U1 3
U2 28
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2012
VL 130
IS 5
BP 897
EP 905
DI 10.1542/peds.2012-0663
PG 9
WC Pediatrics
SC Pediatrics
GA 029OT
UT WOS:000310505900059
PM 23045560
ER
PT J
AU Korzeniewski, SJ
Grigorescu, V
Kleyn, M
Young, W
Birbeck, GL
Todem, D
Romero, R
Chaiworapongsa, T
Paneth, N
AF Korzeniewski, Steven J.
Grigorescu, Violanda
Kleyn, Mary
Young, William
Birbeck, Gretchen L.
Todem, David
Romero, Roberto
Chaiworapongsa, Tinnakorn
Paneth, Nigel
TI Performance Metrics After Changes in Screening Protocol for Congenital
Hypothyroidism
SO PEDIATRICS
LA English
DT Article
DE newborn screening; performance evaluation; congenital hypothyroidism
ID LOW-BIRTH-WEIGHT; TRANSIENT HYPOTHYROXINEMIA; THYROID-FUNCTION; PRETERM
INFANTS; UNITED-STATES; NEONATAL HYPERTHYROTROPINEMIA; DIAGNOSTIC
EFFECTIVENESS; WEEKS GESTATION; NEWBORN; THYROXINE
AB OBJECTIVE: To evaluate Michigan newborn screening for congenital hypothyroidism (CH) protocol changes.
METHODS: This population-based study includes infants born and screened in Michigan (January 1, 1994-June 30, 2010). Screening performance is compared across 4 periods defined by the dried blood spot testing method: (1) thyroxine (T4) with backup thyrotropin, (2) tandem T4 and thyrotropin, (3) primary thyrotropin testing without serial testing, and (4) primary thyrotropin plus serial testing for births weighing,1800 g. Logistic regression is used to test for differences across periods.
RESULTS: Thyrotropin testing exhibited greater specificity overall and greater likelihood of detection with serial testing relative to primary T4 testing. Tandem T4 and thyrotropin testing appeared more sensitive relative to other protocols, yet it produced significantly more false-positives, and detection may have been affected by overdiagnosis and misclassification. Central CH was no longer detected once T4 testing ceased.
CONCLUSIONS: Primary thyrotropin plus serial testing for infants at risk for later rising thyrotropin outperformed other newborn screening strategies for classic CH, although 2 false-negatives occurred among normal birth weight infants admitted to the NICU during this testing period. Tandem T4 and thyrotropin screening outperformed other strategies for detection of both classic and central CH combined, although it is associated with increased operating costs. Additional research is necessary to weigh the benefits of increased sensitivity against additional program operating costs. Pediatrics 2012;130:e1252-e1260
C1 [Korzeniewski, Steven J.; Romero, Roberto; Chaiworapongsa, Tinnakorn] NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA.
[Korzeniewski, Steven J.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Grigorescu, Violanda; Kleyn, Mary; Young, William] Michigan Dept Community Hlth, Lansing, MI USA.
[Birbeck, Gretchen L.; Todem, David; Paneth, Nigel] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
RP Korzeniewski, SJ (reprint author), Wayne State Univ, Hutzel Womens Hosp, Sch Med, Dept Obstet & Gynecol, 4 Brush Off 4817,3990 John R St, Detroit, MI 48201 USA.
EM sKorzeni@med.wayne.edu
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services; National Institutes of Health (NIH)
FX This research was supported in part by the Perinatology Research Branch,
Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services. Funded by the National
Institutes of Health (NIH).
NR 51
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Z9 1
U1 0
U2 4
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2012
VL 130
IS 5
BP E1252
EP E1260
DI 10.1542/peds.2011-3340
PG 9
WC Pediatrics
SC Pediatrics
GA 029OT
UT WOS:000310505900025
PM 23045555
ER
PT J
AU Wu, LM
Austin, J
Hamilton, JG
Valdimarsdottir, H
Isola, L
Rowley, S
Warbet, R
Winkel, G
Redd, WH
Rini, C
AF Wu, Lisa M.
Austin, Jane
Hamilton, Jada G.
Valdimarsdottir, Heiddis
Isola, Luis
Rowley, Scott
Warbet, Rachel
Winkel, Gary
Redd, William H.
Rini, Christine
TI Self-efficacy beliefs mediate the relationship between subjective
cognitive functioning and physical and mental well-being after
hematopoietic stem cell transplant
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE cancer; oncology; cognitive functioning; self-efficacy; quality of life;
distress
ID QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; BONE-MARROW-TRANSPLANTATION;
CANCER-PATIENTS; MARITAL-STATUS; SOCIAL SUPPORT; BREAST-CANCER; THERAPY;
REHABILITATION; SCALE
AB Objective Cognitive problems are commonly reported by hematopoietic stem cell transplant (HSCT) survivors and are associated with poorer physical and mental well-being. It was hypothesized that adverse effects of subjective cognitive impairment occur because cognitive difficulties reduce survivors' confidence that they can manage HSCT-related symptomsthat is, self-efficacy for symptom management.
Methods Hematopoietic stem cell transplant survivors (n=245), 9 months to 3 years post-HSCT, completed measures of subjective cognitive functioning, self-efficacy for symptom management, and clinically important outcomes: depressed mood, anxiety, and quality of life. Mediation analyses using bootstrapping were conducted to investigate whether effects of subjective cognitive impairment on these outcomes were mediated by self-efficacy for cognitive, emotional (SE-Emotional), social (SE-Social), and physical (SE-Physical) symptom management.
Results Self-efficacy mediated relations between subjective cognitive impairment and depressed mood (total indirect effect=-0.0064 and 95% CI -0.0097 to -0.0036), anxiety (total indirect effect=-0.0045, CI -0.0072 to -0.0021), and quality of life (total indirect effect=0.0952, CI 0.0901 to 0.2642). SE-Emotional was a unique mediator when the outcome was depressed mood and anxiety. SE-Social, SE-Physical, and SE-Emotional were specific mediators when outcome was quality of life.
Conclusions Findings support the conclusion that subjective cognitive impairment reduces HSCT survivors' confidence in their ability to manage common post-HSCT symptoms, with implications for physical and mental well-being. Interventions that help enhance survivors' self-efficacy, particularly self-efficacy for the management of emotional symptoms, are likely to benefit HSCT survivors who report subjective cognitive impairment. Copyright (c) 2011 John Wiley & Sons, Ltd.
C1 [Wu, Lisa M.; Valdimarsdottir, Heiddis; Winkel, Gary; Redd, William H.; Rini, Christine] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA.
[Austin, Jane] William Paterson Univ, Dept Psychol, Wayne, NJ USA.
[Hamilton, Jada G.] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA.
[Isola, Luis] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
[Rowley, Scott] Hackensack Univ, John Theurer Canc Ctr, Med Ctr, Hackensack, NJ USA.
[Warbet, Rachel] Mt Sinai Hosp, New York, NY 10029 USA.
[Rini, Christine] Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA.
[Valdimarsdottir, Heiddis] Reykjavik Univ, Dept Psychol, Reykjavik, Iceland.
RP Wu, LM (reprint author), Mt Sinai Sch Med, Dept Oncol Sci, 1 Gustave L Levy Pl,Box 1130, New York, NY 10029 USA.
EM lisa.wu@mssm.edu
FU American Cancer Society [RSGPB-07-285-01-CPPB]; National Cancer
Institute [2R25CA081137-11A1]
FX We wish to thank Katie Basmajian, MA, AnnaMarie Vu, BA, and Jennifer
Chee-Chait, BA, for their assistance in data collection for this
project. This research was supported by funding from the American Cancer
Society (PI: Rini; grant #RSGPB-07-285-01-CPPB) and the National Cancer
Institute (grant #2R25CA081137-11A1). The authors have no financial
interests to disclose.
NR 45
TC 10
Z9 10
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD NOV
PY 2012
VL 21
IS 11
BP 1175
EP 1184
DI 10.1002/pon.2012
PG 10
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 032RE
UT WOS:000310735900006
PM 21739524
ER
PT J
AU Sutin, AR
Zonderman, AB
AF Sutin, A. R.
Zonderman, A. B.
TI Depressive symptoms are associated with weight gain among women
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Body mass index; depressed affect; depressive symptoms; longitudinal;
weight gain
ID BODY-MASS INDEX; SCALE CES-D; QUALITY-OF-LIFE; GENERAL-POPULATION;
GENDER-DIFFERENCES; PSYCHIATRIC-DISORDERS; LONGITUDINAL DATA;
OLDER-ADULTS; BIRTH COHORT; RISK-FACTOR
AB Background. Many studies have linked depression and obesity; few have more than two assessments of depressive symptoms and adiposity to address the potential bidirectional relationship between adiposity and depressive symptoms from young adulthood through old age. We tested whether baseline depressive symptoms are associated with changes in weight, whether baseline adiposity is associated with changes in depressive symptoms, and whether these associations vary by sex.
Method. Participants (n = 2251; 47% female) were from the Baltimore Longitudinal Study of Aging (BLSA). Using hierarchical linear modeling (HLM) on 30 years of data, the trajectory of adiposity and depressive symptoms over adulthood was estimated from >10 000 observations (mean = 4.5 assessments per participant) of body mass index (BMI; kg/m(2)), waist circumference and hip circumference and >10 000 observations (mean = 4.5 assessments per participant) of the Center for Epidemiological Studies Depression Scale (CES-D). Baseline depressive symptoms and adiposity were then tested as predictors of the trajectory of adiposity and depressive symptoms respectively. Additional analyses tested for sex-specific associations.
Results. Sex moderated the association between depressive symptoms and weight gain such that women who experienced depressed affect had greater increases in BMI (b(interaction) = 0.12, S.E. = 0.04), waist (b(interaction) = 0.22, S.E. = 0.10) and hip circumference (b(interaction) = 0.20, S.E. = 0.07) across the adult lifespan, controlling for relevant demographic and behavioral covariates. Baseline adiposity was unrelated to the trajectory of depressive symptoms (median b = 0.00) for both sexes.
Conclusions. Women who experience symptoms of depression tend to gain more weight across adulthood than men who experience such symptoms. Whether an individual was normal weight or overweight was unrelated to changes in depressive symptoms across adulthood.
C1 [Sutin, A. R.; Zonderman, A. B.] NIA, NIH, DHHS, Baltimore, MD 21224 USA.
RP Sutin, AR (reprint author), NIA, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM sutina@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institutes of Health (NIH), National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health (NIH), National Institute on Aging.
Dr A. R. Sutin had full access to all of the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis. The funder had no role in the design and conduct of the
study; in the collection, analysis and interpretation of the data; or in
the preparation, review or the decision to submit.
NR 71
TC 17
Z9 17
U1 2
U2 13
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD NOV
PY 2012
VL 42
IS 11
BP 2351
EP 2360
DI 10.1017/S0033291712000566
PG 10
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 031HI
UT WOS:000310629600010
PM 22475128
ER
PT J
AU Smallridge, RC
Ain, KB
Asa, SL
Bible, KC
Brierley, JD
Burman, KD
Kebebew, E
Lee, NY
Nikiforov, YE
Rosenthal, MS
Shah, MH
Shaha, AR
Tuttle, RM
AF Smallridge, Robert C.
Ain, Kenneth B.
Asa, Sylvia L.
Bible, Keith C.
Brierley, James D.
Burman, Kenneth D.
Kebebew, Electron
Lee, Nancy Y.
Nikiforov, Yuri E.
Rosenthal, M. Sara
Shah, Manisha H.
Shaha, Ashok R.
Tuttle, R. Michael
CA Amer Thyroid Assoc Anaplastic Thyr
TI American Thyroid Association Guidelines for Management of Patients with
Anaplastic Thyroid Cancer
SO THYROID
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; INTENSITY-MODULATED RADIOTHERAPY; PHASE-II
TRIAL; HYPERFRACTIONATED ACCELERATED RADIOTHERAPY; COMPARATIVE GENOMIC
HYBRIDIZATION; CLINICAL-PRACTICE GUIDELINE; COLONY-STIMULATING FACTOR;
FINE-NEEDLE ASPIRATION; IN-SITU HYBRIDIZATION; PROGNOSTIC-FACTORS
AB Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multi-disciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC.
Methods: Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop.
Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations.
Conclusions: These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.
C1 [Smallridge, Robert C.] Mayo Clin, Jacksonville, FL 32224 USA.
[Ain, Kenneth B.] Vet Affairs Med Ctr, Lexington, KY USA.
[Asa, Sylvia L.] Univ Hlth Network, Princess Margaret Hosp, Toronto, ON, Canada.
[Asa, Sylvia L.; Brierley, James D.] Univ Toronto, Toronto, ON, Canada.
[Bible, Keith C.] Mayo Clin, Rochester, MN USA.
[Burman, Kenneth D.] Washington Hosp Ctr, Washington, DC 20010 USA.
[Kebebew, Electron] NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
[Lee, Nancy Y.; Shaha, Ashok R.; Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Nikiforov, Yuri E.] Univ Pittsburgh, Pittsburgh, PA USA.
[Rosenthal, M. Sara] Univ Kentucky, Program Bioeth, Lexington, KY USA.
[Shah, Manisha H.] Ohio State Univ, Columbus, OH 43210 USA.
RP Smallridge, RC (reprint author), Mayo Clin, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM smallridge.robert@mayo.edu
FU Thyroid Cancer Survivors Association; Joan Shey of the Light of Life
Foundation; Pfizer, Inc. (New York, NY); Eisei Inc. (Woodcliff Lake,
NJ); Amgen Inc. (Thousand Oaks, CA); Genzyme Corp. (Cambridge, MA);
Daiichi Sankyo, Inc. (Parsippany, NJ); Daiichi Sankyo; Genzyme
FX We wish to thank Ms. Kathleen Norton (Mayo Clinic, Jacksonville, FL) for
her invaluable editorial assistance in preparation of this document. We
gratefully acknowledge financial contributions to this project from the
Thyroid Cancer Survivors Association and from Joan Shey of the Light of
Life Foundation.; J.D.B. is a consultant for OXiGENE, Inc. (South San
Francisco, CA). K. D. B. is a consultant for UpToDate, Inc. (Waltham,
MA) and Medscape WebMD LLC (New York, NY), and received clinical
research support from Pfizer, Inc. (New York, NY), Eisei Inc. (Woodcliff
Lake, NJ), Amgen Inc. (Thousand Oaks, CA), and Genzyme Corp. (Cambridge,
MA). M.H.S. received clinical research support from Daiichi Sankyo, Inc.
(Parsippany, NJ). R.C.S. received research support from Daiichi Sankyo
for a clinical trial. R.M.T. received research support from Genzyme and
is a consultant for Novo Nordisk (Princeton, NJ), AstraZeneca (Waltham,
MA), Veracyte (South San Francisco, CA), and Genzyme. K.B.A., S.L.A.,
K.C.B., E.K., N.L., Y.E.N., M.S.R., and A.R.S. have no financial
disclosures.
NR 235
TC 141
Z9 144
U1 1
U2 16
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD NOV
PY 2012
VL 22
IS 11
BP 1104
EP 1139
DI 10.1089/thy.2012.0302
PG 36
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 033KK
UT WOS:000310794400004
PM 23130564
ER
PT J
AU Tsang, V
Fry, RC
Niculescu, MD
Rager, JE
Saunders, J
Paul, DS
Zeisel, SH
Waalkes, MP
Styblo, M
Drobna, Z
AF Tsang, Verne
Fry, Rebecca C.
Niculescu, Mihai D.
Rager, Julia E.
Saunders, Jesse
Paul, David S.
Zeisel, Steven H.
Waalkes, Michael P.
Styblo, Miroslav
Drobna, Zuzana
TI The epigenetic effects of a high prenatal folate intake in male mouse
fetuses exposed in utero to arsenic
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Arsenic; Folate; Epigenetics; DNA methylation; Transplacental exposure;
CD1 mice
ID LOW-BIRTH-WEIGHT; FOLIC-ACID-SUPPLEMENTATION; INDUCED SKIN-LESIONS;
DRINKING-WATER; HEPATOCELLULAR-CARCINOMA; CD1 MICE; POSTNATAL
DIETHYLSTILBESTROL; CARDIOVASCULAR-DISEASE; METHYLATION CAPACITY;
PLACENTAL EXPRESSION
AB Inorganic arsenic (iAs) is a complete transplacental carcinogen in mice. Previous studies have demonstrated that in utero exposure to iAs promotes cancer in adult mouse offspring, possibly acting through epigenetic mechanisms. Humans and rodents enzymatically convert iAs to its methylated metabolites. This reaction requires S-adenosylmethionine (SAM) as methyl group donor. SAM is also required for DNA methylation. Supplementation with folate, a major dietary source of methyl groups for SAM synthesis, has been shown to modify iAs metabolism and the adverse effects of iAs exposure. However, effects of gestational folate supplementation on iAs metabolism and fetal DNA methylation have never been thoroughly examined. In the present study, pregnant CD1 mice were fed control (i.e. normal folate, or 2.2 mg/kg) or high folate diet (11 mg/kg) from gestational day (GD) 5 to 18 and drank water with 0 or 85 ppm of As (as arsenite) from GD8 to 18. The exposure to iAs significantly decreased body weight of GD18 fetuses and increased both SAM and S-adenosylhomocysteine (SAH) concentrations in fetal livers. High folate intake lowered the burden of total arsenic in maternal livers but did not prevent the effects of iAs exposure on fetal weight or hepatic SAM and SAH concentrations. In fact, combined folate-iAs exposure caused further significant body weight reduction. Notably, iAs exposure alone had little effect on DNA methylation in fetal livers. In contrast, the combined folate-iAs exposure changed the CpG island methylation in 2,931 genes, including genes known to be imprinted. Most of these genes were associated with neurodevelopment, cancer, cell cycle, and signaling networks. The canonical Wnt-signaling pathway, which regulates fetal development, was among the most affected biological pathways. Taken together, our results suggest that a combined in utero exposure to iAs and a high folate intake may adversely influence DNA methylation profiles and weight of fetuses, compromising fetal development and possibly increasing the risk for early-onset of disease in offspring. (c) 2012 Elsevier Inc. All rights reserved.
C1 [Drobna, Zuzana] Univ N Carolina, Dept Nutr, Michael Hooker Res Ctr 2003, Chapel Hill, NC 27599 USA.
[Fry, Rebecca C.; Rager, Julia E.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA.
[Niculescu, Mihai D.; Zeisel, Steven H.] Univ N Carolina, Dept Nutr, UNC Nutr Res Inst, Chapel Hill, NC 27599 USA.
[Waalkes, Michael P.] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Drobna, Z (reprint author), Univ N Carolina, Dept Nutr, Michael Hooker Res Ctr 2003, CB 7461, Chapel Hill, NC 27599 USA.
EM drobnazu@med.unc.edu
FU National Institutes of Health Grant [DK056350]; National Institute of
Environmental Health Sciences [P30ES010126]; American Institute for
Cancer Research/World Cancer Research Fund (AICR/WCRF); National
Toxicology Program and National Institute of Environmental Health
Sciences (NIEHS)
FX We acknowledge Laurie Bennie and Mrs. Felecia Walton for their
assistance during the mice dissection. This work has been supported in
part by National Institutes of Health Grant DK056350 to the University
of North Carolina at Chapel Hill's Nutrition Obesity Research Center, by
a grant from the National Institute of Environmental Health Sciences
(P30ES010126), and by the American Institute for Cancer Research/World
Cancer Research Fund (AICR/WCRF) to Z.D. This research was supported by
the National Toxicology Program and National Institute of Environmental
Health Sciences (NIEHS). This article may be the work product of an
employee or a group of employees of the NIEHS, NIH: however, the
statements contained herein do not necessarily represent the statements,
opinions or conclusions of the NIEHS, NIH or the United States
Government. The content of this publication does not necessarily reflect
the views or the policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 123
TC 18
Z9 19
U1 1
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD NOV 1
PY 2012
VL 264
IS 3
BP 439
EP 450
DI 10.1016/j.taap.2012.08.022
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 031VG
UT WOS:000310670000016
PM 22959928
ER
PT J
AU Adjemian, J
Weber, IB
McQuiston, J
Griffith, KS
Mead, PS
Nicholson, W
Roche, A
Schriefer, M
Fischer, M
Kosoy, O
Laven, JJ
Stoddard, RA
Hoffmaster, AR
Smith, T
Bui, D
Wilkins, PP
Jones, JL
Gupton, PN
Quinn, CP
Messonnier, N
Higgins, C
Wong, D
AF Adjemian, Jennifer
Weber, Ingrid B.
McQuiston, Jennifer
Griffith, Kevin S.
Mead, Paul S.
Nicholson, William
Roche, Aubree
Schriefer, Martin
Fischer, Marc
Kosoy, Olga
Laven, Janeen J.
Stoddard, Robyn A.
Hoffmaster, Alex R.
Smith, Theresa
Bui, Duy
Wilkins, Patricia P.
Jones, Jeffery L.
Gupton, Paige N.
Quinn, Conrad P.
Messonnier, Nancy
Higgins, Charles
Wong, David
TI Zoonotic Infections Among Employees from Great Smoky Mountains and Rocky
Mountain National Parks, 2008-2009
SO VECTOR-BORNE AND ZOONOTIC DISEASES
LA English
DT Article
DE Incidence; National Park Service; Prevalence; Vector-borne; Zoonoses
ID BORNE RELAPSING FEVER; WEST-NILE-VIRUS; TOXOPLASMA-GONDII INFECTION;
LINKED-IMMUNOSORBENT-ASSAY; UNITED-STATES; SPOTTED-FEVER;
IMMUNOGLOBULIN-G; INTERSTATE OUTBREAK; PROTECTIVE ANTIGEN;
BACILLUS-ANTHRACIS
AB U.S. National Park Service employees may have prolonged exposure to wildlife and arthropods, placing them at increased risk of infection with endemic zoonoses. To evaluate possible zoonotic risks present at both Great Smoky Mountains (GRSM) and Rocky Mountain (ROMO) National Parks, we assessed park employees for baseline seroprevalence to specific zoonotic pathogens, followed by evaluation of incident infections over a 1-year study period. Park personnel showed evidence of prior infection with a variety of zoonotic agents, including California serogroup bunyaviruses (31.9%), Bartonella henselae (26.7%), spotted fever group rickettsiae (22.2%), Toxoplasma gondii (11.1%), Anaplasma phagocytophilum (8.1%), Brucella spp. (8.9%), flaviviruses (2.2%), and Bacillus anthracis (1.5%). Over a 1-year study period, we detected incident infections with leptospirosis (5.7%), B. henselae (5.7%), spotted fever group rickettsiae (1.5%), T. gondii (1.5%), B. anthracis (1.5%), and La Crosse virus (1.5%) in staff members at GRSM, and with spotted fever group rickettsiae (8.5%) and B. henselae (4.3%) in staff at ROMO. The risk of any incident infection was greater for employees who worked as resource managers (OR 7.4; 95% CI 1.4,37.5; p = 0.02), and as law enforcement rangers/rescue crew (OR 6.5; 95% CI 1.1,36.5; p = 0.03), relative to those who worked primarily in administration or management. The results of this study increase our understanding of the pathogens circulating within both parks, and can be used to inform the development of effective guidelines and interventions to increase visitor and staff awareness and help prevent exposure to zoonotic agents.
C1 [Adjemian, Jennifer; Weber, Ingrid B.] Ctr Dis Control & Prevent CDC, Epidem Intelligence Serv, Off Workforce & Career Dev, Atlanta, GA USA.
[Adjemian, Jennifer; McQuiston, Jennifer; Nicholson, William; Roche, Aubree] CDC, Rickettsial Zoonoses Branch, Div Vector Borne Dis, Atlanta, GA 30333 USA.
[Weber, Ingrid B.; Griffith, Kevin S.; Mead, Paul S.; Schriefer, Martin] CDC, Bacterial Dis Branch, Div Vector Borne Dis, Ft Collins, CO USA.
[Weber, Ingrid B.; Fischer, Marc; Kosoy, Olga; Laven, Janeen J.] CDC, Arboviral Dis Branch, Div Vector Borne Dis, Ft Collins, CO USA.
[Stoddard, Robyn A.; Hoffmaster, Alex R.; Smith, Theresa; Bui, Duy] CDC, Bacterial Special Pathogens Branch, Div High Consequence Pathogens & Pathol, Atlanta, GA 30333 USA.
[Wilkins, Patricia P.; Jones, Jeffery L.; Gupton, Paige N.] CDC, Parasit Dis Branch, Div Parasit Dis, Atlanta, GA 30333 USA.
[Quinn, Conrad P.; Messonnier, Nancy] CDC, Meningitis & Vaccine Preventable Dis Branch, Div Bacterial Dis, Atlanta, GA 30333 USA.
[Higgins, Charles; Wong, David] Natl Pk Serv, Off Publ Hlth, Washington, DC USA.
[Higgins, Charles; Wong, David] Natl Pk Serv, Off Publ Hlth, Albuquerque, NM USA.
RP Adjemian, J (reprint author), NIAID, Epidem Intelligence Serv, Lab Clin Infect Dis, Quarters 15 B-1,8 West Dr,MSC 2665, Bethesda, MD 20892 USA.
EM Jennifer.adjemian@nih.gov
NR 60
TC 10
Z9 11
U1 0
U2 13
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-3667
EI 1557-7759
J9 VECTOR-BORNE ZOONOT
JI Vector-Borne Zoonotic Dis.
PD NOV
PY 2012
VL 12
IS 11
BP 922
EP 931
DI 10.1089/vbz.2011.0917
PG 10
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 033FW
UT WOS:000310780600002
PM 22835153
ER
PT J
AU Kashiwakura, JI
Okayama, Y
Furue, M
Kabashima, K
Shimada, S
Ra, C
Siraganian, RP
Kawakami, Y
Kawakami, T
AF Kashiwakura, Jun-ichi
Okayama, Yoshimichi
Furue, Masutaka
Kabashima, Kenji
Shimada, Shinji
Ra, Chisei
Siraganian, Reuben P.
Kawakami, Yuko
Kawakami, Toshiaki
TI Most Highly Cytokinergic IgEs Have Polyreactivity to Autoantigens
SO ALLERGY ASTHMA & IMMUNOLOGY RESEARCH
LA English
DT Article
DE Atopic dermatitis; mast cell; cytokine; IgE; autoantigen;
histamine-releasing factor
ID FC-EPSILON-RI; MAST-CELL SURVIVAL; RECALCITRANT ATOPIC-DERMATITIS;
IMMUNOGLOBULIN-E; HIGH-AFFINITY; MEDIATED AUTOIMMUNITY;
ASPERGILLUS-FUMIGATUS; NC/NGA MICE; OMALIZUMAB; INDUCTION
AB Purpose: Monomeric IgE molecules, when bound to the high-affinity receptor, exhibit a vast heterogeneity in their ability to induce survival promotion and cytokine production in mast cells. At one end of this spectrum, highly cytokinergic IgEs can induce potent survival promotion, degranulation, cytokine production, migration, etc., whereas at the other end, poorly cytokinergic (PC) IgEs can do so inefficiently. In this study, we investigated whether IgEs recognize autoantigens and whether IgEs' binding of autoantigens correlates with difference s in HC versus PC properties. Methods: Enzyme-linked immunosorbent assays were performed to test whether IgEs bind antigens. Histamine-releasing factor in human sera was quantified by western blotting. Cultured mast cells derived from human cord blood were used to test the effects of human sera on cytokine production. Results: Most (7/8) of mouse monoclonal HC IgEs exhibited polyreactivity to double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), beta-galactosidase, thyroglobulin and/or histamine-releasing factor. By contrast mouse PC IgEs failed to react with these antigens. A human monoclonal HC IgE also showed polyreactivity to histamine-releasing factor, dsDNA and ssDNA. Interestingly, sera from atopic dermatitis patients showed increased reactivity to ssDNA and beta-galactosidase and increased levels of histamine-releasing factor. Some atopic dermatitis patients, but not healthy individuals, had substantial serum levels of HRF-reactive IgE. Sera from atopic dermatitis patients with high titers of DNA-reactive IgE could induce several fold more IL-8 secretion in human mast cells than sera from healthy individuals. Conclusions: The results show that most HC, but not PC, IgEs exhibit polyreactivity to autoantigens, supporting the autoimmune mechanism in the pathogenesis of atopic dermatitis.
C1 [Kashiwakura, Jun-ichi; Kawakami, Yuko; Kawakami, Toshiaki] La Jolla Inst Allergy & Immunol, Div Cell Biol, La Jolla, CA 92037 USA.
[Kashiwakura, Jun-ichi; Okayama, Yoshimichi; Ra, Chisei] Nihon Univ, Grad Sch Med Sci, Adv Med Res Ctr, Div Mol Cell Immunol & Allergol,Itabashi Ku, Tokyo, Japan.
[Furue, Masutaka] Kyushu Univ, Dept Dermatol, Fukuoka 812, Japan.
[Kabashima, Kenji] Univ Occupat & Environm Hlth, Dept Dermatol, Kitakyushu, Fukuoka 807, Japan.
[Shimada, Shinji] Univ Yamanashi, Dept Dermatol, Yamanashi, Japan.
[Siraganian, Reuben P.] NIDR, Receptors & Signal Transduct Sect, OIIB, NIH, Bethesda, MD USA.
RP Kawakami, T (reprint author), La Jolla Inst Allergy & Immunol, Div Cell Biol, 9420 Athena Circle, La Jolla, CA 92037 USA.
EM toshi@liai.org
RI Kabashima, Kenji/G-2521-2014; Kawakami, Toshiaki/O-1616-2015
OI Kabashima, Kenji/0000-0002-0773-0554;
FU NIH [R01 AI050209]; Intramural Research Program of the National
Institutes of Health, NIDCR
FX The authors thank Drs. Shane Crotty and Rachel Soloff for providing
normal sera. This study was funded in part by an NIH grant R01 AI050209
(T.K.). RPS was supported by the Intramural Research Program of the
National Institutes of Health, NIDCR. This is Publication No. 1465 from
the La Jolla Institute for Allergy and Immunology.
NR 50
TC 18
Z9 19
U1 0
U2 3
PU KOREAN ACAD ASTHMA ALLERGY & CLINICAL IMMUNOLOGY
PI JONGNO-GU
PA RM 1705, KUMHO BLDG 327-2, CHANGSINDONG, JONGNO-GU, SEOUL 110-540, SOUTH
KOREA
SN 2092-7355
J9 ALLERGY ASTHMA IMMUN
JI Allergy Asthma Immunol. Res.
PD NOV
PY 2012
VL 4
IS 6
BP 332
EP 340
DI 10.4168/aair.2012.4.6.332
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 028ED
UT WOS:000310404700004
PM 23115729
ER
PT J
AU Ben Mortenson, W
Demers, L
Fuhrer, MJ
Jutai, JW
Lenker, J
DeRuyter, F
AF Ben Mortenson, W.
Demers, Louise
Fuhrer, Marcus J.
Jutai, Jeffrey W.
Lenker, James
DeRuyter, Frank
TI How Assistive Technology Use by Individuals with Disabilities Impacts
Their Caregivers A Systematic Review of the Research Evidence
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Review
DE Self-Help Devices; Caregivers; Outcomes Assessment; Review
ID LONG-TERM-CARE; RANDOMIZED CONTROLLED-TRIALS; QUALITATIVE RESEARCH;
OUTCOMES RESEARCH; PERSONAL CARE; OLDER PERSONS; HOME; DEVICES;
INTERVENTIONS; MOBILITY
AB Mortenson WB, Demers L, Fuhrer MJ, Jutai JW, Lenker J, DeRuyter F: How assistive technology use by individuals with disabilities impacts their caregivers: a systematic review of the research evidence. Am J Phys Med Rehabil 2012;91:984-998.
Informal caregivers are a critical yet frequently unacknowledged part of the healthcare system. It is commonly presumed that providing assistive technology will decrease the burden of their care provision; however, no review has evaluated the evidence behind this assumption. Therefore, a systematic review was undertaken to evaluate evidence of the impact of assistive technology use by care recipients on their informal caregivers. Data sources included EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science, PsychINFO, PubMed, and active researchers in this area. Twenty-two studies met the specified inclusion criteria. Collectively, the findings suggest that assistive technology use helps caregivers by diminishing some of the physical and emotional effort entailed in supporting individuals with disability. However, confidence in this causal connection is limited because of the study designs that were used. This undermines the understanding of the impacts of assistive technology use on the users' informal caregivers.
C1 [Ben Mortenson, W.] Simon Fraser Univ, Gerontol Res Ctr, Harbour Ctr 2800, Vancouver, BC V6B 5K3, Canada.
[Ben Mortenson, W.; Demers, Louise] Inst Univ Geriatr Montreal, Ctr Rech, Montreal, PQ, Canada.
[Fuhrer, Marcus J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Demers, Louise] Univ Montreal, Ecole Readaptat, Montreal, PQ, Canada.
[Jutai, Jeffrey W.] Univ Ottawa, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada.
[Jutai, Jeffrey W.] Bruyere Res Inst, Ottawa, ON, Canada.
[Lenker, James] SUNY Buffalo, Dept Rehabil Sci, Buffalo, NY 14260 USA.
[DeRuyter, Frank] Duke Univ, Dept Surg, Div Speech Pathol & Audiol, Durham, NC USA.
RP Ben Mortenson, W (reprint author), Simon Fraser Univ, Gerontol Res Ctr, Harbour Ctr 2800, 515 W Hastings St, Vancouver, BC V6B 5K3, Canada.
RI Mortenson, William/L-7441-2013
OI Mortenson, William/0000-0002-0183-6163
FU National Institute on Disability and Rehabilitation Research
[H133A060062]; Canadian Institutes of Health Research (CIHR) [232262]
FX Supported by the National Institute on Disability and Rehabilitation
Research (grant no. H133A060062) and the Canadian Institutes of Health
Research (CIHR) (grant no. 232262). Personal financial support for Dr
Mortenson was provided by a CIHR postdoctoral fellowship in the area of
Aging and Mobility from the Institute of Aging. Presented at the
American Congress of Rehabilitation Medicine-American Society of
Neurorehabilitation Conference, October, Montreal, PQ (Mortenson WB,
Demers L, Jutai J, Fuhrer MJ, Lenker J, DeRuyter F: Impacts of assistive
technology interventions on informal caregivers of adults with chronic
physical impairments: A systematic review. 2010) and at the 2011
Disability, Aging and Technology, Disability, Aging and Technology,
June, Toronto, ON (Mortenson WB, Demers L, Jutai J, Fuhrer MJ, Lenker J,
DeRuyter F: Impacts of assistive technology interventions on informal
caregivers. 2011) (portions of the findings).
NR 64
TC 0
Z9 0
U1 1
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD NOV
PY 2012
VL 91
IS 11
BP 984
EP 998
DI 10.1097/PHM.0b013e318269eceb
PG 15
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 027NR
UT WOS:000310359900009
ER
PT J
AU Kiley, JP
Senior, RM
AF Kiley, James P.
Senior, Robert M.
TI Pulmonary research in 2013 and beyond: a National Heart, Lung, and Blood
Institute perspective
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Editorial Material
ID CARDIOVASCULAR HEALTH; VIRAL-INFECTION; INNATE IMMUNE;
LYMPHANGIOLEIOMYOMATOSIS; ACTIVATION; MORTALITY; FIBROSIS; CELLS; GENE;
DISEASE
C1 [Kiley, James P.] NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2, Bethesda, MD 20892 USA.
[Senior, Robert M.] Washington Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63110 USA.
RP Kiley, JP (reprint author), NHLBI, Div Lung Dis, NIH, Rockledge Ctr 2, Suite 10042,6701 Rockledge Dr,MSC 7952, Bethesda, MD 20892 USA.
EM kileyj@nhlbi.nih.gov
NR 34
TC 1
Z9 1
U1 0
U2 2
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 NOV
PY 2012
VL 303
IS 9
BP L729
EP L732
DI 10.1152/ajplung.00305.2012
PG 4
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 031MT
UT WOS:000310646200001
PM 22962017
ER
PT J
AU Tripp, A
Oh, H
Guilloux, JP
Martinowich, K
Lewis, DA
Sibille, E
AF Tripp, Adam
Oh, Hyunjung
Guilloux, Jean-Philippe
Martinowich, Keri
Lewis, David A.
Sibille, Etienne
TI Brain-Derived Neurotrophic Factor Signaling and Subgenual Anterior
Cingulate Cortex Dysfunction in Major Depressive Disorder
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID DRIVEN BDNF TRANSCRIPTION; PREFRONTAL CORTEX; SUICIDE SUBJECTS;
GENE-EXPRESSION; SCHIZOPHRENIA; BEHAVIOR; AMYGDALA; CIRCUITRY; FEATURES;
STRESS
AB Objective: The subgenual anterior cingulate cortex is implicated in the pathology and treatment response of major depressive disorder. Low levels of brain-derived neurotrophic factor (BDNF) and reduced markers for GABA function, including in the amygdala, are reported in major depression, but their contribution to subgenual anterior cingulate cortex dysfunction is not known.
Method: Using polymerase chain reaction, we first assessed the degree to which BDNF controls mRNA expression (defined as BDNF dependency) of 15 genes relating to GABA and neuropeptide functions in the cingulate cortex of mice with reduced BDNF function (BDNF-heterozygous [Bdnf(+/-)] mice and BDNF exon-IV knockout [Bdrif(KIV)] mice). Gene expression was then quantified in the subgenual anterior cingulate cortex of 51 postmortem subjects with major depressive disorder and comparison subjects (total subjects, N=102; 49% were women) and compared with previous amygdala results.
Results: Based on the results in Bdnf(+/-) and Bdnf(KIV) mice, genes were sorted into high, intermediate, and no BDNF dependency sets. In postmortem human subjects with major depression, BDNF receptor (TRKB) expression, but not BDNF, was reduced. Postmortem depressed subjects exhibited down-regulation in genes with high and intermediate BDNF dependency, including markers of dendritic targeting interneurons (SST, NPY, and COR7) and a GABA synthesizing enzyme (GAD2). Changes extended to BDNF-independent genes (PVALB and GAD1). Changes were greater in men (potentially because of low baseline expression in women), displayed notable differences from prior amygdala results, and were not explained by demographic or clinical factors other than sex.
Conclusions: These parallel human/mouse analyses provide direct (low TRKB) and indirect (low expression of BDNF-dependent genes) evidence in support of decreased BDNF signaling in the subgenual anterior cingulate cortex in individuals with major depressive disorder, implicate dendritic targeting GABA neurons and GABA synthesis, and, together, suggest a common BDNF-/GABA-related pathology in major depression with sex- and brain region-specific features.
C1 [Sibille, Etienne] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
Univ Paris Sud, Fac Pharm, Chatenay Malabry, France.
NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA.
Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD USA.
RP Sibille, E (reprint author), Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
EM sibilleel@upmc.edu
RI Lewis, David/G-4053-2014; Guilloux, Jean-Philippe/B-3726-2015;
Martinowich, Keri/F-9841-2012;
OI Lewis, David/0000-0002-3225-6778; Guilloux,
Jean-Philippe/0000-0003-0982-3751; Martinowich, Keri/0000-0002-5237-0789
FU NIMH [MH-084060, MH-085111, M-H084053]; Bristol-Myers Squibb;
Bristol-Myers Squibb Foundation; Curridium, Ltd.; Pfizer
FX Supported by NIMH grants MH-084060 and MH-085111 to Dr. Sibille and
grant M-H084053 to Dr. Lewis.; Dr. Lewis currently receives
investigator-initiated research support from Bristol-Myers Squibb, the
Bristol-Myers Squibb Foundation, Curridium, Ltd., and Pfizer; he has
also previously served as a consultant to Bristol-Myers Squibb in the
areas of target identification and validation and new compound
development. The other authors report no financial relationships with
commercial interest.
NR 40
TC 46
Z9 48
U1 4
U2 18
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 NOV
PY 2012
VL 169
IS 11
BP 1194
EP 1202
DI 10.1176/appi.ajp.2012.12020248
PG 9
WC Psychiatry
SC Psychiatry
GA 031RA
UT WOS:000310658400012
PM 23128924
ER
PT J
AU Kulik, LM
Fisher, RA
Rodrigo, DR
Brown, RS
Freise, CE
Shaked, A
Everhart, JE
Everson, GT
Hong, JC
Hayashi, PH
Berg, CL
Lok, ASF
AF Kulik, L. M.
Fisher, R. A.
Rodrigo, D. R.
Brown, R. S., Jr.
Freise, C. E.
Shaked, A.
Everhart, J. E.
Everson, G. T.
Hong, J. C.
Hayashi, P. H.
Berg, C. L.
Lok, A. S. F.
CA A2ALL Study Grp
TI Outcomes of Living and Deceased Donor Liver Transplant Recipients With
Hepatocellular Carcinoma: Results of the A2ALL Cohort
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE HCC; loco-regional therapy; MELD score; Milan criteria; recurrence;
survival
ID SURVIVAL; RECURRENCE; CRITERION; EXPANSION; PRIORITY; THERAPY
AB Hepatocellular carcinoma (HCC) represents an increasing fraction of liver transplant indications; the role of living donor liver transplant (LDLT) remains unclear. In the Adult-to-Adult Living Donor Liver Transplantation Cohort Study, patients with HCC and an LDLT or deceased donor liver transplant (DDLT) for which at least one potential living donor had been evaluated were compared for recurrence and posttransplant mortality rates. Mortality from date of evaluation of each recipient's first potential living donor was also analyzed. Unadjusted 5-year HCC recurrence was significantly higher after LDLT (38%) than DDLT (11%), (p = 0.0004). After adjustment for tumor characteristics, HCC recurrence remained significantly different between LDLT and DDLT recipients (hazard ratio (HR) = 2.35; p = 0.04) for the overall cohort but not for recipients transplanted following the introduction of MELD prioritization. Five-year posttransplant survival was similar in LDLT and DDLT recipients from time of transplant (HR = 1.32; p = 0.27) and from date of LDLT evaluation (HR = 0.73; p = 0.36). We conclude that the higher recurrence observed after LDLT is likely due to differences in tumor characteristics, pretransplant HCC management and waiting time.
C1 [Fisher, R. A.] Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA 23284 USA.
[Kulik, L. M.] Northwestern Univ, Dept Med & Surg, Chicago, IL 60611 USA.
[Rodrigo, D. R.] Univ Michigan, Dept Surg, Ann Arbor, MI USA.
[Brown, R. S., Jr.] Columbia Univ Coll Phys & Surg, Dept Med & Surg, New York, NY 10032 USA.
[Freise, C. E.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Shaked, A.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA.
[Everhart, J. E.] Univ Colorado, Dept Med, Denver, CO USA.
[Everson, G. T.] NIDDKD, Bethesda, MD 20892 USA.
[Hong, J. C.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA.
[Hayashi, P. H.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Berg, C. L.] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Lok, A. S. F.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
RP Fisher, RA (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Hosp, Dept Surg, Richmond, VA 23284 USA.
EM rafisher@vcu.edu
OI Yang, Shuman/0000-0002-9638-0890
FU Bayer/Onyx; Speaking and Teaching: Bayer/Onyx; Bristol-Myers Squibb;
GlaxoSmithKline; Schering-Plough; Roche; Gilead; Hep C Connection;
Pharmassett; Vertex; GSK; Tibotec; Human Genome Sciences/Novartis;
GlobeImmune; OrthoBiotech; Medtronic; Pfizer; Eisai; Abbott; Conatus;
ZymoGenetics; PSC Partners
FX Laura M. Kulik-Advisory Committees: Bayer/Onyx; Grant/Research Support:
Bayer/Onyx; Speaking and Teaching: Bayer/Onyx.; Anna S. Lok-Consulting:
Roche, Gilead, Bristol-Myers Squibb, Bayer; Grant/Research Support:
Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, Roche, Gilead.;
Greg T. Everson-Advisory Committee or Review Panels: Roche, Merck, Three
Rivers, Hep C Connection; Board membership: HepQuant LLC, PSC partners;
Consulting: Genentech; Grant/Research Support: Roche, Pharmassett,
Vertex, GSK, Schering-Plough, Bristol-Myers Squibb, Tibotec, Human
Genome Sciences/Novartis, GlobeImmune, OrthoBiotech, Medtronic, Pfizer,
Eisai, Abbott, Conatus, ZymoGenetics, PSC Partners; Management Position:
HepQuant LLC; Patent Held/Filed: University of Colorado.
NR 33
TC 38
Z9 39
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD NOV
PY 2012
VL 12
IS 11
BP 2997
EP 3007
DI 10.1111/j.1600-6143.2012.04272.x
PG 11
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 029EW
UT WOS:000310478600018
PM 22994906
ER
PT J
AU Charafeddine, AH
Kim, EJ
Maynard, DM
Yi, H
Weaver, TA
Gunay-Aygun, M
Russell, M
Gahl, WA
Kirk, AD
AF Charafeddine, A. H.
Kim, E. J.
Maynard, D. M.
Yi, H.
Weaver, T. A.
Gunay-Aygun, M.
Russell, M.
Gahl, W. A.
Kirk, A. D.
TI Platelet-Derived CD154: Ultrastructural Localization and Clinical
Correlation in Organ Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE Costimulation; platelets; trauma
ID SOLUBLE CD40 LIGAND; RENAL-ALLOGRAFT REJECTION; ACUTE CORONARY
SYNDROMES; ACTIVATED T-CELLS; ALPHA-GRANULES; MONOCLONAL-ANTIBODY;
ENDOTHELIAL-CELLS; SAMPLE TYPE; PLASMA; EXOCYTOSIS
AB CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, the release of platelet derived CD154 and its consequences have not been investigated in a clinical transplant setting. To better characterize the relationship between platelet activation and CD154 release, we investigated CD154 release by platelets obtained from normal individuals, and patients with two genetic defects that influence platelet granule development. Using these unique patient populations and immune-electron microscopy, we confirmed that CD154 was an alpha granule and not a cell surface protein, and thereafter optimized the methods for its in vivo measurement in humans. We then investigated plasma CD154 levels in kidney and liver transplant recipients and found no evidence that CD154 levels fluctuated systemically as a result of kidney or liver transplant procedures. Paradoxically, we found that kidney transplant patients had significantly lower systemic CD154 levels during episodes of rejection. These data suggest that the immune effects of CD154 are likely mediated through local and not systemic mechanisms, and discourage the use of CD154 as a peripheral biomarker in organ transplantation.
C1 [Charafeddine, A. H.; Kim, E. J.; Yi, H.; Weaver, T. A.; Russell, M.; Kirk, A. D.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA.
[Gunay-Aygun, M.] NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA.
RP Kirk, AD (reprint author), Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA.
EM adkirk@emory.edu
FU Intramural Research Program of the National Human Genome Research
Institute; National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health; Georgia Research
Alliance; McKelvey Foundation
FX The authors gratefully acknowledge Marquita Kilgore, Sumeet Bahl, Shine
Thomas, Ewa Turner and Sean Crawford for their expert technical
assistance. This work was funded in part by the Intramural Research
Program of the National Human Genome Research Institute and the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health. ADK is supported by the Georgia Research Alliance
and by the McKelvey Foundation.
NR 34
TC 8
Z9 8
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD NOV
PY 2012
VL 12
IS 11
BP 3143
EP 3151
DI 10.1111/j.1600-6143.2012.04241.x
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA 029EW
UT WOS:000310478600034
PM 22947105
ER
PT J
AU Duell, EJ
Lucenteforte, E
Olson, SH
Bracci, PM
Li, D
Risch, HA
Silverman, DT
Ji, BT
Gallinger, S
Holly, EA
Fontham, EH
Maisonneuve, P
Bueno-de-Mesquita, HB
Ghadirian, P
Kurtz, RC
Ludwig, E
Yu, H
Lowenfels, AB
Seminara, D
Petersen, GM
La Vecchia, C
Boffetta, P
AF Duell, E. J.
Lucenteforte, E.
Olson, S. H.
Bracci, P. M.
Li, D.
Risch, H. A.
Silverman, D. T.
Ji, B. T.
Gallinger, S.
Holly, E. A.
Fontham, E. H.
Maisonneuve, P.
Bueno-de-Mesquita, H. B.
Ghadirian, P.
Kurtz, R. C.
Ludwig, E.
Yu, H.
Lowenfels, A. B.
Seminara, D.
Petersen, G. M.
La Vecchia, C.
Boffetta, P.
TI Pancreatitis and pancreatic cancer risk: a pooled analysis in the
International Pancreatic Cancer Case-Control Consortium (PanC4)
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE case-control studies; pancreatitis; pancreatic cancer; pooled analysis;
risk factors
ID ABO BLOOD-GROUP; HEREDITARY PANCREATITIS; ALCOHOL-CONSUMPTION;
CIGARETTE-SMOKING; HISTORY; TOBACCO; INFLAMMATION; MECHANISMS;
ALLERGIES; ONSET
AB Pancreatitis is a known risk factor for pancreatic cancer; however, an unknown fraction of the disease is thought to be a consequence of tumor-related duct obstruction.
A pooled analysis of a history of pancreatitis and risk of pancreatic cancer was carried out considering the time interval between diagnoses and potential modification by covariates. Adjusted pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated from 10 case-control studies (5048 cases of ductal pancreatic adenocarcinoma and 10 947 controls) taking part in the International Pancreatic Cancer Case-Control Consortium (PanC4).
The association between pancreatitis and pancreatic cancer was nearly three-fold at intervals of > 2 years between diagnoses (OR: 2.71, 95% CI: 1.96-3.74) and much stronger at intervals of < 2 years (OR: 13.56, 95% CI: 8.72-21.90) probably reflecting a combination of reverse causation and antecedent misdiagnosis of pancreas cancer as pancreatitis. The younger (< 65 years) pancreatic cancer cases showed stronger associations with previous (> 2 years) pancreatitis (OR: 3.91, 95% CI: 2.53-6.04) than the older (>= 65 years) cases (OR: 1.68, 95% CI: 1.02-2.76; P value for interaction: 0.006).
Despite a moderately strong association between pancreatitis (diagnosed before > 2 years) and pancreatic cancer, the population attributable fraction was estimated at 1.34% (95% CI: 0.612-2.07%), suggesting that a relatively small proportion of pancreatic cancer might be avoided if pancreatitis could be prevented.
C1 [Duell, E. J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Barcelona 08907, Spain.
[Lucenteforte, E.; La Vecchia, C.] Inst Pharmacol Res Mario Negri, Dept Epidemiol, Milan, Italy.
[Lucenteforte, E.] Univ Florence, Dept Preclin & Clin Pharmacol Mario Aiazzi Mancin, Florence, Italy.
[Olson, S. H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Bracci, P. M.; Holly, E. A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA.
[Li, D.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Risch, H. A.; Yu, H.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06510 USA.
[Silverman, D. T.; Ji, B. T.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gallinger, S.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Fontham, E. H.] Louisiana State Univ, Sch Publ Hlth, New Orleans, LA USA.
[Maisonneuve, P.] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy.
[Bueno-de-Mesquita, H. B.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. B.] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Ghadirian, P.] Univ Montreal Hosp Ctr CRCHUM, Res Ctr, Epidemiol Res Unit, Montreal, PQ, Canada.
[Kurtz, R. C.; Ludwig, E.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Yu, H.] Univ Hawaii, Canc Res Ctr Hawaii, Canc Epidemiol Program, Honolulu, HI 96813 USA.
[Lowenfels, A. B.] New York Med Coll, Dept Surg, Valhalla, NY 10595 USA.
[Seminara, D.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Petersen, G. M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Petersen, G. M.] Mayo Clin, Coll Med, Dept Gastroenterol, Rochester, MN USA.
[Petersen, G. M.] Mayo Clin, Coll Med, Dept Med Genet, Rochester, MN USA.
[La Vecchia, C.] Univ Milan, Dept Occupat Hlth, Milan, Italy.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, P.] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA.
RP Duell, EJ (reprint author), Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Canc Epidemiol Res Program, Avda Gran Via 199-203, Barcelona 08907, Spain.
EM eduell@iconcologia.net
RI Gallinger, Steven/E-4575-2013;
OI Duell, Eric J/0000-0001-5256-0163; La Vecchia,
Carlo/0000-0003-1441-897X; Lucenteforte, Ersilia/0000-0001-5608-5902;
Maisonneuve, Patrick/0000-0002-5309-4704
FU National Cancer Institute (NCI); Prevention, Control and Population
Research Goldstein Award; society of MSKCC; Geoffrey Beene Cancer
Research Fund; National Institutes of Health [5R01CA098870, CA59706,
CA108370, CA109767, CA89726, CA121846]; Stamford Hospital; National
Institutes of Health, National Cancer Institute, Division of Cancer
Epidemiology and Genetics; Rombauer Pancreatic Cancer Research Fund;
California Department of Public Health; National Cancer Institute's
Surveillance, Epidemiology, and End Results Program [N01-PC-35136];
Centers for Disease Control and Prevention's National Program of Cancer
Registries [U55/CCR921930-02]; Italian Association for Cancer Research
(AIRC) [10068]; Ministry of Health, Welfare, and Sports (formerly
Ministry of Welfare, Health, and Culture) of the Netherlands; Commission
of the European Communities; Fonds de recerche du Quebec - Sante (FRSQ);
U.S. National Institutes of Health [CA98380]; CD Smithers Foundation;
Spanish Ministry of Health [ISCIII RETICC RD06/0020]
FX The PanC4 consortium gratefully acknowledges the National Cancer
Institute (NCI) for partial support for its annual meetings.; The
Pancreatic Cancer Family Registry at MSKCC was supported by the
Prevention, Control and Population Research Goldstein Award; the society
of MSKCC; and the Geoffrey Beene Cancer Research Fund. The Yale study
was supported in part by National Institutes of Health grant
5R01CA098870; the cooperation of 30 Connecticut hospitals, including
Stamford Hospital, in allowing patient access, is gratefully
acknowledged. The Yale study was approved by the State of Connecticut
Department of Public Health Human Investigation Committee. Certain data
used in the Yale study were obtained from the Connecticut Tumor Registry
in the Connecticut Department of Public Health. The NCI study was funded
by the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics.
The UCSF study was supported in part by National Institutes of Health
grants (CA59706, CA108370, CA109767, CA89726, and CA121846) and by the
Rombauer Pancreatic Cancer Research Fund. The collection of cancer
incidence data for the UCSF study was supported by the California
Department of Public Health as part of the statewide cancer reporting
program; the National Cancer Institute's Surveillance, Epidemiology, and
End Results Program under contract N01-PC-35136 awarded to the Northern
California Cancer Center; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
#U55/CCR921930-02 awarded to the Public Health Institute. The Milan
study was supported by the Italian Association for Cancer Research
(AIRC, Project no. 10068). The SEARCH study and the investigators were
partially supported by The Ministry of Health, Welfare, and Sports
(formerly Ministry of Welfare, Health, and Culture) of the Netherlands
and the 'Europe against Cancer' program of the Commission of the
European Communities; and Fonds de recerche du Quebec - Sante (FRSQ).
The MD Anderson study was supported by the U.S. National Institutes of
Health (CA98380). Financial support for ABL from the CD Smithers
Foundation. EJD supported by the Spanish Ministry of Health (ISCIII
RETICC RD06/0020). The authors assume sole responsibility for analyses
and interpretation of these data.
NR 30
TC 54
Z9 54
U1 0
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2012
VL 23
IS 11
BP 2964
EP 2970
DI 10.1093/annonc/mds140
PG 7
WC Oncology
SC Oncology
GA 027SG
UT WOS:000310373100031
PM 22767586
ER
PT J
AU Wang, JB
Jiang, Y
Liang, H
Li, P
Xiao, HJ
Ji, J
Xiang, W
Shi, JF
Fan, YG
Li, L
Wang, D
Deng, SS
Chen, WQ
Wei, WQ
Qiao, YL
Boffetta, P
AF Wang, J. B.
Jiang, Y.
Liang, H.
Li, P.
Xiao, H. J.
Ji, J.
Xiang, W.
Shi, J. F.
Fan, Y. G.
Li, L.
Wang, D.
Deng, S. S.
Chen, W. Q.
Wei, W. Q.
Qiao, Y. L.
Boffetta, P.
TI Attributable causes of cancer in China
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE cancer; modifiable risk factors; population attributable fraction; China
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EMERGING TOBACCO HAZARDS;
RISK-FACTORS; ALCOHOL-DRINKING; REPRODUCTIVE FACTORS; BREAST-CANCER;
LIFE-STYLE; MORTALITY; SMOKING; BURDEN
AB Most cancers are due to modifiable lifestyle and environmental risk factors, and are potentially preventable. No studies have provided a systematic quantitative assessment of the burden of cancer mortality and incidence attributable to known risk factors in China.
We calculated the proportions of cancer deaths and new cases attributable to known risk factors in China, based on the prevalence of exposure around 1990 and national data on cancer mortality and incidence for the year 2005.
Chronic infection is the main risk factor for cancer in China, accounting for 29.4% of cancer deaths (31.7% in men and 25.3% in women), followed by tobacco smoking (22.6% with 32.7% in men and 5.0% in women), low fruit intake (13.0%), alcohol drinking (4.4%), low vegetable intake (3.6%) and occupational exposures (2.7%). The remaining factors, including environmental agents, physical inactivity, the use of exogenous hormones and reproductive factors are each responsible for < 1.0%.
Modifiable risk factors explain nearly 60% of cancer deaths in China, with a predominant role of chronic infection and tobacco smoking. Our findings could provide a basis for cancer prevention and control programs aimed at reducing cancer risk in other developing countries.
C1 [Wang, J. B.; Jiang, Y.; Liang, H.; Shi, J. F.; Wang, D.; Wei, W. Q.; Qiao, Y. L.] Chinese Acad Med Sci, Canc Inst Hosp, Dept Canc Epidemiol, Beijing 100021, Peoples R China.
[Wang, J. B.; Jiang, Y.; Liang, H.; Shi, J. F.; Wang, D.; Chen, W. Q.; Wei, W. Q.; Qiao, Y. L.] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wang, J. B.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Li, P.] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat Hlth, Chongqing, Peoples R China.
[Li, P.] Chongqing Med Univ, Sch Publ Hlth, Dept Environm Hlth, Chongqing, Peoples R China.
[Xiao, H. J.; Deng, S. S.] Sichuan Univ, Sch Publ Hlth, Chengdu 610064, Peoples R China.
[Ji, J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA.
[Xiang, W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Shi, J. F.] NSW Canc Council, Canc Epidemiol Res Unit, Woolloomooloo, NSW, Australia.
[Fan, Y. G.] Tianjin Med Univ, Gen Hosp, Tianjin Lung Canc Inst, Tianjin, Peoples R China.
[Li, L.] Xinjiang Med Univ, Peoples Hosp Xinjiang Prov, Dept Gynecol, Urumqi, Peoples R China.
[Chen, W. Q.] Chinese Acad Med Sci, Canc Inst Hosp, Natl Off Canc Prevent & Control, Beijing 100021, Peoples R China.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, P.] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA.
[Boffetta, P.] Int Prevent Res Inst, Lyon, France.
RP Qiao, YL (reprint author), Chinese Acad Med Sci, Canc Inst Hosp, Dept Canc Epidemiol, 17 S Pan Jia Yuan Lane, Beijing 100021, Peoples R China.
EM qiaoy@cicams.ac.cn
RI Qiao, You-Lin/B-4139-2012; Jiang, Yong/B-4103-2012
OI Qiao, You-Lin/0000-0001-6380-0871; Jiang, Yong/0000-0002-1892-1196
FU International Agency for Research on Cancer (Lyon, France) [GEE/08/19];
Cancer Institute, Chinese Academy of Medical Sciences (Beijing, China)
[JK2011B19]
FX International Agency for Research on Cancer (Lyon, France; Grant number:
CRA No GEE/08/19) and Cancer Institute, Chinese Academy of Medical
Sciences (Beijing, China; Grant number: JK2011B19). The sponsor of the
study had no role in study design, data collection, data analysis, data
interpretation, decision to publish or preparation of the manuscript.
NR 40
TC 22
Z9 23
U1 0
U2 14
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD NOV
PY 2012
VL 23
IS 11
BP 2983
EP 2989
DI 10.1093/annonc/mds139
PG 7
WC Oncology
SC Oncology
GA 027SG
UT WOS:000310373100034
PM 22689178
ER
PT J
AU Byzova, NA
Zherdev, AV
Eskendirova, SZ
Baltin, KK
Unysheva, GB
Mukanov, KK
Ramankulov, EM
Dzantiev, BB
AF Byzova, N. A.
Zherdev, A. V.
Eskendirova, S. Z.
Baltin, K. K.
Unysheva, G. B.
Mukanov, K. K.
Ramankulov, E. M.
Dzantiev, B. B.
TI Development of immunochromatographic test system for rapid detection of
the lipopolysaccharide antigen and cells of the causative agent of
bovine brucellosis
SO APPLIED BIOCHEMISTRY AND MICROBIOLOGY
LA English
DT Article
ID PROTEIN-G; MONOCLONAL-ANTIBODIES; SEROLOGICAL DIAGNOSIS; ASSAY; ABORTUS;
CONJUGATE; MILK
AB A rapid method for detection of the surface lipopolysaccharide antigen and the cells of the causative agent of bovine brucellosis was developed. The method represents a sandwich format immunochromatographic assay. The contact between the sample and the test strip with immobilized immunoreagents initiates the fluid movement along the membrane components of the test strip, immunochemical reactions, and the formation of colored bands. The novel method requires 10 minutes to determine the lipopolysaccharide antigen of the cell wall of the brucellosis causative agent at concentrations down to 10 ng/mL and the Brucella abortus cells at concentrations down to 10(6) cells/mL (5 x 10(4) cells in the sample). The specificity of the immunodetection was confirmed. The designed test system can be used for the rapid field diagnosis of brucellosis in cattle.
C1 [Byzova, N. A.; Zherdev, A. V.; Dzantiev, B. B.] Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia.
[Eskendirova, S. Z.; Baltin, K. K.; Unysheva, G. B.; Mukanov, K. K.; Ramankulov, E. M.] Natl Ctr Biotechnol Republ Kazakhstan, Astana, Kazakhstan.
RP Byzova, NA (reprint author), Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia.
EM nbyzova@inbi.ras.ru
RI Ramanculov, Erlan/E-2823-2013; Zherdev, Anatoly/G-2916-2013; Dzantiev,
Boris/C-6125-2014
OI Zherdev, Anatoly/0000-0003-3008-2839;
NR 36
TC 0
Z9 0
U1 0
U2 12
PU MAIK NAUKA/INTERPERIODICA/SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0003-6838
EI 1573-8183
J9 APPL BIOCHEM MICRO+
JI Appl. Biochem. Microbiol.
PD NOV
PY 2012
VL 48
IS 6
BP 590
EP 597
DI 10.1134/S0003683812060026
PG 8
WC Biotechnology & Applied Microbiology; Microbiology
SC Biotechnology & Applied Microbiology; Microbiology
GA 025ZN
UT WOS:000310237200010
ER
PT J
AU Cheng, TJ
Wang, YL
Bryant, SH
AF Cheng, Tiejun
Wang, Yanli
Bryant, Stephen H.
TI FSelector: a Ruby gem for feature selection
SO BIOINFORMATICS
LA English
DT Article
ID BIOINFORMATICS
AB The FSelector package contains a comprehensive list of feature selection algorithms for supporting bioinformatics and machine learning research. FSelector primarily collects and implements the filter type of feature selection techniques, which are computationally efficient for mining large datasets. In particular, FSelector allows ensemble feature selection that takes advantage of multiple feature selection algorithms to yield more robust results. FSelector also provides many useful auxiliary tools, including normalization, discretization and missing data imputation.
C1 [Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Cheng, Tiejun/A-5344-2010
OI Cheng, Tiejun/0000-0002-4486-3356
FU Intramural Research Program of the National Institutes of Health,
National Library of Medicine
FX Intramural Research Program of the National Institutes of Health,
National Library of Medicine.
NR 8
TC 4
Z9 4
U1 1
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
J9 BIOINFORMATICS
JI Bioinformatics
PD NOV 1
PY 2012
VL 28
IS 21
BP 2851
EP 2852
DI 10.1093/bioinformatics/bts528
PG 2
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA 025AR
UT WOS:000310155300022
PM 22942017
ER
PT J
AU Kaur, JS
Coe, K
Rowland, J
Braun, KL
Conde, FA
Burhansstipanov, L
Heiney, S
Kagawa-Singer, M
Lu, Q
Witte, C
AF Kaur, Judith S.
Coe, Kathryn
Rowland, Julia
Braun, Kathryn L.
Conde, Francisco A.
Burhansstipanov, Linda
Heiney, Sue
Kagawa-Singer, Marjorie
Lu, Qian
Witte, Catherine
TI Enhancing life after cancer in diverse communities
SO CANCER
LA English
DT Article
DE community networks; cancer; quality of life; health disparities;
palliative care; comprehensive cancer care; spirituality
ID QUALITY-OF-LIFE; BREAST-CANCER; AFRICAN-AMERICANS; MENTAL-HEALTH;
SURVIVORS; CARE; POPULATION; ETHNICITY; BELIEFS; PAIN
AB BACKGROUND: Although large numbers of cancer survivors exist in every community, including minority communities, there is a significant gap in knowledge about best practices for these patients. METHODS: The Community Networks Program, funded by the National Cancer Institute Center to Reduce Cancer Health Disparities, has developed and tested unique services for these communities. These programs have used community-based participatory research techniques under a framework of diffusion of innovation and communications theory. RESULTS: This article describes some specifically tailored interventions that may be useful to a wide range of providers working with the underserved. CONCLUSIONS: Enhancing life after cancer can be achieved in underserved communities by supplementing local resources. Cancer 2012. (c) 2012 American Cancer Society.
C1 [Kaur, Judith S.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
[Coe, Kathryn] Indiana Univ Purdue Univ, Dept Publ Hlth, Indianapolis, IN 46202 USA.
[Rowland, Julia] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,US Dept HHS, Bethesda, MD 20892 USA.
[Braun, Kathryn L.] Univ Hawaii, Honolulu, HI 96822 USA.
[Conde, Francisco A.] Queens Med Ctr, Honolulu, HI USA.
[Burhansstipanov, Linda] Native Amer Canc Res, Pine, CO USA.
[Heiney, Sue] Univ S Carolina, Coll Nursing, Columbia, SC 29208 USA.
[Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Dept Asian Amer Studies, Los Angeles, CA USA.
[Lu, Qian] Univ Houston, Dept Psychol, Houston, TX USA.
[Witte, Catherine] Phoenix Indian Med Ctr, Oncol Ctr Excellence, Phoenix, AZ USA.
RP Kaur, JS (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA.
EM kaur.judith@mayo.edu
RI Coe, Mary Kasthryn/F-3636-2014
OI Coe, Mary Kasthryn/0000-0003-1284-3841
FU National Institutes of Health (NIH) [U01 CA114630]; NIH [U01 CA114609,
U01 CA11469]; Susan G. Komen for the Cure [POP0202135, POP0503920]; NCI
[R25 CA 101938, NCI U01 CA 114609]
FX 'Imi Hale-Native Hawaiian Cancer Network is funded by National
Institutes of Health (NIH) grant U01 CA114630. Mayo Clinic's Spirit of
EAGLES Community Network Program is funded by NIH grant U01 CA114609.
Southwest American Indian Collaborative Network is funded by NIH grant
U01 CA11469. Native American Cancer Education for Survivors is supported
by Susan G. Komen for the Cure (POP0202135 and POP0503920) and NCI (R25
CA 101938 and NCI U01 CA 114609).
NR 50
TC 4
Z9 4
U1 4
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
J9 CANCER-AM CANCER SOC
JI Cancer
PD NOV 1
PY 2012
VL 118
IS 21
BP 5366
EP 5373
DI 10.1002/cncr.27491
PG 8
WC Oncology
SC Oncology
GA 024BQ
UT WOS:000310083000022
PM 22434384
ER
PT J
AU Glaros, TG
Stockwin, LH
Mullendore, ME
Smith, B
Morrison, BL
Newton, DL
AF Glaros, Trevor G.
Stockwin, Luke H.
Mullendore, Michael E.
Smith, Brian
Morrison, Bethanie L.
Newton, Dianne L.
TI The "survivin suppressants" NSC 80467 and YM155 induce a DNA damage
response (vol 70, pg 207, 2012)
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Correction
C1 [Glaros, Trevor G.; Stockwin, Luke H.; Mullendore, Michael E.; Smith, Brian; Morrison, Bethanie L.; Newton, Dianne L.] NCI, Biol Testing Branch, Dev Therapeut Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Newton, DL (reprint author), NCI, Biol Testing Branch, Dev Therapeut Program, SAIC Frederick Inc, Bldg 320,Room 9, Frederick, MD 21702 USA.
EM newtondianne@mail.nih.gov
NR 1
TC 1
Z9 1
U1 0
U2 4
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 NOV
PY 2012
VL 70
IS 5
BP 763
EP 764
DI 10.1007/s00280-012-1971-2
PG 2
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 029ZO
UT WOS:000310537600016
ER
PT J
AU Covo, S
Ma, WJ
Westmoreland, JW
Gordenin, DA
Resnick, MA
AF Covo, Shay
Ma, Wenjian
Westmoreland, James W.
Gordenin, Dmitry A.
Resnick, Michael A.
TI Understanding the origins of UV-induced recombination through
manipulation of sister chromatid cohesion
SO CELL CYCLE
LA English
DT Article
DE UV; recombination; cohesin; double-strand breaks
ID DOUBLE-STRAND BREAKS; MITOTIC GENE CONVERSION; DNA-DAMAGE RESPONSE;
HOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; YEAST-CELLS;
PYRIMIDINE DIMERS; ULTRAVIOLET-LIGHT; GAMMA-RAYS; X-RAYS
AB Ultraviolet light (UV) can provoke genome instability, partly through its ability to induce homologous recombination (HR). However, the mechanism(s) of UV-induced recombination is poorly understood. Although double-strand breaks (DSBs) have been invoked, there is little evidence for their generation by UV. Alternatively, single-strand DNA lesions that stall replication forks could provoke recombination. Recent findings suggest efficient initiation of UV-induced recombination in G(1) through processing of closely spaced single-strand lesions to DSBs. However, other scenarios are possible, since the recombination initiated in G(1) can be completed in the following stages of the cell cycle. We developed a system that could address UV-induced recombination events that start and finish in G(2) by manipulating the activity of the sister chromatid cohesion complex. Here we show that sister-chromatid cohesion suppresses UV-induced recombination events that are initiated and resolved in G(2). By comparing recombination frequencies and survival between UV and ionizing radiation, we conclude that a substantial portion of UV-induced recombination occurs through DSBs. This notion is supported by a direct physical observation of UV-induced DSBs that are dependent on nucleotide excision repair. However, a significant role of nonDSB intermediates in UV-induced recombination cannot be excluded.
C1 [Covo, Shay; Ma, Wenjian; Westmoreland, James W.; Gordenin, Dmitry A.; Resnick, Michael A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Covo, S (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM covos@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU NIEHS (NIH, DHHS) [1Z01ES065073]
FX We thank Drs. Steve Roberts and Kin Chan for critically evaluating this
manuscript. This work was supported by the Intramural Research Program
of the NIEHS (NIH, DHHS) under project 1Z01ES065073 to M.A.R.
NR 49
TC 3
Z9 3
U1 1
U2 31
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD NOV 1
PY 2012
VL 11
IS 21
BP 3937
EP 3944
DI 10.4161/cc.21945
PG 8
WC Cell Biology
SC Cell Biology
GA 030PV
UT WOS:000310583500014
PM 22987150
ER
PT J
AU Konforte, D
Diamandis, EP
van Venrooij, WJ
Lories, R
Ward, MM
AF Konforte, Danijela
Diamandis, Eleftherios P.
van Venrooij, Walther J.
Lories, Rik
Ward, Michael M.
TI Autoimmune Diseases: Early Diagnosis and New Treatment Strategies
SO CLINICAL CHEMISTRY
LA English
DT Editorial Material
C1 [Diamandis, Eleftherios P.] Mt Sinai Hosp, Joseph & Wolf Lebovic Ctr, Dept Pathol & Lab Med, Toronto, ON M5T 3L9, Canada.
[Konforte, Danijela; Diamandis, Eleftherios P.] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Diamandis, Eleftherios P.] Univ Hlth Network, Dept Clin Biochem, Toronto, ON, Canada.
[van Venrooij, Walther J.] Radbound Univ, Nijmegen Ctr Mol Life Sci, Nijmegen, Netherlands.
[Lories, Rik] Katholieke Univ Leuven, Dept Rheumatol, Louvain, Belgium.
[Ward, Michael M.] NIAMSD, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
RP Diamandis, EP (reprint author), Mt Sinai Hosp, Joseph & Wolf Lebovic Ctr, Dept Pathol & Lab Med, 60 Murray St,Box 32,Flr 6,Rm L6-201, Toronto, ON M5T 3L9, Canada.
EM ediamandis@mtsinai.on.ca
OI Diamandis, Eleftherios/0000-0002-1589-820X
NR 0
TC 2
Z9 2
U1 0
U2 3
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD NOV
PY 2012
VL 58
IS 11
BP 1510
EP 1514
DI 10.1373/clinchem.2012.189480
PG 5
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 029IS
UT WOS:000310489300003
PM 22761474
ER
PT J
AU Ho, JE
Mahajan, A
Chen, MH
Larson, MG
McCabe, EL
Ghorbani, A
Cheng, S
Johnson, AD
Lindgren, CM
Kempf, T
Lind, L
Ingelsson, E
Vasan, RS
Januzzi, J
Wollert, KC
Morris, AP
Wang, TJ
AF Ho, Jennifer E.
Mahajan, Anubha
Chen, Ming-Huei
Larson, Martin G.
McCabe, Elizabeth L.
Ghorbani, Anahita
Cheng, Susan
Johnson, Andrew D.
Lindgren, Cecilia M.
Kempf, Tibor
Lind, Lars
Ingelsson, Erik
Vasan, Ramachandran S.
Januzzi, James
Wollert, Kai C.
Morris, Andrew P.
Wang, Thomas J.
TI Clinical and Genetic Correlates of Growth Differentiation Factor 15 in
the Community
SO CLINICAL CHEMISTRY
LA English
DT Article
ID ACUTE CORONARY SYNDROME; MACROPHAGE INHIBITORY CYTOKINE-1; CHRONIC
HEART-FAILURE; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; DISEASE;
PREDICTION; MARKER; ASSOCIATION; ACTIVATION
AB BACKGROUND: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively.
METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasctilature in Uppsala Seniors) study.
RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h(2) = 0.38; P = 2.5 X 10(-11)). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10(-32) for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines.
CONCLUSIONS: In ambulatory individuals, both cardio-metabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation. (C) 2012 American Association for Clinical Chemistry
C1 [Ho, Jennifer E.; Ghorbani, Anahita; Januzzi, James; Wang, Thomas J.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA.
[Ho, Jennifer E.; Chen, Ming-Huei; Larson, Martin G.; Cheng, Susan; Johnson, Andrew D.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Ho, Jennifer E.; Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Mahajan, Anubha; Lindgren, Cecilia M.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Chen, Ming-Huei; McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Dept Med, Boston, MA 02215 USA.
[Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA.
[Kempf, Tibor; Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, D-3000 Hannover, Germany.
[Lind, Lars] Uppsala Univ, Dept Med, Uppsala, Sweden.
[Lind, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
[Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Vasan, Ramachandran S.] Boston Univ, Dept Med, Div Cardiol & Prevent Med, Boston, MA 02215 USA.
[Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB-800,55 Fruit St, Boston, MA 02114 USA.
EM tjwang@partners.org
RI Johnson, Andrew/G-6520-2013;
OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768;
Ramachandran, Vasan/0000-0001-7357-5970
FU E. Ingelsson; Swedish Research Council; Swedish Heart and Lung
Foundation; Swedish Foundation for Strategic Research; Royal Swedish
Academy of Sciences; Swedish Diabetes Foundation; Swedish Society of
Medicine; Novo Nordisk Fonden; J. Januzzi, Roche; Siemens; BG Medicine;
Thermo Fisher Scientific; K.C. Wollert; Roche Diagnostics; A.P. Morris,
Wellcome Trust [WT081682, WT064890, WT090532]
FX E. Ingelsson, Swedish Research Council, Swedish Heart and Lung
Foundation, Swedish Foundation for Strategic Research, Royal Swedish
Academy of Sciences, Swedish Diabetes Foundation, Swedish Society of
Medicine, and Novo Nordisk Fonden; J. Januzzi, Roche, Siemens, BG
Medicine, and Thermo Fisher Scientific; K.C. Wollert, GDF15 test kits
from Roche Diagnostics; A.P. Morris, Wellcome Trust (WT081682, WT064890,
and WT090532).
NR 40
TC 19
Z9 21
U1 0
U2 1
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD NOV
PY 2012
VL 58
IS 11
BP 1582
EP 1591
DI 10.1373/clinchem.2012.190322
PG 10
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 029IS
UT WOS:000310489300014
PM 22997280
ER
PT J
AU Chen, WY
Xu, Z
Merke, DP
McDonnell, NB
AF Chen, Wuyan
Xu, Zhi
Merke, Deborah P.
McDonnell, Nazli B.
TI CH-8 Phenotype in Steroid 21-Hydroxylase Deficiency: Fact or Fancy?
Reply
SO CLINICAL CHEMISTRY
LA English
DT Letter
ID RCCX MODULE; GENES
C1 [McDonnell, Nazli B.] NIA, Clin Invest Lab, Biomed Res Ctr, Baltimore, MD 21224 USA.
[Merke, Deborah P.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocrinol & Genet PDEGEN, Bethesda, MD USA.
[McDonnell, Nazli B.] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
RP McDonnell, NB (reprint author), NIA, Clin Invest Lab, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
NR 3
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
J9 CLIN CHEM
JI Clin. Chem.
PD NOV
PY 2012
VL 58
IS 11
BP 1601
EP 1603
DI 10.1373/clinchem.2012.194118
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA 029IS
UT WOS:000310489300019
ER
PT J
AU Deeken, JF
Tjen-A-Looi, A
Rudek, MA
Okuliar, C
Young, M
Little, RF
Dezube, BJ
AF Deeken, John F.
Tjen-A-Looi, Angelique
Rudek, Michelle A.
Okuliar, Catherine
Young, Mary
Little, Richard F.
Dezube, Bruce J.
TI The Rising Challenge of Non-AIDS-Defining Cancers in HIV-Infected
Patients
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY;
SQUAMOUS-CELL CARCINOMA; WOMENS INTERAGENCY HIV; HEPATITIS-C VIRUS;
LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; POSITIVE PATIENTS;
HODGKIN-LYMPHOMA
AB Since the advent of HAART, patients with HIV infection have seen a significant improvement in their morbidity, mortality, and life expectancy. The incidence of AIDS-defining illnesses, including AIDS-defining malignancies, has been on the decline. However, deaths due to non-AIDS-defining illnesses have been on the rise. These so-called non-AIDS-defining cancers (NADCs) include cancers of the lung, liver, kidney, anus, head and neck, and skin, as well as Hodgkin's lymphoma. It is poorly understood why this higher rate of NADCs is occurring. The key challenge facing oncologists is how to administer chemotherapy effectively and safely to patients on antiretroviral therapy. The challenge to clinicians caring for HIV-infected patients is to develop and implement effective means to screen, treat, and prevent NADCs in the future. This review presents data on the epidemiology and etiology of NADCs, as well as ongoing research into this evolving aspect of the HIV epidemic.
C1 [Deeken, John F.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hematol Oncol, Washington, DC 20007 USA.
[Tjen-A-Looi, Angelique; Young, Mary] Georgetown Univ, Med Ctr, Div Infect Dis, Washington, DC 20007 USA.
[Okuliar, Catherine] Georgetown Univ, Med Ctr, Div Internal Med, Washington, DC 20007 USA.
[Rudek, Michelle A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA.
[Little, Richard F.] NCI, Clin Invest Branch CTEP, Bethesda, MD 20892 USA.
[Dezube, Bruce J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med Hematol Oncol, Boston, MA 02215 USA.
RP Deeken, JF (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA.
EM john.deeken@gunet.georgetown.edu
FU National Cancer Institute [U01CA121947]; National Institute of Allergy
and Infectious Disease [U01AI34994]
FX This work was supported in part by grant number U01CA121947 from the
National Cancer Institute to the AIDS Malignancy Clinical Trials
Consortium (J. D., M. A. R.), as well as grant number U01AI34994 from
the National Institute of Allergy and Infectious Disease to the Women's
Interagency HIV Study (M. Y.).
NR 88
TC 68
Z9 72
U1 2
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD NOV 1
PY 2012
VL 55
IS 9
BP 1228
EP 1235
DI 10.1093/cid/cis613
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 021IF
UT WOS:000309877800015
PM 22776851
ER
PT J
AU Kang, SY
Hallett, M
Sohn, YH
AF Kang, Suk Y.
Hallett, Mark
Sohn, Young H.
TI Synchronized finger exercise reduces surround inhibition
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Surround inhibition; Dystonia; Motor-evoked potentials; TMS
ID FOCAL HAND DYSTONIA; HUMAN MOTOR CORTEX; PRIMARY SOMATOSENSORY CORTEX;
INTRACORTICAL INHIBITION; ORGANIZATION; MUSCLE; CONNECTIONS; MODULATION;
ACTIVATION; ATTENTION
AB Objective: To investigate whether hand muscle repetitive use reduces surround inhibition (SI) as observed in patients with focal hand dystonia, we performed a transcranial magnetic stimulation (TMS) study in 15 healthy right-handed volunteers.
Methods: TMS was set to be triggered by self-initiated flexion of the index finger at 3 ms after movement onset. Motor evoked potentials (MEPs) of the abductor digiti minimi (ADM) were measured before and at 0, 10, 20 and 30 min after 'single' (little finger abduction) and 'dual' (both index finger flexion and little finger abduction) exercise at 0.5 Hz for 30 min. SI was calculated as (mean control MEP - mean self-triggered MEP) x 100/mean control MEP.
Results: Compared to single exercise, dual exercise produced significantly larger and longer-lasting enhancements of self-triggered MEPs, and greater reduction in calculated SIs.
Conclusions: This result demonstrates that synchronized finger exercise can reduce SI between the involved muscles possibly due either to the strengthening of the excitatory connections or to the weakening of the inhibitory connections between them, and may illustrate the association between hand muscle repetitive use and disturbed SI observed in FHD.
Significance: The operation of surround inhibition can be reduced by practicing synchronous movements. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Dept Neurol, Seoul 120752, South Korea.
[Kang, Suk Y.; Sohn, Young H.] Yonsei Univ, Coll Med, Brain Res Inst, Seoul 120752, South Korea.
[Kang, Suk Y.] Hallym Univ, Coll Med, Dept Neurol, Kangnam Sacred Heart Hosp, Seoul, South Korea.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Sohn, YH (reprint author), Yonsei Univ, Coll Med, Dept Neurol, 250 Seongsanno, Seoul 120752, South Korea.
EM yhsohn62@yuhs.ac
FU Brain Korea 21 Project for Medical Science, Yonsei University; NINDS
Intramural Program
FX This work was supported by the Brain Korea 21 Project for Medical
Science, Yonsei University. Dr. Hallett is supported by the NINDS
Intramural Program. The authors report no conflict of interest.
NR 25
TC 10
Z9 10
U1 0
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD NOV
PY 2012
VL 123
IS 11
BP 2227
EP 2231
DI 10.1016/j.clinph.2012.04.019
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 016VB
UT WOS:000309546600017
PM 22608486
ER
PT J
AU Lancaster, CS
Bruun, GH
Peer, CJ
Mikkelsen, TS
Corydon, TJ
Gibson, AA
Hu, S
Orwick, SJ
Mathijssen, RHJ
Figg, WD
Baker, SD
Sparreboom, A
AF Lancaster, C. S.
Bruun, G. H.
Peer, C. J.
Mikkelsen, T. S.
Corydon, T. J.
Gibson, A. A.
Hu, S.
Orwick, S. J.
Mathijssen, R. H. J.
Figg, W. D.
Baker, S. D.
Sparreboom, A.
TI OATP1B1 Polymorphism as a Determinant of Erythromycin Disposition
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID CYTOCHROME-P450 3A ACTIVITY; BREATH TEST; IN-VIVO; POPULATION
PHARMACOKINETICS; WEEKLY DOCETAXEL; CYP3A4 ACTIVITY; CANCER-PATIENTS;
METABOLISM; INHIBITION; VARIANTS
AB Previous studies have demonstrated that the pharmacokinetic profile of erythromycin, a probe for CYP3A4 activity, is affected by inhibitors or inducers of hepatic solute carriers. We hypothesized that these interactions are mediated by OATP1B1 (gene symbol, SLCO1B1), a polypeptide expressed on the basolateral surface of hepatocytes. Using stably transfected Flp-In T-Rex293 cells, erythromycin was found to be a substrate for OATP1B1*1A (wild type) with a Michaelis-Menten constant of similar to 13 mu mol/l, and that its transport was reduced by similar to 50% in cells expressing OATP1B1*5 (V174A). Deficiency of the ortholog transporter Oatp1b2 in mice was associated with a 52% decrease in the metabolic rate of erythromycin (P = 0.000043). In line with these observations, in humans the c.521T > C variant in SLCO1B1 (rs4149056), encoding OATP1B1*5, was associated with a decline in erythromycin metabolism (P = 0.0072). These results suggest that impairment of OATP1B1 function can alter erythromycin metabolism, independent of changes in CYP3A4 activity.
C1 [Lancaster, C. S.; Gibson, A. A.; Hu, S.; Orwick, S. J.; Baker, S. D.; Sparreboom, A.] St Jude Childrens Res Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA.
[Bruun, G. H.; Corydon, T. J.] Aarhus Univ, Dept Biomed, Aarhus, Denmark.
[Peer, C. J.; Figg, W. D.] NCI, Clin Pharmacol Program, Off Clin Director, Bethesda, MD 20892 USA.
[Mikkelsen, T. S.] Aarhus Univ Hosp, Dept Pediat Oncol & Hematol, DK-8000 Aarhus, Denmark.
[Mathijssen, R. H. J.] Erasmus MC Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands.
RP Sparreboom, A (reprint author), St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA.
EM alex.sparreboom@stjude.org
RI Figg Sr, William/M-2411-2016;
OI Corydon, Thomas Juhl/0000-0003-3588-6350
FU American Lebanese Syrian Associated Charities; National Cancer Institute
grant [5R01CA151633-01]; ASCPT's 2012 David J. Goldstein Trainee Award;
US Public Health Service Cancer Center Support [3P30CA021765]
FX We thank Richard Kim and Jeffrey Stock for providing the Oatp1b2(-/-)
mice and Lubin Lan and Erin Schuetz for their assistance with carrying
out the erythromycin breath tests in mice. This work was supported in
part by the American Lebanese Syrian Associated Charities, US Public
Health Service Cancer Center Support grant 3P30CA021765 (to S.D.B.), and
National Cancer Institute grant 5R01CA151633-01 (to A.S.). The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the funding agencies. This work was
previously presented, in part, at the 113th Annual Meeting of the
American Society for Clinical Pharmacology and Therapeutics (ASCPT),
held 14-17 March 2012 in National Harbor, MD. C.S.L. was a recipient of
ASCPT's 2012 David J. Goldstein Trainee Award in connection with this
study.
NR 43
TC 10
Z9 10
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2012
VL 92
IS 5
BP 642
EP 650
DI 10.1038/clpt.2012.106
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 027QF
UT WOS:000310367400032
PM 22990751
ER
PT J
AU Sissung, TM
Reece, KM
Spencer, S
Figg, WD
AF Sissung, T. M.
Reece, K. M.
Spencer, S.
Figg, W. D.
TI Contribution of the OATP1B Subfamily to Cancer Biology and Treatment
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Article
ID TRANSPORT; TISSUES
AB The organic anion transporter 1B (OATP1B) subfamily consists of OATP1B1 and OATP1B3.(1) These transporters have generally been considered liver-specific; however, recent evidence demonstrates that they are also expressed in extrahepatic tissues and in some tumors. This review discusses the potential influence of extrahepatic OATP1B expression on homeostasis and pathophysiology and its implications for pharmacotherapy in general.
C1 [Sissung, T. M.; Spencer, S.; Figg, W. D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.
[Reece, K. M.; Figg, W. D.] NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA.
EM wdfigg@helix.nih.gov
RI Figg Sr, William/M-2411-2016
NR 5
TC 5
Z9 5
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2012
VL 92
IS 5
BP 658
EP 660
DI 10.1038/clpt.2012.127
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 027QF
UT WOS:000310367400034
PM 23010650
ER
PT J
AU Lerner, I
Bentin, S
Shriki, O
AF Lerner, Itamar
Bentin, Shlomo
Shriki, Oren
TI Spreading Activation in an Attractor Network With Latching Dynamics:
Automatic Semantic Priming Revisited
SO COGNITIVE SCIENCE
LA English
DT Article
DE Word recognition; Semantic priming; Neural networks; Distributed
representations; Latching dynamics
ID STIMULUS-ONSET ASYNCHRONY; PRIMED-LEXICAL DECISION; VISUAL WORD
RECOGNITION; NEURAL-NETWORKS; MODEL; MEMORY; ASSOCIATION; BRAIN;
ATTENTION; RETRIEVAL
AB Localist models of spreading activation (SA) and models assuming distributed representations offer very different takes on semantic priming, a widely investigated paradigm in word recognition and semantic memory research. In this study, we implemented SA in an attractor neural network model with distributed representations and created a unified framework for the two approaches. Our models assume a synaptic depression mechanism leading to autonomous transitions between encoded memory patterns (latching dynamics), which account for the major characteristics of automatic semantic priming in humans. Using computer simulations, we demonstrated how findings that challenged attractor-based networks in the past, such as mediated and asymmetric priming, are a natural consequence of our present models dynamics. Puzzling results regarding backward priming were also given a straightforward explanation. In addition, the current model addresses some of the differences between semantic and associative relatedness and explains how these differences interact with stimulus onset asynchrony in priming experiments.
C1 [Shriki, Oren] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
[Lerner, Itamar; Bentin, Shlomo] Hebrew Univ Jerusalem, Interdisciplinary Ctr Neural Computat, IL-91905 Jerusalem, Israel.
[Bentin, Shlomo] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel.
RP Shriki, O (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
EM oren70@gmail.com
OI Shriki, Oren/0000-0003-1129-4799
FU Intramural NIH HHS [Z99 MH999999]
NR 89
TC 8
Z9 8
U1 6
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-0213
J9 COGNITIVE SCI
JI Cogn. Sci.
PD NOV-DEC
PY 2012
VL 36
IS 8
BP 1339
EP 1382
DI 10.1111/cogs.12007
PG 44
WC Psychology, Experimental
SC Psychology
GA 030XI
UT WOS:000310603000001
PM 23094718
ER
PT J
AU Pia, L
Neppi-Modona, M
Cremasco, L
Gindri, P
Dal Monte, O
Folegatti, A
AF Pia, Lorenzo
Neppi-Modona, Marco
Cremasco, Luigi
Gindri, Patrizia
Dal Monte, Olga
Folegatti, Alessia
TI Functional independence between numerical and visual space: Evidence
from right brain-damaged patients
SO CORTEX
LA English
DT Article
DE Visual line bisection; Mental number line; Unilateral neglect; Visual
space; Numerical space
ID MENTAL NUMBER LINE; SPATIAL REPRESENTATION; UNILATERAL NEGLECT;
BISECTION; SEQUENCES
AB What is the relationship between numerical and visual space? Here we tried to shed new light on this debated issue investigating whether and how the two forms of representation are associated or dissociated when co-activated. We carried out a series of visual-numerical bisection experiments on a large group of right brain-damaged patients (N = 32) with and without left neglect. We examined (a) the degree of association between the pathological rightward error in the bisection of numerical intervals and left neglect (Experiment 1); (b) if the size of the numerical interval modulates spatial errors in bisection tasks in which numerical and visual space representations are co-activated (Experiment 2). The results showed that (a) numerical bisection error and left spatial neglect are doubly dissociated and that, when both are present, they are not correlated; (b) the size of the numerical interval did not affect the spatial bisection error but influenced the numerical bisection error. These data suggest that attentional processes involved in the navigation along visual space and numerical internal representations are independent neurocognitive operations. We must emphasize that our findings should be taken with caution because they are based mainly on negative results. (C) 2012 Elsevier Srl. All rights reserved.
C1 [Pia, Lorenzo; Neppi-Modona, Marco; Dal Monte, Olga; Folegatti, Alessia] Univ Turin, Dept Psychol, I-10123 Turin, Italy.
[Pia, Lorenzo; Neppi-Modona, Marco] Univ Turin, NIT, I-10123 Turin, Italy.
[Cremasco, Luigi] Fdn Don Carlo Gnocchi, Turin, Italy.
[Cremasco, Luigi] Ctr Santa Maria Ai Colli, Turin, Italy.
[Gindri, Patrizia] Sanit Garrison San Camillo, Turin, Italy.
[Dal Monte, Olga] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA.
[Dal Monte, Olga] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Rockville, MD USA.
RP Pia, L (reprint author), Univ Turin, Dept Psychol, Via Po 14, I-10123 Turin, Italy.
EM lorenzo.pia@unito.it
OI dal monte, olga/0000-0002-7823-4769; Pia, Lorenzo/0000-0002-0360-3152
FU PRIN grant
FX These works was in part supported by a PRIN grant to Lorenzo Pia, Marco
Neppi-Modona and Alessia Folegatti.
NR 27
TC 10
Z9 10
U1 0
U2 3
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD NOV-DEC
PY 2012
VL 48
IS 10
BP 1351
EP 1358
DI 10.1016/j.cortex.2012.04.005
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 028IV
UT WOS:000310416900009
PM 22608781
ER
PT J
AU Ryall, JG
AF Ryall, James G.
TI The role of sirtuins in the regulation of metabolic homeostasis in
skeletal muscle
SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
LA English
DT Review
DE hypertrophy; nicotinamide adenine dinucleotide; satellite cells; SirT1;
NAD
ID DEPENDENT GENE-EXPRESSION; ACTIVATED PROTEIN-KINASE; CALORIE
RESTRICTION; TRANSCRIPTION FACTORS; SIRT1 ACTIVATION; HISTONE H3;
LIFE-SPAN; ACETYLATION; DEACETYLASE; INTERACTS
AB Purpose of review
To discuss recent findings regarding the role of the histone deacetylase sirtuin SirT1 in anabolic and catabolic signaling pathways in skeletal muscle.
Recent findings
Since its discovery as a regulator of peroxisome proliferator-activated receptor g-coactivator 1 alpha transcriptional activity, SirT1 has received much attention for its role in the regulation of tissue-specific and whole body regulation of metabolic processes. Although these early seminal discoveries identified SirT1 as a central player in metabolism, it is only more recently that we have begun to understand the complexities of SirT1 signaling. In addition to peroxisome proliferator-activated receptorgamma-coactivator 1 alpha, SirT1 has been found to regulate the activity and/or transcription of protein kinase B, mammalian target of rapamycin, forkhead box O 1 and 3a and myogenic determination factor, all of which are central players in the regulation of energy status in skeletal muscle, via actions on catabolic and anabolic signaling.
Summary
SirT1-mediated regulation of skeletal muscle metabolism (and indeed, whole body metabolism) likely occurs at numerous levels, from cell membrane receptors to transcription factors and histones. The end result of these regulatory actions of SirT1 is to maintain cellular homeostasis.
C1 NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Ryall, JG (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM jgryall@gmail.com
OI Ryall, James/0000-0003-4702-1143
FU Overseas Biomedical Research Fellowship from the National Health and
Medical Research Council of Australia (NHMRC); Intramural Research
Program of the National Institute of Arthritis, and Musculoskeletal, and
Skin diseases (NIAMS) at the National Institutes of Health
FX J.G.R. is supported by an Overseas Biomedical Research Fellowship from
the National Health and Medical Research Council of Australia (NH&MRC)
and the Intramural Research Program of the National Institute of
Arthritis, and Musculoskeletal, and Skin diseases (NIAMS) at the
National Institutes of Health.
NR 47
TC 9
Z9 9
U1 0
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1363-1950
J9 CURR OPIN CLIN NUTR
JI Curr. Opin. Clin. Nutr. Metab. Care
PD NOV
PY 2012
VL 15
IS 6
BP 561
EP 566
DI 10.1097/MCO.0b013e3283590914
PG 6
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 027OI
UT WOS:000310362000007
PM 23075935
ER
PT J
AU Mahnke, YD
Beddall, MH
Roederer, M
AF Mahnke, Yolanda D.
Beddall, Margaret H.
Roederer, Mario
TI OMIP-013: Differentiation of human T-cells
SO CYTOMETRY PART A
LA English
DT Article
ID EXPRESSION
C1 [Mahnke, Yolanda D.; Beddall, Margaret H.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mahnke, YD (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5608, Bethesda, MD 20892 USA.
EM mahnkey@mail.nih.gov
NR 8
TC 5
Z9 6
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
J9 CYTOM PART A
JI Cytom. Part A
PD NOV
PY 2012
VL 81A
IS 11
BP 935
EP 936
DI 10.1002/cyto.a.22201
PG 2
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 027WV
UT WOS:000310385700003
PM 23027685
ER
PT J
AU Jeong, J
Cesario, J
Zhao, YG
Burns, L
Westphal, H
Rubenstein, JLR
AF Jeong, Juhee
Cesario, Jeffry
Zhao, Yangu
Burns, Lorel
Westphal, Heiner
Rubenstein, John L. R.
TI Cleft palate defect of Dlx1/2-/- mutant mice is caused by lack of
vertical outgrowth in the posterior palate
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE Dlx; cleft palate; palatogenesis; craniofacial development; mice
ID CRANIAL NEURAL CREST; SECONDARY PALATE; HOMEOBOX GENES; MOUSE EMBRYOS;
DOWN-SYNDROME; DLX GENES; EXPRESSION; MORPHOGENESIS; FOREBRAIN; GROWTH
AB Background: Mice lacking the activities of Dlx1 and Dlx2 (Dlx1/2-/-) exhibit cleft palate, one of the most common human congenital defects, but the etiology behind this phenotype has been unknown. Therefore, we analyzed the morphological, cellular, and molecular changes caused by inactivation of Dlx1 and Dlx2 as related to palate development. Results: Dlx1/2-/- mutants exhibited lack of vertical growth in the posterior palate during the earliest stage of palatogenesis. We attributed this growth deficiency to reduced cell proliferation. Expression of a cell cycle regulator Ccnd1 was specifically down-regulated in the same region. Previous studies established that the epithelial-mesenchymal signaling loop involving Shh, Bmp4, and Fgf10 is important for cell proliferation and tissue growth during palate development. This signaling loop was disrupted in Dlx1/2-/- palate. Interestingly, however, the decreases in Ccnd1 expression and mitosis in Dlx1/2-/- mutants were independent of this signaling loop. Finally, Dlx1/2 activity was required for normal expression of several transcription factor genes whose mutation results in palate defects. Conclusions: The functions of Dlx1 and Dlx2 are crucial for the initial formation of the posterior palatal shelves, and that the Dlx genes lie upstream of multiple signaling molecules and transcription factors important for later stages of palatogenesis. Developmental Dynamics 241:17571769, 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Jeong, Juhee; Cesario, Jeffry; Burns, Lorel] NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA.
[Zhao, Yangu; Westphal, Heiner] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Mammalian Genes & Dev, Program Genom Differentiat, Bethesda, MD USA.
[Rubenstein, John L. R.] Univ Calif San Francisco, Dept Psychiat, Nina Ireland Lab Dev Neurobiol, San Francisco, CA 94158 USA.
RP Jeong, J (reprint author), NYU, Coll Dent, Dept Basic Sci & Craniofacial Biol, 345 E 24 th St,Room 902D, New York, NY 10010 USA.
EM jj78@nyu.edu; john.rubenstein@ucsf.edu
FU NIH/NIDCD [R01 DC05667]; March of Dimes; NIH/NIDCR [K99/R00 DE019486];
NIH/NICHD intramural research program; Weston Havens Foundation;
Hillblom Foundation; Nina Ireland; NIH [NIDCD R01 DC05667, NIDCR K99/R00
DE019486]; NICHD intramural research program
FX Grant sponsor: NIH/NIDCD; Grant number: R01 DC05667; Grant sponsor:
March of Dimes; Grant sponsor: NIH/NIDCR; Grant number: K99/R00
DE019486; Grant sponsor: NIH/NICHD intramural research program; Grant
sponsor: Weston Havens Foundation; Grant sponsor: Hillblom Foundation;
Grant sponsor: Nina Ireland.; We thank Regeneron for Lhx6 mutant mice
(MAID #406); Purvi Patel for genotyping mice and embryos; Hideyo Ohuchi,
Joy Yang, and Jun Aruga for in situ hybridization probes; Jason Long,
Jeremy Cholfin, Inma Cobos, Greg Potter, and Andrea Faedo for sharing
reagents and ideas; and Gail Martin, Ophir Klein, Ross Metzger, Maria
Barna, and the members of Rubenstein lab and Martin lab for helpful
discussions. This work was funded by grants from NIH (NIDCD R01
DC05667), March of Dimes, Weston Havens Foundation, Hillblom Foundation
and Nina Ireland to J.L.R.R., a grant from NIH (NIDCR K99/R00 DE019486)
to J.J., and by funds from the NICHD intramural research program to H.W.
NR 59
TC 7
Z9 8
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD NOV
PY 2012
VL 241
IS 11
BP 1757
EP 1769
DI 10.1002/dvdy.23867
PG 13
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 026NF
UT WOS:000310285300010
PM 22972697
ER
PT J
AU Ren, RQ
Oakley, RH
Cruz-Topete, D
Cidlowski, JA
AF Ren, Rongqin
Oakley, Robert H.
Cruz-Topete, Diana
Cidlowski, John A.
TI Dual Role for Glucocorticoids in Cardiomyocyte Hypertrophy and Apoptosis
SO ENDOCRINOLOGY
LA English
DT Article
ID HUMAN MINERALOCORTICOID RECEPTOR; INDUCED MYOCARDIAL APOPTOSIS;
CONGESTIVE-HEART-FAILURE; RAT VENTRICULAR MYOCYTES;
NECROSIS-FACTOR-ALPHA; CARDIAC CELL-DEATH; GENE-EXPRESSION;
CARDIOVASCULAR-DISEASE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; NUCLEAR
RECEPTORS
AB Glucocorticoids and their synthetic derivatives are known to alter cardiac function in vivo; however, the nature of these effects and whether glucocorticoids act directly on cardiomyocytes are poorly understood. To explore the role of glucocorticoid signaling in the heart, we used rat embryonic H9C2 cardiomyocytes and primary cardiomyocytes as model systems. Dexamethasone (100 nM) treatment of cardiomyocytes caused a significant increase in cell size and up-regulated the expression of cardiac hypertrophic markers, including atrial natriuretic factor, beta-myosin heavy chain, and skeletal muscle alpha-actin. In contrast, serum deprivation and TNF alpha exposure triggered cardiomyocyte apoptosis, and these apoptotic effects were inhibited by dexamethasone. Both the hypertrophic and anti-apoptotic actions of glucocorticoids were abolished by the glucocorticoid receptor (GR) antagonist RU486 and by short hairpin RNA-mediated GR depletion. Blocking the activity of the mineralocorticoid receptor had no effect on these glucocorticoid-dependent cardiomyocyte responses. Aldosterone (1 mu M) activation of GR also promoted cardiomyocyte hypertrophy and cell survival. To elucidate the mechanism of the dual glucocorticoid actions, a genome-wide microarray was performed on H9C2 cardiomyocytes treated with vehicle or dexamethasone in the absence or presence of serum. Serum dramatically influenced the transcriptome regulated by GR, revealing potential glucocorticoid signaling mediators in both cardiomyocyte hypertrophy and apoptosis. These studies reveal a direct and dynamic role for glucocorticoids and GR signaling in the modulation of cardiomyocyte function. (Endocrinology 153:5346-5360, 2012)
C1 [Ren, Rongqin; Oakley, Robert H.; Cruz-Topete, Diana; Cidlowski, John A.] NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU National Institutes of Health, National Institute of Environmental
Health Sciences
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 79
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Z9 35
U1 0
U2 11
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2012
VL 153
IS 11
BP 5346
EP 5360
DI 10.1210/en.2012-1563
PG 15
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 027NL
UT WOS:000310359300023
PM 22989630
ER
PT J
AU Galperin, MY
Mekhedov, SL
Puigbo, P
Smirnov, S
Wolf, YI
Rigden, DJ
AF Galperin, Michael Y.
Mekhedov, Sergei L.
Puigbo, Pere
Smirnov, Sergey
Wolf, Yuri I.
Rigden, Daniel J.
TI Genomic determinants of sporulation in Bacilli and Clostridia: towards
the minimal set of sporulation-specific genes
SO ENVIRONMENTAL MICROBIOLOGY
LA English
DT Review
ID SUBTILIS SPORE COAT; SEGMENTED FILAMENTOUS BACTERIA; RESPONSE REGULATOR
SPO0A; SP-NOV.; ANAEROBIC BACTERIUM; ENDOSPORE FORMATION; COG DATABASE;
TRANSCRIPTIONAL PROGRAM; LIFE-CYCLE; FAM. NOV
AB Three classes of low-G+C Gram-positive bacteria (Firmicutes), Bacilli, Clostridia and Negativicutes, include numerous members that are capable of producing heat-resistant endospores. Spore-forming firmicutes include many environmentally important organisms, such as insect pathogens and cellulose-degrading industrial strains, as well as human pathogens responsible for such diseases as anthrax, botulism, gas gangrene and tetanus. In the best-studied model organism Bacillus subtilis, sporulation involves over 500 genes, many of which are conserved among other bacilli and clostridia. This work aimed to define the genomic requirements for sporulation through an analysis of the presence of sporulation genes in various firmicutes, including those with smaller genomes than B. subtilis. Cultivable spore-formers were found to have genomes larger than 2300 kb and encompass over 2150 protein-coding genes of which 60 are orthologues of genes that are apparently essential for sporulation in B. subtilis. Clostridial spore-formers lack, among others, spoIIB, sda, spoVID and safA genes and have non-orthologous displacements of spoIIQ and spoIVFA, suggesting substantial differences between bacilli and clostridia in the engulfment and spore coat formation steps. Many B. subtilis sporulation genes, particularly those encoding small acid-soluble spore proteins and spore coat proteins, were found only in the family Bacillaceae, or even in a subset of Bacillus spp. Phylogenetic profiles of sporulation genes, compiled in this work, confirm the presence of a common sporulation gene core, but also illuminate the diversity of the sporulation processes within various lineages. These profiles should help further experimental studies of uncharacterized widespread sporulation genes, which would ultimately allow delineation of the minimal set(s) of sporulation-specific genes in Bacilli and Clostridia.
C1 [Galperin, Michael Y.; Mekhedov, Sergei L.; Puigbo, Pere; Smirnov, Sergey; Wolf, Yuri I.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Rigden, Daniel J.] Univ Liverpool, Inst Integrat Biol, Liverpool L69 7ZB, Merseyside, England.
RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM galperin@ncbi.nlm.nih.gov
RI Galperin, Michael/B-5859-2013;
OI Galperin, Michael/0000-0002-2265-5572; Rigden,
Daniel/0000-0002-7565-8937
FU National Institutes of Health at the National Library of Medicine
FX We are grateful to Eugene Koonin for guidance throughout this project,
Boris Belitsky (Tufts University), Tatiana Gaidenko (UC Davis) and
Vladimir Levdikov (University of York) for critical comments and to
Natalya Yutin for providing the ribosomal protein tree used in Fig. S2.
This work was supported by the Intramural Research Program of the
National Institutes of Health at the National Library of Medicine.
NR 146
TC 71
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U1 3
U2 71
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-2912
J9 ENVIRON MICROBIOL
JI Environ. Microbiol.
PD NOV
PY 2012
VL 14
IS 11
BP 2870
EP 2890
DI 10.1111/j.1462-2920.2012.02841.x
PG 21
WC Microbiology
SC Microbiology
GA 029DR
UT WOS:000310475500002
PM 22882546
ER
PT J
AU Loverdo, C
Park, M
Schreiber, SJ
Lloyd-Smith, JO
AF Loverdo, Claude
Park, Miran
Schreiber, Sebastian J.
Lloyd-Smith, James O.
TI INFLUENCE OF VIRAL REPLICATION MECHANISMS ON WITHIN-HOST EVOLUTIONARY
DYNAMICS
SO EVOLUTION
LA English
DT Article
DE Models; simulations; mutations; reproductive strategies
ID RNA-POLYMERASE-II; RETROVIRAL MUTATION-RATES; IN-VIVO;
REVERSE-TRANSCRIPTASE; POPULATION-GENETICS; LETHAL MUTAGENESIS; RHESUS
MACAQUES; MOSAIC-VIRUS; BURST SIZE; EMERGENCE
AB Viruses replicate their genomes using a variety of mechanisms, leading to different distributions of mutations among their progeny. Yet, models of viral evolution often only consider the mean mutation rate. To investigate when and how replication mechanisms impact viral evolution, we analyze the early dynamics of within-host infection for two idealized cases: when all offspring virions from an infected cell carry the same genotype, mutated or not; and when mutations occur independently across offspring virions. Other replication life histories fall between these extremes. Using branching process models, we study the probability that viral infection becomes established when mutations are lethal, and in the more general case of two strains of different fitness. For a given mean mutation rate, we show that a lineage of viruses with correlated mutations is less likely to survive than with independent mutations, but when it survives, the viral population grows faster. While this holds true for all parameter regimes, replication life history has a quantitatively significant influence on viral dynamics when stochastic effects are important and when mutations are crucial for survival-conditions typical of evolutionary escape situations.
C1 [Loverdo, Claude; Park, Miran; Lloyd-Smith, James O.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
[Schreiber, Sebastian J.] Univ Calif Davis, Dept Evolut & Ecol, Davis, CA 95616 USA.
[Schreiber, Sebastian J.] Univ Calif Davis, Ctr Populat Biol, Davis, CA 95616 USA.
[Lloyd-Smith, James O.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Loverdo, C (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
EM loverdo@ucla.edu
RI Lloyd-Smith, James/K-4080-2012;
OI Lloyd-Smith, James/0000-0001-7941-502X; Loverdo,
Claude/0000-0002-0888-1717
FU National Science Foundation [EF-0928690, EF-0928987]; De Logi Chair in
Biological Sciences; RAPIDD program of the Science & Technology
Directorate; Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX The authors thank S. Blumberg, C. Strelioff, and R. Ke for providing
useful comments on earlier drafts of this manuscript. All authors are
supported by the National Science Foundation grants EF-0928690 and
EF-0928987. JLS is grateful for the support of the De Logi Chair in
Biological Sciences, and the RAPIDD program of the Science & Technology
Directorate, Department of Homeland Security, and the Fogarty
International Center, National Institutes of Health.
NR 56
TC 8
Z9 8
U1 1
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-3820
J9 EVOLUTION
JI Evolution
PD NOV
PY 2012
VL 66
IS 11
BP 3462
EP 3471
DI 10.1111/j.1558-5646.2012.01687.x
PG 10
WC Ecology; Evolutionary Biology; Genetics & Heredity
SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics &
Heredity
GA 029EM
UT WOS:000310477600012
PM 23106710
ER
PT J
AU Pepper, JW
AF Pepper, John W.
TI Drugs that target pathogen public goods are robust against evolved drug
resistance
SO EVOLUTIONARY APPLICATIONS
LA English
DT Article
DE biomedicine; cancer medicine; contemporary evolution; disease biology;
evolutionary medicine; evolutionary theory; experimental evolution;
microbial biology; natural selection
ID DIGITAL EVOLUTION; GROUP SELECTION; MECHANISMS; COVARIANCE
AB Pathogen drug resistance is a central problem in medicine and public health. It arises through somatic evolution, by mutation and selection among pathogen cells within a host. Here, we examine the hypothesis that evolution of drug resistance could be reduced by developing drugs that target the secreted metabolites produced by pathogen cells instead of directly targeting the cells themselves. Using an agent-based computational model of an evolving population of pathogen cells, we test this hypothesis and find support for it. We also use our model to explain this effect within the framework of standard evolutionary theory. We find that in our model, the drugs most robust against evolved drug resistance are those that target the most widely shared external products, or public goods, of pathogen cells. We also show that these drugs exert a weak selective pressure for resistance because they create only a weak correlation between drug resistance and cell fitness. The same principles apply to design of vaccines that are robust against vaccine escape. Because our theoretical results have crucial practical implications, they should be tested by empirical experiments.
C1 [Pepper, John W.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Pepper, John W.] Santa Fe Inst, Santa Fe, NM 87501 USA.
RP Pepper, JW (reprint author), NCI, Canc Prevent Div, 6130 Execut Blvd,MSC 7315, Bethesda, MD 20892 USA.
EM pepperjw@mail.nih.gov
RI Pepper, John/O-1662-2013
OI Pepper, John/0000-0001-9888-0437
FU NSF DDIG [1010669]
FX My doctoral student William W. Driscoll chose not to be listed as
co-author on this paper, but was fully qualified to be. He wrote most of
the software, carried out simulation experiments, collected results, and
contributed substantially to writing. He was supported by NSF DDIG
#1010669.
NR 18
TC 18
Z9 22
U1 2
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-4571
J9 EVOL APPL
JI Evol. Appl.
PD NOV
PY 2012
VL 5
IS 7
BP 757
EP 761
DI 10.1111/j.1752-4571.2012.00254.x
PG 5
WC Evolutionary Biology
SC Evolutionary Biology
GA 030BW
UT WOS:000310543800009
PM 23144661
ER
PT J
AU Beall, S
DeCherney, AH
AF Beall, Stephanie
DeCherney, Alan H.
TI Management of tubal ectopic pregnancy: methotrexate and salpingostomy
are preferred to preserve fertility
SO FERTILITY AND STERILITY
LA English
DT Editorial Material
ID SYSTEMIC METHOTREXATE; EXPECTANT MANAGEMENT
C1 [Beall, Stephanie; DeCherney, Alan H.] NIH, Bethesda, MD 20892 USA.
RP Beall, S (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
NR 5
TC 5
Z9 5
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD NOV
PY 2012
VL 98
IS 5
BP 1118
EP 1120
DI 10.1016/j.fertnstert.2012.07.1115
PG 3
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 028TW
UT WOS:000310447300014
PM 22884016
ER
PT J
AU Ferrell, RJ
Rodriguez, G
Holman, D
O'Connor, K
Wood, JW
Weinstein, M
AF Ferrell, Rebecca J.
Rodriguez, German
Holman, Darryl
O'Connor, Kathleen
Wood, James W.
Weinstein, Maxine
TI Hypoestrogenic "inactive phases'' at the start of the menstrual cycle:
changes with age and reproductive stage, and relationship to follicular
depletion
SO FERTILITY AND STERILITY
LA English
DT Article
DE Follicular depletion; hypoestrogenic; inactive phase; female
reproductive aging; perimenopause
ID MENOPAUSAL TRANSITION; OVARIAN-FOLLICLES; WOMEN; OVULATION; PATTERNS;
PERIMENOPAUSE; VARIABILITY; ESTRADIOL; FREEDOM; LENGTH
AB Objective: To investigate hypoestrogenic "inactive phases'' (IP) in the follicular phase of the menstrual cycle, with respect to age, reproductive stage, and follicular depletion.
Design: Analysis of prospectively collected menstrual bleed and estrone-3-glucuronide data.
Setting: Center for Population and Health, Georgetown University.
Patient(s): White women (n = 88, aged 25-59 years, mean = 44.7 years) from the population-based Biodemographic Models of Reproductive Aging (BIMORA) project.
Intervention(s): None.
Main Outcome Measure(s): The IP durations by age and reproductive stage. Estimated follicular depletion rate based on IP durations.
Result(s): Mean IP duration and variability decreased and then increased with age/reproductive stage. The proportion of very short (<= 1 day) IP durations increased and then decreased with age/stage. Long IPs occurred most, but not exclusively, in the oldest age/latest stage. Follicular depletion rate estimates were a plausible 2%-4% per year of age, but these models were a poor fit because IP durations did not consistently increase across ages/stages.
Conclusion(s): Follicular depletion models alone do not explain the observed pattern of IPs. Our data suggest that IPs reflect both follicular depletion and hyperstimulation in premenopausal and perimenopausal women. Knowledge of underlying IP patterns in the menstrual cycle could inform decisions about hormone sampling and contraception during the perimenopause. (Fertil Steril (R) 2012;98:1246-53. (C)2012 by American Society for Reproductive Medicine.)
C1 [Ferrell, Rebecca J.] NIA, NIH, Bethesda, MD 20892 USA.
[Rodriguez, German] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA.
[Holman, Darryl; O'Connor, Kathleen] Univ Washington, Dept Anthropol, Seattle, WA 98195 USA.
[Holman, Darryl; O'Connor, Kathleen] Univ Washington, Ctr Studies Demog & Ecol, Seattle, WA 98195 USA.
[Wood, James W.] Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA.
[Wood, James W.] Penn State Univ, Populat Res Inst, University Pk, PA 16802 USA.
[Weinstein, Maxine] Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA.
RP Ferrell, RJ (reprint author), NIA, NIH, 7201 Wisconsin Ave,Room 2C212, Bethesda, MD 20892 USA.
EM rebecca.ferrell@nih.gov
FU [NIH R01AG015141]; [NIH R01HD034159]; [NIH F32HD007994]; [NIH
R24HD042828]
FX Supported by grants NIH R01AG015141, NIH R01HD034159, NIH F32HD007994,
and NIH R24HD042828.
NR 43
TC 2
Z9 2
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD NOV
PY 2012
VL 98
IS 5
BP 1246
EP +
DI 10.1016/j.fertnstert.2012.07.1101
PG 11
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 028TW
UT WOS:000310447300035
PM 22901850
ER
PT J
AU Britten, JL
Malik, M
Levy, G
Mendoza, M
Catherino, WH
AF Britten, Joy Lynne
Malik, Minnie
Levy, Gary
Mendoza, Mirian
Catherino, William H.
TI Gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate and
GnRH antagonist cetrorelix acetate directly inhibit leiomyoma
extracellular matrix production
SO FERTILITY AND STERILITY
LA English
DT Article
DE Leiomyoma; leuprolide acetate; cetrorelix acetate; collagen 1A1;
versican; fibronectin
ID MESSENGER-RIBONUCLEIC-ACID; UTERINE LEIOMYOMAS; DOUBLE-BLIND; HUMAN
MYOMETRIUM; GENE-EXPRESSION; IN-VITRO; FIBROIDS; GROWTH; CELLS; VERSICAN
AB Objective: To determine the direct effect that GnRH analogues leuprolide acetate and cetrorelix acetate have on extracellular matrix in human leiomyoma and patient-matched myometrial cells.
Design: Laboratory study.
Setting: University hospital.
Patient(s): None.
Intervention(s): Cell culture, proliferation studies, and messenger RNA and protein analysis.
Main Outcome Measure(s): Expression of GnRHR1, COL1A1, fibronectin, and versican variant V0 in treated leiomyoma cells and patient-matched myometrial cells.
Result(s): Leiomyoma cells were treated with GnRH analogues for 6, 24, and 120 hours. Leuprolide treatment for 6 hours resulted in an increase in expression of GnRHR1 (4.02 +/- 0.12-fold), COL1A1 (6.41 +/- 0.29-fold), fibronectin (9.69 +/- 0.18-fold), and versican variant V0 (7.58 +/- 0.43-fold). Leiomyoma cells treated with cetrorelix for 6 hours showed a decreased expression of GnRHR1 (0.5 +/- 0.15-fold), COL1A1 (3.79 +/- 0.7-fold), fibronectin (0.92 +/- 0.09-fold), and versican variant V0 (0.14 +/- 0.07-fold). Leuprolide treatment of leiomyoma cells at high concentrations (10(-5) M) did not result in an increase in protein production. Cetrorelix treatment of leiomyoma cells for 6 hours showed an increase in fibronectin protein production (3.14 +/- 0.09-fold). Protein production of leiomyoma cells treated with cetrorelix for 120 hours demonstrated a decrease in GnRHR1 (0.51 +/- 0.07-fold), COL1A1 (0.35 +/- 0.07-fold), fibronectin (1.94 +/- 0.08-fold), and versican variant V0 (0.77 +/- 0.19-fold).
Conclusion(s): Our findings demonstrate that GnRH analogue treatment directly regulated COL1A1, fibronectin, and matrix proteoglycan production. The reduction in versican variant V0 gene expression caused by cetrorelix treatment, and its association with the osmotic regulation of leiomyomas, presents a new and innovative approach to therapy for this disease. (Fertil Steril (R) 2012; 98: 1299-307. (C)2012 by American Society for Reproductive Medicine.)
C1 [Britten, Joy Lynne; Malik, Minnie; Levy, Gary; Mendoza, Mirian; Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA.
[Levy, Gary; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM william.catherino@usuhs.edu
OI Malik, Minnie/0000-0003-1129-6575
FU EMD Serono Pharmaceutical; Ferring Pharmaceutical
FX This work was made possible by generous grants from EMD Serono and
Ferring Pharmaceuticals.
NR 48
TC 10
Z9 11
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD NOV
PY 2012
VL 98
IS 5
BP 1299
EP 1307
DI 10.1016/j.fertnstert.2012.07.1123
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 028TW
UT WOS:000310447300043
PM 22901846
ER
PT J
AU Zheng, G
Wu, CO
Kwak, M
Jiang, WH
Joo, J
Lima, JAC
AF Zheng, Gang
Wu, Colin O.
Kwak, Minjung
Jiang, Wenhua
Joo, Jungnam
Lima, Joao A. C.
TI Joint Analysis of Binary and Quantitative Traits With Data Sharing and
Outcome-Dependent Sampling (vol 36, pg 263, 2012)
SO GENETIC EPIDEMIOLOGY
LA English
DT Correction
ID RHEUMATOID-ARTHRITIS; POLYMORPHISM; ASSOCIATION; SEVERITY
C1 [Zheng, Gang; Wu, Colin O.; Kwak, Minjung] NHLBI, Bethesda, MD 20892 USA.
[Jiang, Wenhua; Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Joo, Jungnam] Natl Canc Ctr, Geonggi Do, South Korea.
RP Zheng, G (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA.
NR 7
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
BP 717
EP 719
DI 10.1002/gepi.21666
PG 3
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200005
ER
PT J
AU Liu, CY
Dupuis, J
Larson, MG
Levy, D
AF Liu, Chunyu
Dupuis, Josee
Larson, Martin G.
Levy, Daniel
TI Association Testing of Mitochondrial Genome Using Pedigree Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Liu, Chunyu; Levy, Daniel] Framingham Heart Study NHLBI, Framingham, MA USA.
[Dupuis, Josee; Larson, Martin G.] Boston Univ, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 16
BP 724
EP 724
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200022
ER
PT J
AU Edwards, TL
Edwards, DRV
Papanicolaou, GJ
North, KE
AF Edwards, Todd L.
Edwards, Digna R. Velez
Papanicolaou, George J.
North, Kari E.
CA African Amer BMI GWAS Consortium
TI Evidence of Recent Positive Selection in Africans at Known and Novel BMI
Loci
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Edwards, Todd L.; Edwards, Digna R. Velez] Vanderbilt Univ, Nashville, TN 37212 USA.
[Papanicolaou, George J.] NHLBI, Bethesda, MD 20892 USA.
[North, Kari E.] Univ N Carolina, Chapel Hill, NC 27515 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 19
BP 725
EP 725
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200025
ER
PT J
AU Liu, JH
Chen, GK
Blot, WJ
Strom, SS
Berndt, SI
Kittles, RA
Rybicki, BA
Isaacs, W
Ingles, SA
Stanford, JL
Diver, WR
Witte, JS
Hsing, AW
Nemesure, B
Rebbeck, TR
Cooney, KA
Xu, JF
Kibel, AS
Hu, JJ
John, EM
Gueye, SM
Watya, S
Signorello, LB
Hayes, RB
Wang, ZM
Chu, L
Klein, EA
Goodman, P
Yeboah, E
Tettey, Y
Cai, QY
Kolb, S
Ostrander, EA
Zeigler-Johnson, C
Yamamura, Y
Neslund-Dudas, C
Haslag-Minoff, J
Wu, W
Thomas, V
Allen, GO
Murphy, A
Chang, BL
Zheng, SL
Leske, MC
Wu, SY
Ray, AM
Hennis, AJM
Thun, MJ
Carpten, J
Casey, G
Chanock, SJ
Stram, DO
Henderson, BE
Haiman, CA
Conti, DV
AF Liu, Jinghua
Chen, Gary K.
Blot, William J.
Strom, Sara S.
Berndt, Sonja I.
Kittles, Rick A.
Rybicki, Benjamin A.
Isaacs, William
Ingles, Sue A.
Stanford, Janet L.
Diver, W. Ryan
Witte, John S.
Hsing, Ann W.
Nemesure, Barbara
Rebbeck, Timothy R.
Cooney, Kathleen A.
Xu, Jianfeng
Kibel, Adam S.
Hu, Jennifer J.
John, Esther M.
Gueye, Serigne M.
Watya, Stephen
Signorello, Lisa B.
Hayes, Richard B.
Wang, Zhaoming
Chu, Lisa
Klein, Eric A.
Goodman, Phyllis
Yeboah, Edward
Tettey, Yao
Cai, Qiuyin
Kolb, Suzanne
Ostrander, Elaine A.
Zeigler-Johnson, Charnita
Yamamura, Yuko
Neslund-Dudas, Christine
Haslag-Minoff, Jennifer
Wu, William
Thomas, Venetta
Allen, Glenn O.
Murphy, Adma
Chang, Bao-Li
Zheng, S. Lilly
Leske, M. Cristina
Wu, Suh-Yuh
Ray, Anna M.
Hennis, Anselm J. M.
Thun, Michael J.
Carpten, John
Casey, Graham
Chanock, Stephen J.
Stram, Daniel O.
Henderson, Brian E.
Haiman, Christopher A.
Conti, David V.
TI Models for Admixture Mapping in a Regression Framework
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Liu, Jinghua; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Stram, Daniel O.; Henderson, Brian E.; Haiman, Christopher A.; Conti, David V.] Univ So Calif, Los Angeles, CA 90089 USA.
[Blot, William J.; Signorello, Lisa B.; Cai, Qiuyin] Vanderbilt Univ, Nashville, TN USA.
[Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Hsing, Ann W.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kittles, Rick A.] Univ Illinois, Chicago, IL USA.
[Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Detroit, MI USA.
[Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Seattle, WA USA.
[Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Witte, John S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Nemesure, Barbara; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anselm J. M.] SUNY Stony Brook, Stony Brook, NY USA.
[Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Abramson Canc Ctr, Philadelphia, PA USA.
[Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Xu, Jianfeng; Zheng, S. Lilly] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA.
[Kibel, Adam S.; Haslag-Minoff, Jennifer; Wu, William] Washington Univ, St Louis, MO 63130 USA.
[Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA.
[John, Esther M.; Chu, Lisa] Canc Prevent Inst Calif, Fremont, CA USA.
[Gueye, Serigne M.] Hop Gen Grand Yoff, Dakar, Senegal.
[Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda.
[Hayes, Richard B.] NYU, Langone Med Ctr, New York, NY 10003 USA.
[Wang, Zhaoming] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH USA.
[Goodman, Phyllis] Fred Hutch Canc Ctr, Seattle, WA USA.
[Yeboah, Edward; Tettey, Yao] Univ Ghana, Sch Med, Legon, Ghana.
[Cai, Qiuyin] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Ostrander, Elaine A.] NHGRI, Canc Genet Branch, Bethesda, MD USA.
[Murphy, Adma] Northwestern Univ, Evanston, IL 60208 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 26
BP 727
EP 727
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200032
ER
PT J
AU Peng, B
Racine, B
Chen, HS
Mechanic, L
Clarke, L
Gillanders, E
Feuer, E
AF Peng, Bo
Racine, Ben
Chen, Huann-Sheng
Mechanic, Leah
Clarke, Lauren
Gillanders, Elizabeth
Feuer, Eric
TI Genetic Simulation Resources (GSR): A Website for the Registration and
Discovery of Genetic Data Simulators
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Peng, Bo] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Chen, Huann-Sheng; Mechanic, Leah; Gillanders, Elizabeth; Feuer, Eric] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RI Chen, Huann-Sheng/D-6328-2013
OI Chen, Huann-Sheng/0000-0002-5905-8050
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 49
BP 733
EP 734
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200055
ER
PT J
AU He, J
Chen, GK
Blot, WJ
Strom, SS
Berndt, SI
Kitties, RA
Rybicki, BA
Isaacs, W
Ingles, SA
Stanford, JL
Diver, RW
Witte, JS
Hsing, AW
Nemesure, B
Rebbeck, TR
Cooney, KA
Xu, JF
Kibel, AS
Hu, JJ
John, EM
Gueye, SM
Watya, S
Signorello, LB
Hayes, RB
Wang, ZM
Chu, LW
Klein, EA
Goodman, P
Yeboah, E
Tettey, Y
Cai, QY
Kolb, S
Ostrander, EA
Zeigler-Johnson, C
Yamamura, Y
Neslund-Dudas, C
Haslag-Minoff, J
Wu, W
Thomas, V
Allen, GO
Murphy, A
Chang, BL
Zheng, LS
Leske, CM
Wu, SY
Ray, AM
Hennis, AJM
Thun, MJ
Carpten, J
Casey, G
Chanock, SJ
Henderson, BE
Haiman, CA
Stram, DO
AF He, Jing
Chen, Gary K.
Blot, William J.
Strom, Sara S.
Berndt, Sonja I.
Kitties, Rick A.
Rybicki, Benjamin A.
Isaacs, William
Ingles, Sue A.
Stanford, Janet L.
Diver, Ryan W.
Witte, John S.
Hsing, Ann W.
Nemesure, Barbara
Rebbeck, Timothy R.
Cooney, Kathleen A.
Xu, Jianfeng
Kibel, Adam S.
Hu, Jennifer J.
John, Esther M.
Gueye, Serigne M.
Watya, Stephen
Signorello, Lisa B.
Hayes, Richard B.
Wang, Zhaoming
Chu, Lisa W.
Klein, Eric A.
Goodman, Phyllis
Yeboah, Edward
Tettey, Yao
Cai, Qiuyin
Kolb, Suzanne
Ostrander, Elaine A.
Zeigler-Johnson, Charnita
Yamamura, Yuko
Neslund-Dudas, Christine
Haslag-Minoff, Jennifer
Wu, William
Thomas, Venetta
Allen, Glenn O.
Murphy, Adam
Chang, Bao-Li
Zheng, Lilly S.
Leske, Cristina M.
Wu, Suh-Yuh
Ray, Anna M.
Hennis, Anselm J. M.
Thun, Michael J.
Carpten, John
Casey, Graham
Chanock, Stephen J.
Henderson, Brian E.
Haiman, Christopher A.
Stram, Daniel O.
TI Polygenes and Estimated Heritability of Prostate Cancer in an African
American Sample Using GWAS Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [He, Jing; Chen, Gary K.; Ingles, Sue A.; Casey, Graham; Henderson, Brian E.; Haiman, Christopher A.; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Blot, William J.; Signorello, Lisa B.] Int Epidemiol Inst, Rockville, MD USA.
[Strom, Sara S.; Yamamura, Yuko] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Berndt, Sonja I.; Hsing, Ann W.; Wang, Zhaoming; Chu, Lisa W.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kitties, Rick A.] Univ Illinois, Dept Med, Chicago, IL USA.
[Rybicki, Benjamin A.; Neslund-Dudas, Christine] Henry Ford Hosp, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA.
[Isaacs, William] Johns Hopkins Hosp & Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD USA.
[Stanford, Janet L.; Kolb, Suzanne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Diver, Ryan W.; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, Inst Human Genet, San Francisco, CA 94143 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Urol, Inst Human Genet, San Francisco, CA USA.
[Nemesure, Barbara; Leske, Cristina M.; Wu, Suh-Yuh; Hennis, Anselm J. M.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.; Zeigler-Johnson, Charnita; Chang, Bao-Li] Abramson Canc Ctr, Philadelphia, PA USA.
[Cooney, Kathleen A.; Ray, Anna M.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA.
[Xu, Jianfeng; Zheng, Lilly S.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA.
[Kibel, Adam S.; Haslag-Minoff, Jennifer; Wu, William] Washington Univ, Dept Surg, Div Urol, St Louis, MO USA.
[Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Coral Gables, FL 33124 USA.
[Hu, Jennifer J.; Thomas, Venetta; Allen, Glenn O.] Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Coral Gables, FL 33124 USA.
[John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Gueye, Serigne M.] Hop Gen Grand Yoff, Dakar, Senegal.
[Watya, Stephen] Makerere Univ, Mulago Hosp, Dept Surg, Urol Unit, Kampala, Uganda.
[Hayes, Richard B.] NYU, Dept Environm Med, Langone Med Ctr, Div Epidemiol, New York, NY 10016 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Yeboah, Edward; Tettey, Yao] Univ Ghana, Sch Med, Legon, Ghana.
[Cai, Qiuyin] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Med, Div Epidemiol, Nashville, TN 37235 USA.
[Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
[Murphy, Adam] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
[Carpten, John] Translat Genom Res Inst, Phoenix, AZ USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 58
BP 736
EP 736
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200064
ER
PT J
AU Bailey-Wilson, JE
Parker, MM
Szymczak, S
Li, Q
Cropp, CD
Nothen, MM
Hetmanski, JB
Ling, H
Pugh, EW
Duggal, P
Taub, MA
Ruczinski, I
Scott, AF
Marazita, ML
Murray, JC
Mangold, E
Beaty, TH
AF Bailey-Wilson, Joan E.
Parker, Margaret M.
Szymczak, Silke
Li, Qing
Cropp, Cheryl D.
Nothen, Markus M.
Hetmanski, Jacqueline B.
Ling, Hua
Pugh, Elizabeth W.
Duggal, Priya
Taub, Margaret A.
Ruczinski, Ingo
Scott, Alan F.
Marazita, Mary L.
Murray, Jeffrey C.
Mangold, Elisabeth
Beaty, Terri H.
TI Using Whole Exome Sequencing to Identify Rare Causal Variants for Oral
Clefts in Multiplex Families with a Focus on Syrian Families
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Bailey-Wilson, Joan E.; Szymczak, Silke; Li, Qing; Cropp, Cheryl D.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Parker, Margaret M.; Hetmanski, Jacqueline B.; Duggal, Priya; Taub, Margaret A.; Ruczinski, Ingo; Beaty, Terri H.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Nothen, Markus M.; Mangold, Elisabeth] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Marazita, Mary L.] Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15260 USA.
[Murray, Jeffrey C.] Univ Iowa, Childrens Hosp, Iowa City, IA 52242 USA.
RI Szymczak, Silke/C-6625-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 66
BP 738
EP 739
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200072
ER
PT J
AU Yang, XH
Jacobs, K
Cullen, M
Boland, J
Burdett, L
Malasky, M
Rotunno, M
Yeager, M
Chanock, S
Tucker, M
Goldstein, A
AF Yang, Xiaohong
Jacobs, Kevin
Cullen, Michael
Boland, Joseph
Burdett, Laurie
Malasky, Michael
Rotunno, Melissa
Yeager, Meredith
Chanock, Stephen
Tucker, Margaret
Goldstein, Alisa
TI Characterization of Rare Variants in Melanoma-associated Genes in
Melanoma-prone Families without CDKN2A/CDK4 Mutations using Exome
Sequencing Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Yang, Xiaohong; Jacobs, Kevin; Cullen, Michael; Boland, Joseph; Burdett, Laurie; Malasky, Michael; Rotunno, Melissa; Yeager, Meredith; Chanock, Stephen; Tucker, Margaret; Goldstein, Alisa] NIH, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 67
BP 739
EP 739
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200073
ER
PT J
AU Ritchie, MD
Setia, SZ
Armstrong, GD
Armstrong, L
Bradford, Y
Crawford, DC
Crosslin, DR
de Andrade, M
Doheny, KF
Hayes, MG
Jarvik, GP
Kullo, I
Li, RL
McCarty, CA
Mirel, D
Olson, L
Purcell, S
Pugh, EW
Tromp, G
Kuivaniemi, H
Lotay, V
Gottesman, O
Haines, JL
AF Ritchie, Marylyn D.
Setia, Shefali Z.
Armstrong, Gretta D.
Armstrong, Loren
Bradford, Yuki
Crawford, Dana C.
Crosslin, David R.
de Andrade, Mariza
Doheny, Kimberly F.
Hayes, M. Geoffrey
Jarvik, Gail P.
Kullo, Iftiklhar
Li, Rongling
McCarty, Cathy A.
Mirel, Daniel
Olson, Lana
Purcell, Shaun
Pugh, Elizabeth W.
Tromp, Gerard
Kuivaniemi, Helena
Lotay, Vaneet
Gottesman, Omri
Haines, Jonathan L.
TI Merging Genomic Data for Research in the Electronic MEdical Records and
GEnomics Network: Lessons Learned in eMERGE
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Ritchie, Marylyn D.; Setia, Shefali Z.; Armstrong, Gretta D.] Penn State Univ, University Pk, PA 16802 USA.
[Armstrong, Loren; Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Bradford, Yuki; Crawford, Dana C.; Olson, Lana; Haines, Jonathan L.] Vanderbilt Univ, Nashville, TN USA.
[Crosslin, David R.; Jarvik, Gail P.] Univ Washington, Seattle, WA 98195 USA.
[de Andrade, Mariza; Kullo, Iftiklhar] Mayo Clin, Rochester, MN USA.
[Doheny, Kimberly F.; Pugh, Elizabeth W.] Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD 21218 USA.
[Li, Rongling] NHGRI, NIH, Bethesda, MD USA.
[McCarty, Cathy A.] Essentia Rural Hlth, Duluth, MN USA.
[Purcell, Shaun; Lotay, Vaneet; Gottesman, Omri] Mt Sinai Sch Med, New York, NY USA.
RI Jarvik, Gail/N-6476-2014
OI Jarvik, Gail/0000-0002-6710-8708
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 71
BP 740
EP 740
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200077
ER
PT J
AU Mandal, DM
Haskins, M
Bencaz, A
Hutchinson, J
Chambliss, J
Rothschild, H
Bailey-Wilson, JE
AF Mandal, Diptasri M.
Haskins, Matthew
Bencaz, Angelle
Hutchinson, Jill
Chambliss, Jessica
Rothschild, Henry
Bailey-Wilson, Joan E.
TI Histologic Types and Risk Factors in Familial Lung Cancer Cases from
Southern Louisiana
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Mandal, Diptasri M.; Haskins, Matthew; Bencaz, Angelle; Hutchinson, Jill; Chambliss, Jessica; Rothschild, Henry] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA.
[Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 81
BP 743
EP 743
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200087
ER
PT J
AU Zaitlen, N
Lindstrom, S
Pasaniuc, B
Cornelis, M
Genovese, G
Pollack, S
Barton, A
Bowden, DW
Eyre, S
Freedman, BI
Field, JK
Groop, L
Haugen, A
Henderson, BE
Hicks, PJ
Hocking, LJ
Kolonel, LN
Landi, MT
Langefeld, CD
Le Marchand, L
Meister, M
Morgan, AW
Raji, OY
Risch, A
Scherf, D
Steer, S
Walshaw, M
Waters, KM
Wilson, AG
Wordsworth, P
Zienolddiny, S
Tchetgen, ET
Haiman, C
Hunter, DJ
Plenge, RM
Worthington, J
Christiani, DC
Schaumberg, DA
Chasman, DI
Altshuler, D
Voight, B
Kraft, P
Patterson, N
Price, AL
AF Zaitlen, Noah
Lindstrom, Sara
Pasaniuc, Bogdan
Cornelis, Marilyn
Genovese, Giulio
Pollack, Samuela
Barton, Anne
Bowden, Donald W.
Eyre, Steve
Freedman, Barry I.
Field, John K.
Groop, Leif
Haugen, Aage
Henderson, Brian E.
Hicks, Pamela J.
Hocking, Lynne J.
Kolonel, Laurence N.
Landi, Maria Teresa
Langefeld, Carl D.
Le Marchand, Loic
Meister, Michael
Morgan, Ann W.
Raji, Olaide Y.
Risch, Angela
Scherf, David
Steer, Sophia
Walshaw, Martin
Waters, Kevin M.
Wilson, Anthony G.
Wordsworth, Paul
Zienolddiny, Shanbeh
Tchetgen, Eric Tchetgen
Haiman, Christopher
Hunter, David J.
Plenge, Robert M.
Worthington, Jane
Christiani, David C.
Schaumberg, Debra A.
Chasman, Daniel I.
Altshuler, David
Voight, Benjamin
Kraft, Peter
Patterson, Nick
Price, Alkes L.
TI Informed Conditioning on Clinical Covariates Increases Power in
Case-control Association Studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Zaitlen, Noah; Lindstrom, Sara; Pasaniuc, Bogdan; Cornelis, Marilyn; Pollack, Samuela; Tchetgen, Eric Tchetgen; Hunter, David J.; Christiani, David C.; Schaumberg, Debra A.; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Genovese, Giulio; Plenge, Robert M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Barton, Anne; Eyre, Steve; Worthington, Jane] Univ Manchester, Manchester M13 9PL, Lancs, England.
[Field, John K.; Raji, Olaide Y.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England.
[Henderson, Brian E.; Waters, Kevin M.; Haiman, Christopher] Univ So Calif, Los Angeles, CA 90089 USA.
[Hicks, Pamela J.; Langefeld, Carl D.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Hocking, Lynne J.] Univ Aberdeen, Aberdeen AB9 1FX, Scotland.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Honolulu, HI 96822 USA.
[Landi, Maria Teresa] NIH, Bethesda, MD USA.
[Steer, Sophia] Kings Coll London, London, England.
[Wilson, Anthony G.] Univ Sheffield, Sheffield S10 2TN, S Yorkshire, England.
RI Altshuler, David/A-4476-2009; Barton, Anne/N-2053-2014; Zienolddiny,
Shanbeh/O-7392-2015
OI Altshuler, David/0000-0002-7250-4107; Barton, Anne/0000-0003-3316-2527;
NR 0
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 88
BP 745
EP 745
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200094
ER
PT J
AU Cropp, CD
Simpson, CL
Wahlfors, T
George, A
Jones, MS
Harper, U
Ponciano-Jackson, D
Tammela, T
Schleutker, J
Bailey-Wilson, JE
AF Cropp, Cheryl D.
Simpson, Claire L.
Wahlfors, Tiina
George, Asha
Jones, MaryPat S.
Harper, Ursula
Ponciano-Jackson, Damaris
Tammela, Teuvo
Schleutker, Johanna
Bailey-Wilson, Joan E.
TI Unraveling Phenotype Heterogeneity in Prostate Cancer Susceptibility in
Finland Utilizing Covariate-Based Analysis
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Cropp, Cheryl D.; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Wahlfors, Tiina] Univ Tampere, Inst Biomed Technol, BioMediTech, FIN-33101 Tampere, Finland.
[George, Asha] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Jones, MaryPat S.; Harper, Ursula; Ponciano-Jackson, Damaris] NHGRI, Genom Core, Genome Technol Branch, NIH, Rockville, MD USA.
[Tammela, Teuvo] Univ Tampere, Tampere Univ Hosp, Dept Urol, FIN-33101 Tampere, Finland.
[Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 93
BP 746
EP 747
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200099
ER
PT J
AU Szymczak, S
Li, Q
Kim, Y
Dasgupta, A
Malley, JD
Bailey-Wilson, JE
AF Szymczak, Silke
Li, Qing
Kim, Yoonhee
Dasgupta, Abhijit
Malley, James D.
Bailey-Wilson, Joan E.
TI A Two-stage Random Forest Approach to Identify Genetic Variants Using
Recombination Hotspot Information
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Szymczak, Silke; Li, Qing; Bailey-Wilson, Joan E.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Kim, Yoonhee] NHGRI, Genometr Sect, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Dasgupta, Abhijit] NIH, Clin Sci Sect, Inst Arthrit & Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA.
[Malley, James D.] NIH, Ctr Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
RI Szymczak, Silke/C-6625-2013
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 115
BP 752
EP 753
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200120
ER
PT J
AU Lu, C
Latourelle, J
O'Connor, GT
Dupuis, J
Kolaczyk, ED
AF Lu, Chen
Latourelle, Jeanne
O'Connor, George T.
Dupuis, Josee
Kolaczyk, Eric D.
TI Network-guided Sparse Regression Modeling for Detection of Gene by Gene
Interactions
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Lu, Chen] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Latourelle, Jeanne; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02215 USA.
[Latourelle, Jeanne] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Latourelle, Jeanne; O'Connor, George T.; Dupuis, Josee] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA.
[Dupuis, Josee] Boston U, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee] Boston U, Program Bioinformat, Boston, MA USA.
[Kolaczyk, Eric D.] Boston Univ, Dept Math & Stat, Program Bioinformat, Boston, MA 02215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 117
BP 753
EP 753
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200122
ER
PT J
AU Li, Q
Szymczak, S
Bailey-Wilson, JE
AF Li, Qing
Szymczak, Silke
Bailey-Wilson, Joan E.
TI Test for Two-SNP Interaction Adjusting for Long Range Linkage
Disequilibrium
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Li, Qing; Szymczak, Silke; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, Bethesda, MD USA.
RI Szymczak, Silke/C-6625-2013
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 124
BP 755
EP 755
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200129
ER
PT J
AU Buck, K
Hein, R
Haeberle, L
Garcia-Closas, M
Chatterjee, N
Chang-Claude, J
AF Buck, Katharina
Hein, Rebecca
Haeberle, Lothar
Garcia-Closas, Montserrat
Chatterjee, Nilanjan
Chang-Claude, Jenny
TI Empirical-Bayes Approach to Investigate Gene-environment Interactions in
Large Consortia
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Buck, Katharina; Chang-Claude, Jenny] German Canc Res Ctr, Heidelberg, Germany.
[Hein, Rebecca] Univ Cologne, Cologne, Germany.
[Haeberle, Lothar] Univ Hosp Erlangen, Erlangen, Germany.
[Garcia-Closas, Montserrat] Inst Canc Res, London, England.
[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, London, England.
[Chatterjee, Nilanjan] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 129
BP 756
EP 757
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200134
ER
PT J
AU Nickels, S
Truong, T
Hein, R
Stevens, K
Buck, K
Gaudet, MM
Haeberle, L
Spurdle, A
Behrens, S
Eilber, U
Figueora, J
Dunning, AM
Chenevix-Trench, G
Pharoah, P
Easton, DF
Hall, P
Schmidt, M
Garcia-Closas, M
Milne, RL
Chang-Claude, J
AF Nickels, Stefan
Truong, Therese
Hein, Rebecca
Stevens, Kristen
Buck, Katharina
Gaudet, Mia M.
Haeberle, Lothar
Spurdle, Amanda
Behrens, Sabine
Eilber, Ursula
Figueora, Jonine
Dunning, Alison M.
Chenevix-Trench, Georgia
Pharoah, Paul
Easton, Douglas F.
Hall, Per
Schmidt, Marjanka
Garcia-Closas, Montserrat
Milne, Roger L.
Chang-Claude, Jenny
TI Evidence of Gene-environment Interaction Between Common Breast Cancer
Susceptibility Loci and Established Environmental Risk Factors
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Nickels, Stefan; Behrens, Sabine; Eilber, Ursula; Chang-Claude, Jenny] Univ Cologne, German Canc Res Ctr DKFZ, Div Canc Epidemiol, Cologne, Germany.
[Truong, Therese] Univ Cologne, INSERM, Natl Inst Hlth & Med Res, CESP Ctr Res Epidemiol & Populat Hlth, Cologne, Germany.
[Hein, Rebecca] Univ Cologne, PMV Res Grp, Dept Child & Adolescent Psychiat & Psychotherapy, Cologne, Germany.
[Stevens, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Gaudet, Mia M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Haeberle, Lothar] Erlangen Univ Hosp, Dept Obstet & Gynecol, Erlangen, Germany.
[Chenevix-Trench, Georgia] Queensland Inst Med Res, Genet & Populat Hlth Div, Brisbane, Qld 4006, Australia.
[Figueora, Jonine] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Dunning, Alison M.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB2 1TN, England.
[Hall, Per] Karolinska Inst, Stockholm, Sweden.
[Schmidt, Marjanka] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 127
BP 756
EP 756
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200132
ER
PT J
AU Franceschini, N
Dreisbach, A
Kao, WL
North, KE
Nalls, M
Fox, C
Cupp, A
AF Franceschini, Nora
Dreisbach, Albert
Kao, W. Linda
North, Kari E.
Nalls, Michael
Fox, Caroline
Cupp, Adrienne
TI Gene-by-Smoking Interaction Analyses of Kidney Traits in the NHLBI
Candidate-gene Association Resources CARe Cohorts
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Franceschini, Nora; North, Kari E.] Univ N Carolina, Chapel Hill, NC 39216 USA.
[Dreisbach, Albert] Univ Mississippi, Jackson, MS USA.
[Kao, W. Linda] Johns Hopkins Univ, Baltimore, MD 20892 USA.
[Nalls, Michael] NIA, Neurogenet Lab, NIH, Bethesda, MD 02115 USA.
[Fox, Caroline] Harvard Univ, NHLBI, Framingham Heart Study & Ctr Populat Studies & En, Sch Med, Boston, MA USA.
[Cupp, Adrienne] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Cupp, Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 135
BP 758
EP 759
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200140
ER
PT J
AU Joshi, AD
Lindstrom, S
Ziegler, RG
Figueroa, JD
Gapstur, SM
Haiman, CA
Riboli, E
Kraft, P
Gaudet, MM
AF Joshi, Amit D.
Lindstrom, Sara
Ziegler, Regina G.
Figueroa, Jonine D.
Gapstur, Susan M.
Haiman, Christopher A.
Riboli, Elio
Kraft, Peter
Gaudet, Mia M.
TI A Comparison of Approaches for Genome-wide Gene-environment Interaction
Analyses in the Risk of Estrogen Receptor (ER)-Negative Breast Cancer
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Joshi, Amit D.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Ziegler, Regina G.; Figueroa, Jonine D.] NCI, Bethesda, MD 20892 USA.
[Gapstur, Susan M.; Gaudet, Mia M.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA.
[Riboli, Elio] Imperial Coll London, Sch Publ Hlth, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 137
BP 759
EP 759
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200142
ER
PT J
AU Lobach, I
Fan, RZ
AF Lobach, Iryna
Fan, Ruzong
TI Genotype-based Bayesian Analysis of Gene-Environment Interactions with
Multiple Genetic Markers and Misclassification in Environmental Factors
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Lobach, Iryna] NYU, Sch Med, New York, NY 10003 USA.
[Fan, Ruzong] NICHD, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 153
BP 764
EP 764
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200158
ER
PT J
AU Wang, ZM
Jacobs, KB
Yeager, M
Hutchinson, A
Sampson, J
Tucker, M
Chanock, SJ
AF Wang, Zhaoming
Jacobs, Kevin B.
Yeager, Meredith
Hutchinson, Amy
Sampson, Joshua
Tucker, Margaret
Chanock, Stephen J.
TI Second Generation DCEG Reference Set Improves Performance of Genotype
Imputation
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Wang, Zhaoming; Jacobs, Kevin B.; Yeager, Meredith; Hutchinson, Amy] NCI, SAIC Frederick, DCEG, Bethesda, MD 20892 USA.
RI Tucker, Margaret/B-4297-2015
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 162
BP 766
EP 766
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200167
ER
PT J
AU Hiraki, LT
Joshi, A
Lindstrom, S
Chan, AT
Chanock, S
Kraft, P
AF Hiraki, Linda T.
Joshi, Amit
Lindstrom, Sara
Chan, Andrew T.
Chanock, Stephen
Kraft, Peter
TI Building and Assessing Protein-Protein Interaction Networks from Genome
Wide Association Results in Cancer
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Hiraki, Linda T.; Joshi, Amit; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chanock, Stephen] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 178
BP 771
EP 771
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200183
ER
PT J
AU Chen, H
Meigs, JB
Dupuis, J
AF Chen, Han
Meigs, James B.
Dupuis, Josee
TI Sequence Kernel Association Test in Family Data
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Cambridge, MA 02138 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 181
BP 772
EP 772
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200186
ER
PT J
AU Simpson, CL
Green, T
Doan, B
Amos, CI
Pinney, SM
Kupert, EY
de Andrade, M
Yang, P
Schwartz, AG
Fain, PR
Gazdar, A
Minna, J
Wiest, JS
Rothschild, H
Mandal, D
You, M
Coons, TA
Gaba, C
Anderson, MW
Bailey-Wilson, JE
AF Simpson, Claire L.
Green, Tiffany
Doan, Betty
Amos, Christopher I.
Pinney, Susan M.
Kupert, Elena Y.
de Andrade, Mariza
Yang, Ping
Schwartz, Ann G.
Fain, Pam R.
Gazdar, Adi
Minna, John
Wiest, Jonathan S.
Rothschild, Henry
Mandal, Diptasri
You, Ming
Coons, Theresa A.
Gaba, Colette
Anderson, Marshall W.
Bailey-Wilson, Joan E.
TI Fine-Mapping in a Covariate-based Genomewide Linkage Scan of Lung Cancer
Susceptibility
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 18-20, 2012
CL Stevenson, WA
SP Int Genet Epidemiol Soc (IGES)
C1 [Simpson, Claire L.; Green, Tiffany; Doan, Betty; Bailey-Wilson, Joan E.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Amos, Christopher I.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX USA.
[Pinney, Susan M.; Kupert, Elena Y.; You, Ming; Anderson, Marshall W.] Med Coll Wisconsin, Milwaukee, WI USA.
[de Andrade, Mariza; Yang, Ping] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48202 USA.
[Fain, Pam R.] Univ Colorado, Boulder, CO 80309 USA.
[Wiest, Jonathan S.] NCI, NIH, Bethesda, MD 20892 USA.
[Rothschild, Henry; Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, Baton Rouge, LA 70803 USA.
[Gaba, Colette] Univ Toledo, Toledo, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2012
VL 36
IS 7
MA 191
BP 774
EP 775
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 021VJ
UT WOS:000309913200196
ER
PT J
AU Holz, LE
Yoon, JC
Raghuraman, S
Moir, S
Sneller, MC
Rehermann, B
AF Holz, Lauren E.
Yoon, Joo Chun
Raghuraman, Sukanya
Moir, Susan
Sneller, Michael C.
Rehermann, Barbara
TI B Cell Homeostasis in Chronic Hepatitis C Virus-Related Mixed
Cryoglobulinemia Is Maintained Through Naive B Cell Apoptosis
SO HEPATOLOGY
LA English
DT Article
ID MONONUCLEAR-CELLS; ANTIVIRAL THERAPY; INFECTION; RECEPTOR; ACTIVATION;
VASCULITIS; PROTEIN; DISORDERS; RITUXIMAB; ANTIBODY
AB Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. Although the formation of inflammation-triggering immune complexes is driven by clonal expansions of autoreactive B cells, we found total B cell numbers paradoxically reduced in HCV-infected patients with MC. HCV patients with MC (n = 17) also displayed a reduced number and a reduced frequency of naive B cells compared with HCV-infected patients without MC (n = 19), hepatitis B virusinfected patients (n = 10), and uninfected controls (n = 50). This was due to an increased sensitivity of naive B cells to apoptosis resulting in a reduction in the size of the naive B cell subset. In addition, 4-fold expansion and skewing (lower T1/T2-ratio) of the immature B cell subset was noted in MC patients, suggesting that apoptosis of naive B cells triggered the release of B cell precursors from bone marrow in an attempt to maintain normal B cell numbers. Following treatment of MC with the B celldepleting antibody rituximab, the size of all B cell subsets, the T1/T2-ratio, and the cyroglobulin levels all normalized. Cryoglobulin levels correlated with in vivo proliferation of T2 B cells, suggesting a link between the skewing of the T1/T2 ratio and the formation of immune complexes. Conclusion: This study provides insight into the mechanisms maintaining B cell homeostasis in HCV-induced MC and the ability of rituximab therapy to restore normal B cell compartments. (HEPATOLOGY 2012;56:16021610)
C1 [Holz, Lauren E.; Yoon, Joo Chun; Raghuraman, Sukanya; Rehermann, Barbara] NIDDKD, Immunol Sect, Liver Dis Branch, Bethesda, MD 20892 USA.
[Moir, Susan; Sneller, Michael C.] NIAID, Immunoregulat Lab, NIH, DHHS, Bethesda, MD 20892 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM rehermann@nih.gov
RI Yoon, Joo Chun/D-3675-2012
OI Yoon, Joo Chun/0000-0001-9395-8418
FU National Institutes of Health intramural research program
FX Supported by the National Institutes of Health intramural research
program (National Institute of Diabetes and Digestive and Kidney
Diseases and National Institute of Allergy and Infectious Diseases).
NR 24
TC 14
Z9 14
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2012
VL 56
IS 5
BP 1602
EP 1610
DI 10.1002/hep.25821
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 030BR
UT WOS:000310543100005
PM 22556016
ER
PT J
AU Sarkar, M
Bacchetti, P
French, AL
Tien, P
Glesby, MJ
Nowicki, M
Plankey, M
Gange, S
Sharp, G
Minkoff, H
Peters, MG
AF Sarkar, Monika
Bacchetti, Peter
French, Audrey L.
Tien, Phyllis
Glesby, Marshall J.
Nowicki, Marek
Plankey, Michael
Gange, Stephen
Sharp, Gerald
Minkoff, Howard
Peters, Marion G.
CA WIHS
TI Lower liver-related death in African-American women with human
immunodeficiency virus/hepatitis C virus coinfection, compared to
Caucasian and Hispanic women
SO HEPATOLOGY
LA English
DT Article
ID CHRONIC HEPATITIS-C; UNITED-STATES; FIBROSIS PROGRESSION;
GENETIC-VARIATION; MORTALITY; INFECTION; HIV
AB Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV-positive or -negative individuals. We conducted a cohort study of HIV/HCV coinfected women followed in the multicenter Women's Interagency HIV Study to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox's proportional hazards models. The eligible cohort (n = 794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African-American coinfected women had significantly lower liver-related mortality, compared to Caucasian (hazard ratio [HR], 0.41; 95% confidence interval [CI]: 0.19-0.88; P = 0.022) and Hispanic coinfected women (HR, 0.38; 95% CI: 0.19-0.76; P = 0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons: 0.82-1.03; log-rank test: P = 0.8). Conclusions: African-American coinfected women were much less likely to die from liver disease, as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality. (HEPATOLOGY 2012;56:16991705)
C1 [Sarkar, Monika; Peters, Marion G.] Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, San Francisco, CA 94143 USA.
[Bacchetti, Peter] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[French, Audrey L.] John H Stroger Jr Hosp Cook Cty, Dept Med, CORE Center, Chicago, IL USA.
[Tien, Phyllis] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA.
[Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, Div Infect Dis, New York, NY USA.
[Nowicki, Marek] Univ So Calif, Dept Med, Los Angeles, CA USA.
[Plankey, Michael] Georgetown Univ, Dept Med, Div Infect Dis, Washington, DC USA.
[Gange, Stephen] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Sharp, Gerald] NIAID, Epidemiol Branch, NIH, Div Acquired Immune Deficiency Syndrome, Bethesda, MD 20892 USA.
[Minkoff, Howard] Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA.
RP Sarkar, M (reprint author), Univ Calif San Francisco, Dept Med, Div Gastroenterol & Hepatol, 513 Parnassus Ave,Room S-357, San Francisco, CA 94143 USA.
EM monika.sarkar@ucsf.edu
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases [UO1-AI-35004,
UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, UO1-AI-42590];
National Institute of Child Health and Human Development [UO1-HD-32632];
National Cancer Institute; National Institute on Drug Abuse; National
Institute on Deafness and Other Communication Disorders; National
Institutes of Health [T32 DK060414]
FX The Women's Interagency HIV Study is funded by the National Institute of
Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834,
UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the
National Institute of Child Health and Human Development (UO1-HD-32632).
The study is cofunded by the National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders. Additional support was received through
the National Institutes of Health (T32 DK060414; to M.S.).
NR 25
TC 8
Z9 8
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2012
VL 56
IS 5
BP 1699
EP 1705
DI 10.1002/hep.25859
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 030BR
UT WOS:000310543100015
PM 22618868
ER
PT J
AU Lee, YM
Jun, HS
Pan, CJ
Lin, SR
Wilson, LH
Mansfield, BC
Chou, JY
AF Lee, Young Mok
Jun, Hyun Sik
Pan, Chi-Jiunn
Lin, Su Ru
Wilson, Lane H.
Mansfield, Brian C.
Chou, Janice Y.
TI Prevention of hepatocellular adenoma and correction of metabolic
abnormalities in murine glycogen storage disease type Ia by gene therapy
SO HEPATOLOGY
LA English
DT Article
ID MOUSE; CARCINOMA; LIVER; GLUCOSE-6-PHOSPHATASE; DEFICIENCY; MANAGEMENT;
TRANSPORT; SERIES; MICE
AB Glycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-alpha activity depends on the G6P transporter (G6PT) that translocates G6P from the cytoplasm into the ER lumen. The functional coupling of G6Pase-alpha and G6PT maintains interprandial glucose homeostasis. We have shown previously that gene therapy mediated by AAV-GPE, an adeno-associated virus (AAV) vector expressing G6Pase-alpha directed by the human G6PC promoter/enhancer (GPE), completely normalizes hepatic G6Pase-alpha deficiency in GSD-Ia (G6pc(-/-)) mice for at least 24 weeks. However, a recent study showed that within 78 weeks of gene deletion, all mice lacking G6Pase-alpha in the liver develop HCA. We now show that gene therapy mediated by AAV-GPE maintains efficacy for at least 70-90 weeks for mice expressing more than 3% of wild-type hepatic G6Pase-alpha activity. The treated mice displayed normal hepatic fat storage, had normal blood metabolite and glucose tolerance profiles, had reduced fasting blood insulin levels, maintained normoglycemia over a 24-hour fast, and had no evidence of hepatic abnormalities. After a 24-hour fast, hepatic G6PT messenger RNA levels in G6pc(-/-) mice receiving gene therapy were markedly increased. Because G6PT transport is the rate-limiting step in microsomal G6P metabolism, this may explain why the treated G6pc(-/-) mice could sustain prolonged fasts. The low fasting blood insulin levels and lack of hepatic steatosis may explain the absence of HCA. Conclusion: These results confirm that AAV-GPEmediated gene transfer corrects hepatic G6Pase-alpha deficiency in murine GSD-Ia and prevents chronic HCA formation. (HEPATOLOGY 2012;56:17191729)
C1 [Lee, Young Mok; Jun, Hyun Sik; Pan, Chi-Jiunn; Lin, Su Ru; Wilson, Lane H.; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD 21046 USA.
RP Chou, JY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
RI Jun, Hyun Sik/C-6799-2013;
OI Mansfield, Brian/0000-0002-8533-2789
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institutes of
Health; Children's Fund for Glycogen Storage Disease Research
FX Supported by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health, and The Children's Fund for Glycogen
Storage Disease Research.
NR 27
TC 16
Z9 16
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2012
VL 56
IS 5
BP 1719
EP 1729
DI 10.1002/hep.25717
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 030BR
UT WOS:000310543100017
PM 22422504
ER
PT J
AU Oishi, N
Kumar, MR
Roessler, S
Ji, JF
Forgues, M
Budhu, A
Zhao, XL
Andersen, JB
Ye, QH
Jia, HL
Qin, LX
Yamashita, T
Woo, HG
Kim, YJ
Kaneko, S
Tang, ZY
Thorgeirsson, SS
Wang, XW
AF Oishi, Naoki
Kumar, Mia R.
Roessler, Stephanie
Ji, Junfang
Forgues, Marshonna
Budhu, Anuradha
Zhao, Xuelian
Andersen, Jesper B.
Ye, Qing-Hai
Jia, Hu-Liang
Qin, Lun-Xiu
Yamashita, Taro
Woo, Hyun Goo
Kim, Yoon Jun
Kaneko, Shuichi
Tang, Zhao-You
Thorgeirsson, Snorri S.
Wang, Xin Wei
TI Transcriptomic profiling reveals hepatic stem-like gene signatures and
interplay of miR-200c and epithelial-mesenchymal transition in
intrahepatic cholangiocarcinoma
SO HEPATOLOGY
LA English
DT Article
ID HUMAN LIVER-CANCER; HEPATOCELLULAR-CARCINOMA; TUMOR-METASTASIS;
E-CADHERIN; MICRO-RNA; TGF-BETA; CELLS; IDENTIFICATION; EXPRESSION;
EPCAM
AB Intrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecular characteristics are largely unknown. In this study, we conducted transcriptomic profiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumor specimens from Asian patients using Affymetrix messenger RNA (mRNA) and NanoString microRNA microarrays to search for unique gene signatures linked to tumor subtypes and patient prognosis. We validated the signatures in an additional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC cases into two main subgroups, one of which shared gene expression signatures with previously identified hepatocellular carcinoma (HCC) with stem cell gene expression traits. ICC-specific gene signatures could predict survival in Asian HCC cases and independently in Caucasian ICC cases. Integrative analyses of the ICC-specific mRNA and microRNA expression profiles revealed that a common signaling pathway linking miR-200c signaling to epithelial-mesenchymal transition (EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR-200c resulted in an induction of EMT, whereas activation of miR-200c led to a reduction of EMT including a reduced cell migration and invasion in ICC cells. We also found that miR-200c and neural cell adhesion molecule 1 (NCAM1) expression were negatively correlated and their expression levels were predictive of survival in ICC samples. NCAM1, a known hepatic stem/progenitor cell marker, was experimentally demonstrated to be a direct target of miR-200c. Conclusion: Our results indicate that ICC and HCC share common stem-like molecular characteristics and poor prognosis. We suggest that the specific components of EMT may be exploited as critical biomarkers and clinically relevant therapeutic targets for an aggressive form of stem cell-like ICC. (HEPATOLOGY 2012;56:17921803)
C1 [Oishi, Naoki; Kumar, Mia R.; Roessler, Stephanie; Ji, Junfang; Forgues, Marshonna; Budhu, Anuradha; Zhao, Xuelian; Wang, Xin Wei] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Andersen, Jesper B.; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ye, Qing-Hai; Jia, Hu-Liang; Qin, Lun-Xiu; Tang, Zhao-You] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China.
[Yamashita, Taro; Kaneko, Shuichi] Kanazawa Univ, Liver Dis Ctr, Kanazawa, Ishikawa, Japan.
[Yamashita, Taro; Kaneko, Shuichi] Kanazawa Univ, Kanazawa Univ Hosp, Kanazawa, Ishikawa, Japan.
[Woo, Hyun Goo] Ajou Univ, Dept Physiol, Sch Med, Suwon 441749, South Korea.
[Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea.
[Kim, Yoon Jun] Seoul Natl Univ, Coll Med, Liver Res Inst, Seoul, South Korea.
RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Bldg 37,Rm 3044A, Bethesda, MD 20892 USA.
EM xw3u@nih.gov
RI Kim, Yoon Jun/J-2746-2012; Wang, Xin/B-6162-2009;
OI Andersen , Jesper B/0000-0003-1760-5244
FU Intramural Research Program of the center for Cancer Research, the U.S.
National Cancer Institute [Z01 BC 010313, Z01 BC 010876]
FX Supported in part by the Intramural Research Program of the center for
Cancer Research, the U.S. National Cancer Institute (Z01 BC 010313 and
Z01 BC 010876).
NR 52
TC 84
Z9 87
U1 3
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2012
VL 56
IS 5
BP 1792
EP 1803
DI 10.1002/hep.25890
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 030BR
UT WOS:000310543100024
PM 22707408
ER
PT J
AU Tanaka, N
Gonzalez, FJ
AF Tanaka, Naoki
Gonzalez, Frank J.
TI Bile Acids in Nonalcoholic Steatohepatitis: Inserting Nuclear Receptors
Into the Reply
SO HEPATOLOGY
LA English
DT Letter
C1 [Tanaka, Naoki; Gonzalez, Frank J.] Natl Canc Inst, Natl Inst Hlth, Lab Metab, Bethesda, MD USA.
RP Tanaka, N (reprint author), Natl Canc Inst, Natl Inst Hlth, Lab Metab, Bethesda, MD USA.
FU Intramural NIH HHS [ZIA BC005708-19]
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2012
VL 56
IS 5
BP 2009
EP 2009
DI 10.1002/hep.25811
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 030BR
UT WOS:000310543100052
PM 23115012
ER
PT J
AU Kahn, JA
Burk, RD
Squires, KE
Kapogiannis, BG
Rudy, B
Xu, JH
Gonin, R
Liu, N
Worrell, C
Wilson, CM
AF Kahn, Jessica A.
Burk, Robert D.
Squires, Kathleen E.
Kapogiannis, Bill G.
Rudy, Bret
Xu, Jiahong
Gonin, Rene
Liu, Nancy
Worrell, Carol
Wilson, Craig M.
TI Prevalence and Risk Factors for HPV in HIV-Positive Young Women
Receiving Their First HPV Vaccination
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE human papillomavirus; vaccine; epidemiology; women; HIV
ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA;
HUMAN-IMMUNODEFICIENCY-VIRUS; PARTICLE VACCINE; NATURAL-HISTORY;
ADOLESCENT GIRLS; AFRICAN WOMEN; DNA DETECTION; CANCER; LESIONS
AB Background: The objectives of this study were to describe the prevalence and risk factors for HPV infection among HIV-infected young women receiving their first quadrivalent HPV (HPV-6, -11, -16, and -18) vaccine dose.
Methods: We recruited 16- to 23-year-old women from 14 sites for an HPV vaccine trial. At the first visit, they completed a questionnaire and were tested for cervicovaginal HPV DNA (41 types) and HPV serology (4 vaccine types). Factors associated with any HPV, type-specific HPV, and high-risk (cancer-associated) HPV infections were identified using univariate and multivariable logistic regression.
Results: The mean age of participants (N = 99) was 21.4 years, 30.3% were on antiretroviral therapy, 74.7% were positive for >= 1 HPV DNA type, 53.5% for >1 high-risk type, 12.1% for HPV-16, and 5.1% for HPV-18. Most were HPV DNA negative and seronegative for HPV-16 (55.6%) and HPV-18 (73.7%); 45.5% were HPV DNA negative and seronegative for both HPV-16 and -18. Three variables were associated with high-risk HPV DNA in multivariable analysis: non-Hispanic black versus Hispanic ethnicity (adjusted odds ratio [AOR]: 7.06, 95% CI: 1.63 to 30.5), HIV viral load >= 400 versus <400 copies/mL (AOR: 3.47, 95% CI: 1.28 to 9.43), and frequency of vaginal sex in the past 90 days (AOR: 5.82, 95% CI: 1.30 to 26.11 for >= 6 vs 0 times).
Conclusions: The prevalence of >= 1 HPV type was high in these young women, demonstrating the importance of vaccinating before sexual initiation. However, most women were HPV DNA negative and seronegative for high-risk vaccine-type HPV infection, supporting vaccination of sexually experienced HIV-positive young women.
C1 [Kahn, Jessica A.] Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000, Dept Pediat, Cincinnati, OH 45229 USA.
[Kahn, Jessica A.] Univ Cincinnati Coll Med, Cincinnati, OH USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA.
[Burk, Robert D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Squires, Kathleen E.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Med, Philadelphia, PA 19107 USA.
[Kapogiannis, Bill G.; Worrell, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA.
[Rudy, Bret] New York Univ Sch Med, Dept Pediat, New York, NY USA.
[Xu, Jiahong; Gonin, Rene; Liu, Nancy] WESTAT Corp, Rockville, MD 20850 USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
RP Kahn, JA (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Adolescent Med, MLC 4000, Dept Pediat, 3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM jessica.kahn@cchmc.org
FU Adolescent Trials Network for HIV/AIDS Interventions from the National
Institutes of Health (NIH) through the National Institute of Child
Health and Human Development [U01 HD 040533, U01 HD 040474]; NIH
[AI-51519]; Einstein Cancer Research Center from the National Cancer
Institute [P30CA013330]; General Clinical Research Center Program of the
National Center for Research Resources, NIH, Department of Health and
Human Services; Children's National Medical Center [M01RR020359];
University of Pennsylvania/Children's Hospital of Philadelphia
[NCRRUL1-RR-024134]; Louisiana Board of Regents RC/EEP [RC/EEP-06]
FX Supported by The Adolescent Trials Network for HIV/AIDS Interventions
from the National Institutes of Health (NIH) Grants U01 HD 040533 and
U01 HD 040474 through the National Institute of Child Health and Human
Development (B. G. Kapogiannis and C. Worrell). Vaccine and HPV Mean
Geometric Titers were provided through the Investigator-Initiated
Studies Program of Merck & Co, Inc. In addition, R. D. Burk used core
facilities of the Einstein-Montefiore Center for AIDS supported by the
NIH Grant AI-51519 and the Einstein Cancer Research Center Grant
P30CA013330 from the National Cancer Institute. Two of the sites used
their General Clinical Research Center/Pediatric Clinical Research
Center for the study. The centers were supported by grants from the
General Clinical Research Center Program of the National Center for
Research Resources, NIH, Department of Health and Human Services as
follows: Children's National Medical Center Grant M01RR020359 and
University of Pennsylvania/Children's Hospital of Philadelphia Grant
NCRRUL1-RR-024134. The site at Tulane University Health Sciences Center
used its Clinical and Transnational Research Center for the study; the
center was supported in whole or in part by funds provided through the
Louisiana Board of Regents RC/EEP (RC/EEP-06).
NR 55
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1525-4135
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD NOV 1
PY 2012
VL 61
IS 3
BP 390
EP 399
DI 10.1097/QAI.0b013e3182676fe3
PG 10
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 029TR
UT WOS:000310519300023
PM 22820809
ER
PT J
AU Nostramo, R
Tillinger, A
Saavedra, JM
Kumar, A
Pandey, V
Serova, L
Kvetnansky, R
Sabban, EL
AF Nostramo, Regina
Tillinger, Andrej
Saavedra, Juan M.
Kumar, Ashok
Pandey, Varunkumar
Serova, Lidia
Kvetnansky, Richard
Sabban, Esther L.
TI Regulation of angiotensin II type 2 receptor gene expression in the
adrenal medulla by acute and repeated immobilization stress
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID PHENYLETHANOLAMINE N-METHYLTRANSFERASE; CATECHOLAMINE
BIOSYNTHETIC-ENZYMES; DOPAMINE BETA-HYDROXYLASE; MESSENGER-RNA LEVELS;
TYROSINE-HYDROXYLASE; AT(2) RECEPTORS; PC12 CELLS; DIFFERENTIAL
REGULATION; CHROMAFFIN CELLS; AT(1) RECEPTORS
AB While the renin-angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT(1A)) and type 2 (AT(2)) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT(2) receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT(2) receptor mRNA levels, but the decline was more transient. AT(1A) receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine beta-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT(1) receptor antagonist) or with CGP42112 (AT(2) receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic-pituitary-adrenocortical or sympathoadrenal axis in AT(2) receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT(2) receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT(2) receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT(2) receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT(1A) and AT(2) receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis. Journal of Endocrinology (2012) 215, 291-301
C1 [Nostramo, Regina; Tillinger, Andrej; Serova, Lidia; Sabban, Esther L.] New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA.
[Saavedra, Juan M.] NIMH, Pharmacol Sect, DIRP, NIH, Bethesda, MD 20892 USA.
[Kumar, Ashok; Pandey, Varunkumar] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA.
[Kvetnansky, Richard] Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia.
RP Sabban, EL (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA.
EM esther_sabban@nymc.edu
FU American Heart Association [10GRNT442001, APVV-0088-10]; VEGA
[2/0036/11]
FX This work was supported by the American Heart Association (grant no.
10GRNT442001) to E L S and grant nos APVV-0088-10 and VEGA 2/0036/11 to
R K.
NR 55
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Z9 5
U1 0
U2 1
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0022-0795
J9 J ENDOCRINOL
JI J. Endocrinol.
PD NOV
PY 2012
VL 215
IS 2
BP 291
EP 301
DI 10.1530/JOE-12-0181
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 025UR
UT WOS:000310221200009
PM 22911895
ER
PT J
AU Sarkar, S
Jiang, Z
Evon, DM
Wahed, AS
Hoofnagle, JH
AF Sarkar, Souvik
Jiang, Zhen
Evon, Donna M.
Wahed, Abdus S.
Hoofnagle, Jay H.
TI Fatigue before, during and after antiviral therapy of chronic hepatitis
C: Results from the Virahep-C study
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Liver; Anti-viral therapy; Tiredness; Cirrhosis; Peginterferon;
Ribavirin; Side-effects
ID QUALITY-OF-LIFE; GENOTYPE 1 INFECTION; CAUCASIAN AMERICAN PATIENTS;
ALPHA-2A PLUS RIBAVIRIN; VISUAL ANALOG SCALES; VIRUS-INFECTION;
COMBINATION THERAPY; AFRICAN-AMERICAN; PEGINTERFERON; IMPACT
AB Background Si Aims: Fatigue is the most frequent and often debilitating symptom of chronic hepatitis C. It is unclear whether successful therapy of hepatitis C leads to its clinical improvement. In the Virahep-C study, patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a and ribavirin for up to 48 weeks while undergoing assessment of viral kinetics and clinical symptoms.
Methods: Fatigue measurements were conducted, before, during and after therapy, as 'presence' (yes/no) and 'severity' (visual analog scale: 0-100 mm). The clinical, histologic, and virologic features that correlated with the presence and degree of fatigue were assessed focusing upon changes associated with sustained virological response (SVR).
Results: At baseline, 52% (n = 401) of participants reported having fatigue, which was more common in women than men (59% vs. 48%, p = 0.02) and slightly more severe (30 vs. 22 mm, p = 0.056). Fatigue was frequent and worse in cirrhotics versus those with lesser fibrosis (66% vs. 49%; 34 vs. 24 mm). Fatigue did not correlate with other parameters. The proportion of patients and median fatigue scores increased on treatment (52-78%; 25-40 mm, p <0.0001) with higher fatigue noted amongst those who ultimately achieved SVR (p <0.0001). On achieving SVR, there was a significant decrease in both frequency and severity of fatigue compared to their baseline (53-33%; 27-13 mm, both p <0.0001).
Conclusions: Fatigue is common in patients with chronic hepatitis C but is poorly associated with biochemical parameters. Sustained response is accompanied by substantial improvement of fatigue. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Hoofnagle, Jay H.] NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
[Sarkar, Souvik] NIDDKD, Liver Dis Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Jiang, Zhen; Wahed, Abdus S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Evon, Donna M.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Room 9A27,Bldg 31,31 Ctr Dr, Bethesda, MD 20892 USA.
EM Hoofnaglej@extra.niddk.nih.gov
OI Sarkar, Souvik/0000-0002-9358-4257; Wahed, Abdus/0000-0001-6911-7221
FU Roche/Genentech; NIDDK; Roche Pharmaceutics through Roche; Roche
Pharmaceutics through NIDDK; K23 award [Evon: K23-DK089004]
FX D.M.E. had grant funding from Roche/Genentech and served as advisor for
Vertex in the last 12 months. The other authors have no conflicts of
interest to report.; The Virahep-C Study was funded as a cooperative
agreement by NIDDK. Peginterferon, ribavirin, HCV RNA detection assays
and funds for ancillary studies were provided by Roche Pharmaceutics
through a Cooperative Research and Development Agreement (CRADA) between
Roche and NIDDK. (See Acknowledgements) NCT Trial Number: NCT00038974.
Further support for this study was from the Intramural Program of NIDDK
and a K23 award (Evon: K23-DK089004).
NR 40
TC 29
Z9 29
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD NOV
PY 2012
VL 57
IS 5
BP 946
EP 952
DI 10.1016/j.jhep.2012.06.030
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 028IW
UT WOS:000310417000005
PM 22760009
ER
PT J
AU Pandiyan, P
Yang, XP
Saravanamuthu, SS
Zheng, LX
Ishihara, S
O'Shea, JJ
Lenardo, MJ
AF Pandiyan, Pushpa
Yang, Xiang-Ping
Saravanamuthu, Senthil S.
Zheng, Lixin
Ishihara, Satoru
O'Shea, John J.
Lenardo, Michael J.
TI The Role of IL-15 in Activating STAT5 and Fine-Tuning IL-17A Production
in CD4 T Lymphocytes
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS;
HELPER-CELL DIFFERENTIATION; TH17 CELLS; RHEUMATOID-ARTHRITIS; LYMPHOID
HOMEOSTASIS; FAMILY CYTOKINES; TRANSGENIC MICE; GROWTH-FACTOR; GM-CSF
AB IL-15 is an important IL-2-related cytokine whose role in Th17 cell biology has not been fully elucidated. In this study, we show that exogenous IL-15 decreased IL-17A production in Th17 cultures. Neutralization of IL-15 using an Ab led to increases in IL17A production in Th17 cultures. Both Il15(-/-) and Il15r(-/-) T cell cultures displayed higher frequency of IL-17A producers and higher amounts of IL-17A in the supernatants compared with those of wild-type (WT) cells in vitro. IL-15 down-modulated IL-17A production independently of retinoic acid-related orphan receptor-gamma t, Foxp3, and IFN-gamma expression. Both Th17 cells and APCs produced IL-15, which induced binding of STAT5, an apparent repressor to the Il17 locus in CD4 T cells. Also, in a model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), Il15(-/-) mice displayed exacerbated inflammation-correlating with increased IL-17A production by their CD4(+) T cells-compared with WT controls. Exogenous IL-15 administration and IL-17A neutralization reduced the severity of EAE in Il15(-/-) mice. Taken together, these data indicate that IL-15 has a negative regulatory role in fine-tuning of IL-17A production and Th17-mediated inflammation. The Journal of Immunology, 2012, 189: 4237-4246.
C1 [Pandiyan, Pushpa; Zheng, Lixin; Lenardo, Michael J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Pandiyan, Pushpa] Case Western Reserve Univ, Sch Dent Med, Dept Biol Sci, Cleveland, OH 44106 USA.
[Yang, Xiang-Ping; O'Shea, John J.] NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA.
[Saravanamuthu, Senthil S.] NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA.
[Ishihara, Satoru] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 11N246, Bethesda, MD 20892 USA.
EM pxp226@case.edu; lenardo@nih.gov
FU intramural research program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Research
Council, National Academy of Sciences
FX This work was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. P. P. was partially supported by a fellowship from
the National Research Council, National Academy of Sciences.
NR 56
TC 25
Z9 26
U1 2
U2 8
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2012
VL 189
IS 9
BP 4237
EP 4246
DI 10.4049/jimmunol.1201476
PG 10
WC Immunology
SC Immunology
GA 025OO
UT WOS:000310200600009
PM 22993203
ER
PT J
AU Maloveste, SM
Chen, D
Gostick, E
Vivian, JP
Plishka, RJ
Iyengar, R
Kruthers, RL
Buckler-White, A
Brooks, AG
Rossjohn, J
Price, DA
Lafont, BAP
AF Maloveste, Sebastien M.
Chen, Dan
Gostick, Emma
Vivian, Julian P.
Plishka, Ronald J.
Iyengar, Ranjini
Kruthers, Robin L.
Buckler-White, Alicia
Brooks, Andrew G.
Rossjohn, Jamie
Price, David A.
Lafont, Bernard A. P.
TI Degenerate Recognition of MHC Class I Molecules with Bw4 and Bw6 Motifs
by a Killer Cell Ig-like Receptor 3DL Expressed by Macaque NK Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE RECEPTOR; SIMIAN IMMUNODEFICIENCY; HLA-B; RHESUS
MACAQUES; INHIBITORY RECEPTOR; CYNOMOLGUS MACAQUES; CRYSTAL-STRUCTURE;
VIRUS-INFECTION; KIR HAPLOTYPES; COMPLEX
AB The killer cell Ig-like receptors (KIRs) expressed on the surface of NK cells recognize specific MHC class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In HIV infection, survival is linked to host KIR and MHC-I genotypes. In the SIV macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. In this study, we describe, to our knowledge, the first in-depth characterization of KIR- MHC interactions in pigtailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation, and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif, but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs. The Journal of Immunology, 2012, 189: 4338-4348.
C1 [Maloveste, Sebastien M.; Chen, Dan; Lafont, Bernard A. P.] NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Vivian, Julian P.; Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia.
[Plishka, Ronald J.; Iyengar, Ranjini; Kruthers, Robin L.; Buckler-White, Alicia] NIAID, Lab Mol Microbiol Core, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Brooks, Andrew G.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia.
RP Lafont, BAP (reprint author), NIAID, Nonhuman Primate Immunogenet & Cellular Immunol U, Mol Microbiol Lab, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA.
EM blafont@niaid.nih.gov
RI Rossjohn, Jamie/F-9032-2013; Lafont, Bernard/B-7236-2014; Price,
David/C-7876-2013;
OI Rossjohn, Jamie/0000-0002-2020-7522; Price, David/0000-0001-9416-2737;
Brooks, Andrew/0000-0002-4085-9683
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; National Health and
Medical Research Council of Australia (NHMRC); Association for
International Cancer Research; NHMRC Australia Fellowship
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, the National Health and Medical Research Council
of Australia (NHMRC), and the Association for International Cancer
Research (J.R. and A.G.B.); J.R. is supported by an NHMRC Australia
Fellowship.
NR 56
TC 10
Z9 10
U1 0
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 NOV 1
PY 2012
VL 189
IS 9
BP 4338
EP 4348
DI 10.4049/jimmunol.1201360
PG 11
WC Immunology
SC Immunology
GA 025OO
UT WOS:000310200600020
PM 23041569
ER
PT J
AU Gern, JE
Pappas, T
Visness, CM
Jaffee, KF
Lemanske, RF
Togias, A
Bloomberg, GR
Cruikshank, WW
Lamm, C
Tuzova, M
Wood, RA
Lee, WM
AF Gern, James E.
Pappas, Tressa
Visness, Cynthia M.
Jaffee, Katy F.
Lemanske, Robert F.
Togias, Alkis
Bloomberg, Gordon R.
Cruikshank, William W.
Lamm, Carin
Tuzova, Marina
Wood, Robert A.
Lee, Wai Ming
TI Comparison of the Etiology of Viral Respiratory Illnesses in Inner-City
and Suburban Infants
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID CHILDHOOD ASTHMA; RHINOVIRUS ILLNESSES; YOUNG-CHILDREN; BIRTH COHORT;
VIRUSES; LIFE; INFECTIONS; PATHOGENS; SENSITIZATION; BRONCHIOLITIS
AB Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct.
Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction.
Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%-21%), compared with Madison (6%).
Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.
C1 [Gern, James E.; Pappas, Tressa; Lemanske, Robert F.; Lee, Wai Ming] Univ Wisconsin, Dept Pediat, Madison, WI 53706 USA.
[Gern, James E.; Lemanske, Robert F.] Univ Wisconsin, Dept Med, Madison, WI 53706 USA.
[Visness, Cynthia M.; Jaffee, Katy F.] Rho, Chapel Hill, NC USA.
[Togias, Alkis] NIAID, NIH, Bethesda, MD 20892 USA.
[Bloomberg, Gordon R.] Washington Univ, Sch Med, St Louis, MO USA.
[Cruikshank, William W.; Tuzova, Marina] Boston Univ, Med Ctr, Boston, MA 02215 USA.
[Lamm, Carin] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Gern, JE (reprint author), K4-918 CSC,600 Highland Ave, Madison, WI 53792 USA.
EM gern@medicine.wisc.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH) [NO1-AI-25496, NO1-AI-25482]; National Center
for Research Resources, NIH [RR00052, M01RR00533, 1UL1RR025771,
M01RR00071, 1UL1RR024156, 5UL1RR024992-02]; Merck; Astra Zeneca;
GlaxoSmithKline
FX This work was supported in whole or in part by the National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH;
contract numbers NO1-AI-25496 and NO1-AI-25482); and by the National
Center for Research Resources, NIH (grants RR00052, M01RR00533,
1UL1RR025771, M01RR00071, 1UL1RR024156, and 5UL1RR024992-02).; J. E. G
is a consultant for GlaxoSmithKline, Biota, Centocor, Boehringer
Ingelheim, MedImmune, Gilead, Theraclone, Synairgen, and Pulmatrix; has
research funding from Merck, Astra Zeneca, and GlaxoSmithKline; and
holds stock options in 3V BioSciences. R. A. W is a consultant to the
Asthma and Allergy Foundation of America. All other authors report no
potential conflicts.
NR 26
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U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2012
VL 206
IS 9
BP 1342
EP 1349
DI 10.1093/infdis/jis504
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 022BT
UT WOS:000309930700005
PM 23014674
ER
PT J
AU Lederman, ER
Davidson, W
Groff, HL
Smith, SK
Warkentien, T
Li, Y
Wilkins, KA
Karem, KL
Akondy, RS
Ahmed, R
Frace, M
Shieh, WJ
Zaki, S
Hruby, DE
Painter, WP
Bergman, KL
Cohen, JI
Damon, IK
AF Lederman, Edith R.
Davidson, Whitni
Groff, Harold L.
Smith, Scott K.
Warkentien, Tyler
Li, Yu
Wilkins, Kimberly A.
Karem, Kevin L.
Akondy, Rama S.
Ahmed, Rafi
Frace, Michael
Shieh, Wun-Ju
Zaki, Sherif
Hruby, Dennis E.
Painter, Wendy P.
Bergman, Kimberly L.
Cohen, Jeffrey I.
Damon, Inger K.
TI Progressive Vaccinia: Case Description and Laboratory-Guided Therapy
With Vaccinia Immune Globulin, ST-246, and CMX001
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID T-CELL RESPONSES; SMALLPOX VACCINATION; MONKEYPOX; VIRUS; INFECTION;
CHALLENGE; CONTACT; MICE
AB Progressive vaccinia (PV) is a rare but potentially lethal complication that develops in smallpox vaccine recipients with severely impaired cellular immunity. We describe a patient with PV who required treatment with vaccinia immune globulin and who received 2 investigational agents, ST-246 and CMX001. We describe the various molecular, pharmacokinetic, and immunologic studies that provided guidance to escalate and then successfully discontinue therapy. Despite development of resistance to ST-246 during treatment, the patient had resolution of PV. This case demonstrates the need for continued development of novel anti-orthopoxvirus pharmaceuticals and the importance of both intensive and timely clinical and laboratory support in management of PV.
C1 [Lederman, Edith R.; Davidson, Whitni; Smith, Scott K.; Li, Yu; Wilkins, Kimberly A.; Karem, Kevin L.; Frace, Michael; Shieh, Wun-Ju; Zaki, Sherif; Damon, Inger K.] Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA USA.
[Warkentien, Tyler; Akondy, Rama S.; Ahmed, Rafi] Emory Univ, Sch Med, Vaccine Ctr, Atlanta, GA USA.
[Lederman, Edith R.; Groff, Harold L.] USN, Div Infect Dis, San Diego Med Ctr, San Diego, CA USA.
[Hruby, Dennis E.] Siga Technol, Corvallis, OR USA.
[Painter, Wendy P.] Chimerix, Durham, NC USA.
[Bergman, Kimberly L.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Cohen, Jeffrey I.] Natl Inst Allergy & Immunol, NIH, Bethesda, MD USA.
RP Lederman, ER (reprint author), San Diego State Univ, Grad Sch Publ Hlth, Hardy Tower 119,5500 Campanile Dr, San Diego, CA 92182 USA.
EM erlederman@yahoo.com
OI Akondy, Rama/0000-0003-4737-5240
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases (to J. I. C.).
NR 22
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Z9 18
U1 1
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2012
VL 206
IS 9
BP 1372
EP 1385
DI 10.1093/infdis/jis510
PG 14
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 022BT
UT WOS:000309930700009
PM 22904336
ER
PT J
AU Redd, AD
Collinson-Streng, AN
Chatziandreou, N
Mullis, CE
Laeyendecker, O
Martens, C
Ricklefs, S
Kiwanuka, N
Nyein, PH
Lutalo, T
Grabowski, MK
Kong, XR
Manucci, J
Sewankambo, N
Wawer, MJ
Gray, RH
Porcella, SF
Fauci, AS
Sagar, M
Serwadda, D
Quinn, TC
AF Redd, Andrew D.
Collinson-Streng, Aleisha N.
Chatziandreou, Nikolaos
Mullis, Caroline E.
Laeyendecker, Oliver
Martens, Craig
Ricklefs, Stacy
Kiwanuka, Noah
Nyein, Phyu Hninn
Lutalo, Tom
Grabowski, Mary K.
Kong, Xiangrong
Manucci, Jordyn
Sewankambo, Nelson
Wawer, Maria J.
Gray, Ronald H.
Porcella, Stephen F.
Fauci, Anthony S.
Sagar, Manish
Serwadda, David
Quinn, Thomas C.
TI Previously Transmitted HIV-1 Strains Are Preferentially Selected During
Subsequent Sexual Transmissions
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENETIC DIVERSITY; HETEROSEXUAL
TRANSMISSION; INFECTION; VARIANTS; UGANDA; RAKAI; IDENTIFICATION;
SUBTYPES; COUPLES
AB Background. A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear.
Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9).
Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1-discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner's HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03).
Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
C1 [Redd, Andrew D.; Collinson-Streng, Aleisha N.; Laeyendecker, Oliver; Fauci, Anthony S.; Quinn, Thomas C.] NIAID, Lab Immunoregulat, DIR, NIH, Bethesda, MD 20892 USA.
[Mullis, Caroline E.; Laeyendecker, Oliver; Manucci, Jordyn; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Grabowski, Mary K.; Kong, Xiangrong; Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Chatziandreou, Nikolaos; Nyein, Phyu Hninn; Sagar, Manish] Harvard Univ, Sch Med, Brigham & Women Hosp, Boston, MA 02115 USA.
[Martens, Craig; Ricklefs, Stacy; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,DIR,NIH, Hamilton, MT USA.
[Kiwanuka, Noah; Lutalo, Tom; Sewankambo, Nelson; Serwadda, David] Rakai Hlth Sci Program, Entebbe, Uganda.
[Lutalo, Tom] Uganda Virus Res Inst, Entebbe, Uganda.
[Sewankambo, Nelson] Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
[Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda.
RP Quinn, TC (reprint author), NIAID, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA.
EM tquinn2@jhmi.edu
RI Laeyendecker, Oliver/B-9331-2009;
OI Sagar, Manish/0000-0001-9803-6594; Sewankambo,
Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760
FU Division of Intramural Research, National Institutes of Allergy and
Infectious Diseases (NIAID), National Institutes of Health; NIAID [R01
A134826, R01 A134265, R01 AI077473]; Eunice Kennedy Shriver National
Institute of Child Health & Human Development [5P30HD06826]; World Bank
STI Project, Uganda; Henry M. Jackson Foundation; Fogarty Foundation
[5D43TW00010]; Bill and Melinda Gates Institute for Population and
Reproductive Health at the Bloomberg School of Public Health, Johns
Hopkins University
FX This work was supported in part by funding from the Division of
Intramural Research, National Institutes of Allergy and Infectious
Diseases (NIAID), National Institutes of Health; the NIAID (grants R01
A134826, R01 A134265 and R01 AI077473 to M. S.); the Eunice Kennedy
Shriver National Institute of Child Health & Human Development (grant
5P30HD06826); the World Bank STI Project, Uganda; the Henry M. Jackson
Foundation; the Fogarty Foundation (grant 5D43TW00010); and the Bill and
Melinda Gates Institute for Population and Reproductive Health at the
Bloomberg School of Public Health, Johns Hopkins University.
NR 39
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U1 1
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2012
VL 206
IS 9
BP 1433
EP 1442
DI 10.1093/infdis/jis503
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 022BT
UT WOS:000309930700016
PM 22997233
ER
PT J
AU Gandhi, M
Greenblatt, RM
Bacchetti, P
Jin, CS
Huang, Y
Anastos, K
Cohen, M
DeHovitz, JA
Sharp, GB
Gange, SJ
Liu, CL
Hanson, SC
Aouizerat, B
AF Gandhi, Monica
Greenblatt, Ruth M.
Bacchetti, Peter
Jin, Chengshi
Huang, Yong
Anastos, Kathryn
Cohen, Mardge
DeHovitz, Jack A.
Sharp, Gerald B.
Gange, Stephen J.
Liu, Chenglong
Hanson, Susan C.
Aouizerat, Bradley
CA Women's Interagency HIV Study
TI A Single-Nucleotide Polymorphism in CYP2B6 Leads to > 3-Fold Increases
in Efavirenz Concentrations in Plasma and Hair Among HIV-Infected Women
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID NONNUCLEOSIDE REVERSE-TRANSCRIPTASE; TANDEM MASS-SPECTROMETRY; ROUTINE
CLINICAL-PRACTICE; HIV-1-INFECTED INDIVIDUALS; LIQUID-CHROMATOGRAPHY;
CONTAINING REGIMENS; POPULATION PHARMACOKINETICS; ANTIRETROVIRAL
THERAPY; PROTEASE INHIBITORS; UNSELECTED COHORT
AB Background. Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women.
Methods. We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors.
Results. Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure.
Conclusions. This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.
C1 [Gandhi, Monica] Univ Calif San Francisco, Div HIV AIDS, Dept Med, San Francisco, CA 94122 USA.
[Greenblatt, Ruth M.; Huang, Yong] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94122 USA.
[Greenblatt, Ruth M.; Bacchetti, Peter; Jin, Chengshi] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94122 USA.
[Anastos, Kathryn] Albert Einstein Univ, Dept Med, Bronx, NY USA.
[DeHovitz, Jack A.] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA.
[Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA.
[Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Gange, Stephen J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Liu, Chenglong] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA.
[Hanson, Susan C.; Aouizerat, Bradley] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94122 USA.
[Aouizerat, Bradley] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94122 USA.
RP Gandhi, M (reprint author), Univ Calif San Francisco, Div HIV AIDS, Dept Med, 405 Irving St,2nd Fl, San Francisco, CA 94122 USA.
EM monica.gandhi@ucsf.edu
OI Gange, Stephen/0000-0001-7842-512X
FU National Institute of Allergy and Infectious Diseases (NIAID) [K23
A1067065, R01 AI 65233, UO1-AI-35004, UO1-AI-31834, UO1-AI-34994,
UO1-AI-34989, UO1-AI-34993, UO1-AI-42590]; National Center for Research
Resources via the University of California San Francisco Clinical and
Translational Science Institute [UL1 RR024131]; NIH Roadmap for Medical
Research [KL2 RR024130]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [UO1-HD-32632]; National Cancer
Institute; National Institute on Drug Abuse; National Institute on
Deafness and Other Communication Disorders
FX This work was supported by the National Institute of Allergy and
Infectious Diseases (NIAID; K23 A1067065 to M. G. and R01 AI 65233 to R.
M. G.). Additional funding was also provided by the National Center for
Research Resources via the University of California San Francisco
Clinical and Translational Science Institute (UL1 RR024131) and by the
NIH Roadmap for Medical Research (KL2 RR024130 to B. A.).; The WIHS is
funded by the NIAID (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994,
UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(UO1-HD-32632). The study is cofunded by the National Cancer Institute,
the National Institute on Drug Abuse, and the National Institute on
Deafness and Other Communication Disorders.
NR 48
TC 18
Z9 20
U1 0
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2012
VL 206
IS 9
BP 1453
EP 1461
DI 10.1093/infdis/jis508
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 022BT
UT WOS:000309930700018
PM 22927450
ER
PT J
AU Venkatesh, BA
Lima, JAC
Bluemke, DA
Lai, SH
Steenbergen, C
Liu, CY
AF Venkatesh, Bharath Ambale
Lima, Joao A. C.
Bluemke, David A.
Lai, Shenghan
Steenbergen, Charles
Liu, Chia-Ying
TI MR proton spectroscopy for myocardial lipid deposition quantification: A
quantitative comparison between 1.5T and 3T
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE myocardial fat; proton spectroscopy; fat fraction
ID MAGNETIC-RESONANCE-SPECTROSCOPY; TO-NOISE RATIO; FREQUENCY-DOMAIN
METHODS; TRIGLYCERIDE CONTENT; FAT QUANTIFICATION; DIABETES-MELLITUS;
HUMAN BRAIN; REPRODUCIBILITY; RESOLUTION; STEATOSIS
AB Purpose: To evaluate 3T magnetic resonance spectroscopy (MRS)-derived myocardial fat-signal fractions in comparison with those from 1.5T MRS. Materials and Methods: We conducted phantom, ex vivo and in vivo myocardial specimen evaluations at both 1.5T and 3T using 1H-MRS. A phantom with nine fat-water emulsions was constructed to assess the accuracy of the spectroscopy measurements. Ex vivo spectroscopy data were acquired in 70 segments from 21 autopsy heart slices. In vivo spectroscopy data were acquired in the interventricular septum from 22 human volunteers. Results: Phantom experiments demonstrated that 1.5T and 3T measurements were highly correlated with the reference values (r = 0.78, P < 0.05). The ex vivo and in vivo experiments demonstrated an increase in signal-to-noise ratio (SNR) of 45 +/- 73% and 76 +/- 72% at 3T compared to 1.5T (P < 0.05). The mean fat-signal fraction was similar at 3T and 1.5T (1.11 +/- 1.18 vs. 1.00 +/- 1.09, respectively, P = NS) in ex vivo studies but were significantly different in the in vivo studies (2.47 +/- 1.46 vs. 1.56 +/- 1.34, P < 0.05). The fat-signal fractions from 3T and 1.5T correlated fairly well in all experiments. Conclusion: 3T MRS has significantly greater SNR and could potentially be more accurate as compared to 1.5T for quantification of myocardial fat fraction in in vivo studies. J. Magn. Reson. Imaging 2012;36:12221230. (c) 2012 Wiley Periodicals, Inc.
C1 [Venkatesh, Bharath Ambale; Lima, Joao A. C.; Bluemke, David A.; Liu, Chia-Ying] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA.
[Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Lai, Shenghan; Steenbergen, Charles] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
RP Liu, CY (reprint author), Johns Hopkins Univ Hosp, Dept Radiol, MRI Room 110,600 N Wolfe St, Baltimore, MD 21287 USA.
EM Cliu51@jhmi.edu
RI Ambale Venkatesh, Bharath/F-4941-2016;
OI Ambale Venkatesh, Bharath/0000-0002-2330-2373; Bluemke,
David/0000-0002-8323-8086
FU National Institutes of Health (NIH) [R21HL098827]
FX Contract grant sponsor: National Institutes of Health (NIH); Contract
grant number: R21HL098827.
NR 33
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD NOV
PY 2012
VL 36
IS 5
BP 1222
EP 1230
DI 10.1002/jmri.23761
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 027ZO
UT WOS:000310392800024
PM 22826193
ER
PT J
AU Fernandez-Duenas, V
Gomez-Soler, M
Jacobson, KA
Kumar, ST
Fuxe, K
Borroto-Escuela, DO
Ciruela, F
AF Fernandez-Duenas, Victor
Gomez-Soler, Maricel
Jacobson, Kenneth A.
Kumar, Santhosh T.
Fuxe, Kjell
Borroto-Escuela, Dasiel O.
Ciruela, Francisco
TI Molecular determinants of A2AR-D2R allosterism: role of the
intracellular loop 3 of the D2R
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE A2AR; D2R; FRET; oligomerization; allosterism; fluorescent agonist
ID ADENOSINE A(2A) RECEPTORS; GLUTAMATE TYPE-1-ALPHA RECEPTOR; HAMSTER
OVARY CELLS; DOPAMINE-D-2 RECEPTORS; ELECTROSTATIC INTERACTION; BASAL
GANGLIA; LIVING CELLS; AGONIST; HETEROMERIZATION; INTERNALIZATION
AB In the CNS, an antagonistic interaction has been shown between adenosine A2A and dopamine D2 receptors (A2ARs and D2Rs) that may be relevant both in normal and pathological conditions (i.e., Parkinson's disease). Thus, the molecular determinants mediating this receptorreceptor interaction have recently been explored, as the fine tuning of this target (namely the A2AR/D2R oligomer) could possibly improve the treatment of certain CNS diseases. Here, we used a fluorescence resonance energy transfer-based approach to examine the allosteric modulation of the D2R within the A2AR/D2R oligomer and the dependence of this receptorreceptor interaction on two regions rich in positive charges on intracellular loop 3 of the D2R. Interestingly, we observed a negative allosteric effect of the D2R agonist quinpirole on A2AR ligand binding and activation. However, these allosteric effects were abolished upon mutation of specific arginine residues (217222 and 267269) on intracellular loop 3 of the D2R, thus demonstrating a major role of these positively charged residues in mediating the observed receptorreceptor interaction. Overall, these results provide structural insights to better understand the functioning of the A2AR/D2R oligomer in living cells.
C1 [Fernandez-Duenas, Victor; Gomez-Soler, Maricel; Ciruela, Francisco] Univ Barcelona, Unitat Farmacol, Fac Med, Dept Patol & Terapeut Expt, Barcelona 08907, Spain.
[Jacobson, Kenneth A.; Kumar, Santhosh T.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Fuxe, Kjell; Borroto-Escuela, Dasiel O.] Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
RP Ciruela, F (reprint author), Univ Barcelona, Unitat Farmacol, Fac Med, Dept Patol & Terapeut Expt, Barcelona 08907, Spain.
EM fciruela@ub.edu
RI Jacobson, Kenneth/A-1530-2009; Borroto-Escuela, Dasiel/F-3627-2014;
Ciruela, Francisco/A-5096-2013
OI Fernandez Duenas, Victor/0000-0001-7834-2965; Jacobson,
Kenneth/0000-0001-8104-1493; Borroto-Escuela,
Dasiel/0000-0002-5736-373X; Ciruela, Francisco/0000-0003-0832-3739
FU Ministerio de Ciencia e Innovacion [SAF2011-24779, CSD2008-00005]; ICREA
Academia from the Catalan Institution for Research and Advanced Studies;
NIDDK Intramural Research Program of the National Institutes of Health,
Bethesda, MD, USA
FX This work was supported by grants SAF2011-24779 and Consolider-Ingenio
CSD2008-00005 from Ministerio de Ciencia e Innovacion and ICREA
Academia-2010 from the Catalan Institution for Research and Advanced
Studies to FC. Also, VF-D, MG-S, and FC belong to the "Neuropharmacology
and Pain" accredited research group (Generalitat de Catalunya, 2009 SGR
232). Support to KAJ and TSK from the NIDDK Intramural Research Program
of the National Institutes of Health, Bethesda, MD, USA is acknowledged.
We also thank Esther Castano, Eva Julia, and Benjamin Torrejon, from the
Scientific and Technical Services (SCT)-Bellvitge Campus of the
University of Barcelona for the technical assistance.
NR 31
TC 19
Z9 19
U1 1
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD NOV
PY 2012
VL 123
IS 3
BP 373
EP 384
DI 10.1111/j.1471-4159.2012.07956.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 019MJ
UT WOS:000309743600006
PM 22924752
ER
PT J
AU Ye, DY
Bakhtian, KD
Asthagiri, AR
Lonser, RR
AF Ye, Donald Y.
Bakhtian, Kamran D.
Asthagiri, Ashok R.
Lonser, Russell R.
TI Von Hippel-Lindau disease and pregnancy Response
SO JOURNAL OF NEUROSURGERY
LA English
DT Editorial Material
ID CEREBELLAR HEMANGIOBLASTOMA
C1 [Ye, Donald Y.; Bakhtian, Kamran D.; Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Ye, DY (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
NR 10
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD NOV
PY 2012
VL 117
IS 5
BP 816
EP 817
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 027UW
UT WOS:000310380300005
ER
PT J
AU Ye, DY
Bakhtian, KD
Asthagiri, AR
Lonser, RR
AF Ye, Donald Y.
Bakhtian, Kamran D.
Asthagiri, Ashok R.
Lonser, Russell R.
TI Effect of pregnancy on hemangioblastoma development and progression in
von Hippel-Lindau disease Clinical article
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE hemangioblastoma; pregnancy; von Hippel-Lindau disease; tumor growth;
oncology
ID CENTRAL-NERVOUS-SYSTEM; CEREBELLAR HEMANGIOBLASTOMA;
SURGICAL-MANAGEMENT; NATURAL-HISTORY
AB Object. Prior cases suggest that pregnancy increases the development and progression of CNS hemangioblastomas and/or peritumoral cysts. To determine the effect of pregnancy on CNS hemangioblastomas and peritumoral cysts, the authors prospectively evaluated serial clinical and imaging findings in patients with von Hippel-Lindau (VHL) disease who became pregnant and compared findings during pregnancy to findings in the same patients when they were not pregnant as well as to findings from a cohort of VHL patients who did not become pregnant.
Methods. Female VHL disease patients enrolled in a prospective natural history study who were of reproductive age (16-35 years at study entrance) were included. Analysis of serial clinical and imaging findings was performed.
Results. Thirty-six consecutive female VHL disease patients harboring 177 hemangioblastomas were included (mean follow-up [+/- SD] 7.5 +/- 2.3 years). Nine patients (25%) became pregnant (pregnancy cohort). The mean rates of development of new hemangioblastomas and peritumoral cysts in these women during pregnancy (0.4 +/- 0.4 tumors/year; 0.1 +/- 0.2 cysts/year) did not differ significantly (p > 0.05) from the mean rates in the same group during nonpregnant periods (0.3 +/- 0.4 tumors/year: 0.1 +/- -0.1 cysts/year) or from the rate in the 27 patients who did not become pregnant (the no-pregnancy cohort: 0.3 +/- 0.5 tumors/year; 0.1 0.2 cysts/year). Hemangioblastoma growth rates were similar (p > 0.05) during pregnancy (mean 29.8% +/- 42.7% increase in volume per year) compared with during nonpregnant periods (41.4% +/- 51.4%) in the pregnancy cohort and the no-pregnancy cohort (34.3% +/- 55.3%). Peritumoral cyst growth rates during pregnancy (571.0% +/- 887.4%) were similar (p > 0.05) to those of the no-pregnancy cohort (483.9% +/- 493.9%), but the rates were significantly higher for women in the pregnancy cohort during nonpregnant periods (2373.6% +/- 3392.9%; p < 0.05 for comparison with no-pregnancy cohort). There was no significant difference (p > 0.05) in the need for resection or the mean age at resection between the pregnancy (28% of hemangioblastomas in cohort; mean patient age at resection 30.2 +/- 2.6 years) and no-pregnancy cohorts (19%; 32.3 +/- 5.6 years).
Conclusions. Pregnancy is not associated with increased hemangioblastoma or peritumoral cyst development or progression in patients with VHL disease. (http://thejns.org/doi/abs/10.3171/2012.7.JNS12367)
C1 [Ye, Donald Y.; Bakhtian, Kamran D.; Asthagiri, Ashok R.; Lonser, Russell R.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM lonserr@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX This research was supported by the intramural program at the National
Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 27
TC 12
Z9 12
U1 0
U2 2
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD NOV
PY 2012
VL 117
IS 5
BP 818
EP 824
DI 10.3171/2012.7.JNS12367
PG 7
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 027UW
UT WOS:000310380300006
PM 22937928
ER
PT J
AU Heiss, JD
Suffredini, G
Bakhtian, KD
Sarntinoranont, M
Oldfield, EH
AF Heiss, John D.
Suffredini, Giancarlo
Bakhtian, Kamran D.
Sarntinoranont, Malisa
Oldfield, Edward H.
TI Normalization of hindbrain morphology after decompression of Chiari
malformation Type I Clinical article
SO JOURNAL OF NEUROSURGERY
LA English
DT Article
DE Chiari malformation Type I; syringomyelia; decompression; magnetic
resonance imaging; surgical
ID CEREBELLAR TONSILS; SYRINGOMYELIA; PATHOPHYSIOLOGY
AB Object. Chiari malformation Type I (CM-I) is characterized by hindbrain deformity. We investigated the effects of craniocervical decompression surgery on the anatomical features of hindbrain deformity with a prospective MRI study of patients with CM-I.
Methods. A prospective longitudinal study was conducted in 48 patients with CM-I (39 with syringomyelia) treated with craniocervical decompression. Clinical examinations and cervical MRI were performed before surgery and 1 week, 3-6 months, and annually after surgery. Hindbrain deformity was defined by tonsillar ectopia, pointed cerebellar tonsils, and/or cervicomedullary protuberance. The length of the clivus, basiocciput (sphenooccipital synchondrosis to basion), supraocciput (internal occipital protuberance to opisthion), and anteroposterior (AP) width of CSF pathways at the foramen magnum were measured and compared with those from 18 healthy volunteers (control group).
Results. Before surgery, the patients' posterior fossa bones were short and their CSF pathways were narrow. All patients had tonsillar ectopia (mean [+/-SD] 12.3 +/- 5.1 mm; normal 0.3 +/- 1.0). The majority of patients had pointed tonsils and more than two-thirds exhibited a cervicomedullary protuberance. Clivus and basiocciput lengths were significantly shorter than the values obtained in the control group. However, the supraocciput length did not differ significantly from control measurements. The mean bulbopontine sulcus distance superior to the basion was 9.5 +/- 2.6 mm (vs 13.6 +/- 2.8 mm in controls; p < 0.0001). The AP widths of the CSF pathways at the level of the foramen magnum were significantly narrowed. After surgery, CSF pathways significantly expanded both ventrally and dorsally. By 3-6 months after surgery, pointed tonsils became round, cervicomedullary protuberance disappeared, and tonsillar ectopia diminished by 51% (to 6.0 +/- 3.3 mm; p < 0.0001).
Conclusions. The cerebellar tonsils and brainstem assumed a normal appearance within 6 months after craniocervical decompression. These findings support the concept that the CM-I is not a congenital malformation of the neural elements but rather an acquired malformation that arises from pulsatile impaction of the cerebellar tonsils into the foramen magnum. Clinical trial registration no.: NCT00001327. (http://thejns.org/doi/abs/10.3171/2012.8.JNS111476)
C1 [Heiss, John D.; Suffredini, Giancarlo; Bakhtian, Kamran D.; Oldfield, Edward H.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Sarntinoranont, Malisa] Univ Florida, Soft Tissue Mech & Drug Delivery Lab, Gainesville, FL USA.
[Oldfield, Edward H.] Univ Virginia, Dept Neurosurg, Charlottesville, VA USA.
RP Heiss, JD (reprint author), Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, 10 Ctr Dr,10-3D20,MSC-1414, Bethesda, MD 20892 USA.
EM heissj@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
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.
NR 8
TC 14
Z9 15
U1 0
U2 3
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 0022-3085
J9 J NEUROSURG
JI J. Neurosurg.
PD NOV
PY 2012
VL 117
IS 5
BP 942
EP 946
DI 10.3171/2012.8.JNS111476
PG 5
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 027UW
UT WOS:000310380300029
PM 22978540
ER
PT J
AU Heiss, JD
Snyder, K
Peterson, MM
Patronas, NJ
Butman, JA
Smith, RK
DeVroom, HL
Sansur, CA
Eskioglu, E
Kammerer, WA
Oldfield, EH
AF Heiss, John D.
Snyder, Kendall
Peterson, Matthew M.
Patronas, Nicholas J.
Butman, John A.
Smith, Rene K.
DeVroom, Hetty L.
Sansur, Charles A.
Eskioglu, Eric
Kammerer, William A.
Oldfield, Edward H.
TI Pathophysiology of primary spinal syringomyelia Clinical article
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Article
DE syringomyelia; physiology; ultrasonography; surgery; cerebrospinal
fluid; magnetic resonance imaging; myelography
ID CEREBROSPINAL-FLUID FLOW; CT METRIZAMIDE MYELOGRAPHY; CHIARI I
MALFORMATION; POSTTRAUMATIC SYRINGOMYELIA; THECOPERITONEAL SHUNT;
CORD-INJURY; IDIOPATHIC SYRINGOMYELIA; CERVICAL SPONDYLOSIS;
CRITICAL-APPRAISAL; ARACHNOID CYST
AB Object. The pathogenesis of syringomyelia in patients with an associated spinal lesion is incompletely understood. The authors hypothesized that in primary spinal syringomyelia, a subarachnoid block effectively shortens the length of the spinal subarachnoid space (SAS), reducing compliance and the ability of the spinal theca to dampen the subarachnoid CSF pressure waves produced by brain expansion during cardiac systole. This creates exaggerated spinal subarachnoid pressure waves during every heartbeat that act on the spinal cord above the block to drive CSF into the spinal cord and create a syrinx. After a syrinx is formed, enlarged subarachnoid pressure waves compress the external surface of the spinal cord, propel the syrinx fluid, and promote syrinx progression.
Methods. To elucidate the pathophysiology, the authors prospectively studied 36 adult patients with spinal lesions obstructing the spinal SAS. Testing before surgery included clinical examination; evaluation of anatomy on T1-weighted MRI; measurement of lumbar and cervical subarachnoid mean and pulse pressures at rest, during Valsalva maneuver, during jugular compression, and after removal of CSF (CSF compliance measurement); and evaluation with CT myelography. During surgery, pressure measurements from the SAS above the level of the lesion and the lumbar intrathecal space below the lesion were obtained, and cardiac-gated ultrasonography was performed. One week after surgery, CT myelography was repeated. Three months after surgery, clinical examination, T1-weighted MRI, and CSF pressure recordings (cervical and lumbar) were repeated. Clinical examination and MRI studies were repeated annually thereafter. Findings in patients were compared with those obtained in a group of 18 healthy individuals who had already undergone T1-weighted MRI, cine MRI, and cervical and lumbar subarachnoid pressure testing.
Results. In syringomyelia patients compared with healthy volunteers, cervical subarachnoid pulse pressure was increased (2.7 +/- 1.2 vs 1.6 +/- 0.6 mm Hg, respectively; p = 0.004), pressure transmission to the theca] sac below the block was reduced, and spinal CSF compliance was decreased. Intraoperative ultrasonography confirmed that pulse pressure waves compressed the outer surface of the spinal cord superior to regions of obstruction of the subarachnoid space.
Conclusions. These findings are consistent with the theory that a spinal subarachnoid block increases spinal subarachnoid pulse pressure above the block, producing a pressure differential across the obstructed segment of the SAS, which results in syrinx formation and progression. These findings are similar to the results of the authors' previous studies that examined the pathophysiology of syringomyelia associated with obstruction of the SAS at the foramen magnum in the Chiari Type I malformation and indicate that a common mechanism, rather than different, separate mechanisms, underlies syrinx formation in these two entities. Clinical trial registration no.: NCT00011245. (http://thejns.org/doi/abs/10.3171/2012.8.SPINE111059)
C1 [Heiss, John D.; Smith, Rene K.; DeVroom, Hetty L.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Kammerer, William A.] NIH, Dept Anesthesia, Bethesda, MD 20892 USA.
[Snyder, Kendall] George Washington Univ, Sch Med, Washington, DC USA.
[Peterson, Matthew M.] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Sansur, Charles A.] Univ Maryland, Dept Neurosurg, Baltimore, MD 21201 USA.
[Eskioglu, Eric] Phys Reg Healthcare Syst, NeuroVasc & Stroke Inst, Naples, Italy.
[Oldfield, Edward H.] Univ Virginia Hlth Syst, Dept Neurol Surg, Charlottesville, VA USA.
RP Heiss, JD (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,l0-5D37,MSC-1414, Bethesda, MD 20892 USA.
EM heissj@ninds.nih.gov
RI Butman, John/J-2780-2013
OI Butman, John/0000-0002-1547-9195
FU Intramural Research Program of the NINDS at the NIH
FX This research was supported by the Intramural Research Program of the
NINDS at the NIH.
NR 75
TC 32
Z9 32
U1 0
U2 4
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD NOV
PY 2012
VL 17
IS 5
BP 367
EP 380
DI 10.3171/2012.8.SPINE111059
PG 14
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA 027VD
UT WOS:000310381100001
PM 22958075
ER
PT J
AU Bennett, NJ
Tabarani, CM
Bartholoma, NM
Wang, DL
Huang, DN
Riddell, SW
Kiska, DL
Hingre, R
Rosenberg, HF
Domachowske, JB
AF Bennett, Nicholas J.
Tabarani, Christy M.
Bartholoma, Nadine M.
Wang, Dongliang
Huang, Danning
Riddell, Scott W.
Kiska, Deanna L.
Hingre, Robert
Rosenberg, Helene F.
Domachowske, Joseph B.
TI Unrecognized Viral Respiratory Tract Infections in Premature Infants
during their Birth Hospitalization: A Prospective Surveillance Study in
Two Neonatal Intensive Care Units
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID SYNCYTIAL VIRUS; BRONCHOPULMONARY DYSPLASIA; PRETERM INFANTS; OUTBREAK;
EPIDEMIOLOGY; CYTOKINES; NURSERY
AB Objective To determine the frequency and effects of nosocomial respiratory viral infections (RVIs) in premature neonates, including those who may be asymptomatic.
Study design We performed a year-long surveillance for RVIs in infants < 33 weeks gestational age admitted to 2 Syracuse neonatal intensive care units. Infants were enrolled within 3 days of neonatal intensive care unit admission and were sampled for RVIs until discharge using a multiplex polymerase chain reaction assay capable of detecting 17 different respiratory viruses or subtypes.
Results Twenty-six of 50 prematurely born infants (52%) tested positive for a respiratory virus at least once during their birth hospitalization. Testing positive for a respiratory virus was significantly associated with longer length of stay (70 days vs 35 days, P = .002) and prolonged ventilatory support (51 vs 13 days, P = .002). Infants who tested positive for a respiratory virus during their birth hospitalization had more than twice the rate of developing bronchopulmonary dysplasia (P < .05).
Conclusion Nosocomial RVIs were frequent in our study population, despite the absence of clinical indicators of illness. Length of hospital stay was significantly longer and a diagnosis of bronchopulmonary dysplasia was more common in infants who had respiratory viruses detected. (J Pediatr 2012;161:814-8).
C1 [Bartholoma, Nadine M.; Riddell, Scott W.; Kiska, Deanna L.] Upstate Golisano Childrens Hosp, Dept Clin Pathol, Syracuse, NY USA.
[Bennett, Nicholas J.; Tabarani, Christy M.; Hingre, Robert; Domachowske, Joseph B.] Upstate Golisano Childrens Hosp, Dept Pediat, Syracuse, NY USA.
[Wang, Dongliang] SUNY Upstate Med Univ, Dept Publ Hlth & Prevent Med, Syracuse, NY USA.
[Huang, Danning] SUNY Buffalo, Dept Biostat, Buffalo, NY 14260 USA.
[Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Bennett, NJ (reprint author), CT Childrens Med Ctr, Div Infect Dis, 282 Washington St, Hartford, CT 06106 USA.
EM njb35@cantab.net
FU Children's Miracle Network of New York; National Institute of Allergy
and Infectious Diseases, Division of Intramural Research [Z01-AI000943]
FX Funded by the Children's Miracle Network of New York (to J.D. and N.B.)
and the National Institute of Allergy and Infectious Diseases, Division
of Intramural Research (Z01-AI000943 to H.R.). The authors declare no
conflicts of interest.
NR 15
TC 20
Z9 23
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD NOV
PY 2012
VL 161
IS 5
BP 814
EP +
DI 10.1016/j.jpeds.2012.05.001
PG 8
WC Pediatrics
SC Pediatrics
GA 027RJ
UT WOS:000310370600012
PM 22694859
ER
PT J
AU Bailey, RL
Fulgoni, VL
Keast, DR
Lentino, CV
Dwyer, JT
AF Bailey, Regan L.
Fulgoni, Victor L., III
Keast, Debra R.
Lentino, Cindy V.
Dwyer, Johanna T.
TI Do Dietary Supplements Improve Micronutrient Sufficiency in Children and
Adolescents?
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID MULTIVITAMIN-MULTIMINERAL SUPPLEMENTS; NUTRIENT INTAKE; ADULTS;
NONUSERS; USERS; NUTRITION; MINERALS; ENERGY; HEALTH
AB Objective To examine if children use supplements to fill gaps in nutritionally inadequate diets or whether supplements contribute to already adequate or excessive micronutrient intakes from foods.
Study design Data were analyzed for children (2-18 years) from the National Health and Nutrition Examination Survey 2003-2006, a nationally representative, cross-sectional survey (n = 7250). Diet was assessed using two 24-hour recalls, and dietary supplement use was assessed with a 30-day questionnaire.
Results Prevalence of supplements use was 21% (<2 years) and 42% (2-8 years). Supplement users had higher micronutrient intakes than nonusers. Calcium and vitamin D intakes were low for all children. Inadequate intakes of phosphorus, copper, selenium, folate, and vitamins B-6 and B-12 were minimal from foods alone among 2-8 year olds. However, among 9-18 year olds, a higher prevalence of inadequate intakes of magnesium, phosphorus, and vitamins A, C, and E were observed. Supplement use increased the likelihood of intakes above the upper tolerable intake level for iron, zinc, copper, selenium, folic acid, and vitamins A and C.
Conclusions Even with the use of supplements, more than a one-third of children failed to meet calcium and vitamin D recommendations. Children 2-8 years old had nutritionally adequate diets regardless of supplement use. However, in children older than 8 years, dietary supplements added micronutrients to diets that would have otherwise been inadequate for magnesium, phosphorus, vitamins A, C, and E. Supplement use contributed to the potential for excess intakes of some nutrients. These findings may have implications for reformulating dietary supplements for children. (J Pediatr 2012;161:837-42).
C1 [Bailey, Regan L.; Lentino, Cindy V.; Dwyer, Johanna T.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Fulgoni, Victor L., III] Nutr Impact LLC, Battle Creek, MI USA.
[Keast, Debra R.] Food & Nutr Database Res Inc, Okemos, MI USA.
[Dwyer, Johanna T.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Dwyer, Johanna T.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
RP Bailey, RL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Rm 3B01, Bethesda, MD 20892 USA.
EM baileyr@mail.nih.gov
OI Dwyer, Johanna/0000-0002-0783-1769
FU United States Department of Agriculture Research Service
[58-1950-7-707]; Office of Dietary Supplements at the National
Institutes of Health; Fortification Committee of the International Life
Sciences Institute, North American Branch
FX Supported in part by the United States Department of Agriculture
Research Service (agreement 58-1950-7-707) and the Office of Dietary
Supplements at the National Institutes of Health. Data generation was
funded by the Fortification Committee of the International Life Sciences
Institute, North American Branch. The authors declare no conflicts of
interest.
NR 29
TC 26
Z9 26
U1 1
U2 30
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD NOV
PY 2012
VL 161
IS 5
BP 837
EP +
DI 10.1016/j.jpeds.2012.05.009
PG 9
WC Pediatrics
SC Pediatrics
GA 027RJ
UT WOS:000310370600016
PM 22717218
ER
PT J
AU Freimuth, RR
Freund, ET
Schick, L
Sharma, MK
Stafford, GA
Suzek, BE
Hernandez, J
Hipp, J
Kelley, JM
Rokicki, K
Pan, S
Buckler, A
Stokes, TH
Fernandez, A
Fore, I
Buetow, KH
Klemm, JD
AF Freimuth, Robert R.
Freund, Elaine T.
Schick, Lisa
Sharma, Mukesh K.
Stafford, Grace A.
Suzek, Baris E.
Hernandez, Joyce
Hipp, Jason
Kelley, Jenny M.
Rokicki, Konrad
Pan, Sue
Buckler, Andrew
Stokes, Todd H.
Fernandez, Anna
Fore, Ian
Buetow, Kenneth H.
Klemm, Juli D.
TI Life sciences domain analysis model
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
AB Objective Meaningful exchange of information is a fundamental challenge in collaborative biomedical research. To help address this, the authors developed the Life Sciences Domain Analysis Model (LS DAM), an information model that provides a framework for communication among domain experts and technical teams developing information systems to support biomedical research. The LS DAM is harmonized with the Biomedical Research Integrated Domain Group (BRIDG) model of protocol-driven clinical research. Together, these models can facilitate data exchange for translational research.
Materials and methods The content of the LS DAM was driven by analysis of life sciences and translational research scenarios and the concepts in the model are derived from existing information models, reference models and data exchange formats. The model is represented in the Unified Modeling Language and uses ISO 21090 data types.
Results The LS DAM v2.2.1 is comprised of 130 classes and covers several core areas including Experiment, Molecular Biology, Molecular Databases and Specimen. Nearly half of these classes originate from the BRIDG model, emphasizing the semantic harmonization between these models. Validation of the LS DAM against independently derived information models, research scenarios and reference databases supports its general applicability to represent life sciences research.
Discussion The LS DAM provides unambiguous definitions for concepts required to describe life sciences research. The processes established to achieve consensus among domain experts will be applied in future iterations and may be broadly applicable to other standardization efforts.
Conclusions The LS DAM provides common semantics for life sciences research. Through harmonization with BRIDG, it promotes interoperability in translational science.
C1 [Fore, Ian; Buetow, Kenneth H.; Klemm, Juli D.] NCI CBIIT, Rockville, MD 20852 USA.
[Fernandez, Anna] Booz Allen Hamilton, Rockville, MD USA.
[Stokes, Todd H.] Emory Univ, Atlanta, GA 30322 USA.
[Stokes, Todd H.] Georgia Tech, Dept Biomed Engn, Atlanta, GA USA.
[Buckler, Andrew] BBMSC, Wenham, MA USA.
[Rokicki, Konrad; Pan, Sue] SAIC Inc, Mclean, VA USA.
[Kelley, Jenny M.] NCI, Lab Populat Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Hipp, Jason] Univ Michigan Hlth Syst, Dept Pathol, Ann Arbor, MI USA.
[Hernandez, Joyce] Merck Sharp & Dohme Corp, Global Clin Data External Stand, Whitehouse Stn, NJ USA.
[Suzek, Baris E.] Georgetown Univ, Dept Biochem & Mol Biol, Washington, DC USA.
[Stafford, Grace A.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Sharma, Mukesh K.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA.
[Schick, Lisa] ScenPro Inc, Richardson, TX USA.
[Freund, Elaine T.] 3rd Millennium Inc, Waltham, MA USA.
[Freimuth, Robert R.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
RP Klemm, JD (reprint author), NCI CBIIT, 2115 E Jefferson St, Rockville, MD 20852 USA.
EM klemmj@mail.nih.gov
OI Buckler, Andrew/0000-0002-0786-4835; Fore, Ian/0000-0002-2926-9324
FU National Cancer Institute
FX This work was supported by contracts from Booz Allen Hamilton and
SAIC-Frederick on behalf of the National Cancer Institute as part of the
caBIG (R) Integrative Cancer Research Workspace.
NR 35
TC 2
Z9 2
U1 3
U2 14
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD NOV
PY 2012
VL 19
IS 6
BP 1095
EP 1102
DI 10.1136/amiajnl-2011-000763
PG 8
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 028FP
UT WOS:000310408500026
PM 22744959
ER
PT J
AU Shaikh, Q
Kamal, AK
AF Shaikh, Quratulain
Kamal, Ayeesha Kamran
TI Sarpogrelate- another new antiplatelet agent?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID PREVENTION; INFARCTION; ASPIRIN; TRIAL; RISK
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Programme, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Stroke Serv & Vasc Fellowship Programme, Fogarty Int Ctr, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 3
TC 0
Z9 0
U1 0
U2 0
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD NOV
PY 2012
VL 62
IS 11
BP 1253
EP 1253
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 024RP
UT WOS:000310126600031
PM 23866425
ER
PT J
AU Kong, R
Li, H
Georgiev, I
Changela, A
Bibollet-Ruche, F
Decker, JM
Rowland-Jones, SL
Jaye, A
Guan, YJ
Lewis, GK
Langedijk, JPM
Hahn, BH
Kwong, PD
Robinson, JE
Shaw, GM
AF Kong, Rui
Li, Hui
Georgiev, Ivelin
Changela, Anita
Bibollet-Ruche, Frederic
Decker, Julie M.
Rowland-Jones, Sarah L.
Jaye, Assan
Guan, Yongjun
Lewis, George K.
Langedijk, Johannes P. M.
Hahn, Beatrice H.
Kwong, Peter D.
Robinson, James E.
Shaw, George M.
TI Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal
Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; PROXIMAL
EXTERNAL REGION; MEMORY B-CELLS; MEDIATED NEUTRALIZATION; V3-SPECIFIC
ANTIBODIES; POTENT NEUTRALIZATION; ANTIGENIC STRUCTURE; CORECEPTOR
USAGE; CONSERVED REGION
AB Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (NAbs) against primary HIV-2 strains (T. I. de Silva, et al., J. Virol. 86: 930-946, 2012; R. Kong, et al., J. Virol. 86:947-960, 2012; G. Ozkaya Sahin, et al., J. Virol. 86:961-971, 2012). Here, we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (MAbs), 14 of which were newly generated from 9 chronically infected subjects. All 15 MAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2(7312A) and HIV-2(ST). Ten of 15 MAbs neutralized a third heterologous primary virus strain, HIV-2(UC1). The median 50% inhibitory concentrations (IC(50)s) for these MAbs were surprisingly low, ranging from 0.007 to 0.028 mu g/ml. Competitive Env binding studies revealed three MAb competition groups: CG-I, CG-II, and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions, and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3), the epitope of CG-II antibodies to a conformational region centered on the carboxy terminus of V4, and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency, and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive NAbs. The availability of 15 human MAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity, and immunogenicity.
C1 [Kong, Rui; Li, Hui; Bibollet-Ruche, Frederic; Hahn, Beatrice H.; Shaw, George M.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kong, Rui; Decker, Julie M.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Kong, Rui; Decker, Julie M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Georgiev, Ivelin; Changela, Anita; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA.
[Rowland-Jones, Sarah L.] John Radcliffe Hosp, Med Res Council, Human Immunol Unit, Weatherall Inst Mol Med, Oxford OX3 9DU, England.
[Jaye, Assan] Med Res Council United Kingdom Labs, Fajara, Gambia.
[Guan, Yongjun; Lewis, George K.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Langedijk, Johannes P. M.] Pepscan Therapeut, Lelystad, Netherlands.
[Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA.
RP Shaw, GM (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM shawg@upenn.edu
FU NIH [AI67854, AI88564, AI87383]; Bill and Melinda Gates Foundation
FX This work was supported by intramural funding to the Vaccine Research
Center, NIAID, and by grants from the NIH (AI67854, AI88564, AI87383),
and grants from the Bill and Melinda Gates Foundation.
NR 85
TC 17
Z9 17
U1 1
U2 12
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2012
VL 86
IS 22
BP 12115
EP 12128
DI 10.1128/JVI.01632-12
PG 14
WC Virology
SC Virology
GA 027MK
UT WOS:000310356400014
PM 22933274
ER
PT J
AU Cardone, G
Brecher, M
Fontana, J
Winkler, DC
Butan, C
White, JM
Stevena, AC
AF Cardone, Giovanni
Brecher, Matthew
Fontana, Juan
Winkler, Dennis C.
Butan, Carmen
White, Judith M.
Stevena, Alasdair C.
TI Visualization of the Two-Step Fusion Process of the Retrovirus Avian
Sarcoma/Leukosis Virus by Cryo-Electron Tomography
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID INDUCED CONFORMATIONAL-CHANGES; VIRAL MEMBRANE-FUSION; LIPID MIXING
STAGE; ENVELOPE GLYCOPROTEIN; LOW PH; RECEPTOR-BINDING; INFLUENZA-VIRUS;
SARCOMA-VIRUS; IMMUNODEFICIENCY-VIRUS; ELECTRON-MICROSCOPY
AB Retrovirus infection starts with the binding of envelope glycoproteins to host cell receptors. Subsequently, conformational changes in the glycoproteins trigger fusion of the viral and cellular membranes. Some retroviruses, such as avian sarcoma/leukosis virus (ASLV), employ a two-step mechanism in which receptor binding precedes low-pH activation and fusion. We used cryoelectron tomography to study virion/receptor/liposome complexes that simulate the interactions of ASLV virions with cells. Binding the soluble receptor at neutral pH resulted in virions capable of binding liposomes tightly enough to alter their curvature. At virion-liposome interfaces, the glycoproteins are similar to 3-fold more concentrated than elsewhere in the viral envelope, indicating specific recruitment to these sites. Subtomogram averaging showed that the oblate globular domain in the prehairpin intermediate (presumably the receptor-binding domain) is connected to both the target and the viral membrane by 2.5-nm-long stalks and is partially disordered, compared with its native conformation. Upon lowering the pH, fusion took place. Fusion is a stochastic process that, once initiated, must be rapid, as only final (postfusion) products were observed. These fusion products showed glycoprotein spikes on their surface, with their interiors occupied by patches of dense material but without capsids, implying their disassembly. In addition, some of the products presented a density layer underlying and resolved from the viral membrane, which may represent detachment of the matrix protein to facilitate the fusion process.
C1 [Cardone, Giovanni; Fontana, Juan; Winkler, Dennis C.; Butan, Carmen; Stevena, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
[Brecher, Matthew; White, Judith M.] Univ Virginia, Dept Cell Biol, Charlottesville, VA USA.
[Brecher, Matthew; White, Judith M.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
RP Stevena, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jw7g@virginia.edu; stevena@mail.nih.gov
RI Fontana, Juan/A-9138-2009
OI Fontana, Juan/0000-0002-9084-2927
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases;
NIH [AI22470]; NIAID [5T32 AI07046-27]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
Diseases. Work in the White laboratory was supported by NIH AI22470.
M.B. was supported in part by an Infectious Disease Training Grant (5T32
AI07046-27) from the NIAID.
NR 55
TC 13
Z9 13
U1 0
U2 20
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2012
VL 86
IS 22
BP 12129
EP 12137
DI 10.1128/JVI.01880-12
PG 9
WC Virology
SC Virology
GA 027MK
UT WOS:000310356400015
PM 22933285
ER
PT J
AU Verma, S
Dimitrova, M
Munjal, A
Fontana, J
Crevar, CJ
Carter, DM
Ross, TM
Khurana, S
Golding, H
AF Verma, Swati
Dimitrova, Milena
Munjal, Ashok
Fontana, Juan
Crevar, Corey J.
Carter, Donald M.
Ross, Ted M.
Khurana, Surender
Golding, Hana
TI Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects
Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza
Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by
Eliciting High-Affinity Antibodies
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRUS-LIKE PARTICLE; BROAD CROSS-PROTECTION; NEUTRALIZING ANTIBODIES;
HEMAGGLUTININ PROTEINS; ELECTRON-MICROSCOPY; IMMUNE-RESPONSES; GLOBULAR
HEAD; YOUNG-ADULTS; INSECT CELLS; A VIRUS
AB Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.
C1 [Verma, Swati; Dimitrova, Milena; Khurana, Surender; Golding, Hana] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
[Verma, Swati; Munjal, Ashok] Banasthali Vidyapith, Dept Biosci & Biotechnol, Banasthali, Rajasthan, India.
[Fontana, Juan] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA.
[Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA USA.
RP Khurana, S (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA.
EM surender.khurana@fda.hhs.gov; hana.golding@fda.hhs.gov
RI Fontana, Juan/A-9138-2009
OI Fontana, Juan/0000-0002-9084-2927
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health; NIH/NIAID [U01AI077771]
FX This work was partly supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health to J.F. and NIH/NIAID award
U01AI077771 to T.M.R.
NR 55
TC 13
Z9 13
U1 1
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2012
VL 86
IS 22
BP 12283
EP 12293
DI 10.1128/JVI.01596-12
PG 11
WC Virology
SC Virology
GA 027MK
UT WOS:000310356400029
PM 22951833
ER
PT J
AU Shi, M
Jagger, BW
Wise, HM
Digard, P
Holmes, EC
Taubenberger, JK
AF Shi, Mang
Jagger, Brett W.
Wise, Helen M.
Digard, Paul
Holmes, Edward C.
Taubenberger, Jeffery K.
TI Evolutionary Conservation of the PA-X Open Reading Frame in Segment 3 of
Influenza A Virus
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CRYSTAL-STRUCTURE; ENDONUCLEASE
AB PA-X is a fusion protein of influenza A virus encoded in part from a +1 frameshifted X open reading frame (X-ORF) in segment 3. We show that the X-ORFs of diverse influenza A viruses can be divided into two groups that differ in selection pressure and likely function, reflected in the presence of an internal stop codon and a change in synonymous diversity. Notably, truncated forms of PA-X evolved convergently in swine and dogs, suggesting a strong species-specific effect.
C1 [Jagger, Brett W.; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Shi, Mang; Holmes, Edward C.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA.
[Wise, Helen M.; Digard, Paul] Univ Edinburgh, Roslin Inst, Edinburgh EH8 9YL, Midlothian, Scotland.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM taubenbergerj@niaid.nih.gov
RI Digard, Paul/B-7717-2008; Shi, Mang/D-5118-2013;
OI Digard, Paul/0000-0002-0872-9440; Holmes, Edward/0000-0001-9596-3552
FU Medical Research Council [G0700815]
NR 10
TC 38
Z9 40
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD NOV
PY 2012
VL 86
IS 22
BP 12411
EP 12413
DI 10.1128/JVI.01677-12
PG 3
WC Virology
SC Virology
GA 027MK
UT WOS:000310356400043
PM 22951836
ER
PT J
AU Traylor, M
Farrall, M
Holliday, EG
Sudlow, C
Hopewell, JC
Cheng, YC
Fomage, M
Ikram, MA
Malik, R
Bevan, S
Thorsteinsdottir, U
Nalls, MA
Longstreth, WT
Wiggins, KL
Yadav, S
Parati, EA
DeStefano, AL
Worrall, BB
Kittner, S
Khan, MS
Reiner, AP
Helgadottir, A
Achterberg, S
Fernandez-Cadenas, I
Abboud, S
Schmidt, R
Walters, M
Chen, WM
Ringelstein, EB
O'Donnell, M
Ho, WK
Pera, J
Lemmens, R
Norrving, B
Higgins, P
Benn, M
Sale, M
Kuhlenbaumer, G
Doney, ASF
Vicente, AM
Delavaran, H
Algra, A
Davies, G
Oliveira, SA
Palmer, CNA
Deary, I
Schmidt, H
Pandolfo, M
Montaner, J
Carty, C
de Bakker, PIW
Kostulas, K
Ferro, JM
van Zuydam, NR
Valdimarsson, E
Nordestgaard, BG
Lindgren, A
Thijs, V
Slowik, A
Saleheen, D
Pare, G
Berger, K
Thorleifsson, G
Hofman, A
Mosley, TH
Mitchell, BD
Furie, K
Clarke, R
Levi, C
Seshadri, S
Gschwendtner, A
Boncoraglio, GB
Sharma, P
Bis, JC
Gretarsdottir, S
Psaty, BM
Rothwell, PM
Rosand, J
Meschia, JF
Stefansson, K
Dichgans, M
Markus, HS
AF Traylor, Matthew
Farrall, Martin
Holliday, Elizabeth G.
Sudlow, Cathie
Hopewell, Jemma C.
Cheng, Yu-Ching
Fomage, Myriam
Ikram, M. Arfan
Malik, Rainer
Bevan, Steve
Thorsteinsdottir, Unnur
Nalls, Mike A.
Longstreth, W. T.
Wiggins, Kerri L.
Yadav, Sunaina
Parati, Eugenio A.
DeStefano, Anita L.
Worrall, Bradford B.
Kittner, Steven
Khan, Muhammad Saleem
Reiner, Alex P.
Helgadottir, Anna
Achterberg, Sefanja
Fernandez-Cadenas, Israel
Abboud, Sherine
Schmidt, Reinhold
Walters, Matthew
Chen, Wei-Min
Ringelstein, E. Bernd
O'Donnell, Martin
Ho, Weang Kee
Pera, Joanna
Lemmens, Robin
Norrving, Bo
Higgins, Peter
Benn, Marianne
Sale, Michele
Kuhlenbaeumer, Gregor
Doney, Alexander S. F.
Vicente, Astrid M.
Delavaran, Hossein
Algra, Ale
Davies, Gail
Oliveira, Sofia A.
Palmer, Colin N. A.
Deary, Ian
Schmidt, Helena
Pandolfo, Massimo
Montaner, Joan
Carty, Cara
de Bakker, Paul I. W.
Kostulas, Konstantinos
Ferro, Jose M.
van Zuydam, Natalie R.
Valdimarsson, Einar
Nordestgaard, Borge G.
Lindgren, Ame
Thijs, Vincent
Slowik, Agnieszka
Saleheen, Danish
Pare, Guillaume
Berger, Klaus
Thorleifsson, Gudmar
Hofman, Albert
Mosley, Thomas H.
Mitchell, Braxton D.
Furie, Karen
Clarke, Robert
Levi, Christopher
Seshadri, Sudha
Gschwendtner, Andreas
Boncoraglio, Giorgio B.
Sharma, Pankaj
Bis, Joshua C.
Gretarsdottir, Solveig
Psaty, Bruce M.
Rothwell, Peter M.
Rosand, Jonathan
Meschia, James F.
Stefansson, Kan
Dichgans, Martin
Markus, Hugh S.
CA Australian Stroke Genetics Collabo
WTCCC 2
Int Stroke Genetics Consortium
TI Genetic risk factors for ischaemic stroke and its subtypes (the
METASTROKE Collaboration): a meta-analysis of genome-wide association
studies
SO LANCET NEUROLOGY
LA English
DT Article
ID SEQUENCE VARIANTS; LOCI; POPULATION; INFARCTION; DISEASES; COMMON;
PRKCH; MAP
AB Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.
Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nudeotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.
Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2.8x10(-16)) and ZFHX3 (p=2.28x10(-8)), and for large-vessel stroke at a 9p21 locus (p=3.32x10(-5)) and HDAC9 (p=2.03x10(-12)). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5x10(-6). However, we were unable to replicate any of these novel associations in the replication cohort.
Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.
C1 [Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London SW17 0RE, England.
[Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Farrall, Martin; Helgadottir, Anna] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia.
[Holliday, Elizabeth G.] Hunter Med Res Inst, Ctr Bioinformat Biomarker Discovery & Informat Ba, Sydney, NSW, Australia.
[Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.
[Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford, England.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Fomage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Ikram, M. Arfan; Hofman, Albert] Consortium Healthy Ageing, Leiden, Netherlands.
[Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.
[Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany.
[Thorsteinsdottir, Unnur; Helgadottir, Anna; Thorleifsson, Gudmar; Gretarsdottir, Solveig; Stefansson, Kan] DeCODE Genet, Reykjavik, Iceland.
[Thorsteinsdottir, Unnur; Helgadottir, Anna; Stefansson, Kan] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Nalls, Mike A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Longstreth, W. T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
[Longstreth, W. T.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wiggins, Kerri L.; Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Yadav, Sunaina; Khan, Muhammad Saleem; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Cerebrovasc Res Unit ICCRU, London, England.
[Parati, Eugenio A.; Boncoraglio, Giorgio B.] Ist Neurol Carlo Besta, Fdn Ist Ricovero Cura Carattere Sci IRCCS, Dept Cereberovasc Dis, Milan, Italy.
[DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA.
[Worrall, Bradford B.; Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Kittner, Steven] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MA USA.
[Kittner, Steven] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Reiner, Alex P.; Carty, Cara] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Achterberg, Sefanja; Algra, Ale] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands.
[Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Neurovasc Res Lab, Dept Neurol, E-08193 Barcelona, Spain.
[Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain.
[Fernandez-Cadenas, Israel; Montaner, Joan] Vall dHebron Hosp, Inst Res, Barcelona, Spain.
[Abboud, Sherine; Pandolfo, Massimo] Lab Expt Neurol, Brussels, Belgium.
[Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Div Neurogeriatr, Graz, Austria.
[Higgins, Peter] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Chen, Wei-Min; Sale, Michele] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Ringelstein, E. Bernd] Univ Munster, Dept Neurol, D-4400 Munster, Germany.
[O'Donnell, Martin] Natl Univ Ireland Galway, Galway, Ireland.
[Ho, Weang Kee; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Krakow, Poland.
[Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] Univ Leuven KU Leuven, Expt Neurol & Leuven Res Inst Neurodegenerat Dis, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Skane Univ Hosp, Dept Neurol, Lund, Sweden.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Lund Univ, Dept Clin Sci Lund, Lund, Sweden.
[Benn, Marianne; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
[Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
[Sale, Michele] Univ Virginia, Dept Internal Med, Div Cardiovasc Med, Charlottesville, VA USA.
[Kuhlenbaeumer, Gregor] Univ Kiel, Inst Expt Med, D-24098 Kiel, Germany.
[Doney, Alexander S. F.; Palmer, Colin N. A.; van Zuydam, Natalie R.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland.
[Vicente, Astrid M.] Inst Natl Sande Dr Ricardo Jorge, Dept Promocao Saude Doencas Cron, Lisbon, Portugal.
[Algra, Ale] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Davies, Gail; Deary, Ian] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[Davies, Gail; Deary, Ian] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Oliveira, Sofia A.] Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal.
[Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[de Bakker, Paul I. W.; Rosand, Jonathan] MIT, Cambridge, MA 02139 USA.
[de Bakker, Paul I. W.; Rosand, Jonathan] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA.
[Kostulas, Konstantinos] Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, Huddinge, Sweden.
[Ferro, Jose M.] Hosp Santa Maria, Ctr Estudos Egas Moniz, Serv Neurol, Lisbon, Portugal.
[Valdimarsson, Einar] Univ Hosp, Landspitali, Reykjavik, Iceland.
[Nordestgaard, Borge G.] Copenhagen Univ Hosp, Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada.
[Pare, Guillaume] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany.
[Mosley, Thomas H.; Rosand, Jonathan] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Furie, Karen] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, New Lambton, NSW, Australia.
[Levi, Christopher] Hunter Med Res Inst, New Lambton, NSW, Australia.
[Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Seattle, Grp Hlth Res Inst, Seattle, WA USA.
[Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England.
[Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
RP Markus, HS (reprint author), St Georges Univ London, Stroke & Dementia Res Ctr, Cranmer Terrace, London SW17 0RE, England.
EM hmarkus@sgul.ac.uk
RI Palmer, Colin/C-7053-2008; Vicente, Astrid/F-8692-2014; Thijs,
Vincent/C-3647-2009; Carty, Cara/B-8683-2013; Deary, Ian/C-6297-2009; de
Bakker, Paul/B-8730-2009; Boncoraglio, Giorgio/B-8647-2011; Montaner,
Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Study,
GoDARTS/K-9448-2016;
OI O'Donnell, Martin/0000-0002-7347-7761; Norrving, Bo/0000-0002-8024-5096;
HO, WEANG KEE/0000-0002-8269-7344; Ikram, Mohammad
Arfan/0000-0003-0372-8585; Traylor, Matthew/0000-0001-6624-8621; Bevan,
Steve/0000-0003-0490-6830; Ferro, Jose/0000-0002-2343-9097; Mitchell,
Braxton/0000-0003-4920-4744; Seshadri, Sudha/0000-0001-6135-2622;
Palmer, Colin/0000-0002-6415-6560; Vicente, Astrid/0000-0001-7134-8037;
Thijs, Vincent/0000-0002-6614-8417; de Bakker, Paul/0000-0001-7735-7858;
Oliveira, Sofia A/0000-0001-7919-4191; Benn,
Marianne/0000-0002-1701-595X
FU Wellcome Trust; UK Medical Research Council (MRC); Australian National
and Medical Health Research Council; National Institutes of Health (NIH)
including National Heart, Lung and Blood Institute (NHLBI); National
Institute on Aging (NIA); National Human Genome Research Institute
(NHGRI); National Institute of Neurological Disorders and Stroke
(NINDS); National Heart, Lung, and Blood Institute (NHLBI)
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367,
R01HL086694]; National Human Genome Research Institute [U01HG004402];
National Institutes of Health (NIH) [HHSN268200625226C]; NHLBI
[N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, N01-HC-55022, R01-HL087641, U01 HL096917, R01-HL093029,
N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129]; NIH Roadmap for
Medical Research [UL1RR025005]; METASTROKE project [HL-093029];
University of Newcastle; Australian National and Medical Health Research
Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G
04S 1623]; Gladys M Brawn Fellowship; Vincent Fairfax Family Foundation
in Australia; Australian NHMRC Fellowship; Department of Health (UK);
Henry Smith Charity; UK-India Education Research Institutive (UKIERI)
from the British Council; National Institute on Aging (NIA) [AG-023629,
AG-15928, AG-20098, AG-027058]; National Center of Advancing
Translational Technologies CTSI [UL1TR000124]; National Institute of
Diabetes and Digestive and Kidney Diseases [DK063491]; European
Community [HEALTH-F4-2007-201413]; Framingham Heart Study; NHLBI's
Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; NINDS [NS17950];
NIA [AG033193]; NIH Genes; Almirall; Astra Zeneca; Berlin Chemie;
Boehringer; Boots Health Care; Glaxo-Smith-Kline; Janssen Cilag; McNeil
Pharma; MSD Sharp Dohme; Pfizer; Portuguese Fundacao para a Ciencia e a
Tecnologia; Jagiellonian University, Krakow Poland [K/ZDS/002848];
Netherlands Heart Foundation [2005B031]; United States National Human
Genome Research Institute (NHGRI) as part of the Genomics and Randomized
Trials Network (GARNET) [U01 HG005160]; NIH; GARNET Coordinating Center
[U01 HG005157]; United States Public Health Service, NINDS, Bethesda,
Maryland [R01 NS34447]; United States National Center for Biotechnology
Information, US National Library of Medicine; WHI-GARNET through the
NHGRI GARNET [U01 HG005152]; NIH Genes, Environment, and Health
Initiative [U01 HG004424]; National Heart, Lung and Blood Institute [N01
HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C,
HL080295, HL087652, HL105756, HL93029]; [PTDC/SAU-GMG/64426/2006]
FX Funding Wellcome Trust, UK Medical Research Council (MRC), Australian
National and Medical Health Research Council, National Institutes of
Health (NIH) including National Heart, Lung and Blood Institute (NHLBI),
the National Institute on Aging (NIA), the National Human Genome
Research Institute (NHGRI), and the National Institute of Neurological
Disorders and Stroke (NINDS).; Atherosclerosis Risk in Communities Study
(ARIC) is a collaborative study supported by National Heart, Lung, and
Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research
Institute contract U01HG004402; National Institutes of Health (NIH)
contract HHSN268200625226C; and NHLBI contracts N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, and grants R01-HL087641, U01 HL096917 (T H Mosley), and
R01-HL093029 (M Fornage). Infrastructure was partly supported by Grant
Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. ARIC analyses performed as part of the METASTROKE project were
supported by grant HL-093029 to M Fornage. Australian Stroke Genetics
Collaboration (ASGC) Australian population control data were derived
from the Hunter Community Study. We also thank the University of
Newcastle for funding and the men and women of the Hunter region who
participated in this study. This research was funded by grants from the
Australian National and Medical Health Research Council (NHMRC Project
Grant ID: 569257), the Australian National Heart Foundation (NHF Project
Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn
Fellowship scheme, and the Vincent Fairfax Family Foundation in
Australia. Elizabeth G Holliday is supported by the Australian NHMRC
Fellowship scheme. Bio-Repository of DNA in Stroke (BRAINS) is partly
funded by a Senior Fellowship from the Department of Health (UK) to P
Sharma, the Henry Smith Charity and the UK-India Education Research
Institutive (UKIERI) from the British Council. Cardiovascular Health
Study (CHS) research was supported by NHLBI contracts N01-HC-85239,
N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01
HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C and NHLBI grants
HL080295, HL087652, HL105756 with additional contribution from the
National Institute of Neurological Diseases and Stroke (NINDS).
Additional support was provided through AG-023629, AG-15928, AG-20098,
and AG-027058 from the National Institute on Aging (NIA). DNA handling
and genotyping was supported in part by National Center of Advancing
Translational Technologies CTSI grant UL1TR000124 and National Institute
of Diabetes and Digestive and Kidney Diseases grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. deCODE
Genetics Work performed at deCODE was funded in part through a grant
from the European Community's Seventh Framework Programme
(FP7/2007-2013), the ENGAGE project grant agreement
HEALTH-F4-2007-201413. Framingham Heart Study (FHS) This work was
supported by the dedication of the Framingham Heart Study participants,
the NHLBI's Framingham Heart Study (Contract Nos. N01-HC-25195 and
N02-HL-6-4278), and by grants from the NINDS (NS17950), the NHLBI
(HL93029), and the NIA (AG033193). Genetics of Early Onset Stroke (GEOS)
Study, Baltimore, USA was supported by the NIH Genes, grants of equal
share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots
Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp
& Dohme, and Pfizer to the University of Muenster. Portugal SAO, JMF,
and AMV are deeply grateful to all study participants, to the genotyping
unit at the Instituto Gulbenkian de Ciencia, and to the Portuguese study
neurologists and nurses for their contributions.; This work was
supported by the PTDC/SAU-GMG/64426/2006 grant, a Cilencia 2008 contract
(SAO) and doctoral fellowships from the Portuguese Fundacao para a
Ciencia e a Tecnologia. Poland: Krakow The study was supported by the
grant from the Jagiellonian University, Krakow Poland: K/ZDS/002848.
SMART-study the Netherlands Genotyping in the SMART Study was made
possible, in part, by a Complementation Grant to P I W de Bakker from
the Biobanking and Biomolecular Research Infrastructure in the
Netherlands (BBMRI-NL). S Achterberg is working in part on a grant from
the Netherlands Heart Foundation, No. 2005B031. VISP The GWAS component
of the VISP study was supported by the United States National Human
Genome Research Institute (NHGRI), Grant U01 HG005160 (PI Michele Sale &
Bradford Worrell), as part of the Genomics and Randomized Trials Network
(GARNET). Genotyping services were provided by the Johns Hopkins
University Center for Inherited Disease Research (CIDR), which is fully
funded through a federal contract from the NIH to the Johns Hopkins
University. Assistance with data cleaning was provided by the GARNET
Coordinating Center (U01 HG005157; PI Bruce S Weir). Study recruitment
and collection of datasets for the VISP clinical trial were supported by
an investigator-initiated research grant (R01 NS34447; PI James Toole)
from the United States Public Health Service, NINDS, Bethesda, Maryland.
Control data obtained through the database of genotypes and phenotypes
(dbGAP) maintained and supported by the United States National Center
for Biotechnology Information, US National Library of Medicine. W H I
Funding support for WHI-GARNET was provided through the NHGRI GARNET
(Grant Number U01 HG005152). Assistance with phenotype harmonisation and
genotype cleaning, as well as with general study coordination, was
provided by the GARNET Coordinating Center (U01 HG005157). Funding
support for genotyping, which was performed at the Broad Institute of
MIT and Harvard, was provided by the NIH Genes, Environment, and Health
Initiative (GEI; U01 HG004424).
NR 31
TC 179
Z9 189
U1 3
U2 37
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD NOV
PY 2012
VL 11
IS 11
BP 951
EP 962
DI 10.1016/S1474-4422(12)70234-X
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 028KW
UT WOS:000310422200011
PM 23041239
ER
PT J
AU Sidransky, E
Lopez, G
AF Sidransky, Ellen
Lopez, Grisel
TI The link between the GBA gene and parkinsonism
SO LANCET NEUROLOGY
LA English
DT Review
ID GENOME-WIDE ASSOCIATION; LEWY BODY DISORDERS; PRECEDING
CLINICAL-MANIFESTATION; GLUCOCEREBROSIDASE N370S ALLELE; NEURONOPATHIC
GAUCHER-DISEASE; MULTIPLE SYSTEM ATROPHY; ALPHA-SYNUCLEIN; EARLY-ONSET;
RISK-FACTOR; COGNITIVE IMPAIRMENT
AB Mutations in the glucocerebrosidase (GBA) gene, which encodes the lysosomal enzyme that is deficient in Gaucher's disease, are important and common risk factors for Parkinson's disease and related disorders. This association was first recognised in the clinic, where parkinsonism was noted, albeit rarely, in patients with Gaucher's disease and more frequently in relatives who were obligate carriers. Subsequently, findings from large studies showed that patients with Parkinson's disease and associated Lewy body disorders had an increased frequency of GBA mutations when compared with control individuals. Patients with GBA-associated parkinsonism exhibit varying parkinsonian phenotypes but tend to have an earlier age of onset and more associated cognitive changes than patients with parkinsonism without GBA mutations. Hypotheses proposed to explain this association include a gain-of-function due to mutations in glucocerebrosidase that promotes alpha-synuclein aggregation; substrate accumulation due to enzymatic loss-of-function, which affects a-synuclein processing and clearance; and a bidirectional feedback loop. Identification of the pathological mechanisms underlying GBA-associated parkinsonism will improve our understanding of the genetics, pathophysiology, and treatment for both rare and common neurological diseases.
C1 [Sidransky, Ellen; Lopez, Grisel] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU National Human Genome Research Institute; National Institutes of Health
FX This work was supported by the Intramural Research Programs of the
National Human Genome Research Institute and the National Institutes of
Health. We thank Julia Fekecs, Wendy Westbroek, and Darryl Leja for
their assistance with the preparation of the figures.
NR 106
TC 100
Z9 102
U1 0
U2 20
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD NOV
PY 2012
VL 11
IS 11
BP 986
EP 998
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 028KW
UT WOS:000310422200014
PM 23079555
ER
PT J
AU Lin, YH
Loewke, JD
Hyun, DY
Leazer, J
Hibbeln, JR
AF Lin, Yu Hong
Loewke, James D.
Hyun, Duk Y.
Leazer, Jay
Hibbeln, Joseph R.
TI Fast Transmethylation of Serum Lipids Using Microwave Irradiation
SO LIPIDS
LA English
DT Article
DE Lepage & Roy; Acetyl chloride; In situ; Transesterification; GC; Fatty
acid profile
ID ACID METHYL-ESTERS; CHROMATOGRAPHY-MASS-SPECTROMETRY; FATTY-ACID; RAPID
TRANSESTERIFICATION; OMEGA-3-FATTY-ACIDS; PHOSPHOLIPIDS; DISEASE; BRAIN
AB Microwave irradiation as the energy source for one-step direct transesterification of fatty acids in human serum lipids was examined in a solvent system of methanol: hexane: acetyl chloride based on a Lepage & Roy assay. Innovative and explosion proof single-mode or multimode microwave accelerated reaction system was employed. Recoveries were calculated as the percentage of fatty acid concentrations measured by microwave assay to those by the reference method of the Lepage & Roy assay that utilized conductive heating at 100 A degrees C for 60 min. Under conditions of 100 A degrees C for 1 min in Single-mode (S4-100 x 1), or 125 A degrees C for 5 min in Multimode (M5-125 x 5), the recoveries were 100-103 % for the total fatty acids and 96-106 % for each categorized fatty acid, including saturates, monounsaturates, n-6 PUFA, and n-3 PUFA. For individual PUFA, the mean recoveries were 102-105 % for 18:2n-6 and 18:3n-3; 99, 109, and 95 % for 20:4n-6, 20:5n-3, and 22:6n-3, respectively. Thus, fatty acid concentrations determined by microwave fatty acid assay were accurate to those results by the reference method, when the microwave conditions were optimal. In summary, the microwave irradiation could replace conductive heating in one-step direct transesterification, and reduce the duration from 60 min to 5 min or less. This methodology may be applied in both the absolute and relative quantification of serum total fatty acids.
C1 [Lin, Yu Hong; Loewke, James D.; Hyun, Duk Y.; Hibbeln, Joseph R.] NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA.
[Leazer, Jay] CEM Corp, Mathews, NC USA.
RP Lin, YH (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Sect Nutr Neurosci, NIH, Bethesda, MD 20892 USA.
EM yulin@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX The authors wish to acknowledge Drs. Norman Salem Jr., Charlie Serhan,
and William E. M. Lands for the valuable advice and encouragement on the
method development. Thanks to Ms. Keller Barnhardt for set-up of the
microwave reaction systems and to Ms. Cindy Clark from the NIH Library
Writing Center for assistance with manuscript editing. This project was
funded by the Intramural Research Program of the National Institute on
Alcohol Abuse and Alcoholism, National Institutes of Health.
NR 24
TC 4
Z9 4
U1 3
U2 15
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0024-4201
J9 LIPIDS
JI Lipids
PD NOV
PY 2012
VL 47
IS 11
BP 1109
EP 1117
DI 10.1007/s11745-012-3714-x
PG 9
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 025XD
UT WOS:000310229400009
PM 23015312
ER
PT J
AU Adeva, MM
Souto, G
Blanco, N
Donapetry, C
AF Adeva, Maria M.
Souto, Gema
Blanco, Natalia
Donapetry, Cristobal
TI Ammonium metabolism in humans
SO METABOLISM-CLINICAL AND EXPERIMENTAL
LA English
DT Review
DE Metabolic alkalosis; Glutamate dehydrogenase; Glutamine synthetase;
Glutaminase; Hyperammonemia
ID N-ACETYLGLUTAMATE-SYNTHASE; FULMINANT HEPATIC-FAILURE; UREA CYCLE
DISORDERS; ACUTE LIVER-FAILURE; LYSINURIC PROTEIN INTOLERANCE; PHOSPHATE
SYNTHETASE-I; INDUCED HYPERAMMONEMIC ENCEPHALOPATHY; ACYLCARNITINE
TRANSLOCASE DEFICIENCY; HUMAN GLUTAMATE-DEHYDROGENASES; PROGRESSIVE
SPASTIC DIPLEGIA
AB Free ammonium ions are produced and consumed during cell metabolism. Glutamine synthetase utilizes free ammonium ions to produce glutamine in the cytosol whereas glutaminase and glutamate dehydrogenase generate free ammonium ions in the mitochondria from glutamine and glutamate, respectively. Ammonia and bicarbonate are condensed in the liver mitochondria to yield carbamoylphosphate initiating the urea cycle, the major mechanism of ammonium removal in humans. Healthy kidney produces ammonium which may be released into the systemic circulation or excreted into the urine depending predominantly on acid-base status, so that metabolic acidosis increases urinary ammonium excretion while metabolic alkalosis induces the opposite effect. Brain and skeletal muscle neither remove nor produce ammonium in normal conditions, but they are able to seize ammonium during hyperammonemia, releasing glutamine. Ammonia in gas phase has been detected in exhaled breath and skin, denoting that these organs may participate in nitrogen elimination. Ammonium homeostasis is profoundly altered in liver failure resulting in hyperammonemia due to the deficient ammonium clearance by the diseased liver and to the development of portal collateral circulation that diverts portal blood with high ammonium content to the systemic blood stream. Although blood ammonium concentration is usually elevated in liver disease, a substantial role of ammonium causing hepatic encephalopathy has not been demonstrated in human clinical studies. Hyperammonemia is also produced in urea cycle disorders and other situations leading to either defective ammonium removal or overproduction of ammonium that overcomes liver clearance capacity. Most diseases resulting in hyperammonemia and cerebral edema are preceded by hyperventilation and respiratory alkalosis of unclear origin that may be caused by the intracellular acidosis occurring in these conditions. (C) 2012 Elsevier Inc. All rights reserved.
C1 [Adeva, Maria M.; Donapetry, Cristobal] Hosp Gen Juan Cardona, La Coruna 15406, Spain.
[Souto, Gema] NIH, Ctr Clin, Bethesda, MD USA.
[Blanco, Natalia] United Surg Partners, La Coruna, Spain.
RP Adeva, MM (reprint author), Hosp Gen Juan Cardona, C Pardo Bazar S-N, La Coruna 15406, Spain.
EM madevaa@yahoo.com
NR 183
TC 60
Z9 60
U1 10
U2 96
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0026-0495
J9 METABOLISM
JI Metab.-Clin. Exp.
PD NOV
PY 2012
VL 61
IS 11
BP 1495
EP 1511
DI 10.1016/j.metabol.2012.07.007
PG 17
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 030GD
UT WOS:000310557900001
PM 22921946
ER
PT J
AU Cho, H
Kamenyeva, O
Yung, S
Gao, JL
Hwang, IY
Park, C
Murphy, PM
Neubig, RR
Kehrl, JH
AF Cho, Hyeseon
Kamenyeva, Olena
Yung, Sunny
Gao, Ji-Liang
Hwang, Il-Young
Park, Chung
Murphy, Philip M.
Neubig, Richard R.
Kehrl, John H.
TI The Loss of RGS Protein-G alpha(i2) Interactions Results in Markedly
Impaired Mouse Neutrophil Trafficking to Inflammatory Sites
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID STAPHYLOCOCCUS-AUREUS; CHEMOKINE RECEPTORS; SIGNAL-TRANSDUCTION;
BONE-MARROW; PROTEIN; CXCR2; INFECTION; MIGRATION; MICE; DESENSITIZATION
AB Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein G alpha(i) subunits to exchange GDP for GTP. By limiting the duration that G alpha(i) subunits remain GTP bound, RGS proteins modulate chemoattractant receptor signaling. Here, we show that neutrophils with a genomic knock in of a mutation that disables regulator of G-protein signaling (RGS)-G alpha(i2) interactions accumulate in the bone marrow and mobilize poorly to inflammatory sites. These defects are attributable to enhanced sensitivity to background signals, prolonged chemoattractant receptor signaling, and inappropriate CXCR2 downregulation. Intravital imaging revealed a failure of the mutant neutrophils to accumulate at and stabilize sites of sterile inflammation. Furthermore, these mice could not control a nonlethal Staphylococcus aureus infection. Neutrophil RGS proteins establish a threshold for G alpha(i) activation, helping to coordinate desensitization mechanisms. Their loss renders neutrophils functionally incompetent.
C1 [Cho, Hyeseon; Kamenyeva, Olena; Hwang, Il-Young; Park, Chung; Kehrl, John H.] NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Yung, Sunny; Gao, Ji-Liang; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Neubig, Richard R.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
RP Cho, H (reprint author), NIAID, Cell Mol Immunol Sect B, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM hcho@niaid.nih.gov; jkehrl@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX This research was supported by the intramural research program of the
National Institute of Allergy and Infectious Diseases.
NR 45
TC 17
Z9 17
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2012
VL 32
IS 22
BP 4561
EP 4571
DI 10.1128/MCB.00651-12
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 029ZA
UT WOS:000310536000006
PM 22966200
ER
PT J
AU Chrousos, GP
Licinio, J
Gold, PW
AF Chrousos, G. P.
Licinio, J.
Gold, P. W.
TI In memoriam: Wylie Walker Vale, Jr
SO MOLECULAR PSYCHIATRY
LA English
DT Biographical-Item
C1 [Chrousos, G. P.] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Chrousos, G. P.] Aghia Sophia Childrens Hosp, Athens, Greece.
[Chrousos, G. P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Licinio, J.] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
[Gold, P. W.] NIMH, Bethesda, MD 20892 USA.
RP Chrousos, GP (reprint author), Univ Athens, Sch Med, GR-11527 Athens, Greece.
EM chrousge@med.uoa.gr
RI Licinio, Julio/L-4244-2013
OI Licinio, Julio/0000-0001-6905-5884
NR 1
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 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2012
VL 17
IS 11
BP 1052
EP 1053
DI 10.1038/mp.2012.132
PG 2
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 030DQ
UT WOS:000310549600001
PM 23096955
ER
PT J
AU French, CA
Jin, X
Campbell, TG
Gerfen, E
Groszer, M
Fisher, SE
Costa, RM
AF French, C. A.
Jin, X.
Campbell, T. G.
Gerfen, E.
Groszer, M.
Fisher, S. E.
Costa, R. M.
TI An aetiological Foxp2 mutation causes aberrant striatal activity and
alters plasticity during skill learning
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE Foxp2; in vivo recording; KE family; motor-skill learning; speech and
language; striatum
ID LANGUAGE DISORDER; INHERITED SPEECH; BASAL GANGLIA; HUMAN BRAIN; GENE;
EXPRESSION; MICE; IDENTIFICATION; ABNORMALITIES; IMPAIRMENT
AB Mutations in the human FOXP2 gene cause impaired speech development and linguistic deficits, which have been best characterised in a large pedigree called the KE family. The encoded protein is highly conserved in many vertebrates and is expressed in homologous brain regions required for sensorimotor integration and motor-skill learning, in particular corticostriatal circuits. Independent studies in multiple species suggest that the striatum is a key site of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to investigate the effects of the KE-family mutation on the function of striatal circuits during motor-skill learning. We uncovered abnormally high ongoing striatal activity in mice carrying an identical mutation to that of the KE family. Furthermore, there were dramatic alterations in striatal plasticity during the acquisition of a motor skill, with most neurons in mutants showing negative modulation of firing rate, starkly contrasting with the predominantly positive modulation seen in control animals. We also observed striking changes in the temporal coordination of striatal firing during motor-skill learning in mutants. Our results indicate that FOXP2 is critical for the function of striatal circuits in vivo, which are important not only for speech but also for other striatal-dependent skills. Molecular Psychiatry (2012) 17, 1077-1085; doi: 10.1038/mp.2011.105; published online 30 August 2011
C1 [French, C. A.; Costa, R. M.] Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, P-2780901 Oeiras, Portugal.
[French, C. A.; Campbell, T. G.; Fisher, S. E.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Jin, X.; Gerfen, E.; Costa, R. M.] NIAAA, Sect Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD USA.
[Groszer, M.] Univ Paris 06, INSERM, UMR S839, Inst Fer Moulin, Paris, France.
[Fisher, S. E.] Max Planck Inst Psycholinguist, Dept Language & Genet, Nijmegen, Netherlands.
RP Costa, RM (reprint author), Inst Gulbenkian Ciencias, Champalimaud Neurosci Programme, Rua Quinta Grande 6, P-2780901 Oeiras, Portugal.
EM ruicosta@fchampalimaud.org
RI Fisher, Simon/E-9130-2012; Campbell, Thomas/A-6964-2014; Campbell,
Thomas/C-2498-2014;
OI Fisher, Simon/0000-0002-3132-1996; Campbell, Thomas/0000-0002-4508-0089;
Campbell, Thomas/0000-0002-4508-0089; French,
Catherine/0000-0003-2072-8413; Costa, Rui/0000-0003-0495-8374
FU Human Frontier Science Program short-term fellowship; Royal Society
Research Fellowship; Wellcome Trust [075491/Z/04, 080971]; Division of
Intramural Clinical and Basic Research of the National Institute on
Alcohol Abuse and Alcoholism, US National Institutes of Health;
Champalimaud Neuroscience Programme; European Research Council [STG
243393]; Max Planck Society
FX We thank Sonali Darbar, Rathi Puliyadi, Terrell D Holloway and Amber Luo
for excellent technical assistance; John Burkhardt and Shih-Chieh Lin
for help with Matlab; Emma Doran for running the operant learning task;
and the staffs of the British Heart Foundation Functional Genetics
Facility and the NIAAA vivarium for mouse husbandry. This work was
supported by a Human Frontier Science Program short-term fellowship (to
CAF); a Royal Society Research Fellowship (to SEF); the Wellcome Trust
(075491/Z/04; 080971); the Division of Intramural Clinical and Basic
Research of the National Institute on Alcohol Abuse and Alcoholism, US
National Institutes of Health; the Champalimaud Neuroscience Programme;
the European Research Council (STG 243393); and the Max Planck Society.
NR 35
TC 36
Z9 36
U1 3
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2012
VL 17
IS 11
BP 1077
EP 1085
DI 10.1038/mp.2011.105
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 030DQ
UT WOS:000310549600004
PM 21876543
ER
PT J
AU Nguyen, LS
Jolly, L
Shoubridge, C
Chan, WK
Huang, L
Laumonnier, F
Raynaud, M
Hackett, A
Field, M
Rodriguez, J
Srivastava, AK
Lee, Y
Long, R
Addington, AM
Rapoport, JL
Suren, S
Hahn, CN
Gamble, J
Wilkinson, MF
Corbett, MA
Gecz, J
AF Nguyen, L. S.
Jolly, L.
Shoubridge, C.
Chan, W. K.
Huang, L.
Laumonnier, F.
Raynaud, M.
Hackett, A.
Field, M.
Rodriguez, J.
Srivastava, A. K.
Lee, Y.
Long, R.
Addington, A. M.
Rapoport, J. L.
Suren, S.
Hahn, C. N.
Gamble, J.
Wilkinson, M. F.
Corbett, M. A.
Gecz, J.
TI Transcriptome profiling of UPF3B/NMD-deficient lymphoblastoid cells from
patients with various forms of intellectual disability
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE intellectual disability; Nonsense-mediated mRNA decay; RNA-SEQ; UPF3A;
UPF3B
ID MESSENGER-RNA DECAY; EXON-JUNCTION COMPLEX; MENTAL-RETARDATION;
GENE-EXPRESSION; FILAMIN-A; MUTATIONS; UPF1; NMD; SURVEILLANCE;
COMPONENTS
AB The nonsense-mediated mRNA decay (NMD) pathway was originally discovered by virtue of its ability to rapidly degrade aberrant mRNAs with premature termination codons. More recently, it was shown that NMD also directly regulates subsets of normal transcripts, suggesting that NMD has roles in normal biological processes. Indeed, several NMD factors have been shown to regulate neurological events (for example, neurogenesis and synaptic plasticity) in numerous vertebrate species. In man, mutations in the NMD factor gene UPF3B, which disrupts a branch of the NMD pathway, cause various forms of intellectual disability (ID). Using Epstein Barr virus-immortalized B cells, also known as lymphoblastoid cell lines (LCLs), from ID patients that have loss-of-function mutations in UPF3B, we investigated the genome-wide consequences of compromised NMD and the role of NMD in neuronal development and function. We found that similar to 5% of the human transcriptome is impacted in UPF3B patients. The UPF3B paralog, UPF3A, is stabilized in all UPF3B patients, and partially compensates for the loss of UPF3B function. Interestingly, UPF3A protein, but not mRNA, was stabilised in a quantitative manner that inversely correlated with the severity of patients' phenotype. This suggested that the ability to stabilize the UPF3A protein is a crucial modifier of the neurological symptoms due to loss of UPF3B. We also identified ARHGAP24, which encodes a GTPase-activating protein, as a canonical target of NMD, and we provide evidence that deregulation of this gene inhibits axon and dendrite outgrowth and branching. Our results demonstrate that the UPF3B-dependent NMD pathway is a major regulator of the transcriptome and that its targets have important roles in neuronal cells. Molecular Psychiatry (2012) 17, 1103-1115; doi: 10.1038/mp.2011.163; published online 20 December 2011
C1 [Nguyen, L. S.; Jolly, L.; Shoubridge, C.; Corbett, M. A.; Gecz, J.] SA Pathol, Dept Med Genet, Adelaide, SA, Australia.
[Nguyen, L. S.; Shoubridge, C.; Gecz, J.] Univ Adelaide, Dept Paediat, Adelaide, SA, Australia.
[Chan, W. K.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA.
[Huang, L.; Wilkinson, M. F.] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA.
[Laumonnier, F.; Raynaud, M.] INSERM, U930, Tours, France.
[Laumonnier, F.] CNRS, ERL3106, Tours, France.
[Laumonnier, F.; Raynaud, M.] Univ Tours, UMR Imaging & Brain, Tours, France.
[Raynaud, M.] CHRU Tours, Serv Genet, Tours, France.
[Hackett, A.; Field, M.] GOLD Serv, Newcastle, NSW, Australia.
[Rodriguez, J.; Srivastava, A. K.] Greenwood Genet Ctr, JC Self Res Inst, Greenwood, SC 29646 USA.
[Lee, Y.; Long, R.; Addington, A. M.; Rapoport, J. L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA.
[Suren, S.] UCL Inst Child Hlth, Neural Dev Unit, London, England.
[Hahn, C. N.] SA Pathol, Dept Mol Pathol, Ctr Canc Biol, Adelaide, SA, Australia.
[Gamble, J.] Univ Sydney, Centenary Inst Canc Med & Cell Biol, Sydney, NSW 2006, Australia.
RP Gecz, J (reprint author), Womens & Childrens Hosp, Dept Genet Med, SA Pathol, 72 King William Rd, Adelaide, SA 5006, Australia.
EM jozef.gecz@adelaide.edu.au
RI Jolly, Lachlan/B-5892-2015; Shoubridge, Cheryl/A-1571-2016; Laumonnier,
Frederic/N-1165-2016
OI Jolly, Lachlan/0000-0003-4538-2658; Gecz, Jozef/0000-0002-7884-6861;
Shoubridge, Cheryl/0000-0002-0157-3084; Laumonnier,
Frederic/0000-0003-2567-0708
FU Australian NHMRC Project [453457]; Women's and Children's Hospital
Foundation; NH&MRC Principal Research Fellowship; MS McLeod Foundation
FX We thank the members of the families studied for participation and
Brigitte Jauffrion and Lucianne Vandeleur for help with cell culture.
This work was supported by grants from the Australian NH&MRC Project
Grant 453457 to JoG, and the Women's and Children's Hospital Foundation
Grant to LJ and JoG. JoG is supported by NH&MRC Principal Research
Fellowship. LSN's PhD scholarship was supported by the MS McLeod
Foundation.
NR 62
TC 28
Z9 28
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2012
VL 17
IS 11
BP 1103
EP 1115
DI 10.1038/mp.2011.163
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 030DQ
UT WOS:000310549600007
PM 22182939
ER
PT J
AU Amin, N
Byrne, E
Johnson, J
Chenevix-Trench, G
Walter, S
Nolte, IM
Vink, JM
Rawal, R
Mangino, M
Teumer, A
Keers, JC
Verwoert, G
Baumeister, S
Biffar, R
Petersmann, A
Dahmen, N
Doering, A
Isaacs, A
Broer, L
Wray, NR
Montgomery, GW
Levy, D
Psaty, BM
Gudnason, V
Chakravarti, A
Sulem, P
Gudbjartsson, DF
Kiemeney, LA
Thorsteinsdottir, U
Stefansson, K
Van Rooij, FJA
Aulchenko, YS
Hottenga, JJ
Rivadeneira, FR
Hofman, A
Uitterlinden, AG
Hammond, CJ
Shin, SY
Ikram, A
Witteman, JCM
Janssens, ACJW
Snieder, H
Tiemeier, H
Wolfenbuttel, BHR
Oostra, BA
Heath, AC
Wichmann, E
Spector, TD
Grabe, HJ
Boomsma, DI
Martin, NG
Van Duijn, CM
AF Amin, N.
Byrne, E.
Johnson, J.
Chenevix-Trench, G.
Walter, S.
Nolte, I. M.
Vink, J. M.
Rawal, R.
Mangino, M.
Teumer, A.
Keers, J. C.
Verwoert, G.
Baumeister, S.
Biffar, R.
Petersmann, A.
Dahmen, N.
Doering, A.
Isaacs, A.
Broer, L.
Wray, N. R.
Montgomery, G. W.
Levy, D.
Psaty, B. M.
Gudnason, V.
Chakravarti, A.
Sulem, P.
Gudbjartsson, D. F.
Kiemeney, L. A.
Thorsteinsdottir, U.
Stefansson, K.
Van Rooij, F. J. A.
Aulchenko, Y. S.
Hottenga, J. J.
Rivadeneira, F. R.
Hofman, A.
Uitterlinden, A. G.
Hammond, C. J.
Shin, S-Y
Ikram, A.
Witteman, J. C. M.
Janssens, A. C. J. W.
Snieder, H.
Tiemeier, H.
Wolfenbuttel, B. H. R.
Oostra, B. A.
Heath, A. C.
Wichmann, E.
Spector, T. D.
Grabe, H. J.
Boomsma, D. I.
Martin, N. G.
Van Duijn, C. M.
CA kConFab Investigators
TI Genome-wide association analysis of coffee drinking suggests association
with CYP1A1/CYP1A2 and NRCAM
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE coffee; P450; NRCAM; CAB39L; Parkinson's disease; CYP1A1/CYP1A2
ID TYPE-2 DIABETES-MELLITUS; AGED FINNISH MEN; PSYCHOMOTOR PERFORMANCE;
PARKINSONS-DISEASE; CYP1A2 GENOTYPE; GENE-EXPRESSION; BLOOD-PRESSURE;
MESSENGER-RNA; HUMAN BRAIN; CAFFEINE CONSUMPTION
AB Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N = 18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values = 1.6 x 10(-11) and 2.7 x 10(-11)), which were also in strong linkage disequilibrium (r(2) = 0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value = 3.9 x 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value = 7.1 x 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value = 2.2 x 10(-05)) and Parkinson's disease pathways (P-value = 3.6 x 10(-05)). Molecular Psychiatry (2012) 17, 1116-1129; doi: 10.1038/mp.2011.101; published online 30 August 2011
C1 [Amin, N.; Isaacs, A.; Broer, L.; Aulchenko, Y. S.; Oostra, B. A.; Van Duijn, C. M.] Erasmus MC, Dept Epidemiol, Unit Genet Epidemiol, NL-3015 GE Rotterdam, Netherlands.
[Byrne, E.; Johnson, J.; Chenevix-Trench, G.; Wray, N. R.; Montgomery, G. W.; Martin, N. G.] Queensland Inst Med Res, Dept Genet, Brisbane, Qld 4006, Australia.
[Walter, S.; Van Rooij, F. J. A.] Erasmus MC, Dept Publ Hlth, NL-3015 GE Rotterdam, Netherlands.
[Nolte, I. M.; Snieder, H.] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, Groningen, Netherlands.
[kConFab Investigators] Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia.
[Vink, J. M.; Hottenga, J. J.; Boomsma, D. I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Rawal, R.; Doering, A.; Wichmann, E.] Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany.
[Mangino, M.; Spector, T. D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Teumer, A.] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany.
[Keers, J. C.; Snieder, H.; Wolfenbuttel, B. H. R.] Univ Med Ctr Groningen, Univ Groningen, LifeLines Cohort Study, Groningen, Netherlands.
[Keers, J. C.; Snieder, H.; Wolfenbuttel, B. H. R.] Univ Med Ctr Groningen, Univ Groningen, Biobank, Groningen, Netherlands.
[Baumeister, S.] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
[Biffar, R.] Ernst Moritz Arndt Univ Greifswald, Ctr Oral Hlth, Dept Prosthodont Gerodontol & Dent Mat, Greifswald, Germany.
[Petersmann, A.] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Dahmen, N.] Johannes Gutenberg Univ Mainz, Dept Psychiat, D-6500 Mainz, Germany.
[Levy, D.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Levy, D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA.
[Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, B. M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, B. M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Chakravarti, A.] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Chakravarti, A.] Johns Hopkins Univ, Dept Epidemiol & Med, Baltimore, MD USA.
[Sulem, P.; Gudbjartsson, D. F.; Thorsteinsdottir, U.; Stefansson, K.] deCODE Genet, Reykjavik, Iceland.
[Kiemeney, L. A.] Radboud Univ Nijmegen, Dept Urol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, L. A.] Radboud Univ Nijmegen, Dept Endocrinol, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Kiemeney, L. A.] BG Nijmegen, Comprehens Canc Ctr E, Nijmegen, Netherlands.
[Thorsteinsdottir, U.; Stefansson, K.] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Rivadeneira, F. R.; Uitterlinden, A. G.] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands.
[Hammond, C. J.; Shin, S-Y] Wellcome Trust Sanger Inst, Hinxton, England.
[Tiemeier, H.] Erasmus Univ, Med Ctr, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands.
[Wolfenbuttel, B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Oostra, B. A.] Erasmus Univ, Dept Clin Studies, Med Ctr, Rotterdam, Netherlands.
[Heath, A. C.] Washington Univ, Dept Psychiat, St Louis, MI USA.
[Wichmann, E.] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany.
[Grabe, H. J.] Ernst Moritz Arndt Univ Greifswald, Dept Psychiat & Psychotherapy, Stralsund, Germany.
[Van Duijn, C. M.] Netherlands Consortium Hlth Aging, Ctr Med Syst Biol, Leiden, Netherlands.
[Van Duijn, C. M.] Natl Genom Initiat, The Hague, Netherlands.
RP Van Duijn, CM (reprint author), Erasmus MC, Dept Epidemiol, Unit Genet Epidemiol, Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands.
EM c.vanduijn@erasmusmc.nl
RI Wolffenbuttel, Bruce/A-8419-2011; Aulchenko, Yurii/M-8270-2013;
Kiemeney, Lambertus/D-3357-2009; Wray, Naomi/C-8639-2015; Gudnason,
Vilmundur/K-6885-2015; janssens, cecile/L-1075-2015; Montgomery,
Grant/B-7148-2008; mangino, massimo/F-5134-2011;
OI Ikram, Mohammad Arfan/0000-0003-0372-8585; Tiemeier,
Henning/0000-0002-4395-1397; Rivadeneira, Fernando/0000-0001-9435-9441;
Hammond, Christopher/0000-0002-3227-2620; Martin,
Nicholas/0000-0003-4069-8020; Wolffenbuttel, Bruce/0000-0001-9262-6921;
Aulchenko, Yurii/0000-0002-7899-1575; Kiemeney,
Lambertus/0000-0002-2368-1326; Wray, Naomi/0000-0001-7421-3357;
Gudnason, Vilmundur/0000-0001-5696-0084; Montgomery,
Grant/0000-0002-4140-8139; mangino, massimo/0000-0002-2167-7470;
Janssens, A Cecile/0000-0002-6153-4976
FU EUROSPAN (European Special Populations Research Network); European
Commission [018947, LSHG-CT-2006-01947]; Netherlands Organization for
Scientific Research; Erasmus MC; Centre for Medical Systems Biology
(CMSB); Netherlands Brain Foundation (HersenStichting Nederland);
Helmholtz Zentrum Munchen, German Research Center for Environmental
Health, Neuherberg, Germany; German Federal Ministry of Education and
Research (BMBF); German National Genome Research Network (NGFN); Munich
Center of Health Sciences (MC Health) as part of LMUinnovativ; Genetic
basis of anxiety and depression [904-61-090]; Twin-family database for
behavior genomics studies [480-04-004]; ZonMW [31160008]; Center for
Medical Systems Biology (NWO Genomics); Spinozapremie [SPI
56-464-14192]; Neuroscience campus Amsterdam (NCA-VU); Genetics of
Mental Illness [ERC 230374]; Genetic Association Information Network
(GAIN) of the Foundation for the US National Institutes of Health; NWO
[VENI 451-06-004]; National Breast Cancer Foundation and Cancer
Australia [628333]; National Breast Cancer Foundation; National Health
and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia;
Cancer Foundation of Western Australia; Australian National Health and
Medical Research Council [241944, 339462, 389927, 389875, 389891,
389892, 389938, 442915, 442981, 496739, 552485, 552498]; Australian
Research Council [A7960034, A79906588, A79801419, DP0770096, DP0212016,
DP0343921]; FP-5 GenomEUtwin Project [QLG2-CT-2002-01254]; US National
Institutes of Health (NIH) [AA07535, AA10248, AA13320, AA13321, AA13326,
AA14041, MH66206]; Netherlands Scientific Organization [NWO 480-05-003];
Cancer Council Queensland; Erasmus Medical Center and Erasmus University
Rotterdam; Netherlands Organization for Scientific Research (NWO);
Netherlands Organization for Health Research and Development (ZonMw);
Research Institute for Diseases in the Elderly (RIDE); Netherlands
Genomics Initiative; Ministry of Education, Culture and Science;
Ministry of Health, Welfare and Sports; European Commission (DG XII);
Municipality of Rotterdam; Internationaal Parkinson Fonds; Federal
Ministry of Education and Research [01ZZ9603, 01ZZ0103, 01ZZ0403,
03ZIK012]; Ministry of Cultural Affairs; Social Ministry of the Federal
State of Mecklenburg-West Pomerania; Siemens Healthcare, Erlangen,
Germany; Federal State of Mecklenburg, West Pomerania; German Research
Foundation; Federal Ministry of Education and Research Germany;
JanssenCilag; Lundbeck; Eli Lilly; Novartis; AstraZeneca;
SALUS-Institute for Trend-Research and Therapy Evaluation in Mental
Health; Wellcome Trust; European Community [HEALTH-F2-2008-201865-GEFOS,
HEALTH-F4-2007-201413]; Department of Health through the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre; Biotechnology and Biological Sciences Research Council (BBSRC)
[G20234]; National Eye Institute through an NIH/CIDR; Netherlands
Organization of Scientific Research NWO [175.010.2007.006]; Economic
Structure Enhancing Fund (FES) of the Dutch government; Ministry of
Economic Affairs; Ministry for Health, Welfare and Sports; Northern
Netherlands Collaboration of Provinces (SNN); Province of Groningen;
University Medical Center Groningen; University of Groningen; Dutch
Kidney Foundation; Dutch Diabetes Research Foundation
FX ERF: The genotyping for the ERF study was supported by EUROSPAN
(European Special Populations Research Network) and the European
Commission FP6 STRP grant (018947; LSHG-CT-2006-01947). The ERF study
was further supported by grants from the Netherlands Organization for
Scientific Research, Erasmus MC, the Centre for Medical Systems Biology
(CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland).
We are grateful to all patients and their relatives, general
practitioners and neurologists for their contributions and to P Veraart
for her help in genealogy, Jeannette Vergeer for the supervision of the
laboratory work and P Snijders for his help in data collection. We
acknowledge Internationale Stichting Alzheimer Onderzoek (ISAO) and
Hersenstichting Netherlands. KORA: The KORA Augsburg studies were
financed by the Helmholtz Zentrum Munchen, German Research Center for
Environmental Health, Neuherberg, Germany, and supported by grants from
the German Federal Ministry of Education and Research (BMBF). Part of
this work was financed by the German National Genome Research Network
(NGFN). Our research was supported within the Munich Center of Health
Sciences (MC Health) as part of LMUinnovativ. Netherlands Twin
Register(NTR): We acknowledge support from: Genetic basis of anxiety and
depression (904-61-090); Twin-family database for behavior genomics
studies (480-04-004); Genetic determinants of risk behavior in relation
to alcohol use and alcohol use disorder: a developmental perspective
(ZonMW Addiction 31160008), Center for Medical Systems Biology (NWO
Genomics); Spinozapremie (SPI 56-464-14192); Neuroscience campus
Amsterdam (NCA-VU); and Genetics of Mental Illness (ERC 230374).
Genotyping was funded in part by the Genetic Association Information
Network (GAIN) of the Foundation for the US National Institutes of
Health. JMV is financially supported by NWO (VENI 451-06-004). QIMR: We
thank Heather Thorne, Eveline Niedermayr, all the kConFab research
nurses and staff, the heads and staff of the Family Cancer Clinics, as
well as the Clinical Follow-Up Study (funded 2001-2009 by NHMRC and
currently by the National Breast Cancer Foundation and Cancer Australia
no. 628333) for their contributions to this resource, and the many
families who contribute to kConFab. kConFab is supported by grants from
the National Breast Cancer Foundation, the National Health and Medical
Research Council (NHMRC) and by the Queensland Cancer Fund, the Cancer
Councils of New South Wales, Victoria, Tasmania and South Australia, and
the Cancer Foundation of Western Australia. We thank the twins and their
families for their participation. We also thank Ann Eldridge, Marlene
Grace, Kerrie McAloney (sample collection); Lisa Bowdler, Steven Crooks
(DNA processing); Dale Nyholt, Sarah Medland and Scott Gordon
(imputation and genotyping QC); Allan McRae and Peter Visscher for
helpful advice and input. Funding was provided by the Australian
National Health and Medical Research Council (241944, 339462, 389927,
389875, 389891, 389892, 389938, 442915, 442981, 496739, 552485, 552498),
the Australian Research Council (A7960034, A79906588, A79801419,
DP0770096, DP0212016, DP0343921), the FP-5 GenomEUtwin Project
(QLG2-CT-2002-01254) and the US National Institutes of Health (NIH
grants AA07535, AA10248, AA13320, AA13321, AA13326, AA14041, MH66206).;
A portion of the genotyping on which this study was based (Illumina 370K
scans on 4300 individuals) was carried out at the Center for Inherited
Disease Research, Baltimore (CIDR), through an access award to our late
colleague Dr Richard Todd (Psychiatry, Washington University School of
Medicine, St Louis). Statistical analyses were carried out on the
Genetic Cluster Computer, which is financially supported by the
Netherlands Scientific Organization (NWO 480-05-003). GWM and GCTare
supported by the National Health and Medical Research Council (NHMRC)
Fellowship Scheme. JJ was financially supported by the Cancer Council
Queensland. Rotterdam Study (RS-I and RS-II): 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 Genomics Initiative, the Ministry of Education, Culture and
Science, the Ministry of Health, Welfare and Sports, the European
Commission (DG XII) and the Municipality of Rotterdam. The contribution
of inhabitants, general practitioners and pharmacists of the Ommoord
district to the Rotterdam Study is gratefully acknowledged. AI was
financially supported by the Internationaal Parkinson Fonds. The Study
of Health in Pomerania (SHIP): SHIP is part of the Community Medicine
Research net of the University of Greifswald, Germany, which is funded
by the Federal Ministry of Education and Research (grants nos 01ZZ9603,
01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, as well as the
Social Ministry of the Federal State of Mecklenburg-West Pomerania.
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 the Federal State of
Mecklenburg, West Pomerania. The University of Greifswald is a member of
the 'Center of Knowledge Interchange' program of the Siemens AG. HJG was
supported by the German Research Foundation; the Federal Ministry of
Education and Research Germany; speakers honoraria from Bristol-Myers
Squibb, Eli Lilly, Novartis, Eisai, Wyeth, Pfizer, Boehringer Ingelheim,
Servier and travel funds from JanssenCilag, Lundbeck, Eli Lilly,
Novartis, AstraZeneca and SALUS-Institute for Trend-Research and Therapy
Evaluation in Mental Health. Twins UK: The study was funded by the
Wellcome Trust; European Community's Seventh Framework Programme
(FP7/20072013)/grant agreement HEALTH-F2-2008-201865-GEFOS and
(FP7/2007-2013), ENGAGE project grant agreement HEALTH-F4-2007-201413
and the FP-5 GenomEUtwin Project (QLG2-CT-2002-01254). The study also
receives support from the Department of Health through the National
Institute for Health Research (NIHR) comprehensive Biomedical Research
Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership
with King's College London. TDS is an NIHR senior Investigator. The
project also received support from a Biotechnology and Biological
Sciences Research Council (BBSRC) project grant. (G20234). We
acknowledge the funding and support of the National Eye Institute
through an NIH/CIDR genotyping project (PI: Terri Young)'.; We thank the
staff from the Genotyping Facilities at the Wellcome Trust Sanger
Institute for sample preparation, Quality Control and Genotyping led by
Leena Peltonen and Panos Deloukas; Le Centre National de Genotypage,
France, led by Mark Lathrop, for genotyping; Duke University, NC, USA,
led by David Goldstein, for genotyping; and the Finnish Institute of
Molecular Medicine, Finnish Genome Center, University of Helsinki, led
by Aarno Palotie. LifeLines: The LifeLines Cohort Study, and generation
and management of GWAS genotype data for the LifeLines Cohort Study is
supported by the Netherlands Organization of Scientific Research NWO
(grant 175.010.2007.006), the Economic Structure Enhancing Fund (FES) of
the Dutch government, the Ministry of Economic Affairs, the Ministry of
Education, Culture and Science, the Ministry for Health, Welfare and
Sports, the Northern Netherlands Collaboration of Provinces (SNN), the
Province of Groningen, University Medical Center Groningen, the
University of Groningen, Dutch Kidney Foundation and Dutch Diabetes
Research Foundation. We thank Behrooz Alizadeh, Annemieke Boesjes,
Marcel Bruinenberg, Noortje Festen, Ilja Nolte, Lude Franke and Mitra
Valimohammadi for their help in creating the GWAS database, and Rob
Bieringa, Joost Keers, Rene Oostergo, Rosalie Visser and Judith Vonk for
their work related to data-collection and validation. We are grateful to
the study participants, the staff from the LifeLines Cohort Study and
Medical Biobank Northern Netherlands, and the participating general
practitioners and pharmacists.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2012
VL 17
IS 11
BP 1116
EP 1129
DI 10.1038/mp.2011.101
PG 14
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 030DQ
UT WOS:000310549600008
PM 21876539
ER
PT J
AU Guilloux, JP
Douillard-Guilloux, G
Kota, R
Wang, X
Gardier, AM
Martinowich, K
Tseng, GC
Lewis, DA
Sibille, E
AF Guilloux, J-P
Douillard-Guilloux, G.
Kota, R.
Wang, X.
Gardier, A. M.
Martinowich, K.
Tseng, G. C.
Lewis, D. A.
Sibille, E.
TI Molecular evidence for BDNF- and GABA-related dysfunctions in the
amygdala of female subjects with major depression
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE major depression; female; amygdala; BDNF; GABA; somatostatin;
neurotrophic hypothesis
ID NEUROTROPHIC FACTOR EXPRESSION; DORSOLATERAL PREFRONTAL CORTEX;
GAMMA-AMINOBUTYRIC-ACID; GENE-EXPRESSION; ANTIDEPRESSANT MEDICATIONS;
HIPPOCAMPAL VOLUME; GENDER-DIFFERENCES; BIPOLAR DISORDER; SUICIDE
SUBJECTS; MOOD DISORDERS
AB Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the post-mortem brain of MDD subjects paired with matched controls (n = 21 pairs). We focused on the lateral/basolateral/basomedian complex of the amygdala as a neural hub of mood regulation affected in MDD. Among the most robust findings were downregulated transcripts for genes coding for gamma-aminobutyric acid (GABA) interneuron-related peptides, including somatostatin (SST), tachykinin, neuropeptide Y (NPY) and cortistatin, in a pattern reminiscent to that previously reported in mice with low brain-derived neurotrophic factor (BDNF). Changes were confirmed by quantitative PCR and not explained by demographic, technical or known clinical parameters. BDNF itself was significantly downregulated at the RNA and protein levels in MDD subjects. Investigating putative mechanisms, we show that this core MDD-related gene profile (including SST, NPY, TAC1, RGS4 and CORT) is recapitulated by complementary patterns in mice with constitutive (BDNF-heterozygous) or activity-dependent (exon IV knockout) decreases in BDNF function, with a common effect on SST and NPY. Together, these results provide both direct (low RNA/protein) and indirect (low BDNF-dependent gene pattern) evidence for reduced BDNF function in the amygdala of female subjects with MDD. Supporting studies in mutant mice models suggest a complex mechanism of low constitutive and activity-dependent BDNF function in MDD, particularly affecting SST/NPY-related GABA neurons, thus linking the neurotrophic and GABA hypotheses of depression. Molecular Psychiatry (2012) 17, 1130-1142; doi: 10.1038/mp.2011.113; published online 13 September 2011
C1 [Guilloux, J-P; Douillard-Guilloux, G.; Kota, R.; Lewis, D. A.; Sibille, E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15312 USA.
[Guilloux, J-P; Gardier, A. M.] Univ Paris Sud, EA 3544, Fac Pharm, Chatenay Malabry, France.
[Wang, X.; Tseng, G. C.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15312 USA.
[Martinowich, K.] NIMH, Genes Cognit & Psychosis Program GCAP, Bethesda, MD 20892 USA.
[Lewis, D. A.; Sibille, E.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15312 USA.
RP Sibille, E (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 OHara St,BST W1643, Pittsburgh, PA 15312 USA.
EM sibilleel@upmc.edu
RI Lewis, David/G-4053-2014; Guilloux, Jean-Philippe/B-3726-2015;
Martinowich, Keri/F-9841-2012;
OI Lewis, David/0000-0002-3225-6778; Guilloux,
Jean-Philippe/0000-0003-0982-3751; Martinowich, Keri/0000-0002-5237-0789
FU BMS Foundation; Bristol-Myers Squibb; Curridium; Pfizer; National
Institute of Mental Health (NIMH) [MH084060, MH085111, MH084053]
FX David A Lewis currently receives investigator-initiated research support
from the BMS Foundation, Bristol-Myers Squibb, Curridium and Pfizer and
in 2008-2010 served as a consultant in the areas of target
identification and validation and new compound development to
AstraZeneca, BioLine RX, Bristol-Myers Squibb, Merck, Neurogen and SK
Life Science.; This work was supported by National Institute of Mental
Health (NIMH) MH084060 (ES), MH085111 (ES) and MH084053 (DAL). The
funding agency had no role in the study design, data collection and
analysis, decision to publish and preparation of the paper. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the NIMH or the National Institutes of
Health.
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PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2012
VL 17
IS 11
BP 1130
EP 1142
DI 10.1038/mp.2011.113
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 030DQ
UT WOS:000310549600009
PM 21912391
ER
PT J
AU Riazuddin, S
Belyantseva, IA
Giese, APJ
Lee, K
Indzhykulian, AA
Nandamuri, P
Yousaf, R
Sinha, GP
Lee, S
Terrell, D
Hegde, RS
Ali, RA
Anwar, S
Andrade-Elizondo, PB
Sirmaci, A
Parise, LV
Basit, S
Wali, A
Ayub, M
Ansar, M
Ahmad, W
Khan, SN
Akram, J
Tekin, M
Riazuddin, S
Cook, T
Buschbeck, EK
Frolenkov, GI
Leal, SM
Friedman, TB
Ahmed, ZM
AF Riazuddin, Saima
Belyantseva, Inna A.
Giese, Arnaud P. J.
Lee, Kwanghyuk
Indzhykulian, Artur A.
Nandamuri, Pratima
Yousaf, Rizwan
Sinha, Ghanshyam P.
Lee, Sue
Terrell, David
Hegde, Rashmi S.
Ali, Rana A.
Anwar, Saima
Andrade-Elizondo, Paula B.
Sirmaci, Asli
Parise, Leslie V.
Basit, Sulman
Wali, Abdul
Ayub, Muhammad
Ansar, Muhammad
Ahmad, Wasim
Khan, Shaheen N.
Akram, Javed
Tekin, Mustafa
Riazuddin, Sheikh
Cook, Tiffany
Buschbeck, Elke K.
Frolenkov, Gregory I.
Leal, Suzanne M.
Friedman, Thomas B.
Ahmed, Zubair M.
TI Alterations of the CIB2 calcium- and integrin-binding protein cause
Usher syndrome type 1J and nonsyndromic deafness DFNB48
SO NATURE GENETICS
LA English
DT Article
ID OUTER HAIR-CELLS; CA2+ RELEASE; BULLFROGS SACCULUS; BUFFERING PROTEINS;
LOCALIZATION; STEREOCILIA; ADAPTATION; DROSOPHILA; ZEBRAFISH; CHANNELS
AB Sensorineural hearing loss is genetically heterogeneous. Here, we report that mutations in CIB2, which encodes a calcium- and integrin-binding protein, are associated with nonsyndromic deafness (DFNB48) and Usher syndrome type 11 (USH1J). One mutation in CIB2 is a prevalent cause of deafness DFNB48 in Pakistan; other CIB2 mutations contribute to deafness elsewhere in the world. In mice, CIB2 is localized to the mechanosensory stereocilia of inner ear hair cells and to retinal photoreceptor and pigmented epithelium cells. Consistent with molecular modeling predictions of calcium binding, CIB2 significantly decreased the ATP-induced calcium responses in heterologous cells, whereas mutations in deafness DFNB48 altered CIB2 effects on calcium responses. Furthermore, in zebrafish and Drosophila melanogaster, CIB2 is essential for the function and proper development of hair cells and retinal photoreceptor cells. We also show that CIB2 is a new member of the vertebrate Usher interactome.
C1 [Riazuddin, Saima; Giese, Arnaud P. J.; Yousaf, Rizwan; Ahmed, Zubair M.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA.
[Riazuddin, Saima; Giese, Arnaud P. J.; Terrell, David; Cook, Tiffany; Ahmed, Zubair M.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Ophthalmol, Cincinnati, OH USA.
[Riazuddin, Saima; Ahmed, Zubair M.] Univ Cincinnati, Coll Med, Dept Otolaryngol, Cincinnati, OH USA.
[Riazuddin, Saima; Cook, Tiffany; Ahmed, Zubair M.] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati, OH USA.
[Belyantseva, Inna A.; Lee, Sue; Friedman, Thomas B.] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD USA.
[Lee, Kwanghyuk; Andrade-Elizondo, Paula B.; Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Indzhykulian, Artur A.; Sinha, Ghanshyam P.; Frolenkov, Gregory I.] Univ Kentucky, Dept Physiol, Lexington, KY USA.
[Nandamuri, Pratima; Buschbeck, Elke K.] Univ Cincinnati, Dept Biol Sci, McMicken Coll Arts & Sci, Cincinnati, OH 45221 USA.
[Yousaf, Rizwan; Ali, Rana A.; Anwar, Saima; Khan, Shaheen N.] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Hegde, Rashmi S.; Cook, Tiffany] Cincinnati Childrens Hosp Med Ctr, Div Dev Biol, Cincinnati, OH USA.
[Sirmaci, Asli; Tekin, Mustafa] Univ Miami, Miller Sch Med, Dept Human Genet, Miami, FL 33136 USA.
[Parise, Leslie V.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA.
[Basit, Sulman; Ansar, Muhammad; Ahmad, Wasim] Quaid I Azam Univ, Fac Biol Sci, Dept Biochem, Islamabad, Pakistan.
[Wali, Abdul] Baluchistan Univ Informat Technol, Inst Biotechnol, Quetta, Pakistan.
[Ayub, Muhammad] Univ Baluchistan, Inst Biochem, Quetta, Pakistan.
[Akram, Javed; Riazuddin, Sheikh] Allama Iqbal Med Coll, Lahore, Pakistan.
[Riazuddin, Sheikh] Univ Lahore, Lahore, Pakistan.
[Ahmed, Zubair M.] Bahauddin Zakariya Univ, Inst Mol Biol & Biotechnol, Multan, Pakistan.
RP Ahmed, ZM (reprint author), Cincinnati Childrens Hosp Med Ctr, Div Pediat Otolaryngol Head & Neck Surg, Cincinnati, OH USA.
EM zubair.ahmed@cchmc.org
RI Basit, Sulman/B-2947-2013; Nasim Khan, Shaheen/F-2135-2015; Ansar,
Muhammad/F-4808-2015; Ahmad, Wasim/E-9713-2015; Basit,
Sulman/F-6395-2015; Anwar, Saima/C-7477-2016; Ansar,
Muhammad/H-5967-2011;
OI Ansar, Muhammad/0000-0001-5891-7063; Indzhykulian,
Artur/0000-0002-2076-6818; Lee, Kwanghyuk/0000-0001-7781-9696; Cook,
Tiffany/0000-0002-3100-5248; Frolenkov, Gregory/0000-0002-9810-5024;
Basit, Sulman/0000-0003-4294-6825
FU US National Institutes of Health (NIH) [N01-HG-65403]; Research to
Prevent Blindness; Higher Education Commission (Islamabad, Pakistan);
Ministry of Science and Technology (Islamabad, Pakistan); International
Center for Genetic Engineering and Biotechnology (Trieste, Italy)
[08/009]; Cincinnati Children's Hospital Research Foundation (CCHMC);
National Science Foundation [IOS-1050754]; US National Institute on
Deafness and Other Communication Disorders (NIDCD/NIH) [R01 DC03594,
DC011651, R01 HL092544, R01 DC009645, R01 DC008861, R01 DC012564, R00
DC009287, R01 DC011803, R01 DC011748]; NIDCD [DC000039-15]
FX We thank the families for their participation and cooperation. We also
thank G.N. Sarangdhar, R. Rachel, T. Jaworek, V. Ponferrada and K. Gul
for technical assistance and R.J. Morell, J. Schultz, D. Drayna, A.
Swaroop and A.J. Griffith for critique of the manuscript. We thank T.M.
Leisner (University of North Carolina at Chapel Hill) for the generous
gift of antibodies to CIB. Genotyping services were provided to S.M.L.
by the Center for Inherited Disease Research (CIDR). CIDR is fully
funded through a federal contract (N01-HG-65403) from the US National
Institutes of Health (NIH) to Johns Hopkins University. Z.M.A. is a
recipient of a Research to Prevent Blindness Career Development Award.
This work was also supported by funding from the Higher Education
Commission and the Ministry of Science and Technology (Islamabad,
Pakistan) to Sheikh Riazuddin and W.A., the International Center for
Genetic Engineering and Biotechnology (Trieste, Italy) under project
CRP/PAK08-01 contract 08/009 to Sheikh Riazuddin, the Cincinnati
Children's Hospital Research Foundation (CCHMC) Intramural Research
Funds to Saima Riazuddin and Z.M.A., a National Science Foundation grant
(IOS-1050754) to E.K.B., US National Institute on Deafness and Other
Communication Disorders (NIDCD/NIH) research grants R01 DC03594 and
DC011651 to S.M.L., R01 HL092544 to L.V.P., R01 DC009645 to M.T., R01
DC008861 to G.I.F., R01 DC012564 and R00 DC009287 to Z.M.A., and R01
DC011803 and R01 DC011748 to Saima Riazuddin, and intramural funds from
the NIDCD (DC000039-15) to T.B.F.
NR 52
TC 71
Z9 77
U1 4
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2012
VL 44
IS 11
BP 1265
EP 1271
DI 10.1038/ng.2426
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 029KZ
UT WOS:000310495800021
PM 23023331
ER
PT J
AU Lovinger, DM
AF Lovinger, David M.
TI New twist on orphan receptor GPR88 function
SO NATURE NEUROSCIENCE
LA English
DT Editorial Material
ID EXPRESSION; NEURONS
AB Ligands for G protein coupled receptor 88 (GPR88) have not yet been found. A new study finds that GPR88 is important in the physiology of dorsal striatal projection neurons, as well as in behaviors involving this brain region.
C1 NIAAA, Lab Integrat Neurosci, Bethesda, MD USA.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Bethesda, MD USA.
EM lovindav@mail.nih.gov
FU Intramural NIH HHS [Z01 AA000407-06]
NR 15
TC 1
Z9 1
U1 1
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2012
VL 15
IS 11
BP 1469
EP 1470
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 028LX
UT WOS:000310424900002
PM 23103990
ER
PT J
AU Lai, KO
Wong, ASL
Cheung, MC
Xu, P
Liang, ZY
Lok, KC
Xie, H
Palko, ME
Yung, WH
Tessarollo, L
Cheung, ZH
Ip, NY
AF Lai, Kwok-On
Wong, Alan S. L.
Cheung, Man-Chun
Xu, Pei
Liang, Zhuoyi
Lok, Ka-Chun
Xie, Hui
Palko, Mary E.
Yung, Wing-Ho
Tessarollo, Lino
Cheung, Zelda H.
Ip, Nancy Y.
TI TrkB phosphorylation by Cdk5 is required for activity-dependent
structural plasticity and spatial memory
SO NATURE NEUROSCIENCE
LA English
DT Article
ID LONG-TERM POTENTIATION; SINGLE DENDRITIC SPINES; SYNAPTIC PLASTICITY;
HIPPOCAMPAL-NEURONS; PROTEIN-SYNTHESIS; SIGNAL-TRANSDUCTION; NMDA
RECEPTORS; BDNF; LTP; ROLES
AB The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB participate in diverse neuronal functions, including activity-dependent synaptic plasticity that is crucial for learning and memory. On binding to BDNF, TrkB is not only autophosphorylated at tyrosine residues but also undergoes serine phosphorylation at S478 by the serine/threonine kinase cyclin-dependent kinase 5 (Cdk5). However, the in vivo function of this serine phosphorylation remains unknown. We generated knock-in mice lacking this serine phosphorylation (Trkb(S478A/S478A) mice) and found that the TrkB phosphorylation deficient mice displayed impaired spatial memory and compromised hippocampal long-term potentiation (LIP). S478 phosphorylation of TrkB regulates its interaction with the Rac1-specific guanine nucleotide exchange factor TIAM1, leading to activation of Rac1 and phosphorylation of S6 ribosomal protein during activity-dependent dendritic spine remodeling. These findings reveal the importance of Cdk5-mediated S478 phosphorylation of TrkB in activity-dependent structural plasticity, which is crucial for LIP and spatial memory formation.
C1 [Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China.
[Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, Mol Neurosci Ctr, Hong Kong, Hong Kong, Peoples R China.
[Lai, Kwok-On; Wong, Alan S. L.; Cheung, Man-Chun; Xu, Pei; Liang, Zhuoyi; Lok, Ka-Chun; Cheung, Zelda H.; Ip, Nancy Y.] Hong Kong Univ Sci & Technol, State Key Lab Mol Neurosci, Hong Kong, Hong Kong, Peoples R China.
[Xie, Hui; Yung, Wing-Ho] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
[Palko, Mary E.; Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA.
RP Ip, NY (reprint author), Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China.
EM boip@ust.hk
OI Liang, Zhuoyi/0000-0003-1622-524X
FU Research Grants Council of Hong Kong [HKUST 661109, 661309, 660810,
661010, 661111]; University Grants Committee [AoE/B-15/01]; S.H. Ho
Foundation; Croucher Foundation; National Cancer Institute, Center for
Cancer Research, US National Institutes of Health
FX We are grateful to A. Kulkarni (National Institutes of Health) and T.
Curran (University of Pennsylvania) for the Cdk5-/- mice,
L.-H. Tsai (Massachusetts Institute of Technology) for the
p35-/- mice, M. Greenberg (Harvard Medical School) for the
phospho-TIAM1 and phospho-PAK antibodies, W Mobley (University of
California, San Diego) for TIAM1 expression constructs, and L. Reichardt
(University of California, San Francisco) for the chicken antibody to
TrkB. We thank C. Kwong, B. Lai, P. Sun, B. Butt, Y. Liang, H. Chuang,
Y. Dai and K. Ho for their excellent technical assistance, Amy Fu and
Ada Fu for critical reading of the manuscript, and members of the Ip
laboratory for many helpful discussions. This study was supported in
part by the Research Grants Council of Hong Kong (HKUST 661109,661309,
660810, 661010 and 661111), the Area of Excellence Scheme of the
University Grants Committee (AoE/B-15/01) and the S.H. Ho Foundation.
N.Y.I. was the recipient of Croucher Foundation Senior Research
Fellowship, and K.-O.L. and Z.H.C. were the recipients of Croucher
Foundation Research Fellowship. M.E.P. and L.T. were supported by the
Intramural Research Program of the National Cancer Institute, Center for
Cancer Research, US National Institutes of Health.
NR 50
TC 53
Z9 55
U1 1
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2012
VL 15
IS 11
BP 1506
EP 1515
DI 10.1038/nn.3237
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 028LX
UT WOS:000310424900010
PM 23064382
ER
PT J
AU Koya, E
Cruz, FC
Ator, R
Golden, SA
Hoffman, AF
Lupica, CR
Hope, BT
AF Koya, Eisuke
Cruz, Fabio C.
Ator, Robert
Golden, Sam A.
Hoffman, Alexander F.
Lupica, Carl R.
Hope, Bruce T.
TI Silent synapses in selectively activated nucleus accumbens neurons
following cocaine sensitization
SO NATURE NEUROSCIENCE
LA English
DT Article
ID LONG-TERM DEPRESSION; CONTEXT-SPECIFIC SENSITIZATION; RECEPTOR SUBUNIT
COMPOSITION; INDUCED LOCOMOTOR-ACTIVITY; VENTRAL TEGMENTAL AREA;
SYNAPTIC PLASTICITY; IN-VIVO; DOPAMINE NEURONS; BEHAVIORAL
SENSITIZATION; GLUTAMATE TRANSMISSION
AB Cocaine-induced alterations in synaptic glutamate function in nucleus accumbens are thought to mediate drug-related behaviors such as psychomotor sensitization. However, previous studies have examined global alterations in randomly selected accumbens neurons regardless of their activation state during cocaine-induced behavior. We recently found that a minority of strongly activated Fos-expressing accumbens neurons are necessary for cocaine-induced psychomotor sensitization, whereas the majority of accumbens neurons are less directly involved. We assessed synaptic alterations in these strongly activated accumbens neurons in Fos-GFP mice, which express a fusion protein of Fos and GFP in strongly activated neurons, and compared these alterations with those in surrounding non-activated neurons. Cocaine sensitization produced higher levels of 'silent synapses', which contained functional NMDA receptors and nonfunctional AMPA receptors only in GFP-positive neurons, 6-11 d after sensitization. Thus, distinct synaptic alterations are induced in the most strongly activated accumbens neurons that mediate psychomotor sensitization.
C1 [Koya, Eisuke; Cruz, Fabio C.; Ator, Robert; Golden, Sam A.; Hope, Bruce T.] NIDA, Behav Neurosci Branch, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA.
[Hoffman, Alexander F.; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA.
RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, US NIH,US Dept HHS, Baltimore, MD USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; Cruz, Fabio/K-1497-2013; Hoffman,
Alexander/H-3035-2012;
OI Hope, Bruce/0000-0001-5804-7061; Hoffman, Alexander/0000-0002-2676-0628;
Golden, Sam/0000-0002-2104-2272
FU National Institute on Drug Abuse
FX We thank A. Barth for providing the first line of Fos-GFP mice, K.
Knestaut and J. Hug for breeding the Fos-GFP mice, and E. Goldart and R.
Ator for genotyping assistance. We thank S. Hall and T. Shippenberg for
the use of their locomotor activity chambers. We thank S. Kourrich for
many fruitful discussions regarding synaptic plasticity in the nucleus
accumbens. This research was supported by the National Institute on Drug
Abuse, Intramural Research Program.
NR 46
TC 32
Z9 33
U1 1
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2012
VL 15
IS 11
BP 1556
EP 1562
DI 10.1038/nn.3232
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA 028LX
UT WOS:000310424900016
PM 23023294
ER
PT J
AU Friedl, P
Sahai, E
Weiss, S
Yamada, KM
AF Friedl, Peter
Sahai, Erik
Weiss, Stephen
Yamada, Kenneth M.
TI New dimensions in cell migration
SO NATURE REVIEWS MOLECULAR CELL BIOLOGY
LA English
DT Article
ID EXTRACELLULAR-MATRIX; LEUKOCYTE MIGRATION; CANCER; INVASION;
MORPHOGENESIS; COLLAGEN; TISSUE; 3D; PLASTICITY; MODEL
AB Studies of cell migration in three-dimensional (3D) cell culture systems and in vivo have revealed several differences when compared with cell migration in two dimensions, including their morphology and mechanical and signalling control. Here, researchers assess the contribution of 3D models to our understanding of cell migration, both in terms of the mechanisms used to drive single cell and collective cell migration and how migrating cells respond to a changing environment in vivo.
C1 [Friedl, Peter] Radboud Univ Nijmegen, Med Ctr, NL-6500 HC Nijmegen, Netherlands.
[Friedl, Peter] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Sahai, Erik] Canc Res UK, London Res Inst, London WC2A 3LY, England.
[Weiss, Stephen] Univ Michigan, Ann Arbor, MI 48109 USA.
[Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Friedl, P (reprint author), Radboud Univ Nijmegen, Med Ctr, NL-6500 HC Nijmegen, Netherlands.
EM p.friedl@ncmls.ru.nl; erik.sahai@cancer.org.uk; sjweiss@med.umich.edu;
kenneth.yamada@nih.gov
RI Friedl, Peter/A-8961-2010;
OI Yamada, Kenneth/0000-0003-1512-6805; Sahai, Erik/0000-0002-3932-5086
FU Intramural NIH HHS
NR 30
TC 83
Z9 84
U1 6
U2 97
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-0072
J9 NAT REV MOL CELL BIO
JI Nat. Rev. Mol. Cell Biol.
PD NOV
PY 2012
VL 13
IS 11
BP 743
EP 747
DI 10.1038/nrm3459
PG 5
WC Cell Biology
SC Cell Biology
GA 028PQ
UT WOS:000310435000015
PM 23072889
ER
PT J
AU Braganza, MZ
Kitahara, CM
de Gonzalez, AB
Inskip, PD
Johnson, KJ
Rajaraman, P
AF Braganza, Melissa Z.
Kitahara, Cari M.
de Gonzalez, Amy Berrington
Inskip, Peter D.
Johnson, Kimberly J.
Rajaraman, Preetha
TI Ionizing radiation and the risk of brain and central nervous system
tumors: a systematic review
SO NEURO-ONCOLOGY
LA English
DT Review
DE brain cancer; brain tumors; glioma; ionizing radiation; meningioma
ID ATOMIC-BOMB SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER
SURVIVOR; DENTAL X-RAYS; SKIN HEMANGIOMA; INTRACRANIAL MENINGIOMA;
TINEA-CAPITIS; FOLLOW-UP; EPIDEMIOLOGY; RADIOTHERAPY
AB Although exposure to moderate-to-high doses of ionizing radiation is the only established environmental risk factor for brain and CNS tumors, it is not clear whether this relationship differs across tumor subtypes, by sex or age at exposure, or at the low-to-moderate range of exposure. This systematic review summarizes the epidemiologic evidence on the association between ionizing radiation exposure and risk of brain/CNS tumors. Articles included in this review estimated radiation exposure doses to the brain and reported excess relative risk (ERR) estimates for brain/CNS tumors. Eight cohorts were eligible for inclusion in the analysis. Average age at exposure ranged from 8 months to 26 years. Mean dose to the brain ranged from 0.07 to 10 Gy. Elevated risks for brain/CNS tumors were consistently observed in relation to ionizing radiation exposure, but the strength of this association varied across cohorts. Generally, ionizing radiation was more strongly associated with risk for meningioma compared with glioma. The positive association between ionizing radiation exposure and risk for glioma was stronger for younger vs older ages at exposure. We did not observe an effect modification on the risk for meningioma by sex, age at exposure, time since exposure, or attained age. The etiologic role of ionizing radiation in the development of brain/CNS tumors needs to be clarified further through additional studies that quantify the association between ionizing radiation and risk for brain/CNS tumors at low-to-moderate doses, examine risks across tumor subtypes, and account for potential effect modifiers.
C1 [Braganza, Melissa Z.; Kitahara, Cari M.; de Gonzalez, Amy Berrington; Inskip, Peter D.; Rajaraman, Preetha] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA.
[Braganza, Melissa Z.; Johnson, Kimberly J.] Washington Univ, St Louis, MO USA.
RP Braganza, MZ (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA.
EM melissa.braganza@nih.gov
RI Kitahara, Cari/R-8267-2016
FU National Cancer Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health.
NR 40
TC 37
Z9 37
U1 0
U2 15
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2012
VL 14
IS 11
BP 1316
EP 1324
DI 10.1093/neuonc/nos208
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 027SN
UT WOS:000310373800002
PM 22952197
ER
PT J
AU Proescholdt, MA
Merrill, MJ
Stoerr, EM
Lohmeier, A
Pohl, F
Brawanski, A
AF Proescholdt, Martin A.
Merrill, Marsha J.
Stoerr, Eva-Maria
Lohmeier, Annette
Pohl, Fabian
Brawanski, Alexander
TI Function of carbonic anhydrase IX in glioblastoma multiforme
SO NEURO-ONCOLOGY
LA English
DT Article
DE apoptosis; CAIX; hypoxia; invasion; pH
ID TUMOR-CELL GROWTH; BRAIN-TUMORS; CA-IX; EXTRACELLULAR PH;
POOR-PROGNOSIS; GLIOMA-CELLS; IN-VIVO; HYPOXIA; EXPRESSION; SURVIVAL
AB Carbonic anhydrase (CA) IX is over-expressed in glioblastoma; however, its functions in this context are unknown. Metabolically, glioblastomas are highly glycolytic, leading to a significant lactic acid load. Paradoxically, the intracellular pH is alkaline. We hypothesized that CAIX contributes to the extrusion of hydrogen ions into the extracellular space, thereby moderating intra- and extracellular pH and creating an environment conductive to enhanced invasion. We investigated the role of CAIX as a prognostic marker in patients with glioblastoma and its biological function in vitro. CAIX expression was analyzed in 59 patients with glioblastoma by immunohistochemistry. The expression levels were correlated to overall survival. In vitro, U251 and Ln 18 glioblastoma cells were incubated under hypoxia to induce CAIX expression, and RNA interference (RNAi) was used to examine the function of CAIX on cell attachment, invasion, intracellular energy transfer, and susceptibility to adjuvant treatment. High CAIX expression was identified as an independent factor for poor survival in patients with glioblastoma. In vitro, cell attachment and invasion were strongly reduced after knockdown of CAIX. Finally, the effects of radiation and chemotherapy were strongly augmented after CAIX interference and were accompanied by a higher rate of apoptotic cell death. CAIX is an independent prognostic factor for poor outcome in patients with glioblastoma. Cell attachment, invasion, and survival during adjuvant treatment are significantly influenced by high CAIX expression. These results indicate that inhibition of CAIX is a potential metabolic target for the treatment of patients with glioblastoma.
C1 [Proescholdt, Martin A.; Stoerr, Eva-Maria; Lohmeier, Annette; Brawanski, Alexander] Univ Regensburg, Med Ctr, Dept Neurosurg, D-93053 Regensburg, Germany.
[Merrill, Marsha J.] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Pohl, Fabian] Univ Regensburg, Med Ctr, Dept Radiat Oncol, D-93053 Regensburg, Germany.
RP Proescholdt, MA (reprint author), Univ Regensburg, Med Ctr, Dept Neurosurg, Franz Josef Str Allee 11, D-93053 Regensburg, Germany.
EM martin.proescholdt@klinik.uni-regensburg.de
NR 42
TC 29
Z9 29
U1 2
U2 12
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD NOV
PY 2012
VL 14
IS 11
BP 1357
EP 1366
DI 10.1093/neuonc/nos216
PG 10
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 027SN
UT WOS:000310373800006
PM 23074198
ER
PT J
AU Yakel, JL
AF Yakel, Jerrel L.
TI Nicotinic ACh Receptors in the Hippocampus: Role in Excitability and
Plasticity
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Review
ID LONG-TERM POTENTIATION; AMYLOID-BETA-PEPTIDE; STRATUM-ORIENS
INTERNEURONS; CENTRAL CHOLINERGIC SYSTEM; CENTRAL-NERVOUS-SYSTEM; RAT
ENTORHINAL CORTEX; ACETYLCHOLINE-RECEPTOR; SYNAPTIC PLASTICITY;
ALZHEIMERS-DISEASE; DENTATE GYRUS
AB The nicotinic ACh receptors (nAChRs) are in the cys-loop family of ligand-gated ion channels. They are widely expressed throughout the brain, including in the hippocampus where they are thought to be involved in regulating excitability, plasticity, and cognitive function. In addition, dysfunction in hippocampal nAChRs has been linked to a variety of neurological disorders and diseases, including Alzheimer's disease, schizophrenia, and epilepsy. In order to understand how to treat nAChR-related disorders and diseases, it is critical to understand how these receptors participate in normal brain function; this entails not only understanding the biophysical properties of ion channel function and their pattern of expression but also how these receptors are regulating excitability and circuit behavior.
The primary cholinergic input to the hippocampus comes from the medial septum and diagonal band of Broca; however, the mechanistic details are unknown of how activation of cholinergic receptors, either through exogenous nAChR ligands or the activation of endogenous acetylcholine release, regulates hippocampal network activity. This entails direct study of the excitatory and inhibitory neuronal networks, as well as the role of nonneuronal cells, in regulating hippocampal function.
Here, I will review the latest work from my laboratory in which we have attempted to do just that, with the overall goal of learning more about the role of the hippocampal nAChR in synaptic plasticity.
C1 NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop F2-08, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences.
NR 114
TC 21
Z9 21
U1 0
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD NOV
PY 2012
VL 14
IS 11
BP 1249
EP 1257
DI 10.1093/ntr/nts091
PG 9
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 027TN
UT WOS:000310376600001
PM 22472168
ER
PT J
AU Berggren, EK
Mele, L
Landon, MB
Spong, CY
Ramin, SM
Casey, B
Wapner, RJ
Varner, MW
Rouse, DJ
Sciscione, A
Catalano, P
Harper, M
Saade, G
Caritis, SN
Sorokin, Y
Peaceman, AM
Tolosa, JE
AF Berggren, Erica K.
Mele, Lisa
Landon, Mark B.
Spong, Catherine Y.
Ramin, Susan M.
Casey, Brian
Wapner, Ronald J.
Varner, Michael W.
Rouse, Dwight J.
Sciscione, Anthony
Catalano, Patrick
Harper, Margaret
Saade, George
Caritis, Steve N.
Sorokin, Yoram
Peaceman, Alan M.
Tolosa, Jorge E.
CA Eunice Kennedy Shriver Natl Inst
TI Perinatal Outcomes in Hispanic and Non-Hispanic White Women With Mild
Gestational Diabetes
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID LOW-BIRTH-WEIGHT; EPIDEMIOLOGIC PARADOX; PREGNANCY OUTCOMES; MELLITUS;
DISPARITIES; PREVALENCE
AB OBJECTIVE: To compare perinatal outcomes between self-identified Hispanic and non-Hispanic white women with mild gestational diabetes mellitus (GDM) or glucose intolerance.
METHODS: In a secondary analysis of a mild GDM treatment trial, we compared perinatal outcomes by race and ethnicity for 767 women with glucose intolerance (abnormal 50-g 1-hour screen, normal 100-g 3-hour oral glucose tolerance test), 371 women with mild GDM assigned to usual prenatal care, and 397 women with mild GDM assigned to treatment. Outcomes included: composite adverse perinatal outcome (neonatal death, hypoglycemia, hyperbilirubinemia, hyperinsulinemia, stillbirth, birth trauma), gestational age at delivery, birth weight, and hypertensive disorders of pregnancy. Adjusted regression models included: 100-g 3-hour oral glucose tolerance test results, parity, gestational age, body mass index, maternal age at enrollment, and current tobacco use.
RESULTS: The sample of 1,535 women was 68.3% Hispanic and 31.7% non-Hispanic white. Among women with glucose intolerance, Hispanic women had more frequent composite outcome (37% compared with 27%, adjusted odds ratio [OR] 1.62, 95% confidence interval [CI] 1.10-2.37) with more neonatal elevated C-cord peptide (19% compared with 13%, adjusted OR 1.79, 95% CI 1.04-3.08) and neonatal hypoglycemia (21% compared with 13%, adjusted OR 2.04, 95% CI 1.18-3.53). Among women with untreated mild GDM, outcomes were similar by race and ethnicity. Among Hispanic women with treated mild GDM, composite outcome was similar to non-Hispanic white women (35% compared with 25%, adjusted OR 1.62, 95% CI 0.92-2.86), but Hispanic neonates had more frequent hyperinsulinemia (21% compared with 10%, adjusted OR 2.96, 95% CI 1.33-6.60).
CONCLUSION: Individual components of some neonatal outcomes were more frequent in Hispanic neonates, but most perinatal outcomes were similar between Hispanic and non-Hispanic ethnic groups. (Obstet Gynecol 2012; 120: 1099-1104) DOI: http://10.1097/AOG.0b013e31827049a5
C1 Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA.
Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
Univ Texas Hlth Sci Ctr Houston, Dept Obstet & Gynecol, Houston, TX USA.
Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA.
Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA.
Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
Case Western Reserve Univ, Metrohlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH USA.
Wake Forest Univ Hlth Sci, Dept Obstet & Gynecol, Winston Salem, NC USA.
Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX USA.
Univ Pittsburgh, Dept Obstet & Gynecol, Pittsburgh, PA USA.
Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
Northwestern Univ, Dept Obstet & Gynecol, Chicago, IL 60611 USA.
Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
George Washington Univ, Dept Obstet & Gynecol, Biostat Ctr, Washington, DC USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Dept Obstet & Gynecol, Bethesda, MD USA.
RP Berggren, EK (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, 834 Chestnut St,Suite 400, Philadelphia, PA 19107 USA.
EM erica.berggren@gmail.com
RI Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Peaceman, Alan/0000-0002-4515-4850;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD27915, HD34116, HD40485, HD34208, HD27869,
HD40500, HD40560, HD34136, HD40544, HD27860, HD40545, HD53097, HD21410,
HD27917, HD40512, HD53118, HD36801]; General Clinical Research Centers
[M01-RR00034]; National Center for Research Resources [UL1-RR024989,
M01-RR00080, UL1-RR025764, C06-RR11234]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD27915, HD34116, HD40485, HD34208, HD27869, HD40500, HD40560, HD34136,
HD40544, HD27860, HD40545, HD53097, HD21410, HD27917, HD40512, HD53118,
HD36801), General Clinical Research Centers Grant (M01-RR00034), and the
National Center for Research Resources (UL1-RR024989, M01-RR00080,
UL1-RR025764, C06-RR11234) and does not necessarily represent the
official views of the NICHD or the National Institutes of Health (NIH).
NR 24
TC 3
Z9 3
U1 0
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2012
VL 120
IS 5
BP 1099
EP 1104
DI 10.1097/AOG.0b013e31827049a5
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 029RF
UT WOS:000310512500017
PM 23090528
ER
PT J
AU Spong, CY
Berghella, V
Wenstrom, KD
Mercer, BM
Saade, GR
AF Spong, Catherine Y.
Berghella, Vincenzo
Wenstrom, Katharine D.
Mercer, Brian M.
Saade, George R.
TI Preventing the First Cesarean Delivery Summary of a Joint Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
Society for Maternal-Fetal Medicine, and American College of
Obstetricians and Gynecologists Workshop
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; ASSISTED VAGINAL DELIVERY; POSTTERM
PREGNANCY; NULLIPAROUS WOMEN; LABOR; INDUCTION; OUTCOMES; FORCEPS;
RATES; ANALGESIA
AB With more than one third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean delivery. The available information on maternal and fetal factors, labor management and induction, and nonmedical factors leading to the first cesarean delivery was reviewed as well as the implications of the first cesarean delivery on future reproductive health. Key points were identified to assist with reduction in cesarean delivery rates including that labor induction should be performed primarily for medical indication; if done for nonmedical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of "failed induction" should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery are facilitated and encouraged. When discussing the first cesarean delivery with a patient, counseling should include its effect on future reproductive health. (Obstet Gynecol 2012; 120: 1181-93) DOI: http://10.1097/AOG.0b013e3182704880
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA.
Thomas Jefferson Univ, Jefferson Med Coll, Dept Obstet & Gynecol, Div Maternal Fetal Med, Philadelphia, PA 19107 USA.
Brown Univ, Women & Infants Hosp, Brown Alpert Sch Med, Dept Obstet & Gynecol,Div Maternal Fetal Med, Providence, RI USA.
Case Western Reserve Univ, MetroHealth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
Univ Texas Med Branch, Div Maternal Fetal Med, Dept Obstet & Gynecol, Galveston, TX USA.
Soc Maternal Fetal Med, Publicat & Execut Comm, Washington, DC USA.
RP Spong, CY (reprint author), NICHD, Pregnancy & Perinatol Branch, NIH, 6100 Executive Blvd,Room 4B03 MSC 7510, Bethesda, MD 20892 USA.
EM spongc@mail.nih.gov
OI Berghella, Vincenzo/0000-0003-2854-0239
FU Intramural NIH HHS [Z99 HD999999]
NR 39
TC 159
Z9 175
U1 1
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD NOV
PY 2012
VL 120
IS 5
BP 1181
EP 1193
DI 10.1097/AOG.0b013e3182704880
PG 13
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 029RF
UT WOS:000310512500026
PM 23090537
ER
EF